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Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites

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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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References

  1. Linnebank M, Moskau S, Jurgens A, Simon M, Semmler A, Orlopp K, Glasmacher A, Bangard C, Vogt-Schaden M, Urbach H, Schmidt-Wolf IG, Pels H, Schlegel U (2009) Association of genetic variants of methionine metabolism with methotrexate-induced CNS white matter changes in patients with primary CNS lymphoma. Neurooncology 11:2–8

    CAS  Google Scholar 

  2. Vezmar S, Becker A, Bode U, Jaehde U (2003) Biochemical and clinical aspects of methotrexate neurotoxicity. Chemotherapy 49:92–104

    Article  CAS  PubMed  Google Scholar 

  3. Mehta BM, Glass JP, Shapiro WR (1983) Serum and cerebrospinal fluid distribution of 5-methyltetrahydrofolate after intravenous calcium leucovorin and intra-Ommaya methotrexate administration in patients with meningeal carcinomatosis. Cancer Res 43:435–438

    CAS  PubMed  Google Scholar 

  4. Quinn CT, Griener JC, Bottiglieri T, Arning E, Winick NJ (2004) Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid. J Pediatr Hematol Oncol 26:386–388

    Article  PubMed  Google Scholar 

  5. Linnebank M, Linnebank A, Jeub M, Klockgether T, Wullner U, Kolsch H, Heun R, Koch HG, Suormala T, Fowler B (2004) Lack of genetic dispositions to hyperhomocysteinemia in Alzheimer disease. Am J Med Genet 131:101–102

    Article  PubMed  Google Scholar 

  6. van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ (2001) Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood, NJ) 226:243–270

    Google Scholar 

  7. Surtees R, Leonard J, Austin S (1991) Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway. Lancet 338:1550–1554

    Article  CAS  PubMed  Google Scholar 

  8. Bottiglieri T, Godfrey P, Flynn T, Carney MW, Toone BK, Reynolds EH (1990) Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 53:1096–1098

    Article  CAS  PubMed  Google Scholar 

  9. Castagna A, Le Grazie C, Accordini A, Giulidori P, Cavalli G, Bottiglieri T, Lazzarin A (1995) Cerebrospinal fluid S-adenosylmethionine (SAMe) and glutathione concentrations in HIV infection: effect of parenteral treatment with SAMe. Neurology 45:1678–1683

    CAS  PubMed  Google Scholar 

  10. Herrmann W, Obeid R (2007) Biomarkers of folate and vitamin B(12) status in cerebrospinal fluid. Clin Chem Lab Med 45:1614–1620

    Article  CAS  PubMed  Google Scholar 

  11. Levitt M, Nixon PF, Pincus JH, Bertino JR (1971) Transport characteristics of folates in cerebrospinal fluid; a study utilizing doubly labeled 5-methyltetrahydrofolate and 5-formyltetrahydrofolate. J Clin Invest 50:1301–1308

    Article  CAS  PubMed  Google Scholar 

  12. Hawkins RA, O’Kane RL, Simpson IA, Vina JR (2006) Structure of the blood-brain barrier and its role in the transport of amino acids. J Nutr 136:218S–226S

    CAS  PubMed  Google Scholar 

  13. Baehring JM, Fulbright RK (2008) Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients. J Neurol Neurosurg Psychiatry 79:535–539

    Article  CAS  PubMed  Google Scholar 

Download references

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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Correspondence to R. Ackermann.

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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

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