[Transient subacute encephalopathy induced by high-dose methotrexate treatment in children with acute lymphoblastic...

Transient subacute encephalopathy was detected in 4 of 83 patients undergoing treatment with high-dose methotrexate (HD-MTX) and citrovorum factor rescue for childhood acute lymphoblastic leukemia and malignant lymphoma from 1984 to 1991. Subacute encephalopathy occurred in relatively older patients and early in the course of treatment with HD-MTX. The average interval between the HD-MTX course and the onset of the neurologic disturbance was 6.5 days. All 4 patients treated had no neurological sequelae. Laboratory evaluations disclosed nontoxic plasma MTX levels at onset of symptom and not detected in liquor. CT in 4 patients disclosed no abnormality, but MR images revealed abnormal signal intensity patterns of cerebral white matter in 2 cases. In one case the abnormal MR finding resolved after 3 months. The pathogenesis of this neurologic symptom remains unknown, but further HD-MTX treatment may be acceptable in follow-up of MR image, because the prognosis of subacute encephalopathy seems favorable.