title: Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites.
abstract: 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.
authors.affiliation: Dr Senckenberg Institute of Neurooncology, Johann Wolfgang-Goethe University Frankfurt, Schleusenweg 2-16, 60528 Frankfurt, Germany. roman.ackermann@kgu.de
authors.forename: R
authors.initials: R
authors.lastname: Ackermann
authors.forename: A
authors.initials: A
authors.lastname: Semmler
authors.forename: G D
authors.initials: GD
authors.lastname: Maurer
authors.forename: E
authors.initials: E
authors.lastname: Hattingen
authors.forename: F
authors.initials: F
authors.lastname: Fornoff
authors.forename: J P
authors.initials: JP
authors.lastname: Steinbach
authors.forename: M
authors.initials: M
authors.lastname: Linnebank
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D055756:Meningeal Carcinomatosis / Q000188:drug therapy / Q000556:secondary; D008715:Methionine / Q000008:administration & dosage*; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D013118:Spinal Cord Diseases / Q000139:chemically induced* / Q000628:therapy*; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D000964:Antimetabolites, Antineoplastic; D014803:Vitamin B Complex; D008715:Methionine; D008727:Methotrexate