Therapeutic yet toxic: Phenytoin-associated cerebellar atrophy

Abstract: Phenytoin remains a widely utilized and economical antiepileptic medication, yet prolonged administration has been associated with cumulative neurological toxicity, including cerebellar injury, even when serum drug levels fall within the accepted therapeutic range. We describe a case involving a 24-year-old male with a history of epilepsy since early childhood who had been maintained on long-term phenytoin therapy and subsequently developed progressive gait imbalance, truncal instability, dysarthria, and impaired motor coordination. Neurological examination demonstrated prominent cerebellar signs. Laboratory evaluation revealed a serum phenytoin level of 22.4 µg/mL, corresponding to the therapeutic to borderline-elevated range. Brain magnetic resonance imaging showed diffuse cerebral and cerebellar atrophy, and neurophysiological studies supported cerebellar dysfunction in the absence of significant peripheral neuropathy. While a hereditary cerebellar ataxia was initially considered, the temporal relationship with chronic phenytoin exposure, characteristic imaging findings, and partial clinical stabilization following drug withdrawal supported a diagnosis of phenytoin-induced cerebellar degeneration. This report highlights the importance of routine neurological surveillance, early identification of adverse drug effects, and prompt transition to safer antiepileptic alternatives to minimize the risk of irreversible neurological damage.