Optical and Selective Activation of Astrocytes Can Trigger Cortical Spreading
Depression
S.M. Baca, R.T. Jones, C.J. Dietz, I. Mody, A. Charles
Neurology, University of California, Los Angeles, Los Angeles, CA,
USA.
Objectives: We tested the hypotheses that direct optical activation of
astrocytes is sufficient to initiate cortical spreading depression (CSD) and that
CSD can be evoked by methods that do not involve deformation or damage of tissue,
supra-physiological levels of potassium, or the application of exogenous drugs.
Background: CSD is a slowly propagated wave of electrical and vascular
activity that is believed to underlie the migraine aura, and CSD is also triggered
by local injury to the brain. The cellular mechanisms by which CSD could be
spontaneously triggered remain poorly understood. In experimental models, CSD is
commonly elicited by pinprick to the cortical surface, by application of high
concentrations of KCl, or by tetanic electrical stimulation. Here, we investigated a
less invasive, cell-specific method of triggering CSD.
Methods: The channelrhodopsin-2 (ChR2) receptor was selectively
expressed in GFAP+ cells in mice. For in vitro investigations,
hippocampal slices were prepared from these GFAP-ChR2 mice. For
in vivo studies, mice were anesthetized, a thinned-skull
cortical window was made, and a tungsten electrode and fiber optic were inserted
through separate burr holes. For both preparations, a 473nm laser coupled to a fiber
optic activated ChR2, and CSD was visualized with optical intrinsic signal imaging
(OIS) and recorded as changes in local field potential.
Results: In GFAP-ChR2 mice, activation of ChR2 with blue light elicited
CSD, whereas the same intensity and duration of light exposure produced no CSD in
wild-type littermate controls. Similarly, blue light activated spreading depression
in hippocampal slices from GFAP-ChR2 mice but not from controls. The OIS
characteristics of optically triggered CSD were different from those associated with
KCl-evoked CSD, suggesting distinct cellular responses.
Conclusions: These studies indicate that astrocytes can play a primary
role in the initiation of CSD, and that CSD can be generated by a relatively
non-invasive optical approach.
OR2
Magnetic Resonance Angiography Reveals Intracranial but No Extracranial
Arterial Dilatation during Migraine Attacks
F.M. Amin1, M.S. Asghar1, A. Hougaard1, A.E.
Hansen2, V.A. Larsen3, P.J.H. de Koning4,
H.B.W. Larsson2, J. Olesen1, M. Ashina1
1Danish Headache Center, Department of Neurology, Glostrup
Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Glostrup, Denmark; 2Functional Imaging Unit, Diagnostic Department,
Glostrup Hospital, Faculty of Health and Medical Sciences, University of
Copenhagen, Glostrup, Denmark; 3Department of Radiology,
Rigshospitalet, Faculty of Health and Medical Sciences, University of
Copenhagen, Copenhagen, Denmark; 4Division of Image Processing,
Leiden University Medical Center, Leiden, The Netherlands.
Objectives: The aim of the present study was to measure extracranial and
intracranial arteries during attacks of migraine without aura.
Background: Extracranial arterial dilatation has clinically been
considered the cause of pain in patients suffering from migraine without aura.
Methods: We performed high-resolution magnetic resonance angiography
(MRA) in 24 female patients with migraine without aura during spontaneous unilateral
migraine attacks. Fifteen patients were also scanned 30 min after treatment with 6
mg subcutaneous sumatriptan. Primary endpoints were difference in circumference of
extra- and intracranial arterial segments comparing the pain and the non-pain side
and the attack and attack-free day. The extracranial arterial segments included: the
external carotid (ECA), the superficial temporal (STA), the middle meningeal (MMA)
and the cervical part of the internal carotid (ICAcervical) artery. The
intracranial arterial segments were: the cavernous (ICAcavernous) and
cerebral (ICAcerebral) parts of the internal carotid, the middle cerebral
(MCA) and the basilar artery (BA).
Results: We found no dilatation of the ECA, MMA, STA,
ICAcervical or BA (p > 0.05). The
ICAcavernous and ICAcerebral were dilated (10.5%, 10.2%)
on the pain side compared to the non-pain side (p ≤ 0.02). The MCA
was dilated on both sides during attack (p < 0.05).
Administration of sumatriptan caused constriction of the extracranial arteries
(p ≤ 0.034) but the ICAcerebral and the MCA remained
unchanged (p ≥ 0.124).
Conclusions: Migraine pain was not accompanied by extracranial arterial
dilatation and only by slight intracranial dilatation. Sumatriptan relieved the
headache and constricted extracerebral, but did not constrict the dilated cerebral
arteries.
M. Tatsumoto1, T. Eda2, T. Ishikawa3, M.
Ayama3, K. Hirata1
1Neurology, Dokkyo Medical University, Shimotsuga, Tochigi, Japan;
2Education Center of Medical Informatics, International
University of Health and Welfare, Ohtawara, Tochigi, Japan; 3Advanced
Interdisciplinary Sciences, Graduate School of Engineering, Utsunomiya
University, Utsunomiya, Tochigi, Japan.
Objectives: The peak wavelength of intrinsically photosensitive retinal
ganglion cells (ipRGC) differs from those of rod and cone cells. This study was
conducted with the objective of determining whether light stimulation by the peak
wavelength of ipRGC might induce migraines.
Background: Recently, a study revealed that both the extrinsic
photoactivation of ipRGC and the intrinsic photoactivation of melanopsin may be
involved in the exacerbation of migraines by light stimulation. However,
light-induced migraine attacks triggered by the peak wavelength (480nm) of ipRGC
have not yet been reported.
Methods: We investigated the threshold for uncomfortable glare created
by light stimulation. The first study population consisted of 46 consecutive
migraine patients. Headaches were diagnosed based on the ICHD-II
criteria. Light stimulation was achieved using light-emitting diodes through the
interference filter which permeabilized three different specific wavelengths (480nm,
550nm, 610nm). The subjects were allowed to adapt in a darkroom for 5 min. They were
then asked to evaluate the discomfort glare caused by a wavelength chosen at random
from the three kinds used. Each wavelength had seven luminance levels in the range
of 110 to 3900cd/m2.
Results: Migraine patients complained of uncomfortable glare more
frequently than the control patients for all of the wavelengths employed. The
discomfort glare of wavelength (480nm) for migraine patients was significantly
greater than for the control subjects at all luminance levels
(110-1860cd/m2). The discomfort glare of wavelength (550nm) for
migraine patients was significantly greater than for the control subjects at
luminance levels (1330 and 2650cd/m2). The discomfort glare of wavelength
(610nm) for migraine patients was significantly greater than for the control
subjects at luminance levels (1980cd/m2). Light stimulation with the peak
wavelength (480nm) of ipRGC induced migraine attacks more frequently than
extensive-wavelength (550 and 610nm). The light source most frequently perceived as
causing discomfort in the migraine group was the 480nm (39 cases), followed by the
550nm (4 cases) and the 610nm (3 cases).
Conclusions: It is reported that migraine pain was worsened by light,
even in blind patients in whom rod and cone damage had caused the loss of image
formation. Light stimulation with the peak wavelength of ipRGC induced migraine
attacks more frequently than extensive-wavelength (550 and 610nm). We determined
that migraines were easily induced by the peak wavelength (480nm) of ipRGC, though
not in the case of blind migraine patients. These results confirm that ipRGC are
involved in the triggering of migraine attacks by light.
OR4
The Selective Cannabinoid Type-2 Receptor Agonist, JWH-133, Abolishes
Mechanical Allodynia in a Model of Post-Traumatic Headache
1Neurological Surgery, Thomas Jefferson University, Philadelphia,
PA, USA; 2Cancer Biology, Thomas Jefferson University, Philadelphia,
PA, USA.
Objectives: The potential therapeutic mechanisms of a selective
cannabinoid type-2 receptor agonist compared to a CGRP antagonist and triptan agent
in a model of post-traumatic headache will be discussed. The use of rat and mouse
models of post-traumatic headache to study sensitization of the trigeminovascular
system will also be examined.
Background: Post-traumatic headache (PTH) is a prominent symptom of a
concussion and prevalent among patients with mild and moderate traumatic brain
injury. The cannabinoid type-2 receptor (CB2R) has an anti-nociceptive
role in neuropathic and inflammatory pain models; but, until now, modulation of the
CB2R has not been evaluated as a potential therapy for PTH.
CB2R activation (unlike CB type-1 receptor activation), is not
associated with psychoactive effects, making it an ideal therapeutic target. The
mechanism of the CB2R-mediated anti-nociceptive response is unclear.
Methods: A CB2R agonist (JWH-133 at 1 mg/kg) was compared to
a triptan (Sumatriptan), a CGRP antagonist (MK8825), and saline in a model of
controlled cortical impact (CCI) injury. CCI was induced in wild-type and
CB2R knockout mice with and without treatment with the
CB2R agonists (JWH-133 or 0-1966), or a CB2R antagonist
(SR144528). Craniotomy and incision-only mice were included as controls. Baseline
and weekly periorbital and paw von Frey (mechanical) allodynia testing were
performed for up to four weeks post-injury. CGRP immunoreactive trigeminal ganglia
cells and growth-associated protein (GAP-43) in the trigeminal nucleus caudalis
(TNC) were determined using immunohistochemistry and western blot.
Blood-brain-barrier (BBB) permeability was evaluated using sodium fluorescein (NaF)
(BBB disruption is a possible mechanism contributing to sensitization).
Intracellular adhesion molecule (ICAM) mRNA, and tumor necrosis factor-alpha (TNF-α)
mRNA in vehicle and CB2-treated groups were measured using qRT-PCR.
Results: Cortical injury causes a significant reduction in periorbital
and forepaw von Frey mechanical thresholds (p<0.001), but not hindpaw thresholds.
CB2R agonist treatment prevented the reduction of periorbital
thresholds (allodynia) after CCI (p<0.001); allodynia was only partially
attenuated in the Sumatriptan-treated (10 mg/kg) (p<0.05) and CGRP
antagonist-treated (100 mg/kg) (p<0.01) groups. CGRP and GAP-43 co-localize in
the TNC post-injury. CB2R agonist treatment reduced the CCI–induced
increase in GAP-43 levels in the TNC and the number of CGRP positive cells in the
trigeminal ganglia compared to controls (p<0.001). CB2R agonist
treatment significantly attenuated post-CCI increases in BBB permeability, ICAM and
TNF-α mRNA (p<0.05).
Conclusions: CB2R agonist treatment in an in vivo model of
head trauma modulates nociception and peptidergic synaptogenesis. CB2R
stimulation probably works through immune mechanisms; direct neuronal mechanisms may
also be involved.
OR5
Preference of Cortical Spreading Depression for Sensory Cortex
V.B. Bogdanov1, N.A. Schulz1, J.J. Theriot1, K.M.
Krisht2, J.R. Vargas1, D. Kaufmann3, P.M.
Sawant1, J.M. Mendez1, K.C. Brennan1
1Department of Neurology, University of Utah, Salt Lake City, UT,
USA; 2Department of Neurosurgery, University of Utah, Salt Lake City,
UT, USA; 3Anticonvulsant Drug Development Program, University of
Utah, Salt Lake City, UT, USA.
Objectives: Determine the susceptibility of different cortices to
cortical spreading depression.
Background: It is not known why aura is primarily a sensory phenomenon.
It is possible that sensory cortex is intrinsically more susceptible. On the other
hand it may be that aura events in non-sensory cortex are less clearly perceived
(the ‘silent spreading depression’ hypothesis). We tested the susceptibility of
cortex to cortical spreading depression (CSD) and anoxic depolarization (AD) in
mice, in an attempt to understand this question.
Methods: Optical intrinsic signal imaging and field potential recording
in mice.
Results: We first used a large 4*4 mm craniotomy to expose a wide area
(including motor, somatosensory, cingulate, retrosplenial, association, and visual
cortex) to increasing concentrations (8-120 mM) of potassium until CSD was elicited.
Wide field optical intrinsic signal imaging (OIS) allowed identification of the
initial CSD focus. 80% of CSD events began in either barrel cortex or visual cortex
(n=21). Additional experiments with craniotomy extended 2 mm more laterally and
exposing barrel cortex, S2, auditory cortex, primary and lateral secondary visual
cortex showed an identical pattern (n=5). The identity of barrel and visual cortex
was confirmed by generating whisker and visual OIS maps. Because any craniotomy
preparation could bias the onset location of CSD, we performed a separate series of
experiments in which a completely uniform stimulus (systemic anoxia) elicited AD.
Skull was left intact and no head fixation was used, in order to eliminate the
possibility of injury-induced events. All AD events began from barrel cortex
(n=7).
Conclusions: We conclude that CSD is preferentially inducible in primary
sensory cortex in mice. The predilection of aura for primary sensory cortex in
humans may have a similar mechanism.
OR6
Extracranial Projections of Meningeal Afferents and Their Impact on Meningeal
Nociception and Headache
M. Schüler1, K. Messlinger1, M. Dux3, W.L.
Neuhuber2, R. De Col4
1Institute of Physiology and Pathophysiology, University of
Erlangen-Nürnberg, Erlangen, Germany; 2Institute of Anatomy,
University of Erlangen-Nürnberg, Erlangen, Germany; 3Department of
Physiology, University of Szeged, Szeged, Hungary; 4Department of
Anaesthesiology and Operative Intensive Care, Faculty of Clinical Medicine
Mannheim, University of Heidelberg, Mannheim, Germany.
Objectives: Neuronal tracing and functional measurements in rat models
were combined to decipher the extracranial impact on meningeal nociception relevant
to headache generation.
Background: Headaches are caused by activation of intracranial afferents
innervating the dura mater and cerebral blood vessels. An involvement of the
pericranial tissue in headache generation is debated. Anatomical data suggest
innervation of pericranial tissues possibly contributing to an extracranial origin
of headaches.
Methods: For in vivo neuronal tracing, lower molecular weight dextrane
amines were applied to the periost underlying rat temporal muscle. Labelling was
observed two days later in the parietal dura mater, trigeminal ganglion and spinal
trigeminal nucleus and evaluated with confocal and electron microscopy. In the
hemisected rat head extracellular recordings were made from meningeal nerve fibers
activated by extra- and intracranial electrical and mechanical stimulation. In a
similar preparation, release of calcitonin gene-related peptide (CGRP) from the
cranial dura mater during injection of capsaicin into the pericranial muscles like
the temporal and the upper neck muscles was quantified. In vivo the same chemical
stimulation was used while meningeal blood flow was recorded with laser Doppler
flowmetry.
Results: In the parietal dura mater, retrogradely labelled C- and Adelta
fibers were found ramifying extensely. Their branches followed mainly arterial
vessels. More proximally the nerve fibers accompanied the middle meningeal artery
and projected through the spinosus nerve into the trigeminal ganglion. In the
maxillary and mandibular but not ophthalmic division of the trigeminal ganglion
small- and middle-sized neuronal cell bodies were labelled; some fibers could be
traced into the spinal trigeminal nucleus. Electrophysiological recordings showed
that same afferent fibers can have mechanosensitive receptive fields both in the
dura mater of the middle cranial fossa and in the parietal periost. Noxious
stimulation of the deep temporal muscle by capsaicin caused an increase in CGRP
release from the dura mater and elevated the meningeal blood flow.
Conclusions: Retrograde tracing and functional measurements suggest that
collaterals of meningeal nerve fibers innervating the middle cranial fossa project
through the skull into extracranial structures like periost and deep muscles and
form functional connections between extra- and intracranial tissues. This finding
offers a new explanation how noxious stimulation of pericranial tissues can directly
influence meningeal nociception possibly associated with headache generation.
OR7
The Thalamic Reticular Nucleus Is Activated by Cortical Spreading Depression in
Freely Moving Rats: Prevention by Acute Valproate
H. Bolay,1 N. Tepe,1 A. Filiz,1 E.
Dilekoz,2 D. Akcali,1 Y. Sara3
1Neurology & Neuropsyhiatry Centre, Gazi University, Ankara,
Turkey; 2Pharmacology, Gazi University, Ankara, Turkey;
3Pharmacology, Hacettepe University, Ankara, Turkey.
Objectives: The present study is designed to investigate the behavioral
alterations induced by cortical spreading depression (CSD) in freely moving rats and
accompanying activation of certain subcortical brain structures along with TNC.
Background: Pain is a sensation that requires a conscious state of mind
for its full perception, though majority of experimental animal studies addressing
the mechanisms underlying painful conditions, mainly in migraine models, are
conducted under anesthesia. Therefore, behavioral studies in consciously behaving
animals are valuable in translational research in pain disorders such as migraine.
CSD is linked with migraine headache and the available data is scarce regarding its
effects on subcortical brain structures in behaving rats.
Methods: CSD induced behavioral parameters were recorded by using a
combination of an automated behavioral analysis system and a video camera in freely
moving rats. Neuronal activity was also acquired during CSD. Immunohistochemistry
for c-fos was employed to detect activation pattern as well as confirmation of CSD.
The effects of acute valproate administration on behavioral parameters and c-fos
activation were evaluated.
Results: CSD significantly decreased locomotor activity, induced
freezing behavior and immobility in freely behaving rats. Other behavioral
parameters such as grooming, wet dog shake, eating, drinking and rearing were not
significantly altered. Valproate pretreatment decreased CSD-induced freezing
episodes and reversed the CSD-induced reduction in locomotor activity. ECoG
indicated no epileptiform discharges during freezing episodes. In addition to robust
c-fos activation in the cerebral cortex, CSD significantly increased c-fos
expression in trigeminal nucleus caudalis (TNC), amygdala, and thalamic reticular
nucleus (TRN) ipsilaterally. The c-fos activation was prominent in the visual sector
of TRN and not detected in somatosensorial and auditory TRN sectors.
Electrophysiological recordings revealed that CSD could propagate into the TRN.
Whereas acute valproate administration did not alter the electrophysiological
properties of SD in the cortex, it significantly blocked CSD induced c-fos
expression in TNC and TRN, but not in amygdala.
Conclusions: Multiple CSDs activate trigeminal pain nucleus in the
brainstem and reticular nucleus in the thalamus in freely moving rats. Anti-migraine
action of valproate may also include TRN among other sites in the brain. TRN
involvement during CSD in conscious and behaving rats is a novel finding that may
have mechanistic and therapeutic implications as a new target in migraine.
OR8
Stimulation of the Sphenopalatine Ganglion (SPG) for Cluster Headache (CH)
Treatment: Pathway CH-1 Study – Therapeutic Benefit and Patient Satisfaction
after One Year
R. Jensen1, J. Schoenen2, J.M. Láinez3, C.
Gaul4, A. Goodman5, A. Caparso5, A.
May6
1Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark;
2CHR de la Citadelle, Liège University, Liège, Belgium;
3Hospital Clinico Universitario, Universidad de Valencia,
Valencia, Spain; 4University Duisburg-Essen, Essen, Germany;
5Autonomic Technologies, Inc., Redwood City, CA, USA;
6Universitäts-Krankenhaus Eppendorf, Hamburg,
Germany.
Objectives: We aimed to evaluate the sustained benefits of patient
controlled, on-demand SPG stimulation in chronic CH patients implanted with the ATI
Neurostimulator for one year in the Pathway CH-1 (CH-1) study.
Background: Chronic CH is a disabling neurological disorder often
refractory to medical therapy. Novel, effective and well tolerated therapies are
needed. Results of a randomized, controlled, study of on-demand SPG stimulation with
the ATI Neurostimulation System demonstrated effective acute CH pain relief and in
some patients, may be related to decreased attack frequency. Clinically and
statistically significant improvement in quality of life (QoL) and reduction in
headache disability were also reported.
Methods: 43 patients dissatisfied with CH treatment were enrolled in the
CH-1 study; as of December 2012, 32 patients had completed the one-year study; of
those, 23 were enrolled in a Long Term Follow Up (LTFU) study. Nine patients were
not enrolled in LTFU due to early or investigator termination from CH-1. Mean time
from implant to LTFU enrollment was 15 months (range: 12-18). Headache disability
(HIT-6), QoL (SF-36v2) and a Patient Experience Survey (PES) were administered to
all LTFU patients.
Results: At enrollment, 78% (N=18) of patients indicated their “overall
evaluation of the ATI Neurostimulation System for treating their CH” as good or very
good. 78% (N=18) found SPG stimulation a useful therapy in treating their CH. 83%
(N=19) found surgical effects tolerable and the implanted neurostimulator
comfortable or did not notice it and 100% (N=23) found the stimulation sensation
tolerable. 65% (N=15) did not have significant side effects after stimulation. 91%
(N=21) would make the same decision again to treat their CH with the ATI
Neurostimulation System, and 96% (N=22) would recommend the ATI Neurostimulation
System to someone else.
HIT-6 and SF-36v2 improvements were reported at LTFU enrollment. 57% (N=13) of
patients experienced clinically significant improvement in headache disability
compared to baseline (greater than the mean clinically significant difference, -2.3
units). SF-36v2 physical (PCS) and mental (MCS) scores each improved by greater than
or within the clinically significant difference range of 3 to 5 units in 52% (N=12)
and 61% (N=14) of patients, respectively. Overall, 70% (N=16) had clinically
significant improvements in PCS, MCS or both.
Conclusions: Headache disability, QoL and PES results from more than one
year of continued usage indicate that SPG stimulation with the ATI Neurostimulator
is a robust therapy with sustained benefits and a high level of patient
satisfaction.
OR9
Persistent Frequent Nausea as a Predictor of Progression to Chronic Migraine:
Results from the American Migraine Prevalence and Prevention (AMPP)
Study
M.L. Reed1, K.M. Fanning1, D. Serrano1, D.C.
Buse2,3, R.B. Lipton2,3
1Vedanta Research, Chapel Hill, NC, USA; 2Albert
Einstein College of Medicine, Bronx, NY, USA; 3Montefiore Medical
Center, Bronx, NY, USA.
Objectives: Assess persistent frequent headache-related nausea (PFN) in
persons with episodic migraine (EM) in 2007 and 2008 as a predictor of new onset
chronic migraine (CM) in 2009.
Background: Though nausea is a cardinal feature of migraine, its
influence on migraine progression has not been evaluated.
Methods: Using data from the 2007 and 2008 AMPP surveys, we identified
subgroups with episodic ICHD-2 migraine and PFN or no or low frequency nausea
associated with headache (NLFN). PFN was defined by the presence of headache-related
nausea ≥ half the time in both 2007 and 2008. NLFN was defined by nausea < half
the time or absent with headache in both years. Participants with classified with CM
in 2009 if they met symptom criteria for migraine with headaches averaging ≥15
days/month in the past three months. Univariate differences in demographics for PFN
and NLFN were evaluated with Chi-square. Binary logistic regressions were performed
hierarchically to assess progression to CM in 2009 as a function of nausea status in
2007 and 2008. Model 1 assessed demographics (age, sex, annual household income).
Model 2 added headache-related disability (MIDAS Questionnaire). Model 3 added
depression (Patient Health Questionnaire-9). All three models included a migraine
symptom severity composite score (MSS score) to control for the impact of other
headache symptoms (e.g., pain features, photophobia, phonophobia). Odds ratios (ORs)
and 95% confidence intervals were used to (CI) contrast the PFN and NLFN groups on
progression to CM in 2009.
Results: There were 3,182 respondents with headache symptom and
frequency data available for all three years of the analysis. PFN was found in 43.7%
(1,389) of EM respondents and 3.4% (47) progressed to CM. NLFN was seen in 27.6%
(877) of respondents with EM and 1.5% progressed to CM. In comparison with NLFN, PFN
was more common in females (p<0.001) and Caucasians (p<0.05). PFN was
associated with a doubling of the risk of progression to CM after adjusting for
demographics and MSS score (OR 2.14, 95%CI 1.11-4.12, p=0.023). The addition of
headache-related disability minimally attenuated the association (OR 2.00,95%CI
1.03-3.87, p=0.04). With the addition of depression, the OR fell to 1.90 and just
missed statistical significance (95%CI: 0.98-3.71, p=0.059) suggesting the effect
was robust but underpowered in this analysis.
Conclusions: Persistent frequent nausea associated with headache is
common (43.7%) in the migraine population. After controlling for demographics,
migraine symptoms and headache-related disability, those with persistent frequent
headache-related nausea remained about twice as likely to progress to CM compared to
migraineurs with NLFN. Persistent frequent migraine-related nausea could be a marker
for CM progression risk or in the causal pathway.
OR10
Co-Occurrence of Cluster Headache and Trigeminal Neuralgia: Cluster-Tic
Syndrome in the LUCA Population
L.A. Wilbrink1,2, C.M. Weller3, C. Cheung1, J.
Haan1,4, M.D. Ferrari1
1Department of Neurology, Leiden University Medical Centre,
Leiden, The Netherlands; 2Department of Neurosurgery, Maastricht
University Medical Centre, Maastricht, The Netherlands; 3Department
of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands;
4Department of Neurology, Rijnland Hospital, Leiderdorp, The
Netherlands.
Objectives: To determine the prevalence and nature of trigeminal
neuralgia in a large group of cluster headache patients.
Background: Cluster-tic syndrome is a rare headache syndrome in which
trigeminal neuralgia and cluster headache co-occur. The existence of cluster-tic
syndrome as a separate entity is questioned, and figures on prevalence of
simultaneous existence of cluster headache and trigeminal neuralgia are not
available.
Methods: As part of a nationwide study on headache mechanisms in cluster
headache (LUCA), we collected clinical data of 244 cluster headache patients using a
semi-structured telephone interview.
Results: In 11 (4.5%) of cluster headache patients, attacks fulfilling
International Headache Society (ICHD-2) criteria for trigeminal neuralgia were also
present. In all cases trigeminal neuralgia occurred ipsilateral to cluster headache
and in the majority (82%) in the ophthalmic branch. In eight of these eleven
patients (73%) the frequency and time-pattern of trigeminal neuralgia seemed to
parallel cluster headache and was likely a part of the cluster headache spectrum. In
the three remaining patients cluster headache and trigeminal neuralgia were
unrelated in time and appeared to occur independently.
Conclusions: In conclusion, trigeminal neuralgia co-occurred in 11/244
(4.5%) of cluster headache patients. In only 3 (1.2%) patients trigeminal neuralgia
seemed to occur independently from cluster headache episodes.
OR11
Experimental Activation of the Sphenopalatine Ganglion Provokes Cluster-Like
Attacks in Humans
H.W. Schytz1, M. Barløse1, S. Guo1, J.
Selb2, A. Caparso3, R.H. Jensen1, M.
Ashina1
1Department of Neurology, Danish Headache Center, Glostrup,
Denmark; 2Massachusetts General Hospital, Harvard Medical School,
Optics Division, Athinoula A. Martinos Center for Biomedical Imaging,
Charlestown, MA, USA; 3Autonomic Technologies, Inc., Redwood City,
CA, USA.
Objectives: To investigate the effect of low frequency stimulation of
the sphenopalatine ganglion in cluster headache patients.
Background: High frequency (HF) stimulationof the sphenopalatine
ganglion (SPG) is an emerging abortive treatment for cluster headache (CH) attacks.
HF SPG stimulation is thought to exert its effect by physiologically blocking
parasympathetic outflow. We hypothesized that low frequency (LF) SPG stimulation may
activate the SPG, causing increased parasympathetic outflow and thereby provoking
cluster attacks in CH patients.
Methods: In a double-blind randomized cross-over study seven CH patients
implanted with an SPG neurostimulator were randomly allocated to receive HF or LF
stimulation for 3 min on two separate days. We recorded headache characteristics and
autonomic symptoms during and after stimulation.
Results: Six patients completed the study. Three out of 6 patients
(50 %) reported ipsilateral cluster-like attacks during or within
30 min of LF SPG stimulation. These cluster-like attacks were all successfully
treated with the therapeutic HF SPG stimulation. One out of 6 reported a
cluster-like attack with 3 min HF SPG stimulation, which was also successfully
treated with continued HF therapeutic SPG stimulation.
Conclusions: LF SPG stimulation may induce cluster-like attacks with
autonomic features, which can subsequently be treated by HF SPG stimulation.
Efferent parasympathetic outflow from the SPG may initiate autonomic symptoms and
activate trigeminovascular sensory afferents, which may initiate the onset of pain
associated with CH.
OR12
Posterior Hypothalamic Region Deep Brain Stimulation in Short Lasting
Unilateral Neuralgiform Headache with Conjunctival Injection and Tearing
(SUNCT)
S. Miller1, F. Rasul2, G. Lambru1, S.
Lagrata1, M. Hariz2,3, L. Zrinzo2,3, M.
Matharu1
1Headache Group, National Hospital for Neurology and Neurosurgery,
London, United Kingdom; 2Department of Neurosurgery, National
Hospital for Neurology and Neurosurgery, London, United Kingdom;
3Unit of Functional Neurosurgery, Sobell Department of Motor
Neuroscience and Movement Disorders, Institute of Neurology, University College
London, London, United Kingdom.
Objectives: Previous case reports on posterior hypothalamic region deep
brain stimulation (PH-DBS) for SUNCT are limited to a total of three patients
(1-3). We present clinical and outcome data on six new patients with
intractable SUNCT treated with PH-DBS.
Background: SUNCT is a primary headache syndrome characterised by short
lasting attacks of unilateral pain accompanied by prominent lacrimation and redness
of the ipsilateral eye. SUNCT is refractory to standard medical treatments in a
small minority of patients. Neuroimaging studies have suggested a role of the
posterior hypothalamus in its pathogenesis.
Methods: Six SUNCT patients underwent PH-DBS with an MRI-guided and
MRI-verified approach without microelectrode recording. The target on stereotactic
T2-weighted imaging lay between the mammillothalamic tract and the anteromedial
quadrant of the red nucleus. Details of headache characteristics and adverse events
were recorded at regular reviews. Headache load (defined as the [severity (on the
visual analogue score)] x [duration] x [frequency] of the headaches) of each patient
was calculated at each review point.
Results: All leads were within 1.0mm of intended target point on
postimplant imaging. Stimulation was monopolar with a range 0.4-3V throughout the
follow up period. The median follow up period was 9.5 months (range 3-34). Three
patients had pure SUNCT and three multiple headache types (additional cluster and or
migraine). Median improvement in SUNCT headache load at final follow up was 79%
(range 22-100%). Five out of six patients had obtained a 50% or more objective
improvement in headache load at last follow up. No significant difference appeared
to exist between pure SUNCT and mixed headache patients, although clinically the
suggestion was pure patients fared better; this may be due to the short follow up in
some patients.
Conclusions: PH-DBS may be a useful treatment in intractable SUNCT.
Further investigation is needed to discover if those with a single headache syndrome
do better than those with mixed headaches.
OR13
Anxiety and Migraine: A Population-Based Cross-Sectional Study in
Korea
M.K. Chu1, B.-K. Kim2, K. Oh3, J.-M.
Kim4, K.-S. Lee5
1Neurology, Hallym University College of Medicine, Anyang,
Gyeonggi-do, Republic of Korea; 2Neurology, Eulji University School
of Medicine, Seoul, Republic of Korea; 3Neurology, Korea University
Guro Hospital, Korea University School of Medicine, Seoul, Republic of Korea;
4Neurology, Chungnam National University, College of Medicine,
Daejeon, Republic of Korea; 5Neurology, Seoul St.Mary’s Hospital, The
Catholic University of Korea, Seoul, Republic of Korea.
Objectives: To assess the association between anxiety and migraine in a
population-based sample in Korea.
Background: The association between anxiety and migraine has been
observed. However, most studies are reported in Western countries and
population-based studies regarding anxiety and migraine have rarely been reported in
Asian countries including Korea.
Methods: We selected a stratified random population sample of Koreans
over aged 19-69 and evaluated them with a 60-item semi-structured interview designed
to identify headache type using ICHD-2 criteria. We included Goldberg short
screening scale for anxiety (GSSA) scores to assess individuals’ anxiety. We defined
as having anxiety if an individual’s GSSA score was 5 or more.
Results: Of 2762 participants, the 1-year prevalence of all types of
headache and migraine were 47.1% and 5.4% respectively. The 1-year prevalence of
anxiety was 10.0%. Anxiety was more prevalent in women than in men (8.1% vs. 11.8%,
p = 0.001). The highest prevalence of anxiety was found in aged
50-59 in men (9.8%) and aged 19-29 in women (14.3%). Anxiety was more prevalent in
migraine group comparing to non-migraine headache group or non-headache controls
(30.4% vs. 13.3% vs. 5.3%, p<0.001). Migraineurs with
substantial-to-severe impact (HIT-6 score≥56) more commonly had anxiety comparing to
migraineurs with no-to-some impact (HIT score<56) (47.0% vs. 17.1%,
p<0.001). Migraineurs with anxiety reported more frequent
attacks per month (7.4±9.7 vs. 2.6±3.9, p<0.001), more severe
pain intensity (VAS score 7.1±1.5 vs. 5.9±2.0, p<0.001), higher
HIT-6 score (59.3±9.0 vs. 52.3±8.7, p<0.001), higher proportion
of decreased activity (48.9% vs. 26.0%, p=0.006) and absence from
work, school or house chores by headache (28.9% vs. 11.5%, p=0.009)
comparing to migraineurs without anxiety.
Conclusions: Anxiety is prevalent among migraineurs in Korean
population. Migraineurs with anxiety had more severe headache symptoms and more
disabilities comparing to migraineurs without anxiety.
OR14
Nociceptive Trigeminal Neurotransmission Is Inhibited by the Dual Orexin
Receptor Antagonist DORA-12
J. Hoffmann1, W. Supronsinchai1, S. Akerman1, C.J.
Winrow2, J. Renger2, R. Hargreaves2, P.J.
Goadsby1
1Department of Neurology, University of California San Francisco,
San Francisco, CA, USA; 2Neuroscience Department, Merck Research
Laboratories, West Point, PA, USA.
Objectives: The aim of the study was to investigate the efficacy of the
dual orexin receptor antagonist (DORA-12) on neuronal transmission of the
trigeminovascular system in an in vivo model of trigeminal
activation.
Background: The hypothalamus and its ascending and descending
connections to pain processing structures within the brain have been shown to be
involved in the pathophysiology of migraine. Besides its involvement in pain as such
and in the sleep-wake cycle, premonitory symptoms of a migraine attack are mainly of
hypothalamic origin. Preclinical evidence indicates that hypothalamic influence on
migraine and sleep is significantly mediated by the orexinergic system. In animal
models of dural nociceptive activation, the activation of Ox1 and
Ox2 receptors has opposing effects. While administration of orexin A,
which activates Ox1 and Ox2 receptors, inhibits nociceptive
activation, orexin B, which mainly activates Ox2 receptors has
pronociceptive properties. The effect of simultaneous antagonism on both receptors
has not been tested in animal models of migraine.
Methods: In male Sprague-Dawley rats under general propofol anesthesia
(20-25 mgkg-1h-1) the middle meningeal artery (MMA) and its
trigeminal afferents were stimulated using a bipolar stimulating electrode through a
cranial window. Stimulus-evoked and background activity of second order neurons were
recorded using a tungsten electrode placed in the trigeminocervical complex (TCC).
Experimental groups received intravenously administered DORA-12 (1mgkg-1)
or its vehicle (25% hydroxypropyl-beta-cyclodextrin) and neuronal activity was
recorded over 60 minutes.
Results: Stimulus-evoked neuronal activity was significantly inhibited
by intravenously administered DORA-12 when compared against baseline
(p<0.05) while vehicle control had no significant
effect.
Conclusions: The results of the study indicate that the dual orexin
receptor antagonist DORA-12 attenuates central effects of dural-evoked
trigeminovascular nociception in an in vivo model of trigeminal
activation that has been shown to be highly predictive for a potential clinical
efficacy for migraine. The results suggest simultaneous antagonism of both orexin
receptors might offer a novel mechanism for the treatment of migraine.
OR15
Structural Changes in Visual and Auditory Processing Brain Areas of Migraineurs
from the General Population Using Voxel-Based Morphometry (VBM)
I.H. Palm-Meinders1, E.B. Arkink1, H. Koppen2,3, S.
Amlal1, G.M. Terwindt2, L.J. Launer4, M.A. van
Buchem1, M.D. Ferrari2, M.C. Kruit1
1Radiology, Leiden University Medical Center, Leiden, The
Netherlands; 2Neurology, Leiden University Medical Center, Leiden,
The Netherlands; 3Neurology, Haga Hospital, The Hague, The
Netherlands; 4Laboratory of Epidemiology, Demography and Biometry,
National Institutes of Health, Bethesda, MD, USA.
Objectives: To investigate structural brain alterations in a large
sample of migraine patients selected from the MRI Cerebral Abnormalities in
Migraine, an Epidemiological Risk Analysis (CAMERA)-2 study, a 9-year follow-up MRI
study on the progression of brain changes in a population-based sample of
migraineurs.
Background: Previously, VBM studies demonstrated regional structural
brain changes in migraineurs from specialized headache centers. It is unknown
whether brain architecture is regionally altered in migraineurs from the general
population.
Methods: 1.5 T 3D whole brain T1-weighted MRI scans were acquired in 84
migraineurs (52 with aura, 32 without aura) and 35 healthy controls selected from
the Maastricht subpopulation of the CAMERA-2 study. Images were post-processed using
state-of-the-art VBM, applying DARTEL in SPM8, and regional volumes were compared
voxelwise, corrected for age, sex and total intracranial volume (p<0.001,
uncorrected, minimum cluster size of 20 voxels). Subanalyses assessed the influence
of attack frequency (< vs. ≥ 1 attack/month) and disease activity (active vs.
inactive).
Results: Grey matter volume in migraineurs was regionally increased in
the left angular and the right middle temporal gyrus, and the left lateral
geniculate nucleus and decreased in the right occipital gyrus (V3A and MT+
territories). White matter tracts in the occipital lobe showed volume reduction that
was not explained by the presence of white matter hyperintensities in these areas.
These changes were not essentially influenced by migraine subtype, attack frequency
or disease activity.
Conclusions: Cortical visual and auditory processing areas and
connecting white matter pathways are regionally altered in migraineurs from the
general population. These changes may underlie stronger responses in migraineurs to
sensory stimulation, suggesting that cortical hyperexcitability plays a pivotal role
in migraine pathophysiology. The underlying histopathology for these changes still
needs to be elucidated, though. Structural brain changes in inactive migraineurs
question the reversibility of these changes.
OR16
Response Properties, Trajectories and Anatomical Characterization of Primary
Afferent Neurons That Innervate the Calvarial Periosteum
J. Zhao1, D. Levy2
1Anesthesia, BIDMC, Boston, MA, USA; 2Anesthesia,
Harvard Medical School/BIDMC, Boston, MA, USA.
Objectives: To investigate the response properties and trajectories of
primary afferents innervating the calvarial periosteum of the rat.
Background: Headaches are believed to result from the activation and
sensitization of intracranial meningeal nociceptors. However, local anesthesia of
extra-cranial tissues, in particular the scalp, can provide headache relief,
suggesting that activation afferents innervating extra-cranial deep-tissues may also
plays a role in headache genesis. One such potential sensory innervation is that of
the calvarial periosteum. In this work we therefore investigated the response
properties of these afferent as well as their central trajectories.
Methods: The response properties of the calvarial perisoteal afferents
were examine using single unit recording in the trigeminal ganglion of anesthetized
rats. Application of local anesthetic and surgical ablation of peripheral nerve
branches were employed to investigate the trigeminal sensory nerve branches through
which these calvarial periosteal afferents project centrally. Retrograde tracing
were used to characterize the trigeminal cell bodies of calvarial periosteal
afferents.
Results: A total of 90 calvarial periosteal afferents were characterized
using electrophysiology. Afferents had conduction velocities ranging between 0.7 and
40 m/s with most falling in the range of A-delta and C units. All but 2 afferents
were mechanosensitive and most (95%) of the units displayed a slowly adapting
pattern of mechanosensitivity. About 20% of the a-delta and 80% of the C-units
exhibited various degrees of ongoing activity. C-units had higher levels of ongoing
activity. Local application of a mixture of inflammatory mediators (inflammatory
soup) activated 44% of the neurons and led to mechanical sensitization in about 60%
of the units. About 10% of the afferents tested were activated by low pH (5.0), but
none of the units responded to capsaicin. Anatomical studies revealed that the
majority of the afferents innervating the dorsal periosteum, rostral to the lambdoid
suture were branches of the supraorbital nerve, projected primarily to the V1 branch
of the TG and had cell body size ranging from 200-2200 µm2.
Conclusions: The data indicate that the calvarial periosteum is
innervated by mechanosensitive primary afferent neurons with nociceptive features
that project to the TG ganglion primarily through extracranial nerves. Activation
and sensitization of calvarial periosteal afferents may play a role in the
pathogenesis of headaches with extra-cranial origin and perhaps also contribute to
the genesis of post-traumatic headaches.
OR17
Cognitive Dysfunction during a Migraine Attack – A Study on Migraine without
Aura
R. Gil-Gouveia1,2, P. Martins, I1, A.G.
Oliveira3
1Clinical Neurosciences Investigation Unit (UNIC), Instituto de
Medicina Molecular (IMM), Faculdade de Medicina, Universidade de Lisboa, Lisboa,
Portugal; 2Headache Center, Hospital da Luz, Lisboa, Portugal;
3Department of Biostatistics, Faculdade de Ciências Médicas,
Universidade Nova de Lisboa, Lisboa, Portugal.
Objectives: To compare cognitive performance of episodic migraine
patients’ in-between and during attacks of migraine without aura, using an extensive
battery of cognitive and behavioral tests and controlling for potential
confounders.
Background: Cognitive symptoms are significant contributors to patients’
disability during migraine attacks. Frequent complaints include executive symptoms
(attention, planning, judgment, initiative, speed) language and memory. Studies on
neuropsychological performance during migraine attacks have limitations and produced
conflicting data.
Methods: Prospective observational randomized crossover study with two
neuropsychological evaluations of the same subject in two conditions – during an
untreated spontaneous migraine without aura attack and in-between attacks.
Results: Thirty-nine patients (37 females), with an age average of 38.2
years were included and 24 completed the study. Migraine impact in our sample was
mild there was no associated depression. In the majority of tests performed,
subjects always performed worse during the attack, changes attaining statistical
significance in: stroop word reading (p=0.001), stroop color naming (p=0.003),
phonemic verbal fluency (p=0.010), CVLT total learning (p<0.0001), CVLT short
term and delayed recall with (p<0.0001) and without (p=0.001) semantic help and
logical memory delayed recall (p 0.006). Differences were unrelated to age, gender,
literacy, order of and time lapse between evaluations, anxiety and pain intensity
and duration (during the evaluated attack).
Conclusions: Our results suggest that cognitive performance globally
diminishes during the migraine attack, supporting patients’ subjective complaints.
The pattern of cognitive impairment is consistent with a dysexecutive syndrome and
learning defect, suggesting the existence of reversible cortical dysfunction in
pre-frontal and temporal brain areas during the migraine without aura attack.
OR18
Follow-Up of the Secondary Findings from the International Headache Genetics
Consortium Meta-Analysis
V. Anttila1,2,3, N. Eriksson4, International Headache Genetics
Consortium1,2,3,4,5, A. Palotie2,3,5
1Analytical and Translational Genetics Unit, Department of
Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA,
USA; 2Program in Medical and Population Genetics, Broad Institute of
MIT and Harvard, Cambridge, MA, USA; 3Institute for Molecular
Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland;
423andMe, Mountain View, CA, USA; 5Department of Human
Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
Objectives: The objective of this study was to identify new genetic loci
predisposing to migraine, based on the secondary findings from the recent
International Headache Genetics Consortium meta-analysis, and to gain more
information about the genetic susceptibility to migraine.
Background: Migraine is a common, episodic neurovascular disorder with
significant heritability. Eight loci have been reported in genome-wide association
studies (GWAS) thus far. Recently, our Consortium conducted a GWAS meta-analysis of
23,000 migraineurs and 95,000 controls, uncovering genome-wide
significant association at 12 loci (P < 5 ×
10-8), of which 8 are located in or immediately outside genes with
known function in synaptic or neuronal regulation. In addition, we identified 134
independent secondary loci with genome-wide suggestive p-values
<1 × 10-5.
Methods: We performed a replication analysis in a new study cohort from
23andme, with 11,000 migraine patients and 52,000 controls. SNP data at the 146
implicated loci were examined to confirm existing and identify novel variants
predisposing to migraine. In addition, a meta-analysis of the previous study and the
new cohorts was performed, for a total of 34,000 migraineurs and 147,000 controls,
and new pathway- and network analyses of the new loci are presented. All
participants were of European ancestry.
Results: Here, we present the results of the replication analysis from
the new cohorts, as well as a combined meta-analysis of the discovery and
replication studies, identifying four new loci with significant association to
migraine. At one of these loci, significant association is observed to a missense
variant for the first time in migraine. In addition, we report how the newly
identified loci fit in the biological context of the migraine genes from previously
reported GWAS studies.
Conclusions: We report the results of the largest genetic study in
migraine thus far. The added statistical power of the new cohorts allowed us to
demonstrate significant association to several new migraine loci, including the
first common missense variant in common forms of migraine. The implication of the
genes at these loci, and their respective biological pathways and mechanisms, sheds
further light on the pathophysiology of migraine.
OR19
Endogenous Opioids Mediate the sTMS Effects in the Sensory Thalamus of Migraine
Models
A.P. Andreou1,2, J. Fredrick3, P.J. Goadsby2
1Anesthetics, Pain Medicine and Intensive Care, Imperial College
London, London, United Kingdom; 2Headache Group- Department of
Neurology, University of California, San Francisco, San Francisco, CA, USA;
3dba eNeura Therapeutics, Neuralieve, Inc., Sunnyvale, CA,
USA.
Objectives: The current study aimed to investigate whether opioid
mechanisms are potentially involved in the mechanism of action of sTMS.
Background: Recent clinical trials demonstrated that single pulse
transcranial magnetic stimulation (sTMS) can be a promising novel treatment in
migraine with aura. We have previously demonstrated that a potential mechanism of
action of sTMS is blockade of cortical spreading depression and inhibition of third
order thalamic neurons with trigeminovascular input, possibly through interactions
with an ipsilateral cortico-thalamic relay.
Methods: Neurons responding to electrical stimulation of dural vessels
were identified in the ventroposteromedial thalamic nucleus by means of
electrophysiology, in anesthetized rats. The effects of sTMS (170 µs rise time),
delivered over the corresponding hemisphere, were studied on spontaneous and
trigeminovascular activity (Aδ- and C-fibers firing) of third order thalamic
neurons. In a separate set of experiments, the efficacy of sTMS was tested on third
order thalamic neurons in animals that have been pre-treated with intravenous
administration of naloxone (5 mgkg-1), a broad spectrum opioid receptor
antagonist. The effects of naloxone on thalamic activity in the absence of sTMS were
investigated in a different experimental group and compared to animals that received
vehicle control.
Results: sTMS (0.8-1.3 Tesla) significantly decreased spontaneous
neuronal firing of third order thalamic neurons (P < 0.05) and
C-fiber activity in response to dural vessel stimulation (n = 5;
P < 0.05), but had no effect on Aδ-fiber activity
(n = 8; P = 0.29). Pre-treatment with naloxone
blocked the inhibitory actions of sTMS on both the spontaneous neuronal firing and
on C-fiber induced activity (P ≥ 0.29). Naloxone alone had no
significant effect on the firing rate of third order thalamic neurons
(P ≥ 0.46).
Conclusions: The mechanism of action of sTMS in the treatment of
migraine potentially involves modulation of third order ipsilateral thalamic
neurons, possibly through a cortico-thalamic relay. Endogenous opioid transmission
is one of the neurotransmitter pathways involved in this modulation.
OR-WA
Investigating the Premonitory Phase of Migraine with
H215O PET
F.H. Maniyar1, T. Sprenger1, C. Schankin1, T.
Monteith1, P.J. Goadsby1
1Neurology, UCSF Headache Center, San Francisco, CA,
USA.
Objectives: To identify brain areas, if any, activated in the
premonitory phase of migraine using positron emission tomography (PET).
Background: Many migraine patients experience premonitory symptoms
warning them of an impending headache (1). The advantages of investigating the
premonitory phase are several - imaging may give us brain areas involved in the
earliest part of the attack and possibly tell us of the origin of various symptoms
since these occur in the absence of pain.
Methods: We used nitroglycerin (GTN) to trigger premonitory symptoms and
migraine headache (2). Scans were conducted with positron emission tomography (PET)
with H215O to measure regional cerebral blood flow as a
surrogate marker for neuronal activation (3). The main outcome was comparing the
first premonitory scans of all patients (without pain) > baseline scans
(n=8) to identify areas involved in the premonitory phase. As a
sub-group analysis, we then compared patients with and without photophobia i.e.
increased sensitivity to light in the premonitory phase (n=10), and
patients with and without nausea in the premonitory phase (n=10),
to identify areas specifically involved in photophobia and nausea respectively.
Results: 1. Comparing the first premonitory scans of all patients >
baseline scans of all patients showed significant activations in the right
postero-lateral hypothalamus, right ventral midbrain area, right periaqueductal grey
(PAG), right dorsal pons, and various cortical areas including occipital, temporal
and frontal cortex. Premonitory symptoms included tiredness, neck stiffness, thirst,
frequent urination, photophobia, nausea, yawning and mood changes. All patients
developed either right-sided or bilateral but predominantly right-sided
headache.
2. Comparing the premonitory scans of patients with photophobia > premonitory
scans of patients without photophobia showed significant activations in the
extra-striate visual cortex (Broadmann area 18).
3. Comparing the premonitory scans of patients with nausea > premonitory scans of
patients without nausea showed significant activations in the upper dorsal medulla
in the region of nucleus tractus solitarius, dorsal motor nucleus of vagus and
nucleus ambiguus, and the PAG.
Conclusions: Activation of key brain areas in the premonitory phase
before headache suggests that the brain is the prime mover in migraine. Hypothalamic
activation can explain the majority of the premonitory symptoms. Photophobia and
nausea in migraine may arise from primary activation of the occipital cortex and
upper dorsal medullary nuclei respectively rather than resulting from trigeminal
activation (and pain) since these symptoms occurred in the absence of pain and were
associated with these activations.
OR20
Sleep Disturbance and Affective Comorbidity among Episodic
Migraineurs
A.B. Walters1, J.D. Hamer1, T.A. Smitherman1
1Department of Psychology, University of Mississippi, Oxford, MS,
USA.
Objectives: The present study sought to 1) assess the role of sleep
quality, daytime sleepiness, and sleep hygiene among a large sample of episodic
migraineurs; 2) assess relations between sleep disturbance and headache-related
variables; and 3) determine if these relations remain after accounting for comorbid
depression or anxiety.
Background: Previous research has shown that sleep disturbance and
affective comorbidities are common among migraineurs. Despite the well-established
role of insomnia in migraine, its central characteristics (sleep quality, daytime
sleepiness, and sleep hygiene) have rarely been explored among episodic migraineurs.
Further, although affective comorbidities and sleep disturbance commonly co-occur,
few studies have investigated whether sleep disturbance is merely a complication of
the affective disorder (Vgontzas et al., 2008).
Methods: 292 young adults (69.9% female, M age=19.19
years [3.21]) completed measures of headache and headache disability, sleep
disturbance (PSQI, Buysse et al., 1988; SHI, Mastin et al., 2006; ESS, Johns, 1991),
and psychiatric symptomatology (PHQ-9, Kroenke et al., 2001; GAD-7, Spitzer et al.,
2006). Migraine diagnosis was verified with a structured diagnostic interview.
Independent t-tests and chi-square analyses were used to compare migraineurs and
controls on sleep disturbance and psychiatric symptoms. A MANOVA compared groups on
multiple sleep hygiene behaviors. Linear regression analyses were used both to
assess the role of sleep disturbance in predicting headache-related variables
(disability, frequency, and severity).
Results: 78 (26.7%) participants met ICHD-II criteria for episodic
migraine (M = 5.26 headache days/month [3.90]; M
severity = 6.70/10 [1.51]). Compared to controls, episodic migraineurs reported
significantly poorer sleep quality on the PSQI (M = 8.90 vs 6.63,
p < .001) and poorer sleep hygiene on the SHI
(M = 38.27 v. 36.63, p = .046). A
significantly higher proportion of migraineurs reported clinically-significant
levels of poor sleep quality (85.90% v. 62.02%, χ2 < .001) and daytime
sleepiness (54.5% v. 40.7%, χ2 = .037). Individual sleep hygiene
behaviors did not differ significantly between groups, however. Poor sleep quality
predicted greater migraine-related disability (R2 = 16.0%,
p < .0001) and higher headache frequency (R2 =
6.5%, p = .02). Sleep quality remained a significant predictor of
disability even after controlling for depression and anxiety (ΔR2 = 4.5%,
p <.0001).
Conclusions: Poor sleep quality is the component of insomnia that best
characterizes migraine, and its effect on migraine disability is not entirely
attributable to comorbid depression or anxiety. Sleep interventions should consider
means of improving sleep quality rather than sleep hygiene per se. Further, the
effects of these interventions on comorbid depression/anxiety merit continued
evaluation.
OR21
Candesartan Versus Propranolol for Migraine Prophylaxis: A Randomized,
Triple-Blind, Placebo-Controlled, Double Crossover Study
L.J. Stovner1, M. Linde1, G.B. Gravdahl1, T.
Erling1, A.H. Aamodt1,2, T. Sand1, K.
Hagen1
1Department of Neuroscience, Norwegian National Headache Centre,
Norwegian University of Science and Technology (NTNU), and St. Olavs Hospital,
Trondheim, Norway; 2Department of Neurology, Oslo University
Hospital-Rikshospitalet, Oslo, Norway.
Objectives: To see whether the superiority of candesartan over placebo,
shown in one previous study1, could be confirmed, and if so, whether the
effect was comparable to that of propranolol (non-inferiority analysis), and whether
adverse events (AEs) were different.
Background: Drug prevention of attacks is desirable and indicated in
many migraine patients, but it is used in relatively few, possibly because of
limited effect, side effects or contraindications. Candesartan has been shown to be
effective as a migraine prophylaxis in one previous study, but corroboration is
lacking, and no study has compared this drug with first-line preventative drugs.
Methods: This was a triple-blind, double crossover study, with 72 adult
patients with episodic or chronic migraine, recruited in an outpatient clinic and
through advertisements. Participants underwent three 12-weeks’ treatment periods on
either candesartan 16 mg, propranolol slow-release 160 mg, or placebo.
The primary outcome measure was days with migraine headache per 4 weeks. Secondary
measures were days with headache, hours with headache, proportion of responders
(≥50% reduction of migraine days from baseline), and AEs.
Results: In the intention-to-treat analysis, candesartan and propranolol
were both superior to placebo (2.95 ± 2.28, and 2.91 ± 2.16, versus 3.53 ± 2.17
migraine days per month, p=0.02 for both comparisons, Wilcoxon’s paired signed rank
test, blinded statistical analysis). Candesartan was non-inferior to propranolol
(and vice versa). Candesartan and propranolol were also similar on most secondary
measures of efficacy, and superior to placebo. The active substances caused more AEs
than placebo, but the AE profiles differed.
Conclusions: It is confirmed that candesartan 16 mg is effective for
migraine prevention, with an effect size similar to propranolol 160mg, and with
somewhat different AEs. Candesartan should be included in the arsenal of drugs
recommended for migraine prevention.
OR22
Estrogens Modulate Susceptibility to Cortical Spreading Depression in Rat
Independently of 5-HT Neurotransmission
Objectives: To determine the influence of 17β-estradiol (E2) modulation
on KCl-induced CSD and on the suppressive effect of 5-hydroxytryptophan (5-HTP) on
CSD frequency in rat.
Background: The aura symptoms in migraine are most likely due to
cortical spreading depression (CSD). High estrogen levels, like those associated
with pregnancy, are supposed to increase cortical excitability and thus to favor
CSD. Migraine is also considered a “low 5-HT” condition. Serotonin depletion causes
both deficient pain control and changes in cortical excitability in humans
(Hamel, 2007) as well as enhanced CSD susceptibility in rat
(Supornsilpchai et al., 2006). Gonadal hormones influence the
5-HT metabolism. We have previously shown that 5-HTP, the 5-HT precursor, can
decrease CSD frequency in female rats and that this effect varies along the ovarian
cycle (unpublished data).
Methods: Adult female Sprague-Dawley rats (n=8/group)were ovariectomized
and subcutaneously implanted with silastic capsules filled with E2 mixed with
cholesterol (E2) or with cholesterol only (chol).Two weeks later, CSDs were elicited
in half of the animals in each group by applying a cotton ball soaked with 1M KCl
over the occipital cortex and recorded by DC electrocorticogram for 1 hour. In the
remaining animals, the capsules were removed to mimic an abrupt drop in E2 and CSDs
were recorded 20 h later (E2w and cholw groups). One hour before the recording
session all animals received an i.p. injection of 5-HTP (100 mg/kg) or NaCl.
Results: CSD frequency was significantly enhanced in animals treated for
2 weeks with E2 compared to “chol” controls (p=0.025). E2 withdrawal normalized CSD
frequency.5-HTP injections significantly decreased CSD frequency in all animal
groups (p=0.004) and this effect was independent of estrogen levels.
Conclusions: High E2 levels increase the susceptibility to CSD in
ovariectomized females, which might be relevant for the aggravation/appearance of
migraine with aura during pregnancy or intake of estrogen-containing contraceptive
pills. Furthermore, the rapid decrease of CSD frequency after E2 withdrawal may
explain whymigraine with aura attacks, contrary to attacks without aura, are rarely
menstrually-related. Finally, changes in central 5-HT transmission influence CSD
susceptibility in females independently of E2 levels.
OR23
Posterior Insula Does Not Age in Migrainous Women
N. Maleki1, G. Barmettler1, L. Becerra1,2, R.
Burstein3, D. Borsook1,2
1Anesthesia, Boston Children’s Hospital, Boston, MA, USA;
2Psychiatry, McLean Hospital, Belmont, MA, USA;
3Anesthesia and Critical Care, Beth Israel Deaconess Medical Center,
Boston, MA, USA.
Objectives: Recent studies have shown alterations in a number of
cortical regions in migraine patients [1, 2]. The aim of this study was to assess
the effect of aging on migraine brain in order to determine if there are abnormal
patterns of aging in migraine brain.
Background: The posterior insula is an integrative association cortical
region for multisensory-motor processing. Prior findings in migraine patients have
indicated a significant change in the posterior insula in female migraineurs where
female migraineurs had shown to have thicker posterior insula compared with male
migraineurs and healthy controls of both sexes[3]. It has also been shown that the
trigeminovascular neurons of the posterior thalamus project to insula [4], which may
explain some of the common disturbances in neurological functions during
migraine.
Methods: Ninety-two female migraine patients (N=46 migraine patients and
N=46 healthy control subjects) underwent a magnetic resonance imaging (MRI) session
on a 3.0T Siemens scanner. All of the migraine patients were episodic migraineurs
who were selected according to the International Classification for Headache
(ICHD-2; http://www.i-h-s.org/upload/ct_clas/ihc_II) definition for episodic
migraine. In order to be included in the study they had to havesuffered from
migraines for more than three years. Images were processed offline using the
automatic parcellation tools of the Freesurfer image analysis software
(http://surfer.nmr.mgh.harvard.edu/) that enables reconstruction of cortical
surfaces and detection of sub-millimeter differences in cortical thickness between
patients and healthy control subjects.
Results: Vertex-wise comparisons between the two cohorts to determine
the differences between the age and cortical thickness correlation revealed
significant difference between the cohorts in the posterior insula bilaterally.
While in the healthy group there is cortical thinning by age in the migraine group
there was no decline in the cortical thickness in the posterior insula by age.
Conclusions: As part of the normal aging process, the majority of the
cortex regions become progressively thinner. In this study we compared the
differences between the aging of the brains of female migraine patients and
age-gender matched healthy controls. Our findings suggest that the posterior insula
region in migraineurs does not thin by age (which positively correlated with the
duration of the disease (R2=0.804, p-value=2.4e-10)) suggesting that this
may either reflect adaptive or maladaptive responses to migraine.
OR24
Prevalence and Characteristics of Headache in Schoolchildren in Japan: A
Population-Based Study
M. Goto1, Y. Nozaki1,2, R. Kawamata1,2, S.
Matsumoto1,2, T. Yamagata2, M.Y. Momoi2
1Department of Pediatrics, Hitachiomiya Saiseikai Hospital,
Hitachiomiya, Ibaraki, Japan; 2Department of Pediatrics, Jichi
Medical University, Shimotsuke, Tochigi, Japan.
Objectives: The aim of this study was to reveal the prevalence,
characteristics and impact of headache in elementary and junior high schoolchildren
in Japan.
Background: Migraine and tension-type headache (TTH) was reported to
affect approximately 8% and 10%-25% of pupils, respectively. The incidence of
migraine among Japanese junior high school children was reported to be 4.8% in one
study, and only few population-based studies have been done about the prevalence and
the type of headache despite of the disturbing symptoms for pupils. Here we applied
a population-based study to reach the objective.
Methods: Subjects included 3,403 pupils at 13 elementary (6 to 12 years
of age) and 7 junior high schools (12 to 15 years of age) in Hitachi-Omiya City
(population 42,000). They were surveyed using a computer-scored questionnaire
comprising 26 items based on International Classification of Headache Disorders; the
2nd Edition diagnostic criteria for migraine and TTH. These questions probed
thefeatures of headache, effects on daily life, and treatments by physicians or
medications. We obtained informed consent from all pupils and parents.
Results: Responses were obtained from 3,285 pupils (elementary school,
2,115; junior high school, 1,171; recovery rate, 96.5%). Migraine was estimated to
be prevalent among 241 pupils from the result of this investigation (prevalence rate
7.3%; male, 41.9%; female, 57.7%). Among 241 pupils with migraine, thirty-eight
(1.2%) had typical aura, twenty-five (0.8%) had basilar-type, and two (0.06%) had
hemiplegic migraine. TTH was estimated among 222 pupils (prevalence rate 6.8%; male,
48.6%; female, 50.9%). Pupils who had headache more than 15 days in a month were 10
(0.3%) for migraine, and 7 (0.2%) for TTH. The majority of pupils, those with TTH
(162/222, 72.9%), and with migraine (146/241, 60.6%) had not visited physician. The
percentages of pupils who only used over-the-counter drugs were 28.8% (64/222) with
TTH and 34.9% (84/241) with migraine. Absence from school for more than one day per
3 months was reported by 28 pupils with migraine (11.6%) and 17 with TTH (7.7%).
Irritability was reported by 100 students with migraine (41.5%) and 61 with TTH
(27.5%). The common causes of secondary headaches were infection (663/3285, 20.2%),
rhinosinusitis (99 pupils, 3.0%), and ophthalmological problems (59 pupils,
1.8%).
Conclusions: The prevalence of migraine in our study was similar to
those of previously reported studies in other pediatric populations, and the
prevalence of TTH was lower than the previous studies. The facts that the majority
of pupils with headache had not visited physicians suggest at least some of them
were inappropriately treated. Our study also revealed that certain amounts of
children were annoyed by headache-related absence from school and irritability.
Therefore, it is important to educate parents and school officials about headache
preventions strategies in health care programs for children.
OR25
Cardiovascular Profile in Childhood and the Risk of Migraine in
Adulthood
A. Recober1, J. Kruger1, A. Hoang-Tienor1, T.L.
Burns1
1University of Iowa, Iowa City, IA, USA.
Objectives: To identify early life risk factors of migraine.
Background: Obesity and other cardiovascular risk factors have been
associated with migraine. To our knowledge, there are no data from prospective
longitudinal cohorts assessing cardiovascular risk factors in childhood and their
association with migraine in adult life.
Methods: We used data from the Muscatine Study, an ongoing
population-based longitudinal cohort study that began in 1970 and has followed
school-age children into adulthood. Body mass index, triceps skinfold thickness,
total cholesterol, total triglycerides, and diastolic and systolic blood pressure
were measured between 1970 and 1981 in school age participants. Since then, serial
measurements of these and other parameters were obtained from examinations in young-
and middle-adulthood. A screening questionnaire that included the ID Migraine
questions and other socio-demographic information was mailed to members of the
Muscatine Study Longitudinal Adult Cohort (n=677; 296 males and 381 females, mean
age 52). Those who screened positive for migraine underwent a semi-structured
telephone interview by a senior neurology resident (JLK, AHT). Migraine was
diagnosed using the ICHD-II criteria and further information such as age of onset,
frequency of attacks, acute and preventive treatment, etc., was obtained during the
telephone interview. Here, we present preliminary results obtained from the mailed
questionnaires.
Results: We received 419 completed screening questionnaires.
Participation rate was 65% and there were no differences in age, gender or previous
diagnosis of migraine (self-reported diagnosis from a physician), between responders
and non-responders. Analysis of risk factors at the time of the last school survey
examination, mean age 15.4 (SD=1.8), suggested higher total cholesterol (p = 0.0843)
and significantly higher total triglycerides (p = 0.0101) in those with migraine in
adult life. In young-adulthood, mean age 27.6 (SD=4.0), there was suggestion of
higher total cholesterol to HDL ratio (p = 0.0810) and body mass index (p = 0.1098),
and significantly higher diastolic blood pressure (p = 0.0115) in those with
migraines in adult life. Analysis of risk factors from a later adult examination,
mean age 34.9 (SD=3.3), showed higher body mass index (p = 0.0547), significantly
higher total cholesterol to HDL ratio (p = 0.0119), higher total triglycerides (p =
0.0424), and significantly lower HDL cholesterol (p = 0.0113) in those with
migraines in adult life.
Conclusions: These preliminary data analyses suggest that an adverse
lipid profile in childhood is a risk factor for migraine in adulthood. Furthermore,
adult migraineurs had significantly higher diastolic blood pressure as young adults.
Finally, our results are consistent with population studies that have found an
association between migraine and body mass index and unfavorable lipid profile.
Future analysis will utilize telephone interview confirmation of migraine status
(ICHD-II), and will further investigate risk factor associations by fitting
multivariable models to compare cohort members with vs. without migraines.
OR26
Cognitive Behavioral Treatment Plus Amitriptyline Leads to Clinically
Significant Reductions in Headache Frequency and Migraine-Related Disability: A
Randomized Clinical Trial in Pediatric Chronic Migraine
S.W. Powers1, S. Kashikar-Zuck1, J. Allen1, S.
LeCates1, J. Rausch1, A.D. Hershey1
1Cincinnati Children’s Hospital, Cincinnati, OH, USA.
Objectives: Test a combined psychological & pharmacological
intervention (TX) versus a pharmacological intervention plus attention control (CTL)
in youth ages 10-17 diagnosed with chronic migraine.
Background: Up to 50% of patients seen by pediatric headache specialists
are diagnosed with chronic migraine, yet proven treatments do not exist. Randomized
clinical trials are the only means to obtain the needed evidence base to inform
practice. Combined psychological & pharmacological treatment holds promise for
optimal clinical impact based on prior adult trials1 and Cochrane reports
on the efficacy of cognitive behavioral treatment of pediatric chronic
pain2.
Methods: The co-primary endpoints were headache frequency (days measured
by 28-day diary) and migraine-related disability (PedMIDAS). Treatment effects were
measured at baseline, 20 weeks (post treatment), and then at 3, 6, 9, and 12-month
follow-up. Psychological intervention was cognitive behavioral therapy (including
biofeedback); pharmacological intervention was amitriptyline (goal dose of 1
mg/kg/day). Attention control was equal to psychological intervention in terms of
contact frequency & face-to-face time, and involved education and support.
Results: 135 subjects met intent to treat criteria (TX: 64; CTL: 71).
Mean age 14.4 years; 15% minority; 79% female; Mean baseline headache frequency of
21 days; Mean baseline PedMIDAS of 68 (severe disability grade). No differences
between groups at baseline. TX and CTL were safe and well tolerated. Primary
outcomes are presented in a figure. For TX group, a > 50% headache reduction was
seen in 66% at post-treatment, 86% at 12-month f-up; proportion no longer chronic
migraine was 71% at post-treatment, 88% at 12-month f-up; PedMIDAS score < 20
(mild to no disability) was 75% at post-treatment, 88% at 12-month f-up.
Conclusions: Within 20 weeks of combined psychological & medication
treatment, youth with chronic migraine show clinically significant reductions in
headache frequency and migraine-related disability. At 12-month f-up, almost 9 out
of 10 subjects no longer had chronic migraines and were mild to no disability grade.
The results of this combined psychological & medication intervention are at a
level of clinical significance that should immediately impact practice in headache
medicine. These findings demonstrate a greater frequency reduction (-11 per month)
compared to those found in studies of pharmacological treatments approved for
chronic migraine in adults (e.g., topiramate: Published trials3-5: Range
of -3.5 to -5.8 days per month, and onabotulinumtoxinA: Meta Analysis6 =
-2.3 headaches per month).
OR27
Stigma towards Migraine
R.E. Shapiro1, P.B. Reiner2
1Neurological Sciences, University of Vermont College of Medicine,
Burlington, VT, USA; 2Psychiatry, University of British Columbia,
Vancouver, BC, Canada.
Objectives: The objective of the study was to evaluate stigma towards
individuals suffering from migraine.
Background: Migraine is a disabling episodic disorder. In addition to
the clinical features of the syndrome, individuals with migraine are often subject
to stigma by friends, family, and co-workers. However, few empirical data exist on
this phenomenon (Young et al., 2013). We utilized the contrastive vignette technique
to compare attitudes towards individuals with migraine with attitudes towards
individuals with three other episodic disorders: epilepsy, panic disorder, and
asthma.
Methods: We utilized the well-validated Attitudes towards Mental Illness
Questionnaire (AMIQ) to assess stigma (Luty et al., 2006). Subjects were recruited
via the crowdsourcing website Mechanical Turk, and were compensated $0.25 for
completion of the short survey. Subjects were randomly assigned to assess a
fictional vignette of one of four conditions; each condition described an individual
with attacks of migraine, epilepsy, panic disorder, or asthma occurring nearly every
week. Respondents were then presented with the AMIQ. The maximum potential score on
the AMIQ is 500, with higher scores indicating greater stigmatizing attitudes. In
addition to demographic data, subjects were also asked if they had ever had an
episode of the relevant disorder, if they had ever been diagnosed with the relevant
disorder, and if they had a family member or close friend diagnosed with the
relevant disorder.
Results: The survey was completed by 765 individuals. All subjects
resided in the USA and were at least 19 years of age, with a mean age of 28.3 (± 0.3
SEM) years. 60.3 percent of subjects were women. The lowest AMIQ score in this
survey was obtained when the individual in the vignette was described with asthma
(250.1 ± 3.3 SEM). The AMIQ scores for the other vignettes were significantly higher
than that for asthma, but not significantly different from each other: migraine
(266.5 ± 3.4 SEM), panic (267.7 ± 3.7 SEM), and epilepsy (262.3 ± 3.9 SEM).
Conclusions: The data demonstrate that stigma against individuals with
migraine is of equal magnitude to stigma against individuals with epilepsy or panic,
and significantly higher than that for asthma.
OR28
Cardiovascular Contraindications to Triptans in the Migraine Population:
Results from the American Migraine Prevalence and Prevention (AMPP)
Study
1Albert Einstein College of Medicine, Bronx, NY, USA;
2Montefiore Medical Center, Bronx, NY, USA; 3Vedanta
Research, Chapel Hill, NC, USA.
Objectives: Estimate rates of cardiovascular (CV) contraindications to
triptan use in persons with episodic migraine (EM) in the US population and estimate
the population at high risk based on Framingham scores.
Background: Triptans are widely prescribed acute migraine treatments
with well-known CV contraindications.
Methods: Respondents to the 2009 AMPP study reported prior CV
contraindications (events: myocardial infarction, TIA, stroke, claudication and
angina; procedures: coronary angioplasty, stenting or bypass surgery, carotid artery
surgery or stenting, and peripheral artery bypass surgery). ICHD-2 criteria were
used to identify EM cases (ICHD-2 migraine diagnosis with average <15 headache
days/month). The sample was stratified by sex and age (<40, 40-59 and ≥60).
Frequency counts were generated for each CV event and procedure. Observed rates for
CV contraindications were applied to US Census-derived estimates of EM for each age
strata. Modified Framingham Risk scores (derived from self-reported data on age,
sex, body mass index, diabetes, hypertension, smoking, cholesterol) identified
persons free of events and procedures at high risk for silent myocardial
ischemia.
Results: Of 11,799 respondents to the 2009 survey, 6,723 (1,496 males,
5,227 females) met criteria for EM. CV events or procedures were reported by 11.1%
of those aged <40 (n=1,457), 18.7% of those 40-59 (n=3,716) and 33.6% of those
≥60 (n=1,550). Males had slightly higher rates for events and procedures across all
age strata. Census-based projections of net CV events and procedures yielded 4.71
million persons with EM in the US (1.17 million males and 3.54 million females)
where triptan use may be contraindicated. Based on Framingham scores, an additional
1.5 million (0.38 million males and 1.12 million females) are at high risk for
silent myocardial ischemia.
Conclusions: Triptans are contraindicated in an estimated 4.71 million
Americans with migraine based on CV events and procedures. An additional 1.5 million
may be at high risk for silent myocardial ischemia. These individuals have been
shown elsewhere to have substantial unmet treatment needs.
OR29
The Presence of Posterior Circulation Territory (PCT) Infarct-Like Lesions in
Migraine Does Not Depend on Attack Frequency: An MRI Study in 87 Chronic
Migraine (CM) Women
E. Santamarta2, A. Meilán2, A. Saiz2, D.
Larrosa1, E. Cernuda-Morollon1, J. Pascual1
1Neurology, University Hospital Central de Asturias, Oviedo,
Asturias, Spain; 2Radiology, University Hospital Central de Asturias,
Oviedo, Asturias, Spain.
Objectives: To determine whether CM patients are at increased risk of
PCT infarct-like lesions on MRI.
Background: Two general population studies have found that migraine in
general, and especially women with aura, has an increased risk of MRI PCT
infarct-like lesions. In addition, there was a trend for a higher risk of PCT
lesions in those migraine subjects with a higher migraine attack frequency, which
would have obvious clinical and management implications (1,2).
Methods: After signed informed consent, brain MRIs were obtained in
women from our headache clinic meeting CM criteria according to 2006 revised IHC-II.
To keep radiologists blinded we also obtained brain MRIs in 10 episodic migraine
patients. Brain MRIs were acquired on a 1.5T unit Signa LX 9.1 (General Electric
Systems, USA). Protocol includes whole brain weighted images in saggital T1 (5 mm
slices), axial FLAIR T2 (3 mm) and combined proton density and T2 fast spin echo (3
mm). Two independent neuroradiologists carefully analysed all the images.
Results: Brain MRIs were obtained in 87 CM women. Their ages ranged from
18 to 68 years (mean 43.3 years) and the length of CM ranged from 0.5 to 38 years
(mean 9.7). Forty-eight patients (56.3%) had at least one vascular risk factor.
Twenty-eight (32.2%) met overuse criteria. Forty-two women (48.3%) had a previous
history of migraine with aura attacks, though the frequency of auras was below one
per month in all patients except one. Only four were not on preventatives. The
prevalence of right to left shunt with transcraneal echo was 57%. We found PCT
infarct-like lesions in only 3 (3.49%) patients aged 42, 48 and 54 years and with a
history of migraine with and without aura attacks. One of these patients was a
smoker. They had no other vascular risk factor. Right-to-left shunt was seen in two
(one massive and one non-massive) of these patients.
Conclusions: Following the same MRI methodology, the frequency of PCT
lesions in our CM was below that found in the two general population studies.
Therefore, at least for the PCT, frequency of migraine attacks itself does not seem
to be a factor increasing the risk of vascular brain lesions.
OR30
Relative Contribution of Migraine with Aura on Stroke Subtypes in
Women
T. Kurth1,2, Bubes, V2, J.E. Buring2
1Inserm Unit 708 - Neuroepidemiology, Bordeaux, France;
2Division of Preventive Medicine, Brigham and Women’s Hospital,
Boston, MA, USA.
Objectives: To evaluate the relative contribution of migraine with aura
on the incidence of major stroke subtypes in a large prospective cohort of initially
apparently healthy women.
Background: Migraine with aura has been consistently linked with
increased risk of ischemic stroke and there is also some evidence that it increases
risk of hemorrhagic stroke. However, the contribution of migraine with aura to the
occurrence of major stroke subtypes relative to other important vascular risk
factors remains unclear.
Methods: Prospective cohort study of 27,860 women aged ≥45 who were
participating in the Women’s Health Study, were free of any cardiovascular disease
at baseline, and for whom we had self-reported information on migraine and lipid
measurements. Women were followed for medical record-confirmed stroke. A
neurovascular neurologist classified stroke into major subtypes (ischemic,
hemorrhagic, unknown). We used multivariable standardization models to evaluate the
contribution of MA to stroke subtype risk relative to other major vascular risk
factors.
Results: At baseline, 5130 women reported migraine of whom 1435 (40%)
reported migraine with aura. During 15 years of follow-up, 528 total strokes were
confirmed (430 ischemic, 96 hemorrhagic, 2 unknown). The overall incidence rates
(95% confidence intervals) per 1000 women per year were 1.2 (1.1-1.4) for total
stroke, 1.0 (0.9-1.1) for ischemic stroke, and 0.2 (0.2-0.3) for hemorrhagic stroke.
For total, ischemic and hemorrhagic stroke, MA was strong contributor.
Conclusions: In this large, prospective cohort of women, migraine with
aura is a strong relative contributor to increased risk of total, ischemic, and
hemorrhagic stroke. A history of migraine with aura should be considered an
important risk marker for strokes of any kind.
Incidence rate* per 1000 women per year for total, ischemic, and
hemorrhagic stroke, according to risk factors in the Women’s Health
Study (N=27,860).
Risk factor
Total Stroke
Ischemic Stroke
Hemorrhagic Stroke
Incidence Rate (95% CI)
Incidence Rate (95% CI)
Incidence Rate (95% CI)
Migraine with aura
4.3 (3.0-6.0)
3.4 (2.3-5.0)
0.8 (0.3-1.8)
Systolic blood pressure ≥180 mmHg
3.7 (2.2-6.2)
3.1 (1.8-5.5)
0.5 (0.1-2.3)
Body mass index ≥35 kg/m2
3.2 (2.1-4.9)
2.5 (1.5-3.9)
0.8 (0.3-2.6)
History of diabetes
3.9 (2.7-5.6)
3.3 (2.2-4.8)
0.7 (0.1-3.5)
Family history of myocardial infarction
2.9 (2.2-3.7)
2.2 (1.7-3.0)
0.6 (0.3-1.2)
Currently smoking
2.9 (2.3-3.7)
2.5 (1.9-3.3)
0.4 (0.2-0.8)
Data are adjusted for all variables in the Table plus age,
cholesterol, alcohol consumption, exercise, history of hormone
replacement therapy, and postmenopausal status.
CV Events and Procedures
Aged <40
Aged 40-59
Aged ≥60
Myocardial Infarction
6 (0.4%)
112 (3.4%)
104 (8%)
TIA
17 (1.2%)
135 (3.9%)
101 (7.2%)
Stroke
11 (0.8%)
72 (2.1%)
76 (5.4%)
Claudication
85 (6.2%)
294 (8.6%)
182 (13.1%)
Angina
58 (4.2%)
271 (7.9%)
192 (13.7%)
Coronary Bypass Surgery
11 (0.8%)
41 (1.1%)
49 (3.2%)
Coronary Angioplasty/Stenting
15 (1.0%)
114 (3.1%)
100 (6.5%)
Carotid Artery Surgery/Stenting
10 (0.7%)
28 (0.8%)
22 (1.4%)
Peripheral Artery Bypass Surgery
10 (0.7%)
32 (0.9%)
16 (1%)
Respondents with ≥1 Event/Procedure
151 (11.1%)
623 (18.7%)
460 (33.6%)
P1
Factors Underlying Triptan Discontinuation
R. Wells1, S. Markowitz1, E. Baron1, K.
Kalidas1, P. Mathew1, R. Halker1, D.
Dodick1, T. Schwedt1
1American Headache Society Headache Fellows Research Consortium,
Mount Royal, NJ, USA.
Objectives: To identify factors that correlate with triptan
discontinuation among migraine patients.
Background: It is unclear why many patients who are prescribed triptans
do not adhere to treatment. This study investigated correlates of triptan
discontinuation.
Methods: Multi-center cross-sectional survey conducted by Headache
Fellow members of the American Headache Society Headache Fellows Research Consortium
at U.S. tertiary care headache clinics. Subjects were migraine patients who
currently used triptans (use within 3 months and for ≥ 1 year) or previously used
triptans (no use within 6 months; prior use within 2 years). Univariate analyses
compared current triptan users to past users for: migraine characteristics, other
treatments, triptan education, efficacy, side effects, type of prescribing provider,
Migraine Disability Assessment (MIDAS) and Beck Depression Inventory (BDI) scores.
Multivariable logistic regression modeling was used to determine factors that best
correlated with triptan discontinuation.
Results: Compared to current triptan users (n=207), those who had
discontinued use (n=69) were more likely to overuse abortive medications (30 vs.
18%, p=.04), to have ever used opioids for migraine treatment (57 vs. 38%, p=.006),
and have higher MIDAS (median 40 vs. 18, p=.001) and BDI scores (mean 10.3 vs. 7.4,
p=.009). Current triptan users were more likely than discontinuers to have had their
triptan prescribed by a specialist (neurologist, headache specialist, or pain
doctor) (74 vs. 54%, p=.003) and to report headache resolution (53 vs. 14%,
p<.001) or lessened pain (71 vs. 28%, p<.001) from their triptan. On a 1-5
scale (1=strongly disagree, 5= strongly agree), triptan users felt they had more:
control over their migraines (2.9 vs. 2.1), triptan satisfaction (4.0 vs. 2.3),
confidence in their prescribing provider (4.5 vs. 4.0), and were more educated about
triptan use (4.2 vs. 3.7) (p<0.001 for all comparisons). Although both current
and prior users reported similar side effect rates (48 vs. 43%, p=0.49), the main
reasons for discontinuation were lack of effect (44%) and side effects (29%). The
strongest correlate of triptan discontinuation was lack of efficacy (OR=17, 95% CI
[9, 33]). Other factors associated with discontinuation included MIDAS>24 (OR
2.6, [1.5, 4.6]), BDI >4 (OR 2.5, [1.4, 4.5]), and a history of ever using
opioids for migraine therapy (OR 2.2, [1.3, 3.8]).
Conclusions: Current triptan users reported receiving more education
about their triptans, felt they had better control over their migraines, and were
more likely to receive their triptan from a specialist compared to prior users.
Discontinuation was most correlated with lack of efficacy. Discontinuation was also
associated with more migraine related disability, depression, and the use of opioids
for migraines. Although we cannot determine if these factors contributed to
discontinuation or are results of discontinuation, targeting these factors may
decrease the likelihood of triptan discontinuation and improve overall migraine
control.
P2
Education and Decision Making at the Time of Triptan Prescribing: Patient
Expectations vs. Actual Practice
P.G. Mathew1,2, A. Lettich2, R.E. Wells2, J.
Pavlovic2, C.E. Robertson2, K. Mullin2, D.W.
Dodick2, T.J. Schwedt2
1John R. Graham Headache Center, Brigham and Women’s Hospital,
Boston, MA, USA; 2American Headache Society Headache Fellows Research
Consortium, Mount Royal, NJ, USA.
Objectives: To compare patient expectations to actual practice regarding
triptan patient education and the patient’s role in decision making when triptans
are prescribed.
Background: Patient satisfaction and adherence with treatment
recommendations are optimized when education about prescribed treatments and the
level of patient involvement in treatment decisions match patient expectations.
Methods: Multi-center prospective observational study conducted by the
American Headache Society Headache Fellows Research Consortium at tertiary care
academic headache clinics. Subjects were episodic and chronic migraine patients
(n=292) who recently used triptans. Data regarding triptan education that patients
actually received and their involvement in decision making when the triptan was
prescribed, as well as patients’ expectations regarding education and their desired
role in decision making were collected via questionnaires.
Results: The main source of triptan education was the prescriber for
66.1% of patients and self-education for 17.0%, while 6.9% reported receiving no
triptan education. 92.3% felt the prescriber should be the main source of education
while only 3.8% thought self-education should be the main source.
Patients most preferred to receive education about deciding if a triptan should be
taken, when to take the triptan, and triptan side effects; 79.5%, 85.6% and 67.5%
reported having actually received this education, respectively. Patients were less
interested in education about cost and obtaining triptan refills. Patients preferred
to be educated about taking other medications with triptans, the number of triptan
doses they could take per migraine and what to do if the triptan does not work;
61.5%, 86.0%, 60.1% reported having received this education, respectively. Although
patients were less interested in education about triptan mechanism of action, 48%
reported having received such education. Subjects preferred education about the most
common side effects as opposed to “all” possible side effects, and they preferred
discussion rather than handouts.
92.0% of patients want to participate in making triptan treatment decisions with
their prescriber. However, 55.1% reported that the prescriber was the sole decision
maker.
Conclusions: Consistent with patient expectations, the main source of
education about triptans is typically the prescriber. Although patients did not
think that self-learning should be the main source of education, 23.9% reported that
self-learning was their main education source or that they received no triptan
education. Although the majority of patients want to be involved in the triptan
prescription decision making process, over half of patients reported that the entire
decision was made by the prescriber. Triptan education and the decision making
process when prescribing a triptan should be improved to better match patient
expectations.
P3
Early Efficacy of Non-Oral, Acute Anti-Migraine Drugs Evaluated by Comparing
Time-Effect Curves and Pharmacokinetics
P. Tfelt-Hansen
Department of Neurology, Danish Headache Center, Glostrup,
Denmark.
Objectives: Headache relief after oral triptans is usually evaluated in
randomised, controlled trials (RCTs) after 2 h. Migraine patients, however, want
rapid and complete relief. Onset of relief has in some RCTs with non-oral
anti-migraine drugs been estimated as the first time point when the drug is
significantly better than placebo. The difference can, however, at this time point
in very large RCTs be only a few percent and is thus clinically irrelevant. Instead
the time-effect curve for therapeutic gain (TG)(percentage responding to active drug
minus percentage responding to placebo) up to e.g. 2 h should be drawn. This allows
a clinically relevant evaluation of the speed of efficacy and the maximum
effect.
Background: In addition, when combining these time-effect curves with
the known pharmacokinetics for this mode of administration on can get information on
some possible basic pharmacodynamic attributes and mechanism of action of the drugs,
the purpose of this paper.
Methods: The TG for headache relief after intranasal zolmitriptan 5 mg
in a very large RCT (n = 1,868), aiming at evaluating the onset of effect, is shown
in Figure 1 together with plasma concentration from a study in healthy volunteers.
There is a parallel increase in time of TG and plasma concentrations of zolmitriptan
indicating a quick equilibration between drug in blood and effector site.
Results: In contrast, the time-effect curve for TG for headache relief
after orally inhaled DHE 0.5 mg versus plasma concentrations of DHE as shown in
Figure 2 demonstrates a considerable time-lag between response and pharmacokinetics.
This is most likely caused by a slow equilibration between drug in blood and its
effector site. A slower dissociation of DHE than sumatriptan from the 5-HT1B/1D
receptor and and this finding has been used to explain the low recurrence rate after
DHE. In addition, it could explain the slow onset of effect.
Conclusions: These 2 examples illustrate that one cannot simply transfer
early pharmacokinetics to early efficacy in acute migraine treatment and that quite
different Tmax (10 min after orally inhaled DHE and 1.5 h after
intranasal zolmitriptan) may result in similar time-effect curves, Figg. 1 and 2.
Theoretically, the pharmacodynamic delay of DHE could be due to both a vascular
effect or a CNS effect.
P4
Efficacy and Safety of a Novel Breath-Powered™ Powder Sumatriptan Intranasal
Treatment for Acute Migraine
R. Cady1, J. Messina2, J. Carothers2, R.
Mahmoud2
1Headache Care Center, Primary Care Network, Inc, Springfield, MO,
USA; 2OptiNose Inc, Yardley, PA, USA.
Objectives: To compare the efficacy and safety of OptiNose
Breath-Powered sumatriptan powder to placebo in the treatment of patients with
moderate to severe migraine headache.
Background: Patients taking oral triptans commonly cite slow onset of
action, inadequate pain relief, and adverse effects as reasons for
dissatisfaction1; nausea or vomiting can also be a barrier to use.
Adverse effects known as “triptan effects” are most often associated with
formulations and doses that produce higher plasma levels. In a small trial, low dose
sumatriptan powder delivered with an OptiNose Breath Powered device produced a
headache relief rate approaching that previously reported with injections without
the attendant side effects2. These results supported conduct of a larger
trial.
Methods: Single-dose, multicenter, randomized, double-blind,
placebo-controlled, parallel-group study. Patients had history of migraine for ≥1 yr
prior to entry and reported ≥1 headache, but <15 headache days, per month.
Patients were randomized to an OptiNose Breath Powered device containing either 20
mg of sumatriptan powder (15 mg emitted dose) or placebo. Patients treated an attack
reaching moderate or severe intensity and recorded symptoms at scheduled times.
Results: 223 patients received treatment (112 sumatriptan powder and 111
placebo). The mean age was 42 yrs.; 85% were women. For the primary outcome, 68% of
patients in the OptiNose sumatriptan powder group reported pain relief at 120 min
vs. 45% in the placebo group (p<.01). Pain relief curves diverged early, reaching
statistical significance at 30 min (42% vs. 27%; p<.05). At 120 min, 37% of
patients receiving OptiNose sumatriptan powder had reported complete relief compared
with 17% for placebo (p<.01), while 70% vs. 45% reported meaningful relief
(p<.001). Among patients with pain relief at 120 min, 65% sumatriptan powder and
53% placebo (ns) had continued pain relief at 24 hrs. Large reductions in nausea,
phonophobia, and photophobia were reported in both groups; between-group differences
were not statistically signficant. No systemic adverse events were reported in more
than one patient. Only one patient reported mild and transient tingling in the hands
and head. The most common (>5%) AEs reported were product taste (22%), nasal
discomfort (13%), and rhinitis (6%); all transient and generally mild.
Conclusions: This study replicates the previous finding that the
OptiNose Breath Powered device delivering low dose sumatriptan powder produces early
headache relief in a high percentage of patients compared to placebo and to
historical rates with oral treatment, and a high rate of headache relief. Treatment
was well tolerated, with few systemic adverse effects.
P5
The Risk of Serotonin Syndrome with Concomitant Use of Triptan Antimigraine
Drugs and SSRI/SNRI Antidepressants: A Population-Based Surveillance
Study
P. Rizzoli1, R. Burch1, B. Wainger2, C.
Bernstein3, E. Loder1
1Department of Neurology, Brigham and Womens Hospital, John R
Graham Headache Center, Boston, MA, USA; 2Anesthesia, Critical Care
and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA;
3Anesthesia, Critical Care and Pain, and Neurology, Beth Israel
Deaconess Medical Center, Boston, MA, USA.
Objectives: To identify the true risk of serotonin syndrome with
concomitant prescribing of triptan antimigraine medications with SSRI/SNRI type
antidepressant drugs by review of an exposed population.
Background: In 2006 the US Food and Drug Administration (FDA) issued an
Advisory about the risk of serotonin syndrome with concomitant use of drugs from two
widely prescribed medication classes: 1) selective serotonin reuptake inhibitor
(SSRI) and selective norepinephrine reuptake inhibitor (SNRI) antidepressants and 2)
triptan antimigraine drugs.
SSRI/SNRI antidepressants and triptan antimigraine drugs are widely prescribed.
20-25% of triptan users are also prescribed SSRI or SNRI antidepressants. Because
there have been no population-based studies that link co-prescription with the
outcome of serotonin syndrome, the true risk remains unknown.
Methods: We first identified the number of unique patients within the
Partners system who were prescribed a triptan from 2001-2010, and then what
proportion were concomitantly prescribed an SSRI or SNRI. We also examined this
information for each year separately to identify whether the proportion of patients
with co-prescriptions changed over the period of the study, especially following the
2006 FDA warning. Within these populations we searched for the yearly and aggregate
outcome of serotonin syndrome.
Results: From 2001-2010, among 15,221± 3 patients with triptan
monotherapy, there were 216± 3 cases of EPS. Among 5282± 3 patients with
co-prescription there were 135 ±3 cases of EPS. Evaluation by year showed, as
expected, lower case numbers and no decrease in triptan monotherapy or
co-prescription following the Advisory. Nor was there a change in the proportion of
patients diagnosed with EPS, even though one might expect that physicians would be
more alert to possible cases of serotonin syndrome after the Advisory. It does not
appear likely that cases were mistakenly diagnosed as neuroleptic malignant
syndrome. The proportion of patients with EPS in both groups was very low overall
but consistently higher in the triptan-only group than the co-prescription
group.
Conclusions: Triptan monotherapy and co-prescription of triptans and
SSRIs/SNRIs appear to be associated with a low risk of serotonin syndrome. These
preliminary data suggest that the large population of patients with co-existent
affective disorders and migraine may not need to forgo management of one condition
in order to treat the other. They further imply that it may be unwarranted for
decision support systems to issue automatic safety alerts for co-prescriptions.
Finally, it seems likely that detailed analysis may suggest that the FDA Advisory
should be reconsidered.
P6
SumaRT/Nap Verses Naproxen in Treatment and Disease Modification of Migraine: A
Pilot Study
R.K. Cady1, C.P. O’Carroll2, J.K. Dexter1, F.
Freitag3, M.E. Beach4
1Headache Care Center, Springfield, MO, USA; 2Newport
Beach Neurologists, Newport Beach, CA, USA; 3Baylor University
Medical Center, Dallas, TX, USA; 4Clinvest, Springfield, MO,
USA.
Objectives: This pilot study compared 2 acute migraine medications in
treating attacks of migraine and reducing the number of future attacks, thereby
modifying disease progression.
Background: Patients suffering with moderate to severe attacks of
migraine desire acute treatment. As migraine frequency increases, so too can the
risk of medication overuse. Frequent administration of acute medications may act
both as an acute and prophylactic treatment.
Methods: A randomized comparator trial of 39 subjects, 18 to 65 years of
age, with frequent episodic migraine with or without aura, as defined by ICHD-2, in
Stage 2 (3 to 8 headache days per month) or Stage 3 migraine (9 to14 headache days
per month) was conducted at 2 headache centers in the US. Subjects were randomized
1:1 to treat 14 or fewer migraines per month with SumaRT/Nap (Group A) or naproxen
sodium (Group B) for 3 months.
Results: Subjects in Group B had a statistically significant reduction
in migraine headache days at month 3 compared to baseline (p=0.0002): primary
endpoint. Group A had a reduction of migraine headache days but this decrease did
not reach statistical significance over baseline (p=0.2). In addition, subjects in
Group B had a statistically significant reduction of migraine attacks at all three
months of the study compared to baseline. A greater than 50% reduction in the number
of migraine days at month 3 occurred in 43% (6/14) of subjects in Group B compared
to 17% (3/18) of subjects in Group A. SumaRT/Nap was statistically superior to
naproxen at 2 hours in reducing the migraine headache severity. The amount of acute
medication used decreased from Baseline to Months 1-3 for both groups. Both
treatments were well tolerated.
Conclusions: Naproxen sodium provides headache relief at 2 hours and
reduces frequency of headache days and migraine attacks. Despite both groups using
similar quantities of naproxen, this was not seen in SumaRT/Nap. SumaRT/Nap is more
effective as acute treatment at 2 hours in reducing headache severity but does not
significantly reduce attack frequency or the number of headache days. If confirmed,
these results may have implications for migraine progression and MOH.
P7
Sumatriptan Transdermal System Is Significantly Less Likely To Cause Treatment
Emergent Nausea Than Placebo
S.D. Silberstein1, R.B. Lipton2, L. Newman3, C.
O’Neill4, J. Griesser4, M. Pierce4
1Thomas Jefferson University, Philadelphia, PA, USA;
2Albert Einstein College of Medicine, Bronx, NY, USA;
3Roosevelt Hospital Center, NY, NY, USA; 4NuPathe,
Conshohocken, PA, USA.
Objectives: The objective of this study was to compare the incidence of
treatment-emergent nausea (TEN) in patients treated with the sumatriptan
iontophoretic transdermal system (sumatriptan TDS, Zecuity™) or placebo.
Background: TEN develops in up to 20% of patients treated with oral
triptans. It may arise as a treatment-related adverse event or as a consequence of
oral therapy. Assessing non-oral therapies may clarify the mechanisms of TEN and
contribute to improved management.
Methods: This study used a randomized, parallel-group, double-blind,
placebo-controlled design to compare the efficacy and tolerability of the
sumatriptan TDS with placebo. The eligible subset included migraineurs who were free
of nausea at baseline, took study medication, and provided data on nausea at 2
hours. The primary endpoint of this post-hoc analysis was the proportion with TEN at
2 hours.
Results: Among 454 treated patients, 239 were free of nausea at baseline
and eligible for analysis; 130 patients treated with sumatriptan TDS and 109 with
placebo. The incidence of TEN was significantly lower with sumatriptan TDS than with
placebo from 1 hour through 24 hours post-baseline (Figure 1), indicating a
protective effect of active treatment. At 2 hours post-treatment, patients treated
with placebo were three times more likely to have TEN as those treated with
sumatriptan TDS (13.8% vs 4.6%, p <0.001).
Conclusions: Sumatriptan TDS prevents treatment emergent nausea relative
to placebo. This non-oral therapy has benefits not only in relieving nausea, but
also in preventing its emergence.
Proportion with TEN in patients treated with sumatriptan TDS or placebo
(N=239)
P8
Early Response to Intravenous Fluid for Children with Acute Migraine in the
Emergency Department
L. Richer1,2, W. Craig1,2, B. Rowe3
1Pediatrics, University of Alberta, Edmonton, AB, Canada;
2Women and Children’s Health Research Institute, Edmonton, AB,
Canada; 3Emergency Medicine, University of Alberta, Edmonton, AB,
Canada.
Objectives: Assess the early response to intravenous fluid hydration in
children with treatment-resistent migraine.
Background: Children with migraine frequently present to the Emergency
Department (ED) for treatment despite little evidence to support decision-making.
Many ED migraine treatment strategies are preceeded by a bolus of intravenous (IV)
fluid yet there is no data on the efficacy of this intervention. The study will also
support the planning of future trials.
Methods: Single-blind, ‘placebo-challenge’ study of 10 mL/kg IV 0.9%
sodium chloride (NaCl) for children aged 6-17 years presenting to a tertiary
pediatric hospital ED in Canada with treatment-resistant migraine. The primary
outcome was complete headache relief (pain-free) at 30 minutes. Secondary outcomes
included headache relief (change on visual analogue scale (VAS) > 20 mm), nausea,
headache recurrence, and return to ED within 24 hours. Patients were randomized into
two groups: (A) no medication given before 30 minutes and; (B) expectation that
medication may have been given simultaneously. Participants in group B observed a 5
mL syringe with 0.9% NaCl injected into their IV line and were read a standard
script that it ‘may or may not’ have included their medication. All participants
were treated with standard of care following the 30 minute assessment and
followed-up by phone at 24 hours. Analysis was performed blinded to group allocation
using Stata 12.1.
Results: Two-hundred and twelve subjects were screened in a 19-month
period and 46 randomized with a mean age of 13.3 years; 31 (67.4%) females. Five did
not complete the 24-hour follow-up call. Demographics (age, sex) and baseline
characteristics (headache severity, nausea, emesis, hydration, migraine history)
were similar between groups. Complete headache relief (pain-free) was low at 30
minutes with 1/24 in Group A (no expectation) and 1/22 in Group B (expectation;
p=0.7). Headache relief (VAS decrease > 20 mm) at 30 minutes was also similar
(p=0.6) with 6/24 (25%) in group A and 7/22 (31.8%) in group B. Ten participants
(21.7%) had relief in nausea (VAS change > 20 mm). The mean decrease in VAS from
baseline to 30 minutes was similar (p=0.93) with 12.3 mm (95% CI 4.6-20) for group A
and 12.7 mm (95% CI 6.8-18.5) for group B. Following standard care, twenty-one
(n=21/42; 50%) were moderately or extremely satisfied with their treatment. One
participant reported a minor intravenous related adverse event and 3 returned to the
ED in 24 hours.
Conclusions: Only a small proportion of children with migraine in the ED
experienced complete headache relief at 30 minutes after a bolus of IV normal
saline. The ‘expectation of treatment’ did not influence the response rates. Future
ED intervention trials for migraine in children can use IV fluid as a component of
the regimen or a ‘placebo-challenge’ phase without requiring a significant sample
size adjustment. Unlike adult migraine studies in the ED, few children return in 24
hours.
P9
Spinning out of Control: The Black Box of Basilar Migraine
P.G. Mathew1,2,3, S.G. Joshi1, H.U. Sheikh1
1Department of Neurology, John R. Graham Headache Center, Brigham
and Women’s Hospital, Boston, MA, USA; 2Division of Neurology,
Cambridge Health Alliance, Cambridge, MA, USA; 3Harvard Medical
School, Boston, MA, USA.
Objectives: To demonstrate that triptans are a safe and effective
abortive treatment for migraines with basilar type features.
Background: Basilar migraine, also known as basilar-type migraine and
basilar artery migraine, is a migraine sub-type that involves symptoms that are
thought to originate from the brainstem and/or from bilateral simultaneous
hemisphere activation. (1). The term basilar migraine can be traced back to a paper
by Bickerstaff in 1961, which suggested that basilar artery vasoconstriction is part
of the pathophysiology of this primary headache disorder (2). Since the coining of
the term basilar migraine, and its inclusion in the ICHD-II, there has not been any
significant evidence suggesting that posterior circulation oligemia or ischemia
occur as part of the pathophysiology of basilar migraine. Despite the lack of
evidence for basilar artery vasoconstriction, the US Food and Drug Administration
(FDA) mandates that package labeling includes that triptans are contraindicated in
patients with basilar migraine (3). Despite this package label contraindication,
many physicians prescribe triptans to patients that either meet criteria for basilar
migraine or have some features consistent with this diagnosis.
Methods: This retrospective IRB approved study was conducted at the John
R. Graham Headache Center (JGHC). A search was conducted using the electronic
medical record for patients with a diagnosis of migraine with basilar migraine
features who used a triptan between 7/2010-7/2011. The terms utilized for the
migraine with basilar features search were migraine AND basilar, dysarthria,
vertigo, tinnitus, hyperacusia, diplopia, ataxia, altered/loss of consciousness, and
spells. Visual and sensory criteria were not utilized due to the confounding with
migraine with aura that can occur with a text search.
Results: The total number of patients identified was 29. Side effects to
triptans were mild, and occurred in only a few patients. Triptans were effective in
58% of patients.
Conclusions: In this retrospective study, triptans were used safely and
effectively for the abortive treatment of migraines with basilar type features.
There has been no clear evidence that basilar type migraine symptoms occur due to
basilar artery spasm or constriction, and these data suggest that further
justification is warranted regarding the black box warning for the use of triptans
in basilar type migraine. These data also suggest that beta blockers, tricyclic
antidepressants, anti-convulsants, and Botox injections have some efficacy in the
treatment of migraines with basilar type features.
P10
Emergency Treatment of Migraine at Rio de Janeiro. Are the Patients Getting the
Right Thing?
A.V. Krymchantowski1, C.C. Jevoux1
1Headache Center of Rio, Rio de Janeiro, RJ, Brazil.
Objectives: The aim of this study is to evaluate the approach and
treatment provided to migraineurs in emergency departments (ED) of private hospitals
at Rio de Janeiro, Brazil.
Background: Emergency treatment of migraine attacks may vary with
geographical location and resources. In developing countries, the drugs used may not
reflect or fulfill the best options, the evidence-based medicine and even the needs
of the patients.
Methods: Every migraine patient according to the IHS – II, attending the
Headache Center of Rio and previously treated for an attack in an ED belonging to
Hospital Copa D’Or, Quinta D’Or, Barra D’Or or Clinica São Vicente was included if
able to describe medications used and time of permanence at the scene. Written
treatment reports were also used as proof of care delivered. The Hospitals are
located in Rio de Janeiro Municipal area and were chosen arbitrarily and because
they are considered as having high standards by most of the health plans.
Results: Forty one patients (31 women, 10 men, ages 20-76, mean 39,9
years) were included in the period of 2005-2012. The patients had an average
headache frequency of 4,7 attacks/month (1 to 10) and 5 patients (3 women, 2 men)
had migraine without aura and migraine with aura. The remaining patients had
migraine without aura. The average time in the ED was 6,7 hours (2-13h) and only 16
patients (39%) left the hospital with a higher than 50% relief in headache
intensity. Eighty percent of the patients received IV metamizole (dipyrone) whereas
36,6% had IM tramadol and 46,3% received IV nonsteroidal anti-inflammatory
medications (mostly tenoxican). Only 3 (7,3%) patients received injectable
sumatriptan and 6 (14,6%) chlorpromazine. More than one drug was administered to 36
(87,8%) patients.
Conclusions: Although with poor evidence, tramadol is one of the mostly
used medications in EDs of Rio de Janeiro for the acute treatment of migraine.
Metamizole is also commonly used because it is cheap and well tolerated, but not
very effective. Contrarily, sumatriptan is expensive while chlorpromazine usually
demands attention and time during and after administration for patient’s
monitorization. Considering the small percentage of patients leaving the hospital
with higher than 50% headache relief despite the long average duration of care, we
suggest that even the high standard hospitals in Rio change their paradigm of
treatment for migraine attacks. Medical education may be an useful way of improving
that.
P11
Randomized Comparison of the Pharmacokinetics of Sumatriptan Powder Delivered
with the OptiNose Breath Powered™ Intranasal Device to Imitrex Nasal Spray,
Tablet, and Injection
J.C. Messina1, J. Carothers1, R. Mahmoud1
1OptiNose Inc., Yardley, PA, USA.
Objectives: To compare the pharmacokinetics and safety of 20 mg
sumatriptan powder administered with the novel OptiNose Breath Powered intranasal
device with Imitrex 20 mg nasal spray, 100 mg tab, and 6 mg subcutaneous inj.
Background: Intranasal administration of sumatriptan has been proven to
produce relief from migraine with substantially lower systemic exposure than
injection or tablets. However, drug distribution within the nasal cavity from nasal
sprays is inconsistent, with much of the dose dripping out the front of the nose or
swallowed1. This reduces nasal absorption, contributes to bitter
taste, and may reduce predictability of treatment response. OptiNose Breath Powered
devices produce broader, more superior and posterior intranasal deposition than
standard liquid sprays2. A unique OptiNose product is being developed
with an intranasal sumatriptan powder to enhance the speed and extent of nasal
absorption in pursuit of meaningfully improved clinical benefits.
Methods: Single-dose, randomized, 4-period cross-over pharmacokinetic
study in 20 healthy volunteers. After dosing, plasma samples were taken through 14
hours with a 7 day washout between periods.
Results: The nasal formulations produced a substantially lower peak
(Cmax) and total exposure (AUC0-t,0-∞) than the tablet and inj. OptiNose
Breath Powered sumatriptan produced an earlier peak exposure and yielded >60%
higher early plasma exposure (AUC0-15 min and AUC 0-30 min)
than the nasal spray despite emitting 20% less drug. A significantly greater
proportion of sumatriptan was absorbed from the nasal cavity, following
administration with the OptiNose device in the first 30 min after dosing. All
treatments were well tolerated.
Conclusions: Sumatriptan powder delivered with the OptiNose Breath
Powered device is not bioequivalent to any tested sumatriptan product, produces
earlier and faster absorption than any form but injection, and has more efficient
nasal absorption than Imitrex nasal spray.
Pharmacokinetic Parameters
OptiNose 20 mgΩ Mean ±SD (N=20)
Imitrex IN 20 mgΩ Mean ± SD (N=20)
Imitrex Tab. 100 mg Mean ± SD (N=20)
Imitrex Inj. 6 mg Mean ± SD (N=20)
Cmax (ng/mL)
20.8 ± 12.2
16.4 ± 5.7
70.2 ± 25.3
111.6 ± 21.6
AUC0-15min (ng*hr/mL)
2.1 ±1.6
1.2 ± 0.8
0.7±0.7
16.2±4.0
AUC0-30min (ng*hr/mL)
5.8* ± 4.1
3.6 ± 1.9
8.1 ± 5.0
39.7 ± 7.1
AUC0-t (ng*hr/mL)
63.0 ± 20.3
59.1 ± 17.7
292.6 ± 87.5272
127.3 ± 17.3
AUC0-inf (ng*hr/mL)
64.9 ± 20.6
61.0 ± 17.8
308.8 ± 92.4
128.2 ± 17.4
SD=standarddeviation
*the 90% CI of the geometric mean ratios comparing OptiNose 20 mg to
Imitrex IN was above 100% and was below 100% for the comparisons
with Tablet and Inj;
ΩOptiNose device emitted dose is 16mg split between the
two nostrils. ImitrexIN emitted dose is 20mg.
P12
Efficacy of the Sumatriptan Iontophoretic Transdermal System (Zecuity™) in
Migraine Patients with and without Nausea at Baseline
J. Goldstein1, C. O’Neill2, J. Griesser3, M.
Pierce2
1San Francisco Clinical Research Center, San Francisco, CA, USA;
2NuPathe Inc., Conshohocken, PA, USA; 3The Griesser
Group, Conshohocken, PA, USA.
Objectives: This post-hoc analysis of Phase III clinical trial data
evaluates the efficacy of the sumatriptan iontophoretic transdermal system
(sumatriptan TDS) in patients with and without nausea at baseline.
Background: The sumatriptan TDS is a unique delivery system that uses a
low-level electrical current to deliver sumatriptan through the skin. This product
has recently been approved by the FDA for the acute treatment of migraine headaches
in adults with and without aura. Nausea during migraine occurs often and can impact
response to oral medications. Because migraine patients with nausea are less
satisfied with current medications; there is need for an effective product that can
address migraine-related nausea.
Methods: PREDICT (Study NP101- 007) was a randomized, double-blind,
placebo controlled Phase III clinical trial conducted in 469 patients aged 18-65
years who treated one moderate to severe migraine attack with sumatriptan TDS or
placebo. Freedom from pain two hours post patch activation was the primary endpoint.
Secondary endpoints included pain relief and freedom from nausea, photophobia and
phonophobia. This post-hoc analysis evaluated headache pain severity, photophobia,
and phonophobia in patients with and without nausea at baseline.
Results: In the overall patient population, sumatriptan TDS was
significantly more effective than placebo on the primary endpoint of freedom from
pain at two hours post patch activation. This significant difference was also
demonstrated in the secondary endpoints of pain relief and freedom from nausea,
photophobia and phonophobia. Significant pain relief and relief from nausea were
seen as early as one hour post patch activation. At two hours, 84% of patients
receiving sumatriptan TDS were nausea free (p=0.025). Of the patients who reported
nausea at baseline, 69% were nausea free at two hours with sumatriptan TDS vs 44% on
placebo. The occurrence of nausea was less at all time points post sumatriptan TDS
activation vs placebo. Patients with nausea at baseline were more likely to have
severe pain (31%) vs patients without nausea (16%); however the efficacy of
sumatriptan TDS across both primary and secondary endpoints was similar regardless
of the nausea status at baseline.
Conclusions: The sumatriptan iontophoretic transdermal system has
demonstrated efficacy in the treatment of migraine headaches. This post-hoc analysis
demonstrates that the efficacy is maintained regardless of the presence of nausea
and that nausea symptoms and headache pain are rapidly relieved.
P13
Evidence-Based Guideline of the American Headache Society: A Report on the
Pharmacologic Treatment of Acute Migraine in Adults
M.J. Marmura1, S.D. Silberstein1, J. Ailani2
1Department of Neurology, Jefferson Headache Center, Thomas
Jefferson University, Philadelphia, PA, USA; 2Department of
Neurology, Georgetown University, Washington, DC, USA.
Objectives: To provide an updated recommendation for acute migraine
treatment based on evidence in medical literature.
Background: Migraine frequently requires acute pharmacological treatment
for acute attacks. Previous acute guidelines published in 2000 provided guidance for
acute migraine treatment based on published studies and we undertook an update. 1
Members of the guidelines sections of the American Headache Society participated in
this project.
Methods: We performed a standardized literature search for articles
related to acute migraine treatment based on American Academy of Neurology
guidelines from 1998 to 2010. Based on these results, two authors selected abstracts
for full text review. Two reviewers assessed each qualifying study for its quality
of evidence. The authors recommended treatments based on levels of evidence, wtih a
Level A recommendation requiring at least 2 Class I studies and Level B
recommendation 1 Class I or Class II studies.
Results: The migraine specific medications almotriptan, eletriptan,
frovatriptan naratriptan, rizatriptan, sumatriptan, zolmitriptan and
dihydroergotamine nasal spray and inhaler are effective (Level A) and ergotamine and
intravenous ergotamine are probably effective (Level B) for acute migraine.
Multiple non-specific medications are effective in acute migraine including aspirin,
acetominophen, diclofenac, ibuprofen, naproxyn, rofecoxib, butorphenol nasal spray,
codeine, and the combination of acetominophen/aspirin/caffiene (Level A).
Ketoprofen, intravenous ketorolac, metamizole (dipyrone), intravenous magnesium, and
the combination of both isometheptene compounds and tramadol/acetominphen are
probably effective (Level B) for migraine. The antiemetics prochlorpromazine,
droperidol, chlorpromazine, and metoclopramide also are probably effective (Level
B).
There is inadequate evidence for the use of corticosteroids including dexamethasone,
intravenous valproic acid (Level C) and butalbital (Level C) for acute migraine.
Octreotide is probably not effective for acute migraine (Level B).
Conclusions: Multiple options for the acute treatment of migraine exist,
although there are important differences in their relative efficacy and adverse
events.
P14
Total Migraine Freedom (TMF) for Single Pulse Transcranial Magnetic Stimulation
(sTMS) Versus Triptans for the Early Acute Treatment of Migraine
A.J. Starling1, T. Bravo1, R.P. Chiacchierini2, R.B.
Lipton3, P.J. Goadsby4, S.D. Silberstein5, A.
Charles6, S.K. Aurora7, D.W. Dodick1
1Mayo Clinic, Phoenix, AZ, USA; 2R.P. Chiacchierini
& Associates, Rockville, MD, USA; 3Albert Einstein College of
Medicine, Bronx, NY, USA; 4University of California, San Francisco,
San Francisco, CA, USA; 5Thomas Jefferson University, Philadelphia,
PA, USA; 6David Geffen School of Medicine at University of
California, Los Angeles, Los Angeles, CA, USA; 7Swedish Pain Center,
Seattle, WA, USA.
Objectives: To compare the magnitude of the treatment effect for sTMS
versus triptans in randomized placebo-controlled trials using an early treatment
design where treatment was administered while pain was mild.
Background: sTMS is effective and well tolerated for the acute treatment
of migraine with aura. Triptans are the gold-standard for the acute treatment of
migraine. No head-to-head studies have compared the efficacy of sTMS to triptans.
Total Migraine Freedom (TMF) at two hours (2hTMF) is a composite endpoint that
incorporates freedom from pain, photophobia, phonophobia, and nausea. It is a
sensitive, patient-centric, clinically relevant summary measure which more
powerfully measures treatment effects than the four co-primary endpoints it
incorporates.
Methods: The clinical literature was systematically reviewed to identify
placebo or sham-controlled mild pain trials of acute migraine treatment with sTMS or
triptans. We identified one eligible sTMS study and 3 triptan trials. For each study
we computed the absolute risk reductions (ARR) for 2hTMF (2hTMF for active – 2hTMF
for sham/placebo). Data for the sTMS are summarized including all sites and
excluding a single site which had a dramatically high placebo response.
Results: ARR for 2hTMF for the sTMS study were 12.2% for all sites and
26.3% excluding a single site. For triptan trials, ARR for 2h TMF were as follows:
rizatriptan 10mg (27.5%), eletriptan 20mg (10.4%), eletriptan 40mg (41.0%),
sumatriptan 50mg, (21.4%), and sumatriptan 100mg (28.1%).
Conclusions: TMF is a patient-centric, clinically relevant, composite
endpoint. sTMS demonstrates efficacy in a range that overlaps with the triptans for
this robust treatment outcome measure. Head-to-head comparative studies of triptans
with sTMS are recommended.
P15
Blood Pressure Changes after Administration of Dihydroergotamine Via
Intravenous or Orally Inhaled Routes
S. Graff-Radford1, S. Kori2, E. Connors2, X.
Li2, M. Green3, D. Kellerman2
1Cedars-Sinai Medical Center, Los Angeles, CA, USA;
2MAP Pharmaceuticals Inc., Mountain View, CA, USA; 3Mount
Sinai School of Medicine, New York, NY, USA.
Objectives: The objective of this analysis was to compare acute changes
in blood pressure (BP) with intravenous (IV) dihydroergotamine (DHE) and orally
inhaled DHE, and to examine a possible relationship to maximum DHE plasma
concentrations (Cmax).
Background: DHE has often been characterized as a vasoconstrictor with
the potential to produce significant changes in BP. The use of DHE is
contraindicated in patients with ischemic heart disease and uncontrolled
hypertension. Much of the previous experience has been with parenteral
administration and vascular effects may have been related to doses administered and
high initial concentration achieved. A retrospective analysis of three head to head
studies was performed to compare plasma levels and BP changes seen following IV and
orally inhaled DHE.
Methods: Data from three crossover clinical studies compared BP changes
at specific intervals between 10 and 120 minutes post- treatment and Cmax
with DHE administered via oral inhalation (1.0 mg nominal) and DHE administered IV
(1.0 mg).
Results: Change from baseline BP data over 1 hour post-dosing from three
cross-over studies were compared following IV DHE (n=93) or orally inhaled DHE
(n=95). IV DHE produced a consistent pattern of 8-11 mmHg mean increase in systolic
BP at 10 minutes after administration. Orally inhaled DHE resulted in an average
increase in systolic BP of 1-5mmHg. Effects on diastolic blood pressure were of
similar magnitude to the systolic BP changes for both routes of administration. Mean
Cmax values occurred on average before 10 minutes post- dosing, and
were approximately 28,000-45,000 pg/mL with IV DHE and 2500 pg/mL with orally
inhaled DHE. There appears to be a direct relationship between Cmax and
increases in BP. Increases in BP were transient and returned to baseline values by
60-90 minutes irrespective of the route of administration.
Conclusions: These results show that the effect of DHE on BP varies with
the route of administration. IV DHE has a greater effect on BP than orally inhaled
DHE and correlates with the higher Cmax produced with IV DHE. At the
intended therapeutic dose of orally inhaled DHE (1.0 mg nominal), there was no
clinically significant effect on BP.
P16
Cambia Dual Mechanism of Action Involves Inhibition of Prostaglandin Production
and Novel Activation of the Inhibitory Voltage-Dependent M-Type Potassium
Current (i.e., KCNQ2/Q3 Channel Opener)
R. Burstein
Anesthesia and Neuroscience, Harvard Medical School, Boston, MA,
USA.
Objectives: To raise awareness and call attention to the fact that
Cambia may differ from other COX1/COX2 inhibitors by its ability to act as novel
KCNQ2 and KCNQ3 potassium channel opener.
Background: Cambia is a non-steroidal anti-inflammatory drug (NSAID)
indicated for the acute treatment of migraine attacks with or without aura in adults
18 years of age or older. Recent evidence that diclofenac, the active molecule of
Cambia, acts as KCNQ2/Q3 potassium channel opener suggest that its therapeutic
effectiveness in migraine may involve direct inhibition of neuronal excitability and
firing.
Methods: Literature review.
Results: The M-type potassium channel generates subthreshold
voltage-gated K+ current (M-current) that regulates neuronal excitability
by stabilizing membrane potential. As such, modulation of this non-inactivating
K+ channel, whose conductance is in the voltage range of action
potential initiation, inhibits repetitive neuronal firing. In 1998, the KCNQ2/Q3
channel complex has been identified as the molecular correlates of the M-current.
Since then, they have been found: (I) peripherally in the initial segments of C- and
Ad- fibers, and centrally in the spinal cord, thalamus and cerebral cortex, (II) as
potent inhibitors of nociceptive neurons, and (III) as effective anticonvulsants. In
the context of migraine, KCNQ2/Q3 channel openers may reduce the firing of
trigeminovascular neurons in the trigeminal ganglion, medullary dorsal horn and
thalamus, and reverse cortical hyperexcitability – a hallmark of migraine
pathophysiology.
Conclusions: Diclofenac ability to inhibit prostaglandin production,
repetitive neuronal firing and cortical hyperexcitability may allow it to reverse
certain aspects of migraine headache not previously shown to be reversed by other
NSAIDs.
P17
Comparison of Frovatriptan Plus Dexketoprofen (25 mg or 37.5 mg) Versus
Frovatriptan Alone in the Treatment of Migraine Attacks with or without Aura: A
Pilot Study
G. Bussone1, V. Tullo1, F. Valguarnera2, P.
Barbanti3, P. Cortelli4, G. Sette5, G.
Allais6, F. D’Onofrio7, V. Petretta7, M.
Curone1, D. Zava8, D. Pezzola8, C.
Benedetto6
1Clinical Neuroscience, National Neurological Institute Carlo
Besta, Milan, Italy; 2Sestri Ponenete Hospital, Genoa, Italy;
3Irccs San Raffaele Pisana, Rome, Italy; 4Neurological
Science, University of Bologna, Bologna, Italy; 5Sant’Andea Hospital,
Rome, Italy; 6Women’s Headache Center, University of Turin, Turin,
Italy; 7Neurologic Unit, San Giuseppe Moscati Hospital, Avellino,
Italy; 8Istituto Luso Farmaco d’Italia, Milan, Italy.
Objectives: To assess the efficacy and safety of frovatriptan 2.5 mg
plus dexketoprofen (25 or 37.5 mg; FroDex 25 or FroDex 37.5) compared with
frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraines.
Background: Drugs for migraine attacks include triptans and
non-steroidal anti-inflammatory drugs; their combination could provide greater
symptom relief.
Methods: 314 subjects with a history of migraine, with or without aura,
were randomized to Frova, FroDex 25 or FroDex 37.5 and treated one migraine attack.
This was a multicenter, randomized, double-blind, parallel-group, pilot study.
Primary end-point was the proportion pain-free (PF) at 2 hours. Secondary end-points
included sustained pain-free (SPF) and relapse within 48 h.
Results: Frequency (%) of pain-free at 2 h after administration of
Frovatriptan alone, Frovatriptan+Dexketoprofen 25 mg and
Frovatriptan+Dexketoprofen 37.5 mg in the 279 patients of the intention-to treat
population. Asterisks indicate a statistically significant difference (p<0.05)
between the group treated with Frovatriptan alone and the groups treated with
combination therapy. The proportions of subjects PF at 2 hours were better with each
combination therapies than with Frova.
Proportions of SPF at 24 hours were 24% for Frova, 43% for FroDex 25 (p< 0.05) and
42% for FroDex 37.5 (p<0.05). SPF at 48 hours was 23% with Frova, 36% with FroDex
25 and 33% with FroDex 37.5 (p=NS). Relapse was similar for Frova (22%), FroDex 25
(29%) and FroDex 37.5 (28%) (p=NS). Drug-related adverse events were equally low
between the different treatments.
Conclusions: The combination of frova and dexketoprofen improved initial
efficacy at 2 hours compared to frova alone whilst maintaining efficacy at 48 hours
in this study. The safety profiles were comparable. The intrinsic pharmacokinetic
properties of the two single drugs contribute to this improved efficacy profile.
P18
Efficacy of Frovatriptan vs. Other Triptans in Weekend Migraine: Pooled
Analysis of Three Double-Blind, Randomized, Crossover, Multicenter, Italian
Studies
L. Savi1, C. Lisotto2, L. Pinessi1, S.
Omboni3, D. Pezzola4, D. Zava4, G.
Zanchin5
1Neurology II, Headache Center, Department of Neuroscience,
University of Torino, Torino, Italy; 2Ambulatorio per lo Studio, la
Diagnosi e la Terapia delle Cefalee, Ospedale Civile, San Vito al Tagliamento,
Italy; 3Clinical Research Unit, Italian Institute of Telemedicine,
Solbiate Arno, Italy; 4Medical Department, Istituto Lusofarmaco
d’Italia, Peschiera Borromeo, Italy; 5Department of Neurology,
University of Padova, Padova, Italy.
Objectives: To evaluate the efficacy of four different triptans in
weekend vs. workday migraine attacks through a pooled analysis of individual data
from three Italian, randomized, double-blind, cross-over, multinational studies.
Background: Migraine attacks may often occur during days off. Limited
evidence is available on the efficacy of antimigraine drugs in these weekend
migraines.
Methods: Subjects with a history of migraine with or without aura were
randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5
mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg
(study 3). Each patient had to treat 1 to 3 attacks with each drug in no more than 3
months. For this retrospective analysis patients with at least one migraine attack
without aura on any Saturday or Sunday were selected. Within-treatment efficacy
during weekends and workdays was compared.
Results: 188 (54%) of the 346 patients of the intention-to-treat
analysis had weekend migraine and were included in the analysis. A total of 569
attacks occurred during the weekend and 1281 during workdays. The proportion of pain
free at 2 hours did not significantly differ between weekend and workday attacks for
frovatriptan (26% vs. 27%) or for the comparators (34% vs. 32%). Also, pain relief
episodes were similarly distributed between weekend and non-weekend attacks
(frovatriptan: 40% vs. 42%; comparators: 49% vs. 43%, p=NS). Conversely, rate of
relapse at 48 hours was significantly (p<0.05) less during weekend attacks for
frovatriptan (17% vs. 30% workdays), while this was not the case for comparators
(weekends 34% vs. workdays 40%, p=NS).
Conclusions: Our study provides the first evidence that frovatriptan may
represent a particularly favourable option for treating weekend migraine
attacks.
P19
Frovatriptan vs. Other Triptans for the Acute Treatment of Oral
Contraceptive-Induced Menstrual Migraine: Pooled Analysis of Three Double-Blind,
Randomized, Crossover, Multicenter, Italian Studies
G. Allais1, V. Tullo2, S. Omboni3, D.
Pezzola4, D. Zava4, C. Benedetto1, G.
Bussone2
1Department of Gynecology and Obstetrics, Women’s Headache Center,
University of Torino, Torino, Italy; 2Department of Clinical
Neuroscience, National Neurological Institute Carlo Besta, Milano, Italy;
3Clinical Research Unit, Italian Institute of Telemedicine,
Solbiate Arno, Italy; 4Medical Department, Istituto Lusofarmaco
d’Italia, Peschiera Borromeo, Italy.
Objectives: To review the efficacy of frovatriptan vs. other triptans,
in the acute treatment of OCMM through a pooled analysis of three individual
randomized Italian studies.
Background: Oral-contraceptive-induced menstrual migraine (OCMM) is a
particularly severe form of migraine triggered by the cyclic hormone withdrawal.
Methods: Subjects with a history of migraine with or without aura were
randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5
mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg
(study 3). The studies had an identical multicenter, randomized, double-blind,
crossover design. After treating 1 to 3 episodes of migraine in no more than 3
months with the first treatment, patients switched to the other treatment for the
next 3 months. In this retrospective analysis, the subset of 73 of the 280 women of
the intention-to-treat population taking combined oral contraceptives and
experiencing a migraine attack during the withdrawal phase, were analyzed.
Results: The proportion of pain free and pain relief at 2 hours were 25%
and 51% with frovatriptan and 28% and 48% with comparators (p=NS). At 24 hours, 71%
and 83% of frovatriptan-treated patients and 60% and 76% of comparator-treated
patients were pain free (p<0.05 between treatments) and had pain relief (p=NS),
respectively. Relapse at 24 and 48 hours was significantly (p<0.05) lower with
frovatriptan (17% and 21%) than with the comparators (27% and 31%).
Conclusions: Our results suggest that, due to its sustained antimigraine
effect, frovatriptan may be particularly suited for the management of OCCM as
compared to other triptans.
P20
Efficacy of Frovatriptan and Other Triptans in the Treatment of Acute Migraine
of Hypertensive and Normotensive Subjects: A Review of Randomized
Studies
G. Bussone1, S. Omboni2, V. Tullo1, P.
Barbanti3, P. Cortelli4, M. Curone1, C.
Benedetto5, D. Pezzola6, D. Zava6, G.
Allais5
1Department of Clinical Neuroscience, National Neurological
Institute Carlo Besta, Milano, Italy; 2Clinical Research Unit,
Italian Institute of Telemedicine, Solbiate Arno, Italy; 3Unit for
Treatment and Research of Headaches and Pain, IRCCS San Raffaele Pisana, Roma,
Italy; 4Neurological Clinic, Department of Neurological Science,
University of Bologna, Bologna, Italy; 5Department of Gynecology and
Obstetrics, Women’s Headache Center, University of Turin, Torino, Italy;
6Medical Department, Istituto Lusofarmaco d’Italia, Peschiera
Borromeo, Italy.
Objectives: To systematically evaluate the efficacy of frovatriptan and
other triptans in the acute treatment of migraine, in patients classified according
to a history of arterial hypertension, enrolled in three randomized, double-blind,
crossover, Italian studies.
Background: Some studies suggest that the association between high blood
pressure (BP) and migraine might not be uncommon and might induce more severe and
more difficult to treat forms of migraine.
Methods: Subjects with a history of migraine with or without aura were
randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5
mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg
(study 3). After treating up to 3 episodes of migraine in no more than 3 months with
the first treatment, patients switched to the alternate treatment for the next 3
months. The present subgroup analysis assessed triptan efficacy in 60 subjects with
a history of treated or untreated essential arterial hypertension (HT) and in 286
normotensive (NT) subjects.
Results: HT patients were older (45±8 years vs. 37±10 years NT,
p<0.001) and with a higher prevalence of males (27% vs. 15% NT, p<0.05). As
expected, entry BP and heart rate values were higher in HT than NT patients. During
the study, migraine attacks with aura were significantly more prevalent in HT
subjects (21% vs. 13% NT, <0.001). The proportion of pain free at 2 hours did not
significantly differ between HTs and NTs for either frovatriptan (25% vs. 26%) and
the comparators (39% vs. 32%). Pain relief was achieved in significantly (p<0.05)
fewer episodes in HT subjects for either frovatriptan (41% vs. 52% NT) and
comparators (48% vs. 58%). Rate of relapse at 48 hours with frovatriptan was
similarly low in HTs and NTs (29% vs. 31%), while with the comparators it was
significantly (p<0.05) larger in HTs (62%) than in NTs (44%). No difference in
the occurrence of adverse events was reported between HT and NT. No increment in BP
or heart rate values was observed during the study in HT subjects.
Conclusions: Our analysis suggests that HT individuals in general tend
to be less responsive than NT migraineurs to triptan therapy. However, frovatriptan,
in contrast to the other triptans studied, seems to have a sustained antimigraine
effect in both HT and NT patients.
P21
Sumatriptan Transdermal System (TDS) Can Be Correctly Assembled, Applied, and
Activated during Migraine Attacks
K. Meadows1, M. Pierce2, S. Foster1, C.
Jennings1, C. O’Neill2
1The Education & Research Foundation, Lynchburg, VA, USA;
2NuPathe, Conshohocken, PA, USA.
Objectives: To validate the ease of assembly, application, and
activation of the sumatriptan iontophoretic transdermal system (sumatriptan TDS,
Zecuity™) during a migraine attack.
Background: Lontophoresis is a noninvasive drug delivery method that,
using low electrical current, moves solubilized drugs across the skin to the
underlying tissue. With sumatriptan TDS, pre-programmed doses of sumatriptan are
automatically delivered via a transdermal patch, allowing therapeutic drug levels to
be reached without mechanical penetration or disruption of the skin. A usability
study evaluated the ease of assembly, application, and activation of the sumatriptan
TDS.
Sumatriptan TDS Assembly
Methods: This study assessed a single use of sumatriptan TDS in adult
migraineurs and healthcare professionals (HCPs). Subjects were divided into 3
groups: migraineurs trained to use sumatriptan TDS, migraineurs not trained to use
sumatriptan TDS, and HCPs not trained to use sumatriptan TDS. Sixteen subjects
participated in a pre-summative usability test, and 48 subjects participated in a
formal summative test. Subjects were 20–64 years old and 83% female. They rated
usability on a scale of 1–7, with 1 being difficult and 7 being easy.
Results:
Pre-summative testing
Of the 16 sumatriptan TDS patches assembled and applied, 100% were assembled,
applied, and activated successfully. The mean score for ease of assembly was 6.3,
and the mean score for ease of application/activation was 6.8.
Summative testing
Of the 48 sumatriptan TDS patches assembled and applied during summative testing,
100% were assembled, applied, and activated successfully, with no user errors, one
close call, and no operational difficulties observed. Among migraineurs, 3% had a
mild attack, 69% had a moderate attack, and 28% had a severe attack. Across all
three groups, the mean score for ease of assembly was 6.1, and the mean score for
ease of application/activation was 6.8. For subjects who were trained and
subsequently returned to the testing facility for evaluation of usability while in
distress of a mild to severe migraine attack, the number of days between training
and testing ranged from 0–20, with a mean of 3.6.
Conclusions: The results of this study indicate that sumatriptan TDS can
be assembled,applied, and activated safely and successfully during a mild to severe
migraine attack. Across all subject groups in both the pre-summative and summative
testing, including trained and untrained migraineurs in distress of a migraine
attack (97% moderate to severe) and untrained HCPs, patch assembly, application, and
activation was 100% successful. In addition, subjects rated sumatriptan TDS very
high (6.8 out of 7.0) for ease of use.
P22
Enrichment Clinical Trial Designs Do Not Decrease the Placebo Response Rate in
Pediatric Studies: A Systematic Review of Triptan Trials
L. Richer1,2, J. Neilson1
1Pediatrics, University of Alberta, Edmonton, AB, Canada;
2Women and Children’s Health Research Institute, Edmonton, AB,
Canada.
Objectives: To assess the effect of enrichment design, study design, and
route of delivery on the placebo response rate in randomized controlled trials of
triptan medications in the pediatric age group.
Background: Numerous triptan medications approved for use in adults have
failed to demonstrate efficacy in children or adolescents and the high placebo
response rate is often implicated. More recently studies have used enrichment
designs in which particpants who respond to placebo in the early, single-blind,
run-in phase are not randomized to the double-blind phase. A systematic review of
clinical trials for triptan medications was conducted to evaluate and compare the
placebo response rate.
Methods: Seven bibliographic databases, four clinical trial registers,
and the grey literature were searched. 6995 references were identified using a
sensitive search strategy for prospective randomized controlled trials of children
or adolsecents with acute migraine comparing a triptan medication to placebo.
Pain-free and headache relief at 2 hours were the primary efficacy outcome measures.
The proportion of placebo responders and standard error were calculated for each
study and data entered into RevMan 5.2.3 (Cochrane Collaboration) for analysis.
Meta-analysis, forrest plots, and tests for sub-group differences were calculated
using generic inverse variance as the statistical method and the random effects
analysis model.
Results: The placebo response rate overall for all 22 triptan studies
was 21% (95% CI 18-25) for pain-free as the outcome and 48% (95% CI 44-53; 21
studies) for headache relief. The placebo response rate did not significantly
decrease (p=0.22) with the enrichment design studies at 17% (95% CI 9-25; 3 studies;
I2=85%) and normal design at 22% (95% CI 19-26; 19 studies;
I2=65%) for pain-free as the outcome and 47% (95% CI 47-57; 2
studies, I2=0%) and 48% (95% CI 42-54; 19 studies; I2=84%)
respectively for headache relief. No significant differences in the placebo response
rate were observed between oral and intranasal triptan studies for pain-free
(p=0.35) or headache relief (p=0.7). However placebo response rates were
significantly lower (p=0.001) in studies with a cross-over design at 40% (95% CI; 8
studies; I2=58%) compared with 54% (95% CI 49-59; 13 studies;
I2=78%) for headache relief as the outcome, but not statistically
significant (p=0.14) for pain-free at 19% (95% CI 15-22) and 23% (95% CI 18-27)
respectively.
Conclusions: Enrichment designs have not significantly changed the
placebo response rate in randomized contolled trials of triptan medications in the
pediatric age group. Oral versus intranasal delivery also did not alter the placebo
response rate. The cross-over trial however was associated with a signifcantly
decreased placebo response rate with headache relief as the outcome, but was not
significant with pain-free as the outcome. High between study variation was observed
suggesting other mechanisms other than those explored in this study may affect
placebo response.
P23
Comparison of Methods for Delivering Drug to Regions of Deep Intranasal Nerve
Structures: Review of Human Data
P.G. Djupesland1, J. Messina2, R. Mahmoud2
1R&D, OptiNose AS, Oslo, Norway; 2OptiNose US Inc.,
Yardley, PA, USA.
Objectives: Review of publications reporting human
in vivo regional quantification of nasal deposition by gamma
scintigraphy to assess deep delivery of drug to target nerve regions.
Background: Delivery of drug to deep intranasal nerve structures may
improve treatment of a number of neurologic disorders. This includes migraine, where
the trigeminal system is believed to play a key role in the pathophysiology. We
review available data on in vivo human deposition patterns with
devices intended to provide reliable and efficient drug delivery to upper/posterior
nerve structures.
Methods: A MedLine search identified only 5 relevant human
gamma-deposition studies. One study compared a traditional spray pump to nasal
inhalation from a standard nebulizer delivering small particles intended to increase
deposition beyond the nasal valve. Another study compared two spray pumps with
different plume characteristics. In both studies the nasal cavity was divided in 9
segments and ratios between inner (I) and outer (O) segments and upper (U) and lower
(L) segments were reported. Another study compared two novel nasal nebulizers, a
sonic jet nebulizer and a vibrating mesh nebulizer with suction from the exit
nostril. Finally, two studies compared the deposition patterns of traditional spray
pumps to liquid and powder versions, respectively, of novel Breath Powered
Bi-directionalTM delivery devices.
Results: Mean U:L and I:O ratios were higher with the nebulizer vs.
spray pump suggesting more deposition in the upper and posterior regions, but up to
56% of the dose was inhaled to the lungs. The spray pumps were not statistically
different from one another. The comparison of novel nebulizers showed maximum
deposition for both to be 2 cm from the nostril in the horizontal plane,
corresponding to the location of the nasal valve. In the vertical plane the maximum
distribution with the mesh nebulizer was closer to the nasal floor than the sonic
jet nebulizer (0.75 cm vs 1.2 cm). Both Breath Powered delivery devices deposited
significantly higher fractions in the upper posterior parts of the nose compared to
traditional spray pumps (Sum of upper + middle posterior segments: Powder 53.5% ±
18.5 vs. Traditional spray 15.7% ± 13.8, p < 0.02).
Conclusions: Human in vivo testing shows that Breath
Powered devices significantly improve deposition in the intranasal regions where
nerve structures can be targeted for therapeutic benefit in migraine and other
disorders. This delivery is not associated with the inefficient and potentially
dangerous lung inhalation seen with nebulizers. The promise of therapeutic benefit
from reliable, practical deep intranasal delivery may now be achievable.
P24
Patient Satisfaction with MAP0004: Results of an Optional Survey during a
Long-Term Open-Label Safety Study
S. Aurora2, D. Buse3, B. Lu1, D.
Kellerman1, W. Cooper4, S. Kori1
1MAP Pharmaceuticals, Mountain View, CA, USA;
2Department of Neurology, Stanford University, Stanford, CA, USA;
3Montefiore Medical Center, Bronx, NY, USA;
4University of Michigan, Ann Arbor, MI, USA.
Objectives: To assess satisfaction with the TEMPO® inhaler as
a delivery system, and satisfaction with MAP0004 compared to previous migraine
medications.
Background: MAP0004 is an investigational orally inhaled
dihydroergotamine which has been shown to be effective in treating migraine in a
randomized, double blind controlled study. MAP0004 was administered through a TEMPO
inhaler. As the administration involved the use of an inhaler with a potential for
unfamiliarity and inconvenience of administration, subjects were invited to complete
a voluntary survey questionnaire to assess satisfaction with the use of the inhaler
and perceived efficacy of the investigational drug.
Methods: Subjects who participated in an open-label, long-term safety
study and were participating at week 24 were given an option to complete a survey to
assess the ease of use, perceived efficacy, and side effects of the drug. The survey
consisted of 16 questions, categorized into comparison to previous medications (8),
convenience of use (4), medication aftertaste (3) and overall satisfaction (1). The
questionnaire was not a validated instrument. Participation was voluntary and was
completed by subjects at different intervals (24 or 54 weeks) during the study.
Response options to questions ranged from strongly agree to strongly disagree on a
five point scale. Not all questions were answered by every subject and items with
missing and N/A answers were excluded. No formal statistical inferences were made
and responses are presented as a normalized percentage of the responders agreeing or
disagreeing with the statements.
Results: A total of 197 subjects completed at least one survey. As
compared to their previous medications, subjects perceptions of MAP0004, as
reflected in the survey results, included: works more consistently (68%); works
faster (63%); better pain relief (53%); longer pain relief (54%); return to normal
activity faster (63%); works even when taken late (57%); prevents recurrence (62%);
and works better when taken early (83%). 58% preferred MAP0004 over their previous
medications. 88% felt it was easy to use and 83% convenient to use. 64% reported it
to be as convenient to use as their previous medications. 58% reported medication
after taste, but 77% said that after taste was tolerable, and 84% said the taste
would not prevent them from asking for a MAP0004 prescription. 69% indicated that
they would ask for a MAP0004 prescription if the product was available.
Conclusions: In this non-validated survey, the majority of the
respondents preferred MAP0004 over their previous prescription migraine medication.
A majority reported that the inhaler was easy and convenient to use. Survey
participants reported after taste associated with the drug, and indicated that it
would not prevent them from requesting a prescription for the study drug if the
product was available.
P25
Incidence of Adverse Events with MAP0004 Does Not Increase with Increased
Frequency of Dosing: Results from a Long-Term Phase 3 Study
P. Winner2, S. Lucas3, B. Lu1, E.
Connors1, F. Freitag4, S. Kori1
1MAP Pharmaceuticals, Mountain View, CA, USA; 2Palm
Beach Headache Center Premiere Research Institute, West Palm Beach, FL, USA;
3University of Washington Medical Center, Seattle, WA, USA;
4Baylor University Medical Center, Dallas, TX, USA.
Objectives: To evaluate the incidence of adverse events after
administration of one, two and multiple doses per month of MAP0004 over a period of
one year.
Background: The efficacy and safety of MAP0004, an investigational
product candidate which delivers dihydroergotamine (DHE) through the lung via a
breath-synchronized, metered dose inhaler (TEMPO®), has been demonstrated
in treating an acute attack of migraine in placebo-controlled clinical trials. DHE
has a long half-life and prolonged binding to receptors compared to sumatriptan.
This post-hoc analysis was undertaken to evaluate if the properties of DHE would
lead to a cumulative effect, and result in an increase in adverse events after
repeated administration.
Methods: This is a post-hoc analysis of a long term study to evaluate
the safety and tolerability of MAP0004. All adverse events reported by study
subjects during their scheduled study visits during the study period were recorded
and mapped to organ systems and preferred terms according to the MedDRA
classification. The incidence of adverse events in those subjects who
self-administered one dose per month were compared to those who received two doses
per month and three or more doses per month using Fisher’s exact test.
Results: A total of 288 subjects received at least one dose of the study
drug per month for twelve consecutive months. 77 subjects received one dose per
month, 121 received two doses per month, and 90 received three to six doses per
month. The incidence of adverse events was similar in the three groups, and the
incidence of adverse events was not significantly higher in those who averaged three
or more doses per month compared to those who averaged one dose per month. The most
common adverse events, as expected in any population followed over a year, were
upper respiratory infections, but their incidence was similar in all three groups.
Potential DHE related AEs such as nausea, GI symptoms, fatigue, chest symptoms were
also similar in all three groups. Comparisons at the individual event level found
only dizziness and asthma being significantly different when comparing to one dose
per month, and in both cases the incidence was lower with increased doses.
Conclusions: In this post-hoc analysis of a long term safety study,
repeated administration of MAP0004 of up to six doses per month resulted in no
increased incidence of adverse events compared to administration of one or two doses
per month.
P26
The Fixed Combination of Acetaminophen, Acetylsalicylic Acid, and Caffeine Is
Faster and More Effective Than Ibuprofen for Acute Treatment of Patients with
Severe Migraine
J. Goldstein1, M. Hagen2, M. Gold3
1San Francisco Clinical Research Center, San Francisco, CA, USA;
2Novartis Consumer Health SA, Nyon, Switzerland;
3Novartis Consumer Health, Parsippany, NJ, USA.
Objectives: To compare a fixed combination containing acetaminophen,
acetylsalicylic acid, and caffeine with ibuprofen for acute treatment of severe
migraine.
Background: Many migraineurs use only nonprescription medications, but
their effectiveness is not well understood in patients whose attacks feature the
most severe migraine pain. We compared two widely used nonprescription agents in a
patient population representing the full spectrum of migraine, including patients
who require bed rest and/or vomit frequently.
Methods: Subjects (n=1555) with ICHD-2 migraine were included in a
multicenter, double-blind, randomized, parallel-group, placebo-controlled,
single-dose study. No patients were excluded due to severity of symptoms or degree
of disability. They were randomized to receive a single two-tablet dose of either
(1) acetaminophen 250 mg, acetylsalicylic acid 250 mg, and caffeine 65 mg per tablet
(AAC); (2) ibuprofen 200 mg per tablet (IB); or (3) placebo (PLA). The subset of 660
migraineurs whose treated attack had severe pain was extracted for post hoc
analysis.
Results: At most time points, AAC and IB relieved the severe pain and
associated symptoms of migraine significantly better than PLA. AAC was significantly
better than PLA for mean pain relief (PAR) from 45 minutes through 4 hours
(p≤0.004); mean pain intensity difference (PID) from 45 minutes
through 4 hours (p ≤ 0.006); % headache response (HR) from 90
minutes through 4 hours (p≤0.013); % pain-free at 3 and 4 hours
(p≤0.003); functional disability (FD) % reduced to little or
none from 1 through 4 hours (p≤0.005); % free from nausea at 2
hours (p=0.049), from phonophobia from 90 minutes through 4 hours
(p≤0.007), and from photophobia at 2, 3, and 4 hours
(p≤0.036); % used rescue medication over the 4 hours
(p=0.018); and time to meaningful relief (132 minutes vs 180
minutes, p=0.010). AAC was significantly superior to IB for mean
PAR at 45 minutes and at 1, 2, 3, and 4 hours (p<0.04); mean PID
from 60 minutes through 3 hours (p<0.05); % HR at 2 hours
(p=0.04); FD % reduced to little or none at 3 hours
(p=0.013); % free from phonophobia at 3 hours
(p=0.04) and from photophobia at 15 minutes
(p=0.03); and % used rescue medication over the 4 hours
(p<0.001). Compared with IB patients, AAC patients also
reported significantly faster meaningful relief (132 minutes vs 148 minutes,
p=0.026; Fig 1).
Conclusions: In patients with severe migraine pain, AAC and IB are
significantly more effective than PLA, and AAC provides significantly faster and
more effective relief than IB.
P27
Withdrawn by the author.
P28
A Breath-Synchronized Pressurized Metered Dose Inhaler as a Delivery System for
Migraine Treatment
A. Bosco1, S. Gray1, B. Lu1, D.
Kellerman1, R. Cady2
1MAP Pharmaceuticals Inc., Mountain View, CA, USA;
2Headache Care Center, Springfield, MO, USA.
Objectives: The TEMPO® inhaler differs from traditional
press-and-breathe pressurized metered dose inhalers (pMDIs) and healthcare
practitioners may not be aware of these differences and the potential use of oral
inhalation in the treatment of migraine.
Background: Oral inhalation offers advantages as a route of
administration for the treatment of migraine compared with IV and oral
administration. Oral inhalation is non-invasive and inhalers are portable and don’t
require visits to the ER or a physician’s office for administration. Additionally,
the lung provides a large absorptive surface area and a highly permeable membrane in
the alveolar region to allow for rapid absorption of drug into the systemic
circulation, avoiding hepatic first-pass metabolism. A breath-synchronized pMDI, the
TEMPO inhaler, has been developed as an investigational drug product for the
delivery of dihydroergotamine (DHE) to treat migraine in adults (MAP0004).
Methods: The TEMPO inhaler differs from traditional pMDIs in that it is
breath-synchronized, using the patient’s inhalation maneuver to trigger the release
of drug. Once the patient’s inspiratory pressure exceeds the triggering threshold
(∼18-20 mbar), a cradle assembly depresses a pressurized canister filled with DHE
suspended in propellant, dispensing the drug in an aerosol. Breath-synchronization
eliminates the coordination requirements of traditional pMDIs where the patient must
manually depress the pMDI canister while simultaneously synchronizing the release of
drug with a deep inhalation. Poor coordination between actuation and inhalation may
result in a small percentage of drug reaching the lung, as the majority of the
aerosol plume impacts in the oropharynx and is swallowed. The internal flow control
chamber (FCC) in the TEMPO inhaler replaces add-on spacer devices used to reduce
plume velocity and minimize oropharyngeal deposition often seen with traditional
pMDIs. The FCC creates a vortex that suspends and slows down the discharged aerosol
plume. This allows drug particles to be entrained within the patient’s inhaled
airflow and bypass the larynx and deposit in the lung periphery.
Results: The TEMPO inhaler generates a highly reproducible mass of
aerosol within the fine particle range of 1-5 mm (mean = 2.8 mm), which is optimal
for peripheral lung deposition. Data from 4 clinical lots of MAP0004 (DHE in the
TEMPO inhaler) studied in adult migraineurs demonstrate a reproducible emitted mass
of DHE. This, coupled with reduced oropharyngeal deposition and a highly respirable
aerosol plume, results in a reproducible mass of DHE reaching the lung periphery
where it can be rapidly absorbed into the systemic circulation.
Conclusions: The TEMPO inhaler is a novel delivery system for migraine
therapies as it is able to generate and release an aerosol plume consisting of
highly respirable particles that is coordinated with a patient’s inhalation,
reducing oropharyngeal deposition and promoting drug deposition in the lung
periphery for a more homogenous distribution throughout the lungs.
P29
The Efficacy of Acupressure on the P6 Antiemetic Point: Relief of
Migraine-Related Nausea
Z. Medgyessy1, G. Schmid-Ott2
1Department of Headache, Berolina Clinic, Löhne, Germany;
2Department of Psychosomatic, Berolina Clinic, Löhne,
Germany.
Objectives: The aim of the trial was to evaluate the efficacy of
acupressure on the P6 point for the amelioration of migraine related-nausea.
Background: After head pain, nausea is one of the most debilitating
symptoms of migraine.
Methods: 41 Patients, 39 female and 2 male, participated in the trial.
The participants’ average age was 47 years. They had been suffering from migraines
for on average 26 years and had experienced an average of 33,1 migraine days over
the previous three months. The average migraine pain intensity was 7,1 on a score
from 0 (no pain) to 10 (strongest pain); the average intensity of nausea was 6,2 on
a score from 0 (no nausea) to 10 (severest nausea). Patients were instructed to use
the SEA-Band acupressure bands instead of taking antiemetics during their next
migraine attack and to complete and return a migraine attack diary.
Results: After using the acupressure band, 34 (83%) patients noticed a
reduction of nausea. Reported nausea after therapy was 2,9 on the 10-point scale
from 1 (significantly weaker) to 10 (significantly stronger). Eighteen patients
(44%) reported that their nausea was significantly weaker. The relief of nausea was
reported after an average of 28.7 minutes. The average duration of the migraine
attacks was 21,5 hours. The Sea-Band was worn on average for 17.9 hours. Forty
patients (98%) reported that they would use Sea-Band during migraine attacks
again.
Conclusions: Results show, that the use of an acupressure band can
reduce migraine-related nausea. The advantage of this therapy is that it is
drug-free and has no risks or side-effects such as dizziness or tiredness. Its
effect is rapid, and it is easy and inexpensive to use. A randomized trial comparing
drug treatment and acupressure is warranted.
P30
Migraines Induced by Toothaches
R. Sood1, S. Sharma1, D. Thomas1
1Orofacial Pain, UMDNJ, Newark, NJ, USA.
Objectives: Case report.
Background: Migraine- a neurovascular headache is mostly accompanied by
phonophobia, photophobia, nausea, and scalp allodynia. Known triggers include food,
hormonal changes, stress, abnormal sleep, and drugs. Migraine triggered by tooth
pain is clinical observation with minimal literature support.This article describes
two cases of migraines induced by toothaches, both which were completely relieved by
a dose of triptans. The episodes failed to recur once the offending tooth was
treated.
Methods: Case Report 1: A 40-year-old female patient presented with
chief complaints of pain in right face with concomitant headaches and no prior
history of migraine. History of composite restoration (two months ago) with
subsequent tenderness and periapical pathology and progressed to headache over 3
days. Onset as “sensitivity” on the upper right front teeth (6, 7, 8) which
progressed to headache over 2-3 days, throbbing right-sided headache with a pain
level of 8/10 with scalp allodynia, photophobia, and nausea. Pain radiated from
upper right tooth to eye, ear, and right side of the head. Diagnostic block of tooth
#7 reduced “toothache” by 90% but not other pains.
Since she complained of chest pain with worst headache ever, patient was referred to
Emergency Room.Intranasal Sumatriptan administered there reduced pain to 1/10 in
approximately 6 minutes. Root canal treatment done, no more migraine attacks
reported.
Case Report 2: A 26-year-old female patient had chief complaint of pain
in upper left posterior tooth. Pain started two days ago as migraine with classic
symptoms with “pulsating/throbbing” quality for both tooth and headache. Radiograph
confirmed pathology on palatal root of tooth #14. Local anesthetic blockade reduced
“toothache” by approximately 90% and intranasal sumatriptan 10 mg brought headache
to 1/10 in 10 minutes. Endodontic treatment of tooth #14 completed & no further
migraines headaches reported as of four month follow up.
Results: Discussion: As described earlier there are known triggers for
migraine, it may mimic such other pains as toothaches.
Trigeminal vascular model proposed by Moskowitz suggests the involvement of
trigeminal nerve in pain distribution of migraine. Increased excitability to stimuli
within the trigeminal nerve distribution has been implicated in the pathophysiology
of migraine. Role of trigeminal neuronal nociceptive activity is known.
Conclusions: Odontogenic pain has been reported to occur with migraines
but causal/contributory effect of toothache as a trigger needs further study.
Trigeminovascular Pain Pathway of Migraine. Tg = Trigeminal Ganglion; SpV
= Spinal Trigeminal Nucleus; Th = Thalamic Nuclei From Burstein R,
Jakubowski M. Unitary hypothesis for multiple triggers of pain and
strain of migraine. J Comp Neurol. 2005; 493:9–14,
with permission.
P31
Sleep Duration and Sleep Disturbance in Chronic Daily Headache: Results from
Korean Sleep-Headache Study
M.K. Chu1, B.-K. Kim2, K. Oh3, K.-S.
Lee4, J.-M. Kim5
1Neurology, Hallym University College of Medicine, Anyang,
Gyeonggi-do, Republic of Korea; 2Neurology, Eulji University School
of Medicine, Seoul, Republic of Korea; 3Neurology, Korea University
Guro Hospital, Korea University School of Medicine, Seoul, Republic of Korea;
4Neurology, Seoul St.Mary’s Hospital, The Catholic University of
Korea, Seoul, Republic of Korea; 5Neurology, Chungnam National
University, College of Medicine, Daejeon, Republic of Korea.
Objectives: To assess the relationship between sleep duration and sleep
disturbances in individuals with chronic daily headache (CDH).
Background: Sleep disturbance is a common complaint among individuals
with CDH. Sleep disturbance and sleep duration are reported to be closely related.
However, the sleep disturbances of CDH regarding sleep duration were not reported
yet.
Methods: We selected a stratified random population sample of Koreans
aged 19-69 and evaluated them with a 60-item semi-structured interview designed to
identify headache type, sleep duration and sleep disturbances. We assessed weekday
(WD) and weekend (WE) sleep durations. We also investigated sleep disturbances such
as daytime sleepiness, insomnia, sleep apnea using Epworth sleepiness scale (ESS),
insomnia severity index (ISI), Berlin questionnaire (BQ), respectively. We defined a
CDH subjects if a subject reported experiencing headache more than 15 days per month
for more than 3 months during the previous year.
Results: Of 2762 participants, the 1-year prevalence of episodic
headache (EH) and CDH were 45.5% and 1.7%, respectively. WD sleep durations were not
significantly different between EH and CDH groups (p=0.716). CDH
group showed higher ESS score (7.8±5.7 vs. 6.1±4.0, p<0.001),
higher ISI score (8.1±7.1 vs. 5.0±5.3, p<0.001) and higher sleep
apnea risk (≥2 categories in BQ, 11.3%. vs. 5.2%, p<0.001)
comparing to EH groups. WE sleep durations were not significantly different among 3
groups (p=0.54).
Conclusions: Although sleep durations were not significantly different
between EH and CDH groups, individuals with CDH reported more daytime sleepiness,
more insomnia and more sleep apnea comparing to individuals with EH.
P32
Clinical and Demographical Characteristics of Patients with Medication Overuse
Headache in Argentina and Chile: Analysis of Latin American Section of COMOESTAS
Project (Continuous Monitoring of Medication Overuse Headache in Europe and
Latin America: Development and Standardization of an Alert and Decision Support
System)
M.T. Goicochea1, B. Shand2, R. Fadic2, R.
Valenzuela2, J.A. Leston1
1Pain Clinic. Neurology, FLENI, Buenos Aires, Argentina;
2Neurology, Pontificia Universidad Católica de Chile, Santiago de
Chile, Chile.
Objectives: To describe the clinical and demographics characteristics of
240 patients enrolled in COMOESTAS study in Latin American section.
Background: European and U.S studies show that MOH preferentially
affects women (3.5:1) in their 40s and the primary headache is migraine in 65% of
cases. The average time is 20.4 years since headaches onset, 10.3 years of
medication overuse and 5.9 years of chronic daily headache. In these countries the
overused medications changed over the past two decades: MOH due to ergotamines
decreased and abuse of triptans, simple analgesics and combination medications
increased. High frequency of both pain episodes and use of medication, use of more
than one type of drug, chronic backache, higher levels of emotional stress and low
level of pain tolerance are all associated with MOH. Recently, an association with
sleep disorders has been recognized.
Methods: The Latin American section of COMOESTAS project started working
in 2008. The global project has the objective to evaluate the impact of a
communicational platform in the management of these patients.
110 patients were recruited in Chile and 130 in Argentina. A neurologist who
confirmed MOH diagnosis interviewed all of them. History of habits, family and
personal medical history were taken. General and neurological exams were
performed.
Results: Mean patient age was 38.6 years, 80% were women. Mean time
since headaches onset was 21 years and 3.86 years for duration of medications
overuse. Previous diagnoses were migraine without aura: 77.5% and migraine with
aura: 18.8%. 57% of the patients reported emotional stress related to family, work
or other causes; 56% reported insomnia. Most overused medications were acute drug
combinations containing ergotamine (70%), NSAIDS (33.8%) and triptans (5.4%).
Conclusions: Our study with Latin American patients shows three
differences with the reported European and US studies. Migraine had a higher
prevalence as a primary headache. Ergotamine is more frequently abused. Medication
overuse time is significantly shorter, even tough the time since headache onset is
the same. Ergotamine containing medications are the cheapest and more available
headache treatment in our countries. This could explain both the higher migraine
incidence as primary previous headache as its high abuse frequency. The current
overused drugs profile in Latin America is similar to what Europe and US use to have
two decades ago. Changing this situation is one of our priorities.
P33
Obesity in Children with Chronic Daily Headaches: Association with Headache
Type and Disability
S. Ravid1, E. Shahar1, A. Schiff1, S.
Gordon1
1Pediatric Neurology, Meyer Children’s Hospital, Rambam Health
Care Campus, Haifa, Israel.
Objectives: To examine the association between obesity and chronic daily
headaches in children, and the relation to headache type and disability.
Background: The association between obesity and headache has been
well-established in adults, but only a few studies have examined this association in
children.
Methods: The authors retrospectively evaluated 102 children with chronic
daily headaches from their Pediatric Neurology Clinic. Data regarding age, gender,
headache type, duration and disability, along with height and weight were collected.
Body mass index (BMI) was calculated, and percentiles were determined for age and
sex. Headache type and disability were compared between normal weight, at risk for
overweight and overweight children.
Results: A higher prevalence (39.2%) of obesity was found in the whole
study group compared to the general population. The diagnosis of transformed
migraine, but not of chronic tension type headache, was significantly associated
with being at risk for overweight (OR=2.41, 95% CI 1.21-4.67, P=0.01) or overweight
(OR=2.32, 95% CI 1.1-5.56, P=0.04). Regardless of headache type, a high BMI
percentile was associated with increased headache disability and overuse of
medications, but not with duration of attacks.
Conclusions: Obesity and CDH in children are associated. Although
obesity seems to be a risk factor for transformed migraine more than for chronic
tension type headache, it is associated with increased headache disability and
medication overuse regardless of headache type.
P34
Prognostic Factors in the Treatment of Chronic Daily Headache: 6-Month
Prospective, Face-to-Face, Follow-Up Study
N. Karli1, M. Albas1, M. Zarifoglu1
1Neurology, University of Uludag School of Medicine, Bursa,
Turkey.
Objectives: To investigate the prognostic factors that might effect the
responsiveness to the preventive treatment of CDH in a 6-month, prospective,
face-to-face, follow-up study.
Methods: Patients were recruited from headache outpatient clinic and
evaluated by headache experts according to the ICHD-II criteria. Of those who
diagnosed as CDH, both chronic migraine (+medication overuse headache) (CM) and
chronic tension-type headache (+medication overuse headache) (CTTH) included in the
study. Subjects were given preventive treatment according to their CDH type and
general health status. Follow-up visits were scheduled for the 1st, 3rd and 6th
months. At the first visit a questionnaire including demographic characteristics,
patient history, drugs they are still using, life style characteristics, headache
characteristics and body mass index was answered by the subjects. A total of 130
parameters were evaluated. All subjects were given headache diaries and asked to
record required data. Face-to-face evaluation was made at every follow-up visit. A
decrease ≥50% in headache days was accepted as a succesfull treatment. p≤0.05 was
accepted significant.
Results: 108 subjects were included in the study between September 2010
and February 2011. Of those 97 (89.8%) were women (mean age: 41.8±11) and 11 men
(10.2%) (mean age: 40.0±10.8). 75 of the subjects diagnosed as CM and 33 as CTTH. 64
(59.2%) subjects ended up the study by coming the last follow-up visit at month
6.
An interim analysis at month 3 and final analysis at month 6 were made. In CM
subjects’ successful treatment rate was 70.4% and 81% at month 3 and 6 respectively.
Treatment rate was 50% in CTTH sufferers both at month 3 and 6. In the total CDH
group smokers (p≤0.03) and subjects suffering from headache between 15 and 20
days/month (p≤0.01) responded better to the treatment at month 3. Smoking (p=0.04),
mediterrenean diet (p≤0.01) and less tea consuming (less than 4 cups/day) (p=0.04)
suggested a better prognosis at month 6. At month 3 in the CM group employed
subjects (p=0.02), subjects suffering headache between 15-20 days/month (p=0.04) and
headache history less than 10 years (p=0.04) showed better response to the
treatment. At month 6 there was not any significant difference between responders
and non-responders in the CM group. In CTTH group there was not any significant
difference between responders and non-responders both at month 3 and 6.
Conclusions: Smoking, mediterrenean diet and less tea consuming
suggested a better prognosis in the treatment of CDH. In CM group employment, less
headache days and history of headache less than 10 years were the prognostic factors
suggesting a better response to treatment at month 3. In CTTH group none of the
parameters suggested a better response both at month 3 and 6. Also in this group
treatment rates were lower compared to CM group.
P35
Idiopathic Hypertrophic Cranial Pachymeningitis: A Rare Cause of Chronic
Headache and Progressive Cranial Neuropathies: A Case Report
M.G.B. Laguerta1, E. Esposo1, M.S. Martinez2, B.
Mariano3
1Internal Medicine, St. Lukes Medical Center, Quezon City,
Philippines; 2Neurology, St. Luke’s Medical Center, Quezon City,
Philippines; 3Neuro-ophthalmology, St. Luke’s Medical Center, Quezon
City, Philippines.
Objectives: We report a rare case of a 75-year-old male presented with
chronic daily headache for more than one year and later on developed deafness, vocal
cord paralysis, ophthalmoplegia, and loss of vision. On physical examination, there
was ptosis and left gaze palsy, pale optic disc, only light perception on both eyes,
weak gag reflex and gross hearing loss.
Background: Idiopathic hypertrophic pachymeningitis is a rare chronic
fibrosing inflammatory disease characterized by marked diffuse thickening of the
cranial dura that causes progressive neurological deficits by compression of
anatomic structures by the meninx, thickened by inflammation. Headache is probably
related to dural inflammation.
Methods: Work up included cranial MRI that revealed abnormal
pachymeningeal enhancement or thickening of the dura in the posterior fossa,
cavernous sinus and orbital apex and bilateral mastoiditis. CSF analysis showed
elevated CSF protein, negative results for AFB, KOH, VDRL, TB PCR and bacterial
culture, and no malignant cells. ANCA, ANA and RF were negative. Search for occult
malignancies was negative. There was elevated ESR, consistent with an inflammatory
process.Based on MRI, and having ruled out infectious, neoplastic, collagen/vascular
disease as a cause of pachymeningeal enhancement, our diagnosis was Idiopathic
hypertrophic pachymeningitis.
Results: After initiation of pulse corticosteroid therapy, methotrexate
and maintenance prednisone, there was remarkable improvement on hearing, swallowing,
and ocular muscle movement, less headaches and marked regression of pachymeningeal
enhancement on repeat MRI. However, profound vision loss remained unchanged.
Conclusions: A high index of suspicion and recognition of this rare
disease is important because early institution and long-term maintenance of steroid
may result to complete or partial remission of the neurologic deficits and may help
prevent irreversible neurologic sequelae, especially blindness.
P36
Polysomnographic Characteristics of Sleep in Patients with Sleep Disorders Who
Also Have Headaches
D.M. Winegarner1, V.D. Rowe1,2, K.R. VanOwen1,2,
J.A. Hunter1, A. OShea1, C. Huston2, I.S.
Tarantino3, T. Mecum1
1Research, Rowe Neurology Institute, Lenexa, KS, USA;
2Psychiatry, University of Kansas Medical Center, Kansas City, KS,
USA; 3School of Medicine, University of Missouri - Kansas City,
Kansas City, MO, USA.
Objectives: The objective of this retrospective study was to see whether
any differences in polysomnography exist between those patients who have sleep
disorders without headache, and those who have sleep disorders and who also have
headaches of various types.
Background: Recent research in the field of headache has focused on the
relationship between headache and sleep disorders, mostly with sleep disordered
breathing. We wanted to investigate whether any specific differences exist between
PSG’s of patients with and without headache.
Methods: A cohort of 621 patients (210 male and 411 female) who
presented to a Midwestern neurology institute sleep disorders center over the course
of one year for diagnostic polysomnography were studied retrospectively. One hundred
fifty three (153) patients with unclassified headaches were excluded from the
analysis.
Two hundred fifty seven (257) patients did not have a headache diagnosis and were
used as the control group from which patients with the following diagnoses were
compared; Chronic Daily Headache (CDH), Migraine with Aura, and Migraine without
Aura. There were some patients with dual diagnoses, but each group was looked at
individually.
Results: The group was made up of the following with regard to gender:
Chronic Daily Headache: 17 male, 98 female; Migraine with aura: 19 male, 86 female;
Migraine without aura: 8 male, 63 female; No headache diagnosis: 121 male, 136
female.
Conclusions: 1. Headache is common in patients with sleep disorders.
2. No striking differences among the polysomnograms of the headache subtypes of
Chronic Daily Headache, Migraine without Aura, and Migraine with Aura were seen,
though a large number of patients with uncharacterized headache remains a limitation
of this study.
3. A follow-up study of the response of patients with headache to treatment of their
sleep disorders will hopefully shed some further light on the relationship of sleep
disorders and headache.
No Headache Diagnosis
Chronic Daily Headache
Migraine without Aura
Migraine with Aura
WASO (minutes)
86.1
68.9
59.2
56.3
RERA Index (events/hour)
23.7
27.8
24.2
30.1
AHI (events/ hour)
14.7
5.0
7.5
4.6
R-R Intervals >10 beats/ minute
70.4
69.0
70.1
68.4
Stage Wake %
18.1
15.4
13.8
12.6
P37
Manual Therapies for Chronic Primary Headaches: A Systematic Review
A. Chaibi1, M.B. Russell1
1Head and Neck Research Group, Research Centre, Akershus
University Hospital, Lørenskog, Norway.
Objectives: This paper systematically reviewed randomized clinical
trials (RCTs) assessing the efficacy of manual therapies for chronic primary
headaches.
Background: About 3% of the general population suffers from chronic
headache which has significant health, economic and social costs. We reviewed papers
on manual therapies for chronic primary headache.
Methods: The literature search was done on CINHAL, Cochrane, Medline,
Ovid and PubMed. All RCT written in English using either of the manual therapies for
chronic migraine or chronic tension-type headache (CTTH) were evaluated. Headache
diagnoses were preferentially classified according to the criteria of the
International Headache Societies II and relevant revisions. The methodology of each
study was evaluated, covering study population, intervention, measurement of effect,
data presentation and analysis. The maximum score was 100 points, and ≥50 points was
considered to be methodology of good quality.
Results: RCTs on manual therapies for chronic migraine or chronic TTH
reveals favourable effect i.e. massage therapy (MT), physiotherapy (PT), osteopathic
intervention (OI) and spinal manipulative therapy (SMT). A MT study showed
statistical significant improvement in headache intensity post-treatment and
follow-up as compared to control for CTTH (p<0.05), while a PT study also showed
statistical significant improvement in headache intensity at follow-up for CTTH
(p<0.001). Number of headache days was statistically significant improved in an
OI study as compared to control at follow-up for CTTH (0=0.016), while mean headache
intensity reduced the last 4 weeks of treatment and follow-up by 40% and 42% in a
SMT study for chronic migraine. A precise review on manual therapies for chronic
primary headache applying rigorous criteria will however, be presented at the
congress.
Conclusions: Manuel therapy show efficacy in the management of CTTH and
chronic migraine.
P38
Medication Overuse for Treatment of Acute Migraine Attacks as Predictable Cause
of Development of Status Migrainosus
S.L. Sretenovic1, A.I. Stanic2, A.V. Mitrovic3
1Headache and Migraine Centre, University Hospital KBC Zvezdara,
Belgrade, Serbia and Montenegro; 2Headache and Migraine Centre,
University Hospital KBC Zvezdara, Belgrade, Serbia and Montenegro;
3Headache and Migraine Centre, University Hospital KBC Zvezdara,
Belgrade, Serbia and Montenegro.
Objectives: The aim of this paper is to determine what medication, used
for the treatment of migraine attacks, is the most frequent cause of status
migrainosus when being overused.
Background: Numerous studies have revealed that medication overuse to
stop migraine headaches may provoke chronic headaches. It is also known that
medication abuse may provoke prolonged migraine headaches – status migrainosus.
Methods: Unsponsored, prospective study lasted 18 months. It involved
127 patients (F:M= 89:38 of age 36 ± 16) who reported to the Emergency Room of the
Headache Centre with status migrainosus and fulfilled the criteria for chronic
headaches caused by medication overuse in order to treat frequent migraine attacks.
The IHS criteria for status migrenosus and chronic headaches caused by medication
overuse (IHS 2004) were applied. 92 subjects who overused one medication were
divided into 7 groups according to the medication type
(Caffetin=[paracetamol+propyphenazone+coffein+codeine], Diclofenac,
Acetylsalicylate, Sumatriptan, Nimesulide, Paracetamol and Ibuprofen). 35 patients
who overused two or more medications were also divided according to the type of
medications into 3 groups (Caffetin=[paracetamol+propyphenazone+
coffein+codeine]+Diclofenac, Caffetin=[paracetamol
+propyphenazone+coffein+codeine]+Ketoprofen and Diclofenac+Paracetamol).
Results: Out of the total of 92 patients who overused one medication 56
patients (60.87%) used Caffetin. Out of 35 patients who overused 2 medications 23
patients (65.71%) used the combination
Caffetin=paracetamol+propyphenazone+coffein+codeine]+Diclofenac. Both in subjects
who used one medication (p<0.01) and those who used 2 medications (p<0.01),
statistically high differences between overused medications were detected, causing
status migrainosus.
Conclusions: The study reveals that status migrainosus due to medication
overuse is most frequently caused by the overuse of
Caffetin=[paracetamol+propyphenazone+coffein+codeine] administered as mono treatment
and in combination with another medication.
Keywords: migraine, status migrainosus, medication overuse,
Caffetin.
P39
A Multidisciplinary Approach for the Management of a High-Risk, Opioid
Dependent Chronic Orofacial Pain Patient Using High Dose Opioid Therapy. A Case
Report
G. Kanavakis1, G. Maloney1, R. Kulich1, S.
Scrivani1
1The Craniofacial Pain, Headache and Sleep Center, Tufts
University, School of Dental Medicine, Boston, MA, USA.
Objectives: The objective of this abstract is to describe the case of a
21 year old female who visited our pain center witha chief complaint of daily facial
pain and headaches.
Background: Despite all improvements in our knowledge and understanding
of the pathophysiology of chronic facial pain, there are still many questions that
have not been answered adequately regarding the optimal treatment that should be
applied in chronic pain patients.
Methods: When the patient presented to our clinic she was treated for
chronic daily headaches and migraines primarily with pharmacologic means. She also
had a diagnosis of fibromylagia accompanied by psychiatric comorbidities.
The treatment regimen at the time of the initial evaluation included Oxycodone /
Acetaminophen (10/325, q 6 hrs, 1 1/2 years), Cyclobenzaprine (10 mg, q 8 hrs,
intermittently for 3 years), Celecoxib (200 mg bid, 6 months to one year), Diazepam
(10 qd, 4 years), Escitalopram (10 mg qd, 4 years) and
Acetaminophen/Aspirin/Caffeine (3-4 a day, 1 1/2 years). Sumatriptan, Sertraline
hydrochloride and Bupropion had also been tried, but had all failed to provide any
degree of relief. Non-pharmacologic interventions included chiropractic treatment
and massage therapy, again without any therapeutical effect.
Results: After the patient’s first visit, the initial diagnostic
impression was myofascial pain disorder, and possible medication overuse headache.
Secondarily, she had a psychiatric diagnosis of major depression and substance use
disorder.
According to the classification of the American Academy of Orofacial Pain, the
patient met criteria for centrally mediated myalgia, which is a possible result of a
prolonged nociceptive input into the CNS. In addition, she met criteria for probable
medication-overuse headache according to the classification of the International
Headache Society (IHS), as well as DSM IV TR criteria for a major depression
disorder and substance use disorder. Her affective symptoms had been continuously
present for months and included depressed mood, anhedonia, restless sleep, fatigue,
feelings of guilt, thoughts of suicide, and difficulty in functioning due to
impaired concentration.
It was concluded that management of her possible substance uses issues and medication
regimen were priorities. She was referred to an inpatient detoxification unit with
an admission, and then followed with additional treatment recommendations.
Conclusions: This case report emphasizes the fact that long term
treatment with high dose opioids could in many cases have an adverse effect on
treatment and complicate the patient’s clinical diagnosis. Prior to deciding on
treatment modalities, the clinician should first appreciate the effect of the
opioids on the overall symptomatology and make conclusions accordingly.
P40
Incidence of Chronic Headache Diagnoses and Etiologies at
Altitude
X. Alvarado
La Paz, Hospital de Clinicas, La Paz, Bolivia.
Objectives: Establish the incidence of chronic headache diagnoses and
etiologies in patients at altitude.
Background: Introduction:
The prevalence of chronic headache is approximately 4%. Women are affected three
times more often than men. The majority patients suffer from either chronic
tension-type headache, chronic migraine, or medication overuse headache.
Methods: Descriptive study cohort, cross the adult population attended
during February, March and April 2013, in outpatient internal medicine at Hospital
de Clínicas, La Paz Bolivia.
Inclusion criteria:
Chronic headache is encompasses several different specific headache diagnoses
characterized by frequent headaches.
Men and women from age 14.
Exclusion criteria
Under 14 years.
P41
Physical Therapy Management for Chronic Headaches
L. Ginoza1, E. Sigman1
1Division of Biokinesiology & Physical Therapy, University of
Southern California, Los Angeles, CA, USA.
Objectives: The challenges of managing patients with chronic headaches
(CH) are well known. The faculty physical therapy (PT) practice at the University of
Southern California (USC) works closely with USC’s Division of Neurology in the
treatment of patients with CH. The purpose of this presentation is to describe the
role of PT in the management of patients with CH.
Background: Primary goals of PT are to improve the patients’
self-management strategies, reduce the severity and frequency of headaches and
identify postural dysfunction and other triggers that contribute to their headaches.
Therapists develop an individualized treatment program that will improve posture and
body mechanics thereby improving patients’ tolerance for work, home and recreational
activities.
Methods: Comprehensive PT treatment is centered around self-management
to empower patients to utilize awareness of triggers, ideal movement strategies, and
individualized exercises to manage headaches. Through patient education patients can
recognize and manage musculoskeletal, stress and fatigue-related triggers and
utilize proper ergonomics, posture and movement strategies.
Poor posture is often associated with over-activation of musculature which can
trigger pain into the head. Postural endurance therefore focuses on improving the
balance of muscle function in the neck and trunk.
Movement re-education improves muscular efficiency by using optimal movement
strategies during daily activities. Compensatory movement patterns can contribute to
prolonged pain and muscle imbalance leading to chronicity.
Spinal mobilization techniques help improve thoracic and cervical mobility as
decreased mobility in these regions can hinder achievement of pain-free range of
motion and refer pain into the head. Desensitizing myofascial trigger points can
further decrease pain and improve tolerance to movement re-education and
strengthening.
Results: PATIENT CASE A 27-year-old female came to PT with a 13-year
history of headaches and a 2-year history of CH diagnosed as Occipital Neuralgia and
Chronic Migraines. Medications include Depakote, Migrelief, Relpax and Botox.
After 30 sessions over 5 months her HIT-6 score improved by 9 points and average
headache intensity decreased by 50% eliminating the need to take any days off work
during her last two months of treatment (see table).
Conclusions: In conclusion we believe the addition of PT can improve the
quality of life in patients with CH. Furthermore, emerging research has shown that
spinal manipulation techniques play a role in changing cortical excitability (CE)
within the brain. Since differences in CE have been demonstrated in patients with
chronic migraines, this would be an interesting research direction. Future research
is also needed to determine who would benefit most from PT and describing the
mechanisms by which PT helps.
Cervical Right rotation (degrees)
Cervical Left rotation (degrees)
Number of missed Days per month
Average Headache Intensity
HIT -6
Deep Cervical Flexor Endurance (sec)
Deep Cervical Extensor Endurance (sec)
Initial
45 w/ head pain
70
2
8/10
70/76
0
7
Discharge
70
70
0
4/10
61/76
15
35
P42
Exploring the Border-Zone between Episodic Migraine (EM) and Chronic Migraine
(CM): An Examination of Medical Comorbidities in the US Population
D. Serrano1, D.C. Buse2,3, M.L. Reed1, J.M.
Pavlovic2,3, S.E. Vollbracht2,3, C.M. Sollars3,
T.S. Grewal3, R.B. Lipton2,3
1Vedanta Research, Chapel Hill, NC, USA; 2Neurology,
Albert Einstein College of Medicine, Bronx, NY, USA; 3Montefiore
Medical Center, Bronx, NY, USA.
Objectives: To compare rates of medical comorbidities among three
headache-frequency-dependent migraine subgroups: low frequency episodic migraine
(LFEM): 0-9 days/month, high frequency episodic migraine (HFEM): 10-14 days/month,
and CM: ≥15 days/month.
Background: EM is defined by migraine with <15 headache days per
month; however, this may be a heterogeneous group when medical comorbidities are
examined.
Methods: The American Migraine Prevalence and Prevention Study (AMPP) is
a longitudinal, US-population-based study. The proportion of respondents with
self-reported diagnoses of various cardiovascular and pulmonary risk factors and
diseases (CVPRD) was assessed. Odds ratios (ORs) and 95% Wald confidence intervals
(CIs) adjusted for age, sex and income were calculated comparing groups.
Results: Of 18,500 study respondents to the 2005 AMPP survey, 10,609 had
LFEM, 640 had HFEM and 655 had CM. For nearly all CVPRD contrasts disease rates were
not different between CM and HFEM. For example, 24.4% of those with CM had asthma
compared to 22.0% with HFEM (OR=1.2, NS). This absence of difference was true for
bronchitis, chronic obstructive pulmonary disease (COPD), heart disease/angina, high
blood pressure, and stroke. Individuals with CM had significantly higher rates of
high cholesterol compared to HFEM (1.32 [1.03,1.69], p≤0.027). Both CM and HFEM had
significantly higher rates of disease compared to LFEM, though CM significantly
differed on more CVPRD contrasts than HFEM. Effects were adjusted for age, sex and
income. Results of all contrasts for all groups will be presented and discussed.
Pulmonary and Cardiac Comorbidity Profiles of Migraine Subsets.
Condition
HFEM N (%)
CM N (%)
CM vs. HFEM OR (95% CI), p value/significance
Asthma
141 (22.0)
160 (24.4)
1.2 (0.9,1.5)*
Bronchitis
102 (16.0)
126 (19.2)
1.2 (0.7,1.9)*
Emphysema/COPD
21 (3.3)
32 (4.9)
1.38 (0.78,2.44)*
Heart Disease/Angina
53 (8.3)
63 (9.6)
1.06 (0.72,1.58)*
High Blood Pressure
190 (29.7)
221 (33.7)
1.13 (0.88,1.45)*
High Cholesterol
174 (27.2)
224 (34.2)
1.32 (1.03,1.69), p≤0.027
Stroke
18 (2.8)
26 (4.0)
1.28 (0.69,2.38)*
*Indicates non-significance (NS).
Conclusions: The medical comorbidity profiles of HFEM have much in
common with CM, suggesting that HFEM and CM may bear a close biological
relationship. Detection bias may contribute to these findings.
P43
Exploring the Border-Zone between Episodic Migraine (EM) and Chronic Migraine
(CM): An Examination of Psychiatric Comorbidities and Chronic Pain in the US
Population
B.C. Dawn1,2, D. Serrano3, M.L. Reed3, T.S.
Grewal2, J.M. Pavlovic1,2, C.M. Sollars2, D.P.
Schwartz2, R.B. Lipton1,2
1Neurology, Albert Einstein College of Medicine, Bronx, NY, USA;
2Montefiore Medical Center, Bronx, NY, USA; 3Vedanta
Research, Chapel Hill, NC, USA.
Objectives: To compare rates of psychiatric comorbidities and chronic
pain among three groups with migraine defined by headache day frequency: low
frequency episodic migraine (LFEM): 0-9 days/month, high frequency episodic migraine
(HFEM): 10-14 days/month, and CM: ≥15 days/month in a large, US population based
sample.
Psychiatric and Chronic Pain Comorbidity Profiles of Migraine
Subsets.
Condition
LFEM N (%)
HFEM N (%)
CM N (%)
HFEM vs. LFEM OR(95% CI), p value
CM vs. LFEM OR (95% CI), p value
CM vs. HFEM OR (95% CI), p value/significance
Anxiety
1,993 (18.8)
177 (27.7)
198 (30.2)
1.59(1.33,1.91), p≤0.001
1.80 (1.51,2.15), p≤0.001
1.13 (0.88,1.44)*
Bipolar Disorder
298 (2.8)
26 (4.1)
30 (4.6)
1.23 (0.99,1.54), NS
1.56 (1.06,2.31), p=0.02
1.25 (0.93,1.67)*
Depression
1,767 (17.2)
162 (26.0)
192 (30.2)
1.62 (1.34,1.96), p≤0.001
2.00 (1.67,2.40), p≤0.001
1.23 (0.96,1.59)*
Chronic Pain
1,599 (15.1)
150 (23.4)
206 (31.5)
1.69 (1.39,2.05), p≤0.001
2.49 (2.08,2.97), p≤0.001
1.47 (1.14,1.89), p≤0.003
*Indicates non-significance (NS).
Background: EM is defined broadly by migraine with <15 headache days
per month; however, this may be a heterogeneous group when parsed into low and high
frequency EM. HFEM may have more in common with CM than with LFEM in terms of
psychiatric comorbidities.
Methods: The American Migraine Prevalence and Prevention Study (AMPP) is
a longitudinal, US-population-based study. Depression (Patient Health Questionnaire
[PHQ-9]) and respondent self-report of having received a diagnosis of “nervousness
or anxiety”, “bipolar disorder/mania”, and “chronic pain” were assessed. Odds ratios
(ORs) and 95% Wald confidence intervals (CIs) adjusted for age, sex and income were
calculated comparing headache frequency groups.
Results: Among 18,500 eligible study respondents age ≥18 to the 2005
AMPP survey, 10,609 had LFEM, 640 had HFEM and 655 had CM. The proportion of
respondents with anxiety increased with headache frequency from (18.8% to 30.2%) and
was significantly different between CM and LFEM but not between CM and HFEM. The
same pattern was seen with depression and bipolar disorder in that rates increased
with headache frequency and were significantly different between CM and LFEM, but
not between CM and HFEM. Rates of chronic pain also increased across headache
frequency groups (from 15.1% to 31.5%) and were significantly different among all
three groups.
Conclusions: Those with CM have higher rates of psychiatric commodities
and chronic pain than persons with EM; although in the case of psychiatric
comorbidities, rates were not significantly different between CM and HFEM,
suggesting that these two groups may have substantial biological overlap.
P44
Improving the Classification of Migraine Subtypes: An Empirical Approach Based
on Latent Class Analysis
1Neurology, Albert Einstein College of Medicine, Bronx, NY, USA;
2Montefiore Medical Center, Bronx, NY, USA; 3Allergan
Inc., Irvine, CA, USA; 4Vedanta Research, Chapel Hill, NC,
USA.
Objectives: Utilize latent class analysis (LCA) to improve migraine
classification, and validate classification accuracy by testing whether accuracy of
prognosis improves after statistical classification.
Background: Current primary headache classification is symptom-based and
uses somewhat arbitrary boundaries developed by expert consensus. Symptom profiles
and headache frequency are used to distinguish chronic migraine (CM).
Methods: The AMPP study is a longitudinal, US population-based study.
Surveys were mailed to a sample of 24,000 persons with severe headache identified in
2004 and followed annually until 2009. The analysis sample included those with
ICHD-2 migraine, partitioned into episodic migraine (EM: <15 headache days/month)
or CM (≥15 headache days/month), and probable migraine (PM). LCA identified 5
subgroups of migraine (taxa) using data on migraine symptom severity, average
migraine pain intensity, headache-related disability, cutaneous allodynia,
depression, and monthly headache and migraine days as 2005 taxa determinants.
Validity of these taxa was examined by contrasting the rate of CM onset at
follow-up.
Results: 2005 AMPP data were used for LCA and 2006-2009 data were used
to assess taxa prognosis. 12,860 subjects were eligible for classification analysis
(n=10,162 LFEM; n=601 HFEM, n=1,302 PM, n=795 CM). Of these, 3,152 (24.5%), 1,076
(8.4%), 3,896 (30.3%), 2,251 (17.5%) and 2485 (19.3%) were assigned to Taxon 1, 2,
3, 4 and 5, respectively. EM was the largest contributor to each taxa, constituting
more than 80% of each taxon other than Taxon 2. Taxon 2 was enriched with the most
severe spectrum of migraine including the highest concentrations of CM (28.4%) and
HFEM (22.6%), while Taxon 5 represented the least severe end of the spectrum without
CM and only 0.08% HFEM. Validity of taxon assignment was tested by the ability of
taxon membership to predict prognosis. Membership in Taxon 2 predicted increased
risk of progression to CM with only 78% of previously CM-free Taxon 2 remaining
CM-free at follow-up, while 98% of Taxon 5 remained CM-free.
Conclusions: LCA extends traditional clinical syndrome-based diagnoses
suggesting that the currently defined headache frequency boundary may be suboptimal.
LCA can serve as a tool to parse phenotypic heterogeneity of natural subgroups
possibly leading to migraine classification that more closely maps to homogeneous
genotypes.
P45
Quadripulse Repetitive Transcranial Magnetic Stimulation on Visual Cortex for
Chronic Migraine Prevention: A Pilot-Trial
T. Sasso D’Elia1,2, A. Viganò1,2, M. Fataki Likale1,
S.L. Sava1, J. Schoenen1, D. Magis1
1Headache Research Unit University Department of Neurology, ULg,
Liège, Belgium; 2University of Rome La Sapienza, Rome,
Italy.
Objectives: To study in a pilot trial the effect of QP rTMS over the
visual cortex in the preventive treatment of chronic migraine.
Background: Contrasting with episodic migraine, chronic migraine can be
compared to a “never ending attack” (1) with normal habituation of visual-evoked
cortical potentials (VEP) andan increaseof 1st block VEP amplitude
suggesting heightened cortical preactivation levels(2).
Quadripulse repetitive transcranial magnetic stimulation (QP rTMS) is able to durably
modify the excitability of the underlying cortex. QP rTMS with long interstimulus
interval (ISI) has an inhibitory effect, thus reducing the amplitude of
1st block VEP (3).
Methods: We recruited 10 patients (mean age 45.5; 8F, 2M) suffering from
chronic migraine (ICHD-2 1.5.1). Seven also fulfilled the diagnostic criteria for
medication overuse headache (ICHD-2 8.2). All had stable preventive treatment for at
least 2 months.
We applied QP rTMS with a 50ms ISI (4 pulses at 20 Hz every 5 s for 30 minutes) using
a figure-of-eight coil over the visual cortex (Oz). The intensity of the stimulation
was set at 80% of phospheneor 90% of motor thresholds. QP rTMS was applied twice a
week for 4 weeks. Patients filled in a headache diary before, during and after
treatment (T0=the month before QP rTMS; T1=during the 4 weeks of QP rTMS; T2=the
month after QP rTMS).We evaluated depression and anxiety at T0 and T1 respectively
with Beck’s Depression Inventory (BDI) and the State-Trait Anxiety Inventory
(STAI-Y2).
Results: A majority of patients improved significantly after QP rTMS
therapy. Migraine days decreased on average from 20/month at T0 to 11/month at T1
(-47%, p<0.05) and severe attacks were reduced by 54% (p<0.05). Forty % of
patients were 50% responders while 70% reversed from the chronic to the episodic
form of migraine. Acute medication intake was numerically decreased, but this just
fall short of statistical significance. One month after QP rTMS (T2) the clinical
improvement remained stable with an average 10.4 migraine days/month, i.e. 48%
reduction compared to baseline (p<0.05). There were no adverse events. BDI and
STAI scores were similar before and after treatment. Interestingly, medication
overuse did not modify the response to QP rTMS therapy.
Conclusions: This pilot trial demonstrates for the first time that 2
weekly sessions of inhibitory QP rTMS can be effective in the preventive treatment
of chronic migraine, with or without medication overuse. The therapy significantly
reduced migraine days and 70% of patients reversed from chronic to episodic
migraine. Moreover, inhibitory QP rTMS was devoid of any adverse effect. These
results indicate that a large sham-controlled trial is worthwhile in chronic
migraine.
P46
Exploring the Border-Zone between Episodic Migraine (EM) and Chronic Migraine
(CM): An Examination of Sociodemographics and Headache-Related Disability in the
US Population
R.B. Lipton1,2, D.C. Buse1,2, D. Serrano3, C.M.
Sollars2, T.S. Grewal2, B.M. Grosberg1,2, J.M.
Pavlovic1,2, M.L. Reed3
1Neurology, Albert Einstein College of Medicine, Bronx, NY, USA;
2Montefiore Medical Center, Bronx, NY, USA; 3Vedanta
Research, Chapel Hill, NC, USA.
Objectives: To compare sociodemographics and headache-related disability
among three groups with migraine defined by headache day frequency: low frequency
episodic migraine (LFEM): 0-9 days/month, high frequency episodic migraine (HFEM):
10-14 days/month, and CM: ≥15 days/month in a large, US population based sample.
Background: EM is defined by migraine with <15 headache days per
month; however, this may be a heterogeneous group if parsed into low and high
frequency EM when examined by sociodemographics and headache-related disability.
HFEM may have more in common with CM than with LFEM on several dimensions.
Methods: The American Migraine Prevalence and Prevention Study (AMPP) is
a longitudinal, US-population-based study. Sociodemographic variables and
headache-related disability (MIDAS questionnaire) were assessed. Odds ratios (ORs),
rate ratios (RRs) and corresponding 95% Wald confidence intervals (CIs) were
calculated comparing EM groups and CM. Analyses of current employment status were
adjusted for age, sex and income. Ordered logistic regression was used to model
annual household income. Negative binomial regression was used to model
headache-related disability.
Results: Among 18,500 eligible study respondents age ≥18 to the 2005
AMPP survey, 10,609 had LFEM, 640 had HFEM and 655 had CM. In comparison with the
LFEM group, those with HFEM and CM reported significantly lower household income
levels (p < 0.001), were less likely to be employed full time (p < 0.05), and
were more likely to be occupationally “disabled” (p < 0.001). When comparing the
sociodemographic profile between HFEM and CM, there were no significant differences
with regard to these characteristics. Headache-related disability was greatest for
CM, lowest for LFEM and intermediate in HFEM. Respondents with CM were significantly
more likely to miss days of work or school due to headache compared to LFEM (RR
4.67, 95%CI 3.52, 6.20; p≤0.001); but significant differences were not observed
between HFEM and CM.
Conclusions: The impact and burden of migraine were similar in terms of
sociodemographics and headache-related disability between individuals with CM and
those with HFEM. Those with LFEM had significantly less headache-related disability
and burden on several dimensions. The similarities between the HFEM and CM groups
and their distinctions from the LFEM group, when coupled with the documented
transitions between HFEM and CM suggest that these two groups may have substantial
biological overlap.
P47
Withdrawn by the author.
P48
Improving Function by Targeting Function: Efficacy of an Interdisciplinary
Outpatient Program
T.S. Clark2, F.G. Freitag1, R.C. Robinson3, A.
Hands3
1Headache Center, Baylor University Medical Center, Dallas, TX,
USA; 2Center for Pain Management, Baylor University Medical Center,
Dallas, TX, USA; 3Psychiatry, University of Texas Southwestern
Medical School at Dallas, Dallas, TX, USA.
Objectives: Determine efficacy of outpatient interdisciplinary program
in improving function and quality of life after IV treatment for chronic
migraine.
Background: We are unaware of previous studies evaluating structured
interdisciplinary day treatment programs for chronic migraine without concurrent
aggressive medical management of headaches. In light of changing healthcare
parameters, research is needed to evaluate if a time limited program results in
substantial reductions in pain, inactivity due to pain, emotional distress, and
improved functional life activities.
Methods: All patients admitted for inpatient treatment with IV
medications for chronic migraine were evaluated by a psychologist and physical
therapist to select patients appropriate for a 12 day outpatient interdisciplinary
program. Sixty patients (90% female; mean age = 43) with significant distress or
impairment were enrolled. Treatment consisted of 60 hours of integrated physical
therapy, occupational therapy, and cognitive behavioral therapy at an estimated cost
of $12,000. Baseline data was collected upon admission to the program and after thee
weeks of treatment. Domains evaluated included pain severity, interference by pain,
depression, anxiety, activity levels, and patient perception of ability to self
manage pain. Global measures of health were obtained using the 12-Item Short Form
Survey (SF-12) the RAND Medical Outcomes Study.
Results: Nine paired-samples t tests were conducted to
evaluate changes in biopsychosocial outcome measures with the Bonferroni Method
employed to control for Type I error (Bonferroni α =.006). Nine of nine outcome
measures were statistically significant (p < .001). Furthermore,
large effect sizes were found and ranged from .82 for decrease in pain level and
improved perception of control over pain to 2.05 on the Canadian Outcomes
Performance Measure.
Conclusions: Preliminary evidence supports that brief, cost-effective
interventions for migraine sufferers can improve biopsychosocial outcomes in the
areas of pain perception, distress and performance measures.
Measure
Mean (SD) Pre
Mean (SD) Post
p Value
Effect Size d
n
Hours Resting
4.06 (2.91)
1.57 (1.27)
< .001
.87
35
Pain Rating
7.94 (2.70)
5.54 (2.86)
< .001
.82
35
Helpfulness of Pain Mgmt Techniques
3.60 (2.20)
8.17 (1.84)
< .001
1.47
35
Percpetion of Control of Pain
6.46 (2.73)
8.80 (2.17)
< .001
.82
35
Beck Depression Inventory - II
22.89 (11.47)
9.77 (9.30)
< .001
1.56
35
Beck Anxiety Inventroy
19.03 (12.29)
9.80 (9.11)
< .001
1.10
35
Perception of Physical Health
27.60 (8.11)
40.23 (10.83)
< .001
1.53
35
Perception of Mental Health
31.79 (7.94)
43.21 (8.53)
< .001
1.45
34
Canadian Outcome Performance Measure
2.85 (1.17)
6.93 (1.86)
< .001
2.05
40
P49
Day Hospital Withdrawal for Chronic Migraine with Medication Overuse: Results
at 3 Years Follow-Up
L. Grazzi1, F. Andrasik2, S. Usai1, G.
Bussone1
1Clinical Neuroscience, Headache Unit, C. Besta Neurological
Institute and Foundation, Milan, Italy; 2Psychology Department,
University of Memphis, Memphis, TN, USA.
Objectives: Purpose of this study was to determine the clinical course
of a sample of chronic migraine patients with medication overuse 3 years after day
hospital withdrawal.
Background: Patients with chronic headache and medication overuse are
particularly difficult to treat, with no one approach being universally accepted.
Some type of withdrawal program, however, is typically implemented before beginning
a pharmacological prophylaxis treatment. Different withdrawal modalities have been
performed for managing these patients: at first step, in-patient withdrawal has been
confirmed effective in preceding clinical experiences. In recent years new
modalities for withdrawal have been developed as day-hospital setting
withdrawal.
Methods: A group of 202 patients were treated. Patients were suffering
from chronic migraine with medication overuse according with IHS criteria. All
patients were submitted to a day hospital withdrawal and then they were followed
with meetings every 3 months until the first year and then every 6 months until the
last follow-up 3 years after withdrawal.
Results: Eighty patients achieved the last follow-up meeting 3 years
after withdrawal. Patients clinically improved: days of headache per month decreased
significantly from 22.8 (SD 5.8), at baseline to 7.8 (SD 4.9); consumption of
medications per month decreased significantly too from 26.7 (SD 19.9) to 7.4 (SD
5.0) at the last follow-up.
Conclusions: From these results the day hospital setting for withdrawal,
followed by periodic clinical meetings, seems to be effective for this category of
patients to improve significantly at long-term headache frequency and analgesics
intake.
P50
Association of Brain Volume and Cognition in the Chronic and Episodic Migraine
Patients
M. Zarifoglu1, D.K. Sener1, N. Karli1, B.
Hakyemez2, O. Taskapilioglu1, S.E. Ozbek1, M.
Bakar1
1Neurology Department, Uludag University Medical Faculty, Bursa,
Turkey; 2Radiology, Uludag University Medical Faculty, Bursa,
Turkey.
Objectives: To study the association of the Brain Volume and Cognition
in the Chronic and Episodic Migraine Patients.
Background: There are controversies about migraine’s benign nature and
chronic migraine’s damage to the central nervous system. All these questions lead us
to study the correlation between cognitive functions and cortical-subcortical brain
volume in migraine patients.
Methods: Forty patients (20 episodic migraine and 20 chronic migraine),
diagnosed according to ICHD 2004, and 20 control cases are included in the study.
Neuropsychological tests were applied and bilateral cranial subcortical volumes were
measured with automatic segmentation method in all cases.
Results: Left hippocampus and right amygdala were atrophic while left
lateral ventricle volume was larger in chronic migraine group as compared to
episodic group and control. The attention test scores were statistically lower in
the episodic and chronic migraine patients than the control cases. Decreased brain
volume and low scores in neuropsychological tests in migraine patients showed
positive correlation with the duration of migraine disease and number of days with
pain.
Conclusions: There is no study in the literature about brain volume
using automatic segmentation method in migraine patients and its association with
cognition status. Our findings about presence of brain volume changes and attention
deficits are in line with the previous literature findings stating attention
problems and brain volume changes in the migraine patients.
P51
Low Vitamin D Levels in Migraine
C. Alberto da Silva de Jesus1, M.F.P. Peres1,2
1Universidade Federal de São Paulo – UNIFESP/Brazil, São Paulo,
Brazil; 2Instituto Israelita de Ensino e Pesquisa, Hospital Israelita
Albert Einstein/Brazil, São Paulo, Brazil.
Objectives: Assessing the levels of vitamin d in patients with
migraine.
Background: Vitamin D is a lipid soluble vitamin that acts as a hormone,
it is involved in the regulation of cell growth and metabolism, insulin resistance,
endothelial dysfunction, modulation of immune function, and inflammation reduction.
Hypovitaminosis D has been linked to several disorders including hypertension,
diabetes mellitus, depression, multiple sclerosis, metabolic syndrome, and cancer.
Low levels of 25 (OH) vitamin D have been found in chronic pain disorders such as
musculoskeletal pain, headaches, fibromyalgia, but limited information in migraine
is available.
Methods: Migraine patients and controls were consecutive recruited from
June 2011 to December 2012, 298 individuals were included, and signed informed
consent. Individuals were divided in 3 groups: healthy controls (79), episodic
migraine (128), and chronic migraine (91), diagnosis were made according to the
International Classification of Headache Disorders. Serum 25-hydroxyvitamin D levels
were obtained in chemiluminescent immunoassay. Mean 25(OH) vitamin D levels were
compared between groups, 2x2 analysis of different vitamin d cutt offs in 10 ng/ml,
20 ng/ml, and 30 ng/ml.
Results: Migraine patients overall had low 25(OH) vitamin D levels
compared to controls (25,1 ng/ml +- 11,7 vs 27,3 ng/ml +- 8,6, p=0,03). Chronic
migraine patients (22,9 ng/ml +- 11,2) had low levels compared to episodic migraine
(26,1 ng/ml +- 11,0, p=0,004) and controls (27,3 ng/ml +- 8,6, p=0,003).
Significantly more chronic migraine patients were below 20 ng/ml, compared to
episodic migraine and controls (p<0,001), as well as episodic migraine vs
controls (p<0,001).
Conclusions: Migraine is linked to hypovitaminosis D, Chronic migraine
patients have even lower levels. Decrease in Vitamin D may be cause or consequence
of migraine. Further studies are necessary to verify the role of vitamin D in
migraine and other headache disorders.
P52
Increased CGRP Levels in Peripheral Blood as a Biomarker for Chronic
Migraine
E. Cernuda-Morollón1, D. Larrosa1, C. Ramón1, J.
Vega1, P. Martínez-Camblor2, J. Pascual1
1Neurology, University Hospital Central de Asturias, Oviedo,
Asturias, Spain; 2Oficina de Investigación Biosanitaria (OIB),
University Hospital Central de Asturias, Oviedo, Asturias, Spain.
Objectives: To test CGRP levels outside migraine attacks in peripheral
blood as a potential biomarker for CM.
Background: In terms of frequency, migraine can be divided into two
types: episodic (EM) and chronic (CM, ≥15 headache days/month). Around 2% of the
population suffers from CM. During a migraine attack, activation of the
trigemino-vascular system releases of vasoactive neuropeptides, especially
calcitonin gene-related peptide (CGRP), and CM seems to be the result of
sensitization of the pain pathways by repeated episodes of trigeminal activation.
There is no available biomarker for any of the primary headaches, including
migraine.
Methods: Women older than 17 and diagnosed as CM were recruited. Matched
healthy women with no headache history and women with EM served as control groups,
together with a series of patients with episodic cluster headache in a pain-free
period. CGRP levels were determined in blood samples obtained from the right
antecubital vein by ELISA outside a migraine attack and having taken no symptomatic
medication the day before. Due to ethical reasons, preventatives were not
stopped.
Results: We assessed plasma samples from 103 women with CM, 31 matched
healthy women, 43 matched women with EM and 14 patients with episodic cluster
headache matched for age. CGRP levels were significantly increased in CM (74.90
pg/ml) as compared to control healthy women (33.74 pg/ml), females with EM (46.37
pg/ml) and episodic cluster headache patients (45.87 pg/ml). Thresholds of 43.45 and
58.22 pg/ml optimize the sensitivity and specificity to differentiate CM from
healthy controls and episodic migraine, respectively In the CM group, CGRP levels
were increased in women with a history of migraine with aura vs. those only
experiencing migraine without aura. Variables such as age, analgesic overuse,
depression, fibromyalgia, vascular risk factors, history of triptan consumption or
kind of preventative treatment did not significantly influence CGRP levels.
Conclusions: Increased CGRP level measured in peripheral blood outside
migraine attacks and in the absence of symptomatic medication seems to be a reliable
marker for CM.
P53
Somatosensory High-Frequency Oscillations in Chronic Migraine
G. Coppola1,2, E. Iacovelli1, M. Bracaglia1, C. Di
Lorenzo1, F. Pierelli1
1Department of Medico-Surgical Sciences and Biotechnologies,
Sapienza University of Rome Polo Pontino, Latina, Italy; 2Department
of Neurophysiology of Vision and Neurophthalmology, G.B. Bietti
Foundation-IRCCS, Rome, Italy.
Objectives: To assess how migraine chronification changes the activity
of thalamo-cortical connections.
Background: The pathophysiology of chronic migraine (CM) is not
completely clarified, but a crucial role was attributed to central sensitization
mechanisms. Altered thalamo-cortical connections characterize migraine when still
episodic and between attacks.
Methods: Seventeen episodic migraineurs (MO) between attacks and 18
chronic migraine (CM) patients underwent median-nerve somatosensory (SSEPs) (right
stimulation, 500 sweeps, 4.4 repetition rate, 1.2 motor threshold). Patients groups
were compared to a group of 20 healthy volunteers (HV) of comparable age and gender
distribution. Digital filter (band-pass 450-750 Hz) was employed to extract 600Hz
high-frequency oscillations (HFOs) superimposed on the conventional broad-band N20
SSEPs. Two phases of the HFOs were identified: an early which reflects the activity
of the thalamo-cortical fibers, and a later which probably is generated by cortical
pyramidal cells located in somatosensory area 3b.
Results: In CM the reduced early HFOs amplitude found in MO between
attacks disappeared, showing a pattern similar to HVs. This early HFOs normalization
was accompanied by a significant shortened latency of the negative oscillatory
maximum (p=0.01). The amplitude of the late HFOs was significantly greater in CM
than in HV (p=0.01).
Conclusions: Our data document that migraine chronicity alters
thalamo-cortical connections by shortening response time and enhancing amplitude of
the thalamocortical loops and by increasing primary cortical activation. These
findings may be electrophysiological fingerprints of the somatosensory system
central sensitization process that is thought to be the underlining mechanism of
headache chronification. Whether this electro-functional behaviour is primary or
secondary to daily headache remains to be determined.
P54
Treatment of Chronic Migraine: A Three-Month Comparator Study of Naproxen
Sodium vs. SumaRT/Nap (Treximet™)
J.K. Dexter1, R.K. Cady1, R. Nett2, F.
Freitag3, M.E. Beach4
1Headache Care Center, Springfield, MO, USA; 2Texas
Headache Associates, San Antonio, TX, USA; 3Baylor University Medical
Center, Dallas, TX, USA; 4Aerotek, Overland Park, KS,
USA.
Objectives: This exploratory pilot study compared SumaRT/Nap (Group A)
and naproxen sodium (Group B) as both a daily preventive treatment and an episodic
acute treatment in patients with chronic migraine (CM).
Background: Acute medications have not been thoroughly studied in
chronic migraine, yet critical to patient management. Many acute medications have
demonstrated efficacy as both acute and prophylactic medications.
Methods: A double-blind, randomized comparator trial of 28 subjects, 18
to 65 years of age, with IHS defined chronic migraine was conducted at 2 US headache
centers. Study medications were utilized as a daily preventive treatment and if
needed, an acute treatment during Month 1. In months 2 and 3 subjects were allowed
to treat migraine attacks of migraine for up to 14 days per month.
Results: There was a reduction in migraine headache days from baseline
to month 3 in both groups. This reached statistical significance for Group B, but
not Group A at month 3 for per protocol completers: Primary endpoint, p=0.02 vs.
0.25, respectively. There were more dropouts for lack of efficacy in Group B
compared to Group A (5/12 vs.1/16, respectively). Duration of migraine from
treatment to pain-free was better for naproxen than SumaRT/Nap throughout the active
phase of the study. There was a significant reduction of acute medication for Group
B from baseline to month 3. MIDAS scores improved in Group A, from 77 to 56 and
Group B, from 81 to 16. Both treatments were well tolerated with no subject
withdrawals due to AEs or MOH.
Conclusions: This study suggests there is a role for acute medications
in the treatment of chronic migraine. There may be a subset of subjects with CM who
are highly responsive to high doses of naproxen sodium when provided as a daily
preventive for 1 month followed by aggressive episodic treatment for 2 months. This
subset may be identifiable early in an empirical trial of naproxen. Group A had
fewer dropouts for lack of efficacy than Group B, suggesting subjects favored
SumaRT/Nap as acute treatment. There was no evidence SumaRT/Nap reduced headache
days.
P55
Chronic Migraine in Children Associated with Blunted Cardiovascular Autonomic
Reflexes with Orthostatic Stress Despite Increased Sympathetic Activation (A
Pilot Study)
L.P. Richer1,2, J. Neilson1
1Pediatrics, University of Alberta, Edmonton, AB, Canada;
2Women and Children’s Health Research Institute, Edmonton, AB,
Canada.
Objectives: Assess subjective and objective differences in symptoms and
cardiac autonomic reflexes comparing episodic and chronic migraine.
Background: Migraine in children often progresses to chronic migraine.
Orthostatic intolerance (OI) refers to the development of symptoms like dizziness or
lightheadedness on standing an chronic OI is associated with many symptoms including
headache. Based on clinical observations, children often report symptoms of OI when
presenting with chronic migraine. We tested the hypothesis that the chronification
of migraine is associated with objective changes in cardiovascular responses to
orthostatic stress, deep breathing, and Valsalva.
Methods: This pilot study included participants aged 8-17 years with
episodic or chronic migraine based on ICHD-II. The average migraine days per month,
PedMIDAS, and OI symptoms were documented. The primary outcome measures were heart
rate (HR) and mean arterial pressure (MAP) in response to head-up tilt (HUT) for 10
minutes, deep breathing at 6 breaths/min for 8 breaths, and Valsalva to 40 mm Hg for
15 seconds. HR and BP were recorded using continuous electrocardiogram and
non-invasive blood pressure (Finopress®) sampled at 250 Hz. Heart rate variability
(HRV) frequency domain analysis during HUT was performed. Participants were analyzed
in two groups: (1) episodic migraine (EM; < 15 days/mo; i.e. episodic and
frequent migraine) and (2) chronic migraine (CM; > 15 days/mo). Smooth splines
mixed effects models were fit to the data and used to estimate the mean response and
95% confidence interval (CI).
Results: Frequent migraine (7-14 migraines/month) were the predominant
subgroup in the EM group (n=4/5). Symptoms of OI were higher in the CM group, but
not significantly different. During HUT, the CM group had a significantly lower
early heart rate (HR) (Figure 1) and remained lower during the HUT. The MAP pattern
in the CM group was linear and qualitatively different from the normal EM group.
Low-frequency HRV (LF-HRV; a marker of sympathetic activation) was significantly
lower in the CM group during HUT (p=0.03). Responses to deep breathing and Valsalva
were not significantly different.
Conclusions: Children in the CM group had a significantly lower early HR
in response to orthostatic stress and the pattern of MAP was blunted in comparison
to the EM group. These observations may be due to alteration of cardiosympathetic
responses in the CM group despite increased activation. Our pilot data are limited
by sample size and over representation of frequent migraine. Alteration of the
autonomic nervous system may serve as a biomarker of migraine progression and
support alternative therapeutic strategies.
P56
Frequency and Severity of Cutaneous Allodynia in Migraine and Chronic
Migraine
L.L. Florencio1, T.C. Chaves1, F. Dach1, M.C.
Gonçalves1, M.T. Benatto1, G.F. Carvalho1, J.G.
Speciali1, M.E. Bigal2, D.
Bevilaqua-Grossi1
1University of São Paulo, Ribeirão Preto, SP, Brazil;
2Merck & Co., Inc., North Wale, PA, USA.
Objectives: To evaluate the presence and severity of cutaneous allodynia
(CA) in patients with migraine and chronic migraine and to compare the severity
classification among them.
Background: The relationship between migraine and CA have been
arousinginterest once it was recently recognized as a sign of central sensitization
during migraine attacks, suggested as a negative influence on the migraine
pharmacological treatment and pointed out as a risk factor for migraine
chronification. The 12 item Allodynia Symptom Cheklist (ASC-12) is the only tool
available that can detect CA and also assess its severity. Although the
investigation about CA with the ASC-12 has been already done1, we do not
know how it occurs in brazilian population.
Methods: The presence and severity of CA were assessed by the Brazilian
version of the ASC-122 in 64 volunteers, 32 in each group, from a
tertiary outcome headache service. The migraine diagnoses were given by expert
neurologists according to ICHD-II (2004). The ASC-12 scores range from 0-24 points
and classifies the CA as none, mild, moderate and severe. Subjects with a diagnosis
of other concomitant headaches, fibromyalgia, trigeminal neuralgia and systemic
diseases with neuropathy peripheral sensory were excluded. The
X2 test was applied, using SPSS® 16,0, to
compare proportions between groups.
Results: The migraine group (M) was composed with 91% of woman and mean
age of 42 (SD=10) and the chronic migraine group (CM) was composed with 94% of woman
and mean age of 39,7 (SD=11). Eighty four percent of the M had CA, while this
proportion on the CM was eighty one percent (figure 1). In general, no difference
between the proportions of the classifications was found (p>0,05). The relative
frequency of the severity in the sample with any kind of allodynia showed a greater
proportion of severe CA in CM (p<0,05) (figure 2).
Conclusions: The frequency of CA in brazilian patients with migraine is
high, although it seems that migraine attacks frequency do not influence in CA
presence, but it can influence in its severity.
P57
Predictors to Treatment Response in Patients with Chronic Migraines: Can the
Course of the Disease Be Changed?
C. Guerra1, L. Londoño1, M.M. Massaro2, M.
Volcy3
1Neurology, CES Universidad De Ciencias De La Salud, Medellin,
Antioquia, Colombia; 2Epidemiology, INDEC Instituto Neurologico De
Colombia, Medellin, Antioquia, Colombia; 3Neurology-Headache
Specialist, Indocen Instituto De Dolor De Cabeza y Enfermedades Neurologicas,
Medellin, Antioquia, Colombia.
Objectives: To estimate the remission rate and to identify predictors of
remission from MC to ME in a cohort of patients managed by neurologist headache
specialist.
Background: It has been recognized multifactorial evolutionary pattern
that leads to chronic migraine (CM) and probably refractory migraine (RM). The
remission rate to an episodic pattern and factors that allow prediction of
therapeutic response are still unknown.
Methods: We performed a retrospective study of an estimated sample of
adult patients with CM based on the classification criteria ICHD-2 who were treated
by a headache specialist for a year, selected by simple random sampling of medical
records of a neurological institution in Medellin (Colombia). We evaluated clinical
characteristics, comorbidities, treatment and therapeutic response and we compared
those between responders (pattern change from CM to EM) and non-responders using a
multivariate logistic regression model.
Results: We evaluated clinical records of 224 patients with CM. The
average age was 47 years (SD: 13.7), 87.5% were women. Average HA onset was at age
29 (SD: 16.9) and the average HA evolution time was 17 years (SD: 14.4). At first
consultation by headache specialist (HASp), average HA days/month was 25 (SD: 5.7),
38.8% had analgesic overuse and 69.2% had symptoms of anxiety or depression. After
one year, 59.8% of patients remitted to episodic pattern (n = 134), on an average 5
months after first visit (SD: 3.5) decreasing HA days/month from 25+5.8 to 6+4.1;
67.2% of them with low frequency EM (0-9 days/HA/month). Comparing responders and
non-responders there was statistically significant difference in overuse (33.6% vs.
46.7%) but lost significance in the multivariate analysis, which showed sleep
complaints (OR 2.28, 95% CI 1.2 - 4.3), fibromyalgia or chronic pain (OR 2.33, 95 %
CI 1.03 - 5.3) and use of preventive medication (OR 2.15, 95% CI 1.05 - 4.4) to be
associated with bad prognosis; prior to HASp treatment, significant difference in
the frequency of use of TCA (58.2% vs. 80%p 0.001), SSRIs (56% vs. 70% p 0.03), dual
antidepressants (1.5% vs. 14.4% p <0.0001), opioids (61.2% vs. 74.4% p 0.02),
topiramate (6.7% vs. 18.9%, p 0.005) and triptans (6.7% vs. 18.9% p 0.005), and
during the year of following, in the use of Botox® (21.6% vs. 53.3% p <0.0001),
antipsychotics (12.7% vs. 24.4% p 0.01), dual antidepressants (23.9% vs. 42.2% p
0.003), gabapentin (15.7% vs. 46.7% p <0.0001), naratriptan (14.2% vs. 33.3% p
0.001), propranolol (21.6% vs. 11.1% p 0.03) and TCA (67.2% vs. 48.9% p 0.005).
Conclusions: Sleep complaints, fibromyalgia and chronic pain, preventive
medication are independent predictors of no return to episodic pattern. We recommend
that patients with CM should be evaluated early by HASp.
P58
Evidence for Long-Term Efficacy of Peripheral Nerve Stimulation of the
Occipital Nerves in the Management of Chronic Migraine
D. Dodick1, S. Silberstein4, B. Huh2, K.
Slavin3, A. Sharan4, K. Reed5, S.
Narouze6, A. Mogilner7, J. Goldstein8, J.
Vaisman9, SJM, Chronic Migraine Study Investigators10
1Mayo Clinic, Phoenix, AZ, USA; 2Duke Pain &
Palliative Clinic, Durham, NC, USA; 3University of Illinois/Chicago,
Chicago, IL, USA; 4Thomas Jefferson University, Philadelphia, PA,
USA; 5Ascendant Neuro, Dallas, TX, USA; 6Summa Western
Reserve Hospital, Cuyahoga Falls, OH, USA; 7NYU Langone Medical
Center, New York, NY, USA; 8San Francisco Headache Clinic, San
Francisco, CA, USA; 9The Pain and Wellness Center, Peabody, MA, USA;
10SJM, Plano, TX, USA.
Objectives: Provide evidence to support long-term efficacy of PNS of the
occipital nerves in the management of chronic migraine.
Background: Chronic migraine is a debilitating disorder with few
treatment options. Recent studies have shown the utility of PNS of the occipital
nerves in the management of chronic migraine.
Methods: In this IRB-approved, prospective, multicenter, double-blinded
study, patients were implanted with a neurostimulation system (St. Jude Medical,
Plano, TX) and randomized to an Active or Control group for 12 weeks. Patients
continued in an open-label phase of the study which lasted an additional 40 weeks.
Outcomes collected during this phase included headache day reduction (duration >
four hours with moderate/severe peak intensity), migraine-related disability and
distress as assessed by the migraine disability assessment (MIDAS) questionnaire and
the Zung Pain and Distress (PAD) scale, headache pain relief, and satisfaction. All
statistical testing was conducted to assess change from baseline to 1 year
post-implant. Analyses were performed using paired t-tests. An
intent-to-treat (ITT) analysis that included all patients (N=133) as well as an
analysis of only patients that met the criteria for intractable, chronic migraine
(ICM; N=105) was performed for all variables.
Results: For the ITT population, headache days were significantly
reduced by 6.7 (+8.4) days (p<0.001), MIDAS scores were
significantly reduced by 50.9 (+71.9) points to a mean score
of 106.7 (+85.4) points (p<0.001), total PAD scores were
significantly reduced by 10.3 (+14.8) points from a mean
baseline score of 66.8 (+13.6) points (p<0.001). In
addition, 65.4% of patients reported excellent or good headache relief and patient
satisfaction was also high among this patient cohort. Slightly improved results were
noted for the ICM population in which headache days were significantly reduced by
7.7 (+8.7) days (p<0.001), MIDAS scores were significantly
reduced by 57.9 (+71.8) points from a baseline score of 169.7
(+70.6) points (p<0.001), total PAD scores were
significantly reduced by 11.2 (+15.2) points to a score of
57.4 (+16.2) points. In addition, 67.9% of ICM patients
reported excellent or good headache relief and patient satisfaction was also high
among this patient cohort.
Conclusions: The results provide long-term evidence to support efficacy
of PNS of the occipital nerves for the management of chronic migraine.
P59
Therapeutic Effect of Nasal Oxytocin in Chronic Migraine: Dependence on
Cytokines
D.C. Yeomans1,2, M. Angst1, J. Mechanic2, D.
Jacobs2
1Anesthesia, Stanford University, Stanford, CA, USA;
2Trigemina, Inc., Moraga, CA, USA; 3Pharmacology,
University of Minnesota, Minneapolis, MN, USA.
Objectives: Oxytocin receptor (OT-R) expression is known to be driven by
cytokines, and particularly by IL- 6, for which there are early response elements on
the OT-R gene promoter.
Background: As OT-R are on trigeminal nerve neurons, their level should
thus be enhanced by IL-6 as should the analgesic effect of OT for trigeminally
mediated pain wherein there is an inflammatory component, including chronic
migraine.
Methods: This study included a single-dose, placebo-controlled,
double-blind, parallel study of the effects of 32 U of nasally-applied oxytocin in
patients with chronic migraine. The primary inclusion criteria included an incidence
of migraine-type headache of at least 15 days/month and the presence of a headache
for at least 10 hours prior to dosing (to ensure OT-R upregulation) and patients
were washed out of other medications for at least 4 hours. Patients were asked to
rate their pain on a standard 4-point categorical scale (severe, moderate, mild, or
none) just prior to and at 0.5, 1, 2, 4, and 24 hrs after dosing; nausea,
photophobia, and phonophobia were also recorded.
Results: Figure 1 demonstrates that, nasal OT reduced pain by 2
categories in 42% of pts at 2 hrs and 55% at 4 hrs.; compared to 11% and 28% for
placebo. Pts that had taken a NSAID, which blocks IL-6 production, within 24 hrs
prior to dosing showed a strong decrease in effect. Photophobia and Phonophobia were
also decreased compared to placebo.
Conclusions: These results suggest that nasal oxytocin may be a viable
alternative for the treatment of chronic migraine headache.
A.N. Manack1, M.L. Reed2, V. Marske2, D.
Serrano2, K. Fanning2, C. Cunanan1, D.C.
Buse3, R.B. Lipton3
1Allergan Inc, Irvine, CA, USA; 2Vedanta Research,
Chapel Hill, NC, USA; 3Montefiore Medical Center, Bronx, NY,
USA.
Objectives: To describe the methodology and characterize the source
population for the CaMEO study.
Background: Understanding the clinical and epidemiological
characteristics of migraine provides a foundation for optimizing patient treatment
paradigms. CaMEO is a prospective, web-based cohort study that utilized longitudinal
and cross-sectional data collection to characterize migraine clinical course and to
assess aspects of family burden, barriers of care and endophenotypes and
comorbidities among those with migraine.
Methods: Study population included migraine subjects recruited from a
large (2.4 million members) web-based panel. Sampling quotas were used to match the
demographics of the study population to the demographic characteristics in the
general population. People with migraine were identified using ICHD-2 criteria and
subdivided based on headache days per month into episodic (EM) and chronic migraine
(CM). Migraine subjects will complete surveys every 3 months over the course of one
year beginning in the Fall of 2012. Baseline data includes headache features and
frequency, comorbid depression and anxiety, medication use, healthcare consultation,
disability, quality of life. Additionally, subjects will be asked to recruit family
members (spouse and children) living in the household in order to assess
migraine-related burden and impact within the family unit.
Results: Of 489,537 invitees, 80,783 responded to the screening survey
(16.5%) and 16,789 (3.4%) eligibly completed the initial survey. Eligible
respondents were at least 18 years old, spent an appropriate amount of time (≥10
minutes) completing the survey, screened positive for ICHD-2 migraine provided data
on headache frequency and consistently reported age, gender. Eligible respondents
had EM (n=15,313; 92.1%) or CM (n=1,476; 8.8%) and were invited into the 12-month
longitudinal assessment. Additionally, compared to non-responders, responders were
significantly older (average p<0.0001), more likely to be female (p<0.0001),
more likely to be Caucasian (p<0.0001), more likely to be married (p<0.0001),
less likely to be employed full/ part time (p<0.0001), and less likely to have
incomes exceeding $50,000 (p<0.0001).
Conclusions: CaMEO was designed to characterize the course of EM and CM
over 1 year using assessments every 3 months in a community-based web panel of
persons with migraine. Future data will allow for quantification of variations in
headache frequency, disability, comorbidities, and medication use with repeated
assessments over the course of 1 year. CaMEO will also generate data on the impact
of migraine on the family unit, including the perspective of the spouse and child.
Data can be used to define migraine endophenotypes for future genetic studies.
P61
Sociodemographics, Disability and Employment Differences between Persons with
Chronic and Episodic Migraine: Results of the CaMEO (Chronic Migraine
Epidemiology & Outcomes) Study
R.B. Lipton3, D. Serrano2, D.C. Buse3, K.
Fanning2, A.N. Manack1, M.L. Reed2
1Allergan, Inc., Irvine, CA, USA; 2Vedanta Research,
Chapel Hill, NC, USA; 3Montefiore Medical Center, Bronx, NY,
USA.
Objectives: To characterize sociodemographics, headache-related
disability and employment status among individuals with chronic migraine (CM) and
episodic migraine (EM) in a large, US sample.
Background: Previous research suggests that individuals with CM and EM
vary on sociodemographics, headache-related disability and employment status in
addition to headache frequency.
Methods: CaMEO is a prospective, web-based cohort study. Questionnaires
were sent via e-mail to a survey panel constructed to be sociodemographically
representative of the US population beginning in the Fall of 2012. Of 80,783
respondents, 16,789 subjects met an ICHD-2 based case definition for migraine and
were eligible for inclusion. CM and EM were distinguished based on headache days per
month (CM= ICHD-2 migraine diagnosis and ≥15 headache days/ month; EM= ICHD-2
migraine diagnosis and <15 headache days/month). Survey data includes
sociodemographics and headache-related disability (using the Migraine Disability
Assessment Scale [MIDAS]). Herein, we use descriptive and inferential statistics to
contrast those with EM and CM based on responses to the baseline survey.
Results: Of the 16,789 eligible participants meeting ICHD-2 criteria for
migraine, 1,476 (8.8%) had CM and 15, 313 (91.2%) had EM. Respondents with CM showed
a greater female preponderance than those with EM (81.1% vs. 73.8%; p< 0.001)
although mean ages did not differ significantly (40.6 vs. 41.0; p=.32). The sample
was predominately Caucasian and more so for CM (87.5% vs. 83.3%, p<0.001).
Compared to EM, those in with CM completed fewer years of education; 34.9% vs. 45.9%
had bachelor’s degrees or higher (p<0.001). Individual incomes were more likely
to be below the median for CM than EM (69.1% vs. 59.1%; p<0.001). Household
incomes (59.8% vs. 49.5%; p<0.001) were also lower for CM, as well, the CM group
was less likely to be employed full or part time (56.4% vs. 66.0%; p<0.001).
Headache-related disability was significantly higher for CM than EM (mean MIDAS 60.5
vs. 13.1; RR=4.6, p<0.001).
Conclusions: In comparison with EM, persons with CM are more burdened
financially and occupationally as seen in the higher levels of headache-related
disability, unemployment and underemployment with corresponding reductions in
personal and household income. Ongoing data collection will allow us to characterize
the longitudinal course and consequences of CM and EM in the US population.
P62
High Prevalence of Right to Left Shunt in Women with Chronic Migraine Is
Independent of Aura Status
D. Larrosa1, L. Benavente1, J. Vega1, M.
González1, S. Calleja1, E. Cernuda1, J.
Pascual1
1Neurology, University Hospital Central de Asturias, Oviedo,
Asturias, Spain.
Objectives: To study the prevalence and characteristics of right to left
shunt (RtLS) in a series of women with chronic migraine (CM).
Background: The prevalence of RtLS is estimated as 25% of the general
population (1). Prevalence of shunt has been shown to be increased in migraine with
aura and one study has found a high prevalence of shunt in CM (2).
Methods: This series includes 84 women (age 43 years, range 16-61)
meeting diagnostic criteria (IHC-II revised 2006) for CM. There were 41 women with
migraine with aura attacks. We carried out a transcranial doppler study (AplioXG,
model SSA-790A, Toshiba) following the CODICIA study protocol (3).
Results: Forty-eight patients (57%) showed some degree of RtLS.
Twenty-three (53,5%) out of the 43 patients without aura had shunt while twenty-five
(61%) out of the 41 patients with migraine with aura had shunt. There was no
difference in RtLS prevalence in those CM who fullfil aura criteria versus those
without (61% versus 53,5%; odds ratio 1.358, 95% confidence interval 0.57 to 3.235,
p=0.636). Nineteen (39,5%) of the total detected shunts were massive and detected at
rest. In patients with aura, ten (40%) of the 25 shunts were detected at rest and
nine (36%) of them were massive. In patients without aura, nine (39%) of the 23
shunts were detected at rest and ten (43,5%) of them were massive. There was no
difference in RtLS appearance (detected at rest or with Valsalva maneuver) in CM who
fullfil aura criteria and those without (40% versus 39%; odds ratio 1.037, 95%
confidence interval 0.325 to 3.302, p=0.851). There was no difference in RtLS degree
in those with CM who fullfil aura criteria and those without (36% versus 43,5%; odds
ratio 1.367, 95% confidence interval 0.428 to 4.364, p=0.815).
Conclusions: Prevalence of RtLS in women with CM was higher than
expected for the general population and there were not differences according to aura
status. There were no differences in RtLS, both in terms of degree or appearance at
rest or after Valsalva, between patients with or without aura. The clinical
implications of our findings needs to be determined, though they suggest a
relationship between the presence of shunt with an increased frequency of migraine
attacks.
P63
Transient Exacerbation of Headache in Patients Receiving Intravenous
Dihydroergotamine for Inpatient Management of Chronic Migraine
M. Eller1, N.Y. Riggins1, M.M. Church1, C.J.
Schankin1, P.J. Goadsby1
1Neurology, UCSF, San Francisco, CA, USA.
Objectives: To examine for any association between transient headache
exacerbations some patients experience with an inpatient course of intravenous
dihydroergotamine (DHE) and medium term outcome.
Background: Clinical experience suggests a proportion of patients
experience transient headache exacerbations with administration of intravenous
dihydroergotamine (DHE). This may dissuade some clinicians and patients from
completing a full course of inpatient treatment.
Methods: We examined prospectively collected diary data in patients
havingDHE for inpatient management of chronic migraine, and examined the presence of
common side effects associated with intravenous (IV) DHE, as well as the qualitative
medium term outcome.
Results: A total of 19% of 212 chronic migraine patients had a
documented headache exacerbation related to IV DHE. Of these, 66% went on to have a
degree of improvement in the medium term, in comparison to 82% of the patients
without a headache exacerbation related to DHE. The difference was not significant
(p = 0.066). There was no difference in associated nausea
(p = 0.059). Qualitatively, headache exacerbations were more
likely to occur during infusions early in the inpatient course, as well as being
related to a faster rate of infusion.
Conclusions: Transient headache worsening associated with inpatient IV
DHE is a common occurrence. Interestingly, it is also associated with triptan use.
The data support pushing on with treatment in patients with early transient nausea
after DHE since it is likely to settle and outcomes remain good.
P64
Modified Spinal Accessory Nerve Blocks for Effectively Treating Refractory
Migraine
L. Yao
Medicine, The Chester County Hospital, West Chester, PA, USA.
Objectives: To retrospectively review our clinical experience with
modified spinal accessory nerve (SAN) blocks for very effectively treating
refractory migraine.
Background: The current standard care for migraine is often unable to
cure Refractory Migraime, or control and prevent its episodes very well. Long term
of using headache medications has also brought drug side effects. We have used the
modified spinal accessory nerve (SAN) blocks to very effectively treat the patients
with refractory migraine headache.
Methods: Author did an retrospective chart review of his 62 refractory
migraine patients, who received SAN block injections in author’s Pain Clinic from
2009-2011. The patients migraine diagnoses were all confirmed by their neurologists
and author. Twelve patients lost tracks. Total 50 cases were available for this
study. They were: 17-67 years old, 40 women, 10 men, history of refractory migraine
for 1 to 30 years, no current neck pain history, having daily headaches or 1-20
episodes of headache per month, usually at moderate or severe level based on a VAS
pain scale (>5/10), each headache duraton from a few hours to 2-3 days.
They tried the standard care treatment for their chronic refractory migraine, that
included several prescription headache medications, and /or Botox injections. The
treatments they had were either unable to cure and prevent relapses of their
headaches, or unable to control migraine very well. 90% of the patients were found
to have mild tenderness at the ipsilateral spinal accessory nerve point, the
junction of the upper and middle thirds of the sternocleidomastoid (SCM) muscle.
All patients had modified spinal accessory nerve block injections, 1% Lidocaine 1 ml
at the ipsilateral spinal accessory nerve point, either one or both sides, using 27G
1” needle. The each patient received 3-10 sessions of injections in 2-3 weeks
apart.
Primary outcome: After finishing inection course, the patients have either no
migraines or more than 50% improved migraine in frequence of headache episode, pain
level (based on VAS pain scale), pain duraton, and decreased pain medication doses
for a long period of time.
Results: From begining of 2009 to the end of 2012, eleven patients
either had no significant improvement after 5 sessions of injection. Thirty nine
patients(78%), after finishing 3-10 sessions of injection, either have had no
headaches or more than 50% migraine headache improvement at least for more than one
year, some of tem more than three years, so far in the end of 2012. The patients
have discontinued routine prescription headache medications. They just take OTC pain
medications as needed, such as 400 mg ibuprofen or two tablets of Eccedrin
migraine.
Conclusions: The modified spinal accessory nerve block injection is very
successful in the treatment of Refractory Migraine Headache. It can significantly
improve refractory migraine headache for a long period of time. It is also easy to
do and has no side effects.
P65
Barriers to Chronic Migraine Care: Results of the CaMEO (Chronic Migraine
Epidemiology & Outcomes) Study
D.C. Buse3, R.B. Lipton3, M.L. Reed2, D.
Serrano2, K. Fanning2, A.N. Manack1
1Allergan, Inc., Irvine, CA, USA; 2Vedanta Research,
Chapel Hill, NC, USA; 3Montefiore Medical Center, Bronx, NY,
USA.
Objectives: To describe patterns of healthcare consultation and
diagnosis among a large, US population-based sample of chronic migraine (CM).
Background: CM is burdensome to the individual, society, and healthcare
systems; yet it remains largely undiagnosed and under-treated.
Methods: CaMEO is a prospective, web-based cohort study. Questionnaires
were sent via e-mail to a survey panel constructed to be sociodemographically
representative of the US population, beginning in the Fall of 2012. Of 80,783
respondents, 16,789 met ICHD-2 criteria for migraine. Respondents with migraine were
divided into an episodic migraine (EM) group and a CM group with ≥15 headache (HA)
days/month. Collected data includes healthcare visits, medical diagnoses, current
and past treatment, satisfaction with treatments and knowledge, attitude and
behaviors that may be barriers to optimal care. A “doctor” was defined as a
prescribing health-care provider (HCP). “HA Specialists” included all neurologists,
HA or pain specialists. A “non-prescribing HCP” was defined as any HCP that cannot
prescribe medicine (e.g., chiropractor, psychologist).
Results: Of the participants, 1,476 (8.8%) met criteria for CM and
15,313 (91.2%) had EM. Self-reported medical diagnoses in the entire sample with CM
included migraine (59.6%), CM or transformed migraine (13.6%) or chronic daily
headache (11.4%). Of those with CM, 20.5% reported at least one of CM/TM/CDH.
Although not mutually exclusion, of those with CM, 13.6% reported currently seeking
care from a HA Specialist, 41.8% from a doctor and 43.4% from a non-prescribing HCP.
Refer to Table 1 for HA diagnosis rates for CM and related disorders by HCP
type.
Conclusions: Among persons with CM, just one fifth report an appropriate
medical diagnosis (CM/TM/CDH). Adequate diagnostic rates are highest in individuals
treated by headache specialists, intermediate among those consulting doctors and
lowest among those seeking headache care from a nonprescribing HCPs. This is a
barrier, as proper diagnosis is necessary for an optimal treatment plan.
P66
Chronic Migraine (CM) Patients Should Be Screened for Pseudobulbar Affect
(PBA)
D. Kantor
Neurologique, Ponte Vedra, FL, USA.
Objectives: To report a case series of pseudobulbar affect (PBA) in
patients with chronic migraine (CM).
Background: Pseudobulbar affect (PBA) is an under-recognized neurologic
condition characterized by uncontrollable, inappropriate outbursts of laughing
and/or crying that are incongruous or disproportionate to the patient’s emotional
state; PBA occurs secondary to a variety of neurologic conditions, but it has not
previously been reported in patients with chronic migraine (CM). CM shares many
pathophysiological features with other diseases affecting the central nervous
system, yet it was not included in the recent point-prevalence epidemiological data
from the PBA Registry Series (PRISM) of 5,290 neurologic patients. PBA is screened
for using the Center for Neurologic Studies – Lability Scale (CNS-LS), the first
self-report measure of PBA to be established and validated; it consists of subscales
for laughter (4 items) and for crying (3 items), with each item scored on a 5-point
scale (1 = applies never; 5 = applies most of the time) for a total score ranging
from 7 (no symptoms) to 35 (maximum). In the clinical trials leading to the FDA
approval of fixed dose combination dextromethorphan/quinidine (DM/Q) for the
treatment of PBA, more patients treated with placebo had headache than patients
treated with DM/Q (15.6% vs 14.0%). This led to our use of DM/Q for the treatment of
headache; we previously reported a patient with >20 year history of refractory
chronic migraine who responded dramatically (reduction of headache frequency and
severity) to DM/Q. It is unclear, however, whether the therapeutic effect of DM/Q in
CM is due to its efficacy in PBA.
Methods: Retrospective analysis of 5 consecutive chronic migraine (CM)
patients, all of whom completed both the CNS-LS to screen for PBA symptoms and the
Beck Depression Inventory -II (BDI-II) to screen for depression. The CNS-LS
subscores for laughing and crying were also analyzed separately, as was the crying
specific question of the BDI-II.
Results: All 5 CM patients were women, between the age of 40 and 65
years (mean/median age = 50 years). The mean number of headache days per month was
26 and 4 patients met criteria for PBA (CNS-LS≥13), while the other patient had a
CNS-LS = 12. Mean CNS-LS was 15 and median was 14. Mean BDI-II was 15 and median was
13. There appeared to be some correlation (Pearson coefficient, 0.54) between CNS-LS
and BDI-II scores, but depression alone did not explain the presence of PBA.
Conclusions: PBA has not previously been described in patients with
chronic migraine (without other underlying neurologic conditions, such as multiple
sclerosis, amyotrophic lateral sclerosis, stroke, traumatic brain injury,
parkinson’s diseases or Alzheimer’s dementia). This case series suggests that PBA
(in addition to depression) should be screened for in patients with CM. Further
research should be conducted to estimate the prevalence of PBA in CM patients and to
ascertain whether the response of CM to DM/Q is independent of the effect of DM/Q on
PBA.
P67
An Exploratory Study of Calcitonin Gene-Related Peptide in Chronic Migraineurs
Receiving OnabotulinumtoxinA: Implications to Pathophysiology and Treatment
Responsiveness
I.M. Turner1, R.K. Cady2, P. Durham3, J.K.
Dexter2, R. Cady3, R. Browning4
1Neurology, Island Neurological Associates, PC, Plainview, NY,
USA; 2Headache Care Center, Springfield, MO, USA;
3Biology, Missouri State University, Springfield, MO, USA;
4Clinvest, Springfield, MO, USA.
Objectives: To further the understanding of mechanisms of
onabotulinumtoxinA in the treatment of chronic migraine (CM) and implications of
response to acute treatment.
Background: CGRP plays a pivotal role in the pathogenesis of episodic
migraine but its role in chronic migraine is less understood. OnabotulinumtoxinA has
shown to inhibit the release of CGRP while triptans inhibit release of CGRP during
attacks of acute migraine.
Methods: A randomized, placebo-controlled, crossover pilot study was
conducted at 2 headache centers. Following a 30-day baseline period to define the
frequency of headache days and document the diagnosis of CM, 20 patients were
randomized 1:1 to receive onabotulinumtoxinA or saline injection and followed for 3
months. After a 1-month washout period, the groups were crossed over, treated, and
followed for an additional 3 months. All subjects received 0.1 cc of
onabotulinumtoxinA or saline in 31 sites as described in the PREEMPT Study. Saliva
samples were collected at monthly intervals and analyzed for CGRP. Treatment
response to onabotulinumtoxinA and acute medication was monitored via daily diary
records.
Results: Saliva CGRP levels declined from baseline for subjects
receiving onabotulinumtoxinA regardless of response compared to subjects receiving
saline injections. Response to subjects’ usual acute interventions improved for
onabotulinumtoxinA responders (>50% reduction in headache days) compared to
onabotulinumtoxinA non-responders (p=0.08) and saline non-responders (p=0.04). There
were no significant changes observed in saliva CGRP during intensification of
migraine headache or post treatment with a triptan.
Conclusions: This small exploratory study was underpowered for
definitive conclusions. It appears that onabotulinumtoxinA is associated with
reduction of interictal saliva CGRP levels. Because CGRP level did not change during
intensification of migraine or post treatment with triptan treatment, there may be a
unique difference in pathophysiology between episodic and chronic migraine. Subjects
responding to onabotulinumtoxinA had an improved response to usual acute
interventions.
P68
Severity of Cervical Functional Disability in Subjects with Headache
G.N. Ferracini1, T.C. Chaves1, L.L. Florencio1, M.C.
Gonçalves1, G.F. Carvalho1, F. Dach1, M.E.
Bigal2, J.G. Speciali1, D.
Bevilaqua-Grossi1
1Faculty of Medicine of Ribeirão Preto, University of São Paulo,
Ribeirão Preto, São Paulo, Brazil; 2Head of the Merck Investigator
Study Program, Scientific Engagement and Education, North Wales, US,
USA.
Objectives: To evaluate severity of functional disability in subjects
with different types of headache by the Neck Disability Index (NDI).
Background: Neck pain is one of the most frequent complaints in the
general population and can be associated with temporomandibular disorders,
fibromyalgia and headache. Despite of the association between headache disorders and
cervical structures, the headache repercussion on cervical spine function are
unknown.
Methods: We evaluated 77 subjects from a tertiary outcome hospital,
diagnosed by neurologists according to ICHD-II, with the following diagnosis: 38
migraine without aura (M), 12 migraine with aura (MA), 13 chronic migraine (CM), 3
cervicogenic headache (CH), 7 tension-type headache (TTH) and 6 other headaches.
Only volunteers with one type of headache were included, with no history of cervical
lesions and other comorbidities. The NDI is composed by questions about cervical
disability and functionality and the items are scored according to the level of
difficulty to perfom each task or pain severity. The NDI classification levels are:
no disability (0-4), mild (5-14), moderate (15-24), severe (25-34) and complete
disability (>34). For statistical analysis the chi square were used.
Results: Only 13% of the total sample showed no cervical disability, 9%
for group M, 2% MA, 1% MC, 0% CH, 1% TTH and 0% Others. The relative frequency of
cervical disability was higher in the CM (33%) when compared to the other headache
groups, M (11%, p <0.001), MA (14%, p <0.001), CH (0%, p <0.001), TTH (17%,
p <0.001) Others (0%, p <0.001).
Conclusions: The frequency of cervical disability, regardless of level,
is present in all types of headache examined, but the severe level is higher in
chronic migraine.
P69
Prolonged Efficacy of OnabotulinumtoxinA on Migraine-Related Disability Over 8
Consecutive Treatment Cycles
I.M. Turner1, T.M. Harding1, R. Lio1, J.
Regnerus1
1The Center for Headache Care and Research at Island Neurological
Associates, P.C., Plainview, NY, USA.
Objectives: To retrospectively analyze patients with chronic
migraine(CM), who were OnabotulinumtoxinA (OnabotA) responders in regard to a
sustained reduction in migraine-related disability over a prolonged period in our
community-based, out-patient headache center.
Background: Chronic migraine (ICHD-II 1.6) is an extremely disabling
condition that affects approximately 1-2% of the population in North America. The
PREEMPT study that led up to FDA approval for OnabotA for the treatment of CM showed
a significant decrease in headache frequency and duration. We have previously
reported that a sustained decrease in migraine-related disability exists over
approximately 3 treatment cycles with OnabotA. Whether this is a prolonged effect or
transient in nature has been open to question.
Methods: We queried our electronic records system at our community-based
headache center to review CM patients who were treated with OnabotA over 8
consecutive treatment cycles at 12-13 week intervals from January 2010 through
January 2013. All patients had been injected with OnabotA with doses ranging from
155-195 units per the PREEMPT protocol. Migraine Disability Assessment Scores(MIDAS)
were routinely collected at each treatment visit and compared to baseline. The
average scores for the entire cohort were then calculated for each treatment
cycle.
Results: 35 patients were found to meet the above criteria. Average
MIDAS scores showed a sustained decrease over the approximately 2- year period of
regular treatment with OnabotA 155-195 units from approximately 65 at baseline to 39
at the 4-week interval. At the last treatment cycle, the average MIDAS score was
decreased to 23.
Conclusions: The effect of OnabotA on migraine-related disability in
chronic migraine is sustained in patients with chronic migraine who are regularly
(12-13 week intervals) treated with 155-195 units in our community-based,
out-patient headache center retrospective review. Whether or not this is true when
patients return at less regular intervals has not been determined.
P70
Restoring Pain Modulation for Chronic Migraine; by Mild Stimuli of Stretching
Tender Points of the Neck
F. Sakai1, Y. Asano1, Y. Maruki1
1Saitama International Headache Center, Saitama Neuropsychiatric
Institute, Saitama, Japan.
Objectives: The purpose of the study is to reveal the tender point in
the back of the neck in patients with chronic migraine and to know the effect of
stretching exercise by turning the shoulder around the neck axis on the pain in the
tender point. The effect of daily stretching exercise on the chronic migraine was
also investigated.
Background: Chronic migraine is reported to be 2% of the adult
population, but the doctor attendance rate is much higher than episodic migraine.
Among other preventive treatment the benefit of the occipital nerve stimulation is
closely assessed, but its basic concept of treating central sensitization via the
trigeminal-cervical convergence theory is giving rationale to other treatments. It
indicates the possibility for other types of stimulation may be effective to treat
chronic migraine.
Methods: Patients with chronic migraine of ICHD2R (n=128) and age &
sex matched normal volunteers (n=100) were studied. Tender point elicited by finger
pressure was evaluated by double blind methods. Examiner, blind physiotherapist,
palpated the tender point without knowing the diagnosis or treatment. Tenderness was
reported by the patients using VAS method. Headache diary was kept for three months
prior to and after, to count and check the headache days.
Results: On palpation and applying pressure by the examiner’s finger,
intense pain in the C3 region was elicited in 118 patients (92%) with chronic
migraine. Pain radiated to the head in 67%. After neck stretching exercise for 2
minutes, 98% of the patients reported disappearance of tenderness on palpation from
10 to 3.6 +/- 2.2 (p<0.01). Neck stretching exercise for 2 minutes daily over 3
months period reduced the headache days from 24.2 to 13.6 (p<0.01). Normal
volunteers did not show significant tender point in the corresponding region in the
back of the neck.
Conclusions: A strong tender point seen at the C3 region on the back of
the neck in chronic migraine seems to have referred from the central sensitization
through the trigemino-cervical convergence. Disappearance of tender point by turning
the shoulders and stretching the tender point may indicate that a good stimulation
was sent to caudate trigeminal nucleus and modified pain control system.
Physiotherapeutic intervention helps patients restore pain modulation and improve
chronic migraine. NA.
P71
Improvement in Aura and Prodrome in Chronic Migraine (CM) Following Treatment
with Botulinum Toxin Type A (Botox). A Prospective Analysis
N. Thekkootu Pisharam1, M. Khalil1, F. Ahmed1
1Neurology, Hull and East Yorkshire Hospitals NHS Trust, Hull,
East Yorkshire, United Kingdom.
Objectives: Prospective study performed to assess the change in
frequency, duration, and disability with social life, work or activities of daily
living (ADL) by aura and prodrome following treatment with Botox.
Background: Botulinum Toxin A (Botox) is a licensed preventive treatment
in CM recommended by National Institute of Clinical Excellence (N.I.C.E) in UK. The
prevalence of Aura and prodrome in Chronic Migraine is unknown. Studies have shown
improvement in headache days, severity and quality of life following Botox in
CM1. However, we are not aware of the impact of this treatment in
aura or prodromal symptoms and its impact on quality of life.
Methods: Patients with CM with prodrome or aura or both who received
treatment with Botox as per PREEMPT protocol were prospectively interviewed through
structured questionnaire. All patients maintained a headache diary for at least 30
days before and after receiving treatment. Data were collected for the presence of
aura and prodrome; its frequency, duration and severity and impact on social life
and ADL before and after treatment. The Data was statistically analysed using SPSS
17.
Results: Data of 35 patients with chronic migraine were available for
analysis. Males=5 (mean age 56.4, median-55; range 33-77 years). Females=30 (mean
age -44.1, median-45 & range 19-70 years). Overall 28.6% did not suffer any
aura, 71.4% suffered both aura and prodrome, however 100% suffered prodrome. The
result has been tabulated in table 1.
Improvement by
Paired differences
Mean
Median
Std Dev
paired t score
p value
>70%
>50%
Aura frequency(day)
8.86
8
8.31
5.33
0.0001
66.7
75
Aura Duration(Hour)
3.24
0.88
9.67
1.64
0.114
54.2
66.7
Social Life(day)
6.24
4
7.84
3.98
0.001
83.3
88.9
Work/ADL(Day)
5.52
3
7.33
3.76
0.001
83.3
88.9
Aura Severity change
1.52
2.0
7.33
6.56
0.0001
Prodrome frequency(day)
9.63
11
8.01
7.110
0.0001
42.9
62.9
Prodrome duration(hour)
21.06
12
26.97
4.65
0.0001
48.6
65.7
Social life(day)
9.31
8
9.06
6.09
0.0001
59.3
81.5
Work/ADL(day)
8.4
7
9.05
5.49
0.0001
60
80
Prodrome severity change
1.4
1.0
1.03
8.01
0.0001
HIT-6 Paired difference
11.4
10.50
9.25
6.08
0.0001
HIT-6 Impact change
1.04
1
0.96
5.23
0.0001
Grade improved by
3
2
1
0
worse
Aura severity change
24%
28%
28%
16%
4%
Prodrome severity change
14.3%
34.3%
31.4%
17.1%
2.9%
HIT-6 IMPACTGRADE change
7.7%
23.1%
34.6%
34.6%
Conclusions: This is the first observational study looking at 35
patients who received treatment with Botox for prevention of CM. Our data shows that
Botox improves symptoms of aura and prodrome and has a positive impact on quality of
life. The exact mode of action of Botox remains unknown although it is possible that
Botox directly or indirectly affects cortical or sub-cortical areas involved in the
generation of aura or prodrome.
P72
Evaluation of Cerebral Hemodynamics of Patients with Chronic Migraine: Effects
of Amitriptiline
S. Mazman1, H. Akgun1, S. Tasdemir1, O.
Oz1, E. Eroglu1, S. Alay1, U.H.
Ulas1, S. Demirkaya1
1Neurology, Gulhane Military Medical Academy, Ankara,
Turkey.
Objectives: Amitryptiline is a serotonin-nor-epinephrine reuptake
inhibitor. Amitryptiline is used in migraine prophylaxis if attacks occur 2 or more
times in a month and if increase of attacks is present.
Background: Its mechanism of action is largely through serotonin.
Inspired from the vascular theory of migraine pathophysiology, the aim of our study
was to research the effects of amitryptiline on the blood vessels of the brain.
Methods: The study included 11 patients with chronic migraine and a
control group of 11 participants with compatible gender and age characteristics.
With a transcranial Doppler machine with temporal insonation the blood flows of
booth MCA and PCA, pulsatile indexes and VMR’s were measured. The VMR’s were three
times remeasured with breath holding indexes (BHI). The patients received 10 mg of
amitryptiline prophylaxis. The tests performed with transcranial Doppler were
repeated on the 1st month of the treatment. The results before and after the
treatment were compared among the patients and with the results of the control
group.
Results: The average age of the patient group was 40,4. Statistically
significant increase of the right MCA BHI was detected after the treatment
(p=0,043). No significant difference was detected in other pre and post-treatment
data (p>0,05). The BHI’s of the patient group were significantly decreased
compared to the control group. Eventhough with treatment, the right MCA BHI data
were close to the control group, after the treatment they were found to be decreased
again. No statistically significant difference was detected for other data
(p>0,05).
Conclusions: The effect of amitryptiline on migraine headaches through
serotonergic action is known. In our study we found amitryptiline to increase the
BHI of MCA and the data was close to the data of the control group. Amitryptiline
may have an effect on migraine treatment by affecting the vascular bed in the
migraine pathophysiology and partially improving the VMR. There is a need of larger
studies researching the effect of higher amitryptiline doses on cerebrovascular
structures.
P73
Withdrawn by the author.
P74
Botulinum Toxin A for Treatment of Chronic Migraine
L. Grazzi1, S. Usai1, G. Bussone1
1Clinical Neuroscience, Headache Unit, C. Besta Neurological
Institute and Foundation, Milan, Italy.
Objectives: As the significant population of chronic migraine patients,
refractory to common therapeutic prophylaxis, BoNT has been used in our clinical
experience for treating patients referring to our headache centre and suffering from
chronic migraine with medication overuse.
Background: Chronic migraine is a common and debilitating headache
syndrome.
Botulinum neurotoxin (BoNT), a potent toxin produced by the anaerobic bacterium
clostridium botulinum, used for treatment of disorders associated with increased
muscle tone and hyperidrosis, has been recently employed for patients suffering from
chronic migraine.
Methods: Ten patients have been submitted to a withdrawal from
medications in a day hospital setting and after that, they have been treated by BoNT
A injection in multiple sites according to the protocol of the PREEMPT study at the
dosage of 150 U for 31 sites. Every session of local injection (150 U per 31 sites)
was repeated every three months for a period of one year. A second group of 8
patients, after withdrawal, was treated by BoNT A injection, multiple sites, at the
dosage of 100 U; every session of local injection has been repeated every three
months for a period of one year. Number of medication intake and days of headache
per month were recorded by an headache daily diary.
Results: Data concerning the first group of patients evidenced that days
of headache / month decreased during the period of treatment at 150 U (pre 21.4+7.9
post 13.8+10.9 p< 0.01). Also medication intake decreased (pre
19.6+8 post 11.7+9.5 p<0.01).
In the second group of patients, treated with 100 U, results were not significant:
only 3 patients completed the treatment with 4 sessions; 5 patients dropped for
different reasons (side effects, no benefit, low compliance).
Conclusions: Although these results are preliminary they led to intense
efforts to evaluate analgesic properties of BoNT A and to assess their clinical
applicability.
The pharmacological profile of BoNT A makes it a good candidate for migraine
prevention at the adequate dosage of 150 U as proposed in the PREEMP study. Its long
duration of action (3 months) makes it particularly attractive for patients who are
not compliant with the daily use of preventive medications, or if they cannot
tolerate it or when they are refractory to preventive medications. On the other side
we cannot confirm the efficacy of lower dosage (100 U) for patients with chronic
migraine after withdrawal.
P75
Comorbidity of Migraine and Affective Disorders among Substance Dependent
Inpatients
1University of Mississippi, Oxford, MS, USA;
2University of Mississippi Medical Center, Jackson, MS, USA;
3Wake Forest Medical School, Winston-Salem, NC, USA.
Objectives: To examine comorbid migraine and psychiatric disorders among
inpatients with substance use disorders.
Background: Psychiatric comorbidities among migraineurs compound
negative impact of migraine (Saunders et al., 2008; Guidetti et al., 1998), and
inpatients with substance use disorders (SUDs) are at increased risk for affective
disorders (Compton et al., 2003). Data are limited, however, regarding associations
between migraine and these comorbidities within inpatient clinical settings.
Methods: Data were collected from 181 substance-dependent inpatients in
residential substance abuse treatment. Participants were assessed for substance
dependence and other Axis I psychiatric disorders using the Structured Interview for
the DSM-IV (SCID-IV; First et al., 1996) and completed two validated screeners for
migraine (ID Migraine; Lipton et al., 2003; Brief Headache Screen; Maizels &
Burchette, 2003). Inpatients screening positive for migraine on both measures were
classified as migraineurs. Participants also completed self-report measures of
anxiety sensitivity (ASI-III; Taylor et al., 2007), depression and anxiety symptoms
(DASS – 21; Lovibond & Lovibond, 1995), and substance use (DUQ; Lejuez et al.,
2007). Standardized mean differences were used to quantify differences between
inpatients with and without migraine across four theoretically-organized domains of
predictors (demographics, psychiatric disorders, SUDs, and self-reported symptoms).
Predictors within each domain that best discriminated between groups were identified
using a classification tree with Bonferroni corrections. Candidate predictors were
entered into a multivariate logistic regression to predict migraine status, and
replicated using bootstrapping of 500 samples.
Results: Forty-four (24.3%) participants met criteria for migraine.
Migraineurs were more likely to be female (34.8% vs. 18.3%) and reported higher
levels of current anxiety symptoms on the DASS (M = 19.7 [11.0] vs. 11.3 [10.3]).
Having a lifetime diagnosis of generalized anxiety disorder (GAD) or a current
diagnosis of alcohol dependence was associated with greater than three-fold
increased odds of migraine (OR = 3.47 and 3.79, respectively). These 4 predictors
were forced into the final multivariate model, which differentiated well between
those with and without migraine (area under ROC curve = 0.81; 95% CI: 0.73 to
0.88).
Conclusions: Lifetime GAD, current anxiety symptoms, and current alcohol
dependence are the strongest psychiatric predictors of migraine among substance
dependent inpatients. Migraine was also associated with elevated rates of several
other SUDs, but addition of these SUDs did not improve the final model. Future
research should focus on further clarifying relations of migraine with specific
substance categories. Implications for migraine screening and management in SUD
treatment settings are discussed.
P76
Treatment and Social Impact of Cephalic Hypersensitivity Syndrome Relating to
Migraine
T. Shimizu1, K.H. Hirata3, S. Manaka4, I.
Arakawa2
1Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan;
2Hospital and Healthcare Administration, Tokyo Women’s Medical
University, Tokyo, Japan; 3Neurology, Dokkyo Medical University,
Mibu-machi, Tochigi, Japan; 4Neurosurgery, Manaka Hospital, Odawara,
Kanagawa, Japan.
Objectives: In this cohort study, we will report: 1) social impact of
Cephalic Hypersensitivity Syndrome (CHS) and 2) that pertinent use of triptan agents
reduce risk of incidence of CHS, which has been disseminated concept of CHS in Japan
lately.
Background: Pathophysiology of migraine has been commonly explained by
trigeminovascular theory, although recent studies have suggested that the cause of
the migraine stems from cortical hyperexcitability.
Methods: In this study, observation items are: 1) demographics of
subjects, 2) medical magnificent, 3) treatment status, 4) laboratory test:
Varicella-zoster virus (VZV) antibody. This study was conducted in compliant with
Japan ethic guideline for epidemiological study which was established by ministries
of HEALTH, LABOUR, AND WELLFARE and EDUCATION AND SCIENCE, JAPAN.
Results: Of 1000 subjects, the proportion of female in analyzable
subjects (n=964) whose mean age are 46.3±16.0 yrs, were approximately
73.3%.
To identify factors relating to migraine onset, we performed multivariate analysis
using the logistic regression model. Gender, age pre-photophobia and tinnitus were
suggested onset of migraine attack.
Conclusions: We hereby proposed diagnostic criteria of the “CHS” below
[Fig]. Here we defined a new syndrome, “cephalic hypersensitivity syndrome” as a
subliminal cortical hyperexcitability which itself is invisible but apparently seen
as some symptoms such as dizziness and cephalic ringing. The cephalic
hypersensitivity syndrome should be treated to attenuate the excitability by an
appropriate triptan medication during attacks so as to exhibit its recurrence.
Fig. diagnostic criteria of the “Cephalic Hypersensitivity Syndrome (CHS)” According
to statistics on number of patients, those who complain with dizziness and tinnitus
suffering from CHS and now presenting migraine headache consult headache clinics,
were markedly increased lately in Japan because concept of CHS has been disseminated
in multiple Japan medical communities. Furthermore, triptan agents’ sales in Japan
were dramatically increased as compared before and after our presentation of CHS on
basis of a sale statistics.
Logistic Regression Model of Migraine To Explore Relating Factors
P value
OR
95% CI of OR
Lower
Upper
Gender
0.0005
0.2508
0.1158
0.5435
Age
0.0000
0.9500
0.9273
0.9733
Photo(pre)
0.0189
0.2273
0.0657
0.7830
Photo(post)
0.4508
0.6570
0.2204
1.9581
Tinnitus +
0.0118
0.0569
0.0061
0.5293
Tinnitus -
.
.
.
.
OR: odd ratio
P77
Chronification of Migraine Headache and Cervical Abnormalities
1Neurology, Pusan National University, School of Medicine, Busan,
Republic of Korea; 2Korean Hand Acupuncture, Korean Hand Therapy
Institute, Seoul, Republic of Korea.
Objectives: Despite of therapeutic approaches with pharmacological and
nonpharmacological strategies, some migraineurs have progression to chronic course
(choronification). The Chronification of migraine disturbs the quality of patient’s
life. Chronic migraine headache is an enormous burden to individuals and societies
due to high prevalence and considerable direct and indirect economic costs.
Generally speaking there are no abnormal findings in laboratory tests in migraineures
according to the second edition of the International Classification of Headache
Disorders.
Background: In practice chronic migraineurs show some abnormalities in
cervical spine. There are no references that chronic migraineurs have any
abnormalities in cervical spine.
Methods: The procedure was performed during the physical examination
from Jan 2009 to Nov. 2012 at Dept. of Neurology, Busan National University
Hospital. The 200 patients with migraine without aura, who complained of chronic
headache for more than 3 years without other neurological or systemic diseases, were
included in this study.
Cervicogenic headache and neck problems were excluded using criteria of International
Headache Classification. The exact location may be good clue or guide to improve
diagnostic accuracy, we applied Korean Hand Therapy Method to confirm migraine
headache using the location of tender points on the head and neck.
Cervical spine study was included during routine laboratory tests.
Results: Among 200 chronic migraineurs, number of female was 148, that
of male was 52. Mean age was 48 years old.
The X-ray finding of cervical vertebrae in migraineurs (200 persons) were various as
followings, normal pattern 42, loss of normal lordortic curvature of c-spine 57,
diffuse spondylosis with osteopenia 66, mild degenerative cervical spondylosis 51,
mild disc space narrowing C3/4, C4/5, C5/6, C6/7 90, neural foraminal narrowing
75.
The right side of neck pain (110) is more than left side (90).
Conclusions: The chronic migraineurs having chronic progressive course
and long periodic cycles for more than 3 years have some abnormalities on the
radiological study.
It may be helpful to include the cervical spine study in the chronic
migraineurs and to consider the correction of cervical abnormalities for
prevention of chronic processes.
P78
Correlation between the Level of Disability the Cervical Spine and Pressure
Pain Threshold in Patients with Migraine and Chronic Migraine
M.C. Gonçalves1, T.C. Chaves2, G.F. Carvalho1, L.L.
Florencio1, M.C. Giantomassi1, F. Dach2, M.E.
Bigal3, J.G. Speciali2, D. Bevilaqua-Grossi1,
1Department of Biomechanics, Medicine, and Rehabilitation of
Locomotor Apparatus, School of Medicine at Ribeirao Preto, University of Sao
Paulo, Ribeirao Preto, Sao Paulo, Brazil; 2Department of Neuroscience
and Behavioral Sciences, School of Medicine at Ribeirao Preto, University of Sao
Paulo, Ribeirao Preto, Sao Paulo, Brazil; 3Merck Co & Inc., North
Wales, PA, USA.
Objectives: The aim of this study was to determine the correlation
between Neck Disability Index (NDI) and the Pressure Pain Threshold (PPT) of
cervical muscles in patients with migraine and chronic migraine.
Background: The correlation between NDI and cervical mobility was weak
in patients with neck pain, but is not established it how disability is correlated
with the cervical muscle PPT, especially in migraine patients, since this population
showed muscle hypersensitivity and reduced cervical mobility3.
Methods: Of 32 volunteers, 16 had migraine 38 (SD=9) years and 16
chronic migraine 38 (SD=10) years, diagnosed by neurologists acccording ICHD-II
(2004). We excluded women with other concomitant headache, use painkillers in the
last 24 hours, overuse of any medication, systemic degenerative diseases, history of
trauma in the cervical region and diagnosis of neuropathic pain. The NDI
questionnaire was used as interview and PPT was random assessed the in
sternocleidomastoid, trapezius and suboccipital muscles with an algometer (Kratos,
modelo DDK-10). The correlation was by verified Pearson correlation coefficient to a
α=0.05 by SAS 9.2.
Results: There were moderate correlations for the migraine group, r
(-0.53, -0.46 and -0.46) and weak correlations for chronic migraine group, r (-0.26,
-0.16 and -0.18) for regions of the sternocleidomastoid, trapezius and suboccipital
muscles, respectively.
Conclusions: NDI is correlated to the PPT in patients with migraine,
emphasizing the importance of physical and functional assessment.
P79
The Effectiveness of the Injection of Botox in the Treatment of Transformed
Migraine (TM)
Z. Elchami1, M.B. Issa1, R. Tannous1, E.A.
Diaz1, A. Mirambel1
1Pain & Headache Management Center of Excellence,
International Medical Center, Jeddah, Saudi Arabia.
Objectives: The objective of this study is to evaluate the effectiveness
of the injection of Botox in the treatment of transformed migraine (TM).
Background: Transformed migraine (TM) is a chronic, daily headache, with
vascular quality. It usually occurs in people during their 20s and 30s with long
history of migraines. Additionally, patients usually use large doses of analgesics
and experience withdrawal headaches.
Methods: 40 patients were evaluated at the Pain & Headache Center,
IMC, KSA according to IHS classification. Patients were allocated to receive either
Botox injection which was perfomed as per the PREEMPT protocol [155-195 units] every
12 weeks for two cycles. Patients were not required to quit analgesics causing TM.
The primary efficacy end point was mean change in headache days as per 28 days from
baseline to weeks 21-24 post-treatment); or bridge therapy (N=21) as per patients’
preference. (Dihydroergotamine; Valporic acid; Magnesium sulfate; Lornoxicam; and
Granisetron) was provided as per protocol over 3-5 days. Oral bridge therapy
(Eletriptan and Etoricoxib) was administered daily for 15 days. This was followed by
Topiramate 100mg daily for 6 month as a preventive therapy. Inclusive criteria: 19
males, 21 females; ages 20-50 years, with a mean of 34. Exclusive criteria:
pediatrics; patients older than 50, with uncontrolled diabetes, blood pressure,
other neurological deficits; or pregnancy.
Results: Average symptomatic improvement of 79%, according to numeric
pain scale, was recognized in patients receiving Botox therapy and appreciated
within 10-15 days of therapy. However, an average improvement of 60% was recognized
by patients receiving oral bridge therapy and appreciated within one month of
therapy.
Conclusions: Patients who received Botox injection as per PREEMPT
protocol showed more rapid and significant symptomatic improvement of their headache
after the treatment as compared to the oral bridge therapy.
P80
Migraine with Visual and Sensory Aura after Atrial Septal Defect
Closure
L. Green1, C. Ugurlu1, S. Sahai-Srivastava1
1Neurology, University of Southern California, Los Angeles, CA,
USA.
Objectives: To describe a patient with atrial septal defect (ASD)
closure presenting with migraine with visual and sensory aura and to review
literature of similar cases.
Background: Patients with migraine prior to ASD closure commonly report
a decrease or resolution of their headaches after surgery. However, 0.2 to 12% of
patients experience new occurrence of migraine with aura (MA) or worseningof
previous migraines after ASD closure. Ostium secundum comprise about 90% of all
septal defects, and closure is via open-heart surgery or with less invasive cardiac
percutaneous transcatheter closure devices. MA is reported more frequently in
younger females undergoing percutaneous transcatheter closure. Most auras in these
patients are visual and sensory auras are not commonly reported.
Methods: This is a case report and review of literature.
Results: A 22-year old woman presented to our clinic with complaints of
new onset severe headaches associated with visual symptoms, one day after ASD
closure via percutaneous transcatheter Amplatzer septal occluder. A 1.3 cm secundum
type ASD had been diagnosed during workup of shortness of breath. Prior to surgery a
transthoracic echocardiogram revealed 60% ejection fraction and a severely dilated
right ventricle. Patient reported severe generalized throbbing headaches twice daily
lasting over 4 hours. Her visual symptoms including zig zagging lines, a large fixed
blank spot in her vision, photophobia, phonophobia, nausea, difficulty
concentrating, and lightheadedness during these episodes. She also reported two
episodes of numbness of the right cheek and right arm preceding her headache lasting
less than an hour. She did not have a prior history of headaches and family history
was unremarkable for migraine. Neurological examination and MRI of brain were
unremarkable. A diagnosis of chronic MA was made and she was placed on daily
preventative treatment for migraine. She reported that her migraine symptoms were
much more disabling than her previous ASD related symptoms. Various etiologies
leading to pathogenesis of migraine following ASD closure have been postulated
including paradoxical embolism, paradoxical transfer of headache provoking
neurotransmitters, changed intra-atrial pressure, platelet activation on the surface
of the device, nickel allergy, or release of atrial natriuretic peptide associated
with the stretch of the atrial septum caused by the device. Presence of atrial
shunts together with migraine with aura may be infrequently familial. We hypothesize
that in our patient, increase in cardiac output and overall volume to the left side
of the heart may have triggered migraines.
Conclusions: Young patients with valvular surgery should be counseled
extensively regarding the risk of developing MA and its long-term implications.
Migraine is a chronic neurological condition, however contrary to migraine without
aura, MA is emerging as a specific entity with clear-cut risk among women of both
symptomatic and asymptomatic strokes, and is associated with a higher cardiovascular
morbidity and mortality. More research is necessary to confirm our findings.
P81
Withdrawn by the author.
P82
Resolution of Refractory Migraine with Sodium Oxybate
F. Conidi2, F. Conidi1
1Florida Center for Headache and Sports Neurology, Port Saint
Lucie, FL, USA; 2Neurology, Florida State University College of
Medicine, Tallahassee, FL, USA.
Objectives: Is Sodium Oxybate (Xyrem) a possible treatment for
refractory migraine headaches.
Background: There are very few treatment options available for patients
with refractory headache. Many patients with chronic headache experience difficulty
in initiating and maintaining sleep, along with a lack of quality sleep. We
attempted to assess the efficacy of Sodium Oxybate (Xyrem) in a 25 year old female
with an 18 year history of headache and an 8 year history of Chronic/Refractory
Migraine Headache. The patient had been seen at numerous academic headache centers
in the USA and tried on multiple abortive and preventative medications, undergone
inpatient treatment and had a marginal response to a dual neuro-stimulation
trial.
Methods: Retrospective case analysis using a visual analog pain scale
and headache diary. Endpoints included the decrease in number of headache days,
decrease in migraine days, and decrease in headache intensity at 24 weeks (VAS),
decrease in overall disability (VAS). Epworth and pre and post poly-sonograms were
used to measure sleep efficiency, latency to sleep, latency to REM, amount of REM
sleep and alpha intrusion into stage 2 and 3 sleep.
Results: 24 weeks after initiating Sodium Oxybate our patient
experienced improvement in the total number of headache days (-18), Migraine days
(-12). Headache intensity was decreased and there was a marked improvement in
overall disability. Improvements in sleep efficiency, latency, REM latency, and an
improvement in the amount of REM sleep, along with a decrease in the amount of alpha
intrusion into stage 2 and 3 sleep were also seen.
Conclusions: Sodium Oxybate may be an effective treatment for Chronic
and Refractory migraine headaches in patients with underlying issues with sleep.
Further controlled studies are needed.
P83
First Experiences with Onabotulinumtoxin A (Botox) in Patients with Chronic
Migraine in Czech Republic-Preliminary Data
D. Dolezil
Prague Headache Centre, DADO MEDICAL s.r.o., Prague, Czech Republic;
Departmen of Neurology, University Hospital Hradec Králové, Hradec Králové,
Czech Republic.
Objectives: This is the first experience to assess efficacy, safety and
tolerability of onabotulinumtoxin A (BOTOX) as headache prophylaxis in adults with
chronic migraine in Czech Republic.
Background: Several studies have demonstrated a effect of
onabotulinumtoxin A in patient with refractory chronic migraine.
Methods: ICHD-II criteria for chronic migraine were applied to symptoms
described by patients headache. Diagnosis was made by ICHD-II criteria for chronic
migraine. MIDAS and HIT-6 was applied in all patients at week 0 and at follow-up,
three month and six months after first injection. Patients diary was provided for
six months for documentation of headache episode frequency. All patients had poor
headache control, poor quality of life, high disability scores and high acute
medication intake.Subjects were treated to injections every 12 weeks of
onabotulinumtoxin A (150 U). The primary endpoint was mean change from baseline in
headache episode frequency at week 24. The second endpoint was mean change from
baseline in HIT-6 and MIDAS at week 24.
Results: We reported preliminary data of 7 patients (2 males and 5
females), mean age 56 years (median 48 years), who fulfilled ICHD-II criteria for
chronic migraine Mean score on a pain scale of 0-10 were 8 (standard deviation 2) at
week 0, MIDAS grade IV (severe disability) at week 0 and HIT -6 mean score 65
(median 66) at week 0. Two patients (1 male and 1 female) interrupted treatment for
lack of efficiency at week 12. The rest of patients still take the treatment. The
subjects had not any adverse event.
Conclusions: We need to treat more subjects with onabotulinumtoxin A.
Unfortunately, health insurance not covered the treatment of chronic migraine with
onabotulinumtoxin A (Botox) in Czech Republic.
P84
Ending Emesis: Use of Aprepitant To Manage Nausea Associated with Intravenous
Dihydroergotamine (DHE)
D.E. Chou1, J. Corroo2, P.J. Goadsby2
1Department of Neurology, Columbia University Medical Center, New
York, NY, USA; 2Headache Group, Department of Neurology, UCSF Medical
Center, San Francisco, CA, USA.
Objectives: To assess the efficacy and tolerability of oral aprepitant
in controlling nausea associated with intravenous dihydroergotamine (DHE)
administered for medically-refractory migraine.
Background: Intravenous DHE is effective in the treatment of
medically-refractory migraine, particularly when nausea is well-controlled. Many
patients have severe nausea despite the use of multiple anti-emetic medications.
Aprepitant is a selective, high-affinity antagonist of the neurokinin-1
(NK1) receptor that mitigates the emetogenic mechanisms associated
with substance P. It is used in the prevention of postoperative and
chemotherapy-induced nausea and vomiting, but has not been previously studied in the
prevention of DHE-related nausea.
Methods: We reviewed prospectively collected inpatient data on nausea in
patients with migrainous disorders admitted to the UCSF Headache Center for a
five-day course of intravenous DHE and who received oral aprepitant as adjunctive
anti-emetic therapy due to refractory nausea. Peak and average daily nausea scores
were determined pre- and post-aprepitant from patients’ hourly dairies (rating
headache and nausea on a ten-point visual analog graph) and were categorized as mild
(0-3), moderate (4-6), or severe (7-10). The efficacy of aprepitant was assessed via
the following parameters: reduction in either average or peak daily nausea score,
cessation of emesis following administration of aprepitant, and ≥50% reduction in
the number of PRN anti-nausea medications.
Results: A total of twenty-three cases were identified, with admission
diagnoses of chronic migraine with or without aura, medication overuse, and New
Daily Persistent Headache of a migrainous type. In all twenty-three cases,
aprepitant was found to be effective in reducing nausea in at least one of the three
outcome measures; this was also reflected by patients’ subjective report of
effectiveness. Ten of these twenty-three patients (43%) demonstrated a response in
all parameters. In all patients who developed emesis (n=10), the addition of
aprepitant resulted in complete cessation of emesis. In the subgroup of patients
withdrawing from cannabis (n= 6), nausea was noted to be particularly severe and all
patients demonstrated a response in at least two of the three outcome measures. No
side effects from aprepitant were reported by any patients.
Conclusions: Oral aprepitant appears to be a novel, effective, and
well-tolerated treatment for controlling nausea and vomiting related to intravenous
DHE administration. Confirmation of our findings through further prospective studies
would improve current intravenous DHE protocols for the treatment of refractory
headache.
P85
Interventional Therapies at the C1-C3 Nerve Roots for Headache
Disorders
M.M. Johnston1, S.E. Jordan1, A.C. Charles1
1Neurology, University of California, Los Angeles, Los Angeles,
CA, USA; 2Neurology, University of California, Los Angeles, Los
Angeles, CA, USA; 3Neurology, University of California, Los Angeles,
Los Angeles, CA, USA.
Objectives: The objectives of this study are to characterize the pain
referral patterns at the C1-3 levels through multimodal stimulation, and to
investigate the potential efficacy of a novel, brief low temperature radiofrequency
rhizolysis (BLT-RF) as a therapy for patients with occipital pain.
Background: The upper cervical structures are viewed as important
targets for the interventional treatment in primary and secondary headache
disorders. The specific role of the C1-3 nerve roots in the pathophysiology of
headache remains uncertain. Cadaveric studies have shown the presence of dorsal root
ganglia at the C1 level, which suggests a previously unrecognized sensory function.
An increased understanding of the role of C1, C2 and C3 in head pain is important
for the advancement of therapeutic interventions.
Methods: This study is a retrospective review of data from 12 patients
with occipital pain (8 of whom also had migraine) who underwent multi-modal
provocation at the C1, C2, and C3 levels under fluoroscopic guidance, followed by
nerve root block with anesthetic and steroid. 9 patients underwent subsequent BLT-RF
of the C1 spinal nerve and C2 and C3 dorsal root ganglia.
Results: All patients with migraine reported their typical periorbital
or orbital pain with C1 stimulation. Patients without migraine reported occipital or
cervical pain with stimulation at the C1 level. Stimulation of the C2 and C3 level
evoked pain in occipital and cervical distributions, consistent with previous
reports in the literature. Patients who had temporary relief from the nerve block
reported sustained pain relief of >50% from the BLT-RF for up to 11 months.
Conclusions: The periorbital or orbital pain produced by direct
stimulation of the C1 spinal nerve suggests that the C1 nerve root level might be
pertinent in headache disorders where pain occurs in the occipital and periorbital
regions. Therefore, C1 may represent a therapeutic target for migraine and cluster
headaches. The BLT-RF technique appears safe and effective with a longer duration of
pain relief than nerve block with steroids.
P86
Evaluation of the Typical Duration of Migraine Aura: A Clinically-Based
Study
M. Viana1, M. Linde2, G. Sances1, N.
Ghiotto1, E. Guaschino1, G. Nappi1, P.J.
Goadsby3, C. Tassorelli1
1Headache Science Center, C. Mondino National Institute of
Neurology Foundation, IRCCS, Pavia, Italy; 2Norwegian National
Headache Centre, Department of Neuroscience, Norwegian University of Science and
Technology, Trondheim, Norway; 3Headache Group - Department of
Neurology, University of California, San Francisco, San Francisco, CA,
USA.
Objectives: To evaluate the distribution of the duration of each
individual symptoms of non-hemiplegic migraine aura (NHMA) and of the whole NHMA in
a clinically-based population of patients. We also analyze intra- and inter-patient
variability of the duration of the aura.
Background: In the ICHD-II, NHMA duration is considered normal when it
lasts between 5 and 60 minutes, whereas hemiplegic migraine aura can be longer. A
recent systematic review of the topic (Viana et al., Cephalalgia, 2013 in
press) did not find any article exclusively focusing on the duration of
the aura. The pooled analysis of data from the literature on aura duration showed
the prevalence of patients in whom the whole NHMA lasted for more than one hour
varies between 11.6% and 31%.
Methods: We recruited 73 consecutive patients affected by NHMA at the
Headache Center of Pavia and of Trondheim (55 and 18, respectively), with the
intention to include a total of 100 patients. The study received the approval by the
local Ethics Committees and all patients signed an informed consent form. All the
patients prospectively recorded the characteristics of three consecutive attacks in
an ad hoc aura diary that included the the time of onset and the
end of each aura symptoms and the headache. The patient had to describe briefly each
aura symptoms, the main characteristics of headache attacks and the timing of the
analgesic intake. We also collected demographic and clinical data on each
patient.
Results: Of the 73 patients recruited so far, 14 completed the diaries
during three consecutive auras for a cumulative number of 42 auras recorded. Three
patients dropped-out. Visual aura lasted for more than one hour in 13 out of 40
auras (32%), somatosensory aura in 5 out of 15 auras (33%), aphasic symptoms in 1
out of 4 (25%) and the whole aura duration in 15 out of 42 auras (35%). One patient
out of 14 experienced one aura with visual symptoms lasting for 30 minutes in 2
episodes, 90 minutes in a third one.
Conclusions: Our preliminary data seem to indicate that the duration of
NHMA, whether single symptoms or the whole aura, may be longer than one hour in a
significant proportion of migraineurs.
P87
State Depression during the Migraine Cycle: A Prospective Study
M.A. Louter1,2, W.P.J. van Oosterhout1, E.W. van
Zwet3, M.S. van Noorden2, F.G. Zitman2, M.D.
Ferrari1, G.M. Terwindt1
1Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 2Psychiatry, Leiden University Medical Center, Leiden,
The Netherlands; 3Biostatistics, Leiden University Medical Center,
Leiden, The Netherlands.
Objectives: Study the temporal relationship between timing of migraine
attacks and depressive symptoms.
Background: Migraine patients have a three times more increased risk of
depression. No studies have examined the temporal relationship between attacks and
depressive symptoms.
Methods: We performed a prospective diary study in a large cohort of
migraine patients (n=504). Migraine diagnoses were based on ICHD-II criteria.
Participants filled out a daily diary on migraine status and depressive symptoms
during a 1-month period. We randomly selected one whole migraine cycle per
participant. A migraine cycle consisted of a continuous period of 1 inter-ictal day,
3 pre-ictal days and 1 migraine day. Also a recovery day was counted, as the first
headache free day after a migraine cycle. In patients with one migraine day the
recovery day followed directly after the first migraine day. In patients with more
than one migraine day the recovery day was the first headache-free day after a
number of migraine days. Severity of depressive symptoms was defined using 5
questions, covering 5 items from the DSM-IV classification for depression. On each
of these items participants indicated on a 5-point scale (0-4) to what extent this
symptom was present on the current day (total scoring range from 0-20). Primary
analysis was performed using a repeated measurements model with post-hoc testing. In
a secondary analysis we tested whether the presence of depressive symptoms during
the migraine cycle is influenced by lifetime depression.
Results: On the migraine day, participants scored significantly higher
on the depressive symptoms scale (which does not indicate that they fulfil the
criteria for a depression) than on all different days of the migraine cycle
(p<0.001). The total score on the migraine day ranged from 0-18 (median 3).
Persons with a lifetime depression scored significantly higher on all days of the
migraine cycle than participants without a lifetime depression (p<0.001). No
differences between participants with and without a lifetime depression were
observed in the change of the depressive symptoms scores between the days of the
migraine cycle.
Conclusions: Migraine patients report significantly more depressive
symptoms during their migraine day than on all other days of their migraine cycle.
This does not necessarily indicate that they fulfil the criteria for a depression.
Migraine patients who fulfil the criteria for a lifetime depression have higher
scores on all days of the migraine cycle.
P88
Association of History of Migraine with Aura and Larger Infarct Volume in Acute
Stroke
S.J. Nahas1, H.N. Dave2
1Neurology, Thomas Jefferson University, Philadelphia, PA, USA;
2Neurology, Vanderbilt University Medical Center, Nashville, TN,
USA.
Objectives: To determine wither patients who have a history of migraine
or aura develop larger infarcts in acute stroke.
Background: A history of migraine, particularly with aura, is a risk for
stroke. Cortical spreading depression (CSD) is believed to occur both in acute
stroke and migraine aura. Animal models suggest that CSD concurrent with ischemic
stroke may be associated with larger infarcts. Individuals with migraine may be
predisposed to CSD and therefore larger acute infarcts.
Methods: Patients able to communicate presenting to a single
tertiary-care hospital with possible or confirmed acute stroke were interviewed to
determine the presence and nature of current or past headache as well as any
headache occurring within 24 hours of stroke symptom onset. Volumes of confirmed
acute infarcts were measured from diffusion weighted and apparent diffusion
coefficient images. A path model was hypothesized based on potential predictors of
infarct size including stroke location, prior history of migraine, prior history of
aura, and presence of peri-stroke headache.
Results: Data from 139 patients were analyzed using IBM SPSS v 20 with
alpha set at p < 0.05. Results of the path analysis revealed that history of aura
had a significant direct affect on infarct volume. The re-specified model indicated
that without controlling for location, the geometric mean (GM) of the infarct volume
for those without prior aura was 4.04 cm3 while the GM for those with prior aura was
10.89 cm3 (2.69 times larger) (p < 0.0001). After controlling for stroke
location, the GM for those without prior aura was 1.22 cm3 while the GM for those
with prior aura was 3.96 cm3 (3.24 times larger) (p = 0.004).
Conclusions: These data show, for the first time, an association between
history of aura and larger infarcts. Further studies are needed to confirm this
finding and explore its implications.
P89
Reliability of Assessing Lifestyle and Trigger Factors in Patients with
Migraine
K. Zebenholzer1, S. Frantal2, D. Lieba-Samal1, C.
Woeber-Bingoel3, C. Woeber1
1Department of Neurology, Medical University of Vienna, Vienna,
Austria; 2Institute of Medical Statistics, Medical University of
Vienna, Vienna, Austria; 3Department of Child and Adolescent
Psychiatry, Medical University of Vienna, Vienna, Austria.
Objectives: To compare the assessment of lifestyle and trigger factors
in retrospective questionnaires to that in daily diaries, to analyse the correlation
between these two ways of assessment and to examine how often possible trigger
factors actually are followed by headache.
Background: Many lifestyle factors are blamed as triggers for migraine
and headache. But most studies on triggers used patients’ retrospective self-report
and may suffer from recall bias.
Methods: Patients with migraine or probable migraine (without or with
aura, without or with co-existing episodic tension-type headache) filled in two
questionnaires, one on lifestyle in general and one on trigger factors and then kept
a diary. The questionnaires and the diary included the same set of 45 items possibly
related to migraine. The questionnaires covered the previous three months and the
diary had to be kept for the subsequent three months. In the diary, the patients had
to assess each item every day irrespective of the presence of headache and they had
to record the occurrence of headache as well as all headache characteristics
required for diagnosing migraine and tension-type headache according to ICHD-2. We
analysed the agreement between questionnaires and diaries and correlated the
frequency of each variable of the lifestyle questionnaire to its frequency on all
diary days and the frequency of each variable of the questionnaire on trigger
factors to its frequency on day -1 as well as on day -2 and day 0 of headache
onset.
Results: Of 415 patients screened, 327 patients with completed
questionnaires and diaries were analysed (283 female, 44 male, mean age 41.9 years).
We found a statistically significant correlation between lifestyle questionnaire and
diary in 91% of the variables. In contrast, the questionnaire on trigger factors and
the diary entries on days before headache onset correlated in 33% of the variables.
Only 25 – 36% of all days with a certain possible trigger factor actually were
followed by headache on the next day. Similar results were found for the days 0 and
-2 of headache onset.
Conclusions: Comparing retrospective questionnaires to prospective
diaries in patients with migraine, retrospective assessment of lifestyle is
reliable, but headache triggers are overestimated when assessed in questionnaires.
Therefore, prospective diary recordings should be used for assessing reliably the
influence of headache triggers.
P90
Premonitory Symptoms as a Predictor for Migraine Attacks; a Cross-Sectional and
Prospective Study
W.P.J. van Oosterhout1, G.G. Schoonman1, T.
Stijnen2, E.W. van Zwet2, G.M. Terwindt1, M.D.
Ferrari1
1Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 2Medical Statistics, Leiden University Medical Center,
Leiden, The Netherlands.
Objectives: To assess whether migraine attacks can be predicted by
migraine patients based on premonitory symptoms.
Background: A number of migraineurs might be able to predict their
attacks with some degree of accuracy based on premonitory symptoms, which are
reported by over 70% of patients and show large clinical heterogeneity. It is
unclear whether groups of patients with specific premonitory profiles can be
distinguished, elucidating possible distinctive pathophysiologic mechanisms involved
in attack initiation. We aimed to investigate i) how well patients can predict their
next migraine attack, based a) on occurrence of premonitory symptoms, and b) on
subjectively assessed chances; ii) if a subgroup of well-predicting patients can be
identified.
Methods: Prospective premonitory data were collected from migraineurs
(n=711) via the LUMINA website by a web-based diary study in n=711 migraineurs. Data
on occurrence and severity of 43 different premonitory symptoms were collected
during one month. Patients scored each of the symptoms, and rated overall chance
(0-100%) of getting a migraine attack the next day. General Linear Mixed Models were
used to perform prediction analyses.
Results: In the prospective study, n=711 migraineurs reported 1,775
migraine attacks (mean±SD: 2.7±1.5 per person). In total, 88.8% of migraineurs
reported premonitory symptoms, of which hypersensitivity and fatigue complaints were
most common, followed by gastro-intestinal, affective and thermoregulation symptoms.
Overall, premonitory symptoms (PS) were predictive of a migraine attack in the next
three days (OR 4.04; 95%C.I. 0.46-35.81). A subgroup of migraineurs (10.8%) was
classified as predictors, since they were able to well predict the occurrence of a
migraine attack the next day based on an overall 0-100% score.This subgroup was able
to predict a migraine attack within three days very accurately (OR 15.6; 95%C.I.
1.73-139.71).
Conclusions: Migraine patients can, overall, moderately well predict
their next migraine attack, whilst a subgroup are very good predictors. Prediction
of migraine attacks based on occurrence and severity of individual premonitory
symptoms is comparable to a prediction based on an overall assessed chance.
P91
Autonomic Dysfunction in Migraine: Comparison between Migraine Populations with
and without Orthostatic Intolerance
Objectives: (1) To characterize any autonomic dysfunction in a
population of migraineurs suffering from orthostatic intolerance (OI) and compare it
with a population not suffering from OI, and
(2) To assess clinical neurocardiac physiological parameters and morphometrics of
small fiber anatomy, including sudomotor innervation, on skin biopsy, in both
populations.
Background: OI is defined by any combination of the following symptoms
that arise when a patient assumes an upright posture: tachycardia and chest
discomfort, fatiguability and exercise intolerance, lightheadedness and near
syncope, inattention, anxiety, visual obscuration, acral symptoms and lower
extremity weakness. OI is a manifestation of autonomic imbalance and may arise from
central and/or peripheral nervous system dysfunction. The presentation of a migraine
patient with OI is under-recognized and frequently misdiagnosed.
In phase I of this study, 37 male and female adults between 18 and 75 years,
suffering from migraines with and without auras, as defined by the IHS, and who
complained of symptoms of OI were studied with head upright tilt-table (HUT)
testing, clinical autonomic reflex testing, quantitative sudomotor axon reflex
testing (QSART), and punch skin biopsy for morphometric evaluation of small fiber
density.
In phase II an age-matched population of 22 migraineurs with and without auras was
studied in identical fashion, and the two populations were compared with respect to
laboratory features and biopsy evidence of small fiber sensory neuropathy
(SFSN).
Methods: Statistical analyses were both descriptive and comparative.
Associations between quantitative results were estimated with Pearson and Spearman
coefficients. Group comparisons for qualitative data were performed using chi-square
or Fisher’s exact test and comparisons of quantitave data were performed using
T-test or Wilcoxon rank sum test.
Results: Phase 1 and 2 populations were demographically similar and
overwhelmingly female.
In Phase I 36/37 patients (97%) had a positive 45 minute HUT (HUT45) [POTS +/-
orthostatic hypotension (OH) +/-vasovagal response (VVR)] while 15/36 (42%) had a
positive 10 minute HUT (HUT10). 21/37 (57%) phase 1 patients had a positive skin
biopsy for SFSN while 16/37 (43%) had a negative skin biopsy.
Among Phase II patients HUT45 was positive in 15/22(68%) and negative in 7/22(32%).
Positive and negative skin biopsies were distributed equally between both HUT45
positive and HUT45 negative groups.
Conclusions: Using clinical laboratory methods, including 45 minute HUT
testing, detection of POTS, OH and VVR is common among migraineurs with and without
symptoms of OI.
Biopsy presence of SFSN fails to significantly differentiate migraineurs symptomatic
or asymptomatic of OI nor does it distinguish migraineurs with positive HUT45 from
those who are negative.
Peripheral autonomic dysfunction, as measured by morphometric analysis of skin
biopsies, fails to fully explain the cause of OI in migraine sufferers. Central
nervous system dysfunction may also play a role.
P92
Evaluation of Balance in Vestibular Migraine and Migraine Patients without
History of Vertigo
G. Akdal1, B.D. Balci2
1Neurology, Dokuz Eylul University School of Medicine, Izmir,
Turkey; 2School of Physical Therapy and Rehabilitation, Dokuz Eylul
University, Izmir, Turkey.
Objectives: To assess and compare balance and gait between vestibular
migraine (VM) patients and migraine patients without history of vertigo.
Background: VM is the second most common diagnosis in dizzy clinics. In
addition to vertigo attacks, patients with VM might complain being off-balance
causing some difficulties in their daily activities. A few studies show that
migraine patients, even without history of vertigo, have subtle balance
problems.
Methods: 30 definite VM patients, 26 migraine patients without history
of vertigo (migraine only) and 30 subjects without migraine were studied. Twenty-six
migraine only patients and 30 subjects without migraine were the control groups.
Vestibular migraine patients were diagnosed according to Neuhauser criteria afer
neurootological examination including bithermal caloric tests. Balance and gait were
assessed by using of Clinical Test of Sensory Interaction and Balance, Berg Balance
Scale, Dizziness Handicap Inventory, Falls Efficacy Scale and Dynamic Gait Index.
Motion sickness susceptibility questionnaire short-form (MSSQ) was also given.
Kruskal–Wallis one-way analysis of variance was done for statistics using SPSS 15
software.
Results: VM patients demonstrated worse scores in all balance tests
compared with two control groups. Migraine only patients showed significantly worse
balance scores than migraine-free controls. VM patients and migraine only patients
had significantly worse MSSQ childhood section scores than controls, but there was
not any difference between VM and migraine only patients, VM patients had
significantly worse scores in MSSQ adult section than both migraine only patients
and controls.
Conclusions: 1-VM patients have problems in static and dynamic balance
and they have increased risk of falling and motion sickness intolerance. VM patients
need vestibular rehabilitation for a better quality of life.
2-Migraine only patients also showed some significant balance problems. They might
need vestibular rehabilitation for better daily activity performance. Migraine only
patients had compansation in MSSQ adult section interestingly.
P93
Characteristics of Migraine with Aura in a Prospective Clinical
Trial
J.M. Hansen1, P.J. Goadsby2, A. Charles1
1Department of Neurology, Headache Research and Treatment Program,
University of California Los Angeles, Los Angeles, CA, USA; 2Headache
Group, Department of Neurology, University of California, San Francisco, San
Francisco, CA, USA.
Objectives: To describe the clinical presentation of migraine with
typical aura in a large group of patients enrolled in a clinical trial, and to
compare self-reported migraine symptoms to prospective recordings of attacks in the
same patients.
Background: About a third of migraine patients have attacks with aura,
usually one or more neurological symptoms arising from the cortex or brainstem. The
clinical presentation of aura can vary considerably and many descriptions of the
clinical characteristics are based on purely retrospective studies.
Methods: 267 patients with migraine with typical aura according to
current ICHD criteria were enrolled from 16 centers for a clinical trial. We
reviewed data collected for this trial regarding the clinical presentation of
migraine aura, headache, and associated symptoms. Baseline characteristics provided
by patients on inclusion were compared with migraine symptoms collected
prospectively during the study. Only attacks starting with a migraine aura were
recorded.
Results: The majority of patients (70%) reported that more than 50% of
migraine attacks were preceded by aura. Visual aura symptoms were reported by all
patients, the most prevalent symptoms being dots or flashing lights (70.4%), wavy or
jagged lines (46.8%) and blind spots (42.3%). Non-visual aura was less prevalent,
reported by around half the patients. The most prevalent non-visual aura symptoms
were somato-sensory(29.5%), difficulty in recalling or speaking (25.8%) and changes
in smell (18.7%). Symptom intensity for migraine related symptoms (pain, nausea,
photo- and phonophobia) was mainly (≥70%) graded moderate to severe. Patient
reported data prior to the trial indicated a consistently higher symptom score (more
severe phenotype) than in the prospectively collected data, (P<0.01 for all)
(figure 1).
Columns on the left for each symptom are patient-delivered data (N=267
attacks) and columns on the right are from the prospective recordings
(N=365 attacks).
Conclusions: Based on this large clinical collection of data exclusively
from MA attacks, we show that visual aura symptoms are more prevalent than
non-visual aura symptoms. The severity of self-reported migraine symptoms was great
than that recorded in the prospective data set.
P94
Resource Utilization and the HIT-6 Score in Migraine Patients
W.J. Miller2, R. Kaniecki1
1Department of Neurology, University of Pittsburgh, Pittsburgh,
PA, USA; 2School of Medicine, University of Pittsburgh, Pittsburgh,
PA, USA.
Objectives: This study examines the association between migraine
patients’ HIT-6 score and their resource usage as measured by phone contacts and
unscheduled visits with the University of Pittsburgh Headache Center, as well as
emergency department visits.
Background: The Headache Impact Test-6 (HIT-6) score is simple
questionnaire that headache patients can complete while waiting for their headache
provider. It assesses six aspects of a patient’s headaches: pain, daily activities,
social impact, energy level, emotional impact, and concentration. The HIT-6 score
has been validated as a measurement of the impact of headache and its treatment on
an individual’s functional health and well-being. However, no studies have been
performed that examine the HIT-6 score’s ability to predict resource utilization
among migraineurs.
Methods: The study was a retrospective cohort study. Patients visiting
the UPMC Headache Center from April 1, 2010 to August 31, 2010 diagnosed with
migraine headaches were recorded into the data set. A total of 627 patient visits
were recorded with each record representing a unique patient. Patients’ HIT-6 scores
were recorded along with all contacts with the UPMC Headache Center over the
following six months. Cochran-Mantel-Haenszel X2 statistics, single
variable ANOVA models, and logistic regression models were used to test the HIT-6
score’s association with other variables in the data set.
Results: The HIT-6 score was associated with many aspects of lifestyle
disturbance, both relating to the patients’ migraines and not. Positive correlation
was seen between the HIT-6 score and all levels of migraines recorded in the data
set (total, severe, and incapacitating). Additionally, association was seen with
other markers of migraine impact such as ED visits in the previous six months,
presence of insomnia, and medication usage over the previous 30 days. Positive
correlation was also seen with depression rating and anxiety rating (both a 0 – 10
self-assessed rating). Most importantly, HIT-6 scores were statistically associated
with the number of unscheduled contacts a given patient had with the UPMC Headache
Center over the 6 months following the visit where the HIT-6 questionnaire was
administered.
Conclusions: The HIT-6 score is a simple questionnaire, yet a high score
clearly paints a distinct portrait of a patient struggling with high migraine
burden. A high HIT-6 score reveals a patient who may be using significant medication
but is still suffering from debilitating headaches. This patient is more likely to
suffer from depression and anxiety, and is more like to be sleeping poorly.
Additionally, these patients are much more likely to have repeat contact with their
headache provider, defined as either a telephone call or unscheduled visit to the
office. Identification of these migraineurs and devotion of additional education
regarding care plans could potentially reduce costs associated with office
contacts.
P95
Cluster Headache and Depression: A Case-Control Study
M.A. Louter1,2, L.A. Wilbrink1,4, J. Haan1,5, E.W.
van Zwet3, W.P.J. van Oosterhout1, F.G. Zitman2,
M.D. Ferrari1, G.M. Terwindt1
1Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 2Psychiatry, Leiden University Medical Center, Leiden,
The Netherlands; 3Biostatistics, Leiden University Medical Center,
Leiden, The Netherlands; 4Neurosurgery, Maastricht University Medical
Center, Maastricht, The Netherlands; 5Neurology, Rijnland Ziekenhuis,
Leiderdorp, The Netherlands.
Objectives: To investigate the comorbidity of cluster headache and
depression.
Background: Cluster headache is often called suicide headache, and
suicidal tendencies have been reported in 25-55% of patients. However, the
comorbidity of cluster headache and depression has not been extensively studied.
Methods: We performed a large case-control study within LUCA (Leiden
University Cluster headache neuro-Analysis programme). CH diagnoses were based on
ICHD-II criteria. Depression was assessed using validated depression questionnaires
(HADS and CES-D) and supplementary questions on lifetime depression. Data were
analyzed with logistic and linear regression models.
Results: Cluster headache patients (n=462) had an almost three times
higher odds for lifetime depression than healthy controls (n=177) (OR 2.8; 95% CI
1.7-4.5). Furthermore, having chronic cluster headache and having active attacks
(last attack < 1 month) were associated with current depression. The latter seems
to be explained by sleep disturbances (presumably due to nocturnal cluster headache
attacks).
Conclusions: Cluster headache patients have an almost three times
increased risk for lifetime depression. Active depression is presumably explained by
sleep disturbance due to current nocturnal attacks.
P96
Pain Rehabilitation: Can It Help Patients with Intractable Headache?
Y. Zheng1, S. Tepper1, E. Covington1, M.
Mathews1, J. Scheman1
1Neurological Center for Pain, Cleveland Clinic, Cleveland, OH,
USA.
Objectives: To assess the efficacy of chronic pain rehabilitation
programs in treating headache as an alternative to primary or tertiary standard
care.
Background: Incapacitating headaches can have a significant impact on
people’s lives. Studies have investigated both prevalence and medical treatment of
chronic headache, but few have reported on the efficacy of treating these disorders
within a comprehensive, intensive interdisciplinary chronic pain rehabilitation
program (CPRP). CPRPs provide team based comprehensive treatment of headache,
focusing not only on physical pain, but also its association with impaired mood and
function.
Methods: Retrospective analysis of 200 patients (80% female), ages 19 to
75, who completed the CPRP at the Cleveland Clinic, January 2007 - December 2011,
diagnosed using International Headache Society (IHS) criteria with migraine or
headache as a major complaint. Outcome measures included: pain intensity scores
(0-10/10), Depression Anxiety Stress Scale (DASS) scores, (measuring mood), and Pain
Disability Index (PDI) scores, (measuring function). Data were collected at
admission, discharge, 6 months, and 12 months following discharge. Repeated measures
T-test were used.
Results: There was a significant difference in pain intensity scores
between admission (M=6.59, SD=2.34) and discharge (M=3.54, SD = 2.67); t(122)=11.83,
p<0.001. Pain intensity scores decreased by 3.6 points from 6.4 to 2.8, which is
clinically significant.Similarly, there was a significant difference in admission
(M=42.4622, SD=11.62317) and discharge (M=17.6218, SD=13.27496) scores for PDI;
t(118)=18.406, p<.001. PDI scores decreased by an impressive 29.1 points,
shifting from 40.4 (severe disability) to 11.3 (mild disability). There was also a
statistically significant difference between depression scores at admission
(M=19.4837, SD=13.17862) and discharge (M=6.2480, SD=8.25102); t(122)=10.873,
p<.001. An average decrease by 9.9 points for depression indicates a shift from a
score of 15.1 at moderate to 5.2 at normal levels of depression. Admission
(M=14.2724, SD=10.07518) and discharge (M=7.0325, SD=7.59415) scores for anxiety
were also significantly different; t(122)=8.409, p<.001. Anxiety scores dropped
an average of 4.4 points from 11.4 to 6.5, which is a shift of one category from
moderate to mild. Results indicate that individuals had statistically and clinically
significant improvement in pain, mood, and function at all time points.
Conclusions: An interdisciplinary chronic pain rehabilitation approach
for patients diagnosed with headache can be effective in helping to decrease pain,
as well as in normalizing mood and function. Thus, CPRPs may serve as an alternative
treatment to primary and tertiary standard care, and interventional pain anesthesia.
P97
Migraine and Benign Paroxismal Positional Vertigo
B.K. Kim
Neurology, Eulji Hospital, Seoul, Republic of Korea.
Objectives: The aim of our study was to determine one-year prevalence of
migraine in patients with Benign paroxysmal positional vertigo (BPPV) compared to an
age- and sex- matched orthopedic control group.
Background: BPPV is most common cause of episodic vertigo.
Pathophysiological or statistical links between vestibular migraine/Meniere’s
disesae and migraine were documented. A potential link between migraine and BPPV was
also suggested.
Methods: A prospective study was conducted on a consecutive series of
184 patients (68 male, 116 women, aged from 14 to 85) with idiopathic BPPV. The
diagnosis of BPPV was based on typical findings of vertigo and nystagmus by
Dix-Hallpike maneuver and head turning in supine position. The diagnosis of migraine
was made on a personal interview with structured questionnaire according to the
International Classification Headache Disorders (ICHD-2).
Results: The prevalence of migraine was not higher in the BPPV (5.4%)
group compared to the control group (10.8%; p=0.09). All of the 10 patients with
BPPV and migraine were migraine without aura.
Conclusions: One year prevalence of migraine is not increased in
patients with BPPV. It is unlikely that migraine and idiopathic BPPV is
interrelated.
P98
Presence and Disability Related Dizziness in Migraine Patients with and without
Aura
G.F. Carvalho1, T.C. Chaves2, M.C. Gonçalves1, L.L.
Florencio1, F. Dach2, J.G. Speciali2, M.E.
Bigal3, D. Bevilaqua-Grossi1
1Departament of Biomechanics, Medicine and Locomotor Apparatus
Rehabilitation, Faculty of Medicine of Ribeirão Preto, Ribeirão Preto, Brazil;
2Department of Neurosciences, Faculty of Medicine of Ribeirão
Preto, Ribeirão Preto, Brazil; 3Merck Co & Inc., North Wales, PA,
USA.
Objectives: To evaluate the presence and disability related dizziness
using the Dizziness Handicap Inventory (DHI) in migraine patients with aura (MA),
without aura (M) and control group (CG).
Background: The relationship between vestibular disease and dizziness in
migraineurs is well established, showing an increased risk of presenting vertigo and
balance problems. The DHI it’s feasible to measure the self-perceived level of
handicap associated with dizziness assessing physical, emotional and functional
tasks. Higher scores are associated with functional deficits in physical
examinations and history of falls. Nonetheless, the impact of dizziness in
migraneurs is unexplored, especially in patients with aura.
Methods: Women were selected in an outpatient headache clinic and were
diagnosed with MA or M by neurologists experts on headache according to ICHD-II
(2004). Exclusion criteria included history of vestibular problems, systemic
disorders or other primary headaches. Based on a sample size calculation (α=5%,
β=80%) were selected 92 volunteers, 31 with MO (38±10), 31 with MA (37±8) and 30 CG
(33±9), witch were matched to patients by age. To compare dizziness between groups,
logistic regression and odds ratios were calculated. Results of the DHI test were
contrasted using the Kruskal Wallis test to a α<0.05, using SAS 9.2.
Results: A total of 80% of those with MA, 65% of M and 6.5% CG reported
dizziness (p<0.0001). MA increased risk of dizziness by 58 times relative to
controls, and M increased the risk by 25 times. Also DHI scores were significantly
higher in those with migraine relative to controls (p<0.01). Both migraine groups
had average scores classified as moderate impact for all three aspects (physical,
psychological, and functional) compared to controls (p<0.001). The migraine
groups were different to CG on the levels of severities.
Conclusions: The disability related dizziness is greater in migraneurs
than controls, without influence by aura. Presence of migraine, especially with
aura, increases the risk of developing dizziness. The dizziness is prevalent in
individuals with migraine, impacting several aspects of daily life.
P99
Clinical Predictors of Migraine Evolution in Elder Age
1Laboratory of Neurology and Clinical Neurophysiology, First
Sechenov Moscow State Medical University, Moscow, Russian
Federation.
Objectives: The study was focused on revealing clinical predictors of M
evolution/outcomes in M patients after the age of 50.
Background: It is known that migraine (M) could have different evolution
pathways in elder age including total cessation, partial cessation (M aura without
headache - late-life M accompaniment or Fisher’s syndrome) and M
continuation/persistence with typical attacks. M evolution in elder age as well as
factors determining M outcomes were not previously studied.
Methods: M patients suffering both from MO and MA (n=54, F-51, M-3, 50
to 75 y.o.) were divided according to outcome of the disease into 4 groups: 1) total
cessation during >1 year of both pain attacks and aura
(n=11, m.age 60), 2) partial cessation (Fisher’s syndrome) - the loss of pain
attacks during >1 year but with M aura preservation (n=8,
m.age 54), 3) M regress when M attacks became less severe (n=20, m.age 57.5) and 4)
M persistence with typical and severe attacks comparable to those in the middle age
(n=15, m.age 55). All patients underwent clinical intervew with careful history
focused on clinical manifestations during illness course and filled in headache
diary.
Results: According to the data obtained predictors of favorable M
outcomes (total cessation and regress, groups 1 and 3; p<0,05)
included: initial form “M with aura”, low attack frequency in active disease period
(at age 30-40) and complete stabilization of hormonal state by the time of
observation (menopause). Predictors of unfavorable outcomes
(persistence, group 4): initial form “M without aura”, high attack frequency in the
middle age and fluctuating hormonal state by the time of observation (for females
active menstrual cycle or premenopause). For group 2 with the cessation of pain and
preservation of M aura only one predictor was revealed - initial form “M with
aura”.
Conclusions: Main clinical predictors of M outcomes in the elder age
include initial (in active disease period) form of M and attack frequency and the
hormonal state (for female patients presence/absence of hormonal fluctuations).
P100
The Use of the Lamotrigine for Treatment of Migrainous Headache in Missouri
Veterans with Comorbid PTSD
S.A. Lucchese1,2, P. Sahota1,2
1Neurology, University of Missouri School of Medicine, Columbia,
MO, USA; 2Specialty Care, Neurology, Harry S. Truman Veterans
Memorial Hospital, Columbia, MO, USA.
Objectives: The study was performed to assess the possible utility of
lamotrigine for management of headache in the veteran population with PTSD.
Background: Lamotrigine has been shown to have little value for headache
management outside of SUNA/SUNCT or perhaps migraine with aura. Migraine without
aura has not been found to respond well to lamotrigine. It has been shown, though,
to be effective for the treatment of psychiatric disturbances such as bipolar
disorder and PTSD.
Methods: The nature this study was a chart review and retrospective
analysis initiated after it was noticed serendipitously that when lamotrigine was
used to treat the psychiatric symptoms of PTSD in the veteran population in
mid-Missouri some patients diagnosed with migraine headaches without aura reported
decreased headache frequency. Initial headache frequency was compared to frequency
after approximately 6 months of treatment. The final dose of lamotrigine ranged from
100mg/day to 200mg/day with the average being 121mg/day.
Results: Of the initial 15 patients evaluated, 13 reported greater than
50% reduction in headache frequency, which was the cut-off we used to define a good
response to therapy (84.7%). None of the patients noted a dramatic decrease in
headache intensity. The initial headache frequency ranged from 13 a month to daily
with an average of 25.4 headaches per month (standard deviation 6.9). The final
headache frequency ranged from one or less per month to one per day, the average
final frequency being 7.2 per month (standard deviation 8.3), a 75.7% improvement in
headache frequency (standard deviation 22.4).
Conclusions: Our findings indicate that there may be a place to use
lamotrigine for the management of headache with co-morbid PTSD.
Patients n=15
Number
Percent
Standard deviation
non-responders
2
13.3
N/A
responders
13
86.7
N/A
Headache days /mo. ave. at treatment onset
25.4
84.7
6.9
Headache days/mo. ave. at 6 months
7.2
8.3
8.3
Average Headache day reduction
18.2
22.4
22.4
P101
Blood Pressure and Heart Rate during a Migraine Attack
F. Dach1, F. Nobre2, J.G. Speciali1
1Department of Neuroscience and Behavioral Science, Clinical
Hospital, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
2Division of Cardiology, Clinical Hospital, University of São
Paulo, Ribeirão Preto, São Paulo, Brazil.
Objectives: To analyse the behavior of blood pressure (BP) and heart
rate (HR) during the headache of a migraine attack.
Background: There are controversies concerning the relationship between
blood pressure and headache. Moreover, there are no detailed studies on the behavior
of BP and the HR during the headache of a migraine attack.
Methods: Ten patients (nine women), 21 to 43 years-old, with migraine
diagnosis were selected. They had from 3 to 11 days of headache a month, no other
health problem, or use of any medication other than analgesics. Hypertension was
ruled out through 24-hour ambulatory BP monitoring (Dyna-MAPA ABP-Monitor, Cardio
Sistemas Coml. Indl. Ltda, Brazil). The patients were trained to use a home blood
pressure monitoring (HBPM) device (Dyna Klock, I.E.M. GmbH, Germany). To obtain the
measurements from pain-free period, they were asked to measure their BP from 4 to 5
consecutive days, 6 times a day (2 in the morning, 2 in the afternoon, 2 at night)
and to write in a card, simultaneously, if they were symptoms-free or not. We only
considered the measures made on symptoms-free period. To obtain the measurements
from headache period, the patients were asked to perform the HBPM from the beginning
to the end of the headache. During the first two hours of pain, they measured the BP
each 10 minutes, and after that each 15 minutes until the end of the headache.
Patients completed a headache diary in the beginning of headache and once per hour
until the end of the pain in order to certify the migraine attack. Due to ethical
issues, the use of 400 mg of ibuprofen was allowed from the end of the second hour
of pain. To statistical analysis, the mean values of systolic (SBP), diastolic
(DBP), mean blood pressure (MBP) and HR from pain-free period were compared with the
mean values of these variables from headache period.
Results: Comparing the mean values of BP from pain-free period to those
from headache period (SBP 119,09 vs 108,77 – IC95% 7,25-11,58; DBP 76,68 vs 70,35;
IC95% 3,94 – 7,10; MBP 90,69 vs 83,15; IC95% 5,24 – 9,85), we observed a
statistically significant reduction in BP during headache (p≤0,01). Comparing the
mean values of BP from pain-free period with those from headache period divided
hourly for the first four hours of pain, we observed a progressive reduction in BP
(SBP, DBP and MPB) between the first and second hours of pain and a sustained
reduction between the second and fourth hours. With regard to HR, we observed a
statistically significant increase in the mean values during the first hour of
headache with no differences in the remaining hours.
Conclusions: We observed a progressive reduction in BP during the
headache of a migraine attack, and an increase in HR in the first hour of pain.
P102
Optimization of Headache-Patient Satisfaction with an ICHD-II Based Exhaustive
Questionnaire
H. Furuyama1, S. Chiba1, T. Warabi1
1Clinical Brain Research Laboratory, Sapporo Yamanoue Hospital,
Sapporo, Japan.
Objectives: To optimize forms and/or implementation procedure of an
exhaustive headache questionnaire (ExQ) to maximize patients’
satisfaction.
Background: An ExQ is a valuable means of exploring the relationship
between the patients’ symptoms and headache diagnoses. However, it can also be
frustrating because of its length and complexity. In the worst case, that
frustration may precipitate the patients’ withdrawal from a headache specialty
outpatient clinic.
Methods: This study was approved by the ethics committee of our
hospital. Participants: 441 associates of our institution (287
females). The ExQ: From the complete ICHD-II we extracted 247 questions
which could be answered by participants’ statements. These items and additional
symptom-related questions not derived from ICHD-II were subdivided into 16
categories and then arranged in the following order: Patient information, Headache
Impact Test 6 (HIT-6) (1), Migraine Disability Assessment Scale
(MIDAS) (2) and the questions we created. Participants with
headache were asked to base their answers on their own headache experience and then
to evaluate the ExQ whereas those without headache were asked only to evaluate it
‘objectively’. Evaluation of the ExQ: We created an interview form to
help standardize evaluation of the ExQ. It comprised; i. The time required, ii.
Impression of time required to apply the ExQ, iii. Sufficiency (SF:
this indicated whether the ExQ was able to identify adequately the headache
characteristics. iv. overall satisfaction (OS). The latter three items
were measured using a visual analogue scale (VAS) with verbal anchors.
Two copies of this interview form were inserted, one in a random position and the
other at the end of the ExQ section. This randomization enabled us to determine the
correlations between the number of questions and the VAS values. Provisional
headache classification was determined based entirely on ExQ.
Statistics: We evaluated the correlations by Spearman’s rank
correlation coefficient (ρ) because no normal distribution was shown. The
comparisons of first and second interview form values were expressed by the Wilcoxon
signed-rank test.
Results: 224 participants had headache (migraine: 59, tension type
headache: 123). In the first interview form, the headache group’s OS did not
correlate with the number of questions, time required or impression of amount, but
did correlate with SF (ρ=0.6560, p<0.0001). HIT-6, MIDAS and headache types
didn’t affect this correlation. The first and second interview values showed no
significant difference. Only OS correlated with SF. Objective evaluation of the
non-headache group didn’t show any correlation between OS and SF.
Conclusions: OS is improved only if the headache patient feels
sufficient empathy. The answer to “How many questions are enough” ‘is individually
diverse. Multiple questions don’t always lower the patients’ satisfaction. However,
in this study, any modifiable factor which defines SF could not be identified. For
now, it is appropriate to use the ExQ unchanged and allow patients to answer in
sections as inclined.
P103
The Presence of Osmofobia Improves the Diagnosis of ID-Migraine?
M.E. Jurno1,2, J.A. Souza2, D.F. de Resende1, C.S.
Magalhaes e Silva1, C.C. Andrade1, G.N. Ferreira1,
N.F.P. Tavares1, T.M. Pascini1
1Neurology/Headache, Faculdade de Medicina de Barbacena,
Barbacena, Minas Gerais, Brazil; 2Neurology/Headache, Universidade
Federal Fluminense, Niteroi, Rio de Janeiro, Brazil.
Objectives: The advent Migraine extended-ID aims to compare the
ID-Migraine with ID-Migraine plus question about osmophobia for greater accuracy in
the diagnosis of migraine.
Background: Migraine causes a great impact on health of their patients,
affects about 18% of women and 6% of men, with peak prevalence between 25 and 55
years of age. The advent Migraine extended-ID aims to compare the ID-Migraine with
ID-Migraine plus question about osmophobia for greater accuracy in the diagnosis of
migraine.
Methods: It was included in this study a total of 269 patients waiting
for neurological evaluation at the neurologic clinic. Willingly, they completed the
questionnaire ID Migraine with an extra question about osmophobia, considered
positive for the diagnosis of migraine when they responded positively to at least
two of the four questions total. Then, in consultation with the neurologist, we used
the criterias of the International Classification of Headache for the diagnosis of
migraine, enabling, in this way, the comparison between the test result and
diagnosis of the specialist. We calculated the Kappa coefficient, rates of
sensitivity, specificity and accuracy to verify the statistical significance.
Results: The results confirm the relationship of migraine diagnosed
clinically with gender (females are more frequent among patients) and at the age of
study participants (persons <40 years are more frequent among patients). The
results also show that brings osmophobia small gain in sensitivity and little loss
in specificity of ID-Migraine in the diagnosis of migraine, ie without osmophobia is
more than sufficient to diagnose preliminarily migraine.
Conclusions: The question osmofobia didn’t improve the sensitivity and
specificity of the ID-Migraine.
P104
Headache Prevalence and Clinical Features in Patients with Idiopathic
Intracranial Hypertension (IIH)
D. D’Amico1, M. Curone1, S. Bianchi-Marzoli2, G.
Bussone1
1Clinical Neurosciences Department, Headache Unit, Neurological
Institute C. Besta IRCCS Foundation, Milano, Italy;
2Neuro-Ophthalmology Service, Italian Auxological Institute IRCCS
Foundation, Milano, Italy.
Objectives: Aim of this study was to investigate the prevalence and the
main headache features in patients with IIH and to explore possible correlations
with body mass index (BMI) and intracranial pressure (ICP) levels.
Background: Idiopathic intracranial hypertension (IIH) is the syndrome
of elevated intracranial pressure in the absence of space occupying lesions or other
brain disorders. Although IIH may be heterogeneous as far as clinical presentation
headache is one of the most common symptoms.
Methods: Aim of this study was to investigate the prevalence and the
main headache features in patients with IIH, and to explore possible correlations
with body mass index (BMI) and intracranial pressure (ICP) levels. Differences for
age, BMI and ICP between patients with and without headache, as well as differences
between those with and without obesity for ICP, were assessed with Mann-Withney U
test.P-value <.05 was used to set statistical significance. A consecutive
clinical series of IIH patients with demonstration of increased ICP by lumbar
puncture in the recumbent position were enrolled.
Results: Among a total of 40 patients (9M, 31 F mean age at observation
39,8 yrs.), headache was reported by 30 (75 %). Considering the headache features at
least one of which is required for diagnosis of headache attributed to IIH according
to ICHD-II, daily or nearly-daily was present in 73,3 %; diffuse/non-pulsating pain
in 80 %; aggravation by coughing/straining in 56.6 %. The three headache
characteristics were all present in 36,6 %. In 26,7 % headache was pulsating, in 20
% unilateral, and migrainous associated symptoms (nausea or photophobia-phonophobia)
were described in 43,3 %. No differences were found for age, BMI and ICP between
patients with and without headache; no differences were found between those with and
without obesity for ICP, and between those with and without severe intracranial
hypertension for age and BMI.
Conclusions: These results confirm the strong association between
headache and IIH. They indicate that further studies are warranted in order to
assess the possible relationships between this key symptom and other IIH features,
and propose possible changes in the current ICDH-II criteria for headache attributed
to IIH, considering the high frequency of migrainous symptoms as well as the
recently proposed association between chronic migraine and IIH without
papilledema.
P105
Dream-Enacting Behaviour in Migraine Patients: Association with Impaired Sleep
and Severe Headache-Related Disability
K. Suzuki1, T. Miyamoto2, M. Miyamoto1, S.
Suzuki1, Y. Watanabe1, R. Takashima1, A.
Numao1, K. Hirata1
1Department of Neurology, Dokkyo Medical University, Mibu,
Tochigi, Japan; 2Department of Neurology, Dokkyo Medical University
Koshigaya Hospital, Koshigaya, Saitama, Japan.
Objectives: To investigate the clinical correlates of dream-enacting
behaviours (DEB) in migraine patients.
Background: Sleep disorders, nightmares and visual hallucinations have
been reported in migraine patients, which may suggest the involvement of rapid eye
movement (REM) sleep regulation in migraine. However, the association
betweenmigraineand REM sleep behaviour disorder (RBD) has never been studied.
Methods: We performed a cross-sectional, case-control study including
episodic migraine patients (n = 161, mean age 33.1 years) and headache-free control
subjects (n = 140, mean age 33.1 years) under 50 years of age. The Japanese version
of the RBD screening questionnaire was used, and subjects scoring 5 or higher were
defined as having DEB.
Results: A significantly increased frequency of DEB was observed in
migraine patients compared to controls (24.2% vs. 14.3%). Migraine patients with DEB
showed higher scores on the Migraine Disability Assessment and Pittsburgh Sleep
Quality Index and an increased rate of smoking compared to migraine patients without
DEB. Duration of migraine and headache frequency and intensity were not different
between migraine patients with or without DEB.
Conclusions: DEB was associated with impaired sleep and severe
headache-related disability in migraine patients. We suggest that DEB may reflect
brainstem dysfunction and increased brain excitability in migraine patients.
P106
Preliminary Data from a Headache Prevention Program in a Brazilian Public
Financial Institution
M.F. Carvalho1, A.A. Arantes1, D.S. Cortes1, A.F.
Carvalho1, R.O. Cruz1, A.P.P. Mendonça1, R.
Marandino1
1Medical Division, BNDES - Brazilian National Development Bank,
Rio de Janeiro, RJ, Brazil.
Objectives: The purpose of this study is to evaluate the first 25
patients treated for chronic headache in a Brazilian non-medical public
institution.
Background: Chronic headaches patients commonly present with low scores
in quality of life questionaries, loss of job opportunities, absenteeism,
presenteeism, psychiatric and non psychiatric comorbidities, social isolation and
are unemployed(1-3). The medical literature gives us many examples of the
efficacy of medical programs dedicated to the trreatment of chronic headaches, even
when implemented in primary-care non-medical institutions(4). Chronic
headaches are highly prevalent in Brazil(5). In a study performed in the
city of Florianópolis (Santa Catarina State, Brazil), the one-year prevalence of
headache was 80.8% in the general population. The prevalence of migraine,
tension-type headache (TTH) and chronic daily headache (CDH) were, respectively
22.1%, 22.9% and 6.4%(6).
Methods: This is a retrospective analysis of the medical records of the
first 25 patients followed in our Medical Outpatient Clinic for the treatment of
chronic headache.
Results: Twenty five patients presented for the treatment of headache.
Nineteen (76%) were female. The median age was 39.6 years (range 26-67). Thirteen
patients (52%) presented with typical migraine. Eight (32%) had migraine in
association with psychiatric disorders and TTH. Overall, 84% of the patients were
migrainous. Tension-type headache was observed in 10 patients (40%). In two cases of
the TTH group (20%), this was their only diagnosis. In eight patients of the same
group (80%), TTH was associated with migraine and mental illness. Two patients (08%)
were diagnosed as having CDH and analgesic abuse. One patient (4%) had a
cervicogenic headache, and one was diagnosed as having Glioblastoma Multiforme. Nine
patients (36%) were treated with Beta-blockers and 07(28%) with Topiramate.
Non-pharmacological interventions were used when appropriate. Eighteen patients
(72%) reported an improvement of at least 50% of their symptoms. Three patients
(12%) abandoned treatment. The follow-up visits of the five most recent patients are
still pending.
Conclusions: Preliminary data from the first 25 patients treated for
chronic headache in our Institution showed that the most common diagnosis was
migraine with or without aura. This is consistent with the medical literature that
indicates that migrainous patients are usually those who look for prevention
programs more often. Our small-scale study also demostrates that even in a
primary-care non-medical institution, programs dedicated to the prevention of
chronic headaches can be truly effective and should be implemented.
P107
Decubitus as Aggravating Factor of Headache in the Crisis Migrainous
J.P. Macci1, M.C.M. Teles1, C.P. Jabarra1, G.F.
Ferreira1, J.A. De Souza1, P.F.M. Filho1
1Fluminense Federal University, Niteroi, Rio de Janeiro,
Brazil.
Objectives: 1) Check in a sample of patients migraneurs, the percentage
of those who complain of worsening headache during the crisis, by recumbency. 2)
Check if there are differences with respect to worsening by recumbency between the
gender.
Background: The migraine attacks are often disabling. The physical
activity and movements of the lower head are recognized factors of transient
increase in pain intensity during crises. For this reason, many patients seek rest.
In clinical practice, it appears that some patients complained of worsening headache
by lying down, during migraine attacks, preferring to remain seated or reclining
position. This finding, to our knowledge, not been studied.
Methods: A retrospective analysis of medical records. We evaluated the
clinical history of 734 consecutive patients with a chief complaint of headache,
attended in a tertiary clinic since it started using the program Hypatia (tutorial
and database headache). Using the search filters, we selected patients who received
a diagnosis of migraine in any of its forms (1.1 to 1.6 Classification of IHS 2004)
a total of 563 (76.7%). All patients were questioned about the factors worsening
headache, during the crisis, including the decubitus. The who reported worsening by
recumbency were recorded and divided according to gender.
Results: Of the 563 patients (482 women - 85.6%, 81 men - 14.4%)
diagnosed with migraine, 20.8% (n = 117) complained of aggravation by recumbency. Of
these, 89.7% (n = 105) were women and 10.3% were men (n = 12).
Conclusions: The worsening of headache by recumbency is more frequent in
females, as well as migraine. We believe that the increased venous return in the
decubitus and, consequently, the pulse pressure is possibly one of those responsible
for the aggravation of headache by recumbency
P108
Decreased Affective Response and Increased Perceived Exertion to Aerobic
Exercise in Migraine Patients
1Neurologia e Neurocirurgia, Universidade Federal de São Paulo,
São Paulo, Brazil; 2Psicobiologia, Universidade Federal de São Paulo,
São Paulo, Brazil; 3Instituto do Cérebro, Hospital Israelita Albert
Einstein, São Paulo, Brazil.
Objectives: We aimed to study affective response and perceived exertion
to aerobic exercise (AE) in M patients.
Background: Migraine (M) patients have low physical activity levels and
often fail to comply with aerobic exercise and other prescribed treatment
recommendations, but little is known about its mechanisms. Affective response to
aerobic exercise is positively correlated to exercise intensity and predicts 6 and
12-months exercise compliance.
Methods: Ten migraine patients taking no preventive medicine (1m/9f;
age: 37,1±14,2; BMI: 26,9±5,6) and 10 matched control subjects (1m/9f; age:
35,1±10,1; BMI: 24,3±2,2) were included in the study. All subjects signed informed
consent. Cardiopulmonary exercise test (CPET) was performed for determination of
peak oxygen uptake (VO2Peak) and ventilatory threshold (VT). An AE session was
conducted for 30 min at workload corresponding to VT. The Feeling Scale was applied
before (FS pre), during (FS dur; at 15’) and just after termination of AE (FSpos).
For perceived effort assessment, Borg’s Scale was applied at the last minute of AE.
All measurements were undertaken in the interictally period (headache-free day).
Results: M patients and controls had not headaches along the AE session.
Clinical features and maximal CPET parameters were equal in both groups. M patients
had significantly lower VE/VO2 at VT [F(1, 18) = 4,807; p =0,042]
and lower affective response than controls, FSdur [F(1, 18)=5,737;
p = 0,028]. M patients presented a higher exercise effort
perception, Borg’s Scale [F(1, 18) =4,469; p = 0,049].
There were main effect of time and group [F(2, 17) = 5,664;
p = 0,013], but no interaction.
Conclusions: M patients have decreased affective response and increased
perceived exertion response to AE. The AE prescription should be revisited in M
patients regarding the current recommendations for a better compliance.
Characteristics
Migraine (n=10)
Control (n=10)
Sex(%)
Male
1(10)
1(10)
Female
9(90)
9(90)
Age(y)
37,1±14,2
35,1±10,1
BMI(Kg/cm2)
26,9±5,6
24,3±2,2
MwA
7
-
MwoA
3
-
M Dur (y)
12,1±9,4
-
Days with M
10,5±5,5
-
M Freq
8,4±4,4
-
Disability (0-3)
1,56±0,4
-
Cardiopulmonary Data
VO2Peak
29,1±6,8
32,0±3,7
HRmax
177,9±17
185,9±8,6
VT (%VO2Peak)
58,6±9,5
52,9±6,0
HR at LV
127,9±21,0
123,6±13,9
VE (L/min) at VT
30,2±5,3
29,4±4,9
VE/VO2 at VT
23,1±2,9 *
25,6±2,2
VE/VCO2 at VT
29,6±3,7
31,7±2,1
Affective Response
FS Pre
2,9±2,0
4,2±1,4
FS Dur
1,4±1,3 *
2,9±1,4
FS Pos
1,7±1,6
2,8±1,5
Perceptual Response
Borg´s Scale
12,3±1,3 *
11,1±1,2
P109
A 14-Months Study of Change in Disability and Mood State in Patients with
Chronic Migraine Associated to Medication Overuse
M. Leonardi1, A. Raggi1, G. Bussone2, D.
D’Amico2
1Neurology, Public Health and Disability Unit, Neurological
Institute C. Besta IRCCS Foundation, Milano, Italy; 2Clinical
Neurosciences Department, Headache Unit, Neurological Institute C. Besta IRCCS
Foundation, Milano, Italy.
Objectives: The aim of the study was to evaluate changes in disease
severity, disability and mood state in group of patients with CM associated to MO
(CM+MO) who underwent detoxification followed by prophylaxis.
Background: Chronic migraine (CM) and medication overuse (MO) cause a
relevant burden on sufferers and on society, as demonstrated by several studies with
disease specific tools (namely MIDAS), and by recent data with a standardized
generic disability measure based on the international classification of functioning
concepts (WHO-DAS-2).
Methods: Patients were enrolled at hospital admission and re-evaluated
after >12 months. MIDAS was used as a proxy of disease activity, WHO-DAS-2 to
assess disability DBI-2 for mood state. Data from study completers were analysed:
longitudinal differences were tested with ANOVA and effect size. T-test was used to
assess differences in WHO-DAS-2 and BDI-2 between those with MIDAS ≤21 and ≥22 at
follow-up. Differences between baseline and follow-up were calculated; correlation
between MIDAS, WHO-DAS-2 and BDI-2, using Pearson’s index; linear regression was
used to assess change in WHO-DAS-2, using MIDAS and BDI-2 change as predictors.
Results: 69 patients (56 females, age 42.2±12.6) completed the study.
Mean follow-up duration was 14±1.7 months: MIDAS was significantly lower at follow
up (101.9±79.3 at baseline, 52.0±54.3 at follow-up, P<.001). Effect size was
moderate for MIDAS, small for WHO-DAS-2 and BDI-2. In 27.5% of the sample, MIDAS
fell below 21 at follow-up: these patients had significantly lower WHO-DAS-2
(14.5±13.0 Vs. 31.0 ±18.4, P=.001), while BDI-2 was not different. WHO-DAS-2 change
was little correlated to MIDAS change (R=.28, P<.05), and strongly correlated to
changes in BDI-2 Somatic (R=.73, P<.001), Cognitive (R=.69, P<.001) and
Summary scores (R=.76, P<.001). 57.1% of WHO-DAS-2 change variance is explained
by change in BDI-2 and MIDAS scores.
Conclusions: Our study showed a clear clinical improvement 14 months
after detoxification in CM+MO patients: only one-fourth achieved a MIDAS score≤21
(i.e. below severity threshold), but mean MIDAS reduction was around 50%.
Improvement in functioning was demonstrated by decrease in WHO-DAS-2 score: this
reduction, although modest, is largely explained by reduced disease activity and
improved mood state. Our findings indicate that appropriate treatment
(detoxification+prophylaxis) is likely to reduce CM-MO burden, and that recognition
and treatment of mood problems may be a key factor in disability reduction.
P110
Changes in Sodium Valproate Prescription for Migraine Prophylaxis after
Approval of Japanese Insurance Coverage
H. Iwanami1, M. Tatsumoto1, K. Hirata1
1Neurology, Dokkyo Medical University, Shimotsuga, Tochigi,
Japan.
Objectives: To compare migraine prophylaxis associated with sodium
valproate (VPA) as a migraine outpatient prescription at the Department of Neurology
in 2008 and 2012, i.e., before and after Japanese insurance coverage of VPA.
Background: VPA is widely used for the treatment of epilepsy, and has
received approval for several new indications for the treatment of bipolar disorders
and neuropathic pain and migraine prophylaxis. VPA was approved by the Japanese
insurance system for coverage of migraine prophylaxis in 2011.
Methods: The subjects were 200 consecutive migraine patients followed at
the migraine outpatient service of our department of neurology in 2008 and 2012,
i.e., before and after insurance coverage of VPA. We assessed migraine prophylaxis
with 5 frequently used drugs (VPA, clonazepam [CZP], amitriptyline hydrochloride,
lomerizine hydrochloride [approved only in Japan], topiramate).
Results: Of the 200 patients receiving these 5 drugs, there were 66
before insurance coverage of VPA and 148 after insurance coverage of VPA. Among the
66 patients before insurance coverage, 8 used VPA, 37 CZP, 27 amitriptyline
hydrochloride, 5 TPM, and 17 lomerizine hydrochloride. Among the 148 patients after
insurance coverage, 62 used VPA, 54 CZP, 48 amitriptyline hydrochloride, 36 TPM, and
29 lomerizine hydrochloride. Prior to insurance coverage, VPA was used by 8 (4%) of
migraine prophylaxis patients and after insurance coverage by 62 (31%). Monotherapy
was CZP (17 patients) and lomerizine hydrochloride (9) before insurance coverage,
and VPA (28 patients), amitriptyline hydrochloride and lomerizine hydrochloride (17)
after insurance coverage. Reduction of 4-week migraine frequencies in patients
receiving VPA and topiramate was the same, at 43%, after insurance coverage. The
average daily dose of VPA was 209 mg after insurance coverage.
Conclusions: Our results indicate that the frequency of VPA use for
migraines has increased significantly since insurance coverage of VPA for this
indication in Japan. Administrations of VPA and topiramate are equally effective for
decreasing headache frequency in migraine patients.
P111
Expert Consensus Recommendations for the Performance of Peripheral Nerve Blocks
for Headaches: A Narrative Review
A. Blumenfeld1, A. Ashkenazi2, U. Napchan3, S.D.
Bender4, B.C. Klein5, R. Berliner6, J.
Ailani7, J. Schim1, D.I. Friedman8, L.
Charleston IV, 9, W.B. Young10, C.E. Robertson11,
D.W. Dodick12, S.D. Silberstein10, M.S.
Robbins6
1Headache Center of Southern California, Encinitas, CA, USA;
2Doylestown Hospital, Doylestown, PA, USA; 3Headache
Clinic, Middletown Medical, Middletown, NY, USA; 4North Texas Center
for Head, Face & TMJ Pain, Texas A&M University, Baylor College of
Dentistry, Plano, TX, USA; 5Abington Headache Center, Warminster, PA,
USA; 6Neurology, Montefiore Medical Center, Albert Einstein College
of Medicine, Bronx, NY, USA; 7Neurology, Georgetown University
Hospital, Washington, DC, USA; 8Neurology & Neurotherapeutics and
Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA;
9Neurology, Michigan State University College of Human Medicine,
Grand Rapids, MI, USA; 10Neurology, Thomas Jefferson University,
Philadelphia, PA, USA; 11Neurology, Mayo Clinic, Rochester, MN, USA;
12Neurology, Mayo Clinic, Scottsdale, AZ, USA.
Objectives: To describe a standardized methodology for the performance
of peripheral nerve blocks (PNB) in the treatment of headache disorders.
Background: Peripheral nerve blocks (PNBs) have long been employed in
the management of headache disorders, but a wide variety of techniques are utilized
in literature reports and clinical practice.
Methods: The American Headache Society Special Interest Section for PNBs
and other Interventional Procedures (AHS-IPS) convened meetings during 2010-2011
featuring formal discussions and agreements about the procedural details for
occipital and trigeminal PNBs. A subcommittee then generated a narrative review
detailing the methodology.
Results: PNB indications may include select primary headache disorders,
secondary headache disorders, and cranial neuralgias. Special procedural
considerations may be necessary in certain patient populations, including pregnancy,
the elderly, anesthetic allergy, prior vasovagal attacks, an open skull defect,
antiplatelet/anticoagulant use, and cosmetic concerns. PNBs described include
greater occipital, lesser occipital, supratrochlear, supraorbital, and
auriculotemporal injections. Technical success of the PNB should result in cutaneous
anesthesia. Targeted clinical outcomes depend on the indication, and include relief
of an acute headache attack, terminating a headache cycle, and transitioning out of
a medication overuse pattern. Reinjection frequency is variable, depending on the
indications and agents used, and the addition of corticosteroids may be most
appropriate when treating cluster headache.
Conclusions: These recommendations from the AHS-IPS members for PNB
methodology in headache disorder treatment are derived from the available literature
and expert consensus. With the exception of cluster headache, there is a paucity of
evidence, and further research may result in the revision of these recommendations
to improve the outcome and safety of these interventions.
P112
Cabernet Sauvignons from France Do Trigger Migraine More Often Than Those from
South America: An Open Prospective Study
A.V. Krymchantowski1, C.C. Jevoux1
1Headache Center of Rio, Rio de Janeiro, RJ, Brazil.
Objectives: The aim of this study was to evaluate whether cabernet
sauvignon wines from the left margin of the Gironde river, specifically from the
Medoc area, would trigger migraine differently from those made in South America
(SA).
Background: Red wines are known migraine attack triggers. This is may
occur because of the high content of vasoactive substances, like condensed tannins.
Wines can also take on tannins from the oak or other woods used in wine barrels for
storage. Different woods as different terroirs in different
countries affect the type and concentration of tannins as well as the quality of the
wine. French Bordeaux area wines are rich in tannins. Those from the left side of
the Gironde river have more cabernet sauvignon (minimum 75%) compared to those from
the right side margin, which have more merlot. In addition, it seems that South
American (SA) wines made of cabernet sauvignon have less tannin compared to those of
France.
Methods: Twenty eight (14 women, 14 men, ages 25 to 67 years, mean 54,5)
regular patients with migraine according to the International Classification of
Headache Disorders (ICHD-II) from a tertiary center, who were self-considered
regular wine drinkers and who pointed a clear-cut relationship between wine intake
and migraine attacks, were prospectively studied. They were asked to drink half
bottles (375ml) of a SA cabernet sauvignon and a French cabernet sauvignon from the
Medoc or Haut Medoc regions, at their discretion (order, winemaker, time of the day
and presence or absence of food) with a minimum interval of 4 days between the wine
types. In addition, they were asked to avoid any other type of alcoholic beverages
during the time of the study. The patients had to fill out a detailed headache
calendar.
Results: Twenty three patients (13 women, 10 men) completed the study
and had the two half bottles of different cabernets. Among them, the patients
reported a migraine attack within 12 hours of having the French cabernet in 60,9% of
the times (14 out of 23) compared to 39,1% (9 out of 23) who pointed the SA cabernet
as a clear migraine attack trigger. Four patients among the 23 didn’t present
migraine attacks after having the wines, whereas 4 presented attacks after both
wines and 5 reported that the SA cabernet, but not the French, triggered an attack
of migraine.
Conclusions: Despite the open methodology, which challenges definitive
conclusions, we concluded that even among migraineurs who point the red wine as a
migraine trigger, SA cabernet sauvignons triggered migraine attacks in nearly one
third of the times it was consumed. As for French cabernets, it may trigger attacks
in more than half of the times it is taken. Although the reasons are unclear, one
may speculate that the tannin and flavonoid content, which are higher in French
wines, are the most responsible for triggering migraine attacks. Controlled studies
are necessary to confirm these observations.
n=10 French CS
n=10 male South American CS
n=13 female French CS
n=13 female South American CS
Migraine attack
4
6
10
3
NO migraine attack
6
4
3
10
P113
Headache and Stroke
I. Zekja1, S. Mijo1, E. Majko1, S.
Grabova1, D. Dobi1, J. Kruja1
1Neurology, UHC Mother Teresa, Tirana, Albania.
Objectives: To establish realtions between headache and stroke.
Background: The etiology of headache in stroke is not known, and its
relation to migraine and tension-type headache is unclear. The aim of our study was
to investigate and classify headache appearing in stroke patients prospectively,
using the headache classification as determined by the Headache Classification
Committee of the International Headache Society (1988).
Methods: Thirtyfive consecutively admitted patients aged younger than 75
years with acute stroke were examined and questioned about headache and prior
headache complaints; 30 (85%) were able to communicate.
Results: Nine (∼27%) of the 35 patients experienced headache from 3 days
before to 3 days after stroke. Headache occurred in 50% of patients with
intracerebral hemorrhage, in 26% with infarction, and in 15% of patients with
lacunar infarction. The headache in thromboembolic stroke was classified as
tension-type headache (3 patients), migraine-like headache (2 patients), and other
headache (10 patients). Migraine was more frequent in vertebrobasilar stroke. In
patients with unilateral headache and unilateral stroke lesion, the headache was
ipsilateral in 4 of 7 cases. In infarction, severity of headache showed no relation
to lesion size or lesion localization. Patients with previous tension-type headache
and migraine experienced reactivation of known headache equally often.
Conclusions: (1) Headache occurs in one fourth of patients with acute
stroke. (2) Unilateral headache is usually ipsilateral to stroke lesion. (3)
Headache severity is not related to size of ischemic stroke lesion.
P114
Grey Zones of Migraine without Aura Diagnosis
A. Özge1, E.I. Aydinlar2, B. Tasdelen3
1Neurology, Mersin University School of Medicine, Mersin, Turkey;
2Neurology, Acibadem University, School of Medicine, Istanbul,
Turkey; 3Biostatistics, Mersin University School of Medicine, Mersin,
Turkey.
Objectives: To evaluate the diagnostic value of clinical characteristics
of MwoA in ICHD-II in a clinical dataset for obtained grey zones and possible
reasons of this distribution have been discussed.
Background: Concerning migraine without aura (MwoA), the second edition
of the International Classification of headache Disorders (ICHD-II), did not
introduce any major changes to before (ICHD-I). However still many patients fail to
meet the criteria’s such as location, pulsating quality, pain intensity, aggravation
with physical activity, nausea, vomiting, phonophobia and photofobia. Difficulties
of fulfilling the criteria in some patients may lead to locate them in a so called
“grey zone”.
Methods: This study was a tertiary based retrospective clinical study
including 1365 patients with MwoA, after exclusions “possible” diagnosis, known
comorbidities and missed clinical variables, in a dataset including 3286 patients
with migraine. The patients meet all of the criteria of ICHD-II named as Full-MwoA.
When specialist diagnosis accepted as gold standard, one, two, three or more failed
criteria named as Zone I, Zone II and Zone III, respectively. Statistical powers and
variables of the zones calculated and discussed.
Results: Out of 1365 patients 351 (25.7%) were Full-MwoA, 546 (40%)
located in Zone I, 327 (23.9%) located in Zone II and 141 patients (10.3) located in
Zone III. Most important differentiating features of the zones are previous history
of migraine equivalents as periodical vomiting, infantile colic, or motion sickness
before puberty and triggering by menstrual cycle after puberty. Most important
determinates of criteria are severity of the pain and associated photophobia or
phonophobia in all zones.
Conclusions: This study showed us strict criteria of migraine diagnosis
have to be supported by the grey zones definition in all age and gender groups even
in MwoA as a most simple type of migraine.
P115
Withdrawn by the author.
P116
What Does the Headache Patient Want?
P.A.S. Rocha-Filho
Hospital Universitário Oswaldo Cruz, University of Pernambuco, Recife, PE,
Brazil.
Objectives: The purpose of this study was to know what the headache
patient wants when he comes to the doctor.
Background: Headache is an extremely common condition. It is estimated
that globally, among the adult population, 46% have current headache in general, 11%
have current migraine, 42% have current tension-type headache, and 3% have current
chronic daily headache. (1) The average rate of medical consultations due to
headaches is 30.3 per 1000 men and 55.4 per 1000 women. However, only 64% of
patients with migraine and 45% with tension-type headache had previously sought
medical attention, and of these, only 32% returned for ongoing care. (2). A previous
study found that “Pain relief” and “an explanation of what was causing the pain”
were listed with higher frequency among the reasons to have a medical consultation
by both physician and patient groups. (3)
Methods: Consecutive outpatients were asked to fill out a survey form
prior to their first appointment at the headache clinic. The questionnaire includes
specific information including age, sex, duration of headache, frequency of
headache, how many doctors they had seen previously about headache. No attempt was
made to select patients as to specific headache type. In the second part, patients
were asked to choose the most important reason to have that medical consultation
among five options: a. To have an explanation; b. To have a complementary exam; c. A
doctor to follow him/ her for their headache; d. be worried about having a serious
disease; e. Relief of pain. If none of these options was the reason, there was an
open question regarding the patient’s reasons for seeking medical attention for
headaches. The Hospital Anxiety and Depression Scale was used. The diagnoses of
headaches were registered.
Results: Five hundred thirty-two patients were interviewed, 82.5% were
women, the mean age was 42.3 years (SD=16.1). They had seen previously a mean of 2.5
(DP =3.5) doctors because of headache; 32%, more than 2 doctors. They have had
headache for a mean of 14 years (DP=12.5); 60% for more than 5 years. Mean frequency
of headache = 16 days per month (DP= 11.2), 48.1% had chronic daily headache; 23.4%
had tension-type headache; 71.2%, migraine. Reasons to have a medical consultation:
To have an explanation (18.9%); to have a complementary exam (22.2%); A doctor to
follow him/ her for their headache (13.2%); be worried about having a serious
disease (26.2%); Relief of pain (19.5%). There was no association between be worried
about having a serious disease/ have a complementary exam and the gender, years of
study, had been in more than 2 doctors, migraine, tension-type headache, depression,
anxiety or had chronic daily headache.
Conclusions: The most frequent reasons to have a medical consultation
because of headache were “be worried about having a serious disease” and to “have a
complementary exam”. No variables studied were associated with these reasons.
P117
Botulinum Toxin A for the Treatment of Greater Occipital Neuralgia:
Pathophysiological Considerations for Efficacy
G. Pierric1, C. Sylvie1, R. Jean Henri1
1Neurology, Centre Hospitalier D Annecy, Pringy,
France.
Objectives: To evaluate efficacy of botulinum toxin A in
refractivegreater occipital neuralgia.
Background: Greater occipital neuralgia (GON) is rare but can be
responsible for severe intractable headache. Failure of medical treatment as well as
injection therapy with corticosteroids or anaesthetics is not unusual. Botulinum
toxin A (BTx A) or surgical procedures have been already tested as an alternative
tool. Results with BTx A are heterogeneous authorizing Linde et al (2001) to
recommend its use in grade C of recommendation. We make the hypothesis that the
effect of BTx A depends on the presence of a pathological focal dystonia in the
trapezius or semi-spinalis muscles when the nerve become superficial. We evaluate 4
cases of refractive GON fulfilling the IHS criteria for diagnosis uncontrolled by
usual therapy treated with BTx A preceded by electromyography evaluation.
Methods: 4 women were referred for the treatment of refractive GON. They
met International Classification Headache Disorders Criteria for the Greater
Occipital (code 13.8) but have no pain relief with recommend therapy. The mean age
was 61 yo, the duration was over 14 months. All have unilateral GON. NSAIs,
anti-epileptic drugs, analgesics or corticosteroids were inefficient. Brain MRI and
cervical radiolography were unremarquable. BTx A Injection was unilateral with a
minimum of 30 UI in the trapezius at the same site of the pain preceded by
electromyographic detection and completed if needed by injection in the splenius
capitis. Reduction of pain was evaluated by percentage of improvement at 10 days and
3 months. Toxicity was also evaluated systematically. All cases gave their
acceptation before treatment.
Results: All case have abnormalities in electromyography evaluation
before injection. Improvement of pain was of 60% compared with the pain before and
maintain at one month. No side effect was declared. No significant reduction of
rescue therapy was observed in one case.
Conclusions: This preliminary work propose to considerateBTx A as an
alternative and safe treatment for GON. We suggest that before injection an
electromyography evaluation is needed. If observed abnormal activities in trapezius
muscles and in case of refactory GON, BTx A might be an effective treatment and must
be tested. We recommend conducting a double blind controlled trial to validate this
proposition.
P118
Chiropractic Spinal Manipulative Therapy for Cervicogenic Headache: A Single
Blinded, Randomized, Placebo-Controlled Study
A. Chaibi1, M.B. Russell1
1Head and Neck Research Group, Research Centre, Akershus
University Hospital, Lørenskog, Norway.
Objectives: The purpose of this study was to highlight and validate
chiropractic spinal manipulative therapy for cervicogenic headache (CEH).
Background: The prevalence of CEH varies between 0.4-4.1 % in different
studies. Pharmacological management usually has none or minor effect on CEH, while
cervical spinal manipulative therapy has been reported to have an effect. We
conducted a randomized single blinded controlled clinical trial on CEH applying
chiropractic spinal manipulative therapy.
Methods: A single blinded, randomized, placebo-controlled trial of 16
months duration. The trial consisted of 1 month baseline, 3 months treatment and 3,
6, 12 months follow up. Fifteen participants aged 18-70 years with CEH completed the
trial. Participants were randomized into 1 of 3 groups: (i) chiropractic spinal
manipulation, (ii) sham chiropractic manipulation, (iii) control group, not
receiving treatment. Primary outcome was reduction of headache days while secondary
outcomes were reduction in headache intensity, duration, headache index and
medication from initial baseline to post treatment and follow up using headache
diaries.
Results: Results are currently being analyzed and will be presented at
the congress.
Conclusions: To be presented at the congress.
P119
Electron Microscopic and Proteomic Comparison of Terminal Branches of the
Trigeminal Nerve on Patients with and without Migraine Headaches
B. Guyuron1, E. Yohannes1, R. Miller1, H.
Chim1, D. Reed1, M. Chance1
1Plastic Surgery, Proteomics & Bioinformatics, Neurosciences,
Neurology, Case Western Reserve University, Cleveland, OH, USA.
Objectives: The purpose of this study was to compare the ultrastructural
appearance and protein expression of the zygomaticotemporal branch of the trigeminal
nerve (ZTBTN) in patients with and without migraine headaches (MH).
Background: After obtaining IRB approval and diagnosis of MH by a
neurologist, a 5mm segment of the ZTBTN that is routinely removed during migraine
surgery was compared to a similarly sized nerve segment obtained from patients
without a history of MH who underwent an endoscopic forehead lift.
Methods: The detailed cytoarchitectural differences between nerve
segments were examined on the electron microscope. Additionally, using
multidimensional label-free LC-MS platform, nerve segments obtained from 15 migraine
and 15 control subjects were snap frozen at -80°C for the proteomics analysis.
Frozen nerve tissue samples were appropriately prepared and processed for
quantitation and statistical analysis.
Results: Control nerves contained longitudinally oriented myelin sheaths
that had a characteristic wavy appearance compared to migraine nerves which revealed
a more linear organization. Furthermore, in migraine derived nerves, the
neurofilaments were strikingly discontinuous and poorly registered with the myelin
sheaths. Large regions of the nerve contained axons with patchy neurofilament
interspersed with an apparent absence of neurofilaments, suggesting axonal
pathology. Transverse sections through normal nerves revealed the characteristic
arrangement of myelinated and unmyelinated axons. Throughout the migraine derived
nerves, however, the organization of a significant number of the myelin sheaths and
their target axons was disrupted. The most striking feature was the excessive amount
of myelin surrounding the axon. Frequently this myelin was folded and constricted
the axon, leaving little axonal cytoplasm. Analysis of LC-MS/MS datasets identified
170 differentially expressed proteins in an initial study and 77 differentially
expressed proteins in an independent verification analysis that are correlated with
migraine diagnosis. Protein analysis identified significant networks comprised of
highly connected molecular modules potentially related to migraine specific biology.
In migraine nerve samples, molecules that are essential for the establishment of
normal axonal calibers including clusters of neurofilaments, and proteins that are
involved in myelination of axons are down regulated. On the other hand, up
regulation of clusters of proteins that are involved in free radical scavenging
suggests that oxidative insult is also part of migraine pathogenesis, and functions
to protect proteins and lipids against oxidative damage.
Conclusions: This study offers electron microscopic and proteomic
evidence of axonal pathology and deregulation of the myelination process in patients
who have MH compared to those who do not. This study offers the rationale for the
peripheral component of the migraine cascade.
P120
Pain Location of Migraine Headache Is Closely Related with Gold Meridian System
of Korean Hand Therapy
1Neurology, Pusan National University Hospital, Busan/ 1-10
Amidong, Republic of Korea; 2Korean Hand Acupuncture, Korean Hand
Therapy Institute, Seoul, Republic of Korea.
Objectives: The diagnosis of primary headache has not been sufficient
for appropriate treatment. We mainly depend on the history taking and criteria of
International Headache Classification. The criteria are well described but they are
not well interpreted. The location of headache might be crew to diagnosis. The sites
of Botox injection sites are nearly same and the dosage of injection is more than
100 units. We emphasized to manage the patient individually as personalized
medicine. The location is important to treatment of Botox injection.
Background: If the location is determined accurately, the dosage of
Botox might be reduced. There are no standardized methods to decide the location in
clinical practice. In Eastern Asian Medicine, there are Meridian and Acupuncture
Points on the body including on the head. It is well described but it is complicated
to use in practice easily. We need simplified Meridian and Acupuncture Point system.
We propose to use Gold Meridian and Acupuncture Points of Korean Hand Therapy to
determine the location.
Methods: This procedure was performed during physical examination based
on well performed history taking at department of neurology, Pusan National
University Hospital from March 2011 to Feb. 2012. The 200 migraine headache patients
who have no other neurological or systemic diseases were included. We checked pain
location on both sides and sites of head using 20 New Modified Acupuncture Points on
Gallbladder Meridian (CM1-12) and Urinary Bladder (CI1-8) each one side.
Results: The headache points are grouped such as Gallbladder and Urinary
Bladder Gold Meridian System, the migraine headache patients belonged to
Gallbladder, mixed type headache belonged to various combined Gallbladder and
Urinary Bladder Meridian. The pure migraine groups are three, and mixed form
headache group are nine.
Conclusions: The pain location of intractable headache patients
presented as mixed form headache. The location of pains of such headache should be
considered for Botox injection. We can inject small dosage of Botox injection
depending on right or left exact side and sites.
P121
BMS-927711 for the Acute Treatment of Migraine: A Double-Blind, Randomized,
Placebo-Controlled, Dose-Ranging Trial
R. Marcus1, P. Goadsby2, D. Dodick3, D.
Stock1, G. Manos1, T. Fischer1
1Bristol-Myers Squibb, Wallingford, CT, USA; 2Headache
Group, Department of Neurology, University of California, San Francisco, San
Francisco, CA, USA; 3Department of Neurology, Mayo Clinic, Phoenix,
AZ, USA.
Objectives: To determine an effective and tolerable dose range of a new
oral calcitonin gene-related peptide (CGRP) receptor antagonist, BMS-927711, for the
acute treatment of migraine.
Background: CGRP has been closely linked to the pathophysiology of
migraine. CGRP receptor antagonists may be effective in treating migraine by
blocking the activities of CGRP in trigeminal neurons without the vasoconstrictor
liability of triptans and ergotamine derivatives. BMS-927711 is a potent, selective,
competitive human CGRP receptor antagonist that has shown in vivo
efficacy without vasoconstrictor effects. It has been shown to be generally safe and
well tolerated at single (≤1500 mg) and multiple (≤600 mg) doses for 14 days in
healthy volunteers.
Methods: In this randomized, double-blind, parallel-group,
placebo-controlled, dose-ranging study, patients (N=885) were allocated, using an
adaptive design, to one of the following dose groups: BMS-927711 10, 25, 75, 150,
300, or 600 mg; sumatriptan 100 mg (active control); or placebo. Patients were
treated for a single migraine attack. The primary endpoint was pain freedom at 2
hours post-dose using a four-point numeric rating scale (no pain, mild pain,
moderate pain, severe pain).
Results: Of 1026 enrolled patients, 885 were randomized, and 799 were
evaluable. BMS-927711 doses of 75, 150, and 300 mg were more effective than placebo
(15.3%) for pain freedom at 2 hours post-dose (31.4%, p=0.0018; 32.9%, p=0.0005; and
29.7%, p=0.0024, respectively). BMS-927711 doses of 10, 25, and 600 mg were not
statistically different from placebo. The difference in 2-hour post-dose pain
freedom between the sumatriptan group (35.0%) and the placebo group was also
statistically significant (p<0.0001). For the secondary endpoint of sustained
pain freedom from 2 to 24 hours post-dose, BMS-927711 doses (25–600 mg) were
statistically significant compared with placebo (p<0.05). Overall, BMS-927711
doses offered an acceptable tolerability and safety profile within a
single-headache, single-treatment paradigm.
Conclusions: BMS-927711 was effective and generally well tolerated for
acute treatment of migraine at doses of 75, 150, and 300 mg.
P122
Double-Blind, Placebo Controlled, Randomized Clinical Trial Comparing Melatonin
3 mg, Amitriptyline 25 mg and Placebo for Migraine Prevention
M.F.P. Peres1, A.L. Gonçalves2, R.T. Ribeiro3
1Hospital Albert Einstein, Sao Paulo, Brazil;
2Neurology, UNIFESP, Sao Paulo, Brazil; 3Neurology, FMABC,
Santo Andre, Brazil.
Objectives: To test the efficacy and tolerability of melatonin 3 mg and
amitriptyline 25 mg compared to placebo in migraine prevention.
Background: Melatonin has been linked to migraine mechanisms in several
ways. Previous reports have shown therapeutic effects on migraine and other headache
disorders. Amitriptyline has been widely used for migraine prevention, but its
unfavorable side effect profile limits its use. Better tolerable options in migraine
prophylaxis are necessary.
Methods: A randomized, double-blind, placebo-controlled multicentric
study was carried out. Men and women, aged 18-65 years, with migraine with or
without aura, experiencing 2-8 attacks per month, were recruited from the general
population. After a 4-week baseline phase, 196 subjects were randomized to receive
either placebo, amitriptylne 25 mg or melatonin 3 mg for 3 months. The primary
outcome was migraine frequency in number of headache days per month. Secondary
endpoints were migraine intensity, duration, and analgesic use. Tolerability were
also measured in the three groups.
Results: One hundred seventy nine subjects completed the study. Mean
reduction in headache frequency was 2.7 in the melatonin group, 2.18 for
amitriptyline, and 1.18 for placebo. Melatonin significantly reduced headache
frequency compared to placebo (p=0,009), but not to amitriptyline (p=0,19).
Melatonin was as tolerable as placebo and better tolerable when compared to
amitriptyline.
Conclusions: Our study shows that melatonin 3 mg is better than placebo
for migraine prevention, and better tolerable than amitriptyline 25 mg.
P123
Co-Morbid Recurrent Headaches and Major Depressive Disorder: An RCT of
Cognitive Behavior Therapy
P.R. Martin
School of Applied Psychology, Griffith University, Mount Gravatt, Queensland,
Australia.
Objectives: To carry out the first RCT of cognitive behavior therapy
(CBT) designed for individuals suffering from both recurrent headaches and major
depressive disorder.
Background: Meta-analytic reviews have shown that the average reduction
in both migraine and tension-type headache with behavioral treatments to be 33% to
55%. In one of our studies, CBT achieved a 68% reduction. However, 35% to 50% of
recurrent headache sufferers fall into the mildly or moderately depressed
categories, and elevated scores on pre-treatment depression scales predict negative
outcomes for behavioral treatments. Also, numerous epidemiological and clinical
research studies have reported elevated risk of mood disorders in migraine and
chronic daily headache. Presence of psychiatric disorders predicts poorer outcome
for headache treatment. Hence, there is a need for developing treatments for
individuals who suffer from both recurrent headaches and depression.
Methods: 100 participants were recruited who were over 18 years of age
and diagnosed as migraine or tension-type headache (TTH) with a minimum of 6
headache days per month, a minimum chronicity of 12 months, and a stable pattern
over last 6 months; as well as major depressive disorder. A stratified randomization
procedure was used to allocate participants to an intervention group (CBT for
chronic headache and co-morbid depression, 12 sessions) or a control group (Routine
Primary Care, RPC). Stratification within groups was on the basis of headache
diagnosis (migraine vs TTH), and whether patients also had, or did not have, an
anxiety disorder. Measures included diaries for recording headaches and medication,
Beck Depression Inventory (BDI II), Patient Health Questionnaire (PHQ-9), and Beck
Anxiety Inventory (BAI).
Results: The average decrease in headaches in the CBT group from pre- to
post-treatment was 45.0%, compared to a 0.4% increase for the RPC group. The CBT
group was associated with a 57.1% decrease in depression, compared to a 13.4%
decrease for the RPC group (BDI II). The mean BDI scores of the CBT group were 30.6
(‘severe depression’), 13.1 (‘mild depression’), and 10.2 (‘mild depression’), at
pre-treatment, post-treatment and 4-month follow-up, respectively. On an alternative
measure of depression (PHQ-9), the CBT group was associated with a 61.5% decrease
compared to a 27.5% decrease for the RPC group. Anxiety decreased by 49.4% in the
CBT group compared to 13.9% in the RPC group (BAI), and medication consumption
decreased by 42.1% in the CBT group compared to 15.9% in the RPC group. All the
differences between the CBT and RPC groups were statistically significant except for
one which was a trend.
Conclusions: Reported here is a new treatment for a co-morbid group who
suffer from two very disabling disorders that in combination are highly refractory
to treatment. This treatment resulted in substantial reductions in both headaches
and depression, as well as medication consumption and anxiety.
P124
Effectiveness of Brief Intervention Performed by GPs for Medication Overuse
Headache in Primary Care – A Double-Blinded Pragmatic Cluster Randomised
Parallel Controlled Trial
E.S. Kristoffersen1,2, J. Straand1, K. Vetvik3,4,5,
J. Šaltyte-Benth2,4, M.B. Russell3,4, C.
Lundqvist2,4,5
1Department of General Practice, Institute of Health and Society,
University of Oslo, Oslo, Norway; 2Health Service Research Centre,
Akershus University Hospital, Lørenskog, Norway; 3Head and Neck
Research Group, Research Centre, Akershus University Hospital, Lørenskog,
Norway; 4Institute of Clinical Medicine, Campus Akershus University
Hospital, University of Oslo, Nordbyhagen, Norway; 5Department of
Neurology, Akershus University Hospital, Nordbyhagen, Norway.
Objectives: To evaluate the effects of a brief intervention (BI) versus
business as usual (BAU) in the management of medication-overuse headache (MOH) in
primary care.
Background: MOH in the general population can be identified through
screening for headache frequency and using the Severity of Dependence Scale (SDS).
BI is a method that has successfully been applied for detoxification from overuse of
alcohol and illegal drugs.
Methods: A double-blinded pragmatic cluster randomised parallel
controlled trial of BI vs. BAU. Intervention was performed in primary care by
general practitioners (GPs) trained in BI. GPs were recruited from continuing
medical education (CME) groups. A MOH screening questionnaire was sent to all the
GPs’ 18-50 year old patients. Suspected MOH patients were cluster-randomised based
on their GP. Half of the GPs were trained in BI, which was applied to suspected MOH
patients as follows: SDS was scored by the GP and individual feedback was given of
the score and relationship between this, medication overuse and headache. Finally,
advice was given regarding measures to be taken, how the patient should proceed,
possible difficulties and gains. Patients were followed-up after three months with a
clinical interview and neurological examination by a headache expert. The patients
also completed a prospective headache diary before intervention and before the
three-month follow-up.
Results: Ten CME groups with altogether 50 GPs were recruited. The
screening questionnaire was sent to almost 27000 patients aged 18-50 year on these
GPs’ list. Responder rate after two reminders was 42% for the screening
questionnaire. 191 patients were invited to the main study. One-hundred-and-nineteen
patients were recruited, 29 MOH-patients in the intervention arm and 44 MOH-patients
in the BAU-arm. In addition, 17 population controls with chronic headache without
medication overuse and 29 healthy population controls without chronic headache were
recruited.
Simple analgesics were most commonly overused, followed by triptans and combination
analgesics. Medication overuse was significantly more reduced by BI than BAU (69%
versus 27%, p<0.001), and significantly more patients in the BI arm (41%) than in
the BAU arm (18%) were free of both medication overuse and chronic headache (p=0.03)
in the intention-to-treat analysis. More results are currently being analysed and
will be presented at the meeting.
Conclusions: BI represents a simple and effective instrument for
treating MOH patients in the general population by GPs.
P125
Meditation for Migraines: A Pilot Randomized Controlled Trial
R.E. Wells1, R. Burch2, R. Paulsen2, P.
Wayne2, C. Aschenbrenner1, T.T. Houle1, J.C.
Eisenach1, E. Loder2
1Wake Forest Baptist Medical Center, Winston-Salem, NC, USA;
2Brigham and Women’s Hospital, Boston, MA, USA.
Objectives: To assess the safety, feasibility, and effect of Mindfulness
Based Stress Reduction (MBSR) in adults with migraines.
Background: Stress is a well-known trigger for headaches. Research
supports the general benefits of mind/body interventions for migraines, but there
are few rigorous studies supporting the use of specific standardized interventions.
MBSR is a standardized 8 week mind/body intervention that teaches mindfulness
meditation/yoga. Preliminary research has shown MBSR to be effective for chronic
pain syndromes, but it has not been evaluated for the treatment of migraines.
Methods: We randomized adults who met International Classification of
Headache Disorders-II criteria for episodic migraine with or without aura to either
MBSR or usual care. In addition to safety and feasibility, our primary outcome was
change in migraine frequency from baseline to follow-up immediately
post-intervention. Secondary outcomes included change from baseline to follow-up in
migraine severity, duration, and scores on instruments of headache impact/disability
(Migraine Disability Assessment, MIDAS; Headache Impact Test, HIT-6), self-efficacy
(Headache Management Self-Efficacy Scale), and mindfulness (Five Facet Mindfulness
Scale). Mann-Whitney U tests were performed to compare changes seen from baseline to
follow-up in the intervention vs. control group. To estimate effect size, we ran
independent t-tests on the change scores and report the differential change and 95%
confidence intervals (CI).
Results: 19 adults were randomized to either MBSR (n=10) or usual care
(n=9). In the intervention group, no adverse events were reported and MBSR
participation was high, with average daily home practice of 34 +/- 11 minutes and
average attendance of 6/8 classes. There was no statistically significant difference
in migraine frequency between those in the MBSR vs. control groups from before to
after the intervention (p=0.14). At follow-up, those in the MBSR group had less
severe (by 1.26 points/migraine on a 0-10 scale, [-2.6, 0.07], p=0.05) and shorter
migraines (by 2.9 hours, [-6.2, 0.53], p=0.04). The MIDAS and HIT-6 scores were
lower after the intervention compared to before in the MBSR vs. control groups (by
13 [-24, -2], p=0.02 and by 5 [-10, 0.4], p=0.04, respectively). Measures of
self-efficacy and mindfulness improved in the MBSR vs. control group from baseline
to follow-up (by 13 points each [-3, 29], p=0.04 and [1, 25], p=0.03,
respectively).
Conclusions: MBSR is a safe and feasible intervention for adults with
migraines. Although the small sample size of this pilot trial did not provide power
to detect changes in headache frequency, secondary outcomes demonstrated this
intervention had a beneficial effect on migraine duration, severity, disability,
self-efficacy, and mindfulness. Future studies with larger sample sizes are
warranted to further evaluate this intervention for adults with migraines.
P126
Double-Blind, Placebo-Controlled, Crossover Study of Early-Intervention with
Treximet in (Truly) Episodic Migraine
A.H. Calhoun1,2,3, S. Ford4
1Carolina Headache Institute, Chapel Hill, NC, USA;
2Anesthesiology, University of North Carolina, Chapel Hill, NC, USA;
3Psychiatry, University of North Carolina, Chapel Hill, NC, USA;
4Physical Medicine & Rehabilitation, University of North
Carolina, Chapel Hill, NC, USA.
Objectives: Believing that neck pain in migraineurs is integrally
related to migraine, we sought to ascertain whether early treatment with Treximet in
truly episodic migraineurs (those with fewer than 15 days a
month with either headache or neck pain) is more robust than
previously published rates.
Background: We have established the high prevalence of neck pain in
migraine and reported its consistent linear correlation with increasing headache
frequency. We have further shown that its presence is a marker for poorer treatment
outcome and disability.
Triptans have shown relatively disappointing 2-hour pain free rates ranging from
18-58%, with sustained 2-24 hour pain freedom rates ranging from 17-25%. We believe
that many subjects in these studies are not truly episodic but rather discount days
with mild headache and ignore neck pain.
Methods: Successfully screened adult migraineurs who returned baseline
diaries that recorded 2-7 migraine attacks/mon and <15 headache &/or neck
pain days/mon were eligible. Each received a blister pack containing 4 pills (3
Treximet, 1 placebo in random order) to be dispensed for treatment of 4 migraines.
Subjects were instructed to treat within 30 mins of onset of mild headache or neck
discomfort on the first day of discomfort.
Results: 78 subjects were successfully screened and issued baseline
qualification diaries; 20 were disqualified for excessive frequency of headaches
&/or neck pain. An additional 22 subjects were lost to follow-up, leaving 43
qualified and randomized subjects. Pain-free response to treatment and onset of
pain-freedom was much more robust in this population than in previous triptan
trials.
Conclusions: These results support a fundamental re-evaluation of the
role of neck pain in migraine. Results are distinctly better than those published in
conventional trials in which neck pain is not considered and support the hypothesis
that neck pain in migraine may represent hyperalgesia or allodynia. It is notable
that in this carefully selected population of subjects who had twice attested to
their episodic pattern, the greatest reason for disqualification was excessive
frequency of head or neck pain in their baseline qualification diary.
P127
The Prophylactic Treatment of PEMF in the Refractory Migraine Headache,
Double-Blind, Parallel Placebo-Controlled Study
B. Hatef1, B. Majdoleslam4, M. Toghae2, F.
Hashemirad3
1Physiotherapy, Tarbiat Modares University, Tehran, Iran (Islamic
Republic of); 2Neurology, Tehran University of Medical Science,
Tehran, Iran (Islamic Republic of); 3University of Social Welfare and
Rehabilitation Sciences, Tehran, Iran (Islamic Republic of);
4Physiotherapy, University of Social Welfare and Rehabilitation
Sciences, Tehran, Iran (Islamic Republic of).
Objectives: The aim of the study was to investigate the effect of PEMF
therapy on the refractory migraine (RM).
Background: According to the enigmatic etiology of migraine, a
comprehensive treatment that affected all contributing factors in the migraine with
minimal side effects is not provided yet. PEMF as non-pharmacological treatment of
migraine had good effect with weak evidence in the control of migraine.
Methods: 30 RM kept 2 weeks, baseline log of headache activity prior to
being randomized to having placebo or active treatment of PEMF for 30 minutes per
session and 3 days per week, for 2 weeks. The 16 patients of the active group also
were exposed to added 2 weeks and kept the migraine dairy log for 4 follow-up
months. The parameters of PEMF were squared electromagnetic pulses with 10 Hz
frequency and 5 mT intensity.
Results: The results showed an improvement in the headache days
(P<0.000), duration of headaches (P<0.002), missed work (P<0.000) and
numbers of sedative drug (P<0.001) in the active to compare with placebo group
after 2 week. Whiles the intensity of headache did not differ significantly. To
analyze the persistency of treatment in the active group, repeated measurement
indicated significant improvement in the days and duration of headaches (P<0.000)
(Figure 1) missed work (P<0.01) and numbers of sedative drug (P<0.006). The
menstruated dependency only had interaction in the intensity of headache. Then the
PEMF decreased the intensity in the non menstrual migraine patients. MIDAS scores
was significantly decreased after treatment (P<0.000).
Conclusions: PEMF (10 Hz, 5mT) had high beneficial prophylactic effect
with good persistency in the treatment of refractory migraine. The important note is
to control the appropriated dose and response of patient that should be to evaluate
P128
Rapid Rollout of a Pediatric Migraine Prevention Study Conducted in Academic
Research Centers
1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH,
USA; 2Clinical Trials Statistical & Data Management, University
of Iowa, Iowa City, IA, USA.
Objectives: This study provides a pathway for investigators and
institutions who are seeking a successful route for rapid startup of a multicenter
pediatric migraine research study. We detail the infrastructure, strategic decisions
and processes employed in the startup of an investigator initiated pediatric
migraine prevention study funded by NINDS, based at an academic research
institution.
Background: Creation of the study infrastructure included recruitment of
a committed trial team at the central coordinating center(CCC), development of a
collaborative relationship with a co-investigator statistician at an experienced
data coordinating center(DCC), recruitment of site investigators committed to
migraine research with established research sites and adequate potential subjects,
partnering with the funding group to meet the agency’s criteria, and recruitment of
experienced consultants to provide guidance during planning.
Methods: The principal investigators created ongoing collaboration among
the CCC, DCC, the research site investigators and internal and external consultants.
This included: weekly teleconferences, clear timelines /accountability for
deliverables, project management, IND regulatory, budget management, legal
contracting, recruitment/ retention/ marketing, site management, data base
development, and a novel statistical plan. Site investigators received frequent
updates regarding study development. They contributed opinions regarding study
design and became stakeholders. Detailed pre-work resulted in a clinical package
that included a complex protocol based upon a novel statistical design allowing for
three trials in one. Biweekly contact with the research sites maintained momentum at
the sites.
Results: The timeline from date of clinical package delivery to first
patient in was 13 weeks. The timeline from delivery to site activation of the
initial group of 5 sites was 13-20 weeks, compared to the reported 36 weeks for
academic centers. The second group of 10 sites achieved activation at 21 weeks. The
remaining 13 sites were activated by 31 weeks, 5 weeks ahead of the industry
average. To date, 84 % of site have been activated and open to enrollment, with 50 %
of the sites open to enrollment at 24 weeks. The overall average time to site
activation was 26 weeks.
Conclusions: A diverse research team in frequent communication with site
investigators and complex pre-work with clinical package development enabled the
rapid roll out of a multicenter pediatric migraine prevention study. The timeline to
site activation for this pediatric migraine prevention study is ahead of industry
standards.
P129
Randomized, Placebo-Controlled Pilot Trial of a Novel, Noninvasive EEG-Based
Intervention, HIRREM, for Alleviation of Episodic
Migraine
C.H. Tegeler1, C.L. Tegeler1, S.R. Kumar1, D.P.
Turner1, L. Gerdes2, S.W. Lee2, T.T.
Houle1
1Wake Forest School of Medicine, Winston Salem, NC, USA;
2Brain State Technologies, LLC, Scottsdale, AZ, USA.
Objectives: To pilot test high-resolution, relational, resonance-based
electroencephalic mirroring (HIRREMTM) for reduction of headache (HA)
frequency and severity in episodic migraine (MI) and to estimate effect sizes for
use in a larger trial.
Background: Studies have identified altered proportionation of power
across broad-band bins of the EEG frequency spectrum in MI. HIRREM is a novel,
noninvasive technology designed to facilitate relaxation and auto-calibration of
neural oscillations. HIRREM involves collection of EEG data from 2-channel
recordings, analysis of the data at high spectral resolutions (0.001 hertz), and
delivery of auditory tones for resonance in near real time with dynamically varying
dominant EEG frequencies.
Methods: Sixty-three subjects were screened, 33 enrolled, and 30 (16
HIRREM, 14 placebo; mean age 51 ± 11, 26 women) completed an IRB-approved,
randomized, single-blind, placebo-controlled, pilot trial. Individuals assigned to
active HIRREM underwent a series of 90-minute sessions (mean 10.0, range 8-12) over
a mean of 2.7 weeks (range 1-5), each of which consisted of listening to near real
time auditory feedback derived from their own dynamically varying EEG activity.
Individuals assigned to placebo had a comparable number of visits but listened to
randomly generated musical tones. Subjects maintained a daily HA diary prior to
undergoing intervention (2 weeks), during intervention, and for 2 months afterward.
Primary outcome was defined as a joint distribution of HA frequency and intensity
during the post-intervention follow up period. Analysis used a mixed effects, mixed
distributions model to predict probability of an attack, and, when present,
intensity of the attack. Using random effects, the model considers the hierarchical
data structure of multiple diary days nested within a person.
Results: Three subjects had malfunctions in electronic daily diary tools
and were excluded from analysis. Before the intervention, the HIRREM group tended to
have greater likelihood of HA compared to placebo, OR 1.56 (95% CI: 0.97 to 2.53, p
= 0.064). However, during the post-intervention period, the HIRREM group had a
reduction in the likelihood of experiencing headache compared to controls, OR 0.74
(95% CI: 0.55 to 1.03, p = 0.077). This clinically meaningful effect size did not
reach statistical significance in this pilot sample. No adverse events occurred. A
comparable number of subjects in each group (50%) guessed that they received active
HIRREM.
Conclusions: In this pilot trial, a promising effect size for reduction
in headache frequency was observed for the HIRREM intervention beyond that observed
for a placebo condition. The effect size associated with HIRREM as well as its
safety and lack of side effects suggest that larger controlled trials are
warranted.
P130
Atopic Disorders Are More Common in Childhood Migraine Than TTH
N. Öksüz1, S. Ayta2, D.U. Uluduz3, V.
Yildirim4, F. Toros4, A. Özge1
1Neurology, Mersin University School of Medicine, Mersin, Turkey;
2Neurology, Maltepe University School of Medicine, Istanbul,
Turkey; 3Neurology, Istanbul University Cerrahpasa School of
Medicine, Istanbul, Turkey; 4Child and Adolescent Psychiatry, Mersin
University School of Medicine, Mersin, Turkey.
Objectives: In order to determine and investigate the correlates of
atopic disorders in a specific dataset, we performed this retrospective
cross-sectional clinical based study.
Background: There are supportive clinical and pathophysiological data
about the relationship between migraine and atopic disorders far from a
coincidence.
Methods: Data set was composed from three tertiary center web based data
(www.childhoodheadache.org). Headache diagnosis and differential diagnosis had been
made according to ICHD-II and DSV-IV. Migraine (MwA, MwoA and chronic migraine) and
TTH (episodic TTH and chronic TTH) patients included and all other causes of
headache disorders also comorbid headache disorders like migraine plus TTH or
“possible” causes of headache had been excluded.
Results: Out of 765 patients, identical age and gender distributed 293
migraine and 178 TTH, totally 471 patients included the study. After descriptive
statistics accordingly, 49 migraine (16.7%) and 3 TTH (1.7%) reported specific
atopic disorders (p=0.000). Among migraine sufferers MwA (21.6 %) were more frequent
association than MwoA and CTTH (p=0.000). Most common types of atopic disorders were
seasonal rhinitis, conjunctivitis and asthma. There were also a close relationship
between atopic disorders and generalized anxiety disorders of the patients and
positive atopic disorders or migraine history of the families, especially
mothers.
Conclusions: Atopic disorders are common pathophysiological mechanisms
with migraine. Although ICHD-II did not require, atopic disorders have to be
questioned in all patients and relatives, not only accurate diagnosis but also
planning to prophylactic medications such as beta blockers.
P131
Anticephalgic Photoprotective Premedicated Mask: A Report of a Successful Study
of a Treatment for Migraine and/or Tension Headaches
M. Hyson
Neurology, University of Nevada School of Medicine, Las Vegas, NV,
USA.
Objectives: This study was performed to determine the efficacy of an
anticephalgic photoprotective mask in conjunction with a topical medication
containing bryonia and rhus toxicodendron in the treatment of migraine and/or
tension headache.
Background: Many clinicians are seeking headache treatment modalities
with improved safety profiles. A premedicated mask would serve not only as a
delivery system for benign topical medication, but simultaneously provide
photorelief and exert external pressure which may alleviate vascular headaches by
collapsing painfully distended extracranial arteries and reducing peripheral
sensitization.
Methods: Thirty-three patients were given masks and tubes of topical
medication containing the bryonia and rhus toxicodendron. They were instructed to
apply the medication to their frontalis and/or temporalis regions in the event they
should suffer a headache and apply a photoprotective mask. Furthermore, they were
instructed to take their usual oral or parenteral medications if required for the
relief of the headache. They subsequently filled out forms rating the degree of
relief which they attributed to the topical medication and the mask using a 0-10
scale. At the interview following the completion of their participation in the
study, the patients were also simply asked if this form of treatment helped or
not.
Thirty out of 33 patients stated the medication and the mask were effective over and
above the normal degree of relief they were receiving from their oral and/or
parenteral medications. This study demonstrated a significant efficacy rate (91%) in
the treatment of migraine and/or tension headache with the anticephalgic mask in
conjunction with a topical cream containing bryonia and rhus toxicodendron.
Results: Thirty out of 33 patients stated the medication and the mask
were effective over and above the normal degree of relief they were receiving from
their oral and/or parenteral medications. This study demonstrated a significant
efficacy rate (91%) in the treatment of migraine and/or tension headache with the
anticephalgic mask in conjunction with a topical cream containing bryonia and rhus
toxicodendron.
Conclusions: This study demonstrated a significant efficacy rate in the
treatment of migraine and/or tension headache with the anticephalgic mask in
conjunction with a topical cream containing bryonia and rhus toxicodendron.
P132
Stimulation of the Sphenopalatine Ganglion (SPG) for Cluster Headache (CH)
Treatment - Pathway CH-1, a Randomized, Sham Controlled Study
J. Schoenen1, R. Jensen2, M. Lantéri-Minet3, J.M.
Láinez4, C. Gaul5, A. Goodman6, A.
Caparso6, A. May7
1CHR de la Citadelle, Liège University, Liège, Belgium;
2Glostrup Hospital, University of Copenhagen, Copenhagen,
Denmark; 3Hôpital Pasteur, Nice, France; 4Hospital Clinico
Universitario, Universidad de Valencia, Valencia, Spain; 5University
Duisburg-Essen, Essen, Germany; 6Autonomic Technologies, Inc.,
Redwood City, CA, USA; 7Universitäts-Krankenhaus Eppendorf, Hamburg,
Germany.
Objectives: The pain and autonomic symptoms of CH result from activation
of the trigeminal parasympathetic reflex, mediated through the SPG. We aimed to
investigate the safety and efficacy of on-demand SPG stimulation for the treatment
of chronic CH.
Background: CH is a highly disabling neurological disorder. A
multi-center, multiple CH acute treatment study of a novel SPG neurostimulation
therapy has been completed.
Methods: All patients met the ICHD-2 criteria for chronic CH with a
minimum of 4 attacks/week. Patients were implanted with a miniaturized
neurostimulator which, along with a controller, provides on-demand SPG stimulation.
During the blinded experimental period (EXP), each attack was randomly treated with
one of three therapies: full, sub-perception or sham stimulation using a random
insertion of placebo design. Pain relief at 15 minutes (decrease from “moderate” or
“severe” to ‘none’ or ‘mild’ on the 5-point scale), rescue medication use and CH
frequency reduction were analyzed. Responders were defined as acute (pain relief in
≥50% of treated attacks), and/or frequency (≥50% reduction in attack frequency vs.
baseline, with no increases in preventive medications).
Results: 43 patients were enrolled, 38 completed the EXP. The average
baseline CH frequency was 17 attacks/week. Pain relief was achieved in 55% of full
stimulation treated attacks (N=260) compared to 8% with sub-perception (N=254) and
8% with sham stimulation (N=255). Rescue medications were used in 42% of full
stimulation treated attacks compared to 73% of attacks treated with either
sub-perception or sham stimulation. 11 (29%) of the 38 patients were acute
responders, and successfully treated 81% of their CH attacks with SPG stimulation.
16 patients (42%) were frequency responders with an average reduction of 88% at the
end of the EXP compared to baseline.
Clinically significant improvements occurred in 63% (24 of 38) of patients. Of these
24, 8 (33%) were acute responders only, 13 (54%) were frequency responders only, and
3 (13%) were both acute and frequency responders. 10 of the 13 frequency only
responders (77%) did not treat enough attacks to be evaluated for acute response. Of
the 37% (N=14) non-responders, half (N=7) did not treat a sufficient number of
attacks for evaluation of acute response.
Most patients (77%) experienced transient, mild to moderate sensory disturbances
within the first 30 days following implant. Most sensory disturbances remained mild
or resolved at three months post-implant.
Conclusions: Acute, on-demand SPG stimulation using the ATI
Neurostimulation System is an effective and safe novel therapy for chronic CH.
P133
New ICHD-III Cluster Headache Criteria in the LUCA Population
I.F. de Coo1, L.A. Wilbrink1,3, J. Haan1,2, M.D.
Ferrari1, G.M. Terwindt1
1Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 2Neurology, Rijnstate Hospital, Leiderdorp, The
Netherlands; 3Neurosurgery, Maastricht University Medical Center,
Maastricht, The Netherlands.
Objectives: We evaluated the presence of ‘ipsilateral sense of aural
fullness’ and ‘ipsilateral facial flushing’ in our LUCA (Leiden University Cluster
headache Analysis programme) population in subjects: 1) fulfilling the ICHD-II
criteria1 for the diagnosis CH (cluster headache) and 2) most
probably CH (clinical characteristics fulfill all ICHD-II criteria for the diagnosis
CH except one criterion).
Background: The forthcoming ICHD-III criteria for cluster headache will
add ‘ipsilateral sense of aural (ear) fullness’ and ‘ipsilateral forehead/facial
flushing’ as possible accompanying autonomic symptoms.
Methods: In this cross-sectional cohort study a sense of aural fullness
and facial flushing during cluster headache attacks were investigated, using
web-based questionnaires.
Results: Of the 1139 subjects who entered our web-based recruitment
system, 864 subjects (75,9%) returned all necessary questionnaires. According tot
the ICHD-II criteria 535 subjects of the 864 subjects were diagnosed with CH, 205
additional subjects as most probably CH (missing 1 ICHD-II criterion) and 124
subjects as no CH. In 1,5% of these 205 probably CH subjects no autonomic symptoms
was the missing criterion according to the ICHD-II. Of all CH subjects 33.3%
reported an ‘ipsilateral sense of aural fullness’ and 20.0% ‘ipsilateral facial
flushing’ during a cluster headache attack. According to the new ICHD-III criteria 2
out of 205 probably CH subjects would be diagnosed as having cluster headache.
Conclusions: Although ‘ipsilateral sense of aural fullness’ and ‘
ipsilateral facial flushing’ was often reported in our CH subjects, modification of
the ICHD-III criteria of cluster headache with these autonomic symptoms led to a
diagnosis of cluster headache in only 2 more patients.
P134
High Doses of Corticosteroids and Verapamil in Cluster Headache
G. Zanchin1, C. Disco1, F. Mainardi2, F.
Maggioni1
1Department of Neurosciences, Headache Centre of the Veneto
Region, Padua, Italy; 2SS Giovanni e Paolo Hospital, Venice,
Italy.
Objectives: A short course of corticosteroids is considered the most
fast-acting prophylactic therapy of cluster headache (CH), rapidly suppressing
attacks during the time required for verapamil (V) to have effect. However, it is
common experience that the current use of both drugs is often unsatisfactory.
Background: We report our preliminary results of an open clinical study
on a series of patients (P) affected by episodic cluster headache (ECH) treated with
high doses of iv methylprednisolone (MP) and verapamil (V) per os.
Methods: Upon informed consent, a consecutive series of 20 P (6 female,
14 male, 41.1 ± 13.2 years), affected by ECH (ICHD-II 2004) was followed during 29
active cluster periods (CP). EKG and blood chemistry, including cells count,
glucose, electrolytes, liver enzymes, were performed routinely before and after 5
days since the start of therapy, and when deemed appropriate thereafter. P with
controindications for steroids and/or V were excluded. P with at least two prior
clusters were included (cluster/year 1.3 ± 0.6; mean duration 20-40 days for 5 P,
40-90 days for 8 P and up to 300 days for 7 P; attacks/day 2,3 ±1.1). Most P were
recruited within 2 weeks from the beginning and more than a month before the
expected spontaneous end of CP. P received MP 250-500 mg/day iv for 5 days, then 120
mg im for 3 days, 80 mg im for 3 days and prednisone 25 mg per os for 2 days,
tapered in the following 8 days. Concomitantly, oral V was started with progressive
increments up to 320 and 600 mg/day, based on anamnestic data about its previous
efficacy and tolerability.
Results: The 29 CP considered were interrupted within the third day from
the start of MP/V administration. In 22/29 (76%) CP, no recurrence was observed
during a 6 months follow up. V dosage was 320 mg/day in 11 CP, 360 in 3, 400 in 2,
480 in 3, 520 in 2, 640 in 1. In 7/29 (24%) CP, recurrence was observed within the
first month. Among them, in 4 CP, the increment of V up to 400 mg/day in 1 CP, 520
in 2, and 560 in 1 blocked the attacks within a week, with no further recurrence
during a 6 months follow up; whereas, in 3 remaining CP, a reduction of > 50% in
frequency and intensity and of > 75% in the length of active phase was observed
in comparison with previous anamnestic experience.
In all our P, V was gradually tapered in not less than a month, and at least 30 days
after the last attack. Mild side effects were reported by 5 P (5 CP), mainly
moderate anxiety, forunculosis (MP); constipation, transitory asthenia, bradicardia,
isolated ankle oedema with no clinical signs of cardiac involvement (V).
Conclusions: To our knowledge this is the first report about efficacy of
high doses of iv MP and V per os in ECH. If confirmed, our very satisfactory
findings warrant the revaluation of the doses and timing of these drugs with
appropriate clinical trials.
P135
Stimulation of the Sphenopalatine Ganglion (SPG) for Cluster Headache (CH)
Treatment – Pathway CH-1, Impact on Quality of Life (QoL) and Headache
Disability
J.M. Láinez1, J. Schoenen2, R. Jensen3, M.
Lantéri-Minet4, C. Gaul5, A. Goodman6, A.
Caparso6, A. May7
1Hospital Clinico Universitario, Universidad de Valencia,
Valencia, Spain; 2CHR de la Citadelle, Liège University, Liège,
Belgium; 3Glostrup Hospital, University of Copenhagen, Copenhagen,
Denmark; 4Hôpital Pasteur, Nice, France; 5University
Duisburg-Essen, Essen, Germany; 6Autonomic Technologies, Inc.,
Redwood City, CA, USA; 7Universitäts-Krankenhaus Eppendorf, Hamburg,
Germany.
Objectives: We evaluated the impact of on-demand SPG stimulation on
headache disability and QoL in chronic CH patients during the Pathway CH-1
study.
Background: CH is a highly disabling neurological condition in which
most patients report substantial restrictions to their daily living and significant
reductions in their QoL; disability is amplified in patients with chronic CH.
Methods: SPG stimulation was performed with the ATI Neurostimulator, a
miniaturized implantable neurostimulator which, along with a controller, provides
patient controlled SPG stimulation. At the completion of the blinded, randomized
experimental period (EXP), headache disability and QoL were evaluated using the
HIT-6 and SF-36v2 questionnaires. Changes from baseline were compared to the
clinically significant differences (CSD) in the literature [1,2].
Results: 43 patients were enrolled, 38 completed EXP. One patient did
not complete the HIT-6 survey following EXP. Mean age of these 38 patients was 42
years, with an average disease duration of 12 years (range: 2-36). At baseline,
these patients averaged 17 attacks/week; all used triptans as acute therapy, 50%
also used oxygen. 79% of patients used preventive therapy, with the majority (68%)
using verapamil.
Mean baseline HIT-6 headache disability score was 66.2 (severe impact). 22 (58%)
patients improved by greater than the HIT-6 CSD (-2.3 units) following EXP; average
HIT-6 score after EXP was 59. Mean baseline SF-36v2 Physical (PCS) and Mental (MCS)
Component Scores were 38.4 and 33.2, respectively. An improvement at end of EXP of
greater than or within the SF-36v2 CSD (3-5 units) in PCS, MCS or both was observed
in 76% (N=29) of patients.
63% (N=24) of patients experienced either acute pain relief at 15 minutes in ≥50% of
treated attacks, reduction in attack frequency of ≥50% compared to baseline, or both
during EXP. 83% of responders (20 out of 24) reported clinically significant
improvements in either HIT-6 or SF-36v2. An additional 11 patients who were not
considered efficacy responders demonstrated clinically significant improvements in
HIT-6, SF-36v2 or both following EXP. Thus, 35 of 38 patients (92%) showed benefit
from the therapy in terms of acute pain relief, decreased attack frequency, and/or
improvement in disability or QoL.
Conclusions: Patient controlled, on-demand SPG stimulation using the ATI
Neurostimulation System is a safe and effective therapy also associated with
significant clinical improvements in headache disability as well as physical and
mental QoL metrics.
P136
Exacerbation of SUNCT and SUNA Syndromes during Intravenous Dihydroergotamine
Treatment: A Case Series and Pathophysiological Considerations
G. Lambru1, S. Miller1, P. Shanahan1, M.
Matharu1
1Institute of Neurology and the National Hospital for Neurology
and Neurosurgery, London, UK, United Kingdom.
Objectives: We describe a series of patients with SUNCT and SUNA in
comorbidity with chronic migraine (CM) or cluster headache (CH), treated with
intravenous dihydroergotamine (IV DHE), who experienced dramatic worsening of their
SUNCT and SUNA syndromes while on DHE.
Background: Several cases of SUNCT exacerbations with dopamine agonists
in patients with prolactinomas have been described, suggesting that the
dopamine-prolactin axis might play a role in SUNCT pathophysiology. DHE is an ergot
alkaloid derivate with affinity for serotonin and dopamine receptors, known to be
effective in migraine and CH.
Methods: An initial observation that patients with both CM or CH and
SUNCT/SUNA receiving IV DHE had complained of dramatic worsening of their SUNCT/SUNA
led to review of case notes of individuals assessed between 2008 and 2012, with CM
or CH and SUNCT/SUNA, according to ICHD-2 criteria, who underwent at least a trial
of IV DHE.
Results: Twenty-three patients with a diagnosis of SUNCT or SUNA in
comorbidity with CM or CH, who were treated with IV DHE, were identified. Five
patients had a mild improvement of the SUNCT/SUNA (22%), 12 patients had no
appreciable effect (52%), whereas six patients had a dramatic worsening of the
SUNCT/SUNA (30%). Moreover, one chronic CH patient developed a new onset SUNA during
his first IV DHE infusion treatment. Of these seven, three patients had chronic
SUNCT and four chronic SUNA. Four of them had CM in comorbidity; one had CM and
sporadic hemiplegic migraine and two patients had chronic CH. Patients requiring
repeated courses of IV DHE, consistently had exacerbations of SUNCT/SUNA whilst on
treatment. All seven patients required a course of IV lidocaine for 7-10 days in
order to obtain a reduction of the SUNCT and SUNA attacks. Patients 1-4 had normal
MRI brain scans; patient 5 and 7 had ipsilateral vascular loops with the trigeminal
nerve, whereas patient 6 had a pituitary non-secretory adenoma.
Conclusions: A significant proportion of our patients suffered severe
exacerbation of SUNCT or SUNA whilst on IV DHE, whereas patient 5 developed a new
onset SUNA syndrome during his first IV DHE course. We speculate that DHE might
worsen SUNCT and SUNA syndromes through a perturbation in the dopaminergic system.
Moreover the different effect of DHE in migraine and CH compared to SUNCT/SUNA,
might suggest the involvement of different neurochemical pathways in the latter that
require further investigations.
Outcome of IV DHE for CM or CCH (duration)
Baseline attack frequency (SUNCT/SUNA)
Attack frequency during IV DHE
(SUNCT/SUNA)
1
CM: pain free (7 weeks)
10-15/day
SUNCT status (from day 4)
2
CM: >50% improvement (6 weeks)
15-20/day
50-60/day (from day 3)
3
CCH: pain free (3 weeks)
20-30/day
60/day (from day 4)
4
CM: 70% improvement (3 weeks)
15-80/day
SUNA status (from day 3)
5
CCH: ineffective
none
New onset SUNA (from day 5)
6
CM: pain free (1 week)
10-30/day
50-60/day (from day 3)
7
CM: pain free (2 weeks)
40-50/day
>100/day (from day 4)
P137
Cutaneous Allodynia in Cluster Headache Patients in the LUCA
Population
L.A. Wilbrink1,2, M.A. Louter1,3, O.P.M. Teernstra2,
J. Haan1,4, G.M. Terwindt1, M.D. Ferrari1
1Department of Neurology, Leiden University Medical Centre,
Leiden, The Netherlands; 2Department of Neurosurgery, Maastricht
University Medical Centre, Maastricht, The Netherlands; 3Department
of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands;
4Department of Neurology, Rijnland Hospital, Leiderdorp, The
Netherlands.
Objectives: To investigate the prevalence and severity of cutaneous
allodynia in a group of cluster headache patients.
Background: Cutaneous allodynia, the perception of pain in response to
non-noxious stimuli to the skin, is considered as a marker for central
sensitization, and has been described in various pain syndromes, including migraine.
By contrast, the appearance of cutaneous allodynia in cluster headache patients is
still subject of debate.
Methods: This is a cross-sectional study in participants with cluster
headache from the LUCA (Leiden University Cluster headache neuro-Analysis programme)
population. Cluster headache diagnoses were based on ICHD-II criteria. We assessed
allodynia by using the 12-item Allodynia Symptom Checklist (ASC-12). In a
multivariate analysis we controlled for gender, lifetime depression, cluster
headache subtype (chronic vs. episodic), age at onset, and comorbid migraine.
Results: A total of 218 (36%) of 606 patients had allodynia; 107 mild,
62 moderate, and 49 severe allodynia. Cluster headache patients with comorbid
lifetime depression had significantly higher odds for cutaneous allodynia (OR 1.64,
95% CI 1.08-2.51). Significantly higher odds were also found for female gender (OR
2.08, 95% 1.30-3.33) and comorbid migraine (OR 2.00 95% CI 1.05-3.82) and
significantly lower odds for age at onset (OR 0.98, 95% CI 0.96-0.99). Chronic
cluster headache did not attribute to the odds of having allodynia.
Conclusions: Cutaneous allodynia was present in more than one third of
cluster headache patients. Future research is needed to unravel the mechanisms
behind cutaneous allodynia in cluster headache.
P138
A Possibility To Predict Chronic Cluster Headache Refractoriness to
Pharmacological Therapies and Deep Brain Stimulation
M. Nicolodi1, A. Torrini1, V. Sandoval1
1CNS Research, Foundation Prevention and Therapy Primary Pain,
Florence, Italy.
Objectives: Our aim was to enlighten a possible way to predict
refractoriness of chronic cluster headache (CH) to either pharmacological therapies
and deep brain stimulation (DBS).
Background: Till today this question has no answer. Being stated that
sumatriptan, the “king” of the drugs for CH attack, induces activation of central
cholinergic system [1], we also used a pupillometric approach regarding cholinergic
system.
Methods: We used an algorithm including family and personal history of
responders and non responders. Algorithm is a procedure for automated establishing a
final “output”. We also used a pupillometric evaluation of instillation of 1%
tropicamide, a muscarinic antagonist. Pupil diameter was evaluated in standard light
condition before and at 0, 30, 60, 90, 120, 150, 180, 210 min following tropicamide
eye drops instillation, the latter followed a 4-days wash-out period. Results
derived from the comparison between a group of chronic CH classified as responders
and a matched group of non responder chronic CH sufferers. On the ground of response
to either prophylactic treatment administration or to surgical practice we can
divide chronic CH sufferers in two groups: Group A) included 47 non responders (40
males, 7 females; mean age 34.4 + 3.1 SD). Group A was
compared to a matched group – Group B- of 85 chronic CH responding to therapeutic
approaches (76 males, 9 females: mean age 34.3 + 2.9 SD). Pupillary changes were
evaluated in 3 Groups of males: 12 chronic CH sufferers refractory to therapies (age
33.2 + 4.8SD), 12 chronic CH responding to therapeutic approaches (age 33.8 + 4.4
SD) and 12 controls (age 33.1 + 5.7 SD).
Results: Outcomes regarded either pupillopharmacological approach and an
algorithm the output of which was refractory CH. Algorithm evidenced an higher
(p>0.0001) link score regarding items of inheritance taken as input compared to
data set of output. The peak of tropicamide-induced mydriasis was at 90: 5.5 mm
+ 0.24 SD versus 3.1 + 0.55 SD
baseline p> 0.0001 symptomatic side; 6.58 mm + 0.54 SD
versus 3.09 mm + 0.57 SD non symptomatic side eye p>
0.0001 in refractorgy CH sufferers. In chronic CH sufferers responding to
therapeutic approaches 7.1 mm + 0.37 SD versus 2.9
+ 0.6 SD baseline p> 0.0001 symptomatic side; 8.2 mm
+ 0.74 SD versus 3.0 mm + 0.53 SD
non symptomatic side eye p> 0.0001. In healthy control group 7.7 mm
+ 1.2 SD versus 3.2 mm + 10.58 SD
baseline p> 0.0001.
Conclusions: Non responder chronic CH sufferers show the lower
(p>0.0001) mydriatic response. The algorithm profile, giving a score of risk for
refractoriness, mirrored the poorness of response to tropicamide and stressed the
possible role of a neural abnormal trim inherited in some CH. Such an abnormal
inherited trim, seemingly involving cholinergic system, is likely to determine
refractoriness to therapies including DBS.
P139
Marijuana for Chronic Cluster Headache - Its Effect on Cluster Headache History
and on Cholinergic Mydriasis
M. Nicolodi1, A. Torrini1, V. Sandoval1
1CNS Research, Foundation Prevention and Therapy Primary Pain,
Florence, Italy.
Objectives: First question regards the effectiveness of marijuana in
chronic cluster headache (CH) and the distinction between drug-induced pain
tolerance and pain relief. Second question concerned possible effect on cholinergic
system. Third question concerns the impact of marijuana on CH history.
Background: Hypothesis of cholinergic involvement flows from animal data
indicating an inhibition of hippocampal acetylcholine release after acute and
repeated cannabinoids.
Methods: Pain tolerance was evaluated as behavioral manifestations i.e.
movements and vocalization measured by using electronic wrist ergometer and sound
registration. Pain relief was evaluated on a 0-10 VAS. The parameters were applied
to 4 subsequent CH attacks during which sumatriptan or majiuana were used. The
cholinergic receptor function was observed by using a pupillometric approach
following instillation of 1% tropicamide, a muscarinic antagonist. Pupil diameter
was measured before and at 0, 30, 60, 90, 120, 180, 210 min after eye drops
instillation. A 10 years perspective epidemiological study was performed in 2 groups
of men matched for age: Group 1 included CH abusing (n= 100, mean age 31.3 + 4.8)
marjiuana; Group 2 included CH sufferers (n= 100, mean age 31.1 + 5.2) never using
other drug than sumatriptan.
Results: The drug does not abort CH attacks. Sufferers using marijuana
have an higher pain tolerance rating 30% more than CH not using cannabis as shown by
behavioral parameters. VAS score registered no significant decrease following
majiuana consumption compared to baseline in 4 subsequent CH attacks. The peak of
tropicamide-induced mydriasis was at 90: 5.8 mm + 0.142 SD
versus 2.09 + 0.53 SD baseline p> 0.0001 symptomatic side;
6.5 mm + 0.65 SD versus 3.09 mm + 0.59
non symptomatic side eye p> 0.0001 in CH using marijuana. In chronic CH never
using marjiuana 7.9 mm + 0.173 SD versus 2.9
+ 0.54 SD baseline hp> 0.0001 symptomatic side; 8.5 mm
+ 0.65 SD versus 3.1 mm + 0.55 SD
non symptomatic side eye p> 0.0001. In healthy controls 7.9 mm + 1.2 SD versus
3.3 mm + 10.5 8 SD baseline p> 0.0001. Mydriasis of CH
abusers was lower (p>000.1) than controls and non addict CH sufferers.
Epidemiological observation evidenced that eighty-six marijuana abusers suffered
from episodic CH from the beginning till to the end of the observation. The
remainder started an history of chronic CH 2.1 years + 1.6 SD
after starting abuse. Whereas, in the group of sufferers never using cannabis, only
two sufferers became chronic.
Conclusions: A different response to tropicamide challenge distinguishes
controls and non drug user CH from marijuana CH abusers and suggests a defect
induced by marijuana on central cholinergic system. It is not possible to discard
that CH became chronic because of the use of marijuana. It seems noteworthy that
marijuana seemingly only aids to better tolerate pain as shown by behavioral items
and VAS.
P140
Testosterone Cypionate in the Treatment of Episodic Cluster Headache: A Case
Series and Meta Analysis
F. Conidi1, A. Ahn2
1Florida Center for Headache and Sports Neurology, Port Saint
Lucie, FL, USA; 2Department of Neurology, University of Florida
College of Medicine, Gainesville, FL, USA.
Objectives: To obtain preliminary evidence in support of the hypothesis
that testosterone supplementation may be of utility in males with cluster
headache.
Background: Cluster headache is a primary headache disorder in which
several lines of evidence implicate a change in hypothalamic function. Kudrow,
Stillman, and others have reported low or low-normal testosterone levels in patients
with cluster headache, and have indicated benefit with testosterone supplementation.
However, the data for this association with low testosterone, and support for the
benefit of testosterone supplementation is still sparse.
Methods: This is an open-label, unblinded, retrospective case series of
patients with the ICHD-2 diagnosis of cluster headache. Male patients with cluster
headache between the ages of 19-65 were evaluated for testosterone levels. Those
with low or low-normal levels of testosterone but without abnormally high PSA levels
were given 400mg testosterone intramuscular injection. Repeat injections were given
for subsequent cycles of cluster attacks, where available. We also analyzed the
present data together with the previously published experience with
testosterone.
Results: There were 23 patients initially evaluated with cluster
headache, and 17 were evaluated with testosterone and PSA levels. The median
testosterone level was below normal, including 11 patients with low total
testosterone levels, and an additional 4 that had low normal total testosterone
levels. Of these 15 patients, 5 (29%) had a sustained headache-free response to a
single injection of 400 mg testosterone. An additional 3 patients had a marked
decrease in frequency and intensity prior to the resolution of the cluster cycle. An
additional 6 patients received a second dose of 200 mg testosterone with complete
resolution of the headache. A single patient had a complete resolution after a third
injection, again with 200 mg testosterone. A total of 17 cluster cycles were treated
with testosterone injection in this manner, and 14 (82%) of these cycles were
aborted by this approach.
Conclusions: The present evidence suggests that total testosterone
levels are below normal in those with cluster headache. Testosterone injection may
be an effective way to abort the cluster cycle. Present evidence is supportive of a
definitive prospective, randomized, placebo controlled trial.
P141
Non-Invasive Vagus Nerve Stimulation for the Treatment of Cluster Headache: A
Cohort Study
A.D. Nesbitt1,2, J.C.A. Marin1, E. Tomkins3, M.H.
Ruttledge3, P.J. Goadsby1,4
1Neurosciences Division, Royal Free London NHS Foundation Trust,
London, United Kingdom; 2Surrey Sleep Research Centre, University of
Surrey, Guildford, United Kingdom; 3Beaumont Hospital, Dublin,
Ireland; 4Headache Group, University of California, San Francisco,
San Francisco, CA, USA.
Objectives: The objective of this work is to undertake a preliminary
clinical evaluation of treatment outcomes in patients with cluster headache using a
non-invasive vagus nerve stimulation device, CE marked in Europe for the treatment
of headache disorders.
Background: Cluster headache (CH) is a highly disabling primary headache
disorder. Abortive therapy is currently limited by dose restrictions of triptans,
and practicality issues of using oxygen. Preventive medications may not be entirely
effective. Surgical interventions, in particular deep brain stimulation, carry
additional risks.
A need therefore exists for a novel, safe and practical therapeutic approach. We
assessed the usefulness of a new portable, non-invasive vagus nerve stimulation
(nVNS) device, the GammaCore.
Methods: Patients with CH attending one of two headache centres were
offered nVNS treatment in an unbiased fashion. After training, most patients were
instructed to use the device both acutely to treat attacks, and twice daily as a
preventive measure. A few patients used it for acute treatment only. Case notes were
reviewed, and patients questioned during routine follow-up about their experience
with the device and the impact they perceived it had.
Results: Of patients given the device, 21 of 25 (12 male; 12 chronic, 10
of who were considered to be medically intractable, and 9 episodic; median age 46,
range 13-84) had sufficient data available during a median device use period of 12
weeks (range 1-26) to include in analysis. Eighteen reported an overall improvement
in their condition, stating a mean estimated subjective improvement of 51% (SD 30)
from baseline, while three remained the same. Ten patients were able to reduce
significantly or stop their previous abortive treatment, seven reduced it and four
required the same amount as before. Eight patients were very satisfied, ten
satisfied and two equivocally satisfied after using the device. Only one patient
felt dissatisfied. All 21 stated they would recommend this treatment to other
patients with CH.
Patient feedback suggests that nVNS can both abort and significantly improve attack
intensity, as well as reducing attack frequency when used prophylactically. In
addition, prophylactic treatment may offer highly significant improvement in some
patients with otherwise intractable chronic CH.
Conclusions: This is the first evaluation of an entirely new treatment
modality for CH that appears to be well-tolerated and effective in both the acute
and preventive treatment of CH. The significant improvement
achieved in some patients with medically intractable chronic CH suggests that nVNS
should be trialled before intracranial surgical procedures are considered.
These preliminary findings will serve to inform the design of clinical trials aimed
at further clarifying the efficacy of this treatment.
P142
Naratriptan in Prophylactic Treatment of Cluster Headache; the 2nd
Edition
Y. Ito1, N. Araki1, T. Mitsufuji1, T.
Shimazu2, Y. Kato4, Y. Asano2, Y.
Maruki2, N. Tanahashi4, F. Sakai3
1Department of Neurology, Saitama Medical University, 38
Morohongo, Moroyama, Saitama, Japan; 2Saitama Neuropsychiatric
Institute, 6-11-1, Honmachi-higashi, Chuo-ku, Saitama-shi, Saitama, Japan;
3Saitama International Headache Center, 6-11-1, Honmachi-higashi,
Chuo-ku, Saitama-shi, Saitama, Japan; 4Saitama Medical University
International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama,
Japan.
Objectives: The purpose of this study is to determine whether
naratriptan would show efficacy in prophylactic treatment of cluster headache in
Japan.
Background: Naratriptan, 5-hydroxytryptamine1B/D
(5-HT1B/D)-agonist, is an effective medicine for migraine.
Naratriptan has also been reported to reduce the frequency of cluster headache
(1-3).
Methods: We report 13 patients with cluster headache preventively
treated with naratiptan. We used the International Classification of Headache
Disorders; 2nd Edition (ICHD-II) for diagnosing of cluster headache. The
study was conducted in 4 centers (Department of Neurology, Saitama Medical
University, Saitama Neuropsychiatric Institute, Saitama International Headache
Center and Saitama Medical University International Medical Center) and patients
were recruited from these specialized headache outpatient centers. Naratriptan was
taken before they went to bed.
Results: Eleven of 13 patients with cluster headache have shown no
attack after naratriptan treatment. In one case, the frequency of attacks was
decreased by naratriptan. But naratriptan had no effect for her headache in one
case.
Conclusions: It has been suggested that naratriptan might be preventive
medicine for cluster headache because biological half-life of naratriptan is longer
than that of other triptans.
P143
No Olfactory Deficit in Episodic Cluster Headache
S. Naegel1, N. Buckanie1, D. Holle1, F.
Rosenow2, S. Knake2, H.-C. Diener1, Z.
Katsarava1,3, M. Obermann1
1Dept. of Neurology, University Duisburg-Essen, Essen, Germany;
2Dept. of Neurology, University Hospital Giessen-Marburg,
Marburg, Germany; 3Dept. of Neurology, Ev. Hospital Unna, Unna,
Germany.
Objectives: To determine whether patients suffering episodic cluster
headache have a nasal chemosensory performance deficit.
Background: Cluster headache (CH) is a rare primary headache disorder,
which is characterized by strictly unilateral severe headache attacks. Its
pathophysiology is still obscure. Electrophysiological findings in episodic CH
showed an asymmetric facilitation of trigeminal nociceptive processing which is
predominantly located on brainstem level even in remission periods. But as in other
headache syndromes, such as migraine, alterations and disregulation in other senses
are in discussion. A diffusion tensor imaging study detected frontobasal alterations
and the authors suggested an involvement of the olfactory system (Teepker et al.).
Furthermore preliminarily data from a small study using olfactory testing even
suggested alterations in olfactory performance and raised the question of clinical
implications of this finding.
Methods: We investigated 30 patients (mean age: 46y; m:f = 24:6)
suffering episodic cluster headache and currently being in a remission periods,
using the commercially available ‘Sniffin’Sticks’ test battery testing nasal
chemosensory performance. With this system based on pen-like odor dispensing devices
olfactory performance was tested regarding odor threshold, odor discrimination and
odor identification. Determined scores were then compared to the standardized
reference values previously defined in a big control cohort.
Results: Neither in overall olfactory performance (TDI-Value),
calculated as the sum of the subscores, nor in any of those we were able to detect
alterations in olfactory performance. TDI Value (ref.: 30.5) was 31.39±5.49
ipsilateral and 30.47±4.76 contralateral to headache. Scores for threshold,
discrimination and identification behaved comparable and will be presented as
table.
Conclusions: No lack of olfactory performance was observed in the
patient cohort regarding odor threshold, discrimination, identification or
TDI-overall performance. Furthermore no lateralization in nasal chemosensory
performance could be identified in side comparison in all domains. This is in
contrast to previous findings and pulls CH apart from being a multisensory
disorder.
P144
Botulinum Toxin Type A in the Treatment of Episodic and Chronic Form of Cluster
Headache
J.J. Rozniecki1, A. Durko1
1Department of Neurology, Medical University of Lodz, Lodz,
Poland.
Objectives: The aim of the study was to evaluate safety and efficacy of
botulinum toxin injections (in completely new, unchecked paradigm) in patients with
chronic (CCH) or episodic (ECH) cluster headache.
Background: Cluster headache (CH), especially in its chronic form, is
frequently resistant to hardly a few drugs available for this disease, like
steroids, verapamil, valproic acid, lithium and topiramate. Another therapeutic
option for resistant cases is specifically desired. As recently botulinum toxin has
been successfully tried in chronic migraine – another type of daily or almost daily
headache type, it seemed to be worth trying this therapy also in CH. Until now there
has been only 1 original publication on small doses (50 U) of botulinum toxin A in a
group of 12 CH patients [1].
Methods: Twelve patients - 4 with CCH and 8 with ECH (2 women with ECH,
with mean age of 51 years, and 10 men – 6 with ECH and 4 with CCH, with mean age of
50,1 years), with no other concomitant treatment, were injected i.m. with a total
dose of botulinum toxin type A (Botox) of 200 U each, divided into 14-18 portions.
The area of injections covered typical painful region, and was adjusted individually
(“follow the pain”). Decision on re-injections after 90 days depended on whether a
patient suffered from headaches or not, at that time. The effect of treatment was
evaluated as comparison (before and after therapy) of: the number of headaches per
24 hours, number of headaches per month, mean duration of headaches, mean intensity
of headaches, headache index (frequency x duration x intensity), number of days from
injection to significant improvement and to remission.
Results: Ten out of 12 patients evaluated the treatment as beneficial.
They reported improvement in most of estimated parameters, while headache index
after 90 days was significantly lowered in all 10 cases (p<0.05). In
“responders”, the mean time to significant improvement was 15.8 days (11.8 days in
ECH and 21.7 days in CCH) while average time to achieve remission in ECH was 25.3
days. CCH patients had temporal remissions lasting even several months. One patient
with ECH had only partial and short-lasting improvement, while another ECH patient
did not find the treatment helpful at all. No adverse effects (beside asymmetry of
the forehead) were reported.
Conclusions: Botulinum toxin type A in the dose of 200 U injected i.m.
in relatively small fronto-temporal area, evaluated in an open trial, is safe, well
tolerated, and at least partially effective method of treatment in both forms of
CH.
P145
Shunting the Diagnosis: A Case of Secondary Cluster Headache
P.G. Mathew1,2, H.U. Sheikh1, S. Joshi1
1Department of Neurology, John R. Graham Headache Center, Harvard
Medical School, Brigham and Women’s Hospital, Boston, MA, USA;
2Division of Neurology, Harvard Medical School, Cambridge Health
Alliance, Cambridge, MA, USA.
Objectives: The intent of this study is to demonstrate cavernomas as
potential structural causes for secondary cluster headache.
Background: Cavernomas are thin dilated vascular channels that lack
smooth muscle or neural tissue. Their incidence is 0.3-0.5% and are usually
discovered in young adults. The most frequent presentation is seizure, but can
present with focal deficits or headaches. One case reported a tectal cavernoma
causing hydrocephalus requiring shunting and subsequent surgical resection. Another
case reported idiopathic hydrocephalus causing cluster headaches. Other than these
cases, to our knowledge, there are no other reports of cavernomas causing
hydrocephalus or such patients developing secondary cluster headaches.
Methods: A 36 yo woman with history of right hemiplegia and hemisensory
deficits since childhood presented with neck pain and falls. MRI revealed two
cavernomas in the left thalamus extending to the midbrain and tectal region. Two
years later, she developed chronic nausea and headaches. A repeat MRI demonstrated
obstructive hydrocephalus, and a VP shunt was placed with resolution of
hydrocephalus and improvement of nausea. Unfortunately, there was no improvement of
headaches.
Results: Since onset, she had 3-4 headaches per day that occur around
the same time daily. They are located around the left temporal/parietal area,
lasting about 45 minutes. The headaches are throbbing, 7-10/10 with photophobia,
phonophobia, nausea, vomiting, and cutaneous allodynia. During attacks she feels
restless and unable to find a comfortable position. There is unilateral eyelid
drooping with left sided congestion and some runny nose with headaches, but no other
autonomic symptoms. She was started on a trial of verapamil, and reached a dose of
360mg daily. On this dose of verapamil, her headache frequency improved to 1
headache per day with a 5/10 intensity. For abortive therapy, she has used oxygen at
10 LPM with a face mask, which typically terminates a headache within 10
minutes.
Conclusions: The patient’s cavernomas caused obstructive hydrocephalus
requiring intervention. Initially, it was unclear whether her hydrocephalus and/or
cavernomas were contributing to her headaches with cluster features. Subsequent
resolution of her hydrocephalus after VP shunt placement, did not lead to
improvement of her cluster headache symptoms. Therefore, her cavernomas may be
playing a causative role in her cluster headaches. In addition, this case suggests
that verapamil and oxygen may be effective treatments for secondary cluster
headaches.
P146
A Case of Cluster Headache with Polycythaemia Rubra Vera Responding to
Venesection
M. Khalil1, N.P. Thekkootu1, F. Ahmed1
1Department of Neurology, Hull Royal Infirmary,
Kingston-upon-Hull, North Humberside, United Kingdom.
Objectives: First case report of polycythaemia rubra vera presenting
with cluster headache which responded well to venesection.
Background: Cluster headache (CH) is the most frequent type of
Trigeminal Autonomic Cephalalgias (TACs) with a prevalence of 0.1%. CH is more
common in males who smoke. The episodic variant is 6 times more common than the
chronic one. Majority of CH are primary although secondary cases have been described
with intracranial pathologies such as pituitary macroadenoma, meningiomas, and
intracranial large arteries aneurysms.
Headaches of non-specific nature is a presenting feature in a third of patients with
Polycythaemia Rubra Vera (PRV) and other hyperviscosity disorders although
presentation with CH has not been reported before. We report a case of PRV
presenting with CH which responded well to venesection and recurrence of symptoms
with a rise of haematocrit and haemoglobin (Hb).
Methods: A 52 year old gentleman, a lifelong smoker, presented with a 4
month history of recurrent right peri-orbital excruciating headaches on a background
of continuous dull ache. The excruciating attacks would come on between 4-6 times a
day, each lasting 30-75 minutes with ipsilateral autonomic features and extreme
restlessness. The attacks were more common in early hours of morning. A diagnosis of
CH was made and verapamil with a short course of steroid was commenced with oxygen
and subcutaneous imigran as abortive treatment
Routine investigations showed Hb of 18.5, WBC 14, Platelets 520 with a haematocrit of
59. The alkaline phosphatase was 175 and B12 was 950. MRI head was normal
He was referred to haematology where he reported no benefit with verapamil and
steroids although the abortive treatment was successful. Further investigations
confirmed the diagnosis of PRV. He was subjected to venesection with complete
resolution of cluster attacks and the background pain, however the attacks
repetitively recurred with a rise of haematocrit and Hb levels and settled with
further venesection. The patient went in remission on hydroxyurea and remained
cluster-headache free.
Results: Non-specific headaches may be a presenting feature in a third
of patients with hyperviscosity disorder. CH has been reported in patients with
haemochromatosis responding to venesection. As far as we are aware this is the first
report of CH as a presenting feature of PRV.
Conclusions: The poster reviews literature to suggest plausible
mechanisms for CH in PRV and other hyperviscosity disorders although we feel this
may only be a trigger in those with an inherent tendency for a specific headache
disorder.
P147
Recurrent SUNCT Following Prolactinoma Resection in a Pregnant Woman: A Case
Report
M. Stefanidou1, K. Mullin1, M.W. Green1
1Neurology, Icahn School of Medicine at Mount Sinai, New York, NY,
USA.
Objectives: To report the efficacy of peripheral nerve blocks in the
treatment of short-lasting unilateral neuralgiform headache with conjunctival
injection and tearing (SUNCT).
Background: SUNCT is a rare headache syndrome that has been associated
with pituitary adenomas, especially those secreting prolactin or growth hormone. The
observations of headache resolution following tumor resection and with the use of
dopamine agonists suggest a role of the hypothalamo-pituitary axis regulation in the
pathophysiology of the syndrome. No medical treatment has been universally effective
and most agents used raise concerns during pregnancy. Cases in the literature of
treatment with greater occipital nerve stimulation or blocks show either conflicting
results or afford only temporary benefit.
Methods: A 32 year old woman with history of migraine since childhood
developed amenorrhea and persistent galactorrhea immediately following her first
pregnancy. She had elevated prolactin and was diagnosed as having a right-sided
pituitary macroadenoma (prolactinoma). Upon initiation of cabergoline (0.25mg) she
developed frequent ipsilateral attacks of SUNCT. The tumor was resected with
immediate resolution of the headaches. Two weeks later she became pregnant again
with almost immediate recurrence of the same, brief (up to 30 seconds) attacks of
abrupt onset headache in the right periorbital, frontal and temporal regions with
radiation to the neck, associated with conjunctival injection, tearing and nasal
congestion. Evaluation for tumor recurrence with non-contrast MRI showed no gross
postsurgical changes. The headaches were of increasing frequency and severity and by
week 13 of gestation they recurred every 5 minutes and persisted during sleep. A
series of peripheral nerve blocks were performed.
Results: Consecutive 0.5% bupivicaine nerve blocks of the right
occipital, supraorbital, supratrochlear and auriculotemporal nerves, as well as an
ultrasound guided occipital nerve block offered temporary (4-5 hours), but almost
complete pain relief. Short courses of prednisone and use of oxycodone/
acetaminophen for breakthrough pain decreased the frequency, duration and severity
of attacks. She underwent right occipital nerve radio frequency thermo-coagulation
(RFTC) (120 second - 0.5 A pulses). One week later, and while off steroids and
opioids, she experienced significant pain relief lasting one week and followed by an
exacerbation. She is currently at 23 weeks of gestation and we will follow her
clinical course to delivery, expected in May of 2013.
Conclusions: Our patient demonstrates the complex association between
hypothalamo-pituitary hormonal changes and SUNCT, as well as the challenges in
identifying optimal treatment. This is the first case report of ipsilateral greater
occipital nerve pulsed RFTC under ultrasound guidance for SUNCT, offering
substantial, but brief benefit.
P148
Cluster Headache in Brazil: Data from a Nationwide Survey
1UNIFESP, Sao Paulo, Brazil; 2Hospital Albert Einstein,
Sao Paulo, Brazil; 3SBC, Rio de Janeiro, Brazil.
Objectives: To determine the clinical features of cluster headache in
Brazil.
Background: Although less common than migraine and tension-type
headaches, cluster headache is nonetheless an important clinical entity,
particularly given its pain being considered to be one of the most severe known to
man. A nationwide survey may provide data about disease distribution according to
gender, possible identification of risk factors, economic consequences, and social
impact. Information about access to standard care may lead to public healthcare
policies tailored to this specific headache population.
Methods: A comprehensive, self-applicable questionnaire was developed in
Brazilian Portuguese and it has been made available over the internet since
December/2010. Regardless of answering the questionnaire online, all subjects who
had the chance to do so were offered a medical consultation, when again the same
questionnaire was applied by the authors. Test-retest and inter-rater reliability
were calculated using Cohen’s kappa statistic, Cronbach’s alpha coefficient and
Pearson’s correlation coefficient. Only variables with statistically significant
reliability were analyzed.
Results: As of February/2013, 246 subjects had answered the
questionnaire online and fulfilled the CH diagnostic criteria according to the
second International Classification of Headache Disorders (ICHD). The average age of
the subjects was 37,97 ± 4,13. There were 158 male (64,75%) and 86 female (35,25%)
patients. Considering the temporal pattern, 33 (13,41%) evolved into the chronic
form of CH, while 213 (86,58%) presented the episodic form. Notably, 47 (19,10%)
subjects had had pain attacks superior to 180 minutes and 50 (20,32%) had had more
than 8 pain episodes a day. History of present or previous smoking habit was related
by 132 (53,65%) subjects. Comorbid conditions were related by 229 (93,08%) patients,
being anxiety in its several forms the most common with 175 (71,13%). Although 218
subjects had performed ancillary examinations (88,6%), only 114 (46,34%) were
offered oxygen therapy at some point of their disease.
Conclusions: Despite being subject to some biases, our ongoing survey
shows that most characteristics of CH in Brazil are similar to what is found in the
scientific literature. However, the fact that almost 20% of the patients had
presented pain attacks superior to 180 minutes and more than 8 pain episodes a day
may contribute to further review of CH diagnostic criteria. Risk factors other than
smoking habit should be investigated in our population. Furthermore, the disparity
between the performance of ancillary examinations and the use of oxygen therapy
suggests that CH is still under treated in Brazil.
P149
Non-Indomethacin/Nerve Block Approach to Patients with Hemicrania
Continua
J.L. Beams1, M.T. Kline2, T.D. Rozen1
1Neurology, Geisinger Health System, Wilkes Barre, PA, USA;
2Pain Medicine, Center for Pain Medicine, Bryn Mawr, PA,
USA.
Objectives: To describe a non-indomethacin treatment for hemicrania
continua (HC) utilizing anesthesiologic procedures.
Background: HC is an indomethacin-responsive headache syndrome. On
indomethacin patients feel normal, off they have disabling headaches. The risk of
long-term indomethacin therapy is great. There are very few alternative treatments
outside of indomethacin. There is data on occipital nerve stimulators but that can
have considerable morbidities. We present 3 patients who had complete alleviation of
HC with two distinct procedures: C2 ventral rhizotomy and sphenopalatine ganglion
rhizotomy.
Methods: Case reports.
Results: Case 1: 30 year old woman with a daily headache from onset,
100% right sided in the occipitonuchal region. Baseline pain low intensity with pain
exacerbation periods lasting several days with associated ispilateral conjunctival
injection. On exam right upper cervical facet and GON tenderness. HC diagnosed as
became pain free on indomethacin 50mg TID. She had a right C1-C2 facet injection
with complete relief of headache. This was followed by a C2 ventral rhizotomy,
providing pain freedom off indomethacin for one year. Procedure was repeated after
HC recurrence and has now gone 18 months headache free without medication.
Case 2: 24 year old woman with a daily one-sided headache of 7 years duration. Pain
in left temple, face and periorbit. She had congenital blindness in the left eye
enucleated at age 18 for thoughts this was contributing to her headache. Had some
improvement until teeth extraction one year prior to clinic presentation. Post
procedure had extreme worsening of pain. She suffered from continuous low level head
pain with exacerbation periods lasting days with associated agitation, left ptosis
and infraorbital swelling. On indomethacin she became pain free at dose of 75mg TID
thus diagnosis of HC. She underwent a left sphenopalantine ganglion block leading to
pain freedom and ability to discontinue indomethacin. She had a left sphenopalatine
rhizotomy which gave her 4.5 months of pain freedom. Pain returned on a daily basis
requiring repeat radiofrequency. Now 3 months post she is almost headache free.
Case 3: 47 year old man, daily right frontotemporal headache for 27 years. He
complained of persistent pain with exacerbations periods lasting days with
associated agitation, ptosis, conjunctival injection, lacrimation and rhinorrhea. On
indomethacin 75mg TID he became pain free. Due to extremity edema the medication was
discontinued, HC recurred. He underwent a right sphenopalatine ganglion block
allowing complete pain relief. This was followed by a rhizotomy and at one year’s
time he has had total alleviation of his headache without the need of
indomethacin.
Conclusions: Three patients with indomethacin responsive HC who achieved
pain freedom after sphenopalatine ganglion or C2 rhizotomy. As the risks of
long-term indomethacin administration are substantial alternative treatments are
necessary. We now suggest non-indomethacin, non-stimulator options for patients with
HC.
P150
Differential Diagnosis of Chronic Paroxysmal Hemicrania. After Unsuccessful
Microvascular Decompression
F.A. Sampaio1, Y. Sunagawa1, C.O. Cunha1, B.
Puchimada1, R. Sood1, S. Annanthan1, G.M.
Heir1
1Diagnostic Sciences - Division of Orofacial Pain, University of
Medicine and Dentistry of New Jersey, Newark, NJ, USA.
Objectives: Orofacial pain (OFP) often arises from non-odontogenic
sources, and often mimics dental pain causing patients to seek dental remedies.
Common sources of non-odontogenic orofacial pain include musculoskeletal,
neuropathic or neurovascular disorders. In this case, we report a patient who was
initially diagnosed with trigeminal neuralgia and who underwent unsuccessful
microvascular decompression surgery. She was later diagnosed, and treated
successfully for chronic paroxysmal hemicrania (CPH), classified as a trigeminal
autonomic cephalgia (TAC) by the International Headache Society (IHS). She also
incurred an iatrogenic atypical odontalgia/differentiation pain following an
apicoectomy.
Background: A 54-year-old, Caucasian, female presented with chief
complaints of moderate to severe pulsating and stabbing pain in the maxillary right
gingiva and headache of the right side lasting 10-20 minutes. Symptoms also included
nasal congestion and ptosis of the right eye during attacks. Her medical history
includes apicoectomy on teeth number 4 and 5 3 years ago, which is not related to
her current problem, except for the fact that she may have developed an iatrogenic
atypical odontalgia/differentiation pain. However, this is not related to the
problem for which she sought our evaluation. The patient underwent unsuccessful
microvascular decompression as a treatment for trigeminal neuralgia (TN).
Methods: Based on the clinical complaints, observations, radiographic
findings and the succcesful trial of indomethacin, the diagnosis was chronic
paroxysmal hemicrania (CPH) and non-related, iatrogenic atypical
odontalgia/differentiation pain following apicoectomy.
Conclusions: An accurate diagnosis of orofacial pain conditions requires
a detailed examination and knowledge of pain mechanisms. Moreover, a precise
identification of the source of pain is the most important factor leading to a
correct diagnosis, successful treatment and prevention of unnecessary treatment.
P151
Sec-Butyl Propylacetamide (SPD) a Novel Valproic Acid Amide
Analogue Has Anti-Migrain Properties
D. Kaufmann1, S. Bahr2, E.A. Bates2, G.H.
Saunders1, K. Wilcox1, S.H. White1, K.C.
Brennan3
1Pharmacology and Toxicology, University of Utah, Salt Lake City,
UT, USA; 2Chemistry and Biochemistry, Brigham Young University,
Provo, UT, USA; 3Neurology, University of Utah, Salt Lake City, UT,
USA.
Objectives: Evaluation of the antimigraine potential of a novel valproic
acid (VPA) amide analogue, sec-butyl-propylacetamide (SPD).
Background: Migraine is a disabling disorder affecting 12-15% of people
worldwide. Pharmacotherapy is the main treatment for migraine, and there is an
urgent need for novel antimigraine drugs. Sec-butyl propylacetamide
(SPD) is a novel amide analogue of VPA, with greater potency and more rapid
pharmacokinetics. SPD has a wide range of activity in animal models of epilepsy and
is also effective in models of neuropathic and inflammatory pain. Since migraine and
epilepsy are comorbid diseases we evaluated SPD’s anti-migraine potential in two
mouse models for migraine, and evaluated its relevant mechanism of action in cell
culture in-vitro.
Methods: C57BL6 male mice were used in a blinded randomized fashion in
two models for migraine. We evaluated SPD’s potential in reducing the number of
cortical spreading depression (CSD) in-vivo, and evaluated its effect on NTG induced
heat hyperalgesia and mechanical allodynia. SPD’s ability to modify GABA, NMDA,
Kainate and voltage dependent Na+ currents was evaluated in primary culture of
dissociated cortical neurons, and neuroblastoma cell line.
Results: SPD significantly decreased the number of CSDs compared to
control following acute dosing, from 8.3 (± 1.0.) to 4.75 (± 1.1.) in the control
and SPD groups respectively. 60 mg/kg SPD increased the withdrawal threshold for
both NTG induced heat hyperalgesia and mechanical allodynia compared to vehicle in
both time points evaluated, indicating its protective effect for NTG induced
hyperalgesia. SPD was able to increase GABA but not NMDA or AMPA mediated currents
in cortical neurons cell culture. SPD had no effect on voltage dependent sodium
channel currents.
Conclusions: SPD, a novel amide analogue of valproic acid, robustly
suppresses CSD frequency and elevates the threshold of both NTG induced mechanical
allodynia and heat hyperalgesia. SPD may exert its anti-migraine effects through
enhancing cortical inhibition. As a promising novel anti-migraine compound further
evaluation of SPD’s specific mechanism of action is warranted.
P152
A Case Series: IncobotuIinumtoxin A - A Novel Therapy for Refractory Trigeminal
Neuralgia
R. Krel1, T. Mednick1, W. Spinner1
1Neurology, Stony Brook University Hospital, Stony Brook, NY,
USA.
Objectives: To discuss the potential benefits of using
incobotuIinumtoxin A in treating cases of refractory trigeminal neuralgia.
Background: The first patient is an 81 year old male with over 10 years
of V1 distribution trigeminal neuralgia of the right hemifacial region. Patient
reported pain that would “drop him to his knees” and was intractable to multiple
oral medications. His pain was refractory to surgical interventions such as gamma
knife surgery, microvascular decompression and nerve ablation. Patient was started
on onobotuIinumtoxin A (Botox) and after several rounds of injections, patient began
to develop resistance to therapy and was subsequently transitioned to
incobotuIinumtoxin A at the same unit dose with >90% relief in the frequency and
severity of his symptoms.
The second patient is a 36 year old male with a 4 year history of right V3
distribution trigeminal neuralgia. He had also failed multiple oral medications and
gamma knife surgery on two occasions. Patient was started on incobotulinumtoxin A
with an 80% reduction in pain intensity and a 90% reduction in frequency of his pain
symptoms. This benefit was maintained for the duration of three months.
Methods: The first patient was seen every 12 weeks for onobotuIinumtoxin
A injections in a grid like pattern along the V1 territory. After several sessions
of onobotuIinumtoxin A patient was transitioned to incobotuIinumtoxin A. Pain was
assessed via patient pain scale that was administered at every appointment
visit.
The second patient was started on incobotulinumtoxin A injected in a grid like
pattern along the V3 territory. The patient’s pain scale was assessed at 6 and
12week follow-up sessions.
Results: Despite multiple trials of medical and surgical management
patient developed substantial relief with the use of onobotuIinumtoxin A. Due to
development of onobotuIinumtoxin A resistance in the form of shortened duration of
therapeutic activity, patient was transitioned to incobotuIinumtoxin A with a
beneficial result for a 12 week period of time. In the second patient an improvement
in patient symptoms were seen with injections of incobotulinumtoxin A.
Conclusions: Botulinum toxin A has been used as a minimally invasive
therapy for several neurological conditions such as cervical dystonia and
blepharospasm, and has since transcended into being a mainstay therapy for
migraines, tension, and occipital headaches. The cases we describe show that
botulinum toxin A has the potential to become part of the treatment regimen for
trigeminal neuralgia cases that are refractory to both medical and surgical
intervention.
We can furthermore discuss that those patients whom develop resistance to
onobotuIinumtoxin A may be successfully transitioned to incobotuIinumtoxin A.
Incobotulinumtoxin A may also be used an additional medication in the management of
trigeminal neuralgia. These cases, like other similar case reports and studies, show
that botulinum toxin A, and in particular incobotuIinumtoxin A, can become an
integral part of trigeminal neuralgia therapy.
P153
Dedicated Headache Clinic Impact on Care and Cost in a Multispeciality
Clinic
D.M. Ready
Neurology, Scott & White Healthcare, Temple, TX, USA.
Objectives: To measure the impact a dedicated Headache Clinic may have
upon delivery of care in a multispeciality clinic.
Background: With the coming health care changes there many patients will
now have access to services previously unavailable. How this care is delivered will
come under greater scrutiny for its evidence base and cost effectiveness. Migraine
is the second leading cause of disability in the USA so an individual with Migraine
can be assured that there will be attacks that will on occasion require rescue. All
too often today Migraine patients seek that care in an expensive Emergency
Department setting. It is because of these episodes of disabling attacks that
migraine patients are greater consumers of health care resources than other
patients.
Methods: In 2008, our institution started a dedicated headache clinic
that offered “Headache rescue” for established patient suffering with their usual
primary headache. A Family Medicine physician with an interest in headache was
selected as the first director. The utility of offering headache rescue has been
documented with demonstrated patient satisfaction and cost savings. In an attempt
measure the impact of a dedicated headache clinic charts were reviewed from May 2011
– May 2012 and 690 patients established care in our clinic. Randomization for this
review was done by selecting every 9th patient who established care in
our clinic, yielding an n = 70. Of the randomized patients, 17 had visited the ED
one or more times, 14 had CT imaging of the head, and 11 were using opiates for
their headache care.
Results: Patients who established care in our clinic showed a reduction
in ED utilization, CT imaging, and opiate usage by 75%, 93% and, 47%
respectively.
Conclusions: Our review of the data suggests that a dedicated headache
clinic can reduce Emergency Department utilization, imaging and opiate usage. Our
experience suggests that initiating a headache clinic can be a means of providing
appropriate care in a cost effective fashion. Our experience also suggests that
appropriate therapies (prophylaxis, abortive, and rescue) can be delivered in a
primary care or specialty setting.
Indicator
Before enrollment
After enrollment
ED Visits
17
4
CT Head
14
1
Opiate usage
11
6
P154
What Do Patients Know about Their Migraine Medications? An Analysis of Patient
Knowledge about Triptans in Patients Using Triptans
E.P. Baron1, S.Y. Markowitz2, A. Lettich3, E.
Hastriter4, K. Kalidas5, B. Lovell6, D.
Dodick7, T. Schwedt7
1Cleveland Clinic, Cleveland, OH, USA; 2Laniado
Hospital, Netanya, Israel; 3Beth Israel, New York, NY, USA;
4Banner Children’s, Mesa, AZ, USA; 5University of S.
Florida, Tampa, FL, USA; 6Keeler Center for Headache, Ojai, CA, USA;
7Mayo Clinic, Phoenix, AZ, USA.
Objectives: To compare triptan users’ self-perceived vs. actual
knowledge about the triptans in patients receiving vs. not receiving triptan
education.
Background: Patient education on triptan use is crucial for safe and
effective treatment. It is unclear how knowledgeable triptan users are regarding
their triptan, how much education is occurring at triptan prescription, and how much
impact patient education has on actual patient knowledge of triptan use.
Methods: This was a multi-center prospective observational study of 207
migraine patients who use triptans and were seen as new patients at tertiary care
headache clinics in the USA. It was conducted by the American Headache Society
Headache Fellows Research Consortium via standardized questionnaires regarding
self-perceived and actual triptan knowledge, and whether or not education was
received at time of triptan prescription.
Results: Over 87% of subjects received education about when to take the
triptan and number of doses allowed per migraine, 71.5% about triptan side effects,
64.3% for number of triptan doses allowed each week/month, 64.1% for taking other
medications with the triptan, 49.3% for medical contraindications to triptans.
Compared to subjects not educated about when to take triptans, subjects receiving
education had greater actual knowledge for taking triptans immediately after a
headache begins (p=.049), treating when pain is mild (p=.009), and not needing to
fail treatment with over-the-counter (OTC) medications first (p=.001). Compared to
subjects not educated about contraindications to the triptans, subjects receiving
education were more knowledgeable that coronary artery disease (CAD) is a
contraindication (p=.001). Subjects educated about the number of triptan doses
allowed and about taking other medications with the triptans showed no significant
differences in actual knowledge compared to those not receiving education, although
positive trends for increased knowledge were seen. No differences existed in actual
triptan knowledge amongst subjects who thought it is complicated to understand how
and when to take the triptan vs. subjects who did not think it is complicated.
Conclusions: This study supports that education at time of triptan
prescription leads to greater patient knowledge regarding proper triptan use.
Triptan users receiving education better recognized the importance of taking
triptans immediately after a headache begins, treating when pain is mild, not
needing to fail treatment with OTC medications first, and understanding that CAD is
a contraindication to use. Education on triptan side effects, number of doses
allowed each month, taking other medications with triptans, and triptan
contraindications requires improvement.
P155
Headache Hall of Fame - Through Philately
A. Tripathy1, L. Mishra2
1Pediatric Neurology, Blank Children Hospital, Des Moines, IA,
USA; 2Child Psychiatry, Blank Children Hospital, Des Moines, IA,
USA.
Objectives: To review the literature through philately of famous people
who suffered from headaches and migraines.
Background: Since time immemorial, headaches have affected millions of
people. It is one of the oldest conditions affecting humans, with a distinguished
and rich history.
Methods: Literature review. The original postal stamp display (issued by
different countries) of famous people with headaches, is displayed, with a short
biography of the nature of their headaches.
Results: The famous people who suffered or are strongly believed to have
had headaches are classified into several categories according to their respective
fields of excellence. The noted philosophers are
Julius Caesar, Karl Marx and Friedrich Nietzsche. Statesmen and
rulers include John of Arc, Napoleon, Robert Lee and
Princess Margaret. Presidents include Thomas
Jefferson, John Adams, Abraham Lincoln, Ulysses Grant, Woodrow Wilson, Harry S
Truman and John F Kennedy. Eminent scientists include
Blaise Pascal, Charles Darwin, Alexander Graham Bell, Alfred Nobel and Sigmund
Freud. Musicians and composers include Elvis Presley,
Gustav Mahler, Pyotyr Tchaikovsky and Frederic Chopin. Famous writers
and authors were Leo Tolstoy, George Bernard Shaw, Lewis
Carroll, Edgar Poe, George Eliot and Miguel de Cervantes. Famous
artist include Vincent Van Gogh.
Conclusions: Having headaches does not hamper one’s true genius. These
impressive people have enlightened the world and have served as role models,
inspiring people with headaches, who are neither geniuses nor celebrities.
P156
Brain Anatomy and the Expression of Head Pain in the Art of Michelangelo and
Leonardo da Vinci
M.M. Valença
Neuropsychiatry, Federal University of Pernambuco, Recife, Pernambuco,
Brazil.
Objectives: To show that Michelangelo painted the emotional expression
of pain and different aspects of neuroanatomy in the Sistine Chapel.
Background: Previous articles1,2 have suggested that
Michelangelo hid some brain illustrations inside the frescos he had painted.
Methods: The author conducted a meticulous search for anatomical
features in the work of Michelangelo and Leonardo.
Results: Michelangelo painted human figures in the Sistine Chapel. Among
them at least two may represent an attack of severe unilateral headache (note the
hand over one of the sides of the head) occurring in young agitated men
(Last Judgment, Fig 1). The author speculates that they
represent a cluster headache attack. And if so, did Michelangelo believe the origin
of the headache was in the brain, justifying his interest in brain anatomy and the
painting of several anatomical details found in the Sistine Chapel? Many of these
anatomical structures are camouflaged within his fresco The Creation of
Adam, e.g. the carotid siphon, the anterior communicating artery and
the sagittal view of the brainstem (Fig 1). The intriguing interplay of art and
science and the outstanding skills manifested in the drawing of neuroanatomical
details, not yet described at the time, make Michelangelo one of the greatest
neuroanatomists of the Renaissance period. Before Michelangelo, Leonardo had already
used hidden anatomic imaging in his paintings and drawings, perhaps influencing
Michelangelo regarding the method of painting he used in the Sistine Chapel. In
Leonardo’s earliest work (Study of a Tuscan Landscape) the present
author realized that it was made over an illustration of the human sella
turcica (Fig 2), indicating that he already had a particular interest
in the anatomy of the skull. In St Jerome in the Wilderness the
intracranial content (deep venous system) of a hemicranium can be identified in the
image of the lion’s tail, indicating again the inclusion of hidden anatomical
features within his paintings (Fig 2). In Leda and the Swan
Leonardo also depicted the image of a brain camouflaged as a mountain.
Conclusions: In conclusion, in each face found in the Sistine Chapel
Michelangelo purposely painted with different emotional expression, such as
admiration, fear, repentance, tiredness, authority and pain, as in the case of the
possible cluster headache. And the author cogitates that Michelangelo knew that all
were the result of a particular brain status, hence his neuroanatomical curiosity.
P157
The Perception and Satisfaction of Patients Seen at a Rural Physician
Assistant- Directed Headache Specialty Clinic
J.M. Jones
Pacific Rim Headache Center, PLLC, Anacortes, WA, USA.
Objectives: To examine the attitudes and satisfaction of patients seen
at a Physician Assistant-directed headache specialty clinic in a rural setting.
Background: One of the greatest obstacles in preventing chronic headache
sufferers from getting adequate care and higher quality of life is lack of access to
specialty trained providers. It is estimated that there is one UCNS board certified
headache specialist per 200,000 migraine sufferers. These specialists are almost all
located in major urban centers and out of reach, geographically, from the majority
of patients.
Some Physician Assistants (also known as Physician Associates) and Nurse
Practitioners have had many years of high level training in major headache centers
and are qualified to provide a very high level of specialty care in satellite or
free-standing headache centers, thus increasing the accessibility of headache
sufferers to that care. Being cost-effective they can also bring that level of
specialty care to rural or other areas, which could not financially support a UCNS
board certified neurologist.
There are several medico-social parameters that could, theoretically, limit the
ability of PA or NP from providing this service. This study looks at one of those,
patient attitudes and satisfaction.
Methods: An eighteen item questionnaire was given to 100 random patients
via Internet survey or hard copy (for those who were computer literate) who had at
least one completed visit at a PA directed headache specialty clinic. The results of
this questionnaire was tallied and discussed.
Results: Of the 100 patients surveyed 38% of the patients had concerns
about seeing a PA for their headache specialty care prior to the visit, however,
almost 90% had no concerns after the visit was completed. In nine parameters
measuring patient satisfaction with the the care given, almost 90% ranked the
experience as a 8/10 or higher.
Conclusions: While there was a hesitation some patients about seeing a
PA for headache specialty care prior to the first visit, most were very satisfied
after at least one visit. This appears to support the premises that headache
patients can be very satisfied by being seen at a PA directed headache specialty
clinic. Other parameters that need to be explored include other barriers to this
concept, including physician attitudes, medical-economic barriers as well as
eventual patients outcomes. If this concept is developed at a national level as one
avenue of meeting the needs of undeserved headache sufferers, it could be a
significant contribution to headache care in general.
P158
Description of Headache Telehealth Users and Providers-Report of a Web Based
Survey
L.L. Norris
College of Nursing, Wayne State University, Detroit, MI, USA.
Objectives: 1) Describe the characteristics of headache patients who
telephone their headache health care provider.
2) Describe the characteristics of telehealth headache providers.
Background: Telephone calls occur in all aspects of healthcare, headache
being one of many types of healthcare that must manage incoming and outgoing
communication with patients. Telephone communication must be provided in such a way
to accomplish patient safety, quality care, and economic feasibility. There is
limited documentation of the occurrence of telephone calls to a headache clinic. In
order to promote safe, quality and economic telephone care of headache patients, the
characteristics of those involved in the process of telephoning a headache clinic
must be described.
Methods: Human research institutional review was obtained from Wayne
State University. Two different surveys were developed to assess characteristics of
those who telephone their headache clinic and those who make or receive telephone
calls in a headache clinic. These two surveys were imported into a survey
Characteristics of HTU
HA Type
(N=17)
Migraine w/o aura
7
Tension
7
Migraine with aura
5
Other
3
Custer
2
Gender
(N=17)
Female
15
Male
2
Employment
(N=17)
Full time
12
Student
3
Homemaker
2
Part time
1
Age
(N=17)
50 and above
8
40-49
4
22-30
4
31-39
1
18-21
0
Education
(N=17)
College grad
6
Some College
5
Masters or higher
4
HS grad
2
provider and hosted on a website. Advertisement for recruitment of subjects was
accomplished by the website of the American Academy of Ambulatory Care Nurses and
the facebook page of the Migraine Research Foundation.
Results: There was a total of thirty one (N=31) respondents to the
surveys. Seventeen headache telehealth user’s (HTU) responses were obtained and
fourteen headache telehealth provider’s (HTP) responses were obtained.
Conclusions: Most of the survey respondents were female. In the HTU
group a diagnosis of migraine without aura or tension type headache was most
frequent. It is interesting that half of the HTPs reported a personal history of
headache. Both the HTU and HTP groups noted satisfaction with their current headache
clinic telephone practices.
Characteristics of HTP
Gender
N=14
Female
12
Male
2
Practice type
N=14
Outpatient affiliated with a hospital
7
Private practice
5
Academic based clinic
3
Outpatient clinic
1
Inpatient hospital service
1
Other
0
Provider type
N=14
Nurse practitioner
5
Physician
4
Other
2
Nurse
2
Physician assistant
1
Psychologist
0
Administrative/office/clerical
0
Pharmacy/pharmacist
0
Receptionist
0
Medical assistant
0
Tenure
N=14
6 to 10 years
5
Greater than 10 years
4
Greater than 20 years
3
0 to 5 years
2
Educational level
N=13
Other
7
Masters degree
5
Trade school
1
Bachelors degree
0
High school diploma
0
Headache history
N=14
Yes
7
No
7
P159
Emergency Department Management of Headache: An Algorithm for Quality
Improvement
D.A. Nacopoulos1, S. John1, C.C. Bamford2
1Department of Neurology, Cleveland Clinic, Cleveland, OH, USA;
2Center for Headache and Pain, Neurological Institute, Cleveland
Clinic, Cleveland, OH, USA.
Objectives: To propose an algorithm for Emergency Department (ED)
physicians to better evaluate, treat and discharge patients presenting with acute
headache.
Background: Headache is the fourth leading cause of ED visits in the
USA. In the case of primary headache, particularly migraine, prior studies
demonstrate that medical treatment in the ED can be highly variable. At this time,
there is no standardized management protocol directed at acute headaches presenting
to the ED. In addition to initial management, discharge plans seldom include
measures to prevent recurrence or instructions to re-treat if pain persists. An
algorithm providing a step-wise approach on the evaluation and treatment of acute
headache can potentially improve the efficiency of patient management.
Methods: We identified parameters in patients presenting with acute
headache to the ER, that influence decision-making and treatment. These parameters
were arranged in a tier system, and presence of absence of each parameter determined
the next step in an easy to follow flow-diagram. The parameters included initial
pain level, worrisome symptoms/signs (“red flags”), and drug seeking behavior
(“yellow flags”). This was applied to the correct primary headache disorder as
applicable. Clear treatment protocols and further instructions in case of suboptimal
or non response were outlined for each headache disorder. Need for additional
testing, neurological consultation and criteria for admission (McKesson Interqual
admission criteria) were made readily identifiable. Finally, we outlined proper
disposition plan for patients.
Results: An algorithm was created using the above parameters and the
details are outlined in Fig 1. Checklists were made for “red flags” and “yellow
flags” to refer those patients for appropriate evaluation. Criteria for diagnosis of
migraine and cluster were included. Treatment for each using first line, alternative
and second line medications were provided. Exact medications upon discharge along
with follow-up plan were added to the algorithm. We will next be conducting a study
piloting the use of this algorithm in our ED. Quality metrics including pain level,
disposition, follow up, patient and provider satisfaction, and treatment time will
be measured.
Conclusions: Headache management in the ED has been variable to date,
despite it being a leading cause of evaluation in the acute setting. We propose an
algorirthm to better standardize evaluation and treatment that potentially will
improve efficiency of patient care. Once implemented, the results from our study
will provide valuable information to guide efforts to further improve quality and
cost of care for this population.
P160
Training of Physicians Who Treat Patients with Headaches
I.V. Fokin
Municipal Clinical Hospital No.20, Moscow, Russian Federation.
Objectives: Evaluation and improvement of doctors’ training in
management of patients with headaches (HA).
Background: Headache is one of most common patients’ complaints
associated with significant limitations. For example, each patient suffering from
migraine loses 6 working days a year. Total annual work time lost in 2010 to
migraine was equal to 61.8 million man-days all over the country. Besides, there are
expenses which have not been calculated yet, e.g. related to early retirement and
reduced ability to perform domestic work. Hidden costs related to pain, suffering
and poor quality of life have not been evaluated completely. Common belief of most
healthcare providers is that HA is an insignificant or trivial problem. HA-related
physical, emotional, and economic problems are underestimated. HA management is
subpar.
Lack of knowledge among primary healthcare workers is one of clinically relevant
obstacles for effective management of HA. The problem begins in medical colleges
where little attention is paid to the problem thus creating an impression of its
insignificance.
Methods: Routine medical care for HA in 3 Moscow outpatient clinics and
doctors’ training system in 2 medical universities were evaluated.
Sociological study, questioning, expert examination and direct observations were the
methods applied.
Results: Most HA patients seek medical advice in primary healthcare
institutions consulting district physicians and general practitioners. Therefore,
management of HA should start at this level. This approach contributes to early
diagnostics of the disease and to better outcome of its treatment. Therefore,
inclusion of HA management into primary care institutions should become the goal for
healthcare policy both nationwide and locally.
The analysis of syllabi for primary care physicians demonstrated that little
attention was paid to problems of HA diagnostics and management. The same refers to
neurologists rendering specialized HA management. Therefore, new syllabi should be
prepared based on educational standards for HA management. They were developed by
the European Headache Federation (EHF) and should be adapted to the Russian
healthcare system.
Conclusions: Strengthening of the role of primary healthcare in
management of HA patients complies with modern trends in modernization of the
Russian healthcare system, which include development of personnel policy and new
syllabi based on international experience.
New syllabi should be worked out both for medical and postgraduate students.
Postgraduate syllabus for primary care physicians should provide 8 hours of lectures
and 26 hours of practical training with not less than 30% of class hours being
dedicated to HA prevention. Syllabus for neurologists should provide 24 hours of
lectures and 72 hours of practical training.
The syllabi should include up-to-date information and educational technologies,
increase the significance and quality of practical training to improve doctors’
skills in HA management and explain new diagnostic and treatment methods.
The training in accordance with new syllabi will contribute to higher efficacy of
medical care in headaches.
P161
Withdrawn by the author.
P162
Migraine and the Incidence of Ischemic Stroke in Taiwan: A Nationwide
Population-Based Study
1Neurology, Neurological Institute, Taipei Veterans General
Hospital, Taipei, Taiwan Republic of China; 2Medicine, Taipei
Veterans General Hospital, Taipei, Taiwan Republic of China; 3School
of Medicine, National Yang-Ming University, Taipei, Taiwan Republic of
China.
Objectives: To evaluate the association between migraine and ischemic
strokes in regard to status of aura, gender, and age subgroups.
Background: Migraine with aura (MA) has been associated with increased
risk of ischemic stroke consistently; however, most studies do not find such an
association with migraine without aura (MO) (1). Furthermore, no similar study has
been done in Asia.
Methods: Retrospective cohort study of subjects aged 18-70 with
neurologist-diagnosed migraine from 2005 to 2009 from a nationwide population-based
administrative database were included. The comparison cohort consisted of subjects
free from migraine or headache diagnosis, matched for age, gender, and comorbidities
known as stroke risk factors. All subjects were followed till the end of 2010,
death, or any stroke events. The main outcome was hospitalization with ischemic
stroke.
Results: A migraine cohort was identified (n=150,615, F: 73.4%, M:
26.6%), and MA accounted for 10.7% (n=16,050). The migraine and the comparison
cohorts were followed by a mean of 3.0 ± 1.5 years vs. 3.2 ± 2.5 years. In female
subjects ≤ 50 years, MA was strongly associated with ischemic strokes (hazard ratio
[HR]=2.548, 95% confidence interval [CI], 1.258-5.158, p=0.009), whereas MO was also
associated with ischemic strokes (HR=1.564, 95% CI 1.144-2.137, p=0.005), but to a
lesser extent (MA vs. MO, HR: 2.461, 95% CI, 1.595-3.797, p<0.001, adjusted for
age and stroke related comorbidities). No association could be found in female
subjects aged >50 years. In male migraine cohort, no association could be found
in subjects aged ≤ 50 years; however, migraine was associated with a decreased
incidence of ischemic stroke in those aged > 50 years (HR=0.769, 95% CI,
0.605-0.978, p=0.032), especially in those with no stroke risk factors (HR=0.517,
95% CI, 0.315-0.849, p=0.009).
Cumulative incidence of stroke in female migraine cohort, aged ≤ 50
years.
Cumulative incidence of stroke in female migraine cohort, aged >50
years.
Conclusions: In this large cohort follow-up study, migraine in younger
female subjects was associated with increased incidence of ischemic strokes,
especially in those with MA. The reduction of stroke risk in older male subjects
with migraine needs further confirmation.
P163
Migraine Is Associated with a Higher Risk of Transient Global Amnesia: A
Nationwide Population-Based Study
1Department of Neurology, Neurological Institute, Taipei Veterans
General Hospital, Taipei, Taiwan Republic of China; 2Faculty of
Medicine, National Yang-Ming University, Taipei, Taiwan Republic of China;
3Institute of Brain Science, National Yang-Ming University,
Taipei, Taiwan Republic of China; 4Department of Medicine, Taipei
Veterans General Hospital, Taoyuan Branch, Taoyuan, Taiwan Republic of China;
5Department of Medicine, Taipei City Hospital Heping Fuyou
Branch, Taipei, Taiwan Republic of China.
Objectives: This population-based study aimed to investigate whether
migraine was associated with a higher risk of transient global amnesia (TGA).
Background: The pathogenesis of TGA is largely unknown. Several prior
case-control studies revealed a higher frequency of migraine in patients with
TGA.
Methods: We identified patients with migraine aged ≥40 years from the
Taiwan National Health Insurance Research Database (NHIRD) between 2005 and 2009.
Each migraine patient was matched with one randomly selected subject without
migraine for age, sex, and cardiovascular comorbidities. Migraine patients with
antecedent stroke, epilepsy, or TGA were excluded. Both cohorts were followed up
until the end of 2010. We compared the incidence rates of TGA in the two cohorts and
identified the risk factors.
Results: A total of 73,164 patients in the migraine cohort and 73,164
patients in the control cohort were enrolled with a mean follow-up of 3 years. The
migraine cohort had a greater risk of developing TGA than the matched cohort (15.0
vs. 6.0 per 100,000 person-years, incidence rate ratio (IRR) =2.48 (95% confidence
interval (CI) 1.30-5.00, p=0.003). The mean age of incident TGA patients were
younger in migraine cohort than control cohorts (56.6 vs. 61.4 years, p=0.035). When
compared to the matched controls, the association between migraine and TGA was
significant for patients aged ≤ 60 years (hazard ratio [HR] =3.16, 95% CI 1.42-7.00,
p=0.005), females (HR =2.54, 95% CI 1.30-4.96, p=0.006) and patients with migraine
without aura (HR =2.86, 95% CI 1.44-5.68, p=0.003).
Conclusions: This population-based study demonstrates that migraine is
associated with an increased risk of TGA.
P164
Prevalence of Chronic Headache and Its Association with Over-the-Counter
Medication Overuse in Denmark
M.L.S. Westergaard1, C. Glümer2, E. Holme Hansen3,
R.H. Jensen1
1Department of Neurology, Glostrup Hospital, Danish Headache
Center, Glostrup, Denmark; 2Glostrup Hospital, Research Center for
Prevention and Health, Glostrup, Denmark; 3University of Copenhagen,
Department of Pharmacy, Copenhagen, Denmark.
Objectives: To estimate prevalence and associated demographic profile of
chronic headache (CH) in the Danish population; and to compare the demographic
profiles of those with and without overuse of over-the-counter analgesics.
Background: Previous cross-sectional surveys in Denmark showed
prevalence of CH as 3.2% (24 of 740) among adults in 1989; 4.2% (23 of 549) in a
follow-up of the same cohort in 2001; and 4.8% (10 of 207) in a representative
sample of 25-36 year olds in 2001. There have been no previous large-scale
prevalence studies on CH and no population-based data on medication-overuse
headache.
Methods: The Danish National Health Survey of 2010 was used to gather
data on chronic illness, including headache. Data from the self-administered
questionnaire were linked with national statistical databases with information on
respondents’ socioeconomic status.
Results: Completed questionnaires were received from 68,518 individuals
(53% of the targeted sample of 129,150) aged >16 years.
The prevalence of CH was 3.0% (CI 2.9-3.2%), with a M:F ratio of 1:2.1. CH
prevalence was almost evenly distributed in all age groups; but slightly higher
among those 50-59 years (3.6%, CI 3.2-3.9%). There is a clear inverse relationship
with socioeconomic position as determined by education, employment and personal
income. Crude prevalence ratio (PR) was higher among non-western immigrants (PR 2.9,
CI 2.5-3.3), although the ratio was attenuated among second generation migrants (PR
1.4, CI 1.0-2.1). Among those with CH, 51.8% (CI 49.7-54.0%) used over-the-counter
(OTC) analgesics >15 days a month, suggesting medication
overuse in 1.6% (CI 1.5-1.7%) of the population. Among those with chronic headache,
subgroup analysis showed that those with OTC overuse were older (mean 52 vs. 49
years, p<0.001), had a higher proportion of women (70 vs. 64%, p<0.01), and
short education (19% vs. 15%, p<0.05). Full-time employment was lower among those
with OTC overuse (40 vs. 44%, p<0.001), likely owing to the higher proportion of
early retirees (16 vs. 8%, p<0.0001). Marital status, citizenship and personal
income were not significantly different in these two groups.
Conclusions: The prevalence of chronic headache is 3.0% in the Danish
population, among whom OTC analgesic overuse was seen in more than half, suggesting
medication overuse headache in at least 1.6% of the population, pending analysis of
prescription drug use. Prevalence of chronic headache and medication overuse were
inversely associated with socioeconomic position.
P165
Associations between Lifestyle Factors, Chronic Headache and Overuse of
Over-the-Counter Medication
M.L.S. Westergaard1, C. Glümer2, E. Holme Hansen3,
R.H. Jensen1
1Department of Neurology, Danish Headache Center, Glostrup,
Denmark; 2Glostrup Hospital, Research Center for Prevention and
Health, Glostrup, Denmark; 3Department of Pharmacy, Faculty of Health
and Medical Sciences, University of Copenhagen, Copenhagen,
Denmark.
Objectives: To investigate associations between lifestyle factors,
chronic headache (CH) and over-the-counter (OTC) medication overuse.
Background: In a related report, we estimated CH prevalence in Denmark
at 3.0% based on a sample of 68,518 individuals. About half of those with CH took
OTC analgesics >15 days a month. Lifestyle factors are
known to be associated with CH, but may differ among those with and without
medication overuse.
Methods: A representative sample of 129,150 individuals aged
>16 years from two regions of Denmark were invited to
participate in the Danish National Health Survey of 2010. Data on chronic illness
(including headache frequency) and health-related behaviours were gathered using
self-administered questionnaires. Respondents were categorized into three groups: no
chronic headache (–CH), CH without OTC medication-overuse (CH–MO) and CH with
overuse (CH+MO). Health behaviours of interest were compared across the groups
(chi-square for proportions; anova for means). Crude and sociodemographically
adjusted prevalence ratios (PR) were calculated to compare prevalence of CH–MO and
CH+MO across categories of BMI and quintiles of Perceived Stress Scores.
Results: The response rate was 53%. There were 66,431 individuals
classified as –CH; 1005 CH–MO; and 1082 CH+MO. The CH+MO group had the highest
proportion of daily smokers (p<0.0001) and the lowest proportion of
never-smokers (p<0.0001). This group also had the highest proportion of
sedentary individuals (p<0.0001), highest mean BMI
(p<0.0001) and proportion with BMI > 30
kg/m2 (p<0.0001). Compared to those with normal weight, the
prevalence ratios of CH–MOand CH+MO were high not just for the obese but also the
underweight even after adjustment for age, sex, low education and daily smoking. The
prevalence of CH markedly increased with higher stress levels. More
than half of the CH+MO group were in the highest stress quintile.
Alcohol overuse was lower among those with CH (p<0.0001).
Participants 16–34 years old were asked about narcotics use (response
rate 13,851 of 14,231 individuals, 97%). There were no differences in recent use of
cannabis (p=0.16) or narcotics (p=0.36), nor in lifetime use of narcotics
(p=0.15).
Conclusions: In agreement with other population-based studies, we found
associations between unhealthy lifestyle and CH, especially among those with OTC
overuse, emphasizing the need for lifestyle interventions concurrent with medical
management of medication-overuse headache. Dependence-related behaviours seen in
alcohol abuse and drug addiction were not significantly higher among those with OTC
analgesic overuse compared to the general population.
P166
Early Sexual Maturation and Recurrent Headache in Adolescents. The Young-HUNT 3
Study
1Department of Neurology, University of Oslo, Oslo, Norway;
2FORMI, Oslo University Hospital, Oslo, Norway;
3Faculty of Medicine, University of Oslo, Oslo, Norway;
4Department of Complex Epilepsy, Oslo University Hospital, Oslo,
Norway; 5Norwegian Centre for Violence and Traumatic Stress Studies,
NKVTS, Oslo, Norway.
Objectives: To examine whether early sexual maturation is associated
with migraine and tension-type headache in adolescents.
Background: Before puberty migraine affects boys and girls approximately
equally, while after puberty there is an increasing prevalence of migraine in
females. The mechanisms for this gender difference are not fully understood, but
female sex hormones, in particular estrogens, are believed to play a role. In
support of this hypothesis early menarche, which is associated with a prolonged
exposure to high estrogen levels, is associated with a higher prevalence of headache
and migraine in girls. It has however not been established whether this association
is related to female sex hormones, or rather to general changes occurring in puberty
such as the pubertal growth spurt. To disentangle these effects, we examined the
effect of the timing of sexual maturation on headache and migraine in boys and
girls.
Methods: In the population based Young-HUNT 3 study (2006-2008) 3,001
girls and 3,206 boys attending secondary school in the Norwegian county of
Nord-Trøndelag were assessed for the presence of migraine or tension-type headache,
and for timing of sexual maturation by age at menarche (girls) or the Pubertal
Developmental Scale (boys). Logistic regression was used to assess the effect of
timing of sexual maturation on the prevalence of recurrent headache and
migraine.
Results: Early sexual maturation in girls was associated with an
increased prevalence of migraine (OR = 1.68, 95% CI 1.25 – 2.26, p=0.001) and
tension-type headache (OR = 1.45, 95% CI 1.16 – 1.81, p=0.001), when adjusted for
age. No corresponding association was found in boys (migraine OR = 1.01, 95% CI 0.67
– 1.52, p=0.97; tension-type headache OR = 0.97, 95% CI 0.76 – 1.24, p=0.79).
Conclusions: The effect of early sexual maturation on headache and
migraine was specific to girls. This supports a mechanism involving female sexual
hormones, rather than general changes occurring in puberty in both sexes.
P167
Impact of Migraine Burden on Prevalence of Symptoms of Irritable Bowel
Syndrome
J. Stakic1, A. Ojha1, R.G. Kaniecki1
1Neurology, University of Pittsburgh Medical Center, Pittsburgh,
PA, USA.
Objectives: To examine the prevalence of Irritable Bowel syndrome (IBS)
related symptoms (constipation/diarrhea) in migraine patients and determine the
correlation between migraine frequency, disability and the presence of these
symptoms.
Background: There are limited studies looking at the prevalence of IBS
in migraine patients with none found in the literature looking at the impact of
migraine burden on the prevalence of IBS symptoms of constipation and/or diarrhea.
Based on our hypothesis that more frequent and disabling migraine leads to increased
frequency of IBS symptoms, we examined the relationship between migraine frequency,
disability measured by HIT-6 score, and prevalence of constipation/diarrhea symptoms
in a migraine population.
Methods: This is a retrospective cross-sectional study of 498 migraine
patients seen at the University of Pittsburgh Medical Center Headache clinic.
Patients were seen consecutively between October 2011 and June 2012. Migraine was
diagnosed based on ICHD-2 criteria. Migraine frequency, HIT-6 scores, and presence
of symptoms of constipation/diarrhea were recorded for each patient during their
initial visit. Based on HIT-6 score patients were divided in 3 groups: 1) HIT-6 of
<60, 2) HIT-6 of 60-69 and 3) HIT-6 of 70-78. Based on migraine frequency
patients were divided into 2 groups: 1) episodic migraine (patients with <15
headache days per month) and 2) chronic migraine (patients with ≥15 headache days
per month). The prevalence of IBS symptoms of constipation/diarrhea were examined in
episodic and chronic migraine groups, and in the 3 groups categorized by HIT-6 score
and comparisons between IBS symptom prevalence in these groups were evaluated with
the Chi-Square test.
Results: Mean age of subjects was 35.8 +/- 14.7 years with a gender
distribution of 392 females to 106 males. Of the 498 patients, 219 were diagnosed
with episodic migraine and 279 with chronic migraine. HIT-6 scores were available
for 486 patients of whom 90 patients were in the <60 HIT-6 group, 300 patients in
the 60-69 HIT-6 group, and 96 patients in the 70-78 HIT-6 group. One hundred and
fifteen patients (23.1%) reported symptoms of constipation/diarrhea. Patients with
chronic migraine had significantly more IBS symptoms versus those with episodic
migraine (28.7% versus 16 %, p<0.01). Similarly, when compared across the 3 HIT 6
categories, patients had an increased frequency of IBS symptoms with increasing HIT
6 score (13.3% versus 22% versus 36.4%, p<0.01).
Conclusions: Our results demonstrate that not only is there a high
prevalence of IBS symptoms in migraine patients; this prevalence is higher in
patients with more frequent and disabling migraines. This relationship could suggest
a common etiology between the two syndromes, perhaps through dysfunction of the
serotonergic system. Furthermore, if the conditions possess some shared physiology,
it may be possible to reduce IBS symptoms through management of migraine.
P168
Headache and Mental Health among Adolescents
B.A. Blaauw1,2, G. Dyb2,3, K. Hagen4,5, T.L.
Holmen6, M. Linde4,5, J.-A. Zwart7
1Department of Neurology, Vestfold Hospital, Tønsberg, Norway;
2Faculty of Medicine, University of Oslo, Oslo, Norway;
3Norwegian Centre for Violence and Traumatic Stress Studies,
Oslo, Norway; 4Department of Neuroscience, Faculty of Medicine,
Norwegian University of Science and Technology, Trondheim, Norway;
5Norwegian National Headache Centre, Section of Neurology, St. Olavs
Hospital, Trondheim, Norway; 6HUNT Research Centre, Department of
Public Health, Faculty of Medicine, Norwegian University of Science and
Technology, Trondheim, Norway; 7Department of Neurology and FORMI,
Oslo University Hospital, Oslo, Norway.
Objectives: To investigate the association between mental health
symptoms (conduct difficulties, attention difficulties and anxiety/depressive
symptoms) and recurrent headache in adolescents.
Background: The comorbidity of headache and psychiatric disorders is a
well-recognized clinical phenomenon, but there are only limited data regarding this
association among adolescents.
Methods: Young-HUNT 1, a population-based study of 8984 adolescents aged
12-20 years, was conducted in Norway from 1995 to 1997. A follow-up study,
Young-HUNT 2, was conducted four years later and consisted of 2399 adolescents aged
16-20 years. In both studies the participants were interviewed about their headache
complaints and completed a comprehensive questionnaire including self reported
conduct difficulties, attention difficulties and anxiety/depressive symptoms.
Results: In adjusted multivariate analyses based on cross-sectional data
from Young-HUNT 1, recurrent headache was associated with anxiety/depressive
symptoms (OR: 1.7, 95%CI: 1.5-1.9, p<0.001), attention
difficulties (OR: 1.3, 95%CI: 1.1-1.5, p<0.001) and conduct
difficulties (OR. 1.2, 95%CI: 1.0-1.5, p=0.035). In the prospective
part of the study we found that anxiety/depressive symptoms at baseline increased
the likelihood of recurrent headache four years later (OR: 1.5, 95%CI: 1.1-2.0,
p=0.008) and recurrent headache at baseline was associated with
anxiety/depressive symptoms (OR: 1.7, 95%CI: 1.4-2.2, p <
0.001), attention difficulties (OR: 1.3, 95%CI: 1.1-1.7, p=0.018) and conduct
difficulties (OR: 1.4, 95%CI: 1.1-1.8, p=0.006) at follow-up.
Conclusions: The results from the present study show that
anxiety/depression, attention difficulties and conduct difficulties are associated
with recurrent headache among adolescents. There seems to be a bi-directional
association between recurrent headache and anxiety/depressive symptoms.
P169
Triptan Use and Overuse in the French General Population: A Regional
Pharmaco-Epidemiology Database Analysis in 5.3 Million People
A. Donnet4, D. Braunstein1, J. Micallef1, F.
Natali1, V. Allaria-Lapierre3, V. Pradel2, M.
Lanteri-Minet2
1CEIP-Addictovigilance Paca Corse, Marseille, France;
2Département Douleur, Hôpital de Cimiez, Nice, France;
3Direction Régionale du Service Médical de l’Assurance Maladie
PACA-Corse, Marseille, France; 4CETD- Hôpital la Timone, Marseille,
France.
Objectives: A population-based observational study was used to assess
the prevalence, demographics, risk factors of triptan use and overuse.
Background: No data was available on triptan overuse in French general
population.
Methods: The Provence-Alpes Côte d’Azur and Corse Health Care Insurance
Database was analyzed for 18 months (from 05/01/2010 to 12/31/2011). Analysis
included prescriptions for 5.3 million people (8 % of the total French population).
Triptan overuse was defined as more than 30 (International Headache Society
criteria) or 60 (stringent criteria) defined daily doses per 3 months.
Results: Triptans were used by 95549 (1.8%) people; of these, 9297
(9.7%) were overusers by International Headache Society and 2267 (2.4%) were
overusers by stringent criteria. Considering stringent criteria, triptan overuse
corresponded to 20% of the total triptan consumption. Prophylactic medication was
more frequently dispensed in overusers, 57.4% of stringent overusers, than in
non-overusers (29.0%). Antidepressants were more frequently dispensed in overusers,
50.3% of stringent overusers, than in non-overusers (26.3%). Benzodiazepines were
more frequently dispensed in overusers, 70.6% of stringent overusers, than in
non-overusers (50.6%). Sleep drugs were more frequently dispensed in overusers,
37.5% of stringent overusers, than in non-overusers (20.0%).
Conclusions: We could make use of a unique regionalHealth Care Insurance
Database, which coveredthe medication use of 5.3 million people. Of these, 1.8% had
used a triptan at least once in 18 months period and 0.04% (2.4% of all triptan
users) were overusing triptans considering stringent criteria (60 DDD). Overusers
accounted for almost quarter of the totaltriptans consumption.
P170
Episodic Migraine and Obesity: The Influence of Age, Sex, and Race
B.L. Peterlin1, A.L. Rosso2, M.A. Williams3, J.D.
Rosenberg1, J.A. Haythornthwaite4, K.R.
Merikangas5, R.F. Gottesman1, D.S. Bond6, J.-P.
He5, A.B. Zonderman7
1Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA;
2Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA;
3Epidemiology, Harvard School of Public Health, Boston, MA, USA;
4Psychiatry & Behavioral Sciences, Johns Hopkins School of
Public Health, Baltimore, MD, USA; 5Health and Human Services,
National Institute of Mental Health, Bethesda, MD, USA; 6Psychiatry
and Human Behavior, Brown Alpert Medical School, Providence, RI, USA;
7Biomedical Research Center, National Institute on Aging,
Baltimore, MD, USA.
Objectives: To evaluate the association between episodic migraine (EM)
and obesity and the influence of age, sex, and race on this relationship.
Background: Epidemiological and translational data have consistently
identified age, sex, and racial differences in EM prevalence estimates as well as in
adiposity volume and distribution in obese and non-obese states. Controversy exists
as to whether the risk of EM is increased in those with obesity.
Methods: We conducted a cross-sectional study of 3,862 black and white
adult participants interviewed in the National Comorbidity Survey Replicated. EM
diagnostic criteria were based on the International Classification of Headache
Disorders. Body mass index (BMI) was classified as underweight, (<18.5
kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9
kg/m2), and obese (≥ 30 kg/m2). Odds ratios (OR) and 95%
confidence intervals (CI) for migraine were estimated using logistic regression and
adjusted for demographics and health characteristics. Additional, models were
stratified by age (<50/≥50 years old), race (white/black), and sex
(male/female).
Results: The mean BMI was greater in those with EM (27.8±0.30) as
compared to controls (27.1±0.4), p=0.05. The unadjusted prevalence estimates of
obesity were 32.2% among those with EM and 26.0% among controls, p=0.076. In all
participants, the adjusted odds of EM were 81% greater in obese as compared to
normal weighted individuals, (OR 1.81; CI: 1.27, 2.57; p=0.001). In addition,
stratified analyses demonstrated that the odds of EM were greater in obese as
compared to normal weighted individuals who were: 1) <50 years of age (OR 1.86;
CI: 1.20, 2.89; p for trend=0.008), 2) white (OR 2.06; CI: 1.41, 3.01; p for
trend=<0.001), or 3) female (OR 1.95; CI: 1.38, 2.76; p for trend=<0.001), and
were not increased in those ≥ 50 years of age (OR 1.15; CI: 0.61, 2.18, p for
trend=0.71) or men (OR 1.43; CI: 0.71, 2.89, p for trend=0.45). Due to the small
number of black participants with EM, no conclusion could be drawn regarding the
odds of EM in obese black participants alone. Similar findings were demonstrated in
lower frequency EM subgroups.
Conclusions: The odds of EM are increased in those with obesity, with
the strongest relationships among those < 50 years of age, whites, and women.
P171
Headache in Olympic Athletes
G. Egeo1, V. Dall’armi2, L. Fofi1, C.
Aurilia1, S. Bonassi2, G. Berlutti3, C.
Tranquilli3, A. Pelliccia3, P. Barbanti1
1Department of Neurological, Motor and Sensorial Sciences, IRCCS
San Raffaele Pisana, Rome, Italy; 2Clinical and Molecular
Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy; 3Institute of
Sport Medicine and Science, Rome, Italy.
Objectives: To assess prevalence and clinical features of headache in
Olympic athletes.
Background: Headache is a disabling disorder which may be triggered or
worsened by physical activity. Therefore, headache may be a relevant clinical issue
in athletes due to their commitment to intensive physical training and competitions,
as well as the severe restriction in drug use.
Methods: We studied 331 Italian athletes participating to the 2012
Olympic Games. Detailed information on demographic, type of sport, training schedule
and incidence of headache was gathered with self-administered questionnaires.
Specifically, any correlation between the onset of headache and workout or
competition was investigated.
Results: All athletes completed the questionnaire (n = 331; M/F =
212/119; mean age = 25.5 + 6.6; engaged in endurance =142,
power = 52, mixed = 28, skill =109 sport activities). Eighty-nine subjects (26.8%)
reported headache (M/F = 44/45); namely, migraine without aura = 56, probable
migraine without aura = 18; tension mimicking headache = 15. Forty-four athletes
referred headache occurring either in association than outside physical
workout/competition, 13 in association with physical workout/competition and 32
independent from sport activities. We found no correlation between specific type of
sport and incidence or clinical presentation of headache.
Conclusions: Headache is unexpectedly common observation in Olympic
athletes (26.8%), with migraine/probable migraine being the most frequent clinical
presentation. Workout or competition was associated with the attack in the majority
of headache sufferers (64%). The large prevalence and the peculiar limitations in
pharmacological treatment suggests that headache represent an emerging and relevant
issue in athletes.
P172
Headache Management in Community Pharmacies: An Irish Study
E.M. O’Sullivan1, C. Ryan2, B. Sweeney1, S.
Coveney1, S. Marshall3, E. Mitten1
1Headache Clinic, Neurology Department, Cork University Hospital,
Cork, Ireland; 2School of Pharmacy, Queens University Belfast,
Belfast, Northern Ireland, Ireland; 3School of Pharmacy, University
College Cork, Cork, Ireland.
Objectives: To describe the population of patients who attend community
pharmacies requesting acute therapy for headache management.
Background: There is a high prevalence of headache in the general
population, with many people reportedly not receiving the most appropiate treatment.
First line therapy for the treatment and prevention of headache depends on the
diagnosis and severity of symptoms. Most sufferers are managed by general
practitioners and or by community pharmacists, with a minority attending secondary
care services (e.g. a neurologist). There is little information available on
patients who attend their community pharmacist; therefore this project aims to
describe those patients and their management.
Methods: A questionaire was formulated, piloted and refined. There were
three main sections to the questionaire: (i) demographics, (ii) symptoms,and (iii)
treatments. Questions related to symptoms allowed for diagnosis to be established
(based on the ICHD-II guidelines). Treatment options and preferences were analyzed
and compared to diagnosis.
Pharmacists throughout the Munster province of Ireland (n=367), were sequentially
invited to participate and were asked to randomnly select 10 patients to complete
the questionaire. Patients requesting a medication for a headache if aged 18 years
or over were eligible to participate. The study was conducted over six months.Ethics
approval was granted by the local ethics committee.
Results: 43% (158) of pharmacies participated with 1023 questionaires
returned. 76.7% (765) of respondents were female, half of the cohort (51.8%) were
aged between 18 and 39 years. The most common headache diagnosis was episodic
migraine (32%; 327) followed by episodic tension type headache (30.3%; 327),
probable episodic migraine (15.2%; 155),chronic daily headache (10.5%; 107).
Less then 50% (46.7%; 475) had a prior physician diagnosis. Patients were more likely
to have had a diagnosis if the headache was considered severe, if there was a
presence of vomiting and if the headache was a chronic daily headache
(p<0.05).
The most commonly used preparation was paracetamol (71.3%; 729). Aspirin was
underused in all diagnostic categories (85%; 860). Patients with migraine, who had
previously used a triptan, considered it the most effective treatment available
(68.6%; 166). Preventative therapies were prescribed for 28.7% (201) of patients for
whom they were indicated.
Conclusions: This study has some important findings for the long-term
management of headaches. In particular, it was evident that the types of headaches,
patients present with to community pharmacies is largely underdiagnosed, and that
treatment options are not optimized. Impovements need to be prioritized and provided
for in the management of these patients.
P173
Relation between Vitamin D Receptor Gene Polymorphisms and Migraine without
Aura in Iranian Population
A. Zandifar1,2, M. Motaghi1, F. Haghdoost1, M.
Tajaddini2,3, M. Saadatnia4, L. Rafiei2, S.
Zandifar2, N. Manouchehri1, E. Zandifar2, S.H.
Javanmard2
1Medical Student Research Center, Isfahan University of Medical
Sciences, Esfahan, Iran (Islamic Republic of); 2Physiology Research
Center, Department of Physiology, Isfahan University of Medical Sciences,
Esfahan, Iran (Islamic Republic of); 3School of Pharmacy and Isfahan
Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences,
Esfahan, Iran (Islamic Republic of); 4Department of Neurology and
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences,
Esfahan, Iran (Islamic Republic of).
Objectives: The aim of this study was to investigate the association
between migraine and two vitamin D receptor (VDR) polymorphisms (TaqI and FokI) and
also relation between VDR polymorphisms and headache severity.
Background: Inflammation has a key role in migraine pathophysiology.
Vitamin D is an effective anti inflammatory agent. To our knowledge there is no
study to examine relation between VDR polymorphism and migraine.
Methods: In this case-control study we assessed the genotypic and
allelic frequencies of TaqI and FokI polymorphisms in 103 patients with migraine
without aura and 100 healthy subjects using high-resolution melt (HRM) assay.
Patients filled Headache Impact Test (HIT-6) as a tool to assess headache
severity.
Results: Genotype frequencies of vitamin D receptors were significantly
different between control and migraine patients. Heterozygote genotypes (Ff and Tt)
were statistically more frequent in the migraine patients than the control subjects
both for TaqI gene (P=0.018; OR=1.81, 95% CI=1.03-3.18) and FokI gene polymorphisms
(P=0.001; OR=2.91, 95% CI=1.47-5.77). Also f and t alleles were more frequent in the
migraine patients and seem to be potentially the risk factor alleles for developing
migraine according to our results. Total HIT-6 score was significantly different
between FokI heterozygote and homozygote patients (60.32±1.87 vs. 49.87±2.69
respectively, P=0.004).
Conclusions: In conclusion our results showed that TaqI and FokI gene
polymorphisms are associated with migraine without aura in Iranians patients. Also
headache severity in FokI heterozygote patients was significantly more than the
homozygote patients.
P174
Are Migraine and Tension Headaches Categorical Types or on a
Continuum?
D.P. Turner1, T.A. Smitherman2, D.B. Penzien3,
J.A.H. Porter4, T.T. Houle1
1Department of Anesthesiology, Wake Forest School of Medicine,
Winston-Salem, NC, USA; 2Department of Psychology, University of
Mississippi, Oxford, MS, USA; 3Head Pain Center, University of
Mississippi Medical Center, Jackson, MS, USA; 4Advance Neurology and
Pain, Advance, NC, USA.
Objectives: The purpose of this study was to reconsider clinical
perceptions that there exist distinct headache types and to evaluate whether this
distinction varies as a function of age and headache frequency.
Background: Although sophisticated systems have been developed for
classifying headaches, controversy remains as to whether migraine and tension-type
headache (TTH) disorders are separate entities or points on a continuum. If headache
disorders represent a continuum, the utility of the current diagnostic system may be
limited. If an individual headache sufferer experiences different types of attacks
or a continuum of attacks, treatments might best be targeted based on the
phenomenology of the specific attack rather than a diagnostic label.
Methods: A convenience sample of individuals meeting ICHD-II criteria
recruited from headache clinics and community settings (n = 1,530) and undergraduate
courses (n = 2,468) were combined (N = 3,999) for a taxometric analysis. A latent
mode analysis was conducted to examine the dimensional structure of multivariate
data for estimating the parameters of a two-group (migraine versus TTH)
distribution. All diagnostic characteristics (eg, location, quality, secondary
symptoms) thought to distinguish the two headache types were used in the analysis.
The analysis produces a comparison curve fit index (CCFI) ranging from 0
(dimensional) to 1.0 (categorical).
Results: For episodic sufferers, two distinct classes of headache types
were identified that were separated by 1.9 SD units on the latent scale (with the
migraine class occurring at the higher end of the latent scale, CCFI = 0.48).
However, chronic headache sufferers experienced headaches that differed only
dimensionally (CCFI index = 0.23). Headache types were the most distinct at very low
frequency (< 5 days/month) and among older adults, but could be placed on a
continuum with increasing frequency and younger age (< 25 years). Increasing
medication use was associated with an increasing fit of a continuum of symptoms.
Conclusions: This taxometric analysis supports viewing migraine and
tension-type headaches as categorically distinct entities, but only at low headache
frequency. The utility of a discrete diagnostic classification is greatly reduced
with increasing headache frequency and/or abortive medication use. For these types
of headaches, a continuum of symptoms may represent a better means of
conceptualizing headache.
P175
Electronic Methods for Migraine Ascertainment in a Large Integrated Health
Plan: Prevalence of Migraine in a Diverse Community
A.R. Pressman1, A.S. Jacobson1, A. Gelfand2, C.H.
Huynh1, A.L. Avins1
1Division of Research, Kaiser Permanente, Oakland, CA, USA;
2Neurology, UC, San Francisco, CA, USA.
Objectives: We sought to use electronic medical records (EMRs) to
identify and characterize migraine in a large diverse integrated health plan in
Northern California.
Background: One-year prevalence of migraine headache in the USA is
estimated to range from 8-15% overall with women affected at approximately three
times the rate of men. Current methods for migraine ascertainment from headache
clinics are affected by clinic-ascertainment bias and population-based surveys are
costly. With the growing use of EMRs, new methods must be developed and validated
for identifying and tracking migraine prevalence over time.
Methods: From the Kaiser Permanente Northern California (KPNC) EMRs, we
collected all migraine clinic and problem-list diagnoses from 2006-2010 and all
migraine-specific prescriptions (MRX). We chart-reviewed a random sample to develop
an electronic Migraine Probability Algorithm (MPA, scored 0-100), and tested it in a
second independent chart review. Using the MPA and membership data, we calculated
prevalence by age, race, and gender, and assessed utilization, measured by MRX.
Results: We identified 313,174 KPNC members with evidence of migraine
from 2006-2010 (233,620 women, 79,554 men). Gender distribution varied by age group.
From chart review of subjects with varied probability of migraine, at the lowest
threshold, we estimated the algorithm to have positive predictive value of 94% and
sensitivity of 85%. Specificity was back calculated to be >90%. Across all racial
groups, the 5-year period prevalence of migraine among KPNC adults was 17.1% for
women and 5.9% for men (ratio: 2.9). Among children, rates were the same by gender
(<2%) until age 10, when prevalence rose to 5.8% for girls and 3.5% for boys. For
women, prevalence climbed steadily with age, peaked at age 25-29, and then declined
monotonically to 8% after age 85, while men experienced a nearly flat prevalence
(range 5%-6%). Prevalence across ages followed similar patterns regardless of race.
Overall, Caucasians had higher prevalence than Asians, but African Americans did not
differ appreciably. MRX was higher among women than men, 45% and 30%, respectively,
and lowest among Asian men (25%).
Conclusions: EMR techniques can be effectively used to capture migraine,
and resulting prevalence patterns are similar to those reported in the
population-based literature. Prevalence of diagnosed migraine in KPNC was three-fold
higher in women than men, migraine peaked with age in women, but remained flat for
men, and prevalence of migraine among Asian adults was roughly 2/3 that of
Caucasians. These methods for ascertainment of migraine are inexpensive, easy to
implement and can be combined with other EMR data to assess utilization. In
addition, these methods have applications and implications that extend well to other
institutions and as well as other debilitating chronic conditions.
P176
Validation of a Short Migraine Screener in Patients with a TIA or
Stroke
D. van der Willik1, N. Pelzer1, A. Algra2, G.M.
Terwindt1, M.J.H. Wermer1
1Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 2Clinical Epidemiology, Leiden University Medical
Center, Leiden, The Netherlands.
Objectives: To study the test-characteristics of a five-question
migraine screener for diagnosing migraine in patients with a TIA or stroke.
Background: Migraine is an independent risk factor for stroke. To
investigate the relation between migraine and stroke, reliable ascertainment of
migraine history is crucial.
Methods: We included patients who were admitted to the Leiden University
Medical Center with a TIA or stroke between January 2011 and April 2012 and answered
a five-question migraine screener. A semi-structured telephone interview was carried
out to validate the migraine diagnosis according to the ICHD-II criteria by a
trained medical student under supervision of study physicians. In case of ambiguous
symptoms, a headache specialist was consulted. All were blinded for the results of
the screener. The test-characteristics of the screener were calculated with the
final ICHD-II diagnosis as gold standard.
Results: Forty-nine (22.2%) of the 221 included TIA or stroke patients
were diagnosed with life-time migraine. The sensitivity of all five questions
combined was 0.47 (95% CI 0.31-0.62), the specificity 0.97 (95% CI 0.93-0.99), the
positive predictive value (PV) 0.80 (95% CI 0.59-0.93) and the negative PV 0.87 (95%
CI 0.82-0.92).The question with the best test-characteristics was on ever presence
of severe headache accompanied by hypersensitivity to lights and sounds (sensitivity
0.96, 95% CI 0.85-1.00; specificity 0.89, 0.85-0.94; negative PV 0.99, 0.95-1.00;
positive PV 0.71, 0.58-0.82). For assessing a history of migraine aura the question
about visual disturbances lasting 5-60 minutes followed by headache had a good
negative PV (0.99, 0.96-1.00), but a low positive PV (0.38, 0.24-0.53).
Conclusions: The short migraine screener can be used to rule out a
history of migraine in patients with a TIA or stroke. To prevent misclassification
in studies on the relation between migraine and stroke, patients with a positive
screener should be interviewed more extensively to verify the diagnosis.
P177
Do Migraineurs with Vertigo/Dizziness Display Some Common Characteristics?
Results from a Population-Based Study
G. Akdal1, B. Baykal2, M. Ertas3, Turkish Headache
Prevalence Study Group2
1Neurology, Dokuz Eylul University, Izmir, Turkey;
2Neurology, Istanbul University School of Medicine, Istanbul, Turkey;
3Neurology, Liv Medical Center, Istanbul, Turkey.
Objectives: Our aim was to assses the frequency of vertigo/dizziness and
to define the differences between clinical characteristics related to
vertigo/dizziness in a community-based sample of migraneurs.
Background: Migraine and vertigo/dizziness are both common, distressing
and interrelated. They occur together 3 times more than by chance, and both impact
on quality of life, but their exact relationships were not well delineated in the
migrainuers.
Methods: We designed a community- based prevalence study in adults, with
face-to face interviews by specially trained general practitioners using a
structured electronic questionnaire. Comprehensive interview form included
diagnostic questions based on the ICHD-II criteria. The questionnaire assessed all
diagnostic headache features, headache related impact, demographics, comorbidities
and disability assessed by MIDAS questionnaire. Participants were asked to provide
mean number of attacks and days with headache per month during last year and
untreated duration of attack in hours. Descriptive statistics were applied and
Chi-square test, t test and logistic regression test were used for comparisons.
Results: 5323 participants were reviewed. Vertigo/dizziness was
significantly higher in migraineurs when compared to tension type headache sufferes.
There were 534 migraineurs with vertigo/dizziness (MwVD) and 337 patients without
vertigo/dizziness as controls. MwVD patients established 61.3 % of definite
migraineurs. MwVD patients had significantly more nausea/vomiting, more headache
aggravation with head motions and had more visual aura. Frequency of headaches and
pain killers used per month were also significantly high in MwVD patients. MwVD
patients reported significantly more motion sickness, allergy, allodynia and
osmophobia, interestingly. Furthermore MwVD patients had significantly low quality
of life.
Conclusions: Our findings showed that more than half of the migraineurs
in the general population have vertigo/dizziness. These patients showed many
significant differences in clinical characteristics and have low quality of life
when compared to other migrainuers.
P178
Migraine, White Matter Hyperintensities (WMH), and Subclinical Brain Infarction
(SBI) in a Race/Ethnically Diverse Older Cohort: The Northern Manhattan
Study
T.S. Monteith1, H. Gardener1, C. Dong1, M.
Santiago2, E. Mitchell2, T. Rundek1, R.L.
Sacco1, C. Wright1
1Neurology, University of Miami Miller School of Medicine, Miami,
FL, USA; 2Neurology, Columbia University, New York, NY,
USA.
Objectives: Migraine, White Matter Hyperintensities (WMH), and
Subclinical Brain Infarction (SBI) in a Race/Ethnically Diverse Older Cohort: The
Northern Manhattan Study.
Background: Epidemiological studies suggest that migraine is a risk
factor for WMH and SBI1.
Methods: In the Northern Manhattan Study, stroke-free participants
underwent quantitative assessment of WMH volume (WMHV) and SBI. We examined features
of SBI and WMHV in those with migraine without aura (MwO) and migraine with aura
(MA) in a subset of participants with information on migraine determined by
self-report using questions based on the ICHD-2 criteria2. We examined
the association between migraine overall (MO), MA, and MwO, with WMHV using linear
regression, and with SBI using logistic regression.
Results: Of 546 study participants with imaging and headache data (41%
men, mean age at MRI=71±8 yrs, 65% Hispanic, 18% black), 104 (19%) were classified
as having migraines at baseline, 6% with MA, and 13% with MwO. When controlling for
age, sex, race/ethnicity, insurance status, high school completion, time from
baseline to MRI, those with MO at baseline had a 2.2-fold increased odds of SBI (95%
CI 1.2-4.4). The association was stronger among those with MwO compared to those
without migraine (OR 2.8, 95% CI 1.4-5.8). Adjusting further for hypertension,
diabetes mellitus, smoking, mild-moderate alcohol use, BMI, the associations between
SBI and migraine persisted for MO (OR, 95% CI=2.1, 1.0-4.3) and for MwO (OR, 95%
CI=2.6, 1.2-5.7), compared to those with no reported history of migraine. No
association was observed between migraine and WMHV. The analysis for MA did not show
a significant association, but was under-powered.
Conclusions: These results suggest that MwO is associated with SBI, but
not WMHV.
P179
Productivity Impact of Headache on a Heavy-Manufacturing Workforce in
Turkey
M.H. Selekler1, T.J. Steiner1
1Neurology, Kocaeli University Medical Faculty, Izmit/Kocaeli,
Turkey; 2Department of Neuroscience, Norwegian University of Science
and Technology, Trondheim, Norway.
Objectives: To measure productivity losses at a heavy-manufacturing
company with a largely male workforce in north-western Turkey.
Background: Headache disorders are common and disabling and cause
substantial productivity losses through absenteeism from work and impaired
effectiveness at work (presenteeism). These losses are generally higher among
women.
Methods: We used the HALT Index as the survey instrument. We first
assessed productivity losses by surveying the entire workforce. Because we
anticipated a high level of non-participation, we also applied HALT at the annual
health checks provided to all employees by the company’s on-site health clinic.
Results: Mean age of the workforce (n=7,200) was 31 yr. About two thirds
(90% male) were manual workers rotating weekly through early, late and night shifts.
One third (50% male) were clerical or managerial, working a standard 5-day week. Of
7,200 questionnaires distributed in the first assessment, 3,939 (54.7%) were
returned with usable data. Absenteeism of ≥1 day in the previous 3 months was
reported by 360 respondents (9.1%), of whom 4 (0.10%) reported absences of ≥45 days.
Average absenteeism per worker in the entire workforce (ie,
including those with and without headache) was 0.92 days/yr. Lost productivity
through presenteeism equivalent to ≥1 day’s absence in the previous 3 months was
reported by 1,187 (29.4%) of respondents. Average presenteeism-related lost
productivity per worker in the entire workforce was 6.0 days/yr. We estimated that
23,519 days’ productivity was lost per year among respondents (2.3% of workforce
capacity). In the first 6 months of annual health checks, 2,691 employees (37.4%)
attended (94.4% male). Absenteeism was reported by 40 (3.4% of those reporting
headache and 1.5% of the total sample), who recorded 74 days lost in total
(mean/person 1.85). Presenteeism equivalent to ≥1 day lost was reported by 348
(29.9% of those reporting headache and 12.9% of the total sample), who recorded
1,240 days lost in total (mean/person 3.56). We estimated that productivity
equivalent to 41,771 man-days/yr was lost in the entire workforce (2.4% of capacity;
94% due to presenteeism), closely matching the earlier estimate. A small minority
(5.7%) of those with headache, who were only 2.5% of the workforce, accounted for
>45% of presenteeism-related lost productivity.
Conclusions: These estimates were well above expectation informed by
studies in Europe, suggesting a higher prevalence of disabling headache in Turkey
than the European average. The high productivity losses in a largely male workforce
were surprising. Possible factors were the nature of the work – manual labour for
two thirds, often heavy – and rotation weekly through early, late and night shifts
(schedule disturbances are a recognized migraine trigger). The high presenteeism to
absenteeism ratio (16.6:1) was not unexpected: the unemployment situation in Turkey
would make employees reluctant to be absent. There was a highly-disabled
minority.
P180
Using an Opioid or Barbiturate Increases Disability and Nausea during a
Headache Attack among Patients with Migraine
R.A. Nicholson1,2, Z.W. Doelger2, T.R. Smith1,2
1Mercy Clinic Headache Center, St. Louis, MO, USA;
2Mercy Health Research, St. Louis, MO, USA.
Objectives: Evaluate the impact of using an opioid or barbiturate vs
other acute medications on headache severity, associated symptoms, and disability
during an individual attack across multiple attacks among patients who use opioids
or barbiturates.
Background: Patients with migraine who use opioids or barbiturates for
headache attacks experience higher migraine-related disability. It is unclear
whether this is a function of the patient or the medication. There is a paucity of
data regarding the impact of using an opioid or barbiturate vs other medications for
individual headache attacks among patients with a history of using opioids or
barbiturates for some attacks.
Methods: In this prospective, longitudinal study, patients with migraine
who use opioids and/or barbiturates to varying degrees completed up to 6 months of
daily web-based headache diaries collected in real/near-time (total days 16,855;
total headache days 5,218; M = 9.3 headache days a month). The diaries assessed
headache and its characteristics (severity, nausea, vomiting, sensitivity to
light/sound), timing (pain severity at initial dosing), acute medication(s) used,
and disability during the headache (measured via Migraine Disability Index [MIDI];
0-10 scale, higher numbers = higher disability). Medication was placed into three
types: opioid and/or barbiturate (OB); migraine-specific medication (MSM); NSAID
and/or simple analgesic (NSA). OB use at any point was classified as OB, otherwise
grouping was based on first medication type. Log-linked GEE (for scaled outcomes)
and logit-linked GEE (for binary/ordinal outcomes) evaluated the impact of
medication type, pain severity at initial dosing, and their interaction while
controlling for covariates. Sequential Bonferroni adjusted 95% confidence intervals
were used.
Results: Medication use was; MSM (45%), NSA (32%), OB (23%). Pain
severity at first dose was; mild (51%), moderate (37%), severe (12%). Regarding
disability, GEE showed an interaction for medication X pain at dosing (Wald
(4)=58.57, p < .001). Of note, at mild initial dosing, MSM (M= 2.5) and NSA (M =
2.6) had less disability during the headache than OB (M = 3.7, both p < .001). At
moderate initial dosing MSM (M = 4.9) had less disability than OB (M = 5.8, p <
.001). There were no significant differences at severe initial dosing. An
interaction was also seen for nausea (Wald (4)=39.61, p < .001). Of note, at mild
dosing, MSM (M =45%) resulted in less nausea than NSA (M=72%) or OB (M=73%, both p
< .001). No significant differences between medication types were found at
moderate and severe dosing levels. Results for photophobia, phonophobia, and
severity replicated those for nausea.
Conclusions: Among persons who sometimes use an opioid or barbiturate,
taking an opioid or barbiturate when pain is mild or moderate results in higher
disability during individual attacks relative to using other acute medications.
Increased disability appears to be a function of the medication and when it is used
rather than the individual.
P181
Patients with Migraine Internalize Stigma More Readily Than Patients with
Epilepsy
W.B. Young1, J. Kempner2, J.E. Park1
1Neurology, Thomas Jefferson University, Philadelphia, PA, USA;
2Sociology, Rutgers University, New Brunswick, NJ,
USA.
Objectives: To characterize and compare the self-stigmatization process
in episodic and chronic migraine, and in epilepsy.
Background: Enacted stigma is converted into internalized stigma through
the self-stigma process, lowering self-esteem and causing psychological distress. We
have recently shown that patients with migraine have a higher ratio of internalized
to total stigma compared to epilepsy patients.
Methods: We studied 123 episodic migraine (EM) patients, 123 chronic
migraine (CM) patients, and 62 epilepsy (Ep) patients in a clinical setting to
investigate the extent to which stigma attaches to migraine, using epilepsy as a
comparison. We used the stigma scale for chronic illness, a 24-item questionnaire
suitable for studying chronic neurologic diseases, and various disease impact
measures. The SSCI-Enacted includes 11 items and the SSCI-Internalized (SSCI-I) 13
items, dividing stigma into two domains. We analyzed the ratio of SSCI-I to total
SSCI (SSCI-I/SSCI).
Results: Patients with chronic migraine had higher SSCI scores
(54.0±20.2) on the stigma scale for chronic illness than either episodic migraine
(41.7±14.8) or epilepsy patients (44.6±16.3) (p<0.001). Migraine patients
reported less ability to work than epilepsy subjects. Stigma correlated most
strongly with the mental component score of the short form of the medical outcomes
health survey (SF-12), then with ability to work and migraine disability score for
chronic and episodic migraine and the Liverpool impact on epilepsy scale for
epilepsy. Analysis of covariance showed adjusted scores for the stigma scale for
chronic illness were similar for chronic migraine and epilepsy, and lower for
episodic migraine. Ability to work was the strongest predictor of stigma.
We then examined SSCI-I/SSCI, demonstrating that a higher proportion of the stigma
reported by CM (0.634 ± 0.060) and EM (0.622 ± 0.059) patients could be attributed
to internalized stigma than enacted stigma, compared to Ep patients (0.598±
0.074).
For each disease condition, SSCI-I /SSCI did not vary according to age, gender,
income or education, but correlated negatively with ability to work for EM (r =
-0.236, p=0.008), showed a trend for CM (r=-0.174, p=0.055), and did not correlate
with Ep. There was no correlation of SSCI-I/SSCI with the physical component score
of the SF-12, but there was a correlation with the mental component score of the
SF-12 for EM (r=-0.337, p<0.001) and CM (r=-0.259, p=0.004), but not for Ep.
Conclusions: Patients with migraine process stigma differently than
patients with epilepsy. The proportion of internalized stigma to total stigma
correlated most strongly with inability to work for patients with EM than for the
other diseases conditions studied, perhaps because the expectation to work is
greater for EM than for CM or EP.
P182
Migraine Treatment Optimization in Multiple Sclerosis
S. Sahai-Srivastava1, S.L. Wang2, C. Ugurlu1, L.
Amezcua1
1Neurology, University of Southern California, Los Angeles, CA,
USA; 2Internal Medicine, Long Beach Memorial Hospital, Long Beach,
CA, USA.
Objectives: To determine adequate migraine diagnosis and predictors of
treatment optimization in MS including demographics, socioeconomic status,
depression, and MS characteristics.
Background: Migraine is under-diagnosed and under-treated in the general
population. Patients with multiple sclerosis (MS) suffer from a higher incidence of
migraine than patients without MS, but migraine diagnosis and treatment optimization
has not been studied in MS.
Methods: We conducted a cross-sectional interview based study of 233
consecutive patients with MS using detailed questionnaires including the
Migraine-Treatment Optimization Questionnaire (M-TOQ).
Results: Our cohort was predominantly female 156(67%), average age 44
years. 83 (36%) patients had migraine. Based on the results of (M-TOQ), acute
migraine treatment was optimized in only 48 (58%) and was not influenced by race.
However acute migraine treatment was better optimized in episodic 43(62%), rather
than chronic migraineurs 5(36%). The majority of our patients 56(70%) were using
non-specific acute abortive treatment for migraine headaches, of which non-steroidal
anti-inflammatory medications were the most common. Preventative treatment was used
infrequently 12 (14%), of which the most common were anti-epileptics or
antidepressants. The use of complementary and alternative medications was quite high
in this population 56 (70%), the most common modality of treatment reported being
use of cold cloth/ice pack to forehead 47(57%).
Conclusions: As in the general population, the majority of MS patients
with migraine are under-diagnosed. About half of MS migraineurs have non-optimized
treatments regardless of migraine regimen, race, or walking ability. Depression and
episodic rather than chronic migraine were positively correlated with optimized
migraine medications. Socioeconomic factors predicting optimization of migraine
treatment in MS patients include higher education and income, and private treatment
setting. Optimized treatment usage was higher in private clinic. Alternative
treatment was used more in public clinic and abortive treatment usage was similar in
both public and private clinics.
P183
A Generalized Cost-Effectiveness Analysis of Interventions Against Migraine
Using WHO-CHOICE Methodology
M. Linde1, D. Chisholm2, T. Steiner1
1Department of Neuroscience, Norwegian University of Science and
Technology, Trondheim, Norway; 2Department of Mental Health and
Substance Abuse, WHO, Geneva, Switzerland.
Objectives: To identify how health resources may be allocated to an
optimal mix of interventions against migraine by evaluating their cost-effectiveness
(CE) in low, middle and high income countries in different world regions.
Background: CE analysis plays a crucial role in optimizing health-care
resource allocation and clinical decisions. We identified 20 published CE analyses
of migraine interventions. Most (17) applied intervention mix constraints, being
focused on particular drugs (eg, triptans or specific
prophylactics), which hindered comparisons with less costly and more accessible
interventions. Further, all were performed in Europe or North America, with limited
relevance to other regions in view of the large variations in development of health
systems and overhead costs. None compared recommended acute and prophylactic
interventions against doing nothing in real-world settings based on the
epidemiological profile of migraine.
Methods: We modelled >20 interventional strategies, taking account of
coverage and non-adherence. We included first-line acute and prophylactic drugs, and
the expected consequences of adding public health-education and training of
health-care providers. We used CostIt® software to standardize costing. Drugs were
valued at the prices that would be incurred in the international market place,
adjusting to include domestic margin. A health system perspective was taken,
including all costs and the share of overhead resources that could be reallocated to
other interventions. We used PopMod® software to estimate effectiveness of
interventions. We took summary measures of sustained headache relief (for acute
drugs) and reduced attack frequency (for prophylactics) from published evidence. We
used age-standardized attack-incidence rates and ictal disability weights for
migraine from the Global Burden of Disease 2010 study. We expressed net health
effects as disability-adjusted life years (DALYs) averted. We executed a first run
of the model for India.
Results: Of the strategies considered, acute treatment only with an
NSAID was the most cost-effective (US$ 46-47 per DALY averted, which represents a
highly efficient use of health resources). Adding public health-education and/or
training of health-care providers to acute self-management increased costs by US$
0.03-0.04 per capita of the population. CE ratio then became slightly less
favourable but still less than US$ 100 per DALY averted. Adding a triptan for
stepped care increased the CE ratio 30-fold. For prophylaxis, amitriptyline was more
cost-effective than propranolol or topiramate.
Conclusions: Self-management with an NSAID is by far the most
cost-effective intervention for migraine in India, and this is most likely true for
all world regions. Public education and health-care provider training are expected
to accelerate progress towards desired coverage levels, cost relatively little to
implement, and are therefore assumed to be economically attractive.
P184
Public Versus Private Care in Headache. Are There Differences?
1Headache Center of Rio, Rio de Janeiro, RJ, Brazil.
Objectives: This study aimed at comparing patient’s profile, diagnosis,
adherence, treatment strategies and response between headache sufferers attending
two different services in Rio de Janeiro. A public and a private headache
center.
Background: Countries with socialized medicine and/or with a free-of
charge public system may deliver inferior quality care in comparison with private
medicine environments.
Methods: Consecutive patients from both environments were prospectively
compared regarding ages, sex distribution, diagnosis, treatment strategies,
adherence, response (headache frequency decrease of higher than 50%) and requesting
work releasing during the first and second consultations. Adherence was defined as
returning for the following consultation and compliance with treatment
prescribed.
Results: 500 patients from the Headache Center of Rio were compared to
227 patients from The Instituto de Neurologia Deolindo Couto (INDC). Adherence was
identified in 73,1% of the public patients compared to 80,1% in the private center.
Monotherapy was prescribed to 13,4% of the public system patients compared to 33%
whereas 86,2% from the private center versus 67% from the public system received
more than one drug for prevention. Requesting documentation for work releasing was
seen in 2 (0,4%) of the private patients compared to 50 (22%) of those seeking for a
public system care. Regarding decreasing of headache frequency of higher than 50%,
it was presented by 62% of those returning (45% by ITT) in public system compared to
72,6% of those who adhered (58,2% by ITT) in the private setting.
Conclusions: Although most of the public services of Rio deliver poor
quality care, the patients from the INDC did present similar profile of diagnosis,
treatment approach and response when compared to those patients from the first and
more comprehensive headache center of the State. Reasons for that may be the
orientation provided to the attending physicians by the technical coordinator who is
the same of the private setting. In addition, the geographical location of the
public service, in this case better than that from most of the other services, may
have contributed to the better standard of the patients. Interestingly,
significantly more patients with TTH and requesting work releasing were noted in the
public service.
Private N=500
Public N=227
Gender
Female
71,8% (359)
75% (150)
Male
28,2% (141)
25% (57)
Age (years)
Mean
38,7 (4-88)
39,8 (16-76)
Diagnosis
Migraine
58% (290)
45,4% (101)
MOH
35,6% (178)
32,6% (74)
TTH
1,8% (9)
15,4% (35)
TAC
3% (15)
6,6% (15)
Other
1,6% (8)
0,9% (2)
Headache frequency
(days/month)
17
16
Preventive therapy
None
0,4%(2)
0%
1drug
13,4%(67)
33%(75)
> 1 drug
86,2%(431)
67%(152)
Response
Adherent patients
72,6%(363)
62%(141)
ITT
58,2%(291)
45% (102)
Adherence
80,1%(400)
73,1% (166)
P185
Reliability and Validity of the Persian Headache Impact Test (HIT-6)
Questionnaire across Migraine and Tension Type Headache
A. Zandifar1, M. Banihashemi1, F. Haghdoost1, S.S.
Masjedi1, N. Manouchehri1, F. Asgari1, E.
Zandifar2, S. Zandifar2, M. Saadatnia3, M.K.
White4
1Medical Student Research Center, Isfahan University of Medical
Sciences, Isfahan, Iran (Islamic Republic of); 2Physiology Research
Center, Department of Physiology, Isfahan University of Medical Sciences,
Isfahan, Iran (Islamic Republic of); 3Department of Neurology and
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences,
Isfahan, Iran (Islamic Republic of); 4QualityMetric Inc., Lincoln,
RI, USA.
Objectives: The objectives of this study were to validate the Persian
translation of HIT-6, compare the psychometric analysis of HIT-6 between migraine
and tension type headache (TTH) patients, and evaluate the capability of HIT-6 to
differentiate between TTH, chronic and episodic migraine.
Background: Headache impact test questionnaire (HIT-6) is a valid scale
that measures the impact of headache in a one-month period. Up to this date there is
no valid and reliable Persian translation of HIT-6.
Methods: Qualified participants, including 274 patients, diagnosed with
migraine or TTH, were required to complete HIT-6, SF-36v2 and a symptoms
questionnaire on their first visit. At third and eighth week from first visit
participants completed HIT-6. Internal consistency (Cronbach α) and test-retest
reproducibility (Pearson correlation coefficient) were used to assess reliability.
Convergent validity was assessed through measurement of correlation between HIT-6
and headache days per month (HDPM), HIT-6 and numeric rating scale (NRS) and also
between HIT-6 and SF-36.
Results: TTH, episodic migraine and chronic migraine included 24.5%,
61.9% and 13.6% of the participants respectively. Internal consistency among all
patients, TTH and migraine in first visit was 0.74, 0.77 and 0.73 respectively.
Test-retest reliability for HIT-6 between visit 1 and 2 showed a moderate level of
correlation (r=0.50). The total HIT-6 score in the first visit was negatively
correlated with both mental and physical components (r=-0.39 and -0.35 respectively,
P<0.001). Also total HIT-6 score in first visit was modestly correlated with
headache days per month (HDPM) and numeric rating scale (NRS) (r= 0.14 and 0.17
respectively, P<0.001). All questions were significantly correlated with total
HIT-6 score (0.52 to 0.77, P<0.001). There was no significant difference in HIT-6
total score between TTH and migraine.
Conclusions: Persian HIT-6 is a valid and reliable questionnaire for
evaluation of headache; however it cannot differentiate between chronic, episodic
migraine and TTH in Iranian population.
P186
Difference in Dietary Patterns between Migraine with and Migraine without
Aura
P.M. Rist1,2, J.E. Buring1,5, T. Kurth1,3,4,5
1Division of Preventive Medicine, Brigham and Women’s Hospital,
Boston, MA, USA; 2Social and Behavioral Sciences, Harvard School of
Public Health, Boston, MA, USA; 3Unit 708 - Neuroepidemiology,
INSERM, Bordeaux, France; 4University of Bordeaux, Bordeaux, France;
5Epidemiology, Harvard School of Public Health, Boston, MA,
USA.
Objectives: To evaluate the cross-sectional associations of dietary
patterns between migraine with aura and migraine without aura in a large cohort of
women.
Background: People with migraine often report that certain foods,
including wine, chocolate, caffeine, cheese, and processed meats, “trigger” migraine
attacks. However, epidemiologic evidence on migraine triggers or on the dietary
patterns of migraineurs with specific focus on aura is limited. Using data from a
large prospective cohort study of women, we aimed to examine whether intake of foods
that have commonly been reported as migraine triggers was different between women
with migraine with aura and women with migraine without aura.
Methods: We performed a cross-sectional study among 4946 women enrolled
in the Women’s Health Study who reported active migraine at baseline and completed a
131-item food frequency questionnaire. Women were classified as either having
migraine with aura or migraine without aura. We compared women in the top quintile
of average number of servings per day for each food item to those in the lower four
quintiles using logistic regression. For these analyses, we examined intake of
chocolate, caffeine, cottage cheese, cream cheese, other cheeses, bacon, hot dogs,
processed meats, red wine, white wine, liquor and beer because these foods have
previously been reported to be migraine triggers. Models were adjusted for age,
total calories, body mass index, physical activity, smoking status, diabetes,
history of hypertension, treatment for high blood pressure, history of high
cholesterol, and treatment for high cholesterol.
Results: We had 2059 women who experience migraine with aura and 3115
women who experience migraine without aura. Migraineurs with aura were more likely
to consume white wine (odds ratio (OR)=1.18, 95% confidence interval (CI):
1.00-1.39) and less likely to consume chocolate (OR=0.78, 95% CI: 0.65-0.95), bacon
(OR=0.79, 95% CI: 0.68-0.93) and hot dogs (OR=0.74, 95% CI: 0.60-0.91) compared to
those who experience migraine without aura. Results for red wine were marginally
insignificant (OR=1.25; 95% CI: 0.99-1.58). We did not observe significant
differences in intake for any other explored food item.
Conclusions: In this cross-sectional study, we observed different food
intake patterns of common migraine trigger foods among migraineurs with and without
aura. Future research needs to be performed to determine if migraineurs with and
without aura may avoid eating difference food items in order to prevent migraine
attacks and whether these food items truly cause migraine attacks.
P187
Prevalence of Chronic Migraine and Medication Overuse Headache in Eight
Austrian Headache Centres
K. Zebenholzer1, C. Andree2, A. Lechner3, G.
Broessner4, G. Luthringshausen5, A. Wuschitz6,
C. Lampl7, S.-M. Obmann8, K. Berek9, W.
Wurm10, C. Schweiger11, C. Woeber1
1Department of Neurology, Medical University Vienna, Vienna,
Austria; 2CRP Sante, Strassen, Luxembourg; 3Department of
Neurology, Medical University Graz, Graz, Austria; 4Department of
Neurology, Medical University Innsbruck, Innsbruck, Austria;
5University Clinic of Neurology, Doppler Klinik Salzburg, Salzburt,
Austria; 6Private Practice, Vienna, Austria; 7Department
for Remobilisation, KH Barmherzige Schwestern, Linz, Austria;
8Department of Neurology, Klinikum Klagenfurt, Klagenfurt, Austria;
9Department of Neurology, BKH Kufstein, Kufstein, Austria;
10Department of Psychiatry, Medical University Graz, Graz,
Austria; 11LNK Wagner Jauregg, Linz, Austria.
Objectives: To evaluate the prevalence of episodic and chronic headaches
in 8 Austrian headache centres with emphasis on chronic migraine and medication
overuse headache (MOH).
Background: Lifetime prevalence of migraine is 10-18%, of tension-type
headache (TTH) 16-59%. MOH shows a prevalence of 1-1.5%, in headache centres of
30-50%.
Methods: In April and September 2011 all patients who attended the
headache centres for a first-time or control visit were screened for the study.
Participants had to fill-in the Eurolight Questionnaire that covers demographic
data, headache symptoms, information about medication, consultations of the health
system, examinations due to headaches, questions about quality of life, depression
and anxiety. Headaches were diagnosed according to ICHD-II.
Results: Of 598 patients screened, 121 refused participation or were
excluded because of lacking knowledge of German. After excluding 36 patients due to
incomplete data, 441 patients (348 women, 93 men, mean age 39.9 years) were
analysed. The proportion of patients with migraine or probable migraine, TTH or
probable TTH, MOH and other headaches was 68.5%, 12.7%, 16.1%, and 2.7%
respectively. Headache was episodic in 59.6% and chronic in 40.4%. Of the patients
with chronic headaches 42.0% had medication overuse headache, 42.0% had migraine or
probable migraine, 14.2% had TTH or probable TTH and 1.8% had other headaches.
Hospital Anxiety and Depression Scale Scores indicated a certain anxious state in
24.2%, a doubtful anxious state in 18.7% and no anxiety in 57.1%; it indicated a
certain depressive state in 14%, a doubtful depressive state in 18.3% and no
depressive state in 67.7%. Symptoms of anxiety were present in 55.8% of the patients
with chronic headaches and in 34.4% of those with episodic headaches (p<0.001).
Symptoms of depression were present in 45.2% of the patients with chronic headaches
and in 22.2% of those with episodic headaches (p<0.001).
Conclusions: A substantial number of patients seen in specialised
headache centres in Austria have chronic headaches. Among the latter chronic
migraine and MOH account for more than 80% of diagnoses. These patients who
frequently also show signs of depression or anxiety need a comprehensive and
multidisciplinary treatment approach.
P188
Characteristics of Young Adults and Adolescent Presenting to a Headache
Specialty Clinic
H.L. O’Brien1,2, P. Vaughan1, M. Kabbouche1,2, S.
LeCates1, S. White1, J. Bush1, P.
Manning1, A. Segers1, A.D. Hershey1,2
1Neurology, Cincinnati Children’s Hospital Medical Center,
Cincinnati, OH, USA; 2Pediatrics, University of Cincinnati,
Cincinnati, OH, USA.
Objectives: To describe the characteristics of young adults and
adolescent with headache presenting in a multidisciplinary outpatient clinic for
specialty headache treatment.
Background: As an individual develops from childhood into adolescence,
the prevalence of migraine increases. Migraine is often under recognized in young
patients and can have a significant impact on their lives. Young adults represent an
underserved population whose needs are unique and challenging for providers who
treat in solely a pediatric or adult setting. A young adult and adolescent
multidisciplinary clinic was developed to meet the unique needs of this group while
they transition to adulthood.
Methods: A retrospective analysis of 266 patients (ages 15-26) that have
received a multidisciplinary evaluation and treatment for a headache disorders by a
team comprised of a board certified Neurologist and Headache Medicine specialist,
pain psychologist, nurse practitioner and registered nurse. Standardized
questionnaires were completed by each patient providing information about the
headache and health history as well as information pertinent to confirm diagnosis
based on the International Criteria for Headache Disorders 2nd edition.
This was accomplished through a semi-structured interview and a comprehensive
neurological exam.
Results: The female to male ratio was 201:65. The mean age on evaluation
was 16.9 ± 2.5 years old. The mean time from start of headaches to evaluation was
5.6 years. Average headache frequency was 18.7 ±10.1 days per month with an average
severity on a 0-10 numeric pain scale of 6.7 ± 1.7. The mean headache duration was
15.3 hours. Episodic migraine (<15 headache days/month) occurred in 31.2% of the
patients evaluated with chronic migraine (>15 headaches/month) in 68% of the
patients, including 40.2% reported an “always” or daily headache. The diagnosis of
migraine without aura occurred in 96.6% of patients; status migrainosus 49.6%;
migraine with aura 29.3%; medication overuse headache (MOH) 36.8%; menstrually
related migraine without aura 19.5%.
Conclusions: Young adult patients presenting for care for intractable
headaches are more likely to be females who have had nearly a 6 year history of
headaches that they describe as moderate to severe in intensity. These patients are
likely to present with chronic headaches that are primarily migraine without aura.
Recognition of these patient characteristics should prompt early treatment and used
as a tool in providing better outcomes.
P189
Adherence and Persistence to Triptans for Acute Migraine: A Systematic
Literature Review
K. Tsai5, S. Tepper1, L. Bloudek2, A.
Messali2, S. Kori4
1Cleveland Clinic Center for Headache and Pain, Cleveland, OH,
USA; 2Allergan Inc., Irvine, CA, USA; 3University of
Southern California, Los Angeles, CA, USA; 4MAP Pharmaceuticals Inc.,
Mountain View, CA, USA; 5OptumRX, Irvine, CA, USA.
Objectives: Evaluate adherence and persistence to triptan therapy for
the acute treatment of migraine.
Background: Triptans are the most commonly prescribed treatment for
patients with moderate to severe migraine. Clinical trials have demonstrated the
safety and efficacy of triptans. However, observational studies have consistently
reported low patient adherence and persistence over time.
Methods: A systematic literature review was conducted to identify all
studies of patient adherence and persistence to triptan medications.
Results: 86 potentially relevant studies were identified, from which 6
articles met the inclusion and exclusion criteria and were included, along with an
additional 3 articles identified from bibliographic review. This review found that
over 2 years, approximately half of patients were persistent to the first prescribed
triptan. 38% to 56% of patients filled only 1 prescription after starting their
triptan therapy. Over 2 years, 14.8% of patients tried >1 triptan. In a study
conducted in the UK, 9% switched to another triptan, and 41% of the 9% reported the
switch as successful. In the US, 7.4% of those who discontinued the first prescribed
triptan switched to another triptan, while 67.1% had switched to a non-triptan and
25.5% of patients had discontinued all therapy.
Conclusions: Triptans are a valuable treatment option for acute
treatment of migraine. However, studies have shown that adherence and persistence to
therapy is low. This, along with discontinuation and frequent switching behaviors,
suggests that there is a significant proportion of patients not adequately treated
with currently available triptans.
P190
Dementia Outcomes in Elderly with Self-Reported History of Migraine
J. Pavlovic1,2, W. Mowrey3, C.B. Hall3, M.J.
Katz1, R.B. Lipton1,2
1Neurology, Albert Einstein College of Medicine, Bronx, NY, USA;
2Montefiore Headache Center, Bronx, NY, USA;
3Epidemiology & Population Health, Albert Einstein College of
Medicine, Bronx, NY, USA.
Objectives: To examine the risk of incident dementia in community
residing adults over the age of 70 with migraine.
Background: Studies of the relationship of migraine and cognitive
outcomes have been few and conflicting. Study sample characteristics, methods for
identifying migraine, assessments of cognitive outcomes have varied widely. The
Manitoba Aging Study reported that persons with migraine had a 5-fold increased risk
of dementia.
Methods: The Einstein Aging Study (EAS) follows a systematically
recruited, ethnically-diverse community residing sample of adults age 70+ with
annual telephone screening and in-person assessments. Neurologic examination and
comprehensive cognitive assessments are used to determine dementia status based on
DSM-IV criteria at a case conference. Study subjects were said to have “migraine” if
they reported a history of migraine or if they reported headache within the last 3
months at least “some of the time”. Prevalent dementia cases were excluded. Cox
proportional hazards models were used to model time to dementia with migraine
status, demographic factors (sex, education, ethnicity) and APOE-e4 carrier status
as predictor variables. Additional adjustments for overall baseline pain
interference and pain intensity were included. Age was used as the time scale for
these models in order to fully control for age effects.
Results: Of 974 eligible subjects, 136 met criteria for migraine. Among
the 838 individuals without migraine, 76 developed dementia (9.1%). Of 136 with
migraine, 8 developed dementia (5.9%). Cox model shows that migraine was not
significantly associated with dementia onset (Hazard Ratio (HR)=0.60, 95% CI
0.29-1.25). Adjusting for sex, education, and ethnicity (HR=0.56, 95% CI: 0.27-1.18)
and for APOE-e4 carrier status, baseline pain interference and pain severity did not
materially alter the conclusion.
Conclusions: In this cohort, migraine was not a risk factor for incident
dementia. Possible misclassification of migraine status due to remitted and
forgotten migraine could attenuate the measured association. As migraine frequency,
duration, disability and aura status were unknown, this does not exclude an effect
on dementia risk of some migraine subgroups.
P191
Chronic Primary Headaches Are Different from Episodic Primary Headaches:
Experiences from an In Patient Treatment in a Neurological Clinic
M. Volcy1, M.M. Massaro2
1Neurology-Headache, Instituto de Dolor De Cabeza y Enfermedades
Neurologicas -Indocen, Medellin, Antioquia, Colombia; 2Neurology,
Instituto Neurologico De Colombia-INDEC, Medellin, Antioquia, Colombia;
3Neurology, Universidad de Ciencias De La Salud -CES, Medellin,
Antioquia, Colombia.
Objectives: To compare clinical characteristics, therapeutics response
and prognosis in subjects with episodic primary headaches (EPH) or chronic primary
headaches (CPH) carried into an in-patient treatment in a headache unit from a
neurological clinic.
Background: Primary headaches are frequent causes of consultation in the
ER and hospitalization. Still there is a lack of guidelines with strong
medicine-based evidence. There have been discussion about probable differences
between episodic and chronic headaches, although there is not clear data from
in-hospital. There are guidelines and medicine-based evidence for neuroimaging
studies in PH, but still it is found high rates of prescriptions.
Methods: This is a retrospective cohort analytic study of patients with
PH in a in-patient program from a headache unit from a neurological clinic. The
results are presented comparing CPH against EPH according to de variable level
measurement.
There was a retrospective information recolection, the evaluation of the outcome was
prospective from clinical chart. The data was analyzed through the statistical tests
chi square and frequency comparison.
Results: 198 patients were treated between 2009 to 2011. In the CPH, CM
was the most common (88.1%), NDPH (9.8%) and CTTH (2.1%). In the EPH, EM was the
main diagnosis (92.7%). in CPH the in-patient managment was need it because
treatment refractoriness (49%), as in EPH was due to migranous status (69.1%). 38.9%
of patients had neuroimaging abnormalities, but in just 7 patients (3.6%) with CPH
LET to changes in treatment and diagnosis. 69.2% of patients were on prevention, and
91.4% used abortives. There was not possible to determine which IV meditacion had
better efficacy and safety. During the in-patients treatment the average IV
medications was 4.1+/-1.9; subjects with CPH needed higher numbers (4.6 +/-1.8 vs.
2.9+/- 1.4), prolonged infusions (7.5 days +/- 6.1 vs. 2.8+/-1.5). anxiety (58% vs
20%), deppression (57.3% vs 14.5%) and insomnia (48.3% vs 7.3%) were more frequently
asociated with CPH. The in-patient period needed was significantly higher in
patients with CPH (p < 0.001). At discharge, 74.9% were pain free or improved
(AVS <3). Subjects with EPH had better response (87% vs. 70.2%; p= 0.0001 RR 3.62
CI 95% 1.8 – 7.04). CM was a risk factor for a bad in-patient response and prognosis
(RR 4.0 CI 95%: 1.5 - 11).
Conclusions: The in-patient treatment is an effective option to treat
primary headaches, the final results at discharge is directly related to the primary
headache subtype. Although episodic and chronic headaches share clinical features,
the differences in responses and prognosis suggest probably differences in
pathophysiology and associated risk factors. Medicine-based evidence is need it,
specially to cph patients. From our experience, an algorithmic approach is
suggested.
P192
Sinus Pressure and Its Association with the Attack Frequency of Migraine and
Tension-Type Headaches
V.T. Martin1, G.V. Martin1, J.B. Ellison1, L.S.
Levin2, E. Al-Shaikh2, J.A. Bernstein1
1Internal Medicine, University of Cincinnati, Cincinnati, OH, USA;
2Environmental Health, University of Cincinnati, Cincinnati, OH,
USA.
Objectives: 1) To determine if the prevalence of sinus pressure is
greater in patients with migraine (M) and/or tension type headache (TTH) compared to
controls, 2) To ascertain if the self-reported attack frequency of M or TTH differs
between subjects with and without sinus pressure.
Background: Sinus pressure is a common complaint in headache patients
and one that may contribute to the misdiagnosis of migraine as “sinus
headaches”.
Methods: Participants between ages 18-65 years were recruited from one
allergy clinic consisting of rhinitis patients (n=655) and two control internal
medicine (n=187) clinics in Cincinnati, Ohio. Rhinitis patients were categorized
into allergic (AR; n=254), mixed (MR; n=279) and nonallergic (NAR; n=122) rhinitis
based on allergy testing and responses to an irritant index questionnaire. Controls
included patients that self-reported “rarely” or “never” experiencing rhinitis
symptoms to specific allergic and non-allergic triggers. Subjects underwent a
structured verbal interview to determine headache characteristics including the
attack frequency (days/month) and presence/absence of sinus pressure. Subsequently,
each subject was assigned an ICHD headache diagnosis by a blinded headache expert.
Log binomial regression was used to determine if the prevalence of sinus pressure
increased in those with M and TTH after controlling for rhinitis status, age and
gender. Quantile regression was used to compare M and TTH attack frequency between
those with and without sinus pressure at the 25th, 50th and
75th percentiles of these measures after adjusting for gender, age
and preventive medication.
Results: Sixty percent of subjects were female; sinus pressure was
reported by 80%, 68% and 33% of subjects with M, TTH and controls, respectively. The
adjusted risk ratios (RRs) for sinus pressure prevalence were 1.2 (95% CI; 1.1, 1.4)
for M and 1.1 (95% CI; 0.99, 1.2) for TTH. The RRs were significant for all the
rhinitis subtypes (range for RRs: 1.6-1.7; all p values <0.01). For headache
frequency analyses, the ratio of the means in patients with compared to those
without sinus pressure were 2.0, 2.2 and 2.7 for M and 1.4, 2.1 and 2.0 for TTH at
the 25th, 50th and 75th percentiles, respectively
(p values <0.05).
Conclusions: Sinus pressure is more common in migraineurs than those
without M even after accounting for rhinitis. The attack frequency of both M and TTH
headache is significantly increased in patients with sinus pressure. Since sinus
pressure commonly occurs in patients with rhinitis and rhinosinusitis, further work
is needed to determine whether these disorders directly trigger headache attacks or
if patients with more frequent headaches are more likely to experience pressure in
the sinus regions.
P193
The Psychometric Properties of the Persian Migraine-Specific Quality of Life
Questionnaire Version 2.1 (MSQ) in Episodic and Chronic Migraine
A. Zandifar1,2, S. Zandifar2, S.S. Masjedi1, F.
Haghdoost1, F. Asgari1, N. Manouchehri1, M.
Banihashemi1, M. Saadatnia3, E. Zandifar2
1Medical Student Research Center, Isfahan University of Medical
Sciences, Esfahan, Iran (Islamic Republic of); 2Physiology Research
Center, Department of Physiology, Isfahan University of Medical Sciences,
Esfahan, Iran (Islamic Republic of); 3Department of Neurology and
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences,
Esfahan, Iran (Islamic Republic of).
Objectives: The aims of this study were linguistic validation of Persian
MSQ questionnaire, analysis of psychometric properties between chronic and episodic
migraine patients and capability of MSQ to differentiate between chronic and
episodic migraine.
Background: Migraine specific quality of life (MSQ) is a valid and
reliable questionnaire that consists of three dimensions; role restrictive (RR),
role preventive (RP), and emotional function (EF), which evaluates the patients in a
one-month period.
Methods: Participants were diagnosed chronic or episodic migraine
patients from four different neurology clinics. Baseline data included information
from MSQ v. 2.1, MIGSEV, SF-36 and symptoms questionnaire. At the third week from
the baseline, participants filled out MSQ and MIGSEV. Internal consistency (Cronbach
alpha) and test-retest reproducibility (Pearson correlation coefficient) were used
to assess reliability. Convergent validity of MSQ was assessed through measurement
of correlation between MSQ scores (total score and each dimension of MSQ) and two
components of SF-36 (mental and physical) scores. Discriminant validity was assessed
through comparison between different grades of MIGSEV scale in each dimension and in
total MSQ scores. Potency of MSQ to discriminate between chronic and episodic
migraines was evaluated.
Results: A total of 106 participants were enrolled. Chronic and episodic
migraine included 26.8 % and 73.2 % of the participants respectively. Internal
consistencies of MSQ among all patients, chronic and episodic migraine were 0.92,
0.91 and 0.92 respectively. Test-retest correlation of MSQ dimensions between visit
1 and 2 varied from 0.41 to 0.50. All the questions were significantly correlated
with total MSQ score (r=0.44-0.81, P-value<0.001). The total MSQ score in the
first visit was correlated with SF-36 mental and physical scores (0.41 and 0.46
respectively, P<0.001). Comparison of the mean of MSQ scores between the three
grades of MIGSEV showed significant differences (P<0.001). In all visits MSQ
scores were lower in chronic migraine than episodic migraine; however the difference
was not statistically significant.
Conclusions: Persian translation of MSQ is consistent with original
version of MSQ in terms of psychometric properties in both chronic and episodic
migraine patients.
Objectives: The aim of our study was 1) to assess the prevalence of neck
pain in migraineurs; 2) to evaluate the percentage of patients having neck pain as
clear prodromal symptom of their migraine (neck pain outside the headache phase,
without any migraine features, 2-24 h before their onset); 3) to describe clinical
characteristics of neck pain.
Background: Although the pain of migraine is most commonly perceived in
the ophthalmic distribution of the trigeminal nerve, a substantial percentage of
migraineurs are reported to experience pain in the neck and occiput with their
attacks.
Methods: An online questionnaire was set on the homepages of the
Austrian self-helping group (www.shgkopfweh.at) and the headache medical center
seilerstaette Linz (www.kopfschmerz-linz.at). Patients with a clear migraine
(pre-diagnosed by a neurologist) were anonymously asked about the occurrence of neck
pain during different phases of their attacks.
Results: 387 migraineurs, 311 females (80.3%) and 76 male (19.6%)
responded. 261 (67.4%) reported to experience pain in the neck (189, 72.4%
bilateral; 72, 27.6% unilateral): 157 (60.1%) with or immediately (within 2 h)
before their attacks, 68 (26%) exclusively within 2 hours before their attacks and
36 (13.8%) 2-24 h before the attack. None of the patients showed neck pain before or
within the attack without any additional accompanying signs or symptoms of
migraine.
Conclusions: Neck pain is not a prodromal symptom of a migraine attack.
There is support for neck pain being not simply a co-occurring condition in
migraine, but rather related to the disorder itself.
P195
Comparing Electronic and Paper Diary Recordings of Headache among Adolescents
in the General Population
A.-B. Krogh1, B. Larsson2,3, M. Linde1
1Department of Neuroscience, Norwegian University of Science and
Technology, Trondheim, Norway; 2Regional Centre for Child and Youth
Mental Health and Child Welfare, Trondheim, Norway; 3St. Olav’s
Hospital, National Competence Centre for Complex Symptom Disorders, Trondheim,
Norway.
Objectives: (1) To develop and investigate the usefulness of electronic
diary over the Internet (eDiary) of headaches among adolescents in the general
population, and (2) to compare the response rate in eDiary versus paper diary posted
to the investigator (pDiary), and (3) to investigate their response rates on
weekdays versus weekends.
Background: Until recently, the use of pDiaries has been a common method
to estimate the prevalence and temporal changes of headaches among children and
adolescent in prospective recordings, primarily conducted in treatment outcome
studies. The advances in information and communication technologies have resulted in
the development and use of electronic devices and diaries. To which extent this
represents an improvement in evaluation of headache occurrence among adolescents in
the general population is not yet known.
Methods: From a representative and stratified sample (by age, sex and
location) of schools in a county in the midst of Norway, 380 adolescents aged 13-19
in 13 schools were recruited to report on headache occurrence at the end of the day
for a three week period. Five schools (170 students) were randomized to eDiary
recordings and six schools (210 students) to pDiary assessments. All the
participants were asked to answer four questions daily. The eDiary students were
instructed to log on to a PC or smartphone and fill out the eDiary every day. Daily
reminders were sent out to the students via SMS to those who had not logged in after
a particular time point in the evening. With the eDiary, retrospectively headache
recordings were not allowed. An exploratory analysis was done.
Results: The pattern of responses for the e- and pDiaries differed. In
the pDiaries, the students had responded either most days or ≤ 25%. Some of them
admitted in free writing that they had supplemented data in retrospect if they
forgot to answer for a particular day or two. The adherence rate in the eDiary group
was high in that more than 70% of the students supplied data more often than every
other day.
Complete non-participation (no information submitted for a single day) was high for
the pDiary group (53/210 = 25%) compared to the eDiary group (14/170 = 8%).
There was no significant difference in adherence rates between students’ eDiary
recordings on weekdays (1370/2027 = 68%) compared to weekends (605/944 = 64%).
In a user evaluation some participants claimed that lack of Internet had been a
problem for some days.
Conclusions: The eDiary was considered useful by most users. The
documented post-registration in the use of pDiaries is a potential weakness and is
likely to contribute to unreliable and biased estimates, which is overcome by the
use of eDiary. Contrary to our expectation, the eDiary response rate on weekends and
weekdays was similar.
P196
Claim for Medico-Legal Benefits by Patients Suffering from Headache: Results
from a Multi-Centre Headache Clinic Survey
P. Rossi1,2, G. Sances2, E. Guaschino2, F.
Brighina3, G. Nappi2
1INI Grottaferrata, g, Italy; 2Headache Science Center,
National Neurological Institute C. Mondino Foundation, Pavia, Italy;
3Neurologia, Università di Palermo, Palermo, Italy.
Objectives: The aim of this study was to evaluate the rates, pattern,
outcome, satisfaction with and presence of predictors of claim for medico-legal
benefits in a clinical population of headache patients.
Background: No study have ever investigated the claim for medico-legal
benefits in headache patients.
Methods: 317 consecutive patients attending three headache clinics
(Pavia, Grottaferrata and Palermo) were asked to fill in a structured questionnaire
designed to gather information about search for medico-legal protection.
Results: Only twelve% of the patients filling in the questionnaire has
sought medico-legal benefits for headache. The most common reason for not claiming
for medico-legal benefits was “I don’t know about the existence of medico-legal
protection for headache” (58%). Seventy-seven percent of the claims were motivated
by the desire to obtain the recognition of the status of civil invalid, while the
remaining ones were aimed at being granted a justified absence from work because of
the headache attacks. Forty-five percent of the claims were done solely for
headache. The most common source of information was the GP (39%). Fifty-five percent
of the surveyed patients declared that the evaluation from the medico-legal
committee lasted less than ten minutes and only 26% declared to be satisfied by the
medico-legal visit. Seventy percent and 30% of the claims for justified absence from
work and civil invalidity, respectively, were rejected. Sixty-five percent of the
patients receiving the medico-legal benefits considered it as not useful. Predictors
of claiming for medico-legal benefits were geographical area of provenience (OR
3.25, CI1.1-9.9, OR 3.51 CI 1.2-10), the severity of medico-legal impairment as
proposed by the Lombardia Region (class A OR 0.09 CI 0.03-0.28, class B1 OR 0.6 CI
0.2-0.8) and having any other form of medico-legal protection (OR= 0.28 CI
0.12-0.65).
Conclusions: To our knowledge, this is the first study investigating the
phenomenon of claiming for medico-legal benefits for headache worldwide. Our data
indicate that claiming for medico-legal benefits is infrequent, mostly because of
the ignorance about the possibility of receiving such protection. Headache sufferers
claiming for such protection were those more severely disabled and already
benefitting other forms of medico-legal protection. Most of the claims for
medico-legal benefits for headache are rejected after a superficial examination.
Patients being granted the status of ‘civil invalid’ because of their headache,
consider it as not really helpful for their needs.
P197
Restless Legs Syndrome in Migraine; More Prevalent and More Severe
W.P.J. van Oosterhout1, E.J.W. van Someren2, M.A.
Louter1,3, G.G. Schoonman1, G.J. Lammers1, M.D.
Ferrari1, G.M. Terwindt1
1Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 2Clinical Neurophysiology, The Netherlands Institute of
Neuroscience, Amsterdam, The Netherlands; 3Psychiatry, Leiden
University Medical Center, Leiden, The Netherlands; 4Center for Sleep
and Wake Disorders, Medical Center Haaglanden, The Hague, The
Netherlands.
Objectives: Study the prevalence and severity of Restless Legs Syndrome
(RLS) in migraine patients.
Background: RLS and migraine may have a pathogenic link. We aimed to
evaluate i) the association between both migraine and RLS prevalence, as well as RLS
severity, and ii) the correlation between premonitory symptoms and RLS.
Methods: We conducted a cross-sectional study in 2,383 migraine patients
and 154 non-headache controls. Migraine and RLS diagnostic criteria were
administered via a web-based interface. Detailed migraine characteristics were
available, and severity of RLS symptoms were assessed using the International
Restless Legs Syndrome Study Group rating scale. Determinants for RLS and RLS
severity were calculated using multivariate adjusted regression models.
Results: Of the migraine patients, 16.9% reported RLS (fulfilling 4/4
essential criteria) compared to 10.4% of the controls (p=0.034), which remained a
significant difference after adjusting for confounders (p=0.045). RLS severity was
higher among migraineurs than among non-headache controls. Higher attack frequency,
use of prophylactics and history of medication overuse were additional determinants.
Migraineurs with RLS reported more premonitory symptoms (8.0±4.2) when compared with
migraineurs without RLS (7.1±3.9; p<0.001).
Conclusions: Not only is Restless Legs Syndrome more prevalent among
migraineurs, RLS severity is also higher compared to non-headache controls.
Furthermore, migraineurs suffering from RLS report more premonitory symptoms.
P198
Patients’ Perceptions of the Causes of Migraine in Flanders (Belgium): A
Qualitative Study
L. Dikomitis1, M. Bonte2, S. Willems3, K.
Paemeleire2
1Centre for Health and Population Sciences, Hull York Medical
School, Hull, United Kingdom; 2Department of Neurology, Ghent
University Hospital, Ghent, Belgium; 3Department of General Practice
and Primary Health Care, Ghent University, Ghent, Belgium.
Objectives: The aim of this study was to obtain the views of patients in
Flanders on migraine and to examine the ways they deal with it. Elucidation of
patients’ perceptions of what causes a migraine may facilitate its treatment and
management. Ascertaining the sources that patients consult and seek advice will
assist in the development of efficient patient education.
Background: The prevalence of migraine among the Belgian population is
more than 10 per cent. In Flanders and Brussels migraine accounts for an estimated
1,150,000 days of sick leave every year. Despite its considerable impact qualitative
studies of patients’ perceptions of the causes of migraine, and their sources of
information and advice are still scarce.
Methods: This was a qualitative study of 10 migraine sufferers that used
semi-structured interviews. A systematic qualitative methodology was applied to the
fully transcribed interviews. Close reading of each interview transcript was used to
generate codes that formed the basis of a classification of potential domains and
items that shaped the analysis as themes emerged.
Results: Younger patients most commonly related migraine to stomach,
intestinal or bile problems and older patients to problems with cerebral perfusion.
Respondents indicated that they obtained information from their general practitioner
but also from popular views. Based on these beliefs and perceptions patients
attempted to define the ‘ultimate trigger’ in order to reduce their migraine
attacks. The study showed that false theories about the causes of migraine are rife
among migraine sufferers and identified a need for earlier diagnosis and more
reliable information.
Conclusions: This study raised awareness about the importance of health
promotion and the need for concrete, practical information and well-organized
patient education.
Respondent
Age cohort
Gender
Profession
Treatment
1
45-50
Female
Pedagogue
Neurologist
2
75-80
Female
Retired
GP
3
20-25
Female
Nursery teacher
GP
4
40-45
Female
Library assistant
GP
5
35-40
Female
Unemployed
GP/Homeopath
6
35-40
Male
GP
Himself
7
50-55
Female
Housewife
GP
8
50-55
Male
Writer
GP
9
25-30
Female
Teacher
GP
10
30-35
Male
Factory worker
GP/Dietician
P199
Association of Lower Level of Leisure-Related Physical Activity with Primary
Headaches
S. Ashina1, L. Bendtsen2, A.C. Lyngberg3, R.B.
Lipton4, N. Hajiyeva5, R. Jensen2
1Pain Medicine and Palliative Care, Neurology, Albert Einstein
College of Medicine, Beth Israel Medical Center, New York, NY, USA;
2Neurology, Danish Headache Center, University of Copenhagen,
Glostrup, Denmark; 3National Board of Health, Copenhagen, Denmark;
4Neurology, Montefiore Headache Center, Albert Einstein College
of Medicine, Bronx, NY, USA; 5Pain Medicine and Palliative Care,
Albert Einstein College of Medicine, Beth Israel Medical Center, New York, NY,
USA.
Objectives: The primary aim of the study was to assess the association
of pure migraine, pure tension-type headache (TTH) and coexistent headache with the
level of leisure-related physical activity. The secondary aim was to study the
association between the level of leisure-related physical activity and episodic and
chronic mixed headache.
Background: Low physical activity has been associated with higher
prevalence of headaches.
Methods: Total of 1300 subjects was invited to participate in a
cross-sectional population study. A total of 805 eligible subjects completed a
diagnostic headache interview, provided self-reported data on neck pain and back
pain, leisure-related physical activity, demographics and self-rated health. Levels
of leisure-related physical activity were classified according to activities
performed as low, medium and high (reference).
Results: Multinomial logistic regression analysis adjusted for gender,
age, education, neck pain, back pain, poor self-rated health demonstrated that
primary headache (mixed headache) was associated low physical activity (OR=2.54, 95%
CI=1.47-4.39, p=0.001)followed by medium physical activity (OR=1.62, 95%
CI=1.05-2.52, p=0.03). Low physical activity was significantly associated with pure
TTH (OR=2.80, 95%CI=1.38-5.68, p=0.004) and coexistent headache (OR=2.97,
95%CI=1.27-6.99, p=0.01) in the adjusted analysis. Association of pure migraine with
low (OR=1.95, 95% CI=0.86-4.43, p=0.11) and medium physical activity, and coexistent
headache and pure TTH with medium physical activity did not reach statistical
significance. Low activity level is highest in chronic headache (OR=2.97,
95%CI=0.94-9.44, p=0.07) compared to episodic headache (OR=2.42, 95%CI=1.37-4.28,
p=0.002).
Conclusions: Lower level of leisure-related physical activity is
associated with primary headaches. Furthermore, the association is strongest for
coexistent headache followed by pure TTH and pure migraine. The causal the causal
relationship of low activity level to headache chronicity cannot be assessed in our
study.
P200
Real-Time Epidemiology of Migraine Attacks on Social Media
H. van Holsbeeck1, S. Lucas1, M. DeBoer1, C.
Aiello1, T.D. Nascimento1, M.F. DosSantos1,
A.F. DaSilva1,2,3
1Headache & Orofacial Pain Effort (H.O.P.E.), Biologic &
Materials Sciences Department, University of Michigan School of Dentistry, Ann
Arbor, MI, USA; 2Michigan Center for Oral Health Research (MCOHR),
University of Michigan School of Dentistry, Ann Arbor, MI, USA;
3Translational Neuroimaging Laboratory, Molecular & Behavioral
Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
Objectives: We sought to estimate the real-time impact of actual
self-reported migraine attacks in the World Wide Web using twitter by analyzing the
meaning of each single tweet message with the word migraine posted during an entire
seven-day week.
Background: Social media is still underused as a powerful platform in
science to help collect global free-style information regarding new patterns of
patient behavior in Migraine. Nonetheless, measurements based on instant searching
tools available in the internet for social media lead inexorably to misleading
interpretations, due to the diversity of postings that are not all directly related
to patients suffering with the disorder.
Methods: A continuous cross-sectional sample of 21.741 Tweets that
included the search term “migraine” was collected during 7 consecutive days in an
arbitrary month of the year 2011. The data collected included only public
information and all identifiers were coded to avoid linking the subject to the
information gathered. Using different data sets, from the main database, two
investigators developed a coding system. After developing the coding system, a
portion of the undergraduate and graduate students* at the University of Michigan,
School of Dentistry helped to categorize the data in specific variables, which are
consistent with the International Headache Society classification for migraine.
Results: The data was examined using descriptive statistical analyses of
14.028 Tweets, which represents actual self-reports of migraine attacks in real-time
(64.50% of the database). In general, the prevalence of migraine attacks, when
reported, was 73.47% in females, 17.40% in males, and 0.01% transgender (two
subjects self-reported being transgender). The impact of migraine was substantial in
mood, with a prevalence of 43.91%. As a pain descriptor, the word “worst” (14.6%)
was most commonly used, followed by the word “horrible” (6.97%) from the McGill Pain
Questionnaire. Subsequently, in the profanity category, the remark “F-word” was the
most frequently used (5.3%).
Conclusions: Twitter’s limited length capacity permits users to post
their messages in real-time, which is a unique source for epidemiological studies.
The results show a novel method of research to investigate the real-time
epidemiology of migraine attacks, taking advantage of a free form of expression via
a new trend of communication.
*Full list of student co-authors will be displayed on poster/oral presentation.
P201
So Many Migraines, So Few Specialists: Analysis of the Geographic Location of
United Council for Neurologic Subspecialties (UCNS) Certified Headache
Specialists Compared to USA Headache Demographics
N.L. Rosen1, E. Mauser1
1Neurology, Hofstra North Shore LIJ Medical Center, Manhasset, NY,
USA.
Objectives: To compare the number of UCNS certified headache specialists
in the USA to the population of each state, the expected migraine population, and
the expected chronic migraine population.
Background: Migraine affects 11.79% of the US population in its episodic
form and 0.91% of the US population in its chronic form. There are a limited number
of United Council of Neurologic Subspecialties (UCNS) certified physicians in the
field of headache medicine. As of 2013, a physician must complete an accredited
fellowship program in order to sit for the UCNS exam. There is a dissociation
between the number of certified providers and health care recipients in this
area.
Methods: This study located each UCNS certified headache specialist
geographically and compared that data to demographic data about state populations
obtained from the U.S. Census. The expected number of migraine sufferers and chronic
migraine sufferers were calculated based upon recent epidemiologic data. State by
state ratios of UCNS certified physicians to the appropriate disease population were
then compared.
Results: As of the 2012 exam cycle, there are 416 UCNS headache
specialists that are currently practicing in the USA. The states with the highest
number of headache specialists include New York (56), California (29), Ohio (29),
Texas (25), Florida (24), and Pennsylvania (23). 6 states have zero headache
specialists, 8 states have only 1 headache specialist, 5 states have two headache
specialists. The total US population for ages 12 and over is 259,908,563 across 50
states + District of Columbia. The total expected migraine population for ages 12
and over (11.79% of the general population) in the USA is 30,643,219.58. The total
expected chronic migraine population for ages 12 and over (0.91% of the general
population) in the USA is 2,365,167.923. The states with the best ratio of provider
to migraine patients includes the District of Columbia (1:31,419), New Hampshire
(1:33,482), New York (1:34,907), and Nebraska (1:35,740). Besides states with 0
headache specialists, the states with the worst ratios includes Oregon (1:384,232),
Mississippi (1:290,761), Arkansas (1:287,856), and Kansas (1:278,755). The states
with the best ratio of headache specialists to expected chronic migraine population
for ages 12 and over include District of Columbia (1:2,425), New Hampshire
(1:2,584), New York (1:2,694), and Nebraska (1:2,758). Besides states with 0
headache specialists, the states with the worst ratios of headache specialists to
expected chronic migraine population includes Oregon (1:29,656), Mississippi
(1:22,442), Arkansas (1:22,217), and Kansas (1:21,515).
Conclusions: There is a significant association between expected
migraine and chronic migraine population and the number of headache specialists in
each of the USA. More UCNS certified headache specialists and more UCNS accredited
fellowship training programs are needed in order to ameliorate this disparity.
P202
Influence of Tohoku-Pacific Ocean Earthquake on Headache Cases in the Affected
Area
Objectives: The aim of this study was to examine how Tohoku-Pacific
Ocean Earthquake influenced the headache (HA) medicine at our hospital.
Background: On March 11, 2011, Tohoku-Pacific Ocean Earthquake with a
magnitude of 9.0 occurred in East Japan, affecting a part of our hospital located in
Sendai causing serious damage. The tsunami struck 4 km away from our hospital. This
disaster caused considerable damage to various lifelines including food and medical
supplies. Some transportation networks were also paralyzed for several weeks.
Although there were such limitations, our hospital continued to conduct medical
examination of patients including outpatients.
Methods: We compared the situation of outpatient consultation for HA
cases, severity of pain, impact on daily life, and types of HA, which included
migraine, tension-type HA (TTH), cluster HA (CH), and medication-overuse HA
(MOH).
Results: The number of outpatient HA cases before the disaster was 9.5
persons/day, and the occurrence rates of the HA types were 62.2% for migraine, 38.6%
for TTH, 3.0% for CH, and 10.6% for MOH. The number of HA cases decreased remarkably
after the disaster (1.6 persons/day) in March, after which it increased gradually
(8.1 persons/day) in July. After the disaster, although the severity of pain did not
change, the impact on daily life because of migraine became significantly worse (p
< 0.001). The occurrence rate of migraine increased and that of TTH decreased
significantly (p < 0.001). The occurrence rate of MOH increased slightly, and no
change was seen in the occurrence rate of CH.
Conclusions: After the disaster, although the HA outpatient consultation
rate fell evidently, the occurrence rate of severe migraine increased at our
hospital. Although it was difficult to visit a hospital due to difficulties as a
result of the disaster, an HA patient particularly with the high impact on daily
life visited hospital to seek help.
P203
Resource Utilization & Cost of Care for Patients Treated with CAMBIA
Compared to Other Acute Migraine Therapies
A.H. Calhoun
Carolina Headache Institute, Chapel Hill, NC, USA; Anesthesiology, University
of North Carolina, Chapel Hill, NC, USA; Psychiatry, University of North
Carolina, Chapel Hill, NC, USA.
Objectives: To assess and tally resource utilization and cost of care
for migraineurs managed with CAMBIA compared to management with other acute migraine
therapies.
Background: Migraine is a costly and prevalent disorder, particularly
when patients are poorly controlled, present to the ER, receive unnecessary imaging
or transform into chronic migraine. By using an extensive database that captures
millions of insured lives over several years, one could ascertain if treatment with
one agent is associated with lower costs or better patterns compared to another
regimen.
Methods: Retrospective cohort study, utilizing Pharmetrics Plus Health
Plan Claims Database from January 1, 2009 through June 30, 2012. Inclusion criteria
were patients who (1) presented a prescription for CAMBIA, a triptan, or an
ergotamine between July 1, 2009 and December 31, 2011, (2) had 12 months of
continuous benefits eligibility for review, and (3) during the 6 months prior to the
prescription claim, had at least 1 inpatient claim or 2 outpatient claims with a
primary diagnosis code of migraine (ICD-9 code of 346.XX). With the date of the
first prescription as the index date, patients were followed longitudinally from 6
months prior to index to 6 months post index to evaluate their healthcare resource
use and costs.
3 cohorts were compared: patients with a diagnosis of migraine and an index
prescription for (1) CAMBIA, (2) a triptan, or (3) an ergotamine.
Outcome measures included mean number (total & migraine-related) of outpatient
visits, ER visits, and hospitalizations, as well as mean number of migraine-related
procedures, acute migraine medications, and opioid prescriptions.
Cost-related outcomes were adjusted to 2012 US dollars using the medical component of
the Consumer Price Index.
Pre-index variables described the study sample at baseline, and were used in
statistical models as covariates when comparing outcomes. They included
demographics, comorbidity measures, number of prescription classes and drugs
dispensed and filled, all-cause healthcare costs, and use of prophylactic migraine
medication.
All outcomes were compared using the CAMBIA cohort as the reference. Pairwise
comparisons with the CAMBIA cohort and each of the other cohorts were performed
adjusting for differences in the pre-index period variables. The threshold for a
significant P-value was adjusted for multiplicity.
Results: Significant differences were observed for the CAMBIA cohort vs.
other defined cohorts in multiple outcome measures. Additional sub-analyses will be
performed to further explore difference within subgroups. The results of the
retrospective claims analysis provide insights into the different classes of therapy
and their impact on health-related economic outcomes and treatment of migraine.
Conclusions: Migraine treatment with Cambia is associated with
significant differences in healthcare utilization and cost.
P204
Reliability and Validity of the Migraine Disability Assessment (MIDAS)
Questionnaire among Migraine and Tension Type Headache in Iranian
Patients
A. Zandifar1,2, E. Zandifar2, M. Banihashemi1, F.
Haghdoost1, S.S. Masjedi1, N. Manouchehri1, F.
Asgari1, S. Zandifar2, M. Saadatnia3, R.B.
Lipton4,5
1Medical Student Research Center, Isfahan University of Medical
Sciences, Esfahan, Iran (Islamic Republic of); 2Physiology Research
Center, Department of Physiology, Isfahan University of Medical Sciences,
Esfahan, Iran (Islamic Republic of); 3Department of Neurology and
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences,
Esfahan, Iran (Islamic Republic of); 4Albert Einstein College of
Medicine, Bronx, NY, USA; 5Montefiore Medical Center, Bronx, NY,
USA.
Objectives: Linguistic validation of Persian MIDAS, assessment of
psychometric properties between tension type headache (TTH) and migraine and
evaluation of MIDAS capability to discriminate between (TTH), chronic and episodic
migraine were the aims of this study.
Background: MIDAS is valid and reliable short questionnaire for
assessment of headache related disability over a 3-month period that consists of
three domains; school/job dimension, housework dimension and social dimension.
Methods: This was a multicenter study and the cases were diagnosed with
migraine or TTH by a neurologist. First visit data included MIDAS, SF-36 and
symptoms questionnaire. Patients filled out MIDAS in second and third visit within
three and eight weeks after base line visit. Internal consistency (Cronbach α) and
test-retest reproducibility (Pearson correlation coefficient) were used to assess
reliability. Convergent validity of MIDAS was analyzed through the assessment of
correlation between MIDAS and SF-36 scores. We evaluated the MIDAS capability to
differentiate between chronic, episodic migraine and TTH.
Results: Episodic and chronic migraine and TTH included 61.9%, 13.6% and
24.5% of all 274 patients respectively. Internal consistency among all patients, TTH
and migraine in first visit was 0.8, 0.72 and 0.82 respectively. Test-retest
reliability for all questions between visit 1 and 2 varied from 0.55 to 0.69. All
questions were significantly correlated with the total MIDAS score and the related
dimension (P 0.001). Total MIDAS score in the first visit was negatively correlated
with SF-36 mental and physical scores (r=-0.34 and -0.21 respectively, P 0.001). We
found no significant difference in MIDAS scores between TTH and episodic migraine;
however they both had significantly different scores than chronic migraine.
Conclusions: Persian MIDAS is a valid and reliable questionnaire for
migraine and TTH that can differentiate between TTH and chronic migraine and also
between episodic and chronic migraine.
P205
Identification of Subpopulations of Migraine Patients with a Favorable Cost
Profile for Eletriptan
E. Ramos1, L. Liu1, J. Mardekian1, J.
Cabrera2
1Pfizer Inc., New York, NY, USA; 2Rutgers University,
New Brunswick, NJ, USA.
Objectives: To characterize patient populations by total healthcare
costs after initiation of eletriptan versus sumatriptan tablets for migraine.
Background: Identification of patient populations by total healthcare
costs after treatment initiation may optimize management of migraine.
Methods: Patients (18–64 years) with ≥1 prescription claim for
eletriptan or sumatriptan (index date=first prescription fill date) between January
and December 2009 inclusive, were identified from a large nationally (US)
representative, quality controlled, retrospective claims database. Continuous
enrollment during the 12-month pre-index and 12-month post-index periods was
required. Patients from each cohort were matched 1:1 for gender, age, total
pre-index healthcare (outpatient + inpatient + prescription) costs, region of US,
and comorbidities. Classification and Regression Trees (CART) analysis was used to
identify populations with pre- to post-index differences in total healthcare costs.
CART is a nonparametric data mining technique that uses binary decisions to
construct decision trees for differentiating between groups with homogeneous
response variables.
Results: 13,425 sumatriptan and 17,399 eletriptan patients were
identified; 11,508 patients from each cohort were matched. 78% and 62% of patients,
respectively were continuing users. Mean age (SD) was 48 (10) years; 85% was female.
Pre-index (post-index) total annual healthcare costs were $8920 ($10,468) for
sumatriptan and $8921 ($10,783) for eletriptan. An example decision tree constructed
by CART is shown below. This decision tree was based on gender and number of
pre-index office visits. Lower total healthcare costs for eletriptan (-$1,960 and
-$3,392) were observed for male/female patients with a high number (≥18) of
pre-index office visits.
Cohort
Male
Female
# pre index office visits <18
# pre index office visits ≥18
# pre index office visits <18
# pre index office visits ≥18
Eletriptan ($) post - pre
2430
3033
1910
−630
N (%)
1645 (14)
69 (1)
9211 (80)
583 (5)
Sumatriptan ($) post - pre
2669
4993
1267
2762
N (%)
1660 (14)
54 (1)
9323 (81)
471 (4)
Difference ($)
−239
−1960
643
−3392
Conclusions: Overall, at 1 year after the index date, total healthcare
costs were similar between the two groups. However, lower total costs among
eletriptan-treated patients were observed in those with greater resource use.
P206
Referral System for Chronic Headache: Profile and Utilities of the List of
Doctors with High Concern in the Chronic Headache
N. Imai
Department of Neurology, Japanese Red Cross Shizuoka Hospital, Shizuoka,
Japan.
Objectives: To investigate the profile and utilities of the list of
doctors with high concern in the chronic headache.
Background: Headache consultation rates in Japan are very low, and 69.4%
of Japanese patients with migraine have never consulted a physician for headache
(Sakai 1997). A lack of recognition of the existence of headache specialists among
headache patients and practitioners might contribute to the low consultation rates
(Imai 2010). In addition, the headache specialists were insufficient in Shizuoka
Prefecture. For these reasons, we have managed a local medical network, or referral
system, for chronic headache patients in Shizuoka prefecture. To manage the headache
referral system, we listed the doctor who had zeal in the diagnosis and treatment of
chronic headache.
Methods: Doctors who had a lot of chances to treat headache were invited
to join this headache referral system. Start-up meeting was held on 9th September,
2010, and all participants were confirmed to the will of joining the list of doctors
with high concern in the chronic headache.
Results: Although there were only 9 headache specialists in Shizuoka
prefecture, 69 doctors agreed to the registration of the list and were widely
distributed inside Shizuoka prefecture. Each doctor’s work places were 78% in the
clinic, and were 22% in the hospital. Among the 69 doctors, 52% were neurosurgeons,
38% were neurologists, 4% were general physicians and anesthesiologist, and 1% was
dental surgeon. The list gave full details of what chronic headaches each doctors
could diagnose and treat, what examinations each institution could do, and what
medical supplies each doctors could prescribe. Eight months after making the list,
questionnaire was sent to all doctors to evaluate the list and received replies from
49 doctors. Although only 15 doctors used the list, 52 referral patients had visited
and 128 patients were referred to other institution.
Conclusions: Many non-headache specialists who had zeal in the diagnosis
and treatment of chronic headache could join this headache referral system by making
the list. Fifteen doctors used the list, and 180 patients were referred by the list.
The list of doctors with high concern in the chronic headache diagnosis and
treatment may be useful to promote headache referral system.
P207
Naturopathic Medicines for the Prevention of Debilitating Diseases in the USA
of America: Knowledge among the Inhabitants of Houston within Texas
M.A.H. Mollik
Biological Sciences, Peoples Integrated Alliance, Dhaka, Bangladesh; Research
and Development, Prescience Trust Funds, Phoenixville, PA, USA.
Objectives: The studies were to interact with neighborhood naturopathic
physicians as well as residents and document their knowledge on medicinal plants,
their usage, and the types of debilitating diseases treated etc. The formulations
mostly contained single medicinal plant instead of multiple medicinal plants. The
knowledge evolved for along time through trial and error. Scientific studies
conducted on the medicinal plants may lead to discovery of more effective drugs than
in use at present.
Background: Naturopathic medicines are in great demand in both developed
and developing countries in primary health care because of their great efficacy and
no side effects. Today according to the World Health Organization, as many as 80% of
the world’s natives depend on naturopathic medicines for their primary health care
needs. Houston is the largest city in the state of Texas, and the fourth-largest
city in the USA of America, and the naturopathic healing systems are still popular
here.
Methods: The studies were conducted during January 2011 to December 2012
using semi-structured questionnaires, open-ended questionnaires, informal
interviews, and group discussions with neighborhood naturopathic physicians as well
as residents having thorough knowledge about medicinal plants. The data such as
local name of medicinal plants, plant parts used, application etc. were collected.
The voucher samples of the medicinal plants collected during the studies were
properly identified with help of floras.
Results: The studies were includes information on 29 medicinal plants
used for wide range of debilitating diseases. Of these 12 medicinal plants are used
against arthritis, 09 medicinal plants are used against chronic obstructive
pulmonary disease, 06 medicinal plants are used against muscular dystrophy, 05
medicinal plants are used against snake-bite, 03 medicinal plants are used against
dermatitis, 03 medicinal plants is used against paediatrics, and one medicinal plant
is used for centipede poisoning.
Conclusions: An assessment of the scientific literatures revealed that
preliminary studies conducted on some of the above medicinal plants justify their
use to treat specific ailments as practiced by the naturopathic physicians as well
as residents. There is enough scope of the amalgamation of these medicinal plants in
the main stream of prenatal medicines suggest today after the medicinal plants drug
are subjected to the phytochemical and biological screening, together with clinical
trials.
P208
Metabolomics of Migraine: 1H-NMR Study of Cerebrospinal
Fluid
R. Zielman1, R. Postma2, F. Bakels1, W.P.J. van
Oosterhout1, S.A. van der Sar2, G.M. Terwindt1,
A.M.J.M. van der Maagdenberg1,3, A.M. Deelder2, O.A.
Mayboroda2, A. Meissner2, M.D. Ferrari1
1Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 2Technology Focus Area Proteomics & Metabolomics,
Leiden University Medical Center, Leiden, The Netherlands; 3Human
Genetics, Leiden University Medical Center, Leiden, The
Netherlands.
Objectives: The objective of this study was to pinpoint diagnostically
relevant biochemical or pathophysiological markers in CSF of migraine patients with
an exploratory 1H-NMR-based metabolomics approach.
Background: The diagnosis and thus adequate preventive treatment options
of migraine are severely hampered by an incomplete pathophysiological understanding
of the disease and the lack of objective diagnostic markers. As a body fluid in the
closest proximity to the central nervous system, cerebral spinal fluid (CSF) should
reflect the physiology of the central nervous system and as such is valuable for
assessing the functional status of the brain.
Methods: After obtaining informed consent, CSF was obtained,
interictally, via lumbar puncture from patients with hemiplegic migraine, migraine
with aura, migraine without aura, and from healthy controls. CSF was immediately
centrifuged at 4 °C, divided in aliquots, and placed on dry ice within 30 minutes
and stored at -80 °C within one hour. CSF samples were prepared for NMR analysis and
metabolite concentrations were measured by quantitative 1H-NMR
spectroscopy with a Bruker 600 MHz AVANCE II spectrometer. Unsupervised and
supervised multivariate analyses were used for finding the optimal set of predictors
before constructing a non-linear classification model. Univariate analysis (using
Generalized Linear Models) was conducted to ascertain the differential significance
of individual features.
Results: CSF was obtained from 136 subjects, 126 samples passed spectral
and profile quality checks and were used in the analysis. Included in the data
analysis were 18 patients with hemiplegic migraine (F:10, M:8), 38 with migraine
with aura (F:27, M11), 27 migraine without aura (F:15, M12), and 43 healthy controls
(F:22, M:21). Due to a significant gender effect found with PCA (principal component
analysis) analysis, supervised multivariate modeling was carried out for males and
females separately. We have shown that hemiplegic migraine patients can be best
discriminated from controls by a set of five features in the NMR spectrum. Female
migraine with aura patients can be best discriminated from female controls by a set
of six features. Univariate analysis (GLM) showed that there are four features in
the NMR spectrum that are significantly different between the four groups
(hemiplegic migraine, migraine with aura, migraine without aura, and healthy
controls).
Conclusions: Using an exploratory 1H-NMR metabolomics
analysis we have identified a set of features that discriminate migraine patients
from controls. Replication of our findings on a new CSF sample set and detailed
structural elucidation of the characteristic features are our next priorities.
P209
Exploring the Mechanisms Involved in CGRP-Induced Light Aversion in
Mice
E.A. Kaiser1, A. Kuburas1, B.J. Rea1, P.
Poolman3,4, A.E. Tye5, A. Recober2, R.H.
Kardon3,4, A.F. Russo1,2,3
1Molecular Physiology and Biophysics, University of Iowa, Iowa
City, IA, USA; 2Neurology, University of Iowa, Iowa City, IA, USA;
3Center for the Prevention and Treatment of Visual Loss, Iowa
City VA Health Care System, Iowa City, IA, USA; 4Ophthalmology and
Visual Sciences, University of Iowa, Iowa City, IA, USA;
5Neuroscience Program, University of Iowa, Iowa City, IA,
USA.
Objectives: To use genetic, behavioral, and physiological methods
develop new tools that uncover mechanisms involved in CGRP-induced light aversion in
mice.
Background: Calcitonin gene-related peptide is known to play a critical
role in the pathophysiology of migraine. Previously, our work has demonstrated a
role for CGRP in light-aversive behavior in mice as a correlate to migraine-type
photophobia. We have demonstrated that CGRP can induce light aversion in WT and
nestin/hRAMP1 mice, which are sensitized to CGRP based on
conditional expression of hRAMP1 in the nervous system. WT mice show aversion only
with bright light and following habituation to the chamber, whereas
nestin/hRAMP1 show light aversion at low light levels upon
naïve exposure to the chamber. This work has illustrated a critical role for CGRP
and its receptor in eliciting light aversion.
Methods: To further explore sites of CGRP action in light aversion, we
generated a synapsin/hRAMP1 mouse, which conditionally expresses
hRAMP1 in neurons only instead of neurons and glia as with
nestin/hRAMP1 mice. Also we developed an assay to measure the
blink reflex in mice by implanting a telemeter to record electromyography (EMG) of
the orbicularis oculi. Air puff was used to induce a blink. EMG responses were
assessed under various light conditions as well as after CGRP administration.
Results: Interestingly, synapsin/hRAMP1 mice did not
demonstrate CGRP-induced light aversion at low light levels upon naïve exposure as
observed with nestin/hRAMP1 mice. hRAMP1 expression in the nervous
system of synapsin/hRAMP1 mice was similar overall as seen with
nestin/hRAMP1 mice. Initial studies with our new EMG blink
reflex assay indicate that we can successfully record blink responses in mice.
Bright light alone led to an increase in EMG activity in a
nestin/hRAMP1 mouse. Furthermore, bright light and CGRP
increased EMG blink response induced by air puff in a nestin/hRAMP1 mouse.
Conclusions: The lack of CGRP-induced light aversion in
synapsin/hRAMP1 mice suggests that neuronal expression of
hRAMP1 is not sufficient to sensitize mice to CGRP and light. Furthermore, pilot
studies with an EMG blink reflex assay indicate that we have developed a new
non-behavioral tool to study the role of light and CGRP in trigeminal sensitization
and photophobia in mice.
P210
Polymorphisms in CGRP Receptor Genes Associated with Migraine in a Spanish
Population
J. Fernandez-Morales1, I. Fernandez-Cadenas3, M.
Vila-Pueyo4, B. Cormand5, J. Alvarez-Sabin2, J.
Montaner3, A. Macaya4, P. Pozo-Rosich1,2
1Headache and Pain Research Group, Institut de Recerca (VHIR),
Universitat Autònoma de Barcelona, Barcelona, Spain; 2Neurology
Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain;
3Neurovascular Research Laboratory, Institut de Recerca (VHIR),
Universitat Autònoma de Barcelona, Barcelona, Spain; 4Pediatric
Neurology Research Group, Institut de Recerca (VHIR), Universitat Autònoma de
Barcelona, Barcelona, Spain; 5Departament de Genètica, Facultat de
Biologia, Universitat de Barcelona, Barcelona, Spain.
Objectives: We performed a candidate-gene association study to determine
whether 144 Single Nucleotide Polymorphisms (SNPs) in 39 candidate genes are related
to migraine in a Spanish population.
Methods: 876 migraineurs and 801 healthy volunteers were recruited in a
Headache Unit. Only unrelated Mediterranean Caucasian individuals were included.
Polymorphisms were selected from the literature: genes involved in migraine
pathophysiology and involved in pain pathways not previously described in migraine.
TagSNPs were selected from Hapmap data using tagger pairwise selection with
r2>0.8 in the CEU population. SNPs were genotyped with Veracode GoldenGate
technology (Illumina). Statistical analysis for genetic association was performed
using PLINK v1.07 and SNPTEST v2.2.0. Gene expression was assessed by qRT-PCR
through a Taqman assay. Statistics of mRNA expression was performed using
non-parametric tests with SPSS V15.0.
Results: 876 cases and 801 controls were successfully genotyped for 128
SNPs. Statistical analysis of genotype frequencies revealed nominal association for
9 SNPs in 5 candidate genes (p<0.05). Two of them,
CALCRL and RAMP1, encode subunits of the CGRP
receptor. Four SNPs in CALCRL and 2 SNPs in RAMP1 were associated
with migraine. SNPs in CALCRL were found in allelic association with migraine
(p<0.05): rs12621307 A allele OR=1.22 (1.07-1.4), rs6719550C
OR=1.21 (1.05-1.39), rs17464221 T OR=1.24 (1.08-1.44) and rs2063505G OR=0.81
(0.70-0.94). SNPs in RAMP1 were associated in a genotypic recessive model:
rs6741923CC OR=1.63 (1.16-2.29) and rs7578855CC OR=1.38 (1.01-1.74). Rs17862920 in
TRPM8, previously reported to be associated with migraine in a
GWAS study, was replicated. A SNP in SPTAN1 (rs13299607) and
another one in EDNRB (rs2329047) were also associated with the
phenotype in our cohort. Analysis of qRT-PCR data from blood cells showed a
correlation between the rs17464221 TT genotype and reduced CALCRL
subunit expression and rs13299607 TT genotype and also with reduced
SPTAN1 mRNA levels. We did not observe any correlation between
any genotype and expression of RAMP1. EDNRB and
TRPM8 expression was below the detection level of the
assay.
Conclusions: We have found association between CGRP receptor gene
polymorphisms and migraine. Furthermore, there is a correlation between the TT
genotype in rs17464221 and a reduction in the expression of CALCRL.
We have replicated an association for SNPs in TRPM8,
SPTAN1 and EDNRB genes. There is also
correlation between a SPTAN1 genotype and reduction of
expression.
P211
A Single Nucleotide Polymorphism within the Glutathione S-Transferase Gene Is
Significantly Associated with Migraine among Males Only
A.K. Sullivan1, E.J. Atkinson1, F.M. Cutrer1
1Mayo Clinic, Rochester, MN, USA.
Objectives: To investigate genetic factors involved in migraine.
Background: Migraine is a complex trait in which multiple genetic loci
as well as environmental factors are likely to contribute to its clinical
manifestation. Many of the reported genetic associations found in previous studies
thus far have either not been replicated or have had only marginal statistical
significance, likely due to the genetic heterogeneity of the common forms of
migraine.
Methods: We have selected 50 genetic polymorphisms that have been
implicated in previous studies to confer migraine susceptibility. From our DNA
repository of individuals with migraine (the Mayo Migraine Genomic
Library which includes age and gender matched
controls), we have selected 1740 individuals ages 18-50, 1132
cases (240 males, 892 females) and 608 controls (258 males, 350 females).
Results: We have performed logistic regression analyses, and
interestingly have found that a single nucleotide polymorphism within the
Glutathione S-Transferase gene (rs1695) is significantly associated with migraine
among males only (p=0.0019; OR=1.56), but not among female migraineurs (p=0.51;
OR=1.06).
Conclusions: These findings could greatly impact the clinical management
of migraine by suggesting possible underlying mechanisms of migraine susceptibility
leading to development of rational, biologically based therapies.
P212
Genotyping the Risk of Migraine Chronification: The CHROMIG Study
J. Fernandez-Morales1, B. de Vries2, B. Winsvold3,4,
V. Anttila3,9, I. Fernandez-Cadenas5, M. Louter2,
M. Vila-Pueyo6, B. Cormand7, J. Alvarez-Sabin8, J.
Montaner5,8, A. van den Maagdenberg5, A.
Palotie3,9, J.-A. Zwart6, A. Macaya4, G.M.
Terwindt5, P. Pozo-Rosich1,8
1Headache and Pain Research Group, Institut de Recerca (VHIR),
Universitat Autònoma de Barcelona, Barcelona, Spain; 2Neurology
Department, Leiden University Medical Center (LUMC), Leiden, The Netherlands;
3Department of Human Genetics, Wellcome Trust Sanger Institute,
Cambridge, United Kingdom; 4Department of Neurology and FORMI, Oslo
University Hospital and University of Oslo, Oslo, Norway;
5Neurovascular Research Laboratory, Institut de Recerca (VHIR),
Universitat Autònoma de Barcelona (UAB), Barcelona, Spain; 6Pediatric
Neurology Research Group, Institut de Recerca (VHIR), Universitat Autònoma de
Barcelona (UAB), Barcelona, Spain; 7Facultat de Biologia, Departament
de Genètica, Universitat de Barcelona (UB), Barcelona, Spain;
8Neurology Department, Hospital Universitari Vall d’Hebron (HUVH),
Barcelona, Spain; 9Program in Medical and Population Genetics, Broad
Institute of MIT and Harvard, Cambridge, MA, USA.
Objectives: We performed a candidate-gene association study to explore
the genetic background of chronic migraine (CM).
Methods: We genotyped 128 SNPs in 39 candidate genes selected from the
literature. TagSNPs were selected from CEU Hapmap data using a tagger pairwise tool
with r2>0.8. CM patients were recruited in Barcelona (181 CM-801 controls) and
Leiden (81 CM-2078 controls). The SNPs found associated were further tested in a
group of high-frequency migraineurs (Barcelona: 116 HFM-801 controls; Leiden: 110
HFM-2078 controls) in order to identify SNPs with stronger association to
chronification. These SNPs were replicated in a new sample (Barcelona: 70 CM-394
controls; Leiden: 210 CM-896 controls; Norway: 162 CM-495 controls) genotyped using
a Taqman assay, and GWAS data from a Norwegian CM cohort (89 CM-706 controls).
Statistical analyses were performed with PLINK v1.07 and SNPTEST v2.2.0.
Meta-analysis was performed with GWAMA v2.1.
Results: Analysis of 128 SNPs in 262 CM patients and 2,879 controls
revealed 30 nominally associated SNPs (25 SNPs in 12 genes and 5 intergenic
polymorphisms) (p<0.05). These SNPs were then tested in a HFM
study sample (226 cases and 2,879 controls) where only 8 SNPs remained associated.
We hypothesized that these SNPs confer risk to migraine chronification and were
further replicated in a cohort of CM and HFM (442 cases and 1,785 controls).
Although there were some cohort-dependent weak associations, the meta-analysis of
replication data performed in 531 cases and 2,491 controls did not confirm
significant association between these genes and CM.
Conclusions: This is the first study that has tried to find a genetic
predisposition to develop CM. Lack of replication might be explained by the
difficulties of finding comparable cohorts, the the size of the cohorts and the use
of the current IHS CM criteria. Chronic migraine deserves further examination in
more comprehensive and better-powered studies.
P213
The Diagnostic Value of Visual and Auditory Evoked Potentials in Migraine: A
Retrospective Multicenter Study
A. Ambrosini1, A. Kisialiou1, L. Finos2, J.
Àfra3, G. Coppola4,5, L. Di Clemente5, E.
Iezzi1, D. Magis6, P.S. Sàndor7, T. Sasso
D’Elia5,6, A. Viganò5, M. Fataki6, F.
Pierelli5, J. Schoenen6
1IRCCS Neuromed, Pozzilli, Isernia, Italy; 2University
of Padua, Padua, Italy; 3National Institute of Neurosurgery,
Budapest, Hungary; 4IRCCS Bietti Foundation, Rome, Italy;
5University of Rome “La Sapienza”, Rome - Latina, Italy;
6University of Liège, Liège, Belgium; 7University of
Zürich, Zürich, Switzerland.
Objectives: To pool the VEP and IDAP results in episodic migraineurs
(EM) and healthy voluteers (HV) from several centers, and to determine their
usefulness for the diagnosis of migraine.
Background: The diagnosis of migraine is made by history and based on
ICHD criteria. There are at present no reliable diagnostic tests. Some patients may,
however, provide information that is not reliable or incomplete because of recall
bias or a tendency to exaggerate or, on the contrary, to minimize their symptoms.
Many studies have found that migraine patients are characterized between attacks by
a habituation deficit of visual evoked potentials (VEP) and/or increased intensity
dependence of auditory evoked potentials (IDAP).
Methods: We analyzed electrophysiological recordings from 360 HV and 624
EM, part of them blindly. Recordings in EM were performed at least 3 days after or
before an attack: VEP composed of 5 sequential blocks of 50 responses in 77 HV and
231 EM, VEP with 6 blocks of 100 responses in 240 HV and 280 EM, IDAP in 86 HV and
328 EM. Some subjects were tested both for VEP and IDAP. We used
Bonferroni-corrected Mann-Withney tests to compare results between HV and EM.
Thresholds were calculated by Receiver Operating Curve (ROC) analysis based on a 15%
prevalence value for migraine, and used to calculate sensitivity, specificity,
predictive values and efficacy of each test.
Results: Mean percentage habituation of VEP-5x50 were –6.2±22.3 in HV
and + 8.0±28.0 in EM (p=<0.0001), and VEP-6x100 –10.5±17.9 in HV and 7.1±25. 9 in
EM (p=<0.0001). Mean IDAP amplitude stimulus function slopes were 0.45±1.0 in HV
and 1.2±1.1 in EM (p=<0.0001).
For VEP-5x50 sensitivity was 61.0 %, specificity 77.9 %, positive predictive value
(VP+) 89.2 %, negative predictive value (VP-) 40.0 % and efficacy 65.3 %. For
VEP-6x100 sensitivity was 61.4 %, specificity 77.9 %, VP+ 76.4 %, VP- 63.4 % and
efficacy 69.0 %. For IDAP sensitivity was 45.7 %, specificity 87.2 %, VP+ 93.2 %,
VP- 29.6 %, efficacy 54.3 %. In subjects who underwent both VEP and IDAP recordings,
abnormality of at least one of them had a sensitivity of 83.4 %, a specificity of
66.7 %, a VP+ of 94.1 %, a VP- of 38.6 % and an efficacy of 81.1 %.
Conclusions: Taken alone, none of VEP or IDAP has sufficient diagnostic
efficacy to distinguish EM from HV. However, when both tests are combined in the
same patient, abnormality of at least one of them is highly predictive of migraine,
suggesting that VEP and IDAP may be useful for the diagnosis of migraine.
P214
Withdrawn by the author.
P215
Methylation of Migraine-Related Genes in Different Tissues
S. Labruijere1, M.M.P.J. Verbiest2, R. De Vries1,
A.H.J. Danser1, A.G. Uitterlinden2, L. Stolk2, A.
MaassenVanDenBrink1
1Internal Medicine, Division of Vascular Medicine and
Pharmacology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands;
2Internal Medicine, Genetic Laboratory, Erasmus Medical Center
Rotterdam, Rotterdam, The Netherlands.
Objectives: The aim of our study was to investigate the methylation of
different genes in different tissues both relevant to the pathophysiology of
migraine and to examine the role of 17β-estradiol in the methylation. In addition,
we investigated methylation in blood and aorta as a peripheral control.
Background: Migraine is – at least partly – genetic in nature. However,
genes have only clearly been identified for familial hemiplegic migraine. GWAS
studies have identified genes that may be relevant for the more common forms of
migraine, but an additional influence of environmental factors is likely.
Interestingly, the prophylactic effectivity of valproate, a DNA methylation
inhibitor, may point to the involvement of epigenetic mechanisms in migraine.
Migraine is much more common in women of the fertile age than in men, pointing
towards a role for 17β-estradiol, which is known to be involved in epigenetic
mechanisms. Also, CGRP can be regulated via epigenetic mechanisms. Methylation is
often examined in blood, which can easily be obtained, but it is not sure whether
these results can be compared to other tissues.
Methods: Female SD rats (n=11-12 per group) were ovariectomized or
sham-operated and treated with 17β-estradiol or placebo. DNA was isolated from
blood, aorta, dura mater, trigeminal caudal nucleus and trigeminal ganglion. DNA
methylation of 10 migraine-related genes (MTHFR, eNOS, ESR1, GPER, CGRP, USF1, USF2,
RAMP1, CRCP and CRLR) was assessed through bisulphite treatment and sequenom mass
spectrometry.
Results: In none of the genes, we observed a significant effect of
estradiol treatment. Tissue-specific methylation was seen in the CRCP, CRLR, ESR1
and NOS3 genes. The methylation in blood was not correlated to that in the rest of
the tissues. Interestingly, the variation in methylation in some genes in some of
the tissues was very high (e.g., mean: 41%, 5%-95% percentile: 18 to 67% methylation
for the CRCP gene in caudal nucleus), while in other genes or tissues this variation
was very small (e.g., mean 4%, 5%-95% percentile: 2 to 6% methylation for the ESR1
gene in blood). These different variations were specific for the combination of gene
and tissue.
Conclusions: From our results we conclude that (i) DNA methylation is
tissue specific and that methylation of DNA from blood cannot automatically be
extrapolated to methylation of DNA from other tissues; (ii) certain genes in some
tissues are prone to epigenetic regulation, while in other genes or tissues the
methylation is conserved, being less influenced by environmental factors; and (iii)
the variation in methylation that is present in some genes is likely to have reduced
the power of our study when studying effects of estradiol treatment. Thus, we cannot
categorically exclude that the methylation of the genes that we have studied may be
influenced by estradiol.
P216
Genetic Susceptibility in High-Frequent Migraineurs – A Report from
LUMINA
N. Pelzer1, M.A. Louter1,2, J. Haan1,3, B. de
Vries4, A.M.J.M. van den Maagdenberg1,4, M.D.
Ferrari1, G.M. Terwindt1
1Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 2Psychiatry, Leiden University Medical Center, Leiden,
The Netherlands; 3Neurology, Rijnland Hospital, Leiderdorp, The
Netherlands; 4Human Genetics, Leiden University Medical Center,
Leiden, The Netherlands.
Objectives: To investigate whether high-frequent migraineurs have a
higher genetic susceptibility to migraine, reflected in a higher familial occurrence
of migraine.
Background: Migraine is a heterogeneous disorder, in which many genetic
variants contribute to its susceptibility.
Methods: We included migraineurs from the LUMINA (Leiden University
Migraine Neuro-Analysis programme) cohort, recruited via a validated self-reporting,
web-based questionnaire. All migraineurs who had either low attack frequency (≤5
severe headache days/month) or very high attack frequency (≥15 severe headache
days/month) were selected. We calculated the population relative risk (PRR) in both
groups, using the reported proportion of first-degree relatives with migraine and
lifetime prevalence of migraine in the general population (33% for women, 13.3% for
men). Children were excluded from the first-degree relatives, because unaffected
children may still develop migraine. We used linear and logistic regression models
to calculate associations between migraine frequency and the proportion of affected
family members. Migraine subtype, gender and age were included as covariates.
Results: The PRR for female relatives was 1.29 (95% CI 1.17-1.41) in
low-frequent migraineurs (n=1693), and 1.37 (95% CI 1.19-1.55) in high-frequent
migraineurs (n=195). For male relatives, the PRR was 1.45 (95% CI 1.33-1.57) in
low-frequent migraineurs (n=1693) and 1.63 (95% CI 1.26-2.01) in high-frequent
migraineurs (n=194). These differences between PRRs in low- and high-frequent groups
were not statistically significant. Migraine with aura (p<0.001), but not attack
frequency, was associated with higher familial occurrence of migraine.
Conclusions: In LUMINA, genetic susceptibility to migraine was not
higher in high-frequent migraineurs. Having migraine with aura was associated with
higher familial occurrence of migraine.
P217
Genetic Polymorphisms of the Interleikin-6 Receptor (IL-6R) in the Patients
with Chronic Headache
H. Takigawa1, H. Kowa1, K. Nakashima1
1Division of Neurology, Department of Brain and Neurosciences,
Tottori University, Faculty of Medicine, Yonago, Japan.
Objectives: The aim of this study was to investigate theinterleikin-6
receptor (IL-6R) gene polymorphism in chronic headache. We analyzed a polymorphism
Asp-358-Ala in exon 9, which carries have the change of soluble IL-6R corresponding
to the proteolytic cleavage site of IL-6R, strongly influences the soluble IL-6R
level.
Background: There are some hypotheses that an immunologic dysfunction
has been involved in migraine pathogenesis. It is not yet clearly understood what
immunological mechanism leads to migraine headaches. We preliminary demonstrated
that the serum interleikin-6 levels in the patients of migraine with aura were
higher than normal controls.
Methods: Genotyping for IL-6R Asp-358-Ala polymorphism was performed in
65 patients with migraine with aura (MA; 21 males and 44 females, average age: 32.6
years), 138 patients with migraine without aura (MO; 27 males and 111 females,
average age: 36.8 years) and 77 patients with tension type headache (TH; 18 males
and 59 females, average age: 49.8 years) on leukocyte genomic DNA samples by
polymerase chain reaction – restriction fragment-length polymorphism (PCR-RFLP)
analysis. One hundred eighty three normal healthy volunteers composed the control
group (CTL; 55 males and 128 females, average age 58.1 years). The differences in
the frequency of IL-6R alleles and genotypes between groups were evaluated by the
gene-counting method and comparison of groups by the chi-square test. The level of
significance was set at p<0.05.
Results: The distribution of IL-6R genotypes in patients and CTL did not
deviate significantly from Hardy-Weinberg equibrium. The 358-Ala allelic frequency
of MA patients was significantly higher than that of CTL. There was the genotypic
difference between MA patients and CTL.
Conclusions: Our results indicate that IL-6R Asp-358-Ala polymorphism is
a genetic risk factor for patients with MA.
P218
α-Fodrin Is One of the Candidate Molecules for Migraine Diagnostic
Biomarker
E. Nagata1, Y. Moriya1, N. Fujii1, S.
Takizawa1
1Neurology, Tokai University School of Medicine, Isehara,
Japan.
Objectives: The diagnosis of migraine can sometimes be difficult because
some patients do not fulfill the International Headache Society’s criteria for
migraine. Hence, an accurate and reliable diagnostic marker for migraine is
required. In this study, we investigated the diagnostic utility of α-fodrin in
migraine.
Background: We previously verified that the expression of α-fodrin,
which was 1 of the 15 genes that were differentially expressed in lymphoblasts
originating from patients with migraine with aura patients (MA) using cRNA
microarray analysis, increased after cortical spreading depression in an animal
model.
Methods: All patients were carefully interviewed and examined, and
diagnosis was made using the ICHD-II. The patient serums were prepared from
peripheral blood samples obtained from 8 MA, 11 migraine without aura (MO), 6
tension type headache patients (TTH), and 4 healthy controls (C). The serum samples
were collected under the condition that migraineurs and TTH patients had been free
of attack for the preceding one week. We performed Western blot analysis using
anti-α-fodrin, anti-matrix metalloproteinase (MMP) 9, and anti-calpain antibodies
for the serum samples.
Results: In MA, both of 240kDa (full length) and 150kDa (the fragment
after catalysis) protein expressions of α-fodrin were significantly higher than
those of C. However, there was no significant difference on the ratio of 150kDa to
240kDa proteins of α-fodrin between both groups. In MO, the expression levels of
both 240kDa and 150kDa proteins of α-fodrin tended to be higher compared with C. As
for TTH, the expression levels of α-fodrin didn’t differ from C. Meanwhile, the
protein expression levels of cytoskeletal proteinases, MMP9 and calpain, in MA and
MO, tended to increase compared to C.
Conclusions: α-fodrin might play an important role in the
pathophysiology of migraine, and the molecule can serve as a migraine biomarker
superior to MMP9 and calpain.
P219
The Role of Nociceptin in Medication Overuse Headache – A Pilot
Study
S.B. Munksgaard1, C. Ertsey2, K. Tekes3, L.
Bendtsen1, R.H. Jensen1
1Danish Headache Center, Department of Neurology, Glostrup
Hospital, University of Copenhagen, Faculty of Health Sciences, Glostrup,
Denmark; 2Department of Neurology, Semmelweis University, Budapest,
Hungary; 3Department of Pharmacodynamics, Semmelweis University,
Budapest, Hungary.
Objectives: We aimed to test whether patients with MOH have decreased
levels of nociceptin before withdrawal therapy compared with healthy volunteers, and
further, to test if the nociceptin level would increase and normalize after
withdrawal in parallel with the decrease in headache frequency and normalization of
pain perception seen after withdrawal.
Background: Medication overuse headache (MOH) is a chronic, secondary
headache caused by an excessive intake of symptomatic medications for an underlying
headache, most often tension-type headache (TTH) or migraine. The mechanisms behind
MOH are unknown and diagnostic as well as progrognostic biomarkers are searched.
Nociceptin is found in the human trigeminal ganglion colocalised with
calcitonin-gene related peptide (CGRP), substance P, nitric oxide synthase and
Pituitary Adenylate Cyclase-Activiating Polypeptide (PACAP). These are all
substances involved in migraines. PACAP and CGRP are capable of initiating delayed
migraine-like attacks in human and nitric oxide can induce both migraine and TTH.
Previously, decreased levels of nociceptin have been found in patients with migraine
between attacks and the nociceptin concentration was even more decreased during
attacks.
Methods: We drew blood samples on 18 MOH patients before withdrawal and
6 months after withdrawal start and, to reduce the influence of an eventual seasonal
bias, also twice with a 6-month interval on 30 healthy volunteers of matching sex
and age. The subjects were all part of a study to test pain sensitivity in MOH
before and after withdrawal therapy for MOH.
The blood plasma was collected and kept at -80°C until analysed. The plasma was
acidified and freeze dried and then analysed for nociceptin in a radioimmunoassay.
The analyses were done blinded to subject group.
Results: The nociception concentration was 10.13 pg/ml in MOH patient
before withdrawal and 9.74 pg/ml in healthy volunteers (p=0.81). After withdrawal,
the nociceptin level rose to 10.25 in MOH patients (p=0,67).
Surprisingly, the nociceptin level tended to be lower in MOH patients who had more
than 50% reduction in headache frequency compared with the patients with less
headache frequency reduction, both before (8.4 vs 10.3 pg/ml, p=0.38) and after
withdrawal (7.7 vs. 10.9 pg/ml, p=0.06).
Conclusions: The similar levels of nociceptin between healthy volunteers
and MOH patients and in MOH patients before and after withdrawal suggests that
nociceptin is an unspecific biomarker for headache and that MOH may differ in
response from migraine. The interesting tendency to a lower nociceptin level in
responders before withdrawal in this pilot study suggests that biomarkers predicting
the outcome of MOH must be searched.
P220
Genetic Association between Matrix Metalloproteinase MMP9 Polymorphism and
Japanese Patients with Migraine
H. Kowa1, H. Takigawa1, K. Nakashima1
1Division of Neurology, Department of Brain and Neurosciences,
Tottori University, Faculty of Medicine, Yonago, Japan.
Objectives: The pathophysiology of migraine is not yet fully understood
but may involve painful vasodilatation of cerebral blood vessels. To investigate the
role of the matrix metalloproteinase MMP9 genotyping in migraine, we analyzed a
polymorphism -1562 C>T in the promoter region of the MMP9 gene.
Background: The MMP9 -1562 C>T polymorphism was previously reported
to be associated with severity of the atherosclerosis.
Methods: This study consisted of 57 patients suffering from migraine
with aura (MA), 135 from migraine without aura (MO), and 168 non-headache healthy
controls. Genotyping for MMP9 -1562 C>T polymorphism was performed on leukocyte
genomic DNA samples by polymerase chain reaction – restriction fragment-length
polymorphism (PCR-RFLP) analysis. The PCR fragments were electrophoresed in 3%
agarose gels and stained with ethidium bromide. The differences in the frequency of
MMP9 alleles and genotypes between groups were evaluated by the gene-counting method
and comparison of groups by the chi-square test. The level of significance was set
at p<0.05.
Results: The distribution of MMP9 genotypes in patients and controls did
not deviate significantly from Hardy-Weinberg equibrium. We found no difference in
the allelic and genotypic distribution between migraine patients and controls.
Conclusions: Our results support the conclusion that MMP9 -1562 C>T
polymorphism is not a genetic risk factor for Japanese migraineurs.
P221
Psychophysical Properties of Throbbing Pain in a Human Experimental Model of
Pain
M.J. Jordan1, J.L. Holt1, D. Kang2, J.A.
Kairalla3, C.D. King4, R.B. Fillingim4, M.
Ding2, A.H. Ahn1
1Neurology, University of Florida College of Medicine,
Gainesville, FL, USA; 2J. Crayton Pruitt Family Department of
Biomedical Engineering, University of Florida College of Engineering,
Gainesville, FL, USA; 3Biostatistics, University of Florida College
of Public Health and Health Professions, Gainesville, FL, USA;
4Community Health, University of Florida College of Dentistry,
Gainesville, FL, USA.
Objectives: We tested the hypothesis that the psychophysical properties
of throbbing pain could be modeled experimentally in healthy human subjects.
Background: Pain can have a throbbing pulsatile quality, especially when
it is severe and disabling. A throbbing pain quality is associated with a wide range
of acute and chronic pain conditions, is an important diagnostic factor in common
clinical conditions such as migraine, and is the target of presumptive therapy and
clinical management. However, despite its enormous clinical significance there is
scarcely any empirical data to support our fundamental understanding of it. An
experimental model of this clinically relevant pain quality, in healthy human
subjects, would likely be of great utility in understanding the processing of pain
experiences in human health and disease.
Methods: We elicited throbbing pain experiences using the cold pressor
(immersion of the hand in cold water), an experimental model of pain with
established relevance to clinical pain, in an otherwise unselected population of
healthy adult subjects. Subjects continuously recorded their subjective pain
experiences into a digital recording system, while we simultaneously monitored their
physiological responses. The measured psychophysical properties of throbbing pain
included rate of throbbing, latency to onset, and duration of throbbing. Subjects
also described pain qualities more generally using the Short Form McGill Pain
Questionnaire. We also developed and applied normative standards, using a haptic
stimulus control task.
Results: A throbbing pulsating sensation was recorded by 36 (38%) of the
94 study subjects. The psychophysical characteristics of their throbbing experiences
corresponded closely to those found in other clinical settings, such as chronic
migraine and acute dental pain. Accordingly, the rate and rhythm of the recorded
throbbing experiences did not correspond to that of the subjects’ arterial
pulsations. Pain qualities elicited by the cold pressor were otherwise similar
between those with and without throbbing sensations, with the exception of the
quality of shooting pain.
Conclusions: The present findings support the cold pressor as an
effective stimulus for eliciting the throbbing quality of pain. This experimental
model of throbbing pain will provide an experimental platform from which build a
better understanding of this clinically significant pain quality, and to determine a
brain signature, or biomarker, of throbbing pain.
P222
Migraine and Endothelial Dysfunction: An Investigation of Urine Albumin Leakage
in Migraineurs, the HUNT Study, Norway
L.M. Jacobsen1, B.S. Winsvold1,2, S. Romundstad3,4,
A.H. Pripp5, L.M. Pedersen1, M. Bergum6, J.
Holmen3, J.-A. Zwart1,2,7
1FORMI, Oslo University Hospital, Oslo, Norway;
2Department of Neurology, Oslo University Hospital, Oslo, Norway;
3Department of Public Health and General Practice, HUNT Research
Centre, Norwegian University of Science and Technology (NTNU), Levanger, Norway;
4Department of Internal Medicine, Levanger Hospital, Health Trust
Nord-Trøndelag, Levanger, Norway; 5Department of Biostatistics,
Epidemiology & Health Economy, Oslo University Hospital, Oslo, Norway;
6Vestre Viken Hospital Trust, Drammen, Norway;
7Faculty of Medicine, University of Oslo, Oslo, Norway.
Objectives: To investigate urine albumin leakage, representing
endothelial dysfunction, in migraineurs.
Background: The pathology of migraine constitutes both environmental and
genetic factors and the disorder has been associated with an increased risk of
cardiovascular events. Vascular endothelium regulates numerous vascular functions
and abruption of endothelial cell function is often observed in cardiovascular
disease. Interestingly, some studies have also found endothelial dysfunction in
migraine patients. The excretion of small amounts of albumin in urine is believed to
represent endothelial dysfunction and we therefore investigated the urine albumin to
creatinine ratio (ACR) as an indicator of endothelial dysfunction in 304 subjects
with migraine.
Methods: The association between migraine and ACR was investigated in
the second Nord-Trøndelag Health Study (HUNT-2). ACR was measured in 304 subjects
with migraine, 1025 subjects with non-migraine headache and 5428 headache free
subjects. The study was originally designed for investigating ACR in cardiovascular
disease and cases were therefore initially selected based on either 1) self-reported
hypertension/diabetes (morbid sample) or 2) a random sample. Analyses were performed
using analysis of covariance.
Results: There was no association between headache status and ACR in
either the morbid sample (p=0.57, mean ACR: migraine: 3.31,
non-migraine headache: 4.22 and no headache: 3.70.) or the random sample
(p=0.90, mean ACR: migraine: 1.71, non-migraine headache: 1.51
and no headache: 1.76.) when adjusted for age, sex, self-reported diabetes and
hypertensive medication. Similarly, we did not observe any differences in ACR score
between individuals with migraine, non-migraine headache or no headache when morbid
and random groups were combined (p=0.57, mean ACR: migraine: 3.08,
non-migraine headache: 3.43 and no headache: 3.14.). Furthermore, in the combined
sample, no significant differences in ACR scores were found among the headache
sub-types migraine with aura (MA), migraine without aura (MO), headache and no
headache (mean ACR: MA: 2.70, MO: 3.17, non-migraine headache: 3.43 and no headache:
3.14.).
Conclusions: Urine albumin leakage was not more frequently occurring in
migraineurs than in other headache- or headache free subjects. This study did,
therefore, not support the hypothesis of endothelial dysfunction in migraine.
P223
Evaluating the Utility of Salivary Biomarkers as a Clinical Tool in Diagnosing
Patients with Temporomandibular Disorder-Related Pain
T. Tat1, D. Zoukhri1, M. Finkelman1, S.
Dhadwal1, B. Chandwani1, N. Mehta1, E.
Spierings1, S. Scrivani1
1The Craniofacial Pain and Headache Center, Tufts University,
Boston, MA, USA; 2The Craniofacial Pain and Headache Center, Tufts
University, Boston, MA, USA; 3The Craniofacial Pain and Headache
Center, Tufts University, Boston, MA, USA; 4The Craniofacial Pain and
Headache Center, Tufts University, Boston, MA, USA; 5The Craniofacial
Pain and Headache Center, Tufts University, Boston, MA, USA; 6The
Craniofacial Pain and Headache Center, Tufts University, Boston, MA, USA;
7The Craniofacial Pain and Headache Center, Tufts University,
Boston, MA, USA; 8The Craniofacial Pain and Headache Center, Tufts
University, Boston, MA, USA.
Objectives: The purpose of this study was to evaluate the use of the
salivary neuropeptides substance P (SP) and serotonin (5-HT) as a clinical tool to
assess chronic pain in individuals with unresolved TMD.
Background: Chronic temporomandibular disorder (TMD), head, neck, jaw,
and orofacial pain is estimated to affect at least 12% of the U.S. population.As the
exact symptoms of pain in various TMD conditions may not be easily distinguishable,
the diagnostic accuracy of current testing methods is contingent upon subjective
measures. This renders differential diagnoses particularly complicated and
challenging to assess. Saliva analysis may offer an alternate insight into the
patho-physiology of TMD conditions.
Methods: Ten symptomatic patients from The Craniofacial Pain Center at
TUSDM and 11 asymptomatic controls from the local community volunteered for this
study. Unstimulated saliva was collected from Wharton’s duct during the fasting
state between 8:30-10:30 AM. At the time of sampling, subjects’ ratings of pain
intensity according to the 11-point Numerical Graphic Rating Scale (0-10) were
obtained. Samples were analyzed using enzyme-linked immunosorbent assay (ELISA) to
quantitatively determine the levels of SP and 5-HT. Student’s
t-test, Mann-Whitney U test, Spearman’s rank-order correlation, and
Pearson’s correlation were used for statistical analyses.
Results: The amount of SP and 5-HT were elevated in saliva samples from
patients when compared to that in control. However, the mean levels for either SP
(37.48 pg/ml in patients, 27.06 in controls) or for 5-HT (26.16 ng/ml in patients,
19.20 in controls) were not statistically significantly different. When the overall
pain score values were compared to SP or 5-HT, there was no observed correlation
(rho=0.120, p=0.605; rho=0.285, p=0.211, respectively). We also did not observe a
correlation between the two neuropeptides (r=-0.026, p=0.910).
Conclusions: Although salivary SP and 5-HT were increased in patients
versus controls, the difference was not statistically significant. Studies using a
larger sample size are warranted to further determine if these neuropeptides can be
used for TMD-related pain disorders diagnosis.
P224
The Importance of Lactic Acid in Migraines and Fibromyalgia
1Headache and Neuromuscular Service, Neurology Division, Internal
Medicine Department, HC- UFPR, Curitiba, Brazil; 2Headache and
Neuromuscular Service, Neurology Division, Internal Medicine Department,
HC-UFPR, Curitiba, Brazil.
Objectives: To determine the relationship between migraine and
fibromyalgia and levels of lactic acid in the blood.
Background: Lactic acid is a byproduct of both muscle metabolism and the
central nervous system. Changes in metabolism are related to various physiological
and pathological conditions.
Methods: The study of 113 patients was divided into six groups: 1)
healthy subjects (n = 20); 2) patients with fibromyalgia (n = 20); 3) episodic
migraine (n = 20); 4) chronic migraine (n = 20); 5) episodic migraine and
fibromyalgia (n = 13); and 6) fibromyalgia and chronic migraine (n = 20). Blood
levels of lactic acid were measured at four different time points: at rest, during
aerobic exercise, during anaerobic physical activity and while resting after
anaerobic exercise.
Results: Lactic acid increased in all groups during anaerobic physical
activity without predominance for either group. During aerobic physical activity,
all groups increased lactic acid levels, but the increase was more expressive in the
chronic migraine group (p = 0.048) and the chronic migraine with fibromyalgia group
(p = 0.042).
Conclusions: Patients with chronic migraine, with or without
fibromyalgia, may have a disorder involving the metabolism of lactic acid during
aerobic exercise.
P225
Emergency Consultation for Acute Headache in the Antepartum and Postpartum
Periods
R.V. Donepudi1, A.K. Dayal1, M.S. Robbins2
1Division of Maternal-Fetal Medicine, Department of Obstetrics
& Gynecology and Women’s Health, Montefiore Medical Center, Albert Einstein
College of Medicine, Bronx, NY, USA; 2Neurology, Montefiore Headache
Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Objectives: To contrast acute headache in antepartum and postpartum
patients to further characterize the clinical trends, risk factors, and headache
diagnoses in these populations.
Background: Antepartum and postpartum women are at high risk for acute
presentations of primary and secondary headache disorders because of hormonal,
physiological, and procedural factors. The clinical suspicion for various headache
disorders may differ between pregnant and postpartum patients, and rates of headache
diagnoses in these populations are not commonly reported.
Methods: Consecutive inpatient neurology consultations for acute severe
headache in pregnant and postpartum women at an urban, tertiary hospital setting
were captured in an interim analysis from 7/1/09 through 1/31/12 in a retrospective
chart review.
Results: We identified 68 antepartum and 21 postpartum patients (mean
age 29.2 +/- 6.4 years and 31.1 +/- 6.9 years). A secondary headache diagnosis was
more common in both antepartum (57.4%) and postpartum (61.9%) patients, although
migraine was still the most common overall diagnosis. In pregnant patients migraine
was the cause in 42.6%, followed by preeclampsia/eclampsia in 25.0%. Similarly in
postpartum patients, migraine was found in 38.1% and preeclampsia/eclampsia in
33.3%, but post-dural puncture headache was also prevalent (23.8%). Most patients
(73.5%) who presented with headache during pregnancy had a previous history of
headache, in contrast to postpartum patients (38.1%). Imaging was performed in 80.9%
of pregnant and 85.7% of postpartum patients. The only significant findings noted in
postpartum patients were Chiari type I malformation (n=1), pituitary macroadenoma
(n=1) and subarachnoid hemorrhage secondary to reversible cerebral vasoconstriction
syndrome (n=1), of which subarachnoid hemorrhage was the only new diagnosis.
Conclusions: Antepartum and postpartum patients similarly feature
migraine and preeclampsia as the most common etiologies for acute headache.
Postpartum headache patients frequently have post-dural puncture headache. Compared
to pregnant patients with acute headache, postpartum patients differ remarkably by
their lack of previous headache history, which implies anesthesia, labor and
delivery are risk factors for subsequent new onset acute headache.
P226
Changes in the Threshold for Potassium Induced Cortical Spreading Depression
Occurrence during the Natural Estrous Cycle in Mice
T. Ebine1, H. Toriumi1, M. Unekawa1, M.
Funakubo1, T. Iwashita1, M. Shibata1, T.
Shimizu1, N. Suzuki1
1Department of Neurology, School of Medicine, Keio University,
Shinjuku-ku, Shinanomachi, Tokyo, Japan.
Objectives: We explored the change in the threshold for cortical
spreading depression (CSD) occurrence in response to potassium stimulation during
the natural estrous cycle in C57BL/6J mice.
Background: CSD is known to be implicated in a variety of disease
conditions, including migraine aura. Although several studies reported hormonal
effects, few studies have examined the alterations in neuronal excitability with
respect to CSD induction in naturally estrous cycling female animals.
Methods: The natural estrous cycle of mice was divided into 4 phases,
which are proestrus, estrus, metestrus and diestrus. We compared minimum potassium
concentrations necessary to evoke CSD in each phase of the natural estrous cycle.
Initially, 0.025 M potassium was applied to the cranial window, and potassium
concentration was gradually increased by 0.025 M until CSD was induced. We also
measured the serum concentrations of estradiol and progesterone in the four stages
of the estrous cycle by liquid chromatography.
Results: The minimum potassium concentrations to evoke CSD were 0.20 ±
0.05 M in proestrus(n = 7), 0.26 ± 0.05 M in estrus (n = 7), 0.24 ± 0.09 M in
metestrus (n = 9) and 0.11 ± 0.05 M in diestrus (n = 7). In diestrus, the minimum
potassium concentration required to evoke CSD was lower compared to the other three
phases, such that significant differences were observed against estrus and metestrus
(P <0.05). The serum concentration of estradiol was 4.82 ± 4.88 pg/mL in the
proestrus stage (n = 5), 1.55 ± 1.96 pg/mL in the estrus stage (n = 5), 1.47 ± 0.80
pg/mL in the metestrus stage (n = 5) and 2.26 ± 2.63 pg/mL in the diestrus stage (n
= 5). The serum concentration of progesterone was 0.73 ± 0.91 ng/mL in the proestrus
stage, 1.78 ± 1.54 ng/mL in the estrus stage, 0.95 ± 0.67 ng/mL in the metestrus
stage and 0.49 ± 0.48 ng/mL in the diestrus stage.
Conclusions: Our results demonstrated that neuronal excitability
relevant to CSD induction differs among the natural estrous phases in mice. Although
we found that the susceptibility of CSD was increased in the diestrous stage, the
serum estrogen concentration did not reach the maximal level. We therefore infer
that endogenous estrogen does not seem to be a principal determinant of the
threshold for evoking CSD in wild-type mice. The serum concentration of progesterone
was most reduced in the diesterus stage, at which time we observed the lowest
threshold for evoking CSD, and it reached its peak value in the estrus stage, which
showed the highest threshold for evoking CSD. These data raises for the possibility
that decreased progesterone may lower the threshold for evoking CSD during the
diesterus stage. These findings provide important insights regarding the
susceptibility to the development of CSD in the estrous cycle in female mice.
P227
Patients with Menstrually-Related Migraine Lack the Trigeminovascular Menstrual
Cyclicity of Healthy Women
K. Ibrahimi1, W.P. van Oosterhout2, A.H.J. Danser1,
G.M. Terwindt2, M.D. Ferrari2, A.H. van den
Meiracker1, A. MaassenVanDenBrink1
1Div. of Pharmacology and Vascular Medicine, Dept. of Internal
Medicine, Erasmus MC, Rotterdam, The Netherlands; 2Dept. of
Neurology, Leiden University Medical Centre, Leiden, The
Netherlands.
Objectives: We investigated the effect of the menstrual cycle on
trigeminally-induced vasodilation in women.
Background: Transient receptor potential vanilloid type 1 (TRPV1)
receptors on sensory nerve endings of the trigeminal track are important in
mediating migraine attacks by releasing the vasodilator calcitonin gene-related
peptide (CGRP). Variations in female sex hormone levels during the menstrual cycle
may influence the sensitivity of the TRPV1 receptor, the amount of CGRP in
perivascular nerve terminals and hence CGRP release, and/or the response of the
postsynaptic CGRP receptors.
Methods: Capsaicin, the active ingredient of hot chili peppers,
stimulates the TRPV1 receptor and causes CGRP-dependent vasodilation. We set up a
novel model to study trigeminally-induced vasodilation in humans. Using a
laser-Doppler imager we compared the vasodilator effects of capsaicin application
and electrical stimulation on the forehead skin, a trigeminal nerve-innervated
dermatome. Women with menstrually-related migraine (MRM, n=22, age 21 to 45) and
healthy women (n=20, age 19 to 45), not using hormonal contraceptives, were studied
on day 19-21 of their cycle and on day 1-2 of their menstruation. 0.06 mg/ml and 6.0
mg/ml capsaicin solutions were applied to the forehead skin. Electrical stimulation
of the skin was used as a TRPV1-independent stimulus. Blood samples were collected
to measure serum female sex hormone levels.
Results: Healthy women showed a higher dermal blood flow (DBF) response
to capsaicin during day 1-2 of their menstruation (Emax 203±28 a.u. and
497±25 a.u. for 0.06 and 6.0 mg/ml) than during day 19-21 of their cycle
(Emax respectively 156±27 a.u. and 456±24 a.u., P<0.05). In
contrast, MRM women showed no difference in DBF responses during their cycle (day
1-2; Emax respectively 148±20 a.u. and 470±17 a.u., day 19-21;
Emax respectively 154±20 a.u. and 465±20 a.u.). No difference in DBF
response to electrical stimulation of the forehead skin between healthy women and
MRM women was present at either occasion. Surprisingly, estradiol levels in healthy
controls (75±8 pg/ml) were higher than in MRM patients (52±4 pg/ml, p<0.05) on
day 19-21 of the menstrual cycle, whereas estradiol levels on day 1-2 of the
menstruation did not differ (respectively 21±4 pg/ml and 25±5 pg/ml). Levels of
progesterone between healthy controls and MRM patients did not differ at either
point of the cycle.
Conclusions: Women with menstrually-related migraine have a compromised
cyclicity in both the trigeminovascular system and estradiol levels during the
menstrual cycle. Furthermore, the cyclic-related difference in capsaicin, but not in
electrical stimulation dilator responses, suggests that the observed differences in
healthy women are due to changes in the sensitivity of the TRPV1 receptor, likely
sex-hormone related.
P228
Efficacy and Safety of Frovatriptan+Dexketoprofen in Menstrual Related Migraine
(MRM)
G. Allais1, V. Tullo2, F. Valguarnera3, P.
Barbanti4, P. Cortelli5, G. Sette6, C.
Benedetto1, F. D’Onofrio7, V. Petretta7, M.
Curone2, D. Pezzola8, D. Zava8, G.
Bussone2
1Women’s Headache Centre, University of Turin, Turin, Italy;
2Clinical Neuroscience, National Neurological Insitute Carlo
Besta, Milan, Italy; 3Sestri Ponente Hospital, Genoa, Italy;
4Irccs San Raffaele Pisana, Rome, Italy; 5Neurological
Science, University of Bologna, Bologna, Italy; 6Sant’Andrea
Hospital, Rome, Italy; 7Neurological Unit, San Giuseppe Moscati
Hospital, Avellino, Italy; 8Istituto Luso Farmaco d’Italia, Milan,
Italy.
Objectives: To assess the efficacy and safety of frovatriptan
+dexketoprofen in two different dosages (25 or 37.5 mg; FroDex 25 or FroDex 37.5)
compared with frovatriptan alone (Frova) in the subgroup of women with MRM.
Background: Drugs for migraine attacks include triptans and NSAIDs;
their combination could provide greater symptom relief. The association of headache
with menstrual cycles is common. These migraine attacks are particularly difficult
to treat and more disabling than non-MRM migraine attacks.
Methods: This analysis was carried out in women with regular menstrual
periods who were randomized to any of the three treatment sequences, and who treated
one MRM (ITT). Of the 258 females in the main study population 76 had a regular
menstrual cycle and were randomized to Frova, FroDex 25 or FroDex 37.5. This was a
pre-defined sub-group analysis of a multicenter, randomized, double-blind,
parallel-group, pilot study. The primary end-point was the proportion pain-free (PF)
at 2 hours. Secondary end-points included pain relief (PR) and sustained pain-free
(SPF).
Results: Frequency (%) of PF at 2 h with Frova, FroDex 25 and FroDex
37.5 in the 76 females with MRM.* p=0.05 Frova vs FroDex 37.5. Secondary end
points.* p=0.05
Drug-related adverse events were equally low between different treatments.
Conclusions: Combining frova+dexketoprofen resulted in impressive PF and
PR rates at 2 and 4 hours compared to frova alone, whilst maintaining efficacy at 24
and 48 hours. The safety profiles were comparable. The intrinsic pharmacokinetic
properties of the two single drugs contribute to this improved efficacy profile. The
combination of a long lasting triptan together a NSAID with rapid onset of action
might be a good and safe therapeutic strategy for MRM.
Frova N=28
FroDex 25 N=23
FroDex 37.5 N=25
PF at 4 hour
43%
61%
80%*
PR at 2 hours
52%
81%
88%*
PR at 4 hours
80%
90%
96%
Sustained Pain Free at 24 hours
21%
35%
44%
Sustained Pain Free at 48 hours
21%
30%
32%
P229
Comorbid Medical Disorders and Migraine: Does Gender Make a
Difference?
V.T. Martin1, R.E. Thaler1, E. Al-Shaikh2, A.T.
Martin1, L.S. Levin2
1Internal Medicine, University of Cincinnati, Cincinnati, OH, USA;
2Environmental Health, University of Cincinnati, Cincinnati, OH,
USA.
Objectives: 1) To determine if the prevalence of comorbid medical and
psychiatric disorders is increased in male and female migraineurs as compared to
controls and 2) To ascertain if the types of associated comorbid disorders differ
between men and women.
Background: Past studies have demonstrated that certain medical and
psychiatric disorders are more common in migraineurs than controls, but few have
determined if these associations are influenced by gender.
Methods: Consecutive patients that were 18-65 years of age presenting to
the offices of two primary care physicians in Cincinnati, Ohio, were eligible for
participation in the study. Each participant underwent a structured verbal interview
to determine the presence/absence of headache and their clinical characteristics if
present. They were later assigned an ICHD headache diagnosis by a blinded headache
expert. Comorbid medical and psychiatric disorders were determined by validated
written questionnaires, a physician diagnosis or medication usage. Univariate
analyses were first performed separately for each gender to determine which comorbid
disorders were associated with the prevalence of migraine. To adjust for multiple
collinearities, those disorders with p values <0.20 were used as independent
variables in multivariate log binomial models along with age, obesity (BMI ≥ 30) and
current smoking status. The dependent variable was the prevalence of migraine (ICHD
1.1-1.6). Separate multivariate models were performed for each gender.
Results: The study population was comprised of 1272 patients of which
55% were female and the mean age was 46. The prevalence of migraine was 57% in women
(398/694) and 25% in men (145/578). The prevalence ratios (PRs) for migraine were
significantly increased for rhinitis, gastroesophogeal reflux and sleep apnea in
separate multivariate models for men and women (p values <0.05). In contrast, the
PRs for hypertension and anxiety were only significant in the men’s model while
those for depression and smoking were only significant in the women’s model. (Table
1)
Conclusions: The types of medical and psychiatric disorders associated
with migraine differ between men and women. These results suggest that future
studies of migraine comorbidities should include gender specific analyses. In
addition, those patients with a greater number of comorbid medical disorders have an
increased prevalence of migraine regardless of gender.
Variable
Women- Prevalence Ratios (95% CI)
Men- Prevalence Ratios (95% CI)
Age (+10 yrs)
0.92 (0.87, 0.96)
0.80 (0.71, 0.90)
Rhinitis (yes)
1.20 (1.04, 1.38)
1.43 (1.05, 1.95)
Diabetes (yes)
1.11 (0.99, 1.24)
---
Hypertension (yes)
---
1.43 (1.06, 1.94)
Depression (yes)
1.21 (1.09, 1.34)
---
Anxiety (yes)
1.08 (0.97, 1.22)
1.96 (1.53, 2.52)
GERD (yes)
1.26 (1.12, 1.41)
1.51 (1.16, 1.97)
Current Smoking (yes)
1.11 (1.01, 1.22)
0.91 (0.69, 1.19)
Obesity (BMI>30; yes)
---
0.77 (0.59, 0.99)
Sleep Apnea (yes)
1.13 (1.00, 1.27)
1.47 (1.07, 2.01)
P230
Imploding, Exploding and Ocular Migraine Headaches in a Women’s Health Clinic –
Prevalence and Comparison of Methods To Determine Pain Directionality
J. Files1, T. Schwedt1, B. Vargas1, A.
Mayer1, P. David1, M. Ko1, Y.-H.
Chang1, M. Hunt1, S. Patel1, D.
Dodick1
1Mayo Clinic, Phoenix, AZ, USA.
Objectives: Determine the prevalence of imploding, exploding and/or
ocular headaches in women with migraine and investigate the concordance between
physician assignment and patient self-assignment of pain directionality.
Background: The direction that migraine headache pain is felt, imploding
vs. exploding, may be due to differences in underlying mechanisms leading to the
headache and may predict response to migraine treatment. The proportion of migraine
patients with imploding, exploding, and/or ocular pain and the best methods of
determining this pain characteristic are largely unknown.
Methods: 198 patients with migraine presenting to a Women’s Health
Clinic participated with structured clinician-administered interviews and completed
written questionnaires. Following the interview, clinicians classified the
directionality of migraine pain for each patient as imploding, exploding, and/or
ocular. Patients determined the directionality of their own migraine pain by
responding to a written question (“Is your headache pain pushing in or pushing out
of your head or is it located within your eye socket (ocular)? Check all that
apply.”) and by choosing amongst three pictures that graphically represented
imploding, exploding, and ocular pain. Descriptive statistics were used to determine
the prevalence of each headache direction and kappa coefficients were calculated to
determine the concordance between the clinician assignment of directionality,
patient self-assignment via the written question, and patient self-assignment via
selection of the most representative pictures.
Results: Subjects were females between the ages of 18 and 77 years (mean
48 years). Depending upon the method used to assign directionality, 34%-41% of
migraine patients had imploding headaches with or without ocular pain, 18%-45% had
exploding headaches with or without ocular pain, 7%-40% had ocular pain only, and
8%-13% had imploding and exploding headaches with or without ocular pain. The
concordance (Kappa coefficient) between physician assignment of headache
directionality with patient response to the written question was 0.33 (weak to
moderate), between physician assignment and patient assignment via selection of
representative pictures was 0.35 (weak to moderate), and between patient assignment
via written question and via selection of representative pictures was 0.35 (weak to
moderate).
Conclusions: The prevalence of imploding, exploding, and/or ocular
migraine headaches varied substantially depending upon the method of determination.
The concordance between clinician assignment, patient-self assignment via answering
a written question, and patient self-assignment via choosing a representative
picture was low. Improved methods of determining pain directionality are needed.
P231
Headaches, Menstruation and Aspects of Reproductive Life in Young
Women
1Neurology, Padre Albino Integrated Colleges, Catanduva, São
Paulo, Brazil; 2Neurology, Florianopolis University, Florianópolis,
Brazil; 3Merck Investigator Studies Program, Scientific Engagements
and Education, Merck, North Wales, PA, USA.
Objectives: To classify headaches as a function of the menstrual cycle
according to the Second Edition of the International Classification for Headache
Disorders 1, in college students.
To contrast aspects related to women’s reproductive cycle as a function of headache
type.
Background: Although migraine and several other headache types
disproportionally affect women, and that migraine has a well described hormonal
influence, headaches that occur during the menstruation are often not migraine.
Furthermore, it is yet little explored whether migraine, migraine types, or headache
frequency are linked to specific events of the reproductive cycle. Since particular
migraine subtypes seem to be risk factor for more serious diseases2, the
topic is of relevance.
Methods: Sample consisted of 422 college students. A structured
questionnaire were responded and allowed the classification of the headaches
according to the ICHD-II1. Aspects of reproductive life were asked (age
of menarche, use of contraceptives pills, headaches during pregnancy). We contrasted
findings as a function of headache type.
Results: Of a sample of 422 students, 334 (79.1%) had headaches, and 134
(31.8%) had headaches associated to the menstrual cycle. Of them, most were
menstrually related headaches (prevalence of 30.8%).
Overall, median age of menarche was 12.3 years. Women with migraine with aura (MA)
were significantly more likely to have had their menarche at earlier ages than women
without migraine (p = 0.03). Use of hormonal contraceptive pills was strikingly
similar as a function of having or not migraine headaches, having or not aura, and
of number of headache days per month (around 73% for all groups). Interestingly,
during pregnancy, MA and CDH responded to a significantly higher proportion of the
headaches, relative to outside of pregnancy (p < 0.01).
Conclusions: Most female college students are affected by
menstrualheadaches. Although migraine without aura responds by the vast majority,
other headaches such as tension-type headaches, idiopathicstabbing headaches, and
migraine with aura also happen.
The fact that women with MA are equally likely to receive hormonal contraceptives
relative to others raise the question whether providers are assessing risk of
cardiovascular outcomes in some of these women (particularly the obese or those who
smoke).). Furthermore, MA and CDH being relatively more common during pregnancy that
outside pregnancy is an issue that needs to be explored. Finally, mechanisms to
explore menarche happened earlier in women with MO should also be explored since our
study is cross-sectional. It would be of interest to define whether earlier menarche
age is associated with increased risk of MO, if the opposite is true, or if an
unidentified association or pre-disposition would explain the finding.
P232
Impact of Widespread Chronic Pain Report on Health-Related Quality of
Life
J. Stuginski-Barbosa1, F. Dach2, M.E. Bigal3, P.C.R.
Conti1, J.G. Speciali2
1Bauru School of Dentistry, University of São Paulo, Bauru, Sao
Paulo, Brazil; 2Neuroscience and Behavioral Science, School of
Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, Sao Paulo,
Brazil; 3Merck Investigator Study Program, Scientific Engagement and
Education, Chief Medical Officer-Merck, North Wales, PA, USA.
Objectives: The aim of this study was to assess the health-related
quality of life (HRQoL) of women with episodic (EM) or chronic migraine (CM), as
compared to women without headaches. We also assessed the relevance of widespread
chronic pain (WCP) on HRQoL scores.
Background: Migraine and WCP are prevalent and more common in women than
men. The prevalence of WCP in migraine is increase by twofold. Nonetheless WCP is
characterized by a decreased threshold for pain often reflected by dysfunction in
the ascending endogenous modulatory pain systems. Although its relevance as a risk
factor for migraine progression has been documented, the influence of this condition
on the HRQoL of individuals with episodic and chronic migraine is poorly
understood.
Methods: Women with age from 18 to 65 years and a first diagnosis of EM
or CM seen in an outpatient headache clinic from September of 2006 to September of
2008 were invited to participate. They were asked to bring a woman of similar age,
not suffering from headaches, to the initial visit. Migraine was diagnosed as per
the ICHD-2. Questions about WCP followed the protocol of the American College of
Rheumatology. HRQoL was assessed using the Short-Form 36 (SF-36). ANOVA was used to
compare groups with respect to age. Multivariate analysis modeled SF-36 total scores
and specific domains as a function of headache status and WCP using quantile
regression.
Results: Sample consisted of 179 women, 53 in the EM group, 37 in the CM
group and 89 in control group. Groups did not differ by demographics. WCP was
reported by 35.8% of women with EM, 43.2% of those with CM and 16.8% of controls.
Women with EM and WCP were older than those with EM without WCP [p<0.01; 95%CI
(3.33; 17.84)]. Mean scores of SF-36 were 53.6 [standard deviation (SD) = 23.5] for
EM, 44.2 (SD = 18.5) for CM and 61.8 (SD = 21.5) for controls. In multivariate
analysis, SF-36 scores were predicted by CM status [p = 0.02; 95% CI (-18.52;
-1.58). The influence of WCP in the SF-36 scores approached significance (P = .08;
-0.78 [95% CI -1.64; 0.88]). Age did not contribute to the model. In women with EM
WCP was significantly associated with lowest scores, overall [p<0.01; 95%CI
(10.1; 30.15)] and also in role-emotional [p=0.01; 95%CI (11.78; 63.43), physical
functioning [p=0.01; 95% CI (4.64; 32,73)] and role-physical [p<0.01; 95%CI
(10.72; 56.54)].
Conclusions: Women with migraine are at an increased chance of WCP, and
the chance increases as a function of headache frequency. In women with EM, WCP
independently influences HRQoL.
P233
Relation of Migraine and Female Sexual Dsyfunction
D. Eraslan1, P. Yalinay Dikmen2, E. Ilgaz Aydinlar2,
C.E.M. Incesu3
1Psychiatry, Istanbul Psychiatry Institute, Istanbul, Turkey;
2Neurology, Acibadem University School of Medicine, Istanbul,
Turkey; 3Psychiatry, Acibadem University School of Medicine,
Istanbul, Turkey.
Objectives: In this study, we aimed to investigate whether sexual
dysfunction was correlated with the frequency of migraine attacks and
migraine-related disability. The second aim of the study was to find out whether
depression and anxiety levels affected sexual function in female patients with
migraine.
Background: Migraine is a chronic condition that is mainly seen in women
and negatively affects the quality of life. There are only a few studies examining
the relationship between migraine frequency, severity and sexual function.
Depression and anxiety are two phenomenona that affect both headache and sexual
functions. It is also reported that depression and anxiety levels in migraine
sufferers are high.
Methods: Fifty female migraine patients (31.9±6.5) were recruited to
study. Patients fullfilled in sociodermographics form, Migraine disability assesment
scale (MIDAS), Female sexual function index (FSFI), Beck depression inventory (BDI)
and Beck anxiety inventory (BAI). FSFI is a brief, self-report measure of female
sexual function. It consists of 19 questions on 6-domains: desire, subjective
arousal, lubrication, orgasm, satisfaction, and pain.
Results: Ninety per cent of the participants were married, with a mean
(SD) duration of 8.1±6.3 years, and 50% of them had at least one child. Most
patients (90%) had a diagnosis of migraine without aura with a mean duration of
7.2±4.8 years. Mean MIDAS score was 19.3±12.8 and disability was severe in 40 % of
the patients. The mean FSFI score was 20.9±5.9 out of a maximum of 36. Based on
total FSFI score, 45 women had scores less than the cutoff point of 26.55, which is
accepted as low sexual function. Mean BDI score was 13.6± 7.9, 60 % of the patients
had mild, moderate or severe depression and mean BAI score was 16.3±10.8.
There was no significant correlation between FSFI total scores or any FSFI domain and
age, education level, occupational status (whether the subject was actively working
or not), duration of marriage, and having children or not. Also there was no
significant correlation between FSFI and MIDAS scores, migraine duration, migraine
attack frequency, and migraine severity. BDI scores were negatively correlated with
total FSFI score (r=-0.486, P<0.001). FSFI domain scores for desire, arousal,
lubrication, orgasm and satisfaction showed significant negative correlation with
BDI score (r=-0.406, P=0.004; r=-0.510, P<0.001; r=-0.454, P=0.001; r=-0.470,
P=0.001; r=-0.558, P<0.001, respectively). No significant correlation was
detected in relation to FSFI and BAI scores.
Conclusions: In this small clinical sample of female patients with
migraine, sexual dysfunction was very common. It was not associated with migraine
related disability, frequency of attacks and migraine severity or anxiety. The most
important factor predicting sexual dsyfunction in this group was depression.
P234
Prevalence of Menstrual Migraine in the General Population
K.G. Vetvik1,4, E.A. MacGregor2, C. Lundqvist1,3,
M.B. Russell1,4
1Head and Neck Research Group, Research Centre, Akershus
University Hospital, Lørenskog, Norway; 2Barts Sexual Health Centre,
St Bartholomew’s Hospital, London, United Kingdom; 3HØKH, Research
Centre, Akershus University Hospital, Lørenskog, Norway; 4Institute
of Clinical Medicine, University of Oslo, Oslo, Norway.
Objectives: To estimate the prevalence of menstrual migraine in the
general population.
Background: The female preponderance of migraine has been hypothesized
to be secondary to female hormones, since the prevalence is similar in boys and
girls prior to menarche (1). ICHD II provides Appendix criteria for menstrual
migraine and calls for more research before it eventually can be included in the
main body of the classification (2). This is a population based epidemiological
survey of menstrual migraine.
Methods: Five thousand women aged 30-34 years received a posted
screening questionnaire about menstrual migraine. Those with self-reported migraine
in at least half of their menstrual cycles were invited to participate in a
semi-structured interview conducted by a neurologist. Those with ≥180 days/year were
excluded. The ICHD II criteria were used.
Results: The response rate of the questionnaire was 73%. Three hundred
and sixty women met the inclusion criteria. A total of 237 women were interviewed,
76 were not eligible and 47 did not want to participate. The prevalence of menstrual
migraine was 6.1 % in the general population and 17.6% among migraineurs.
Corresponding figures were 0.8% and 2.2% for pure menstrual migraine and 5.3% and
15.4% for menstrually-related migraine.
Conclusions: One out of sixteen women in this population had menstrual
migraine. Pure menstrual migraine was rare.
P235
Evaluation of Cerebral Hemodynamics of Patients with Menstrual
Migraine
S. Tasdemir1, H. Akgun1, S. Mazman1, E.
Eroglu1, S. Alay1, M. Yucel1, O.
Oz1, U.H. Ulas1, S. Demirkaya1
1Neurology, Gulhane Military Medical Academy, Ankara,
Turkey.
Objectives: Migraine is a neurovascular disorder characterized by
autonomic nervous system dysfunction and severe headache attacks. 11% women with
migraine have onset of migraine at menarche and are more likely to experience
menstrual migraine. Only 14% of women with migraine have migraine only in
association with their menstrual periods. Approximately 60% have migraine with
menses and at other times during the menstrual cycle. Migraine is a neurovascular
disorder. Change in the diameter of intracranial arteries is thought to be an
important underlying mechanism in migraine pathophysiology.
Transcranial-Doppler-Ultrasound (TCD) is a non-invasive method to evaluate
intracranial vascular system. The Breath Holding Index (BHI) is a non-invasive
method for evaluation of cerebrovascular reactivity.
Background: This study aimed to evaluate basal cerebral blood flow
velocity and vasomotor reactivity (VMR) in patients with menstrual migraine on the
third day of mensturation and on the tenth day of mensturation by using TCD.
Methods: Our study included 23 patients with menstrual migraine and 20
normal people. Mean blood flow velocity, BHI and PI were measured in the third and
the tenth days of menses of the patients and any day of the control group in MCA and
PCA bilaterally We compared the third and tenth days’ and the control group’s
values.
Results: BHI was significantly decreased in MCA and PCA in migraine
group (p<0.001). Differences Pulsatility index and Mean blood flow were
insignificant in all groups. BHI was significantly increased in PCA in the tenth day
compared to the third day (p :0,005). Differences in BHI in MCA, Pulsatility index
and Mean blood flow velocity in both arteries were insignificant in those days.
Conclusions: Migraine is a neurovasculer disorder. There are no studies
assessing cerebral hemodynamics in patients with menstural migraine. In our study,
we have detected unaffected cerebral blood flow velocities in menstural migraine
patients and reduced vasomotor reactivity in both MCA and PCA. These datas show that
vasomotor reactivity of cerebrovascularstructures reduces in menstrual migraine
periods and improves partially after the menstruation.
P236
Estrogen-Sensitive Migraine: An Exploratory Study of Its Relation to
Menstrual-Cycle and Menstruation Disorders
A. Padamsee1, E.L.H. Spierings1,2,3
1Craniofacial Pain Center, Tufts University School of Dental
Medicine, Boston, MA, USA; 2Neurology, Brigham and Women’s Hospital,
Harvard Medical School, Boston, MA, USA; 3Neurology, Tufts Medical
Center, Boston, MA, USA.
Objectives: The purpose of the study was to determine whether women with
estrogen-sensitive migraine are more likely to have menstrual-cycle and menstruation
disorders. The presence of such disorders may indicate an abnormal hormonal cycle
and given migraine’s hormonal sensitivity, it may be associated with a worse
migraine condition. Hence, we also determined whether women with chronic migraine
are more likely to have menstrual-cycle and menstruation disorders than those with
episodic migraine.
Background: Migraine is a chronic condition of recurring
moderate-to-severe headaches that affects an estimated 6% of men and 18% of women,
with the highest prevalence in those 18 to 49 years of age, generally when women
menstruate. In the majority of menstruating women with migraine, the headaches
consistently occur or consistently worsen with menstruation, here referred to as
estrogen-sensitive migraine.
Methods: We conducted a cross-sectional 42-point questionnaire study of
96 women, 18 to 45 years old, diagnosed with episodic or chronic migraine, to
determine estrogen sensitivity of the headaches as defined above and the occurrence
of the menstrual-cycle disorders, oligomenorrhea, polymenorrhea,
and irregular cycle, and the menstruation disorders, dysmenorrhea
and menorrhagia.
Results: Statistically significant findings included increased frequency
of nausea with migraine (88.8% versus 68.8%; p = 0.05) and moderate
or severe menstrual flow (75.0% versus 56.3%; p = 0.01) in the
women with estrogen-sensitive as compared to non-estrogen-sensitive migraine, and
increased frequency of menstrual-cycle disorders in general (41.2%
versus 22.2%; p = 0.05) and dysmenorrhea (51.0%
versus 28.9%; p = 0.04) in the women with chronic as compared
to episodic migraine.
Conclusions: The worst migraine conditions, that are, estrogen-sensitive
migraine and chronic migraine, are more likely to be associated with menstrual-cycle
and/or menstruation disorders, which may be due to an amplified estrogen cycle in
those women, negatively affecting headache intensity and frequency.
P237
Headache Feature, Comorbidity of Anxiety and Depression, Cognitive Impairment
of Menstrual Migraine
H. Wang1, Z. Guo1, P. Lu1, P. Jian1, Y.
Wang1
1Department of Neurology, Hebei General Hospital, Shijiazhuang,
China.
Objectives: To explore the headache feature, comorbidity of anxiety and
depression, cognitive impairment of menstrual migraine.
Background: Migraine is a severe debilitating disease, of which headache
seriously impact on the quality of life of patients, especially the female. Most
female migraineurs have headache attacks associated with anxiety and depression, but
the cognitive impairment of migraine has not yet been to conclusion.
Methods: Consecutive female patients who suffered from migraine without
aura visited headache clinic of Hebei General Hospital between January 2010 and
October 2011 were analyzed. Headache assessment included headache frequency,
duration of attack, headache level ratings. The Hamilton Anxiety and Depression
Scale were used to assess anxiety and depression associated with migraine, and
Montreal Cognitive Assessment Scale to evaluate cognitive function of migraine
patients.
Results: 256 patients were included in the study, and then were divided
into three group: 57 cases of pure menstrual migraine without aura (PMMO) group, 97
cases of menstrually-related migraine without aura (MRMO) group and 102 cases of
non-menstrually migraine without aura (NMMO) group. Migraine headache frequency
score of the PMMO group was (0.95 ± 0.13), significantly lower than that of MRMO
group (4.78 ± 2.28) and NMMO group (3.56 ± 1.98) (P<0.01). The
score of headache severity and duration of headache attacks were higher in PMMO
group and MRMO group than that of NMMO group (P<0.05), but no
significant difference was detected between the two former. Migraine patients had
higher anxiety or depression incidence that 45.7% of patients with anxiety and
depression. The MRMO group have highest incidence (P<0.05);
Inter-group chi-square test showed that the menstrual related migraine with anxiety
and depression were significantly higher than non-menstrual
migraine(χ2=6.89, P<0.01). 256
female migraine patients without aura were accessed by MoCA Scale; as a result,
migraine patients have a total score 26 points or more and showed no cognitive
decline. Menstrual migraine patients with total score of 26.67 ± 0.56, non-menstrual
migraine patients with cognitive function score 26.81 ± 0.24, t-test showed no
statistically significant difference (t=1.849, P=0.066).
Conclusions: Pure menstrual migraine and menstrual-related migraine
headache patients have longer duration of attacks compared with the non-menstrual
migraine, the extent of their headache is more intense than non-menstrual migraine.
The phenomena may be the result of the sudden drop or fluctuation of estrogen
levels. Pure menstrual migraine, which has lower frequency of attacks, its attacks
can be predicted, and has less interference by other factors, maybe the best choice
for studies of estrogen and migraine relationship. 45.7% of women migraine patients
without aura have anxiety and depression, of which menstrual migraine have highest
incidences. Female migraine patients have no obvious decline in cognitive
function.
P238
Acute Migraine Treatment in Pregnancy: A Retrospective Pilot Study
T.B. Grossman1, A.K. Dayal1, M.S. Robbins2
1Division of Maternal-Fetal Medicine, Department of Obstetrics
& Gynecology and Women’s Health, Montefiore Medical Center, Albert Einstein
College of Medicine, Bronx, NY, USA; 2Department of Neurology,
Montefiore Headache Center, Albert Einstein College of Medicine, Bronx, NY,
USA.
Objectives: To describe therapies employed and subsequent birth outcomes
in pregnant patients presenting with acute severe migraine to a hospital
setting.
Background: Teratogenic concerns and a lack of clinical studies and
guidelines render acute migraine treatment in pregnancy challenging. There is
similarly little information on birth outcomes in these patients who require
hospital care for acute headache, although the baseline risk of preterm delivery
stands at 11.4% nationally.
Methods: Consecutive inpatient neurology consultations for acute severe
headache in pregnant women at an urban, tertiary hospital setting were captured in
an interim analysis from 7/1/09 through 1/31/12 in a retrospective chart review.
Results: We identified 29 pregnant women with acute migraine free of
secondary headache, including preeclampsia. The mean patient age was 29..2.2 years
and gestational age was 27.5 weeks, with most patients presenting in the
3rd trimester (55.2%). Patients were mostly Hispanic (44.8%) or
African American (37.9%), and multiparous, with a mean of 4.3 total pregnancies
leading to an average of 1.5 viable births. Patients had migraine without aura
(62.1%) and with aura (37.9%); 13.8% of patients had chronic migraine and 31.0%
presented in status migrainosus. Most patients were considered high risk (72.4%),
and 75.9% had at least 10 prenatal care visits during the entire pregnancy.
Treatments included oral (86.2%), intravenous (IV) (65.5%), and both oral and IV
medications (62.1%). The most common agent used was oral acetaminophen (79.3%),
followed by IV metoclopramide (58.6%), the combination of oral acetaminophen and IV
metoclopramide (55.2%), an oral or IV opiate (34.5%), oral
acetaminophen/butalbital/caffeine (24.1%), and IV magnesium sulfate (6.9%). In
addition, 10.3% of patients sustained insufficient relief from these agents and
received peripheral nerve blocks (PNBs). No patients presented on migraine
prophylaxis, and one patient was started on prophylactic treatment. The majority of
patients delivered full-term infants (75.9%), 17.2% had pre-term deliveries, and
6.9% were lost to follow-up.
Conclusions: Pregnant patients presenting with acute migraine at our
hospital were treated with a combination of oral and IV medications, most commonly
acetaminophen and IV metoclopramide, but other agents, including opiates and PNBs,
were also employed. The majority of patients experienced full-term vaginal
deliveries, although rates of pre-term deliveries were slightly higher than in the
general population. Prospective studies are indicated to help elucidate the
relationships between acute headache presentations, therapies, and birth
outcomes.
P239
Causes of Discontinuation of Naratriptan Treatment Against Menstrually-Related
Migraine
K. Shimohata1, T. Shimohata2, R. Motegi1, K.
Miyashita1
1Takasaki Pain Clinic, Takasaki, Japan; 2Department of
Neurology, Brain Research Institute, Niigata University, Niigata,
Japan.
Objectives: The aim of the present study is to investigate the adherence
to naratriptan treatment and causes of its discontinuation at an outpatient pain
clinic in Japan.
Background: Menstrually-related migraine (MRM) is the commonest type of
migraine affecting about 40–70% of females suffering from migraine. Several studies
reported the efficacy of oral naratriptan in the treatment of MRM. The aim of the
present study is to investigate the adherence to naratriptan treatment and causes of
its discontinuation at an outpatient pain clinic in Japan.
Methods: We performed a single hospital-based retrospective study. We
enrolled MRM patients who fulfilled the International Classification of Headache
Disorders second edition (ICHD-II) criteria for MRM. We analyzed the efficacy,
adherence, and causes of discontinuation in MRM patients who treated with 2.5mg of
naratriptan between June 2008 and January 2010 using medical records. The efficacy
of naratriptan was evaluated at 2h after medication.
Results: We analyzed 16 patients with MRM. The rate of efficacy was
14/16 (87.5%). No patients experienced adverse effects. However, two patients could
not continue naratriptan treatment. Causes of discontinuation included (1)
difficulty in oral administration of naratriptan due to nausea and vomiting (two
patients), (2) slower-acting of naratriptan than other triptan (one patient), and
(3) difficulty in determining the timing of oral administration of naratriptan (one
patient). Although we instructed the timing of oral administration, they were not
improved by naratriptan. Instead, subcutaneous sumatriptan self-injection improved
their migraine.
Conclusions: Although naratiptan treatment is effective and
well-tolerated for MRM, some patients might not continue the treatment because of
nausea, its slow-acting, and difficulty in determining the timing of oral
administration. In such cases, subcutaneous sumatriptan self-injection may be
effective.
P240
Pain and Stress Profile of Women Who Work in Food and Drug Industries: Findings
from the Survey of New York USA of America
M.A.H. Mollik
Research and Development, Prescience Trust Funds, Phoenixville, PA, USA;
Biological Sciences, Peoples Integrated Alliance, Dhaka,
Bangladesh.
Objectives: New York is a state in the northeastern region of the USA of
America. New York is the 27th-most extensive, the 3rd-most
populous, and the 7th-most densely populated of the 50 USA of America.
The aim of survey was to investigate the role of positive affect in the relationship
between stress and pain, and negative affect in women with chronic pain, and
possible implications of positive affect as an important psychological resource that
a woman may use for coping efforts during periods of pain.
Background: Scientists in the field of positive and negative affect have
shown mixed results. While some have argued that positive and negative affects are
two ends of a single construct, others suggested that these two concepts are
independent from each other.
Methods: 105 women who work in food and drug industries suffering from
osteoarthritis and fibromyalgia were participated in the survey and completed the
initial assessments for demographic data and personality characteristics. They
subsequently completed 15 to 18 weekly interviews regarding pain, stress, negative
and positive affect. After completion of the survey using cross sectional method,
data were analyzed via hierarchical multilevel modeling.
Results: Outcomes showed that weekly increases in pain and stress could
predict negative affect elevations. Higher weekly positive affect as well as higher
average positive affect, weather directly and indirectly in interaction with pain
and stress, resulted in lower levels of negative affect. In addition, increases in
weekly negative affect and higher average negative affect, related to greater levels
of pain in subsequent weeks. In contrast, higher levels of overall positive affect
predicted lower levels of pain in subsequent weeks.
Conclusions: The survey emphasized that when individuals encounter pain
or stress, positive and negative affects are not independent and therefore showed
important role of positive affect in reducing negative affect related to pain and
stress, which could be helpful for women to bear pain and reducing the resulted
tension.
P241
Cranial Autonomic Symptoms Are Common in Pediatric Migraine Patients
A.C. Reider3, A.A. Gelfand1,2, P.J. Goadsby1
1Neurology, UCSF, San Francisco, CA, USA; 2Pediatrics,
UCSF, San Francisco, CA, USA; 3School of Medicine, UCSF, San
Francisco, CA, USA.
Objectives: To determine the prevalence of cranial autonomic symptoms in
children and adolescents with migraine.
Background: Cranial autonomic symptoms, traditionally associated with
the trigeminal autonomic cephalalgias, are also frequently seen in adult migraine.
Many adult and pediatric migraineurs are initially misdiagnosed as having “sinus
headaches”, and the presence of cranial autonomic symptoms may contribute to this
diagnostic confusion. Here we study the prevalence of cranial autonomic symptoms in
pediatric/adolescent migraine patients, as such knowledge may help avoid
misdiagnosis in these children.
Methods: We conducted a cross-sectional study measuring the prevalence
of cranial autonomic symptoms in all pediatric and adolescent migraine patients
evaluated by a single investigator at four different clinical sites over the course
of the study period.
Results: Of 125 pediatric migraineurs, 67% had at least one cranial
autonomic symptom based on current ICHD-II criteria; 70% had at least one symptom
based on proposed ICHD-III criteria. The majority had more than one cranial
autonomic symptom and the symptoms were most often bilateral. Age, gender,
laterality of headache, presence of aura, and whether migraine was episodic versus
chronic did not influence the likelihood of having cranial autonomic symptoms.
Conclusions: In pediatric migraine in patients seeking care, cranial
autonomic symptoms appear to be the rule rather than the exception. Clinicians
should consider migraine when evaluating a child with recurrent headaches and
associated ocular or nasal symptoms to avoid misdiagnosis of migraine as “sinus
headache”.
P242
Outcomes of Greater Occipital Nerve Injections in Pediatric Patients with
Chronic Primary Headache Disorders
A.A. Gelfand1,2, A.C. Reider3, P.J. Goadsby1
1Neurology, UCSF, San Francisco, CA, USA; 2Pediatrics,
UCSF, San Francisco, CA, USA; 3School of Medicine, UCSF, San
Francisco, CA, USA.
Objectives: To report the efficacy of greater occipital nerve injections
in pediatric patients with chronic primary headache disorders.
Background: Chronic primary headache disorders are relatively common in
pediatric patients, and often highly debilitating. Preventive medications generally
take weeks to months to take effect, thus these children may end up hospitalized.
Outpatient treatments with a shorter latency to benefit are needed.
Methods: The study population consisted of patients <18 years seen at
a tertiary Headache Center for a chronic primary headache disorder (chronic
migraine(CM), New Daily Persistent Headache (NDPH), or chronic trigeminal autonomic
cephalalgias (TAC)) who were treated with a 1st-time greater occipital nerve (GON)
injection. Headache classifications met ICHD-II criteria, although medication
overuse could be present, and for those with NDPH more than one migrainous feature
could be present. The proposed ICHD-III criteria for undifferentiated TAC were used.
Injections were performed unilaterally and consisted of a mixture of Depo-medrol and
lidocaine. Data were collected retrospectively from charts using a standardized
abstraction form. Definitions for “benefit” and “significant benefit” were
determined a priori.
Results: Forty-six patients were treated with GON injections.
Thirty-five (76%) had chronic migraine, 9 (20%) had NDPH, and 2 (4%) had a chronic
undifferentiated TAC. Medication overuse was present in 26%. Age ranged from 7-17
years, mean 14.7 (SD 2.5 years). Sixty-five percent were female. Follow-up
information was available on 40 (87%). Overall, 53% benefitted from the injection.
Of these, 52% had significant benefit. Timing of benefit onset ranged from 0-14 days
after the injection, mean 4.7 (SD 4.3) days. Duration of benefit ranged from <1
week to 16 weeks, mean 5.4 (4.9) weeks. Among those with chronic migraine, 62%
benefitted, 56% benefitted significantly. Of those with NDPH, 33% benefitted; only 1
significantly. Neither of the two children with a chronic TAC benefitted. Those with
medication overuse were not less likely to benefit (55% vs. 52%,
p=0.87). Age and sex did not predict outcome. One-third of patients
noted transient tingling/numbness in the distribution of the injected nerve.
Seventeen percent noted <10 minutes of light-headedness immediately following the
injection, 10% had <3 days of local soreness at the site and one patient had
prolonged soreness. There were no instances of significant bleeding or local
alopecia.
Conclusions: GON injections appeared useful in over half of pediatric
patients with chronic primary headache disorders. Given the benign and transient
nature of the side effects, a trial of a GON injection seems worthwhile prior to
admitting a child with a chronic primary headache disorder to the hospital. As this
study was not blinded and involved subjective outcomes, a randomized double-blind
placebo-controlled trial is needed to definitively determine the efficacy of GON
injections in this population.
P243
Interpersonal Victimization, Psychological Distress, and Recurrent Headaches in
Adolescents – The HUNT Study
S.Ø. Stensland1,2, G. Dyb1,2, S. Thoresen1, T.
Wentzel-Larsen1,3, J.-A. Zwart2,4
1Norwegian Centre for Violence and Traumatic Stress Studies, Oslo,
Norway; 2Faculty of Medicine, University of Oslo, Oslo, Norway;
3Centre for Child and Adolescent Mental Health, Eastern and
Southern Norway, Oslo, Norway; 4Department of Neurology/FORMI, Oslo
University Hospital, Oslo, Norway.
Objectives: To examine the relationship between recurrent headache
disorders and interpersonal victimization, possibly mediated through psychological
distress, in adolescents.
Background: Recurrent headache, is a main source of functional
impairment in youth and cooccurs commonly with psychological distress, especially if
trajectories are chronic and disabling. Traumatic events could represent important
precursors.
Methods: A cohort of 10 464 adolescents, aged 12-20 years from the midst
of Norway, were from 2006 through 2008 invited to participate in a cross-sectional
study, encompassing a general health questionnaire, including questions on exposure
to traumatic events, psychological distress, and a validated interview on headache
(the Young-HUNT3 study). Data from the headache interview served as outcome.
Recurrent headache was defined as headache recurring at least monthly during the
past year and was further subclassified into monthly, weekly, and daily complaints.
Subtypes were classified as tension-type, migraine, and/or ‘other’ headache.
Results: The response rate was 73% (7 620). Multiple logistic regression
analysis, adjusted for sociodemographics, showed a steady trend of increasing odds
for recurrent headache with increasing exposure to PTIEs, which was highly
significant in both sexes. The same pattern was reproduced for all frequencies and
subtypes of complaints. The direct effect of exposure to PTIEs decreased after the
hypothesized mediator, psychological distress, was entered into the regression
equation. This attenuation was observed for all recurrent complaints, regardless of
the frequency or subtype of headache, suggesting consistent mediation by
psychological distress. Also, the strength of mediation through psychological
distress increased with increasing exposure to PTIEs and increasing frequency of
complaints.
Conclusions: The empirical evidence of a strong, cumulative relationship
between exposure to traumatic events and recurrent headache, possibly mediated by
psychological distress, has implications for the prevention, assessment, and
treatment of headache and requires a broader biopsychosocial approach that
integrates the somatic and psychological health needs of adolescents. More
specifically, regarding the upcoming revisions for the 3rd edition of the
International Classification of Headache Disorders, our findings suggest an
expansion of a recent proposal to map both psychological distress and adverse
childhood experiences as part of the general assessment of chronic pediatric
headache, to apply to all recurrent headache complaints. Prospective studies are
needed.
P244
Health Related Quality of Life in Children with Migraine. A Controlled
Study
M.E. Jurno1,2, P.F. Moreira Filho2, M.L. Martins1,
R.C. Valerio1, T.J.C. de Almeida1, V.R. Laender1,
D.F. Resende1
1Neurology, Faculdade de Medicina de Barbacena, Barbacena, Minas
Gerais, Brazil; 2Neurology/Headache, Universidade Federal Fluminense,
Niteroi, Rio de Janeiro, Brazil.
Objectives: To measure the impact of migraine on the HRQoL of children,
by applying the Brazilian version of the SF-36 in children with
migraine and in controls.
Background: Headaches are prevalent in the pediatric population.
Migraine significantly impacts the health-related quality of life (HRQoL) of
sufferers.
Methods: In this cross-sectional study, HRQoL was measured with the
SF-36, and scores for the 8 domains of the test were contrasted comparing children
(5 to 14 years) with and without migraine.
Results: Sample consisted of 66 children (30 with migraine and 36
controls). Mean age was 10.9 years for migraine (Standard Deviation - SD = 3 years)
and 10.4 for controls (SD = 3.1 years). Proportion of children with low HRQoL scores
was significantly higher in the migraine group, relative to controls, for the 8
domains of the test:vitality, physical functioning, bodily pain, general health
perceptions, physical role functioning, emotional role functioning, social role
functioning, and mental health.
Conclusions: Children with migraine are significantly impacted in their
HRQoL, relative to children without migraine.
SF 36 Scale
Control
MIGRAINE
Chi2/F
p value
N
%
N
%
Functional Capacity
000-060
0
0
10
33.3
-
<0.001
061-100
36
100
20
66.7
Physical Functioning
000-060
1
2.8
20
66.7
30.79
<0.001
061-100
35
97.2
10
33.3
Pain
000-060
1
2.8
16
53.3
21.88
<0.001
061-100
35
97.2
14
46.7
General Health
000-060
2
5.6
11
36.7
10.01
0.002
061-100
34
94.4
19
63.3
Vitality
000-060
2
5.6
13
43.3
13.29
<0.001
061-100
34
94.4
17
56.7
Social Aspects
000-060
1
2.8
11
36.7
12.63
<0.001
061-100
35
97.2
19
63.3
Emotional Aspects
000-060
4
11.1
13
43.3
8.88
0.003
061-100
32
88.9
17
56.7
Mental Health
000-060
1
2.8
13
43.3
16.10
<0.001
061-100
35
97.2
17
56.7
P245
Burden of Headache in Children and Adolescents – Developing a Questionnaire for
a Global Study
Ç. Wöber-Bingöl1, D. Ugurlu Uludüz2, U. Uygunoglu2,
T.S. Aslan2, M. Kernmayer1, H.-E. Zesch1, G.
Wagner1, A. Siva2, C. Wöber3, T.J.
Steiner4
1Dept of Child and Adolescent Psychiatry, Medical University,
Vienna, Austria; 2Neurology Dept, Cerrahpasa Medical Faculty,
Istanbul, Turkey; 3Dept of Neurology, Medical University, Vienna,
Austria; 4Dept of Neuroscience, Norwegian University of Science and
Technology, Trondheim, Norway.
Objectives: To develop a questionnaire for a global estimation of the
burden of headache in children and adolescents, to assess its feasibility, to
validate the diagnostic questions and to present preliminary data on quality of life
(QoL).
Background: Burden of headache has been assessed in adults worldwide,
but data in children and adolescents are sparse.
Methods: We developed a structured questionnaire for mediated-group
self-administration by pupils in school, including demographic enquiry, questions on
headache prevalence, 12 questions required for diagnosing migraine, tension-type
headache (TTH) and probable medication-overuse headache according to ICHD-II, 13
questions on impact of headache and 12 on QoL. In a pilot study, we offered the
questionnaire to pupils aged 11-17 years in Vienna and Istanbul and performed
face-to-face interviews in randomly selected pupils in Vienna.
Results: We analyzed 711 completed questionnaires: 362 from Vienna and
349 from Istanbul (51% girls; mean age 13.7±1.5 yr). Participation rate was 75% in
Istanbul, 65% in Vienna. The lifetime prevalence of headache was 96.5%; 1-year
prevalence was 89.4%. Occurrence of headache and use of headache medication on all
or most days were reported by 14.5% and 13.2%. Headache lasted hours to all day in
52% and was moderate in 40.2%, severe in 8.5%. Nausea, vomiting, photophobia and
phonophobia were reported by 25.8%, 9.8%, 44.8% and 82.3%. Agreement between the
questionnaire and 52 face-to-face interviews was <50% for headache on all or most
days, frequent use of headache medication and quality of headache. Mean agreement
for other diagnostic questions was 78.1% (range 70.6-100%). Excluding subjects with
headache on all or most days, 47.8% had migraine (definite or probable) and 52.2%
had TTH (definite or probable). Regarding impact of headache, 84% were unable to
concentrate, 49% could not do things they wanted to, 42% were sad and 24% missed
school because of headache on ≥1 day in the previous month. Regarding QoL, overall,
86% felt tired, 72% felt ill and 35% felt alone. Increasing headache duration,
severity and number of fulfilled ICHD-II migraine criteria correlated with
increasing impact of headache in most impact questions, and with decreasing QoL in
7, 4, and 10 respectively of the 12 QoL questions.
Conclusions: This pilot study revealed a marked selection bias towards
subjects with headache. To the questionnaire, pupils over-reported headache and
medication use on all or most days. Otherwise there was fair agreement between
questionnaire and interview in the diagnostic questions. As a consequence of this
pilot study the questionnaire will be adapted and re-evaluated. Meanwhile, these
preliminary findings on impact of headache and QoL suggest considerable burden of
headache.
P246
The Wocach Project. A Innovative Web-Based System for the Study of Headache in
Children and Adolescents. A Preliminary Study of Methodological
Issues
V. Guidetti1, B. Bellini1, F. Lucchese2
1Department of Pediatrics and Pediatric Neuropsychiatry, Sapienza
- University of Rome, Rome, Italy; 2Department of Dynamic and
Clinical Psychology, Sapienza - University of Rome, Rome, Italy.
Objectives: Our aim is to take account of the methodogical opportunities
offered by a web-based model for of the study of epidemiology features of headache
in a large population of children and adolescents from multiple countries all over
the world, taking into account the co-occurring comorbid conditions and the
correlations with disability.
Background: In children and adolescents, headache is one of the most
common pain experiences (Ghandour et al., 2004) that has a high
risk of development of physical and psychiatric morbidities and to persist into
adulthood as a chronic condition. In adolescents, headache is one of the most common
health problems, with a range of 5 to 25% of children and adolescents reporting
severe or frequent headache (Anttila 2006). Perquin et al., (2000)
found that 4.6% of 12-16 year old adolescents suffer from chronic headache. In
addition, headaches have been shown comorbid with a range of physical and mental
health problems including asthma (Lateef et al., 2009), allergies (Lateef et al.,
2009), sleep disorders (Miller et al., 2003), suicidal ideation (Wang et al., 2009),
emotional and behavioral problems (Strine et al., 2006), anxiety and depression
(Guidetti et al., 1998).
Methods: The research is organised in a pyramidal way, in different
geographical areas of the world.
Tests adopted will refer to the following comorbidities: Psychiatry-related; ADHD
field; Epilepsy categories; Sleep disorders; Atopic disorders; Other areas
investigated: Cognitive; Quality of life.
Data retrieval, with specific attention to security and encrypting, will be managed
by “Sapienza” University of Rome. An Electronic Patient Record has been implemented
with automatic protocols for data analysis.
Statistical models adopted:
1) Starting of the study: analysis of comorbidities; identification of differences
between groups (area, age, sex,etc );
2) After 1 year: the same analysis of step 1 will be repeated to control for time
variable (maturation, stability of phenomena observed);
3) Regression analysis and factorial analysis with data recorded for the
identification of factor as predictive of selected pathologies;
4) Analysis of the different clinical approaches adopted; compared with results of
steps 1-3 for the identification of the different power of therapeutic approaches
adopted.
Results: By now, we are collecting data coming from 70 universities and
clinical centers all over the world.
Conclusions: The web-based system, allowing the participants to follow
on-line the developing of the data analysis process, could be a base for the
creation of guidelines for deeper knowledge in headache, comorbidity and predictive
factors.
P247
Metabolic and Imaging Abnormalities in the Evaluation of Children with Cyclic
Vomiting Syndrome
J. Moses1, A. Keilman1, A. Worley1, A.D.
Rothner1, S. Parikh1, K. Radhakrishnan1
1Cleveland Clinic Foundation, Cleveland, OH, USA.
Objectives: To determine the need for imaging in patients with CVS. To
evaluate the role of metabolic testing in this disorder.
Background: Cyclic vomiting syndrome (CVS) is a diagnosis made by
exclusion of other organic diseases. It is considered a migraine variant. It has
been suggested that patients with CVS may have mitochondrial dysfunction. The aim of
the study was to evaluate our CVS patients to determine whether they had associated,
undiagnosed metabolic abnormalities.
Methods: The study included 106 consecutive patients less than 21 years
of age at diagnosis. Information regarding medical history, laboratory and imaging
studies was collected. Metabolic studies in serum and urine were obtained when
patients were well and when patients were in a vomiting cycle, which included serum
amino acids, urine organic acids, and acylcarnitine profile.
Results: The mean age at diagnosis was 8.9 ± 5.0 years. The patient
population was 57% male and 77% Caucasian. Patients reported cycles with median
duration of 24 hours, 18 vomiting episodes per cycle and a peak of 5 emeses per hour
at 4-week intervals. Most patients (88%) reported complete symptom resolution
between episodes. 10% of episodes required IV fluids. Warning symptoms occurred in
63%, typically abdominal pain and nausea (37%). Episode triggers were identified in
66%, intercurrent illness (35%) seen most often, motion sickness in 16%. Autonomic
symptoms were seen in 25%, with fever (13 patients) and hypertension (9 patients).
For prophylactic treatment, amitriptyline was effective in 23 of 40 patients (58%)
and cyproheptadine was effective in 30 of 61 (49%). High dose oral ondansetron
improved or resolved acute symptoms in 56 of 85 (66%). There was a family history of
migraines in 71% of patients, epilepsy in 10%. Personal migraine history was noted
in 26%. Neuroimaging showed previously unknown intra-cranial abnormalities in less
than 10% of patients, none of which explained the vomiting symptoms. Abdominal
ultrasounds (US) showed abnormalities in 15% of patients during an acute episode and
7% of patients when well. The most common finding was renal abnormalities. 61
patients had an upper gastrointestinal series (UGI) done, all of which were normal.
34% of patients completed metabolic testing when well, of which 28% had findings
suggestive of mitochondrial dysfunction. 37% of patients completed metabolic testing
with an acute episode, of which 20% had findings suggestive of mitochondrial
dysfunction. The most common finding was increased alanine.
Conclusions: The initial work-up of these patients could potentially be
more individualized in regards to neuroimaging, abdominal US, and UGI. Almost
one-third of our patients had abnormalities in blood and urine suggesting
mitochondrial dysfunction. Additional, and more detailed metabolic analysis of this
population is being planned at our institution.
P248
Monthly Variation of US Emergency Department Visits for Headaches in
School-Aged Children
S. Kedia1,4, J. Grubenhoff2, A. Kempe1,4, A.D.
Hershey3, S.W. Powers3
1Department of Pediatics, University of Colorado Anschutz Medical
Campus, Aurora, CO, USA; 2Department of Emergency Medicine,
University of Colorado Anschutz Medical Campus, Aurora, CO, USA;
3Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;
4Children’s Outcomes Research, Aurora, CO, USA.
Objectives: To determine the monthly variation of acute US emergency
department (ED) headache visits for school-age children.
Background: Headache disorders are prevalent in children and lead to
significant disability and health-care utilization. School-related stress is a
commonly reported headache trigger for school-aged children. However, studies have
not explored month to month variation of headache exacerbations in children. We
hypothesize that school-aged children will have increased ED visits related to
headaches in the months associated with onset of school.
Methods: From a nationally representative sample of ED visits in the
National Hospital Ambulatory Medical Care Survey from 1997 to 2009, we estimated
number of ED visits associated with ICD-9 diagnosis codes related to headache,
migraine, status migrainosus, or tension-type headache in any of the three diagnosis
code fields. Age stratified multivariate models are presented for month of ED visit
(July set as reference month) and adjusting for gender, race/ethnicity, region,
urban setting, and admission.
Results: There was a national estimate of 320,000 (95% CI 296,000,
344,000) ED visits related to headache diagnosis (1.84 % of total ED visits) in
individuals 5 to 18 years old from 1997 to 2009. Of these, 66.7% were female; 62.2%
were non-Hispanic whites, 22.6% non-Hispanic blacks, 12.0% Hispanic; 79.2% lived in
urban settings; and 3.51% were admitted to hospital from ED. In 5-11 year olds,
there was significant lower ED visits in April (OR 0.38, 95% CI 0.20, 0.73). In
12-18 year olds, there was significant increase in ED visits in January (OR 1.77,
95% CI 1.12, 2.70) and September (OR 1.74, 95% CI 1.18, 2.64).
Conclusions: In adolescents aged 12 to 18 we found increased emergency
department utilization for headache in January and September, in congruence with
school onset. Alternatively, there were no increased utilization in these months for
younger children or young adults. This monthly variation of ED utilization should be
explored further for possible explanations including school related stress, sleep
pattern disturbance, head trauma, and possibly viral etiologies.
P249
Lifestyle Changes for Headache Prevention among School Children in South
Korea
1Department of Pediatrics, School of Medicine, Chosun University,
Gwangju, Republic of Korea; 2Department of Pediatrics, National
Health Insuarance Corporation, Ilsan Hospital, Ilsan, Republic of Korea;
3Department of Pediatrics, College of Medicine, Hallym
University, Seoul, Republic of Korea; 4Department of Pediatrics,
College of Medicine, Korea University, Seoul, Republic of Korea;
5Department of Pediatrics, College of Medicine, Korea University,
Ansan, Republic of Korea; 6Department of Pediatrics, School of
Medicine, Chungbuk National University, Chungju, Republic of Korea;
7Department of Pediatrics, School of Medicine, Pusan National
University, Pusan, Republic of Korea; 8Department of Pediatrics,
School of Medicine, Chonnam National University, Gwangju, Republic of
Korea.
Objectives: We examined lifestyle among school children in South Korea
and analyzed the relationship of lifestyle and headache.
Background: Despite the high prevalence of headaches among school
children, lifestyle of school children with headache has not been well examined.
Methods: We conducted a cross-sectional school based study of a
randomized and proportional sample of 5360 boys and girls. The mean age is
14.02±3.03 (range 7-19 years). The questionnaires collected demographic data in
addition to specific a questions about headache according to the international
classification of Headache Disorder criteria, 2nd Edition. And we analyzed according
to exercise, regular eating, sleep time, fluid intake, and caffeine intake.
Results: School children to exercise have less headache (p=0.02). School
children with eating regularly have less severe headache (p<0.0001, odds
ratio=0.5). School children to sleep more have less headache (p<0.0001). School
children taking more fluid have less headache (p=0.0002). School children taking
more caffeine have more headache (p<0.001).
Conclusions: This is the study of relationship between headaches and
lifestyle of school children in South Korea. We suggest that behavioral the
lifestyle changes should be considered to prevent headaches among school
children.
P250
Olfactory Hallucination in Childhood Primary Headaches: Case Series
S. Donaldson1, F. Akor2, R. Alkilani3, D.
Cahill4
1Foundation Year One Doctor, Harrogate District Hospital,
Harrogate, West Yorkshire, United Kingdom; 2Headache Clinic,
Paediatric Department, Queen’s University Hospital, London, United Kingdom;
3Radiology Department, Queen’s University Hospital, London,
United Kingdom; 4Child and Family Psychotherapist, Paediatric
Department, Queen’s University Hospital, London, United Kingdom.
Objectives: To examine the frequency and characteristics of olfactory
hallucination in children and adolescents with primary headaches.
Background: Olfactory hallucination (OH) refers to perceived smell in
the absence of odorant stimulation. Reports of OH in the paediatric population are
rare. Olfactory aura is yet to be recognised by the International Classification of
Headache Disorders (ICHD-2).
Methods: 838 patients (494 females; 344 males) were eligible for the
assessment of OH. Headache diagnoses on the basis of ICHD- 2 included migraine
(n=536), tension type headaches (n=117) and other primary headache types (n=47). The
remaining 138 patients had not yet specified headaches. The migraine category
included 230 migraine with aura (MA) and 306 migraines without aura (MWA).The study
was a retrospective analysis of prospectively collected data at the paediatric
headache clinic at Queen’s University Hospital between August 2009 and July
2012.
Results: Of the eligible 838 patients, 18 (ages ranging from 6.9 to 15.9
years) had OH during headache attacks. OH included smells such as rotten cheese,
burned plastic and fish tanks.
OH shortly followed the onset of headaches and lasted from 15 to 50 minutes. Use of
painkillers was not helpful to minimise or terminate OH and OH disappeared or
considerably improved among 6 out of 18 patients following sleep. Headache attacks
were never triggered by smell and OH was not present in between headache attacks.
The smells were not experienced by others at the time.
Using the ICHD-2, all patients with OH had migraine (14 MA, 4 MWA). Of those with MA,
nine patients had visual aura; two had somatosensory aura; one had motor aura and
two had a combination of visual and somatosensory aura. In these patients, both OH
and aura occurred in the same headache attacks.
Conclusions: Migraine was the only associated headache type among the 18
patients with OH and migraine with aura was the major linked headache. We found a
prevalence of OH to be approximately 3.4% among migraineurs (6.1% among those with
MA). OH was associated with the onset of migraine headache, occurred in at least two
separate headache attacks, and correlated with other associated symptoms such as
nausea, vomiting, photophobia and phonophobia. In these patients, OH lasted for more
than five minutes and less than an hour, and was then followed by gradual
spontaneous full recovery. The most reasonable hypothesis to explain our findings is
to consider OH as a form of migraine aura. Prior to this study, to the best of our
knowledge, there are 40 reported cases of OH in patients with primary headaches.
Therefore, the entire cohort of patients, including our cases, comprises a total of
58 cases highlighting that OH occurs, although uncommonly, in patients with
migraine.
P251
Attachment, Depression and Anxiety in Children and Adolescents with
Migraine
V. Guidetti1, E. Salvi2, A. Lo Noce2, A.
Antonelli2, F. Lucchese2
1Pediatrics and Child and Adolescent Neuropsychiatry, Sapienza
University, Rome, Italy; 2Psychology, Sapienza University, Rome,
Italy.
Objectives: Investigate the connection between dependence, depression
and anxiety in children with primary headache syndroms.
Background: Few studies on the role of emotional dependence related to
comorbidity. According to them, a significant correlation exists between depression,
anxiety and low-safety perception in connection with attachment figures in children
with migraine.
Methods: The experimental group was made of 100 subjects, 48 m. and 52
f., aged 8 to 14 y.o., with primary headache. Exclusion criteria: subjects with a
diagnosis of secondary headache and p. older than 14 years. The monitoring group was
composed of 100 s. without headache, 49 f. and 51 m., aged between 8 and 14 y.o. The
experimental group presented Migraine Without Aura (60), Migraine With Aura (10),
Tension-Type Headache (15), CDH (10) and BenignParoxysmalVertigo (5).Both groups
were analized with a Security Scale [1] and SAFA scale A and D versions [2].
Security Scale is a self-administrated scale for ch. and adol. exploring the
perception of safety with the mother (PSM) with the father (PSP) and with both
parents (PSC). SAFA is a self-assessment scale for children and adolescents to
assess anxiety (A) and depression (D). Total Anxiety (ANXTOT), Generalized Anxiety
(GA), Social Anxiety (SA), Separation Anxiety (ASP) and School Anxiety (A_SCU).
Total Depression (DEPTOT), Depressed mood (UD), Anhedonia and Apathy (AD), Irritable
Mood (UI), Sense of Inadequacy (SI), Insecurity (I), Feeling of Guilt (SC) and
Despair (DISP) were analized.
Results: t Student statistical analysis revealed a statistically
significant difference between the control g. and the experimental one on PSC (p
< .001) ANX TOT (p < .001), DEP TOT (p = .007). In the variable Anxiety: AG (p
< .001), AS (p < .001), ASP (p < .001), A_SCU (p < .001). The variable
Depression has reported the following values: UD (ns), AD (ns), IU (p < .001), SI
(ns), I (p < .001), SC (ns), DISP (ns). The variable Perception of Safety
reported the following values: PSM (p < .001), PSP (p < .001). In order to
assess significant differences within the group of the variable headache, divided
according to the pathology observed, an Analysis of Variance method (ANOVA) was
employed. The results of Anxiety’s subscales were statistically not significant (p
> .05). Depression scale’s data are not statistically significant (p > .05)
except UD subscale in subgroups Migraine with Aura and Chronic Daily Headache (p =
.024) and UI one,between Tension-Type Headache and Chronic Daily Headache (p = .02).
The variable Perception of Safety, don’t show statistically significant values (p
> .05).
Conclusions: High statistical significance of variables such as A, D,
and Perception of Safety confirming our hypothesis and stressing the importance of a
multifactorial assessment in a clinical studies, in order to provide full support
with an integrated approach, with the aim to obtain a better understanding of the
disorder in question.
P252
Factors Influencing Migraine Recurrence after Acute Inpatient Treatment in
Children and Adolescents
K.M. Cobb1, A.D. Hershey1, H.L. O’Brien1, S.
LeCates1, S. White1, P. Vaughn1, P.
Manning1, A. Segers1, J. Bush1, P.
Horn1, M. Kabbouche1
1Neurology, Cincinnati Children’s Hospital Medical Center,
cincinnati, OH, USA.
Objectives: To evaluate factors that influence the migraine recurrence
rate after infusion and inpatient treatment for intractable migraine.
Background: Recurrence of migraine after acute treatment in an infusion
and inpatient setting is not well documented in children and adolescents. Given the
multifactorial pathogenesis of migraines, multiple factors may influence migraine
recurrence after discharge. It has been reported that treatment with steroids may
reduce the risk of migraine recurrence. The efficacy of steroids as a therapeutic
adjunct has not been established. Studies in the adult population have yielded
conflicting results.
Methods: This study is a retrospective chart review of patients
presenting for treatment of an intractable migraine to the infusion unit or
inpatient unit at Cincinnati Children’s Hospital Medical Center. Data collected
included: age, gender, location of treatment (infusion unit, inpatient unit),
migraine duration, diagnosis, severity, the addition of steroids to treatment
protocols, and recurrence of migraine 48 and 72 hours after discharge. Data was
analyzed using Fisher’s exact tests, logistic regression with backward elimination,
and least squares mean slicing.
Results: Charts from 207 pediatric patients were analyzed. Using
logistic regression analysis: location, gender, diagnosis, and age were all found to
be significant predictors of migraine recurrence (P<0.05).
Patients treated in the infusion unit were more likely to experience recurrence
compared to inpatient admissions (P=0.00024). Male patients with
chronic migraine were significantly more likely to experience recurrence than male
patients with episodic migraine (P=0.0074). Episodic migraine
patients were less likely to experience migraine recurrence with increased age,
while chronic migraine patients more likely to experience migraine recurrence
(P=0.0008). The inclusion of steroids in this study population
showed no significant reduction in migraine recurrence.
Conclusions: Recurrence is an important parameter when treating
intractable migraines. Age, gender, diagnosis, and location of treatment correlate
with migraine recurrence, but the inclusion of steroids does not. Considering these
factors in the management of migraines may improve the outcome of these patients and
reduce the risk of recurrence.
P253
Temperament and Character Traits in Pediatric Episodic and Chronic
Migraine
S. Kedia1,3, B. Wallace4, C.R. Cloninger2, A.
Kempe1,3
1Department of Pediatrics, University of Colorado Anschutz Medical
Campus, Aurora, CO, USA; 2Department of Psychiatry, Washington
University School of Medicine, St. Louis, MO, USA; 3Children’s
Outcomes Research, Aurora, CO, USA; 4Neurosciences Research
Administration, Children’s Hospital Colorado, Aurora, CO, USA.
Objectives: (a) To compare temperament and character personality traits
in children with migraine to normative data; (b) To compare temperament and
character personality traits in children with episodic migraine to chronic
migraine.
Background: Children with headaches are described as having lower level
of vigor, intensified fear, higher emotionality, and being overly ambitious.
Personality traits are associated with medication overuse headache, medication
compliance, and cutaneous allodynia. Our aim was to understand personality traits in
children with migraine and compare traits in those with episodic versus chronic
migraine.
Methods: We conducted an IRB approved cross-sectional study of children
aged 8-17 years old with migraine defined by International Classification of
Headache Disorders – IIR seen by at a tertiary headache clinic. Demographics,
headache type (episodic or chronic), and juvenile temperament character inventory
(JTCI) was collected. For children less than 13, parent report JTCI was used. JTCI
defines four temperament traits—novelty seeking, harm avoidance, reward dependence,
and persistence—and three character traits—self-directedness, cooperativeness, and
self-transcendence. Analysis included one-sample t-test to compare sample to
normative data and two-sample t-test to compare personality traits between episodic
and chronic migraine subgroups.
Results: Forty-nine children with migraine were enrolled with a mean age
of 14.0 years (SD 0.37) and 65.3% female; 20 (40.8%) children with episodic migraine
and 29 (59.2%) children with chronic migraine. Compared to normative data, children
with migraine have higher novelty seeking (p=0.05), higher harm avoidance (p=0.09),
higher self-directedness (p<0.001), and higher self-transcendence (spirituality
domain; p<0.05). Compared to episodic migraine, children with chronic migraines
have higher cooperativeness (p<0.05).
Conclusions: Children with migraine have distinctive personality traits;
however there is no difference in those children with episodic versus chronic
migraine except for cooperativeness trait.
P254
The Psychosocial Impact of Migraine in Adolescents
J.W. Kroner1, S.M. Sullivan1, B.S. Aylward1, H.L.
O’Brien1, M.A. Kabbouche1, A.D. Hershey1, S.W.
Powers1
1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH,
USA.
Objectives: To assess the impact of migraine on psychological and social
functioning in adolescents presenting to a tertiary headache center.
Background: Chronic pain affects 11 to 38% of children and adolescents,
with migraine being one of the most prevalent chronic illness conditions. Chronic
pain is associated with disruptions in domains of normal life, such as school
attendance, school performance, and social functioning, and can result in lower
quality of life.
Methods: The study sample consisted of 115 adolescents 11 to 18 years
old evaluated in a multidisciplinary headache center for treatment of headache pain
and met ICHD-II criteria for migraine with or without aura. Participants completed
psychosocial questionnaires at the initiation of treatment and again 6-months later.
Measures of psychosocial functioning included the Bath Adolescent Pain Questionnaire
(BAPQ), the Social Consequences of Children’s Pain questionnaire (SCP), the Pain
Catastrophizing Scale for Children (PCS), the Pediatric Quality of Life Inventory
(Parent- and self-report, PedsQL), and the Behavior Assessment Scale for Children
(Parent- and self-report; BASC-II).
Results: At baseline, both parent and self-reported quality of life
ratings had a mean of 70.Average parent and self-report symptom scores were not
significantly elevated with the exception of parent reported internalizing symptoms
on the BASC-II (M = 60.86; at-risk range; p<0.0001). Across all
subscales, 56% of parent reported symptoms fell within the at-risk or clinical range
at baseline; this decreased to 31% at the six-month follow-up. Parent-reported
internalizing symptoms significantly decreased from baseline to the six month visit
(p<0.001). In addition, parent reported pain-related
catastrophizing behaviors decreased significantly from baseline to six months
(p<0.05).
Conclusions: On average, adolescents with migraine do not report
significantly elevated symptoms of impairment. At baseline, average parent-reported
internalizing symptoms fell in the at-risk range but were in the normal range at the
6-month follow-up. There is a subset of patients with migraine who did have
clinically elevated symptoms reported which, in turn, can impact treatment
management. Inclusion of psychosocial measures can aid in creating comprehensive
treatment regimens for migraine.
P255
Pain Direction Subtends Different Pathophysiological Mechanisms in Children
with Migraine
M. Valeriani1, E. Iacovelli2, S. Tarantino1, A.
Capuano1, C. Casciani1, F. Vigevano1
1Neuroscience, Ospedale Pediatrico Bambino Gesú, Rome, Italy;
2Medico-Surgical Sciences and Biotechnologies, “Sapienza”
University of Rome, Rome, Italy.
Objectives: To investigate whether migraine adolescents with pain
directed inside (imploding pain) and outside (exploding pain) the head have
different mechanisms underlying their migraineous syndrome.
Background: In adult migraineurs, pain direction (exploding or
imploding) has been associated with a different response to botulinum toxin
treatment (Jakubowski et al., 2006). Thus far, there has been no objective evidence
in favour of the hypothesis that pain direction depends on different
pathophysiological mechanisms.
Methods: In the first study, concerning the somatosensory system
excitability, 18 migraine children were recruited. Ten patients (mean age 14.5±1.4
years, 3 girls, 7 boys) had exploding pain (EP), while 10 patients (mean age
14.1±2.2 years, 4 girls, 6 boys) complained of imploding pain (IP). The recovery
cycle of the short-latency somatosensory evoked potentials (SEPs) was measured and
compared between both patients’groups. Twenty migraine children, 9 with EP (mean age
11.5±1.5 years) and 11 with IP (mean age 11.3±1.7 years) participated to the second
study, investigating the pshychophysiological mechanisms of spatial attention. The
amplitude of the N140 SEP component was measured in a neutral condition (NC), in
which patients were asked to disregard the electrical stimulation, and in a spatial
attention condition (SAC), in which patients had to count silently brief mechanical
targets, made manually by a gauze ball on the tip of the first and the second finger
of the hand ipsilateral to electrical stimulation. The N140 amplitude variations
between NC and SAC were compared between both patients’groups.
Results: As for the somatosensory system excitability, the frontal N30
amplitude recovery cycle was shorter in IP than in EP patients, thus suggesting
higher brain excitability in those patients complaining imploding pain. In the study
about spatial attention mechanisms, the N140 amplitude increase during SAC, as
compared to the baseline, was higher in IP than in EP patients. This suggests that,
as compared with the EP migraineurs, the IP patients had to use a higher amount of
attentional resources to accomplish the task.
Conclusions: The present study is the first to have shown
neurophysiological differences, concerning somatosensory system excitability and
spatial attention, between migraine children with either imploding or exploding
pain. These results suggest that in pediatric migraine pain direction is associated
with different pathophysiological mechanisms.
P256
Headache and Migraine Equivalents: Analysis of 1,134 Children and Adolescents
Referring to a Pediatric Headache Centre
M. Valeriani1, S. Tarantino1, A. Capuano1, M.
Citti1, F. Vigevano1
Objectives: To investigate the prevalence of migraine equivalents (MEs)
in a large population of children referred to a pediatric headache centre.
Background: Migraine equivalents of infancy, childhood and adolescence,
(also called “childhood periodic syndromes”) are common clinical conditions without
headache component, occurring as repeated attacks with complete remission between
episodes. These signs may precede the development of migraine headache by several
years and show a later evolution to more typical migraines. Studies investigating
migraine and migraine equivalents (MEs) have shown data that support their
association, which is not a pure coincidence. The International Classification of
Headache Disorders, 2nd edition (ICHD-II, 2004) includes three MEs, named
as “childhood periodic syndromes”: abdominal migraine (AM, 1.3.2.), cyclical
vomiting (CV, 1.3.1.), and benign paroxysmal vertigo (BPV, 1.3.3.). A fourth
equivalent, benign paroxysmal torticollis (BPT, A 1.3.5.), is presented in the
Appendix. Beyond the childhood periodic syndromes described by ICHD-II, other
clinical entities, such as motion sickness (MS) and limb pain (sometimes referred to
as “growing pain”), are not yet universally accepted and data are still lacking.
Methods: Patients were identified through systematic review of clinical
charts of patients referred to our Headache Centre from June 2007 to April 2011.
Secondary headache, cluster headache or patients who suffered from any other
neurological or internal disease were excluded from our study. The final diagnoses
of headache were made according to International Classification of Headache
Disorders, 2nd edition (ICHD-II).
Results: A total of 1,134 of children/adolescents (52.3% boys and 47.7
girls; mean age 9.8 ± 3.0 years) were included in our study. Migraine was diagnosed
in 73.2% of patients. The remaining patients had tension-type headache (TTH).MEs
were reported in 70.3% of patients. Lower limb pain, motion sickness and abdominal
migraine were the most common MEs. Many patients complained more than one ME (30.6%
of the sample). No statistically significant effect was found between headache
diagnosis and the presence of MEs (χ2=33.2; P=0.27). We found that high
frequency of headache was negatively correlated with the absence of MEs (p = 0.038;
CI: -0.856 – -0.024; OR: 0.644). As regard as the intensity of attacks, we did not
find any significant correlation with MEs.
Conclusions: The main results of the present study were: (1) MEs are a
very common clinical condition in our pediatric headache population; (2) the
presence of MEs shows a significant relationship with the frequency of attacks, but
not with their intensity.
P257
The Multidimensional Impact of Migraine in Adolescents Presenting to
Care
B.S. Aylward1, T.D. Nelson3, J. Kroner1, S.
Sullivan1, J. Kacperski2, H. O’Brien2, M.
Kabbouche2, A.D. Hershey2, S.W. Powers1
1Division of Behavioral Medicine and Clinical Psychology,
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;
2Division of Neurology, Cincinnati Children’s Hospital Medical
Center, Cincinnati, OH, USA; 3Department of Psychology, University of
Nebraska-Lincoln, Lincoln, NE, USA.
Objectives: To examine the broad based impact of migraine in adolescents
presenting to care.
Background: Pediatric migraine is one of the five most prevalent
childhood disorders in the U.S., affecting up to 10% of children and up to 28% of
adolescents. The functional consequences of adolescent migraine can be widespread
and have a negative effect on many domains of normal daily life. The use of an
integrated framework from a systems-based, contextual perspective can aid in
examining the dynamic relationships between migraine pain and its functional
consequences and help practitioners identify those patients whose pain has a
widespread negative impact.
Methods: A longitudinal, multi-method and multifaceted assessment of
migraine in a sample of adolescents presenting to a pediatric headache center was
conducted to identify 1) the baseline impact of migraine across several domains,
including physical and school functioning (e.g., PedMIDAS, school attendance,
functional disability) as well as sleep quality and 2) changes in functioning at
6-months after initiating biobehavioral treatment in a specialty care center.
Results: 115 adolescents participated in the six-month study to examine
baseline and 6-month follow-up functioning after initiating biobehavioral treatment.
Descriptive statistics of functioning across these domains will be presented and
also highlight components of the multidimensional assessment that are most sensitive
to changes in migraine parameters. Briefly, baseline physical functioning as
measured by the Functional Disability Inventory (range 0-60) had a mean of 9.98 (SD
= 8.40). There was a significant improvement in physical functioning at 6-months (M
= 7.55, SD = 6.82, p = .02). Mean PedMIDAS scores at baseline
suggested moderate disability (M = 44.04, SD = 42.81), which significantly improved
by the 6-month visit (M = 19.18, SD = 24.11, p < .001).
Conclusions: Increased attention and research into understanding the
broad impact migraine can have can aid in the development and implementation of
effective and sustainable interventions for adolescents presenting to specialty
care.
P258
GLUT-1 Deficiency Presenting with Hemiplegic Migraine
S.E. Calvert1, S. Mohammad1
1Department of Neurosciences, Royal Children’s Hospital, Brisbane,
Queensland, Australia.
Objectives: To describe a case of GLUT-1 deficiency manifesting with
hemiplegic migraine and absence seizures with good response to the Modified Atkin’s
diet.
Background: Glucose transporter-1 deficiency syndrome (GLUT1-DS) is a
treatable epileptic encephalopathy caused by mutations in the SLC2A1 gene resulting
in impaired glucose transport into the brain. Patients with GLUT-1 deficiency
typically present with seizures resistant to conventional antiepileptic drug
treatment. Paroxysmal dyskinesiaand movement disorders have recently been described
as part of the phenotype. The only effective treatment is the ketogenic diet.
Mutations in SLC2A1 have been reported in children with alternating hemiplegia of
childhood. A case report has documented migraine headaches and GLUT1-DS in two
related children, whose symptoms improved on the ketogenic diet1. Another
case report documented paroxysmal episodic dyskinesia, absence epilepsy and
hemiplegic migraines in a previously undiagnosed 25 years old woman2.
Methods: Case Study.
Results: We report the case of an 8 years old boy with a working
diagnosis of ataxic cerebral palsy who had a 3 year history of weekly headaches with
hemiplegia. These episodes lasted 20-30 mins at a time and were associated with
photopsia, pallor, nausea, phonophobia and photophobia. His mother, maternal uncle,
two maternal aunts and maternal grandmother had similar headaches, sometimes
associated with hemiparesis. He also had a history of blank episodes consistent with
absence seizures. He had upper motor neuron signs in the legs, ataxic gait, scanning
speech and an intention tremor. Previous investigations included two normal brain
MRIs, negative testing for mitochondrial point mutations and normal serum lactate.
CSF tested with the second MRI at 8 years of age showed a glucose of 2.0 mmol/L with
a paired plasma glucose of 5.6 mmol/L (CSF: plasma ratio 0.36). A provisional
diagnosis of GLUT-1 transporter deficiency was later confirmed by a missense
mutation in the SLC2A1 gene. He was started on the Modified Atkins Diet restricting
his carbohydrate intake to 25g/day but liberal fat intake. After three months on the
diet his headaches had resolved; his neurological signs - gait and tremor as well as
his cognition had improved. His headaches recurred when there were lapses in his
diet.
Conclusions: The spectrum of GLUT-1 DS is expanding. We draw attention
to an uncommon presenting symptom of hemiplegic migraine which resolved on treatment
but recurred with lapse in treatment.
P259
Juvenile Migraine and the Role of Autonomic Nervous System: A Clinical
Study
G. Giordano1, F. Brighina2, F. Consolo1, M.
D’Amelio2, V. Raieli1, G. Santangelo1, C.
Spitaleri1, F. Vanadia1
1Child Neuropsychiatry, ARNAS Civico, Palermo, Italy;
2Clinical Neurology, University of Palermo, Palermo,
Italy.
Objectives: Cranial Autonomic Symptoms (CAS) are frequently reported in
adult migraineurs, but the prevalence of CAS in children affected by primary
headaches is unknown. Recent studies suggest a role of nervous autonomic system in
the migraine by the involvement of trigemino autonomic reflex.
Background: We want to evaluate the prevalence of CAS during attacks in
a juvenile population with primary headaches and to study the correlation between
CAS and the main symptoms of migraine.
Methods: A total of 230 children suffering from headache (M 46 F64, aged
4–17) were enrolled in two years period. A short questionnaire investigating the
presence of CAS was administered to all children. The following CAS were included in
our study: conjunctival injection, tearing, palpebral oedema, nasal congestion,
rhinorrhoea, red ear, facial flushing, miosis, ptosis, forehead or facial sweating.
A second short questionnaire about presence of General Autonomic Symptoms (GAS),
including orthostatic hypotension, vasomotors, cutaneous and secretomotors symptoms,
gastrointestinal and digestive disorders, was administerd to 50 children migraineurs
CAS+ and 50 CAS-.
Results: 230 children (105 m, 125 f, aged 4–17 years [age10.7 ± 3.1]
were enrolled. In total, 198 children (86%) (94 m, 104 f) were found to be affected
by migraine with/without aura (Migraine without aura: 173 subjects (75.21%), mean
age 10.8 ± 3.1M89 (51.4) F 84 (48.6%); Migraine with aura: 25 subjects (24.79%),
average age 11.7 ± 2.8 M 5(20%) F20 (80%), and 32 (14%) by Other Primary Headaches
(primary stabbing headache, episodic and chronic tension-type headache). The
prevalence of CAS in headaches was: general population, 116/230 (50.4%);Other
headache 9/32 (28.1%);Migraine 107/198 (54.04%) Migraine without aura 89/173
(51.4%); Migraine with aura 18/25 (72%). CAS occurring more frequently in migraine
than in the other primary headaches (107/198 versus 9/32) p = 0.008). The most
common signs were facial flushing, red ear and conjunctival injection. Two or more
CAS were present in 68.2 % of patients. At the univariate analysis CAS were
significantly associated to the frequency of attacks (P<0.02) and aura
(P<0.05). GAS were more common in CAS+ group than CAS- group (76%>46% -
X2 8.33 p<0.01).
Conclusions: These findings indicate that CAS are rather common in the
course of pediatric migraine and prevalence is more significant than others
headache. The presence of signs associated to local vasodilatation, showes an
important activation of parasympathetic control on cranial vascular tone in this sub
group. The significative association of CAS with frequency of attacks and aura
suggests that activation of parasympathetic system has a role about of severity of
disease in pediatric migraine, supporting the role of the trigemino-autonomic reflex
in the pathophysiology of migraine. The frequency of GAS in CAS+ migraineurs may
mean a more significant general activation of autonomic system.
P260
Frequency of Magnetic Resonance Imaging for Pediatric Migraine Management in a
Tertiary Care Center
G. Barmettler1, N. Maleki1, A. Minster1, A.
Lebel1, L. Becerra1, D. Borsook1
1Anesthesia, Perioperative and Pain Medicine, Boston Children’s
Hospital, Boston, MA, USA.
Objectives: This study presents data on changes in the trend of using
magnetic resonance imaging in pediatric migraine management.
Background: Migraine is a common neurological disorder, which frequently
begins in childhood and extends into adulthood, affecting almost 8% of children and
adolescents. However, pediatric migraine has features unlike that of adult episodic
or chronic migraine as it may present without predominant head pain, occurring
bilaterally for shorter durations, as a variant of migraine, or as a “childhood
periodic syndrome” such as cyclic vomiting syndrome or confusional migraine.
Moreover, pediatric migraine is often under-diagnosed as young children may have
difficulty describing diagnostic characteristics of migraine, and diagnosis relies
on inference from observed behaviors. Often, there is concern of structural changes
or tumors in potential migraine patients, leading to a referral from primary care to
neurology and, as such, magnetic resonance imaging is suggested.
Methods: After obtaining approval from the Institutional Review Board,
we searched the electronic clinical charts of patients from 1996 to 2011. Using
search terms “migraine” and “migraine and MRI,” we employed the search query and
analysis tools on the institution’s electronic charts to determine the number and
trends for both of these search terms.
Results: The results show an exponential increase for both “migraine”
(R2 = 0.98356) and “migraine + MRI” (R2 = 0.97906).
Additionally, the number of patients diagnosed as a “migraineur” has dramatically
increased since 1996 (R2 = 0.8932). Counts for “migraine and MRI” were
normalized to the counts for “migraine” in each year, and that number was used to
calculate the percentage. These percentages suggest that MRI has been incorporated
more often in recent years. The incidence is around 25% to begin with in 1996, and
increases to above 30% in 2005-2007 and from 2007 to 2011 the incidence remains
around 35%, about 10% higher than the beginning in 1996 to 2005.
Conclusions: The number of migraine diagnoses and children seen at this
institution steadily increased since 1996. This increase is concurrent with the
increased use of structural MRI of the brain. There was a 10% increase of MRI with
pediatric migraine, despite increased scrutiny of health care expenses, insurance
regulations and clinical guidelines for use of imaging in evaluating migraine.
Presently, approximately a third of migraine patients seen at this institution
receive a MRI as part of their disease management, as compared to a fourth between
1996 and 2004.
P261
Alexithymia in Tension-Type Headache and Migraine in Children and Adolescents:
A Controlled Study with Celiac Disorder
V. Guidetti1, E. Salvi1, M. Di Tola1, A.
Picarelli1
Objectives: Main aim of the study is comparing migraine, CTTH and Celiac
disorder (CD) patients vs healthy controls in order to understand the role of
alexithymia in primary and secondary disorders. We have compared an organic disease,
such as celiac disorder, with migraine, since both diseases are chronic, and can
influence the personality in our little patients.
Background: Alexithymia is a term used to describe a disorder where
patients have difficulty in expressing their own feelings in words. It was initially
used to denote an adaptive style creating a tendency to develop psychosomatic
symptoms. However, a specific correlation between alexithymia and somatization could
not be satisfactorily established. Alexithymia is poorly studied in headache
disorders, but alexithymic traits have been evidenced both in migraine (1,2) and
tension-type headache (CTTH) (3). Alexithymia has been stated as both a primary and
stable personality construct and a secondary state that is created as a reaction to
medical illnesses.
Methods: They are 432 children, 165 males and 267 females, aged 8-16
years. Four groups have been enrolled: 50 migraine patients (30f,20m); and 82 CTTH
(65f,17m); according to ICHD-II; 100 CD (68f/32m); 200 healthy controls (104f,96m).
The Toronto Alexithymic Scale (TAS-20) has been self-compiled. Data analysis have
been performed considering the three factors of TAS (Factor 1: Difficulties in
identifying feelings; Factor 2: Difficulties in describing feelings; Factor 3:
Outside oriented thought;) plus the total scores. Data have been analysed by Student
t test for independent data calculated among the parameter values assessed in all
groups of patients. The p values £0.05 are considered significant.
Results: Migraine patients are statistically different by normal
controls for each of TAS factors, but they show higher scores than CD only in Factor
3. We did not found differences between migraine and CTTH.
Conclusions: Both Migraine and CTTH patients showed significant
alexithymic traits, but with a lower level than CD. The well-known organic basis of
CD opens intriguing questions on the differences with headache and the possibility
that alexithymia be a psychological reaction to chronic CD. Of interest, the role of
Factor 3 in headache patients that may suggest a primary personality
characteristics: the tendency to be more prone toward external stimuli than internal
ones. Alexithymia seems an important psychological factor involved in Migraine and
CTTH.
P262
Redefining Migraine without Aura in Children - A 7 Year Study Based on ICHD2
Diagnostic Criteria
M V. Francis
Headache and Neuroophthal, Teresa Eye and Migraine Centre, Cherthala, Kerala,
India.
Objectives: To document short duration activity affected headaches in
children without migraine diagnostic associated features and thus to redefine
migraine without aura in children.
Background: Studies show that migraine in children are of shorter
duration and when they present with recurrent activity affected headaches without
out associated features like nausea, vomiting, phonophobia or photophobia, diagnosis
can be a real challenge/ group 14.2 is applied (headache unspecified). This study is
to document such recurrent short duration activity affected throbbing /non throbbing
headaches in children without diagnostic associated features.
Methods: 7 year prospective cohort study. 1042 children, 5 to 15 years
old. Inclusion criteria- 1) recurrent short duration throbbing/non throbbing
headaches (unilateral/bilateral / unilateral spreading bilateral), 2) activity
affected (motionless/lie down/sleep off), 3) no nausea, vomiting, phonophobia or
photophobia, 4) common migraine triggers in this region of India precipitating them,
5) one family member suffering from ICHD2 1.1/1.2/1.6. 6) history, physical,
neurological and neuroocular examinations normal.
Results: Duration of headpain - 5 minutes to 45 minutes. Common regional
triggers - sun exposure, bus travelling, missing meals, strenuous physical exercises
and sleep disturbances. Family history - 83% mothers, 11% fathers and 6% siblings
suffering from ICHD2, 1.1/1.2/1.6.
Conclusions: A new definition of pediatric migraine based on above
findings will be extremely helpful for any clinician in a busy practice. Recurrent
activity affected headaches precipitated by known or regional migraine triggers and
with at least one family member suffering from migraine origin pain (1.1,1.2,1.6) in
the absence of another disorder, should lead one to consider the diagnosis of
migraine without aura in children.
P263
Sleep Disorders of Childhood and Adolescents Migraine and Episodic
TTH
V. Yildirim1, N. Öksüz2, S. Ayta3, G.
Güler1, F. Toros1, B. Tasdelen4, A.
Özge2
1Child and Adolescent Psychiatry, Mersin University School of
Medicine, Mersin, Turkey; 2Neurology, Mersin University School of
Medicine, Mersin, Turkey; 3Neurology, Maltepe University School of
Medicine, Istanbul, Turkey; 4Biostatistics, Mersin University School
of Medicine, Mersin, Turkey.
Objectives: In order to evaluate cross-relationship between primary
headache disorders and sleep disorders, we performed this tertiary clinical based
prospective study. We also aimed search the effect of psychiatric comorbidities
including attention deficit hyperactivity disorders (ADHD).
Background: There are some supportive data about the close relationship
between sleep disorders and primary headache disorders, especially migraine and
episodic-TTH.
Methods: This study performed in Mersin and Maltepe Universities
Childhood and Adolescent Headache Outpatient Department. All patients evaluated by
the Headache Specialist and ICHD-II headache diagnosis have been made. Also after
face-to-face psychiatric evaluation, if they had, DSM-IV diagnosis has been made.
All of the parents of patients filled Turkish translation of Pediatric Sleep
Questionnaire (PSQ)-the extended and Turkish validated version.
Results: Totally 102 patients with migraine (74.5%) or TTH (25.5%)
evaluated. Totally 68.6% of the children reported important sleep disturbances over
the cut-point of PSQ, not only migraine but also ETTH sufferers. Most important
subtype of sleep disturbances was breath problems like snoring, followed by
parasomnias and other sleep disturbances. Only 17.4% of the parent’s had been
reported some supportive data about ADHD over the test scores. There are close
relationship between migraine and sleep disturbances and ADHD, correlated with
headache frequency and severity.
Conclusions: Sleep disturbances are important problems both of children
and adolescents with migraine and ETTH. Sleep problems and headache disturbances
interacts each other’s. Both of them have important effect on life quality of the
kids. This comorbidity has to take into consideration both of management and coping
strategies.
P264
Atypical Presentations of Paroxysmal Hemicrania (PH) Are Common in Children and
Adolescents (C/A)
S. Jessel1, A.D. Rothner1
1Chilld Neurology, Cleveland Clinic Foundation, Cleveland, OH,
USA.
Objectives: To increase recognition of the various presentations of this
uncommon headache in C/A.
Background: PH was described in 1974, the diagnostic criteria were
published in 1988. It is one of the trigeminal autonomic cephalalgias (TAC). PH is
an Indomethacin responsive headache. PH is characterized by repeated attacks of
strictly unilateral, severe, short-lasting pain (2-30 min) occurring with autonomic
features and responds to indomethacin. Data concerning PH in children is scarce. We
investigated the clinical spectrum of PH in C/A to aid in earlier recognition and
treatment, thus preventing both exposure to multiple medications that are unlikely
to work and avoid prolonged suffering.
Methods: A retrospective chart review. IRB approval was obtained.
Subjects had multiple severe HA per day, unilateral location, again under 18.
Anthropometrics, medical history, HA location, pattern, course of treatment and
response were noted.
Results: Fifteen cases of possible PH were identified. We combined these
cases with 20 found in the literature. Female/male ratio was 1:1. Age of onset 7.4
years; the age of diagnosis 9.6 years. In these studies there were 10 typical and 25
atypical cases. We defined cases being “atypical” if they did not show complete
response to indomethacin or were responsive to other medications, had a stuttering
course, variably lacked autonomic symptoms or had a spontaneous remission. Seven did
not get relief on indomethacin. In four of the patients, the duration was more than
30 minutes. In three, the frequency was less than the usual average of 5 attacks per
day. In four patients, the pain was bilateral. In six patients, there were no
autonomic features. Typical and atypical cases will be presented.
Conclusions: There is a predominance of “atypical” presentations both in
our cases and those previously reported. PH may have a stuttering course with fewer
attacks, periods of remission, variable response to indomethacin and variable lack
of autonomic features. Our hypothesis is that there is an evolution to this
disorder. The clinical phenotype may not be fully expressed in C/A and only years
later manifests as the stereotypical picture seen in adults. This may relate to the
immaturity of the central nervous system in C/A, just as migraine varies with age in
terms of frequency, duration and symptoms. It is important to suspect PH in any
child that presents with multiple discrete short lasting headaches occurring in a
single day even if autonomic features are lacking. If no etiology is found or there
is no response to the usual symptomatic and preventive medications a trial of
indomethacin should be considered.
P265
Post Concussion Headache (PCHA) in Children and Adolescents
(C&A)
A. Leubitz1, A.D. Rothner1
1Cleveland Clinic, Cleveland, OH, USA.
Objectives: To determine the features of PCHA in C/A.
Background: Concussions are common in C/A. PCHA in C/A have received
scant attention. There are an estimated 1.6 – 3.8 million concussions annually in
the U.S. Many have PCHA. Details concerning types of HA, duration of symptoms,
imaging data, treatment and prognosis are needed.
Methods: (1) A literature review was performed. (2) We reviewed 67 cases
of PCHA seen 2010-2012. Data regarding age, sex, previous concussion, family history
of HA, and concussion were collected. In all the Glasgow coma scale was >13.
Results: Only three relevant studies were found these included 101
patients. Details were not adequately profiled. Our 67 patients were taken from a
total of 675 New HA patients seen during the same time. 39 were males, sports were
football, hockey, lacrosse and falls. In 28/64 the HA was immediate, in the others
it started after days or weeks. Types of HA include: episodic TTH and chronic daily
headache with superimposed migraine. Pure episodic migraine was rare. Imaging was
negative in all cases, save 3 who showed congenital abnormalities unrelated to the
HA or injury. Concussion symptoms include but are not limited to headache,
dizziness, irritability, anxiety, depression, photophobia, susceptibility to the
effects of alcohol, stubbornness, and memory and concentration impairment. Children
and adolescents are significantly more vulnerable to concussion injury because their
bodies, more importantly their brain and skull, are still developing.
Conclusions: This OPD sample demonstrates that HA following head
injuries are common. That even mild concussions result in prolonged HA which
interfere with school function. Data regarding management in the first 6 weeks is
lacking. If the HA has been present for >6 weeks, education, judicious use of
rescue medication, preventive medication, psychosocial support and lifestyle
approaches are useful. The prognosis is guarded and many HA last > 1 yr.
Additional prospective date regarding PCHA in C/A is needed. Agreement regarding
approach to these patients is lacking in the absence of such data.
P266
Treatment of Acute Pediatric Headache in an Outpatient Infusion Center:
Evaluation and Outcomes
D.T. Duggan1, M.D. Holick1, D.J. Lee1, D.
Lebron1
1Pediatric Neurology, Baylor College of Medicine, Texas Children’s
Hospital, Houston, TX, USA.
Objectives: 1. Identify pediatric patients with severe headaches and
their respective headache types per ICHD-II criteria whose headaches are refractory
to outpatient treatment. 2. Describe various IV medications and combinations used
for treatment of acute headache in children at Texas Children’s Hospital Outpatient
Infusion Center. 3. Describe adverse events reported. 4. Evaluate efficacy of IV
medications and/or combinations in treatment of pediatric acute headache 5. Identify
variables that may confound outcomes of use of IV medication management of pediatric
headache.
Background: Few treatments have been studied for use in treatment of
pediatric migraine or acute headaches in children.
Methods: Retrospective chart review of the electronic medical record of
patients seen and treated in the Headache Clinic at Texas Children’s Hospital. Our
success rate was defined as encounters where a 50% reduction in headache was seen.
Of these encounters, the most frequently used treatment combination determined which
of these treatments were most successful. Magnesium levels were not drawn pre or
post-infusion of magnesium. EKG was obtained pre and post-infusion of Droperidol.
Prior to any infusion in females of child-bearing age, urine HCG was obtained.
Results: There were 55 encounters, 46 which were unique patients. Of
these 46 patients, 14 were males, 32 were females. There were 28 encounters where
pain was reduced by 50% or greater. The most successful medication combinations used
in these encounters were: 0.9% normal saline bolus with valproate and Ketorolac, and
0.9% normal saline bolus with diphenhydramine, metoclopramide and valproate. Of the
most successful combinations, valproate was used most often. There was one
significant adverse event, trembling, assumed to be a side effect of Droperidol
infusion. 16 encounters were admitted to the hospital immediately after their
infusion center visit, due to no or inadequate response to treatment. The average
time of stay was 3 hours and 50 minutes. The longest stay was 6 hours and 46
minutes. The shortest stay was 55 minutes. In this cohort (of 46 patients), 31 were
on a daily preventative. 27 had a diagnosis of chronic daily headache; 20 had
symptoms of dysautonomia.
Conclusions: 51% of patient encounters saw a 50% or greater reduction in
headache. This suggests an alternative method for treatment of acute pediatric
headache other than the emergency room. Our clinic is in close proximity to the
infusion center, making this alternative treatment for our patients feasible. 29%
were admitted to the hospital. The average time of stay was 3 hours and 50 minutes.
This may be shorter in comparison to a typical ER wait and visit. The morbidity was
low, with only one significant adverse event recorded. Patients receiving infusion
had other variables that may have contributed to their outcome (e.g. frequency of
headaches, dysautonomia). Further research is needed to evaluate options in the
acute treatment of pediatric headache.
P267
A Mobile Application To Track Headache Events and Symptoms in
Adolescents
S.M. Sullivan1, J.W. Kroner1, B.S. Aylward1, J.
Kacperski2, H.L. O’Brien2, M.A. Kabbouche2,
A.D. Hershey2, S.W. Powers1
1Behavioral Medicine and Clinical Psychology, Cincinnati
Children’s Hospital Medical Center, Cincinnati, OH, USA; 2Neurology,
Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA.
Objectives: To examine the efficacy of an electronic diary to assess
headache frequency and associated symptoms in adolescents presenting to a tertiary
headache center.
Background: Headache diaries are typically used in both research and
clinical care to track headache frequency, duration, and associated symptoms.
Electronic headache diaries have increasingly been utilized as acceptable for
reporting daily pain and also limit the potential for recall bias associated with
retrospective ratings of pain parameters.
Methods: A mobile application (iMigraine) was developed in collaboration
by a team of researchers, clinicians, and technology experts to enable adolescents
to electronically enter and wirelessly transmit data about headache events and
associated symptoms. As part of a larger longitudinal study, subjects were prompted
to complete momentary assessments of pain occurrence headache events and associated
symptoms up to 3 times a day (morning, afternoon, and evening with a one hour window
to respond) for 45 consecutive days. Participants were incentivized per completed
prompt.
Results: A random sample of 40 adolescents (11-18 years old) meeting
ICHD-II criteria for migraine with aura or migraine without aura were enrolled. On
average, 39 out of 40 subjects completed at least one prompt per day. Subjects were
equally as likely to complete each of the three prompts during the day and adherence
to completing daily prompts was about 66%. Participants reported having a headache
on 49% of days they completed at least one prompt. On average, each participant
reported having 23 headaches during the 45 day period. Objective data on the 40
participants to be presented will include: 1) Descriptive analyses on each of the
headache measures summarized using daily means, variances and frequency
distributions; 2) Non-parametric survival curves for headache events to illustrate
the percentage of patients that report experiencing a headache on a given day for 45
days since the initiation of treatment; and 3) Demonstration of how data can be
presented in a statistical control chart to statistically evaluate clinical
processes in a prospective fashion.
Conclusions: Technology has the potential to transform treatments
provided to youth and their families by giving youth an attractive way to actively
participate in their own health care by recording health symptoms remotely. This can
allow for health symptoms to be assessed remotely and in “real-time” fashion. This,
in turn, can allow for increased patient-provider communication around response to
care, potential factors exacerbating or relieving pain, need to modify treatment
regimens, and/or feedback on symptom management that may significantly impact
individualized clinical care for pediatric headache.
P268
Variability in Adolescent Migraine Symptoms and Correlates of Individual
Symptom Variability
T.D. Nelson1, B.S. Aylward2, J. Peugh2, J.
Kroner2, S. Sullivan2, A.D. Hershey3, S.W.
Powers2
1Department of Psychology, University of Nebraska-Lincoln,
Lincoln, NE, USA; 2Division of Behavioral Medicine and Clinical
Psychology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;
3Division of Neurology, Cincinnati Children’s Hospital Medical
Center, Cincinnati, OH, USA.
Objectives: To systematically investigate daily variability in
adolescent migraine symptoms and its impact on clinical outcomes.
Background: Research and clinical practice on pediatric migraine has
typically used patient recall measures to describe symptoms. These reports can be
useful in reporting typical symptoms and their overall impact, but do not identify
clinically-relevant variability. Electronic momentary assessment measures hold the
potential to capture day-to-day and even within-day variability, facilitating
examination of the potential clinical impact. Research suggests that variability in
pain symptoms may be associated with pain-related impairment. We propose to
systematically investigate this with regard to pediatric migraine.
Methods: A mobile application (iMigraine) was developed by a team
comprised of researchers, clinicians, and technology experts that allowed
adolescents to wirelessly track momentary assessments of pain, stress, affect,
functioning, and energy level (fatigue) using the commercially available Apple iPod
TouchTM device.This longitudinal design was used to examine the
temporal sequencing of pain and its associated impact as well as cross-lagged and
causal modeling of these important constructs.
Results: A random subsample of 40 adolescents ages 11-18 presented to a
specialty care clinic completed ongoing and momentary assessments of migraine pain
and mood for 45 days. On average, 39 out of 40 subjects completed at least one
prompt per day. Subjects were equally as likely to complete each of the three
prompts during the day and adherence to completing daily prompts was about 66%. The
results will a) describe the day-to-day and within-day variability of key migraine
symptoms; b) examine the association between selected demographic variables (e.g.,
gender, age) and symptom variability; and c) explore the association between
individual variability and migraine-related disability.
Conclusions: Findings from the current study will help elucidate the
temporal, dynamic relationships and potential lagged effects between migraine pain,
behavior, and various psychological states. This study will further our
understanding of how adolescent migraine symptoms are experienced on a day-to-day
level and how fluctuations in those symptoms might impact clinical outcomes.
P269
A Review of Medications Prescribed to Pediatric Migraine Patients at Boston
Children’s Hospital
A. Johnson1, N. Maleki1, A. Lebel1, D.
Borsook1
1Anesthesiology, Perioperative and Pain Medicine, Boston
Children’s Hospital, Boston, MA, USA.
Objectives: The primary aim of this study was to determine the most
common medications prescribed to pediatric migraine patients at Boston Children’s
Hospital.
Background: Migraine is a common disorder in children, present as early
as preschool and affecting up to an estimated 23% of high school age patients. Many
are treated with over-the-counter medications such as acetaminophen or ibuprofen,
but prescription medication can be beneficial to pediatric patients. However, the
medications approved for treatment of pediatric migraine differ from those approved
for adult migraine, and a determination of the patterns of prescription to pediatric
patients has yet to be made.
Methods: Using the Boston Children’s Hospital Informatics for
Integrating Biology and the Bedside (i2b2) tool, searches were performed to
determine the most frequently prescribed medications for patients also diagnosed
with migraine, ages 2-17. The migraine diagnoses used were classical migraine,
common migraine, or unspecified migraine.
Once commonly prescribed medications were determined, searches were performed to
determine the number of patients prescribed various types of medication: tricyclic
antidepressants (amitriptyline and nortriptyline), anticonvulsants (gabapentin and
topiramate), triptans (sumatriptan, zolmitriptan, rizatriptan, and eletriptan),
cyproheptadine, butalbital with caffeine and APAP, and anti-nausea drugs
(prochlorperazine, ondansetron, metoclopramide, trimethobenzamide hydrochloride, and
promethazine). Results were categorized by age and gender of patients.
Results: Tricyclic antidepressants were the most frequently prescribed
medications (prescribed to 8.18% of migraine patients), followed by triptans
(7.21%), anticonvulsants (5.23%), cyproheptadine (2.83%), and butalbital with APAP
and caffeine (2.19%). Additionally, pediatric migraine patients were prescribed
anti-nausea medication with greater frequency than preventative or abortive
treatments (9.40%). Amitriptyline was the most commonly prescribed tricyclic
antidepressant (5.06%), and sumatriptan was the most commonly prescribed triptan
(4.72%).
It was found that for all medications but cyproheptadine, the highest rate of
prescription was in the oldest population, 17 years old. However, the highest rate
of cyproheptadine prescription was in the 4 year old population, at 8.54%.
Cyproheptadine also had the highest rate of prescription in a given age group and
gender, with 14.44% of 5 year old female migraineurs receiving the prescription.
Conclusions: Findings from this study indicate that pediatric
migraineurs are prescribed mostly tricyclic antidepressants and cyproheptadine as
prophylactic medication, and that sumatriptan is the most prescribed triptan for
pediatric migraine patients.
Unfortunately, the limitations of i2b2 only allow for comparison between medications.
Many patients in the system have data regarding their diagnoses but not their
medications, and so it is impossible to determine true rates of prescription using
the tool as we have here.
P270
Headache Caused by Cerebral Venous Dysfunction in Children
M. Abramova1, I. Stepanova1, M. Duminskaya1
1Neurology, Neurosurgery and Medical Genetics Department.
Laboratory of Child Cerebrovascular Disorders, Russian National Research Medical
University named after N.I.Pirogov, Moscow, Russian Federation.
Objectives: To define the role of cerebral venous disturbances in
children with different types of headaches.
Background: 1340 patients aged from 3 to 17 years who complained of
headache have been examined.
Methods: Transcranial Doppler (“BIOSS”, “SPECTROMED”), Transcranial
Color Coded Duplex (“Logic P-5”), Magnetic resonance imaging (MRI).
Results: All children with headaches were separated into several groups
according to the clinical and ultrasound findings: migraine headache (30%), tension
type of headache (26%), headache with increase or reduction of arterial pressure
(17%), headache caused by cerebral venous dysfunction (27%). Also there are cerebral
venous hemodynamic disturbances in each of these groups with different intensity -
35, 40 and 35 percents, respectively. The most evident disturbances of cerebral
hemodynamics were observed in children with structural cerebral abnormalities, such
as Chiari I abnormality, hypoplasia of the cerebral venous sinuses. Clinically
cerebral venous hemodynamic disturbances in children was characterized by headaches
(100%), nasal bleeding (60%), sickness and vomiting (40%), noise in ears (35%),
dizziness (30%), vegetative dysfunction, 1% of children had relative deafness, and
8% of children had tics (mostly of face muscles). All examined children complained
of headaches localized in the occipital and parietal regions, that arised during or
after night or a day sleeping. Increase of headaches occured after physical
exercises, and lessons at school. 60% of children had typical nasal bleeding, mostly
abundant and spontaneous as a “fountain”. Evident disturbances of cerebral
hemodynamics in straight sinus, great cerebral vein of Galen, cavernous sinus,
vertebral veins, basilar and vertebral arteries were observed. We worked out a new
approach of transcranial duplex scanning to visualize the cavernous sinus, with
determination of structures and features of venous blood flow. This approach
provides a good overview of forms and peculiarities of the hemodynamics of the
cavernous sinus. Venous outflow in deep brain veins (cavernous sinus, straight
sinus, great cerebral vein of Galen) was registered by ultrasonic Doppler and duplex
methods and were “markers” of disturbances in cerebral venous hemodynamics. A
correlation between TCD, TCCD and MRI data was found. The therapy has been
prescribed in accordance with the data of TDC and duplex scanning. Positive effects
were noticed after a prescription of the therapy at 85% of children.
Conclusions: Thus a venous outflow is stimulated and makes influence on
intracranial venous circulation. These estimation of cerebral venous hemodynamic are
of great importance in clinical manifestations, especially in children. Disturbances
of the cerebral hemodynamics, revealed by ultrasonic methods, determine the tactics
of advising patients (i.e. diagnosis and therapy) with different types of
headaches.
P271
Vestibular Complaints in Children and Adolescents Who Have Episodic Tension
Type Headache and Migraine
A. Özge1, G. Akdal2, S. Ayta3, N. Öksüz1,
G. Güler4, F. Toros4, B. Tasdelen5
1Neurology, Mersin University School of Medicine, Mersin, Turkey;
2Neurology, Dokuz Eylul UNiversity School of Medicine, Izmir,
Turkey; 3Neurology, Maltepe University School of Medicine, Istanbul,
Turkey; 4Child and Adolescent Psychiatry, Mersin University School of
Medicine, Mersin, Turkey; 5Biostatistics, Mersin University School of
Medicine, Mersin, Turkey.
Objectives: In order to determine and evaluate the frequency of
vestibular symptoms-vertigo, dizziness and motion sickness in patients with migraine
and episodic TTH in children, prospective cross-sectional tertiary center based
study were planned. Since Episodic TTH is a bridge diagnosis in this age group,
commonly converted or confused to migraine, both groups were studied.
Background: Headache and vertigo are two common, distressing and
potentially interrelated neurological complaints. The association of migraine and
vertigo is well recognized in adults. On the hand, vertigo is a frequent but under
evaluated complaint in clinical practice even in childhood and adolescence.
Methods: Children and adolescents who were admitted to Neurology and
Child-Adolescent Psychiatry departments with a complaint of headache were evaluated.
Patients, who were diagnosed as Migraine or Episodic TTH (ETTH) according to
ICHD-II, were given a questionnaire including questions about vertigo, dizziness and
motion sickness.
Results: There were 128 patients with migraine or ETTH without any other
medical problem, 87.5% of the patients were migraine and 12.5% were ETTH. Most of
the migraine and ETTH patients had vertigo (71.9%) and dizziness (40.6%) during
their headache attacks and 40.6% of the vertigo and dizziness complaints correlated
with head position and 37.5% did not. Vertigo and dizziness were triggered by
fasting, sleep disorders, computers game. Motion sickness was reported by 43.8% of
the primary headache patients and migraine and ETTH were highly correlated. There
was not any significant difference between migraine and ETTH patients in vertigo,
dizziness and motion sickness complaints. In other words, they were identical in
gender and age and in vestibular complaints.
Conclusions: Our results showed that vertigo and dizziness and motion
sickness were common in migraine and ETTH patients. Since there was not any
significant difference between migraine and ETTH, ETTH might be a prodromal ongoing
phase of the migraine, especially accompanied by vestibular complaints.
P272
Neck-Tongue Syndrome Manifesting in Childhood: A Case Report and Review of the
Literature
A.K. Tripathy1, L. Mishra2
1Pediatric Neurology, Blank Childrens Hospital, Des Moines, IA,
USA; 2Child Psychiatry, Blank Childrens Hospital, Des Moines, IA,
USA.
Objectives: To discuss a case of Neck-tongue Syndrome (NTS) affecting a
child, review literature summarizing the historical aspect, anatomy, pathogenesis
and treatment.
Background: The Neck-Tongue syndrome is an uncommon headache syndrome
characterized by brief stabbing pain in the neck (one side in the upper neck or
occipital region) accompanied by altered sensation (paraesthesia and numbness) in
the ipsilateral half of tongue aggravated by sudden neck movement. There are three
categories of NTS: idiopathic, traumatic or secondary (inflammatory or
degenerative). We have reported the idiopathic or uncomplicated NTS. There is no
anatomic connection between upper cervical spine and the tongue. However, a review
of anatomy helps in understanding the links between two which will be discussed. The
postulated theories for the mechanism are subluxation/compression and muscle spasm.
Inflammatory disease, myelopathy or degenerative disorder are to be excluded. The
treatment is generally conservative with limitation of motion and avoidance of
trauma, coupled with NSAIDs and judicious use of agents for neuropathic pain. Use of
cervical collar or postural training exercises in conjunction with patient education
may be beneficial in cases of idiopathic NTS.
Methods: Case study.
Results: A 13-year old boy who presented with symptoms of neck pain and
tongue numbness was seen in the clinic. Further history from parents revealed that
he had been experiencing symptoms since he was 4 years old. When he turned his head
to one side he used to feel “sharp” pain on left side of neck. The spells were
recurrent and the frequency varied with his activity level. For the last 3 years, in
addition to neck pain, he had been experiencing numbness on the left side of his
tongue. It lasted for a few seconds. Parents had also noticed that sometimes he felt
so numb in his tongue that there was alteration in his voice. There was no loss of
awareness during the spell. The neck and tongue symptoms were consistent from one
episode to next. There was no history of trauma or any cervical instability. He
denied any visual or vestibular complains. There was no history of headache, joint
pain or swallowing difficulties. Unenhanced and enhanced MRI of the brain and
cervical spine were normal. Normal cervical alignment was seen in the MRI without
any disc pathology. No abnormalities were visualized in cervical and upper spinal
thoracic cord. Patient was given a trial with cervical collar and exercise. There is
report of some improvement of his symptoms.
In the discussion, we reviewed the literature including the historical data and then
summarized the pathogenesis and treatment.
Conclusions: This case report illustrates the clinical presentation of
an uncommon condition in children. Clinicians should be made aware of this rare
condition as early recognition is essential for appropriate management and
prevention of unnecessary investigations.
P273
Significance of Continuous Performance Test in Children with
Headaches
K.-H. Lee1, S.B. Woo2
1Pediatrics, Hallym University, Seoul, Republic of Korea;
2Pediatrics, Hallym University, Seoul, Republic of
Korea.
Objectives: The study examines the continuous performance test (CPT) in
children with headaches. Headaches in children have known to be associated with the
difficulty in concentration or school performance. But limited data are available
for the measurement of attention deficit or changes of attention after treatment in
relation with pediatric headaches or CPT.
Background: The computer-based CPT was useful method for scoring the
degree of impaied attention in the children with attention deficit hyperactive
disorder. Children with reccurent headaches often reported impaired school
performance. So it was meaningful to apply the CPT for checking impact of functional
impairment of cognition or attention etc during or after headache attacks.
Methods: We enrolled 14 children and adolescents at Kangnam Sacred Heart
Hospital during March to August in 2012, suffering from primary headaches according
to diagnostic criteria of the international classification of headache disorders
(ICHD-II). The control group was 14 patients with ADHD and no history of recurrent
headaches.
All of them were assessed using advanced test of attention (ATA), one of CPT in
Korea, during the headache attacks and after medication for treatment.
Results: The auditory ADHD indexes (AI) of headache patients were as
high as that of control ADHD group. The visual and auditory AI of the headache
patients in some parts were improved after treatment.
Conclusions: During the headache attacks, attention of children with
headaches was as disable as ADHD patientsin the CPT. The patients showed
statistically improvement of clinical symptoms and AI aftertreatment. The CPT was
efficient test to assess the degree ofdisability and improvement after treatment in
attention of pediatric headaches.
P274
Metacognition and Migraine: A Monitored Research on Psychiatric Comorbidity in
Developmental Age
V. Guidetti1, E. Salvi2, A. Antonelli2, A. Lo
Noce2
Objectives: The purpose of this research is to evaluate the exhibition
of deficits in metacognitive processes in children with migraine.
Background: Metacognition in infants and adolescents with migraine is
scarcely studied.
In addition, scientific literature emphasizes the influence of metacognitive
processes over a specific number of psychiatric diseases such as anxiety and
depression.
Methods: EG 147 S., (100 Mwo; 35 TTH; 12 Mwa; m.a. 10.8) All the S.
respected the ICHD 2 criteria. CG (130 non-clinical S. m.a11.3y.o.), recruited in
schools. Recruiting citeria for CG:absence of migraine and psychic diseases, and of
previous psychotherapy.
Metacognitions Questionnaire for Children (MCQ-C) [2], adapted for
infants in ages between 8 and 13, in order to evaluate the positive and negative
convictions, the cognitive monitoring, anxiety and intrusive thoughts and the
Self-Administration Scale for Infants and Adolescents (SAFA) (3) in two versione: A
(Anxiety) ans D (Depression).
Results: Significant difference emerges between the monitoring and the
experimental group, regarding metacognition features. The results of SAFA test show
an important relation between migraine, anxiery and depression.
Anxiety features, related to Generalized Anxiety (GA), Social Anxiety (SA),
Separation and Loss-related Anxiety (ASP), School Anxiety (A_SCU), present a high
statistical signifiance (p < 0.001), while depression features showed a
satistical importance only in connection with Irritable Humour (HI) and Insicurity
(I) (p < 0.001), depression, Anhedonia and Apathy, Unsuitableness sensation (US),
Guilt feelings and Desperation (DISP) are not significant (p ≥ 0.05).
The intra-group variance analisys (ANOVA), doesn’t show any important element
connected to anxiety features; whereas in regard to depression onlu the UD feature
presents important differences between migraine without aura and tension migraine (p
< 0.035). The factors connected to metacognition, analyzed using the variance
analysis method, don’t show any statistical difference in regard to other migrain
subgroups (MWA, MWO, TTH) (p < 0.05).
Conclusions: Minor consciousness of its thoughts and a more evident
appearance of anxiety and depression in the EG. Cognitive and metacognitive factors
in the comprehension of psychiatric comorbidity in children with migraine are
relevant. Determining the meaning that a child confers to his intrusive thoughts,
which can compromise the quality of his life during the entire developmental
periodis higly usefull. We have compared an organic disease, such as celiac
disorder, with migraine, since both diseases are chronic, and can influence the
personality in our little patients.
P275
Unusual Primary Headaches of Children and Adolescents: Practical Tips for
Physicians
N. Öksüz1, S. Özal1, H. Fidanci1, S.
Karakiliç1, M.Z. Demirtas1, A. Özge1
1Neurology, Mersin University School of Medicine, Mersin,
Turkey.
Objectives: In this presentation eight rare known primary headache
disorders of children and adolescents have been given with practical clues for
physicians.
Background: Childhood and adolescent headaches somehow looks like
adulthood headaches but not known as its.
Methods: All of the cases have been selected from the archives of Mersin
University School of Medicine Childhood and Adolescent Headache Outpatient
Department database and discussed with literature.
This presentation cases diagnosed as retinal migraine, migraine with complex visual
aura, primary stabbing headache, abdominal migraine, vestibular migraine, hypnic
headache, hemicrania continua, benign exertional headaches.
Results: Tip 1. Unilateral unexplained reversibl visual field
disturbance can be a sign of retinal migraine especially in subject with migraine
equivalent or positive family history of migraine.
Tip 2: Unexplained complicated visual hallucination can be a sign of migraine with
aura after exclusion of epileptic syndromes and intracranial abnormality.
Tip 3: Unilateral short-lasting stabbing headache attacks without autonomic features
can be a sign of primary stabbing headache after exclusion of secondary causes.
Tip 4: Unexplained abdominal pain attacks of childhood and adolescents, even adults,
can be a sign of migraine, even abdominal migraine after exclusion of secondary
causes.
Tip 5. Headache associated vertigo attacks can be a sign of Vestibular Migraine,
especially in girls with a positive past history of migraine or family history of
migraine.
Tip 6: Sleep related short duration headache attacks can be a sign of Hypnic headache
after exclusion of secondary causes.
Tip 7. Unilateral sustained headaches at the same side of the head, associated with
cranial autonomic features, can be a sign of Hemicrania Continua after exclusion of
secondary causes.
Tip 8. Headache attacks with triggered by any specific activity such as excercise,
cough, sexual activity etc. can be a sign of Benign Exertional Headaches after
exclusion of secondary causes.
Conclusions: The differential diagnosis of unusual headaches in children
requires a systematic approach. All of the cases with atypical headache syndrome
requires excluding secondary causes of headache.
P276
Headache (HA) in Children and Adolescents (C/A) with Fibrous Dysplasia (FD) of
the Skull
D. Mowls1, A.D. Rothner1
1Cleveland Clinic Foundation, Cleveland, OH, USA.
Objectives: To determine the frequency of HA in C/A with FD of the
skull. To determine if the relationship is causal or incidental.
Background: FD is a disorder in which abnormal fibrous tissue gradually
replaces normal bone. It begins in children and adolescents, and may progress into
adulthood. It may be symptomatic or asymptomatic. It can lead to bone distortion,
expansion, and compression of nervous and vascular structures. The presentation is
dependent on the site of involvement and extent of expansion. Cranial monostotic FD
involves any bone(s) of the cranium, polyostotic FD involves at least one additional
area of the skeleton.
Methods: Data was collected by two methods. (1) A literature review of
C/A with FD of the skull. (2) A retrospective chart review of patients ≤18 years of
age at the Cleveland Clinic Foundation from January 2006 to June 2011 identified
with FD of the skull. Data was collected on clinical features, demographics,
neuroimaging, treatment, and outcome.
Results: Literature on C/A with FD of the skull is limited. A study of
28 children and adolescents with FD with a mean age of 11.4 at presentation was
reviewed. There were 17 boys and 11 girls. FD most often involved the orbital region
and the floor of the anterior cranial fossa as a continuous lesion. The frontal bone
(82%), sphenoid (71%) and ethmoid bone (68%) were involved most commonly. Cosmetic
complaints were present in 23 (82%). Symptoms were headache (25%), visual loss (7%),
proptosis (47%), or other cranial asymmetries (39%). All underwent surgery.
Resection of less then 90% of the FD was a significant predictor of disease
recurrence. Six cases had stenosis on the optic foramen, 4 of which had normal
vision. Of these 4, 3 with optic nerve compression underwent a prophylactic
unroofing of the optic canal. Two presented with impaired vision. One underwent
staged bilateral optic nerve decompressions and is stable. The second had
significant unilateral reduction in visual acuity and profound unilateral optic disk
pallor. 10 cases of monostotic FD were identified. Mean age was 12.8 at diagnosis,
with a 1:1 male to female ratio. Primary reasons for imaging were headache (60%),
vision abnormalilies (20%), nasal abnormalities (10%) and jaw expansion (10%). The
primary bones of involvement were the sphenoid (5), maxilla (3), ethmoids (1), and
occipital (1). Contiguous bone involvement was seen in 7 cases. Optic nerve
compression was present in 4 cases, all of which underwent surgery. None presented
with headache. 6 cases without associated symptoms underwent imaging for HA and were
incidentally diagnosed with FD. It could not be established that the FD caused the
HA in these patients.
Conclusions: We report 10 cases of monostotic FD in C/A. Diagnosis of
cranial FD is often incidental and discovered during imaging for HA. FD does not
cause headache, unless accompanied by associated symptoms such as nerve compression
or bony expansion and deformity. Patients presenting with headache as their only
symptoms should undergo conservative treatment with regular follow-ups. The use of
pamidronate is an option.
P277
Does Internet (I) and Mobile (M) Abuse Interfere with Headache and Somatic
Complaints (SC) in Adolescence (A)?
V. Guidetti1, R. Cerutti2, C. Valastro2, M.
Petescia2, F. Presaghi2
1Pediatrics and Child and Adolescent Neuropsychiatry, Sapienza
University, Rome, Italy; 2Psychology, Sapienza University, Rome,
Italy.
Objectives: Aim of our study is to verify if the abuse of that is
associated with more Headache and other SC.
Background: It is well known that A. use I and M for many h.x day.
Methods: The sample is composed by 764 students (M 396; F 368) (10-16
yo; m.a. 12,39; ds 1.01) of a borough near by Rome.
All the S. received a cluster of self reported questionnaire:
The sample was divided in Internet N-Abusers (<4 h x d.) and Abusers (> 4 h x
d); Mobile N-Abusers (<12 h x d with mobile switched on) and Abusers (>10 h x
d with mobile switched on) according to the Self reported Q.
Chi square Test and Anova was applied.
Results: Headache General (293S.): 145 S, 20,1% (70M; 75 F) referred at
least one attack of M (M. Mwa, Probable M) in the last year, 148 S. 20,3% (78M; 70
F) of TTH.
ABUSERS WITH HEADACHE /MIGRAINE: INTERNET 72/92 8 (p<0,001); MOBILE 247/304
(p<0,001)
No statistical difference between M and TTH, neither in Gender.
MPAS Results:
Inside the Abuser group M present more nausea (p<0.05) and Vertigo (p<0.01). F
more Daytime Sleepiness (P<0.05), Difficulties in falling asleep (p<0.05),
Night Awakeings (p<0.05), Stomachache (p<0.05), Lack of Appetite (p<0.05),
Food Intollerance (p<0.01).
Among headache suffers, females reported higher scores than males on the Addiction
Mobile Scale of SPQ (F: M= 21,80 – DS=10,35 vs M: M=20,70 – DS=9,83). Conversely
gender differences is not observed in the scores regarding Internet Addiction scale
of SPQ. (F: M= 22,59 – DS=10,78 vs M: M=23,33 – DS=10,36).
A positive and statistically significant correlation is highlighted between
Internet addiction (SPQ) and somatic complaints
(CSI) (r=,202 p<0.01), in particular with neurological (r=,179;
p<0.01), cardiovascular (r=,221; p<0.01), and gastrointestinal cluster
symptoms (r=,102; p<0.05), but not with those symptoms related to pain (r=,078;
p>0.05). Conversely, with regard to Mobile addiction a positive
and statistically significant correlation with somatic complaints is observed
(r=,088; p<0.05), especially with the symptoms related to pain (r=,126;
p<0.01).
Adolescents with M and TTH have highest level of somatic complaints in CSI versus non
sufferers (M:1,18; p<0.01) independently of sex but dependently on excessive use
of I and M.
Conclusions: I and M abuse deeply influenced Headache and Migraine in
Adolescence.
Internet and M Checking Q. (IMQ, Cerutti 2005)
M Abuse S (MPAS, Cerutti 2005). Both of them analyze use/ abuse of I and
M
Shorter Promize Q. (SPQ, Christo 2003). All the varieties of Addiction
risks.
Children Somatization Inventory (CSI, Walker 1992) focused on Somatic
Complaints (SC).
Headache Clinical Record. Based on ICHD-2, 2004.
P278
Medical Messages about Headaches in the Traditional Media. A History of
Glorification of High-Tech Therapeutic Approaches and Miseducation. Media
Observatory Alleanza Cefalalgici. How Media Tell Things
P. Rossi1,2, C. Tassorelli2, G. Nappi2
1INI Grottaferrata, Grottaferrata (Rome), Italy;
2Headache Science Center, National Neurological Institute C. Mondino
Foundation, Pavia, Italy.
Objectives: Alleanza Cefalalgici, (Al-Ce.), an Italian organization for
headache sufferers working for increasing awareness on headache, has creates a Media
Observatory (MO), a multidisciplinary team including headache specialists, patients
and journalists with the aim to study and analyze the information about headache
released by traditional media.
Background: 31% of EU citizens consider medicine as the most interesting
issue on news and 64% of the Italians declare to be interested in being informed on
scientific research. Traditional media are the most popular means for medical
information (61% of EU citizens watch regularly or occasionally TV programs about
health and science – Eurobarometer 2007). Media reports about medical issues may
influence general public, policy makers and health professionals. No study has ever
investigated how the traditional media inform about headaches.
Methods: MO monitored the 4 main Italian newspapers and the 6 national
traditional TVs, looking for information regarding headaches. In addition all Al.Ce.
members were invited to inform MO about headaches info/news released by other
sources. For every piece of information, MO evaluated: a) the form of presentation
b) the topic of the news and their c) relevance/usefulness, d) reliability/accuracy,
e) correctness/objectivity, f) comprehensibility. The study lasted six months and
was completed on November 2010.
Results: Forty pieces of information were identified in the study period
(80% from journals and 20% from television). 72.5% of the info were presented as
short news and 20% as in-depth news. 40% of the pieces analyzed were released by
journalists, 27.5% were integrated by specialists’ interview and 23% consisted only
in specialists’ interview. The majorities of the media information was about “new
therapies”(50%), followed by “general information” (13%), “basic research data”
(13%) and “patographies” (13%). The relevance, accuracy and correctness of media
information about headaches was rated as poor/very poor in 35%, 43% and 55% of the
pieces, respectively. The comprehensibility was almost always considered as
good.
Conclusions: The traditional media information about headache is
essentially limited to a sensationalistic and poorly objective glorification of
high-tech therapies creating unrealistic expectations in headache sufferers.
Traditional media dedicate space to popular medical topic such as the headaches but
they seem to do so without an educational project, rather following what the media
experts call a “fast thinking” or “fast coping” strategy.
P279
Hiccups as a Migraine Aura
P. Chaudhry1, D.I. Friedman1
1Department of Neurology and Neurotherapeutics, University of
Texas Southwestern Medical Center, Dallas, TX, USA.
Objectives: To report a case of hiccup as a migraine aura.
Background: The most common migraine aura symptoms are visual and
sensory. Prolonged or intractable hiccups have been well described in the
literature, and may be gastrointestinal, systemic or drug induced. Central nervous
system disorders are associated with intractable hiccups include brain stem lesions
such as vascular malformations, ischemia, or plaques of multiple sclerosis or
neuromyelitis optica1. There has been one case report of intractable
hiccups associated with migraine 2, however the patient had prolonged
hiccups which did not clearly precede his migraine attack.
Methods: A 24-year-old woman had episodic migraine without aura starting
at age 15. Her headaches worsened at age 17. She developed mild dysphagia and tongue
deviation was found on neurologic exam. MRI revealed a Chiari malformation. She
underwent posterior fossa decompression surgery with resolution of her neurological
deficits but she continued to have episodic migraines. A year later, she developed
hiccups which preceded her migraine attacks 90% of the time. Her hiccups lasted
30-60 minutes, and were followed by her typical migraine 30 minutes later. The rate
of hiccups remained constant during their duration. Her headaches were left-sided
and met ICHD-2 criteria for migraine. Her severe migraines lasted 2 hours and
occurred about 3 times a week.
Results: Intractable hiccups have been associated with various central
nervous system causes. Hiccups as a migraine aura has not been described. The
pathophysiology of hiccups is not well understood, but includes afferent, efferent
and central mediators 3. Many of these structures are also involved in
pathogenesis of migraine. The afferent limb includes the sympathetic chain, phrenic
and vagus nerves. The efferent limb (phrenic nerve) includes the complex interaction
between the brainstem and midbrain areas, including respiratory center, phrenic
nerve nuclei, medullary reticular formation, and hypothalamus1,3. The
central connection between afferent and efferent limbs seems to be a nonspecific
anatomic location between the cervical spine (C3 - C5) and the brainstem. Hiccups
have also been linked to phasic autonomic efferent activity4 and
migraineurs are prone to autonomic dysfunction5. GABAergic effects may be
involved. Cortical spreading depression, the likely pathophysiology of aura is
modulated by GABA receptors, and GABA agonists are frequently used as hiccups
treatment. Our patient satisfied the ICHD-2 criteria for migraine although hiccup is
not a stated aura symptom in the ICHD-2 classification. Her Chiari malformation was
unlikely related to her headaches, as her hiccups started after successful
decompression surgery.
Conclusions: Hiccups can present as a primary aura symptom in patients
with migraine.
P280
Effect of Anodal Transcranial Direct Current Stimulation Over the Visual Cortex
on Thermosensitivity Assessed by Quantitive Sensory Testing and Contact Heat
Evoked Potentials
T. Sasso D’Elia1,2, M. Fataki Likale1, S.L. Sava1,
V. De Pasqua1, J. Schoenen1, D. Magis1
1Headache Research Unit University Department of Neurology, ULg,
Liège, Belgium; 2University of Rome La Sapienza, Rome,
Italy.
Objectives: To explore the effect of anodal tDCS over the visual cortex
on thermal Quantitative Sensory Testing (QST) and Contact Heat Evoked Potentials
(CHEPs) in episodic migraine patients interictally and in healthy volunteers.
Background: We have shown that the visual cortex is hyperresponsive in
migraine between attacks because of a habituation deficit likely due to a decreased
preactivation level (1). Moreover, reciprocal interrelations were recently
demonstrated between the visual cortex and the trigeminal pain system (2, 3). Anodal
transcranial Direct Current Stimulation (tDCS) can increase the activity level of
the underlying cortex and thus, is able to increase VEP 1st block
amplitude and habituation (4).
Methods: We recorded 13 patients (EM, 22.1 ±3.7 yrs; 4M) suffering from
episodic migraine in interictal phase and 13 healthy volunteers (HV, 22.8 ± 2.9 yrs;
6M). Migraine preventive drugs were not allowed. Thermal QST was performed with an
ATS thermode (Medoc Ltd, USA). We determined cold and heat detection (CS, WS) and
pain thresholds (CP, HP) on the volar wrist and the forehead. For CHEPs we delivered
20 heat stimuli to the right wrist and forehead (53°C, ISI 10-25 s). CHEP N2-P2
component was recorded from Cz-Fz EEG activity and averaged in 5 successive blocks.
Both QST and CHEPS were recorded before and after a 15-min session of anodal tDCS
performed (anode over Oz, cathode on the chin at an intensity of 1 mA).
Results: Anodal tDCS of the visual cortex did not modify QST values in
neither group of subjects.
In HV tDCS significantly increased the percentage of habituation between
1st and 5th block of the CHEP N2-P2 component obtained
after stimulation of the forehead (p<0.05) and tended to increase the habituation
slope over the 5 blocks of averaging (p=0.08). Anodal tDCS had no effect on the
initial CHEP 1st block amplitude.
In EM, anodal tDCS did not induce any CHEP modification.
Conclusions: Anodal (excitatory) tDCS over visual cortex is able to
increase the habituation of forehead i.e. trigeminal Contact Heat Evoked Potentials
in HV. This suggests that the activation of visual areas is able to decrease
responsiveness of cortical generators of the thermonociceptive response and confirms
the functional link between vision and trigeminal pain processing. Such an effect
may not be demonstrable in migraineurs because the preactivation level of the visual
cortex is lower.
P281
Therapeutic Response to Cranial Peripheral Nerve Stimulation in Patients with
Chronic Refractory Primary Headaches
M. Volcy1, J.M. Solano4, J. Bastidas2, M.M.
Massaro3
1Neurology-Headache, Indocen Instituto De Dolor De Cabeza y
Enfermedades Neurologicas, Medellin, Antioquia, Colombia;
2Neurosurgery, INDEC Instituto Neurologico De Colombia, Medellin,
Antioquia, Colombia; 3Epidemiology, INDEC Instituto Neurologico De
Colombia, Medellin, Antioquia, Colombia; 4Neurology, Universidad de
Antioquia, Medellin, Antioquia, Colombia.
Objectives: To determine the efficay, safety and outcomes of simultanous
supraorbital and occipital nerve stimulation in patients with chronic primary
refractory headaches.
Background: Chronic migraine (CM) and New Daily Persistent Headache
(NPH) are chronic primary headaches (CPH) frequently related to treatment
refractoriness and low quality of life. In the last years it has been proposed
simultaneous supraorbital nerve (SON) and occipital nerves (ON) stimulation (NS)
posses higher efficacy than ON stimulation alone. Currently there is few experience
in Colombia and Latin America with the use of this therapeutic approach.
Methods: Observational study of a cohort of patients with chronic
primary refractory headaches (CPRH) that were subjected to SON and/or ON NS between
May 2010 and July 2012. We included all patients with at least six months of
follow-up after implantation who responded to a first month phase trial. Patients
must have been considered to be chronic, refractory according to AHS 2008, disabled
by the headache, and without uncontrolled neuropsychiatric disease. The surgical
procedure was done after a headache staff meeting. The results are presented with a
comparison of means and proportions for paired samples using non-parametric
statistics.
Results: 15 Patients were subjected to NS in the study period; 14 met
the inclusion criteria. The average age was 41 years (SD: 8.8); 57.1 % were women.
The 85.7 % of the patients had chronic refractory migraine (CRM) and 14.3 % NDPH.
The average evolution time was 16 years (SD: 11.1); before the procedure the average
abortive treatments used was 21 (SD: 3.4) and 19 preventive medications (SD: 4.4);
only one patient had no criterion of analgesics overuse. Half of the patients had
associated anxiety or depression. 78.6 % of the patients showed global improvement,
wich was clinically and statistically significant. Before surgery, except one
patient none of the subjects had headache (HA) free days or HA free hours per month;
after NS, half of the patients reached at least three hours HA free/day (on average
6+3 hours) and at least five days HA free/month (on average 9+4 days). Before
surgery, all patients had moderate to severe HA (VSA > 8, 71.4 % severe HA);
after NS, the 85.7 % of the patients significantly decreased HA intensity to 6 or
less; the average percentage of improvement according to VAS was 51% (SD: 20.2 %).
Similarly, the average percentage of subjective improvement was 55% (SD: 23.2
%).
Conclusions: Simultaneuos SON and ON NS can be an effective and safe
therapy for CPRH patients. Optimal selection of candidates and the successful of NS
therapy it is related always to an interdisciplinary team work. There is a need to
identify the profile of patients that can respond to this treatment.
P282
Hypoxic Preconditioning with Cobalt Chloride Attenuates the Orofacial
Pain
A. Luca1,2, T. Alexa1,2, A. Dondas2, G.D.
Andron2, A.L. Negru2, C.R. Bohotin1,2
1Departament of Pathophysiology, University of Medicine and
Pharmacy “Gr. T. Popa” Iasi, Iasi, Romania; 2Centre for the Study and
Therapy of Pain Iasi, Iasi, Romania.
Objectives: The aim of the study was to investigate the effects of one
dose versus 3 weeks CoCl2 preconditiong on orofacial pain test (OFT) in mice.
Background: Cortical spreading depolarization waves (CSD), massive
temporary neuronal depolarizations that slowly propagate through cerebral cortex
from brain injured tissue could cause hypoxia (1). Hypoxic injuries can be prevented
by preconditioning with cobalt chloride (CoCl2), a hypoxia mimetic, that stabilizes
HIF-1 (degraded in normoxic conditions) (2,3), possible through enhancing the
antioxidant status by the reduction of ROS/NO and by lowering NFkappaB DNA binding
activity and its regulated pro-inflammatory mediators (4).
Methods: Thirty-two BALB/c male mice were divided into 4 groups: 2 of
the groups received CoCl2 12.5 mg/Kg b.w. intraperitoneally – group CoCl2 acute
(single dose 1 hour before formalin injection), group CoCl2 chronic (multiple doses
daily for 3 weeks). 2 groups served as control (group S-acute & group
S-chronic), mice treated with saline in a dose /time manner similar with CoCl2
groups. The time mice spent grooming and rubbing the injected area was reported
separately for the two phases of the OFT. One-way ANOVA followed by Bonferroni’s
post-hoc comparisons tests were performed in statistical analyses.
Results: A single CoCl2 dose decreased the first phase of OFT (p =0.004)
with no effect on the second phase as compared with control group. Hypoxic
preconditioning with CoCl2 for 3w attenuates the pain on the second phase of the OFT
(p=0.041), but have no effect on the first phase when compared with control group.
In the first phase of OFT there was a significant difference (p=0.001) between one
dose analgesic effect (36.98%) vs. repeated dose of CoCl2 effect (1.28%). Although
in the first 3 hours after single CoCl2 injection, the motor activity (activity cage
and Rota rod tests) was significantly disturbed; in the preconditioning experiment
the motor activity recovered starting with the 14th day.
Conclusions: Our results demonstrate that CoCl2 exposure modulates
orofacial pain. Although a single dose of CoCl2 has no significant effect on the
inflammatory orofacial pain, the antinociceptive effect observed in the first phase
must be interpreted with caution as long as the motor coordination and activity were
disturbed. 3 weeks of CoCl preconditiong significantly increased the nociceptive
threshold for the orofacial inflammatory pain.Taken together our data shows that
hypoxia precondition in BALB/c mice has an analgesic effect on the inflammatory
phase of the OFT.
P283
Placebo tDCS Induces Acute Changes in the Endogenous mu-Opioid
System
M.F. DosSantos1, I.K. Martikainen1,2, T.D.
Nascimento1, T.M. Love2, M.D. Deboer1, J.K.
Zubieta2, A.F. DaSilva1,2
1Headache & Orofacial Pain Effort (H.O.P.E.), Department of
Biologic and Materials Sciences and MCOHR, School of Dentistry, University of
Michigan, Ann Arbor, MI, USA; 2Translational Neuroimaging Laboratory,
Molecular and Behavioral Neuroscience Institute (MBNI), University of Michigan,
Ann Arbor, MI, USA.
Objectives: We aimed to investigate the immediate effects of placebo
transcranial Direct Current Stimulation tDCS in the human endogenous mu-opioid
system.
Background: TDCS is widely used method of non-invasive brain stimulation
that has been proved to be safe and effective in patients with chronic pain
disorders, such as: central pain after traumatic spinal cord injury, fibromyalgia,
orofacial pain, and also in chronic migraine. Nevertheless, its mechanisms involved
in pain control as wells as its placebo components are not fully elucidated.
Although different neuroimaging techniques, using magnetic resonance imaging (MRI)
have been applied to investigate tDCS effects, positron emission tomography (PET) is
considered a more sensitive method to detect molecular changes in the central
nervous system function driven by non-invasive brain stimulation.
Methods: A total of nine healthy volunteers were recruited to this
study. All were right-handed, ages between 18 and 65 years old, with no history of
chronic pain (e.g. fibromyalgia or migraine) or systemic disorders (e.g. diabetes or
multiple sclerosis). The protocol included two PET scans for each subject, using a
radiotracer with specific affinity for µ-opioid receptors,
[11C]carfentanil. The first PET provided a baseline evaluation of the
regional mu-opioid receptor (MOR) availability in vivo
(non-displaceable binding potential BPND). Placebo tDCS was only applied
during the early phase of the second PET exam, using the primary motor cortex and
frontal cortex, the most common montage adopted for pain control.
Results: Placebo tDCS was associated with a decrease of
MORBPND, indicating a release of endogenous opioids, in the
periaqueductal grey matter (PAG), left thalamus and posterior cingulate cortex.
Conclusions: Although still preliminary, our results suggest that
clinical outcomes observed with tDCS can be, at least in part, related to placebo
tDCS-induced activation of the endogenous mu-opioid system.
P284
Thin Film Spectacle Coatings for the Treatment of Photophobia and
Migraine
1Ophthalmology, University of Utah, Salt Lake City, UT, USA;
2Neurology, University of Utah, Salt Lake City, UT, USA;
3Electrical and Computer Engineering, University of Utah, Salt
Lake City, UT, USA.
Objectives: To determine if thin film spectacle coatings may be used to
reduce photophobia, migraine frequency and migraine severity.
Background: Nearly all migraine patients report photophobia (light
sensitivity) during a migraine and many migraineurs report that light may trigger an
attack. Some patients are chronically light sensitive (1). The pathway that mediates
photophobia appears to involve intrinsically photosensitive retinal ganglion cells
(IPRGCs) and trigeminal afferents (2,3). These retinal ganglion cells do not require
input from photoreceptors to be activated by light and have been shown to be
responsible for circadian rhythm entrainment and the pupillary light reflex. As
such, these cells constitute a pathway separate from the visual pathway (4). IPRGCs
contain the chromophore melanopsin. Melnopsin has an action spectrum that peaks at
480 nm, in the blue-green region of the visible spectrum.
We used thin film technology to design a lens coating that when applied to standard
spectacles would function as an optical notch filter, blocking out the light that
activates IPRGCs. We hypothesized that wearing spectacles that integrated this
filter, subjects would experience less light sensitivity, fewer migraines, and a
decrease in headache severity.
Methods: This research was approved by the IRB and informed consent was
obtained prior to enrollment. We recruited 50 subjects who met IHS criteria for
migraine with or without aura and chronic migraine. We utilized two sets of glasses:
Our interventional glasses blocked light at 480 nm and our sham glasses blocked
light at 620 nm. Subjects were randomized to wear one set of spectacles for two
weeks. After a two-week washout period, subjects crossed over to wear the other
glasses for two weeks. Both the investigators and the subjects were masked as to
which glasses were being worn throughout the trial. Photophobia, migraine frequency
and migraine severity were measured using headache diaries, a photophobia
questionnaire, and the Headache Impact Test (HIT-6™). Analysis was performed on an
intention-to-treat basis. Primary outcome was change in HIT-6 induced by the two
pairs of glasses compared to baseline. Secondary outcome was improvement in headache
frequency and severity as measured by the diaries and questionnaires.
Results: Two patients have been treated with prototype filters and both
experienced dramatic improvements in light sensitivity, headache frequency and
headache severity. Because of this anecdotal success, we have initiated a
prospective, randomized, double-masked crossover study. This clinical trial is not
yet complete, but will be completed prior to the Annual Meeting. Results will be
presented at the Annual Meeting.
Conclusions: We hope to demonstrate that modulation of light at 480 nm
can be used prophylactically in the treatment of migraine and chronic daily
headache.
P285
Cutaneous Allodynia Influences the Analgesic Effect of Transcutaneous
Electrical Nerve Stimulation Therapy in Headache Sufferers
D. Salvino1, M. Curcio1, M. Trimboli1, R.
Paletta1, M.R. Mazza1, A. Quattrone1, F.
Bono1
1Neurology, University Magna Graecia, Catanzaro,
Italy.
Objectives: To test if cutaneous allodynia influences the response to
treatment with TENS in headache sufferers.
Background: Transcutaneous electrical nerve stimulation (TENS) therapy
has been reported to be effective in the management of headache symptoms. It has
been suggested that the presence of cutaneous allodynia decreases the response to
treatment with triptans in migraine.
Methods: One hundred and forty –five consecutive headache sufferers were
randomized to be treated either with real or sham TENS therapy. Cutaneous allodynia
and pain were assessed using 12 item allodynia symptom checklist (ASC-12) and 10 cm
–visual analogue scale (VAS), before the treatment and during the follow-up.
Patients were grouped in 2 groups according to cutaneous allodynia total score:
Group 1 consisted of 59 patients with a score from 0 to 5 (non-allodynic patients),
and Group 2 consisted of 86 patients with a score above 6 (allodynic patients). TENS
therapy was administered at the back of the head bilaterally for 30 minutes, three
times a day for two consecutive weeks. During the follow-up, all patients were
examined at 15, 30 and 60 days in order to evaluate the analgesic effect of TENS
therapy. Primary end-point was change in number of headache free-days (>50%).
Results: A significant change in number of headache free-days above 50%
was observed in 53 (49%) out of 108 patients treated with real TENS. Of these
patients thirty-seven respondents (82%) were non allodynic. While 47 (75%) out of
the 63 non respondents were allodynic patients. Only 2 (5%) out of the 37 patients
were responsive to sham TENS therapy. Of note, we observed that the analgesic effect
of TENS therapy lasted about 60 days in these patients.
Conclusions: Cutaneous allodynia influences the analgesic effect of
transcutaneous electrical nerve stimulation therapy in headache sufferers,
suggesting that TENS therapy may be useful in the short management of headache
sufferers without severe cutaneous allodynia.
P286
Combined Occipital and Supraorbital Neurostimulation for Chronic Migraine
Headaches: A Multicenter Retrospective Analysis of 171 Consecutive
Patients
K.L. Reed3, K. Will1, R. Bulger1, S.
Datta5, M.P. Rupert4, S.L. Linder2
Objectives: To present the results of a retrospective analysis of 171
consecutive patients with chronic migraine treated by combined occipital nerve and
supraorbital nerve stimulation (ON-SONS).
Background: In 1999 we introduced occipital nerve stimulation (ONS) as a
novel treatment for occipital neuralgia. Others extended the methodology to migraine
headaches with the results suggesting a lower response rate than that for occipital
head pain. Hypothesizing that the addition of supraorbital stimulation may improve
the results for chronic migraine, we developed the associated procedure and in 2009
reported positive results in a series of patients treated by combined ON-SONS.
Thereafter, we further perfected the methodology and to date have implanted combined
systems in over 300 patients. Here we report the results of a retrospective analysis
of 171 consecutive patients from 5 implanting specialists across 3 different
centers.
Methods: Between May 1, 2009 and April 18, 2012 our group implanted
combined ON-SONS systems in 171 patients. Following a review of the medical record,
each patient received a survey request. Included were scores for the Migraine
Disability Assessment (MIDAS) and a set of clinical parameters, including headache
frequency and severity, medication usage, and overall patient satisfaction.
Results: 162 patients (126 female; 34 male) responded to the survey. 24
were adolescents, ages 14 to 19. All suffered from chronic migraine that had failed
to respond to conservative management. The average time since permanent implant was
14 mo. 85% of patients reported over 50% improvement in HA frequency (HA days/mo)
and/or severity (VAS 0-10). The average HA days/mo decreased by 73% (27 to 7), and
the average severity of the headaches, when they occurred, improved by 59% (9 to 4).
50% saw virtually complete resolution of headaches (0-1/mo). 71% of patients
decreased medication usage by over 50%, and 38% were able to completely discontinue
all routine headache medications. The MIDAS score improved by 76% (avg 208 to 50).
87% felt the treatment to have been successful, and 93% would recommend it to
others. 93% of patients preferred the combined ON-SONS mode, as opposed to a mode
that stimulated only the ONs.
Conclusions: Combined ON-SONS provides effective therapy for some
patients with intractable chronic migraine headaches. The degree of responsiveness
reported here was markedly improved over that reported by most studies evaluating
ONS alone, including the large multicenter (Medtronic, St. Jude) study groups. The
data strongly supports the addition of SONS to ONS (alone) when evaluating these
patients for PNS therapy.
P287
Combined Occipital and Supraorbital Neurostimulation for Chronic Migraine
Headaches in Adolescents (Ages 14-19): A Retrospective Analysis of 23
Consecutive Patients
K.L. Reed3, S. Linder2, K. Will1, R.
Bulger1
1Presbyterian Hospital of Dallas, Dallas, TX, USA;
2Medical City Hospital, Dallas, TX, USA; 3Reed Migraine
Centers, Dallas, TX, USA.
Objectives: To present the results of a retrospective survey of
adolescent patients with severe, intractable chronic migraine treated with combined
occipital-supraorbital neurostimulation (ON-SONS).
Background: In 1999 we introduced occipital nerve stimulation as a novel
treatment for occipital neuralgia. Hypothesizing that the addition of supraorbital
stimulation may improve the results for chronic migraine, we developed the
associated procedure and in 2009 reported positive results in a series of patients
treated by combined occipital nerve-supraorbital nerve stimulation. Thereafter, we
further perfected the treatment methodology, and to date have implanted the combined
system in over 300 patients, including a growing series of adolescents.
Methods: Between December 14, 2009 and May 3, 2012 our group implanted
combined ON-SON stimulation systems in 23 adolescent patients. Following a review of
the medical record, each patient received a survey request. Included were scores for
the Migraine Disability Assessment (MIDAS) and a set of clinical parameters,
including headache frequency and severity, medication usage, overall patient
satisfaction, and patient preference for either the combined or single modality
therapy (ON-SONS vs. ONS).
Results: All 23 patients (14 female; 9 male) responded to the survey.
Their ages ranged from 14-19 (mean 16). All suffered from chronic migraine that had
failed to respond to conservative management. The average time since permanent
implant was 12 mo. 87% of patients reported over 50% improvement in HA frequency (HA
days/mo) and/or severity (VAS 0-10). The average HA days/mo decreased by 79% (29 to
6), and the average severity of the headaches, when they occurred, improved by 80%
(9 to 2). 76% saw virtually complete resolution of headaches (0-1/mo). 86% of
patients decreased medication usage by over 50%, and 57% were able to completely
discontinue all routine headache medications. The MIDAS score improved by 68% (avg
243 to 77). 87% overall felt the treatment to have been successful and all would
recommend it to others. All patients could have their stimulators programmed to
stimulate only the ONs or the combined ON-SONs. Almost all (95%) used both frontal
and occipital stimulation modes exclusively.
Conclusions: Combined ON-SONS provides effective therapy for some
patients with intractable chronic migraine headaches. The degree of responsiveness
reported here was markedly improved over that reported by most studies evaluating
ONS alone, including the large multicenter (Medtronic, St. Jude) study groups. The
data strongly supports the addition of SONS to ONS (alone) when evaluating these
patients for PNS therapy.
P288
Neuromodulation: Model-Based Control of Cortical Excitability in Early and Late
Aura Phase
M.A. Dahlem
Cardiovascular Physics Lab, Humboldt University Berlin, Berlin,
Germany.
Objectives: We investigated statistical properties in a computational
model to gain a dynamical understanding of spontaneous episodes of spreading
depression (SD) and we suggest a novel neuromodulation approach by model-based
control that prevents these episodes.
Background: SD is the key to the subtype of migraine with aura (MA).
Computational, mathematical, and animal models of SD have been extensively
investigated by many research groups. SD is a transient pattern forming cortical
state. During the course of SD, the ion homoeostasis is massively perturbed in the
cortex by initially seizure-like discharges, followed by a nearly complete depletion
of ion gradients across cell membranes. The recovery last several minutes.
Methods: We analyze spontaneous episodes of SD in computer simulations
of localized SD wave fragments formed in the gyrified human cortex obtained by
fMRI.
Results: The results supports the controversial idea that SD can have a
causal relationship with the headache phase in migraine. In particular three
predictions are discussed: (i) that the cascade initiating the pain phase depends on
a sufficiently large area instantaneously affected by SD, (ii) that SD in migraine
without aura (MO) is neither lasting long nor propagating far enough to cause
noticeably aura symptoms because the initial perturbation covers a large area, and
(iii) that only from a smaller ictogenic focus SD can break away and propagate as a
localized wave. This would also explain, why, on average, the headache is reported
to be less severe in MA than in MO.
Conclusions: Neuromodulation techniques that target SD waves must
stimulate in the early and late phase of SD with different protocols to individually
attack pathways of aura and pain formation.
P289
Safety and Efficiency of Supraorbital Transcutaneous Neurostimulation with the
Cefaly® Device for Headache Treatment: Outcome of a Prospective Registry on
2,313 Patients
D. Magis1, P. Rigaux2, J.-Y. Mignolet2, S.L.
Sava1, T. Sasso D’Elia1, J. Schoenen1
1Headache Research Unit. Department of Neurology, University of
Liege, Liege, Belgium; 2STX Med, Herstal, Belgium.
Objectives: The objective of this short survey was to assess the
satisfaction of patients using the supraorbital transcutaneous neurostimulator
Cefaly® for headache prophylaxis and to record their self-reported adverse
events.
Background: Supraorbital transcutaneous neurostimulation (STN) has
recently demonstrated its efficacy over sham stimulation in episodic migraine
prevention (1) but its safety and performance in larger cohorts of “all coming”
headache sufferers are unknown.
Methods: The adverse events (AEs) and willingness to continue STN
therapy were prospectively monitored in patients renting the Cefaly® device
(STX-Med, Belgium) to treat their headaches. The evaluation was performed at the end
of the rental period (40 or 80 days). Patients were coming from Belgium and France
which are countries where the Cefaly® device is available as OTC for rent and
sale.
Results: From September 2009 to June 2012, 2313 headache patients (1641
females, 672 males, aged 14-87 years) accepted to provide a follow-up after STN
treatment (by phone call and/or email). Basically, all of them had been contacted as
they had mentioned a regular triptan use prior to STN therapy; a majority was
therefore likely to suffer from migraine. Among the 2313 users, 53.4% were satisfied
with STN treatment and were willing to buy the Cefaly® device, while the other 46.6%
stopped the therapy. Ninety-nine patients (ie 4.3%) reported one or more AEs but
none of them were serious. A large majority (91%) could be anticipated and was
likely to be related to the stimulation, and for 9% the relationship with STN was
questionable (for example palpitations or panic attack during the night following a
session of STN). The most frequent AEs were local pain/intolerance to paresthesia
(47 patients, ie 46%), sleep disorders (mostly sleepiness/fatigue, sometimes
insomnia, 19 patients, ie 18.6%), headache occurrence after stimulation (12
patients, ie 11.7%) and local reactions related to STN (7 patients, ie 6.7%).
Conclusions: This registry of more than 2000 patients confirms that STN
is a safe and well-tolerated technique. More than 50% of patients wanted to buy the
device after the rental period, which emphasizes its probable effectiveness in a
majority of them.
P290
There Is No Venostenotic Idiopathic Intracranial Hypertension without
Papilledema in Headache Sufferers. Clinical Findings and CSF Pressure
Measurements
M. Curcio1, D. Salvino1, M. Trimboli1, M.R.
Mazza1, R. Paletta1, A. Quattrone1, F.
Bono1
1Neurology, University Magna Graecia, Catanzaro,
Italy.
Objectives: To determine the frequency and the clinical findings of
non-venostenotic idiopathic intracranial hypertension (IIH) without papilledema
(IIHWOP) in headache sufferers.
Background: Bilateral transverse sinus stenosis (BTSS) is common in
patients with IIH with papilledema. However, it is less clear whether BTSS is always
present in patients with IIHWOP.
Methods: In a prospective study from July 2010 to December 2012, 60
headache sufferers (51 men and 9 women, mean age 42 years, SD 13; mean BMI = 32, SD=
5) who fulfilled the diagnostic criteria for IIHWOP underwent 3D-PC MR venography of
the brain the day before lumbar CSF pressure measurement. All patients underwent
lumbar puncture (LP) in order to measure lumbar CSF opening pressure and to monitor
CSF pressure for 1 h through a lumbar needle.
Results: Cerebral MR venography displayed BTSS in 37 (62%) out of 60
patients with established IIHWOP. While, 23 (38%) patients had normal appearances of
both transverse sinuses. Comparing those patients with non-venostenotic IIHWOP vs
venostenotic IIHWOP, there was difference in CSF opening pressure and mean CSF
pressure. Moreover, chronic tension-type headache and tinnitus were more common in
non-venostenotic patients.
Conclusions: Our findings highlight that non-venostenotic IIHWOP may
occur in headache sufferers, suggesting that BTSS is only one of the contributing
factors in IIHWOP.
P291
Vertigo: Think Migraine
R. Rao1, S. Lal2, J. Sinacore3
1Department of Primary Care, Loyola University Medical Center,
Maywood, IL, USA; 2Department of Neurology, Loyola University Medical
Center, Maywood, IL, USA; 3Dept of Epidemiology and Preventive
Medicine, Loyola University, Maywood, IL, USA.
Objectives: This study aims to identify the clinical predictors of the
diagnosis of migraine associated vertigo(MAV) amongst a group of patients who were
referred for Electronystagmography.
Background: Vestibular cause is often suspected when vertigo is the
presenting symptom. Bedside testing and ENG (Electronystagmography) are commonly
used to diagnose vestibular causes of vertigo. When a vestibular cause is not found,
clinicians often navigate the maze of non-vestibular causes of vertigo. In this
scenario, one of the diagnostic possibilities that is worthy of consideration is
MAV. In the past decade, MAV has drawn research interest to establish its validity
as a clinical entity. This paper seeks to understand the clinical predictors of MAV
amongst patients with vertigo.
Methods: The study was a retrospective chart study at a tertiary health
center with electronic medical records. IRB approval was obtained. Data was
requested from a computerized data base of people who have had an ENG performed
between the time period of January 1, 2005 to December 30, 2010.
Of these, patient who were 18 yrs. or older with the presenting complaint of vertigo
were included in the study. 128 patients met the inclusion criteria. Clinical
diagnosis of MAV was gathered before ENG (stage 1), after ENG (stage 2) and at
follow up visit (stage 3). Those who were diagnosed with MAV at stage 2 were managed
with standard treatments for migraine, including abortive and/ or prophylactic
treatments. The clinical predictors evaluated were age, gender, duration of vertigo,
otic, neurologic and migraine associated symptoms at stage 1, ENG results,
audiometry and neuroimaging results (when available). In addition, Pre ENG and Post
ENG diagnosis of Migraine associated vertigo were studied as clinical predictors, to
determine if ENG results influenced the final clinical diagnosis of MAV.
A decision tree analysis was performed to identify predictors of diagnosis of MAV at
stage 3.
The follow up (stage 3) diagnosis was organized in two categories: MAV and other.
Using a technique known as Classification and Regression Trees (CART), an analysis
was conducted to predict the dichotomized follow up diagnosis from the fifteen
demographic and clinical variables mentioned above. The worth of the method is
determined by the degree of classification accuracy. Only two
of the fifteen predictors made it into the tree. 10-fold cross validation was done.
The overall classification accuracy was 85%.
Results: Diagnosis of MAV at stage 2 was the best predictor of diagnosis
of MAV at stage 3.
Age over 44 yrs. was the next best predictor of MAV.
Neither Migraine associated symptoms at stage 1 nor ENG results by themselves were
strong predictors of MAV.
Conclusions: When bed side testing yields unclear results and ENG is
performed in patients, it can be valuable in excluding peripheral vestibular cause
and reliably diagnose MAV. When peripheral vestibular cause is excluded by ENG,
vertigo by itself may be the only symptom of MAV.
P292
A Record of Retinal Artery Vasospasm with Transient Monocular Visual Loss with
Subsequent Headache
K. Kuroshima1, S. Kawabata1, S. Ura1, K.
Yoshida1, I. Ota2
1Department of Neurology, Asahikawa Red Cross Hospital, Asahikawa,
Japan; 2Department of Ophthalmology, Asahikawa Red Cross Hospital,
Asahikawa, Japan.
Objectives: In order to clarify the mechanism of development in this
case, we conducted this study.
Background: Transient monocular visual impairment with subsequent
migraine headache is known as retinal migraine. However, the characteristics of the
headache sometimes do not satisfy the criteria of migraine. It is also difficult to
confirm the dynamic vasospasm. We report here a case of headache observed with
retinal artery spasm.
Methods: A 29-year-old women who came to our hospital because of
transient monocular right visual loss. She had histories of typical aura with
non-migraine headache as well as typical aura without headache several times a year
for these 9 years. She had taken medication for pituitary microadenoma for 5 years.
One the day she came to our hospital, she felt blurry vision in her right eye
subsequent visual field constriction. The symptoms resolved completely after 5
minutes and then mild headache appeared. After the second episode of visual
symptoms, she visited our hospital. During the attacks her visual acuity was under
light perception. Her general medical and other neurologic examinations were normal.
Magnetic resonance brain imaging and angiography were normal.
Results: We recorded her fundus through a slit-lamp microscope and a
non-contact concave lens during the episode of visual loss. During the attack the
record showed narrowing of the retinal arteries and veins and disc pallor, and
relative afferent pupillary defect (RAPD) was observed. In the late phase of the
attacks, we confirmed the reperfusion of the retinal circulation. After the episode
resolved, the retinal vessels, especially the veins, were dilated and the disc was
hyperemic.
Conclusions: RAPD indicates possible existence of mild optic neuropathy.
Therefore, her visual symptoms may be due to not only retinal ischemia but also
optic nerve ischemia.
Her visual dysfunction was monocular and completely resolved followed by headache. We
surmised, therefore, that this case is diagnosed as retinal migraine, but failure to
accompany the headache does not satisfy the criteria of retinal migraine.
P293
Reduced Circulating Endothelial Progenitor Cells in Reversible Cerebral
Vasoconstriction Syndrome
1Department of Neurology, Taipie Veterans General Hospital,
Taipei, Taiwan Republic of China; 2Faculty of Medicine and Brain
Research Center, National Yang-Ming University School of Medicine, Taipei,
Taiwan Republic of China.
Objectives: To investigate the numbers of circulating endothelial
progenitor cells (EPCs) in patients with reversible cerebral vasoconstriction
syndromes (RCVS).
Background: The pathophysiology of RCVS remains elusive. Endothelial
dysfunction might play a role, but direct evidences are lacking. We hypothesized
that patients with RCVS might have a reduced capacity of circulating EPCs to repair
the dysfunctional endothelial vasomotor control.
Methods: We prospectively recruited RCVS patients (within 2 weeks of
disease onset) and healthy controls. Flow cytometry was used to quantify the numbers
of circulating EPCs defined as KDR+CD133+,
CD34+CD133+, CD34+KDR+
double-positive mononuclear cells. The mean flow velocities of middle cerebral
arteries and Lindegaard index (LI) in patients with RCVS were recorded via
transcranial color-coded sonography on the same day of blood drawing.
Results: This study recruited 23 patients with RCVS and 17 healthy
controls (age: 49.1±8.0 vs. 41.6±14.5 yrs, p=0.072; M/F: 4/19 vs. 4/13, p=0.702).
Patients with RCVS had reduced numbers of CD34+KDR+
(0.009±0.006% vs. 0.017±0.011%, p=0.026) and KDR+CD133+ cells
(0.031±0.015% vs. 0.043±0.022%, p=0.041), but not CD34+CD133+
EPCs (0.046±0.028% vs. 0.054±0.034%, p=0.395), in comparison with controls. After
controlling for age, the adjusted P values were 0.010 for
CD34+KDR+, 0.052 for KDR+CD133+, and
0.384 for CD34+CD133+ EPCs. The numbers of
CD34+KDR+ cells were negatively correlated with the LI
(r=-0.489, p=0.034).
Conclusions: Patients with RCVS had reduced circulating EPCs, which was
correlated with the severity of vasoconstrictions. Endothelial dysfunction might
contribute to the pathogenesis of RCVS.
P294
Head and Neck Cancer Masquerading as Trigeminal Neuralgia
C. Ugurlu1, L. Green1, S. Sahai-Srivastava1
1Neurology, University of Southern California, Los Angeles, CA,
USA.
Objectives: To describe 2 patients with head and neck cancer presenting
as Trigeminal Neuralgia (TGN) and to review literature of similar cases.
Background: Trigeminal Neuralgia is idiopathic in nature, the commonest
cause being arterial compression. There are no case reports of either tongue or
nasopharyngeal cancer presenting as TGN in literature.
Methods: This is a case report and review of literature.
Results: Case 1: A 54-year-old Caucasian man presented with 2 types of
severe right sided face pain for 2 years; a constant 3/10 pain with frequent
exacerbations radiating to the jaw, ear, right side of tongue and throat and a
second type of short –lasting sharp, stabbing pain on his face and jaw described as
10/10 triggered by chewing or talking. Neurological examination, routine laboratory
workup and MRI of brain were unremarkable. He was diagnosed with TGN and
glossopharyngeal neuralgia. Repeat brain MRI showed a loop of the PICA artery draped
across cranial nerve (CN) IX and the superior cerebellar artery draped across the
distal portion of right trigeminal nerve, before entering the Meckel cave. Patient
was referred to neurosurgery and had posterior fossa microvascular decompression of
CN V and IX. After surgery, he was pain free for a few weeks, but gradually the pain
recurred and escalated to severe intractable similar to the previous pattern and
distribution. Repeat brain MRI was unremarkable. Patient failed standard oral
therapy; he was unable to open his mouth due to pain. Ultimately, lesions in oral
cavity were detected by speech therapy; confirmed as carcinomas by biopsy. There
were no metastases on head and neck imaging. Patient was treated with chemotherapy
and surgery.
Case 2: A 77 year-old retired Chinese man presented with right sided face pain and
sensitivity while brushing teeth and eating especially in the morning for a year.
Past medical history was significant for double vision diagnosed as possible stroke
1 year ago and left foot drop diagnosed 4 months ago. Neurologic examination showed
hypersensitivity and allodynia on the right trigeminal nerve area in V1, V2
distribution along with a right 6th nerve palsy and left lower extremity motor
weakness especially on dorsiflexion. Babinski was positive on left side. Electro
diagnostic studies showed severe left sided peroneal neuropathy and a possible L5-S1
radiculopathy bilaterally. MRI of the brain was unremarkable except for multiple
periventricular white matter changes. He was treated with multiple medications
including gabapentin. Repeat brain MRI after several months due to continuous pain,
showed right posterior nasopharyngeal mass with extension to the cavernous sinus,
oral fossa, and parapharyngeal space. Biopsy of the mass confirmed nasopharyngeal
squamous cell carcinoma with invasion to the cavernous sinus. Patient was treated
with radiation.
Conclusions: Two cases are described in which carcinoma was masquerading
as trigeminal neuralgia. These cases have some atypical features and were not
responsive to any of the treatment given. Brain imaging for trigeminal neuralgia
should emphasize the oropharynx and nasopharynx.
P295
Potential Reduction in Headache Rate and Cost of Care Following Lumbar Puncture
at a Single Tertiary Care Hospital
Y. Dakka
Neurology, Henry Ford Hospital, Detroit, MI, USA.
Objectives: To determine the rate of post-lumbar puncture headache at a
tertiary care hospital using standard 20-gauge Quinke needles and the potential
cost-savings of switching to a Sprotte needle.
Background: AAN guidelines recommend the use of Sprotte needles because
of lower rates of headache following lumbar puncture in randomized trials.
Methods: We retrospectively reviewed the charts of all patients who had
a lumbar puncture in the outpatient neurology clinic at Henry Ford Hospital in
Detroit, Michigan between January 2004 and December 2005. Baseline data collected
included demographic features, medical history, weight, and antithrombotic use.
Outcome data included occurrence of headache, back pain or epidural hematomas within
two weeks of the procedure. Rates of headache, back pain, and epidural hematomas
were calculated. Costs associated with the use of the current system were compared
with the projected costs of switching to a Sprotte needle system. Historical
literature for headache rates was used for the Sprotte needle system.
Results: 274 patients underwent lumbar puncture (62% women, mean age
55). Of these, 38 (14%) had a post-lumbar puncture headache; 12 patients were
admitted for a total of 21 hospital days. There were three days of hospitalization
for back pain. No patients had an epidural hematoma. The rate of headache associated
with the Sprotte needle according to published literature is 4%. The total cost
associated with the use of the Quinke needle (including kit and care of the patient
with headache) was $64,327. The projected cost of using a Sprotte needle is $22,919.
The estimated cost-savings would be approximately $20,000 per year.
Conclusions: Our analysis indicates that in our institution use of a
Sprotte needle would potentially be associated with less adverse events and less
cost.
P296
Magnetic Resonance Angiographic Screening of Aneurysms in Migraine
M. Oh1, M. Kim1
1Department of Neurology, Seoul National University Hospital,
Seoul, Republic of Korea.
Objectives: The present study screens aneurysms in migraineurs using
magnetic angiographic (MRA) images to differentiate aneurismal migraine from general
migraine patients and to delineate fundamental characteristics.
Background: As brain neuroimaging technology has advanced, decreasing
morbidity from cerebral aneurysm to subarachnoid hemorrhage (SAH) has been
observed.It is still difficult to detect and properly deal with suspicious aneurysm
in migraineurs. These patients are asymptomatic prior to aneurisms growing to a
certain size, or they are hard to distinguish from general migraine patients.
Current aneurysm research is now trending towards describing unruptured aneurisms’
natural history and epidemiology. Headache including migraine in the case of
unruptured cerebral aneurysms may be caused by small hemorrhages involving the
nerve, destruction of the aneurismal sac, direct pressure on nerves or pain
structures or pressure on the adjacent free edge of the tentorium. Known risk
factors include age, female gender, smoking, hypertension, excessive use of alcohol,
having one or more affected relatives with SAH and autosomal dominant polycystic
kidney disease.
Given the uncertainty in the literature, we propose defining fundamental
characteristics of migraineurs who have had aneurysms that can discriminate them
from general migraine patients. The present study screens for aneurysms in
migraineurs using magnetic angiographic images. This allowed comparison and
estimation of detection rate, aneurismal features and outcome demographics between
the aneurismal migraineurs and non aneurismal migraineurs.
Methods: All 4,416 study subjects were interviewed and completed
self-reported questionnaires on headache. Of that group 1,773 were screened for
aneurysm by MRA. Detection rates of aneurysm, size, number, morphology and locations
were evaluated. Based upon MRA findings, subjects were grouped into aneurismal
migraineurs and those without aneurysm.
Results: The incidental aneurysm rate was 3.6% (63/1773). The mean age
was 56.0 years, with a higher proportion of women (p=0.005). The
average size of aneurysms was is 3.5 ± 2.13 mm, and none were ruptured. There was
proportionally more of anterior circulation than posterior. During follow-up all
patients were in good condition. Of the risk factors surveyed smokers were 37.5% of
males, 0% of female, while drinking was 12.5% of the males and 3.6% of the females.
Symptoms differing by aneurismal migraineurs include ‘pain location’
(p=.025), ‘double vision’ (p=.026),
‘aggravation by hormone therapy’ (p=.039) and ‘had a history of
migraine in youth’ (p= .021).
Conclusions: This study surveyed found that characteristics of
aneurismal migraineurs followed literatures descriptions of aneurysm sufferers
rather than migraine. The natural history of aneurysm can suggestive of influences
from the social environment and population based on gender. The findings of
different clinical characteristics warrant further study to be of predictive value
for screening incidental aneurysms in migraineurs.
P297
Non-Neuropathic Non-Stabbing Peripheral Face Pain: Masseter Myalgia
M.J.H.L. Mulder1, E.L.H. Spierings1,2,3
1Craniofacial Pain Center, Tufts University School of Dental
Medicine, Boston, MA, USA; 2Neurology, Brigham and Women’s Hospital,
Harvard Medical School, Boston, MA, USA; 3Neurology, Tufts Medical
Center, Boston, MA, USA.
Objectives: The purpose of the study was to describe the presentation of
face pain secondary to masseter myalgia and to review the studies related to its
treatment. The presentation is described on the basis of patients seen personally by
the second author. For review of the studies related to its treatment, an extensive
literature search was conducted.
Background: When peripheral in location, non-neuropathic non-stabbing
face pain is muscular in nature, originating from the muscles of mastication,
particularly the masseter muscles. The cause is a dysfunction of those muscles,
resulting in myalgia, leading to masseter tension or spasm, described in the
literature under a variety of terms.
Methods: For review of the treatment of masseter myalgia, we searched
the literature using PubMed® utilizing the following terms: orofacial muscle pain,
facial pain with masticatory hyperactivity, localized myalgia of the masticatory
system, masseter muscle pain and spasm, masticatory muscle pain, masticatory
myofascial pain, myofascial pain of the jaw muscles, myofascial pain of the
masticatory muscles, myofascial temporomandibular disorder, myogenous facial pain,
myogenous craniomandibular disorder, myogenous pain of the masticatory muscles,
myogenous temporomandibular disorder, temporomandibular disorder of myogenous
origin, and tendomyopathy of the masticatory musculature.
Results: Among the patients seen by the second author since 2009, we
identified 34 with master myalgia. The majority of them were women (88.2%) and their
average age at presentation was 44.6 ± 12.6 (S.D.) years. The median pain suffering
was 6.0 years (range: 0.2-34 years). In 85.3% the pain occurred daily and in 52.9%
it was bilateral. Chewing or eating made it worse in 50.0% and talking in 29.4%. On
examination, tightness of the masseter muscle(s) was present in 58.8% and tenderness
also in 58.8%. Studies related to the following treatments were found: self care,
physical therapy, laser therapy, dry needling, acupuncture, appliance therapy, and
pharmacotherapy, including botulinum toxin.
Conclusions: Non-neuropathic non-stabbing peripheral face pain mostly
affects women, generally occurs daily, and is equally often unilateral and
bilateral. Chewing, eating, and talking are the most common aggravating factors and
tightness or tenderness of the masseter muscle(s) is often found on examination. The
majority of the studies related to its treatment involve a relative small number of
patients involved and are not placebo- or sham-controlled.
P298
Coexistence of “Headache Attributed to Airplane Travel” and “Free/Scuba Diving
Headache”
F. Mainardi1, F. Maggioni2, C. Lisotto3, G.
Zanchin2
1Headache Centre, Division of Neurology, SS Giovanni e Paolo
Hospital, Venice, Italy; 2Headache Centre, Department of
Neurosciences, Padua University School of Medicine, Padua, Italy;
3Headache Unit, San Vito al Tagliamento Hospital, San Vito al
Tagliamento Hospital, Italy.
Objectives: The term “Airplane headache” (AH) refers to a recently
described form, whose attacks are strictly related to airplane travel, mostly to the
landing phase.
Background: We studied AH features in a large series of patients
(1).
Methods: Through a detailed questionnaire we identified, in a series of
85 AH cases, 9 patients suffering from headache attacks also occurring during free
or scuba diving.
Results: These patients (5 females, 4 males, mean age 37 years ± 12),
who complained of AH attacks during landing in more than 50% of their flights,
referred the occasional onset of jabbing, severe, unilateral headaches in the
fronto-temporal region during free or scuba diving. They described this headache as
presenting with the same features, as compared with that experienced during landing.
Equally, no accompanying symptoms were reported. Three patients free-dove, attaining
the maximum depth of 5-8 meters and six patients scuba-dove, reaching an average
depth of approximately 20 meters; the pain started shortly after the ascent,
reaching its peak in a few minutes. No concomitant airways disturbance was reported
during diving. In 8 cases the pain occurred in >30% of the dives; one patient
complained of the headache occasionally. Brain MRI, Angio-MRI, and cranial CT-scan
for sinuses were normal.
Conclusions: The coexistence of headache with peculiar, overlapping
features triggered by these different situations, landing and ascending after
diving, supports the hypothesis of a shared pathophysiological mechanism, i.e. the
rapid change of external pressure, which occurs in both conditions, not paralleled
with an adequate compensation inside the cranial sinuses.
P299
Periorbital Neuralgias - A 7 Year Study
F.M. Francis
Headache and Neuroophthal, Teresa Eye and Migraine Centre, Cherthala,
India.
Objectives: To document cranial neuralgias manifesting in the
orbito-periorbital region.
Background: Cranial neuralgias manifesting in the orbito- periorbital
region are not well studied. They can be confused with many other local
ocular/orbital disorders and diagnoses can often be missed and expensive
investigations ordered.
Methods: 7 year prospective study done in two South indian coastal
clinics. ICHD2 diagnostic criteria (group 13) applied in all. 32400 headache
patients were screened during this period. Age group 10 to 70 years.
Results: Head or facial pain attributed to acute Herpez zoster (8),
optic neuritis (7), ocular diabetic neuropathy (7), External compression headaches
(5), Central post stroke pain (5), Other terminal branch neuralgias (5), post
herpetic neuralgias (4), Headache attributed to ingestion or inhalation of a cold
stimulus (4), Cold stimulus headache (3), V1 trigeminal neuralgia (3), Persistent
idiopathic facial pain (3), Supraorbital neuralgias (2), nasociliary neuralgias (2),
Probable ophthalmoplegic migraine (2), Tolosa hunt syndrome (2), persistent
idiopathic facial pain (2), Nummular headache (2), Facial pain attributed to
Multiple sclerosis (1). Acute orbito-periorbital pain lasting from 3 days to 15
days, before the appearance of diagnostic signs, was the initial manifestation in
five of the above neuralgias (herpez, optic neuritis, diabetic neuropathy,
ophthalmoplegic migraine and Tolosa hunt syndrome). External compression
precipitated migraine with out aura headaches in 2.
Conclusions: Cranial neuralgias manifesting in the periorbital region
are rare. Five ominous periorbital neuralgias may initially manifest only with
moderate to severe pain and diagnostic signs appeared later. Diagnosing them by
applying ICHD2 criteria will definitely help in successful treatment and to avoid
unnecessary expensive investigations.
P300
New Onset Hemicrania Continua after Acoustic Neuroma Resection
K. Kalidas1, W. Levy2
1Neurology, University of South Florida, Tampa, FL, USA;
2Mental Health and Behavioral Sciences, James A Haley Veterans
Administration, Tampa, FL, USA.
Objectives: To describe a case of new onset hemicrania continua after an
acoustic neuroma resection.
Background: Hemicrania continua is by definition a unilateral,
continuous headache of moderate intensity with superimposed exacerbations of severe
pain accompanied, by at least one of the following ipsilateral to the pain:
conjunctival injection, lacrimation, nasal congestion, rhinorrhea, ptosis or miosis.
A complete response to Indomethacin is required for the diagnosis. The majority of
cases of hemicrania continua arise without an identifiable trigger. However,
secondary etiologies such as internal carotid artery dissection, brainstem stroke,
pineal cyst, head trauma, pituitary tumor, ipsilateral tumor of clinoid process at
base of skull, HIV infection, and lung adenocarcinoma have been reported.
Methods: Case report.
Results: Case:
A 73 year old woman with a history of hypertension presented with symptoms of
dizziness, difficulty with balance, numbness and weakness to the left hand and
hearing loss. MRI imaging revealed a large left sided acoustic neuroma which
compressed the left pons, cerebellar punduncle and cerebellar hemisphere requiring
surgical intervention. Two days post resection she developed a left sided headache.
She described a continuous headache in the left temporal and frontal region with
intermittent escalations of pain associated with left sided lacrimation and
rhinorrhea. Escalations of her pain with associated autonomic symptoms occurred 3 to
4 times per day, with some escalations lasting as long as 40 minutes. After 2 weeks
of treatment with oral Indomethacin 50mg twice daily, she reported resolution of her
headache and associated autonomic symptoms.
Discussion: In patients with hemicrania continua, functional imaging
studies have demonstrated activation of the contralateral posterior hypothalamus,
the ipsilateral dorsal pons and ventrolateral midbrain. The headache described in
this case presentation was likely precipitated by surgical intervention and residual
post-surgical changes involving the left pons. This case report demonstrates
anatomoclinical evidence of the involvement of brainstem structures in the
pathophysiology of hemicrania continua.
Conclusions: This study provides an example of new onset hemicrania
continua secondary to a structural pathology in the brainstem.
P301
Orofacial Pain Following Invasive Dental Procedures: A Dozen Cases
S. Dhadwal1, E.L.H. Spierings1,2,3
1Craniofacial Pain Center, Tufts University School of Dental
Medicine, Boston, MA, USA; 2Neurology, Brigham and Women’s Hospital,
Harvard Medical School, Boston, MA, USA; 3Neurology, Tufts Medical
Center, Boston, MA, USA.
Objectives: The purpose of the study was to describe the presentation of
orofacial pain following invasive dental procedures as well as the putative
mechanisms involved.
Background: Orofacial pain following invasive dental procedures, such as
tooth extraction, root-canal treatment, or occlusion alteration, is not uncommon.
Postoperative symptoms ensuing from such procedures, such as pain, sensitivity to
hot or cold, or numbness, generally resolve within a few hours or days. However,
sometimes pain persists at the site of the procedure or develops at another site and
may result in consultation of specialists other than dentists, particularly
neurologists.
Methods: Ten of the twelve patients presented here were seen by the
authors at the Craniofacial Pain Center of Tufts University School of Dental
Medicine. The remaining two cases were obtained from the literature; they were the
only cases generated by an extensive literature review.
Results: The patients in the cases presented range in age from 36 to 66
years; ten of them are women. The offending dental procedure was a tooth extraction
in six, endodontic treatment in two, anesthetic injection in two, prosthetic-tooth
placement in one, surgical adjustment of teeth in one, and professional dental
hygiene in one (one patient had two procedures: surgical adjustment of the teeth and
tooth extraction). The resulting orofacial pain was ipsilateral to the side of the
procedure and located on the left in eight and on the right in four. It involved the
cheek in seven patients, the jaw in four, the teeth/gum in three, the upper lip in
two, the anterior neck in two, and the ear, pre-auricular area, retro-auricular
area, temple, and side of the nose each in one. Examination revealed signs
suggestive of quantitatively-altered nerve function in four
(hypoesthesia or hyperesthesia) and of
qualitatively-altered nerve function in three
(allodynia, dysesthesia, or paresthesia).
Conclusions: Review of the cases suggests that orofacial pain following
invasive dental procedures, unless caused by local pathology, is either
musculoskeletal or neuropathic, resulting from muscle and nerve injury,
respectively. The muscle injury seems to be caused by the force applied during tooth
extraction and/or the wide and prolonged opening of the mouth or from an altered
occlusion causing strain on the muscles of mastication. The nerve injury seems to
mostly result from anesthetic injection and/or endodontic treatment. With
neuropathic pain, the pain tends to be limited in location and not necessarily
lancinating or burning in nature, while with pain of musculoskeletal origin, it
tends to be more widespread.
P302
Allergic Migraine and Migrainous Allergy
F.M. Francis
Headache and Neuroophthalmology, Teresa Eye and Migraine Centre, Alleppey,
India.
Objectives: To document allergic inflammations triggering migraine
without aura attacks and vice versa.
Background: It is documented that mast cell degranulation can promote a
state of excitation of trigeminal nociceptors and can activate a pain pathway
undelying migraine headache. It is also tempting to hypothesise that excitation of
trigeminal neurons can cause mast cells to degranulate.
Methods: Prospective cohort study spanning 8 years. 260 patients. age
group 10 to 50 years. ICHD2 migraine without aura diagnostic criteria applied.
Allergic disorders were diagnosed from symptoms, local signs and referral to
concerned specialists.
Results: Nasal allergy (allergic rhinitis) precipitated migraine without
aura (1.1) in 98 patients and probable migraines (1.6) in 33. 18 reported brief
migraine like attacks missing two criteria. Ocular allergy, both(seasonal and
perennial) triggered migraine without aura in 33 and probable migraine in 19.Scalp
allergy and bronchial allergy were reported by 8 and 7 respectively. Headache
started either immediately after allergic manifestations or just the subsidence of
allergic symptoms. 44 patients reported various allergic manifestations during the
course of their migraine episodes (migrainous allergy).
Conclusions: This study should yield better insight into the
pathophysiology of both diseases and an opportunity to treat both with a single
drug. This documentation of allergic migraine and migrainous allergy shows that
allergic inflammations increased the risk for migraine and vice versa. This
bidirectional association helps the clinician to explain the causative molecular
mechanisms and genetic origin of these two disorders in the most simple way to their
patients.
P303
CSF Leakage Might Be a Cause of Postrural Tachycardia Syndrome
(PoTS)
T. Mitsufuji
Neurology, Saitama Medical University, Moroyama Town, Saitama Pref,
Japan.
Objectives: To examine CSF leakage might cause postural tachycardia
syndrome (PoTS) or not.
Background: It is well-known that both CSF leak and postrural
orthostatic tachycardia syndrome (PoTS) causes postural headache. Both of them cause
postural headache that means they feel severe headache when they take upright
position. We experienced 3 CSF leak patients and one post-lumbar headache patient
from June 2011 to June 2012. We checked whether they are complicated with PoTS or
not.
Methods: We had 3 CSF leak patients and one post-lumbar headache patient
in our hospital from June 2011 to June 2012. We did Schellong test or head-up tilt
test to all of them in order to confirm to be complicated with PoTS or not before
starting the treatment of CSF leakage or post-lumbar headache. And after the symptom
disappeared we checked Schellong test or head-up tilt test again.
Three CSF leak patients were made a diagnosis with MRI or RI cisternography. And one
CSF leak patient is complicated delayed orthostatic hypotension (OH). All of them
were treated with bed rest and peripheral intravenous infusion of the isotonic
fluid. And they were completely recovered.
All of them were examined whether PoTS was complicated with or not by Schellong test
or head-up tilt test twice, before and after the treatment.
Results: One CSF leak patient was complicated with delayed OH. And
another 3 cases were complicated with PoTS. Delayed OH or PoTS were recovered after
the symptom disappeared.
Conclusions: CSF leakage might cause postural headache complicated with
PoTS.
P304
Headache Attributed to Refractive Errors and Refractive Migraines
F.M. Francis
Headache and Neuroophthal, Teresa Eye and Migraine Centre, Cherthala,
India.
Objectives: To document refractive errors precipitating migraine without
aura attacks.
Background: Headache attributed to refractive errors (ICHD2, 11.3.2) are
mild, frontal and in the eyes and associated with uncorrected / miscorrected
refractive errors. These errors can also trigger migraine attacks (1.1/1.6) in
migraineurs if visual task is prolonged.
Methods: 7 year prospective cohort study. 478 patients. age group 10 to
50 years. ICHD2 diagnostic criteria applied (1.1/1.6/11.3.2).
Results: Headache attributed to refractive errors were documented in 341
patients. Refractive migraines without aura were diagnosed in 137 patients. The
causative refractive errors were presbyopia (78), hyperopia (31), astigmatism (22).
Miscorrected errors triggered migraines in 6 patients. All of them were getting
migraine without aura attacks either at presentation or in the past when exposed to
the common migraine triggers in this region. All were given proper refractive
correction and 72, who came for follow up reported significant relief of their
migraines, both refractive and non refractive.
Conclusions: This study shows that uncorrected and mis corrected
refractive errors can cause mild frontal headaches in susceptible persons and can
trigger migraine without aura (1.1/1.6) attacks in known migraineurs.
P305
Primary Headaches Interfere with the Efficacy of Temporomandibular Disorders
Management
A.L. Porporatti1, Y.M. Costa1, J.
Stuginski-Barbosa1, P.C.R. Conti1
1Prosthodontics - Section of Orofacial Pain, University of São
Paulo - Bauru School of Dentistry, Bauru, São Paulo, Brazil.
Objectives: The aim of this cross-sectional study is to evaluate the
influence of Primary Headache (PH) on efficacy of a Temporomandibular Disorder (TMD)
conservative therapy.
Background: PH has an excitatory effect in myofascial and jaw pain
conditions and individuals with headache may experience more severe and frequent
symptoms of TMD and vice versa. However the relationship between these two entities
is not well established in literature yet. Some studies have shown that TMD therapy
reduces the complaint of headache in both intensity and frequency when treating
articular and muscular pain related to TMD, nevertheless, to the best our knowledge,
the impact of PH on TMD therapy efficacy has not been published yet.
Methods: This study performed 1200 evaluations in medical records from
an orofacial pain clinic in University of São Paulo, Brazil. The sample was composed
of 400 medical records divided into 4 groups: I) Muscular TMD through AAOP criteria
(n=64); II) Muscular TMD + PH based on International Headache Society (IHS)
fulfilling the criteria for migraine and/or tension-type headache (n=48); III)
Muscular TMD + Articular TMD through AAOP criteria (n=173); and IV) Muscular TMD +
Articular TMD + PH (n=115). All groups had undergone a conservative TMD therapy for
three months with a rigid acrylic upper full coverage stabilisation appliance and
counselling for habits and behavioural changes. No specific headache management was
done. Current pain intensity was investigated according to self-reported pain on
Visual Analogue Scale (VAS) at baseline and after three months of TMD therapy. The
results were analyzed with repeated measures ANOVA with a significance level of
5%.
Results: A conservative therapy with stabilisation appliance and
counselling for habits and behavioural changes were effective in the TMD pain relief
in all groups (p<0.05). Significant results revealed a better pain improvement
for group I (70.74%) compared to group II (46.32%) and for group III (66.44%)
compared to group IV (42.56%) (p<0.05).
Conclusions: This study could elucidate the important effect that
headache may have in the TMD management, and the approach of both pain conditions
together may promote a better pain improvement for patients.
P306
The Effect of Trigeminal Neurectomy on Cortical Spreading Depression in
Migraine Model Rat
R. Masuda1, J. Hamada1, E. Kitamura1, K.
Nishiyama1
1Department of Neurology, Kitasato University School of Medicine,
Sagamihara, Kanagawa, Japan.
Objectives: The objective of this study is to investigate both the acute
and the chronic effect of trigeminal neurectomy (TN) on cortical spreading
depression (CSD), and to elucidate trigeminovascular system function upon cortical
excitability.
Background: Migraine is a recurrent neurological disorder characterized
by throbbing headache associated with nausea, vomiting, photophobia and phonophobia.
The pathogenesis of migraine is still unclear, but many evidences indicate that the
migraine may depend on the activation and sensitization of the trigeminovascular
pain pathway. Also cortical spreading depression has important role in
pathophysiology of migraine with aura. Recent study suggested that CSD activate
peripheral and central trigeminovascular neurons. Another PET study of migraine
shown that photophobia is linked with visual cortex hyperexcitability. But
interaction of cortical excitability and trigeminovascular system is not fully
understood.
Methods: (For acute TN model) 6 rats were used. Male Sprague-Dawley
rats, weighing 350-600g, were anesthetized with isoflurane and ventilated
mechanically with 30% O2. The nasociliary nerve (NCN), a cerebrovascular
branch of the trigeminal nerve in the rat, was approached from the left orbit.
Parietal cortical blood flow (CoBF) was continuously monitored with the
laser-Doppler flowmeter. A hydrogen electrode was placed in the other parietal open
cranial window to measure direct current potential (DCP). CSDs were induced with
application of 1M KCl solution with the volume of 3µl on parietal lobe surface
through another open cranial window. DCP and CoBF were measured for 60min after
application of KCl to compare induced CSDs before and after the NCN neurectomy.
(For chronic TN model) 5 male rats were used for this experiment. They were
anesthetized and also underwent NCN neurectomy by the same mathod. CSDs were
triggered and measured in the same way one week after NCN neurectomy.
The CSD data were analyzed by paired-T test in acute TN model and unpaired-T test in
chronic TN model.
Results: In acute TN model, the number of CSD was decreased from 9.0 to
5.8, significantly (P < 0.05). In chronic TN model, number of CSD is
significantly less than sham operation, 9.0 vs. 1.0, (P < 0.01).
Conclusions: Both acute and chronic cerebral vascular branch of
trigeminal nerve neurectomy suppressed generation of CSD. This result suggests that
the trigeminovascular interaction may modulate cortical excitability in migraine
with aura.
P307
Modulation of Trigeminovascular Activity by Leptin: A Novel Antinociceptive
Mechanism?
M. Martins-Oliveira1,2,3, J. Hoffmann1, S. Akerman1,
P.J. Goadsby1
1Department of Neurology, Headache Group, University of California
San Francisco, San Francisco, CA, USA; 2Department of Experimental
Biology, Faculty of Medicine of University of Porto, Porto, Portugal;
3Institute for Molecular and Cellular Biology (IBMC), University
of Porto, Porto, Portugal.
Objectives: To study the effect of acute administration of leptin on
neuronal firing in the trigeminocervical complex (TCC) in response to dural
electrical stimulation of the middle meningeal artery (MMA).
Background: Fasting, by skipping meals for example, is a recognized
trigger of headache in susceptible individuals. Leptin is a peptide hormone encoded
by the mouse obese gene (ob) and is mainly secreted by white
adipocytes. Plasma levels of leptin are regulated to reflect body energy stores:
levels of leptin fall in response to fasting and are increased in several models of
murine obesity. Leptin signaling decreases feeding and increases energy expenditure
by activating the long form of its receptor (Ob-Rb) in areas of the brain including
the brainstem, midbrain, hypothalamus, thalamus, and cortex. Interestingly,
circulating leptin concentration is important in regulating its receptor gene
expression. Furthermore, previous data indicates that migraine patients have lower
serum leptin levels in headache-free periods, compared to healthy individuals.
Methods: Adult male Sprague-Dawley rats were anesthetized with
pentobarbitone (60 mg.kg-1) and cannulated for measurement of blood
pressure and intravenous administration of supplementary anesthesia with propofol
(15-20 mg.kg-1.hr-1). The parietal bone was removed over the
MMA for electrical stimulation of the dura mater and electrophysiological recording
of second order neurons in the TCC was made using a tungsten electrode. Rats
received either rat recombinant leptin in a dosage of 1 mg.kg-1 or 3
mg.kg-1 (i.v.) dissolved in sterile water, or sterile water alone as
the control group. The effects of leptin on TCC neuronal activity in response to MMA
stimulation were recorded.
Results: Leptin 1 mg.kg-1 significantly reduced cell firing
in response to trigeminovascular activation within the TCC (p <
0.05). This effect reached a maximum inhibition of nearly 13% at 45 minutes
post-infusion of leptin. Infusion of leptin 3 mg.kg-1 and sterile water
alone had no significant effect on MMA stimulation-evoked firing.
Conclusions: The data show leptin at 1 mg.kg-1 inhibits
stimulus-evoked trigeminal activity, which might explain, in part, why fasting, a
condition characterized by low levels of circulating leptin, may have a role in
headache. The lack of effect of the higher leptin dose (3 mg.kg-1) may
represent the effect of an inverted U-shaped dose response. Studying the effects of
lower doses of leptin may dissect the dose-response effect of leptin in the
trigeminovascular system. Exploring the interaction between feeding physiology and
trigeminovascular nociceptive mechanisms may contribute to our understanding of this
very common trigger.
P308
Effective Connectivity in EEG alpha and Beta Bands during Visual Stimulation in
Migraine with and without Aura
M. de Tommaso1, S. Stramaglia3, G. Trotta3, M.
Pellicoro3, A. Salvati1, D. Mezzapesa1, E.
Vecchio1, D. Marinazzo2
1SMBNOS Department, University of Bari, Bari, Italy;
2Data Analysis, University of Ghent, Ghent, Belgium;
3Physics Department, University of Bari, Bari, Italy.
Objectives: A still unclear point in migraine pathophysiology regards
the origin of aura symptoms perception. The aim of this study was to evaluate
effective connectivity and information flow in high density ongoing EEG together
with Functional Magnetic Resonace Imaging under visual stimulation in the interictal
phase of migraine patients with and without aura compared to non migraine
controls.
Background: The results of functional and effective connectivity
represent a significant added value to neuroscience, since they allow to pinpoint
the temporal pattern of activation and information transfer between cortical areas
(1). Preliminary evaluation enabled to observe a different pattern of effective
connectivity in fast EEG rhythm in migraine with and without aura, employing an
ustructured visual stimulus and few recording electrodes (2).
Methods: EEG was recorded by 65 scalp electrodes from 20 migraine
without aura patients (MO), 20 migraine with aura patients (MA) and 10 healthy
subjects (control group (N)). Visual stimulus consisted in black and white
checkerboard gratings with two spatial frequencies (0.5 and 2.0 cpd) at 5 and 10Hz
(10 and 20 reversal/s). The same stimulus was employed to obtain FMRI in 10 migraine
with aura, 10 without aura patients and 6 controls. Non linear Granger causality and
transfer entropy were evaluated filetring the EEG in alpha and beta bands.
Results: The intensity of directed interactions in beta band, revealed
by Granger causality, increased in MA compared to both MO patients and controls,
with an information flow from the occipital to the frontal cortex. The FMRI showed a
larger recruitment of posterior cortical areas during visual stimulation, including
parietal and posterior temporal zones.
Conclusions: There were clear differences in ongoing EEG and FMRI under
visual stimulation, which emerged between the two forms of migraine, probably
subtended by increased cortical activation in migraine with aura, and compensatory
phenomena of reduced connectivity and functional networks segregation, occurring in
patients not experiencing aura symptoms. Clinical manifestation of aura symptoms may
be subtended by a peculiar neuronal connectivity pattern.
P309
Trigeminal Pain Is Increased by High-Fat Diet Induced Obesity in
Mice
A. Recober1, A.K.S. Luu1, H.L. Rossi1, S.D.
Kothari1, O. Lara1
1Neurology, University of Iowa, Iowa City, IA, USA.
Objectives: To assess trigeminal pain in obese mice using two objective
and quantitative behavioral assays.
Background: Obesity has been associated with multiple pain disorders,
including migraine. However, most animal models used to study mechanisms of head
pain have limitations and don’t assess the affective component of pain. We have
recently found that diet-induced obesity increases neuronal activation in the
trigeminal nucleus caudalis evoked by a low dose of capsaicin (Rossi et al., 2012).
This suggests that obesity may prime the trigeminal pathway making it responsive to
normally innocuous stimuli. To translate these findings to animal behavior, we used
an operant facial pain assay and conditioned place aversion to determine whether
obese mice are responsive to subthreshold doses of capsaicin.
Methods: We used C57BL/6J mice fed high-fat or regular diet. In the
operant facial pain assay, water-deprived mice have to place their face against a
thermal painful stimulus in order to access water. We measured the number of licks
at the water bottle. Mice were tested before and after facial application of
capsaicin cream (0.025%). The conditioned place aversion test consists of two
connected compartments with different tactile cues. During the two preconditioning
sessions, mice were allowed to freely explore the apparatus. Conditioning occurred
on the next two consecutive days. In the morning, mice received bilateral saline eye
drops and were confined to one of the compartments. In the afternoon, mice received
bilateral capsaicin eye drops (0.1% or 0.01%) and were confined to the other
compartment. On day 5, they were tested in the apparatus with free access to both
sides, without corneal stimulus. We determined the time they spent on the side
paired with the painful stimulus relative to the pre-conditioning baseline.
Results: In the operant facial pain assay, all mice exhibited normal
response to increasing temperatures, but capsaicin only had an effect on obese mice.
The number of licks after capsaicin cream application was less than half in obese
than control mice (p=0.01). Mice on regular diet did not respond to this dose of
capsaicin. In the conditioned place aversion test, all animals displayed aversion
for the side paired with 0.1% capsaicin. However, 0.01% capsaicin only induced
aversion in the obese mice, which spent 60% less time on the capsaicin-paired side
(p=0.01).
Conclusions: Taken together, our results suggest that diet-induced
obesity in mice causes increased sensitivity of the trigeminal pain pathway.
Furthermore, these studies investigate higher pain processing. This is an advantage
over models based on reflex responses to pain and will facilitate future
translational research.
P310
A Translational Approach to Studying Triptan-Induced Reversal of Established
Central Sensitization of Trigeminovascular Neurons
S. Akerman1, J. Hoffmann1, P.J. Goadsby1
1Neurology, Headache Group, University of California, San
Francisco, San Francisco, CA, USA.
Objectives: To study the effects of the migraine trigger, glyceryl
trinitrate (GTN), on the responses of noxious and innocuous dural and cutaneous
inputs on trigeminovascular neurons, and determine the effects of a triptan,
5-HT1B/1D receptor agonist, on these responses after established
GTN-induced trigeminovascular sensitization.
Background: Migraine is thought to involve activation and sensitization
of trigeminovascular neurons that engages nociceptive pathways resulting in head
pain. Existing animal models of prolonged central trigeminovascular sensitization
use dural inflammatory mediators, which is difficult to translate to patients. GTN
is a trigger of migraine in patients, causing a delayed attack after several hours,
and has been demonstrated to activate background firing of trigeminovascular
neurons. Its prolonged effects on trigeminovascular neurons and the subsequent
effects on dural and cutaneous inputs are unknown.
Methods: Rats were anesthetized with pentobarbitone (80
mgkg-1) and cannulated for measurement of blood pressure and
intravenous administration of supplementary anesthesia with propofol (15-20
mgkg-1hr-1-i.v. infusion). An established model of
trigeminovascular nociception was employed, which uses noxious and innocuous dural
and cutaneous stimulation, to activate the ophthalmic division of the trigeminal
nerve. These neuronal responses were measured at intervals, after a low (1.0 mg/kg,
sc) or high (10 mg/kg, sc) dose of GTN and followed for 3 hours. In some experiments
naratriptan (10 mg/kg, iv) was given after 2 hours.
Results: GTN caused sensitization of central trigeminovascular neurons
for up to at least 3 hours. Dural-evoked (F2.9,31.8 =
4.6, P < 0.01) and spontaneous background
(F4.3,47.8 = 5.2, P < 0.005)
neuronal firing in the trigeminocervical complex was significantly increased after
GTN (10 mg/kg), but there were no changes after lower dose GTN (1.0 mg/kg). Neuronal
responses to cutaneous noxious (F4,32 = 41.3,
P < 0.001) and innocuous (F4,32
= 3.3, P < 0.05) stimulation of the ophthalmic dermatome were
also significantly increased by only 10 mg/kg GTN. When naratriptan (10 mg/kg, iv)
was given after 2 hours, these responses were significantly reversed back to
baseline.
Conclusions: These data demonstrate that only the higher dose of GTN is
able to activate and sensitize central trigeminovascular neurons over a prolonged
period, for up to 3 hours, similar to the time interval of delayed migraine in
patients. GTN causes hypersensitivity to both noxious and innocuous dural and
cutaneous inputs. These responses to established central trigeminovascular
sensitization are all reversed by the migraine treatment, 5-HT1B/1D
receptor agonist, similar to migraine relief demonstrated in the clinic of
GTN-induced migraine. GTN-induced sensitization of trigeminovascular neurons
represents a translational model of the pathophysiological neuronal changes
occurring during migraine, and reflects the migraineurs response to triptan
treatment.
P311
Mitochondrial Dysfunction in a Rat Model of Chronic Migraine
N.T. Fried1, M.L. Oshinsky1
1Neurology, Thomas Jefferson University, Philadelphia, PA,
USA.
Objectives: To investigate if mitochondrial dysfunction contributes to
the development of chronic trigeminal pain.
Background: Impairment of mitochondria in migraine patients has been
observed. Clinical studies show that coenzyme Q10 (CoQ10) and riboflavin, both
thought to increase activity of the electron transport chain (ETC), are effective in
reducing migraine frequency. In light of these clinical observations, we tested a
rat model of chronic migraine for deficiencies in mitochondrial respiration. We then
used acetate, a mitochondria substrate known to induce headache in this rat model
and not in naive rats, to see if the observed deficiencies impacted acetate
utilization by the mitochondria. This model uses repeated infusion of an
inflammatory soup (IS) on the dura of awake rats to induce long-lasting
sensitization of the trigeminal system that outlasts the last infusion by >8
weeks.
Methods: To assess behavioral sensitization, periorbital pressure
thresholds were determined by applying a range of von Frey monofilaments. Rats that
had transitioned to chronic periorbital sensitivity had thresholds of ≤ 2.0g,
whereas naive rats have a threshold of 8-10g. To determine the effects of
mitochondrial respiration on the development of sensitivity, CoQ10 (200mg/kg) was
administered daily during the infusion period and acetate (20 mg/kg i.p) was
administered after the rats had transitioned. We used a qPCR gene chip to compare
mitochondrial gene expression in rats who received IS infusions vs. rats who
received saline infusions. Mitochondrial respiration was measured in brain slices of
the trigeminal nucleus caudalis (TNC), spinal cord, and cortex using the Seahorse XF
analyzer.
Results: Concurrent administration of CoQ10 was sufficient to prevent
the transition to chronically low periorbital thresholds. Administration of acetate
increased periorbital sensitivity by 50%. mRNA expression in the TNC, showed
significant changes in mitochondria related genes. Specifically, transcription of
ETC complex III and IV components were decreased and fatty acid metabolism enzymes
were increased. Transitioned rats had threefold less spare respiratory capacity than
naïve rats. Also, transitioned rats did not utilize acetate as a substrate as
efficiently as naïve rats. The addition of 1mM acetate increased respiration to only
105±6% of baseline OCR (Oxygen Consumption Rate) in transitioned rats, whereas in
naïve, acetate increased respiration to 124±7% of baseline OCR.
Conclusions: These data indicate decreased mitochondrial function in
rats with chronically low trigeminal thresholds within the TNC. Behaviorally,
administration of acetate as a substrate for mitochondria to transitioned rats
increased periorbital sensitivity while supplementing mitochondrial function with
CoQ10 throughout the infusion period prevented low periorbital sensitivity.
Respiratory analysis indicates a decreased spare respiratory capacity in
transitioned animals and a lesser ability to utilize acetate as a substrate.
Analysis of mRNA expression suggests that the decreased mitochondrial respiration
may be due to a malfunctioning of complex III and IV in the ETC.
P312
Neuropeptide Y Inhibits Neuronal Activation in the Trigeminocervical Complex:
Implications in Pain Processing in Migraine Pathophysiology
M. Martins-Oliveira1,2,3, S. Akerman1, P.J.
Goadsby1
1Department of Neurology, Headache Group, University of California
San Francisco, San Francisco, CA, USA; 2Department of Experimental
Biology, Faculty of Medicine of University of Porto, Porto, Portugal;
3Institute for Molecular and Cellular Biology (IBMC), University
of Porto, Porto, Portugal.
Objectives: To determine the effect of systemic administration of NPY on
neuronal activity in the trigeminocervical complex (TCC) in response to dural
electrical stimulation of the middle meningeal artery (MMA).
Background: Neuropeptide Y (NPY) is a neuropeptide abundant in the
central and peripheral nervous systems, acting on six G-protein coupled receptor
subtypes (Y1-6). It is involved in regulation of the cardiovascular
system, pain modulation, appetite control and circadian rhythm synchronization. NPY
is abundantly synthesized by neurons of the hypothalamic arcuate nucleus, a key
brain area of energy homeostasis regulation, and is one of the most potent
orexigenic peptides whose expression is up-regulated by fasting. NPY Y1
and Y2 receptors are present in human and rat trigeminal ganglia and NPY
is known to inhibit neurogenic dural vasodilation and plasma protein extravasation
via NPY Y1 and NPY Y2 receptors, respectively. Moreover,
migraine symptomatology can include changes in appetite. It is, therefore, important
to elucidate the role of NPY system in modulating trigeminovascular neurons to help
in our understanding of its potential role in migraine pathophysiology.
Methods: Adult male Sprague-Dawley rats were anesthetized with
pentobarbitone (60 mg/kg) and cannulated for measurement of blood pressure and
intravenous administration of supplementary anesthesia with propofol (15-20
mg/kg/hr). The parietal bone was removed over the MMA for electrical stimulation of
the dura mater and electrophysiological recording of second order neurons in the TCC
was made using a tungsten electrode. Rats received either human NPY in a dosage of
10 µg/kg, 30 µg/kg or 100 µg/kg (i.v.) dissolved in sterile water, or sterile water
alone as the control group. The effects of NPY on TCC neuronal activity in response
to MMA stimulation were recorded.
Results: NPY (30 µg/kg) significantly reduced cell firing in response to
trigeminovascular activation within the TCC (p < 0.001,
n=9). This effect reached a maximum inhibition of nearly 16% at
25 minutes post-infusion. Injection of NPY 100 µg/kg significantly reduced cell
firing (p < 0.05, n=7) showing 18% of
inhibition at 45 minutes. Infusion of NPY 10 µg/kg or sterile water alone had no
significant effect on MMA stimulation-evoked firing.
Conclusions: This study demonstrates that NPY dose-dependently inhibits
stimulus-evoked trigeminal activity. It is possible that disruption of the NPY
system through its role in the regulation of appetite might explain fasting as a
potential headache trigger in susceptible individuals. Understanding how energy
homeostasis is regulated in migraine, through the NPY system, and how this might
influence the modulation of the trigeminovascular activity will improve our
understanding of the pathophysiology of migraine.
P313
Dural Fibroblasts Play an Active Role in Headache Pathophysiology
X. Wei1, O. Melemedjian1, G. Dussor1
1Pharmacology, The University of Arizona College of Medicine,
Tucson, AZ, USA.
Objectives: Determine whether dural fibroblasts release factors that
promote nociceptive signaling from the meninges using preclinical models.
Background: Afferent nociceptive signaling from the meninges is proposed
to be a necessary event in the pathophysiology of many forms of headache. However,
the events within the meninges that drive afferent activity in meningeal nociceptors
are not clear. Fibroblasts are a major cell type in the dura but these cells have
traditionally been thought of as producing the extracellular matrix proteins that
constitute the dura and not as active participants in headache pathophysiology. The
purpose of these studies was to determine whether dural fibroblasts release factors
that activate/sensitize dural afferents and produce headache-like behavior in
preclinical models.
Methods: Dura mater was removed from male Sprague-Dawley rats and dural
fibroblasts were cultured for 3 days until confluent. Confluent fibroblast cultures
were then stimulated for 1 hour with vehicle or 5µg/mL lipopolysaccharide (LPS), an
activator of toll-like receptor 4 (TLR4). Cultures were washed to remove LPS and
conditioned media was collected for 5 hours. Fibroblast media conditioned with
either vehicle or LPS stimulation was applied to rat trigeminal ganglion neurons
in vitro that had been retrogradely labeled from the dura 7 days earlier.
Patch-clamp electrophysiology was performed to determine whether conditioned media
increased the excitability of identified dural afferents. A preclinical behavioral
model was also used where conditioned media was applied directly to the rat dura to
determine the presence of cutaneous facial and hindpaw allodynia.
Results: Application of fibroblast media conditioned with LPS to
identified dural afferents in vitro produced a significant increase in the number of
action potentials evoked by depolarizing ramp current injections, indicating the
presence of sensitizing agents in the media following LPS stimulation. Media
collected from fibroblast cultures stimulated with vehicle did not produce any
effect on action potential firing. Similarly, LPS-fibroblast media applied to the
dura of awake rats caused the development of cutaneous facial and hindpaw allodynia
that peaked at 2 hours and returned to baseline by 5 hours. Vehicle conditioned
media did not produce allodynia.
Conclusions: Fibroblasts stimulated with LPS release factors capable of
sensitizing and/or activating dural afferents indicating that they can play an
active role in the pathophysiology of headache. The identity of these factors is not
yet known but is currently being investigated. Although the current findings using
LPS as a stimulus are most applicable to bacterial infections of the meninges,
stimuli relevant to other forms of headache may also promote the release of
activating/sensitizing factors from fibroblasts. Knowledge of the role fibroblasts
play in headache pathophysiology may provide an avenue for novel therapeutic targets
for the treatment of headache.
P314
Abnormal Synaptic Morphology and Neuronal Ca2+-Homeostasis in
Migraine Mutant Mice
K. Eikermann-Haerter1, M. Arbel-Ornath2, K.
Kuchibhotla2, E.S. Yu1, C. Lattarullo2, D.
Thyssen2, N. Yalcin1, I. Rosen1, A.
Arreguin1, M. Climov1, F. Keles1, A.
Belcher2, B. Sengul1, A. Negro1, E.
Hudry2, M.D. Ferrari3, A.M. van den
Maagdenberg3, B. Bacskai2, C. Ayata1
1Neurovascular Research Laboratory, Dept of Radiology,
Massachusetts General Hospital, Boston, MA, USA; 2MassGeneral
Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston,
MA, USA; 3Medical Center, Leiden University, Leiden, The
Netherlands.
Objectives: To assess neuronal structure and intracellular
Ca2+-levels ([Ca2+]i) at baseline, during and
after CSD in transgenic mice for familial hemiplegic migraine.
Background: Familial hemiplegic migraine (FHM) is caused by
gain-of-function mutations (e.g., S218L) of Cav2.1. Excitatory
neurotransmission may be enhanced, and, in vivo, FHM1 mice show
enhanced susceptibility to cortical spreading depression (CSD). CSD, the
electrophysiologic event underlying migraine, is a transient disruption of membrane
ionic gradients that propagates across cortex.
Methods: In vivo 2-photon microscopy images of cortical
layers were obtained 5 weeks after intracortical injection of the genetically
encoded Ca2+-indicator Yellow Cameleon (AAV2-YC3.6), in female wild type
(WT) and S218L transgenic mice. YFP/CFP ratios were measured, and exact
[Ca2+]i can be determined because YC3.6 is a FRET based
indicator. SD was evoked by KCl (300 mM). Before and
after CSD, we assessed a cortical volume of 600x600x100µm
depth. During CSD, we performed single-plane timecourse movies
30-40 µm deep (Fig. 1).
Results: At baseline, [Ca2+]i was higher in S218L.
During CSD, [Ca2+]i abruptly increased by ∼3-fold, and then
declined to a plateau. The onset of calcium increase, peak and plateau
[Ca2+]i were higher in S218L, in both axons and dendrites.
Acute and transient structural changes of neurons during CSD (e.g. density,
diameter, or duration of dendritic beading) did not differ (Fig. 1, 2A).
We found structural differences in neuropil, at baseline and after CSD. At baseline,
the average area of an axonal varicosity was larger in S218L (A). Ten minutes after
CSD, the density of axonal varicosities increased, and their area decreased. The
percentage of mushroom type spines increased. In S218L, the diameter of dendritic
spine head increased (Fig. 2B).
Conclusions: FHM1 mutations increase [Ca2+]i at
baseline and during CSD, and alter axonal morphology as well as lasting structural
changes after CSD.
P315
Sleep Deprivation Enhances Susceptibility to Cortical Spreading
Depression
A. Negro2, J. Seidel1, E.S. Yu1, N.
Yalcin1, L. Shorser-Gentile1, I. Rosen1, A.
Arreguin1, V. Ramalingam3, N. Chamberlin3, P.
Martelletti2, M.A. Moskowitz1, C. Ayata1, K.
Eikermann-Haerter1
1Neurovascular Research Laboratory, Dept of Radiology,
Massachusetts General Hospital, Boston, MA, USA; 2Department of
Clinical and Molecular Medicine, Sapienza University, Rome, Italy;
3Division of Sleep Medicine, Dept of Neurology, Beth Israel Deaconess
Medical Center, Boston, MA, USA.
Objectives: To investigate the effect of sleep deprivation, a well-known
migraine trigger, on cortical spreading depression (CSD) susceptibility.
Background: Many factors that modulate migraine (e.g. sex hormones,
migraine prophylactic drugs) have been shown to also modulate in the same direction
susceptibility to CSD, the electrophysiologic event underlying migraine. Changes in
sleep rhythm and sleep deprivation are well-known migraine triggers. Sleep
deprivation modulates neocortical excitability both in humans and in animal models.
Sleep deprivation can facilitate the migraine chronification and trigger
attacks.
Methods: Acute sleep deprivation was induced for 6h or 12h starting with
daylight, using the “gentle handling method” (Eur J Neurosci 2002; 16: 1163-7) in
male Sprague-Dawley rats (340±40g). Control group was kept in the same environment
but undisturbed to allow sleep. Following sleep deprivation, rats were anesthetized,
and femoral artery cannulated to monitor arterial blood gas and blood pressure. Rats
were intubated and ventilated to maintain a normal systemic physiologic state. CSD
susceptibility was assessed by measuring the frequency of CSDs evoked by topical KCl
(1M), or using the direct cathodal stimulation intensity threshold (bipolar
electrode, 1-800mC). Amplitude, propagation speed, and duration of CSD were also
recorded. All experiments were done blinded. Data are mean ± standard deviation.
Results: Sleep deprivation increased the frequency of CSDs [Figure 1;
(p=0.01 and 0.007, 6h and 12h sleep deprivation, resp.)] and decreased the
electrical CSD threshold [Figure 2; (p=0.095 and 0.037, 6h and 12h sleep
deprivation, resp.)] in a duration-dependent manner compared to controls. Other CSD
parameters and systemic physiology did not differ between groups.
Conclusions: In keeping with other migraine modulators, sleep
deprivation enhances CSD susceptibility to explain its mechanism as a migraine
trigger. Our data underscore the importance of CSD as a migraine substrate that can
be targeted therapeutically.
P316
Interhemispheric Differences of fMRI Responses in Migraine with Unilateral
Aura
A. Hougaard1, F.M. Amin1, M.B. Hoffmann2, E.
Rostrup3, H.B.W. Larsson3, M.S. Asghar1, V.A.
Larsen4, J. Olesen1, M. Ashina1
1Danish Headache Center, Department of Neurology, Glostrup
Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Glostrup, Denmark; 2Visual Processing Laboratory, Ophthalmic
Department, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany;
3Functional Imaging Unit, Department of Diagnostics, Glostrup
Hospital, Faculty of Health and Medical Sciences, University of Copenhagen,
Glostrup, Denmark; 4Department of Radiology, Rigshospitalet,
Copenhagen, Denmark.
Objectives: To examine the cerebral responsivity of cortical visual
areas to visual stimulation in patients with migraine with unilateral visual
aura.
Background: Migraine sufferers with aura often report visual discomfort
outside of attacks and many consider bright or flickering light an
attack-precipitating factor.
The nature of this brain hypersensitivity and its relation to the underlying
pathophysiology of the migraine aura is unknown. Using fMRI measurements during
visual stimulation we examined the visual cortical responsivity of patients with
migraine with aura. We applied a highly sensitive within-patient design by assessing
functional interhemispheric differences in patients consistently experiencing visual
aura in the same visual hemifield.
Methods: We recruited 20 patients with frequent fixed-side visual aura
attacks (>= 90% of auras occurring in the same visual hemifield) and 20 age and
sex matched healthy controls and compared the fMRI blood oxygenation level dependent
(BOLD) responses to visual stimulation between symptomatic and asymptomatic
hemispheres during the interictal phase and between migraine patients and
controls.
Results: BOLD responses were selectively increased in the in the
symptomatic hemispheres. This was found in the inferior parietal lobule (P=0.002),
the inferior frontal gyrus (P=0.003) and the superior parietal lobule (P=0.017). The
affected cortical areas comprise a visually driven functional network involved in
oculomotor control, guidance of movement, motion perception, visual attention, and
visual spatial memory. The patients also had significantly increased response in the
same cortical areas when compared to controls (P<0.05).
Conclusions: We discovered a very specific and lateralized alteration of
a visually driven functional network, which may explain the commonly reported visual
discomfort and dysfunction in migraine with aura.
P317
Altered Resting-State Connectivity of the Visual Network in Migraine
1Neurological Institute, Taipei Veterans General Hospital, Taipei,
Taiwan Republic of China; 2College of Medicine, National Yang-Ming
University, Taipei, Taiwan Republic of China; 3Institute of Brain
Science, National Yang-Ming University, Taipei, Taiwan Republic of
China.
Objectives: To identify if the intrinsic brain connectivity of the
visual cortex is altered in migraine.
Background: Visual cortex excitability is abnormal in migraine. During
interictal periods of migraine, there is lack of habituation in visual evoked
potentials or magnetic fields. Moreover, the phosphene threshold is reduced in
transcranial magnetic stimulation studies. The mechanism of visual cortex
excitability changes remains uncertain, whereas an alteration of the functional
connectivity between visual cortex and other cortical regions may be the
culprit.
Methods: Resting-state functional magnetic resonance imaging data from
18 patients with migraine without aura during interictal state and 18 age- and
sex-matched healthy control subjects were analyzed using dual-regression independent
components analysis, which is a data-driven approach for the identification of
multiple independent brain networks. Resting-state connectivity was evaluated in the
medial visual network (MVN, bilateral primary visual cortex) to identify regions of
interest with different connectivity between groups (migraine vs. control). The
connectivity in the default mode network (DMN) was also assessed to serve as a
non-visual control.
Results: Patients with migraine showed reduced connectivity between MVN
and the left prefrontal cortex (superior frontal gyrus, SFG), a region with
prominent role in cortical inhibition (corrected P<0.05 vs.
controls). In migraine patients, the strength of connectivity between MVN and the
left SFG was not correlated with headache parameters (headache frequency and history
length). The connectivity in DMN did not differ between migraine patients and
controls.
Conclusions: These findings extend the role of visual cortex in migraine
pathophysiology, featured by a connectivity change which may disrupt cortical
inhibition.
P318
Photophobia in Obese Mice: Implications for Migraine
A. Recober1, A.K.S. Luu1, H.L. Rossi1
1Neurology, University of Iowa, Iowa City, IA, USA.
Objectives: To assess the effects of obesity on photophobia using a
mouse model of trigeminal pain.
Background: Neuroinflammation driven by overnutrition may represent one
of the underlying mechanisms in the association between obesity and migraine. We
hypothesize that obesity may prime pain pathways, rendering them more sensitive to
otherwise innocuous stimuli. We have recently shown that diet-induced obesity in
mice enhances nociceptive activation in the trigeminal nucleus caudalis (TNC) in
response to a very low dose of capsaicin (Rossi et al., 2012). The
trigeminal system is implicated in photophobia, an important migraine symptom. To
translate our findings to animal behavior, we have modified the light-dark test to
assess photophobia in mice.
Methods: We assessed light avoidance in C57BL/6J mice fed high-fat or
regular diet. We used the light aversion test, an assay based on the natural
conflict between exploration and light avoidance. Mice were tested individually in a
chamber with two identical covered compartments, one of them dark and the other one
lit (1000 lux, equivalent to an overcast day). We measured the percentage of time
spent in each compartment. To control for anxiety, we tested the effects of diazepam
(0.2, 1, and 2 mg/kg IP) and measured serum corticosterone. We also assessed the
effect of systemic sumatriptan (0.4, 4, and 40 mg/kg IP). To determine whether
photophobic behavior correlates with the neuronal changes observed in the TNC, we
tested light aversion after treatment with a low dose of subcutaneous capsaicin
(0.01%) in the face.
Results: Control mice spent about the same amount of time in the light
and dark sides of the modified light-dark box. Obese mice spent about 10% less time
in light than controls (p<0.005). This light avoidance was not reversed by
diazepam or systemic sumatriptan. Furthermore, corticosterone levels were similar in
both diet groups. After capsaicin treatment, obese mice spent more than 75% of the
time in the dark while control mice did not respond to this dose of capsaicin.
Conclusions: Our results suggest that activation of the trigeminal
system with capsaicin induces light avoidance, a surrogate of photophobia, in obese
mice but not in lean mice. The lack of effect of diazepam and similar levels of
corticosterone in both diet groups support the concept that light avoidance in this
test represents photophobia and not anxiety. Ongoing studies will address central
effects of sumatriptan and its role in blocking evoked photophobia.
P319
Intracranial Pathology and Headache – A Population Based Imaging Study (MRI
HUNT)
L.-M. Honningsvåg1, K. Hagen1, A. Håberg1, L.J.
Stovner1, M. Linde1
1Department of Neuroscience, Norwegian University of Science and
Technology, Trondheim, Norway.
Objectives: Examine the relationship between headache and MRI
findings.
Background: While some intracranial pathology is known to cause
headache, it is disputed whether other pathology like intracranial cysts can.
Previous studies on this have mostly included selected clinical populations. We
present the intracranial pathology among self-reported headache sufferers and
headache free in an unselected cohort drawn from a large epidemiological study (the
HUNT 3 study, 2006-08).
Methods: Among participants in HUNT 3, those who had answered the
headache questionnaire and who had also participated in the population-based imaging
study of the head among persons between 50 and 65 years (MRI-HUNT, 2007-09) were
included in this study (n=864). The neuroradiologists reviewing the images were
blinded for personal data, but additional medical information was gathered after the
review to diagnose with certainty multiple sclerosis, progressive supranuclear
paralysis and to differentiate between silent and clinical infarctions. Based on the
headache status in HUNT 3, the participants were categorized as headache sufferers
or non-sufferers, and the number of individuals with intracranial pathology was
compared between the groups. Pearson chi-square was used for all analyses except for
conditions in which n was expected to be <5 (meningiomas, microhemorrhages and
cerebral contusions) where Fisher’s Exact Test was used. Demographic characteristics
between MRI-study participants and MRI-study invited non-participants were quite
similar (1).
Results: Macropathology as a whole were quite common in both groups, but
it was not associated with headache (p = 0.37). Examining sub-groups with various
pathologies, headache was significantly (p = 0.04) more common among individuals
with rare pathology, i.e. each occurring in <1% (occlusion of carotis interna,
arteria cerebri media stenosis, carotid siphon stenosis, venous angioma, cavernous
hemangioma, arteriovenous malformation, postoperative alterations, hypophyseal
expansion, Chiari malformation, calcification of the parenchyma, grey matter
heterotopia, multiple sclerosis, progressive supranuclear paralysis, vestibular
schwannoma, malignant neoplasm and mega cisterna magna).
Conclusions: In this MRI-examination of an unselected cohort, there was
no difference in intracranial macropathology among headache sufferers and
non-sufferers. Interestingly, however, headache was more likely among those with
rare pathology.
Total
Non sufferers
Headache sufferers
Pathology
N
N
%
N
%
p
Included
864
552
100
312
100
No pathology
714
461
83.5
253
81.1
0.37
Macropathology
150
91
16.5
59
18.9
0.37
Total Infarction
39
29
5.3
10
3.2
0.16
Silent infarction
25
18
3.3
7
2.2
0.39
Clinical infarction
14
11
2.0
3
1.0
0.25
Cyst
50
31
5.6
19
6.1
0.78
Non-arachnoidal
17
11
2.0
6
1.9
0.94
Arachnoidal
33
20
3.6
13
4.2
0.69
Aneurysm
15
10
1.8
5
1.6
0.82
Meningioma
9
5
0.9
4
1.3
0.73
Microhemorrhage
12
7
1.3
5
1.6
0.77
Cerebral contusion
9
3
0.5
6
1.9
0.08
Rare pathology
32
15
2.7
17
5.4
0.04
P320
Distribution of Glutamate and Glutamate Transporters in the Trigeminovascular
System; Their Relationship to CGRP and CGRP Receptor Components
S. Eftekhari1, L. Edvinsson1,2
1Department of Clinical Sciences, Division of Experimental
Vascular Research, Lund University, Lund, Sweden; 2Department of
Clinical Experimental Research, Glostrup Research Institute, University of
Copenhagen, Glostrup Hospital, Glostrup, Denmark.
Objectives: To study the distribution of glutamate, the vesicular
glutamate transporter 1 and 2 (VGLUT1 and VGLUT2) in dura mater, trigeminal ganglion
(TG) and the spinal trigeminal nucleus (STN).Their relation to CGRP and its receptor
components- calcitonin receptor-like receptor (CLR) and receptor activity modifying
protein 1 (RAMP1).
Background: Glutamate is suggested to play a significant role in
migraine pathophysiology. The role of glutamate in migraine is implicated by data
from animal and human studies. These studies suggest that there is a link between
migraine pathology and the glutamate system, putatively in two ways. (i) The second
order neurons in the brainstem contain glutamate as a main signaling molecule. (ii)
Some of the trigeminal neurons contain glutamate as a co-transmitter. The
neuropeptide calcitonin gene related peptide (CGRP) is suggested to play an
important role in migraine and CGRP receptor antagonists have antimigraine
efficacy.
Methods: Immunofluorescence was used to study the distribution of
glutamate, VGLUT1 and VGLUT2 in dura mater, TG and the STN.Their relation to CGRP
and its receptor components, CLR and RAMP1 was studied.
Results: Glutamate immunoreactivity was found in thin fibers, while
VGLUT1 was expressed in thicker fibers in dura mater. Glutamate and the glutamate
transporters expression was found in neurons of the TG and around fiber bundles in
the superficial laminae of STN.Glutamate positive neurons were found in STN. In TG,
some satellite glial cells displayed glutamate and VGLUT2 immunoreactivity.
Glutamate positive neurons rarely co-expressed CGRP in TG, only few smaller cells
expressed both markers. Double-staining of VGLUT1 or VLUT 2 and CGRP showed no
co-expression in any of the areas. Double-staining of VGLUT1 and CLR showed
co-expression in the thick fibers of dura mater. Double-staining of VLGUT1 and CLR
showed that they could be expressed in the same cells, mainly in larger TG neurons.
Not all VGLUT1 positive neurons were positive for CLR. No co-expression was found
between VLUT2 and the CGRP receptor components.
Conclusions: Glutamate expression was found in thin fibers in dura
mater, medium-sized trigeminal neurons and at the level of STN. VGLUT1 was instead
expressed in thicker fibers and larger neurons. In addition, some satellite glial
cells displayed glutamate and VGLUT2 immunoreactivity. Interestingly, we found
co-expression of VLUT 1 and the CGRP receptor components. These results suggest that
there may be an interaction between the glutamatergic system and CGRP receptors.
P321
Attentional Control Abnormalities in Migraineurs in between Headache
Attack
M.J.S. Mickleborough1, L.; Gould, T.C. Handy2, P.; Babyn, R.
Borowsky1
1University of Saskatchewan, Saskatoon, SK, Canada;
2University of British Columbia, Vancouver, BC, Canada.
Objectives: The goal of this study was is to examine attentional control
in migraineurs in between headache attacks.
Background: Previous research indicates that people with migraine, as
compared to controls, have increased excitability in visual cortex in between
headache attacks. For example, migraineurs’ visual cortical response to repetitive
innocuous visual stimuli such as a checkerboard reversal does not show normal
habituation effects. Specifically, while the amplitude of visual-evoked potentials
to repeated stimuli normally diminish over time, migraineurs show no evidence of
this sensory attenuation. Given that visual cortical excitability can be modulated
by attention, we predicted that abnormal attentional control may be playing at least
some role in the visual cortical abnormalities found in migraine.
Methods: We compared responses of migraineurs (with and without aura) to
non-migraine control subjects in canonical visual spatial cuing tasks. Using three
separate experiments, we assessed responses in: behavioral reaction times,
event-related-potentials (ERPs), and functional magnetic resonance imaging
(fMRI).
Results: We have three key findings when comparing migraineurs to the
non-migraine controls. First, the reaction time results suggests that migraineurs
have increased reflexive orienting responses to sudden-onset stimuli in the visual
periphery. Second, the ERP results suggest migraineurs have increased cortical
responses to unattended or “to-be-ignored” visual events. Finally, the fMRI results
suggest that migraineurs have altered functioning in the frontal-parietal
attentional control network.
Conclusions: Together, this evidence suggests that migraineurs have
interictal abnormalities in attentional control that specifically relate to the
detection of and reaction to objects that are normally outside the focus of
attention. Given that the key role of attention is the allocation of processing
resources, these attentional abnormalities could be contributing to interictal
visual cortical excitability in migraine.
P322
Impact of a Spontaneous Migraine Attack in the Endogenous µ-Opioid System
In Vivo
T.D. Nascimento1, T. Love3, M.F. DosSantos1, I.K.
Martikainen1,3, C.M. Cummiford3, M. DeBoer1,
R.A. Koeppe4, T. Hall5, S. Petty5, E.
Maslowski5, Y.R. Smith6, J.-K. Zubieta3, A.F.
DaSilva1,2,3
1Headache & Orofacial Pain Effort (H.O.P.E.), Biologic &
Materials Sciences Department, University of Michigan School of Dentistry, Ann
Arbor, MI, USA; 2Michigan Center for Oral Health Research (MCOHR),
University of Michigan School of Dentistry, Ann Arbor, MI, USA;
3Translational Neuroimaging Laboratory, Molecular & Behavioral
Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA;
4PET Physics Section, Division of Nuclear Medicine, Radiology
Department, University of Michigan, Ann Arbor, MI, USA; 53DLab,
University of Michigan, Ann Arbor, MI, USA; 6Department of Obstetrics
and Gynecology, University of Michigan, Ann Arbor, MI, USA.
Objectives: We reported for the first time the impact of a spontaneous
migraine attack in the µ-opioid system of a patient’s brain in vivo using Positron
Emission Tomography and a novel 3D-Immersive & Interactive Neuronavigation
(3D-IIN).
Background: MRI-based studies show that migraine appears to result, and
possibly to endure, from the alteration of specific neural processes in the central
nervous system. However, information is lacking on the molecular impact of those
changes, especially over the endogenous opioid system during migraine attacks.
Methods: We aimed to investigate, using a novel 3D immersive and
interactive neuronavigation (3D-IIN) approach, the endogenous µ-opioid transmission
in the brain during a migraine attack in vivo.
A 36-year-old female, who has been suffering with migraine for ten years, was scanned
in the typical spontaneous headache (ictal) and non-headache (interictal) migraine
phases using Positron Emission Tomography (PET) with the selective radiotracer
[11C]carfentanil, produced in cycloton in the vicinity, which
measures in vivo the µ-opioid receptor availability in the brain
(non-displaceable binding potential - µORBPND). Both PET scans,
(potentially) interictal or ictal, were scheduled during separated mid-late
follicular phases. During ictal PET session her spontaneous headache attack reached
severe intensity levels; progressing to nausea, and vomiting at the end of the scan
session.
Results: There were significant reductions in µORBPND in
pain-modulatory regions during the ictal phase, including cingulate cortex, nucleus
accumbens, thalamus and periacqueductal gray matter (PAG); indicating that µORs are
preoccupied by endogenous µ-opioids released in response to the ongoing pain.
Conclusions: To our knowledge, this is the first time that changes in
µORBPND during a migraine attack are reported, and also explored
using a novel 3D neuronavigation approach, allowing for advanced investigation of
the actual data in a full virtual reality. Either by the changes in occupancy or
number of µ-opioid receptors available, these findings could explain why opioids are
controversial as a prophylactic treatment for patients with migraine, since
prolonged opioid therapy has been linked with its endurance and worsening.
P323
Heavily T2-Weighted Magnetic Resonance Myelography in Post-Lumbar Puncture
Headache
1Department of Neurology, Taipei Veterans General Hospital, Taipei
City, Taiwan Republic of China; 2Department of Radiology, Taipei
Veterans General Hospital, Taipei City, Taiwan Republic of China;
3School of Medicine, National Yang-Ming University, Taipei City,
Taiwan Republic of China.
Objectives: (1) To characterize post-lumbar puncture (LP) CSF leakage
with heavily T2-weighted magnetic resonance myelography (HT2W MRM), (2) to explore
the radiological correlates of post-LP headache (PLPH).
Background: About one third of patients undergoing diagnostic LPs
develops PLPH, and its correlation with the characteristics of CSF leakage remains
unknown.
Methods: Patients indicated for diagnostic LPs were enrolled
prospectively. HT2W MRM was carried out after LP. CSF leakage on HT2W MRM was
assessed with four measures: CSF leaks along the nerve roots, epidural CSF
collections, retrospinal CSF collections, and subcutaneous CSF collections. Images
were interpreted by a blinded neuroradiologist. Comparisons were made focusing on
PLPH.
Results: In total, 79 patients (50F/29M, age 48.0±14.6 years, range
18-83) completed the study, and 24 (30.4%) had PLPH. There was evidence of post-LP
CSF leakage in 61 patients (77.2%): epidural CSF collections in 29 (36.7%), CSF
leaks along the nerve roots in 44 (55.7%), retrospinal CSF collections in 33
(41.8%), and subcutaneous CSF collections in 27 (34.2%). CSF leakage beyond L3-4 was
seen in 57 (72.2%). Epidural CSF collections were mostly seen between mid-T to upper
L regions, and CSF leaks along the nerve roots centered around upper L and upper T
regions. Retrospinal and subcutaneous CSF collections were seen at the L-S regions.
Patients with PLPH had higher percentages and more segments of CSF leaks along the
nerve roots (91.7% vs 40.0%, p<0.001) (2.4±2.2 vs 1.1±1.9 segments, p=0.010) and
epidural CSF collections (66.7% vs 23.6%, p<0.001) (5.0±5.8 vs 0.9±2.3 segments,
p=0.003) than those without, and the distributions were more cephalad. Multivariate
logistic regression analysis identified two factors associated with PLPH: the
presence of CSF leaks along the nerve roots (odds raio [OR] = 18.2, 95%
CI=3.0-112.1, p=0.002) and the length of epidural CSF collections (OR=1.3 per
segment, 95% CI=1.1-1.5, p=0.002).
Conclusions: PLPH is associated with a greater amount and a more
cephalad distribution of CSF leakages following LPs. Visualization of CSF leakages
on HT2W MRM after diagnostic LP is common, and extravasation beyond the level of LP
is frequently observed.
P324
Modulation of Migraine-Related Cortical Excitability by Adenosine and Its
Receptors
I. Keselman1, J. Zyuzin1, A. Charles1
1Neurology, UCLA, Los Angeles, CA, USA.
Objectives: This study explores the potential role of different types of
adenosine receptors in basic mechanisms of migraine, with the goal of identifying
new treatments that target these receptors.
Background: Migraine is a complex brain disorder that involves signaling
by multiple neurotransmitters. The modulation of migraine by caffeine, a
nonselective adenosine receptor antagonist, suggests that adenosine and its
receptors (ARs) play significant roles in the disorder. There are four types of ARs:
A1, A2a, A2b and A3. These are expressed in neurons, glia and vessels at different
levels. A1R and A2aR are the two subtypes most highly expressed in CNS. New
therapies targeting adenosine receptors are currently in development for a variety
of disorders.
Methods: Confocal videomicroscopy was used to quantify the effects of
adenosine receptor agonists and antagonists on the activity of cortical neurons and
astrocytes in culture. Optical intrinsic signal imaging and field potential
recordings in anesthetized mice were used to investigate the effects of adenosine
receptor agonists and antagonists on cortical spreading depression evoked by
KCl.
Results: Adenosine (100 nM to 1 µM) rapidly and reversibly inhibited
spontaneous calcium transients caused by action potential firing in cortical
neurons. CCPA, a selective A1R agonist mimicked the adenosine effects. Two
non-selective AR antagonists, Caffeine and CGS15943, activated calcium transients in
cortical neurons indicating inhibition of ongoing tonic adenosine receptor
activation. This effect was reproduced by an A1 selective receptor antagonist,
DPCPX, pointing to a role for the A1R in adenosine-medicated neuronal effects.
Adenosine was also able to inhibit glutamate-induced neuronal activation suggesting
important neuromodulatory properties for ARs. Each of the AR compounds tested
(non-selective AR antagonists, Caffeine and CGS15943; A1R selective antagonist,
DPCPX; A1R selective agonist, CCPA; A2R selective antagonist, SCH 58261, and A2R
selective agonist, CGS21680) had specific effects on cortical bursting activity,
intracranial vascular tone, and on individual phases of cortical spreading
depression.
Conclusions: Adenosine receptors are involved in multiple basic
mechanisms of migraine. Adenosine and its receptors represent an attractive target
for acute and preventive migraine therapies.
P325
Influence of Caffeine on Nociceptive Responses of the Trigeminocervical Complex
after Orofacial Formalin Model
J.W. Park1, S.R. Han2, S.B. Lee1, H.E.
Shin1
1Department of Neurology, Uijeongbu St Mary Hospital, The Catholic
University of Korea, Uijeongbu Si, Gyeongi-do, Republic of Korea;
2Department of Neurology, St’ Vincents Hospital, The Catholic
University of Korea, Suwon, Gyeongi-do, Republic of Korea.
Objectives: We investigated the influence of the caffeine on pain
pathways involving trigeminocervical complexes (TCC) using a orofacial formalin
injection model.
Background: Medication overuse has been known to be one of major
contributing factors to worsening of headache. Caffeine is a kind of medication that
usually overused in clinical field, but the exact mechanism of caffeine on
nociceptive pathway is unclear.
Methods: In Spraque Dawley rats, we divided into subgroups depending on
the caffeine administration: acute treatment group (50mg/kg, intraperitoneal
injection), chronic treatment groups (1g/L or 2g/L, in combination in the drinking
water per oral for 4 weeks), chronic treatment and withdrawal group (2g/L, in
combination in the drinking water per oral for 4 weeks, then withdrawal for 1 week).
After caffeine treatment or withdrawal, formalin was delivered into the left
periorbital area and nocicepetive pain behavior was measured by monitoring the time
spent rubbing the injected area during 60 min after formalin injection. The sensory
threshold for mechanical stimulation, assessed by the von Frey monofilament
threshold (VFMF) was also measured after treatment.
Results: In acute treatment of caffeine groups, formalin induced pain
behavior was not different to vehicle treatment. Chronic treatment of caffeine
significantly attenuated formalin-induced pain behavior (P <0.05). After
withdrawal caffeine, formalin-induced pain behavior was significantly increased
compared to chronic caffeine treatment group (P < 0.01). Sensory thresholds for
VFMF did not changed in acute and chronic treatment of caffeine compared to vehicle.
After withdrawal of caffeine, threshold for VFMF was significantly decreased (P <
0.01) from baseline.
Conclusions: Chronic treatment of caffeine showed the inhibitory effect
on nociceptive pathways from trigeminal nerve endings to the TCC and withdrawal of
caffeine after chronic treatment decreased sensory threshold to mechanical
stimuli.
P326
The Role of the Orexin-2 Receptor in the Nucleus Raphe Magnus on
Trigeminovascular Nociceptive Transmission
W. Supronsinchai1,2, J. Hoffmann1,3, S. Akerman1,
P.J. Goadsby1
1Department of Neurology, University of California, San Francisco,
San Francisco, CA, USA; 2Department of Physiology, Faculty of
Dentistry, Chulalongkorn University, Bangkok, Thailand; 3Department
of Neurology, Charité Universitätsmedizin, Berlin, Germany.
Objectives: To examine the effects of local orexin 2 receptor
(OX2) modulation in the NRM on trigeminocervical complex (TCC)
neurons in response to nociceptive activation of trigeminal afferents innervating
the craniovascular dura mater.
Background: The orexins are hypothalamic neuropeptides whose neurons
project to the brainstem nuclei and spinal cord and are involved in the processing
of nociceptive transmission. The nucleus raphe magnus (NRM), in the brainstem, is
also involved in spinal and trigeminal nociceptive processing, yet the role of the
orexins in the NRM is unknown.
Methods: Adult male Sprague-Dawley rats were anesthetized with
pentobarbitone sodium (60 mgkg-1). We examined the effects of
microinjecting orexin A and orexin B into the NRM, on the trigeminal neuronal
activity, in response to electrical stimulation of trigeminal afferents that
innervate the middle meningeal artery, its branches, and periarterial dura mater
(MMA). The responses were challenged with a specific OX2 receptor
antagonist.
Results: Microinjection of orexin A or orexin B 100 µM into the NRM
facilitated TCC neuron firing (p < 0.05). Pretreatment with an
OX2 receptor antagonist intravenously 5 min before orexin A or orexin
B microinjection into the NRM blocked the facilitation of TCC neuron firing
(p < 0.05). In addition, intravenous OX2 receptor
antagonist administration had no effect on TCC neuron firing (p
> 0.05).
Conclusions: The present study demonstrates thatorexin microinjection
into the NRM has facilitated trigeminovascular nociceptive transmission. High
concentration of orexin A and orexin B have pronociceptive effects on
trigeminovascular nociception that are mediated by OX2 receptors. This
implicates OX2 receptors in NRM descending control of pain modulation in
response to electrical stimulation of the MMA. Understanding the role of orexinergic
control of trigeminal nociceptive transmission in the NRM may improve our knowledge
of the pathophysiology of migraine and other primary headache disorders.
P327
Influences of Smoking and Caffeine Consumption on Trigeminal Pain
Processing
D. Holle1, A. Heber1, S. Naegel1, H.-C.
Diener1, Z. Katsarava1,2, M. Obermann1
1Department of Neurology, University Duisburg-Essen, Essen,
Germany; 2Department of Neurology, Evangelisches Krankenhaus Unna,
Unna, Germany.
Objectives: To investigate whether smoking or caffeine consumption
influences trigeminal pain processing.
Background: The influence of caffeine and smoking on pain processing is
well described in literature. Various analgesic as well as nociceptive properties of
both conditions have been reported, previously. Smoking and caffeine consumption are
quite common in the general population, and even more pronounced in some patient
populations (e.g. smoking in cluster headache). Caffeine itself can induce or
exacerbate some pain entities (e.g. migraine, caffeine-withdrawal headache). Smokers
are more prone to develop back pain and other pain conditions. Additionally, higher
pain intensity scores have been reported in smokers.
Methods: Sixty healthy subjects were investigated using simultaneous
recordings of the nociceptive blink reflex (nBR) and pain related evoked potentials
(PREP) following nociceptive electrical stimulation on both sides of the forehead
(V1). Thirty subjects were investigated before and after smoking a cigarette, thirty
subjects before and after taking a tablet of 300mg of caffeine.
Results: After smoking PREP showed decreased N2 (182.15 ms vs. 176.89
ms; p<0.005) and P2 latencies (131.35 ms vs. 128.32 ms; p<0.05) indicating
central facilitation at supraspinal (thalamic or cortical) level. NBR showed a
decreased area under the curve (AUC) (110.52 (x10-3) (µV xms) vs. 97.09 (x10-3) (µV
xms); p<0.05) indicating central desensibilisation at brainstem level. After
caffeine intake no significant changes were observed comparing nBR and PREP results
before and after consumption.
Conclusions: Smoking influences trigeminal pain processing on
supraspinal and brainstem level. This observation might contribute to the further
understanding of the pathophysiology of pain disorders that are associated with
excessive smoking habits such as cluster headache. Additionally, it adds infomation
how smoking itself influences pain processing and might alter pain perception. In
contrast, caffeine consumption does not alter trigeminal pain processing
significantly. Therefore, previous smoking has to be taken in account when
performing electrophysiological studies to avoid bias of study results.
P328
Implication of TRPM8 in the TRPV1-Mediated Trigeminal Nociception
Y. Kayama1, M. Shibata1, T. Takizawa1, T.
Shimizu1, H. Toriumi1, T. Ebine1, M.
Funakubo1, T. Iwashita1, H. Sato1, N.
Suzuki1
1Department of Neurology, Keio University School of Medicine, 35
Shinanomachi, Shinjuku-ku, Japan.
Objectives: We aimed to explore the distribution of TRPM8 in the
trigeminal ganglion and brainstem and the functional interaction between TRPM8
(transient receptor protein melastatin subfamily, member 8) and TRPV1 (transient
receptor potential vanilloid subfamily, member 1) using a cell-based assay.
Background: Recent genome-wide association studies have identified TRPM8
as an important gene that determines the susceptibility to migraine.
Methods: Immunostaining for TRPM8 and TRPV1 in the trigeminal ganglion
and brainstem was performed using Sprague-Dawley rats.
We transfected a plasmid vector bearing the full-length TRPM8 cDNA
expression cassette into PC12 cells stably expressing an EGFP-TRPV1 fusion protein.
Using these cells, we examined the effect of pharmacological TRPM8 activation on
capsaicin-induced JNK phosphorylation. The experimental protocol is shown in
Figure.
Results: In the trigeminal ganglion, TRPM8 immunoreactivity was found in
small neurons (diameter 21.2 ± 3.4µm, n =120), a portion of which was also positive
for TRPV1 (4.3 ± 1.6%, n =1044). In the brainstem, TRPM8 immunoreactivity was
observed in neurons of the medullary reticular nucleus, a region closely related to
pain processing. Consistently, we observed the up-regulation of c-Fos expression in
glutamine synthase-positive astrocytes in the medullary reticular formation
following TRPV1 stimulation with capsaicin in the trigeminal area.
Capsaicin induced dose-dependent JNK phosphorylation in PC12 cells stably expressing
an EGFP-TRPV1 fusion protein. Pre-treatment with icilin, a specific TRPM8 agonist,
attenuated such capsaicin-induced JNK phosphorylation, implying that TRPM8 has an
antagonistic action against TRPV1 with regard to JNK phosphorylation.
Conclusions: From the above data, there seem to be functional
interactions between TRPM8 and TRPV1 at least at the levels of the primary sensory
neurons and brainstem in vivo. Notably, TRPM8 and TRPV1 can act antagonistic to each
other in a cell autonomous manner. It is inferred that some derangement of the
functional interactions between TRPM8 and TRPV1 may play a role in the
pathophysiology of migraine.
P329
Cortical Modulation Affects Visual Evoked Potentials Differently in Migraineurs
Compared to Healthy Controls
P.M. Omland1, M. Uglem1, M. Engstrøm1,2, M.
Linde1,2, K. Hagen1,2, T. Sand1,2
1Department of Neuroscience, Norwegian University of Science and
Technology, Trondheim, Norway; 2Department of Neurology and Clinical
Neurophysiology, St. Olavs Hospital, Trondheim, Norway.
Objectives: To investigate the effect of navigated high-frequency
repetitive transcranial magnetic stimulation (rTMS) on visual evoked potentials
(VEP) in interictal migraineurs, preictal migraineurs and in healthy controls.
Background: The effect of rTMS on VEP may provide insight in how
cortical excitability is altered in migraine. The migraine cortex may have a reduced
homeostatic plasticity and therefore a reduced ability to counteract increases in
cortical excitability. If so, rTMS should affect VEP differently in migraineurs
compared to healthy controls. Because visual subsystems may be differently affected
in migraineurs, VEPs were performed with both small 8’ and large 65’ checks. In
addition, if the cortical excitability in migraine changes in the period before a
migraine attack, rTMS may have a different effect on VEP in preictal compared to
interictal migraine.
Methods: Forty-three migraineurs and 34 healthy controls participated in
the study. Thirty-two healthy controls, 25 interictal migraine and 7 preictal
migraine (< 48 hours prior to headache) remained after exclusions. Four subjects
in the attack phase and one in the postictal period (< 48 hours after headache)
were excluded. Five migraineurs were excluded because of drowsiness. Two healthy
controls and one interictal migraineur were excluded because of technical
difficulties.
rTMS output was set to phosphene threshold or 110% of motor threshold if phosphene
threshold was >75% of stimulator output or if no phosphene was observed. VEPs
using 8’ and 65’ checks were averaged in six blocks of 100 before, directly after
and >25 minutes after rTMS.
The investigators were blinded for diagnosis during rTMS and recordings of VEPs.
During visual determination of VEP-peaks, the investigator was blinded for diagnosis
and block number. The primary habituation measure, linear VEP amplitude change over
the six blocks, were analysed with repeated measures ANOVA.
Results: VEP habituation was found in interictal and preictal migraine
and healthy controls before rTMS. There were no differences in VEP habituation
between the groups before rTMS. With 65’ checks, N70-P100 habituation was decreased
in interictal migraine compared to healthy controls after rTMS (p = 0.013). With 8’
checks, N70-P100 and P100-N145 habituation was decreased in preictal migraine
compared to interictal migraine and healthy controls after rTMS (p < 0.016).
Conclusions: Migraineurs may have a vulnerability to develop attacks
because of a reduced ability to counteract changes in cortical excitability.
Differences between the healthy controls and interictal migraine was only found for
65’ checks, therefore the magnocellular visual subsystem may be affected in the
period between attacks. The effect of rTMS in preictal migraine was only different
from the other groups with 8’ checks, therefore the parvocellular visual subsystem
may be affected in the period before a migraine attack.
P330
Optical Measurement of Craniofacial Autonomic Function: A Tool for
Quantification of Autonomic Dysfunction in Headache
M. Cortez1, J. Theriot2, S. Baggaley2, K.C.
Brennan2
1Neurology, Mayo Clinic, Scottsdale, AZ, USA;
2Neurology, University of Utah, Salt Lake City, UT, USA.
Objectives: To develop a clinically feasible protocol for measurement of
craniofacial autonomic function.
Background: Craniofacial autonomic outflow is altered in several
headache disorders. While systemic sudomotor, adrenergic, and cardiovagal responses
are widely tested, there is currently no routinely available, standardized method of
measuring craniofacial autonomic phenomena.
Methods: Subjects were placed supine and imaged under green, red and
blue light. A high sensitivity CCD camera was used to image the upper 2/3 of the
face. A pulse oximetry probe was placed on the earlobe. A twin-bore tube was
inserted into one nostril, and the contralateral nostril was occluded. Imaging and
pulse oximetry were recorded before, during and after stimulation with ammonia
vapor, which was directed into the nostril via vacuum pump. Additional testing in
selected cases included correlation with Schirmer’s test and slit-lamp evaluation,
as well as pharmacological blockade.
Results: Data was collected in 11 subjects. At baseline, low frequency
fluctuations in skin reflectance were noted, that were distinguishable from
reflectance changes due to heartbeat. Between 1-3 seconds after ammonia stimulus,
bilateral consensual pupillary dilation, followed by relative constriction, was
observed. During and shortly following the pupillary constriction phase, reflectance
over the forehead, nose and cheeks decreased bilaterally (most prominent
ipsilaterally), concurrent with a reduction in spontaneous vascular fluctuations.
Scleral/conjunctival reflectance also decreased bilaterally, and tearing increased
ipsilaterally. Imaging at multiple wavelengths, as well as slit lamp exam with a
similar paradigm, suggested that the mechanism of reflectance change is an increase
in blood volume due to vasodilation.
Conclusions: Our optical, multi-modal measure of craniofacial
trigeminovascular autonomic function fills a gap in current clinical measurement of
autonomic function. This technique is clinically feasible and may enhance our
ability to further characterize migraine and facial neuralgia-related autonomic
changes.
P331
Distinctive Anatomical and Physiological Features of Migraine Aura Revealed by
20 Years of Patient Recording
J.M. Hansen1, P. VanValkenburgh1, S.M. Baca1, A.
Charles1
1Department of Neurology, David Geffen School of Medicine at
University of California, Los Angeles, Headache Research and Treatment Program,
Los Angeles, CA, USA.
Objectives: To present detailed characterization of a large number of
visual auras recorded in one patient over two decades.
Background: Descriptions of the migraine aura have been presented as
prospective self-observations by physicians and other professionals who had migraine
with aura or migraine aura without headache.
Methods: A patient documented and made detailed drawings of 1000 aura
attacks over 20 years. Drawings were made in real time with documentation of the
aura wavefront at 1 minute time intervals.
Results: Most aura attacks originated centrally (within 10 degrees
eccentricity), but there were also other distinct sites of initiation in the visual
field (figure 1).
Figure showing the complete visual field up to 26.5° eccentricity. The right visual
field of the patient is from (0-180°) and the left visual field is from (180-360°).
Consistent patterns of aura initiation, propagation, and termination were observed
in both right and left visual fields. Auras preferentially propagated first through
lower nasal field (69-77 % of all auras) before travelling to upper and temporal
fields, on both sides.
Some auras propagated from peripheral to central regions of the visual field -- these
typically followed the same path as those travelling in the opposite direction. The
mean velocity of the perceived visual phenomenon did not differ between attacks
starting peripherally (17.6 mm/min ± 1.06) and centrally (16.2 mm/min ± 0.59),
(P = 0.41). Based on duration and imaging we estimated the
speed of the underlying cortical event to be 2.1-3.1 mm/min.
Conclusions: These results indicate that there can be multiple distinct
sites of aura initiation in a given individual, and that there are consistent
patterns of aura propagation that indicate non-concentric patterns of spread.
Structural and functional imaging studies are currently being performed to define
the anatomical correlate of this individual’s aura.
Points of aura origin, N=800.
P332
Lateral Inhibition in Somatosensory Cortex of Migraine without Aura Patients
between Attacks
G. Coppola1,2, M. Bracaglia1, E. Iacovelli1, C. Di
Lorenzo1, F. Pierelli1
1Department of Medico-Surgical Sciences and Biotechnologies,
Sapienza University of Rome Polo Pontino, Latina, Italy; 2Department
of Neurophysiology of Vision and Neurophthalmology, G.B. Bietti
Foundation-IRCCS, Rome, Italy.
Objectives: Our objective was to investigate lateral inhibition within
the somatosensory cortex in a group of migraine without aura (MO) patients compared
to healthy volunteers (HVs) by stimulating two peripheral nerves simultaneously,
while recording somatosensory evoked potentials (SEPs).
Background: Cortical potentials evoked by various sensory stimuli are
characterized interictally in migraine by lack of habituation. Both deficient
intracortical inhibition and low cortical pre-activation levels have been claimed in
explaining this phenomenon. However, they are not mutually exclusive, since the
latter could induce the former via reduced lateral inhibition.
Methods: Somatosensory evoked potentials were elicited by electrical
stimulation of the right median and ulnar nerve at the wrist separately and
simultaneously (2Hz repetition rate, 1.2 motor threshold, 300 sweeps per condition),
in 21 MO patients between attacks and in 17 healthy volunteers (HVs). We measured
parietal N20-P25 amplitudes and we evaluated the ratio MU/(M+U)*100, where MU is the
SSEP amplitude obtained simultaneously stimulating both median and ulnar nerves
(MU), and M+U is the sum of amplitudes obtained by stimulating each nerve separately
(M+U). Higher ratio of SSEP suppression means less inhibition. This ratio was
considered an index of cortical lateral inhibition (ICLI) between afferent inputs
from the two peripheral nerves. Habituation was calculated as the slope of the
linear regression between the 1st and the 3rd block of 100
averaged sweeps.
Results: SSEP N20-P25 amplitudes decreased along the blocks in HV
(-0.08%), whereas they significantly increased in MO patients (+0.22%, p=0.03). On
grand-average, ICLI resulted similar between groups (60.5% and 60.9% respectively in
HV and MO, p=0.94). The habituation slope was positively correlated with ICLI only
when data of HV and MO patients were combined (r=0.331, p=0.04).
Conclusions: These results suggest that lateral inhibitory mechanisms
within the somatosensory cortex may contribute to induce the interictal lack of
habituation of N20-P25 SSEPs amplitude seen in migraine patients. This
interpretation is supported by the positive correlation we observed between
habituation and ICLI: in other words, the more marked the habituation deficit the
less pronounced the lateral inhibition. However, since the correlation is
significant only if the data from HV and MO patients are pooled, this suggest that
it is a more general phenomenon related to the habituation mechanisms, not specific
to migraine.
P333
Cerebellar Function in Migraine Patients and Its Relation with Cerebellar
Ischemic Lesions
H. Koppen1, .H. Palm-Meinders, I3, B. Koutstaal1,
H.-J. Boele4, B.K. Koekoek4, J. van der Geest4,
L.J. Launer5, M.A. van Buchem3, G.M. Terwindt2,
M.D. Ferrari2, M.C. Kruit3, C.I. de Zeeuw4
1Neurology, Hagahospital The Hague, The Hague, The Netherlands;
2Neurology, Leiden University Medical Center, Leiden, The
Netherlands; 3Radiology, Leiden University Medical Center, Leiden,
The Netherlands; 4Neuroscience, Erasmus Medical Center, Rotterdam,
The Netherlands; 5National Institute on Aging, NIH, Bethesda, MD,
USA.
Objectives: To asses cerebellar function in a large population-based
case-control study, by evaluating the function with four validated tests, and
correlate the outcomes with MRI imaging of the cerebellum.
Background: Previous studies showed cerebellar lesions in migraineurs,
and diminished cerebellar function was reported in other studies. So far, direct
comparison between lesions and functional cerebellar outcomes was lacking.
Methods: The population-based CAMERA study included 282 participants,
200 migraine patients (111 migraine with aura,) and 82 controls, with a mean age of
57 years (range 43-72), 72% were female. As a positive control group, we evaluated a
small set (n=12) of patients with Familial Hemiplegic Migraine with a proven
mutation in the CACAN1A gene (FHM1, 42 years (range 19-64, 67%
female). The Purdue peg board task, the block design test from the Wechsler Adult
Intelligence Scale (WAIS) III, the prism adaptation test and the eyeblink
conditioning task were performed. All tests were done inter-ictally and
investigators were blinded for all participant characteristics.
Results: Results: From the CAMERA cohort, migraineurs (independent of
subtype) and controls all performed equally on all four cerebellar tests. MRI showed
a cerebellar infarct-like lesion in 21 (7%) participants, 18 of them were
migraineurs. Migraineurs with these lesions on MRI performed worse on the pegboard
task, a specific test for fine motor skills, number of pegs with both hands was 9.5
compared with 10.8 in the non-infarcted migraineurs, p<0.05.
FHM1 patients, as a positive control group, showed deficits on all four tests; Peg
assembly (p=0.04); block design mean scaled score (p<0.001); prism adaptation
(p<0.001), timing of conditioned eyeblink responses (p< 0.05). No MRI images
were obtained in the FHM group.
Conclusions: Migraine patients (independent of subtype) and controls
have comparable inter-ictal cerebellar function. Importantly, migraineurs with one
or more small cerebellar infarct-like lesion have diminished fine motor skills.
P334
Navigated High Frequency Transcranial Magnetic Stimulation in Interictal
Migraineurs: Abnormal Modulation of Thermal Thresholds
M. Uglem1, P.M. Omland1, M. Engstrøm1,2, K.
Hagen1,2, M. Linde1,2, T. Sand1,2
1Department of Neuroscience, Norwegian University of Technology
and Science, Trondheim, Norway; 2Department of Neurology and Clinical
Neurophysiology, St. Olavs Hospital, Trondheim, Norway.
Objectives: To investigate how thermal detection and pain thresholds
vary after navigated 10 Hz repetitive transcranial magnetic stimulation (n-rTMS) on
the secondary sensory cortex (SII) in healthy controls (CO), interictal (MINT) and
preictal (MPRE) migraineurs.
Background: High frequency rTMS on the motor cortex and various other
sites has been shown to modulate experimental pain. The secondary sensitive cortex
is largely involved in pain processing, but it has not been widely used as a target
for pain modulation by rTMS (Mylius, Borckardt et al. 2012). However, one study
suggested that n-rTMS on SII was most effective to increase heat pain thresholds in
healthy subjects (Valmunen, Pertovaara et al. 2009). Our aim was accordingly to
investigate this effect in interictal and preictal migraineurs.
Methods: Detection and pain thresholds for cold and heat were recorded
before, after sham rTMS and after active n-rTMS on SII. Sham rTMS was performed with
the coil tilted 90 degrees. Thirty-eight migraineurs and 31 healthy controls were
analysed in this blinded study. Repeated measures ANOVA (with site and stimulus as
within-subjects factors and diagnosis as between-subject factor) were applied.
Results: Cold pain thresholds (CPTd = 32°C-CPT) increased after rTMS
compared to sham in CO, but decreased in MINT (ANOVA group x stimulus interaction
p=0.006). RTMS had the same effect on heat pain thresholds (HPTd = HPT-32°C) with an
increase in CO and a decrease in MINT (p=0.030). Thresholds after rTMS also differed
from baseline for both CPTd (p=0.041) and HPTd (p=0.030). Heat detection thresholds
(HDTd) decreased after rTMS in MPRE compared to CO (p=0.035).
Conclusions: Our results imply that cold and heat pain sensitivity is
modulated differently by n-rTMS in CO and MINT as MINT patients become more
sensitive while CO become less sensitive. The results suggest that a normal
protective mechanism, preventing increased cortical excitability after SII
activation, is altered in MINT. Our results also suggest that sensory detection of
heat is modulated differently in MPRE and CO.
P335
A History of Migraine Accelerates Infarct Growth in Stroke Patients
K. Eikermann-Haerter1, K.Y. Park2, J. Helenius2, L.
Pearlman1, R. Avery2, E.M. Arsava2, A.
Negro1, A. Daneshmand1, H. Ay2, C.
Ayata1
1Neurovascular Research Laboratory, Dept of Radiology,
Massachusetts General Hospital, Boston, MA, USA; 2A.A. Martinos
Biomedical Imaging Center, Massachusetts General Hospital, Boston, MA,
USA.
Objectives: To assess acute stroke evolution in patients with a
documented migraine history.
Background: Migraine is an independent stroke risk factor, particularly
in otherwise healthy persons. A migraine history increases stroke risk, especially
in young females suffering from migraine with aura (6-fold). Recent animal
experiments suggest that migraine mutations increase brain vulnerability to ischemia
via excitatory mechanisms (Circulation 2012; 125:335). Migraine mutant mice develop
higher number of ischemic depolarizations and accelerated infarct growth during
hyperacute stroke, with worse outcomes. Anti-excitatory treatment prevents this
severe stroke phenotype.
Methods: We retrospectively analyzed lesion volumes on
diffusion-weighted imaging (DWI), and the volume of perfusion defect on
perfusion-weighted imaging (PWI) using mean transit time (MTT), from consecutive
patients in Massachusetts General Hospital stroke database (years 2003-2012).
Measurements were done blinded to migraine status.
Results: A total of 155 stroke patients had reliably documented presence
or absence of a migraine history (Figure 1). Stroke patients with a migraine history
were younger and more often female, compared to those without. Migraineurs less
frequently had coronary artery disease or diabetes. The frequency of posterior
circulation lesions was significantly higher in migraineurs. Otherwise, groups were
comparable. In patients with PWI scans, DWI-PWI mismatch was calculated on spatially
co-registered DWI and MTT maps, as a marker for viable tissue at risk for
infarction. In migraineurs, a larger area of the perfusion defect showed DWI
changes, resulting in smaller DWI/PWI mismatches. Indeed, a larger proportion of
migraineurs showed no mismatch (i.e., DWI/PWI>0.9; Figure 2, *p=0.011, †p=0.002),
indicating that the entire perfusion defect was already infarcted.
Conclusions: Our data show that a history of migraine, particularly with
aura, is associated with accelerated acute infarct growth. A prospective
case-control study is warranted to confirm and extend these data. With regard to
stroke treatment, data suggest a shorter therapeutic window for acute stroke
interventions in migraineurs, due to rapid loss of salvageable brain tissue.
P336
Unilateral Cranial Autonomic Symptoms in Migraine: A Retrospective Case Series
on 757 Patients
C. Aurilia1, V. Dall’Armi2, G. Egeo1, L.
Fofi1, S. Bonassi2, P. Barbanti1
1Headache and Pain Unit, Dept. of Neurological, Motor and
Sensorial Sciences, IRCCS San Raffaele Pisana, Rome, Italy; 2Clinical
and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy.
Objectives: To extend our previous findings on frequency and
characteristics of migraine with unilateral cranial autonomic symptoms (UAs) in a
retrospective study on a large case series in an Headache Centre.
Background: UAs (i.e. lacrimation, conjunctival injection, eyelid oedema
and nasal congestion), the hallmark of trigemino-autonomic cephalalgias, also occur
in a proportion of migraine patients during the attack. In a previous study on 177
migraineurs attending an Headache Centre we reported UAs in 45.8% of patients.
Methods: We retrospectively investigated all consecutive migraine
patients seen at our Headache and Pain Unit from 1st January 2010 to
31st December 2012. Demographic information and detailed clinical
migraine features were gathered using a structured questionnaire with face-to-face
interviews. We compared demographic and clinical characteristics of migraineurs with
UAs with those of migraine patients without UAs.
Results: We studied 757 consecutive migraineurs (M/F = 153/604; age =
39.05 + 12.7 yrs). Two hundred eighty-three patients (37.4%)
reported the presence of at least one UAs homolateral to pain during the attack.
Migraine patients with UAs showed longer disease duration (20.8 ± 13.1
vs 18.2 ± 13.3 yrs) (p <0.009), higher pain
severity (p <0.005), more strictly unilateral pain (59%
vs 41%) (p <0.001), longer attack duration
(p <0.001) and more frequent allodynia (57% vs 29%)
(p <0.001) compared to migraineurs without UAs.
Conclusions: In a large retrospective study we report that UAs occur in
almost 1 out of 3 migraineurs referred to headache centres. This proportion is
slightly lower than that previously reported by our group on a smaller patient
sample. The present study confirms that migraineurs with UAs have more severe and
more strictly unilateral headache and adds new data revealing that they have longer
disease duration and attack duration and more frequent allodynia during the attack.
We suggest to carefully consider this migraine phenotype in epidemiological and
pharmacological studies on migraine.
P337
A New Electronic Tool for Mapping Spatial and Temporal “Hotspots” in Migraine
Pain
G. Barmettler1, N. Maleki1, J. Brawn2, S.
Scrivani4, R. Burstein3, L. Becerra1, D.
Borsook1
1Anesthesia, Boston Children’s Hospital, Boston, MA, USA;
2Clinical Neurosciences, Oxford, Oxford, United Kingdom;
3Anesthesia, Beth Israel Deaconess Medical Center, Boston, MA,
USA; 4Craniofacial Pain Center, Tufts University, Boston, MA,
USA.
Objectives: This study introduces a novel tool for electronically
collecting data on the patterns of migraine headache onset and progression.
Background: Migraine pain is a common, yet not well understood headache
pathology, which occurs in 11.7% of US households. Here, we present an electronic
tool to quantitatively capture the pattern of migraine pain onset and distribution
as the headache progresses in localized areas of the head and neck: a tool for
understanding migraine pain distribution and locating migraine “hotspots.”
Methods: This study was approved by IRB, and all subjects gave informed
consent prior to using this tool. Study data were collected and managed using REDCap
electronic data capture tools, a secure web-based application that supports research
study data capture.
A total of 44 segments were defined on a schematic map of face, head and neck. The
segmentation was based on previous reports of migraine pain, and by the distribution
of the nerves in these regions as confirmed by Gray’s Anatomy, Fig
784. The segments were color-coded and the subjects were advised to identify the
origin of pain at headache onset and regions when the headache was full-blown. Next,
patients were asked to identify all regions in which they typically experienced
pain.
Results: Implementing this tool in our research study, 36 migraineurs
successfully used this pain survey tool to capture “pain hotspots” and the changes
and evolution of pain over the course of a migraine. Consistent with previous
findings, 58.3% of migraineurs indicated that they experience throbbing pain in the
right temple region, and 55.6% indicated throbbing pain in the left temple. A
tertiary care study has previously described migraine pain prevalence at 58% for the
temple region. Pain in the frontal region increased from 25% to 42% of migraine
patients as a typical migraine progressed, while pain in the area behind the eyes
decreased from 39% to 28% and then to 19% as a migraine progressed.
Conclusions: The pain map survey is a useful tool for understanding
migraine pain and its underlying mechanisms. Using the data captured in the survey,
this novel tool could be used to create maps of pain “hotspots” and serve as a
quantitative measurement of the spreading of pain during migraine. Additionally, it
could be useful for understanding complex headache cases, providing information to
systematically include or exclude migraine headache based on the pain pattern
presented and to verify if the trigeminal nerve network is closely linked to
migraine headache attacks. Furthermore, this tool could be developed into a
streamlined clinical application for personal use and documentation of each migraine
headache by patients. Using this compiled information, physicians could have a
comprehensive understanding of each patients’ unique headache characteristics and
patterns.
P338
Withdrawn by the author.
P339
Effect of Cortical Spreading Depression on the Phosphorylation of ERK in the
Trigeminal Ganglion of Rat
T. Iwashita1, T. Shimizu1, M. Shibata1, H.
Toriumi1, Y. Kayama1, T. Ebine1, T.
Takizawa1, M. Funakubo1, N. Suzuki1
1Department of Neurology, School of Medicine, Keio University,
Tokyo, Japan.
Objectives: In this study we examined the effect of CSD on the
phosphorylation of ERK in the TG.
Background: In migraine pathophysiology, cortical spreading depression
(CSD) and activation of the trigeminovascular system are known to contribute to aura
and headache, respectively. However, the relation between CSD and activation of the
trigeminal nerve is still obscure. Phosphorylation of extracellular signal-regulated
kinase (ERK) in sensory neurons by noxious stimulation is considered to contribute
to pain hypersensitivity, and we have already reported the occurrence of
phosphorylation of ERK in the trigeminal ganglion (TG) after stimulation of dural
TRPV1, which is a major nociceptive receptor.
Methods: Sprague-Dawley male rats were used for the experiment. D.C.
electrodes were set on the bilateral exposed parietal cortex under anesthesia. We
also installed a small open cranial window near the electrode to induce CSD using 1M
KCl solution. In the first experiment, animals were divided into three groups.
Bilateral TGs were dissected immediately (group-2; n =6) or at 30 minutes (group-3;
n =6), after the first wave of CSD. As control (group-1; n =6), saline was applied
on the open cranial window instead of 1M KCl solution.In another experiment, animals
were divided into two groups. Capsazepine (50 nM), which is an antagonist of the
TRPV1 receptor, was injected into the cisterna magna (group-5; n =6). For control,
vehicle (20% DMSO in saline) was injected instead of capsazepine (group-4; n =6). In
both groups, 1M KCl was applied on the cranial window to induce CSD, and 30 minutes
later, bilateral TGs were dissected. In both experiments, the specimens were used
for western blot analysis to observe the expression of pERK and total-ERK. The
ratios of the intensity of pERK to total ERK were calculated using the image
analysis software.
Results: The ratios of pERK/ total-ERK were 1.82 ± 0.48 for ERK1 and
2.97 ± 0.76 for ERK2 in group-3, 1.12 ±0.45 for ERK1 and 1.24 ± 0.63 for ERK2 in
group-2. The ratios of pERK/ total-ERK showed significantly higher levels in group-3
compared with group-1, however there was no significant difference between group-1
and group-2.
The ratios of pERK/ total-ERK were 0.23 ± 0.35 for ERK1 and 0.35 ± 0.43 for ERK2 in
group-5. The ratios of pERK/ total-ERK showed significantly attenuated levels in
group-5 compared with group-4. The frequencies of CSD occurrence during 30 minutes
were 4.7 ± 0.5 times in group-4 and 4.7 ± 1.4 times in group 5, and there was no
significant difference between group-4 and group-5.
Conclusions: Our data demonstrated that CSD caused the phosphorylation
of ERK in TG, and these responses were inhibited by TRPV1 antagonist. From the above
findings, it is inferred that CSD may cause the nociceptive response to TG via
TRPV1, and activate trigeminovascular system.
P340
Gray Matter Changes in Vestibular Migraine
M. Obermann1, S. Nägel1, D. Holle1, N.
Theysohn2, H.-C. Diener1, Z. Katsarava1
1Department of Neurology, University of Duisburg-Essen, Essen,
Germany; 2Department of Neuroradiology, University of Duisburg-Essen,
Essen, Germany.
Objectives: To determine structural gray matter differences in patients
with vestibular migraine and healthy controls in comparison to reported brain
changes in migraine with and without aura.
Background: Dizziness and vertigo are common complaints of patients with
migraine either in form of aura preceding the migraine attack or in form of
autonomic symptoms during the attack, similar to nausea and vomiting. The strong
relation of vestibular symptoms with migraine lead to the term vestibular migraine,
but it remains uncertain as to whether it is a variant of migraine with or without
aura, or whether it may represent a separate disorder.
Methods: 27 patients with vestibular migraine (mean age 42 years, 21
women) were compared to 27 age and gender matched healthy controls using voxel-based
morphometry (VBM). The images of all subjects were acquired in a 1.5 T Siemens
Avanto Scanner using a high resolution MPRAGE sequence with a voxelsize of 1x1x1
mm3. For the analysis we used the “new segment” and the DARTEL
algorythm of SPM8 (www.fil.ion.ucl.ac.uk/spm/).
Results: Patients with vestibular migraine showed a marked decrease of
gray matter in the middle and superior temporal gyrus, cingulate gyrus, insula,
inferior parietal, visual, as well as prefrontal cortex. No increase of gray matter
was observed in this regard.
Conclusions: The brain regions with decrease in gray matter identified
in vestibular migraine are quite similar to what was described previously in
migraine with and without aura. These areas play a pivotal role in human
somatosensory and nociceptive processing, but also are partly involved in
multisensory vestibular control. The superior temporal, inferior parietal, as well
as insula may point toward the pathophysiological origin of the common complaint of
vertigo and dizziness in patients with migraine in general and vestibular migraine
in particular. Further research is needed to directly compare migraine without aura,
migraine with aura and vestibular migraine to further elucidate this interesting
relation.
P341
Thermo-Sensitivity in Migraine between Attacks: A Study of Quantitive
Thermo-Sensory Testing and Contact Heat Evoked Potentials
M. Fataki Likale1, T. Sasso D’Elia1,2, V. De
Pasqua1, S.L. Sava1, D. Magis1, J.
Schoenen1
1Headache Research Unit University Department of Neurology, ULg,
Liège, Belgium; 2University of Rome La Sapienza, Rome,
Italy.
Objectives: To study cephalic and extracephalic cutaneous thermal
sensory and pain thresholds using Quantitative Sensory Testing (QST) and amplitude
as well as habituation of Contact Heat Evoked cortical Potentials (CHEPs) in
episodic migraine patients between attacks and, for comparison, in healthy
volunteers.
Background: Cutaneous allodynie occurs during migraine attacks, chiefly
in the trigeminal territory, and is also reported more prevalent than in healthy
controls between attacks (1). Electrophysiologically, migraine is characterized
between attacks by a habituation deficit of various evoked cortical responses.
Including laser evoked potentials (2).
Methods: We enrolled 15 patients (mean age: 21.86 ±3.6 yrs; 4M, 11F)
suffering from episodic migraine without aura (ICHD-21.1) in the interictal phase
and 15 healthy volunteers (22.6 ± 2.6 yrs; 6M, 9F). Patients had no preventive
treatment and no analgesic drug intake during the 72 h preceding the recordings.
Thermal QST was performed with an ATS thermode (Medoc Ltd, USA). We determined cold
and heat detection (CS, WS) and pain thresholds (CP, HP) on the volar wrist and on
the forehead. All thresholds were randomly assessed 3 times and averaged off
line.
For CHEPs we delivered 20 heat stimuli (53°C – baseline temperature: 42°C) with a
CHEP stimulator (Medoc Ltd, USA) to the right volar wrist or forehead with a
randomized inter-stimulus interval between 10 and 25 seconds. EEG activity was
recorded from Cz-Fz and off-line averaged in 5 sequential blocks for N2-P2 amplitude
and habituation (% and slope over the 5 blocks) measurements.
Results: Thermal QST was on average not different between migraine
patients and healthy neither at the wrist nor at the frontal site.
In both patients and controls the CHEP N2-P2 amplitude was significantly larger when
the forehead was stimulated compared to the wrist (p<0.05).
There was no difference in CHEP amplitude or habituation between migraine patients
and healthy subjects, but in patients the habituation slope was steeper in the
forehead than at the wrist (p<0.05).
Conclusions: Between attacks, thermal sensory perception and pain
thresholds are on average normal in migraine without aura both in the trigeminal
territory and the upper limb. The same holds true for contact heat evoked cortical
potentials. By contrast with LEPs, habituation of CHEPs is increased rather than
decreased in migraine patients.
Overall these results do not favor persistent central sensitization between attacks
in migraine without aura.
P342
Changes in Calcitonin Gene-Related Peptide (CGRP) Receptor Component and Nitric
Oxide Receptor (sGC) Immunoreactivity in Rat Trigeminal Ganglion Following
Nitroglycerin Pretreatment
K. Seiler1, J.I. Nusser1, J.K. Lennerz2, W.L.
Neuhuber3, K. Messlinger1
1Institute of Physiology and Pathophysiology, University of
Erlangen-Nürnberg, Erlangen, Germany; 2Institute of Pathology,
University of Ulm, Ulm, Germany; 3Institute of Anatomy, University of
Erlangen-Nürnberg, Erlangen, Germany.
Objectives: In the present study we examined changes in
immunofluorescence of the CGRP receptor components (CLR and RAMP1) and soluble
guanylyl cyclase (sGC), the intracellular receptor for NO, in rat trigeminal
ganglia, after pretreatment with nitroglycerin (GTN).
Background: Nitric oxide (NO) is thought to play an important role in
the pathophysiology of migraine. Infusion of the nitrovasodilator glyceroltrinitrate
(GTN), which mobilizes NO in the organism, is an approved migraine model in humans;
the underlying nociceptive processes can partly be examined in animal experiments.
Calcitonin gene-related peptide (CGRP) is regarded as another key mediator in
migraine. Increased plasma levels of CGRP have been found during spontaneous as well
as nitrovasodilator-induced migraine attacks.
Methods: In the present study we performed GTN pretreatment and examined
changes in immunofluorescence of CGRP receptor components and soluble guanylyl
cyclase (sGC), the intracellular receptor for NO, in rat trigeminal ganglia.
Results: In vehicle-treated animals, 42% of the trigeminal ganglion
neurons were immunopositive for RAMP1 and 41% for CLR. While CLR-immunopositivity
was unchanged after GTN pretreatment, there was an increase in neurons
immunopositive for RAMP1 to 46%. sGC-immunopositive neurons,were on average smaller
than sGC-immunonegative neurons, and the percentage decreased from 51% in vehicle to
48% after GTN infusion.
Conclusions: Prolonged infusion of GTN resulted in decreased fractions
of sGC- and increased fractions of RAMP1-immunopositive neurons in different
divisions of the trigeminal ganglion. The observed alterations are likely
immunophenotypic correlates of the pathophysiological processes underlying
nitrovasodilator-induced and spontaneous migraine attacks.
P343
Interictal Alterations of Pain Processing Pathway in Migraine Patients with
Cutaneous Allodynia
N. Chen1, L. He1, P. Wang1
1Department of Neurology, West China Hospital of Sichuan
University, Chengdu, Sichuan Province, China.
Objectives: The present study aimed to find out the cerebral functional
alterations related to the establishment of central sensitization in migraineurs,
using blood oxygen level-dependent functional magnetic resonance imaging (BOLD
fMRI).
Background: Cutaneous allodynia (CA) is a characteristic of central
sensitization, predicting migraine progression and poor response to therapy. Whether
it attributes to persistent functional changes in the central nociceptive pathway is
still unknown.
Methods: The experiment was performed in 15 migraineurs with CA (MWCA),
19 patients without CA (MWoCA) and 20 matched healthy controls. Demographic and
headache characteristics were collected from all participants, and they all
underwent MRI scanning in the absence of headache. Each subject was given
transcutaneous electrical nerve stimulation (TENS) at the left forehead during fMRI
scanning, achieving to a previously determined level of pain sensation (i.e. VAS =
40).
Results: Demographic and headache characteristics were balanced between
migraine groups. The contrast images of both migraine groups comparing to healthy
controls exhibited decreased activation of various brain regions (e.g. cerebellum
and insulae), which probably take part in the pathophysiological procedure of
migraine. The direct comparison between the two migraine groups revealed that
activation in the dorsal pons and contralateral (right) inferior parietal lobule of
WMCA subjects were significantly lower than it in WMoCA ones.
Conclusions: The interictal dysfunction of pain processing pathway may
be responsible for (at least relevant to) central sensitization in migraine
patients, via abnormal modulations of nociceptive transmission.
P344
A Pilot fMRI Study of Patients with Tension-Type Headache
P. Wang1, N. Chen1, L. He1
1Department of Neurology, West China Hospital of Sichuan
University, Chengdu, Sichuan Province, China.
Objectives: We conduct a pilot study using blood oxygen level Dependent
Functional MRI (BOLD fMRI) to explore whether TTH patients have functional changes
compared to healthy subjects.
Background: Tension-type headache (TTH) is the most common type of
primary headache. Previous studies showed gray matter (GM) decreased in patients
suffering chronic tension-type headache (CTTH) through magnetic resonance imaging
(MRI) and voxel-based morphometry (VBM), suggesting the brain structure has small
changes in CTTH. Considering structural network may affect functional connectivity
via GM decrease in TTH patients, we wannan know whether TTH patients have functional
changes compared to healthy subjects.
Methods: We included TTH patients assessed by ICHD-II and age-, gender-
and education-matched healthy controls in our study. We firstly collected and
compared their clinical characteristics, and then used a 3.0-T MRI system to obtain
MRI data, and analyzed rest functional MRI (rfMRI) data by regional homogeneity
(ReHo) method.
Results: Ten subjects with TTH and ten matched controls were included.
There were no significant differences in demographic features and cognitive function
between groups, but the scores reflecting the degrees of anxiety and depression of
TTH group were significantly higher than those of the controls (p<0.05). Compared
with healthy controls, TTH patients showed that ReHo value increased in bilateral
lentiform nucleus and caudate, which may play an important part in pain
processing.
Conclusions: Our study provided evidence to support the above brain
regions may be abnormal in pain process in TTH patients.
P345
Capsaicin-Induced Nerve Fiber Degeneration in the Spinal Tract of the
Trigeminal Nucleus
M. Shibata1, T. Ebine1, T. Nagai2, H.
Toriumi1, T. Shimizu1, T. Iwashita1, M.
Funakubo1, T. Takizawa1, Y. Kayama1, N.
Suzuki1
1Department of Neurology, School of Medicine, Keio University,
Tokyo/Shinjuku, Japan; 2Electron Microscopy Research Center, School
of Medicine, Keio University, Tokyo/Shinjuku, Japan.
Objectives: The aim of this study is to explore the effect of repetitive
capsaicin trigeminal stimulation on the morphology of nerve fibers of the spinal
tract of the trigeminal nucleus (TNS).
Background: TRPV1 (transient receptor potential vanilloid subfamily
member 1) is expressed in sensory neurons and serves as a transducer of various
noxious stimuli into pain signals, and it is implicated in the pathophysiology of
migraine1). TRPV1 agonists have been used for treating intractable
pain conditions. Notably, capsaicin, a well-known TRPV1 agonist, is shown to be
effective in aborting migraine attacks2). Recent evidence shows that
TRPV1 stimulation induces morphological changes of sensory neurons and nerve
fibers3).
Methods: Male C57BL/6J mice (n = 9) were used. A patch containing 10 mM
capsaicin was applied to the left V1 region of the face for 30 minutes. A
vehicle-containing patch was applied to the same region on the contralateral side.
The patch application was repeated daily and mice were sacrificed at Day 3, 5 and 7
(n = 3 each) after the initial patch application. The mice were transcardially
perfused with 2.5% glutaraldehyde/0.1 M cacodylate-buffer and brainstem sections
harboring TNS were prepared. Electron microscopic analysis of TNS nerve fibers was
performed.
Results: Capsaicin induced a significant reduction in the proportion of
myelinated nerve fibers with the diameter of ≤ 1.0 mm in the whole myelinated nerve
fibers examined at Day 3 compared to the vehicle-treated side (13.3% ± 2.7 % [mean ±
SD] vs. 36.7% ± 6.6%, p = 0.005, t-test). The proportion did not significantly
differ at Day 5 (13.7% ± 6.0%), but exhibited a significant increase to 29.3% ± 5.8%
at Day 7 (p = 0.025). At Day 7, there was a trend for the decreased proportion of
nerve fibers with the diameter of ≤ 2.0 and >1.0 mm on the capsaicin-treated side
compared to the vehicle-treated side (28.7% ± 10.9% vs. 39.7% ± 7.7%, p = 0.228).
Capsaicin also caused a time-dependent decrease in the proportion of unmyelinated
nerve fibers (11.7% ± 0.31% at Day 3, 6.4% ± 0.2% at Day 5, and 5.4% ± 4.8% at Day
7).
Conclusions: Repetitive capsaicin administration causes the degeneration
of both myelinated and unmyelinated fibers in TNS. Myelinated fibers with the
smaller diameter appear to be more vulnerable than those with the larger diameter,
and the increase in the proportion of myelinated nerve fibers with the diameter of ≤
1.0 mm between Day 5 and Day 7 was likely to be explained by concomitant
degeneration of larger nerve fibers. Capsaicin-induced unmyelinated nerve fiber
degeneration in TNS is a time-dependent process. Such degenerative changes may be
relevant to the anti-nociceptive action of capsaicin.
P346
Inflammation Induced Activation of pERK1/2 and NF-κB Show Co-Localization with
CGRP and Its Receptor Components in Rat Trigeminal Ganglion
A. Csati1,2, J. Tajti1,2, L. Vecsei1,3, K.
Warfvinge2, L. Edvinsson2
1Department of Neurology, University of Szeged, Szeged, Hungary;
2Department of Clinical Sciences, Division of Experimental
Vascular Research, Lund University, Lund, Sweden; 3Neuroscience
Research Group, Hungarian Academy of Sciences and University of Szeged, Szeged,
Hungary.
Objectives: Temporomandibular joint inflammation induced activation of
mitogen-activated protein kinase pERK1/2 and transcription factor NF-κB is in
connection with the sensory neurotransmitter CGRP and its receptor components in rat
trigeminal ganglion.
Background: The trigeminal ganglion plays central role in cranial pain
syndromes. It has been shown that calcitonin gene-related peptide (CGRP) has a wide
biological function in the sensory system. In the trigeminal ganglion CGRP is
expressed in small- and medium-sized neurons and fibers, while its receptor
components (calcitonin receptor-like receptor - CLR - and the receptor activity
modifying protein 1 - RAMP1 -) in large neurons and satellite glial cells. Previous
studies have shown that acute inflammation induced by injection of complete Freund’s
adjuvant into the temporomandibular joint (TMJ) resulted in phosphorylation of the
mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 (pERK1/2)
in satellite glial cells. Activation of pERK1/2 initiates induction of nuclear
factor kappa B (NF-κB) which was present in the cytoplasm of small- and medium-sized
neurons in the trigeminal ganglion.
Methods: We hypothesize that there is a connection between the activated
protein kinase and CGRP receptor components and between the transcription factor and
CGRP in rat trigeminal ganglion using immunohistochemistry.
Results: We observed co-localization between activated pERK1/2 and
CLR/RAMP1 in the satellite glial cells after TMJ activation. In addition, double
staining of small- and medium-sized neurons with NF-κB and CGRP revealed that some
cells were only NF-κB positive, others only CGRP positive, and a number contained
both markers (double-stained).
Conclusions: CGRP-containing small- and medium-sized neurons may release
CGRP, acting on CLR/RAMP1-containing satellite glial cells and large neurons in the
trigeminal ganglion. Our results indicate that following TMJ stimulation there is
activation of satellite glial cells, activation of mitogen-activated protein kinase
pERK1/2, an inflammatory transcription factor NF-κB, the sensory neurotransmitter
CGRP and its receptor components. This suggests that TMJ induced inflammation can
elicit a cascade of events in the trigeminal ganglion that may be involved in
cranial pain developments.
P347
White Matter Abnormalities in Corpus Callosum in Episodic and Chronic Migraine
Patients: A Tractography Study
M.L. Peñas4, D. Argibay2, S. Herrero1, C. de la
Cruz1, M.I. Pedraza1, J.M. Sierra3, A.L.
Guerrero1, S. Aja2
1Neurology, Hospital Clinico Universitario, Valladolid, Spain;
2Teoría de la Señal, Universidad de Valladolid. Escuela Técnica
Superior de Ingenieros de Telecomunicación, Valladolid, Spain;
3Radiology, Centro Diagnóstico Valladolid, Valladolid, Spain;
4Neurology, Hospital Virgen de la Concha, Zamora,
Spain.
Objectives: We aimed to characterize and compare microstructural changes
in corpus callosum in patients with episodic and chronic migraine. We analyzed
indices derived from diffusion tensor magnetic resonance imaging (DT-MRI) study.
Background: DT-MRI can detect cerebral white matter abnormalities non
displayed on conventional MRI sequences. Some studies have shown abnormal white
matter properties in several brain regions in migraine patients, including corpus
callosum, as well as a correlation between some of the indices studied and frequency
of migraine attacks or comorbidity with depressive or anxious disorders. Chronic
migraine is the most severe end of the broad spectrum of migraine; chronicity in
migraine is not simply an increased quantity of headache days, but rather a
qualitative shift, perhaps based on pathophysiological differences.
Methods: We selected 12 patients (1 male, 11 females) attended in a
headache clinic in a tertiary hospital. Episodic migraine (Group A) was diagnosed
accordingly to ICHD-II. For chronic migraine (Group B) we considered ICHD-II revised
criteria. We administered six-item Headache Impact Test (HIT-6) and Hospital Anxiety
and Depression Scale (HADS). A GE Signa 1.5 T MR scanner was used in this study. We
analyzed genu, body, and splenium parts of corpus callosum. Computation of the fiber
tracts was made by means of a forth order Runge-Kutta algorithm to interpolate the
vector field composed by the major eigenvector of the diffusion tensor at each
voxel. Each of the image voxels belonging to the white matter were considered as a
seed for fiber trajectory estimation. Once all the fiber tracts had been computed,
the bundle of interest was selected using a set of regions of interests (ROIs).
Indices considered were fractional anisotropy (FA), relative anisotropy (RA), mean
diffusivity (MD), tract integrity, lineal, planar and spherical coefficients and
eigenvalues (EV). Independent sample t-test was used to test the differences of
indices means between Group A and B.
Results: Five patients (1 male, 4 females, 35.6 ± 5.2 years) were
included in group A, and seven (all females, 34.5 ± 11.4) in Group B. We found no
differences between groups A and B in HIT-6 score (60.6 ± 3.2 vs 64.4 ± 4), or HADS
anxiety (4.6 ± 2 vs 3.7 ± 4) and depression (1.8 ± 2.1 vs 2.1 ± 4.4) scores. Chronic
migraine patients showed significantly lower MD in ROIs of the body part of corpus
callosum (0.099 ± 0.006 vs 0.117 ± 0.009, p:0.003). This difference between both
groups was also consistently observed in the three EV of ROIs considered.
Conclusions: In spite of the short number of patients considered,
compared with episodic migraine, chronic migraineurs showed significantly more white
matter abnormalities in body part of corpus callosum.
P348
New Onset Migraine with Aura after Treatment Initiation with
Ivabradine
W. Supronsinchai1,3, T. Sprenger2, P.J. Goadsby1
1Department of Neurology, University of California, San Francisco,
San Francisco, CA, USA; 2Department of Neurology and Division of
Neuroradiology, University Hospital Basel, Basel City, Basel, Switzerland;
3Department of Physiology, Faculty of Dentistry, Chulalongkorn
University, Bangkok, Thailand.
Objectives: We report on the case of a patient with new onset migraine
with aura after treatment initiation with the novel ion channel blocker, ivabradine
and explore the effect of this drug on the laboratory model of CSD.
Background: Migraine with aura is a complex neurological disorder
modeled in animals by cortical spreading depression (CSD). It is less usual to find
complete animal models for disease so any opportunity to test a human effect back at
the bench is welcome.
Methods: The patient, a 24 year old woman who developed new onset
episodic migraine with visual aura shortly after treatment initiation with
ivabradine for frequency control in hypertrophic cardiomyopathy. Before starting
ivabradine, she had infrequent and low intensity headache without typical migrainous
features, and without migraine aura. With ivabradine treatment, she developed
frequent attacks of migraine with aura attacks.
Adult male Sprague-Dawley rats were separated into two groups, control and
ivabradine. In both groups CSD was induced by topical application of 3 mg KCl on the
frontal cortex. After inducing one CSD and recording of the respective DC shift and
cerebral blood flow (CBF), ivabradine (2 mg kg-1, i.v.) or saline
(control group) was administered, and DC shifts and CBF were recorded with a glass
microelectrode and laser Doppler flow meter, respectively, for one hour.
Results: Six-teen rats received either ivabradine or saline and the
number of DC shifts and CBF changes induced by CSD were measured in both groups. The
number of DC shifts was 9±2, and 9±1 in the control and ivabradine treated groups,
respectively. The average amplitude of the DC shifts was 19.7±3.2 and 21.4±3.8 mV
and the duration of the DC shifts was 46.8±12.6 and 45.0±15.0 seconds in the control
and ivabradine treated groups, respectively. The difference between groups was not
statistically significant in any parameter of DC shifts as well as in terms of
hyperemia as determined by CBF measurement (p>0.05).
Conclusions: The clinical case suggests that ivabradine may have
facilitatory effects on the development of migraine aura. However, we were unable to
prove that the drug influences the susceptibility of the brain to CSD. Further
knowledge about the exact biological and clinical properties of ivabradine with its
more widespread use may help to better understand the frequency of effects on
migraine and aura as well as the potential mechanisms.
P349
Transcranial Doppler in the Objective Diagnosis of Primary Cephalgia
C. Moreira1, H. Stokes1, A. Stokes1
1Neuology, Hospital General San Juan de Dios, Guatemala,
Guatemala.
Objectives: Determination of the usefulness of transcranial doppler in
the objective diagnosis of primary cephalgia.
Determination of the utility of transcranial doppler in the objective diagnosis of
primary cephalgia.
Background: Determination of the usefulness of transcranial doppler in
the objective diagnosis of primary cephalgia, Patients with migraine primary
headaches showed an increase of 30-35% in blood flow velocity (BFV).
Methods: Three groups of 25 patients each were studied: the first group
consisting of patients with migraine primary headaches, the second group with
tension-type headache, and the third group with symptomatic headaches of varying
etiologies. Transcranial Doppler (TCD) was used.
Results: Patients with migraine primary headaches showed an increase of
30-35% in blood flow velocity (BFV). The measurable effects of vasoconstriction were
observed in the cervical blood vessels, such as the interior and exterior carotid
arteries, with a lower incidence on the common carotid artery. Intracranially the
findings were less conspicuous, showing a higher degree of alteration in the middle
cerebral artery and a lower degree in the ophthalmic arteries.
The cerebral artery normal BFV was measured as 30-60 meters per second (m/s), while
the BFV of altered blood vessels was measured above 80 m/s.
Conclusions: Since TCD is a non-invasive technology with a relative ease
of use by trained hands, which allows not only an objective measurement of the
cervical and cerebral BFV, but also the determination of the pulsatility and
resistance indexes. TCD, besides being one of a handful of methods for objectively
evaluating the cerebral arteries, is an essential tool in the verification of
primary cephalgia and cases that reach a migrainous state and a valuable aid in
functional prognosis.
P350
Quadrigeminal Plate Lipoma Presenting with Migraine with Visual Aura
Y. Celik1, E. Unlu2
1Neurology, Trakya University School of Medicine, Edirne, Turkey;
2Radiology, Trakya University School of Medicine, Edirne,
Turkey.
Objectives: Migraine has been associated with a variety of structural
brain lesion, including tumors and clinically silent infarct-like lesions in the
posterior circulation territory and white matter hyperintensities.
Background: The association of midbrain lesions and migraine has been
described in the literature, as has migraine associated with midbrain lesions.
Intracranial lipomas located in the quadrigeminal plate and ambient cistern account
for 13 % and 43 % and are less symptomatic. The most common symptoms in the
quadrigeminal lipomas are epilepsy, behavioural abnormalities, increased
intracranial pressure, mass effect, and hydrocephalus.
Methods: We report the case of a patient presenting migraine with visual
aura located in the quadrigeminal area.
Results: A 36-year-old woman with daily attacks of migraine with visual
aura is presented. The aura always occurred on the left and the migraine headache
always on the left side of the head.
Conclusions: The case is discussed in the light of our present
understanding of the pathogenesis of the migraine attack. The brainstem lesions
could induce periaquaductal gray matter and trigeminothalamic pathway and cause
migraine with aura.
P351
Visual Auras May Explain a Cause of Migraine
P.G. VanValkenburgh
California State University, Long Beach, CA, USA.
Objectives: Pinpoint the origins of migraine in occipital cortex.
Background: It is commonly accepted that visual aura indicates Cortical
Spreading Depression (CSD), or depolarization, which is a neuro-chemical disturbance
leading to some migraines. The goal here was to identify repeating aura/CSD
origins.
Methods: More than 1,000 visual auras were logged on one person over 15
years, with their progressions plotted in degrees of visual angle at 1-minute
intervals, and then matched to MRI images and precise 3-D models of the same visual
cortex.
Results: It appears that these aura (and CSD) paths correlate with the
calcarine sulcus, where the origins of CSD consistently correlate with rare
irregularities such as pits or kinks deep in the fundus, and progress as a traveling
“spot” of about 5x10 mm, and not as a radially expanding front.
Conclusions: Natural spontaneous human CSD seems to be explainable as
propagation of a transient local pressure increase, when the effect of normal cyclic
swelling in neurons and astrocytes (due to ion flux), is amplified in the tight
folding of outer cortical layers I and II. When constrained in sulci irregularities,
it might create a traveling “spot” of extra-cellular compression, excreting
potassium, and preceding CSD. This suggests research into a new prophylaxis for
migraine.
P352
Capturing the Aversive State of Headache Pain Preclinically
M. De Felice1, N. Eyde1, D.W. Dodick2, G.O.
Dussor1, M.H. Ossipov1, F. Porreca1
1Pharmacology, University of Arizona, Tucson, AZ, USA;
2Neurology, Mayo Clinic Arizona, Phoenix, AZ, USA.
Objectives: Preclinical evaluation of headache pain by assessment of
reward from pain relief.
Background: One impediment in discovery of new therapies for migraine
has been a lack of preclinical models of headache.
Pain is aversive at threshold and demands a behavioral response, i.e., relief. Relief
of pain is a reward in humans and in animals. Human neuroimaging studies demonstrate
that cerebral systems implicated in pain processing and reward are integrated with
multiple overlapping brain areas including the anterior cingulate cortex (ACC). We
have shown that relief of ongoing pain in rats with non-opioid treatments (e.g.,
peripheral nerve block) activates the mesolimbic dopaminergic reward circuit in a
model of post-surgical pain.
We made the assumption that activation of dural nociceptors with a cocktail of
inflammatory mediators (IM) would elicit headache pain in rat. Our previous studies
show that activation of dural nociceptors engages pain facilitation mechanisms from
the rostral ventromedial medulla (RVM). Inactivation of the RVM with local
anesthetic is thus expected to produce relief of ongoing pain.
Methods: Rats received either IM or synthetic interstitial fluid (SIF)
onto the dura mater via previously implanted cannulae to elicit headache pain. Three
hr after the dural treatment, lidocaine was microinjected into the RVM. Behavior was
assessed with conditioned place preference (CPP) where animals learn to associate a
context with a rewarding treatment, in this case, “pain relief” from RVM lidocaine.
Drugs were microinjected within the nucleus accumbens (NAc) or the rostral anterior
cingulate cortex (rACC). Immunohistochemistry and microdialysis measurements were
also performed.
Results: RVM lidocaine produced CPP selectively in rats receiving dural
IM. Following RVM lidocaine, increased c-FOS expression and dopamine release were
observed in the NAc selectively in IM rats and CPP was blocked by intra-NAc
α-flupenthixol, a dopaminergic antagonist. Intravenous treatment with
CGRP(8-37),3hr post dura-injection, produced CPP selectively in
IM-treated rats. Elimination of pain-induced aversiveness by prior rACC lesion, or
treatment with s.c. sumatriptan, or i.v. CGRP(8-37) abolished RVM
lidocaine-induced CPP in IM-treated rats. S.c. sumatriptan (30 min post dura
injection) prevented NAc dopamine release in IM treated rats receiving RVM
lidocaine.
Conclusions: Treatments that are not intrinsically rewarding can become
rewarding in the presence of pain. Headache pain was unmasked in rats by assessment
of motivated behavior to seek relief captured through CPP. The relief of headache
pain activates the dopaminergic reward pathway to produce negative reinforcement of
behavior. Medications effective for treatment of migraine headache in humans abolish
CPP from pain relief. These studies provide a platform for understanding migraine
pathophysiology and for the discovery of new mechanisms that may translate to
effective therapies for headache pain.
P353
Effect of 5-HT Receptor Antagonist on Cortical Spreading Depression in
Rats
S. Akuzawa1, H. Kaku2, K. Ni1
1Pharmacology Research Labs., Astellas Pharma Inc., Tsukuba-shi,
Japan; 2Chemistry Research Labs., Astellas Pharma Inc., Tsukuba-shi,
Japan.
Objectives: In this study, the effects of ASP1017FM, pizotifen malate
and topiramate on KCl-induced cortical spreading depression (CSD) in rats were
evaluated.
Background: It has been reported that CSD generated within brain is
playing an important role in the pathophysiology of migraine.Among
neurotransmitters, 5-hydroxytryptamine (5-HT; serotonin) has important roles in the
pathophysiology of migraine. Almost all 5-HT receptor antagonists such as
methysergide, pizotifen, cyproheptadine and amitryptyline which are used as migraine
prophylactics display relatively high affinity to 5-HT2B and
5-HT7 receptors and these affinities have been shown to correlate
with pharmaceutically active doses of these agents.
Methods: Male Sprague-Dawley rats were treated with ASP1017FM, pizotifen
malate and topiramate as single daily oral administrations for 6 weeks.On the last
treatment day, animals were anaesthetized and operated. The direct current
(DC)-potential changes were recorded with an electrometer. A cotton ball soaked with
1 mol/L KCl was placed on the pial surface and kept moist by placing 5µL of KCl
solution every 15 minutes. The number of KCl-induced CSD was counted for 2 hours.
The number of KCl-induced CSD was counted for 2 hours.
Results: In control rats chronically administered vehicle, topical KCl
application induced 15.4 ± 0.4 of CSD in 2 hours. Six weeks’ treatment with each of
the three test drugs decreased the number of the KCl-induced CSD in rats. Chronic
treatment with ASP1017FM, pizotifen malate, and topiramate suppressed CSD, with the
minimum effective doses of 0.1, 3, and 60 mg/kg po, respectively.
Conclusions: The effect of ASP1017FM, a new selective 5-HT2B
and 5-HT7 dual receptor antagonist, on KCl-induced CSD in rats was
evaluated. Additionally, the effects of the anti-migraine prophylactic drugs
pizotifen malate and topiramate, on CSD were also evaluated. Results showed that six
weeks treatment of ASP1017FM, pizotifen malate, and topiramate suppressed
KCl-induced CSD in rats. These findings suggest that both 5-HT2B and
5-HT7 receptor may contribute to suppressing effect of
serotonin-related agents on CSD and ASP1017FM may be effective as an anti-migraine
prophylactic drug.
P354
Effect of CGRP Antagonism in Nitroglycerin-Induced Hyperalgesia
R. Greco2, S.A. Mangione2, F. Blandini3, G.
Sandrini1, G. Nappi4, C. Tassorelli1
1Headache Science Centre, Neurological Institute C. Mondino
Foundation and University of Pavia, Pavia, Italy; 2Headache Science
Centre, Neurological Institute C. Mondino Foundation, Pavia, Italy;
3Lab. of Functional Neurochemistry, Neurological Institute C. Mondino
Foundation, Pavia, Italy; 4Headache Science Centre, Neurological
Institute C. Mondino Foundation, Pavia, Italy.
Objectives: The aim of the present study was to test the analgesic
effect of CGRP receptor antagonist MK885, in two animal models of pain: the tail
flick test and the formalin test, following ‘sensitization’ by nitroglycerin.
Background: The release of calcitonin gene-related peptide (CGRP) from
trigeminal nerves plays a central role in the pathophysiology of migraine. Clinical
evidence shows an anti-migraine effect for CGRP antagonists. Systemic administration
of nitroglycerin (NTG), a nitric oxide (NO) donor, consistently provokes
spontaneous-like migraine attacks in migraine sufferers. In the rat, systemic NTG
induces a condition of hyperalgesia, probably via the activation of cerebral/spinal
structures involved in pain transmission.
Methods: Male Sprague-Dawley rats were treated systemically with
nitroglycerin. Thei nocicpetive response to the tail flick test and to the formalin
test were evaluated in baseline conditions and following co-administration of the
CGRP antagonist M8825.
Results: MK8825 counteracts nitroglycerin-induced hyperalgesia in both
nocicecptive tests. The results also show that M8825 reduces the nociceptive
behavior when administered both simultaneously or prior (30-60 minutes before) to
nitroglycerin.
Conclusions: These data suggest that MK8825 may represent a potential
tool for the treatment of migraine by interacting with upstream mechanisms in the
cascade of events that mediate the attack.
P355
Intravenous Administration of CGRP in Unanaesthetized Rats Causes Increase
Expression of c-Fos in the Nucleus Tractus Solitarius and Caudal Ventrolateral
Medulla, but Not in the Trigeminal Nucleus Caudalis
D.K. Bhatt1, R. Ramachandran1, S.L.T. Christensen1,
S. Gupta1, K.B. Ploug1, I. Jansen-Olesen1, J.
Olesen1
1Department of Neurology, Glostrup Hospital, Faculty of Health and
Medical Sciences, University of Copenhagen, Glostrup, Denmark.
Objectives: The human GTN infusion model has been translated to the rat.
We hypothesize that CGRP infusion in unanaesthetized freely moving rats will induce
migraine like pain reflected by increase in Fos expression in TNC, without
intervening factors such as anaesthesia, acute surgery and severe hypotension.
Background: CGRP and glyceryl trinitrate (GTN) infusion in humans
provokes headache resembling spontaneous migraine, and CGRP receptor antagonists are
effective against acute migraine.What is still fiercely contested, is the site of
action of CGRP and CGRP receptor antagonists.
Methods: CGRP was infused in freely moving rats. The effect of infusion
of CGRP (0.25 µg kg-1 min-1 and 1.00 µg kg-1
min-1, for 20 min) on diameter of middle meningeal artery (MMA) and
on mean arterial blood pressure (MABP) in anaesthetized rats was recorded by using
the genuine closed-cranial window (CCW) model. TNCs were isolated at different time
points after infusion. The level of Fos mRNA and protein expression in TNC were
analyzed by qPCR and immunohistochemistry. FOS stained nuclei were also counted in
the nucleus tractus solitaries (NTS) and caudal ventrolateral medulla (CVLM),
integrative sites in the brain stem for processing cardiovascular signals. We also
studied mRNA expression of CGRP and its receptor component in trigeminovascular and
other pain processing structures in the brain.
Results: Intravenous (i.v.) infusion of CGRP (0.25 µg kg-1
min-1 and 1.00 µg kg-1 min-1, for 20 min)
caused a significant drop in MABP both in the unanaesthetized rats (-19 ± 4 % and
-33 ± 6 %) and in the anaesthetized rats (-34 ± 3% and -41 ± 4 %), and the same
doses caused significant increase in MMA diameter (154 ± 28 % and 162 ± 28 %) in the
CCW model. No significant activation of c-Fos in TNC at mRNA and protein level was
observed. A significant (p<0.05) increase in c-Fos protein was observed in NTS
and CVLM in the brain stem. The mRNA expression profile showed that CGRP and its
receptor components are widely distributed in trigeminovascular and other pain
processing structures. The mRNA expression of CGRP and its receptor components in
TNC was unaffected 2 h after CGRP infusion.
Conclusions: The mRNA expression of CGRP receptors in various central
pain pathways suggests involvement of CGRP in migraine. Incontrast to our previous
studies with GTN, i.v infusion of CGRP had no effect on expression of Fos in TNC.
The CGRP infusion model in the naïve rat seems unsuitable for studying activation of
second order trigeminal neurons.
P356
Expression, Localization and Neuro-Modulatory Properties of the IP Receptor in
Migraine Relevant Tissues
M. Myren1, R. Ramachandran1, D. Amrutkar1, A.
Hay-Schmidt2, I. Jansen-Olesen1, S. Gupta1, J.
Olesen1
1Department of Neurology, Danish Headache Centre, Glostrut
Research Institute, Faculty of Health and Medical Sciences, University of
Copenhagen, Copenhagen, Denmark; 2Deparment of Neuroscience and
Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen,
Copenhagen, Denmark.
Objectives: To study the expression and localization of IP
receptor and effect of its agonist on KCl induced CGRP release in
migraine relevant tissues.
Background: Prostaglandins I2 (PGI2) and
calcitonin gene-related peptide (CGRP) are able to induce headache in humans.
PGI2 acts via a G-protein coupled receptor ‘IP’.
Methods: The mRNA and protein expression of the IP receptor was studied
by real-time PCR and western blotting, respectively. Co-localization of the IP
receptor and CGRP in the rat trigeminal ganglion (TG) and trigeminal nucleus
caudalis (TNC) was studied by immunofluoresence. The effect of IP receptor agonists
and antagonists on immunoreactive CGRP (iCGRP) release was investigated in freshly
isolated rat dura mater, TG and TNC by ELISA.
Results: The IP receptor was significantly more expressed in the rat
dura mater than in the cerebral arteries on both mRNA and protein levels. mRNA and
protein for the IP receptor were significantly more expressed in TG than in TNC. We
found that IP receptors and CGRP are co-localized in the neurons of TG and on the
nerve fibres in TNC. In dura mater, the iloprost, an IP receptor agonist
significantly decreased KCl induced iCGRP release from 61.5 ± 14.05 pg/ml to 41.4 ±
7.1 pg/ml and it was not reversed by the IP receptor antagonist, CAY10441 or the
EP1>EP3 receptor antagonist, SC51322. In TG iloprost
had no effect on KCl induced iCGRP release. Per se iloprost had no effect on basal
iCGRP release in dura mater and TG.
Conclusions: We found the IP receptor was expressed in migraine relevant
tissues. In TG the IP receptors were co-localized with CGRP. Thus, the IP receptor
might be a target for development of future anti-migraine drugs.
P357
The Feverfew Constituent, Parthenolide, Inhibits Transient Receptor Potential
Ankyrin 1-Mediated Responses: Relevance for Migraine Treatment
S. Materazzi1, S. Benemei1,2, R. Nassini1, P.
Geppetti1,2
1Dept. of Health Sciences, Clinical Pharamcology and Oncology
Unit, Univ. of Florence, Florence, Italy; 2Headache Center, Univ. of
Florence, Florence, Italy.
Objectives: We hypothesized that parthenolide inhibits TRPA1 on
trigeminal nerves, thereby reducing nociception and sensory neuropeptide
release.
Background:Tanacetum parthenium L. (feverfew) has long been known as a
migraine remedy and, according to positive results of clinical trials, it is
currently recommended for migraine prevention. However, the mechanism responsible
for such protective action remains unknown. The sesquiterpene lactone, prthenolide,
a major ingredient of feverfew, is a reactive molecule that can interact with
nucleophilic sites of the transient receptor potential ankyrin 1 (TRPA1) channel.
The role of TRPA1 in migraine pathophysiology has been suggested by the observation
that both the reactive α,β-unsaturated aldehyde and TRPA1 agonist, acrolein, and one
major volatile ingredient of the headache tree, umbellulone, target TRPA1 to produce
a CGRP-dependent meningeal vasodilatation.
Methods: We used cultured cells, isolated rat tissues, rats and wild
type and TRPA1 deleted mice. Electrophysiological and calcium imaging responses,
neuropeptide release, smooth muscle motility were evaluated
in vitro. Allodynic and nociceptive responses, and changes in
meningeal blood flow were studied in vivo.
Results: Parthenolide selectively activates recombinant (transfected
cells) or constitutive (rat/mouse trigeminal neurons) TRPA1, and by TRPA1
stimulation releases calcitonin gene-related peptide (CGRP) from trigeminal nerve
endings. However, parthenolide behaves as a partial agonist at neuronal TRPA1 of rat
urinary bladder, desensitizes the recombinant TRPA1, and, by channel targeting,
renders TRPA1-expressing nerve terminals unresponsive to any stimulus. These effects
result in inhibition of nociceptive responses selectively evoked by TRPA1 agonists,
and of CGRP release from trigeminal neurons and CGRP-mediated meningeal
vasodilatation evoked by different and unselective stimuli.
Conclusions: These three novel actions of parthenolide (TRPA1 partial
agonism, selective channel desensitization, and unselective defunctionalization of
peptidergic TRPA1-expressing trigeminal neurons) may contribute to the protective
effect of feverfew in migraine.
P358
VIP and PACAP in the Circulation after Sumatriptan
J.M. Hansen1, J. Fahrenkrug2, J. Petersen3, T.
Wienecke1, K.S. Olsen3, M. Ashina1
1Department of Neurology, Glostrup Hospital, Faculty of Health
Sciences, University of Copenhagen, Danish Headache Center, Glostrup,
Copenhagen, Denmark; 2Department of Clinical Biochemistry, Bispebjerg
Hospital, Copenhagen, Denmark; 3Department of Anesthesiology,
Glostrup Hospital, Glostrup, Copenhagen, Denmark.
Objectives: To examine the effect of sumatriptan on Vasoactive
Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase-Activating Polypeptide
(PACAP) levels in vivo, under conditions without trigeminovascular
system activation.
Background: The triptans, 5-hydroxytryptamine
(5-HT1B/Dreceptor agonist), are effective and well tolerated in acute
migraine management. Triptans may lead to a decreased release of neuropeptides such
as calcitonin gene-related peptide (CGRP) but potentially also other neuropeptides,
as VIP and PACAP.
Methods: In 16 healthy volunteers, we sampled blood from the internal
and external jugular, the cubital veins and the radial artery before and after
administration of subcutaneous sumatriptan.
Results: We found no difference in VIP and PACAP concentrations between
the internal and external jugular, the cubital veins and the radial artery
(P > 0.05), and the circulating levels of VIP and PACAP did
not change over time (P > 0.05). VIP (squares) and PACAP
(triangles) before and after 6 mg subcutaneous sumatriptan(median ± SEM).
Conclusions: Sumatriptan did not change the levels of circulating VIP
and PACAP in the intra or extra cerebral circulation in healthy volunteers. Under
baseline conditions, without trigeminovascular activation, sumatriptan does not
affect the release of neuropeptides VIP and PACAP.
P359
The Effects of Acute Intrathecal and Intraperitoneal Glyceryl Trinitrate
Administration on Orofacial Pain in Mice
T. Alexa1,2, A. Dondas2, A. Luca1,2, A.L.
Negru2, G. Andron2, C.R. Bohotin1,2
1Pathophysiology, University of Medicine and Pharmacy “Gr. T.
Popa” Iasi, Iasi, Romania; 2Centre for the Study and Therapy of Pain
Iasi, Iasi, Romania.
Objectives: The aim of the study was to investigate the effects of acute
intraperitoneal (i.p.) and intrathecal (i.t.) administration of glyceryl trinitrate
(GTN) on orofacial pain in mice.
Background: GTN administration is considered a reliable experimental
model of migraine, based on the GTN neuronal effects on the integrative-nociceptive
structures. The underlying mechanisms are not known, but a central effect might be
responsible for its effects, such as a change in neuronal excitability and synaptic
transmission of various CNS areas involved in pain and behavior. The actions of
glyceryl trinitrate (GTN) are the result of its bioconversion into nitric oxide (NO)
that increases the intracellular concentration of cyclic guanosine monophosphate,
which produces pain modulation in the central and peripheral nervous system.
Methods: Thirty-two BALB/c male mice were divided into 4 groups: two of
the groups received GTN injections - i.p. GTN 10 mg/Kg b.w. (group GTN i.p.) and
i.t. GTN 0.01 mg/kg b.w. (group GTN i.t.) and the other two groups served as control
and were administered i.p. or i.t. equivalent volumes of saline (group S-i.p. &
group S- i.t.) and were treated in a dose/time manner similar with GTN groups. Two
hours after the injection, the formalin orofacial test was performed. The time mice
spent grooming and rubbing the injected area was reported separately for the first
phase (5 minutes) and the second phase (20 minutes). The results were analyzed by
means of ANOVA one-way testing (Bonferroni coefficient).
Results: Intrathecal GTN administration had a significant effect on both
phases of the formalin induced orofacial pain (p=0,025 and 0=0,013) when compared
with intrathecal administration of saline. Intraperitoneal administration of GTN had
an analgesic tendency (p=0,054) on phase one and no statistically significant effect
(p>0,05) on phase two when compared to control.
The analgesic effects of intrathecal administration was superior to that of
intraperitoneal administration (p=0,002).
Conclusions: The effects of nitroglycerine on pain are controversial.
Some studies report that GTN, by increasing NO concentration, can develop and
maintain persistent hyperalgesia in rats. Other studies indicate the fact that
increased NO concentration can have an antinociceptive effect and that GTN
administration can lead to analgesia.
In our study, intrathecal GTN administration in mice exerted analgesic effects on
both acute and inflammatory pain, proving to be superior to intraperitoneal
administration. Taken together, our results demonstrate that the manner in which a
substance is administered and metabolized influences greatly its effect on pain.
P360
The Relationship of Headache and Insomnia Reviewed and That of Insomnia and
Migraine Studied with Eszopiclone
1Craniofacial Pain Center, Tufts University School of Dental
Medicine, Boston, MA, USA; 2Neurology, Brigham and Women’s Hospital,
Harvard Medical School, Boston, MA, USA; 3Neurology, Tufts Medical
Center, Boston, MA, USA; 4Associated Neurologists of Southern
Connecticut, Fairfield, CT, USA; 5Hartford Hospital, Hartford, CT,
USA; 6School of Pharmacy, Northeastern University, Boston, MA,
USA.
Objectives: The purpose of the review was to summarize the literature
and analyze it in light of the nature of the headache-insomnia relationship. The
purpose of the study with eszopiclone was to determine whether improving insomnia in
migraineurs improves headache.
Background: Headache, including migraine, and insomnia are very common
and burdensome complaints worldwide. Globally, the percentage of the general
population with headache is 47%, including 10% with migraine, and the prevalence of
insomnia in general is 30% to 48% of the general population.
Methods: For the review, an extensive literature search was conducted
using the terms, “headache”, “migraine”, “insomnia”, “sleep”, “sleep deprivation”,
and “sleep loss”, on the search engines, PubMed®, ScienceDirect®, Medline®, and
Google Scholar®. In the context of the study, we treated 79 subjects with ICHD-II
migraine with or without aura and DSM-IV primary insomnia for 6 weeks with 3 mg
eszopiclone or placebo at bedtime, using a randomized, double-blind design.
Results: The review suggested that headache or migraine is associated
with insomnia, while only severe insomnia is associated with
headache or migraine. In addition, it was found that insomnia is a risk factor for
headache or migraine onset and for increased headache frequency, specifically for
tension headache and migraine. Of the 79 subjects randomized in the study, 75 were
evaluable, 35 in the eszopiclone group and 40 in the placebo group. The study showed
that of the sleep variables, total sleep time, sleep latency, night-time awakenings,
and sleep quality, only the number of night-time awakenings during the 6-week
treatment period was significantly lower in the eszopiclone group than in the
placebo group. Of the three sleep-related daytime variables, alertness, fatigue, and
functioning, this was also the case for fatigue. The headache variables, frequency,
duration, and intensity, however, did not show statistically significant differences
from placebo during the 6-week treatment period.
Conclusions: As insomnia appears a risk factor for headache or migraine
onset, patients with insomnia should probably be routinely evaluated for headache.
As it also seems to be a risk factor for increased headache frequency, particularly
in tension headache and migraine, patients with these disorders should probably be
routinely treated for insomnia, if present, as part of their overall management. In
the study, we attempted to test this approach for migraine using eszopiclone to
treat insomnia but the medication did not sufficiently improve insomnia for the test
to be valid.
P361
How Long Do I Have To Wait? Interval for the Effect of Different Triptans in
Acute Migraine. A Study in Mexican Population
Marfil R ivera, A. Siller Reyes1, M.F. de la Cruz González1,
J.G. Garza Martínez1, A.T. Cantú Macías1, J.A.
Garza-Villarreal1
1Servicio de Neurología, Hospital Universitario, UANL, Monterrey,
Nuevo León, Mexico.
Objectives: To determine the interval for the effect and its degree of
different triptans in Mexican migranous patients during treatment of acute
attacks.
Background: The interval for the onset of the effect of most triptans
has not been studied properly. There are no studies in Mexican population on this
issue.
Methods: Inclusion criteria were: adult patients, any gender, migraine
w/wo aura according to IHS criteria and treatment of al least two attacks. Period of
study: july 1, 2011 – november 30, 2012. Data were obtained retrospectively and
prospectively. The patients were instructed to use the triptan indicated by his/her
physician and to look at the onset of the anagesic effect, measured in minutes, the
interval to achieve 50% release (T1) and > 80% (T2), as well as side effects.
Pain intensity was measured with a visual analogue scale. To investigate interval
difference, we used repeated measures ANOVA with within-subjects factors with 2
levels (T1 vs. T2) and between-subjects factors with 3 levels (ELT, RZT, ZMT). We
also performed a post-hoc analysis using Bonferroni correction for multiple
comparisons.
Results: 56 patients were studied, 47 female. 23 with eletriptan (ELT),
18 with zolmitriptan (ZMT) and 15 with rizatriptan (RZT). Mean age for the group was
34.8 (16 min - 52 max) with no differences between subgroups of triptans or gender.
Migraine w/a were 49 and wo/a were 7. Mean (SD) T1/T2 for all the patients were 30
(±29)/62 (±58) min, and for the subgroups (ELT/RZT/ZMT): T1 24.45 (±15.56)/39.73
(±47.23)/28.89 (±17.95), and T2 47.04 (±32.83)/81.33 (±96.15)/64 (±35.22). The
dispersion measured by the standard deviation was greater in the RZT than ELT and
ZMT. As expected, we found a significant difference between Intervals (T1/T2: F (1,
52) = 54.35, p < .001). However, there was no significant interaction between
Interval and triptans, nor we found an effect of the triptans. Overall, although the
mean interval was greater in the RZT, the type of triptan did not affect the
interval.
Conclusions: Our resuls show that the onset o triptan effect is shorter
than reported in this sample of Mexican population. Although the sample size is
small, all three triptans studied showed no difference in interval. Should this be
corroborated, it could change the recomendations for their use.
P362
Headache Following Mild TBI in Children: What Are the Risks?
H.K. Blume1, N. Temkin3, J. Wang2, V.S.
Monica2, K.M. Jaffe2, D. Durbin5, A.
Dorsch4, F.P. Rivara2
1Child Neurology, Seattle Children’s Hospital, Univ. of
Washington, Seattle, WA, USA; 2Harborview Injury Prevention Center,
Seattle, WA, USA; 3Biostatistics and Neurological Surgery, Univ. of
Washington, Seattle, WA, USA; 4Pediatric Psychology, Mary Bridge
Chidlren’s Hospital, Tacoma, WA, USA; 5Emergency Medicine, The
Children’s Hospital of Philadelphia, Philadelphia, WA, USA.
Objectives: To determine the risk factors for headache 3 and 12 months
after mild traumatic brain injury (mTBI) in children ages 5-17 years.
Background: Headache is the most common complaint following mild TBI.
However, there are little data regarding risk factors for prolonged post-traumatic
headache following concussion or mild TBI in children and adolescents.
Methods: This is a prospective cohort study of children with mTBI
(n=402) or arm injury (n=122) in which we analyzed the prevalence of and risks
factors for headache 3 and 12 months after injury. Parents completed surveys at the
time of injury and 3 and 12 months thereafter. Headache was defined as any headache
in the week prior to survey completion. Persistent headache was defined as having
headache at both the 3- and 12- month follow-up surveys. We used multivariate
logistic regression to determine which factors were associated with both 3 month and
persistent headache risk.
Results: Three months after injury, 43% of those with mTBI and 26% of
those with arm injury had headache [RR: 1.7 (95% CI:1.2-2.3)]. Persistent headache
was more common after mTBI than arm injury (28% vs. 19%), but this difference was
not statistically significant [RR: 1.2 (95% CI:0.9-1.5)]. Headache 3 months after
mTBI was associated with female sex [OR:2.9 (95% CI:1.7-5.0)], family history of
headache [OR: 1.8 (95% CI:1.1-2.9), pre-injury chronic pain [OR:6.7 (95%
CI:1.4-32.6)], prior NSAID use [OR: 2.2 (95% CI:1.2-3.4)], lower pre-injury quality
of life [OR: 0.96 (95% CI:0.94-0.98)], and loss of consciousness (LOC) with amnesia
[OR: 2.6 (95% CI: 1.4-4.8)] at the time of injury. Presence of intracranial
hemorrhage or skull fracture was not associated with headache risk. Persistent
headache was associated with female sex, family history of headache, chronic pain
prior to injury, lower quality of life, prior NSAID use, and low income, but was not
associated with injury characteristics.
Conclusions: Both pre-injury factors and injury characteristics are
associated with headache 3 months after pediatric mTBI. Clinical indicators of
injury severity such as LOC and amnesia were associated with headache risk but skull
fracture and intracranial hemorrhage were not. The risk for persistent headache
after mTBI was associated with pre-injury patient characteristics rather than injury
severity. Although there are limited data on the optimal treatment of post-traumatic
headache in pediatrics, given our findings, providers should consider early
intervention for patients with multiple risk factors for prolonged headache
following mTBI.
P363
Comparison of the Post-Concussion Syndrome (PCS) in OEF/OIF Veterans with
Traumatic Brain Injury (TBI) Due to Blast Injury (BI) or Direct Head Trauma
(DHT) Over Periods up to 8 Years
J.R. Couch1, K.S. Stewart1, P. Wisdom1
1Neurology, University of Oklahoma Medical School, Oklahoma City,
OK, USA.
Objectives: Compare symptoms of the PCS produced by pure blast injury
with those produced by DHT within periods of 1-4 and 5-8 years post-injury.
Background: TBI is a major problem of the military OEF/OIF campaigns. An
issue of importance is whether pure blast injury (BI) without Direct Head Trauma
(DHT) produces brain injury similar to that with DHT. This study compares the
Post-Concussion Syndrome (PCS) produced by these two mechanisms of TBI with
follow-up over a period of up to 8 years after TBI.
Methods: Veterans of OEF/OIF Campaigns were screened for
deployment-related TBI (D-TBI) as part of a general medical examination. Those with
a possible D-TBI were referred for a TBI evaluation including a Beck Depression
Inventory and a screen dealing with the TBI and the post-concussion syndrome (PCS).
Screen symptoms were graded on a 5 point scale from none to very severe based on
pain and interference with function. Items chosen to represent the PCS were: 1.
Headache, 2. Dizziness, 3. Balance Problems, 4. Poor Coordination, 5. Difficulty
with decisions, and 6. the BDI score. Patients were queried about duration of loss
of consciousness and associated symptoms immediately after the TBI, and about
symptoms present within the last 30 days. Blast injury was divided into categories
of Primary, Secondary, Tertiary, and Quarternary. Only subjects with primary (blast
wave only) or secondary (blast plus dust sand or small shrapnel) BI were used. DHT
subjects had TBI related to falls, assaults or other circumstances with direct
trauma to the head without any associated blast. TBI was graded as mild (dazed or
loss of consciousness [LOC] of <30 minutes) or moderate-severe (LOC> 30
minutes).
Subjects were divided by time between TBI and date of evaluation in the TBI Clinic
into periods of 1-4 and 5-8 years. Comparisons were made with the Likelihood Ratio
Chi Square test.
Results: The study deals with the first 500 subjects evaluated in the
TBI Clinic. For1-4 years post-TBI, there were 56 blast and 63 DHT subjects. For 5-8
years post-TBI, there were 28 blast and 50 DHT subjects. In comparing the
primary/secondary blast versus the DHT subjects, there was no difference in the
occurrence of symptoms #1-5 above representing the PCS with the exception of poor
coordination in subjects 5-8 years post-TBI in which No difficulty
and mild/moderate difficulty with poor coordination occurred 3.3
and 1.7 times as often in DHT as opposed to blast subjects (p=.008). There was no
difference between groups in the occurrence of Depression. The results will be
presented in detail.
Conclusions: With the exception of poor coordination at 5-8 years after
TBI, There is essentially no difference in the PCS produced by blast or direct head
trauma over an 8 year follow-up.
P364
Medication Usage Patterns in Headache after Mild Traumatic Brain
Injury
C. DiTommaso1, J.M. Hoffman1, S.M. Lucas2,3, S.S.
Dikmen1, N. Temkin1,3, K.R. Bell1
1Rehabilitation Medicine, University of Washington, Seattle, WA,
USA; 2Neurology, University of Washington, Seattle, WA, USA;
3Neurological Surgery, University of Washington, Seattle, WA,
USA.
Objectives: We sought to examine self-report of treatment for headache
in the first year following mild traumatic brain injury.
Background: Mild traumatic brain injury (mTBI) and mTBI sequelae are
commonly managed by non-specialists. Therefore, an understanding of post-injury
problems, such as headache, and subsequent management is crucial for improving care
and long-term outcomes. Recent studies suggest that headaches after mTBI are common
with multiple headache phenotypes. Outside of previous opinion papers, few studies
have guided primary care treatment of these complicated headaches or examined the
effectiveness of the interventions suggested.
Methods: 212 subjects admitted to a Level 1 trauma hospital with mTBI
were prospectively enrolled and evaluated within 7 days of injury, and at 3, 6, and
12 months after injury.
Results: The sample was primarily male (76%), white (75%), injured in
vehicle crashes (58%) and had completed high school (83%). Thirty seven percent of
subjects lived within the county surrounding the hospital, 26% resided in
neighboring counties, and an additional 37% were living in outlying areas or outside
of the state. A high headache burden (never less than 58% of respondents at each
period) was reported at 3, 6, and 12 months after injury, with headaches meeting
ICHD-2 criteria for migraine, probable migraine, tension, cervicogenic, and
unclassifiable headaches. Despite the diverse nature of headaches, more than 70% of
those with headache at each time period used acetaminophen or a non-steroidal
anti-inflammatory drug (NSAID) for headache control. Few participants, 19% of those
with migraine and 32% of those with unclassifiable headaches, endorsed complete
relief (vs. partial or no relief) after medication use. The majority of individuals
with unclassifiable headache reported never taking medication.
Conclusions: Headaches after mTBI are frequent and are not well managed.
Results suggest that many individuals with mTBI may be self-treating their headaches
by utilizing over-the-counter pain relief medications. These medications, however,
are not providing effective treatment for this population. Further research must be
conducted to guide treatment and educate providers.
P365
Retrospective Review of Efficacy and Safety of Acupuncture for Treatment of
Active Duty Service Members with Headaches after Non-Penetrating Blast
Exposure
T. Johnson1, J. Gordon2
1Marine and Sailor Concussion Recovery Center, Naval Hospital,
Camp Lejeune, NC, USA; 2Family Medicine Residency, Naval Hospital,
Camp Lejeune, NC, USA.
Objectives: Determine if acupuncture augmenting interdisciplinary care
of Active Duty Service Members (ADSMs) with headaches after non-penetrating blast
exposure is a safe and effective treatment.
Background: Traumatic Brain Injury (TBI) is defined as a force applied
to the head that disrupts brain function. After a decade of combat with frequent
blast exposure, some ADSMs may suffer from headaches, as well as changes in mood,
memory, sleep and balance. These symptoms, often subtle in mild TBI (mTBI), can
impair performance and negatively impact quality of life. Many ADSMs with a history
of blast exposure suffer from post traumatic stress disorder as well as mTBI.
Affected patients are typically started on several medications to address varying
symptoms. The medications are not always effective, and frequently have adverse side
effects.
A National Institutes of Health consensus statement concluded that acupuncture for
headache was a treatment option but further research was indicated.1 We
report on the results of a retrospective study of acupuncture in conjunction with
medications and rehabilitation in ADSMs with a diagnosis of headache following blast
exposure being treated in an interdisciplinary clinic.
Methods: Medical records of ADSMs with a history of combat related
non-penetrating blast exposure resulting in a diagnosis of mTBI with subsequent
headaches that consented to treatment with acupuncture in the Marine and Sailor
Concussion Recovery Center at Naval Hospital Camp Lejeune from January to June 2012
were reviewed after approval by our Research Review Committee and the Naval Medical
Center Portsmouth Institutional Review Board. A search of the Department of Defense
electronic medical record identified 21 ADSMs who met the inclusion criteria for
this retrospective review.
Results: Battlefield Acupuncture (BFA), an auricular acupuncture
consisting of acupuncture points Cingulate Gyrus, Thalamus, Omega 2, Point Zero
Prime, and Shen Men was administered in 18/21 patients. Auricular Trauma Protocol
consisting of acupuncture points Hypothalamus, Amygdala, Hippocampus, Master
Cerebral, Point Zero, and Shen Men was administered in 2/21. Koffman cocktail
protocol, consisting of acupuncture points Large Intestines 4 bilaterally, Liver 3
bilaterally, Governor Vessel 20, Yin Tang 2 was administered in 2/21 (one patient
had both Koffman and BFA). Patients also received various acupuncture treatments
based on their specific headache location and symptoms. Eighty-one percent (17/21)
of patients reported improvement, 10% (2/21) reported no change and 10% (2/21) had
no outcome documented.
Conclusions: Acupuncture is a safe, complementary therapy for treating
headaches following non-penetrating blast exposure. Larger, prospective studies are
indicated to compare acupuncture to standard therapy.
Views expressed are the authors’ and do not reflect policy or positions of the
Departments of the Navy or Defense, or US Government.
P366
Resolution of Sports Related Chronic Post Traumatic Headache and Prolonged
Post-Concussion Syndrome after Onabotulinum Toxin Injection
F. Conidi
Florida Center for Headache and Sports Neurology, Stuart, FL, USA; Neurology,
Florida State University College of Medicine, Tallahassee, FL, USA.
Objectives: Is onabotulinum toxin type A an effective treatment for
chronic post traumatic headache related to sports concussion.
Background: Onabotulinum toxin type A BTX-A is the only FDA approved
medication for Chronic Migraine.
Methods: Case Report of a 15 year old male with chronic post traumatic
headache and prolonged post concussion syndrome.
Results: This is the first case report of its kind where onabotulinum
toxin type A has been used to treat chronic post traumatic headache secondary to
sports concussion. Our patient experienced a complete resolution of his headache and
associated concussion symptoms shortly after injection with onabotulinum toxin type
A and continued to experience complete resolution of his symptoms 6 months after
initial injection. He was able to return to baseline physical function and his
academic performance improved to baseline as well. The author discusses the
mechanism and physiology of concussion in sports, mechanism of post traumatic
migraine and its relationship to the cervical spine, and outlines possible anatomic
and physiological connections. The author also discusses the current literature
relating to sub concussive events and their relation to mild traumatic brain injury.
He also outlines the underlying mechanism of greater, lesser, supraorbital and
auriculotemporal nerve blocks and the underlying mechanism of BTX-A in the treatment
of headache (including a review of the literature). Finally he poses the following
question for discussion. In patients with prolonged post concussion symptoms where
headache is the predominant symptom. Is the patient experiencing prolonged post
concussion syndrome or are the symptoms attributable to chronic post traumatic
migraine?
Conclusions: BTX-A may be an effective treatment in very select athletes
with chronic post traumatic headache and prolonged post concussion syndrome.
P367
Safety, Pharmacokinetics, and Pharmacodynamics of LY2951742: A Monoclonal
Antibody Targeting CGRP
J. de Hoon1, D. Montieth2, S. Vermeersch1, A. Van
Hecken1, E. Abu-Raddad2, E. Collins2, T.
Schuetz3, J. Scherer2, D. Grayzel3
1Center for Clinical Pharmacology, University Hospitals Leuven
& Department of Pharmaceutical and Pharmacological Sciences, Leuven,
Belgium; 2Eli Lilly and Company, Indianapolis, IN, USA;
3Arteaus Therapeutics, LLC, Cambridge, MA, USA.
Objectives: The objective of this Phase 1 study is to determine the
safety, pharmacokinetics (PK), and pharmacodynamics (PD) of LY2951742 (LY), a novel
antibody that binds to calcitonin gene-related peptide (CGRP).
Background: LY is a potent, selective monoclonal antibody targeting
calcitonin gene-related peptide (CGRP) and is being developed as a potential therapy
for migraine prevention. CGRP induces vasodilation via the CGRP receptor and is
implicated in neurogenic inflammation. As such, CGRP may play a pivotal role in
migraine pathophysiology, and neutralization of the ligand may provide an
alternative means for migraine prevention.
Methods: A Phase 1, first-in-human, double-blind, randomized,
placebo-controlled trial was performed in healthy volunteers. Subjects received
subcutaneous injections of either placebo, or 1, 5, 25, 75, 200, or 600 mg as a
single dose, or four (4) repeat administrations of150 mg of LY every 14 days.
Results: LY was well tolerated. There was no relationship between dose
and the type or number of adverse events, changes from pre-dose in vital signs or
vascular tone as measured by pulse wave analyses, laboratory values, or ECG
parameters. No clinically meaningful difference in adverse events vs. placebo was
observed. PK was linear; peak serum concentration (Tmax) ranged from 7-14 days, and
the terminal elimination half-life (T1/2) ranged from 25-30 days. PD was assessed
using laser Doppler imaging (LDI) to determine inhibition of dermal blood flow
induced by capsaicin. PD effects were robust and persisted 42 days following a
single dose and 99 days following repeat administration.
Conclusions: LY was well tolerated after both single and repeat
administrations. There was no dose dependent difference in either type or frequency
of Adverse Events, and no clinically meaningful difference when compared to placebo.
PK was linear and dose-proportional. PD effects using LDI were robust and durable
after both single and repeat administrations. Based on these data, further
exploration of LY2951742 as a potential therapy for migraine prevention is
warranted.
P368
Role of Caffeine Cessation in Migraine Management
C.-B. Lee1, C.-S. Chung1
1Department of Neurology, Samsung Medical Center, Seoul, Republic
of Korea.
Objectives: To evaluate the efficacy of caffeine cessation in migraine
management.
Background: Caffeine is a well known ‘modifiable lifestyle factor’ in
migraine, however no clear relationship has been described between modifying
caffeine habit and following migraine improvement. Therefore caffeine cessation has
been neglected by most of the patients or physicians.
Methods: Subjects were the patients who were newly diagnosed as episodic
migraine in Samsung Medical Center between March 2012 and July 2012. All patients
were advised to eliminate caffeine thoroughly without tapering. Change of migraine
pattern following caffeine elimination was assessed after 1 month. Patients were
divided by patient who quit caffeine completely, reduced the intake amount 50% or
more, or reduced less than 50% or not changed at all. Treatment efficacy was
regarded as ‘Partial improve’ if the patient had half reduction in frequency or less
disabling attacks. ‘Marked Improve’ is when the patient had more than half reduction
in frequency with less disabling attacks. Patients with no improve of headache were
categorized as ‘No Improve’.
Results: Among 116 patients who are taking caffeine regularly, 21
patients were treated with prophylactic medication from the beginning. Other 95
patients were advised to quit caffeine completely for 1 month without any daily
medication. A total of 72 patients were analyzed.
43 (59.7%) patients eliminated caffeine at once, 22 (30.6%) patient reduced and 7
(9.7%) patient did not change their intake at all. 16 patients (37.2%) out of 43 who
eliminated caffeine at once reported marked improve of headache. On the other hand,
only 9.9% of the patients who reduced caffeine and none of the patient who didn’t
change their caffeine habit, achieved remarkable headache improvement. Complete
caffeine cessation was clearly related to headache improvement, than reducing or not
changing the caffeine intake (p<0.001). Compared with the patients who quit
caffeine completely, patients who continued caffeine, either reducing or not,
headache improvement were definitely less achieved (OR 15.345, p<0.001).
Conclusions: According to our observation, migraine improvement can be
achieved by only changing caffeine consumption habit, especially when its completely
eliminated. Physicials should pay more attention to patient’s life syle and caffeine
cessation must be recommended as an effective baseline non-pharmacological
therapeutic strategy before initiating pharmacological treatment or trying more
invasive procedures.
P369
A Screen of Prophylactic Anti-Migraine Medications in a Chronic Nitroglycerin
Mouse Model
A.A.A. Pradhan1,2, I. Tarash1, B. McGuire1, A.
Charles1
1Neurology, University of California Los Angeles, Los Angeles, CA,
USA; 2Neuropsychiatry, University of California Los Angeles, Los
Angeles, CA, USA.
Objectives: The objective of this study was to validate a novel mouse
model of chronic migraine by testing known and potential prophylactic migraine
therapies.
Background: Migraine is a highly debilitating disorder that affects a
large portion of the population. Unfortunately, current therapies for chronic
migraine are often ineffective or poorly tolerated. The development of novel
migraine therapies has been slow due to the small number of clinically relevant
animal models. We have recently developed a new model of chronic migraine using
chronic intermittent nitroglycerin, a known migraine trigger in humans.
Methods: Nitroglycerin was administered IP to male and female mice every
second day for 9 days. Basal and nitroglycerin-evoked mechanical hypersensitivity
was evaluated using manual von Frey hair stimulation of the hindpaw.
Results: Acute nitroglycerin administration evoked mechanical
hyperalgesia in a dose dependent manner. Chronic intermittent treatment with
nitroglycerin induced a progressive and sustained basal hypersensitivity which was
also dose dependent. The prophylactic migraine treatment, topiramate, effectively
attenuated the basal hypersensitivity induced by chronic nitroglycerin. We also
determined the effects of other known and novel anti-migraine medications -
DL-propranolol, a beta blocker; amiloride, an acid sensing ion channel inhibitor;
and memantine, a NMDA receptor antagonist.
Conclusions: Overall, these studies indicate that progressive
hyperalgesia induced by chronic intermittent treatment with nitroglycerin in mice
represents a new translational model for migraine progression. This model
establishes a novel screening tool for testing potential anti-migraine
therapies.
P370
Translational Pharmacodynamics of CGRP Monoclonal Antibody LY2951742 in
Capsaicin-Induced Dermal Blood Flow Model
S. Vermeersch1, A. Van Hecken1, E. Abu-Raddad1, R.
Benschop2, D. Montieth2, J. Scherer2, D.
Grayzel3, J. de Hoon1, E. Collins2
1Center for Clinical Pharmacology, University Hospitals Leuven
& Department of Pharmaceutical and Pharmacological Sciences, Leuven,
Belgium; 2Eli Lilly and Company, Indianapolis, IN, USA;
3Arteaus Therapeutics, LLC, Cambridge, MA, USA.
Objectives: The objective of the study is to evaluate the effects of
LY2951742 (LY) on dermal blood flow (DBF) in an experimental model of capsaicin
induced vasodilation in both preclinical animal models and clinical studies.
Background: LY is a potent, selective monoclonal antibody that
neutralizes CGRP, and is being developed as a potential therapy for migraine
prevention. CGRP induces potent vasodilation, is implicated in neurogenic
inflammation, and may play a pivotal role in migraine pathophysiology.
In previously conducted pharmacodynamic (PD) studies, small molecule CGRP receptor
antagonists inhibited DBF induced by capsaicin as measured by laser Doppler
perfusion imaging (LDI). Small molecule CGRP receptor antagonists that exhibited
potent pathway inhibition in this model went on to show clinical efficacy in the
treatment of acute migraine.
Methods: The PD effects of LY were evaluated by assessing capsaicin
induced vasodilation via LDI. Preclinical studies were conducted in rats, and
cynomolgus monkeys, using subcutaneous (SC) and intravenous (IV) administration of
LY, respectively. Subjects in a Phase 1 trial of LY received single SC doses ranging
from 5mg to 600mg, or four (4) repeat administrations of 150 mg every 14 days.
Results: Doses of 4 mg/kg SC (rats) and 5 mg/kg IV (monkeys)
demonstrated robust inhibition of capsaicin induced DBF. In monkeys significant
inhibition of capsaicin induced DBF persisted for >29 days. In humans, the
inhibitory effect on DBF was dose-dependent, starting at 5mg between Days 28-42. At
doses of 75mg and higher inhibition was significant on Day 3 and remained almost
maximal until Day 42.
Conclusions: PD assessment using LDI provided a useful biomarker for
assessing the durability and magnitude of effect on DBF after administration of
LY2951742. Results were scalable and predictable across species. Utilization of this
PD model provides a means for understanding a PK and PD relationship that may assist
in the clinical development of LY2951742 for migraine prevention, and in the
translational research of other CGRP pathway inhibitors.
P371
RN307, a Humanized CGRP Function-Blocking Antibody with Potential as a
Treatment for Migraine Prophylaxis
K.T. Poulsen1, Y.N. Abdiche1, P. Strop1, A.
Rajpal1, J. Pons1, D.L. Shelton1
1Rinat Laboratories, Pfizer Inc., South San Francisco, CA,
USA.
Objectives: The purpose of this study was to characterize the in vitro
and in vivo properties of RN307, a humanized CGRP function-blocking antibody with
potential use in migraine.
Background: CGRP is a 37 amino acid neuropeptide with two isoforms,
alpha and beta. The sequence of both isoforms is identical between human and
cynomolgus monkey. CGRP has a well established role in migraine and there is
abundant clinical evidence for the therapeutic effect of CGRP signaling blockade.
RN307 is a humanized antibody of the IgG2Δa isotype that binds to human CGRP and
blocks its binding to and activation of the CGRP receptor.
Methods: The binding affinities of RN307 towards human CGRP were
determined in solution at 25°C using the kinetic exclusion assay (KinExA).
The structure of the CGRP:RN307 complex was determined by standard X-ray
crystallography techniques utilizing molecular replacement method.
Surface plasmon resonance (SPR) binding assays were used to map the epitope of RN307
by screening a panel of CGRP variants that incorporated an Alanine scan, point
mutations, fragments, and acid/amide modifications. SPR was also used to determine
the specificity of RN307 to CGRP via solution competition with other CGRP family
members; adrenomedullin, calcitonin and amylin.
To better understand the activity of RN307 in vivo, the antibody was tested in a
cynomolgus monkey capsaicin flare model.
Results: RN307 bound human alpha and human beta CGRP with equilibrium
dissociation constant (KD) values of 9.5 and 4.0 respectively, which were
indistinguishable within the 95% confidence limit of each global fit.
The crystal structure of the RN307 Fab in complex with the CGRP peptide revealed that
RN307 has a deep pocket that binds to CGRP residues 29-37. Nearly 70% of the surface
area of residues 29-37 are solvent inaccessible with the amidated Phe37 being
located deepest in the binding pocket. Consistent with the structure of RN307:CGRP
complex, the screening of CGRP variants showed that RN307 binding is most sensitive
to substitutions of CGRP residues Gly33 and Phe37 and that amidation of the extreme
N-terminal residue (Phe37) is required for high affinity binding.
To determine the specificity of RN307, it was premixed with a large molar excess of
either amylin, calcitonin or adrenomedullin (CGRP family members). Results were
comparable to the control response (RN307 plus buffer) demonstrating that RN307 did
not form a detectable complex with these peptides and therefore is specific to CGRP
alone.
Treatment of cynomolgus monkeys with a single dose of RN307 resulted in a potent,
dose dependent, and long lasting inhibition of capsaicin induced flare with an ED50
of 5.8mg/kg at two weeks and 15.9mg/kg at 8 weeks post dose.
Conclusions: These results demonstrate that RN307 is a high affinity,
highly specific, potent and long lasting CGRP function blocking antibody which makes
it a promising therapeutic for migraine prophylaxis.
P372
Gabapentin for the Prophylaxis of Migraine in Adults. Update of a Cochrane
Review
M. Linde1, W.M. Mulleners2, E.P. Chronicle3, D.C.
McCrory4,5
1Department of Neuroscience, Norwegian University of Science and
Technology, Trondheim, Norway; 2Department of Neurology, Canisius
Wilhelmina Ziekenhuis, Nijmegen, The Netherlands; 3(Deceased),
Department of Psychology, University of Hawaii at Manoa, Manoa, HI, USA;
4Department of Medicine, Duke University Medical Center, Durham,
NC, USA; 5Center for Health Services Research in Primary Care, Durham
Veterans Affairs Medical Center, Durham, NC, USA.
Objectives: To assess the evidence on efficacy and tolerability of
gabapentin for preventing attacks in adults with episodic migraine.
Background: Some antiepileptic drugs are marketed for migraine
prophylaxis. In evidence-based treatment guidelines, the European Federation of
Neurological Societies lists gabapentin as a drug of third choice (only probable
efficacy) and the American Academy of Neurology and American Headache Society list
it as Level U (inadequate or conflicting data to support or refute medication use).
This review updates an existing Cochrane review1 and will be published in
The Cochrane Library.
Methods: We searched PubMed/MEDLINE (1966 to 2013), EMBASE (1974 to
2013) and the Cochrane Central Register of Controlled Trials, and handsearched
Headache and Cephalalgia to January 2013. Two
independent reviewers selected studies and extracted data. For migraine frequency,
mean differences (MDs) from placebo were calculated for each study and across all
studies. For dichotomous data on responders (≥50% reduction in migraine frequency),
odds ratios (ORs) were similarly calculated. Safety data from single-dose studies
were summarized and numbers-needed-to-harm (NNHs) calculated.
Results: Five trials of gabapentin and one of its prodrug gabapentin
enacarbil met the inclusion criteria (1009 total patients). For attack frequency,
three trials of gabapentin 900 mg, 1200 mg and 1800 mg daily respectively found no
significant reduction whereas one of gabapentin titrated to 2400 mg daily found a
small but significant reduction (MD -0.80; 95% CI -1.55 to -0.05). Pooled results
across these four studies (n=352; MD -0.44; 95% CI -1.43 to 0.56) were negative. One
trial of gabapentin enacarbil (n=523) was also negative. For responders, one trial
of gabapentin titrated to 1800 mg daily found no difference between active and
placebo and one of gabapentin titrated to 2400 mg daily found a small but
significant superiority of gabapentin (OR 2.79; 95% CI 1.09 to 7.17). Pooled results
(n=235; OR 1.59; 95% CI 0.57 to 4.46) were negative. On this measure, the trial of
gabapentin enacarbil (n=523) was also negative. Adverse events from gabapentin were
common.
Conclusions: The evidence derived from all published trials of
gabapentin and its prodrug gabapentin enacarbil suggest that it is not efficacious
for the prophylaxis of episodic migraine in adults.
P373
Effect of Acupuncture Stimulation on Cerebral Blood Flow Using Arterial Spin
Labeling MRI in Patients with Migraine
T. Kikuchi1, S. Yamaguchi1, N. Araki2, H.
Matsuda4, N. Honda3, T. Mimura1
1Center for Oriental and Integrated Medicine, Saitama Medical
University, Moroyama Town, Saitama, Japan; 2Department of Neurology,
Saitama Medical University, Moroyama Town, Saitama, Japan;
3Department of Radiology, Saitama Medical Center, Kawagoe City,
Saitama, Japan; 4Integrative Brain Imaging Center, National Center of
Neurology and Psychiatry, Kodaira City, Tokyo, Japan.
Objectives: To clarify the mechanism of action of acupuncture in
patients with migraine, we compared the effects of acupuncture stimulation on
cerebral blood flow in patients with migraine and healthy controls, by using
arterial spin labeling (ASL) of MRI without contrast material.
Background: Although the acupuncture therapy for migraine is as
effective as standard preventive medicine, its specific effects have been doubted
since its precise mechanism is not scientifically clear.
Methods: The subjects were 10 patients with migraine who met the
diagnostic criteria of the International Classification of Headache Disorders;
2nd Edition [3 males and 7 females, mean age: 39.2 ± 11.2 years (mean
± S.D.)] and 10 healthy controls (6 males and 4 females, mean age: 32.3 ± 9.2
years). The sites of acupuncture stimulation included ST8 located slightly superior
to the bulge of the temporalis muscle, ST6 located anterior and superior to the
angle of the jaw at the prominence of the masseter muscle, GB21 located in the upper
trapezius muscle, and GB12 located in the splenius muscle. Acupuncture was performed
using nonmagnetic silver needles (diameter: 0.2 mm, length: 50 mm) for 10 minutes.
The method for measuring cerebral blood flow was as follows: 3TMRI (Siemens’
MAGNETOM Verio) was used and the pulsed ASL method was employed. The patients were
allowed to rest for 30 minutes or more and then cerebral blood flow was measured
between attacks 6 times, for 4 minutes each time; namely, before stimulation, 5
minutes after the start of stimulation, 10 minutes after start of stimulation,
immediately after its completion, and 15 and 30 minutes after its completion. The
cerebral blood flow images obtained were statistically analyzed by Statistical
Parametric Mapping to compare the images at rest and thereafter. The images at rest
in patients and controls were also evaluated.
Results: Both in patients and controls, blood flow in the pars
opercularis or cingulate gyrus, islet and thalamus/hypothalamus increased 5 and 10
minutes after the start of stimulation. However, the increase was more prominent in
patients. Furthermore, the increase of blood flow at the same sites persisted longer
immediately after, and 15 and 30 minutes after stimulation in patients than in
controls. In addition, cerebral blood flow specifically increased in the anterior
part of the parietal lobe of patients.
Conclusions: These results of this study suggested a difference in
responsiveness to acupuncture stimulation in migraine patients and healthy
controls.
P374
Migraine Prophylactic Drugs Suppress Peri-Infarct Depolarizations and Improve
Stroke Outcomes
J.H. Lee1, K. Eikermann-Haerter2, A. Daneshmand2,
E.S. Yu2, Y. Zheng2, B. Sengul2, A.
Can2, N. Yalcin2, C. Ayata2
1Division of Drug Discovery Research, Korea Research Institute of
Chemical Technology, Daejeon, Republic of Korea; 2Neurovascular
Research Laboratory, Dept of Radiology, Massachusetts General Hospital, Boston,
MA, USA.
Objectives: To test whether migraine prophylactic drugs that suppress
spreading depolarization protect against ischemic stroke.
Background: Migraine is an independent stroke risk factor. Excitatory
mechanisms have been implicated in pathogenesis of both migraine and stroke. It has
recently been shown that migraine mutations increase brain vulnerability to ischemia
via excitatory mechanisms (Circulation 2012;125: 803-812). Migraine
mutant mice developed a higher number of peri-infarct depolarizations (PIDs) upon
experimental stroke, associated with accelerated infarct growth and worsened
outcomes. PIDs are related to spreading depression (SD), the electrophysiologic
event underlying migraine aura, and enlarge infarcts by worsening the metabolic
mismatch.
Methods: Mice (C57BL6/J) were treated for 6 weeks with the migraine
prophylactic and antiepileptic drugs lamotrigine (LTG, 30mg/kg/d, p.o.), topiramate
(TPM, 80mg/kg/d, p.o.), or vehicle. We measured: i) SD susceptibility by topical KCl
or direct cathodal stimulation, ii) anoxic depolarization latency and PID frequency
during filament occlusion of the middle cerebral artery (fMCAO), and iii) infarct
volumes and neurological deficits 24h after stroke onset. In electrophysiological
studies, mice were ventilated, and blood pressure and blood gas monitored and
maintained
within normal range. Data are mean ± standard deviation. *p<0.05 vs. vehicle.
Results: Chronic treatment with LTG or TPM suppressed SD susceptibility
in mice. A stronger electrical stimulus was necessary to induce SD, and the
cumulative SD duration upon topical KCl was reduced. Both drugs also delayed the
onset of anoxic depolarization upon fMCAO, and suppressed the frequency and
cumulative duration of PIDs during 105min of fMCAO (A). Consequently, both drugs
improve stroke outcomes, by reducing infarct size (infarct and ischemic swelling
volumes; colored and white bars, respectively) and improving neurological function
24h after 1h fMCAO (B).
Conclusions: These data further support the notion that increased stroke
risk in migraineurs is related to enhanced susceptibility to ischemic
depolarizations, and suggest that migraine prophylaxis may improve stroke
outcomes.
P375
Does Medication Overuse Matter? Response to Botulinum Toxin Type A in Chronic
Migraine in Patients with or without Medication Overuse
F. Ahmed1, M. Khalil1, V. Quarshie1
1Department of Neurology, Hull Royal Infirmary,
Kingston-upon-Hull, North Humberside, United Kingdom.
Objectives: To identify differences in responder rates between
analgesics misusers and non misusers with chronic migraines treated with botulinum
toxin type A (Botox).
Background: Chronic Migraine (CM) represents the most disabling form of
the headache disorder. 50-80% of CM sufferers overuse painkillers as defined by the
International Headache Society (IHS) criteria for medication overuse. It remains
uncertain whether analgesic overuse is a cause or complication of CM. For effective
management of CM, analgesic overuse must be addressed, although there is lack of
consensus on whether preventive treatment is introduced before or after
detoxification. The only controlled trial evidence comes from a small study of
topirmate in CM (1) in which patients with medication overuse responded equally to
those without overuse.
Data from Hull prospective study of Botulinum Toxin types A (Botox) in CM was
analysed to compare response rate among patients with or without analgesic
overuse.
Methods: Adults with CM were offered BOTOX after discussion of treatment
options. Patients were injected intramuscularly as per PREEMPT (2), and maintained a
headache diary for 30 days before/after treatment. Medication overuse was defined as
use of simple analgesics on > 15 days a month or
> 10 days a month for triptans, opioids or combined
analgesics
Data were collected for the number of headache; migraine and crystal clear (headache
free) days. A responder was defined as >50% reductions in
headache, migraine days, or an increment in crystal clear days twice that of the
baseline in a 30-day period and the results were compared for the two groups. We
also compared the 50% & 75% responder rate between groups.
Results: Full data were available on 139 patients; results are
illustrated in table 1. Table 2 illustrates the responder rate between the 2 groups
of patients. Patients with medication overuse were slightly older and had more
headache, migraine days and less crystal clear days before treatment. The median
changes of all three parameters after treatment were similar in the two groups; 50%
and 75% responder rates showed no difference.
Conclusions: Patients with medication overuse responds equally well to
preventive treatment with Botulinum Toxin with significant reduction in the number
of painkiller days.
Non misusers
Misusers
Number
74
65
Median age (range)
42.5 (19-69)
48 (19-91)
Male: female
15: 59
10: 55
Headache days (median)
Before
24
28
after
15.5
20
Med. change
-8.5
-8
Migraine days (median)
Before
12
17
After
6
10
Med. Change
-6
-7
Crystal clear days (median)
Before
6
2
After
15
10
Med. Change
+9
+8
Simple analgesics days (median)
Before
8
20
After
5
12
Med. change
-3
-8
HIT-6 (median)
Before
69.5
68
After
58
62
Med. Change
-11.5
-6
Non misusers (74)
Misusers (65)
P value
50% responders
53 (71.6%)
46 (70.7%)
Ns
75% responders
34 (45.9%)
35 (53.8%)
Ns
P376
Hull Prospective Analysis of Botulinum Toxin Type A (Botox) Use in the
Treatment of Chronic Migraine
M. Khalil1, V. Quarshie1, F. Ahmed1
1Department of Neurology, Hull Royal Infirmary,
Kingston-upon-Hull, North Humberside, United Kingdom.
Objectives: To identify the change in frequency of chronic migraine
symptoms before and after treatment with BOTOX in real-life settings.
Background: Botulinum toxin type A (BOTOX) is licensed for the
prophylaxis of headaches in adults with chronic migraine (CM)1. A
prospective study was performed to examine the change in frequency of CM symptoms
before and after treatment with BOTOX in real-life settings.
Methods: Adults with CM were offered BOTOX after discussion of treatment
options. Patients were injected intramuscularly as per PREEMPT1, and
maintained a headache diary for 30 days before/after BOTOX treatment. Data were
collected for the number of headache; migraine and crystal clear (headache free)
days. A responder was defined as >50% reductions in
headache, migraine days, or an increment in crystal clear days twice that of the
baseline in a 30-day period.
Results: Full data were available on 162 patients (32 males (mean age
47.3 years; range 26-76 years); 130 females (mean age 42.9 years, range 19-70 years)
who received BOTOX. 129/162 (79.6%) tried 3 preventive treatments and 70/150 (46.7%)
were overusing analgesics as defined of International Headache Society2.
The median number of headache days reduced from 26 before BOTOX to 18 after BOTOX
(p<0.001); the median number of migraine days reduced from 13 before to 8 after
(p<0.001); the median number of crystal clear days increased from 4 before to 12
after (p<0.001). Of the cohort, 30% reported >50%
reduction in headache days, 51% a >50% reduction in
migraine days and 58% a >50% increase in crystal clear
days. Triptan days reduced from 6 before BOTOX to 3 after (p<0.001). Data on days
off work was available for 56/162 patients; in these, the median number of days off
work per month reduced from 3.5 before to 2 after BOTOX (p < .01). The quality of
life and well being was measured using HIT-6 questionnaire that changed from 69 to
60 (p<.001) after treatment 18/162(11.1%) reported adverse events; 10 with pain
at injection sites, 1 with worsening headache, 3 with partial ptosis,3 could not
frown and 1 fainted during Rx.
Conclusions: BOTOX is a valuable addition to preventive treatment
options in patients with CM. It significantly reduces the number of headache and
migraine days, and significantly increases the number of crystal clear days in a
real-life settings.
Patient response to BOTOX treatment
Outcome
≥50% reduction n (%)
≥75% reduction n (%)
Headache days
49/162 (30%)
27/162 (16%)
Migraine days
83/162 (51%)
37/162 (22%)
Crystal clear days
≥ 2-fold increase n (%)
≥ 3-fold increase n (%)
94/162 (58%)
67/162 (41%)
Any of the above categories responders
116/162 (71%)
82/162 (50%)
All of the above categories responders
40/162 (24%)
13/162 (8%)
P377
Placebo Spectacles - An Excellent Non Pharmacological Treatment for Pediatric
Migraine
F.M. Francis
Headache and Neuroophthal, Teresa Eye and Migraine Centre, Cherthala,
India.
Objectives: to document excellent placebo spectacle response in children
with migraine without aura (1.1/1.6).
Background: Studies show high placebo response in pediatric migraine.
Clinical trials and other non pharmacological interventions record placebo headpain
relief of upto 50% in children.
Methods: Prospective cohort study spanning 7 years. 2422 children. Age
group 5 to 15 years. ICHD2 migraine without aura diagnostic criteria applied in all.
Inclusion criteria – 1) children with a diagnosis of ICHD 2 migraine without aura
(1.1/1.2/1.6), 2) history of abortive / prophylactic treatment failure, 3) fed up
with different drug regimens, 4) dislike to scientific drugs, 5) subsiding with drug
treatment but recurring, 6) past history of some one in the family got better with
spectacle wear, 7) adverse effect of current/past drugs, 8) minimal improvement/ no
blurring of vision with +/_ 0.25 SPH /CYL (placebo spectacles), 9) no eye strain
symptoms other than migraine pain occasionally involving the periorbital region.
Exclusion criteria - all with documented refractive errors and typical eye strain
symptoms.
Results: All were advised avoidance of all possible triggers (known and
regional) and 2days / week of abortive medications as a treatment option initially.
1792 (74%) reported more than 50% improvement within a week of wearing spectacles.
Improvement lasted from 3 months to one year. 574 (32%) of these children reported
complete relief of their recurrent migraine pain during a follow up period of 2
years.
Conclusions: This study proves that constant(day time) wearing of
placebo spectacles along with trigger avoidance will be an excellent non
pharmacological way of treating migraine in children.
P378
The Influence of Migraine Prophylactic Drug on Hyperleptinemia as a Risk of
Chronic Migraine
E. Kitamura1, J. Hamada1, N. Kanazawa1, Y.
Hamada2, R. Masuda1, K. Nishiyama1
1Neurology, Kitasato University School of Medicine, 1-15-1,
Kitasato, Minamiku, Sagamihara, Kanagawa, Japan; 2Fuculty of
enveronomental information, Keio University, 5322, Endoh, Fujisawa, Kanagawa,
Japan.
Objectives: It is known that obesity is one of the risks of migraine
chronification. Furthermore, it is speculated that obese person’s hyperleptinemia
have some kinds of association with migraine. In this time, we examined the effect
of migraine prophylactic drugs on Zucker fatty rat cortical spreading depression
(CSD) model to clarify the relation between hyperleptinemia and migraine.
Background: There are some reports about increased body weight and
abdominal obesity are concerned with pathogenesis of migraine. Although migraine
prevalence does not vary with BMI, the risk of transformation of episodic migraine
attacks to chronic form has been found to be high in obese migraineurs. It is
speculated that several adipocytokines such as Leptin which plays an integral role
in feeding and obesity have some kinds of association with migraine. We have
examined the effect of Leptin on the rat CSD model to clarify the relations between
Leptin and migraine. Our recent data suggest that Leptin modulates the pathological
mechanisms of migraine, and episodic migraine may be transformed into chronic
migraine by chronic hyperleptinemia.
Methods: Thirty male Zucker fatty rats were used. Migraine prophylactic
drugs (amitriptyline 20mg/kg, DL-propranolol 20mg/kg, valproate 200mg/kg, topiramate
80mg/kg) or saline (as vehicle) was administered intraperitoneally once a day for 28
days (respectively n=6). After that, under anesthetizing condition by administering
α-chloralose and urethane intraperitoneally, a tracheostomy was performed for
controlled ventilation. To investigate physiological parameter and blood gas, right
femoral artery was catheterized. A laser-Doppler probe was placed on the cerebral
cortex through the left bone fenestration for measuring cerebral blood flow (CBF).
The two other bone fenestrations were opened for measuring direct current (DC)
potential of CSD, and for dropping KCl solution. After 1.0 mol KCl solution was
dropped through the bone fenestration to induce CSD, we measured the CBF, DC
potential, the number of CSD, the duration of CSD.
Results: The number of CSD was significantly decreased by all migraine
prophylactic drugs (amitriptyline: 6.3±1.0, DL-propranolol: 7.7±1.0, valproate:
7.7±1.0, topiramate: 6.5±1.3) compared with vehicle rats (15.8±1.8). The duration of
CSD were significantly decreased by all migraine prophylactic drugs (amitriptyline:
33.7±8.5, DL-propranolol: 66.0±5.0, valproate: 61.7±8.2) except for topiramate
compared with vehicle rats (60.7±6.0). There was no significant difference with
between administration of all migraine prophylactic drugs and vehicle in % change of
CBF and DC potential.
Conclusions: Inflammatory cytokines and CGRP which have some
relationship with pathogenesis of migraine are increased by leptin. These results
suggest that migraine prophylactic drugs can inhibit transformation of episodic
migraine into chronic due to hyperleptinemia.
P379
The Effects of Single Versus Subchronic Administration of Riboflavin on
Orofacial Formalin-Induced Pain and Nociception
A. Dondas1, A. Luca1,2, T. Alexa1,2, A.
Negru1, C.R. Bohotin1,2
1Centre for the Study and Therapy of Pain, Iasi, Romania;
2Pathophysiology, University of Medicine and Pharmacy “Gr. T.
Popa”, Iasi, Romania.
Objectives: To identify whether vitamin B2 subchronic administration has
an influence on orofacial formalin-induced pain (OFP) in mice.
Background: Riboflavin supplementation has been recommended widely as a
safe and effective prophylactic therapy for migraine. Brain energy metabolism in
migraine has been found to be abnormal in all types of migraine, making the
migrainous brain hyper-responsive to many stimuli [1]. The theory of migraine as a
deficit of mitochondrial energy metabolism seems to have abundant support [2].
Riboflavin is the central component of the cofactors FAD (which is reduced to
FADH2 in complex II of the mitochondrial electron transport chain)
and FMN (which is reduced to FMNH2 in complex I).
Methods: Thirty-four adult BALB/c male mice were divided into 4 groups.
Groups I (n=8) and II (n=9) received a single i.p. injection of 50 mg/kg b.w.
riboflavin and saline, respectively. Groups III (n=8) and IV (n=9) received daily
i.p. injection of 50 mg/kg b.w. riboflavin and saline, respectively, for 30 days.
One hour after the last injection, the mice were injected with 20 µL of 5% formalin
into the whisker pad and the intensity of the orofacial pain was assessed. The data
was analyzed by one-way ANOVA followed by Bonferroni’s post hoc test. The thermal
nociceptive response of the mice was also recorded at two days intervals using the
hot plate and tail flick tests.
Results: A single riboflavin dose induces a decrease of 31.13% on the
first phase of OFP test (not statistically significant), and a 45.3% decrease on the
second phase (p=0.014) as compared with the saline group. For the subchronic group,
there was no statistically significant difference, although for the second phase
there was a 30.36% decrease (p=0.09) in the grooming behavior of the mice. In the
first phase of OFP, the difference between one dose and repeated doses of riboflavin
was close to reaching significance (p=0.07), but no difference was observed in the
second phase. There were no modifications in the hot plate test along the recorded
30 days. In the tail flick test, the response latencies significantly increased for
the first 10 days (p<0.05), then slowly returned to the baseline values.
Conclusions: Our results suggest that vitamin B2 acute injection has an
analgesic effect on OFP and on the tail flick test for the first 10 days of
administration (probably the time needed for the reserves of riboflavin to be
replenished). Thirty days administration of riboflavin didn’t modify neither
nociception nor inflammatory pain, although the second phase of the OFP test was
diminished by a p value of 0.09.
P380
Preventive Effect of Cyproheptadine Hydrochloride in Patients with Frequent
Migraine
H. Okuma1, K. Iijima1, T. Yasuda1, K.
Tokuoka1, Y. Kitagawa1
1Neurology, Tokai University Hachioji Hospital, Hachioji /
Ishikawa-cho, Japan.
Objectives: In this study, we investigated the preventive effect of
cyproheptadine hydrochloride in whom no other conventional preventive treatments had
been previously effective.
Background: Cyproheptadine hydrochloride is rarely used in adults
because of medication of sleepiness. For this reason, no reports of this drug have
been reported in patients with migraine in Japan.
Methods: The migraine preventive effect of cyproheptadine hydrochloride
was investigated in 12 of 132 migraine patients treated at our hospital. These 12
subjects had received all of the unsuccessful migraine prophylaxis with
lomerizine,valproic acid and topiramate, or had discontinued such treatments due to
adverse reactions.
Initial drug of cyproheptadine hydrochloride was 4mg before sleep. In those who
experienced no clinically significant sleepiness following the treatment, the drug
was orally administered 4mg after breakfast as well. Drug efficacy was evaluated by
examining the frequency of migraine one month and three months after the treatment
was initiated.
Results: The frequency of migraine was dramatically reduced in all
patients by 7 to 10 days after starting treatment. Almost no migraine attacks were
observed in 9 of the 12 patients for 1 month. In the other two patients, the
frequency of monthly migraine was reduced to about 1 time. The average frequency of
migraine during the three-month period was an average of 2.6 times. These results
demonstrate that cyproheptadine hydrochloride had significant effect in preventing
migraine.
Conclusions: Currently, antidepressants, beta-blockers, antiepileptic
agents, or calcium antagonists are in Japan available to prevent frequent,
intractable migraine in adults. The results of this study demonstrate that
cyproheptadine hydrochloride is effective as a migraine preventive treatment for
Japanese patients in whom such conventional drugs have shown no efficacy or for
those who have difficulty in using them due to side effects.
P381
Efficacy of Botulinum Toxin Type A Botox® for Chronic Migraine, Results from a
Headache Center in Medellin- Colombia
A.C. Ramirez2, F.I. Alvarez2, M. Volcy1
1Neurology - Headache, Indocen Instituto De Dolor De Cabeza y
Enfermedades Neurologicas, Medellin, Antioquia, Colombia; 2Research,
Centro De Investigacion Clinica CIC, Medellin, Antioquia, Colombia.
Objectives: Longitudinal study of a cohort to evaluate the effectiveness
and safety of preventive treatment with botulinum toxin type A Botox ® (BTA-A) in
patients with chronic migraine (CM) and medication overuse (MOH).
Background: CM is the main cause of chronic primary headaches, patients
frequently are a challenge. Few medications have demonstrated efficacy as
pharmacological option for CM. BTX-A is considered one of the most important
treatments; nevertheless, there is still little experience in Colombia and Latin
America with it use.
Methods: It was made a descriptive analysis of all demographic variables
to describe population characteristics. To determine the effectiveness of BTX-A
treatment in CM and MOH, several variables were measured in different moments for
furhter comparison. All of these variables were calculated in different moments of
the treatment; statistical tests used were Friedman test, ANOVA and Tests of
multiple ranges with percentages of minimum significant differences of Fisher to
determine if the opposing differences were statistically significant.
Results: 190 patients were evaluated in a two year period follow up. The
age average was of 45.2 years (with a 9 year-old minimum age and a 93 year-old
maxim). On average, migraine turned chronic at 26.26 years (with a 3 year-old
minimum age and 72 year-old maxim). Most of the patients had on average 24 days of
abortive overuse. After treatment patients referred subjective improvement on
average 7.48 (first cycle), 6.47 (second cycle) and 6.24 (last cycle); friedman test
between each cycle p = 0-000. The number of headache (HA) days/month before and
after each treatment cycle was divided in three categories: 1. Mild (less than 4
days with HA a month) 2. Moderate (Between 5 and 7 days) and 3. Severe (more than 8
days). Before BTX-A, just one patient was in category 1 (0.52%) while 96.84% were in
category 3; after treatment it was noticed an increase in number of patients in the
mild category (23, 12.1%) and reduction of patients in category 3 (76, 40%). The F
reason is similar to 52,1919 and P value of F test smaller than 0,05, a
statistically significant difference exists among the variables with a level of
confidence of 95,0%. It can be appreciated that the number of HA free days after
each cycle increased; on average 2.6 (first cycle), 3.4 (second cycle) and 3.7 (last
cycle). The F reason in this case is similar to 15,9159 and P value of F test
smaller than 0,05, a statistically significant difference exist among the variables
with a level of confidence of 95,0%. There was not statistically significant
differences in the percentage of improvement after each treatment. Globally it was
achieved improvement of 64.34 (first cycle), 67.44 (second cycle), 68.37 (last
cycle).
Conclusions: CM it is a difficult to treat disorder, with few efective
medications available. Prevention with BTX-A demonstrated to be an efective
pharmacological option for CM.
P382
Long Term Safety of Methysergide
R. Peatfield
Princess Margaret Migraine Clinic, Charing Cross Hospital, London, United
Kingdom.
Objectives: Methysergide (Deseril; Sansert) was introduced as a headache
prophylactic drug by Sicuteri in 1959. It soon became clear that a small minority of
patients (perhaps 1:5000) developed fibrotic complications, especially
retroperitoneally, though this risk can be reduced by using no more than 6mg daily
for no more than six consecutive months.
Background: Over the years many other proven agents have been preferred,
but nevertheless it remains very useful in specialised clinics seeing patients
unresponsive to more familiar drugs. While many patients are able to stop for 4
weeks, in some the recurrence is so severe that it seems kinder to allow them to
take it continuously.
Methods: I have reviewed the records of 38 patients, 27 with migraine
and 11 cluster headache.
Results: Six with migraine and 8 with cluster headache had successful
short courses, 5 with migraine had side-effects and 9 (6 with migraine) did not
respond. There were 10 long-term migraine patients - 4 for over 10 years and 6 for
over 5 years; most took 6mg daily, though one used 8mg, and another was happy on
1mg. They all had regular echocardiograms and renal tract ultrasound screening, and
none have developed any significant fibrosis.
Conclusions: The short-term tolerability of methysergide seems
comparable to many other agents, and it seems safe in the longer term, so long as
the dose is below 6mg, and regular checks are made. We would not expect
complications with these small numbers; in such difficult circumstances the likely
benefit needs to be weighed against the very small risk.
P383
Official Treatment Guidelines in Migraine Treatment Should Be like Caesar’s
Wife. A Critical Review of the Content and Practical Consequences of 3 Recent
Guidelines for Migraine Prevention
P. Tfelt-Hansen
Department of Neurology, Danish Headache Center, Glostrup,
Denmark.
Objectives: Treatment guidelines by distinguished society like AAN and
AHS, European Federation of Neurological Society and Canadian Neurological Society
should be and are evidence-based. In addition, “ common sense” should be used when
the evidence is judged.
These 3 societies have published guidelines for preventive of migraine and the
content and possible resulting consequences for the practical use of these drugs
will be reviewed.
Background: Only AAN has extensive formal rules for constructing
guidelines with graded treatment recommendations from evidence (randomized,
controlled trials). The major inherent problem for the AAN/AHS guidelines from 2012
is that the recommendations are based solely on efficacy and tolerability is not
taken into account. Thus topiramate is recommended as an effective drug (and it was
superior to placebo in a large trial program) without the clinically very useful
information that 24% (93/384) of patients treated with topiramate 100 mg in 3
pivotal RCTs discontinued the trials because of adverse events. In addition, in
several cases of recommendation of drugs as possible effective in the AAN/AHS
guidelines the judgment of the evidence must be considered dubious.
Methods: In the European guidelines from 2009 gabapentin is recommended
as a third choice drug despite the fact that a Cochrane review from 2008 recommended
that the drug needed further evaluation, Venlafaxine with one placebo-controlled RCT
(and two open studies) was recommended as a second choice drug, whereas lisinopril
and candesartan with one similar placebo-controlled RCT each were recommended only
as third choice drugs.
In the Canadian guidelines verapamil is given a weak recommendation (low quality of
evidence) and one can question whether the drug should be recommended at all since
it has only been compared with placebo in 2 extremely small RCTs (n = 12 and 14).
Magnesium is given a strong recommendation (low quality of evidence) with one
positive and 2 negative placebo-controlled RCTs. It is stated that “ there is some
evidence for benefit and side effects are minimal”.
Results: In none of these 3 treatment guidelines is the problem of
comparative preventive RCTs in migraine without placebo-control taken into account.
The placebo-response in preventive RCTs in migraine varies from 20 to 70% and the
inclusion of placebo is therefore mandatory in comparative RCTs in order to “test
the reactivity of the patient sample”, as has been recommended by the IHS and
EMEA.
Conclusions: As illustrated above migraine treatment guidelines should
not, despite being developed by leading headache and methodological experts, be
regarded as sacrosanct documents and should be open for discussion.
P384
Botulinum Toxin A as a Treatment for Hemiplegic Migraine: 3 Cases
C.E. Robertson1, I. Garza1
1Neurology, Mayo Clinic, Rochester, MN, USA.
Objectives: To report 3 cases of hemiplegic migraine (HM) that responded
well to onabotulinumtoxinA (BTX), 150 units given every 3 months.
Background: Compared to patients with typical migraine with aura,
patients with HM tend to have more prolonged aura symptoms. In some cases,
reversible unilateral weakness may last days to weeks. There are no randomized
trials on prophylactic therapy for HM, but there is anecdotal evidence supporting
the use of verapamil, acetazolamide, and lamotrigine.
Methods: Three case reports.
Results:
Case 1: 18 year-old F with severe daily migraines associated with
visual, sensory, and motor aura (true weakness) lasting about 20 minutes each. She
had some improvement on divalproex sodium and amitriptyline, decreasing severe
migraine with aura to only 2 days/week. Since starting trimestral BTX (after 3
sessions) she has had only mild headaches without sensory/motor aura.
Case 2: 47 year-old F with migrainous headaches following right
posterior frontal stroke. She had 25 days/month of headache with 15-17 days of
severe migraine with aura. Aura involved numbness/paresthesias in the left lower
face spreading to left hand/arm (15 min) then left leg (25 min). Ten minutes after
numbness onset, she would develop left facial droop followed by gradual arm then leg
weakness. Some headaches would have associated visual aura as well, lasting hours.
Numbness would last the duration of the headache (1 to 6 days). Weakness would not
resolve entirely until 12 hours after the end of the headache. Verapamil helped
headaches, but was associated with arrhythmia. Patient failed multiple other
preventative agents. She has had 3 sets of BTX injections and reports averaging
10-12 headache days/month with mild aura 2 days/week and severe aura with weakness
every 6 weeks. Effect starts one week after injections and wears off after 10 weeks
on average.
Case 3: 44 year-old F with migraine with aura described as right facial
numbness/paresthesias that spread gradually to right arm, associated with right arm
weakness. While weak, she is unable to hold a glass in her hand, and has to lean
down to brush her teeth as she is too weak to bring her hand to her face.
Frequently, migraine will have visual aura as well. Sensorimotor aura may last 0.5-1
day, up to 3-4 days. She had daily headaches with typical migraines with aura 15
days/month. Verapamil helped some but was associated with constipation. She failed
other preventatives due to side effects. She has now had four sets of BTX injections
and reports 10 days/month of migraine headache, with only 3-4 days/month of aura.
The aura is less severe, with mild numbness and no weakness.
Note: Case 3 had a daughter with motor aura (no genetic testing) but other cases had
no family history of aura.
Conclusions: To the authors’ knowledge, there is only one other case
report describing the successful treatment of HM with botulinum toxin.1
Combined with the current cases, there is suggestion that BTX may be another
treatment option for the prophylaxis of HM.
P385
The Effectiveness of Cymbalta in the Treatment of Cervicogenic Migraine
(CM)
E.H. AbdElKarim1, Z. Elchami1, E. Umlas1, D.
Fayed1, D. Magayano1
1Pain & Headache Management Center of Excellence,
International Medical Center, Jeddah, Saudi Arabia.
Objectives: The objective of the study is to evaluate the effectiveness
of Cymbalta in the treatment of Cervicogenic Migraine (CM).
Background: The treatment of CM is considered a challenge for most
clinicians, as symptoms can be similar, due to its anatomic and pathophysiologic
complexities. Successful treatment usually requires multi-disciplinary approach.
Methods: 80 patients were evaluated according to IHS classification of
secondary headaches at the Pain & Headache Center, IMC, KSA. Patients were
randomly allocated to either Cymbalta alone or in combination with Tizanidine for 6
months. Both groups were allowed to have an average of 10 sessions of physical
therapy. First group (N=38) received Cymbalta 60mg once daily and Tizanidine 2mg at
bed time, while the second group (N=42) received Tizanidine 2mg only. Inclusive
criteria: 36 males, 44 females; ages between 25-65 years, with a mean of 45.
Exclusive criteria: pediatrics, patients older than 55, with uncontrolled diabetes
and blood pressure, and other neurological deficits.
Results: Average improvement of 76% and 59% were seen in patients who
were treated with the combination therapy (Cymbalta and Tizanidine), and Tizanidine
alone, respectively.
Conclusions: Patients receiving the combination therapy of Cymbalta and
Tizanidine showed more significant improvement compared to those receiving
Tizanidine alone.
P386
Reversible Sensory Ataxia Induced by Memantine Therapy for Chronic
Migraine
E.V. Vintayen1, B.M. Grosberg1, H.L. Geyer1, M.S.
Robbins1
1Neurology, Montefiore Medical Center, Albert Einstein College of
Medicine, Bronx, NY, USA.
Objectives: To describe the unique association of a dose-related sensory
ataxia in the treatment of chronic migraine (CM) with memantine.
Background: Memantine, a low- to moderate-affinity noncompetitive
antagonist of the N-methyl-D-aspartate (NMDA) type of glutamate receptor, is widely
approved for the treatment Alzheimer’s disease at a maximum dosage of 10 mg twice
daily. However, higher doses have been administered off-label for chronic headache
prophylaxis. Known adverse effects include neurological symptoms but not sensory
ataxia, defined as the loss of coordination secondary to disrupted sensory input
into the central nervous system.
Methods: Case report from a tertiary medical center.
Results: After numerous treatment failures with other agents, a
39-year-old woman with refractory CM was initiated on memantine for headache
prophylaxis, increasing weekly by 5 mg/day increments until she reached a dose of 15
mg in the morning and 20 mg at night. At a dose of 25 mg daily, she noted spatial
perception difficulties, distal extremity paresthesias, and mental clouding, which
progressed with further increases to 35 mg daily. Neurological examination revealed
marked impairment of proprioception and vibratory sensation in the hands and feet,
pseudoathetosis of the fingers, and a postural tremor. A Romberg sign was floridly
positive. There was no dysmetria or dysdiadochokinesia but her gait was cautious,
slow, and wide-based. Memantine was gradually tapered off over a 5-week period, and
her neurological symptoms and examination normalized over several months. Diagnostic
testing including MRI, serologic, cerebrospinal fluid, and nerve conduction studies
revealed no other cause of the sensory ataxia.
Conclusions: The temporal contiguity between memantine initiation and
the onset of sensory ataxia, as well as the dramatic improvement upon cessation of
memantine, suggests a causal relationship. High doses of memantine may be associated
with a reversible sensory ataxia, perhaps by overblockade of specific NMDA receptor
subtypes which are found in high concentrations on afferent A-fibers. Patients with
diffuse peripheral and central sensory sensitization, including individuals with CM,
may be more susceptible to such adverse effects.
P387
Efficacy of Osteopathic Manipulative Treatment in the Prophylaxis of Migraine
without Aura
L. Triggiani1, G. Giannotti1
1Center for the Diagnosis and Treatment of Headaches and Facial
Pain, San Giovanni Battista - Order of Malta Hospital, Rome, Italy.
Objectives: Our objective was to evaluate the efficacy of osteopathic
manipulative treatment (OMT) in the prophylaxis of migraine without aura in patients
that were not taking preventive therapies.
Background: Complementary and alternative treatment (CAM) is used more
often among adults with migraines or severe headaches. However, there are few report
using OMT to specifically treat migraines or severe headaches and research data on
OMT use for headache disorders remain poorly documented.
Methods: All patients included in the study had to compile an Headache
Diary during the study and the MIDAS questionnaire at the beginning and the end of
the study. Total duration of follow-up was six months, during this period the
patients may take only symptomatic medications for their headache. During the first
quarter the patients had to record frequency, intensity and duration of the attacks.
In the second quarter they had 5 OMT: 3 OMT weekly, the 4th following 2 weeks, and
the 5th following 1 month. All data recorded during the first and the second quarter
were comapred. Dysfunctional anatomical segments were also assessed.
Results: Twenty-two patients, respectively 19 women and 3 men were
included. At the end of the study the mean of migraine days per month was decreased
with respect to the beginning (20.73 vs. 15.36, Δ 5.37, p=0.018). The mean of days
of consumption of medications was decreased at the end of the study with respect to
the beginning (14.82 vs. 8.68, Δ 6.14, p=0.001). The mean level of pain intensity
was decreased at the end of the study with respect to the beginning (6.05 vs. 4.64,
Δ 1.41, p=0.0005). The mean score of MIDAS was 20.1±19.3 before OMT and 12.4±10.2 at
the end of the study period (p=0.0862). 5.7% of anatomical segments was disordered.
Sygma and spheno-basilar synchondrosis were the anatomical segments more frequently
affected.
Conclusions: The results of this study indicate that OMT is an
efficacious treatment for the prophylaxis of migraine without aura.
Considering that these therapies often carry a very low risk of serious side effects
and frequently are much less expensive than pharmacologic therapies, there is a need
for further rigorous research employing mixed method designs and utilizing large
national samples to understand the effectiveness and mechanisms of CAM treatments in
adults with migraines or severe headaches.
P388
Clozapine as Add on Therapy for Difficult Migraine Patients
A.V. Krymchantowski1, C.C. Jevoux1
1Headache Center of Rio, Rio de Janeiro, RJ, Brazil.
Objectives: The aim of this study is to evaluate whether the atypical
neuroleptic clozapine, which acts on serotoninergic, dopaminergic and noradrenergic
systems, may help improve the treatment response in migraineurs who did not present
headache frequency reduction of higher than 50%, despite the previous use of
numerous drugs.
Background: Difficult-to-treat migraineurs are frequently seen in
tertiary centers. Although these patients pose a challenge to physicians, personnel
and even other patients, underlying mechanisms and effective treatments are still
uncertain. Neuroleptics such as quetiapine, chlorpromazine and others have been used
although with poor evidence of its efficacy.
Methods: It was an open study carried out in two headache clinics during
the period of 2009-2012. Every migraineur, according to the IHS-II classification,
who did not respond to at least 5 pharmacological preventive agents used alone or in
combination, in addition to complain of sleep problems, was prospectively studied.
Clozapine was added to patients already in use of other agents in a single daily
dose at bedtime, starting with 12,5mg and was titrated every 14 days to 25mg and
37,5mg. The dosages of the other pharmacological agents in use were not adjusted
during the previous two months. A detailed headache calendar had to be filled by all
patients.
Results: Eighteen patients (12 women, 6 men, ages 27-62 years, mean 45)
were included and 15 completed the use of the drug. After 2 months (one month with
37,5mg) the patients were evaluated regarding the decreasing of headache frequency
of higher than 50%. The average headache frequency before the use of clozapine was
10 days/month and after was of 9,4 days/month. Adverse effects were reported by 12
(80%) and gaining weight, somnolence and drowsiness were the most reported events.
Fever was presented by 3 patients. Two patients among the 15 did not reach 37,5mg
and remained with 25mg/day due to fear of side effects.
Conclusions: It is not known why some headache sufferers do well with
the use of neuroleptics. Psychiatric comorbidities don’t seem to explain it since
the dosages used are much lower than that for psychiatry. However, the modulatory
effect of these drugs on various neurotransmitter systems may play a role. Despite
the open methodology, clozapine does not seem to be useful for the prevention of
migraine even as add on therapy. Controlled studies with higher doses are necessary
to confirm these observations.
P389
Once Daily Gastroretentive Gabapentin Formulation for Episodic Migraine
Prophylaxis: The First Case Report
D. Kantor
Neurologique, Ponte Vedra, FL, USA.
Objectives: To report the use of a once daily gastroretentive gabapentin
(G-GR) formulation for the prophylaxis of episodic migraine.
Background: Gabapentin is a calcium channel α2δ ligand that increases
γ-aminobutyric acid (GABA) concentrations in the brain; it has been hypothesized to
play a role in migraine prophylaxis. However, according to the 2012 updated
evidence-based guideline report of the Quality Standards Subcommittee of the
American Academy of Neurology and American Headache Society, the evidence is
conflicting or inadequate to support or refute the use of gabapentin for migraine
prevention (Level U recommendation). There are known side effects and limitations to
the use of immediate release gabapentin (G-IR), and the conflicting data may be due
to the difficulty in patients attaining and sustaining optimal dosages (due to side
effects and frequency of administration). Gralise® is a once daily G-GR
formulation approved by the U.S. Food and Drug Administration (FDA) for the
management of postherpetic neuralgia (PHN); PHN patients seem to respond to G-GR
without the same burden of side effects that limit dose titration of G-IR. We
hypothesized that G-GR may play a beneficial role in the prophylaxis of episodic
migraine.
Methods: Case report.
Results: A 36-year-old woman with a 15-year history of episodic
migraines without aura (frequency 7 migraines/month, intensity 4-6/10) presented to
a headache specialist; her body-mass index (BMI) was 27 kg/m2. In the
past, she had attempted topiramate (up to a dose of 200 mg/day), which was
discontinued secondary to cognitive side effects and propranolol 80 mg three times a
day, which was discontinued due to hypotension. She refused to attempt
antidepressants for migraine prophylaxis due to her concerns regarding the potential
for neuropsychiatric side effects. G-GR was initiated at 300 mg with her evening
meal, and it was titrated up over 2 weeks to 1800 mg with her evening meal. The
patient denied any side effects and within the first month of treatment, her
migraine frequency reduced to 3 migraines/month (average intensity 3/10). By the
third month of treatment, her migraine frequency had reduced to 1–2 migraines/month
(average intensity 2-3/10). 6 months after initiation of G-GR, her migraine
frequency remains at 1 migraine/month (average intensity 2/10). The patient denies
any treatment-emergent side effects and is satisfied with her migraine
prophylaxis.
Conclusions: This case report suggests that G-GR should be further
studied in case series, prospective open-label studies and, eventually, randomized
double-blind placebo controlled trials for the prophylaxis of episodic migraines.
Our patient may respond even further with escalating doses of G-GR beyond 1800 mg a
day, and perhaps with administration with the morning, rather than evening, meal or
even twice a day (with breakfast and dinner) dosing. However, dosing deviations from
that approved for PHN may have the disadvantage of increased side effects. Dose
finding trials, including serial measurement of serum gabapentin, will be invaluable
in helping to elucidate the potential role of G-GR in the prophylaxis of episodic
migraines.
P390
Efficacy and Tolerability of Acetazolamide in Migraine Prophylaxis and
Klinefelter Syndrome: A Case Report
R. Nardello1, P. Glorioso1, M. Saladino1, M.
Moscarelli1, A. Fontana1, S. Mangano1
1Dipartimento di Scienze per la Promozione della Salute e Materno
Infantile “G. D’Alessandro”, University of Palermo, Palermo, PA,
Italy.
Objectives: We describe an interesting case of migraine headaches with
aura in a 47, XXY male Klinefelter Syndrome (KS) intreatment with Acetazolamide and
resolutionof symptoms.
Background: A 16-year-old boy presented to the outpatient clinic
migraine headaches throbbing, onset evening that lasts for a week and is presented
once a month with aura, associated with nausea and vomiting.
Methods: The boy is a preterm at 28 WG for gestosis, the birth weight
was 800 gr. He presented psychomotor retardation, and flat feet, and scoliosis. On
neurological examination cranial nerves were intact. Detailed testing of motor
strength, sensory exam, gait and coordination was also normal, as were his reflexes.
Plantar responses were flexor bilaterally. The EEG was normal. He presented tall
stature, abdominal adiposity and small testicles. The karyotype 47, XXY showed the
presence of KS. The final diagnosis was new onset migraine headache with aura in
patient with KS. Due to the frequency of his headaches and the disability associated
he was treated with a prophylactic medication, before with Levetiracetam and then
Topiramate and then Flunarizine without resolution of symptoms.
Results: Afterintroduction prophilaxis with acetazolamidein an oral dose
of 500 mg dailysymptoms haveresolved. Patients with KS have reduced testosterone and
increased circulating estradiol. Migraine is suspected to be intimately connected
with increased circulating levels of estradiol. In our patient the 17-B- extradiolo
at the same timeof migraine attackswas high. After introduction prophylaxis with
acetazolamide for a period of six mounth thepatient experienceda reduction
inmigraine attacks.
Conclusions: Our case report supports the importance of hormonal
influences in migraine headaches, while alerting physicians to consider unusual
causes of hormonal dysregulation, such as KS in male patients presenting with
new-onset headaches.
P391
Relationship between Migraine-Related Disability and Somatosensory
Amplification
B. Goksan Yavuz1, E. Ilgaz Aydinlar2, P. Yalinay
Dikmen2, K. Ogel1, C.E.M. Incesu1
1Psychiatry, Acibadem University School of Medicine, Istanbul,
Turkey; 2Neurology, Acibadem University School of Medicine, Istanbul,
Turkey.
Objectives: The aim of this study was to evaluate the associations
between migraine related disability and somatosensory amplification, depression,
anxiety, and stress.
Background: Somatosensory Amplification Scale (SSAS) evaluates the
extent to which individuals are sensitive to their bodies1. Previous
studies have shown that the SSAS was also significantly correlated with depression
and anxiety 2,3. Although the above psychiatric conditions are well known
to be comorbid with migraine, less is known about the relationship of migraine and
the experience of somatic sensation.
Methods: Fifty-five migraine patients (31.9±7.2;42 female, 13 male) and
28 control subjects without migraine (31.8±5.8;19 female, 9 male) were recruited for
the study. Sociodemographic form, Migraine Disability Assessment Scale (MIDAS), the
Pittsburgh Sleep Quality Index (PSQI), Depression-anxiety-stress Scale (DASS), and
SSAS were administered to the subjects.
Results: The mean duration of migraine was 8.7±6.8 years. The mean MIDAS
score was 23.5± 34.4 and disability in 61.1 % of the patients was moderate or
severe. According to the PSQI score, 43.6 % of the migraine patients had more than
the cutoff point of 5, which was accepted as sleep disturbance. According to the
DASS score, 38.2 % of the migraine patients had mild, moderate or severe depression;
61.8 % of the migraine patients had mild, moderate or severe anxiety; and 52.7 % of
the migraine patients had mild, moderate or severe stress levels.
The mean PSQI, Depression Anxiety Stress Scale, and SASS scores in the migraine
patients were significantly higher than in the control subjects: PSQI (5.5±2.8 vs
4.5±2.7, p=0.05); depression (10.0±8.7 vs 7.0±8.7, p=0.03); anxiety (10.2±7.3 vs
7.8±8.3, p=0.03); stress (16.5±8.2 vs 12.6±8.8, p=0.02), SSAS (29.9±6.6 vs 26.1±7.1,
p=0.03) respectively.
In the migraine patients, MIDAS was significantly correlated with the SASS (r=0,287,
p=0,001), PSQI (r=0,332, p=0,002) and depression levels (r=0,271, p=0,005).
Conclusions: This study showed that migraine-related disability was more
prevalent in patients with higher levels of depression, sleep disturbances and high
somatosensory amplification. The relationship between migraine and depression and
sleep problems is well known. However, the association between migraine and somatic
amplification has only recently been established. People who have a tendency to
experience somatic sensations as intense and disturbing can evidently suffer more
from painful symptoms and their social and occupational functioning may be affected
more severely. Therefore, it is suggested that patients with migraine may also be
evaluated not only for depression and anxiety but also for somatic
amplification.
P392
Effect of Pharmacological Prophylaxis Treatment or Combination of
Pharmacological and Psychological Management on Outcome of Migraine
Patients
L. Triggiani1, G. Santamorena1
1Center for the Diagnosis and Treatment of Headaches and Facial
Pain, San Giovanni Battista - Order of Malta Hospital, Rome, Italy.
Objectives: To evaluate the effect of pharmacological treatment or
combination of pharmacological and psychological management on outcome among
migraine patients.
Background: Longitudinal data demonstrate a complex bidirectional
association between mood disorders and migraine. Psychological factors frequently
co-exist with many headache disorders. Treatment of a co-existing mood disorder with
cognitive behavioural techniques, may therefore reduce the impact of migraine.
Methods: All patients underwent an examination by a neurologist and
psychologist. The diagnosis was done according the International Headache
Classification. For the psychological assessment 4 scales are used: the Cognitive
Behavioural Assessment for Evaluation of Outcomes (CBA-VE), the Eysenck Personality
Questionnaire Revised (EPQ-R) short scale version, the Somatization
Scale from the SCL-90R (SOM), and a generic scale for the study of self-esteem
(SES). The Headache Impact Test (HIT-6) was also administered. Pharmacological
prophylaxis was prescribed to all patients (Ph), while those disabled by more
frequent migraine received also a psychological intervention (Ph+Psy). The outcome
was evaluated after 6 months.
Results: 54 patients (34 W and 10 M) were included. Mean age was 39.4 ±
13.2 years. 36 patients received only pharmacological prophylaxis, while 18 received
also the psychological intervention. The results of the 4 scales used for the
psychological assessment showed statistically significant difference only for the
CBA-VE scores in the dimensions of anxiety (28.2 ± 10.6 vs 21.4 ±
12.1 p=0.05), depression (28.3 ± 10.7 vs 20.6 ± 13.3 p=0.04), and
psycho-social trouble (24.5 ± 13.4 vs 16.3 ± 11.7 p=0.02). The
HIT-6 was higher in Ph+Psy with respect to Ph patients (62.4 ± 4.2
vs 57.0 ± 6.6 p=0.07). At the outcome evaluation 61.1% of
Ph+Psy with respect to 33.3% Ph patients (p=0.05) showed reduction of the frequency
of migraine with mean HIT-6 of 44.8 ± 12.5 vs 48.5 ± 5.3 p=0.6, and
lower rates of dropouts (11.1 vs 47.2% p<0,01).
Conclusions: These results indicate that the use of psychological
techniques can help people cope with their pain more effectively. It would thus
appear logical to view medical and psychological approaches as potentially
synergistic rather than mutually exclusive in the prophylaxis treatment of
migraine.
P393
Family Psychiatric History Influences Healthcare Utilization and Disability
among People with Severe Migraine
M.T. Minen1, E.K. Seng2,3, K.A. Holroyd4
1Departments of Neurology and Psychiatry, Massachusetts General
Hospital, Boston, MA, USA; 2Psychology, VA Connecticut Healthcare
System, West Haven, CT, USA; 3Psychiatry, Yale School of Medicine,
New Haven, CT, USA; 4Psychology, Ohio University, Athens, OH,
USA.
Objectives: To examine the relationship between family history of
psychiatric disorders and disability and healthcare utilization.
Background: Migraine is highly comorbid with anxiety and depression.
Familial aggregation of both migraine and depression are well recognized. Family
history of psychiatric disorders could influence healthcare utilization,
particularly for nonpharmacologic treatments.
Methods: We conducted a secondary analysis of baseline data from the
Treatment of Severe Migraine Trial. People with severe migraines (n
= 232) were recruited from referrals and flyers. During clinical assessment,
neurologists asked participants about the number of family members with anxiety and
depression, and previous headache treatment history. Participants completed measures
of disability (Headache Disability Inventory) and psychiatric symptoms [Beck
Depression (BDI) and Anxiety (BAI) Inventories]. Only participants with complete
histories of previous treatment (n = 225) were included in these
analyses. A series of regressions examined the relationship between disability and
headache healthcare utilization and family history of depression and anxiety, alone
and controlling for psychiatric symptoms.
Results: Participants were 78.7% women with a mean age of 39.5 (SD =
10.0); 15.6% reported family history of anxiety, and 29.3% reported family history
of depression. In the last two years, participants reported seeing a physician for
headaches 3.1 (SD = 3.8) times, with 28.4% going to urgent care. 39.1% of
participants reported using nonpharmacologic treatment for headache in the prior two
years, with the highest rates of chiropractic manipulation (27.1%) and massage
(18.2%), and few using biofeedback (0.4%), relaxation training (4.4%), psychotherapy
(1.8%), physical therapy (4.9%) or acupuncture (1.8%). Alone, family history of
anxiety was associated with higher levels of disability, t(229)=2.23, p<0.05,
r=0.15, although this was not significant [t(228) = 0.9,
p> .05,partial r = .06) when controlling
for BAI [t(229)=8.82, p<0.05, partial r=.50]. Controlling for
BAI, family history of anxiety was associated with trying non-pharmacologic
treatments for headache OR=2.56 (95% CI=1.21, 5.42), but no other health care
utilization variable. Family history of depression was not associated with
disability or healthcare utilization alone or controlling for BDI; the BDI was
associated with the HDI [t(df)=-2.5, p<0.05, partial r=-.16] and trying
non-pharmacologic treatments for headache [OR=1.05 (95% CI 1.00, 1.09)].
Conclusions: Reported family history of anxiety and depression did not
independently contribute to disability beyond psychiatric symptoms. Family history
of anxiety, but not depression, was associated with using non-pharmacologic
treatments for headache. Participants reported low rates of utilization for
nonpharmacologic treatments with grade-A evidence.
P394
Are Brown Scale for Attention-Deficit Disorder Scores Predictive for Compliance
in Migrainous Patients?
C. Condello1, L. Pinessi1, L. Savi1
1Neuroscience, Molinette Hospital, University of Turin, Headache
Center, Turin, Italy.
Objectives: To evaluate a possible relationship between high scores in
Brown Scale for Attention-Deficit Disorder (ADD) and compliance in therapy and diary
keeping.
Background: Compliance to therapy and recording of attacks in
migraineurs is sometimes unsatisfactory. Well estabilished comorbidity with
depression and anxiety disorders have been considered responsible, as well as the
chronic nature of the illness and the patient beliefs in its essential
benignity.
In recent years, there is a growing interest in adult ADD, due to its prevalence,
co-morbidity, and negative psychosocial impact. The disorder can present in many
ways, such as restlessness, dysphoria, lack of concentration, failure to plan
activities and work. Epidemiological studies have demonstrated that ADD in adults is
common, affecting an estimated 3 – 4% of the population, and recent findings point
to a co-morbidity of migraine, based on the use of population surveys with
questionnaires and following prescription patterns of anti-migraine and anti-ADD
drugs.
Methods: We screened all consecutive patients who came to our Centre for
Headaches in October and November 2012 with Beck Depression Inventory, STAI scales
for anxiety and Brown Scale for ADD, the only validated tool for detection of ADD
symptoms in Italian population.
All of our patients are requested to fill in a headache diary that we routinely
record at every follow-up visit.
We included only patients with diagnosis of migraine, with or without aura, defined
according to ICHD-II, >18 years old and in follow up for 1 year at least.
Exclusion criteria were a diagnosis of other primary or secondary headache,
psychiatric comorbidity and lack of comprehension of Italian language.
Compliance was evaluated by the investigator and scored on a 4-step grid
(“excellent”, “good”, “poor”, “absent”) according to the filling in of diary and
adherence to therapy of the previous year.
Evaluation of Brown Scales was conducted after assigning of compliances scores, to
avoid bias.
A regression analysis was conducted to evaluate a possible influence of scores at
Brown Scale for ADD on compliance.
Results: Sixty patients were eligible for study (48 women, 12 men),
after exclusion of 7 patients with non-migrainous headache and 1 patient with
bipolar disorder. Mean age was 46,78 years old, mean values of Beck, STAI I and II
were, 9,6038, 41,9057 and 45,2453 respectively. Mean score at Brown Scale was
35,23.
Higher score at Brown Scale was predictive of worse compliance in filling in the
headache diary (p<0,05), but not of worse adherence to therapy.
All results are controlled for sex, age and depression and anxiety scores.
Conclusions: ADD is a frequent condition in adult population and often
comorbid with migraine.
It is possible that higher scores at Brown Scales, validated for ADD initial
detection, could be predictive factors for lack of compliance in reporting attacks
of migraine on headache diary, our best tool to evaluate effectiveness of preventive
and acute therapy.
These interesting results would benefit from a replication on a larger sample.
P395
Does Posttraumatic Stress Disorder Influence the Relationship between
Psychological Trauma and Headache in Veterans?
E.K. Seng1,2, M.A. Driscoll1,2, C.A. Brandt1,2, H.
Bathulapalli1,2, J. Goulet1,2, S.G.
Haskell1,2
1VA Connecticut Healthcare System, West Haven, CT, USA;
2Yale School of Medicine, New Haven, CT, USA.
Objectives: To examine the influence of posttraumatic stress disorder
(PTSD) symptoms on the relationship between psychological trauma and headache in
veterans of the conflicts in Iraq and Afghanistan (OEF/OIF).
Background: Psychological trauma and PTSD have been associated with
higher rates of headache. It is unclear whether the relationship between trauma and
headache is independent of PTSD, or if this relationship occurs primarily in the
context of PTSD. OEF/OIF Veterans have high rates of headaches, traumas, and
PTSD.
Methods: This study examines cross-sectional survey data from the Women
Veterans Cohort Study from 228 male and 323 female OEF/OIF veterans (total
n = 551) who were recruited through mailings sent to 8465
OEF/OIF veterans in New England, Indiana and Illinois, or flyers in Connecticut and
Indiana. 693 veterans completed the baseline survey from 7/2008-12/2011. 551
veterans responded to the study inclusion item, “During the past 12 months, have you
taken prescription medication for headaches,” which is nonspecific to headache type
and identifies clinically significant headache. Measures included PTSD symptoms
(Post-traumatic Stress Disorder Checklist, Military Version) and trauma [Traumatic
Life Events Questionnaire, Combat Exposure Scale, and military sexual trauma (sexual
harrassement and rape)]. Logistic regression examined associations between trauma
and headache. Single mediator models were later estimated using the bias-corrected
bootstrap method. Where assumptions were met, PTSD was tested as a mediator between
trauma and likelihood of taking prescription headache medication.
Results: 139 veterans reported taking prescription headache medication
in the prior year. Alone, a higher number of lifetime traumas was associated with
higher odds of taking prescription medication (OR = 1.10, 95% CI = 1.01, 1.16). PTSD
symptoms mediated this association [Indirect effect =.009 (SE=.002), 95% CI (.004,
.014)]. A greater number of childhood (OR = 1.07, 95% CI = 1.03, 1.12) and adulthood
interpersonal traumas (OR = 1.06, 95% CI = 1.02, 1.10) were both associated with
higher odds of taking prescription headache medication. PTSD symptoms mediated both
of these associations [Childhood indirect effect=-.012 (SE=.004), 95% CI (.005,
.022); Adulthood indirect effect=-.018 (SE=.005) 95% CI (.008, .030)]. Neither
combat trauma (OR = .97, 95% CI = .94, 1.01) nor rape (OR = .77, 95% CI = .39, 1.51)
was associated with taking a prescription headache medication. Notably, military
sexual harassment was associated with decreased odds of taking prescription headache
medication (OR = .57, 95% CI = .38, .86) but the assumptions of mediation were not
met.
Conclusions: This preliminary evidence suggests that PTSD symptoms may
play an important role in the relationship between psychologically traumatic events
and headache. The relationship between traumatic events occurring during military
service and headache may differ from other traumatic events.
P396
Relations between Alcohol Use and Migraine among Young Adults
1Psychology, University of Mississippi, Oxford, MS,
USA.
Objectives: To assess relations between alcohol consumption variables
and migraine.
Background: Research on relations between alcohol use and migraine has
produced mixed findings, likely attributable in part to the debated role of alcohol
in precipitating migraine attacks. Many migraineurs identify drinking alcohol as a
trigger for migraine attacks (Fukui et al., 2008; Kelman, 2007), but little research
has explored whether specific alcohol consumption variables (eg, frequency,
quantity, binge episodes) distinguish migraineurs from those without migraine or are
related to impact of migraine. The current study supplements explored relations
between these alcohol variables and migraine-related variables in young adults, a
population of interest because of their high rates of alcohol consumption and
migraine.
Methods: 192 students (72.9% female, M age = 19.84) completed a battery
of headache and psychological measures including the Rutgers Alcohol Problem Index
(RAPI; White & Labouvie, 1989) and the Daily Drinking Questionnaire (DDQ;
Collins et al., 1985). Ninety-three students were identified as migraineurs using a
structured headache diagnostic interview (87% female; 93.5% with episodic migraine)
and also completed the Migraine Disability Assessment Questionnaire (MIDAS; Stewart
et al., 2001). MANOVA was used to quantify mean differences in consumption variables
(frequency, quantity, binge episodes, alcohol-related negative consequences) between
episodic migraineurs and controls. Among episodic migraineurs, multivariate
regression analyses assessed the variance in headache impact (frequency, severity,
and disability) attributable to these alcohol variables.
Results: Migraineurs reported having 7.13 drinks/week (vs 9.37 for
controls), drinking on 1.55 days/week (vs 1.94 for controls), and engaging in 2.39
binge episodes during the past month (vs 2.63). The overall MANOVA comparing groups
on these drinking-related variables was nonsignificant, F (4,181) =
1.603, p = .176. The multivariate regression analysis with the
combined criterion variables was also nonsignificant, F (12, 204) =
1.326, p = .206. Headache frequency, severity, and disability were
not individually associated with any of the consumption variables (R2s=
0.1% - 3.9%).
Conclusions: Young adults with episodic migraine do not differ from
those without migraine in frequency or quantity of alcohol consumption, severity of
alcohol-related negative consequences, or number of binge episodes. Among a college
population, alcohol consumption appears largely unrelated to the impact of migraine.
Given the prevalence of migraineurs who report alcohol as a trigger, these data
highlight a need for future studies to assess how migraineurs assign causality to
alcohol as a trigger and to probe its role as a trigger through further experimental
manipulations.
P397
Epicrania Fugax: Relationship between Severity and Psychological Profile in a
Large Series of Patients
A. López-López1, M.L. Cuadrado2, I. Muñoz3, S.
Hernández-Díaz1, C.M. Ordas2, C. de la Cruz3,
J. Porta-Etessam2, A.L. Guerrero3, J.L.
González-Gutiérrez1
1Psychology, Universidad Rey Juan Carlos, Madrid, Spain;
2Neurology, Hospital Clínico Universitario San Carlos, Madrid,
Spain; 3Neurology, Hospital Clínico Universitario, Valladolid,
Spain.
Objectives: Our aim was to analyze the relationship between the
frequency and intensity of pain paroxysms, response to treatment and several
psychological variables in a large group of patients diagnosed with Epicrania Fugax
(EF).
Background: EF is a novel condition consisting of brief painful
paroxysms stemming from a particular area of the head, and quickly radiate forwards
or backwards with a wide linear or zigzag movement through the territories of
different nerves. Pain intensity is usually moderate or severe, and quality mostly
electric.
Methods: 24 patients (16 women, 8 men; mean age 49.6, SD 16.9)
fulfilling the proposed diagnostic criteria for EF were recruited at the headache
units of two hospitals; 21 of them had forward EF, while 3 had backward EF.
Personality traits (NEO-FFI; Costa & McCrae, 1992), perception of stress (PSS;
Cohen, Kamarck & Mermelstein, 1983), usual coping strategies (Brief COPE;
Carver, 1997), and psychiatric symptoms (SCL-90-R; Derogatis, 1983) were assessed.
Pain frequency was measured using an ordinal scale, and pain intensity was evaluated
using a 10-point visual analogue scale (usual, minimum and maximum intensity, plus a
composite measure resulting of arithmetic mean).
Results: Intra-group analyses (Spearman’s rho) showed significant
negative associations between frequency of episodes and self-blame (-0.55;
p<0.05), venting (-0.68; p<0.01), neuroticism (-0.56; p<0.01), hostility
(-0.50; p < 0.05), paranoid ideation (-0.51; p<0.05), psychoticism (-0.05;
p<0.05), and interpersonal sensitivity (-0.56; p<0.01). Intensity was
inversely related to venting (-0.50; p<0.05), obsessive-compulsive symptoms
(-0.50; p<0.05) and agreeableness (-0.60; p<0.01). Non-parametric tests
(Kruskal-Wallis) showed significant differences in the distribution of hostility
among patients with complete, partial, or no response to treatment (c2 =
7.41; p<0.05).
Conclusions: Some psychological variables normally associated with
negative health outcomes were linked to a minor severity in EF patients.
Neuroticism, self-blame, hostility, paranoid ideation, psychoticism and
interpersonal sensitivity were related to lesser frequency of pain paroxysms, while
obsessive-compulsive symptoms were related to lesser pain intensity. Moreover,
patients scoring higher in hostility showed a better response to treatment. We can
consider a possible restriction in the experience of emotions in patients suffering
from EF. As a rule, the aforementioned variables might be indicative of negative
health outcomes, but they may also reveal a better capability for experiencing
emotions. This hypothesis is reinforced by the inverse relationship between the
capability for expressing emotions in response to stress (venting) and the severity
of pain symptoms in our patients with EF.
P398
Confusional Migraine: A Further Understanding of Its Symptomatology and
Possible Comorbidities
M.T. Minen1, J. Camprodon1
1Neurology and Psychiatry, Massachusetts General Hospital, Boston,
MA, USA.
Objectives: As new International Classification of Headache Disorders
are considered, we offer some presentations of confusional migraine, a migraine
variant.
Background: Confusional migraine is a term used by many clinicians that
has not been placed in the ICHD. Recent literature reveals that the diagnosis of
confusional migraine is no longer confined to children, it can occur in adults.
However, little is known about these patients since it is a rare disorder.
Methods: We present four new cases with cognitive problems and
behavioral changes occurring in distinct confusional states with confusional
migraine as a possible unifying diagnosis. We looked at the cognitive presentation,
migraine characteristics, comorbid mood, anxiety and sleep disorders, history of
abuse and family history of migraine, epilepsy and psychiatric disorders. We report
findings on the neurological exams, neuropsychiatric rating scales, EEG and MRI.
Results: Descriptions of the episodes included inattentiveness,
disruption of awareness, emotional “lability/storm” unresponsiveness, and acute loss
of tone with speech difficulties. Neurologic examination revealed that cognition was
well preserved on limited in office testing. Migraine attacks included photophobia
and phonophobia in 75% and accompanying sensory symptoms (scalp allodynia, burning
or tingling, facial paresthesias, left hemibody numbness) in 75%. All had one or
more psychiatric diagnoses (75% mood disorders, 50% anxiety). All had sleep problems
(75% insomnia, 25% sleep walking disorder). Half reported a history of physical
abuse. There was a family history of psychiatric disorder, epilepsy and migraine in
75%, 50% and 50% respectively. All four patients had EEGs which did not show any
epileptiform activity. Brain imaging was non-contributory to the clinical
symptoms.
Conclusions: We propose that confusional migraine may be more common
than initially thought. Interestingly, all four patients had underlying mood and/or
anxiety disorders as well as sleep disorders. Thus, patients with confusional
migraine may have a mixed bag of comorbid diagnoses. Confusional migraine should be
included in the ICHD criteria, and future work should be undertaken to elucidate a
common paradigm implicating confusional migraine and its comorbidities.
P399
Bio-Neurofeedback and Cognitive Behavioral Therapy Combined with Pharmacologic
Therapies in Patients with Primary Headache
P.A. Sanchez1, A.M. Cardona1, M. Massaro1, M.
Volcy1
1Antioquia, Indocen Instituto De Dolor De Cabeza y Enfermedades
Neurologicas, Medellin, Antioquia, Colombia.
Objectives: To describe the usefulness of the Bio-Neurofeedback
technique and CBT combined with medication treatment in patients suffering from
primary headache.
Background: Taking into account the limitations of abortive and
preventive headache treatments, behavioral therapy combined with biofeedback
techniques BNF-BCT constitute a therapeutic modality with rigorous scientific
methodology that improves the quality of life for migraine sufferers providing
multifaceted and comprehensive treatment. To our knowledge, in Colombia there is not
any other a clinical experience or studies on this topic.
Methods: Through an observational study patients with primary headache
(PHA) were evaluated before and after the BNF-BCT. The behavioral therapy was
performed at least once a week for at least five sessions and included: BFB (EMG) in
frontal muscles, relaxation techniques, creative visualization and positive
self-affirmations. Clinical characteristics were evaluated though different
variables; impact questionnaires MIDAS and HIT-6 were screened before and after
BNF-BCT Protocol. In addition, affective disorders were looked at, displaying the
typical cognitive schema of those evaluated. Nonparametric statistical tests were
used.
Results: 78 patients were included. 91% (n = 71) were women, with an
average age of 44+14 years with an average headache evolution
time of 15 +13.4 years. 52.6% of patients had associated affective psychological
disorders such as depression and anxiety. Only 6.4% had no associated symptoms in
the prodromal phase or during the headache chronification stage. The majority of
subjects reported hours or days prior to headache associated symptoms as
nausea-vomiting (50.0%), phonophobia (65.4%) and photophobia (56.4%). 84.6% of
patients used preventive and abortive medications, while just 6.4% were using
painkillers.
52.5% of patients had endured headache for over 10 years, while the remaining 47.4%
have had it for a period between 1 to 10 years.
At the beginning of BNF-BCT, through HIT-6 66.7% of patients scored in the severe
headache impact and 21.8% reported moderate impact.
Regarding the MIDAS the monthly headache days were 17.7 +9. After BNF-BCT (average
sessions 11 SD: 7.6), the HIT-6 score improved in 46.2%, while worsen in 9% of
patients. MIDAS score significantly reduced afterbehavioral treatmenton average6
days (17.7+-9 days of pain/ month versus 11.6 +-9.3, P <0.0001); similar results
were obtainedwiththe average abortive consumption per week (from 4.5+-3.4to 2.7+-1.8
(p <0.0001).
Taking into consideration the years of chronification and response to BNF-BCT, it was
found better results in the group of patients with less than 10 years (41% of the
population. N = 32, 53.1%), than subjects with more than 10 years (59%, n = 46,
41.3%).
Conclusions: Biofeedback can be used in the context of behavioral
interventions as a proven successful non-medical treatment for PHA. The results of
this study support the usefulness in our population; it seems patients with shorter
evolution time do better.
P400
Psychotherapist Administered Biofeedback Provides Headache Improvement and
Associated Psychological Benefits
S. Gomez1, A. Borsuk1, R. Kaiser1
1Department of Neurology, Jefferson Headache Center, Thomas
Jefferson University Hospital, Philadelphia, PA, USA.
Objectives: This study was performed to determine the impact of
time-limited biofeedback treatment provided by a trained psychotherapist on headache
sufferers.
Background: Subjects volunteered to be a part of the study and were
referred for treatment by their neurologist in hopes that biofeedback treatment
would help control their pain. Most subjects continued to take preventive
medication.
Methods: Headache frequency, intensity, and level of impairment were
recorded in a self-report questionnaire asking subjects to rate each factor before
and after their six sessions of treatment.
Results: After six sessions, results showed a decrease in frequency,
intensity, and level of impairment for the majority of clients. In addition, there
were a number of supplementary benefits including an improvement in quality of sleep
and the management of general stress and anxiety.
Conclusions: The results suggest that the administration of biofeedback
by a trained psychotherapist provides benefits for patients that go beyond pain
reduction and should be considered regularly as a headache treatment option.
P401
Onset Headache in First-Ever Ischemic Stroke: A Study of Taiwan Stroke Registry
in 11,523 Patients
1Graduate Institute of Clinical Medicine Science, China Medical
University, Taichung, Taiwan Republic of China; 2Department of
Neurology, Lin-Shin Hospital, Taichung, Taiwan Republic of China;
3Department of Neurology, Neurological Institute, Taipei Veterans
General Hospital, Taipei, Taiwan Republic of China; 4Faculty of
Medicine, Institute of Brain Research and Brain Research Center, National
Yang-Ming University School of Medicine, Taipei, Taiwan Republic of China;
5Taiwan Stroke Society, Taipei, Taiwan Republic of
China.
Objectives: To assess if onset headache is an ominous sign in patients
with first-ever ischemic stroke.
Background: An association between headache and ischemic stroke is
well-known but its clinical significance is not determined. Discrepancy in
definitions might have led to mixed results.
Methods: A large population of ischemic stroke patients was obtained
from the Taiwan Stroke Registry, a government-funded prospective study recruiting
42,883 patients with acute stroke since August 1, 2006. Ischemic stroke subtypes
were classified by the TOAST criteria. Clinical features and impact on stroke
outcomes, including in-hospital stroke-in-evolution, changes in NIHSS at discharge,
and Barthel index and modified Rankin scale (mRS) up to six months after stroke were
compared between those with and without onset headache.
Results: After excluding patients with hemorrhagic stroke, younger than
18 years old, a previous stroke history, and poor communication, the final analyzed
sample was 11,523 patients. Of them, 848 patients reported having onset headache
(7ċ4%). Patients with specific etiology, large artery atherosclerosis, or
cardio-embolism were more likely to have onset headache than those with small vessel
disease. Patients with onset headache were younger, predominantly female, and more
likely to have posterior circulation ischemic lesions. Compared to patients without
onset headache, those with onset headache had a lower frequency of
stroke-in-evolution (4.5% vs. 6.7%. adjusted RR: 0.67, 95% CI: 0.53-0.76,
p<0.001), greater improvement in NIHSS score upon discharge (0.08 vs. -0.20,
p=0.02), and higher mean Barthel index scores (86.5±24.0 vs. 83.9±25.3, adjusted
difference: 1.3, 95% CI: -.06-2.89, p=0.032) and a lower frequency with mRS higher
than 2 (27.6% vs. 31.5%, adjusted RR: 0.89, 95% CI: 0.79-0.99, p=0.022) at one-month
follow-up. There was also a trend for better functional outcome in three- and
six-month follow-ups.
Conclusions: With a well-characterized definition, this large-scale
study demonstrated onset headache is associated with modest but significantly better
outcomes after stroke. Onset headache depicts a characteristic group of stroke
patients and should be explored in evaluating patients with acute stroke.
P402
Reversible Cerebral Vasoconstriction Syndrome and Cervical Artery Dissection in
20 Patients
J. Mawet1,2, M. Boukobza3, J. Franc3, M.
Sarov1,2, M.-G. Bousser1, A. Ducros2
1Neurology, Head and Neck Clinic, Lariboisière Hospital,
Assistance Publique des Hôpitaux de Paris, Paris, France; 2Emergency
Headache Centre, Head and Neck Clinic, Lariboisière Hospital, Assistance
Publique des Hôpitaux de Paris, Paris, France; 3Neuroradiology
Departement, Head and Neck Clinic, Lariboisière Hospital, Assistance Publique
des Hôpitaux de Paris, Paris, France.
Objectives: Our study aims at describing clinical-radiological
characteristics in a prospective series of patients having both confirmed reversible
cerebral vasoconstriction syndrome (RCVS) and cervical artery dissection (CAD).
Background: RCVS is a clinical-radiological syndrome characterized by
severe acute headaches, with or without seizures and focal signs, and a multifocal
constriction of cerebral arteries resolving spontaneously within three months. A few
cases of CAD associated with RCVS have been reported.
Methods: From January 2004 to December 2011, we prospectively recruited
patients with confirmed RCVS, based on angiographically proven reversible
vasoconstriction, and CAD.
Results: Twenty patients (18 females, 2 males) had RCVS and CAD. Main
associated conditions were migraine (12/20) and postpartum (5/18). Clinical features
included severe headache in all patients, neck pain in 15, focal neurological
deficit in 9, and seizures in 4. Pain was the only symptom in 10 patients. All
patients had multifocal cerebral vasoconstriction. Twelve patients had brain
lesions, cortical subarachnoid haemorrhage in 11, posterior reversible
encephalopathy syndrome in 4, intracerebral haemorrhage in 3, and infarcts in 4.
CAD involved one artery in 13 patients and multiple arteries in 7. CAD mostly
affected vertebral arteries (25 of 30 CAD). Only one vertebral CAD was associated
with a related symptomatic infarct.
At 3 months, 18 patients had fully recovered, all patients showed reversal of
cerebral vasoconstriction, and 21 dissected arteries had normalized whereas 9
arteries had not, showing residual stenosis (7) and/or aneurysm (3).
Conclusions: Our study suggests that the association of RCVS and CAD is
not so rare. It points to the need for a systematic study of cervical arteries in
RCVS, and of intracranial arteries in CAD patients with worsening or recurrent
headache.
P403
Withdrawn by the author.
P404
Reversible Cerebral Vasoconstriction and Cervical Carotid Vasoconstriction in
Migraineurs
Y. Unno
Neurology, Kawakita General Hospital, Suginami-ku, Tokyo, Japan; Neurology,
Roppongi Hills Clinic, Minato-ku, Tokyo, Japan.
Objectives: The purpose of this study is to evaluate clinical
characteristics of cerebral vasoconstriction in migraineurs.
Background: Reversible cerebral vasoconstriction syndrome (RCVS) had
been become a topic as one of the conditions responsible for thunderclap headache.
Recently there are a few reports of cervical carotid vasoconstriction (CCV) of
unknown etiology. Cerebral vasoconstriction in migraineurs should not be
misdiagnosed because the risk of stroke may increase if they use triptans.
Case 1
Case 2
Case 3
Age, Gender
40, female
41, female
40, female
previous headache
migraine without aura
migraine without aura
migraine with aura
Trigger factor
Caesarean section
unknown
unknown
Character of headache
intermittent, sharp, severe pain, different from previous
headache
intermittent, sharp, severe pain, different from previous
headache
continuous, moderate pain, same as previous headache except
for lasts 3 days
Blood pressure
hypertensive
hypertensive
normal
Intracranial vessels
multiple constriction and dilatation
multiple constriction and dilatation
multiple constriction and dilatation
Extracranial vessels
normal
normal
constriction
Course of vasoconstriction
normalized at 79 days
normalized at 129 days
improved once, exacerbated at 120 days
Complication
none
subarachnoid hemorrhage
cerebral infarction
Methods: Patients who visited our Headache Clinics between August 2010
and December 2010, and had been diagnosed as having cerebral vasoconstriction were
prospectively assessed. MRA was repeated until cerebral vasoconstriction
improved.
Results: One hundred and eight patients were diagnosed as having
migraine and underwent MRI. Reversible cerebral vasoconstriction was confirmed in 3
patients (2.8%). Clinical characteristics and neuroimagings of these cases were as
follows. Case 1 and 2 were diagnosed as having RCVS. Case 3 was diagnosed as having
idiopathic CCV.
Conclusions: Dysfunctional regulation of cerebral vascular tone under
the predisposition and/or precipitating factors might be the central element in the
pathogenesis of RCVS, but relationship between RCVS and CCV remains unclear. From
the present cases and the review of past reports, both conditions were common in 30s
and 40s, more women. However, patients with CCV were more migraineurs, has less
frequent thunderclap headache, more frequent cerebral infarction, and long duration
of repeated vasoconstriction. Sympathetic dysfunction is suggested in migraineurs
even during headache-free period, and may be more strongly influenced in CCV than
RCVS. Cerebral vasoconstriction is not uncommon among migraineurs. The pathogenesis
of cerebral vasoconstriction may be multifactorial. Further clinical data are
required to elucidate this intriguing condition.
P405
Diagnostic Criteria for the Pseudotumor Cerebri Syndrome in Adults and
Children
D.I. Friedman1, K.B. Digre3, G. Liu2
1Neurology & Neurotheraputics and Ophthalmology, University of
Texas Southwestern Medical Center, Dallas, TX, USA; 2Neurology and
Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, PA,
USA; 3Neurology and Ophthalmology, University of Utah, Salt Lake
City, UT, USA.
Objectives: To update the diagnostic criteria for the pseudotumor
cerebri syndrome based on advances made since the last revision in 2002.
Background: Problems with the term IIH, over- and misuse of the
diagnosis “IIH without papilledema,” greater awareness of the associated radiologic
abnormalities, and a better understanding of this condition in children and what
constitutes a normal CSF opening pressure in this age group, necessitate a revision
to the nomenclature [pseudotumor cerebri syndrome (PTCS)] and diagnostic criteria
for all age groups.
Methods: We revised the 2002 classification and diagnostic criteria.
Results: 1. Required for diagnosis of the PTCS
A. Papilledema
B. Normal neurological examination except for cranial nerve abnormalities
C. Neuro-imaging: Normal brain parenchyma without evidence of hydrocephalus, mass, or
structural lesion and no abnormal meningeal enhancement on magnetic resonance
imaging (MRI), with and without gadolinium, for obese females, and MRI, with and
without gadolinium, and MR venography for others. If MRI is unavailable or
contraindicated, contrast-enhanced computed tomography may be used.
D. Normal CSF composition
E. Elevated LP opening pressure (> 250 mm CSF in adults and > 280 mm CSF in
children (250 mm H2O if the child is not sedated and not obese) in a properly
performed lumbar puncture
2. Diagnosis of PTCS without papilledema
In the absence of papilledema, a diagnosis of PTCS can be made if B-E from above are
satisfied, and in addition the patient has a unilateral or bilaterial sixth nerve
palsy.
In the absence of papilledema or sixth nerve palsy, the diagnosis is “suggested” but
not established if B-D from above are satisfied, in addition to A and C below.
A. Elevated LP opening pressure (> 250 mm CSF in adults and > 280 mm CSF in
children (250 mm H20 if the child is not sedated and not obese) in a properly
performed lumbar puncture
B. Unilateral or bilateral abducens nerve palsy
C. Neuroimaging signs (at least three):
i. Empty sella
ii. Flattening of the posterior sclerae
iii. Distention of the perioptic subarachnoid space +/- a tortuous optic nerve
iv. Transverse venous sinus stenosis.
Conclusions: Further study will determine the specificity and
sensitivity of these criteria.
P406
HIV and Headache: A Case-Control Study
P.A.S. Rocha-Filho1, R.C.S. Torres1
1Hospital Universitário Oswaldo Cruz, University of Pernambuco,
Recife, Pernambuco, Brazil.
Objectives: The aims of the present study were to compare
the prevalence and headache characteristics between those infected or not by HIV
virus.
Background: Headache is one of the most common medical complaints
reported by individuals suffering from human immunodeficiency virus (HIV), but
limited and conflicting data exist regarding their prevalence and
characteristics.
Methods: Case-control study. Cases: consecutive HIV infected patients
who sought medical assistance in the AIDS clinic of Hospital Oswaldo Cruz and
Hospital Correia Picanço; CD4+ T lymphocyte > 500/mm3, without the use
of highly active antiretroviral therapy (HAART). Controls: consecutive patients who
sought medical assistance in the Basic Health Care Units (general practice
physician) for several reasons but without history of HIV infection. A
semi-structured interview, the Headache Impact Test (HIT-6) and the Hospital Anxiety
and Depression Scale were used.
Results: Two hundred thirty-five patients were interviewed, 80 of them
with HIV infection. The mean age of the study group was 38 years (SD=17); 62% were
women. The headache prevalence in HIV group was 90% and among those without HIV was
67% (p<0.01; chi-square test). The HIV group had significant lower frequency and
lower impact of headache. There were no differences between the groups regarding
migraine and tension-type headache prevalence, headache intensity or depression and
anxiety symptoms.
Conclusions: Patients with HIV infection had a higher prevalence of
headache compared with those without history of HIV infection, but had a lower
frequency and impact of headache.
P407
Frequency of Chronic Headache Resulting Stroke
N.J. Milovanovic Kovacevic1, N.L. Zaric1
1Intensive Care, St. Sava Hospital for Cerebral and Vascular
Diseases, Belgrade, Serbia and Montenegro.
Objectives: Our study was to determine whether the percentage of the
stroke patients with a chronic headache as its consequence, treated in our hospital
during 2011, differs from the data in similar centres in the EU and the US.
Background: Apart from direct and evident neurological deficiencies
specifically related to localisation of lesion,stroke patients, both in acute and
later stages, develop numerous functional disorders and complications. Headache is a
common symptom in pre-stroke and on-going stroke patients and is not uncommon as a
consequence of a stroke.
Methods: During the year 2011, 5,476 stroke patients were treated in St.
Sava Hospital. 4,005 patients survived. Out of them, 3610 were ischemic stroke
patients and 395 were hemorrhagic stroke patients.Our data have been obtained based
on the regular monthly check-ups of the patients. The patients came for these
check-ups with questionnaires and calendars where they circled each day with a
headache. The criterion for the diagnostics of chronic headaches has been set up
according to the criteria defined by HIS, which means that the patients have
suffered from headaches for 15 days or more over a period of six months.
Results: Our study shows that 761 patients have had chronic headache as
a consequence of a stroke, which makes 19.1% of the total number of patients.
Conclusions: Having compared these results to those in studies conducted
in the EU and the US, which show 16 – 20% of the patients, we have not established a
significant difference in the percentages of stroke patients with a chronic headache
as its consequence.
P408
Secondary Trigeminal Neuralgia Caused by Pharyngeal Squamous Cell Carcinoma – A
Case Report
H.-Y. Kim
Department of Anesthesiology and Pain Medicine, Seoul National University
Hospital, Seoul, Republic of Korea.
Objectives: This case report is to present atypical trigeminal neuralgia
that may be misdiagnosed as classical trigeminal neuralgia or temporomandibular
joint disorder.
Background: Trigeminal neuralgia (TN) is characterized by recurrent
paroxysms of unilateral facial pain that typically is severe, lancinating, and
activated with cutaneous stimulation. To be more exact, there are two types of TN,
classical TN and atypical TN. The feature of classical TN is the same as
forementioned things and the feature of atypical TN is constant, burning pain. The
cause of atypical TN includes aneurysm, tumor, and multiple sclerosis.
Methods: We describe the case of a 49-year old male presenting with
right sided facial pain. He was diagnosed with temporomandibular joint disorder in
the dental clinic and he was on medical treatment, but symptoms were aggravated day
by day. He was referred to pain clinic for further evaluation. Radiologic
evaluation, including MRI, showed a parapharyngeal tumor.
Results: We consult to the department of oncology, he was scheduled for
radiation and chemotherapy.
Conclusions: The clinical factors of suspicion for atypical TN are
constant, burning nature of pain, pain of multi-dermatome level, sensory deficit,
age under seventies, male gender. Moreover, we should consider not only intracranial
tumor but also paraphayngeal tumor for underlying disease generating atypical
TN.
P409
Retrospective Analysis of Headache Patients Treated by Neurosurgeons at
Emergency Department in Japanese Rural Area
M. Honda1, T. Anda1
1Neurosurgery, Shunan Memorial Hospital, Kudamatsu,
Japan.
Objectives: In some area, headache (HA) has been believed to be
initially treated by neurosurgeons to triage subarachnoid hemorrhage (SAH),
intracerebral hemorrhage (ICH), cerebral infarction (CI), arterial dissection and/or
brain tumor. In rural area with sparse physicians as well as neurologist,
neurosurgeons would be initial HA doctors. We have introduced neurosurgery hotline
to bypass any physicians and to triage stroke as well as traumatic brain injury to
shorten the diagnostic process and to initiate stroke treatment as soon as possible
with the policy of “Time is Brain”. Here we reviewed our registries at emergency
department (ED) visitors during off-hour and clarify the profile of headache
patients of our small community.
Background: We are only board certified stroke doctors. Patients showing
stroke suggestive symptoms are all directly referred to us, in addition to head
injuries and several types of seizures. We reviewed our cases for the last 3 years
and report the prevalence and clinical features of stroke. The hotline received
emergency calls during off-hours between 5:30 PM and 8:45 AM and whole holiday
hours.
Methods: We studied 110 consecutive HA patients of all 546 hotline
registry during 3 years of periods. All but 2 patients received at least one of or
both or all of CT, MRI and lumber puncture. We retrieved clinical information
Primary HA
50 (45.5%)
Stroke
27 (24.5%)
hypertension
17 (15.5%)
inflammatory disease
6
sinusitis
3
epilepsy
2
BPPV
2
skull fracture
1
hearing disturbance
1
hyperventilation
1
hypoglycemia
1
unknown
1
Stroke HA (n=27)
Non stroke HA (n=83)
p value Odds Ratio (95%CI) if applicable
age
62.7±2.7
53.5±2.32
p=0.015
Male: female
17:10
36:47
p=0.12
ambulance
19 (70.4%)
16(19.3%)
p<0.0001 9.95 (3.75-26.34)
admission
26 (96.3%)
8 (9.6%)
p<0.0001 269.75 (39.4-1732.5)
Onset to arrival (min) (excluded pts beyond 1day after
onset)
727.0±322.2 (110.2±33.2)
1068.2±221.9 (281.7±34.1)
p=0.22 (p=0.003)
including, HA type, final diagnoses, prognosis, transfer methods and interval from
onset of HA to ED arrival.
Results: Total 104 CT scan (92.7%), 46 MRI (41.8%) and 12 lumbar
punctures were performed to investigate HA. 27 stroke (24.5%) were documented,
following 48 primary HA (43.6%). In stroke, there were 14 SAH, 6 ICH, 5 vertebral
artery dissections and 2 CI. 35 patients (32.7%) were transferred by ambulance car
with 19 of 27 stroke (54.9%) and 11 of 14 SAH prevalence. Stroke patients were older
(62.7 years vs. 53.5, p=0.015) and more transferred by ambulance car (70.4% vs.
19.3%, p=0) with shorter interval from HA onset (110.2minutes vs. 281.7, p=0.003)
than non stroke HA.
Conclusions: Aged HA patients transferred by ambulance car highly
predict stroke related HA. Further investigation should be performed to triage life
threatening HA. In this area, HA patients seemed to take the privilege of HA and
stroke triage. Neurosurgeons have the important role to treat stroke patients in the
areas with sparse HA doctors.
P410
New Persistent Daily Headache with Normal Neurological Findings – Rare Primary
or Secondary Phenomena Caused by Carotid-Cavernous Fistula?
S. Ljubisavljevic1, M. Spasic1, D. Stojanov2
1Clinic for Neurology, Clinical Centre of Nis, Nis, Serbia and
Montenegro; 2Center for Radiology, Clinical Centre of Nis, Nis,
Serbia and Montenegro.
Objectives: We report a case of a patient which has diagnosed with CCF
initially presented with persistent daily headache followed by promptly neurological
progression.
Background: Carotid cavernous fistulas (CCF) are a dural arteriovenous
fistulas which include pathological communications between the arterial system and
the venous cavernous sinus situated at the wall of the cavernous sinus (CS). It can
be demonstrated by wide range clinical presentations, like ophthalmic signs and
symptoms (proptosis, chemosis, and visual loss), cranial nerve pareses, bleeding
from the cranial structures and intracranial hemorrhage.
Methods: Twenty eight years old women has presented with 3 months
history of daily left side headache, predominantly localized in left eye profound,
without free after analgotherapy. Parallel with headache development she described
sensation as a heart sound in pain area. Her mother died since some brain AV
malformations. On examination, she had no ophthalmoplegia, proptosis and chemosis
with normal neurological status. Auscultation under her left eye has found a
whir.
Results: Digital subtraction angiography was performed and revealed a
left side ophthalmic and facial venous dilatation with CS dilatation during all the
time beginning from early arterial phase. As a result of panangiography detected a
direct fast flow CCF, without presentation of left ICA intracranial parts with
promptly retrograde venous swelling into the ophthalmic and facial venous and
petrous sinus. During three days in neurological examination have occurred fully
left side ophtalmoplegia with diplopia, left side ptosis and hypestesis in V1 area.
The stent assisted coil embolization with complete occlusion of the fistula was
performed with completed clinical recovery.
Conclusions: In the small number of cases CCF can be presented by
minimal symptoms such as new persistent daily headache. This condition must be
diagnosed and treated promptly since it has a high risk of clinical progression and
irreversible neurological demages.
P411
Giant Cell Arteritis Associated with Orbital Pseudotumor
S. Reddi1, S. Vollbracht1
1Neurology, Albert Einstein College of Medicine, Bronx, NY,
USA.
Objectives: To present a patient with giant cell arteritis (GCA)
associated with orbital pseudotumor.
Background: GCA is a systemic inflammatory vasculitis of unknown
etiology that affects medium and large sized arteries. It characteristically affects
the elderly and can result in a wide array of systemic, neurologic, and
ophthalmologic complications of which visual loss and permanent visual impairment
are a major cause of morbidity. Orbital pseudotumor, also known as Idiopathic
Orbital Inflammatory Syndrome (IOIS) is a benign, non-infective, inflammatory
condition of the orbit and can be a rare presenting sign of GCA.
Methods: Case report.
Results: An 83-year-old woman presented to the emergency department (ED)
with a 5-day history of right-sided headache and facial pain. The pain was located
in the right frontotemporal and periorbital regions, was gradual in onset, severe in
intensity, throbbing, constant in quality and associated with ipsilateral
lacrimation, decreased vision and jaw claudication. She also reported a 20-pound
weight loss over 2-weeks, myalgias and fatigue.
Exam was significant for allodynia over the right V1-V3 dermatomes and right temporal
artery tenderness. Visual acuity was 20/70 in the right eye and 20/50 in the left.
Labs revealed an erythrocyte sedimentation rate (ESR) of 127 and c-reactive protein
(CRP) of 3.7. Right temporal artery biopsy revealed occlusive calcified
atherosclerosis with no evidence of GCA. T1 weighted images on MRI of the brain and
orbits with gadolinium demonstrated enhancement of the right optic nerve sheath and
surrounding retro-bulbar fat consistent with IOIS. Based on high clinical suspicion
of GCA, she was started on prednisone 60mg daily. Symptoms improved and she was
discharged on prednisone 60mg daily.
One month later, after stopping prednisone for a week, she presented with sudden
onset bilateral vision loss. Her examination was unchanged with the exception of
bilateral visual acuity to hand motion only. ESR and CRP remained elevated at 50 and
13.2 respectively. MRI of the brain and orbits without gadolinium revealed
improvement of the previously seen increased right-sided retro-bulbar signal. The
patient was treated with high dose intravenous steroids for 3 days with improvement
in visual function and was discharged on prednisone 60mg daily. ESR several months
later was 31.
Conclusions: IOIS can be an uncommon presentation of GCA and clinical
suspicion for GCA should be high in cases of IOIS, even in the absence of other
symptoms.
P412
Acute Headache with Encephalopathy Featuring a Transient Diffusion Weighted
Imaging Splenium Lesion in Herpes Simplex Virus Encephalitis
D. Schick1, M.S. Robbins1
1Neurology, Montefiore Medical Center, Albert Einstein College of
Medicine, Bronx, NY, USA.
Objectives: To describe a patient who presented with severe headache,
fever and encephalopathy and was found to have a transient diffusion weighted
imaging (DWI) lesion in the splenium of the corpus callosum.
Background: Reversible splenium lesions have been described in various
clinical contexts, many of which may feature headache prominently, including
epilepsy syndromes, anticonvulsant withdrawal, hypoglycemia, and numerous infectious
meningoencephalitides. However, this association has not been previously reported
with HSV, the most commonly diagnosed severe encephalitis.
Methods: Case report from a tertiary medical center.
Results: A 20-year-old male presented with headache, fever, confusion,
visual hallucinations, and nausea over two days. Lumbar puncture revealed a
lymphocytic pleocytosis and 2439 copies/mL of HSV on polymerase chain reaction. MRI
brain showed a centrally located lesion in the splenium of the corpus callosum,
hypointense on T1-weighted and hyperintense on T2-weighted and FLAIR images. It
demonstrated restriction on DWI and was hypointense on corresponding apparent
diffusion coefficient mapping. Additionally, the patient had hyperintensities on
T2-weighted, FLAIR, and to a milder extent DWI images in the medial temporal lobes
and right basal ganglia. He improved markedly after a 28 day course of acyclovir but
was left with residual frequent headaches, imbalance and memory loss. These imaging
findings largely resolved on repeat MRI six days later and completely resolved
nineteen days later.
Conclusions: Disorders featuring secondary headache, including HSV
encephalitis, may be associated with a transient DWI lesion in the splenium. When
encountered in meningoencephalitis, this abnormality may not be particular to a
specific pathogen but instead relate to the degree of acquired white matter
pathology. The etiology of the splenium lesions is not fully understood but may
relate to intramyelinic edema and inflammatory infiltrates or osmotic demyelination
caused by fluid imbalance. This association may be underrecognized even in HSV
encephalitis based on the lesion’s transient radiographic presence.
P413
Hadache in HIV-1 Infected Patients
M. De Marinis1, D. Galasso1, E. Colaizzo2, C.
Fimiani2
1Deparment of Neurology and Psychiatry, Sapienza University of
Rome, Rome, Italy; 2Department of Clinical Medicine, Sapienza
University of Rome, Rome, Italy.
Objectives: The present study was performed in HIV-1 infected patients
without cerebral complications in order to investigate the prevalence and features
of “headache attributed to HIV infection”, but also to investigate the prevalence of
primary headaches and their changes during HIV infection. The possible correlations
between headache and clinical features of HIV infection (duration of infection,
antiretroviral therapy, CD4 cell count, etc.) were also considered.
Background: Although Headache attributed to HIV/AIDS was coded to point
9.3 of the International Classification of Headache Disorders (2004), not many
studies have been performed in this field. The identity of a specific headache due
to HIV infection is still controversial. In addition, the presence of primary
headaches (migraine, tension type headache, etc.) has not been considered in most
studies.
Methods: We performed a retrospective study in 130 consecutive HIV-1
infected patients without cerebral complications and 130 age and sex matched healthy
controls.
All patients were visited in blind by two different neurologists expert in the
headache field. A detailed questionnaire was used to record the features of HIV
infection (duration of infection, CD4 cell count, antiretroviral therapies, etc.).
The diagnosis of headache was established according to the IHS classification
criteria. The prevalence and features of primary headaches were studied in patients
and controls. Any kind of headache which began after the HIV infection was
considered.
Results: At the time of the study, a history of migraine was present in
29 patients (22%) and 16 controls (12%). The features of migraine did not change
after the diagnosis of HIV infection, but a considerable number of patients, 13/29
(45%), developed migraine after the infection. Tension-type headache was present 25
patients (19%) and 33 controls (25%). Out of the 25 patients with tension-type
headache, only 15 (12%) developed the headache after the infection. In 6 patients
(5%) headache was related to the intake of a specific antiretroviral therapy.
The prevalence of migraine was significantly higher in patients that in controls
(p<0.05). No correlation was found between this headache and the clinical
features of the HIV infected patients. The relatively high prevalence of migraine in
patients may be due to a vascular involvement in HIV infection.
Conclusions: It is not clear if the “tension-type headache” that
occurred in our 15 patients after the infection may be considered as a “headache
attributed to HIV infection”. It is possible that the new treatments for HIV
infected patients changed their clinical evolution as well as the occurrence of a
specific headache.
P414
Are Occlusal Devices Effective on the Headache Improvement in Subjects with
Temporomandibular Disorders? A Systematic Review
Y.M. Costa1, A.L. Porporatti1, J.
Stuginski-Barbosa1, P.C.R. Conti1
1Prosthodontics, Bauru School of Dentistry, Bauru, Sao Paulo,
Brazil.
Objectives: The aim of this review is to assess whether the treatment
with occlusal devices is effective to improve headache in TMD patients.
Background: There is a concept that the TMD management of primary
headache patients may headache pain frequency. Although some studies already were
done to determine the efficacy of occlusal devices on headache pain improvement
associated to TMD, their results have not been pooled as a systematic review.
Methods: A structured literature search was conducted in MEDLINE and
other databases. All randomized controlled trials (RCT) for occlusal appliances
treatment in TMD and headache patients were considered. Selection criteria included
Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and
evaluation of headache in intensity and/or frequency. A quality analysis was
conducted using PEDro scale.
Results: Of 2128 references, 3 RCT were included. The total sample was
205 subjects diagnosed with myofascial pain and/or arthralgia or osteoarthritis. The
occlusal devices tested are stabilization, prefabricated, resilient and control
appliances. Headache improvement ranges from 30-50% at the 12 months follow-up
independent of device type.
Conclusions: Despite these positive results, the evidence available is
insufficient to support the use of occlusal devices in the management of headache
associated with TMD.
P415
Three-Dimensional Ultrasound Based Analysis of Cervical Spine Motion – Clinical
Significance in Cervicogenic Headache
H.K. Knackstedt
Department of Neurology, Innlandets Hospital Trust, Elverum, Norway; Head and
Neck Research Group, Research Centre, Akershus University Hospital, Oslo,
Lørenskog, Norway; Faculty Division Akershus University Hospital, University of
Oslo, Nordbyhagen, Norway.
Objectives: To investigate the dysfunction in anatomical structures of
the craniocervical junction in persons with cervicogenic headache (CEH).
Background: Restriction of the range of motion (ROM) in the cervical
spine as well as symptoms and sign of neck involvement are part of the main criteria
of cervicogenic headache. CEH i s often worsen by neckmovement, sustained awkward
head position, external pressure of the cervical or occipital region on the
symptomatic side. Neck pain and cervical muscle tenderness is also prominent in
primary and secondary headache but is not necessarily related to restriction in the
cervical range of motion.
Methods: A case control study of 46 consecutive persons with CEH, 22
consecutive with headache attributed to whiplash associated headache (WLaH) and 19
consecutive persons with migraine. The criteria of the Cervicogenic Headache
International Study Group (CHISG) were used for diagnosing CEH; otherwise the
criteria of the International Classification of Headache Disorders (ICHD II) were
applied. All participants had a clinical interview, and a physical and neurological
examination. Cervical range of motion (ROM) was measured with the Zebris CMS20
ultrasound based motion analyses system (Zebris Meditac GmbH, Isny, Germany). The
first aim was to evaluate the ROM in the sample of patients with CEH, WLaH and
migraine to determine if the cervical ROM could discriminate between those groups.
And the second aim was to determine whether the ROM is improving after blockade of
the greater occipital nerve in patients with CEH. All participants were assessed in
all neck movements actively and passively. Participants with cervicogenic headache
were examined before and after blockage of the greater occipital nerve.
Results: To be presented at congress.
Conclusions: To be presented at congress.
P416
Chronic Migraine after Cocaine Use
L. Green1, C. Ugurlu1, S. Sahai-Srivastava1
1Neurology, University of Southern California, Los Angeles, CA,
USA.
Objectives: To describe a patient who developed chronic migraine after
snorting cocaine and to review literature of similar cases.
Background: Cocaine is a powerfully addictive drug that has serious
neurologic consequences from its use. The potential neurological side effects of
cocaine use include intracranial hemorrhage, ischemic stroke, cerebral vasculitis,
brain abscess and psychiatric illnesses. Cocaine-induced headaches are estimated to
occur in over 60% of users related to cocaine use. There are three types of
headaches described with its use; an immediate bi-temporal, short-lasting headache,
a second type of headache occurring during binge use located in the frontal region
and the third type of headache during withdrawal from cocaine. All these headaches
are short lasting up to 72 hours and only one case is reported to have lasted 1
week. There are no reported cases of chronic migraine developing after a single
cocaine use except for one abstract from 1989 describing 6 patients with
self-limited headaches from cocaine use lasting 4 weeks to 9 months.
Methods: This is a case report and review of literature.
Results: The patient is a 22-year old right-handed male college student
who presented with chronic daily headaches that started 6 hours after snorting
cocaine and had been persistent for 9 months. He had intermittently snorted cocaine
three times, prior to this event and had not experienced any headaches. His pain was
described as a very intense, throbbing, 9/10 at its worst, located in the
bi-temporal region, and radiating posteriorly, superimposed on a constant background
headache of 2-3/10 with daily exacerbations to 5/10 to 6/10. He has zero headache
free days per month and experiences 10 severe headache days per month. There is no
proceeding aura, or any associated neurological symptoms. Triggers for the headache
include sleeping too much and alcohol consumption. Patient reported no previous
history of headaches and there was no family history of migraine headaches. His
neurological examination and MRI imaging of the brain were unremarkable. According
to the International Headache Society Guidelines cocaine-induced headache onset is
within the first hour after use and the headache should resolve within 72 hours. The
diagnostic criteria include bilateral pain, a frontotemporal location, a pulsating
quality, and being aggravated by physical activity. Our patient is unique in the
fact that his headache started 6 hours after cocaine use, and has persisted for the
past 9 months even though he completely stopped using cocaine. He fulfills the I.H.S
criteria for chronic migraines.
Conclusions: One case is described in which chronic daily migraine
developed after snorting cocaine. Cocaine blocks the serotonin uptake and alteration
in central pathways of serotonergic transmission has been shown in chronic migraine.
We hypothesize that the cocaine use may have triggered the onset of chronic migraine
via central neurotransmission dysfunction of the raphe-cortical serotonergic
pathway. More research is necessary to confirm our findings.
P417
Masticatory Muscle Tenderness in Temporomandibular Disorders and Primary
Headaches Patients
Y.M. Costa1, A.L. Porporatti1, J.
Stuginski-Barbosa1, P.C.R. Conti1
1Prosthodontics, Bauru School of Dentistry, Bauru, Sao Paulo,
Brazil.
Objectives: To evaluate association between anterior temporalis (AT)
tenderness to palpation, parafunctional habits and diagnostic of masticatory muscle
disorders, tension type headache (TTH) and migraine.
Background: The association between headache and temporomandibular
disorders (TMD) is not fully understood. Both conditions are highly frequent with
similar clinical presentation, besides the main complaint of head pain, such as
muscle tenderness to palpation, the presence of trigger points, and a very strong
impact in the patient’s quality of life.
Methods: Retrospective analysis was conducted with patient records of
the Orofacial Pain Clinic of Bauru School of Dentistry, among 1996 and 2009.
Diagnostic of masticatory muscle disorders followed the American Academy of
Orofacial Pain guidelines and International Headache Society criteria were used to
diagnose TTH and migraine. According to physical examination, patients were
classified in two groups: presence (group I) or absence (group II) of AT tenderness
to palpation. Self-reported presence of parafunctional habits was also addressed.
Chi-Square test with a 5% of significance accounted for statistical analysis.
Results: A total of 635 dental records were analyzed. Mean age was 35.7
years and 84% were women. Tenderness to palpation was found in 52% of the entire
sample and 80% presented parafuncional habits. Eighty six percent (86%) of group I
was diagnosed with masticatory muscle disorders, 34% with TTH, 16% with migraine and
84% reported parafunctional habits. Among those with parafunctional habits, 75% had
masticatory muscles disorders, 27% had TTH and 13% had migraine. Significant
association was found between presence of tenderness to palpation and parafunctional
habits (p=0.009), masticatory muscle disorders (p<0,001) and TTH
(p<0,001).
Conclusions: Anterior temporalis tenderness to palpation is associated
with masticatory muscles disorders, TTH and frequently found in patients with
parafunctional habits. Processes of trigeminal sensitization may account for these
findings suggesting a sharing of pathophysiology mechanisms.
P418
Subarachnoid Hemorrhage Resulting Vasospasm and Related Headache
N.L. Zaric1, N. Milovanovic-Kovacevic1
1Intensive care, Hospital for cerebrovascular diseases St.Sava,
Belgrade, Serbia and Montenegro.
Objectives: The aim of our study was to determine frequency
and intensity of the headache following vasospasm after SAH, using transcranial
color dopler ultrasonology (TCD) for diagnosis of middle cerebral artery (MCA)
spasm.
Background: Vasospasm of a cerebral vessel remains a major source of
morbidity and mortality after subaracnoid hemorrhage (SAH) and can expose the
patient to a delayed ischemic deficit (1-7% of all strokes). Vasospasm occurs in 70%
of patients after SAH and can begin 3–14 days after the first bleed, most commonly
between 7–10 days. Patients may go “in and out” of vasospasm throughout 21days.
Symptoms of SAH include a severe headache with a rapid onset, that belongs to
symptomatic headaches and is classified in the 6th group (IHS classification).
Methods: The study included 69 patients (age 55+/-10 years) after
aneurysmal SAH, admitted to the St Sava Hospital from January 1 to December 31,2011.
At least one DSA (used as the reference standard) was performed between day 3 and 14
after SAH. At the same time TCD ultrasound was performed routinely every 24–48 hours
to monitor possible development of vasospasm and its gravity. A blood flow velocity
of more than 120cm/s suggested severe vasospasm. Changes in vessel diameter are
inversely proportional to the mean flow velocity (MFV). MCA/ICA index and blood flow
velocity (BFV) of the M1 and M2 branches were measured with TCD and compared with
clinical findings of the presence of headache, its frequency and intensity
established by taking the history from the patients or relatives.
Results: PSV and MFV for both M1 and M2 were significantly higher in
patients with spasm than in those without spasm (p>0.01) and MCA/ICA index was
>3. The ROC curve identified the best cut-off point for M1 (PSV250; MFV125 cm/s)
and for M2 (PSV160; MFV 80 cm/s). Comparison of TCD and DSA was possible in 58
cases. DSA showed vasospasm in 46 cases, confirmed by TCD in 31 cases (67%). About
one third of sufferers have no symptoms apart from the characteristic headache.
Those with mild to medium spasm (MFV–M1 < 120 cm/s) described headache as a dull
lingering pain. Those with severe vasospasm (MFV > 200 cm/s) experienced sudden
and strong pain that referred to a “thunderclap headache”, which further increased
to a headache described as “like being kicked in the head”, or the “worst ever”.
This headache often pulsated towards the occiput (the back of the head).
Conclusions: Although headache starts suddenly its further intensity may
increase gradually. Our results confirm that frequency rate and intensity of
headache is proportionate to vasospasm and that severe headache is most common in
patients with vasospasam of high degree, occuring between 3-7 days after SAH. The
study also proves that TCD is a convenient, safe and effective method that can be
used to confirm rapidly the clinical findings and is certainly much less “invasive”
than cerebral angiography.
P419
The Outcomes of Interventional Pain Management for Treatment of Intractable
Headaches Refractory to Conventional Medical Managements
B. Taimoorazy
Guardian Headache and Pain Management Institute, Bloomington, IL,
USA.
Objectives: The objectives of this abstract presentation is to highlight
the importance of considering interventional pain management approach and making
proper referrals for treatment of intractable primary or secondary headaches.
Background: Secondary headaches account for about 2% of non-traumatic
headache disorders. The prevalence of secondary headaches increases with advancing
age, most probably due to degenerative changes in the cervical spine and vascular
disorders. As such, the prevalence of secondary headaches can be as high as 11% in
those over 75 years of age. Diagnosis and appropriate treatment of this condition
historically has been very challenging for primary care physicians and even for
neurologists.
Methods: Between May of 2011 and May of 2012, a total of 88 patients
with a variety of intractable head pain conditions were referred to our center due
to lack of response to all the conventional preventive/abortive therapies. Every
patient had seen at least one primary care physician or internist and at least one
neurologist. The average duration of headache activity was 6.5 years. A variety of
target specific interventional pain management procedures were implemented to treat
this group of intractable head pain conditions.
Results: This study demonstrates an interestingly high percentage of
secondary headaches as our center usually receives referrals with difficult to treat
head pain conditions. Headaches due to cervical facet joint arthropathy (referred
pain due to convergence of somatic afferents from cervical nerves and trigeminal
nucleus caudalis onto the same segments of cervical spinal cord), were the most
prevalent condition across all age groups. This condition responded extremely
favorably to controlled double block technique for cervical medial branch nerves,
followed by radiofrequency ablation of the offending nerves resulting in complete to
near complete resolution of the intractable head pain. The next most successful
outcomes occurred following cervical epidural steroid injections and sphenopalatine
ganglion blocks using a trans- nasal application of 4% lidocaine on a cotton-tipped
applicator. Overall we successfully have treated 80.7% of the referred patients with
an interventional pain management approach.
15.9% of patients were diagnosed with classic migraine and responded to medical
management with optimization of their preventive and abortive medications and 3.4%
were diagnosed with hemicrania continua and were treated successfully with
indomethacin.
Conclusions: This study reflects the importance of considering
appropriate interventional pain management techniques to treat intractable head pain
conditions. In 80.7% of the referred patients this approach virtually resulted in
the resolution of difficult to treat headaches and commitment to polypharmacy. In
our study only 19.3% of our patients required optimization of medical management to
control the headache activity.
P420
New Daily Persistent Headache with Migraine Features in Association with
Multiple Cranial Neuropathy, Primary or Secondary Headache?: A Case
Report
M. Volcy1, E. Jaramillo2
1Neurology-Headache, Indocen Instituto De Dolor De Cabeza y
Enfermedades Neurologicas, Medellin, Antioquia, Colombia; 2Neurology,
CES Universidad De Ciencias De La Salud, Medellin, Antioquia,
Colombia.
Objectives: To highlight the difficulty to make definitive diagnosis in
a case of a difficult to treat patient with a new daily persistent headache (NDPH)
with migraine features, secondary to an inflammatory systemic disease.
Background: Managing the headache patient, specially the one with recent
daily onset can be a difficult task. Altought not approved in the ICHD-2 criteria,
NDPH can frequently share migraine features making such classification problematic.
In 30% of patients CM can be abrupt. A strong possibility exists that many patients
with NDPH simply have CM, with similar underlying biology. Many migraine-like
headaches (MLH) have been previously described.
Methods: Retrospective case report.
Results: We report a previously healthy 51-year-old man who developed
left ear tinnitus and bilateral diminished hearing during a one-year period. Three
months later, he went onto tympanostomy tube placement without significant
improvement. Two months later, he presented to the emergency room (ER) with sudden
onset throbbing headache, moderate to severe intensity, of global localization,
associated with nausea, photophobia, severe cranial allodynia and worsening with
physical activity that did not respond to OTC analgesics. A diagnosis of acute
sinusitis was made, receiving antibiotics for 8 days. A week later, due to the
headache, he returned to the ER and had a paranasal sinuses CT scan that reported
bilateral otomastoiditis and nasal rim compression causing nostrils obstruction, he
went onto nose decompressing surgery, with no headache relief. A couple of weeks
later, he developed left peripheral facial nerve palsy, with headache worsening.
Because of this he underwent left mastoidectomy. Because of no treatment response he
had a MRI of the brain done, which showed bilateral otomastoiditis with postsurgical
changes in the left side, and leptomeningeal enhancement of the cerebellopontine
angle. A lumbar puncture (LP) showed lymphocytic response with no other relevant
abnormalities. One month after he complained of dysphagia and worse bilateral
hearing loss, a fibronasolaringoscopy showed right vocal cord palsy associated with
X cranial nerve compromise. After an intensive workout, the only persistent abnormal
findings had been high erythrocyte sedimentation rate, elevated C-reactive protein
and lymphocytic response on the CSF after three LP. A chest CT scan showed diffuse
bronchial infiltration, although not conclusive, pulmonary and meningeal
tuberculosis or neurosarcoidosis were suspected and treatment was given for both
conditions; bacterial partially treated sub acute meningitis was ruled out.
Nevertheless, after three months of in-patient managment the headache has been
refractory to any sort of abortive and preventive treatment (oral, nerve block, IV
infusion).
Conclusions: NDPH likely is a heterogeneous syndrome; many different
secondary and primary headache disorders may be overlooked when considering a such
diagnosis.
P421
Systemic Lupus Erythematosus (SLE) Presenting as Thunderclap
Headache
H.U. Sheikh2, R. Burch2
1Neurology, John R Graham Headache Center- Harvard Medical School,
Boston, MA, USA; 2Neurology, John R Graham Headache Center- Harvard
Medical School, Boston, MA, USA.
Objectives: To describe a secondary thunderclap headache caused by
Neuropsychiatric Systemic Lupus Erythematosus (NPSLE).
Background: Thunderclap headache presents as an instantaneous severe
headache. Secondary causes are common, including subarachnoid hemorrhage or
reversible cerebral vasoconstriction syndrome. Since there can be a number of other
etiologies, an extensive work up for secondary causes is necessary. Headache is
frequently diagnosed in patients with SLE, with prevalence rates varying from
66-80%. Headache is included as a criterion for NPSLE and is included in the
standard measure for NPSLE disease activity. Migraine and tension-type headaches are
the two most common phenotypes. Thunderclap headache has not been previously
described. We present thunderclap headache as a likely manifestation of NPSLE.
Methods: Case Report.
Results: A 51 year old woman with no previous history of headaches
developed a sudden onset, severe, 10/10 headache. The headache started while she was
doing light housework and reached maximum intensity within seconds. Pain was located
in the right retro-orbital and frontal regions, stabbing in quality, associated with
mild nausea and photophobia. In the ER, she also complained of blurry vision and
right arm paresthesias and numbness. Evaluation included CTA, MRI brain and lumbar
puncture, all of which were normal except for MRI which showed extensive white
matter disease in a non-specific pattern. The day following admission, her
paresthesias recurred and she underwent repeat MRI/A which did not show an acute
infarct or stenosis. Her initial thunderclap headache lasted for several hours, but
on discharge, she continued with moderate daily headaches. She was seen in follow
up, and further work up revealed an elevated ANA. She was started on steroids.
Although not certain, it is plausible that her thunderclap headache was caused by
NPSLE, given that she has no other clear explanation.
Conclusions: Several studies have shown that headaches are more common
in patient with SLE than in controls. One study showed a prevalence of 75.7% in SLE
patients compared with 66% of controls. Another case control study showed that 36%
of patients with SLE had migraines without aura, higher than in control patients.
NPSLE occurs in up to 56% of all patients with SLE. The neuropsychiatric
manifestations range from change in mood and cognition to more dramatic
manifestations, including psychosis, seizures, cerebrovascular accidents and
headaches. A case report describes NPSLE mimicking hemiplegic
migraines in a 39 year woman with 2 episodes of mild left hemiparesis, blindness in
left visual field and aphasia lasting 2 hours, followed by nausea and non-pulsatile
headache on each occasion. A skin biopsy of her rash showed SLE. The authors
proposed that SLE should be considered in the differential for hemiplegic migraines.
However, there are no previous reports of thunderclap headache as a manifestation of
NPSLE. If additional cases are collected, NPSLE could be considered as a cause of
thunderclap headaches.
P422
Treatment of Episodic Tension-Type Headache with a Novel Formulation of
Ibuprofen Sodium
E. Packman1, R. Leyva2, D. Kellstein2
1Institute for Applied Pharmaceutical Research, Philadelphia, PA,
USA; 2Pfizer Consumer Healthcare, Madison, NJ, USA.
Objectives: To evaluate the overall efficacy and onset of analgesia of a
novel formulation of ibuprofen sodium (IBUNa) tablets compared to
standard ibuprofen (IBU) tablets and placebo in the treatment of episodic
tension-type headache (ETTH).
Background: Tension-type headache is the most common type of primary
headache and is often treated with over-the-counter (OTC) analgesics such as IBU.
Rapid onset of action is a desirable attribute of OTC analgesics; therefore,
considerable effort has been expended to develop faster-absorbed and therefore
potentially faster-acting formulations. A novel tablet formulation containing 256mg
of IBUNa (equivalent to 200mg of standard IBU) has recently been
developed.This formulation is absorbed faster than standard IBU tablets and as fast
as solubilized IBU and IBU lysinate, and has a faster onset of action than standard
IBU in the treatment of dental pain.
Methods: This was a randomized, double-blind, single-center,
parallel-group study. Subjects 18 to 65 years of age with a history of ≥4 ETTH
attacks of at least moderate severity per month for the previous 6 months were
eligible. Subjects who reported to the study center with at least moderately severe
baseline headache pain were randomized 2:2:1 to receive a single oral dose of
IBUNa tablets (2×256mg; equivalent to 400mg standard IBU),
Motrin® tablets (IBUMot; 2×200mg), or placebo. Primary
endpoints were the time-weighted sum of pain relief rating (PRR) and pain intensity
difference (PID) scores over 3 hours (SPRID 0-3), and time to meaningful pain relief
(TMPR) as assessed by the double-stopwatch method. Secondary endpoints included time
to first perceptible pain relief (TFPR) confirmed by TMPR; sum of PRR and PID scores
(PRID) at 1, 2, and 3 hours post-dose; and time-weighted sum of PRR, PID, and PRID
scores over 2 and 3 hours post-dose.
Results: A total of 226 eligible subjects were randomized to
IBUNa (n=91), IBUMot (n=89), and placebo (n=46).
Demographics and baseline characteristics were comparable between groups. Both
IBUNa and IBUMot had significantly better mean SPRID 0-3
scores than placebo (P<.001), but were not significantly
different from each other. Results for summed secondary endpoints were similar.
Median TMPR was significantly faster for subjects in both active treatment groups
(IBUNa=40.6 min and IBUMot=48.5 min) than in the placebo
group (>180 min; P<.001). Although TMPR was not significantly
different between the IBUNa and IBUMot groups using the
protocol-specified statistical analysis (P=.253), a
post-hoc analysis that assigned higher weight to earlier
timepoints suggested that IBUNa provided faster TMPR and TFPR than
IBUMot (P=.022 and .020, respectively). No adverse
events were reported.
Conclusions: This study demonstrates that a novel formulation of
IBUNa is effective and safe in the treatment of ETTH, with a
numerically faster onset of analgesia than standard IBU tablets. A
post-hoc analysis suggested that IBUNa is
appreciably faster-acting than standard IBU.
P423
Pericranial Tenderness in Chronic Tension-Type Headache. The Akershus Study of
Chronic Headache
K. Aaseth1,2, R.B. Grande1, C. Lundqvist1,3, M.B.
Russell1,2
1Head and Neck Research Group, Research Centre, Akershus
University Hospital, Loerenskog, Norway; 2Institute of Clinical
Medicine, University of Oslo, Nordbyhagen, Norway; 3Helse Oest Health
Services Research Centre, Akershus University Hospital, Loerenskog,
Norway.
Objectives: To explore the relationship between chronic tension-type
headache (CTTH) and pericranial muscle tenderness in a population-based sample.
Background: Few data excist on CTTH in the general population. Several
studies have shown that pericranial muscle tenderness is increased in tension-type
headache sufferes, however, the mechanisms involved are not fully understood.
Methods: An age- and gender- stratified random sample of 30,000 persons
aged 30-44 years from the general population received a mailed questionnaire. Those
with a self-reported chronic headache were interviewed and examined by neurological
residents. The questionnaire response rate was 71% and the rate of participation in
the interview was 74%. The International Classification of Headache Disorders II was
used. Pericranial muscle tenderness was assessed by a total tenderness score (TTS)
involving 8 pairs of muscles and tendon insertions. Cross-sectional data from the
Danish general population using the same scoring system were used for
comparison.
Results: The tenderness scores were significantly higher in women than
men in all muscle groups. The TTS of both gender was significantly higher in those
with than without co-occurrence of migraine (19.4 vs 16.8, p = 0.02). The analysis
by gender showed the same tendency (in men 13.8 vs 11.5, p = 0.2, and in women 20.5
vs 19.0, p = 0.2). The linear regression analysis revealed that the TTS of both
gender was significantly associated with decreasing age (p < 0.01) and increasing
headache intensity (p = 0.04). The TTS was not influenced by medication overuse or
headache duration, i.e. hours per day, days per month or years. People with CTTH had
a significantly higher TTS compared with the general population.
Conclusions: People with CTTH have increased pericraniell tenderness.
Increased pericranial muscle tenderness is associated with co-occurrence of
migraine. Future studies should adress whether the increased muscle tenderness is
primary or secondary to the headache.
P424
The Effectiveness of Etoricoxib Plus Lidocaine Patches 5% in the Treatment of
Allodynia in Chronic Daily Tension Headache (CDTH)
Z. Elchami1, E.H. AbdElKarim1, M. Dusaran1, R.
Massoud1
1Pain & Headache Management Center of Excellence,
International Medical Center, Jeddah, Saudi Arabia.
Objectives: The objective of the study is to evaluate the effectiveness
of the combination therapy of Etoricoxib tapering plus lidocaine patches 5% in the
treatment of allodynia of CDTH.
Background: Most common among adults, “tension-type” headaches may
appear periodically (episodic, less than 15 days/month) or daily (chronic, more than
15 days/month), these headaches may last from 30 minutes to several days. Chronic
daily tension headaches (CDTH) come and go over prolonged period. On the other hand,
allodynia, meaning “other pain,” is a pain that results from a stimulus that is not
normally painful. Up to 80% of persons with migraine experience at least one symptom
of allodynia during a headache attack. Allodynia is not referred pain, although it
can occur outside the area stimulated. It is also not hyperalgesia, which is a pain
stimulus more painful than usual.
Methods: 150 patients, evaluated according to IHS classification at the
Pain & Headache Center, IMC, KSA, were randomly allocated to receive either
Etoricoxib tapering alone or in combination with lidocaine patches 5% for 3 months.
First group (N=76) received Etoricoxib tapered over 30-day period (60mg BID [8days],
90mg OD [10days], 60mg OD [12days]) in combination with the application of lidocaine
patches daily applied for 12 hours to the allodynic area at bed time for 3 months.
Second group (N=74) received only Etoricoxib taper for 3 months. Inclusive criteria:
66 males, 84 females; ages between 25-70 years, with a mean of 47. Exclusive
criteria: pediatrics, patients older than 60, with uncontrolled diabetes and blood
pressure; pregnancy and other neurological deficits.
Results: Average improvement of 79%, as per numeric pain scale, was seen
in patients receiving combination therapy (Etoricoxib and lidocaine patches 5%),
appreciated within 3 days and sustained for up to 12 months. However, an average
improvement of only 60% was seen in patient receiving Etoricoxib taper alone,
appreciated within 3 weeks and sustained for 6-9 months.
Conclusions: Patients receiving Etoricoxib plus lidocaine patch 5%
showed more significant, faster symptomatic improvement and sustained effect for
longer period than those receiving only Etoricoxib taper.
P425
Reduction of Current Tension-Type Headache Pain Intensity after a Sitting
Position Neck and Upper Thoracic Spinal Massage and Manipulation
Y. Jahangiri Noudeh1, N. Vatankhah1, H.R.
Baradaran2
1School of Medicine, Tehran University of Medical Sciences,
Tehran, Iran (Islamic Republic of); 2Department of Epidemiology,
Tehran University of Medical Sciences, Tehran, Iran (Islamic Republic
of).
Objectives: To investigate whether a simple manual technique could be
effective in reducing current tension-type headache pain intensity.
Background: The risk of development of medication-overuse headache
limits use of analgesic drugs in treatment of acute headaches. Headache sufferers
are frequent users of complementary techniques such as manual therapies and
chiropractic care. However, there is already no rigorous evidence that manual
therapies have positive effect in the evolution of tension-type headaches.
Methods: A total of 19 subjects (all males; mean age: 24.9±5.3 years)
with an onset of a tension-type headache (TTH), underwent a simple neck and upper
thoracic massage and manipulation. Headache pain intensity was measured on referral,
immediately after and one-hour after the massage and manipulation, using a verbal
analogue scale ranging from 0 to 10.
Results: Mean headache pain score on referral was 5.0±1.5; and reduced
to 1.7±1.4 immediately after (P<0.0001) and 0.9±1.4 one-hour after the
intervention (P=0.006). 13 subjects (68.4%) did not demand analgesic drug during
follow-up, and no adverse event or headache pain intensification occurred. In
logistic regression analysis, “subjects’ age”, “headache pain score on referral” and
“headache location” were not significantly associated with 50% or more reduction in
the headache pain intensity.
Conclusions: The study showed that our simple sitting-position neck
massage and cervico-thoracic manipulation technique significantly reduced the pain
intensity of a current tension-type headache.
Parameter
Measure
Age (years)
24.9±5.3
Headache pain score on referral (out of 10)
5.0±1.5
Headache laterality
Unilateral
2 (10.5%)
Bilateral
17 (89.5%)
PRP50 (at least 50% reduction of headache pain
intensity) immidiately after the manipulation
Yes
12 (63.2%)
No
7 (36.8%)
PRP50 (at least 50% reduction of headache pain
intensity) after one hour of the manipulation
Yes
17 (89.5%)
No
2 (10.5%)
Drug demand during one hour after the
manipulation
Yes
6 (31.6%)
No
13 (68.4%)
Pleasure level from the manipulation
Excellent
7 (36.8%)
Very good
8 (42.1%)
Good
4 (21.1%)
Exposure Parameter
Odds Ratio (95% CI)
P value
Age (years)
0.84 (0.65 – 1.08)
0.178
Headache pain score on referral (out of 10)
0.51 (0.004 – 64.59)
0.787
Headache location (bilateral compared to unilateral
headache)
0.99 (0.51 – 1.92)
0.966
P426
Is Indomethacin Still Required? Long-Term Course in 19 Patients with Hemicrania
Continua
C. de la Cruz1, E. Cortijo1, L. Lopez-Mesonero1, M.
Ruiz1, M.I. Pedraza1, S. Herrero1, A.L.
Guerrero1
Objectives: We aim to analyze the long-term course of a series of 19
patients diagnosed with hemicrania continua (HC) and the requirement of indomethacin
over time.
Background: Hemicrania continua (HC) is an uncommon primary headache,
characterized by continuous unilateral pain, and superimposed exacerbations
frequently associated with autonomic features. According to the International
Classification of Headache Disorders, 2nd Edition (ICHD-II), a complete
response to therapeutic doses of oral or parenteral indomethacin is required as a
diagnostic criterion. It is considered an unremitting syndrome but its natural
history is not well-known. There are cases in the literature documenting HC
remission after treatment with indomethacin but the role of this drug as a
disease-modifying agent is under discussion.
Methods: We evaluated consecutive patients with HC attended in an
outpatient headache office located in a tertiary hospital over a five-year period
(January 2008 to January 2013). In every patient we gathered demographic and
clinical variables. We assessed indomethacin response with a standard oral trial up
to 250 mg per day during 10 days. To confirm HC diagnosis we took special care to
assure complete response to indomethacin before discontinuation of the therapy due
to side effects. In those patients with a prolonged tolerance to the initially
effective dosage, we analyzed their long-term course.
Results: Forty five patients (34 females, 11 males) out of 2130 (2.1%)
attended in the mentioned clinic during inclusion period were diagnosed with HC.
Mean age at diagnosis was 51.3 ± 14.8 years (range: 22-76). In all patients pain was
strictly unilateral. Temporal pattern was always chronic and unremitting. Patients
rated the continuous pain 5 ± 1.6 and exacerbations as 8.3 ± 1.3 on a verbal
analogical scale (VAS). All of them presented exacerbations, and 12 (26.7%) did not
report associated autonomic symptoms. All our cases responded to indomethacin; in 20
of them (44.4%), and due to side effects, alternative treatments were required.
Follow-up was not possible in five patients and in one additional case diagnosis was
too recent. So we finally considered long-term course with indomethacin in 19
patients (15 females, 4 males, and mean age at diagnosis 52.7 ± 16.6 years). They
were proposed to reduce indomethacin dose every 3 to 6 months in order to check
headache intensity. All patients were able to decrease indomethacin from an
initially established effective dosage of 144.7 ± 36.8 milligrams (range 50-250) to
40.8 ± 41 (0-100) milligrams, after 11.1 ± 5.2 months (range: 3-21). In 6 cases a
suppression of indomethacin was achieved; 3 of these patients and 11 among those
with a partial dose reduction presented a persistent mild pain that they preferred
to a higher dose of indomethacin.
Conclusions: Long-term course in our series suggests that, at least in a
subset of patients, indomethacin could alter the natural history of Hemicrania
Continua.
P427
Long-Term Headache and Stroke Outcomes in Reversible Cerebral Vasoconstriction
Syndrome (RCVS)
S. John1, L. Calabrese2, K. Uchino3, S.
Tepper4, M. Stillman4, R. Hajj-Ali2
1Neurology, Cleveland Clinic Foundation, Cleveland, OH, USA;
2Rheumatology, Cleveland Clinic Foundation, Cleveland, OH, USA;
3Cerebrovascular Center, Cleveland Clinic Foundation, Cleveland,
OH, USA; 4Neurological Center for Pain, Cleveland Clinic Foundation,
Cleveland, OH, USA.
Objectives: i) To assess headache and stroke outcomes using validated
measures ii) To determine the impact of RCVS on health related quality of life
(QoL).
Background: RCVS is characterized by acute onset of severe headaches,
with or without neurologic deficit with evidence of reversible cerebral
vasoconstriction. Natural history and long term outcomes of RCVS have not been
thoroughly investigated.
Methods: Prospective cohort analysis of patients recruited from the RCVS
registry was conducted. Validated questionnaires were mailed to the patients. The
forms included: Headache screening form, Headache Impact Test (HIT-6), Migraine
Disability Assessment Test (MIDAS), Barthel Index (BI), EuroQoL (EQ-5D-5L) and
Patient Health Questionnaire (PHQ-9).
Results: The RCVS registry had a total of 57 patients. Three patients
refused, 26 were lost to follow-up, 8 never replied, and 20 participated. Median
follow-up time from diagnosis to answering questionnaires was 91.5 months (range
10-254). Of the 20 patients (90% female), 19 (95%) presented with thunderclap
headache and had ischemic stroke (50%), subarachnoid (45%) or intracerebral (15%)
hemorrhage. Eleven (55%) patients continued to have headache, but majority (91%)
reported improvement in character with only 1 patient having worsening. Headache
impact on life measured by HIT-6 showed that 2 (13%) patients had a severe impact
(HIT score >60). The mean MIDAS score was 10.67 and 2
(13%) patients had severe disabling headaches (MIDAS
score> 21). Sixteen (94%) patients were independent by
BI scores > 85 (11 patients scored 100). EQ-5D-5L
measurements showed that 12 (71%), 14 (82%) and 12 (71%) patients had no problems
with mobility, self-care and leisure respectively. PHQ-9 scores revealed that only 1
(6%) patient had severe depression (PHQ score 20-27).
Conclusions: These data on long term outcomes in patients with RCVS
suggests that half of them will continue to have headache, although decreased in
severity and frequency. Although close to three-quarter of patients suffered an
initial ischemic stroke or hemorrhage, almost all were independent with little
disability. Pain and anxiety however decreased the QoL.
P428
Headache and Transient Ischaemic Attacks: Features of Neurological Clinics,
Hemodynamics and Stroke Risk in Patients with Different TIA Subtypes
O.Y. Fartushna
Neurological Department, Bogomolets National Medical University, Kiev,
Ukraine.
Objectives: Objective is to study the frequency, location,
characteristics, features of neurological clinics, hemodynamics, DW-MRI findings,
and prognostic role of headaches (H) which occurred in TIA patients according to
diferent TIA subtypes to increase the efficiency of secondary stroke prevention.
Background: Transient ischemic attacks (TIA) are strong predictors of
subsequent stroke, disability and death. Nearly half of all strokes occur within the
first 2 days after TIA. Headache is a frequent premonitory symptom of cerebral
ischemia. However, clinical features and prognostic role of it in patients with
differnt transient cerebralishaemia subtypes (as to TOAST criteria) isn’t clear
yet.
Methods: The clinical, Doppler ultrasound, DW-MRI, transthoracic
echocardiography diagnosing has been made for 178 patients in acute period of TIA.
Cases were reviewed by two neurologists to establish the correlation with the
diagnosis. TIAs were divided into 2 groups according to the H: 1-TIA with H
temporarily related to other symptoms of TIA (n=61(34.3%)) and 2-without H
(n=117(65.7%)). Development of stroke was considered the primaryendpoint.Observation
period was 2 years.
Results: Stroke developed in 27 (40.9%) patients after TIA with H and in
18 (16.1%) cases - without it (OR (95%CI)=19,6 (19.09-20.1), p<0.001). Patients
with TIA onset of H had a significantly greater volume (p<0.05) and duration
(p<0.001) of neurological deficit, presence of acute ischaemic lesion on DW MRI
(p<0.05) compared with persons with TIA without H. Most often H were determined
for cardioembolic (39.4%) and small-vessel occlusion (25.8%) TIA. TIAs manifested by
frontal H was more frequently associated with TIAs in the carotid territory;
occipital-nuchal headache was more common in vertebrobasilar TIA(p<0.05).
Conclusions: The duration and volume of the neurological deficit as the
risks of stroke were higher in patients with TIA with H than without it and differ
depending on TIA pathological subtypes and vascular territory.
P429
Cardiac Cephalagia in a Patient with Unstable Angina: The First Case
Report
K. Vongvaivanich
Comprehensive Headache Clinic, Neuroscience Center, Bangkok Hospital Medical
Center, Bangkok Hospital Group, Bangkok, Thailand.
Objectives: We reported a case of headache associated with unstable
angina.
Background: The relationship between headache and ischemic heart disease
had been recognized since 1978 by Walter HC. The term of cardiac cephalalgia was
defined by Lipton and diagnostic criteria was published in the second edition of the
International Classification of Headache Disorders. Cardiac cephalalgia is a rare
disorder, currently there is only 36 cases reported worldwide.
Methods: We reported a case of cardiac cephalagia and reviewed the
relevance published literatures.
Results: A 52 year-old Thai male presented to the Comprehensive Headache
Clinic at Bangkok Hospital Medical Center with progressive side-locked headache
while walking for 1 week. After walking for 500 meters, he had chest pain followed
by left-sided throbbing headache. The pain is moderate intensity at left temporal
area, without nausea or vomiting. There was no photophobia, phonophobia, or any
autonomic symptoms. The attack occcurs approximately 3 times per day, each episodes
last for a few minutes, and went away after rest. There was no history of previous
headache or head injury. His cardiovascular risk factors are hyperlipidemia and
heavy smoker.
His neurological examination was unremarkable. Brain MRI and MRA showed no
intracranial abnormality. Cardiologist consultation was done. Resting ECG showed
right bundle branch block. Exercise stress test showed no change in baseline ECG, no
chest pain, and no headache during exercise. He was diagnosed as unstable angina and
was prescribed medications.
10 days later, he was admitted to the hospital due to frequent chest pain and more
severe headache. ECG did not show any significant changes. Laboratory tests showed
elevated cardiac enzymes. He was diagnosed with Non-ST elevated myocardial
infarction. Coronary angiogram showed 85% tubular narrowing at left anterior
descending artery. Percutaneous coronary intervention was performed. The final
angiogram revealed no residual stenosis and TIMI III flow. After the procedure, his
headache subsides, and resolved completely in 3 days. On last follow up, 2 weeks
after the intervention, he reported no headache.
Conclusions: Our patient fitted almost all of the criterias for cardiac
cephalalgia. The missing criterias are nausea which occur in only 23% of cases and
myocardial infarction which presented later. From this patient, we postulated that
unstable angina can also produce headache similar to cardiac cephalalgia, and that a
patient with this symptom could develop myocardial infarction later on. In our
knowledge, this is the first case that presented with headache associated with
unstable angina who later developed myocardial infarction. The ICHD-II criteria for
cardiac cephalalgia might need to be revised
P430
Headache in Hospitalized Patients. Analysis of 35 Cases
S.G. Villate1, G.A. Ortiz1, C.F. Buonanotte2
1Córdoba, Sanatorio Allende, Nueva Córdoba, Córdoba, Argentina;
2Córdoba, Sanatorio Allende, Cerro de las Rosas, Córdoba,
Argentina.
Objectives: To evaluate causes of headache in hospitalized patients.
Background: Headache is a pain syndrome secondary to multiple causes, in
addition to the primary forms. In the ambulatory setting and urgent care, the
prevalence of primary headaches is higher. Headache in an inpatient can be worrisome
for the treating physician, even more in the context of an underlying cause of
admission. Currently, there are no studies reporting the prevalence of headaches in
inpatients.
Methods: We evaluated 1324 hospitalized patients in a community
hospital, between May and October 2011, of which 35 fulfilled inclusion
criteria.
Results: Primary headache was diagnosed in 45.7%; whereas 54.3% had
secondary headaches. Migraine was the main primary headache. Headache atributed to
hypoxia was the most common secondary headache, found mostly in patients admitted
for surgical reasons, or associated to pulmonary infections.
Conclusions: In our study, the frequency of primary and secondary
headaches in hospitalized patients was similar.
P431
Catastrophic Reversible Cerebral Vasoconstriction Syndrome Associated with
Serotonin Syndrome
Objectives: To report fulminant cases of reversible cerebral
vasoconstriction syndrome (RCVS) in the setting of serotonin syndrome (SS).
Background: RCVS is characterized by acute onset of severe headaches,
with or without neurologic deficit, with evidence of reversible cerebral
vasoconstriction. It is often benign and prognosis is generally considered
favorable. In the largest prospective study on RCVS, only 4% of patients were
disabled from strokes and there were no fatalities.
Methods: Case series.
Results: Case 1
A 45-year old female with depression on escitalopram presented to a hospital with
thunderclap headache and confusion. She was given intravenous dihydroergotamine and
multiple doses of hydromorphone. Initial MRI brain showed T2 hyperintensities in the
cerebellum fossa resembling Posterior Reversible Encephalopathy Syndrome. Repeat MRI
2 days later showed focal T2 hyperintensity in the frontal subarachnoid space
consistent with a bleed. She also intermittently spiked fevers and developed
rigidity. Ten days after symptom onset, she acutely deteriorated becoming comatose
with decrebrate posturing. Repeat imaging revealed large bi-hemispheric infarcts
with significant edema. A cerebral angiogram showed severe segmental vessel
narrowing in all vascular distributions. Infusion of intra-arterial (IA) nicardipine
resulted in minimal improvement. Aggressive medical and surgical management of
raised intracranial pressure was unsuccessful. Worsening examination and imaging
prompted withdrawal of care.
Case 2
A 57-year old female with depression on wellbutrin and citalopram with recent dose
increase was admitted with dizziness. She developed acute confusion followed by a
seizure and unresponsiveness. On examination, she was rigid, diaphoretic, febrile,
and tachycardic with labile blood pressures and subsequently developed decerebrate
posturing. CT and MRI of the brain showed bilateral parieto-occipital strokes with
normal brainstem. Cerebral angiogram showed severe diffuse irregularities
predominantly in the posterior circulation and IA nicardipine was administered with
slight improvement. A subsequent angiogram 8 days after symptom onset showed
improvement of the vascoconstriction. She clinically improved and was eventually
discharged.
Serum/cerebrospinal fluid testing for vasculitis in both patients was negative and
both were treated with verapamil.
Conclusions: Both cases satisfied Sternbach criteria for SS and although
reversal of cerebral vascoconstriction was not demonstrated in Case 1, this likely
represents a forme fruste of RCVS. Serotonergic agents are known triggers of RCVS,
but the concurrent presence of SS likely precipitated the malignant course in our
patients. Severe clinical and angiographic manifestations should be considered as
part of the spectrum of RCVS.
P432
Tilted Metamorphopsia as an Accompanying Symptom of Nummular Headache: A Case
Report
S. Herrero-Velázquez1, C. de la Cruz1, P. Mulero1,
J. Baron1, C. Rodríguez1, M.I. Pedraza1, M.L.
Peñas1, A.L. Guerrero1, M.L. Cuadrado2
Objectives: We aim to report a non-previously described symptom
associated with nummular headache.
Background: Inverted or tilted perception disorder consists of the
illusion of a visual field rotation, with no other changes in the characteristics of
the objects or the scene. Its most frequent etiology is cerebral ischemia although
it has been described in association with other conditions, including migraine.
Nummular headache was incorporated in the Appendix of the ICHD-II. It is defined as
a pain circumscribed to a rounded area of the head surface. The pain probably stems
from extracranial sensitive branches of the trigeminal nerve.
Methods: A 21 year-old-woman presented with a 3-year history of an
episodic pain confined to a circular area of 5 x 5 cm over her left frontal scalp.
Pain attacks occurred three times per week and lasted between 20 and 60 minutes.
Pain was described as pressing, with an intensity of 5 out of 10 on a visual
analogue scale. No triggers were identified. Pain episodes were consistently
accompanied by photopsias, photophobia and phonophobia, and were aggravated by
physical activity. Moreover, during pain attacks the patient perceived objects as
tilted 30 degrees in the frontal plane in a counterclockwise direction. The
neurological exam was unremarkable. Brain magnetic resonance imaging and blood tests
including erythrocyte sedimentation rate and antinuclear antibodies were obtained
with no abnormalities. Gabapentin achieved a nearly complete response.
Results: The perception of spatial orientation relies on visual,
vestibular and propioceptive inputs integrated at higher-level cortical networks.
The reported cases of tilted vision have been linked to a variety of cerebral
lesions, mainly located in the parieto-occipital region and the vestibulo-cerebellar
system. During the migraine aura, patients may experience different visual
phenomena, including scintillating scotomas, fortification spectra, polyopia,
palinopsia, dyschromatopsia, and metamorphopsias (i.e. changes in shape, size or
orientation of the perceived objects). All these visual disturbances are probably
related to cortical spreading depression. On the other hand, nummular headache has
been classified among the epicranias. The confinement of the pain and the local
enhancement of pain sensitivity to a small cranial area suggest a peripheral origin.
Nevertheless, some migrainous features, such as nausea, photophobia, phonophobia, or
pain exacerbation by physical activity, have been occasionally encountered in
patients with nummular headache. Here we report a patient with a nummular-type of
headache with visual aura and other migraine accompaniments.
Conclusions: According to the present description, central mechanisms
might be involved in some cases fulfilling diagnostic criteria for nummular
headache. Alternatively, this patient might be suffering from an atypical migraine
with aura with a well-circumscribed pain.
P433
Diagnostic Dilemmas with Acute Headache Attacks and Seizures
R. Jimenez-Chinea1, K. Standley1, M. Freeman1, A.
Bozorg1
1Neurology, University of South Florida, Tampa, FL, USA;
2Neurology, Tampa General Hospital, Tampa, FL, USA.
Objectives: To review the diagnosis and treatment of a young man with
uncontrolled seizures masquerading as acute headache attacks in the pre-ictal and
ictal phases.
Background: Headaches and seizures are comorbid, sharing
pathophysiological mechanisms and common clinical features. Typically the
delineation or correlation between the two is clear. However, comorbid diseases
present challenges in both differential diagnosis and concomitant diagnosis.
Although the overlap of these two entities is well known, seizures presenting as
acute episodic headache attacks in the pre-ictal and ictal phases has not been well
described. Headache has been reported to be the most predominant clinical
manifestation of seizure, although rare. Pre-ictal and ictal headaches are typically
short-lived, and the patient may be amnestic for this pain given the altered
awareness during the seizure. Continuous video EEG can facilitate the diagnosis of
comorbid epilepsy and migraine.
Methods: An extensive chart review focused on the atypical features of
acute headache attacks, the use of continuous video EEG, and anti-epileptic
medication selection was performed. A literature search on headache and epilepsy was
completed and analyzed.
Results: The patient presented with unrelenting acute headache attacks,
and due to the patient’s complicated prior neurologic history and risk factors for
seizure, the patient was recorded with continuous video EEG for 24 hours.
Interestingly, four seizures were captured on this recording, which correlated with
the patient’s headache attacks. Despite the patient being unaware of ictal
phenomena, clinical signs of seizure were captured on video. Electrographically, the
events were stereotyped with a clear ictal pattern lasting 3-5 minutes, with
evidence of rhythmic theta slowing in the right centro-temporal leads prior to a
generalized delta seizure pattern. With optimization of anti-epileptic medications
and control of the seizures, the headaches resolved.
Conclusions: The differentiation of transient neurologic changes poses
diagnostic challenges and differentiation between etiologies can be difficult based
on history alone. This case demonstrates the importance of identifying atypical
features of headache that could suggest an underlying seizure disorder. In addition,
the importance of the use of continuous video EEG is evident as a correlation
between the ictal EEG pattern and the symptoms of the patient was apparent.
Anti-epileptic medication selection in patients with concurrent seizures and
headache should be aimed at optimization of treatment with minimization of
polypharmacy to reduce side effects. While the link between headaches and epileptic
seizures is being researched, there are still deficiencies. Literature review
emphasizes the need for further research into the relationship between acute
headache attacks and seizure in the pre-ictal and ictal phases on a
pathophysiological, clinical, and treatment basis.
P434
Sumavel for Cyclic Vomiting Syndrome in Adults: A Case Report
A.P. Pruitt1, A.H. Calhoun1,2,3
1Carolina Headache Institute, Chapel Hill, NC, USA;
2Anesthesiology, University of North Carolina, Chapel Hill, NC, USA;
3Psychiatry, University of North Carolina, Chapel Hill, NC,
USA.
Objectives: To highlight Cyclic Vomiting Syndrome (CVS) in Adults and
present a case report of successful abortive therapy with Sumavel.
Background: Originally thought to be a pediatric disease, CVS is a
profoundly disabling disorder that affects adults as well as children. It is
characterized by recurrent, stereotypic episodes of incapacitating nausea and
vomiting, separated by completely asymptomatic intervals. Up to 93% of patients
experience prodromal symptoms, marked by nausea, pallor, heightened sensory
sensitivity, and and fatigue. Most sufferers can identify “triggers” that
precipitate attacks, such as menstruation, lack of sleep, certain foods, extreme
physical exertion, and stress.
The most common acute treatments are IV fluids and potent anti-emetics, but a recent
open-label clinical trial in Japan showed efficacy of intranasal or injectable
sumatriptan in Pediatric CVS. Because of its similarity to “abdominal migraine”,
therapeutic trials have been conducted with traditional migraine preventives, such
as amitryptiline, topiramate, propranolol, and cyproheptadine, which have shown
promise in preventing recurrent attacks.
The prevalence of CVS is unknown, but sufferers usually experience long delays in
diagnosis and frequent misdiagnosis.
Results: Case Report: Mrs. P is a 29 year old white female with a
history of infrequent migraines since late adolescence. Her migraines were typically
moderately-severe, associated with mild nausea (never vomiting), photophobia and
osmophobia. They responded well to triptans. Family history was positive for
migraine, including a sister who had been diagnosed with “abdominal migraine” in
childhood.
At age 25, Mrs. P experienced the abrupt onset of CVS. She had no history of any
prior gastrointestinal complaints, and an evaluation by an academic
gastroenterologist was unrevealing.
Attacks would stereotypically begin on first awakening and persist until bedtime,
with severe nausea and vomiting all day. No previous treatments had ever afforded
even partial or temporary relief, including prescription antiemetic suppositories.
She had never tried a triptan for an attack, since—with no associated headache—she
had not related the vomiting episodes to migraine.
With her most recent attack, Mrs. P was instructed to use Sumavel in a therapeutic
trial. Immediately after the injection, she was able to sleep. When she awoke an
hour later, she felt well. Her appetite returned and she remained asymptomatic. In
her four years of suffering with CVS, this was the first attack that had ever been
aborted or even minimally ameliorated.
Conclusions: CVS not only is highly co-morbid with migraine, but it has
been found to share a high association with two migraine-associated mitochondrial
DNA polymorphisms. With these clinical and biologic associations, and with CVS’s
response to migraine preventives, controlled studies are warranted to assess its
response to injectable sumatriptan.
P435
An Unusual Case of Short Lasting Unilateral Neuralgiform Headache with
Conjunctival Tearing (SUNCT) with Prolonged Aura and Onset during Sexual Orgasm
Responding to Topiramate
F. Ahmed1, F. Maniyar1
1Department of Neurology, Hull Royal Infirmary, Hull, East
Yorkshire, United Kingdom.
Objectives: We report a case of SUNCT with prolonged aura with onset of
first attack during sexual orgasm responding to high dose topiramate.
Background: Trigeminal Autonomic Cephalalgia (TAC) are rare. Cluster
headaches comprise the majority of them with SUNCT being the rarest and shortest in
duration. Majority of cases of SUNCT are primary with a few cases occurring
secondary to posterior fossa or pituitary lesions. Although activities like exercise
or blowing of nose can trigger SUNCT, onset during sexual orgasm has not been
described. Short lasting sensory aura has been described in TACs but prolonged aura
has not been described so far in relation with SUNCT. Lastly treatment of SUNCT is
difficult; with lamotriginebeing the commonest effective reported. Topiramate has
been shown to be effective in SUNCT but the doses used have been lower. Topiramate
is particularly effective in treating migraine with aura.
Methods: A 42 year female with previous history if infrequent migraines
and visual aura (MA) experienced severe acute left occipital, temporal and
peri-orbital pain during orgasm. This was associated with ipsilateral lacrimation,
conjunctival injection and rhinorrheoa. It lasted 2 minutes with a spontaneous
recurrence after 20 minutes. The severity and frequency of pain episodes increased
over the next several days with a maximum of 40 episodes a day and 16 attacks an
hour. During a typical attack she would get several small stabs, each lasting for
2-3 seconds, with the total duration of the attack being 15-150 seconds. She
complained of mild double vision on looking to the left, reduced hearing on the left
and veering to the left on walking. On examination she had left conjunctival
injection with Horner’s Syndrome, partial left sixth nerve weakness, mild left
sensorineural deafness and minimal cerebellar signs all on the left side with ataxic
gate. All signs resolved completely within 3 weeks except a partial residual
Horner’s syndrome. Her CT head, CT angiogram, MRI with gadolinium and diffusion
weighted imaging with enhanced views of pituitary were normal with normal serum
prolactin.
Results: A diagnosis of SUNCT with prolonged aura was made and the
patient was commenced on lamotrigine but failed to notice any benefit on 100 mg bd.
A trial of indomethacin was given but she develped a rash on 50 mg tds without
getting any relief. She failed to respond to Greater Occipital Nerve Block. She
developed drowsiness on a small dose of carbamazepine and experienced no improvement
with Gabapentin at a dose of 2.4 gm per day. She was put on topiramate to which she
responded initially with reduction of day time attacks followed by complete
resolution at a dose of 400 mg bd.
Conclusions: This is the first reported case of SUNCT with prolonged
aura with onset during sexual orgasm and responsive to high dose topiramate. We feel
the excellent response to topiramate is related to the duration of aura.
P436
How To Diagnose Mild or Moderate Form Headaches Caused by Symptomatic Cyst of
the Septum Pellucidum
K. Takagi1, K. Yamazaki1, R. Hishida1, M.
Arai1, S. Nojima1, H. Kobayashi1
1Neurology, Tokyo Medical University, Amimachi-cyuou, Inashikigun,
Ibaraki, Japan.
Objectives: We have experienced four mild or moderate cases of headaches
caused by symptomatic cyst of the septum pellucidum (sCSP). We considered important
points for diagnosis of these headaches in their data including cerebrospinal fluid
(CSF) pressure and the ocular fundus in a few of four cases.
Background: Headaches caused by sCSP are extremely rare. Clinical
features of severe form of these are known as intolerable headaches with vomiting.
But mild or moderate form headaches are not known well. In our former study, we
revealed characteristics of mild or moderate form of them.
Methods: We have experienced four cases of headaches caused by sCSP from
May 2007 to December 2012. MRI of all cases revealed an expansive CSP. All of them
had mild or moderate headaches. We gave them questionnaires asking about clinical
features in headache. We checked effects of oral administration of isosorbide on
their headaches.
Results: Case 1 is a 30-year-old man. His headache started 2 years ago.
It is like occipital neuralgia, sharp and very short lasting pain, without nausea,
vomiting, photophobia, phonophobia and aggravation by routine physical activity. He
felt headache everyday, but it is a momentary pain. In this case we didn’t examine
CSF pressure and the fundus of the eye. Oral administration of isosorbide is
effective as same as Case 3 and 4. Neurosurgeons performed endoscopic fenestration
toward the CSP, and after the operation his headache completely vanished.
Case 2 is a 36-year-old woman. Her headache started 16 years ago. It is moderate
bilateral throbbing pain like migraine with nausea, phonophobia and aggravation by
routine physical activity without vomiting and photophobia, but it ceased
spontaneously within 30 minutes without any medication. Frequency is once a month.
CSF pressure was 200 mmH2O and no papilledema were observed.
Case 3 is a 36-year-old woman. Her headache started 2 months ago. It is continuous
moderate bilateral throbbing pain with photophobia, phonophobia and aggravation by
routine physical activity without nausea and vomiting. No papilledema were observed.
Her headache aggravated gradually. Several months later she recovered
spontaneously.
Case 4 is a 18-year-old man. His headache started 6 years ago. It is moderate
bilateral throbbing pain like migraine with photophobia, phonophobia and aggravation
by routine physical activity without nausea and vomiting, but it ceased
spontaneously within 20 minutes with no medication. Frequency is fifth a month. CSF
pressure was 280 mmH2O and no papilledema were observed.
Conclusions: We thought the clinical features of mild or moderate form
headaches caused by sCSP is like migraine without vomiting, but duration is within
30 minutes. It is extremely shorter than migraine. Their CSF pressure was not so
high and no papilledema were observed. We thought revealing clinical atypicality,
checking effects of oral administration of isosorbide and MRI are the most important
points for diagnosis.
