Population-Based Analysis of Cluster Headache-Associated Genetic Polymorphisms.

Cluster headache is a disorder with increased hereditary risk. Associations between cluster headache and polymorphism rs2653349 of the HCRTR2 gene have been demonstrated. The less common allele (A) seems to reduce disease susceptibility. The polymorphism rs5443 of the GNB3 gene positively influences triptan treatment response. Carriers of the mutated T allele are more likely to respond positively compared to C:C homozygotes, when treated with triptans. DNA was extracted from buccal swabs obtained from 636 non-related Southeastern European Caucasian individuals and was analyzed by real-time PCR. Gene distribution for the rs2653349 was G:G = 79.1%, G:A = 19.2%, and A:A = 1.7%. The frequency of the wild-type G allele was 88.7%. The frequencies for rs5443 were C:C = 44.0%, C:T = 42.6%, and T:T = 13.4%. The frequency of the wild-type C allele was 65.3%. The frequency distribution of rs2653349 in the Southeastern European Caucasian population differs significantly when compared with other European and East Asian populations, and the frequency distribution of rs5443 showed a statistically significant difference between Southeastern European Caucasian and African, South Asian, and East Asian populations. For rs2653349, a marginal statistically significant difference between genders was found (p = 0.080) for A:A versus G:G and G:A genotypes (OR = 2.78), indicating a higher representation of male homozygotes for the protective mutant A:A allele than female. No statistically significant difference was observed between genders for rs5443. Cluster headache pathophysiology and pharmacotherapy response may be affected by genetic factors, indicating the significant role of genotyping in the overall treatment effectiveness of cluster headaches.

[Clinical profile of cluster headaches in Japan].

This study examined the clinical profile of cluster headache (CH) in Japan and the potential presence of features peculiar to Japan. Subjects comprised 110 consecutive new CH patients (83 males, 27 females; mean age, 38.1 ± 11.7 years). While 85% of patients had visited other medical institutions, only 19% had received a correct diagnosis. Mean delay in diagnosis was 8.1 years. The common clinical features of the present report and previous Japanese reports were as follows: 1) a low prevalence of chronic CH; 2) a low prevalence of sense of restlessness; 3) an uncoupling of a sense of restlessness and restless behavior; 4) approximately half of all patients experiencing CH attacks ranging in duration from 1-2 hours; 5) the location of CH most commonly reported as retro-orbital; and 6) lacrimation representing the most consistently reported autonomic feature. The common clinical features from 1) to 3) were seen in other East-Asia countries. Both frequencies of locations of CH and autonomic features differed between Caucasian and East-Asian populations. These characteristics may reflect ethnic and/or cultural differences between Eastern and Western CH patients.

MTHFR 677C>T polymorphism and cluster headache.

BACKGROUND: An association between the 677C>T polymorphism (rs1801133) in the methylenetetrahydrofolate reductase gene (MTHFR) and cluster headache is plausible, but has not been investigated. OBJECTIVE: To investigate this association among Caucasians. METHODS: Case-control study among 147 cluster headache patients and 599 population-based age- and gender-matched controls. Cluster headache was diagnosed according to the criteria of the International Headache Society. Genotypes of the MTHFR 677C>T polymorphism were detected by restriction fragment length polymorphism analysis. We used logistic regression analysis to investigate the association between cluster headache and genotypes with additive, dominant, and recessive models. We considered a Bonferroni-corrected P value <.004 as significant. RESULTS: Mean age at study entry among patients was 44.9 years (SD 11.4), of whom 76.2% were men. The genotype distribution among controls and patients was in Hardy-Weinberg equilibrium. The genotype and allele distribution did not differ between patients with any cluster headache and controls. We also did not find an association when assuming additive, dominant or recessive genetic models. When we looked at subgroups, the effect estimates suggested an increased risk for chronic cluster headache (dominant model: odds ratio = 2.82; 99.6% confidence interval = 0.72-11.07; P = .03). CONCLUSIONS: Data from our case-control study do not indicate an association between genotypes of the MTHFR 677C>T polymorphism and cluster headache overall. Subgroup analyses suggested that carriers of the MTHFR 677T allele may have an increased risk for chronic cluster headache. This may be regarded as hypothesis-generating and should be further investigated in independent studies.

Websites offer helpful information concerning consultation with headache specialists.

Patients with severe primary headache may benefit from consultation with headache specialists, but doctor attendance rates in Japan are very low. More headache patients might consult headache specialists if these specialists were more widely recognized by the public. To determine what information prompted patients to seek consultation with a headache specialist, we questioned 256 primary headache patients about the source of the helpful information concerning consultation with headache specialists. From 191 patients, a total of 235 responses to the questionnaire were obtained. The most common response was 'websites' (33.2%), followed by 'professionals' (23.8%), 'acquaintances' (20.9%), 'print media' (6.8%) and 'TV/radio' (3.4%). Patients who indicated websites showed the most severe pain and highest impact of headache, and accounted for 52.4% of those with cluster headaches. Development of websites concerning headache specialists would seem likely to increase doctor attendance rates for patients with primary headache.

Delayed diagnosis of cluster headache in African-American women.

The male-to-female ratio has fallen in cluster headache over the last several decades and is now 2.1:1. Unfortunately, women still are not diagnosed accurately. This lack of appropriate diagnosis appears related to the misconception that cluster headache rarely occurs in women. Compounding this misconception, there seems to be an ethnic bias. We report cluster headache in five African-American women in whom diagnosis was delayed due to gender, ethnicity, and, most importantly, an inability to make a correct diagnosis of cluster headache. Cluster headache diagnostic criteria are no different in men or women and have no ethnic boundaries. Clinical features such as disordered chronobiology and abnormal behavior often suggest the diagnosis. Migrainous features occur commonly in cluster headache and, when present, should not exclude the diagnosis. Likewise, neither race nor sex should exclude the diagnosis. The diagnosis of cluster headache is easily made by considering unilateral orbital, supraorbital or temporal location; short duration (15-180 minutes, untreated), and ipsilateral autonomic dysfunction involving the eye or nose.