Hemiplegic and Basilar-type Migraine: Epidemiology, Genetics, and Mechanisms

Abstract

Migraine is a frequent primary paroxysmal headache disorder. Within the migraine spectrum, rare variants can be recognized, such as hemiplegic migraine and basilar-type migraine. Hemiplegic migraine can occur sporadically or run in families with an autosomal dominant inheritance pattern. Genetic research in familial hemiplegic migraine has led to the identification of three genes so far. The CACNA1A gene is associated with the FHM1 phenotype, the ATP1A2 gene with FHM2, and the SCN1A gene with FHM3. A large phenotypic variety is seen, without a clear genotype-phenotype relation. While additional cerebellar ataxia predominantly is associated with the FHM1 phenotype, all three are associated with epileptic phenomena. Mutated genes in all three types of FHM are important in ion transport, defining FHM—and probably migraine in general—as an “ionopathy.” Functional studies of FHM1, FHM2, and FHM3 link the effects to the initiation of cortical spreading depression. With the identification of the three genetic subtypes of FHM, confirmation of a migraine diagnosis by molecular tests has become available.