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

T Pakeerathan; J Havla; C Schwake; A Salmen; S Bigi; M Abegg; D Brügger; T Ferrazzini; A-K Runge; M Breu; B Kornek; G Bsteh; A Felipe-Rucián; M Ringelstein; O Aktas; M Karenfort; E Wendel; I Kleiter; K Hellwig; T Kümpfel; C Thiels; T Lücke; R Gold; K Rostasy; I Ayzenberg

doi:10.1007/s00415-022-11256-y

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

J Neurol. 2022 Dec;269(12):6366-6376. doi: 10.1007/s00415-022-11256-y. Epub 2022 Jul 23.

Authors

T Pakeerathan¹, J Havla^{2

3}, C Schwake¹, A Salmen⁴, S Bigi^{4

5

6}, M Abegg⁷, D Brügger⁷, T Ferrazzini⁷, A-K Runge⁴, M Breu⁸, B Kornek⁹, G Bsteh⁹, A Felipe-Rucián¹⁰, M Ringelstein^{11

12}, O Aktas¹¹, M Karenfort¹³, E Wendel¹⁴, I Kleiter^{1

15}, K Hellwig¹, T Kümpfel², C Thiels¹⁶, T Lücke¹⁶, R Gold¹, K Rostasy¹⁷, I Ayzenberg¹⁸

Affiliations

¹ Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44791, Bochum, Germany.
² Institute of Clinical Neuroimmunology, LMU Hospital, Ludwig-Maximilians Universität München, Munich, Germany.
³ Data Integration for Future Medicine (DIFUTURE) Consortium, LMU Hospital, Ludwig-Maximilians Universität München, Munich, Germany.
⁴ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ Institute for Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁶ Division of Child Neurology, Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland.
⁷ Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁸ Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
⁹ Department of Neurology, Medical University of Vienna, Vienna, Austria.
¹⁰ Department of Pediatric Neurology, Universitat Autònoma de Barcelona, Vall d'Hebron Hospital, Barcelona, Spain.
¹¹ Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
¹² Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
¹³ Department of General Paediatrics, Neonatology and Paediatric Cardiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
¹⁴ Department of Pediatric Neurology, Olgahospital, Stuttgart, Germany.
¹⁵ Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.
¹⁶ Department of Neuropediatrics, University Children's Hospital, Ruhr-University, Bochum, Germany.
¹⁷ Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Witten, Germany.
¹⁸ Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44791, Bochum, Germany. ilya.ayzenberg@rub.de.

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 mm³, 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.

Keywords: Children; MOGAD; Multiple sclerosis; Myelin-oligodendrocyte-glycoprotein IgG; Optic neuritis; Optical coherence tomography; Pediatric patients; Visual evoked potential.

MeSH terms

Atrophy / pathology
Humans
Multiple Sclerosis* / complications
Optic Neuritis* / diagnosis
Retina / diagnostic imaging
Retina / pathology
Retinal Degeneration* / pathology
Retrospective Studies
Tomography, Optical Coherence / methods
Vision Disorders