[Diphenylhydantoin, epilepsy, cerebellar atrophy--histological and electron microscope examinations (author's...

Neuropathological investigations of CNS of two epileptic patients (a man and a woman), who had been treated over years with diphenylhydantoin, disclosed in both cases severe cerebellar atrophy, with almost complete loss of Purkinje cells. Hypoxic tissue alterations were found neither in cerebellum nor in cerebrum. Ultrastructural examination of formalin fixed tissue revealed in cytoplasm of degenerating Purkinje cells multilamellar structures similar to those reported by other authors, presumably consisting of proliferated cisternae of endoplasmic reticulum, degenerating mitochondria and "multilamellar cytoplasmic bodies". However, these findings are very probably not specific; they were detected also in Purkinje cells of a non-epileptic patient of the same age-group, suddenly deceased by car accident. Reversible cerebellar dysfunction is a common manifestation of acute phenytoin toxicity. However, further factors can influence the action of DPH, leading to chronic intoxication and irreversible cerebellar damage. A review of these factors is given. The periodic monitoring of serum DPH-concentration is emphasized.