Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode

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Abstract

Background

Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MS ^ped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD ^ped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode.

Methods

Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls.

Results

Thirteen MOGAD ^ped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MS ^ped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGAD ^ped compared to MS ^ped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm ³, p < 0.001). Neither other macular layers nor P100 latency differed. MOGAD ^ped developed global atrophy affecting all peripapillary segments, while MS ^ped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGAD ^ped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016).

Conclusion

First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.

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Most cited references 38

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Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

Alan Thompson, Brenda Banwell, Frederik Barkhof … (2018)

The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

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MOG encephalomyelitis: international recommendations on diagnosis and antibody testing

S. Jarius, F Paul, O Aktas … (2018)

Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM (“red flags”) that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation.

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ISCEV standard for clinical visual evoked potentials: (2016 update).

J Vernon Odom, Michael Bach, Mitchell Brigell … (2016)

Visual evoked potentials (VEPs) can provide important diagnostic information regarding the functional integrity of the visual system. This document updates the ISCEV standard for clinical VEP testing and supersedes the 2009 standard. The main changes in this revision are the acknowledgment that pattern stimuli can be produced using a variety of technologies with an emphasis on the need for manufacturers to ensure that there is no luminance change during pattern reversal or pattern onset/offset. The document is also edited to bring the VEP standard into closer harmony with other ISCEV standards. The ISCEV standard VEP is based on a subset of stimulus and recording conditions that provide core clinical information and can be performed by most clinical electrophysiology laboratories throughout the world. These are: (1) Pattern-reversal VEPs elicited by checkerboard stimuli with large 1 degree (°) and small 0.25° checks. (2) Pattern onset/offset VEPs elicited by checkerboard stimuli with large 1° and small 0.25° checks. (3) Flash VEPs elicited by a flash (brief luminance increment) which subtends a visual field of at least 20°. The ISCEV standard VEP protocols are defined for a single recording channel with a midline occipital active electrode. These protocols are intended for assessment of the eye and/or optic nerves anterior to the optic chiasm. Extended, multi-channel protocols are required to evaluate postchiasmal lesions.

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Author and article information

Contributors

I. Ayzenberg:

ORCID: http://orcid.org/0000-0002-6009-792X

ilya.ayzenberg@rub.de

Journal

Journal ID (nlm-ta): J Neurol

Journal ID (iso-abbrev): J Neurol

Title: Journal of Neurology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0340-5354

ISSN (Electronic): 1432-1459

Publication date (Electronic): 23 July 2022

Publication date PMC-release: 23 July 2022

Publication date (Print): 2022

Volume: 269

Issue: 12

Pages: 6366-6376

Affiliations

[1 ]GRID grid.5570.7, ISNI 0000 0004 0490 981X, Department of Neurology, St. Josef-Hospital, , Ruhr-University Bochum, ; 44791 Bochum, Germany

[2 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Institute of Clinical Neuroimmunology, LMU Hospital, , Ludwig-Maximilians Universität München, ; Munich, Germany

[3 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Data Integration for Future Medicine (DIFUTURE) Consortium, LMU Hospital, , Ludwig-Maximilians Universität München, ; Munich, Germany

[4 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Department of Neurology, Inselspital, Bern University Hospital, , University of Bern, ; Bern, Switzerland

[5 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Institute for Social and Preventive Medicine, , University of Bern, ; Bern, Switzerland

[6 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Division of Child Neurology, Department of Pediatrics, University Children’s Hospital Bern, , University of Bern, ; Bern, Switzerland

[7 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Department of Ophthalmology, Inselspital, Bern University Hospital, , University of Bern, ; Bern, Switzerland

[8 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, , Medical University of Vienna, ; Vienna, Austria

[9 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Neurology, , Medical University of Vienna, ; Vienna, Austria

[10 ]GRID grid.7080.f, ISNI 0000 0001 2296 0625, Department of Pediatric Neurology, , Universitat Autònoma de Barcelona, ; Vall d’Hebron Hospital, Barcelona, Spain

[11 ]GRID grid.411327.2, ISNI 0000 0001 2176 9917, Department of Neurology, Medical Faculty, , Heinrich-Heine-University Düsseldorf, ; Düsseldorf, Germany

[12 ]GRID grid.411327.2, ISNI 0000 0001 2176 9917, Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, , Heinrich-Heine-University Düsseldorf, ; Düsseldorf, Germany

[13 ]GRID grid.411327.2, ISNI 0000 0001 2176 9917, Department of General Paediatrics, Neonatology and Paediatric Cardiology, , Heinrich-Heine-University Düsseldorf, ; Düsseldorf, Germany

[14 ]GRID grid.459687.1, ISNI 0000 0004 0493 3975, Department of Pediatric Neurology, , Olgahospital, ; Stuttgart, Germany

[15 ]Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany

[16 ]GRID grid.5570.7, ISNI 0000 0004 0490 981X, Department of Neuropediatrics, University Children’s Hospital, , Ruhr-University, ; Bochum, Germany

[17 ]GRID grid.412581.b, ISNI 0000 0000 9024 6397, Department of Pediatric Neurology, Children’s Hospital Datteln, , University Witten/Herdecke, ; Witten, Germany

Author information

I. Ayzenberg http://orcid.org/0000-0002-6009-792X

Article

Publisher ID: 11256

DOI: 10.1007/s00415-022-11256-y

PMC ID: 9618526

PubMed ID: 35869995

SO-VID: 336cd557-a20e-4b54-89df-25f21cca15a6

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 16 May 2022

Date revision received : 22 June 2022

Date accepted : 23 June 2022

Funding

Funded by: Universitätsklinikum der Ruhr-Universität Bochum (1007)

Open Access :

Open Access funding enabled and organized by Projekt DEAL.

Custom metadata

ScienceOpen disciplines: Neurology

Keywords: optical coherence tomography,visual evoked potential,optic neuritis,myelin-oligodendrocyte-glycoprotein igg,mogad,multiple sclerosis,pediatric patients,children

Data availability:

ScienceOpen disciplines: Neurology

Keywords: optical coherence tomography, visual evoked potential, optic neuritis, myelin-oligodendrocyte-glycoprotein igg, mogad, multiple sclerosis, pediatric patients, children

Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode

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Conclusion

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Karger: Neurology and Neuroscience

Most cited references 38

Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

MOG encephalomyelitis: international recommendations on diagnosis and antibody testing

ISCEV standard for clinical visual evoked potentials: (2016 update).

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