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 μg 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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Acknowledgement
The Dr. Senckenberg Institute of Neurooncology and the Hertie Chair for Neurooncology are supported by the charitable foundations Dr. Senckenberg Foundation and Hertie Foundation.
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Ackermann, R., Semmler, A., Maurer, G.D. et al. Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites. J Neurooncol 97, 425–427 (2010). https://doi.org/10.1007/s11060-009-0028-9
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DOI: https://doi.org/10.1007/s11060-009-0028-9