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Multicenter Study
. 2024 Nov;271(11):7222-7231.
doi: 10.1007/s00415-024-12666-w. Epub 2024 Sep 9.

Rapid differentiation of MOGAD and MS after a single optic neuritis

T Pakeerathan  1 , J Havla  2 , C Schwake  1 , A Salmen  1 , M Ringelstein  3   4 , O Aktas  3 , M Weise  3 , J A Gernert  2 , B Kornek  5   6 , G Bsteh  5   6 , A-K Pröbstel  7   8   9 , A Papadopoulou  7   9   10 , L Kulsvehagen  7   8   9 , A B Ayroza Galvão Ribeiro Gomes  7   8   9 , N Cerdá-Fuertes  8   9   10 , F C Oertel  11   12 , A S Duchow  11   12 , F Paul  11   12 , J P Stellmann  13   14 , N Stolowy  15 , K Hellwig  1 , C Schneider-Gold  1 , T Kümpfel  2 , R Gold  1 , P Albrecht  3   16 , I Ayzenberg  17
Affiliations
Multicenter Study

Rapid differentiation of MOGAD and MS after a single optic neuritis

T Pakeerathan et al. J Neurol. 2024 Nov.

Abstract

Background: Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS) and myelin-oligodendrocyte-glycoprotein IgG-associated disease (MOGAD). This study evaluated the applicability of optical coherence tomography (OCT) for differentiating between both diseases in two independent cohorts.

Methods: One hundred sixty two patients from seven sites underwent standard OCT and high-contrast visual acuity (HCVA) testing at least 6 months after first ON. Of these, 100 patients (32 MOGAD, 68 MS) comprised the primary investigational cohort, while 62 patients (31 MOGAD, 31 MS) formed a validation cohort. A composite score distinguishing between MOGAD and MS was developed using multivariate logistic regression.

Results: Bilateral simultaneous ON occurred more frequently in MOGAD compared to MS (46.9 vs. 11.8%, p < 0.001). OCT revealed more peripapillary retinal nerve fiber layer (pRNFL) atrophy in all segments in MOGAD compared to predominantly temporal pRNFL atrophy in MS (p < 0.001). HCVA was better preserved in MS (p = 0.007). pRNFL thickness in all except for temporal segments was suitable for differentiating MOGAD and MS. Simultaneous bilateral ON and critical atrophy in nasal (< 58.5 µm) and temporal superior (< 105.5 µm) segments were included into the composite score as three independent predictors for MOGAD. The composite score distinguished MOGAD from MS with 75% sensitivity and 90% specificity in the investigational cohort, and 68% sensitivity and 87% specificity in the validation cohort.

Conclusion: Following a single ON-episode, MOGAD exhibits more pronounced global pRNFL atrophy and lower visual acuity after ON compared to MS. The introduced OCT-based composite score enabled differentiation between the two entities across both cohorts.

Keywords: Multiple sclerosis; Myelin oligodendrocyte glycoprotein IgG-associated disease; Myelin-oligodendrocyte-glycoprotein IgG; Optic neuritis; Optical coherence tomography; Visual evoked potential.

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Conflict of interest statement

Declarations Conflicts of interest T. Pakeerathan has no conflicts of interest related to this study. J. Havla reports grants from the Friedrich-Baur-Stiftung, Merck and Horizon, personal fees and non-financial support from Alexion, Horizon, Roche, Merck, Novartis, Biogen, BMS, Hexal and Janssen, and non-financial support from the Guthy-Jackson Charitable Foundation and The Sumaira Foundation. C. Schwake has no conflicts of interest. A. Salmen received speaker honoraria for activities with Bristol Myers Squibb, CSL Behring, Novartis, and Roche, and research support by the Baasch Medicus Foundation, the Medical Faculty of the University of Bern and the Swiss MS Society. M. Ringelstein received speaker honoraria from Novartis, Bayer Vital GmbH, Roche, Alexion, Horizon and Ipsen and travel reimbursement from Bayer Schering, Biogen Idec, Merz, Genzyme, Teva, Roche, Horizon, Alexion and Merck, none related to this study. O. Aktas reports grants from the German Ministry of Education and Research (BMBF) and the German Research Foundation (DFG); grants and personal fees from Biogen and Novartis; and travel support and personal fees from Alexion, Almirall, MedImmune, Merck Serono, Roche, Sanofi, Viela Bio/Horizon Therapeutics and Zambon. M. Weise has no conflicts of interest. JA. Gernert reports travel expenses and non-financial support from Merck, outside the submitted work, and received a research grant from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; SFB/TRR 274, ID 408885537). B. Kornek received speaker honoraria from Bayer, Biogen, Celgene-BMS, Merck, Novartis, Roche, Sanofi Genzyme, and Teva and participated in advisory boards from Celgene-BMS, Merck, Novartis, Sanofi Genzyme, and Roche. No COIs related to this study. G. Bsteh has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Janssen, Lilly, Merck, Novartis, Roche, Sanofi-Genzyme and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. He has received financial support in the past 12 months by unrestricted research grants (Celgene/BMS, Novartis). No COIs related to this study. A-K. Pröbstel received speaker and/or consultation honoraria or travel funding from Roche, Merck, Novartis not related to this work. A. Papadopoulou received speaker-fees/fees for advisory boards from Sanofi-Genzyme, Eli Lilly, AbbVie, Lundbeck and TEVA and travel support from Bayer AG, Teva and Hoffmann-La Roche. Her research was supported by the University- and University Hospital of Basel, the Swiss Multiple Sclerosis Society, the “Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung”, the “Freie Akademische Gesellschaft Basel” and the Swiss National Science Foundation (Project number: P300PB_174480). L. Kulsvehagen has no conflicts of interest. AB. Ayroza Galvão Ribeiro Gomes has received a research grant from Roche, and travel grants from Roche and Biogen. She was a recipient of an ECTRIMS Clinical Fellowship and a Swiss Government Excellence Scholarship in 2020. N. Cerdá Fuertes has no conflicts of interest. F. Oertel received fellowship support by the National Multiple Sclerosis Society (US), American Academy of Neurology, Hertie foundation for excellence in clinical neuroscience and the Deutsche Gesellschaft für Neurologie – all unrelated to this project. AS. Duchow has no conflicts of interest related to this study. F. Paul has received honoraria and research support from Alexion, Bayer, Biogen, Chugai, MerckSerono, Novartis, Genyzme, MedImmune, Shire, and Teva Pharmaceuticals, and serves on scientific advisory boards for Alexion, MedImmune, Novartis, and UCB. He has received funding from Deutsche Forschungsgemeinschaft (DFG Exc 257), Bundesministerium für Bildung und Forschung (Competence Network Multiple Sclerosis), Guthy-Jackson Charitable Foundation, EU Framework Program 7, and National Multiple Sclerosis Society of the USA. He serves on the steering committee of the N-Momentum study with inebilizumab (Horizon Therapeutics) and the OCTiMS Study (Novartis). He is an associatee editor with Neurology, Neuroimmunology, and Neuroinflammation and academic editor with PloS One. JP. Stellmann has no conflicts of interest related to this study. N. Stolowy has no conflicts of interest. K. Hellwig received speaker's, board honoraria, and research support from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva. Her department received grant support from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, and Teva. C. Schneider-Gold has received public speaking honoraria and/or compensation for advisory boards/consultation fees from Alexion Pharmaceuticals, Amicus Therapeutics, argenx, Bayer Schering, Hormosan Pharma, Immunovant, Janssen, Lupin Pharmaceuticals, Roche Pharma, Teva Pharmaceuticals, and UCB. All not related to the content of this study. T. Kümpfel has received received speaker honoraria and/or personal fees for advisory boards from Novartis Pharma, Roche Pharma, Alexion/Astra Zeneca, Horizon, Merck, Chugai and Biogen. The Institution she works for has received grant support for her research from Bayer-Schering AG, Novartis and Chugai Pharma in the past. All not related to the content of this study. R. Gold received speaker’s and board honoraria from Baxter, Bayer Schering, Biogen Idec, CLB Behring, Genzyme, Merck Serono, Novartis, Stendhal, Talecris, and Teva. His department received grant support from Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, and Teva. All not related to the content of this study. P. Albrecht received research grants, speaker honoraria and travel grants and served on scientific advisory boards from Allergan/Abbvie, Celgene/BMS, Biogen, Merz, Janssen, Merck, Novartis, Roche, and received speaker honoraria from Bayer Schering, Hexal, Lilly, Sanofi, TEVA, none related to this study. I. Ayzenberg has received travel grants from Alexion, BMS, Biogen Idec and Guthy-Jackson Charitable Foundation, served on scientific advisory boards for Merck, Roche, Alexion, Horizon, Sanofi and received research support from Diamed, none related to this study. Ethical approval Written informed consent was obtained from all patients and their legal representatives participating in the study. The local ethics committees approved the study protocol in accordance with the Declaration of Helsinki (1964) in its currently applicable version. Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request.

Figures

Fig. 1
Fig. 1
Flow chart of patients included in the investigational cohort. We included 100 MOGAD or MS patients after the first ON episode who were identified in the participating centers. Depending on the diagnosis the patients were divided into two groups: group (1) 32 MOG-IgG-patients with initial manifestation > 18 years and group (2) 68 MS patients with initial manifestation > 18 years
Fig. 2
Fig. 2
Exemplary OCT ringscans and prevalence of pathological results in MOGAD and MS patients. Exemplary OCT ringscans show the typical atrophy patterns in MOGAD and MS patients after ON with a predominantly temporal pRNFL thinning in MS patients compared to the global retinal atrophy in MOGAD patients. The prevalence of pathological results, two standard deviations below the mean based on the data from healthy cohorts reported by Heidelberg Engineering, is visually represented in the figure for MOGAD-ON (in red letters) and MS-ON (in green letters)
Fig. 3
Fig. 3
pRNFL thickness and precise composite score in MOGAD-ON and MS-ON. Figure 3 consists of diagrams, visualizing the distribution of A temporal superior pRNFL thickness B nasal pRNFL thickness in MOGAD-ON and MS-ON. Further the figure shows C the formula for the precise composite score, the ROC curves with the cut-offs for D pRNFL TS, E pRNFL N and F the precise composite score
See this image and copyright information in PMC

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