Hemiplegic Migraine: Clinical Features, Links with Basilar-type Migraine, Current and Future Treatment

Abstract

Hemiplegic migraine (HM) is a rare variety of migraine with aura characterized by the presence of a motor weakness during the aura. The HM has two main forms according to the familial history: cases where at least one first-or second-degree relative has aura including motor weakness have familial hemiplegic migraine (FHM), and cases without such familial history have sporadic hemiplegic migraine (SHM). FHM is the only variety of autosomal dominant migraine and all three known genes encode ion-transporters. Typical HM attacks include a motor weakness that is always associated to other aura symptoms, the most frequent being sensory, visual, and speech disturbances. In addition, basilar-type symptoms occur in up to 70% of the patients. Severe attacks may occur in FHM as well as in SHM with prolonged hemiplegia, confusion, coma, fever, and seizures. The clinical spectrum also includes permanent cerebellar signs (nystagmus, ataxia, dysarthria) and less frequently various types of seizures and mental retardation. A genetic diagnosis is now possible by screening the two major genes involved in FHM (CACNA1A and ATP1A2). Treatment of FHM and SHM is based on what is done in other varieties of migraine with aura. According to the new physiopathologic insights, preventive treatments by various antiepileptic agents seem promising.

Novel missense mutation in the ATP1A2 gene associated with atypical sporadic hemiplegic migraine

“…Even if reported mutations are scattered throughout the gene, the majority of them are concentrated in the intracellular linker between the fourth and fifth transmembrane segments, which may affect the correct folding of the protein 21 22. On the contrary, we found a novel mutation in the ninth transmembrane domain, which could be responsible for the atypical phenotype, since different mutations in FHM genes partly account for clinical variability 6. However, more extensive clinical studies are needed to establish a genotype-phenotype correlation.…”

“…Mean age at onset ranges from 11 to 13 years old in pure FHM and from 8 to 19 years old in SHM 1. Attacks may begin as early as age 5 years or start later in life, even at 75 years old 2 6. So far, FHM is linked to mutations in three genes, CACNA1A (FHM1-MIM#301011), ATP1A2 (FHM2-MIM#182340) and SCN1A (FHM3-MIM#182389), which encode for ion transporters.…”

“…Recently, also proline-rich transmembrane protein 2 (PRRT2-MIM#614386) has been associated with HM 7. The clinical spectrum of HM varies from pure forms to those associated with other neurological disorders such as impaired consciousness, epileptic seizures, permanent cerebellar ataxia or mental retardation 6…”

A Young Man Presenting with Acute Encephalopathy, Hemiparesis, and Headache

“…For example, although aura symptoms generally persist for 1-6 h, up to 40% of patients can experience one or more atypical attacks in which the aura may last for several days (16). Additionally, headache may not be present in all cases; 4% of FHM patients experience headache only during some of their attacks, whereas 1% never experience headache during attacks (1) .…”