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

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.