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Updated: May 30, 2026

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Intrathecal methotrexate neurotoxicity: clinical correlates and antidotal treatment
Yoram Finkelstein1, Shoshana Zevin, Bianca Raikhlin-Eisenkraft
1Department of Neurology, Shaare Zedek Medical Center and Faculty of Health Sciences, Ben-Gurion University, Jerusalem 91031, Israel.
Abstract:
The neurotoxicity of methotrexate (MTX) is more severe when administered intrathecally (IT) than by the oral and intravenous (IV) routes, and has been reported even with a single administration of therapeutic doses of 12 or 15mg. Prompt recognition and treatment are essential to improve the outcome after massive IT-MTX overdose. Treatment options include CSF drainage or CSF exchange, ventriculolumbar perfusion, IT corticosteroids to reduce CSF inflammation and IV leucovorin to reduce systemic toxicity. Toxicity resulting from IT injection of leucovorin is controversial. CSF drainage and exchange are particularly effective if performed soon after the overdose. In this paper we describe a protocol of treatment for severe cases of IT-MTX overdose in excess of 100mg. The mainstay of treatment is dilution and removal from CSF of excessive methotrexate alongside with specific antidotal therapy.
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