EXPERIMENTAL BENZNIDAZOLE ENCEPHALOPATHY .1. CLINICAL-NEUROLOGICAL ALTERATIONS

Benznidazole (N-benzyl-2-nitro-1-imidazoleacetamide) is an antiprotozo an agent of the nitroimidazole group used extensively in South America to treat Chagas' disease. In humans, its most important side effect i s peripheral polyneuropathy, the frequency of which is dose related. T o evaluate this effect, we administered benznidazole to adult, male, m ongrel dogs at doses ranging from 5 to 40 mg/kg/day (0.5 to 4 times th e dose used to treat chagasic patients). Subsequent neurological exami nation revealed apathy, ataxia, spastic tetraplegia with hyperreflexia of stretching reflexes, balance disorders and asymmetrical gait. Thes e alterations appeared earlier and were more intense at the higher dos es. Drug withdrawal also left dose- and time-dependent sequelae like a taxia, hypertonia, hyperreflexia and alterations of balance. No periph eral neuropathy was detected. The present findings suggest that a care ful reevaluation of the side effects of benznidazole in humans is nece ssary. (C) 1997 Elsevier Science B.V.