Cluster headache (CH) is diagnosed according to criteria of the International Headache Society (IHS), but, in clinical practice, these criteria seem too restrictive. As part of a nation-wide study, we identified a group of patients who met all criteria minus one (IHS-CH-1), and assessed in which way they differed from CH patients meeting all criteria (IHS-CH). We performed a nation-wide questionnaire study for CH and CH-like syndromes, including questions based on the IHS criteria, and additional features such as restlessness during attacks, nocturnal onset of attacks, circadian rhythmicity of attacks and response to treatment. IHS-CH and IHS-CH-1 patients were compared. Of 1452 responders to two questionnaires, 1163 were IHS-CH and 289 were IHS-CH-1. The majority of the IHS-CH-1 patients were classified as such because their attacks exceeded 3 h (64%, median attack duration: 5 h), or came in a frequency of less than 1 per 2 days (16%). Age at onset was similar between the groups. The male to female ratio was 3.7 : 1 in the IHS-CH group and around 1.6 : 1 in the IHS-CH-1 groups (P < 0.005). Patients with attacks exceeding 3 h less often reported a circadian rhythmicity (IHS-CH-1: 49%, IHS-CH: 64%), episodic periodicity (IHS-CH-1: 65%, IHS-CH: 78%), nocturnal attacks (IHS-CH-1: 67%, IHS-CH: 78%), smoking (IHS-CH-1: 90%, IHS-CH: 80%) and restlessness during attacks (IHS-CH-1: 64%, IHS-CH: 76%) than IHS-CH patients (P < 0.005). Photo- or phono-phobia (IHS-CH-1: 67%, IHS-CH: 54%) and nausea (IHS-CH-1: 38%, IHS-CH: 27%) were more frequently reported by patients who reported to have attacks exceeding 3 h (P < 0.005). Similar proportions reported effect of verapamil on their attacks (IHS-CH-1: 54%, IHS-CH 61%). We conclude that average attack duration exceeding 3 h was frequently the reason for not fulfilling IHS CH criteria. Symptoms often accompanying CH such as restlessness, nocturnal attacks and an episodic attack pattern were relatively frequently present in IHS-CH-1 patients with longer attacks. These patients may therefore be diagnosed with CH. Attack frequency may not be a useful criterion for the diagnosis of CH. The upper limit of 3 h should be increased in future diagnostic criteria.

It is very likely that genetic factors play a role in the pathophysiology of cluster headache (CH). As CH shares its paroxysmal character with migraine, and migraine has been described in coexistence with CH in some families, we hypothesized that both diseases might share a genetic aetiology. In this study, we tested whether the migraine CACNA1A gene on chromosome 19 is involved in CH in an extended pedigree. Haplotype analysis did not reveal an obvious disease haplotype, and SSCP analysis of all 47 exons of the CACNA1A gene did not reveal a causative mutation. CH in this family is not caused by mutations in the CACNA1A gene.

Background Familial hemiplegic migraine (FHM) is a rare monogenic migraine subtype characterised by attacks associated with transient motor weakness. Clinical information is mainly based on reports of small families with only short follow-up. Here, we document a prospective 15-year follow-up of an extended family with FHM type 2. Patients and methods After diagnosing FHM in a patient with severe attacks associated with coma and fever, we identified eight more family members with FHM and one with possible FHM. All family members were prospectively followed for 15 years. In total 13 clinically affected and 21 clinically non-affected family members were genetically tested and repeatedly investigated. Results A novel p.Arg348Pro ATP1A2 mutation was found in 14 family members: 12 with clinical FHM, one with psychomotor retardation and possible FHM, and one without FHM features. In 9/12 (75%) family members with genetically confirmed FHM, attacks were severe, long-lasting, and often associated with impaired consciousness and fever. Such attacks were frequently misdiagnosed and treated as viral meningitis or stroke. Epilepsy was reported in three family members with FHM and in the one with psychomotor retardation and possible FHM. Ataxia was not observed. Conclusion FHM should be considered in patients with recurrent coma and fever.

Cluster headache (CH) typically presents in clusters of attacks of intense (peri)orbital, unilateral pain. The distribution of the pain implies involvement of central and/or peripheral trigeminal pathways. These can be investigated by means of trigeminal somatosensory evoked potentials (TSEP) and blink reflexes (BR). We aimed to relate functional changes in trigeminal sensory pathways to the presence of cluster periods. TSEP and BR were performed in 28 episodic CH patients during a cluster period and repeated in 22 outside a cluster period. TSEP latencies (N1, P1 and N2) and amplitude (N1-P1 and P1-N2) and BR latencies (R1, R2 ipsilateral and R2 contralateral) were compared between sides, during and outside a cluster period and with healthy control data (n = 22). During a cluster period, N2 TSEP latencies were longer on the symptomatic side compared with the non-symptomatic side (27.2 +/- 3.0 ms vs. 26.3 +/- 3.4 ms, P = 0.02), and compared with the same side outside the cluster period (26.7 +/- 3.1 ms vs. 25.1 +/- 3.0 ms, P = 0.01). N1, P1 and N2 latencies on the symptomatic side in patients during the cluster period (14.8 +/- 2.3 ms, 20.4 +/- 2.5 ms and 27.2 +/- 3.0 ms, respectively) were significantly longer than those of healthy controls (13.4 +/- 1.9 ms, 18.8 +/- 2.4 ms and 25.0 +/- 2.6 ms, respectively, P < 0.03). Outside the cluster period, N1 latencies of both sides (15.3 +/- 2.8 ms symptomatic side and 15.4 +/- 2.6 ms asymptomatic side) were longer compared with controls (13.4 +/- 1.9 ms, P < 0.04). TSEP amplitudes and BR latencies revealed no significant differences. We conclude that abnormalities of the afferent trigeminal pathway are present in patients with cluster headache, most prominent during the cluster period, and on the symptomatic side. This seems primarily due of changes within the higher cerebral regions of the system.