Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Cephalalgia 2009 Dec
PMID:The FHM1 mutation S218L: a severe clinical phenotype? A case report and review of the literature. 1943 26

Mutations in the CACNA1A gene on chromosome 19 have been associated with a variety of clinical disorders, including familial hemiplegic migraine type 1 and episodic ataxia type 2 (EA2). We report a patient with 2 distinct attack types, one representing EA2 and the other, basilar-type migraine. Genetic testing revealed a novel nonsense mutation in the CACNA1A gene at codon position 583. Treatment with acetazolamide relieved both types of attacks. We hypothesize that the CACNA1A gene mutation may contribute to both typical EA2 and typical basilar-type migraine, extending the spectrum of clinical manifestations associated with CACNA1A mutations.
Headache 2009 Jul
PMID:CACNA1A nonsense mutation is associated with basilar-type migraine and episodic ataxia type 2. 1948 77

A 34-year-old man was admitted with his unsteady gait, difficulty in speech and a paroxysmal severe headache accompanied with sensori-motor disturbance of the right extremities and aphasic symptom. His family history was unremarkable. His unsteadiness has progressed very slowly from childhood. He noted to be inarticulate at the age of 18 years. At the age of 33 years, he suddenly had an attack of severe throbbing headache, which was mainly left parietal, with nausea and photophobia. During the headache, his right extremities were paralyzed and he became aphasic. He had lost a partial memory of the event All these symptoms had gone within 24 hours. Thereafter, the same headache occurred about once a month. Neurological examination revealed a mild truncal ataxia and ataxic dysarthria. Electroencephalography (EEG) showed intermittent delta waves restricted over the left fronto-temporal region. Brain MRI showed a moderate atrophy of superior cerebellar vermis and anterior cerebellar lobe. The diagnosis of sporadic hemiplegic migraine (SHM) with cerebellar ataxia was made. Our case was very similar to familial hemiplegic migraine (FHM) 1, of which some families are accompanied with transient amnesia, cerebellar ataxia and EEG abnormality. Although we did not detect any mutations in CACNA1A gene previously reported in FHM1, our case might share same pathogenesis with FHM1.
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PMID:[Case of sporadic hemiplegic migraine with cerebellar ataxia]. 1959 4

An association between hemiplegic migraine (HM) and episodic ataxia type 2 (EA2) has been described; both disorders are linked to mutations in the CACNA1A gene. Although confusion occurs in 21% of patients with HM, we found only one case in the literature of confusional episodes associated with ataxia without hemiplegia. These findings raise the possibility of confusional episodes being part of both the HM and EA2 phenotype. However, a patient with episodic ataxia, confusional spells and CACNA1A gene mutations has not been identified. We describe four individuals, spanning three generations of a family, with episodic ataxia without hemiplegia and confusion, in association with a CACNA1A mutation. We follow with a description of the relationship between the CACNA1A mutations and the three syndromes, suggesting a potential need for a new classification in which the conditions can be subsumed.
Cephalalgia 2010 Jun
PMID:Link between confusional migraine, hemiplegic migraine and episodic ataxia type 2: hypothesis, family genealogy, gene typing and classification. 1962 85

Sporadic and familial hemiplegic migraines (SHM and FHM) are rare paroxysmal disorders characterized by motor aura and headache. The distinction is based on whether other family members are affected. The majority of FHM families have a mutation in one of the ion channels CACNA1A, ATP1A2 and SCN1A. SHM is sometimes caused by a de novo mutation in one of the genes. Clinical trials of SHM and FHM have not been conducted. Seizure in FHM is secondary to cerebral edema and fever among other factors. The regional cerebral blood flow is reduced during the reversible aura symptoms. Triptans and ergotamine are contraindicated in the management of SHM and FHM based on the pathophysiology. Nimodipine is contraindicated. Acute and prophylactic management are otherwise based on the management principle of the migraine without aura and migraine with aura.
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PMID:Management of sporadic and familial hemiplegic migraine. 2018 61

The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.
Curr Pain Headache Rep 2010 Aug
PMID:Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects. 2049 66

A female patient presented with horizontal gaze nystagmus, mild cerebellar ataxia, recurrent headache and hemiplegia since childhood with cerebellar atrophy on magnetic resonance imaging. Genetic analysis revealed a CACNA1A gene mutation, leading to a diagnosis of familial hemiplegic migraine (FHM1). FHM is very rare, but should be considered as a differential diagnosis for childhood cerebellar symptoms and/or cerebellar atrophy. To avoid missing FHM1, a detailed clinical history including headache or hemiplegia is essential. Oral acetazolamide during the aura phase, comprising mild headache and abnormal leg sensation, relieved these symptoms in this patient, suggesting that acetazolamide could represent a first line of treatment.
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PMID:Genetic diagnosis and acetazolamide treatment of familial hemiplegic migraine. 2054 93

Several episodic neurological diseases, including familial hemiplegic migraine (FHM) and different types of epilepsy, are caused by mutations in ion channels, and hence classified as channelopathies. The classification of FHM as a channelopathy has introduced a new perspective in headache research and has strengthened the idea of migraine as a disorder of neural excitability. Here we review recent studies of the functional consequences of mutations in the CACNA1A and SCNA1A genes (encoding the pore-forming subunit of Ca(V)2.1 and Na(V)1.1 channels) and the ATPA1A2 gene (encoding the alpha(2) subunit of the Na(+)/K(+) pump), responsible for FHM1, FHM3, and FHM2, respectively. These studies show that: (1) FHM1 mutations produce gain-of-function of the Ca(V)2.1 channel and, as a consequence, increased glutamate release at cortical synapses and facilitation of induction and propagation of cortical spreading depression (CSD); (2) FHM2 mutations produce loss-of-function of the alpha(2) Na(+)/K(+)-ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na(V)1.5 channels. These findings are consistent with the hypothesis that FHM mutations share the ability to render the brain more susceptible to CSD, by causing excessive synaptic glutamate release (FHM1) or decreased removal of K(+) and glutamate from the synaptic cleft (FHM2) or excessive extracellular K(+) (FHM3).
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PMID:Biological science of headache channels. 2081 11

Insight into the molecular mechanisms involved in primary headaches is important to identify drug targets for improving treatment of patients, but essentially lacking. Genetic research is increasingly successful in pinpointing these mechanisms. Most progress has been made for Familial Hemiplegic Migraine, a rare subtype of migraine with aura. Three genes (CACNA1A, ATP1A2 and SCN1A) have been identified that all encode ion transporters. Cellular and transgenic mouse studies suggest that neuronal hyperexcitability and increased susceptibility to cortical spreading depression, the correlate of migraine aura, are important molecular mechanisms in migraine. Investigating monogenic diseases in which migraine is a prominent feature such as CADASIL, which is caused by mutations in the NOTCH3 gene, can help understanding the pathology of migraine. Candidate gene association studies and linkage studies in the common forms of migraine were less successful. Except for the MTHFR gene no gene variant has been identified yet. Convincingly demonstrated genetic findings in other primary headaches such as cluster headache and tension-type headache are even rarer. However, with current technical possibilities of massive genotyping and international efforts to collect large well-phenotyped patient cohorts, the first gene variants for various primary headache types are likely to be discovered in the coming decade.
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PMID:Genetics of headaches. 2081 12

We report the case of a 9-year-old girl with early-onset developmental delay, chronic ataxia and prolonged hemiplegic migraine episodes bringing about progressive deterioration. Two days into one episode, diffusion-weighted magnetic resonance imaging disclosed unilateral striatal abnormal signal consistent with cytotoxic edema, which evolved into atrophy on follow-up scans. Mutational screen of CACNA1A gene identified a de novo p.Tyr1387Cys mutation.
Headache
PMID:Acute striatal necrosis in hemiplegic migraine with de novo CACNA1A mutation. 2208 23


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