Journal of Neurological Sciences 150 (1997) 13–25 Experimental benznidazole encephalopathy: II. Electroencephalographic and morphological alterations a,b c a Carmen Lucia Leite Flores-Vieira , Leila Chimelli , Regina Maria Franc ¸a Fernandes , a, * Amilton Antunes Barreira a ˜ Departments of Neurology, Psychiatry and Medical Psychology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, 14048-900 ˜ Ribeirao Preto, SP , Brazil b ˜ ˜ Department of Physiology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, 14048-900 Ribeirao Preto, SP , Brazil c ˜ ˜ Department of Pathology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, 14048-900 Ribeirao Preto, SP , Brazil Received 30 December 1995; revised 23 October 1996; accepted 28 November 1996 Abstract We describe electroencephalographic (EEG) and morphological alterations in the CNS of dogs treated with benznidazole. The relationship between dose, duration of treatment and intensity of lesions observed was examined and used to establish anatomo-clinical associations. Two predominant EEG patterns were noted in treated dogs. Most of the animals (Group I) that received acute treatment with high doses (30 mg/kg/day) for 15 days followed by treatment at a lower dose (10 mg/kg/day) exhibited a type 2, EEG pattern, i.e., low voltage desynchronized with fast activity (LVFA). In contrast, most of the animals (Group II) that received short-term acute treatment with high doses (40 mg/kg/day) for 7 days followed by chronic treatment at lower doses (20 and 5 mg/kg/day) presented a type 1 EEG pattern, high voltage diffuse with slow activity (HVSA). Even after the drug was discontinued, the animals presented mild EEG alterations. These alterations, observed during and after treatment with benznidazole, suggest the presence of encephalopathy with multifocal characteristics. Several morphological alterations were observed in the animals, the most important being: lymphocytic inflammatory infiltrate, neuronal degeneration, satellitosis, demyelination and axonal degeneration, microglial proliferation, necrosis and gliosis. Such alterations involved the meninges, cerebral cortex, hemispheric white matter and subcortical gray matter, brain stem, cerebellum, and, less frequently, the spinal cord. No histopathological alterations were detected in the peripheral nerves. All encephalic levels were involved in all animals treated although the use of the high doses for 15 days (Group I) appeared to result in more lesions in the subcortical gray matter and the lower brainstem when compared to the use of high doses for 7 days (Group II) which led to greater involvement of the cerebral cortex, hemispheric white matter, cerebellum and medulla.  1997 Elsevier Science B.V. Keywords: Benznidazole; Chagas’ disease; Experimental encephalopathy; Electroencephalographic and morphological alterations 1. Introduction former drug (Rogulja et al., 1973). Treatment with met- ronidazole induces symmetrical and spongiform lesions in Various studies involving different experimental models the cochlear, vestibular and cerebellar roof, and paramedial have been conducted to determine the effect of nitroim- lesions in the anterior colliculus and superior olivary nuclei idazole drugs. Rats receiving metronidazole and mis- (Griffin et al., 1980). No changes are observed in the onidazole exhibit symmetrical and spongiform lesions in peripheral nervous system (PNS) of rats receiving mis- the vestibular and olivary nuclei, occasionally involving onidazole and / or metronidazole at doses similar to those the cochlear and cerebellar roof nuclei in the case of the administered in man (Bradley et al., 1977). Degenerative changes and a loss of the Purkinje cells of the cerebellum * has been reported in dogs treated with 50 mg / kg / day of Corresponding author: Tel.: (55-16) 633-0866; fax: (55-16) 633-9606; ¨ e-mail: aabarrei@fmrp.usp.br benznidazole for 3–20 days (Scharer, 1972). 0022-510X / 97 / $17.00  1997 Elsevier Science B.V. All rights reserved PII S0022-510X(97)05362-8