Cerebellar Atrophy in Phenytoin‐Treated Mentally Retarded Epileptics

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Abstract
The relationship among the serum concentration of phenytoin, pneumoencephalographic measurements describing, in particular, cerebellar atrophy and various other clinical variables was analyzed statistically in a series of 131 phenytoin-treated mentally retarded epileptics. Phenytoin intoxication was diagnosed retrospectively in 73 patients (56%), of whom 18 had persistent loss of locomotion. Mean duration of intoxication until locomotion was lost was 22.8 .+-. 23.6 mo. There was a temporal relationship between high serum level and loss of locomotion. Degree of brain atrophy in the posterior fossa was most severe in these 18 patients with severe intoxication. Frequency of cerebellar and/or brain stem atrophy in the present series was 28%, the same as in mentally retarded epileptics without phenytoin treatment from the same institution. That phenytoin levels correlated significantly with heights of the 4th ventricle suggests that overdosage and/or underlying disease were probable causes of cerebellar impairment and atrophy. Brain-damaged mentally retarded epileptics appear to be unusually susceptible to the drug''s side effects. This antiepileptic drug is not recommended for patients with no locomotor ability or with marked cerebellar signs and symptoms. To prevent intoxication in susceptible patients, careful observation of patients and routine monitoring of phenytoin levels in blood are stressed.