Neurological Complications of the Treatment of Pediatric Neoplastic Disorders

Neurological complications resulting from childhood cancer treatments are common. Treatment for childhood neoplastic disorders is often multimodal and may include procedures, cranial irradiation, chemotherapy, transplant, and immunotherapy, each of which carries distinct neurological risks. Procedures, such as lumbar punctures, are commonly used in this population for diagnostic purposes as well as intrathecal medication administration. Surgery is associated with an array of potential neurological complications, with posterior fossa syndrome being a common cause of morbidity in pediatric brain tumor patients after neurosurgical resection. Cranial irradiation can cause late neurological sequelae such as stroke, cerebral vasculopathy, secondary malignancy, and cognitive dysfunction. Neurotoxic effects of chemotherapeutic agents are common and include neuropathy, coagulopathy causing stroke or cerebral sinovenous thrombosis, encephalopathy, seizures, cerebellar dysfunction, myelopathy, and neuropsychologic difficulties. Hematopoietic stem cell transplant has a high risk of neurological complications including central nervous system infection, seizures, and stroke. Immunotherapies, including chimeric antigen receptor-modified T-cells (CAR T-cells) and immune checkpoint inhibitors, are emerging as potentially effective strategies to treat some types of childhood cancer, but may carry with them substantial neurotoxicity which is just beginning to be recognized and studied. With evolving treatment protocols, childhood cancer survivorship is increasing, and the role of the neurologist in managing both the acute and chronic neurological consequences of treatment is becoming more important. Prevention, early recognition, and treatment of therapy-associated neurotoxicity are imperative to ensuring children can remain on the most effective therapeutic regimens and to improve the neurological function and quality of life of childhood cancer survivors.