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A 69-year-old woman presented with subacute sensory neuropathy and autonomic dysfunction of 9 months' duration, associated with high serum titers of anti-Hu antibodies. A small cell carcinoma of the lung was diagnosed by biopsy. She died after cardiorespiratory arrest. At autopsy, spinal and autonomic ganglia showed subacute inflammation with diffuse endoneurial T-cell, B-cell, and plasma cell infiltration. The cytoplasm and nuclei of some ganglion neurons displayed IgG immunocytochemical positivity. CD8+ T cells were tightly attached to, and indented the cell surface of, IgG-positive and IgG-negative neurons. This observation suggests that both cytotoxic T-cell-mediated attack against neurons and humoral mechanisms play a role in paraneoplastic subacute sensory neuronopathy.

Paraneoplastic syndromes of the central nervous system (PNS) consist of a variety of neurologic disorders including encephalomyelitis (limbic encephalitis, brainstem encephalitis, and acute myelitis), sensory neuronopathy, subacute cerebellar degeneration, visual paraneoplastic syndrome, stiffman syndrome, and motor neuron disease. [1-3] For the clinician, it is often difficult to arrive at a reliable diagnosis of the neurologic syndrome and to detect the underlying tumor. Neurologic signs and symptoms, although often stereotypic, are not specific. In two-thirds of cases the underlying tumor is not discovered until after the first neurologic symptoms. [4] Furthermore, the neoplasm may be small and difficult to detect. [5-7] PNS are frequently associated with serum autoantibodies reactive with neuronal antigens that are also present in the underlying tumor. These antibodies include (1) the anti-Yo antibody, also called "type 1 anti-Purkinje cell antibody" (PCA-1), "APCA-1," or "type I antibody"; (2) the anti-Hu antibody, also called "type 1 anti-neuronal nuclear antibody" (ANNA-1) or "type IIa antibody"; and (3) the anti-Ri antibody, also called "type 2 anti-neuronal nuclear antibody" (ANNA-2) or "type IIb antibody" Table 1. A clinical diagnosis of PNS is supported by the finding of these specific anti-neuronal antibodies. The detection of these antibodies should also lead to a focused search for specific underlying neoplasms. [8-12] View this table: Table 1. Criteria for identification of paraneoplastic anti-neuronal antibodies A major problem in comparing results obtained by different groups of investigators has been that individual laboratories have employed different laboratory techniques for detection of these antibodies. Although identification of these antibodies has rested on immunohistochemistry and Western blot analysis, not all laboratories have used Western blot analysis to identify the molecular weight of detected antigens. Furthermore, material from a number of animal species has been used, methods of preparing substrates for Western blot are not always spelled out, and concentrations of serum and …