Évolutions conceptuelles des syndromes neurologiques paranéoplasiques

Paraneoplastic neurological syndromes (PNS) are rare dysimmune diseases which to date had been defined by the presence of a neurological disorder associated with cancer, but without cancer cells invading the nervous system. The discovery and description of circulating autoantibodies specific for PNS have revolutionized diagnosis and knowledge of these syndromes. Until recently, it was thought that these autoantibodies were only makers of the disease without playing any role in its pathogenesis. The recent description of autoantibodies directed against membrane targets with the capacity to play a direct pathogenic role has transformed the concept of PNS, especially since more than 50% of patients can apparently have the neurological syndrome and its autoantibodies directed against membrane targets without ever developing cancer. Consequently, classifications based on the nature of the antigen and its target recognized by the membrane or intracellular autoantibody and the presence of cancer are no longer essential. For autoantibodies having an intracellular target, cancer is nearly always associated (more than 90% of cases), disorders are related to neuron death, patients exhibit little sensitivity to immunomodulator treatments, and cell immunity appears to play a major role. On the contrary, in patients with an autoantibody targeting a membrane protein or receptor, cancer is rare (less than 50% of cases), disorders are related to reversible neuron dysfunction, patients are generally sensitive to immunomodulators, and humor immunity appears to play the main role.