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( Headache 2011;51:201-207) An association between the 677C>T polymorphism (rs1801133) in the methylenetetrahydrofolate reductase gene ( MTHFR) and cluster headache is plausible, but has not been investigated. To investigate this association among Caucasians. 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. 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). 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. [ABSTRACT FROM AUTHOR]

( Headache 2010;50:1031-1040) Background.— Many studies support an association between migraine and cardiovascular disease (CVD). This association appears particularly in migraine with aura and is also modified by additional factors. Objective.— We sought to investigate whether the association between migraine and CVD in addition to aura status is affected by certain migraine features. Methods.— Cohort study among 27,840 women, participating in the Women's Health Study. We had detailed self-reported information on migraine and migraine features among women with active migraine (migraine during the year prior to baseline). Incident CVD events were confirmed after medical record review. We used Cox proportional hazards models to evaluate the association between migraine and incident CVD. The results have been presented in part before. We ran additional analyses according to migraine features. Results.— At baseline, 5125 (18.4%) women reported history of migraine; 39.7% of the 3610 women with active migraine indicated aura. During a mean of 11.9 years of follow-up, 708 CVD events occurred. Migraine with aura doubled the risk for CVD, ischemic stroke, and myocardial infarction. With regard to ischemic stroke, this association seemed stronger in the absence than in the presence of migraine features. This was most pronounced in the absence (hazard ratio = 3.27; 95% CI = 1.93-5.51; P < .0001) than in the presence of nausea/vomiting (hazard ratio = 0.91; 95% CI = 0.43-1.93; P = .80). In contrast, the association with myocardial infarction did not reveal a certain pattern. Conclusions.— These data suggest that the association between migraine with aura and ischemic stroke may differ by absence or presence of migraine features. [ABSTRACT FROM AUTHOR]

( Headache 2010;50:588-599) Background.— Data on the association between the MTHFR 677C>T and ACE D/I polymorphisms and migraine including aura status are conflicting. Objective.— The objective of this study is to perform a systematic review and meta-analysis on this topic. Methods.— We searched for studies published until March 2009 using electronic databases (MEDLINE, EMBASE, Science Citation Index) and reference lists of studies and reviews on the topic. Assessment for eligibility of studies and extraction of data was performed by 2 independent investigators. For each study we calculated the odds ratios (OR) and 95% confidence intervals (CI) assuming additive, dominant, and recessive genetic models. We then calculated pooled ORs and 95% CIs. Results.— Thirteen studies investigated the association between the MTHFR 677C>T polymorphism and migraine. The TT genotype was associated with an increased risk for any migraine, which only appeared for migraine with aura (pooled OR = 1.48, 95% CI 1.02-2.13), but not for migraine without aura. Nine studies investigated the association of the ACE D/I polymorphism with migraine. The II genotype was associated with a reduced risk for migraine with aura (pooled OR = 0.71, 95% CI 0.55-0.93) and migraine without aura (pooled OR = 0.84, 95% CI 0.70-0.99). Results for both variants were driven by studies in non-Caucasian populations. Results among Caucasians did not suggest an association. Extractable data did not allow investigation of gene–gene interactions. Conslusions.— The MTHFR 677TT genotype is associated with an increased risk for migraine with aura, while the ACE II genotype is protective against both migraine with and without aura. Results for both variants appeared only among non-Caucasian populations. There was no association among Caucasians. [ABSTRACT FROM AUTHOR]

Objective.— To investigate the role of three common polymorphisms in the β2-adrenoceptor gene in migraine. Background.— Migraine has been associated with increased risk of cardiovascular disease and asthma in which β2-adrenoceptors play an important role; β-adrenoceptor antagonists are used in migraine prevention. However, the role of variants in the β2-adrenoceptor gene in migraine is unclear. Methods.— Association study among 23,753 white women, participating in the Women's Health Study, for whom we had information on migraine at baseline and genotype status of the polymorphisms rs1042713 (Gly16Arg), rs1042714 (Gln27Glu), rs1800888 (Thr164Ile). Migraine was self-reported and we distinguished between any history of migraine, active migraine with and without aura, and prior migraine (history of migraine but not active migraine) in our analyses. Results.— At baseline 4339 women reported any history of migraine. Of these, 3041 had active migraine (1221 migraine with aura, 1820 migraine without aura) and 1298 prior migraine. No migraine was reported by 19,414 women. Genotype- and haplotype-based analyses did not show an association of any of the gene variants tested with any history of migraine. The multivariable-adjusted odds ratios (ORs) (95% confidence intervals) for any history of migraine in the additive model were 1.0 (0.96-1.05) for rs1042713, 1.0 (0.95-1.05) for rs1042714, and 0.84 (0.68-1.05) for rs1800888. In the haplotype analysis the ORs ranged from 0.83 (0.67-1.03) to 1.01 (0.94-1.07) with Gly16-Glu27-Thr164 as the reference. We also did not find associations in the genotype- and haplotype-based analyses within migraine-specific subgroups. Conclusions.— Our results do not support a role of 3 investigated polymorphisms in the β2-adrenoceptor gene in migraine pathophysiology. [ABSTRACT FROM AUTHOR]

Background.— Recent findings suggest an association between the renin-angiotensin system and migraine. However, genetic studies are scarce and controversial. Objective.— To investigate the association between the AGTR1 1166A > C and AGT Met235Thr polymorphisms with migraine and migraine aura status. Methods.— We performed an association study among 25,000 Caucasian US women, participating in the Women's Health Study, with information on the AGTR1 1166A > C and AGT Met235Thr polymorphisms. Migraine and migraine aura status were self-reported. We distinguished between any history of migraine, active migraine with aura, active migraine without aura, and prior migraine (history of migraine, but not in the year prior to baseline). We used logistic regression to investigate the genotype–migraine association. Results.— At baseline, 4577 (18.3%) women reported any history of migraine; 39.5% of the 3226 women with active migraine indicated aura. The polymorphisms were not associated with migraine or migraine-specific subgroups. We also did not find a significant interaction between the polymorphisms. Conclusions.— Data from this large cohort of Caucasian women do not suggest an association of polymorphisms in the renin-angiotensin system with migraine or aura status. Future studies should focus on haplotype analyses and additional gene–gene as well as gene–environment interactions. [ABSTRACT FROM AUTHOR]

The article reports on the case of a 50 year old man who presented to physicians with a history of cluster headaches that were triggered by the consumption of alcoholic beverages. A discussion of trigger factors which are associated with cluster headaches, and of the role that alcohol may play in the development of cluster headaches, is presented.

Background.—The hypocretin receptor 2 ( HCRTR2) G1246A polymorphism has been associated with the risk for cluster headache. Since the hypothalamic hypocretin/orexin system projects throughout the nervous system and affects multiple vegetative functions including generation of rhythmicity, vasomotion, autonomic symptoms as well as modulation of nociception, it may also be linked with migraine. Objective.—We thus sought to evaluate whether the HCRTR2 G1246A polymorphism is associated with the risk for migraine. Methods.—We prospectively established a cohort of 146 unrelated patients with migraine. The control group consisted of 279 healthy volunteers. We genotyped patients and controls for the HCRTR2 G1246A polymorphism and examined an association with presence or absence of migraine. Results.—Genotype and allele frequencies were not significantly different between migraine patients and controls (genotype distribution: χ2= 4.13, 2 df, P= .13; allele distribution: χ2= 0.9, 1 df, P= .34). Conclusion.—Our study does not support a major contribution of the HCRTR2 G1246A polymorphism to the pathogenesis of migraine in contrast to its effects in cluster headache. [ABSTRACT FROM AUTHOR]

Background.—Oxygen and triptans are drugs of first choice to abort cluster headache attacks. However, clinical predictors of treatment response are unavailable. Objective.—We aimed to identify predictors of acute treatment response among patients with cluster headache. Methods.—We investigated 246 cluster headache patients with available information on personal, headache, and lifestyle characteristics as well as effectiveness of acute medication use. We used logistic regression models to identify potential predictors of triptan and oxygen response. Results.—Triptans were effective in 137 of the 191 users and oxygen in 134 of the 175 users. We only identified increasing age (OR 0.96, 95% CI 0.93–0.99; P= .013) as a negative predictor for triptan response, while nausea/vomiting (OR 0.41, 95% CI 0.18–0.91; P= .029) and restlessness (OR 0.09, 95% CI 0.01–0.66; P= .019) were negative predictors of oxygen response. Conclusions.—Few clinical features seem to predict treatment nonresponse in cluster headache. More refined studies aiming at physiological and genetic characteristics seem promising in the future. [ABSTRACT FROM AUTHOR]

Background.—Cluster headache (CH) is a rare but severe headache form with a distinct clinical presentation. Misdiagnoses and mismanagement among these patients are high. Objective.—To characterize clinical features and medical treatment in patients with CH. Methods.—We established a cohort of 246 clinic-based and non-clinic-based CH patients. The diagnosis of CH was verified according to International Headache Society (IHS) criteria. We used standardized questionnaires to assess associated factors as well as success or failure of treatments. Results.—The majority (75.6%) was not treated before at our clinic—77.6% were males; 74.8% had episodic CH, 16.7% had chronic CH, in the remaining patients, the periodicity was undetermined because they were newly diagnosed. Cranial autonomic features were present in 98.8%, nausea and vomiting in 27.8%, and photophobia or phonophobia in 61.2% of CH patients. Most (67.9%) reported restlessness during attacks and 23% a typical migrainous aura preceding the attacks. The rate of current smoking was high (65.9%). Half of the patients reported that alcohol (red wine in 70%) triggered CH attacks. Eighty-seven percent reported the use of drugs of first choice (triptans 77.6%, oxygen 71.1%) with sumatriptan subcutaneous injection being the most effective drug for acute therapy (81.2%). The most frequently used preventive medications were verapamil (70.3%) and glucocorticoids (57.7%) with equally high effectiveness. Conclusions.—Apart from the IHS criteria additional features like nausea/vomiting and migrainous aura may guide the diagnosis of CH. A large number of CH patients do not receive adequate treatments. [ABSTRACT FROM AUTHOR]