Immunotherapeutic approaches to paraneoplastic neurological disorders

Paraneoplastic neurological disorders (PNDs) are disturbances of the nervous system function in cancer patients, which are not due to a local effect of the tumour or its metastases. This review focuses on the neuromuscular PND and central nervous system (CNS) PND, which are by far the most problematic group to treat. Most of these clinically well-defined syndromes are associated with lung cancer, especially small cell lung cancer (SCLC), lymphoma and gynaecological tumours. Since auto-antibodies directed against proteins expressed in neurones and tumour cells have been found, PNDs are suspected to be autoimmune. In neuromuscular PND, immunosuppressive therapies, plasmapheresis and iv. immunoglobulins (iv. Ig) have proven to be effective. In PND of the CNS, therapy of the tumour itself or immunosuppressive drugs seem to have little effect on the neurological syndromes. Plasmapheresis reduces the auto-antibody titre in the sera of these patients, but does not lead to a clinical improvement. This review presents an overview on the pathogenesis of PND and the possible benefit of an early immunosuppressive or immunomodulatory treatment, especially treatment with iv. immunoglobulins.