Intracarotid BCNU leukoencephalopathy

Intracarotid 1,3-bis(2-chloroethyl)-1-nitrosurea (BCNU) is now a frequently used chemotherapeutic agent for high-grade glial neoplasms. The toxicity from such therapy has not been well-documented. A 50-year-old man with a left frontoparietal grade 4 astrocytoma received three injections of intracarotid BCNU, 400 mg each, over a 2-month period. No radiation or other chemotherapy was ever given. He tolerated the BCNU injections well, with some reduction of tumor bulk, until the third dose. After his last injection, his condition gradually deteriorated; he became obtunded, and died 5 weeks later. At autopsy, the brain showed extensive cavitation and coagulative necrosis, fibrinoid vascular necrosis, edema, swollen axons, and bizarre cellular morphologic features confined to the BCNU perfusion territory. Grade 4 astrocytoma remained in the right hemisphere and in the left occipital lobe, sites outside the area of BCNU perfusion. Intracarotid BCNU can result in a severe leukoencephalopathy similar to that seen with methotrexate or delayed radionecrosis.