Polymorphisms in the Renin-Angiotensin System and Migraine in Women

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.     

Association between polymorphisms in the beta2-adrenoceptor gene and migraine in women

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.     

Endothelial nitric oxide synthase (Glu298Asp) polymorphism is an independent risk factor for migraine with aura

OBJECTIVE: The aim of the present study was to evaluate whether the functional endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism, which has been demonstrated to decrease the endothelial NOS activity, might be a risk factor for migraine. BACKGROUND: It has widely demonstrated that nitric oxide (NO) is involved in migraine pathogenesis. Several genetic risk factors have been associated with migraine, but no study has unraveled a possible relationship between migraine and eNOS Glu298Asp. Methods.-One hundred fifty-six migraine patients and 125 healthy nonheadache volunteers entered the study. Demographic and clinical characteristics were carefully recorded, and a neurological workup was performed. RESULTS: eNOS AspAsp homozygous patients had a 3-fold time risk for migraine with aura (MA) when compared to migraine without aura (MO) patients (OR-3.02, 95% CI-1.21 to 7.51), and more than 2-fold time increased risk when compared to control subjects (OR-2.21, 95% CI-1.00 to 5.04). In migraine patients, no difference in age at onset, mean attack's intensity, family history for any of the studied comorbidities, or the presence of comorbidities was found in eNOS AspAsp homozygous compared to eNOS GluGlu or eNOS GluAs carriers. CONCLUSIONS: Homozygous Asp298, a common variant of the eNOS gene, is an independent risk factor for MA in this study population.     

Alcohol Dehydrogenase 2 Genotype and Risk for Migraine

( Headache 2010;50:85-91)
Background/Objectives.— Alcohol has been traditionally considered a possible migraine trigger factor. Alcohol-dehydrogenase (ADH) enzymes are thought to play important roles in the metabolism of ethanol. Relevant polymorphism has been found only for 2 of the ADH genes (mapped on chromosome ): ADH 1B, betapolypeptide ( ADH2 ) and ADH3 . The polymorphism rs1229984, located in the third exon of the human ADH2 gene, causes the amino acid substitution Arg48His. The aim of this study was to investigate the possible association between ADH2 polymorphism and the risk for migraine and for triggering migraine attacks.
Methods.— We studied the frequency of the ADH2 genotypes and allelic variants in 197 patients with migraine and 255 healthy controls using allele-specific PCR amplification and Msl I-RFLP's analyses.
Results.— The frequencies of ADH2 Arg/His genotype and of ADH2 His allele were significantly lower in patients with migraine when compared with those of controls, and were unrelated with the age of onset of migraine attacks, family history of migraine or presence of aura. The frequency of the allelic variant ADH2 His ( ADH2*2 ) was significantly higher in the group of patients who reported triggering of migraine by alcohol when compared with the group who reported no effect.
Conclusion.— The results of the present study suggest that ADH2 Arg/His genotype should be associated with a decreased risk for migraine, while the ADH2 His allelic variant should be related with the risk for triggering migraine attacks after alcohol consumption in our population of migraine patients.     

No association between bipolar disorder risk polymorphisms in ANK3 and CACNA1C and common migraine

(Headache 2011;51:713‐725) Background.— Migraine and bipolar disorder are characterized by a high level of co‐morbidity, and a common familial–genetic basis has recently been hypothesized for the 2 disorders. Genome‐wide association studies have reported strong evidence of association between the polymorphisms rs10994336[T] in the ANK3 gene and rs1006737[A] in the CACNA1C gene and risk of bipolar disorder. Objective.— The aim of this study was to evaluate the hypothesis of a genetic linkage between migraine and bipolar disorder by investigating the familial transmission of the 2 bipolar disorder risk polymorphisms, in a sample of family trios with probands with childhood migraine, and unrelated controls. Methods.— Our sample comprised 192 family trios, each with a proband with childhood migraine (137 migraine without aura, 44 migraine with aura) and 228 unrelated controls. The markers rs10994336 and rs1006737 were genotyped using a TaqMan single nucleotide polymorphism Genotyping Assay. The transmission disequilibrium test analysis for the family trios and the case–control analysis were performed using the program UNPHASED. Results.— The allelic and genotypic transmission disequilibrium test analysis did not show any evidence of transmission distortion of the 2 markers in both migraine overall (rs10994336: OR = 1.61, P = .11; rs1006737: OR = 1.12, P = .49) and in the migraine without aura and migraine with aura subgroups. Likewise, the case–control analysis of alleles and genotypes frequencies did not show any evidence of association. Conclusion.— In the present study, we did not find evidence for association between the bipolar disorder risk polymorphisms rs10994336 in the ANK3 gene and rs1006737 in the CACNA1C gene in migraine. However, as these are variants that have a small effect on the risk of bipolar disorder (OR < 1.5), we cannot exclude a similar small effect on migraine susceptibility with the present sample size.     

Increased Dopamine Is Associated With the cGMP and Homocysteine Pathway in Female Migraineurs

( Headache 2010;50:109-116)
Background.— The group of catecholamines, which include dopamine, adrenaline, and noradrenaline, are neurotransmitters which have been considered to play a role in the pathogenesis of migraine. However, the impact of catecholamines, especially dopamine on migraine as well as the exact mechanisms is not clear to date as previous studies have yielded in part conflicting results.
Objective.— This study aimed to produce a comprehensive examination of dopamine in migraineurs.
Methods.— Catecholamines and various parameters of the homocysteine, folate, and iron metabolism as well as cyclic guanosine monophosphate (cGMP) and inflammatory markers were determined in 135 subjects.
Results.— We found increased dopamine levels in the headache free period in female migraineurs but not in male patients. Increased dopamine is associated with a 3.30-fold higher risk for migraine in women. We found no significant effects of aura symptoms or menstrual cycle phases on dopamine levels. Dopamine is strongly correlated with cGMP and the homocysteine—folate pathway.
Conclusion.— We show here that female migraineurs exhibit increased dopamine levels in the headache free period which are associated with a higher risk for migraine.     

Single Nucleotide Polymorphisms of the Serotonin Transporter Gene in Migraine – An Association Study

We report a case–control study with 251 unrelated migraine patients and 192 unrelated healthy controls to evaluate an association between the polymorphisms of the 5‐HT transporter (5‐HTT) gene rs2066713 and rs1979572 and different migraine phenotypes. We found a genetic association for the A allele of rs1979572 for migraine with aura (MA) especially in women as well as a significant lower prevalence for MA for carrier of the A allele of rs2066713 in women. These findings support previous results suggesting that the 5‐HTT gene is involved in the polygenic etiology of MA. These data further suggest that women are more likely to be clinically affected by mutations in the 5‐HTT gene than men.     

Effect of polymorphisms of endothelial nitric oxide synthase on ischemic stroke: a case-control study in a Chinese population

BACKGROUND: Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) plays a key role in vascular regulation and atherosclerosis, therefore, eNOS may be a candidate gene for ischemic stroke (IS). However, it is still controversial whether eNOS polymorphisms are a risk factor for IS. METHODS: Three polymorphisms of the eNOS gene (-922A/G, -786T/C, 894G/T) were determined by using TaqMan SNP genotyping assay in 309 Chinese patients with IS and 309 Chinese controls. RESULTS: The frequency of eNOS -922 G allele was significantly higher in the patients than the controls (12.14% vs 8.09%, P=0.018). The distribution of eNOS genotypes differed insignificantly between the 2 groups. The frequency of the eNOS -786 CC genotype was higher in the patients than the controls (OR=3.819, P=0.029). With respect to -922A/G, the AG+GG genotype increased the risk for IS (OR=1.523, P=0.047). After adjustment for confounding factors, the odds ratios of -786 CC and -922 variant genotype (AG+GG) for IS were 4.580 and 1.656, respectively. However, haplotype analysis revealed the frequencies of Hap4 (GCG) and Hap7 (GCT) were significantly higher in the patients than the controls (P=0.035, 0.042). CONCLUSIONS: eNOS -922A/G and -786T/C may affect the susceptibility to IS and certain haplotypes of the eNOS gene may be associated with a higher susceptibility to IS.     

Incomplete Posterior Circle of Willis: A Risk Factor for Migraine?

Background.— Migraine is associated with vascular risk factors and white matter abnormalities (WMA). Cerebral hypoperfusion is known to be one mechanism underlying WMA and a few studies have shown that an incomplete circle of Willis (CW) may predispose to cerebral hypoperfusion. This study assessed the relationship between the morphologic characteristics of the CW and migraine.
Methods.— This case–control study was carried out in the Amiens University Hospital. Patients undergoing 3-dimensional time of flight magnetic resonance angiography of the CW from January 1 to June 30, 2006 were included (n = 124). A definitive diagnosis of migraine was established in 47 patients: 23 (48.9%) experienced migraine without aura and 24 (51.1%) migraine with aura. The remaining 77 patients with other neurologic disorders constituted the control group. The posterior CW was graded as complete when both posterior communicating arteries and the P1 segments of the posterior cerebral artery were present on visual examination and incomplete when one of these vessels was missing (interobserver agreement: K_total = 0.746).
Results.— Incomplete posterior CW was significantly more common in migraineurs than in the control group (49% vs 18%; P  < .001). On multivariate analysis, incomplete posterior CW was the sole independent factor associated with migraine (OR: 6.5; 95% CI: 2.6-16.2; P  < .001). No difference was found between migraineurs with and without aura.
Conclusions.— Despite some methodological limitations, our results showed that incomplete posterior CW was associated with migraine.     

Acute Confusional Migraine May Be a Presenting Feature of CADASIL

Objective.— Characterize the phenomenon of acute confusional migraine (ACM) among Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients and emphasize the possibility of CADASIL in adults with ACM.
Background.— ACM, well described in children, has rarely been reported in adults. Although 30-60% of CADASIL patients have migraine, acute confusional state during migraine has not been described. We describe 7 patients with ACM that complicated up to 50% of the migraine episodes.
Design/Methods.— Detailed neurologic evaluation was performed in 20 CADASIL patients; International Classification of Headache Disorders 2nd edition criteria were used to diagnose migraine.
Results.— The mean age was 51 years. Fourteen patients reported headache and 11 met the criteria for migraine (mean age of onset 25). Seven patients experienced concomitant confusion, within 3 years of migraine onset. Confusion occurred either abruptly or insidiously, at the onset of aura or headache, lasting for 2-48 hours, and ending abruptly. These episodes were stereotypic, characterized by disorientation with agitation, and retrograde amnesia for the episodes. Patients reported disorientation to time and place, inability to recognize friends and relatives, difficulty with finding directions home, fear of getting lost, inability to analyze traffic lights or tell time. Patients reliably predicted the episodes and felt the need to seek a safe place for protection. Severity of the episodes progressed, but a striking improvement occurred after the first stroke.
Conclusion.— ACM may be a presenting feature and important clue, enabling CADASIL to be recognized up to a decade or earlier than at present. Therefore, a brain MRI and/or testing for Notch3 mutations should be considered in adult patients with ACM.     

Migraine,Migraine Features,and Cardiovascular Disease

(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.     

Seasonal Variation of Migraine in an Arctic Population

Objectives.— To investigate seasonal variation of migraine headache in a population residing in an extreme Arctic locale.
Background.— Exposure to light may trigger migraine attacks and patients may also be hypersensitive to light between the attacks. In previous studies of migraine in Northern latitudes we have demonstrated that patients with migraine experience more attacks in the summer. In order to confirm this finding and gain more insight into a possible north-south effect of seasonal migraine variation, we performed a population-based study in Svalbard, which is one of the northernmost populated areas of the world.
Method.— A postal questionnaire was mailed to all inhabitants aged 12 years or older living in Svalbard and the migraine diagnosis made by a structured telephone interview.
Results.— Of a total of 1569, 1029 (66%) returned the questionnaire. Of them, 184 (18%) experienced headache within the recent year prior to the study that could not be explained by alcohol, trauma, or viral infections. Eighty-eight individuals had migraine according to the revised criteria set by the International Headache Society. Nineteen (22%) reported seasonal variation of migraine. Ten (12%) experienced more migraine in the light season, while 9 (10%) got worse in the dark season. No differences in proportions of migraine with aura (MA) and migraine without aura (MO) could be detected. Also, the frequency of MA patients who used sunglasses to avoid migraine headache was nonstatistically increased compared with MO.
Conclusion.— There was no indication of more seasonal variation of headache in a population of otherwise healthy people with migraine living in an extreme Arctic area with long periods of midnight sun and polar nights with complete darkness. The strength of conclusion, however, is significantly limited by a low response rate and small sample size.     

Decreased collagen-induced platelet aggregation and increased platelet arginine levels in migraine: a possible link with the NO pathway

We studied whole blood platelet aggregation induced by collagen, platelet activating factor (PAF) and measured basal platelet L-arginine (L-arg) levels, as an indirect index of the nitric oxide (NO) pathway in migraine. Migraine, both with and without aura groups, showed a reduced aggregation to collagen, but not to PAF, compared with control subjects. Platelet L-arg levels were significantly increased in migraine with aura sufferers, whereas the plasma levels were in the same range in migraineurs and controls. Platelet hyperesponsiveness to collagen stimulation in migraine may be linked to an increased availability of the amino acid precursor and an abnormal NO synthesis.     

MTHFR 677C>T and ACE D/I Polymorphisms in Migraine: A Systematic Review and Meta‐Analysis

(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.     

Haplotype analysis confirms the association between the HCRTR2 gene and cluster headache

Background.— Several studies suggested that genetic factors play a role in cluster headache (CH) susceptibility. We found a significant association between the 1246 G>A polymorphism of the hypocretin receptor-2 ( HCRTR2 ) gene and the disease. This association was confirmed in a large study from Germany but was not replicated in a dataset of CH patients from Northern Europe.
Objective.— The purpose of this study was to further evaluate the association between CH and the HCRTR2 gene using new polymorphisms, estimating the frequency of different gene haplotypes, searching for gene mutations, and evaluating the effects of the examined polymorphisms on hypocretin binding sites.
Methods.— We genotyped 109 CH patients and 211 healthy controls for 5 new polymorphisms of the HCRTR2 gene and we inferred different gene haplotypes. Complete HCRTR2 sequencing was undertaken for 11 independent CH patients, 5 of whom had a positive family history. The effects of the 1246 G>A polymorphism on the hypocretin binding sites were evaluated using different computer-assisted analyses.
Results.— Three new polymorphisms of the HCRTR2 gene resulted significantly associated with CH. The GTAAGG haplotype resulted more frequent in cases than in controls (OR: 3.68; 95% CI: 1.85-7.67). No point mutation of the HCRTR2 gene was found. Binding analyses showed that the 1246 G>A polymorphism (substitution of valine at position 308 by isoleucine) has no effect on the hypocretin binding sites but could influence the dimerization process of the receptor.
Conclusion.— Our data confirm previous studies suggesting that the HCRTR2 gene or a linked locus significantly modulates the risk for CH. In addition, we suggest that the V308I substitution of the HCRTR2 may interfere with the dimerization process of the receptor, thereby influencing its functional activity.     

Tumor necrosis factor gene polymorphism in migraine

OBJECTIVE: To better define the involvement of human leukocyte antigen region (HLA) genes in migraine via an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with migraine with and without aura. BACKGROUND: Migraine without aura and migraine with aura are disorders involving multiple factors-environmental and genetic. In a previous study, we hypothesized a protective role for the HLA-DR2 antigen, providing additional basis for the proposed genetic heterogeneity between migraine without aura and migraine with aura. The cytokines produced by TNF genes are polypeptide effectors of inflammatory reaction and endothelial function.METHODS: Tumor necrosis factor (TNF)-308 (TNF-308A and TNF-308G alleles) and lymphotoxin alpha (TNFB*1 and TNFB*2 alleles) polymorphisms were analyzed by the NcoI-cleaved polymerase chain reaction-amplified fragments in 47 patients with migraine without aura, 32 patients with migraine with aura, and 101 migraine-free controls.RESULTS: The frequency of TNFB*2 allele was significantly increased in our patients with migraine without aura as compared with the control group (78.72% versus 61.4%, Pc =.004), but no significant differences were found between patients with migraine with aura and controls. Additionally, there was a significant decrease of TNFB*1 homozygotes in patients with migraine without aura compared with the control group (2.13% versus 16.8%, Pc =.0201). Carriage of the TNFB*2 allele confers a high risk for the development of migraine without aura. No significant association was found at TNF-308 polymorphism. CONCLUSION: These data support the hypothesis that lymphotoxin alpha could be a susceptibility gene in migraine without aura and confirm previous data indicating that migraine with and without aura are distinct entities with different genetic backgrounds.     

EDNRA和eNOS基因多态性与动脉瘤性蛛网膜下腔出血预后的相关性

目的 探讨内皮型一氧化氮合酶(eNOS)基因及内皮素受体A型(EDNRA)基因与颅内动脉瘤性蛛网膜下腔出血(aSAH)的预后的相关性.方法 aSAH共60例,详细收集所有患者的一般情况,预后标准采用改良Rankin量表(modified Rankin Scale,mRS)进行评分.应用限制性片段长度多态性聚合酶链反应(PCR-RFLP)方法对EDNRA基因3个多态位点(rs5335、rs6842241、rs6841581位点)及eNOS基因2个多态位点(G-894T、T-786C位点)进行研究,分析上述多态位点基因型及等位基因频率在不同预后病例中的分布.结果 预后良好38例(63.3％),预后差者22例(36.7％).预后良好组与预后差组EDNRA与eNOS基因型及等位基因频率分布差异无统计学意义.结论 在本组病例中,eNOS及EDNRA基因型及等位基因分布与aSAH的预后无明显相关.     

Familial migraine with aura: association study with 5-HT1B/1D, 5-HT2C, and hSERT polymorphisms

BACKGROUND: The serotonergic system has a significant role in the pathophysiology and pharmacology of migraine. OBJECTIVE: To study the association between the occurrence of migraine with aura and 5-HT(1B/1D) and 5-HT(2C) receptor gene and the human serotonin transporter (hSERT) gene polymorphisms in 18 unrelated families with multiple affected members. METHOD: Two polymorphisms in the 5-HT(1B/1D) receptor gene and one polymorphism in the 5-HT(2C) receptor gene were studied by restriction fragment length polymorphism analysis. Allelic variation of the hSERT, with 9, 10, and 12 copies of a "repetitive element," was studied by polymerase chain reaction amplification of the variable number tandem repeat region. RESULTS: Allelic distribution of 5-HT(1B/1D) and 5-HT(2C) receptor gene polymorphisms in affected patients did not differ in either of the control groups (unaffected relatives or unrelated healthy individuals). A trend toward a significant effect of the 12-repeat hSERT allele as a risk factor for migraine with aura versus unrelated controls was observed. CONCLUSION: Our data do not support the involvement of 5-HT(1B/1D) and 5-HT(2C) receptor gene polymorphisms in migraine with aura, yet do suggest a possible role for a locus at or near the hSERT gene in the susceptibility to migraine with aura.     

Expanding Access to Triptans: Assessment of Clinical Outcome

Objective.— To evaluate whether access to more liberal quantities of rizatriptan improves clinical outcome in patients with episodic migraine.
Background.— Currently many pharmacy benefit programs limit the number of triptan tablets/injections per month based on perceived cost savings and the belief that too-frequent use of triptans may lead to medication overuse headache and headache chronification.
Methods.— This observer-blind, randomized, parallel-group study enrolled 197 subjects with migraine with or without aura. Subjects completed a 3-month baseline period to establish migraine frequency and then were randomly assigned to receive 9 (formulary limit [FL]) or 27 (clinical limit [CL]) tablets of 10 mg rizatriptan orally disintegrating tablet (ODT) per month for 3 months. The primary endpoint was change in the mean number of migraine days from the baseline to treatment period.
Results.— There was no statistically significant difference between the FL and CL groups in mean number of migraine days (FL-CL LS mean: −0.08 [−0.39, 0.23]; P  = .613). Subjects in the CL group treated attacks at lower headache severity. No CL subjects were reported to have developed chronic migraine despite utilization of greater than 10 rizatriptan ODT tablets per month. Rizatriptan was generally well tolerated by both groups.
Conclusion.— Providing a greater quantity of rizatriptan ODT 10 mg did not reduce the number of migraine days compared with providing 9 tablets per month for this population with episodic migraine with a frequency of 3-8 migraines per month. Regardless of quantity provided, rizatriptan was generally well tolerated.     

Migraine and prothrombotic genetic risk factors

It has been suggested that during attacks of migraine both platelet activation and plasma coagulability are increased. We investigated the prevalence of several prothrombotic genetic risk factors in patients with migraine: factor V R/Q 506, factor II 20210 G/A, decanucleotide insertion/deletion in the factor VII promoter, and the platelet HPA-1 and HPA-2 alloantigenic systems, by genotypic identification in an age- and sex-matched case-control study including 106 patients with migraine (49 with aura, and 57 without aura). The prevalence of all genotypes was similar among case patients and controls. No association in relation to the type of migraine was detected in the factor II, factor VII, HPA-1, or HPA-2 polymorphisms. Our results showed a high prevalence of factor V Leiden in those patients with migraine with aura (6.1%), though that association was not statistically significant. The studied prothrombotic genetic factors do not seem to be associated with the development of migraine and, therefore, are not likely relevant in the previously reported hypercoagulability and platelet hyperaggregability in this disease.