EXPERIMENTAL BENZNIDAZOLE ENCEPHALOPATHY .2. ELECTROENCEPHALOGRAPHIC AND MORPHOLOGICAL ALTERATIONS

We describe electroencephalographic (EEG) and morphological alteration s in the CNS of dogs treated with benznidazole. The relationship betwe en dose, duration of treatment and intensity of lesions observed was e xamined and used to establish anatomo-clinical associations. Two predo minant EEG patterns were noted in treated dogs. Most of the animals (G roup I) that received acute treatment with high doses (30 mg/kg/day) f or 15 days followed by treatment at a lower dose (10 mg/kg/day) exhibi ted a type 2, EEG pattern, i.e., low voltage desynchronized with fast activity (LVFA). In contrast, most of the animals (Group II) that rece ived short-term acute treatment with high doses (40 mg/kg/day) for 7 d ays followed by chronic treatment at lower doses (20 and 5 mg/kg/day) presented a type 1 EEG pattern, high voltage diffuse with slow activit y (HVSA). Even after the drug was discontinued, the animals presented mild EEG alterations. These alterations, observed during and after tre atment with benznidazole, suggest the presence of encephalopathy with multifocal characteristics. Several morphological alterations were obs erved in the animals, the most important being: lymphocytic inflammato ry infiltrate, neuronal degeneration, satellitosis, demyelination and axonal degeneration, microglial proliferation, necrosis and gliosis. S uch alterations involved the meninges, cerebral cortex, hemispheric wh ite matter and subcortical gray matter, brain stem, cerebellum, and, l ess frequently, the spinal cord, No histopathological alterations were detected in the peripheral nerves. All encephalic levels were involve d in all animals treated although the use of the high doses for 15 day s (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 cerebra l cortex, hemispheric white matter, cerebellum and medulla. (C) 1997 E lsevier Science B.V.