Abstract: Background: Neuromyelitis optica spectrum disease (NMOSD) is divided into AQP4-IgG positive, MOG-IgG positive and serological negative cases according to the serology. The differences in clinical and imaging characteristics of patients with different serological NMOSD are not clear yet. Objective: We established a long-term follow-up cohort of pediatric patients to understand the differences among different serological NMOSD. Design: Dynamic bidirectional cohort study. Methods: Children diagnosed with NMOSD in the Department of Pediatrics, Peking University First Hospital from January 2012 to March 2021 were enrolled in the cohort, and information on clinical characteristics was collected based on a pre-designed clinical observation scale, with retrospective collection of previous clinical data (clinical symptoms and signs since the first diagnosis, and previous clinical characteristics for those diagnosed in other hospitals), and observation of clinical characteristics at hospital follow-up. The cohort endpoint was time from onset to last follow-up ≥6 months. The cohort was divided into 3 groups as AQP4-IgG-positive, MOG-IgG-positive and serologically negative (negative for both antibodies). Main outcome measures: Clinical characteristics of different serological NMOSD children. Results: Of the 46 cases of NMOSD, there were 21, 12 and 13 cases in the MOG-IgG-positive, AQP4-IgG-positive and serologically negative groups, respectively, with no statistically significant differences in age at onset, median disease duration from onset to final follow-up and number of episodes in the 3 groups, and statistically significant differences in sex composition ratios, with AQP4-IgG-positive being more common in females. There were 74 clinical phenotypes for the first attack, and the differences in cerebral syndrome and brainstem symptom in the 3 groups were statistically significant.Cerebral syndrome was common in the MOG-IgG-positive group (42.9%) and the serology-negative group (43.8%), and brainstem symptom was common in the AQP4-IgG-positive group (33.3%) and the serology-negative group (23.1%).During the course of the disease, there were 196 phenotypes in total, and the differences between the 3 groups were statistically significant for different serotypes of TM, cerebral syndrome, brainstem symptom, and postrema symptom, with TM being the most common phenotype in the AQP4-IgG-positive group (43.9%), brain syndrome common in the MOG-IgG-positive group (36.2%) and serology-negative group (34.4%), brainstem symptom common in the AQP4-IgG-positive group (17. 1%) and serologically negative group (18.0%), and postrema symptom common in the AQP4-IgG-positive group (12.2%). A total of 134 sites of brain MR involvement were acquired, mainly in the subcortical white matter (59.0%) and brainstem (47.8%) and a total of 42 sites of spinal MR involvement were acquired, with statistically significant differences in the subcortical white matter, paraventricular white matter, corpus callosum, thalamus, basal ganglia, and brainstem among the three groups with different serotypes.Subcortical white matter was more prevalent in the MOG-IgG-positive and serologically negative groups, paraventricular white matter was more predominant in the AQP4-IgG positive and serologically negative groups, corpus callosum was common in the AQP4-IgG positive group, thalamus was common in AQP4-IgG positive and MOG-IgG positive groups, basal ganglia was common in MOG-IgG positive group, and brainstem was common in AQP4-IgG positive group. Statistically significant differences were found among three groups with different serotypes of thoracic and longitudinally extensive transverse myelitis.The differences were statistically significant and were commonly involved in all 3 groups, with AQP4-IgG positive being more common (94.1% and 100%). A total of 94 acute cerebrospinal fluid and 46 autoimmune antibody data were collected, and the differences in number of nucleated cells of different serotypes, proteins and different autoimmune antibodies were not statistically significant in the 3 groups. Final follow-up EDSS scores were obtained from 46 cases with a median score of 1.5 (0-4.5) and no statistically significant differences were found among the 3 different serotypes. Conclusion: AQP4-IgG positivity was more common in females. Cerebral syndrome was common in MOG-IgG-positive and serologically negative NMOSD. Postrema syndrome was common in AQP4-IgG-positive children. Subcortical white matter involvement was the most common in MOG-IgG-positive and antibody-negative children, and longitudinally extensive transverse myelitis was the most common in children with AQP4-IgG-positive.

Key words: Children, Neuromyelitis optica spectrum diseases, MOG-IgG, AQP4-IgG