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

Pediatr Hematol Oncol. 2010 Feb;27(1):46-52. doi: 10.3109/08880010903341904.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asparaginase / therapeutic use
  • Child
  • Cytarabine / therapeutic use
  • Daunorubicin / therapeutic use
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / injuries
  • Epilepsy, Tonic-Clonic / chemically induced
  • Genetic Predisposition to Disease
  • Humans
  • Hyperhomocysteinemia / complications*
  • Hyperhomocysteinemia / genetics
  • Injections, Spinal
  • Leukoencephalopathies / chemically induced*
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / physiology
  • Polymorphism, Single Nucleotide*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / complications*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Prednisone / therapeutic use
  • Remission Induction
  • Sinus Thrombosis, Intracranial / chemically induced
  • Sinus Thrombosis, Intracranial / etiology*
  • Sinus Thrombosis, Intracranial / genetics
  • Vincristine / therapeutic use

Substances

  • Cytarabine
  • Vincristine
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Asparaginase
  • Prednisone
  • Methotrexate
  • Daunorubicin