Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites

J Neurooncol. 2010 May;97(3):425-7. doi: 10.1007/s11060-009-0028-9. Epub 2009 Oct 11.


Methotrexate (MTX)-associated myelopathy is a rare but serious subacute complication of MTX-based chemotherapy. We report the case of a woman with breast cancer and meningeal carcinomatosis who developed severe progressive myelopathy after four cycles of intrathecal MTX administration. We substituted high doses of the key metabolites of the methyl-transfer pathway: S-adenosylmethionine (SAM), 200 mg three times daily i.v.; folinate, 20 mg four times daily i.v.; cyanocobalamin, 100 microg once daily i.v.; and methionine, 5 g daily p.o. The patient's paraparesis improved rapidly thereafter, and magnetic resonance (MR) imaging showed resolution of the intramedullary lesions. Genetic analyses revealed homozygosity for the A allele of methylenetetrahydrofolate reductase (MTHFR) c.1298A>C (p.E429A), whereas other genetic variants of folate/methionine metabolism associated with MTX neurotoxicity were not present. Substitution with multiple folate metabolites may be a promising strategy for the treatment of MTX-induced neurotoxicity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Meningeal Carcinomatosis / drug therapy
  • Meningeal Carcinomatosis / secondary
  • Methionine / administration & dosage*
  • Methotrexate / adverse effects*
  • Middle Aged
  • Spinal Cord Diseases / chemically induced*
  • Spinal Cord Diseases / therapy*
  • Vitamin B Complex / administration & dosage*


  • Antimetabolites, Antineoplastic
  • Vitamin B Complex
  • Methionine
  • Methotrexate