Neurological sequelae following Dilantin® overdose in a patient and in experimental animals

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Abstract
The patient reported had received large amounts of Dilantin (up to 1 g a day) for 2 to 4 weeks before admission. She also had phenobarbital, Librium, and Mysoline in smaller amounts. She was admitted to the hospital stuporous with marked nystagmus and so ataxic that she was unable to stand or sit. These signs diminished after the drugs were discontinued, but twenty months later she still had nystagmus and was unable to walk without support. Dilantin in usual dosages was adequately metabolized and the toxic signs and persisting sequelae were thought to be due to prolonged overdosage of Dilantin and possibly to interference with Dilantin metabolism by phenobarbital when the latter was also given in large amounts. To clarify further the mechanisms of Dilantin intoxication with neural injury, rats and cats were given the drug in various amounts and length of time. Loss of Purkinje cells, edema of Bergmann''s glial layer, and degenerative cell changes were seen in the cerebellums of animals that were kept intoxicated for fourteen days or longer. Shorter periods of intoxication produced minimal histological changes or no changes in the cerebellum. The Dilantin blood levels of rats and cats ranged from 30 to 61 [mu]g/ml and the cerebellar tissue levels from 50 to 120 [mu]g/ml/g of wet tissue. The cerebellum and brainstem usually contained more Dilantin/g of wet tissue than the cerebral hemispheres.