Encephalomyelopathy following high‐dose BCNU therapy

Autopsies were performed on four patients who had been treated with high‐dose BCNU therapy for visceral, cutaneous, or lymphoid malignancies. Three had developed an encephalopathy or encephalomyelopathy within five weeks before death. In all four patients distinctive lesions were found within the central nervous system that were either (1) discrete foci of swollen axis cylinders and myelin vacuolization or (2) larger, symmetric areas of edema with white and gray matter necrosis. Fibrinoid necrosis and fibrin microthrombi were much more prominent in the latter. The small discrete foci of axonal and myelin alterations are similar, if not identical, to lesions previously associated with cranial radiation or combined cranial radiotherapy and chemotherapy. The larger lesions share features with “methotrexate encephalopathy” and delayed radionecrosis. The presence of these lesions in these patients, who had not received cranial radiation, suggests that high‐dose BCNU therapy alone is associated with, and may produce, certain distinctive structural changes in the central nervous system. The presence of fibrinoid necrosis and fibrin microthrombi suggests that this possible pathologic effect of BCNU could be mediated by the drug's effect on the cerebrospinal vasculature.