Methotrexate Induced Cerebellar Leukoencephalopathy (P6.009)

Objective: To present a rare case of methotrexate induced cerebellar leukoencephalopathy with long term oral methotrexate use. Case presentation: A 59 year old female with rheumatoid arthritis treated with methotrexate and folate supplementation for greater than 10 years presented to the neurology clinic with signs of brain stem and cerebellar dysfunction. Symptoms included a slowly progressive ataxic gait, vertigo, nausea, vomiting, and bilateral tinnitus. Patient’s physical exam revealed a left upper and lower limb ataxia with a wide base ataxic gait. MRI of her brain demonstrated symmetrical white matter lesions involving both cerebellar hemispheres, extending to the middle cerebellar peduncles without any post-gadolinium enhancement. An extensive investigation including infectious, vasculitic, autoimmune, paraneoplastic and cytologic studies in the serum and CSF were unremarkable. Vitamin B12 serum level was normal with an elevated homocysteine level. Methotrexate-induced encephalopathy was established. One month after discontinuation of methotrexate, the patient reported significant improvement in her gait and resolution of her nausea and vomiting. A repeat MRI of her brain five months after discontinuing her methotrexate demonstrated a significant decrease in the degree of T2 hyperintense signals within the white matter in the cerebellar hemispheres and middle cerebral peduncles. Discussion: Methotrexate-induced encephalopathy is a rare complication in MTX therapy. It ranges from mild reversible leukoencephalopathy to irreversible and even fatal disseminated necrotizing leukoencephalopathy. The involvement of the cerebellum is quite rare. Exact mechanism of this toxicity remains unclear. It has been proposed that homocysteine elevation and its excitatory effect on NMDA receptors is partially responsible. Early recognition of the condition and the withdrawal of methotrexate can improve outcomes. Genetic polymorphisms in methylenetetrahydrofolate reductase may influence the side effects of methotrexate. Pharmacogenetic screening needs to be considered for risk stratification of those at higher risk of toxicity before initiating therapy. Disclosure: Dr. Goshgarian has nothing to disclose. Dr. Alwaki has nothing to disclose. Dr. Lugo has nothing to disclose. Dr. Grover has nothing to disclose.