A Neuropathologic Study of Disseminated Necrotizing Leukoencephalopathy Following Intrathecal Methotrexate Therapy
Neuropathologic findings of a case of disseminated necrotizing leukoencephalopathy following intrathecal methotrexate therapy are described. A five-year-old boy with acute lymphocytic leukemia was seen over a twenty-two month course and was administered methotrexate intrathecally for meningeal leukemia. After the seventh intrathecal administration he developed akinetic mutism and decorticated rigidity which persisted until the patient's death seventeen months later. Neuropathologically, there were widespread necrotic lesions with scattered lipid-laden macrophages and extensive astrocytic gliosis mainly in the white matter of the cerebrum and cerebellum in addition to meningeal and perivascular infiltration by leukemia cells. Nerve cell loss was considerable in the thalamus, cerebellar cortex, dentate nucleus, pontine nucleus and inferior olivary nucleus. The disseminated necrotizing leukoencephalopathy in this case was thought to be caused mainly by the direct toxic effect of intrathecally administered methotrexate and not by irradiation or leukemia cell infiltration.
