Paraneoplastic Disorders of the Central Nervous System
Although the discovery of antineuronal antibodies has facilitated the diagnosis of paraneoplastic neurological disorders (PNDs), the recognition and treatment of these disorders remain a challenge. Some antineuronal antibodies have a more syndrome-specific association than others, and some syndromes evoke a paraneoplastic etiology more frequently than others. Because antineuronal antibodies may occur in cancer patients without PND, their detection does not necessarily imply that a neurological disorder is paraneoplastic. This review analyzes these issues and suggests a diagnostic strategy based on criteria derived from clinical and immunological findings and the presence or absence of cancer. We provide an update on the clinical features and treatment of classic PND of the central nervous system, with the proposal of a general treatment strategy. In addition, we analyze the evidence of a hypothetically effective antitumor immunity in patients with PND, which if confirmed would have implications for treatment of the cancer and PND.

The term "paraneoplastic neurological disorders" (PNDs) refers to a group of syndromes mediated by immune responses triggered by tumors that express nervous system proteins. As a result of these immune responses, discrete or multifocal areas of the nervous system degenerate, causing diverse symptoms and deficits. These immune responses are often associated with specific antineuronal antibodies that can be used as diagnostic markers of the PND and underlying cancer. Not all paraneoplastic antibodies have the same clinical significance. Some antibodies may associate with one or a limited number of neurological syndromes or histological types of cancer, while others are less specific or may occur without neurological symptoms. There are PNDs with cerebrospinal fluid (CSF) and pathological evidence of being associated with inflammatory, likely immune-mediated mechanisms but no specific antibodies or target antigens have been identified. Beside these disparities, most paraneoplastic immune responses have in common the property of being triggered at early stages of cancer, when the tumor or metastases are limited or undetectable by conventional diagnostic techniques. This, along with the detection of cytotoxic T-cell responses to onconeuronal antigens, has suggested that the small tumor burden in PND patients is largely due to an effective anticancer immunity. If correct, the use of immunosuppressants would favor tumor growth, which is not supported by clinical data. These findings and dilemmas are assessed in this review. Because the main advance in the management of PND has resulted from refined clinical and immunological diagnostic criteria and improved diagnostic tests, a major focus of this review is an update of these criteria, with the proposal of a treatment strategy.