Leukoencephalopathy following the administration of methotrexate into the cerebrospinal fluid in the treatment of primary brain tumors

Four children having recurrent primary malignant posterior fossa tumors de-developed a leukoencephalopathy during treatment with methotrexate administered via a ventriculocisternal catheter. Symptoms and signs, including visual disturbances; seizures, quadriparesis, and organic dementia appeared from 3 to 15 months following the initiation of methotrexate therapy. At autopsy all four patients had severe leukoencephalopathy, chiefly involving die central white matter of the cerebral hemispheres; one patient had no residual tumor. All patients had received earlier irradiation, but the lesions within the brain are believed not to represent irradiation necrosis. It is postulated that the changes occurring within the brain are secondary to the disturbances in brain folic acid metabolism produced by the methotrexate; this effect may have been accentuated by the blockage of the cerebrospinal fluid pathways, the delayed effects of irradiation, or the administration of anticonvulsants. Intrathecal methotrexate is capable of eradicating certain intracranial malignancies, but its administration must be more judicious in order to avoid lethal complications.