Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 2: Results from 108 lumbar punctures in 80 pediatric patients.

Sven Jarius, Christian Lechner, Eva M Wendel, Matthias Baumann, Markus Breu, Mareike Schimmel, Michael Karenfort, Adela Della Marina, Andreas Merkenschlager, Charlotte Thiels, Astrid Blaschek, Michela Salandin, Steffen Leiz, Frank Leypoldt, Alexander Pschibul, Annette Hackenberg, Andreas Hahn, Steffen Syrbe, Jurgis Strautmanis, Martin Häusler, Peter Krieg, Astrid Eisenkölbl, Johannes Stoffels, Matthias Eckenweiler, Ilya Ayzenberg, Jürgen Haas, Romana Höftberger, Ingo Kleiter, Mirjam Korporal-Kuhnke, Marius Ringelstein, Klemens Ruprecht, Nadja Siebert, Kathrin Schanda, Orhan Aktas, Friedemann Paul, Markus Reindl, Brigitte Wildemann, Kevin Rostásy

Journal: Journal of neuroinflammation 2021;17(1):262

PMID: 32883358

Abstract

BACKGROUND

New-generation, cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD).

OBJECTIVE

To describe systematically the CSF profile in children with MOG-EM.

MATERIAL AND METHODS

Cytological and biochemical findings (including white cell counts [WCC] and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgM/IgA fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster [MRZ] reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF L-lactate) from 108 lumbar punctures in 80 pediatric patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively.

RESULTS

Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in 89% of samples (N = 96), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 29). If present at all, intrathecal IgG synthesis was low, often transient and mostly restricted to acute attacks. Intrathecal IgM synthesis was present in 21% and exclusively detectable during acute attacks. CSF WCC were elevated in 54% of samples (median 40 cells/μl; range 6-256; mostly lymphocytes and monocytes; > 100/μl in 11%). Neutrophils were present in 71% of samples; eosinophils, activated lymphocytes, and plasma cells were seen only rarely (all < 7%). Blood-CSF barrier dysfunction (as indicated by an elevated albumin CSF/serum ratio) was present in 46% of all samples (N = 79) and at least once in 48% of all patients (N = 67) tested. CSF alterations were significantly more frequent and/or more pronounced in patients with acute spinal cord or brain disease than in patients with acute ON and varied strongly depending on attack severity. CSF L-lactate levels correlated significantly with the spinal cord lesions load (measured in vertebral segments) in patients with acute myelitis (p = 0.0099). An analysis of pooled data from the pediatric and the adult cohort showed a significant relationship of QAlb (p < 0.0005), CST TP (p < 0.0001), and CSF L-lactate (p < 0.0003) during acute attacks with age.

CONCLUSION

MOG-IgG-associated EM in children is characterized by CSF features that are distinct from those in MS. With regard to most parameters, no marked differences between the pediatric cohort and the adult cohort analyzed in Part 1 were noted. Our findings are important for the differential diagnosis of pediatric MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.

Address: Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. [email protected].; Division of Pediatric Neurology, Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.; Department of Pediatrics, Olgahospital, Klinikum Stuttgart, Stuttgart, Germany.; Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.; Division of Pediatric Neurology, Children's Hospital, Medical University of Augsburg, Augsburg, Germany.; Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Düsseldorf, Germany.; Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, Children's Hospital, University of Duisburg-Essen, Duisburg, Germany.; Division of Pediatric Neurology, University Hospital for Children and Adolescents, Leipzig, Germany.; Department of Neuropediatrics, University Children's Hospital, Ruhr-University Bochum, Bochum, Germany.; Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner Children's Hospital, University of Munich, Munich, Germany.; Department of Pediatrics, Bozen Hospital, Bozen, Italy.; Department of Pediatrics, Division of Pediatric Neurology, Klinikum Dritter Orden, Munich, Germany.; Neuroimmunology, Institute of Clinical Chemistry and Department of Neurology, Christian-Albrechts-University Kiel and Medical University Hospital Schleswig-Holstein, Kiel, Germany.; Department of Neuropediatrics and Muscle Disorders, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Division of Pediatric Neurology, University Children's Hospital Zurich, Zurich, Switzerland.; Department of Pediatric Neurology, University Children's Hospital Giessen, Giessen, Germany.; Division of Child Neurology and Inherited Metabolic Diseases, Department of General Pediatrics, Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.; Department of Neurology, Children's Clinical University Hospital, Riga, Latvia.; Department of Pediatrics, Division of Neuropediatrics and Social Pediatrics, Medical University RWTH Aachen, Aachen, Germany.; Department of Pediatrics, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.; Department of Pediatrics, Women's and Children's Hospital, Linz, Austria.; Department of Pediatric Neurology, Children's Hospital Neuburg, Neuburg, Germany.; Department of Neurology, St Josef Hospital, Ruhr-University Bochum, Bochum, Germany.; Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.; Institute of Neurology, Medical University of Vienna, Vienna, Austria.; Department of Neurology, St Josef Hospital, Ruhr-University Bochum, Bochum, Germany.; Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gGmbH, Berg, Germany.; Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, Düsseldorf, Germany.; Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich Heine University Dusseldorf, Düsseldorf, Germany.; Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine, and Charité Universitätsmedizin Berlin, Berlin, Germany.; Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.; Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany. [email protected].
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