The natural history and long-term outcome of alternating hemiplegia of childhood (AHC) was studied by questionnaire within a large cohort of 157 patients, as part of the European Network for Research on Alternating Hemiplegia (ENRAH) project. The study was largely retrospective and, for 2 years, prospective. Patients were aged from 9 months to 52 years at time of inclusion. Median age at diagnosis was 20 months. All had hemiplegic attacks, 91% had abnormal ocular movements, 86.5% reported episodes of bilateral weakness, 88% tonic/dystonic attacks, 53% epileptic seizures, 72% had chorea, and 92% mental retardation. Premonitory signs or aura were reported in 41% patients, and sleep inhibited attacks in the majority (83%) of cases. A relaxing environment (music, massage) had a beneficial effect. Children with abnormal ocular movements and hypotonia improved in adulthood, whereas the severity of other symptoms in the whole cohort did not change over the course of the illness. Gait was unsteady in 84%, and school attendance and employment were severely impacted. Seven patients died, some during severe plegic attacks or seizures. Severe hemiplegic/dystonic attacks did not increase risk of poor outcome. The natural history of AHC in individual patients was highly variable and fluctuating and, as a group, did not indicate a progressive and degenerative course. Risk of sudden death in a minority was associated with more severe neurological impairment. Various treatments were employed, all receiving flunarizine as prophylactic agent of non-epileptic events, partially effective in 74%. AEDs had no significant effect on non-paroxysmal events and only occasional control of paroxysmal symptoms. Diazepam sometimes reduced the duration of dystonic attacks. [1]

COMMENT. AHC is characterized by episodes of hemiplegia, dystonic and other non-epileptic paroxysmal events (paroxysmal nystagmus, autonomic disorder), epileptic seizures, and global neurological impairment. Between episodes, patients are neurologically impaired, with ataxia, athetosis or chorea, the majority developing mental retardation. Onset is in infancy, sometimes in the neonatal period. Consciousness is preserved during episodes. The pathophysiology has been compared to hemiplegic migraine, but differs in the development of fixed neurological impairment and retardation.