Families have been described in which this condition is the result of a mutation in an ion channel (familial hemiplegic migraine; alternating hemiplegia of childhood). Of the known loci, which together account for more than half of cases, the most common one is in the gene coding for the P/Q-type calcium channel α subunit (CACNA1A). A second locus is in the gene for the Na+/K+-adenosine triphosphatase (ATPase) channel (ATP1A2) and a rarer subtype is caused by mutations in a sodium channel α-subunit gene (SCNA1). These, however, do not account for all cases, indicating that other mutations will inevitably be discovered. It is reasonable to surmise that many of the nonfamilial cases of hemiplegic migraine are also caused by these mutations.
By their nature, these channelopathies would be expected to have clinical and genetic overlap with other neurologic diseases. Indeed, there are shared traits between some of the genetic forms of familial hemiplegic migraine and both episodic and degenerative cerebellar diseases (Goadsby, 2007). Ducros and colleagues have found a variety of other neurologic features in these families, including persistent cerebellar ataxia and nystagmus in 20 percent; others had attacks of coma and hemiplegia from which they recovered. Also notable because of genetic overlap are an acetazolamide-responsive ataxia that has in common other mutations in the CACNA1A gene, and the cerebrovascular disorder known as CADASIL, discussed in Chap. 33, which, in rare families, presents with hemiplegic migraine but instead is related to the Notch3 gene on the same chromosome (19).
Complicating the situation is the undoubted existence of sporadic migraine with transient hemiplegia that has no familial trait (see further on under Transient Ischemic Attacks and Stroke with Migraine). Neurologic symptoms lasting more than an hour or so should prompt investigation for alternative causes, but none may be found. Instances of hemiplegic migraine may account for some of the inexplicable strokes in young women and older adults of both sexes, as also discussed further on. The treatment of these conditions is discussed in a later section.
In some individuals, migraine attacks, for unaccountable reasons, may increase in frequency for several months. As many as three or four attacks may occur each week, leaving the scalp on one side continuously tender. When this occurs for more than half of the days in a month, the International Headache Society terms the condition chronic migraine.
An even more difficult clinical problem is posed by migraine that lapses into a debilitating condition of severe continuous headache (status migrainosus; defined by the Headache Society as lasting greater than 72 h). The pain is initially unilateral, later more generalized, more or less throbbing, but with a constant superimposed ache and is disabling; vomiting or nausea is common at the outset but abates. The absence of prior headaches should raise concern about a more serious cause. Status migrainosus sometimes follows a head injury or a viral infection, but most cases have no explanation.