Putative Metronidazole Neurotoxicosis in a Cat

Abstract

Abstract.A presumptive case of metronidazole toxicity in a 3.4-kg adult cat is described. The cat had been treated for suspected inflammatory bowel disease with an anti-inflammatory dose of prednisone and metronidazole (73.5-147 mg/kg PO q24h) for approximately 40 days prior to presentation. Clinical signs were primarily related to the central nervous system, including acute tetraparesis, unresponsiveness, tremors, and vocalization. The patient was euthanatized after 12 days of supportive care. Necropsy revealed no significant macroscopic lesions. Histologic evaluation revealed multifocal, fairly well-demarcated foci of necrosis in the brainstem, extending from the diencephalon to the medulla oblongata. To our knowledge, this is the first report to document histologic lesions associated with metronidazole administration in a cat.

MR Imaging of Metronidazole-Induced Encephalopathy: Lesion Distribution and Diffusion-Weighted Imaging Findings

“…[19][20][21][22] A toxicologic study 19 in rats demonstrated well-demarcated usually symmetric lesions in the vestibular nuclei, cochlear nuclei, rostral colliculus, cerebellar nuclei, and olivary nuclei after the administration of high doses of metronidazole, and these lesions were characterized as spongiform changes within neurons. A similar experimental study in dogs demonstrated the degeneration and selective loss of Purkinje cells 20 and mild swelling of axon sheaths in vestibular-cerebellar white matter tracts and leukomalacia near the vestibular nerve radix.…”

“…21 According to a recent study in cats, multifocal well-demarcated foci of necrosis were present in central brain stem regions from the diencephalon to the medulla oblongata. 22 However, no documented data are available B A C Fig 2. A 55-year-old man with ischemic colitis (patient 6). A, Axial T2-weighted (TR/ TE ϭ 5000/110) images demonstrate bilateral symmetric hyperintense lesions in the dorsal medulla, vestibular, abducens, and focal tegmental lesions of the superior olivary nuclei of the dorsal pons, dentate nuclei of the cerebellum, the tectum of the midbrain, and the splenium of the corpus callosum.…”

Intoxicação por metronidazol em cão – relato de caso

“…Os achados histopatológicos incluem degeneração e desmielinização axonal (GREAVES, 2000), perda de células de Purkinje cerebelares (MARCH, 2003), edema de axônios da substância branca dos tratos vestibular-cerebelar e leucomalácia próximo à raiz do nervo vestibular (OLSON et al, 2005).…”

“…Estas áreas continham marcante aumento do número de macrófagos e células da micróglia, principalmente células gitter, muitos contendo material granular fagocitado. Alguns eosinófilos foram verificados, pequenos glóbulos arredondados de mielina degenerada de coloração escura e eosinofílica e aumento de capilares, frequentemente com células endoteliais discretamente edemaciadas (OLSON et al, 2005).…”

“…Foi proposto que essa especificidade pode ser responsável por uma possível interferência do metronidazol com processos metabólicos (CAYLOR;CASSIMATIS, 2001). Outros autores propuseram que o mecanismo incluiria a ligação do metronidazol com o RNA, DNA e neurotransmissores inibitórios, como nos receptores GABAérgicos nos sistemas vestibular e cerebelar (OLSON et al, 2005;SARNA;BROWNELL;FURTADO, 2009). …”