Fatal acute encephalomyelitis after a single dose of intrathecal methotrexate

Pharmacotherapy. 2004 May;24(5):673-6. doi: 10.1592/phco.24.6.673.34742.


A 40-year-old Hispanic man with acute lymphoblastic leukemia was treated with a single dose of intrathecal methotrexate 12 mg for prophylaxis against leptomeningeal spread of tumor. The day after methotrexate administration, the patient complained of severe back pain and urinary retention. The diagnosis of encephalomyelitis was made on day 3 after methotrexate administration, and by day 6 mechanical ventilation was begun secondary to ascending paralysis. By day 8 the patient was comatose, with minimal signs of brain activity and little hope for recovery; on day 12 he died. Although neurotoxicity is a frequent complication of methotrexate therapy, fatal acute neurotoxicity is extremely uncommon, especially in adults. The mechanisms of methotrexate toxicity remain unclear, and no effective treatment exists to prevent its occurrence. This patient rapidly progressed from mild neurotoxicity to fatal encephalopathy after one dose of intrathecal methotrexate during his third cycle of chemotherapy. Clinicians should be aware of the signs and symptoms of neurotoxicity during treatment, as well as predisposing factors that put patients receiving methotrexate at risk for neurotoxic effects.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects*
  • Encephalomyelitis / chemically induced*
  • Encephalomyelitis / physiopathology
  • Fatal Outcome
  • Humans
  • Injections, Spinal
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy


  • Antimetabolites, Antineoplastic
  • Methotrexate