Cerebellar sclerosis in pediatric cancer patients

Cerebral cortical sclerosis is an acquired condition that has rarely been described in cancer patients. We reviewed necropsy findings in all children with cancer who died at the Children's Hospital of Philadelphia during the 20 year period 1963-1982 and found cerebellar sclerosis in 14 children with cancer (12 with acute lymphoblastic leukemia, 1 each with neuroblastoma and osteogenic sarcoma). The lesions were focal (3), multifocal (9) or diffuse (2). They occurred more frequently in children with acute lymphoblastic leukemia who had received intravenous methotrexate therapy. Ten of these 12 children had also received whole brain irradiation. The pathogenesis of the cerebellar sclerosis is unknown, but it is possible that extrinsic cerebellar compression by tumor or chronically increased intracranial pressure may have played a role in 6, ischemia/hypoxia in 3, and methotrexate toxicity in 2. No clear associations could be ascertained in 3. Methotrexate may be a previously unrecognized cause of cerebellar cortical injury. In addition, oncologic treatment regimens that include other central nervous system-penetrating drugs and irradiation may sensitize cerebellar cortex and make it more susceptible to other cerebellar sclerosis-causative factors.