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Departments of Neurology (Drs. Dalmau, Furneaux, and Posner) and Pathology (Dr. Rosenblum), Memorial Sloan-Kettering Cancer Center, and Cornell University Medical Center, New York, NY; and the Department of Neurology (Dr. Graus), Hospital Clinic i Provincial, Barcelona, Spain.
We studied the nervous systems and tumors of five patients with anti-Hu-positive paraneoplastic encephalomyelitis/sensory neuronopathy (PEM/PSN) to determine if the autoantibody found in the serum and CSF was also present in those tissues. Immunohistochemical studies of the nervous system revealed the presence of IgG bound predominantly to the nuclei of most of the neurons and the cytoplasm of some glial cells. IgG was also present to a lesser degree in the neuropil. In brains of patients who died of cancer without the paraneoplastic syndrome, IgG was present in the immediate perivascular areas and to a very limited degree in the neuropil. There was no IgG in neurons, and in only some of the controls a few glial cells showed IgG immunoreactivity in the cytoplasm. The amount of anti-Hu IgG relative to total IgG in various brain regions and tumor was determined by quantitative Western blot analysis. The proportion of anti-Hu IgG was greater in some areas of the brain and tumor than in serum and CSF. Control brains did not contain anti-Hu IgG. There was a limited correlation among (1) the principal clinical symptoms, (2) regions of major tissue injury, and (3) the quantitative anti-Hu IgG distribution. We conclude that although the role of the antibody in the pathogenesis of the disease is still uncertain, its specific localization in the nervous system and tumor suggests an immunologic etiology of this paraneoplastic syndrome.
Address correspondence and reprint requests to Dr. Jerome B. Posner, Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.
Supported in part by grants from FISS (90/1144), Madrid, Spain, and National Institutes of Health (NS26064) and the American Cancer Society (PDT-359).
Presented in part at the 42nd annual meeting of the American Academy of Neurology, Miami Beach, FL, May 1990.
Received February 1, 1991. Accepted for publication in final form April 12, 1991.
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