The Genetics of Migraine Without Aura and Migraine With Aura

Cephalalgia ◽  
1993 ◽  
Vol 13 (4) ◽  
pp. 245-248 ◽  
Author(s):  
Michael Bjørn Russell ◽  
Jes Olesen
Keyword(s):  
Migraine With Aura ◽  
Migraine Without Aura ◽  
Familial Aggregation ◽  
Familial Hemiplegic Migraine ◽  
Hemiplegic Migraine ◽  
Future Studies ◽  
Progressive Ataxia ◽  
Reduced Penetrance ◽  
Genetically Determined ◽  
Selection Of

Studies of twins, spouses and familial aggregation strongly suggest that migraine without aura (MO) and migraine with aura (MA) are genetically determined. The mode of inheritance is most likely multifactorial in both MO and MA. However, autosomal dominant inheritance with reduced penetrance cannot be excluded in either MO or MA. At present the only evidence for genetic heterogeneity of MA is familial hemiplegic migraine with slowly progressive ataxia. This phenomenon can also be explained by linkage of different genes. All existing studies have been characterized by one or more of the following methodologic shortcomings: selection of probands from clinic populations, information obtained by questionnaire, family history obtained through probands, insufficient description of the attacks, lack of distinction between MO and MA. Useful strategies for future studies of migraine genetics are discussed.

Sporadic Hemiplegic Migraine is an Aetiologically Heterogeneous Disorder

Cephalalgia ◽  
2003 ◽  
Vol 23 (9) ◽  
pp. 921-928 ◽  
Author(s):  
LL Thomsen ◽  
E Ostergaard ◽  
SF Romer ◽  
I Andersen ◽  
MK Eriksen ◽  
...  
Keyword(s):  
Relative Risk ◽  
General Population ◽  
Migraine With Aura ◽  
Migraine Without Aura ◽  
Familial Aggregation ◽  
Familial Hemiplegic Migraine ◽  
Danish Population ◽  
Hemiplegic Migraine ◽  
First Degree Relatives ◽  
Increased Risk

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.

A single-fibre EMG Study of Neuromuscular Transmission in Migraine Patients

Cephalalgia ◽  
2005 ◽  
Vol 25 (10) ◽  
pp. 817-821 ◽  
Author(s):  
I Domitrz ◽  
A Kostera-Pruszczyk ◽  
H Kwieciñski
Keyword(s):  
Neuromuscular Transmission ◽  
Migraine Without Aura ◽  
Familial Hemiplegic Migraine ◽  
Single Fibre ◽  
Healthy Controls ◽  
Hemiplegic Migraine ◽  
Visual Aura ◽  
Different Types ◽  
Healthy Control ◽  
Genetically Determined

It is known that mutations of CACNA1A, which encodes a neuronal P/Q Ca2+ 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 Ca2+ channels in a subgroup of migraineurs with aura.

Is Familial Hemiplegic Migraine a Hereditary form of Basilar Migraine?

Cephalalgia ◽  
1995 ◽  
Vol 15 (6) ◽  
pp. 477-481 ◽  
Author(s):  
J Haan ◽  
GM Terwindt ◽  
RA Ophoff ◽  
PLJM Bos ◽  
RR Frants ◽  
...  
Keyword(s):  
Blood Flow ◽  
Migraine Without Aura ◽  
International Headache Society ◽  
Familial Hemiplegic Migraine ◽  
Control Group ◽  
Artery Blood Flow ◽  
Hemiplegic Migraine ◽  
Ihs Criteria ◽  
Genetically Determined ◽  
Pathophysiologic Mechanisms

We studied aura symptoms in 83 patients from 6 unrelated families suffering from familial hemiplegic migraine. Fifty-five of the patients reported symptoms that allowed us to categorize them as basilar migraine (BM) patients, in accordance with the International Headache Society (IHS) criteria. In a control group of 33 patients suffering from migraine with aura and 33 patients suffering from migraine without aura, 9 patients complained of vertigo, and only one patient of diplopia during one of her attacks. None of these control patients fulfilled the IHS criteria for BM We suggest that familial hemiplegic migraine and BM may share certain pathophysiologic mechanisms, which may consist of a (genetically determined) disturbance of basilar artery blood flow.

scholarly journals Migraine: Calcium Channels and Glia

2021 ◽  
Vol 22 (5) ◽  
pp. 2688
Author(s):  
Marta Kowalska ◽  
Michał Prendecki ◽  
Thomas Piekut ◽  
Wojciech Kozubski ◽  
Jolanta Dorszewska
Keyword(s):  
Migraine With Aura ◽  
Migraine Without Aura ◽  
Spreading Depression ◽  
Adult Population ◽  
Familial Hemiplegic Migraine ◽  
Trigeminovascular System ◽  
Hemiplegic Migraine ◽  
Monogenic Form ◽  
Calcitonin Gene

Migraine is a common neurological disease that affects about 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura and migraine without aura. According to the neurovascular theory of migraine, the activation of the trigeminovascular system (TGVS) and the release of numerous neuropeptides, including calcitonin gene-related peptide (CGRP) are involved in headache pathogenesis. TGVS can be activated by cortical spreading depression (CSD), a phenomenon responsible for the aura. The mechanism of CSD, stemming in part from aberrant interactions between neurons and glia have been studied in models of familial hemiplegic migraine (FHM), a rare monogenic form of migraine with aura. The present review focuses on those interactions, especially as seen in FHM type 1, a variant of the disease caused by a mutation in CACNA1A, which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel.

Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura

Cephalalgia ◽  
2010 ◽  
Vol 30 (10) ◽  
pp. 1179-1186 ◽  
Author(s):  
Jakob Møller Hansen ◽  
Anne Werner Hauge ◽  
Jes Olesen ◽  
Messoud Ashina
Keyword(s):  
Migraine With Aura ◽  
Migraine Headache ◽  
Migraine Without Aura ◽  
Familial Hemiplegic Migraine ◽  
Calcitonin Gene Related Peptide ◽  
Hemiplegic Migraine ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Post Infusion ◽  
Migraine Pathogenesis

Introduction: Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP infusion triggers delayed migraine-like attacks in patients with migraine without aura (MO). In contrast to patients with MO, in prior studies patients with familial hemiplegic migraine (FHM) did not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (MA) unknown. In the present study we examined the migraine inducing effect of CGRP infusion in patients suffering from MA and healthy controls. Methods: Fourteen patients suffering exclusively from migraine with typical aura (MA) and 11 healthy volunteers received a continuous intravenous infusion of 1.5 µg/min CGRP over 20 minutes. Headache and other migraine symptoms were scored every 10 minutes for one hour and self recorded hourly thereafter and until 13 hours post-infusion. Results: CGRP infusion induced significantly more delayed headaches in MA patients (12 out of 14) than in controls (2 out of 11) ( p = 0.001). Furthermore, significantly more MA patients (57%; 8 out of 14) fulfilled criteria for an experimentally induced migraine attack after CGRP than controls (0%; 0 out of 11) ( P = 0.003). Four patients (28%) reported aura symptoms after CGRP infusion. Conclusion: CGRP triggered migraine-like attacks without aura in patients suffering exclusively from MA. It also triggered a typical aura in 28% of the patients. These data indicate similar neurobiological pathways responsible for triggering migraine headache in MA and MO patients, and suggest differences between MA/MO and FHM.

Evidence for a separate type of migraine with aura

Neurology ◽  
2003 ◽  
Vol 60 (4) ◽  
pp. 595-601 ◽  
Author(s):  
Lise L. Thomsen ◽  
Elsebet Ostergaard ◽  
Jes Olesen ◽  
Michael B. Russell
Keyword(s):  
Migraine With Aura ◽  
Telephone Interview ◽  
Clinical Symptoms ◽  
Familial Hemiplegic Migraine ◽  
Computer Search ◽  
Hemiplegic Migraine ◽  
Motor Weakness ◽  
National Patient Register ◽  
National Patient ◽  
Sequential Appearance

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.

Trigger factors for familial hemiplegic migraine

Cephalalgia ◽  
2011 ◽  
Vol 31 (12) ◽  
pp. 1274-1281 ◽  
Author(s):  
Jakob Møller Hansen ◽  
Anne Werner Hauge ◽  
Messoud Ashina ◽  
Jes Olesen
Keyword(s):  
Migraine With Aura ◽  
Response Rate ◽  
Bright Light ◽  
Familial Hemiplegic Migraine ◽  
Population Based ◽  
Trigger Factor ◽  
Trigger Factors ◽  
Hemiplegic Migraine

Objective: The aim was to identify and describe migraine trigger factors in patients with familial hemiplegic migraine (FHM) from a population-based sample. Methods: 127 FHM patients were sent a questionnaire listing 16 trigger factors. Distinction was made between attacks of hemiplegic migraine (HM) and migraine with aura (MA) or without aura (MO) within each patient. Results: The response rate was 59% (75/127) of whom 57 (76%) had current HM attacks. Sixty-three per cent (47/75) reported at least one factor triggering HM, and 36% (27/75) reported at least one factor that often or always caused HM. Twenty per cent (15/75) reported only HM, whereas FHM in combinations with MA and MO were reported by 80% (60/75). Stress (with attacks either following or during the stress), bright light, intense emotional influences and sleeping too much or too little were the trigger factors mentioned by most. Conclusion: Many FHM patients report trigger factors and one-third reported at least one trigger factor often or always triggering FHM. The typical triggers are the same as for MA. Patients should be educated to avoid these factors. The role of trigger factors in the onset of new or first attacks of FHM remains unknown.

scholarly journals Involvement of astrocyte and oligodendrocyte gene sets in migraine

Cephalalgia ◽  
2015 ◽  
Vol 36 (7) ◽  
pp. 640-647 ◽  
Author(s):  
Else Eising ◽  
Christiaan de Leeuw ◽  
Josine L Min ◽  
Verneri Anttila ◽  
Mark HG Verheijen ◽  
...  
Keyword(s):  
Migraine With Aura ◽  
Genetic Background ◽  
Migraine Without Aura ◽  
Protein Modification ◽  
Association Studies ◽  
Cell Types ◽  
Familial Hemiplegic Migraine ◽  
Genome Wide Association Studies ◽  
Brain Disorder ◽  
Gene Sets

Background Migraine is a common episodic brain disorder characterized by recurrent attacks of severe unilateral headache and additional neurological symptoms. Two main migraine types can be distinguished based on the presence of aura symptoms that can accompany the headache: migraine with aura and migraine without aura. Multiple genetic and environmental factors confer disease susceptibility. Recent genome-wide association studies (GWAS) indicate that migraine susceptibility genes are involved in various pathways, including neurotransmission, which have already been implicated in genetic studies of monogenic familial hemiplegic migraine, a subtype of migraine with aura. Methods To further explore the genetic background of migraine, we performed a gene set analysis of migraine GWAS data of 4954 clinic-based patients with migraine, as well as 13,390 controls. Curated sets of synaptic genes and sets of genes predominantly expressed in three glial cell types (astrocytes, microglia and oligodendrocytes) were investigated. Discussion Our results show that gene sets containing astrocyte- and oligodendrocyte-related genes are associated with migraine, which is especially true for gene sets involved in protein modification and signal transduction. Observed differences between migraine with aura and migraine without aura indicate that both migraine types, at least in part, seem to have a different genetic background.

Genetic Analysis of 27 Spanish Patients with Hemiplegic Migraine, Basilar-Type Migraine and Childhood Periodic Syndromes

Cephalalgia ◽  
2008 ◽  
Vol 28 (10) ◽  
pp. 1039-1047 ◽  
Author(s):  
E Cuenca-León ◽  
R Corominas ◽  
N Fernàndez-Castillo ◽  
V Volpini ◽  
M del Toro ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Migraine With Aura ◽  
Genetic Heterogeneity ◽  
Familial Hemiplegic Migraine ◽  
Base Change ◽  
Hemiplegic Migraine ◽  
Rare Type

Familial hemiplegic migraine (FHM) is a rare type of migraine with aura. Mutations in three genes have been described in FHM patients: CACNA1A (FHM1), ATP1A2 (FHM2) and SCN1A (FHM3). We screened 27 Spanish patients with hemiplegic migraine (HM), basilar-type migraine or childhood periodic syndromes (CPS) for mutations in these three genes. Two novel CACNA1A variants, p.Val581Met and p.Tyr1245Cys, and a previously annotated change, p.Cys1534Ser, were identified in individuals with HM, although they have not yet been proven to be pathogenic. Interestingly, p.Tyr1245Cys was detected in a patient displaying a changing, age-specific phenotype that began as benign paroxysmal torticollis of infancy, evolving into benign paroxysmal vertigo of childhood and later becoming HM. This is the first instance of a specific non-synonymous base change being described in a subject affected with CPS. The fact that the molecular screen identified non-synonymous changes in< 15± of our HM patients further stresses the genetic heterogeneity underlying the presumably monogenic forms of migraine.

Motor Cortex Excitability in Patients with Migraine with Aura and Hemiplegic Migraine

Cephalalgia ◽  
2000 ◽  
Vol 20 (1) ◽  
pp. 45-50 ◽  
Author(s):  
KJ Werhahn ◽  
K Wiseman ◽  
J Herzog ◽  
S Foörderreuther ◽  
M Dichgans ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Migraine With Aura ◽  
Silent Period ◽  
Intracortical Inhibition ◽  
Familial Hemiplegic Migraine ◽  
Hemiplegic Migraine ◽  
Cortical Hyperexcitability ◽  
Motor Cortex Excitability ◽  
Patient Groups ◽  
Intracortical Inhibition And Facilitation

We studied the excitability of the motor cortex using transcranial magnetic stimulation (TMS) in 12 patients with migraine with aura (MA) and nine patients with familial hemiplegic migraine (FHM). Motor thresholds at rest, the duration of the cortical and peripheral silent period and intracortical inhibition and facilitation using paired-pulse TMS at intervals of 2 to 15 ms were measured with patients free of attacks for at least 48 h. In contrast to previous reports we could not find any significant differences between patient groups and compared to controls ( n = 17) in the parameters tested. The results suggest that there are no interictal changes of excitability of the motor cortex in migraine. This study does not support the concept of general cortical hyperexcitability in migraine secondary to a genetic predisposition or a structural alteration of inhibitory interneurones in the cortex due to repeated parenchymal insults during attacks.

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