ANTIAMPHIPHYSIN ANTIBODIES WITH SMALL-CELL LUNG-CARCINOMA AND PARANEOPLASTIC ENCEPHALOMYELITIS

Paraneoplastic encephatomyelitis developed as the presenting feature o f small-cell lung carcinoma in 3 patients. Two patients with paraneopl astic encephalomyelitis manifested predominantly as subacute sensory n euronopathy did not improve after prednisone treatment and chemotherap y. The third patient had severe axial and limb rigidity and myoclonus, which partially improved after chemotherapy and treatment with intrav enous immunoglobulin and prednisone. Serum from each patient immunocyt ochemically stained the neuropil and to a lesser degree the neuronal c ytoplasm in human cerebral and cerebellar cortex. On immunoblots of hu man neuronal extracts, each patient's serum contained high-titer IgG a ntibodies reacting with a protein band of apparent molecular mass 125 kd. This autoantibody pattern is indistinguishable from antibodies rec ently identified in several women with breast carcinoma and stiff-man syndrome. Screening of a human brain complementary DNA expression libr ary with patient serum yielded clones whose sequence is identical to t hat of the synaptic vesicle-related protein amphiphysin. Reverse trans criptase-polymerase chain reaction demonstrated expression of amphiphy sin in 8 of 10 small-cell lung carcinomas and in 5 of 14 breast carcin omas. These observations highlight the clinical and serological hetero geneity of paraneoplastic central nervous system disorders: Patients w ith a given clinical syndrome may have different antineuronal antibodi es, and patients with a given autoantibody specificity have differing clinical presentations.