Intrathecal methotrexate induced lethal subacute neurotoxicity

Abstract

Methotrexate inhibits dihydrofolate reductase and it is widely used in the treatment of leukemia, lymphoma and other tumors in paediatric patients. There has been described that can produce neurotoxicity for still not well clarified mechanisms. Neurological toxicity can be acute, subacute or chronic, according to  the time of manifestation after the administration of the drug. Neurological symptoms often are reversible, but occasionally methotrexate can produce the death of the patient or cause important sequels. For this reason is important to monitor patients in risk. Magnetic resonance imaging is very useful in diagnosis, showing alterations in diffusion-weighted imaging of a precocious way. Several pharmacological treatments have been proved but none of them have demonstrated its efficiency until now. We present the case of a 15-year-old boy diagnosed of acute B-cell lymphoblastic leukemia in complete remission and without central nervous system leukemic involment postinduction and consolidation therapy. After the administration neurotoxicity. Neurological symptoms were deteriorating progressively up to a persistent coma with serious alterations in magnetic resonance imaging and electroencephalogram pattern. Clinic did not improve with any treatment. The patient died after limitation of therapeutic effort of agreement by the family.