Significance of Myelin Oligodendrocyte Glycoprotein Antibodies in CSF: A Retrospective Multicenter Study

Although the diagnosis of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is based on serum MOG antibodies (MOG-Abs) positivity, patients with coexisting or restricted MOG-Abs in the CSF have been reported. The aim of this study is to characterize the relevance of CSF MOG-Abs positivity in clinical practice.Eleven medical centres retrospectively collected clinical and laboratory data of adult and pediatric patients with suspected inflammatory CNS disease and MOG-Abs positivity in serum and/or CSF, using live cell-based assays. Comparisons were performed using parametric or non-parametric tests, as appropriate. Potential factors of unfavourable outcomes were explored by Cox proportional hazard models and logistic regression.The cohort included 255 patients: 139 (55%) females and 132 (52%) children (i.e. <18 year-old). Among them, 145 patients (56.8%) had MOG-Abs in both serum and CSF (MOG-Abs seropositive and CSF positive), 79 (31%) only in serum (MOG-Abs seropositive and CSF negative), and 31 (12%) only in CSF(MOG-Abs seronegative and CSF positive).MOG-Abs seronegative and CSF positivepredominated in adults (22% vs 3% of children), presented more commonly with motor (n=14, 45%) and sensory symptoms (n=13, 42%), and all but 4 (2 MS, 1 polyradiculoneuritis, 1 Susac syndrome) had a final diagnosis compatible with MOGAD. When comparing seropositive patients according to MOG-Abs CSF status,MOG-Abs seropositive and CSF positivepatients had a higher EDSS at nadir during the index event (median 4.5, IQR 3.0-7.5 vs. 3.0, IQR 2.0-6.8,p=0.007) and presented more commonly with sensory (45.5% vs. 24%,p=0.002), motor (33.6% vs 19%,p=0.021), and sphincter symptoms (26.9% vs 7.8%,p=0.001) thanMOG-Abs seropositive and CSF negative. At last follow-up,MOG-Abs seropositive and CSF positivecases had more often persistent sphincter dysfunction (17.3% vs 4.3%,p=0.008).Compared with seropositive patients, thoseMOG-Abs seronegative and CSF positivehad higher disability at last follow-up (p≤0.001) andMOG-Abs seronegative and CSF positivestatus was independently associated with an EDSS ≥3.0.Paired serum and CSF MOG-Abs positivity is common in MOGAD and is associated with a more severe clinical presentation. CSF only MOG-Abs positivity can occur in patients with a phenotype suggestive of MOGAD and is associated with a worse outcome. Taken together, these data suggest a clinical interest in assessing CSF MOG-Abs in patients with a phenotype suggestive of MOGAD, regardless of the MOG-Abs serostatus.