Sporadic hemiplegic migraine is an aetiologically heterogeneous disorder

In order to better understand sporadic hemiplegic migraine (SHM) and particularly its relation to familial hemiplegic migraine (FHM), migraine without aura (MO) and typical migraine with aura (typical MA), we investigated the occurrence of MO and typical MA among probands with SHM and their first-degree relatives. The pattern of familial aggregation of MO and typical MA was assessed by population relative risk calculations. A total of 105 SHM probands and 483 first-degree relatives were identified in the Danish population. Compared with the general population, SHM probands had no increased risk of MO, but a highly increased risk of typical MA. First-degree relatives of all SHM probands had an increased risk of both MO and typical MA, whereas first-degree relatives of probands with exclusively SHM had no increased risk of MO but an increased risk of typical MA. Our data suggest that SHM is a genetically heterogeneous disorder.     

Migraine without aura and migraine with aura are inherited disorders

The familial occurrence and mode of inheritance were analysed in families with migraine without aura (MO) and migraine with aura (MA). The probands were found among 4000 persons from the general population. All persons with MA were included as probands, and an equivalent number of probands with MO was selected as a random sample among those with MO. Spouses and first-degree relatives were blindly interviewed. All interviews were performed by one neurological research fellow. The distinct familial patterns indicate that MO and MA have a different aetiology. Compared with the general population, the first-degree relatives of probands with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold increased risk of MO, indicating that both genetic and environmental factors are important in MO. The first-degree relatives of probands with MA had a four-fold increased risk of MA while spouses had no increased risk of MA, indicating that MA is determined largely by genetic factors. The complex segregation analysis indicate that both MO and MA have multifactorial inheritance without generational difference.     

Migraine without aura and migraine with aura are distinct disorders. A population-based twin survey

OBJECTIVE: To investigate the co-occurrence of migraine without aura (MWOA) and migraine with aura (MWA) in a population-based twin survey. BACKGROUND: Migraine without aura and MWA are multifactorial disorders. If MWOA and MWA share common genes, co-occurrence should be observed more frequently than expected, ie, the product of the prevalence in the general population. MATERIAL AND METHODS: The study population included all living Danish monozygotic (MZ) and same-gender dizygotic (DZ) twin pairs born between 1953 and 1960: 5360 twins (2026 MZ, 3334 DZ). The sample included 2840 men and 2520 women. All received a posted questionnaire, and those with possible migraine were interviewed via telephone by trained physicians (V.U. or M.G.). Twins who did not respond to the questionnaire and who had a co-twin with possible migraine were contacted by telephone. The questionnaire response rate was 87% (4660 of 5360), and the telephone interview was participated in by 90% (2035 of 2272). The physician interviewers were unaware of questionnaire answers, zygosity, and the clinical diagnosis of the co-twin. The criteria of the International Headache Society were used to establish a diagnosis of migraine. RESULTS: Lifetime prevalence in the twin sample: 7% of men and 19% of women had MWOA, while 7% of men and 8% of women had MWA. Lifetime prevalence of MWA in twin pairs with MWOA: MZ men, 2% (1 of 47); MZ women, 6% (5 of 90); DZ men, 9% (7 of 75); and DZ women, 10% (19 of 182). Lifetime prevalence of MWOA in twin pairs with MWA: MZ men, 3% (1 of 33); MZ women, 5% (3 of 58); DZ men, 9% (4 of 44); and DZ women, 13% (10 of 76). The observed and the expected numbers of twins with co-occurrence of MWOA and MWA based on the prevalence in the general population were not significantly different in either men or women (men, P=.1 and women, P=.5). CONCLUSION: The results strongly suggest that MWOA and MWA are distinct disorders, and identification of common genes for MWOA and MWA, thus, should not be expected to result from future genetic research.     

Migrainous disorder and its relation to migraine without aura and migraine with aura. A genetic epidemiological study

Migrainous disorder was analysed in a large population-based study of 4000 forty-year-old males and females. All interviews were conducted by one physician and the diagnostic criteria of the International Headache Society were used. Of the 48 people with migrainous disorder, 40 had migrainous disorder without aura and 9 had migrainous disorder with aura One person had co-occurrence of migrainous disorder with and without aura. The lifetime prevalence of migrainous disorder was 2.5% with a male: female ratio of 1:1.2. The first-degree relatives of probands with migrainous disorder were blindly interviewed. Compared with the general population, first-degree relatives of probands with migrainous disorder without aura had a slightly but less increased risk of migraine without aura than first-degree relatives of probands with migraine without aura. First-degree relatives of probands with migrainous disorder with aura had no increased risk of migraine with aura. We conclude that migrainous disorder without aura in some people is a type of migraine without aura and in other people not. Migrainous disorder with aura may be unrelated to migraine with aura.     

Genetics in primary headaches

This tutorial describes different methods and results of genetic studies of primary headaches. A positive family history is imprecise, because it does not specify the number of affected, family size or relation to the proband. Nor does it include an interview of the possibly affected family members. Calculation of the familial aggregation after confirmation of the diagnosis by a physician is more precise. Compared to the general population, first-degree relatives of probands with migraine without aura, migraine with aura, chronic tension-type headache and cluster headache has a significantly increased risk of the proband’s disorder. These data are confirmed in twin studies. The primary headaches are caused by a combination of genetic and environmental factors. A major breakthrough was identification of 3 different genes all causing the rare autosomal dominant inherited familial hemiplegic migraine. The genes encode ion channels. So far no genes have been identified to cause the more common types of primary headaches.     

The family history of migraine. Direct versus indirect information

Migraine assessed by proband report was evaluated in a family study of migraine. A clinical interview of spouses and first-degree relatives by a physician was used as an index of validity. The operational diagnostic criteria of the International Headache Society were used. Of the 378 probands from the general population, 126 had migraine without aura, 127 had migraine with aura, 17 had both migraine without aura and migraine with aura and 108 had never had migraine. Spouses ( n = 229) and first-degree relatives ( n = 1109) were included in the analyses. Sensitivity, specificity, predictive values and chance-corrected agreement rate for the diagnosis of migraine were 49%, 93%, 81% (PV_pos), 77% (PV_neg) and 0.47, respectively. The corresponding values for migraine without aura were 58%, 87%, 63% (PV_pos), 84% (PV_neg) and 0.46 respectively, while the values for migraine with aura were 52%, 88%, 61%, (PV_pos), 83%, (PV_neg) and 0.42, respectively. Migraine assessed by proband report is not satisfactory for diagnosing migraine in relatives, since the number of affected relatives is highly underestimated. Our results emphasize the necessity of a clinical interview of the relatives in family studies of migraine.     

Familial clustering of migraine: further evidence from a Portuguese study

Objective.— Our aim was to evaluate familial aggregation of migraine in a large group of Portuguese families, and to assess if familial aggregation differs between MA and MO.
Methods.— Familial aggregation was evaluated by estimating relative risk (RR) of migraine in 143 first-degree relatives of 50 probands with MA, in 196 first-degree relatives of 94 probands with MO and also in proband's spouses. Probands were enrolled in the study from a clinical sample and a population sample was used as reference.
Results.— A significantly increased risk of migraine was found in both first-degree relatives of MO probands (RR = 3.7; 95% CI: 3.2-4.3) and of MA probands (RR = 3.6; 95% CI: 3.1-4.3), comparatively to the general population. Risk for spouses was not increased. First-degree relatives of MA probands and MO probands had a significantly increased risk of both MA and MO compared to the general population. In the group of MA probands, RR of MA in first-degree relatives reached a significant 4-fold increase when compared with RR of MO (RR_MA|MA = 12.2, 95%CI: 7.7-19.5; RR_MO|MA = 3.1, 95%CI: 2.5-3.8), while, in the group of MO probands, RR of MA was not significantly increased when compared with RR of MO (RR_MA|MO = 5.3, 95%CI: 3.1-9.2; RR_MO|MO = 4.0, 95%CI: 3.5-4.7).
Conclusions.— The present study focus on familial aggregation of migraine in a Portuguese population. Our results demonstrate a substantial familial risk of migraine with evidence of both common and specific etiologic mechanisms for either migraine subtypes.     

Headache in juvenile myoclonic epilepsy

The objective of this study was to assess the prevalence of and risk factors for primary headaches in juvenile myoclonic epilepsy (JME). Headache was classified in 75 patients with JME using a questionnaire, and its prevalence was correlated with the literature on the general population and clinical data. Headache was present in 47 patients. Thirty-one had migraine [20 migraine without aura (MO), 11 migraine with aura (MA)]. Fourteen patients with migraine had tension-type headache (TTH) in addition. Sixteen had only TTH. Comparison with the general population revealed a significantly higher prevalence of migraine (RR 4.4), MO (3.6), MA (7.3) and TTH (3.4) in JME. Risk factors for migraine and MO were female gender and for MA family history of migraine in first-degree relatives. Migraine and MA were associated with fairly controlled generalized tonic clonic seizures, MO with absences. Together with its strong genetic background, JME appears to be an attractive homogenous subtype of epilepsy for genetic research on migraine.     

Prevalence of migraine in Croatia: a population-based survey

OBJECTIVES: The aim of the present study was to estimate the prevalence of migraine among Croatian adults. This is the first epidemiological study of migraine in Croatia in which the operational diagnostic criteria of the International Headache Society have been applied. METHODS: The study population consisted of all residents (aged 15 to 65 years) of Bakar, County of The Coast and Gorski Kotar, Croatia. A population-based survey was undertaken using a "face-to-face, door-to-door" interview METHOD: The participation rate was 73.3%. All participants were screened for headache history according to the International Headache Society criteria. Headache screen positive responders (65.7%) were interviewed by trained medical students with a structured detailed interview focused on migraine. RESULTS: A total of 720 lifetime migraineurs were identified. The lifetime prevalence of migraine was 22.9% (95% confidence interval, 20.9 to 25.1) in women, 14.8% (95% confidence interval, 13.1 to 16.8) in men, and 19% (95% confidence interval, 17.6 to 20.5) in both sexes. The highest lifetime prevalence of migraine was in women in the age group 40 to 49 years (38.1%). Among 636 active migraineurs, 399 (62.7%) were women and 237 (37.3%) were men; 55.8% had migraine without aura, 35.2% migraine with aura, and 6.9% migraine both with and without aura. The 1-year prevalence of migraine, migraine without aura, migraine with aura, and migraine both with and without aura in women was 18%, 11.3%, 8.6%, and 2.2%, respectively. In men, the 1-year prevalence of migraine, migraine without aura, migraine with aura, and migraine both with and without aura was 12.3%, 7.3%, 3%, and 0.7%, respectively. CONCLUSIONS: The prevalence of migraine in this Croatian population showed rates quite similar to those reported in neighboring countries, such as Italy and France. Further studies are needed to estimate the prevalence rates of migraine in the total Croatian population.     

Relationship between migraine and patent foramen ovale: a study of 121 patients with migraine

BACKGROUND: Migraine is a common neurological disorder, the origins of which remain unknown. Patent foramen ovale (PFO) is considered to have a role in migraine. The relationship between migraine and patent foramen ovale may be stronger in patients suffering from migraine with aura compared to patients with common migraine. OBJECTIVES: The aim of the study was to evaluate the frequency of PFO in patients with migraine with aura (MA+) and compare it with the prevalence of PFO in migraine patients without aura (MA-), and in a healthy age-matched control group. We investigated PFO association with migraine, considering such factors as: A type of migraine aura, frequency of attacks, familial occurrence, sex and age of patients. Patients.-121 patients: 61 patients suffering from migraine with aura, 60 without aura and 65 normal controls. The group of patients with migraine with aura was divided into subgroups regarding to the type of aura. METHODS: In order to detect PFO the contrast transcranial Doppler was performed during Valsalva maneuver. RESULTS: The presence of PFO was found in 33/61 (54%) patients with MA(+) compared to 15/60 (25%) without aura and 16/65 (25%) control subjects. The difference between MA(+) patients and MA(-) patients and the difference between MA(+) patients and control group was statistically significant (P < .05). There was no association between type of migraine aura and PFO, as well as we found no association between PFO and frequency of attacks, familial occurrence, sex and age of patients and PFO. CONCLUSIONS: Our findings suggest possible association of migraine with aura and PFO. It seems that PFO does not influence the type of aura and frequency of attacks of migraine as well as it is not associated with familial occurrence of migraine.     

Familial occurrence of chronic tension-type headache

Chronic tension-type headache (CTTH) assessed by proband report was evaluated in a family study of CTTH. A clinical interview of first-degree relatives by a physician was used as index of validity. Familial occurrence of CTTH in first-degree relatives was also investigated. Patterns of familial aggregation of CTTH were assessed by calculating the population relative risk. A neurological resident carried out all the interviews of probands and their first-degree relatives. The operational diagnostic criteria of the International Headache Society were used. The 122 probands had 377 first-degree relatives. Sensitivity, specificity, predictive values, and chance-corrected agreement rate for the diagnosis CTTH were 68%, 86%, 53% (PVpos), 92% (PVneg), and 0.48, respectively. The low sensitivity of CTTH assessed by proband report indicates that a clinical interview by a physician is necessary in family studies of CTTH. Clinically interviewed parents, siblings, and children had a 2.1 to 3.9-fold significantly increased risk of CTTH compared with the general population. The gender of the probands did not influence the risk of CTTH among first-degree relatives. The significantly increased familial risk of CTTH and no increased risk of CTTH in spouses suggest that a genetic factor is involved in CTTH.     

Epidemiology of migraine

One-year migraine prevalence rates in the general population for Western countries vary from 4% to 9% in men and from 11% to 25% in women. Non-Western countries report lower figures. Incidence rates for people under 30 years of age vary from 1.5 to 6 per 1000 person-years in men and from 3 to 24 per 1000 person-years in women. Data on the prevalence of migraine in general, on the gender ratio and on the variations in prevalence in the different age ranges are fairly comparable and can be regarded as very close to reality. On the contrary, data on the incidence of migraine, on the prevalence of different migraine subtypes, such as migraine with aura and the so-called migrainous disorder, and on the frequency of migraine attacks show a striking discordance that somewhat undermines their reliability. The main critical points in prevalence and incidence studies are migraine definition and the methodological approaches used for case screening. Even if International Headache Society (IHS) classification is certainly an improvement over previous tools used in epidemiological studies, the diagnostic criteria for migraine without aura are quite scanty and not easily remembered by subjects belonging to the general population, and those for migraine with aura appear not only difficult to translate for use in a questionnaire or an interview, but also too loose. In particular, the lack of any low-end limit for aura duration may cause an overestimation of migraine with aura prevalence.     

Epidemiology of migraine

The 1988 International Headache Society (IHS) classification has greatly contributed to overcoming the obstacles that had made it difficult in the past to compare results of surveys on headache epidemiology. For migraine without aura, the more recent studies of the general adult population indicate lifetime prevalence rates between 6% and 10% for men and between 15% and 26% for women. One–year prevalence rates are between 2% and 15% for men and between 4% and 35% for women. Rates of frequent migraine are 6% in men and 14% in women. Migraine occurs in 3%–6% of prepubertal children with no significant differences between girls and boys. The prevalence of migraine without aura increases progressively from the age of 12 years up to about the age of 40, when it begins to record a gradual, progressive decrease down to 1%–4% in the elderly. For migraine with aura, recent epidemiological investigations by Rasmussen and Olesen indicate a lifetime prevalence rate of 6% and a one-year prevalence rate of 4%.     

中国南方人群家族性偏瘫型偏头痛家系CACNA1A基因多态性相关研究

背景:偏头痛与遗传学之间的联系早已受到关注,遗传流行病学和分离研究证实,偏头痛存在显著的遗传危险性。目的:通过检测偏头痛患者和家族性偏瘫型偏头痛家族外周血CAC-NA1A基因3个常见的突变位点,分析探讨中国南方人群家族性偏瘫型偏头痛与CACNA1A基因突变之间的关系。设计:抽样调查。单位:中山大学附属第一医院和深圳市宝安西乡人民医院。对象:所有病例均来源中山大学附属第一医院门诊和深圳市宝安西乡人民医院。①家族性偏瘫型偏头痛患者组10例患者。②家族性偏瘫型偏头痛亲属组:家系A和B共12例。③无家族性偏瘫型偏头痛家族史的偏头痛患者组53例。④健康对照10名。方法:采用聚合酶链反应扩增CACNL1A4基因的第13,16,17外显子。采用SSCP方法对2个家族性偏瘫型偏头痛家族10例患者及12名无症状亲属和53例无家族性偏瘫型偏头痛家族史的有先兆偏头痛患者及10名健康对照的外周血标本进行检测,分析CACNA1A基因的3个常见突变位点(T666M,R583Q和D715E)在家族性偏瘫型偏头痛家族中的表现形式。主要观察指标:①聚合酶链反应扩增CACNL1A4基因第13,16,17外显子的结果。②SSCP分析13,16,17外显子的突变结果。结果:参加实验的家族性偏瘫型偏头痛患者10例,家族性偏瘫型偏头痛亲属12例,无家族性偏瘫型偏头痛家族史的偏头痛患者53例,健康对照组10名,均进入结果分析。①第13,16,17外显子的目的片段长度分别为247,268,204bp。②CACNA1A基因3个常见的突变T666M,R583Q和D715E在2个家族性偏瘫型偏头痛家族10例家族性偏瘫型偏头痛患者,12名无症状亲属和53例无家族性偏瘫型偏头痛家族史的有先兆偏头痛患者及10名健康对照者中均未检测到。结论:在中国人群家族性偏瘫型偏头痛家族中未发现有T666M,R583Q和D715E3个突变。     

Hungarian migraine epidemiology

OBJECTIVE: A population-based epidemiological survey of migraine without aura and migraine with aura completed by mailed questionnaire in Hungary. The diagnosis and classification of migraine was according to the criteria of the International Headache Society. METHODS: The validity of the self-administered headache questionnaire was evaluated by a neurologist using clinical interviews. The study population was a random sample of 2000 men and women aged between 15 and 80 years. The questionnaire was completed by 813 of 1910 people (392 men and 421 women), providing a 42.6% participation rate. RESULTS: Sixty-seven percent of these people experienced some kind of headache during their lives. The 1-year prevalence of migraine without aura was 7.6% (the female/male ratio was 3:1), while the 1-year prevalence of migraine with aura was 2% (female/male ratio was 2:1). Most migraineurs experienced headache attacks 1 to 4 times monthly, which lasted 24 hours. The most characteristic accompanying signs were nausea and phonophobia. Stress, sleep deprivation, hot weather, and fasting were the most common precipitating factors of a migraine attack. In the migraine with aura group, the most common aura was a visual disturbance. Only 43% of migraineurs had ever consulted a physician for headache, and only 15% of patients had missed work or school because of a migraine attack in the previous year. Most of the patients suffering from migraine without aura were between 20 and 40 years old, while migraineurs with aura were over 40 years old. According to this investigation, the prevalence of migraine was not lower than in Western countries.     

Genetic and environmental factors associated with migraine in schoolchildren

OBJECTIVE: The aim of this study was to find the prevalence of migraine and headache in schoolchildren in the United Arab Emirates and to determine the genetic and environmental factors associated with these conditions. METHODS: A cross-sectional population study was performed from October 1995 to June 1996. Subjects were selected by a multistage stratified sampling procedure. Data were collected by screening questionnaires followed by clinical interviews. Twelve primary schools and 1400 schoolchildren of United Arab Emirates nationality resident in the Al Ain City, Dubai, and Sharjah emirates were recruited for this study. A total of 1159 (82.7%) schoolchildren gave their consent to the study. RESULTS: The estimated prevalence rates for headache and migraine were 36.9% and 13.7%, respectively. The prevalence of headache is increased with age, the highest prevalence being in 13-year-old children (17.5%). Of the 159 children who fulfilled the diagnostic criteria for migraine, 76 were boys whose mean age (+/- SD) was 10.3 years +/- 2. 8 years, and 83 were girls (mean age 9.9 +/- 2.5 years). Of the children who had migraine, 20 (12.6%) had migraine without aura, and 13 (8.2%) had migraine with aura. The most common migraine symptoms in schoolchildren had been aggravated by physical activity (47.2%) and a positive family history of migraine (46.5%). The most common illnesses were infectious illnesses (41.5%). There was a strong relationship between migraine and the timing of examinations (46.5%). The most common environmental exposure for migraine was found to be playing on a computer (45.9%), followed by loud noise (41.5%), and a hot climate (37.1%). In familial occurrence of headache among immediate relatives, the most frequently affected relative was the mother (17.6%). CONCLUSION:.-Headache and migraine are common in childhood and may be influenced by social, familial, environmental, and psychological factors.     

A single-fibre EMG study of neuromuscular transmission in migraine patients

It is known that mutations of CACNA1A, which encodes a neuronal P/Q Ca(2+) channel, are present in patients with familial hemiplegic migraine, and possibly in other types of migraine as well. This calcium channel is also involved in neuromuscular transmission. To assess if the single-fibre EMG (SFEMG) method can demonstrate a neuromuscular transmission deficit in migraine, a group of 26 patients with different types of migraine and 20 healthy control subjects were studied. The migraine patients were divided into three groups: 8 patients with migraine without aura (MoA), 12 with migraine with aura excluding visual aura (MA) and 6 with visual aura (VA). A SFEMG of the voluntarily activated extensor digitorum communis muscle was performed. The SFEMG results were normal in the healthy controls and the MoA group (migraine without aura). Slight neuromuscular transmission disturbances were present in 6/12 (50%) of patients with MA and in 1/6 (17%) of patients with VA. We suggest that abnormal neuromuscular transmission detectable by SFEMG may reflect a genetically determined dysfunction of the P/Q Ca(2+) channels in a subgroup of migraineurs with aura.     

Contingent negative variation in subjects at risk for migraine without aura.

Migraine is a complex disease with a significant genetic background. One possible strategy to investigate the genetics of migraine is the evaluation of functional vulnerability markers or biological elementary endophenotypes in individuals with the greatest probability of developing the disorder (high-risk design). In this study the contingent negative variation (CNV) was recorded in 35 high-risk subjects with a positive family history of migraine without aura (FHP), 35 low-risk individuals without a positive family history (FHN), and 35 migraineurs (migraine without aura). FHP subjects and migraine patients differed significantly from FHN individuals with regard to amplitude and habituation slope of the early CNV component (initial CNV or iCNV). FHP participants demonstrated the same iCNV abnormalities and distribution among iCNV characteristics as migraineurs. The amplitude of the iCNV correlated significantly with the relative number of subjects suffering from migraine among first- and second-degree relatives. The higher the density of affected individuals in the family, the more pronounced were the CNV abnormalities in relatives. This study provides evidence that the familial factor contributes to the abnormal amplitude, and to a lesser degree, habituation of the iCNV, and that the iCNV may be used as a functional-genetic vulnerability marker in further research of migraine genetics.     

Clinical characteristics of 362 patients with familial migraine with aura

The objectives of the present study were to describe the clinical characteristics of patients with severe familial non-hemiplegic migraine with aura (NHMA) and to compare these data to those from cases in previous population-based Danish studies using the same methodology. NHMA families were recruited from the Danish patient registry and from Danish neurology practices. A total of 362 NHMA patients were diagnosed according to the 1988 International Headache Society criteria using a validated semistructured physician-conducted interview. Visual aura occurred in almost every NHMA attack. In aura without headache visual aura occurred primarily in isolation. Aura without headache was most common in older, male patients. Several clinical characteristics of familial NHMA differed from migraine with aura in the general population: firstly, the age at onset was lower, secondly, the age at cessation was higher, thirdly, aura symptoms were more severe and finally, the co-occurrence of migraine without aura was higher in familial NHMA. There seems to be a correlation between more severe symptoms and familial aggregation. These results have both clinical and scientific implications.     

Migraine, chronic tension-type headache, and cluster headache in an Ethiopian rural community

Fifteen-thousand-five hundred adults (³20 years) in a rural district in Ethiopia with a population of 250 000 were studied for chronic headache. Door-to-door survey was performed by trained lay health workers using a questionnaire with a high degree or reliability and validity. The 1-year prevalence of migraine headache was 3.0% (4.2% for females and 1.7% for males) with the peak age specific rate in the fourth decade. Migraine headache was about three times more common in females than in males at any decade. Two-thirds of migraine sufferers had rather frequent attacks. The most frequent trigger factors were emotional stress (90%), changes of weather (78%), physical exhaustion (75%), and smell (70%). Migraine with aura was rare. Family occurrence of migraine in first-degree relatives was 30%. The 1-year prevalence of chronic tension-type headache was 1.7%, while cluster headache was found to be extremely rare. Compared to similarly performed surveys, the prevalence of migraine among rural Ethiopians was less than among Nigerian Africans.