Clinical and experimental studies of phenytoin-induced hyperkinesias.

Phenytoin administration occasionally leads to the induction of hyperkinetic movement disorders. The pathophysiologic basis of this phenomena is unknown, but thought to be a toxic effect of phenytoin. Study of two cases of this disorder and a review of the literature suggest that antecedant pathologic changes in the basal ganglia are prerequisites for the development of phenytoin-induced hyperkinesias. In an animal model of tardive dyskinesia, phenytoin was found to enhance neuroleptic-induced behavioral supersensitivity but have no effect in control animals. We conclude that phenytoin induced hyperkinesias reflect a specific effect of phenytoin on an abnormal neural substrate and suggest the presence of an otherwise silent pathological alteration of the corpus striatum. The diagnostic value of an episode of phenytoin-induced hyperkinesia is discussed.