Glutathione S-transferase polymorphisms: susceptibility to migraine without aura

Migraine is considered to be a polygenic multifactorial disease with various environmental and genetic etiologies. We investigated glutathione S-transferase (GST) P1 Ile(105)Val, T1 and M1 polymorphisms in 174 Japanese headache sufferers and 372 Japanese controls. The headache group consisted of 38 cases of migraine with aura, 95 migraine without aura (MWOA) and 41 tension-type headache sufferers. The M1 homozygous deletion genotype was significantly higher in MWOA (64%) compared with controls (46%; p < 0.01; odds ratio = 2.18, 95% confidence interval: 1.32-3.61, adjusted for age and gender). In a comparison of the current smokers, the M1 null frequencies in MWOA were further increased. GSTM1 may be one of the genetic risk factors for MWOA in the Japanese population.     

Angiotensin-converting enzyme gene deletion polymorphism determines an increase in frequency of migraine attacks in patients suffering from migraine without aura

Many authors have reported an association between the angiotensin-converting enzyme (ACE)-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Previous reports showed an association between migraine without aura and ACE-D allele polymorphism. The study is aimed to evaluate if the DD genotype could also be associated with the frequency and duration of migraine without aura. In 302 patients suffering from migraine without aura (at least for 1 year), with no history of cardiovascular diseases and major risk factors for ischemic events, the genotypes of the ACE gene, plasma ACE activity, and the frequency (weekly) and duration of migraine attacks were evaluated. No drugs were given before (4 weeks) and during the study. The same evaluations were performed in 201 subjects without migraine. The molecular biologist and the physician evaluating the patient data were blinded to the clinical history and ACE-DD gene determination. Genotypes were determined by polymerase chain reaction amplification. Plasma ACE activity was performed by the HPLC method. The groups were similar for sex, age and smoking habit (migraines: 302 patients (200 F/102 M), mean age 37.8 +/- 8.2 years; control: 201 subjects (127 F/74 M), mean age 37.5 +/- 9.3 years). Patients with migraine without aura showed higher incidence of the ACE-DD gene (48.34%) than control subjects (37.32%), p < 0.05. The frequency of migraine (average attacks per week) was higher in patients with DD (2.11 +/- 1.9) than in patients with ID (1.54 +/- 1. 44), p < 0.05. No difference in duration of migraine attacks (hours per week) was observed. Plasma ACE activity was increased in patients with the ACE-DD gene. Our data suggest that ACE-DD gene polymorphism could have an important role in determining migraine attacks and the frequency of these attacks. Further data are needed through further studies, especially on the biomolecular level.     

Involvement of the CACNA1A gene containing region on 19p13 in migraine with and without aura

OBJECTIVE: To assess the involvement of the 19p13 familial hemiplegic migraine (FHM) locus in migraine with and without aura. BACKGROUND: Migraine with and without aura are likely to be polygenetic multifactorial disorders. FHM is a rare dominantly inherited type of migraine with aura. In about 50% of families, FHM is caused by mutations in the P/Q-type calcium channel alpha(1A)-subunit (CACNA1A) gene on chromosome 19p13. The CACNA1A gene is thus a good candidate gene for "nonhemiplegic" migraine with or without aura. METHODS: The authors performed an affected sibpair analysis using flanking and CACNA1A intragenic markers. The authors assessed the occurrence of shared parental marker alleles among 189 affected siblings from 36 extended families with typical migraine with or without aura. RESULTS: Sibling pairs with any form of migraine had inherited the same 19p13 CACNA1A-containing region significantly more frequently than expected by chance (maximum multipoint lod score = 1.22). This result was almost exclusively dependent on the increased sharing found in sibling pairs with migraine with aura (maximum multipoint lod score = 1.41). The locus-specific relative risk for a sibling (lambda(s)) to suffer from migraine with aura, defined as the increase in risk of the trait attributable to the 19p13 locus, was lambda(s) = 1.56. When combining migraine with and without aura, lambda(s) was 1.22. CONCLUSIONS: The increased allele sharing in the CACNA1A gene region on 19p13 is consistent with an important involvement of this region in migraine, especially migraine with aura.     

Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1

Migraine is the most common type of chronic episodic headache. To find novel susceptibility genes for familial migraine with and without aura, a genomewide screen was performed in a large family from northern Sweden. Evidence of linkage was obtained on chromosome 6p12.2-p21.1, with a maximum two-point lod score of 5.41 for marker D6S452. The patients with migraine shared a common haplotype of 10 Mb between markers D6S1650 and D6S1960.     

STin2基因多态性与偏头痛关联性研究

目的 探讨中国东北地区汉族人群中5-羟色胺转运体基因STin2多态性与偏头痛遗传易感性关系.方法 研究对象包括150例偏头痛患者(其中无先兆偏头痛M0 111例,有先兆偏头痛MA 39例)及105例正常对照.详细记录临床资料,提取DNA.运用多聚酶链式反应和电泳分析技术,检测偏头痛组及对照组STin2基因多态性,并比较两组基因型及等位基因频率.结果 偏头痛组STin2基因型总体分布与对照组相比无显著性差异(x2=5.509,df =2,P=0.064),但MO患者STin2.12/12基因型频率为45.9％,对照组为31.4％,两者比较有统计学意义(x2 =4.785,df=1,P=0.036),STin2.9等位基因在MA患者中有增加的趋势(MA组为5.1％,而对照组为0.9％).结论 STin2.12/ 12基因型可能增加偏头痛发病风险.     

Association between a 19 bp deletion polymorphism at the dopamine beta-hydroxylase (DBH) locus and migraine with aura

Migraine is a debilitating neurological disorder, affecting 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is unclear. Our previous work has investigated dopamine related migraine candidate genes and has reported a significant allelic association with migraine of a microsatellite localised to the promoter region of the dopamine beta-hydroxylase (DBH) gene. The present study performed an association analysis in a larger population of case-controls (275 unrelated Caucasian migraineurs versus 275 controls) examining two different genetic DBH polymorphisms (a functional insertion/deletion promoter and a coding SNP A444G polymorphism). Although no significant association was found for the SNP polymorphism, the results showed a significant association between the insertion/deletion variant and disease (chi(2)=8.92, P=0.011), in particular in migraine with aura (chi(2)=11.53, P=0.003) compared to the control group. Furthermore, the analysis of this polymorphism stratified by gender, revealed that male individuals with the homozygote deletion genotype had three times the risk of developing migraine, compared to females. The DBH insertion/deletion polymorphism is in linkage disequilibrium with the previously reported migraine associated DBH microsatellite and this insertion/deletion polymorphism is functional, which may explain a potential role in susceptibility to migraine.     

无先兆偏头痛的神经影像学研究进展

无先兆偏头痛是常见原发性头痛,不断的反复发作可能增加心、脑血管疾病患病的风险, 或增加某些脑区细微病变的风险,并有可能导致某些大脑区域的神经功能损伤,对患者的生活质量造 成严重影响,现对无先兆偏头痛的神经影像学研究进展进行阐述,旨在为无先兆偏头痛的临床诊断提 供影像学的帮助。     

Precipitating factors of migraine attacks in patients with migraine without aura

To study the distribution of triggers of migraine in a selected population, 100 patients who fulfilled the diagnostic criteria for migraine without aura as proposed by the International Headache Society were evaluated by means of a personal interview. Stress was the most cited trigger, triggering migraine in 76%. Afterwards, in descending order of frequency, were cited sensorial stimuli (75%), sleep deprivation (49%), hunger (48%), environmental factors (47%), food (46%), menses (39%), fatigue (35%), alcohol (28%), sleep excess (27%), caffeine (22%), physical exertion (20%), head trauma (20%), trips (4%), sexual activity (3%), medications (2%), neck movements (2%), smoking (1%) and the use of a low pillow (1%). It is concluded that certain factors seem to play an important role in the triggering of migraine.     

Comparison of cortical excitability in chronic migraine (transformed migraine) and migraine without aura. A transcranial magnetic stimulation study

We studied the excitability of the motor cortex in patients with migraine without aura (MWOA) (n = 20) and with chronic migraine (CM) (n = 20) using transcranial magnetic stimulation (TMS). By using a 90-mm circular coil placed over the vertex and recording of the first dorsal interosseous muscle, we measured thresholds, latencies and amplitudes of motor evoked potentials and duration of cortical silent periods in patient groups and in controls (n = 20). No differences were found between groups for threshold, latency and amplitude values. However, the duration of the cortical silent period was longer in CM patients, being significantly different from both controls and MWOA. We suggest that either this difference in cortical excitability may develop during transformation from MWOA to CM or different pathophysiological mechanisms may play a role in these two headache syndromes. Received: 28 December 2001, Received in revised form: 19 March 2002, Accepted: 21 March 2002     

Variation of the serotonin transporter gene SLC6A4 in the susceptibility to migraine with aura

To replicate a reported association between migraine with aura (MA) and a promoter polymorphism in the serotonin transporter gene (SLC6A4), we performed a case-control study in a large German sample comprising 472 patients with MA and 506 controls. Neither this polymorphism nor a systematic analysis with single nucleotide polymorphisms capturing the main haplotype diversity of the SLC6A4 locus provided evidence for a contribution of SLC6A4 to the predisposition of complex inherited MA.     

中国南方人偏头痛CACNAlA基因多态性相关研究

研究目的:通过检测偏头痛患者和FHM家族外周血CACNAlA基因三个常见的突变位点,分析探讨中国南方人FHM与CACNAlA基因突变之间的关系。2.方法:采用SSCP方法对2个FHM家族10个受试者及12个无症状亲属和53个无FHM家族史的有先兆偏头痛及10个健康对照的外周血标本进行检测,分析CACNAlA基因的三个常见突变位点(T666M、R583Q和D715E)在FHM家族中的表现形式。3.结果:CACNAlA基因三个常见的突变T666M、R5830和D715E在2个FHM家族10个受试者12个无症状亲属和53个无FHM家族史的有先兆偏头痛及10个健康对照中均未检测到。4.结论:在中国人FHM家族中未发现有T666M、R583Q和D715E三个突变。FHM以及有先兆偏头痛与CACNAlA基因的相关性有待进一步研究。     

Evaluation of placebo use in migraine without aura, migraine with aura and episodic tension-type headache acute attacks

This study presents an evaluation of placebo response in the acute treatment of migraine with or without aura and episodic tension type headache. We studied patients admitted between March 1st,1997 and November 31st,1999 in two Emergency Room Units. Three groups had been defined, each one with 30 participants: migraine without aura (MWOA), migraine with aura (MWA) and episodic tension-type headache (ETTH). Patients were participating of a randomized study to evaluate efficacy of 4 different drugs; those randomized to receive placebo were included. We evaluated pain and associated symptoms. After one hour of placebo administration, 50% of MWOA patients, 23.3% of MWA and 26.7% of ETTH had presented pain relief. The mean of this relief, evaluated by the numerical pain scale, was 41.6%, 23.1% and 36%, respectively. Use of placebo is essential in evaluating the therapeutic role of drugs used in the treatment of acute headache.     

A study of symptomatic drug use in migraine without aura

We assessed the attack drugs taken by 200 migraine without aura patients (International Headache Society criteria, 1988) between 1989 and 1991. A detailed pharmacological history regarding the acute attack therapy adopted up until our initial visit was gathered, including the type of drug used, dosage, administration route, the time of starting therapy, treatment efficacy, and the frequency and types of undesirable effects, all of which were subsequently compared with the guidelines (1993) of the Italian Society for the Study of Headache (SISC). The most commonly used are non steroidal anti-inflammatory drugs (NSAIDs). We observed a similar high frequency in the use of combinations, particularly prophyphenazone and barbituric acid. The pirazolones, such as noramidopyrine and prophyphenazone, are also widely used as single agents, even though they are not considered by the guidelines. Our study underlines the fact that current drug use differs in several respects from the guidelines.

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Sommario Abbiamo esaminato il trattamento farmacologico dell'attacco acuto, usato da 200 pazienti sofferenti di emicrania senza aura (criteri IHS 1988), visitati nel periodo 1989–1991. È stata raccolta una dettagliata analisi farmacologica sulle terapie d'attacco usate dai pazienti nel corso della loro storia cefalalgica precedentemente alla prima visita presso il nostro ambulatorio. Sono state studiate le seguenti variabili: tipo di farmaco usato, dosaggio e via di somministrazione, efficacia del trattamento, frequenza e tipo degli effetti indesiderati; questi parametri sono stati confrontati con le linee guida della Società Italiana per lo Studio delle Cefalee (SISC, 1993). I farmaci più comunemente usati sono gli antiinfiammatori non steroidei; abbiamo osservato un analogo uso delle associazioni, in particolare propifenazone ed acido barbiturico. I pirazolonici propifenazone ed amidopirina, non consigliati nelle linee guida, sono anch'essi largamente usati. Il nostro studio evidenzia il fatto che l'utilizzo corrente dei farmaci differisce in molti aspetti da quello suggerito dalle linee guida.

     

Genetic TPH2 variants and the susceptibility for migraine: association of a TPH2 haplotype with migraine without aura

The serotonergic system plays a major role in the etiology of migraine. The rate-limiting enzyme in serotonin homeostasis and availability is tryptophan hydroxylase (TPH). The TPH2 isoform is responsible for the cerebral serotonin biosynthesis. To investigate the role of genetic variation in TPH2 in the pathogenesis of migraine eight haplotype tagging SNPs covering the whole TPH2 gene where chosen using Haploview and genotyped in 503 migraineurs and 515 healthy controls. Association analysis was performed on a single SNP and haplotype basis using χ ² and logistic regression analysis. Single SNP analysis revealed a weak association with migraine, which did not remain after correction for multiple testing. Haplotype analyses revealed association of a haplotype with migraine without aura. Stratification by aura and triptan response did not reveal a positive association with the investigated polymorphisms. These results suggest a possible influence of genetic variation in TPH2 in the pathogenesis of migraine.     

TCD发泡试验对西宁地区无先兆性偏头痛与右向左分流的相关性研究

目的 探究经颅多普勒(TCD)发泡试验对地处中高海拔的西宁地区无先兆性偏头痛患者右向左分流(RLS)发生率的检测作用.方法 选取2018年11月至2020年7月西宁市第一人民医院收治的偏头痛患者273例(观察组),同期健康体检者200例(对照组),均进行TCD发泡试验,观察RLS的发生率.结果 观察组RLS阳性107例...     

New international classification of migraine with aura (ICHD-2) applied to 362 migraine patients

The International Classification of Headache Disorders 2nd edition (ICHD-2) subdivides migraine with aura (MA) differently from the ICHD-1 and includes new diagnostic criteria. The aim of the present study was to evaluate how the new classification works in practice and in comparison with the ICHD-1. The patients were recruited from a screen of the Danish National Patient Registry and from Danish neurologists. We included 362 patients diagnosed with MA according to the ICHD-1 in a validated semistructured physician-conducted interview. According to the ICHD-2, 89% (322 of 362) had MA and 11% (40 of 362) had probable MA. The MA patients had one or more ICHD-2 subtype of MA: 54% (173 of 322) had typical aura with migraine headache (MA-MH), 40% (129 of 322) had typical aura with non-migraine headache (MA-NMH), 37% (120 of 322) had aura without headache (MA-WOH), and 7% (26 of 322) had basilar-type migraine (MA-B). Of patients with MA-MH 34% (59 of 173) had co-occurrence of MA-WOH, 9% (16 of 173) had co-occurrence of MA-B and 5% (8 of 173) had co-occurrence of both MA-WOH and MA-B. Of patients with MA-NMH 27% (35 of 129) had co-occurrence of MA-WOH. Only 6% (18 of 322) of the MA patients had exclusively MA-WOH and <1% (2 of 322) had exclusively MA-B. Patients with MA-MH had an earlier age at onset (P = 0.044), an increased lifetime number of MA attacks (P = 0.054) and a higher co-occurrence of migraine without aura (P = 0.002) than patients with MA-NMH. Patients with MA-B tended to have an earlier age at onset and more severe attacks and patients with MA-WOH had a higher age at onset and less severe attacks than patients with MA-MH. The variations between ICHD-2 subtypes of MA indicate that patients with similar subtype of MA share phenotype and very likely have similar underlying aetiology.