Paraneoplastic neurological disorders

Paraneoplastic neurological disorders (PNDs) are rare, often devastating, autoimmune disorders affecting any part of the nervous system. PNDs have an autoimmune etiology, but the details of the pathogenesis are not fully known. Further, the pathophysiology appears to differ from one disorder to another. PNDs were first clinically recognized several years ago with descriptions of sensory neuronopathy, limbic encephalitis, and cerebellar degeneration in patients with cancer. PND appears to represent an aberrant manifestation of an effective antitumor immune response. There are two aspects of the pathogenesis of PND: (1) the generation of a vigorous immune response to cancer and (2) a break in immune tolerance that allows this response to target the nervous system. PND can be divided into two groups based on the type of associated autoantibodies. The first group of antibodies that may be associated with PND is antibodies against cell surface antigens, including neuronal ion channels. The second and larger group consists of antibodies directed against intracellular antigens in the nucleus or cytoplasm of neurons. The symptoms of PND vary and follow from the area of the nervous system affected. The loss of Purkinje cells in paraneoplastic cerebellar degeneration results in severe cerebellar ataxia. The loss of dorsal root ganglia cells in paraneoplastic sensory neuronopathy results in profound sensory loss, sensory ataxia, and pseudoathetosis.