Clinical Information

Antineuronal autoantibodies specific for amphiphysin (a 128-kDa synaptic vesicle-associated protein) are found in a paraneoplastic context. These IgG antibodies were initially described as a serological marker of paraneoplastic stiff-man syndrome associated with breast carcinoma. They are now more aptly recognized as a marker of autoimmune encephalomyeloneuritis, sensory neuronopathy, and assorted neuromyopathic disorders associated with small-cell lung carcinoma or breast carcinoma. Amphiphysin antibody is sometimes detected in patients with lung or breast carcinoma without evidence of neurological disease.

Only 1 of 30 patients identified as seropositive for amphiphysin antibodies in the Mayo Clinic Neuroimmunology Laboratory exhibited any stiff-person phenomena (n=63: 39% women, 12% men). Only 10% of women (some with lung carcinoma) and 4% of men fulfilled diagnostic criteria for stiff-man syndrome. Overall, cancer was detected in 79.4% of seropositive patients (at last follow-up). Lung carcinoma (small cell) accounted for 61% of cancers and 35% had breast carcinoma (42% for women).

Amphiphysin seropositivity implicates antineuronal autoimmunity as the basis for a variety of neurological presentations and focuses the patient's subsequent investigation to a search for breast carcinoma or small-cell lung carcinoma.