Central paraneoplastic neurological syndromes. Part 2. Practical, theoretical and mechanistic considerations of treatment with drugs and biologicals.
New information about paraneoplastic neurological syndromes, or the remote effects of cancer, has raised more questions than answers. The underlying mechanisms of brain injury remain to be elucidated. A brief review of autoimmunity provides a basis for exploring hypotheses of induction of the immune system by a tumor in the periphery and its subsequent attack on the brain. Onconeural antigens shared by tumors and the brain are the targets of immunologically mediated injury. What provokes the immune system to inappropriately autoaggress and cause autoimmune disease is unknown, but the mechanisms of molecular mimicry or superantigens provide plausible explanations. The root of the problem appears to be a failure of immunoregulation on some level. The more precisely the immunological defect can be defined, the more select the possible therapy. Selective immunotherapies, now available or in preclinical and clinical trials, have great therapeutic potential but require precise information on the underlying immunological problem. These data will provide new directions for immunologic research and therapy in CNS paraneoplastic syndromes.
Pranzatelli
M R
MR
The National Pediatric Myoclonus Center and the Department of Pharmacology, The George Washington University, Washington, DC 20004, USA.