Overview of paraneoplastic syndromes of the nervous system
- Josep Dalmau, MD, PhD
Josep Dalmau, MD, PhD
- ICREA Professor of Neurology
- Hospital Clinic/IDIBAPS, University of Barcelona, Spain
- Adjunct Professor of Neurology
- University of Pennsylvania
- Myrna R Rosenfeld, MD, PhD
Myrna R Rosenfeld, MD, PhD
- Professor of Neurology
- Hospital Clinic/IDIBAPS, University of Barcelona, Spain
- Adjunct Professor of Neurology
- University of Pennsylvania
Paraneoplastic neurologic syndromes are a heterogeneous group of disorders caused by mechanisms other than metastases, metabolic and nutritional deficits, infections, coagulopathy, or side effects of cancer treatment. These syndromes may affect any part of the nervous system, from cerebral cortex to neuromuscular junction and muscle (table 1), either damaging one area (eg, Purkinje cell, presynaptic cholinergic synapses) or multiple areas (eg, encephalomyelitis).
This topic provides an overview of the pathogenesis, diagnosis, and treatment of paraneoplastic disorders. Individual syndromes are discussed separately. (See "Paraneoplastic syndromes affecting peripheral nerve and muscle" and "Paraneoplastic syndromes affecting the spinal cord and dorsal root ganglia" and "Paraneoplastic and autoimmune encephalitis" and "Paraneoplastic cerebellar degeneration" and "Opsoclonus myoclonus syndrome" and "Paraneoplastic visual syndromes".)
Although the pathogenesis of paraneoplastic neurologic syndromes is incompletely understood, immunologic factors are believed to be important because antibody and T-cell responses against nervous system antigens have been described for many of these disorders. The immunologic response is directed against shared antigens that are ectopically expressed by the tumor, but otherwise exclusively expressed by the nervous system (picture 1) [1,2], or rarely by the nervous system and testes . For unknown reasons, the immune system identifies these antigens as foreign and mounts an immune attack against them. One report suggests that the immune system can mount a T-cell response to a normal protein when it is expressed in a cancer cell, suggesting that normal self-antigens may be processed differently in cancer cells than in the normal cells .
Antibodies that occur in paraneoplastic disorders have been divided in two categories depending on the location of the antigen.
●Antibodies directed against intracellular neuronal proteins (called classical paraneoplastic or onconeuronal antibodies) – These antibodies belong to the category of "well-characterized" paraneoplastic antibodies (table 2 and table 3), and their detection almost always indicates the presence of an underlying tumor. Examples include Hu (also known as type 1 anti-neuronal nuclear antibody [ANNA-1]), Ri (also known as type 2 anti-neuronal nuclear antibody [ANNA-2]), Yo (also known as Purkinje cell cytoplasmic antibody type 1 [PCA-1]), amphiphysin, Ma2, Tr (also known as delta/notch-like epidermal growth factor-related receptor [DNER]), collapsin response-mediator protein-5 (CRMP-5), and recoverin. These antibodies are surrogate markers of the paraneoplastic disorder, but in most of these disorders, the pathogenic mechanism is believed to be mediated by cytotoxic T-cells.
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