Clinical And Prognostic Analysis Of Autoantibody-Associated CNS Demyelinating Disorders In Children

Objective: To analyze the positive and recurrence rates of different autoantibody-associated acquired demyelination syndromes(ADS)in children,and explore the clinical,radiological,and prognostic features of the myelin oligodendrocyte glycoprotein antibody(MOG-ab)and aquaporin-4antibody(AQP4-ab)associated disease.This study also explored the correlation between MOG-ab level and prognosis,and summarized steroid maintenance therapy approaches for MOG-ab-positive children.Methods: A total of 160 children presenting with acquired demyelinating syndromes(ADS)between January 2016 and December 2019 were tested for MOG-ab and AQP4-ab.Clinical data,MRI scans,and prognostic analyses were compared between MOG-ab-positive and AQP4-ab-positive children.Correlation between antibody level and prognosis were found in MOG-ab-positive children as well as treatment response to immunosuppressants.Results:(1)Of the 160 included children with ADS,the MOG-ab positivity rate(47.4%)was significantly higher than the AQP4-ab(5%)positivity rate.The recurrence rate for AQP4-ab disease(71.4%)was higher than that of MOG-ab disease(30.1%).For 135 children with both MOG-ab and AQP4-ab tested,the median age at onset was 7(IQR,5-10)years,and the median follow-up period was 19 months.64 patients had MOG-abs and the male to female ratio was 1:1.2,with a median age of 7(5-10)years old.8patients had AQP4-abs and the male to female ratio was 1:3,with a median age of 9(5.75-10.5)years old.There was no significant difference in gender or age of onset between the two groups.(2)In MOG-ab-positive children,acute disseminated encephalomyelitis(ADEM)was the most common initial phenotype(53.1%),followed by optic neuritis(ON)(21.9%)and encephalitis other than ADEM(20.3%).A pattern of polyfocal,blurred and poorly demarcated lesions in both gray matter and white matter was most common in cranial MRI,and the involvement of bilateral and deep gray matter nuclei was specific.(3)Steroid maintenance therapy longer than 6months after the initial attack was associated with a lower risk of a second relapse in MOG-ab-positive children.Immunosuppressants generally reduced the annual recurrence rate of MOG-ab-positive children.On serial serum MOG antibody analysis,clinical relapse occurred in 34.6% of children with persistent seropositivity,but none of the children who converted to seronegative status experienced relapse.(4)Symptoms of myelitis were more predominant in patients with AQP4-abs either at onset or relapse,and area postrema syndrome was specific.Longitudinally extensive transverse myelitis and the involvement of cervicothoracic segments were the main manifestation in spinal MRI.(5)When compared with AQP4-ab-positive children,MOG-ab-positive children more frequently presented with ADEM,had deep gray matter lesions on MRI,had a better clinical and radiological recovery,and were less likely to have sustained disability.(6)In MOG-ab-positive and AQP4-ab-positive children,maintenance therapy was a protective factor for recurrence,but presenting optic neuritis was a predictor of earlier relapse.A high Expanded Disability Status Scale score at onset was associated with sustained disability.Conclusion: The MOG antibody is more common in children with ADS than the AQP4 antibody.MOG-ab-positive children are characterized by distinct clinical and radiological features.Although some MOG-ab-positive children experience relapsing courses or have persistently seropositive status,they still predict a better outcome than AQP4-ab-positive children.