Abstract

Background: Neurotoxicity associated with intrathecal antineoplastic drugs represents a significant clinical challenge in neurology. Among the most devastating complications is myelopathy, an infrequent entity with usually irreversible neurological consequences. Objectives: To perform a comprehensive analysis of all reported cases of myelopathy due to intrathecal antineoplastic agents, including conventional and emerging agents, characterizing their clinical and radiological patterns, prognostic factors, and therapeutic options. Design: Systematic review and meta-analysis of cases following the PRISMA methodology adapted for rare case series (1990-2024). Main Results: Of 487 records identified, 67 cases from 3 publications met the inclusion criteria. Methotrexate was the most frequently implicated agent (47.8%), followed by conventional cytarabine (19.4%), pemetrexed (14.9%), liposomal cytarabine (11.9%), and trastuzumab (11.9%). The temporal distribution revealed five distinct patterns. Magnetic resonance imaging (MRI) was quite sensitive, detecting abnormalities in 92.5% of cases. Regarding prognosis, complete neurological recovery was observed in only 16.4% of patients, demonstrating its poor prognosis. Conclusions: Intrathecal antineoplastic myelopathy is a defined nosological entity with distinctive clinical and radiological characteristics that vary depending on the causative agent. Our findings describe the main characteristics and suggest a pathophysiological mechanism based on the time of presentation.

Keywords

toxic myelopathy, intrathecal chemotherapy, methotrexate, cytarabine, pemetrexed, trastuzumab, neurotoxicity, systematic review