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