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The influence of MOGAD on diagnosis of multiple sclerosis using MRI

Nature Reviews Neurology volume 20, pages 620–635 (2024)Cite this article

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Abstract

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS. This Expert Recommendation summarizes the outcomes from a Magnetic Resonance Imaging in MS workshop held in Oxford, UK in May 2022, in which MS and MOGAD experts reflected on the pathology and clinical features of these disorders, the contributions of MRI to their diagnosis and the clinical use of the MOG antibody assay. We also critically reviewed the literature to assess the validity of distinctive imaging features in the current MS and MOGAD criteria. We conclude that dedicated orbital and spinal cord imaging (with axial slices) can inform MOGAD diagnosis and also illuminate differential diagnoses. We provide practical guidance to neurologists and neuroradiologists on how to navigate the current MOGAD and MS criteria. We suggest a strategy that includes useful imaging discriminators on standard clinical MRI and discuss imaging features detected by non-conventional MRI sequences that demonstrate promise in differentiating these two disorders.

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Fig. 1: Distinct pathophysiological mechanisms in multiple sclerosis and myelin oligodendrocyte glycoprotein antibody-associated disease.
Fig. 2: Brain pathology in myelin oligodendrocyte glycoprotein antibody-associated disease.
Fig. 3: Orbital MRI findings in myelin oligodendrocyte glycoprotein antibody-associated disease.
Fig. 4: Schematic representation of lesion topography and characteristics in multiple sclerosis and myelin oligodendrocyte glycoprotein antibody-associated disease.
Fig. 5: Brain involvement in myelin oligodendrocyte glycoprotein antibody-associated disease.
Fig. 6: Typical spinal cord imaging features in myelin oligodendrocyte glycoprotein antibody-associated disease.
Fig. 7: Brain lesion resolution in myelin oligodendrocyte glycoprotein antibody-associated disease.
Fig. 8: Flowchart showing the use of MRI in the diagnosis of multiple sclerosis, considering myelin oligodendrocyte glycoprotein antibody-associated disease.

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Acknowledgements

The authors thank M. L. Rato for the design of Figs. 1 and 4, R. França for helping with the design of Fig. 8 and V. Camera and M. Pisa for their help in testing some of the versions of the Fig. 8 flowchart.

Author information

Authors and Affiliations

  1. NMO Service, Department of Neurology, Oxford University Hospitals, Oxford, UK

    Ruth Geraldes, M. Isabel Leite & Jacqueline Palace

  2. Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK

    Ruth Geraldes, Silvia Messina, Patrick Waters, Romina Mariano, Gabriele C. DeLuca, M. Isabel Leite & Jacqueline Palace

  3. Wexham Park Hospital, Frimley Health Foundation Trust, Slough, UK

    Ruth Geraldes & Silvia Messina

  4. Neurology–Neuroimmunology Department, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

    Georgina Arrambide & Jaume Sastre-Garriga

  5. Division of Child Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Brenda Banwell

  6. Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Brenda Banwell

  7. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Brenda Banwell

  8. Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Àlex Rovira

  9. Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy

    Rosa Cortese

  10. Center for Brain Research, Medical University of Vienna, Vienna, Austria

    Hans Lassmann

  11. Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

    Mara Assunta Rocca & Massimo Filippi

  12. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Mara Assunta Rocca & Massimo Filippi

  13. Vita-Salute San Raffaele University, Milan, Italy

    Mara Assunta Rocca & Massimo Filippi

  14. NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK

    Declan Chard & Tarek Yousry

  15. National Institute for Health Research (NIHR) University College London Hospitals (CLH) Biomedical Research Centre, London, UK

    Declan Chard

  16. Multiple Sclerosis Centre, Department of Neurosciences, San Camillo-Forlanini Hospital, Rome, Italy

    Claudio Gasperini

  17. Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, UK

    Yael Hacohen

  18. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité — Universitätsmedizin Berlin, Berlin, Germany

    Friedemann Paul

  19. Department of Neurology, Medical University of Graz, Graz, Austria

    Christian Enzinger

  20. Division of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, Graz, Austria

    Christian Enzinger

  21. Research Center for Clinical Neuroimmunology and Neuroscience, University Hospital and University, Basel, Switzerland

    Ludwig Kappos

  22. Department of Neuroinflammation, Queen Square MS Centre, UCL Queen Square Institute of Neurology, London, UK

    Olga Ciccarelli

  23. University College London Hospitals (UCLH) National Institute for Health and Research (NIHR) Biomedical Research Centre (BRC), London, UK

    Olga Ciccarelli

  24. Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands

    Frederik Barkhof

  25. Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, UK

    Frederik Barkhof

Authors
  1. Ruth Geraldes
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  2. Georgina Arrambide
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  13. Romina Mariano
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  14. Friedemann Paul
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  15. Gabriele C. DeLuca
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  24. Jacqueline Palace
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Consortia

MAGNIMS Study Group

  • Àlex Rovira
  • , Mara Assunta Rocca
  • , Claudio Gasperini
  • , Christian Enzinger
  • , Ludwig Kappos
  • , Jaume Sastre-Garriga
  • , Tarek Yousry
  • , Olga Ciccarelli
  • , Massimo Filippi
  • , Frederik Barkhof
  •  & Jacqueline Palace

Contributions

R.G., G.A., B.B., A.R., R.C., H.L., S.M., M.A.R. and P.W. researched data for the article. R.G., B.B., A.R., H.L., P.W. and J.P. contributed substantially to discussion of the content. R.G., G.A. and J.P. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Ruth Geraldes or Jacqueline Palace.

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Competing interests

R.G. has received support for scientific meetings and courses from Bayer, Biogen, Merck, Novartis and Janssen and honoraria for advisory work or talks from Biogen, Novartis, UCB and MIAC. G.A. has received compensation for consulting services, speaking honoraria or participation in advisory boards from Roche and Horizon Therapeutics; and travel support for scientific meetings from Novartis, Roche, Horizon Therapeutics, ECTRIMS and EAN. She serves as an editor for Europe for Multiple Sclerosis Journal — Experimental, Translational and Clinical and as a member of the editorial and scientific committee of Acta Neurológica Colombiana. She is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee, the European Biomarkers in Multiple Sclerosis (BioMS-eu) steering committee and the MOGAD Eugene Devic European Network (MEDEN) steering group. B.B. has received or will potentially receive financial compensation for consultancy for Novartis, Roche, UCB, Horizon Therapeutics, Biogen and Immunic Therapeutics for advice on clinical trial design. B.B. is funded by the National Multiple Sclerosis Society and NIH and was previously funded by the Canadian Multiple Sclerosis Society. A.R. serves or has served on scientific advisory boards for Novartis, Sanofi-Genzyme, Synthetic MR, TensorMedical, Roche and Biogen and has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck-Serono, Teva Pharmaceutical Industries, Novartis, Roche, Bristol-Myers and Biogen, is Chief Marketing Officer and co-founder of TensorMedical and receives research support from Fondo de Investigación en Salud (PI19/00950 and PI22/01589) from Instituto de Salud Carlos III, Spain. R.C. has received speaker honoraria and/or travel support from Roche, Merck, Sanofi-Genzyme, Novartis, Janssen and UCB. H.L. has received honoraria from Novartis, Sanofi, Genzyme, BMS and UCB Biopharma for lectures, unrelated to the topic of this manuscript. S.M. has received travel grants from Roche, Merck and Sanofi and has received speaking honoraria from UCB. M.A.R. has received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen and Roche and speaker honoraria from AstraZeneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono, Novartis, Roche, Sanofi and Teva. She receives research support from the MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research and Fondazione Italiana Sclerosi Multipla. She is Associate Editor for Multiple Sclerosis and Related Disorders. P.W. has received research grants from Euroimmun, CSL Behring and patent royalties for antibody testing (W02010046716A1). He is the Co-Director of the Oxford Autoimmune Neurology Diagnostic Laboratory (Oxford University, Oxford, UK) where MOG-IgG1 autoantibodies are tested, and both he and the University of Oxford receive royalties for antibody tests for LGI1 and CASPR2 (W02010046716A1). He has received honoraria or consulting fees from Biogen Idec, F Hoffmann La-Roche, Mereo BioPharma, Retrogenix, UBC, Euroimmun, University of British Columbia and Alexion; and travel grants from the Guthy-Jackson Charitable Foundation. Work in the Oxford Autoimmune Neurology Diagnostic Laboratory is supported by the UK National Health Service Commissioning service for NMOSD. D.C. is a consultant for Hoffmann-La Roche. In the past 3 years, he has been a consultant for Biogen and has received research funding from Hoffmann-La Roche, the International Progressive MS Alliance, the MS Society, the Medical Research Council and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre and a speaker’s honorarium from Novartis. He co-supervises a clinical fellowship at the National Hospital for Neurology and Neurosurgery, London, which is supported by Merck. C.G. reports personal fees from Biogen, Merck Serono, Teva Pharmaceuticals, Sanofi Genzyme, Almirall, Novartis, Roche and Bayer, outside the submitted work. R.M. undertook graduate studies funded by the Rhodes Trust and the Oppenheimer Memorial Trust. F.P. has received honoraria and research support from Alexion, Bayer, Biogen, Chugai, Merck Serono, 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 of inebilizumab (Horizon Therapeutics) and the OCTiMS Study (Novartis). He is an associate editor for Neurology, Neuroimmunology, and Neuroinflammation and academic editor with PLoS ONE. G.C.D. has received support from the NIHR Biomedical Research Centre (BRC), Oxford; and research funding from the Oxford BRC, MRC(UK), UK MS Society, National Health and Medical Research (Australia), Department of Defense (USA), European Charcot Foundation, American Academy of Neurology (AAN), Merck-Serono and Oxford-Quinnipiac Partnership. G.C.D. has also received travel expenses from Genzyme, Merck Serono, Novartis, Roche, the MS Academy and AAN and honoraria as an invited speaker or faculty for Novartis, Roche, the MS Academy and AAN. C.E. reports personal fees from Biogen, Bayer HealthCare Pharmaceuticals, Merck Serono, Novartis, Shire, Genzyme, Teva Pharmaceuticals, Sanofi, Celgene and Roche, outside the submitted work. L.K. received no personal compensation. His institutions (University Hospital Basel/Stiftung Neuroimmunology and Neuroscience Basel) have received and used exclusively for research support payments for steering committee and advisory board participation, consultancy services and participation in educational activities from Bayer, BMS, Celgene, Dörries-Frank Molnia & Pohlmann, Eli Lilly, EMD Serono, Genentech, Glaxo Smith Kline, Janssen Pharmaceuticals, Japan Tobacco, Merck, MH Consulting, Minoryx, Novartis, F. Hoffmann-La Roche, Senda Biosciences, Sanofi, Santhera, Shionogi, TG Therapeutics and Wellmera; licence fees for Neurostatus-UHB products; and grants from Novartis, Innosuisse and Roche. M.I.L. is funded by the NHS (Myasthenia and Related Disorders Service and National Specialized Commissioning Group for Neuromyelitis Optica, UK) and by the University of Oxford, UK. She has been awarded research grants from the UK Association for Patients with Myasthenia (Myaware), Muscular Dystrophy Campaign (MDUK) and the University of Oxford. She has received speaker honoraria and travel grants from UCB Pharma and Horizon Therapeutics and consultancy fees from UCB Pharma. She serves on scientific or educational advisory boards for UCB Pharma, Argenx and Horizon Therapeutics and on the Steering Committee for Horizon Therapeutics. J.S.-G. reports grants and personal fees from Sanofi Genzyme and personal fees from Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche and Teva Pharmaceuticals, outside the submitted work, and is a member of the Editorial Committee of Multiple Sclerosis Journal and Director of the Scientific Committee of Revista de Neurologia. T.Y. reports personal fees from Biogen, Novartis, Bayer HealthCare Pharmaceuticals and Hikma, outside the submitted work, and has received research support from Biogen, GlaxoSmithKline, Novartis and Schering. O.C. is an NIHR Research Professor (RP-2017-08-ST2-004); over the past 2 years, she has been a member of an independent data and safety monitoring board for Novartis; she gave a teaching talk in a Merck local symposium and contributed to an Advisory Board for Biogen; she is Deputy Editor of Neurology, for which she receives an honorarium; she has received research grant support from the MS Society of Great Britain and Northern Ireland, the NIHR UCLH Biomedical Research Centre, the Rosetree Trust, the National MS Society and the NIHR-HTA. M.F. is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche and Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda and TEVA; participation in advisory boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme and Takeda; and scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis and Sanofi-Genzyme. He receives research support from Biogen Idec, Merck Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research and Fondazione Italiana Sclerosi Multipla. F.B. is supported by the NIHR biomedical research centre at University College London Hospitals. F.B. is part of the steering committee or a data safety monitoring board member for Biogen, Merck, ATRI/ACTC and Prothena, is a consultant for Roche, Celltrion, Rewind Therapeutics, Merck, IXICO, Jansen and Combinostics, has research agreements with Merck, Biogen, GE Healthcare and Roche and is a co-founder and shareholder of Queen Square Analytics. J.P. has received support for scientific meetings and honoraria for advisory work from Merck Serono, Novartis, Chugai, Alexion, Roche, Medimmune, Argenx, Vitaccess, UCB, Mitsubishi, Amplo and Janssen, and grants from Alexion, Argenx, Clene, Roche, Medimmune and Amplo Biotechnology. She holds patent ref. P37347WO, a licence agreement with Numares multimarker MS diagnostics and shares in AstraZeneca. Her group has been awarded an ECTRIMS fellowship and a Sumaira Foundation grant to start later this year. A Charcot fellow worked in Oxford 2019–2021. She acknowledges partial funding to the Oxford University Hospitals Trust by Highly Specialized Services NHS England. She is on the medical advisory boards of the Sumaira Foundation and MOG project charities, is a member of the Guthy Jackon Foundation Charity and is on the Board of the European Charcot Foundation, the steering committee of MAGNIMS and the UK NHSE IVIG Committee. She is Chair of the NHSE neuroimmunology patient pathway and has been an ECTRIMS Council member on the educational committee since June 2023. She is also on the Association of British Neurologists advisory groups for MS and neuroinflammation and neuromuscular diseases. Y.H. declares no competing interests.

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Geraldes, R., Arrambide, G., Banwell, B. et al. The influence of MOGAD on diagnosis of multiple sclerosis using MRI. Nat Rev Neurol 20, 620–635 (2024). https://doi.org/10.1038/s41582-024-01005-2

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  • DOI: https://doi.org/10.1038/s41582-024-01005-2

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