Evidence for a separate type of migraine with aura

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.

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Sporadic Hemiplegic Migraine

Cephalalgia ◽

10.1111/j.1468-2982.2004.00788.x ◽

2004 ◽

Vol 24 (12) ◽

pp. 1016-1023 ◽

Cited By ~ 53

Author(s):

LL Thomsen ◽

J Olesen

Keyword(s):

General Population ◽

Migraine Without Aura ◽

Clinical Symptoms ◽

Familial Hemiplegic Migraine ◽

Headache Disorders ◽

Degree Relative ◽

Hemiplegic Migraine ◽

Motor Weakness ◽

Increased Risk

Sporadic hemiplegic migraine (SHM) is defined as migraine attacks associated with some degree of motor weakness/hemiparesis during the aura phase and where no first degree relative (parent, sibling or child) has identical attacks. The present review deals with recent scientific studies according to which: The SHM prevalence is estimated to be 0.005%; SHM patients have clinical symptoms identical to patients with familial hemiplegic migraine (FHM) and significantly different from patients with migraine with typical aura (typical MA); SHM affected had no increased risk of migraine without aura (MO), but a highly increased risk of typical MA compared to the general population; SHM patients only rarely have mutations in the FHM gene CACNA1A; SHM attacks in some cases can be treated with Verapamil. The reviewed data underlie the change in the International Classification of Headache Disorders 2nd edition where SHM became separated from migraine with typical aura or migraine with prolonged aura. All cases with motor weakness should be classified as either FHM or SHM.

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Trigger factors for familial hemiplegic migraine

Cephalalgia ◽

10.1177/0333102411415878 ◽

2011 ◽

Vol 31 (12) ◽

pp. 1274-1281 ◽

Cited By ~ 22

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.

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The FHM1 Mutation S218L: A Severe Clinical Phenotype? A Case Report and Review of the Literature

Cephalalgia ◽

10.1111/j.1468-2982.2009.01884.x ◽

2009 ◽

Vol 29 (12) ◽

pp. 1337-1339 ◽

Cited By ~ 14

Author(s):

S Debiais ◽

C Hommet ◽

I Bonnaud ◽

MA Barthez ◽

S Rimbaux ◽

...

Keyword(s):

Autosomal Dominant ◽

Cerebral Oedema ◽

Clinical Phenotype ◽

Pregnant Patient ◽

Familial Hemiplegic Migraine ◽

Review Of The Literature ◽

Severe Phenotype ◽

Hemiplegic Migraine ◽

Motor Weakness ◽

Cacna1a Gene

Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of migraine with aura that is characterized by motor weakness during attacks. FHM1 is associated with mutations in the CACNA1A gene located on chromosome 19. We report a severe, prolonged HM attack in a young pregnant patient who had the S218L FHM1. This CACNA1A mutation has been associated with HM, delayed cerebral oedema and coma following minor head trauma. The case history we report suggests a specific, severe phenotype and the co-occurrence of HM and epilepsy related to the S218L FHM1 mutation.

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Familial Hemiplegic Migraine with an ATP1A4 Mutation: Clinical Spectrum and Carbamazepine Efficacy

Brain Sciences ◽

10.3390/brainsci10060372 ◽

2020 ◽

Vol 10 (6) ◽

pp. 372

Author(s):

Giangennaro Coppola ◽

Grazia Maria Giovanna Pastorino ◽

Luigi Vetri ◽

Floriana D’Onofrio ◽

Francesca Felicia Operto

Keyword(s):

Clinical Condition ◽

Clinical Symptoms ◽

Familial Hemiplegic Migraine ◽

The Other ◽

Carrier Status ◽

Maternal Grandmother ◽

Hemiplegic Migraine ◽

Italian Family ◽

Whole Exome

An Italian family with familial hemiplegic migraine (FHM) with the absence of mutations in the known genes associated with this disorder, namely ATP1A2, ATP1A3, CACNA1A, and SCN1A, has recently been reported. Soon afterward, whole exome sequencing allowed the identification of the carrier status of a heterozygous ATP1A4 mutation c.1798 C >T, in four affected members of this family. Here we compare the clinical symptoms of the affected family members with those from the other FHM families linked to mutations in the known genes associated with this disorder. A further two-year follow-up, including clinical response to carbamazepine administered to the proband and the maternal grandmother due to a worsening of the migraine symptoms, is reported. The clinical condition of the proband’s brother, carrying the same mutation and suffering from congenital ventricular and supraventricular extrasystoles, isdiscussed as well.

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

Cephalalgia ◽

10.1111/j.1468-2982.2008.01645.x ◽

2008 ◽

Vol 28 (10) ◽

pp. 1039-1047 ◽

Cited By ~ 40

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.

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A novel ATP1A2 gene mutation in familial hemiplegic migraine and epilepsy

Cephalalgia ◽

10.1177/0333102413498941 ◽

2013 ◽

Vol 34 (1) ◽

pp. 68-72 ◽

Cited By ~ 11

Author(s):

Cinzia Costa ◽

Paolo Prontera ◽

Paola Sarchielli ◽

Alessandra Tonelli ◽

Maria Teresa Bassi ◽

...

Keyword(s):

Autosomal Dominant ◽

Febrile Seizures ◽

Familial Hemiplegic Migraine ◽

Hemiplegic Migraine ◽

Specific Symptom ◽

Motor Weakness ◽

Generation Family ◽

Atp1a2 Gene ◽

Generalized Epilepsy ◽

Febrile Seizures Plus

Background Familial hemiplegic migraine (FHM) is a rare autosomal dominant migraine subtype, characterized by fully reversible motor weakness as a specific symptom of aura. Mutations in the ion transportation coding genes CACNA1A, ATP1A2 and SCN1A are responsible for the FHM phenotype. Moreover, some mutations in ATP1A2 or SCN1A also may lead to epilepsy. Case Here we report on a three-generation family with five patients having a novel ATP1A2 mutation on exon 19, causing guanine-to-adenine substitution (c.2620G>A, p.Gly874Ser) that co-segregated in the five living relatives with migraine, four of whom had hemiplegic migraine. Moreover, three patients presented with epilepsy, one of whom had generalized epilepsy with febrile seizures plus (GEFS+). Conclusions The present study provides further evidence on the involvement of ATP1A2 mutations in both migraine and epilepsy, underlying the relevance of genetic analysis in families with a comorbidity of both disorders.

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Familial Hemiplegic Migraine with Severe Attacks: A New Report withATP1A2Mutation

Case Reports in Neurological Medicine ◽

10.1155/2016/3464285 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

E. Martínez ◽

R. Moreno ◽

L. López-Mesonero ◽

I. Vidriales ◽

M. Ruiz ◽

...

Keyword(s):

Ct Perfusion ◽

Familial Hemiplegic Migraine ◽

Sudden Onset ◽

Normal Brain ◽

Hemiplegic Migraine ◽

Perfusion Study ◽

Motor Weakness ◽

Atp1a2 Gene ◽

Type Headache

Introduction. Familial hemiplegic migraine (FHM) is a rare disorder characterized by migraine attacks with motor weakness during the aura phase. Mutations in CACNA1A, ATP1A2, SCN1A, and PRRT2 genes have been described.Methods. To describe a mutation in ATP1A2 gene in a FHM case with especially severe and prolonged symptomatology.Results. 22-year-old woman was admitted due to migraine-type headache and sudden onset of right-sided weakness and aphasia; she had similar episodes in her childhood. Her mother was diagnosed with hemiplegic migraine without genetic confirmation. She presented with fever, decreased consciousness, left gaze preference, mixed aphasia, right facial palsy, right hemiplegia, and left crural paresis. Computed tomography (CT) showed no lesion and CT perfusion study evidenced oligohemia in left hemisphere. A normal brain magnetic resonance (MR) was obtained. Impaired consciousness and dysphasia began to improve three days after admission and mild dysphasia and right hemiparesis lasted for 10 days. No recurrences were reported during a follow-up of two years. We identified a variant in heterozygous state in ATP1A2 gene (p.Thr364Met), pathogenic according to different prediction algorithms (SIFT, PolyPhen2, MutationTaster, and Condel).Conclusion. Prolonged and severe attacks with diffuse hypoperfusion in a FHM seemed to be specially related to ATP1A2 mutations, and p.T364M should be considered.

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

Cephalalgia ◽

10.1046/j.1468-2982.2000.00011.x ◽

2000 ◽

Vol 20 (1) ◽

pp. 45-50 ◽

Cited By ~ 55

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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The Genetics of Migraine Without Aura and Migraine With Aura

Cephalalgia ◽

10.1046/j.1468-2982.1993.1304245.x ◽

1993 ◽

Vol 13 (4) ◽

pp. 245-248 ◽

Cited By ~ 52

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.

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An Epidemiological Survey of Hemiplegic Migraine

Cephalalgia ◽

10.1046/j.1468-2982.2002.00371.x ◽

2002 ◽

Vol 22 (5) ◽

pp. 361-375 ◽

Cited By ~ 72

Author(s):

L Lykke Thomsen ◽

M Kirchmann Eriksen ◽

S Faerch Romer ◽

I Andersen ◽

E Ostergaard ◽

...

Keyword(s):

Sex Ratio ◽

Statistical Method ◽

Epidemiological Survey ◽

Case Finding ◽

Danish Population ◽

Hemiplegic Migraine ◽

National Patient Register ◽

National Patient ◽

Capture Recapture ◽

Finding Method

The objective of the present study was to use systematic nation-wide case-finding methods to establish the prevalence and sex ratio of hemiplegic migraine (HM) in the entire Danish population of 5.2 million inhabitants. Affected patients were identified from three different recruitment sources: the National Patient Register, case records from private practising neurologists and advertisements. Based on the observed number of affected patients from each case-finding method, it was attempted to estimate the total number of affected patients by means of the statistical method known as capture- recapture. Two hundred and ninety-one affected patients were identified; 147 were familial HM from 44 different families, 105 were sporadic HM and 39 were unclassifiable HM. The HM sex ratio (M: F) was 1: 3. Based on the identified number of affected patients the prevalence of HM at the end of 1999 was estimated to be 0.01% in Denmark, where the familial and sporadic form were equally frequent.

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