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

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 MOG-EM. Material and methods: Cytological 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.

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

“…IgG/A/M immunoglobulin G/A/M, QIgG/A/M CSF/serum IgG/A/M ratios, QAlb CSF/serum albumin ratio 8/36, in the acute brain subgroup, vs. 0%, or 0/26, in the acute ON subgroup). This is all highly similar to what was observed in the adult cohort [26]. See Table 1 and Supplementary Figure 1 for further details.…”

“…An increased CSF white cell count (WCC) was found in 56/103 (54.4%) samples, which is almost exactly the rate found in adults [26], with a median of 40 cells/μl (range 6-256). WCC ≥ 50 cells/μl, which are very rare in MS (and thus considered a 'red flag' that should prompt physicians to challenge the diagnosis MS) [35,40], were present in 21.4% (22/103) of samples and thus with virtually the same frequency as in adults.…”

“…Not only the frequency but also the degree of intrathecal synthesis (IS) was low: QIgG was elevated in only 50% of the OCB-positive samples (which is similar to the 41.2% of samples in the adult cohort). In those samples with elevated QIgG, the intrathecal IgG fraction exceeded the first decile (values < 10% may result from imprecision of nephelometric IgG testing and should thus not be taken as proof of IS according to current guidelines [38]); in only 30% of cases, the median IF-IgG was only 7.6% (range 0.03-27%), and the median absolute amount of intrathecally produced IgG was just 2.4 mg/l (range 0.01 to 15.4 mg/l); similar values were found in the adult cohort (19%, 10.5%, and 2.3 mg/l, respectively) [26].…”

“…CSF-restricted OCB were positive in only 11/96 (11.5%) samples (OCB pattern 2 [OCBs that are exclusively present in the CSF but not in serum] in 7/96 or 7.3%; pattern 3 [same as pattern 2 plus identical OCBs in the CSF and serum] in 4/96 or 4.2%), and QIgG was elevated in only 14/78 (18%) (median QIgG 2.4; range 1.5-7) ( Table 2). This compares to an almost identical rate of OCB-positive and QIgG-positive samples of 13.2% and 8%, respectively, in the adult cohort [26]. In 7/96 (7.3%) samples, identical OCB in serum and CSF but no CSF-restricted bands were present (pattern 4).…”

“…In Part 1 of this article series, we report on the CSF findings in MOG-EM in adults [26]. For the present study, we systematically and comprehensively analyzed the results of 108 lumbar punctures (LP) from a cohort of 80 pediatric patients of mainly Caucasian descent with MOG-IgG-associated EM.…”