Paraneoplastic neurological syndromes associated with anti-amphiphysin antibodies

Abstract

Objective To investigate the clinical features of paraneoplastic neurological syndromes associated with anti-amphiphysin antibody in Peking Union Medical College Hospital (PUMCH). Methods Patients with an acute or subacute neurological presentation that was suspected to be paraneoplastic in PUMCH from 2012 to 2015 were screened for anti-amphiphysin antibody. Samples of serum or cerebrospinal fluid were tested by the immunoblotting. Clinical features of patients with anti-amphiphysin antibody were analyzed. Results Anti-amphiphysin antibody was identified in the serum of 13 among 15 000 patients, 6 of which were male and 7 were female, the mean age being 54 years. Neurological manifestations included limbic encephalitis (n=4), peripheral neuropathy (n=3; 1 sensory, 1 neuropathy and paraproteinaemia, 1 multiple mononeuropathy), stiff-person syndrome(SPS, n=2), paraneoplastic cerebellar degeneration (n=1), brainstem encephalitis and paraneoplastic opsoclonus-myoclnia (n=1) , dysautonomia (n=1), myoclonus (n=1). Four of the 13 patients had additional syndrome of inappropriate antidiuretic hormone secretion. Cancer was detected in 6 patients (6/13), including small-cell lung cancer (n=5), and breast cancer (n=1). Coexisting autoantibodies were identified in 6 patients (6/13). All the patients with cancer developed neurological symptoms before the diagnosis of cancer. The mean interval from neurological symptom onset to cancer detection overall was 13.83 weeks. The mean follow-up for the 5 patients in whom a malignant neoplasm was not detected was 32.2 months. Seven patients were treated with immunotherapy, including intravenous immunoglobulin (IVIG) and methylprednisolone. Five of these patients had favorable responses, 1 patient did not improve after immunotherapy, 1 patient′s symptoms were aggravated after short-term remission. Conclusions The results suggest that anti-amphiphysin antibody is a rare autoantibody. Despite emphasis on its association with paraneoplastic SPS, its associated spectrum of neurological disorders is much broader. Many patients with anti-amphiphysin antibody developed neurological symptoms instead of SPS and are only partially associated with cancer. Immunotherapy, including IVIG or steroid, would be beneficial. Key words: Amphiphysin; Autoantibodies; Paraneoplastic neurologic syndromes