Recognition of a distinctive paraneoplastic syndrome (Table 77-1) should prompt a search for cancer, because treatment of tumor may improve the course of PNDs; many of these disorders also occur without cancer. Diagnosis is based on the clinical pattern, exclusion of other cancer-related disorders, confirmatory serum or CSF antibodies, or occasionally electrodiagnostic testing. Most PNDs are mediated by immune responses triggered by neuronal proteins expressed by tumors. PNDs associated with immune responses against intracellular antigens often respond poorly to treatment (Table 77-2), whereas those associated with antibodies to synaptic or neuronal cell surface proteins are more responsive to immunotherapy (Table 77-3). For any type of PND, if antibody testing is negative, the diagnosis rests on the demonstration of cancer and the exclusion of other cancer-related or independent disorders. Combined whole-body CT and PET scans often uncover tumors undetected by other tests.