Cephalalgia

Health administrators, policy makers, and educators have attempted to increase guideline adherence of migraine medications while reducing inappropriate use of opioid- and barbiturate-containing medications. We evaluated the burden of migraine and proportion of guideline-concordant care in a large, national health care system over time.

We conducted a time-series study using data from the Veterans Health Administration (VHA) electronic health record. Veterans with migraines were identified by ICD-9 code (346.X). Prescriptions and comorbid conditions were evaluated before and after migraine diagnosis. Chi-square tests and logistic regression were performed.

A total of 57,064 veterans were diagnosed with migraine headache (5.3%), with women significantly more likely diagnosed (11.6% vs. 4.4%, p < 0.0001). The number of veterans diagnosed with migraine has significantly increased over the years. By 2012, triptans were prescribed to 43% of people with migraine, with no difference by gender. However, triptan prescriptions increased from 2004 to 2012 in men, but not women, veterans. Preventive medicines showed a significant increase with the year of migraine diagnosis, after controlling for age, sex, race, and for comorbidities treated with medications used for migraine prevention.

The burden of migraines is increasing within the VHA, with a corresponding increase in the delivery of guideline-concordant acute and prophylactic migraine-specific medication.

A model for the testing of novel anti-migraine drugs should preferably use healthy volunteers for ease of recruiting. Isosorbide-5-mononitrate (5-ISMN) provokes headache in healthy volunteers with some migraine features such as pulsating pain quality and aggravation by physical activity. Therefore, this headache might respond to sumatriptan, a requirement for validation of any model. The hypothesis of the present study was that sumatriptan is effective in 5-ISMN-induced headache in healthy individuals.

In a double-blind, randomised, crossover design, 30 healthy volunteers of both sexes received 5-ISMN 60 mg on two separate days, each day followed by oral self-administered placebo or sumatriptan 50 mg. Headache response and accompanying symptoms were registered in a questionnaire by the participants themselves.

5-ISMN induced a reproducible headache in all 30 participants. The headache had several migraine-like features in all participants and 20 individuals developed a migraine-like attack. Median peak headache score was 5 on both experimental days (p = 1.00). There was no reduction, but instead an increase in headache intensity 2 hours after sumatriptan (p = 0.003). Difference in area under the headache score curve (AUC) 0–4 hours between sumatriptan and placebo was not significant (p = 0.30).

5-ISMN is a very powerful inducer of migraine-like headache in healthy individuals but the headache does not respond to sumatriptan. The model is not useful for future drug testing.

The objective of this article is to characterize olfactory stimulation as a trigger of headaches attacks and differentiation between migraine and other primary headaches.

The study was prospective and experimental, with comparison of groups. A total of 158 volunteers (73 men and 85 women) were diagnosed with primary headaches, according to the criteria of the International Classification of Headache Disorders, Third Edition (beta version) (ICHD-3β). The study was conducted by two examiners; one of them was assigned to diagnose the presence and type of primary headache, while the other was responsible for exposing the volunteers to odor and recording the effects of this exposure.

Of the 158 volunteers with headache, there were 72 (45.6%) cases of migraine and 86 (54.4%) with other primary headaches. In both groups, there were differences in headache characteristics (χ²= 4.132; p = 0.046). Headache attacks (25/72; 34.7%) and nausea (5/72; 6.9%) were triggered by odor only in patients with migraine, corresponding to 19.0% (30/158) of the sample, but in none with other primary headaches (χ²= 43.78; p < 0.001). Headache occurred more often associated with nausea (p = 0.146) and bilateral location (p = 0.002) in migraineurs who had headache triggered by odor. Headache was triggered after 118 ± 24.6 min and nausea after 72.8 ± 84.7 min of exposure to odor.

The odor triggered headache attacks or nausea only in migraineurs. Therefore, headache triggered by odors may be considered a factor of differentiation between migraine and other primary headaches and this trigger seems very specific of migraine.

The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) is not known. Published cases have documented coexisting cervical artery dissection and unruptured aneurysms, raising the possibility that ultrastructural vessel wall abnormalities underlie the development of vascular lesions as well as RCVS.

In this retrospective study we compared the frequency of neurovascular abnormalities in 158 consecutive RCVS patients, 44 patients with primary angiitis of the central nervous system (PACNS, positive controls), and 177 non-stroke patients with acute neurological symptoms (non-arteriopathy controls).

Coexisting neurovascular abnormalities were significantly higher (p < 0.001) in RCVS (23%) as compared to the PACNS (5%) or non-arteriopathy groups (8%). Cervical artery dissections were noted only in the RCVS group (8%, p < 0.001). The RCVS group had more unruptured aneurysms than PACNS (13% vs. 5%, p = 0.099) or non-arteriopathy controls (13% vs. 7%, p = 0.05). Seven RCVS patients also had other vascular malformations (venous anomaly, cavernous malformations, fibromuscular dysplasia). There was no significant association between coexisting vascular abnormalities and brain lesions or discharge clinical outcome in the RCVS group.

The high prevalence and heterogeneous anatomy of coexisting vascular lesions suggest that subtle ultrastructural arterial wall abnormalities may contribute to their development and also predispose to RCVS.

Due to compelling evidence in support of links between sex, stress, sympathetic post-ganglionic innervation, dural immune cells, and migraine, our aim was to characterize the impacts of these factors on the type and proportion of immune cells in the dura.

Dural immune cells were obtained from naïve or stressed adult male and female Sprague Dawley rats for flow cytometry. Rats with surgical denervation of sympathetic post-ganglionic neurons of the dura were also studied.

Immune cells comprise ∼17% of all cells in the dura. These included: macrophages/granulocytes (“Macs”; 63.2% of immune cells), dendritic cells (0.88%), T-cells (4.51%), natural killer T-cells (0.51%), natural killer cells (3.08%), and B-cells (20.0%). There were significantly more Macs and fewer B- and natural killer T-cells in the dura of females compared with males. Macs and dendritic cells were significantly increased by stress in males, but not females. In contrast, T-cells were significantly increased in females with a 24-hour delay following stress. Lastly, Macs, dendritic cells, and T-cells were significantly higher in sympathectomized-naïve males, but not females.

It may not only be possible, but necessary to use different strategies for the most effective treatment of migraine in men and women.

To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations.

We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta-analysis with standardised mean differences (SMD) as effect measures.

Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased β-endorphin (β-EP) in both chronic (four studies, SMD: –1.37, 95% CI: –1.80, –0.94) and interictal episodic migraine patients (three studies, SMD: –1.12, 95% CI: –1.65, –0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and β-EP (chronic, interictal and ictal) was decreased.

Glutamate, β-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.

The purpose of this systematic literature review is to assess the benefits of workplace-based occupational therapies and interventions, including acute and preventive medication, on headache intensity and frequency, related disability as well as work-related outcomes.

A search of the literature was conducted in PubMed, MEDLINE, Cochrane library, CINAHL and Embase using terms related to headache, workplace and occupational health. The Cochrane Collaboration’s risk of bias assessment tool was used on individual studies to assess internal validity and the Grading of Recommendations Assessment, Development, and Evaluation system was applied to studies by clinical outcome and used to rate quality of evidence.

Fifteen articles were included in the systematic review. None of them were classified as low risk of bias according to the Cochrane Collaboration’s tool for assessing risk of bias. This systematic review found preliminary low-quality evidence suggesting that exercise and acupuncture can reduce workers’ headache pain intensity, frequency and related disability.

Although this systematic review provided preliminary low evidence in favour of work-based intervention, studies with more rigorous designs and methodologies are needed to provide further evidence of the effectiveness of workplace-based headache management strategies.

The nature of the migraine aura and its role in migraine pathophysiology is incompletely understood. In particular, the mechanisms underlying aura initiation and the causal relation between aura and headache are unknown. The scientific investigation of aura in patients is only possible if aura can be triggered. This paper reviews potential methods for the experimental provocation of migraine aura.

We systematically searched PubMed for studies of experimental migraine provocation, including case reports of patients with aura and reports of the occurrence of aura following exposure to any kind of suspected trigger.

We identified 21 provocation studies, using 13 different prospective provocation methods, and 34 case reports. In the prospective studies, aura were reported following the administration of intravenous and sublingual glyceryl trinitrate, visual stimulation, physical activity, calcitonin gene-related peptide infusion, chocolate ingestion, and the intravenous injection of insulin. In addition, carotid artery puncture has consistently been reported as a trigger of aura.

No safe and efficient method for aura provocation exists at present, but several approaches could prove useful for this purpose.

Paraganglioma is a rare neuroendocrine tumour arising anywhere along the paravertebral sympathetic and parasympathetic chains. In the neck, paraganglioma may affect the carotid body (carotid body tumour).

We describe a 43-year-old woman who presented with a reversible vasoconstriction syndrome associated with a posterior reversible encephalopathy syndrome following a surgery for a left carotid paraganglioma (with a past medical history of surgery for a right carotid paraganglioma a few months before).

A consequence of a baroreflex modification is discussed in order to explain the rare occurrence of such symptoms.

The objective of this report is to establish a biomarker for the CGRP-interfering effect of antimigraine drugs.

We quantified the effect of sumatriptan on the trigeminal nerve-mediated rise in forehead dermal blood flow (DBF), induced by capsaicin application (0.6 mg/ml) and electrical stimulation (0.2–1.0 mA), in a randomised, double-blind, placebo-controlled, crossover study in healthy male (n = 11, age ± SD: 29 ± 8 years) and female (n = 11, 32 ± 7 years) individuals.

DBF responses to capsaicin were attenuated by sumatriptan (ΔDBF, mean ± SEM: 82 ± 18 AU, p = 0.0002), but not by placebo (ΔDBF: 21 ± 12 AU, p = 0.1026).

We demonstrated that sumatriptan inhibits increases in DBF, induced by the release of, most likely, CGRP. Thus, our model may be used as a biomarker to establish the trigeminovascular effects of (potential) antimigraine drugs, such as CGRP receptor antagonists or antibodies directed against CGRP or its receptor.