Experimental benznidazole encephalopathy: II. Electroencephalographic and morphological alterations

• Published in: Journal of the neurological sciences 1997-09, Vol.150 (1), p.13-25
• Main Authors: Flores-Vieira, Carmen Lucia Leite, Chimelli, Leila, Maria França Fernandes, Regina, Antunes Barreira, Amilton
• Format: Article
• Language: English
• Subjects: Animals; Benznidazole; Biological and medical sciences; Brain - drug effects; Brain - pathology; Brain Diseases - chemically induced; Brain Diseases - pathology; Brain Diseases - physiopathology; Cerebellum - drug effects; Cerebellum - pathology; Chagas' disease; Dogs; Drug toxicity and drugs side effects treatment; Electroencephalographic and morphological alterations; Electroencephalography - drug effects; Experimental encephalopathy; Medical sciences; Microglia - drug effects; Microglia - pathology; Nerve Degeneration; Neurons - drug effects; Neurons - pathology; Neurotoxins; Nitroimidazoles - toxicity; Peripheral Nerves - drug effects; Peripheral Nerves - pathology; Pharmacology. Drug treatments; Reference Values; Toxicity: nervous system and muscle; Tropical medicine; Trypanocidal Agents - toxicity
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(97)05362-8

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.