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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cerebellar atrophy in phenytoin-treated mentally retarded epileptics.

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. The mean duration of phenytoin intoxication until locomotion was lost was 22.8 +/- 23.6 months. There was a temporal relationship between the high serum level of phenytoin and the loss of locomotion. The degree of brain atrophy in the posterior fossa was most severe in these 18 patients with severe phenytoin intoxication. The 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 in serum correlated significantly with the heights of the fourth ventricle suggests that an overdosage of phenytoin or an underlying disease, or both, were the probable causes of cerebellar impairment and atrophy. Thus brain-damaged mentally retarded epileptics appear to be unusually susceptible to the side effects of phenytoin. This antiepiliptic drug is therefore not recommended for patients with no locomotor ability or with marked cerebellar signs and symptoms. To prevent phenytoin intoxication in susceptible patients, careful observation of the patients and routine monitoring of phenytoin levels in blood are stressed.[1]


  1. Cerebellar atrophy in phenytoin-treated mentally retarded epileptics. Iivanainen, M., Viukari, M., Helle, E.P. Epilepsia (1977) [Pubmed]
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