Frequency of Factor V Leiden in Juvenile Migraine With Aura

Patients with migraine are known to be at risk for stroke. It has been reported that in a group of patients with cerebral ischemia and the Leiden mutation of factor V, 67% had classical migraine. We have studied the frequency of this mutation in a group of Italian children and adolescents affected by migraine with aura.
The Leiden mutation was detected in 2 (3.5%) of 57 patients and in 8 (3.7%) of 219 controls. The 2 patients carrying the mutation had no peculiar characteristics as compared with the rest of the migrainous population. In our study, the frequency of the Leiden mutation in patients was not different from that of controls. These data contrast with those collected in the Finnish population and in a group of northwestern Italian adult patients, but agree with results previously reported from The Netherlands.     

Screening for genetic and acquired thrombophilia in a cohort of young migrainous patients

Abstract Growing evidence suggests a possible relationship between migraine and thrombotic risk factors. The aim of this study was to analyze the possible relationship between migraine and acquired and genetic thrombophilia in a young population. We compared 16 migrainous adolescents, 12 children with tension-type headache, and controls in terms of frequencies of prothrombotic polymorphisms (factor V Leiden, C677T mutation of 5,10 methylenetetrahydrofolate reductase, G20210A mutation of prothrombin), platelet aggregability, anticoagulant antibodies, blood lipid pattern, serum folate and vitamin B12 levels, homocysteinemia, coagulation parameters, and family history for migraine and precocious thrombotic events. This study confirms the link between migraine and increased platelet responsiveness. Overall, 62.5% of migrainous patients carried at least three thrombophilic factors. Our preliminary data suggest that, in order to assess prevention strategies, it could be appropriate to perform a complete thrombophilia screening in young patients suffering from migraine and with a family history of thrombosis.     

Leukocyte mitochondrial DNA A to G polymorphism at 11084 is not a risk factor for Japanese migraineurs

Mitochondrial dysfunction has been reported in patients with migraine. We investigated leukocyte mitochondrial DNA 11084 A to G polymorphism in 166 Japanese migraineurs and 483 Japanese controls. The migraine group consisted of 43 patients suffering from migraine with aura (MWA) and 123 from migraine without aura (MOA). The frequency of the transition was 7.2% (12/166) in the migraine group and 7.3% (35/483) in the controls. The frequency of the transition was 4.7% in MWA and 8.1% in MOA. There was no significant difference among the groups (chi-square test). The mitochondrial DNA 11084 A to G transition was more common in Japanese subjects than reported in Caucasians; however, this polymorphism is not a genetic risk factor for migraine in Japanese patients.     

正常人和血栓性疾病患者抗活化的蛋白C现象和FⅤLeiden的研究

目的：研究抗活化的蛋白Ｃ（ＡＰＣＲ）现象和凝血因子Ⅴ基因突变（ＦⅤＬｅｉｄｅｎ）在我国健康人群中的发生情况及在血栓病发病机制中的作用。方法：用活化部分凝血活酶时间（ＡＰＴＴ）为基础的ＡＰＣＲ法检测了武汉健康对照组３２名、武汉血栓病患者３８例和德国洪堡血栓病患者１０６例，并对武汉１２例及洪堡１０６例血栓病患者进行了ＦⅤ基因分析。结果：ＡＰＣＲ发生率正常对照组为３．１％，武汉病例组为７９％，洪堡病例组为２２．６％；前两组间无显著差异（Ｐ＞０．０５），洪堡病例组显著高于前两组（Ｐ＜０．０５），其中４５．８％患者（１１例）存在ＦⅤＬｅｉｄｅｎ。结论：ＡＰＣＲ和ＦⅤＬｅｉｄｅｎ的发生存在着地区、种族差异，在中国人中，ＦⅤＬｅｉｄｅｎ可能不是引起ＡＰＣＲ的主要原因。     

Prevalence of vertigo, dizziness, and migrainous vertigo in patients with migraine

OBJECTIVE: The aim of this study was to determine the lifetime prevalence of vertigo and dizziness in patients with migraine as compared with controls and to establish the lifetime prevalence of migrainous vertigo. BACKGROUND: Dizziness and vertigo are relatively frequent complaints in general population; however, the prevalence of migrainous vertigo has not been extensively studied so far. METHODS: The study included 327 migraine patients and 324 controls who do not suffer from frequent headaches. The study and control group were assessed clinically and through diagnostic workup for having vertigo, dizziness, hypotension, and sideropenic anemia. RESULTS: Vertigo or dizziness was experienced by 51.7% of migraine patients (MVL group) and 31.5% in the control group (CVL group), P < .0001. Among the MVL group, 23.2% of patients met the criteria for migrainous vertigo. There was no difference between the MVL group and CVL group in frequency of attacks or the pattern of symptom appearance in relation to head movement. Patients in the MVL group more frequently had hypotension, P = .011. Patients with migraine with aura significantly more often had migraine attacks in association with vertigo or dizziness, P < .0001. CONCLUSION: The lifetime prevalence of migrainous vertigo is relatively frequent in migraine patients, especially in migraine with aura.     

Vertigo, Motion Sickness and Migraine

SYNOPSIS
The frequency of vestibular symptoms in 104 headache patients during the headache-free phase was studied. The group was comprised of 84 patients with migraine (24 classical and 60 common) 12 with tension and 8 with cluster headache. Fifty-four headache-free subjects served as controls. All the participants filled out a vestibular symptom questionnaire.
Patients with classical migraine reported significantly more vestibular symptoms than the controls. Specifically they had more dizzy spells (r = 0.002) and vertigo episodes (r = 0.01) not associated with the headache. They also had more frequent motion sickness spells. Of the classical migraine patients reporting motion sickness 87% experienced it at least once in 6 weeks compared to only 11% of the controls. Classical migraine patients also probably have an especially "sensitive" vestibular system, as evidenced by increased tendency to visual vertigo (r = 0.005) and significantly increased dizziness when they themselves were spinning.
The common migraine patients showed a tendency to vestibular impairment that was not statistically significant. Recent findings of vestibular function abnormalities in this group may suggest an evolving dysfunction that is not yet symptomatic. Patients with tension and cluster headache did not differ from the controls in all the vestibular symptoms studied.
In summary, our findings indicate clearly a vestibular impairment in classical migraine. The relation to "benign recurrent vertigo," problems in the relationship of the occurrence of motion sickness to migraine and the possible mechanism causing the vestibular dysfunction are discussed.     

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.     

Familial occurrence of migraine with aura in a population-based study

OBJECTIVE: To better define a possible genetic basis for migraine with aura (MWA). METHODS: We investigated the familial occurrence of migraine with aura in a sample of (MWA) subjects recruited from an epidemiologic study of migraine with aura involving the general population. The sample with migraine with aura (n = 26) was selected out of a total of 1392 subjects (842 women and 550 men) representative of the general population aged 18 to 65 years in the southern Italian town of San Severo. A family history of migraine with aura was determined via direct interviews with all living first-degree relatives of the 26 subjects who could be reached by investigators, 119 people: 71 women and 48 men. The diagnosis of migraine with aura was made according to the 1988 International Headache Society (IHS) criteria. RESULTS: Of the 26 subjects with migraine with aura, 7 (6 women and 1 man) had a positive family history, with a total of 7 first-degree relatives affected by the disease (1 mother, 2 fathers, 1 brother, 1 sister, and 2 children). Based on the lifetime prevalence rate of migraine with aura (1.6%) in the San Severo general population, the relative risk of migraine with aura in the first-degree relatives of the subjects was 3.68 (4.16 for women and 2.77 for men). CONCLUSION: Our subjects' relative risk rate for familial occurrence of migraine with aura was similar to that reported by one investigator, but markedly lower than that reported by another group.     

Quality of life in young Italian patients with primary headache

OBJECTIVE: To compare the quality of life of young Italian patients with headache with that of the juvenile Italian population free of chronic disease. METHODS: The Quality of Life Headache in Youth (QLH-Y) Questionnaire developed by Dutch investigators was translated into Italian and validated in a young Italian population. The forward/backward translation and, for psychometric testing, the factor analysis and Cronbach coefficient alpha were used. A new instrument (Questionnaire for Young Subjects Affected by Primary Headache) was developed to assess psychological, physical, and social functioning and functional status and was used to compare the quality of life of the patients with headache with that of headache-free controls. For psychometric testing (via the questionnaire), we selected a sample of 394 subjects (178 males and 216 females, aged 10 to 18 years): 320 subjects from three schools of North Italy and 74 patients with headache from the Paediatric Headache Center of Padua. In the latter group, 48 patients had tension-type headache and 26 had migraine without aura, according to the International Headache Society diagnostic criteria. RESULTS: The data derived from the comparison of 84 headache-free subjects (control group) and the 74 young patients with headache confirmed that primary headache negatively influenced the latter's quality of life: patients scored significantly (P<.05) lower on psychological, physical, and social functioning than the headache-free controls. CONCLUSIONS: Quality of life is compromised significantly in young patients with primary headache disorders. The questionnaire used in this study is a valid and reliable self-administered instrument that may facilitate clinical research in headache.     

Association between migraine and HLA–DRB1 gene polymorphisms

We examined the distribution of HLA–DRB1 alleles in a cohort of 255 Italian migraine patients and in a control group of 325 healthy subjects. The frequency of DRB1*12 allele was found to be significantly reduced (p=0.02) in patients with migraine while the DRB1*16 allele was significantly increased (p=0.04) in comparison with controls. When the patients were divided into disease subgroups (migraine with and without aura), HLA–DRB1**16 allele was significantly increased (p<0.05) only in migraine without aura patients. We conclude that, in Italian patients, migraine is associated with different alleles of the HLA–DRB1 locus. Our data suggest the presence of a genetic susceptibility factor for migraine within the HLA region.     

Platelet Antibodies in Patients With Migraine

The reported decrease of platelet serotonin receptors in patients with migraine could be due to an autoimmune reaction. We, therefore, examined sera from 42 migraineurs without aura, 26 migraineurs with aura, and 107 headache-free blood donors for platelet-reactive antibodies using the platelet adhesion immunofluorescence test, the NIH-lymphocytotoxicity test, and the monoclonal antibody-specific immobilization of platelet antigens test. IgG antibodies against non-HLA class I platelet antigens were found in 9.5% of patients with migraine without aura, 7.6% of patients with migraine with aura, and in 7.5% of controls; IgM antibodies were found in 11.9% of patients with migraine without aura, in 30.8% of patients with migraine with aura, and in 13.1% of controls. Most antibodies ware directed against glycoprotein complexes IIb-IIIa (fibrinogen receptor) or IB-IX (thrombin receptor). Two patients with migraine without aura but no patient with migraine with aura nor any control subject had IgG antibodies of unknown specificity. One patient (2.4%) with migraine without aura and two patients (7.7%) with migraine with aura, as well as 2 controls (1.9%) had IgM antibodies not further specified. The differences in frequency of platelet antibodies of known or unknown specificity in patients with migraine without aura and migraine with aura and controls were not statistically significant. Therefore, our data do not support the hypothesis of a pathophysiologically relevant autoimmune reaction against platelet serotonin receptors in the majority of patients with migraine. We can not exclude the occurrence of antibodies against neuron-specific serotonin receptors.     

Evaluation of a highly specific functional test for the detection of factor V Leiden

In the present study, a new functional test for the detection of increased resistance of coagulation factor V to degradation by activated protein C (factor V Leiden mutation) was evaluated. The STA-STACLOT APC-R Test (Diagnostica Stago, Asnieres, France) is based on the specific activation of factor X by Crotalus viridis helleri snake venom. The results are given as clotting time in seconds of the patient's plasma in the presence of venom and activated protein C. The intra-assay coefficient of variation was 2.17% (n=20) for samples within the normal range, and 1.70% and 1.42% (n=20) for the plasma of a heterozygous or a homozygous carrier of the factor V Leiden mutation, respectively. The inter-assay coefficient of variation (n=10) was 7.75% for the plasma of a healthy donor, 5.05% for the plasma of a heterozygous carrier and 3.38% for the plasma of a homozygous individual. The normal range (5th-95th percentile) of 136.4 s-174.7 s was derived from the clotting time of the plasma of 38 healthy controls. Values below 136 s were found in every sample from patients carrying the factor V Leiden mutation (n=52), whereas no patient with protein C (n=11) or protein S deficiency (n=10) had reduced clotting times. Homozygous carriers of the factor V Leiden mutation had clotting times shorter than 66.0 s and heterozygous carriers had clotting times longer than 80.0 s. Thus, based upon the individual clotting time, patients homozygous for factor V Leiden mutation could easily be distinguished from normals or heterozygous individuals. The influence of coagulation factor X, V, or II deficiency on the STACLOT APC-R Test was evaluated and revealed prolonged clotting times at factor V activities below 50%. In the presence of lupus anticoagulant the specificity of the STA-STACLOT APC-R Test was clearly decreased. In the present study, we clearly show that the STA-STACLOT APC-R Test is able to discriminate carriers of the factor V Leiden mutation from healthy controls or patients with protein C or protein S deficiency.     

A thromboembolic predisposition and the effect of anticoagulants on migraine

OBJECTIVE: To investigate the presence of thromboembolic risk factors and the effect of low-dose acenocoumarol therapy on migraine in patients who spontaneously reported a reduction of their migraine attacks during previous therapeutic use of anticoagulants. BACKGROUND: The positive effect of anticoagulants on migraine has been described in case reports and observational studies. It remains unclear whether this concerns only a select group of migraineurs with certain common characteristics. METHODS: In 4 migraineurs with a self-reported reduction of attack frequency during previous use of anticoagulants (international normalization ratio [INR], 2.5:4.0), the presence of thromboembolic risk factors and the effect of low-dose acenocoumarol therapy (INR, 1.5:2.0) on migraine attacks were prospectively investigated in an open study. RESULTS: All patients had one or more thromboembolic risk factors. Two patients, both with factor V Leiden heterozygosity, experienced a clear improvement of migraine during low-dose acenocoumarol therapy. CONCLUSIONS: Our findings support the hypothesis that migraine, as a phenotype, has different underlying mechanisms, amongst which a thromboembolic tendency. In this group of patients, oral anticoagulants may be a suitable form of migraine prophylaxis, but this needs further clinical investigation.     

Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course

The objectives of this study were: (1) to assess relative frequency of migraine in multiple sclerosis (MS) patients using the validated self-administered diagnostic questionnaire, and to compare the migraine rates in MS outpatients to age- and gender-matched historical population controls; (2) to compare clinical and radiographic characteristics in MS patients with migraine and headache-free MS patients. We conducted a cross-sectional study to assess the demographic profiles, headache features and clinical characteristics of MS patients attending a MS clinic using a questionnaire based on the American Migraine Prevalence and Prevention (AMPP) study. We compared the relative frequency of migraine in MS clinic patients and AMPP cohort. We also compared clinical and radiographic features in MS patients with migraine to an MS control group without headache. Among 204 MS patients, the relative frequency of migraine was threefold higher than in population controls both for women [55.7 vs. 17.1%; prevalence ratio (PR) = 3.26, p < 0.001] and men (18.4 vs. 5.6%; PR = 3.29, p < 0.001). In a series of logistic regression models that controlled for age, gender, disease duration, β-interferon use, and depression, migraine in MS patients was significantly associated (p < 0.01) with trigeminal and occipital neuralgia, facial pain, Lhermitte’s sign, temporomandibular joint pain, non-headache pain and a past history of depression. Migraine status was not significantly associated with disability on patient-derived disability steps scale or T2 lesion burden on brain MRI. Migraine is three-times more common in MS clinic patients than in general population. MS–migraine group was more symptomatic than the MS–no headache group.     

The Course of Frequent Episodic Migraine in a Large Headache Clinic Population: A 12-Year Retrospective Follow-Up Study

Background.— Despite its high prevalence, little is known about the clinical course of migraine. Presented here are the findings of a 12-year follow-up study involving patients diagnosed at baseline with frequent episodic migraine.
Objective.— The main objectives were to determine the long-term outcome of patients with frequent episodic migraine and to identify factors predictive of a favorable vs less favorable prognosis.
Methods.— A total of 374 subjects (200 women, 174 men) were selected randomly from a total population of 2812 patients initially diagnosed before December 31, 1996, with episodic migraine and at baseline experiencing 1 to 6 attacks per month. Their subsequent migraine course was evaluated via telephone interviews conducted between 2005 and 2006.
Results.— Migraine attacks had ceased in 110 (29%) of the 374 patients (57 women and 53 men). The remaining 264 subjects continued to experience migraine attacks at follow-up, and a change in attack frequency was reported by 80% (of whom 80% reported fewer attacks). Sixty-six percent reported a change in pain intensity over time, and of these 83% reported milder pain. Only 6 subjects (6/374 = 1.6%) had developed chronic migraine.
Conclusion.— These data from a headache clinic population suggest that migraine has a favorable prognosis in most patients. Whether the findings reflect the natural history of the disorder or interval improvements in headache management remains conjectural.     

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.     

Joint hypermobility syndrome: A common clinical disorder associated with migraine in women

Preliminary studies suggested that headache disorders are more common in patients with joint hypermobility syndrome (JHS). The objectives of this study were to determine if the prevalence, frequency, and disability of migraine differ between female patients with JHS and a control population. Twenty-eight patients with JHS and 232 controls participated in the case-cohort study. Participants underwent a structured verbal interview and were assigned a diagnosis of migraine based on criteria of the International Classification of Headache Disorders, 2nd Edition. The primary outcome measures were the prevalence, frequency, and headache-related disability of migraine. Logistic regression was used for the prevalence analysis and Poisson regression for the frequency and disability analyses. Results indicated that the prevalence of migraine was 75% in JHS patients and 43% in controls. The adjusted odds ratio for the prevalence of migraine was 3.19 (95% CI 1.24, 8.21] in JHS patients. The rate ratios for migraine frequency and headache-related disability were 1.67 (95% CI 1.01, 2.76) and 2.99 (95% CI 1.66, 5.38), respectively, for JHS patients. Our study suggests that JHS is a clinical disorder strongly associated with an increased prevalence, frequency, and disability of migraine in females.     

Inherited prothrombotic risk factors and cerebral venous thrombosis

Fifteen patients with cerebral venous thrombosis were ascertained retrospectively. Their case notes were reviewed, and stored or new blood was assayed for factor V Leiden (FVL) mutation, prothrombin gene mutation 20201A, and 5,10 methylene tetrahydrofolate reductase (MTHFR) C677T mutation. A clinical risk factor was identified in 13 patients--the oral contraceptive pill (5), puerperium (1), HRT (1), mastoiditis (1), dehydration (1), lumbar puncture and myelography (1), carcinoma (1), lupus anticoagulant (2). In addition, two patients had the FVL mutation and five (one of whom also had the FVL mutation) were homozygous for the MTHFR mutation. The latter showed a higher than expected frequency compared to 300 healthy controls from South Wales (OR 3.15.95% Cl 1.01-9.83). No patient had the prothrombin 20201A mutation. Two patients died and three had a monocular visual deficit following anticoagulation (13) or thrombolytic (2) treatment, but there was no association between the presence of a primary prothrombotic risk factor and outcome. These results confirm the importance of investigating patients for both clinical predisposing factors and primary prothrombotic states.     

EEG and Topographic Frequency Analysis in Common and Classic Migraine

Electroencephalographic (EEG) changes occurring in patients with migraine have received much attention. However, almost equal number of reports indicate the predominance of normal and abnormal findings. We studied the EEG in symptom-free, otherwise healthy, unmedicated 18-28 year-old patients: 22 with common migraine, 20 with classic migraine, and 20 age-matched controls. The routine EEG findings in the three groups revealed mild non-specific slowing in 2 (9%), 3 (15%) and 2 (10%), respectively. Simultaneously, topographic EEG mapping and frequency analysis were performed in 13 consecutive patients with common migraine, 10 patients with classic migraine and 11 age-matched controls. EEG mapping showed minimal regional differences with lower power in the alpha range in patients with eyes closed. The peak alpha power, as well as its reactivity, were lower among patients than controls. This difference reached statistical significance only for patients with classic migraine versus controls in the left occipital region. Patients also had slightly faster peak alpha frequency. No frank right-left asymmetry was observed in the peak alpha power, neither among the controls, nor the patients. All the findings were rather minor. They may suggest some difference in the posterior background activity in the EEG in migraine patients as compared to the controls, but are not useful in differentiating migraine from non-migraine patients.     

ICE CREAM HEADACHE AND ORTHOSTATIC SYMPTOMS IN PATIENTS WITH MIGRAINE

SYNOPSIS
Migraine is arbitrarily defined; biological markers for the condition are needed. Two stereotyped phenomena which may be manifestations of central vasomotor instability have been studied in migraineurs and in control subjects. These phenomena are (1) "ice cream headache", the brief frontal pain that results from cold food contacting the roof of the oropharynx and (2) the presence of vertigo, visual obscurations, and/or scintillating scotomata following rapid postural shifts of the head.
Hospitalized (non-neurologic) patients (60 women, 48 men) were interviewed regarding the presence, quality, and intensity of the two phenomena. A history of headache was then elicited in some detail. The headache histories were assessed by the usual arbitrary criteria for migraine; this was done by an independent observer without knowledge of the presence of ice cream headache or postural symptoms. In the non-headache, control population (49), 31% had experienced mild ice cream headache; in the migraine group (59), 93% had experienced ice cream headache (p<.001), usually (77%) as a moderate to severe discomfort. Half of the migraineurs took precautions when ingesting cold foods. Of the controls, 8% had brief vertigo or lightheadedness with rapid postural shifts; postural symptoms were present in 68% of the migraine group (p>.001), most of whom (75%) reported that scintillating scotomata accompanied vertigo. Both syndromes occurred more regularly and more prominently in the migraine population.