Necrotizing leukoencephalopathy and treated multiple myeloma. An autopsy case without intrathecal chemotherapy or irradiation of the brain.

A 48-year-old woman with multiple myeloma, developed progressive neurological disturbances one year after the bone marrow remission. There was neither intrathecal chemotherapy nor brain irradiation. She received cyclophosphamide, phenylalanine mustard, urethane, and prednisolone intravenously or orally. At postmortem examination the cerebral hemispheres had a conspicuous destruction of white matter, consistent with a necrotizing leukoencephalopathy with focal and diffuse demyelination. No myeloma cells were found in the nervous system. Alzheimer type II glias and abnormal glias closely resembling Alzheimer type I glia were numerous in the affected white matter. No oligodendroglias with intranuclear inclusions were found. No virus particles were detected by electron microscope. The neuropathological changes had features similar to those seen in leukoencephalopathy with intrathecal administration of methotrexate. The glial abnormality, the most striking feature in the present case, strongly suggests toxic and metabolic disturbances. It appears that the leukoencephalopathy of the present case developed on the more complicated etiopathogenesis. However, it would be emphasized that the side-effects of the drugs could be considered as one of the etiologica factors causing the glial abnormality.