Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome

Abstract

Background and ObjectiveThe spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody–associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG‐IgG titers in children with MOGAD in correlation with clinical presentation and disease course.MethodsIn this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG–positive.ResultsOne hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG–negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG–negative.DiscussionIn this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG–negative, are shown to have a significantly reduced relapse risk.

Acute disseminated encephalomyelitis (ADEM) following COVID-19 vaccination: A systematic review

“…The lack of oligoclonal bands restricted to the CSF, the absence of periventricular lesions, variations in clinical symptoms, and the clinical evolution of ADEM are not in favor of Multiple Sclerosis (MS), although requiring a long follow-up for ruling out the dissemination in time which is the core characteristic of MS [ 58 ]. In addition, memory impairments, seizures, and psychiatric symptoms along with the presence of autoantibodies which are the typical manifestations of autoimmune encephalitis are not common features in ADEM [ 59 ]. The MOG antibody–associated disorder (MOGAD) consists of ADEM, transverse myelitis, and optic neuritis.…”

Serum MOG-IgG titers should be performed routinely in the diagnosis and follow-up of MOGAD: No

“…A recent pediatric MOGAD study of 116 children reported similar onset titers (median (interquartile range) = 1280 (640–5120) vs 1280 (640–5120), p = 0.291) in those with or without subsequent relapsing disease with a median follow-up of 3 years in the monophasic group. 5 In addition, analyzing follow-up samples on a research basis has improved our understanding of the dynamics of MOG-IgG serology but unfortunately the routine incorporation of follow-up MOG-IgG into clinical practice is premature. In 62 children with a median follow-up of 4 years, 14 relapsed.…”

“…6 This pattern continues in adults where 22/38 (58%) of the monophasic patients had persistent MOG-IgG over a median of 17.5 months while 9/32 (28%) of the seroreverters relapsed. 7 The median time to relapse of 0.5–1 year 5,6 further limits the utility of MOG-IgG “persistence” in predicting a relapse. Finally, on terminology, seroreversion is a somewhat misleading term in the context of MOGAD where it frequently describes circulating MOG-IgG dropping below a cut-off rather than becoming undetectable.…”

“…5 Of these, 7/9 (78%) are just one doubling dilution below the assay cut-off, and only one individual has undetectable MOG-IgG and thus the majority of “seronegative” patients still have circulating MOG-IgG. 5 Therefore, the decision to initiate maintenance attack prevention treatment is best made based on clinical data and generally reserved for those with two or more relapses irrespective of MOG-IgG titer or persistent positivity. Finally, routine use of MOG-IgG titers in follow-up means exposing adults and children with MOGAD to frequent sampling over years without the results influencing their treatment plan, with significant costs and inconvenience for the patient.…”

“…MOG-IgG titers can be influenced by immunotherapy and by timing of sampling with titers highest at disease onset and a reduction over time despite increases around relapses in some patients. 5,8 The variable sample timing and wide range of treatments used in typical MOGAD clinical practice makes interpretation of titer results and applying them to clinical decision making very challenging. While live CBAs offer optimal sensitivity and specificity for MOGAD, 9 widely discordant results have been reported between live and fixed CBAs and thus standardizing results across assays continues to be very difficult.…”