Multicenter Study

. 2023 Mar 14;100(11):e1095-e1108.

doi: 10.1212/WNL.0000000000201662. Epub 2022 Dec 16.

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

Sara Carta¹, Álvaro Cobo Calvo¹, Thaís Armangué¹, Albert Saiz¹, Christian Lechner¹, Kevin Rostásy¹, Markus Breu¹, Matthias Baumann¹, Romana Höftberger¹, Ilya Ayzenberg¹, Carolin Schwake¹, Maria Sepulveda¹, Eugenia Martínez-Hernández¹, Gemma Olivé-Cirera¹, Georgina Arrambide¹, Mar Tintoré¹, Raphael Bernard-Valnet¹, Renaud Du Pasquier¹, Fabienne Brilot¹, Sudarshini Ramanathan¹, Kathrin Schanda¹, Alberto Gajofatto¹, Sergio Ferrari¹, Elia Sechi¹, Eoin P Flanagan¹, Sean J Pittock¹, Vyanka Redenbaugh¹, Markus Reindl¹, Romain Marignier¹, Sara Mariotto²

Affiliations

¹ From the Neurology Unit (S.C., A.G., S.F., S.M.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Italy; Servei de Neurologia-Neuroimmunologia (A.C.C., G.A., M.T.), Centre d'Esclerosi Múltiple de Catalunya, (CEMCAT), Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, Spain; Pediatric Neuroimmunology Unit (T.A.), Sant Joan de Déu Children's Hospital, University of Barcelona, Spain; Neuroimmunology and Multiple Sclerosis Unit (T.A., A.S., M.S., E.M-H., G.O-C.), Service of Neurology, Hospital Clinic de Barcelona, Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and, University of Barcelona, Spain; Division of Pediatric Neurology (C.L., M.B.), Department of Pediatric and Adolescent Medicine, Medical University of Innsbruck, Austria; Division of Pediatric Neurology (K.R.), University of Witten/Herdecke Childrens' Hospital, Datteln, Germany; Division of Pediatric Pulmonology (M.B.), Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria; Division of Neuropathology and Neurochemistry (R.H.), Department of Neurology, Medical University of Vienna, Austria; Department of Neurology (I.A., C.S.), St. Josef-Hospital, Ruhr-University Bochum, Germany; Department of Clinical Neurosciences (R.B-V., R.d.P.), Service of Neurology, Lausanne University Hospital and University of Lausanne, Switzerland; Faculty of Medicine and Health and Brain and Mind Centre (F.B.), Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, School of Medical Sciences, The University of Sydney, Australia; Translational Neuroimmunology Group (S.R.), Kids Neuroscience Centre, Children's Hospital at Westmead; Sydney Medical School and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney; Department of Neurology (S.R.), Concord Hospital, Sydney, Australia; Clinical Department of Neurology (K.S., M.R.), Medical University of Innsbruck, Austria; Department of Medical, Surgical and Experimental Sciences (E.S.), University of Sassari, Italy; Department of Neurology, Department of Laboratory Medicine and Pathology (E.P.F., S.J.P., V.R.), Mayo Clinic College of Medicine and Science, Rochester; Service de Neurologie (R.M.), Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France.
² From the Neurology Unit (S.C., A.G., S.F., S.M.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Italy; Servei de Neurologia-Neuroimmunologia (A.C.C., G.A., M.T.), Centre d'Esclerosi Múltiple de Catalunya, (CEMCAT), Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, Spain; Pediatric Neuroimmunology Unit (T.A.), Sant Joan de Déu Children's Hospital, University of Barcelona, Spain; Neuroimmunology and Multiple Sclerosis Unit (T.A., A.S., M.S., E.M-H., G.O-C.), Service of Neurology, Hospital Clinic de Barcelona, Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and, University of Barcelona, Spain; Division of Pediatric Neurology (C.L., M.B.), Department of Pediatric and Adolescent Medicine, Medical University of Innsbruck, Austria; Division of Pediatric Neurology (K.R.), University of Witten/Herdecke Childrens' Hospital, Datteln, Germany; Division of Pediatric Pulmonology (M.B.), Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria; Division of Neuropathology and Neurochemistry (R.H.), Department of Neurology, Medical University of Vienna, Austria; Department of Neurology (I.A., C.S.), St. Josef-Hospital, Ruhr-University Bochum, Germany; Department of Clinical Neurosciences (R.B-V., R.d.P.), Service of Neurology, Lausanne University Hospital and University of Lausanne, Switzerland; Faculty of Medicine and Health and Brain and Mind Centre (F.B.), Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, School of Medical Sciences, The University of Sydney, Australia; Translational Neuroimmunology Group (S.R.), Kids Neuroscience Centre, Children's Hospital at Westmead; Sydney Medical School and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney; Department of Neurology (S.R.), Concord Hospital, Sydney, Australia; Clinical Department of Neurology (K.S., M.R.), Medical University of Innsbruck, Austria; Department of Medical, Surgical and Experimental Sciences (E.S.), University of Sassari, Italy; Department of Neurology, Department of Laboratory Medicine and Pathology (E.P.F., S.J.P., V.R.), Mayo Clinic College of Medicine and Science, Rochester; Service de Neurologie (R.M.), Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France. sara.mariotto@gmail.com.

PMID: 36526426
PMCID: PMC10074465
DOI: 10.1212/WNL.0000000000201662

Multicenter Study

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

Sara Carta et al. Neurology. 2023.

. 2023 Mar 14;100(11):e1095-e1108.

doi: 10.1212/WNL.0000000000201662. Epub 2022 Dec 16.

Authors

Affiliations

¹ From the Neurology Unit (S.C., A.G., S.F., S.M.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Italy; Servei de Neurologia-Neuroimmunologia (A.C.C., G.A., M.T.), Centre d'Esclerosi Múltiple de Catalunya, (CEMCAT), Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, Spain; Pediatric Neuroimmunology Unit (T.A.), Sant Joan de Déu Children's Hospital, University of Barcelona, Spain; Neuroimmunology and Multiple Sclerosis Unit (T.A., A.S., M.S., E.M-H., G.O-C.), Service of Neurology, Hospital Clinic de Barcelona, Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and, University of Barcelona, Spain; Division of Pediatric Neurology (C.L., M.B.), Department of Pediatric and Adolescent Medicine, Medical University of Innsbruck, Austria; Division of Pediatric Neurology (K.R.), University of Witten/Herdecke Childrens' Hospital, Datteln, Germany; Division of Pediatric Pulmonology (M.B.), Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria; Division of Neuropathology and Neurochemistry (R.H.), Department of Neurology, Medical University of Vienna, Austria; Department of Neurology (I.A., C.S.), St. Josef-Hospital, Ruhr-University Bochum, Germany; Department of Clinical Neurosciences (R.B-V., R.d.P.), Service of Neurology, Lausanne University Hospital and University of Lausanne, Switzerland; Faculty of Medicine and Health and Brain and Mind Centre (F.B.), Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, School of Medical Sciences, The University of Sydney, Australia; Translational Neuroimmunology Group (S.R.), Kids Neuroscience Centre, Children's Hospital at Westmead; Sydney Medical School and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney; Department of Neurology (S.R.), Concord Hospital, Sydney, Australia; Clinical Department of Neurology (K.S., M.R.), Medical University of Innsbruck, Austria; Department of Medical, Surgical and Experimental Sciences (E.S.), University of Sassari, Italy; Department of Neurology, Department of Laboratory Medicine and Pathology (E.P.F., S.J.P., V.R.), Mayo Clinic College of Medicine and Science, Rochester; Service de Neurologie (R.M.), Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France.
² From the Neurology Unit (S.C., A.G., S.F., S.M.), Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Italy; Servei de Neurologia-Neuroimmunologia (A.C.C., G.A., M.T.), Centre d'Esclerosi Múltiple de Catalunya, (CEMCAT), Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, Spain; Pediatric Neuroimmunology Unit (T.A.), Sant Joan de Déu Children's Hospital, University of Barcelona, Spain; Neuroimmunology and Multiple Sclerosis Unit (T.A., A.S., M.S., E.M-H., G.O-C.), Service of Neurology, Hospital Clinic de Barcelona, Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and, University of Barcelona, Spain; Division of Pediatric Neurology (C.L., M.B.), Department of Pediatric and Adolescent Medicine, Medical University of Innsbruck, Austria; Division of Pediatric Neurology (K.R.), University of Witten/Herdecke Childrens' Hospital, Datteln, Germany; Division of Pediatric Pulmonology (M.B.), Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria; Division of Neuropathology and Neurochemistry (R.H.), Department of Neurology, Medical University of Vienna, Austria; Department of Neurology (I.A., C.S.), St. Josef-Hospital, Ruhr-University Bochum, Germany; Department of Clinical Neurosciences (R.B-V., R.d.P.), Service of Neurology, Lausanne University Hospital and University of Lausanne, Switzerland; Faculty of Medicine and Health and Brain and Mind Centre (F.B.), Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, School of Medical Sciences, The University of Sydney, Australia; Translational Neuroimmunology Group (S.R.), Kids Neuroscience Centre, Children's Hospital at Westmead; Sydney Medical School and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney; Department of Neurology (S.R.), Concord Hospital, Sydney, Australia; Clinical Department of Neurology (K.S., M.R.), Medical University of Innsbruck, Austria; Department of Medical, Surgical and Experimental Sciences (E.S.), University of Sassari, Italy; Department of Neurology, Department of Laboratory Medicine and Pathology (E.P.F., S.J.P., V.R.), Mayo Clinic College of Medicine and Science, Rochester; Service de Neurologie (R.M.), Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation, Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France. sara.mariotto@gmail.com.

PMID: 36526426
PMCID: PMC10074465
DOI: 10.1212/WNL.0000000000201662

Abstract

Background and objectives: 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.

Methods: Eleven medical centers 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 nonparametric tests, as appropriate. Potential factors of unfavorable outcomes were explored by Cox proportional hazard models and logistic regression.

Results: The cohort included 255 patients: 139 (55%) women 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 positive 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 multiple sclerosis, 1 polyradiculoneuritis, and 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 positive patients had a higher Expanded Disability Status Scale (EDSS) at nadir during the index event (median 4.5, interquartile range [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) than MOG-Abs seropositive and CSF negative. At the last follow-up, MOG-Abs seropositive and CSF positive cases had more often persistent sphincter dysfunction (17.3% vs 4.3%, p = 0.008). Compared with seropositive patients, those MOG-Abs seronegative and CSF positive had higher disability at the last follow-up (p ≤ 0.001), and MOG-Abs seronegative and CSF positive status were independently associated with an EDSS ≥3.0.

Discussion: Paired serum and CSF MOG-Abs positivity are common in MOGAD and are 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.

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Conflict of interest statement

T. Armangué received speaker honoraria from Biogen, Sanofi-Aventis, and Novartis not related to this manuscript; A. Saiz reports compensation for consulting services and speaker honoraria from Merck-Serono, Biogen-Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd, Novartis, Roche, Alexion, and Janssen; C. Lechner has served as a consultant for Roche but has no conflict of interest with this manuscript; I. Ayzenberg served on scientific advisory boards for Roche, Merck, and Alexion and received research support from Diamed, none related to this article; M. Sepulveda has received speaker honoraria from Biogen and Roche Pharma; E. Martínez-Hernández has received speaker honoraria from Biogen; G. Arrambide has received speaking honoraria and compensation for consulting services or participation in advisory boards from Sanofi, Merck, and Roche; travel expenses for scientific meetings from Novartis, Roche, Stendhal, and ECTRIMS; is editor for Europe of the Multiple Sclerosis Journal – Experimental, Translational, and Clinical; and is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee. F. Brilot has received research funding from the National Health and Medical Research Council (Australia), Multiple Sclerosis Research Australia, NSW Health, Novartis, and the University of Sydney. She has received speaker honoraria from Novartis, Biogen, Merck, and Limbic Neurology, has been on advisory boards for Merck and Novartis. and is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee. S. Ramanathan has received research funding from the National Health and Medical Research Council (Australia), the Brain Foundation (Australia), the Royal Australasian College of Physicians, and the University of Sydney. She is supported by an NHMRC Neil Hamilton Fairley Early Career Fellowship (APP1141169). She serves as a consultant on an advisory board for UCB and Limbic Neurology, and has been an invited speaker for Biogen, EXCEMED, and Limbic Neurology. S. Ferrari received support for attending scientific meetings by Shire, Sanofi-Genzyme, Roche, and Euroimmun; E. P. Flanagan has served on advisory boards for Alexion, Genentech, and Horizon Therapeutics. He has received speaker honoraria from Pharmacy Times. He received royalties from UpToDate. He was a site primary investigator in a randomized clinical trial on inebilizumab in neuromyelitis optica spectrum disorder run by MedImmune/Viela-Bio/Horizon Therapeutics. He has received funding from the NIH (R01NS113828). He is a member of the medical advisory board of the MOG project. He is an editorial board member of the Journal of the Neurologic Sciences and Neuroimmunology Reports. A patent has been submitted on DACH1-IgG as a biomarker of paraneoplastic autoimmunity. M. Reindl is supported by research grants from the Austrian Science Fund (FWF project P32699), the Austrian Research Promotion Agency, Euroimmun, and Roche; consulting fees and advisory board from Roche (to institution) and payments for antibody assays (MOG, AQP4, and other autoantibodies) to institution (University Hospital and Medical University of Innsbruck, Austria). R. Marignier serves on scientific advisory board for Alexion, Horizon Therapeutics, Roche, and UCB; has received honoraria from Alexion, Biogen, Merck, Novartis, and Roche. S. Mariotto received support for attending scientific meetings by Merck and Euroimmun and received speaker honoraria from Biogen. The other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. Radiologic Findings of MOG-Abs Seronegative and CSF Positive Patients**
Spinal cord MRI displayed short T2-hyperintense lesions in the cervical and thoracic spinal cord (C2-C3, C6, T8) and a longitudinally extensive lesion (T11-L1) involving conus medullaris (A) that had patchy postcontrast enhancement (B). Transversal section on the cervical spinal cord showed T2-hyperintensity, more evident on the left (C). The follow-up MRI performed 7 months after the clinical episode and intravenous steroids treatment showed an almost complete normalization (D). A follow up MRI of a MOG-Abs seronegative and CSF positive patient who had a LETM showing marked spinal cord atrophy of the thoracic segment (E). Orbital MRI of a patient with bilateral optic neuritis showed bilateral anterior optic nerve thickening (F) and postcontrast enhancement (bilateral, left optic nerve enhancement not shown, G).

Figure 2. Kaplan-Meier Analysis Estimation of Time to Reach a First Relapse Between MOG Abs Seropositive (MOG-Abs Seropositive and CSF Negative, and MOG-Abs Seropositive and CSF Positive) and CSF MOGAbs Restricted (MOG-Abs Seronegative and CSF Positive) Patients
Median Time to Reach the First Relapse was 6.6 months (Range 1.0–177.0) for seropositive patients and 7.3 months (Range 2.0–34.1) for seronegative patients (p = 0.970). Abbreviation: MOG-Abs = myelin oligodendrocyte glycoprotein antibodies.

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Comment in

Should We test for IgG Antibodies Against MOG in Both Serum and CSF in Patients With Suspected MOGAD?
Kim HJ, Palace J. Kim HJ, et al. Neurology. 2023 Mar 14;100(11):497-498. doi: 10.1212/WNL.0000000000206805. Epub 2022 Dec 16. Neurology. 2023. PMID: 36526427 No abstract available.

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

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

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