Other cerebellotoxic agents

DRUGS Anticonvulsants Phenytoin Clinical findings Phenytoin is the anticonvulsant drug which is the most frequently implicated in drug-induced cerebellar ataxia. Toxicity develops either during chronic treatment or as a consequence of an acute overdose. Patients exhibit cerebellar signs ranging from a mild vestibulo-ocular cerebellar syndrome including nystagmus and ataxic gait, to a marked pancerebellar syndrome comprising nystagmus, ocular dysmetria, slurred speech, limb ataxia, and broadbased ataxic gait (Utterbock, 1958; Selhorst et al., 1972). In the case of chronic administration for epilepsy, the delay between initiation of treatment and onset of ataxic signs varies from several days to several years. The cerebellar syndrome may be completely reversible after reduction of doses or withdrawal of the drug, or can be irreversible. Most clinicians agree that patients exhibiting irreversible signs have a higher phenytoin serum level and a longer history of epilepsy than those with reversible signs (Munoz-Garcia et al., 1982). In addition, these patients were usually taking a greater number of drugs. In rare conditions, phenytoin-induced cerebellar ataxia may be associated with a peripheral neuropathy or a slight cognitive deterioration. In the case of overt or silent cerebellar disease, patients are at risk of developing marked ataxia when phenytoin is administered. For instance, in hereditary myoclonus epilepsy, phenytoin worsens myoclonic jerks and generates severe ataxia. Phenytoin is also toxic during the prenatal period. Indeed, pontocerebellar hypoplasia has been described following intrauterine exposure in humans (Gadisseaux et al., 1984; Squier et al., 1990).