Background Although there were criteria for diagnosis of neuromyelitis optica (NMO) and multiple sclerosis (MS),it is still difficult to differentiate NMO from MS,due to the overlapping clinical manifestations.Therefore it is necessary to characterize clinical features of NMO and MS patients in the mainland of China,to simplify the process of disease diagnosis,and to identify criteria for the differential diagnosis of NMO and MS.Methods A total of 138 Chinese Han patients from the mainland of China including 73 NMO,60 MS and 5 MS-like patients with positive NMO-IgG were included in the study.Clinical records were reviewed retrospectively and the results of clinical examination,laboratory experiments,magnetic resonance imaging (MRI) and evoked potentials (EPs) were compared between NMO and MS patients.In addition,the relationship between the NMO-IgG serologic status and clinical characteristics were analyzed.Results Compared with MS patients (1.3∶ 1.0),more female prevalence was observed in NMO patients (4.2∶ 1.0; P=0.003).There were also statistically significant differences in visual EPs,oligoclonal bands,brainstem lesions in MRI and longitudinally extensive spinal cord lesions (LESCLs) between NMO and MS patients.Brainstem lesions observed in brain MRI were found in 17.9％ of MS patients,over 3.7 times higher than in NMO patients (4.8％,P=0.024).When stratified NMO patients by NMO-IgG,LESCLs were found in 42.1％ of NMO-IgG-negative NMO patients,over 3.5 times higher than in NMO-IgG-positive patients (11.9％,P=0.008).Statistical difference was also observed in CD4+/CD8+ ratios between NMO-IgG-positive and-negative NMO patients.Conclusions Comprehensive analysis of MRI,laboratory and EPs data can facilitate differential diagnosis of MS and NMO.In addition,the combination of LESCLs and brain MRI findings failing to satisfy MRI criteria for MS is highly sensitive and specific for NMO.