Significance of Myelin Oligodendrocyte Glycoprotein Antibodies in CSF
Sara Carta, Álvaro Cobo‐Calvo, Thaís Armangué, Albert Saiz, Christian Lechner, Kevin Rostásy, Markus Breu, Matthias Baumann, Romana Höftberger, Ilya Ayzenberg, Carolin Schwake, María Sepúlveda, Eugenia Martínez‐Hernández, Gemma Olivé-Cirera, Georgina Arrambide, Mar Tintoré, Raphaël Bernard‐Valnet, Renaud Du Pasquier, Fabienne Brilot, Sudarshini Ramanathan, Kathrin Schanda, Alberto Gajofatto, Sérgio Ferrari, Elia Sechi, Eoin P. Flanagan, Sean J. Pittock, Vyanka Redenbaugh, Markus Reindl, Romain Marignier, Sara Mariotto
Abstract
<h3>Background and Objectives:</h3> 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. <h3>Methods:</h3> 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. <h3>Results:</h3> 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 (<b>MOG-Abs seropositive and CSF positive</b>), 79 (31%) only in serum (<b>MOG-Abs seropositive and CSF negative</b>), and 31 (12%) only in CSF <b>(MOG-Abs seronegative and CSF positive)</b>. <b>MOG-Abs seronegative and CSF positive</b> predominated 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, <b>MOG-Abs seropositive and CSF positive</b> patients 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, <i>p</i>=0.007) and presented more commonly with sensory (45.5% vs. 24%, <i>p</i>=0.002), motor (33.6% vs 19%, <i>p</i>=0.021), and sphincter symptoms (26.9% vs 7.8%, <i>p=</i>0.001) than <b>MOG-Abs seropositive and CSF negative</b>. At last follow-up, <b>MOG-Abs seropositive and CSF positive</b> cases had more often persistent sphincter dysfunction (17.3% vs 4.3%, <i>p=</i>0.008)<i>.</i> Compared with seropositive patients, those <b>MOG-Abs seronegative and CSF positive</b> had higher disability at last follow-up (<i>p</i>≤0.001) and <b>MOG-Abs seronegative and CSF positive</b> status was independently associated with an EDSS ≥3.0. <h3>Conclusion:</h3> 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.