Intrathecal Methotrexate, Central Nervous System Toxicity, and Response to NMDA Antagonism - An Adult Case Series

Abstract

Methotrexate (MTX) is administered for treatment of central nervous system (CNS) hematologic cancers, prophylaxis of CNS dissemination of certain hematological cancers, and in solid tumor leptomeningeal disease. MTX treatment can be limited by CNS toxicity. Dextromethorphan is used to treat MTX neurotoxicity, with most data derived from pediatric case series. In this report, we profile four adult patients who developed intrathecal (IT) MTX neurotoxicity to better characterize their response to dextromethorphan treatment. A case series of four patients who developed neurologic symptoms attributed to IT MTX neurotoxicity subsequently treated with dextromethorphan was devised. Demographic data, clinical characteristics, electroencephalography results, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) characteristics, and dextromethorphan treatment outcomes were described. Of the four patients developing MTX neurotoxicity, neurologic symptoms developed over a timeframe of two to fourteen days from the precedent MTX exposure. Radiologic phenotypes included subcortical white matter diffusion-restricting lesions, bi-hemispheric subcortical white matter T2-FLAIR hyperintensities, as well other findings described in the report. Time elapsed from initiation of dextromethorphan to neurologic symptom resolution ranged from 1 to 2 days. The profiles of four adult patients developing suspected IT MTX neurotoxicity syndromes with subsequent response to Dextromethorphan add further data to guide management of such patients.