Paraneoplastic Neurological Syndromes

Paraneoplastic neurological syndromes (PNS) occur in patients with cancer typically before any other clinical suspicion of an underlying tumor. PNS are considered autoimmune disorders caused by an immunologic response against an antigen (onconeural antigen) expressed in the tumor and brain. This view is supported by the presence of autoantibodies against onconeural antigens in serum and CSF of patients with PNS. PNS are rare, with an incidence between 0.9 and 0.4 cases/100,000 people/year. The most common tumors are lung, mostly small cell lung carcinomas (SCLC), breast, and ovarian tumors, thymoma, and Hodgkin lymphoma. Prompt diagnosis is important to prevent the development of severe disability. The first diagnostic criteria for PNS were published in 2004, and the diagnosis was based on the presence of neurological syndromes that frequently associate with cancer (classical syndromes) or the presence of onconeural antibodies. In the 2021 revised criteria, a definite diagnosis of PNS can be accomplished when the patient presents a neurological syndrome with high risk (previously known as classical) or intermediate risk to associate with a tumor, neuronal antibodies with a high risk (>70%) (onconeural antibodies) or intermediate risk (30–70%) of cancer, and histological diagnosis of a tumor that is expected by the type of associated antibody or expresses the antigen recognized by the antibody. Although the 2021 diagnostic criteria do not capture all PNS, as they do not allow to diagnose as definite PNS neurologic syndromes without neuronal antibodies, the updated criteria represent a step forward to differentiate true PNS from neurologic syndromes that coincide in time with cancer diagnosis.