Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1:\xa0Results from 163 lumbar punctures in 100 adult patients

Sven Jarius,Romana Höftberger,Tania Kümpfel,Hannah Pellkofer,Jürgen Haas,Martin W Hümmert,Friedemann Paul,Ilya Ayzenberg,Mirjam Korporal‐Kuhnke ,Tobias Zrzavy,Ingo Kleiter,Kevin Rostásy ,Corinna Trebst,Christian Lechner,Markus Reindl,Klemens Ruprecht,Kaï Fechner ,Susanna Asseyer,Mathias Buttmann,Orhan Aktaş ,Luisa Klotz,Nasrin Asgari,Kathrin Schanda,Rafik Tobia,Nadja Siebert,Paulus Rommer ,Marius Ringelstein,Martin Weber,Brigitte Wildemann

doi:10.1186/s12974-020-01824-2

Abstract

BackgroundNew-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).ObjectiveTo describe systematically the CSF profile in MOG-EM.Material and methodsCytological and biochemical findings (including white cell counts and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgA/IgM 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 163 lumbar punctures in 100 adult patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively.ResultsMost strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in almost 90% of samples (N = 151), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 62). If present, intrathecal IgG (and, more rarely, IgM) synthesis was low, often transient and mostly restricted to acute attacks. CSF WCC was elevated in > 50% of samples (median 31 cells/μl; mostly lymphocytes and monocytes; > 100/μl in 12%). Neutrophils were present in > 40% of samples; activated lymphocytes were found less frequently and eosinophils and/or plasma cells only very rarely (< 4%). Blood–CSF barrier dysfunction (as indicated by an elevated albumin CSF/serum ratio) was present in 48% of all samples and at least once in 55% of all patients (N = 88) tested. The frequency and degree of CSF alterations were significantly higher in patients with acute myelitis than in patients with acute ON and varied strongly depending on attack severity. CSF l-lactate levels correlated significantly with the spinal cord lesion load in patients with acute myelitis (p < 0.0001). Like pleocytosis, blood–CSF barrier dysfunction was present also during remission in a substantial number of patients.ConclusionMOG-IgG-positive EM is characterized by CSF features that are distinct from those in MS. Our findings are important for the differential diagnosis of MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.

Highlights

myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-positive EM is characterized by cerebrospinal fluid (CSF) features that are distinct from those in multiple sclerosis (MS)
In summary, our study, the first to review comprehensively and systematically the CSF findings in MOG-IgG-associated encephalomyelitis (MOG-EM) in a large cohort of patients of mainly Caucasian descent, demonstrates that (i.) in sharp contrast to classic MS, intrathecal IgG synthesis is rare in MOG-IgGpositive EM, as shown both qualitatively and quantitatively; and (ii.), if present, intrathecal IgG synthesis is low in most patients, often transient, and mainly restricted to acute attacks
Our data show that (iii.) CSF findings in acute myelitis differ substantially and significantly from those in acute optic neuritis (ON), which is of high potential clinical relevance; that (iv.) CSF findings in “monophasic” MOG-EM are not significantly different from those in relapsing MOG-EM; and that, different from MS, (v.) the degree of CSF alteration depends significantly on disease activity and attack severity in MOGIgG-positive patients

Summary

Introduction

Over the past few years, several studies using newgeneration cell-based assays (CBA) have demonstrated a robust association of immunoglobulin G (IgG) autoantibodies targeting full-length, conformationally intact human myelin oligodendrocyte glycoprotein (MOG) with (mostly recurrent) optic neuritis (ON), myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like and acute-disseminated encephalomyelitis (ADEM)-like presentations, rather than with classic multiple sclerosis (MS) [1,2,3,4,5,6,7,8,9,10,11,12,13]. 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. Only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; termed MOG antibody-associated disease, MOGAD)

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Conclusion