Michael Bjørn Russell

Increased familial risk and evidence of genetic factor in migraine

Abstract Objective: To investigate familial occurrence of migraine with and without aura. Design: Familial occurrence of migraine with and without aura among first degree relatives and spouses of probands with migraine with or without aura and those who had never had migraine. All interviews of first degree relatives and spouses were done blindly by a neurological resident. The operational diagnostic criteria of the International Headache Society were used. Setting: population from Copenhagen County. Subjects: The 378 probands had 1109 first degree relatives and 229 spouses. Main outcome measures: Patterns of familial aggregation of migraine with and without aura as assessed by calculation of the population relative risk. Results: Compared with the general population the first degree relatives of probands with migraine without aura had 1.9 times the risk of migraine without aura and 1.4 times the risk of migraine with aura. The first degree relatives of probands with migraine with aura had nearly four times the risk of migraine with aura and no increased risk of migraine without aura. The first degree relatives of probands who had never had migraine had no increased risk of migraine either with or without aura. Spouses of probands with migraine without aura had 1.4 times the risk of migraine without aura whereas spouses of probands with migraine with aura had no increased risk of migraine with aura. Conclusion: The different familial patterns indicate that migraine without aura and migraine with aura have a different aetiology. Migraine without aura seems to be caused by a combination of genetic and environmental factors whereas migraine with aura is probably determined largely or exclusively by genetic factors.

Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management.

Hemiplegic migraine is a rare form of migraine with aura that involves motor aura (weakness). This type of migraine can occur as a sporadic or a familial disorder. Familial forms of hemiplegic migraine are dominantly inherited. Data from genetic studies have implicated mutations in genes that encode proteins involved in ion transportation. However, at least a quarter of the large families affected and most sporadic cases do not have a mutation in the three genes known to be implicated in this disorder, suggesting that other genes are still to be identified. Results from functional studies indicate that neuronal hyperexcitability has a pivotal role in the pathogenesis of hemiplegic migraine. The clinical manifestations of hemiplegic migraine range from attacks with short-duration hemiparesis to severe forms with recurrent coma and prolonged hemiparesis, permanent cerebellar ataxia, epilepsy, transient blindness, or mental retardation. Diagnosis relies on a careful patient history and exclusion of potential causes of symptomatic attacks. The principles of management are similar to those for common varieties of migraine, except that vasoconstrictors, including triptans, are historically contraindicated but are often used off-label to stop the headache, and prophylactic treatment can include lamotrigine and acetazolamide.

Epidemiology and genetics of cluster headache

Cluster headache, the most severe primary headache, is characterised by unilateral pain, ipsilateral autonomic features, and, in many cases, restlessness. Recent epidemiological studies indicate that the prevalence of cluster headache is about one person per 500. Genetic epidemiological surveys indicate that first-degree relatives are five to 18 times-and second-degree relatives, one to three times-more likely to have cluster headache than the general population. Inheritance is likely to be autosomal dominant with low penetrance in some families, although there may also be autosomal recessive or multifactorial inheritance in others. To date, no molecular genetic clues have been identified for cluster headache. Identification of genes for cluster headache is likely to be difficult because most families reported have few affected members and genetic heterogeneity is likely. Future focus should be on ion channel genes and clock genes. This review summarises the epidemiology and genetics of cluster headache.

The relative role of genetic and environmental factors in migraine without aura

Objective: To clarify the relative role of genetic and environmental factors in the etiology of migraine without aura (MO). Methods: The study population consisted of 5,360 twins, 1,013 monozygotic (MZ) and 1,667 same-gender dizygotic (DZ) twin pairs, from the population-based Danish Twin Registry. A total of 87% completed a simple validated questionnaire screening for migraine. All twin pairs, in whom at least one twin had self-reported migraine or severe headache with accompanying symptoms, were interviewed via telephone by a physician. Ninety percent of the eligible twins were interviewed. Probandwise concordance rates and correlations in liability were calculated, and structural equation model-fitting analyses were applied to quantitate the relative role of genetic and environmental factors in the etiology of MO. Results: The probandwise concordance rate was higher in MZ than DZ twin pairs (0.43 versus 0.31; 95% CI, 0.36 to 0.49 versus 0.26 to 0.36). The correlation in liability was higher in MZ than in DZ twin pairs (0.62 versus 0.41; 95% CI, 0.50 to 0.74 versus 0.29 to 0.53). Structural equation model fitting indicated a highly significant genetic component, because a model with both genetic and environmental components fitted significantly better than a model with only environmental components. The best fitting model implied that the liability to MO resulted from additive genetic effects (61%; 95% CI, 49 to 71%)) and individual-specific environmental effects (39%; 95% CI, 29 to 51%). Conclusion: This study indicates that genetic factors play a role in the etiology of migraine without aura. The genetic variability is additive, with a negligible contribution of nonadditive genetic effects. The genetic contributions were similar in men and women despite a higher prevalence in women. Environmental factors are equally important and these factors are individual to the migraineurs.

Evidence for a separate type of migraine with aura: Sporadic hemiplegic migraine

Objective: To compare clinical characteristics of patients with sporadic hemiplegic migraine (SHM) with those of patients with migraine with typical aura (MA) and patients with familial hemiplegic migraine (FHM). Methods: The authors used a computer search of Denmark’s National Patient Register to screen the population for patients with migraine with aura with motor weakness, and also examined case records from headache clinics and private practicing neurologists and placed advertisements. The authors screened patients and their relatives with a semi-structured validated telephone interview. All recruited patients were then interviewed by a physician and given a neurologic examination. Results: A total of 105 patients with SHM were identified. Seventy-two percent had four typical aura symptoms: visual, sensory, aphasic, and motor. All had at least two symptoms present during SHM attacks. A gradual progression and sequential appearance of aura symptoms was typical; compared with MA, the duration of each aura symptom was usually prolonged and bilateral motor symptoms were more frequent. Of the patients with SHM, 72% fulfilled the criteria for basilar migraine during SHM attacks. The aura was usually followed by headache, as is common in FHM but not MA. Conclusions: Patients with sporadic hemiplegic migraine had clinical symptoms identical to familial hemiplegic migraine and significantly different from migraine with typical aura. Sporadic hemiplegic migraine is a separate entity, and should be classified with familial hemiplegic migraine.

Genetic epidemiology of Charcot-Marie-Tooth in the general population.

Background and purpose: The frequency of different Charcot–Marie–Tooth (CMT) genotypes has been estimated in clinic populations, but prevalence data from the general population are lacking.

Prevalence of Secondary Chronic Headaches in a Population-Based Sample of 30-44-Year-Old Persons. The Akershus Study of Chronic Headache

We studied secondary chronic headaches (≥ 15 days/month for at least 3 months) in a random sample of 30 000 persons aged 30-44 years. They received a mailed questionnaire. Those with self-reported chronic headache within the last month and/or year were invited to an interview and examination by a neurological resident. The criteria of the International Classification of Headache Disorders (ICHD-II) were applied. The questionnaire response rate was 71%, and the participation rate of the interview was 74%. Of the 633 participants, 298 had a secondary chronic headache. The 1-year prevalence of secondary chronic headache was 2.14%, i.e. chronic posttraumatic headache 0.21%, chronic headache attributed to whiplash injury 0.17%, post-craniotomy headache 0.02%, medication-overuse headache (MOH) 1.72%, cervicogenic headache 0.17%, headache attributed to chronic rhinosinusitis 0.33% and miscellaneous headaches 0.04%. The majority of those with ICHD-II-defined secondary chronic headache had MOH, while about one-third had other secondary headaches often in combination with MOH.

Genetics of tension-type headache

The objective of this study was to investigate the importance of genetics in tension-type headache. A MEDLINE search from 1966 to December 2006 was performed for “tension-type headache and prevalence” and “tension-type headache and genetics” The prevalence of tensiontype headache varies from 11 to 93%, with a slight female preponderance. Co-occurrence of migraine increases the frequency of tension-type headache. A family study of chronic tension-type headache suggests that genetic factors are important. A twin study analysing tension-type headache in migraineurs found that genetic factors play a minor role in episodic tension-type headache. Another twin study analysing twin pairs without co-occurrence of migraine showed a significantly higher concordance rate among monozygotic than same-gender dizygotic twin pairs with no or frequent episodic tension-type headache, while the difference was minor in twin pairs with infrequent episodic tensiontype headache. Frequent episodic and chronic tension-type headache is caused by a combination of genetic and environmental factors, while infrequent episodic tensiontype headache is caused primarily by environmental factors.

A Norwegian population‐based study on the risk and prevalence of obstructive sleep apnea The Akershus Sleep Apnea Project (ASAP)

The Berlin Questionnaire (BQ) is a widely used screening tool for obstructive sleep apnea (OSA), but its performance in the general population setting is unknown. The prevalence of OSA in middle‐aged adults is not known in Norway. Accordingly, the aims of the current study were to evaluate the utility of the BQ for OSA screening in the general population and to estimate the prevalence of OSA in Norway. The study population consisted of 29 258 subjects (aged 30–65 years, 50% female) who received the BQ by mail. Of these, 16 302 (55.7%) responded. Five‐hundred and eighteen subjects were included in the clinical sample and underwent in‐hospital polysomnography. Screening properties and prevalence were estimated by a statistical model that adjusted for bias in the sampling procedure. Among the 16 302 respondents, 24.3% (95% confidence interval (CI) = 23.6–25.0%) were classified by the BQ to be at high‐risk of having OSA. Defining OSA as an apnea–hypopnea index (AHI) ≥5, the positive predictive value of the BQ was estimated to be 61.3%, the negative predictive value 66.2%, the sensitivity 37.2% and the specificity 84.0%. Estimated prevalences of OSA were 16% for AHI ≥ 5 and 8% for AHI ≥ 15. In conclusion, the BQ classified one out of four middle‐aged Norwegians to be at high‐risk of having OSA, but the screening properties of the BQ were suboptimal. The estimated prevalence of OSA was comparable to previous estimates from general populations in the USA, Australia and Europe.

Familial occurrence of migraine without aura and migraine with aura

We report a study of 121 probands (patients) with migraine without aura (MO) and 72 probands with migraine with aura (MA), diagnosed according to the operational diagnostic criteria of the International Headache Society and selected from 35 general practices in Denmark. The probands were interviewed about the presence of MO and MA among their first-degree relatives. Compared with the general population, the first-degree relatives of probands with MO had a threefold increase of MO, and only one first-degree relative of one proband with MO had MA. First-degree relatives of probands with MA had a twofold increase of both MA and MO. Compared with the general population, few spouses had MO and MA. This threefold and twofold increase in family risk of MO and MA, combined with the lack of increased risk in spouses, strongly suggests that MO and MA are genetically determined.