Autoantibody screening for the diagnosis of autoimmune cerebellitis

Objective To establish a test of autoantibody-panel for the diagnosis of autoimmune cerebellitis (AC) and determine the prevalence of AC in patients with cerebellar ataxia of unknown etiology. Methods Autoantibody screening tests with indirect immunofluorescence were performed in serum and cerebrospinal fluid (CSF) samples of 400 previously 'idiopathic’ Chinese patients with cerebral ataxia (inpatients and outpatients in Peking Union Medical College Hospital or referred from hospitals of Beijing Encephalitis Group from 2016 to 2018). Immunotherapy was given to autoantibody positive patients and the effectiveness of immunotherapy was assessed. Detailed AC autoantibodies panel included anti-glutamate decarboxylase 65 (GAD65) antibody, anti-Tr (delta notch-like epidermal growth factor-related receptor (DNER)) antibody, anti-zinc finger protein 4 (ZIC4) antibody, anti-inositol 1, 4, 5-trisphosphate receptor 1 (ITPR1) antibody, anti-homer protein homolog 3 (Homer 3) antibody, anti-neurochondrin (NCDN) antibody, anti-carbonic anhydrase-related protein (CARP) antibody and anti-Purkinje cell antibody 2 (PCA2) antibody. Results Eight out of 400 (2%) ataxia patients were positive for this AC panel tests, of whom two were positive for anti-GAD65 antibody, two for anti-Tr antibody, one for anti-PCA2 antibody, one for anti-Homer 3 antibody and two were positive for serum anti-NCDN antibody. Autoantibodies against ZIC4, ITPR1 and CARP were not detected in this cohort. Two of the eight ataxia patients also presented with limbic encephalitis, and only one anti-GAD antibody patient was screened with underlying small cell lung carcinoma (SCLC). All the eight patients received immunotherapy and four experienced partial response. Conclusions Autoimmune cerebellitis is the cause of acquired cerebellar ataxia. Tests of autoantibodies associated with AC have diagnostic value for paraneoplastic and non-paraneoplastic cerebellar ataxia. Immunotherapy may yield partial response in patients with AC. Key words: Autoimmune diseases of the nervous system; Autoantibodies; Encephalitis; Cerebellar ataxia