Paraneoplastic Neurological Syndromes

Abstract

Paraneoplastic neurological syndromes (PNS) are immune-mediated disorders associated with cancer. PNS usually appear in a subacute manner and may affect any level of the nervous system. They generally develop before cancer and PNS recognition leads to cancer diagnosis. Prompt tumor treatment is important to stabilize or improve PNS symptoms. Although PNS may sometimes occur without antibodies, two major groups are identified depending on the antibodies present in the serum or the CSF. Antibodies against intracellular antigens (also called onconeural antibodies) seem to play no direct role in neurological symptoms (with exceptions) but are good markers of cancer, so their detection is very useful to classify a neurological syndrome as paraneoplastic. Although these antibodies are thought to have no pathogenic effect, the immune system still plays a major role, probably mediated by cytotoxic T cells. PNS with onconeural antibodies respond poorly to immunotherapy, with the exception of anti-Ma2 PNS. A second group of antibodies against synaptic and cell surface proteins occur in well-defined neurological syndromes, which are not always PNS and may appear in younger patients without cancer. These antibodies alter the location or function of their antigens, generating the neuronal dysfunction that is the underlying cause of these PNS. Early immunotherapy improves prognosis at least in the most frequent disorders (anti-NMDA receptor encephalitis, anti-LGI1 encephalitis). In all PNS, irrespective of the group, appropriate tumor screening should be undertaken. The work-up should include the search for the most common cancers reported in PNS patients according to the age and the associated autoantibodies.