LEUKOENCEPHALOPATHY ASSOCIATED WITH METHOTREXAT: A CASE REPORT

Abstract

INTRODUCTION: Methotrexate is a folate antagonist with antineoplastic and immunomodulatory action. Neurotoxicity is usually mild; however, neurological symptoms have been observed in patients with long-term low dose oral administration. CASE REPORT: A 39-year-old woman developed leukoencephalopathy during treatment with oral methotrexate (MTX) at a low dose. She began a headache clinic, cognitive impairment and harm of his work activities. Magnetic Resonance Imaging (MRI) of the brain was compatible with the diagnosis and the biopsy was compatible with leukoencephalopathy without evidence of infectious agents. Even with medication discontinuation, there was progression of the disease with cerebellar involvement, apraxia, language impairment, memory deficit, sphincter dysfunction and spastic tetraparesis with severe impact on daily activities. After a few months of interruption, the patient remained stable. DISCUSSION: There are few reports of low MTX induced oral toxicity in the literature, however, the white matter changes observed in MRI as well as the clinical picture are compatible with reported cases of leukoencephalopathy secondary to MTX. The absence of findings in CSF contributes to the exclusion of differential diagnoses. The literature describes clinical manifestations of progressive dysarthria, ataxia, unstable gait, and cognitive dysfunction. The pathogenesis is related to the increase of adenosine accumulation, elevation of homocysteine and its excitatory effect on the n-methyl-Daspartate receptor (NMDA) and some therapeutic proposals based on these mechanisms have been elucidated. CONCLUSION: MTX-induced encephalopathy is associated with administration intravenous or intrathecal administration of the drug, but there are reports after oral use, even at low doses. Early diagnosis directly interferes with the prognosis. therefore, it is necessary to consider a detailed investigation in view of possible differential diagnoses.