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.
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.
Mahadeo
Kris M
KM
Division of Pediatric Hematology-Oncology, Children's Hospital at Montefiore, Bronx, New York 10467, USA. krismd03@hotmail.com
Dhall
Girish
G
Panigrahy
Ashok
A
Lastra
Carlos
C
Ettinger
Lawrence J
LJ
D019943:Amino Acid Substitution; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000627:therapeutic use; D002648:Child; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced; D020022:Genetic Predisposition to Disease; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000235:genetics; D007278:Injections, Spinal; D056784:Leukoencephalopathies / Q000139:chemically induced*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D011241:Prednisone / Q000627:therapeutic use; D012074:Remission Induction; D012851:Sinus Thrombosis, Intracranial / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D014750:Vincristine / Q000627:therapeutic use
D003561:Cytarabine; D014750:Vincristine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin