Alternating hemiplegia of childhood: clinical manifestations and long-term outcome

We present our analysis of 44 patients with alternating hemiplegia of childhood. The clinical course usually consisted of three phases. The first was dominated by abnormal eye movements and dystonic episodes, the second by hemiplegic spells and psychomotor regression, and the third by persistent developmental delay and fixed neurologic deficits. The age of onset was 0-54 months (mean = 7.9 +/- 13 months). The presenting signs included abnormal ocular movements in 65%, dystonia in 60%, and hemiplegia in 32%. Patients with an early onset of the disorder and an early appearance of hemiplegic spells faired the poorest developmentally. Developmental delay was present in 91%, ataxia in 68%, choreoathetosis in 50%, and seizures in 18%. Laboratory investigations suggested mitochondrial abnormalities and cerebrovascular dysfunction in several patients. Numerous therapies were largely ineffective. Flunarizine reduced the duration, severity, and frequency of the hemiplegic attacks in 78%. Patients who received flunarizine did not differ developmentally from those who did not. Our data suggest that flunarizine does not adversely affect and may favorably influence the outcome in patients with alternating hemiplegia of childhood. Additionally, the occurrence of autosomal-dominant cases of the syndrome, although rare, suggests that, in addition to mitochondrial dysfunction, genetic factors may be important.