Reversal of CNS-prophylaxis-related leukoencephalopathy after CSF shunting: case histories of identical twins

We report the case histories of identical twin brothers who developed concordant acute lymphoblastic leukemia at the age of 4 years and who later developed leukoencephalopathy and hydrocephalus related to central nervous system prophylaxis by, in the first case intrathecally administered methotrexate and, in the second by intrathecally administered methotrexate and cranial irradiation. The delayed encephalopathy developed 9 and 22 months respectively after the first dose of intrathecal methotrexate. Both patients underwent cerebrospinal fluid shunting mainly for their hydrocephalus. The imaging studies have shown that both hydrocephalus and leukoencephalopathy have improved significantly after ventriculoperitoneal shunt insertion. We review the pathophysiology of prophylaxis-related encephalopathy in leukemia patients and summarize its clinical, histological, and radiological characteristics. We also discuss the possible contribution of altered cerebrospinal fluid dynamics in the development of leukoencephalopathy.