Migraine is a common neurological disorder characterized by painful episodes sometimes preceded by transient neurological symptoms and reversible defined migraine aura. Rarer forms of migraine are hemiplegic migraine, familial and sporadic, the retinal migraine and migraine equivalents. For the two most common forms of migraine with and without aura, the prevalence appears to be higher in femal...

Migraine is a public health problem of great impact on both the patient and society. The overall migraine prevalence in western countries is 6–8% in men and 15–25% in women. It has been calculated that about 5% of the general population have at least 18 days of migraine per year, and that at least 1% — that is, more than 2.5 million people in North America — have at least one day of migraine pe...

Latent class analysis was performed on migraine symptom data collected in a Dutch population sample (N = 12,210, 59% female) in order to obtain empirical groupings of individuals suffering from symptoms of migraine headache. Based on these heritable groupings (h(2) = 0.49, 95% CI: 0.41-0.57) individuals were classified as affected (migrainous headache) or unaffected. Genome-wide linkage analysi...

Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant form of migraine with aura that is caused by mutations of the α2-subunit of the Na,K-ATPase, an isoform almost exclusively expressed in astrocytes in the adult brain. We generated the first FHM2 knock-in mouse model carrying the human W887R mutation in the Atp1a2 orthologous gene. Homozygous Atp1a2(R887/R887) mutants died just ...

Studies of migraine with aura (MA) have shown familial aggregation of the disorder, which cannot be explained by simple mendelian inheritance. The interest in a genetic basis for the disorder has increased after identification of three genetic loci for familial hemiplegic migraine (FHM), which is a rare subtype of MA with autosomal dominant inheritance. Both genetic and environmental factors se...

Advances in molecular biology have increased our understanding of both inherited and sporadic forms of neurological disease. In this review, the impact of these advances is discussed in relation to specific neurological conditions. These include the hereditary neuropathies and ataxias, Huntington's disease, and the muscular dystrophies, as well as Alzheimer's disease, Parkinson's disease, and m...

The discovery of mis-sense mutations in the alpha1A subunit of the P/Q-type calcium channel in patients with familial hemiplegic migraine indicates the potential involvement of dysfunctional ion channels in migraine. The periaqueductal gray (PAG) region of the brainstem modulates craniovascular nociception and, through its role in the descending pain modulation system, may contribute to migrain...

Familial hemiplegic migraine (FHM) is an autosomal dominant inherited subtype of severe migraine with aura. Mutations causing FHM (type 3) have been identified in SCN1A, the gene encoding neuronal voltage-gated Na(v)1.1 Na(+) channel alpha subunit, but functional studies have been done using the cardiac Na(v)1.5 isoform, and the observed effects were similar to those of some epileptogenic mutat...

CACNA1A mutations cause a range of disorders with diverse, sometimes overlapping clinical features. Point mutations, including missense mutations, nonsense mutations, splicing mutations and small deletions/insertions, result in a variety of phenotypes including episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1 (FHM1). These 2 conditions show clinical overlap with spinocerebel...

Background—Migraine is an independent risk factor for stroke. Mechanisms underlying this association are unclear. Familial hemiplegic migraine (FHM), a migraine subtype that also carries an increased stroke risk, is a useful model for common migraine phenotypes because of shared aura and headache features, trigger factors, and underlying glutamatergic mechanisms. Methods and Results—Here, we sh...