Семейная гемиплегическая мигрень: генетика, симптомы и диагностика.

Familial hemiplegic migraine (FHM) is an autosomal dominant type of hemiplegic migraine that typically includes weakness of half the body which can last for hours, days, or weeks. It can be accompanied by other symptoms, such as ataxia, coma, and paralysis. Migraine attacks may be provoked by minor head trauma. Some cases of minor head trauma in patients with hemiplegic migraine can develop into delayed cerebral edema, a life threatening medical emergency. Clinical overlap occurs in some FHM patients with episodic ataxia type 2 and spinocerebellar ataxia type 6, benign familial infantile epilepsy, and alternating hemiplegia of childhood. Three genetic loci for FHM are known. FHM1, which accounts for about 50% of FHM patients, is caused by mutations in a gene coding for the P/Q type calcium channel α subunit, CACNA1A. FHM1 is also associated with cerebellar degeneration. FHM2, which accounts for less than 25% of cases, is caused by mutations in the / ATPase gene ATP1A2. FHM3 is a rare subtype of FHM and is caused by mutations in a sodium channel α subunit coding gene, SCN1A. These three subtypes do not account for all cases of FHM, suggesting the existence of at least one other locus (FHM4). Also, nonfamilial cases of hemiplegic migraine are seen, termed sporadic hemiplegic migraine. These cases seem to have the same causes as the familial cases and represent de novo mutations. Sporadic cases are also clinically identical to familial cases with the exception of a lack of known family history of attacks.

FHM signs overlap significantly with those of migraine with aura. In short, FHM is typified by migraine with aura associated with hemiparesis, and in FHM1, cerebellar degeneration, which can result in episodic or progressive ataxia. FHM can also present with the same signs as benign familial infantile convulsions and alternating hemiplegia of childhood. Other symptoms are altered consciousness (in fact, some cases seem related to head trauma), gaze evoked nystagmus, and coma. Aura symptoms, such as numbness and blurring of vision, typically persist for 30–60 minutes, but can last for weeks to months. An attack resembles a stroke, but unlike a stroke, it resolves in time. These signs typically first manifest themselves in the first or second decade of life.

See the equivalent section in the main migraine article. FHM mutations are believed to lead to migraine susceptibility by lowering the threshold for cortical spreading depression generation. The FHM1 and FHM3 mutations occur in ion channels expressed in neurons. These mutations may lead to both the hyper and hypoexcitable neurons that might underlie cortical spreading depression. How the mutations seen in FHM2 patients might lead to FHM symptoms is even less clear, as the gene mutated in FHM2 is expressed primarily in astrocytes. One proposal states that the depolarization of astrocytes caused by haploinsufficiency of the ATP1A2 / ATPase causes increased release of compounds such as adenosine from astrocytes. These compounds then interact with neighboring neurons, altering their excitability and leading to cortical spreading depression and migraine.

The final locus for FHM maps to the q arm of chromosome 1. A number of attractive candidate genes occur in this area, though no mutations in them have yet been linked to FHM4.

Other genes associated with this condition are proline rich transmembrane protein 2 (PRRT2) and SLC4A4, which encodes the electrogenic NaHCO3 cotransporter NBCe1.

Prenatal screening is not typically done for FHM, but it may be performed if requested. As penetrance is high, individuals found to carry mutations should be expected to develop signs of FHM at some point in life.

See the equivalent section in the main migraine article. People with FHM are encouraged to avoid activities that may trigger their attacks. Minor head trauma is a common attack precipitant, so FHM sufferers should avoid contact sports. Acetazolamide or standard drugs are often used to treat attacks, though those leading to vasoconstriction should be avoided due to the risk of stroke.

Migraine itself is a very common disorder, occurring in 15–20% of the population. Hemiplegic migraine, be it familial or spontaneous, is less prevalent, at 0.01% prevalence according to one report. Women are three times more likely to be affected than males.