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Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites
R Ackermann1, A Semmler, G D Maurer
1Dr Senckenberg Institute of Neurooncology, Johann Wolfgang-Goethe University Frankfurt, Schleusenweg 2-16, 60528 Frankfurt, Germany. roman.ackermann@kgu.de
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.
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