Subacute methotrexate neurotoxicity and cerebral venous sinus thrombosis in a 12-year old with acute lymphoblastic leukemia and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: Homocysteine-mediated methotrexate neurotoxicity via direct endothelial injury

Kris M. Mahadeo, Girish Dhall, Ashok Panigrahy, Carlos Lastra, Lawrence J. Ettinger

Research output: Contribution to journalArticle

20 Scopus citations


From as early as the 1970s methotrexate has been associated with disseminated necrotizing leukoencephalopathy and other neurotoxic sequelae. Yet, a clear mechanism for methotrexate-induced neurotoxicity has not been established. The authors describe the case of a 12-year-old male with acute lymphoblastic leukemia and a homozygous methylenetetrahydrofolate reductase C677T mutation, who developed subacute methotrexate-induced toxicity and cerebral venous thrombosis after receiving intrathecal methotrexate. The role of homocysteine as a possible mediator in methotrexate-induced neurotoxicity via direct endothelial injury is discussed.

Original languageEnglish (US)
Pages (from-to)46-52
Number of pages7
JournalPediatric Hematology and Oncology
Issue number1
StatePublished - Feb 8 2010



  • ALL
  • Homocysteine
  • Leukemia
  • Methotrexate
  • Neurotoxicity of therapy
  • Thrombosis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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