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Neuromyelitis optica

Abstract

Neuromyelitis optica (NMO; also known as Devic syndrome) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. In most patients, NMO is caused by pathogenetic serum IgG autoantibodies to aquaporin 4 (AQP4), the most abundant water-channel protein in the central nervous system. In a subset of patients negative for AQP4-IgG, pathogenetic serum IgG antibodies to myelin oligodendrocyte glycoprotein, an antigen in the outer myelin sheath of central nervous system neurons, are present. Other causes of NMO (such as paraneoplastic disorders and neurosarcoidosis) are rare. NMO was previously associated with a poor prognosis; however, treatment with steroids and plasma exchange for acute attacks and with immunosuppressants (in particular, B cell-depleting agents) for attack prevention has greatly improved the long-term outcomes. Recently, a number of randomized controlled trials have been completed and the first drugs, all therapeutic monoclonal antibodies, have been approved for the treatment of AQP4-IgG-positive NMO and its formes frustes.

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Fig. 1: Prevalence estimates.
Fig. 2: Incidence estimates.
Fig. 3: Mechanisms of disease in individuals with AQP4-IgG.
Fig. 4: Supposed mechanisms of disease in patients positive for MOG-IgG.
Fig. 5: Manifestations of NMO.
Fig. 6: MRI findings in NMO.
Fig. 7: Typical OCT findings in NMO compared with MS and a HC.
Fig. 8: Proposed management algorithm for acute attacks in patients with a diagnosis of NMOSD according to the IPND criteria or of MOG-IgG-associated disease.
Fig. 9: Proposed long-term management of patients with NMOSD according to the IPND criteria except MOG-IgG-positive cases.

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Acknowledgements

B.W. thanks the Dietmar Hopp Stiftung, Germany, and Merck Serono for funding research on AQP4-IgG-positive NMOSD and MOG encephalomyelitis. The authors are grateful to C. Chien and J. Kuchling as well as to H. Zimmermann (Charité – University Medicine Berlin) for kindly providing some of the MRI and OCT images shown in this review.

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Contributions

Introduction (S.J.); Epidemiology (H.J.K. and S.J.); Mechanisms/pathophysiology (S.J., B.W., M.L.); Diagnosis, screening and prevention (S.J., F.P., H.J.K.); Management (S.J., B.G.W., B.W., H.J.K., M.L., F.P.); Quality of life (M.L.); Outlook (B.G.W., S.J.); Overview of Primer (S.J.).

Corresponding author

Correspondence to Sven Jarius.

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Competing interests

F.P. served on scientific advisory boards of MedImmune and Novartis; received travel funding and/or speaker honoraria from Alexion, Bayer, Biogen, Chugai, MedImmune, Merck Serono, Novartis, Sanofi-Aventis/Genzyme, Shire and Teva; is an associate editor of Neurology, Neuroimmunology & Neuroinflammation; is an academic editor of PLoS ONE; consulted for Alexion, Biogen, MedImmune, SanofiGenzyme and Shire; received research support from Alexion, Bayer, Biogen, Merck Serono, Novartis, Sanofi-Aventis/Geynzme and Teva; and has received research support from the Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, German Ministry of Education and Research, German Research Council, Guthy–Jackson Charitable Foundation, National MS Society and Werth Stiftung of the City of Cologne. B.G.W. receives royalties from Hospices Civil de Lyon, Oxford University, RSR Ltd, and MVZ Labour PD Dr Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for NMO and related disorders (‘NMO-IgG: A Marker Autoantibody of Neuromyelitis Optica’); serves on an adjudication committee for clinical trials in NMO being conducted by Alexion and MedImmune, and consults for Chugai and Mitsubishi-Tanabe regarding a clinical trial for NMO. M.L. received consulting fees from Alexion, Genentech, and Viela Bio for participation in scientific advisory boards and receives consulting fees from Quest Diagnostics. H.J.K. received a grant from the National Research Foundation of Korea; consultancy/speaker fees from Alexion, Celltrion, Eisai, HanAll BioPharma, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and Viela Bio; is a steering committee member for MedImmune/Viela Bio; co-editor for Multiple Sclerosis Journal and associated editor for the Journal of Clinical Neurology. B.W. received research grants and/or honoraria from Bayer, Biogen, Deutsche Forschungsgemeinschaft (DFG), Dietmar Hopp Foundation, German Federal Ministry of Education and Research (BMBF; FKZ 01GI1602A), Klaus Tschira Foundation, Merck Serono, Novartis, Sanofi Genzyme and Teva. S.J. declares no competing interests.

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Nature Reviews Disease Primers thanks H. Lassmann, T. Matsushita, T. Misu, M. Mori and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Optic neuritis

(ON). Inflammation of the optic nerve.

Transverse myelitis

(TM). Inflammation of the spinal cord.

Acute disseminated encephalomyelitis

(ADEM). Sudden onset, widespread, polyfocal inflammatory demyelination of the brain and spinal cord, typically following infection or vaccination.

Autoimmune astrocytopathy

An autoimmune disorder primarily directed against astrocytes.

Area postrema syndrome

(APS). Intractable nausea, vomiting or hiccups caused by a lesion in the dorsal medulla oblongata.

Longitudinally extensive transverse myelitis

(LETM). Spinal cord inflammation that extends over three or more vertebral segments.

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Jarius, S., Paul, F., Weinshenker, B.G. et al. Neuromyelitis optica. Nat Rev Dis Primers 6, 85 (2020). https://doi.org/10.1038/s41572-020-0214-9

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