Cephalalgia

It has been suggested that migraine attacks strike according to circadian patterns and that this might be related to individual chronotype. Here we evaluated and correlated individual chronotypes, stability of the circadian rhythm, and circadian attack timing in a large and well-characterised migraine population.

In 2875 migraine patients and 200 non-headache controls we assessed differences in: (i) distribution of chronotypes (Münich Chronotype Questionnaire); (ii) the circadian rhythm’s amplitude and stability (Circadian Type Inventory); and (iii) circadian timing of migraine attacks. Data were analysed using multinomial and linear regression models adjusted for age, gender, sleep quality and depression.

Migraineurs more often showed an early chronotype compared with controls (48.9% versus 38.6%; adjusted odds ratio [OR] = 2.42; 95% confidence interval [CI] = 1.58–3.69; p < 0.001); as well as a late chronotypes (37.7% versus 38.1%; adjusted OR = 1.69; 95% CI = 1.10–2.61; p = 0.016). Migraineurs, particularly those with high attack frequency, were more tired after changes in circadian rhythm (i.e. more languid; p < 0.001) and coped less well with being active at unusual hours (i.e. more rigid; p < 0.001) than controls. Of 2389 migraineurs, 961 (40.2%) reported early morning attack onset.

Migraine patients are less prone to be of a normal chronotype than controls. They are more languid and more rigid when changes in circadian rhythm occur. Most migraine attacks begin in the early morning. These data suggest that chronobiological mechanisms play a role in migraine pathophysiology.

Cortical spreading depression (CSD) related diseases such as migraine, cerebrovascular diseases, and epilepsy have been associated with reactive astrocytosis, yet the mechanisms of these tissue changes remain unclear. CSD-induced inflammatory response has been proposed to play a role in some neurological disorders and thus may also contribute to reactive astrocytosis.

Using ex vivo brain slices and in vitro astrocytic cultures, we aimed to characterize CSD related changes in astrocytes and markers of inflammation by immunocyto- and immunohistochemistry. CSD was induced by application of KCl (3 mol/l) on neocortical tissues. The application of KCl was repeated weekly over the course of four weeks.

CSD induced an increase in the mean number and volume of astrocytes in rat brain tissue when compared to controls, whereas no changes in neuronal numbers and volumes were seen. These cell-type specific changes, suggestive of reactive astrocytosis, were paralleled by an increased expression of protein markers indicative of astrocytes and neuroinflammation in ex vivo brain slices of animals undergoing CSD when compared to sham-treated controls. Cultured astrocytes showed an increased expression of the immune modulatory enzyme indoleamine 2,3-dioxygenase and an elevated expression of the pro-inflammatory markers, IL-6, IL-1β, and TNFα in addition to increased levels of toll like receptors (TLR3 and TLR4) and astrocytic markers after induction of CSD.

These findings indicate that CSD related reactive astrocytosis is linked to an upregulation of inflammatory markers. Targeting inflammation with already approved and available immunomodulatory treatments may thus represent a strategy to combat or ameliorate CSD-related disease.

Headache disorders are widespread and disabling. They are common in Georgia, especially headache on ≥15 days/month (HA ≥ 15), but there are no headache services.

We established headache services meeting local needs, investigating feasibility, consumer uptake and satisfaction, and cost, with an exit strategy bequeathing effective, self-sustaining services that could be rolled out nationwide.

We created headache centres in Tbilisi and Gori offering free expert care for three visits over three months, and affordable medication thereafter. The primary outcome measure was the percentage of patients using the service beyond the free period – a measure of both satisfaction and sustainability.

Of 1,445 patients (age 43.7 ± 12.4 years; 10.5% male), 49.8% had episodic migraine, 22.5% episodic tension-type headache, 25.7% HA ≥ 15 (24.5% overusing medication) and 2.0% trigeminal autonomic cephalalgias. Only 454 (31.4%) and 51 (3.5%) returned for second and third visits; in these, headache improved and treatment costs decreased. As information about the service spread, five other headache clinics opened in Tbilisi and Kutaisi (western Georgia). Pharmaceutical companies reduced prices (sumatriptan 100 mg from US$7 to US$1).

The study failed to achieve its primary outcome, but sustainable headache services operating to international standards were successfully implemented nonetheless, with demand increasing.

To evaluate the impact of treatment success on depression and anxiety symptoms in medication-overuse headache (MOH) and whether depression and anxiety can be predictors of treatment outcome.

All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion over a six-month period. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale.

A total of 663 MOH patients were evaluated, and 492 completed the entire protocol. Of these, 287 ceased overuse and reverted to an episodic pattern (responders) and 23 relapsed into overuse. At the final evaluation, the number of patients with depressive symptoms was reduced by 63.2% among responders (p < 0.001) and did not change in relapsers (p = 0.13). Anxious symptomatology was reduced by 43.1% in responders (ps < 0.001) and did not change in relapsers (p = 0.69). At the multivariate analysis, intake of a prophylactic drug and absence of symptoms of depression at six months emerged as prognostic factors for being a responder (OR 2.406; p = 0.002 and OR 1.989; p = 0.019 respectively), while lack of antidepressant drugs and presence of symptoms of depression at six months were prognostic factors for relapse into overuse (OR 3.745; p = 0.004 and OR 3.439; p = 0.031 respectively).

Symptomatology referred to affective state and anxiety can be significantly reduced by the treatment of MOH. Baseline levels of depression and anxiety do not generally predict the outcome at six months. Their persistence may represent a trait of patients with a negative outcome, rather than the consequence of a treatment failure.

To determine the natural course of cluster headache.

We screened patients with cluster headache who were diagnosed at Samsung Medical Center and lost to follow-up for ≥5 years. Eligible patients were interviewed by phone about the longitudinal changes in headache characteristics and disease course. Remission was defined as symptom-free 1) for longer than twice the longest between-bout period and 2) for ≥5 years.

Forty-two patients lost to follow-up for mean 7.5 (range, 5.0–15.7) years were included. The length of the last bout did not differ from the first one, while the last between-bout period was longer than the first one (p = 0.012). Characteristics of cluster headache decreased over time: Side-locked unilaterality (from 92.9% to 78.9%), seasonal and circadian rhythmicity (from 63.9% to 60.9% and from 62.2 to 40.5%, respectively), and autonomic symptoms (from 95.2% to 75.0%). Remission occurred in 14 (33.3%) patients at a mean age of 42.3 (range, 27–65) years, which was not different from the age of last bouts in active patients (p = 0.623). There was a trend for more seasonal and circadian predilection at baseline in the active group (p = 0.056 and 0.063, respectively) and fewer lifetime bouts and shorter disease duration in patients in remission (p = 0.063 and 0.090).

This study first shows the natural courses of cluster headache. Features of cluster headache become less prominent over time. Remission occurred regardless of age. Although no single predictor of remission was found, our data suggest that remission of cluster headache might not be a consequence of more advanced age, longer duration of disease, or accumulation of lifetime bouts.

Previous functional and structural imaging studies have revealed that subcortical structures play a key a role in pain processing. The recurring painful episodes might trigger maladaptive plasticity or alternatively degenerative processes that might be detected by MRI as changes in size or microstructure. In the current investigation, we aimed to identify the macro- and microstructural alterations of the subcortical structures in episodic cluster headache.

High-resolution T1-weighted and diffusion-weighted MRI images with 60 gradient directions were acquired from 22 patients with cluster headache and 94 healthy controls. Surface-based segmentation analysis was used to measure the volume of the subcortical nuclei, and mean diffusion parameters (fractional anisotropy, mean, radial and axial diffusivity) were determined for these structures. In order to understand whether the size and diffusion parameters could be investigated in a headache lateralised manner, first the asymmetry of the size and diffusion parameters of the subcortical structures was analysed. Volumes and diffusion parameters were compared between groups and correlated with the cumulative number of headache days. To account for the different size of the patient and control group, a bootstrap approach was used to investigate the stability of the findings.

A significant lateralisation of the size (caudate, putamen and thalamus) and the diffusion parameters of the subcortical structures were found in normal controls. In cluster headache patients, the mean fractional anisotropy of the right amygdalae, the mean axial and mean diffusivity of the right caudate nucleus and the radial diffusivity of the right pallidum were higher. The mean anisotropy of the right pallidum was lower in patients.

The analysis of the pathology in the subcortical structures in episodic cluster headache reveals important features of the disease, which might allow a deeper insight into the pathomechanism of the pain processing in this headache condition.

The blood-brain barrier (BBB) has been hypothesized to play a role in migraine since the late 1970s. Despite this, limited investigation of the BBB in migraine has been conducted. We used the inflammatory soup rat model of trigeminal allodynia, which closely mimics chronic migraine, to determine the impact of repeated dural inflammatory stimulation on BBB permeability.

The sodium fluorescein BBB permeability assay was used in multiple brain regions (trigeminal nucleus caudalis (TNC), periaqueductal grey, frontal cortex, sub-cortex, and cortex directly below the area of dural activation) during the episodic and chronic stages of repeated inflammatory dural stimulation. Glial activation was assessed in the TNC via GFAP and OX42 immunoreactivity. Minocycline was tested for its ability to prevent BBB disruption and trigeminal sensitivity.

No astrocyte or microglial activation was found during the episodic stage, but BBB permeability and trigeminal sensitivity were increased. Astrocyte and microglial activation, BBB permeability, and trigeminal sensitivity were increased during the chronic stage. These changes were only found in the TNC. Minocycline treatment prevented BBB permeability modulation and trigeminal sensitivity during the episodic and chronic stages.

Modulation of BBB permeability occurs centrally within the TNC following repeated dural inflammatory stimulation and may play a role in migraine.

The association between RLS and migraine is still debated. The aim of this study is to investigate the prevalence and grade of RLS in Chinese patients with migraine and to evaluate the relationship between RLS and migraine.

A multi-center case-control study of contrast-enhanced transcranial Doppler was conducted in 931 consecutive patients with migraine (240 of 931 had migraine with aura and 691 of 931 were in the migraine without aura group) and 282 were healthy adults. Clinical trial no. NCT02425696.

The prevalence of RLS was 63.8% and 39.9% in the migraine with aura group (MA+) and migraine without aura group (MA−), respectively, significantly higher than that of the healthy group (29.4%, p < 0.001; p < 0.001). The positive rate of large RLS in the MA+ group and MA− group was 32.1% and 16.5%, respectively, significantly higher than healthy group (6.4%, p < 0.001; p < 0.001). There was no difference among groups in terms of positive rate of permanent RLS (p = 0.704).

This multi-centre case-control study suggested that there is an association between RLS and migraine with and without aura, especially when the shunt is large.

Carbon monoxide (CO) is an endogenously produced signalling molecule that has a role in nociceptive processing and cerebral vasodilatation. We hypothesized that inhalation of CO would induce headache and vasodilation of cephalic and extracephalic arteries.

In a randomized, double-blind, placebo-controlled crossover design, 12 healthy volunteers were allocated to inhalation of CO (carboxyhemoglobin 22%) or placebo on two separate days. Headache was scored on a verbal rating scale from 0–10. We recorded mean blood velocity in the middle cerebral artery (VMCA) by transcranial Doppler, diameter of the superficial temporal artery (STA) and radial artery (RA) by high-resolution ultrasonography and facial skin blood flow by laser speckle contrast imaging.

Ten volunteers developed headache after CO compared to six after placebo. The area under the curve for headache (0–12 hours) was increased after CO compared with placebo (p = 0.021). CO increased VMCA (p = 0.002) and facial skin blood flow (p = 0.012), but did not change the diameter of the STA (p = 0.060) and RA (p = 0.433).

In conclusion, the study demonstrated that CO caused mild prolonged headache but no arterial dilatation in healthy volunteers. We suggest this may be caused by a combination of hypoxic and direct cellular effects of CO.

Fifty-three percent of adolescent girls report headaches at the onset of menses, suggesting fluctuations of ovarian hormones trigger migraine during puberty.

To determine if urinary metabolites of estrogen and progesterone are associated with days of headache onset (HO) or severity in girls with migraine.

This was a pilot study and included 34 girls with migraine balanced across three age strata (pre-pubertal (8–11), pubertal (12–15), and post-pubertal (16–17) years of age). They collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide (E1G) and pregnandiol glucuronide (PdG) and the daily change was calculated (ΔE1G, ΔPdG). Pubertal development was assessed by age, pubertal development score (PDS), and menstrual cycle variance. The primary outcome measures were HO days and headache severity. Generalized linear mixed models were used, and included the hormonal variables and three different representations of pubertal development as covariates.

Models of HO days demonstrate a significant age*PdG interaction (OR 0.85 [95% CI 0.75, 0.97]) for a 1 standard deviation increase in PdG and three-year increase in age. A separate model showed a significant PDS*PdG interaction (OR −0.85 [95% CI; 0.76, 0.95]). ΔPDG was associated with headache severity in unadjusted models (p < 0.017).

Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine.

The migraine brain is believed to have altered cortical excitability compared to controls and between migraine cycle phases. Our aim was to evaluate post-activation excitability through post-movement beta event related synchronization (PMBS) in sensorimotor cortices with and without sensory discrimination.

We recorded EEG of 41 migraine patients and 31 healthy controls on three different days with classification of days in relation to migraine phases. During each recording, subjects performed one motor and one sensorimotor task with the right wrist. Controls and migraine patients in the interictal phase were compared with repeated measures (R-) ANOVA and two sample Student’s t-test. Migraine phases were compared to the interictal phase with R-ANOVA and paired Student’s t-test.

The difference between PMBS at the contralateral and ipsilateral sensorimotor cortex was altered throughout the migraine cycle. Compared to the interictal phase, we found decreased PMBS at the ipsilateral sensorimotor cortex in the ictal phase and increased PMBS in the preictal phase. Lower ictal PMBS was found in bilateral sensorimotor cortices in patients with right side headache predominance.

The cyclic changes of PMBS in migraine patients may indicate that a dysfunction in deactivation and interhemispheric inhibition of the sensorimotor cortex is involved in the migraine attack cascade.

The objective of this study was to analyse the prevalence and the clinical features of headache as a presenting symptom of glioma.

We interviewed 527 consecutive adult patients with histologically confirmed glioma, admitted to the Regina Elena National Cancer Institute between 2010 and 2015. We defined four headache phenotypes: Tension-type-like headache (TTH), migraine-like headache, worsening of a pre-existing headache (WPH) and classic brain tumour headache (BTH). Logistic regression analysis was carried out to investigate potential risk factors for headache at presentation of glioma.

12.5% (n = 66) of patients with glioma indicated headache as a presenting symptom of their disease. Of these, 31 patients (47%) had TTH, while BTH and WPH were reported by 28 (42%) and seven (11%) patients, respectively. We did not find any case of migraine-like headache. Infratentorial (p = 0.038) and right-sided tumours (p = 0.013) were more frequently associated with the presence of headache at onset. Patients with TTH were older than patients with BTH and WPH (p = 0.035). BTH was less frequently associated with other neurological signs (p < 0.0001). The multivariate logistic regression analysis showed the localization of the brain tumour in the left hemisphere to be a protective factor for the development of headache.

Our study includes a very large series of patients with glioma, providing a description of headache phenotype at first presentation of disease and investigating possible factors that may influence the clinical features of headache.

To explore the role of microvascular pathology in migraine, we investigated the association between migraine and retinal microvascular damage.

We included 3270 participants (age ≥ 45 years, 63% women) from the population-based Rotterdam Study (2006–2009). Participants with migraine were identified using a validated questionnaire based on ICHD-II criteria (n = 562). Retinopathy signs were graded on fundus photographs. Retinal arteriolar and venular caliber were measured by semi-automatic assessment of fundus photographs. Associations of migraine with retinopathy and retinal microvascular calibers were examined using logistic and linear regression models, respectively, adjusting for age, sex, and cardiovascular risk factors.

Migraine was not associated with the presence of retinopathy (odds ratio (OR): 1.09, 95% confidence interval (CI) 0.62; 1.92). In the fully adjusted model, adjusting for the companion vessel, persons with migraine did not differ in retinal arteriolar or venular caliber compared to persons without migraine (mean difference in standardized arteriolar caliber −0.05 (95%CI −0.13; 0.03); in standardized venular caliber −0.00 (95%CI −0.09; 0.08)). Migraine subtypes, including migraine with aura, were also not associated with retinal microvascular damage.

Our findings suggest that migraine is not associated with retinopathy or difference in retinal microvascular caliber. Further studies are needed to confirm these results.

Brain excitability is changed in migraine but not fully characterized yet. This study explored if somatosensory gating is altered in migraine and linked to migraine chronification.

Paired electrical stimuli were delivered to the left index fingers of 21 patients with migraine without aura (MO), 22 patients with chronic migraine (CM), and 36 controls. The first and second responses to the paired stimuli were obtained from the contralateral primary (cSI), contralateral secondary (cSII) and ipsilateral secondary (iSII) somatosensory cortices to compute the gating ratios (second vs. first response strengths).

The first and second cSI responses and gating ratios differed in all groups (p < 0.05); the responses were typically smaller in the MO and CM groups. The cSI gating ratio increased as a continuum across controls (0.73 ± 0.04, p < 0.001), MO (0.83 ± 0.04) to CM (0.97 ± 0.06) and was higher in CM vs. controls (p < 0.001). When MO and CM were combined, cSI gating ratio was associated with headache frequency (r = 0.418, p = 0.005). Paired responses and gating ratios of cSII and iSII did not differ among the groups.

Somatosensory gating is altered in migraine and associated with headache chronification. Further studies must clarify if this abnormal sensory modulation is a true gating deficit independent of low preexcitation level.

Migraine is highly prevalent in women (18%). Peak morbidity affects their most productive years, coinciding with peak fertility. Hormonal contraception is often tailored for migraine prevention. Estrogen-containing contraceptives may be contraindicated in women experiencing migraine with aura due to the risk of vascular events. While improvements in migraine with a progestin-only pill (POP), which inhibits ovulation are documented, the strength and quality of evidence has not been formally evaluated.

To determine the effectiveness of progestin-only contraceptives for migraine treatment by systematic review and meta-analysis.

MEDLINE, EMBASE and Cochrane Libraries were searched (1980 to September 2016) for studies on progestin-only treatments for migraine. Studies in English on >4 non-menopausal women aged 18–50 with migraine diagnosed by formal criteria were included.

Data were quality-assessed using the GRADE system. A random effects model was used for pooled analyses.

Pooled analyses of four studies demonstrated that desogestrel 75 mcg/day, POP significantly but modestly reduced the number of migraine attacks and migraine days. Reduced intensity and duration, reduced analgesic and triptan use were observed, along with improved headache-related quality of life. GRADE analysis indicated evidence was low to very low for each outcome measure. Adverse effects resulted in treatment cessation for <10% of participants. Two studies compared desogestrel POP to a combined oral contraceptive, demonstrating similar migraine outcomes for both treatments.

The desogestrel POP shows promise in improving migraine in women. Current evidence is observational and based on small samples of women using only one oral progestin-only formulation. Further randomized trials on additional progestin-only contraceptives are required to confirm their role in migraine management.

To report demographics and characteristics of reversible cerebral vasoconstriction syndrome (RCVS) in the Korean cohort.

We prospectively recruited patients with definite (imaging-proven) RCVS and probable (imaging-negative) RCVS who visited Samsung Medical Center between June 2012 and September 2016. Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of RCVS without typical causes (“idiopathic RCVS”) were compared with those of RCVS with identifiable causes (“secondary RCVS”). International Classification of Headache Disorders (ICHD)-3 beta criteria for 6.7.3 RCVS and 6.7.3.1 probable RCVS were tested.

A total of 138 patients (104 definite and 34 probable RCVS) were included in this study. Patients with definite RCVS were predominantly female (85.6%) and middle-aged (mean, 50.7 [range, 23–82] years). Probable RCVS was associated with less female predominance (70.6%, p = 0.049), more typical manifestations (p < 0.001), and none of neurological complications. One-hundred and one (97.1%) patients with definite RCVS had headache, but the typical “recurrent and/or triggered” thunderclap headache was reported in only 83 (82.2%). In most patients with definite RCVS (84.6%), RCVS was idiopathic, while only 16 (15.4%) had secondary causes. Compared to those with secondary RCVS, patients with idiopathic RCVS were older (52.8 ± 11.42 vs. 39.1 ± 9.55 years, p < 0.001). Patients with secondary RCVS had more complications than those with idiopathic RCVS (40.5% vs. 12.5%, p = 0.018). Among idiopathic RCVS patients, 33 (37.5%) reported a preceding event or a change in lifestyle, environment, health, or medication within one month before onset.

In our cohort, RCVS was benign and idiopathic in most patients, and occurred frequently in middle-aged women. Manifestations of RCVS were more diverse than previously recognized, and forms without any headache existed. Different genetic, social, and environmental factors should be taken into account to unveil the spectrum and pathophysiology of RCVS.

A subgroup of migraineurs experience an increase in attack frequency leading to chronic migraine.

We assessed in rats the roles of dose and repeat administration of systemic isosorbide dinitrate (ISDN), a nitric oxide donor, on the occurrence and development of cephalic/face and extracephalic/hindpaw mechanical allodynia as a surrogate of migraine pain, and the effect of acute systemic sumatriptan and olcegepant and chronic systemic propranolol on these behavioral changes.

A single high (H-ISDN) but not low (L-ISDN) dose of ISDN induces a reversible cephalic and extracephalic mechanical allodynia. However, with repeat administration, L-ISDN produces reversible cephalic but never extracephalic allodynia, whereas H-ISDN induces cephalic and extracephalic allodynia that are both potentiated. H-ISDN-induced cephalic allodynia thus gains persistency.

Sumatriptan and olcegepant block single H-ISDN-induced behavioral changes, but only olcegepant reduces these acute changes when potentiated by repeat administration. Neither sumatriptan nor olcegepant prevent chronic cephalic hypersensitivity. Conversely, propranolol blocks repeat H-ISDN-induced chronic, but not acute, behavioral changes.

Repeated ISDN administration appears to be a naturalistic rat model for migraine progression, suitable for screening acute and preventive migraine therapies. It suggests frequent and severe migraine attacks associated with allodynia may be a risk factor for disease progression.

Clear definitions of study populations in clinical trials may facilitate application of evidence to clinical populations. This review aimed to explore definitions of study populations in clinical trials on migraine, tension-type headache, cluster headache, and cervicogenic headache.

We performed a systematic review of clinical trials investigating treatment efficacy for migraine, tension-type headache, cluster headache, and cervicogenic headache. We extracted data on diagnosis, inclusion criteria and baseline headache characteristics.

Of the 229 studies reviewed, 205 studies (89.5%) defined their populations in adherence to the International Classification of Headache Disorders (ICHD) criteria. Some studies (n = 127, 55.5%) specified diagnosing through interview, clinical examination and diary entry. The most commonly reported inclusion criteria were pain intensity for migraine and tension-type headache studies (n = 123, 66.1% and n = 21, 67.7%, respectively), episode frequency (n = 5, 71.4%) for cluster headache studies, and neck-related pain for cervicogenic headache studies (n = 3, 60%). Few studies reported details on the extent to which diagnostic criteria were present at baseline.

ICHD is routinely used in defining populations in headache studies. Details of baseline headache characteristics were not as consistently reported.

Nummular headache is a rare, recently described topographic headache defined by the circumscribed coin-shaped area of pain. It is classified as a primary headache. There is debate about whether it is due to a peripheral or central disturbance, and its relationship to migraine.

We report two patients with presumed nummular headache secondary to Langerhans cell histiocytosis, both with resolution of their headaches after surgical resection.

Imaging in patients with clinical features of nummular headache is recommended, as this and other cases highlight that it may be symptomatic. There are no distinguishing clinical features to separate nummular headache from secondary mimics, and treatment of the underlying cause may be curative.

To investigate the relationship between primary headache types and accomplished or attempted suicide in countries from all world regions.

Data were obtained using a questionnaire about suicide due to headache in a face-to-face interview with 203 physicians with expertise in headaches. They came from 48 countries, and from all continents.

Primary headaches cause one suicide per 1,000,000 population each year (1% of the suicide rate due to all causes). Cluster headache and migraines account for 70–80% of them. Suicide attempts are 10 times more frequent than accomplished suicides. Cluster headache poses more risk than migraine. This risk is not often acknowledged, and is increased if there is previous psychiatric history. More than half of the physicians interviewed think it could be reduced with a more aggressive treatment of headaches.

Cluster headache and migraine are not always benign, and are the cause of the majority of suicides due to headache.

Hemicrania continua (HC) is a primary headache syndrome characterized by a unilateral, moderate, continuous headache with exacerbations marked by migrainous and cranial autonomic symptoms. However, clinical phenotypes similar to primary HC may be subtended by several disorders.

We report the case of a 62-year-old man experiencing, over the previous year, a headache completely consistent with HC and its absolute responsiveness to indomethacin therapy. Later, the patient developed diplopia caused by sixth cranial nerve palsy ipsilateral to headache. In this frame, clinical, laboratory and neuroimaging characteristics supported the diagnosis of idiopathic hypertrophic pachymeningitis (IHP).

IHP is a rare fibrosing inflammatory disorder leading to a localized or diffuse dura mater thickening. IHP clinical manifestations are a progressively worsening headache and signs related to cranial nerves involvement and venous sinus thrombosis. Here, we report, for the first time, a HC phenotype subtended by IHP.