Disseminated necrotizing leukoencephalopathy

A 30-year-old male with chronic myelogenous leukemia was treated by intrathecal instillation of methotrexate and cytosine arabinoside because of meningeal infiltration of leukemic cells. He developed neurlogical signs of bilateral cerebral dysfunction with progressive deterioration and died. The neuropathological changes consisted of multiple small areas of demyelination and coagulative necrosis that were randomly disseminated in the cerebral white matter. There was a remarkable decrease of glial nuclei and occasional deposits of mineral salts. Numerous axonal swellings were observed within and around the necrotizing foci. A moderate astrocytosis and mild status spongiosus were found in the surrounding white matter. The etiological relationship of these changes to intrathecal methotrexate is discussed.