Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis

Sven Jarius¹, Orhan Aktas², Ilya Ayzenberg³, Judith Bellmann-Strobl^{4

5

6

7}, Achim Berthele⁸, Katrin Giglhuber⁸, Vivien Häußler⁹, Joachim Havla^{10

11}, Kerstin Hellwig³, Martin W Hümmert¹², Ingo Kleiter^{3

13}, Luisa Klotz¹⁴, Markus Krumbholz^{15

16

17}, Tania Kümpfel¹⁰, Friedemann Paul^{4

5

6

7}, Marius Ringelstein^{2

18}, Klemens Ruprecht⁴, Makbule Senel¹⁹, Jan-Patrick Stellmann^{9

20

21}, Florian Then Bergh²², Hayrettin Tumani¹⁹, Brigitte Wildemann²³, Corinna Trebst²⁴; Neuromyelitis Optica Study Group (NEMOS)

Affiliations

¹ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
² Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
³ Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
⁴ Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Experimental and Clinical Research Center, a Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁶ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
⁷ NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
⁸ Department of Neurology, School of Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany.
⁹ Department of Neurology and Institute of Neuroimmunology and MS (INIMS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁰ Institute of Clinical Neuroimmunology, LMU Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
¹¹ Data Integration for Future Medicine (DIFUTURE) Consortium, Ludwig-Maximilians-Universität München, Munich, Germany.
¹² Department of Neurology, Hannover Medical School, Hannover, Germany.
¹³ Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.
¹⁴ Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
¹⁵ Department of Neurology and Pain Treatment, Immanuel Klinik Rüdersdorf, University Hospital of the Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
¹⁶ Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
¹⁷ Department of Neurology and Stroke, University Hospital of Tübingen, Tübingen, Germany.
¹⁸ Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹⁹ Department of Neurology, University of Ulm, Ulm, Germany.
²⁰ APHM, Hopital de la Timone, CEMEREM, Marseille, France.
²¹ Aix Marseille Univ, CNRS, CRMBM, Marseille, France.
²² Department of Neurology, University of Leipzig, Leipzig, Germany.
²³ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
²⁴ Department of Neurology, Hannover Medical School, Hannover, Germany. trebst.corinna@mh-hannover.de.

PMID: 37022481
PMCID: PMC10267280
DOI: 10.1007/s00415-023-11634-0

Review

Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis

Sven Jarius et al. J Neurol. 2023 Jul.

. 2023 Jul;270(7):3341-3368.

doi: 10.1007/s00415-023-11634-0. Epub 2023 Apr 6.

Authors

Affiliations

¹ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
² Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
³ Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
⁴ Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁵ Experimental and Clinical Research Center, a Cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁶ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
⁷ NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health, and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
⁸ Department of Neurology, School of Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany.
⁹ Department of Neurology and Institute of Neuroimmunology and MS (INIMS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁰ Institute of Clinical Neuroimmunology, LMU Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
¹¹ Data Integration for Future Medicine (DIFUTURE) Consortium, Ludwig-Maximilians-Universität München, Munich, Germany.
¹² Department of Neurology, Hannover Medical School, Hannover, Germany.
¹³ Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.
¹⁴ Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
¹⁵ Department of Neurology and Pain Treatment, Immanuel Klinik Rüdersdorf, University Hospital of the Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
¹⁶ Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany.
¹⁷ Department of Neurology and Stroke, University Hospital of Tübingen, Tübingen, Germany.
¹⁸ Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹⁹ Department of Neurology, University of Ulm, Ulm, Germany.
²⁰ APHM, Hopital de la Timone, CEMEREM, Marseille, France.
²¹ Aix Marseille Univ, CNRS, CRMBM, Marseille, France.
²² Department of Neurology, University of Leipzig, Leipzig, Germany.
²³ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
²⁴ Department of Neurology, Hannover Medical School, Hannover, Germany. trebst.corinna@mh-hannover.de.

PMID: 37022481
PMCID: PMC10267280
DOI: 10.1007/s00415-023-11634-0

Abstract

The term 'neuromyelitis optica spectrum disorders' (NMOSD) is used as an umbrella term that refers to aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica (NMO) and its formes frustes and to a number of closely related clinical syndromes without AQP4-IgG. NMOSD were originally considered subvariants of multiple sclerosis (MS) but are now widely recognized as disorders in their own right that are distinct from MS with regard to immunopathogenesis, clinical presentation, optimum treatment, and prognosis. In part 1 of this two-part article series, which ties in with our 2014 recommendations, the neuromyelitis optica study group (NEMOS) gives updated recommendations on the diagnosis and differential diagnosis of NMOSD. A key focus is on differentiating NMOSD from MS and from myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD), which shares significant similarity with NMOSD with regard to clinical and, partly, radiological presentation, but is a pathogenetically distinct disease. In part 2, we provide updated recommendations on the treatment of NMOSD, covering all newly approved drugs as well as established treatment options.

Keywords: Aquaporin-4 (AQP4); Autoantibodies; Cerebrospinal fluid (CSF); Clinical presentation; Diagnosis; Diagnostic criteria; Differential diagnosis; MOG antibody-associated disease (MOGAD); MOG antibody-associated encephalomyelitis (MOG-EM); Magnetic resonance imaging (MRI); Myelin oligodendrocyte glycoprotein (MOG); Myelitis; Neuromyelitis optica (NMO); Neuromyelitis optica spectrum disorders (NMOSD); Optic coherence tomography (OCT); Optic neuritis; Serology.

PubMed Disclaimer

Conflict of interest statement

SJ reports no conflicts of interest. OA has received speaking honoraria and travel grants from Alexion, Almirall, Biogen, Celgene, Merck, Novartis, Roche, and VielaBio. IA has received speaking honoraria and scientific advisory board compensation from Alexion, Roche, Merck Serono, Santhera, and Sanofi Genzyme and research support from Chugai and Diamed. JBS has received speaking honoraria and travel grants from Bayer Healthcare, sanofi-aventis/Genzyme, and Biogen and compensation for serving on a scientific advisory board from Roche. AB has received consulting and/or speaking fees from Alexion, Bayer Healthcare, Biogen, Celgene, and Roche. His institution has received compensations for clinical trials from Alexion, Biogen, Merck, Novartis, Roche, and Sanofi. VH reports no conflicts of interest. JH reports a grant for OCT research from the Friedrich-Baur-Stiftung, personal fees and non-financial support from Merck, Alexion, Novartis, Roche, Santhera, Biogen, Heidelberg Engineering, and Sanofi Genzyme, and non-financial support from the Guthy-Jackson Charitable Foundation; he is partially funded by the German Federal Ministry of Education and Research [grant numbers 01ZZ1603[A-D] and 01ZZ1804[A-H] (DIFUTURE)]. KH reports no conflicts of interest. MH reports no conflicts of interest. IK has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Alexion, Almirall, Bayer, Biogen, Hexal, Horizon, Merck, Neuraxpharm, Sanofi, and Roche/Chugai. LK has received compensation for serving on scientific advisory boards from Alexion, Biogen, BMS, Celgene GmbH, Genzyme, Horizon, Janssen, Merck Serono, Novartis, and Roche. She has received speaker honoraria and travel support from Bayer, Biogen, Celgene GmbH, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera, and Teva; she receives research support from German Research Foundation, IZKF Münster, IMF Münster, Biogen, Immunic AG, Novartis, and Merck Serono. MK has received travel funding, speaker honoraria, and research support from Bristol Myers Squibb, Merck, Novartis, and Roche. TK has received speaker honoraria and/or personal fees for advisory boards from Novartis Pharma, Roche Pharma, Alexion/Astra Zeneca and Biogen; the Institution she works for has received grant support for her research from Bayer-Schering AG, Novartis and Chugai Pharma. FP has received grants from Guthy Jackson Charitable Foundation, German Research Foundation, German Federal Ministry of Education and Research, Novartis, Bayer, Biogen Idec, Teva, Alexion, Roche, Horizon, Sanofi-Aventis/Genzyme, Merck Serono, Chugai, German Research Council, Werth Stiftung of the City of Cologne, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, National Multiple Sclerosis (USA), MedImmune, Shire, and Alexion, and has a patent on Foveal Morphometry pending to Nocturne GmbH; he is Academic Editor at PLoS ONE and Associate Editor of Neurology^® Neuroimmunology & Neuroinflammation. MR has received speaker honoraria from Novartis, Bayer Vital GmbH, Roche, Alexion, and Ipsen and travel reimbursement from Bayer Schering, Biogen Idec, Merz, Genzyme, Teva, Roche, and Merck. KR has received research support from Novartis Pharma, Merck Serono, German Ministry of Education and Research, European Union (821283-2), Stiftung Charité (BIH Clinical Fellow Program) and Arthur Arnstein Foundation, speaker honoraria from Bayer, and travel grants from Guthy Jackson Charitable Foundation. MS has received consulting and/or speaker honoraria from Alexion, Bayer, Biogen, Bristol-Myers-Squibb, Merck, Roche, and Sanofi Genzyme. She has received research funding from the Hertha-Nathorff-Program. PS reports no conflict of interest. FTB has received personal compensation for advisory board participation or speaking, and through his institution has received research support for investigator-initiated studies or for attending scientific meetings, from Actelion, Alexion, Bayer-Schering, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, Teva, UCB, German Research Foundation (DFG), and German Federal Ministry of Education and Research (BMBF). HT has received honoraria for consultation and expert testimony from Alexion Pharma, Bayer, Biogen, Janssen, MERCK, Novartis, Roche, Sanofi Genzyme, and Teva. BW has received grants from the German Ministry of Education and Research, German Research Foundation, Dietmar Hopp Stiftung, Klaus Tschira Stiftung, and Merck, and personal fees from Alexion, Bayer, Biogen, Roche. CT has received honoraria for consultation and expert testimony from Alexion Pharma Germany GmbH, Chugai Pharma Germany GmbH, and Roche Pharma GmbH.

Figures

**Fig. 1**
Proposed algorithm for the diagnosis of NMOSD. *AQP4-IgG* aquaporin-4 immunoglobulin G antibodies, *CSF* cerebrospinal fluid, *MOG-EM/MOGAD* myelin oligodendrocyte glycoprotein (MOG) antibody-associated encephalomyelitis/MOG autoantibody-associated disease, *MRI* magnetic resonance imaging, *OCT* optic coherence tomography

See this image and copyright information in PMC

References

1. Aktas O, Smith MA, Rees WA, Bennett JL, She D, Katz E, Cree BAC, group NMs, the NMsi Serum glial fibrillary acidic protein: a neuromyelitis optica spectrum disorder biomarker. Ann Neurol. 2021;89:895–910. doi: 10.1002/ana.26067. - DOI - PMC - PubMed
1. Alvarenga MP, do Carmo LF, Vasconcelos CCF, Alvarenga MP, Alvarenga-Filho H, de Melo Bento CA, Paiva CLA, Leyva-Fernandez L, Fernandez O, Papais-Alvarenga RM. Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis. Sci Rep. 2021;11:152. doi: 10.1038/s41598-020-80535-3. - DOI - PMC - PubMed
1. Aly L, Strauss EM, Feucht N, Weiss I, Berthele A, Mitsdoerffer M, Haass C, Hemmer B, Maier M, Korn T, Knier B. Optical coherence tomography angiography indicates subclinical retinal disease in neuromyelitis optica spectrum disorders. Mult Scler. 2022;28:522–531. doi: 10.1177/13524585211028831. - DOI - PMC - PubMed
1. Anamnart C, Tisavipat N, Owattanapanich W, Apiwattanakul M, Savangned P, Prayoonwiwat N, Siritho S, Rattanathamsakul N, Jitprapaikulsan J. Newly diagnosed neuromyelitis optica spectrum disorders following vaccination: case report and systematic review. Mult Scler Relat Disord. 2022;58:103414. doi: 10.1016/j.msard.2021.103414. - DOI - PubMed
1. Asgari N, Skejoe HP, Lillevang ST, Steenstrup T, Stenager E, Kyvik KO. Modifications of longitudinally extensive transverse myelitis and brainstem lesions in the course of neuromyelitis optica (NMO): a population-based, descriptive study. BMC Neurol. 2013;13:33. doi: 10.1186/1471-2377-13-33. - DOI - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis

Affiliations

Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD) - revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). Part I: Diagnosis and differential diagnosis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical