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      Asymptomatic spinal lesions in patients with AQP4‐IgG‐positive NMOSD: A real‐world cohort study

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          Abstract

          Objective

          This study aims to explore the frequency and influencing factors of asymptomatic spinal lesions (ASLs) and their impact on subsequent relapses in patients with AQP4‐IgG‐positive NMOSD (AQP4‐NMOSD) in a real‐world setting.

          Methods

          We retrospectively reviewed clinical information and spinal MRI data from AQP4‐NMOSD patients who had at least one spinal cord MRI during their follow‐ups. Kaplan–Meier curves and Cox proportional hazards models were employed to ascertain potential predictors of remission ASLs and to investigate factors associated with subsequent relapses.

          Results

          In this study, we included 129 patients with AQP4‐NMOSD and reviewed 173 spinal MRIs during attacks and 89 spinal MRIs during remission. Among these, 6 ASLs (3.5%) were identified during acute attacks, while 8 ASLs (9%) were found during remission. Remission ASLs were linked to the use of immunosuppressive agents, particularly conventional ones, whereas no patients using rituximab developed ASLs ( p = 0.005). Kaplan–Meier curve analysis indicated that patients with ASLs had a significantly higher relapse risk (HR = 4.658, 95% CI: 1.519–14.285, p = 0.007) compared to those without. Additionally, the use of mycophenolate mofetil (HR = 0.027, 95% CI: 0.003–0.260, p = 0.002) and rituximab (HR = 0.035, 95% CI: 0.006–0.203, p < 0.001) significantly reduced the relapse risk. However, after accounting for other factors, the presence of ASLs did not exhibit a significant impact on subsequent relapses (HR = 2.297, 95% CI: 0.652–8.085, p = 0.195).

          Interpretation

          ASLs may be observed in patients with AQP4‐NMOSD. The presence of ASLs may signify an underlying inflammatory activity due to insufficient immunotherapy. The administration of immunosuppressive agents plays a key role in the presence of remission ASLs and the likelihood of subsequent relapses.

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          Most cited references22

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          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          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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            International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

            Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.
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              A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.

              Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis. Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity. NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease. NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.
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                Author and article information

                Contributors
                qxue_sz@163.com
                ayfytyh@126.com
                Journal
                Ann Clin Transl Neurol
                Ann Clin Transl Neurol
                10.1002/(ISSN)2328-9503
                ACN3
                Annals of Clinical and Translational Neurology
                John Wiley and Sons Inc. (Hoboken )
                2328-9503
                04 February 2024
                April 2024
                : 11
                : 4 ( doiID: 10.1002/acn3.v11.4 )
                : 905-915
                Affiliations
                [ 1 ] Department of Neurology Second Affiliated Hospital of Anhui Medical University Hefei 230601 China
                [ 2 ] Department of Neurology The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University Hefei 230011 China
                [ 3 ] Department of Neurology First Affiliated Hospital of Soochow University Suzhou 215006 China
                [ 4 ] Department of Radiology The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University Hefei 230011 China
                Author notes
                [*] [* ] Correspondence

                Qun Xue, Department of Neurology, First Affiliated Hospital of Soochow University, Suzhou 215006, China. E‐mail: qxue_sz@ 123456163.com

                and

                Yanghua Tian, Department of Neurology, Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China. Tel: 86‐551‐62922328; 86‐13955188448; Fax: 86‐551‐62923704; E‐mail: ayfytyh@ 123456126.com

                [ # ]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-2304-9993
                https://orcid.org/0000-0002-9144-148X
                https://orcid.org/0000-0001-5038-0599
                Article
                ACN352007 ACN3-2023-12-1057.R2
                10.1002/acn3.52007
                11021673
                38311755
                bc6240d0-bba6-4f4d-a661-1b53bed1d7af
                © 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 10 January 2024
                : 05 December 2023
                : 10 January 2024
                Page count
                Figures: 3, Tables: 4, Pages: 915, Words: 6885
                Funding
                Funded by: Key Research and Development Plan of Jiangsu Province
                Award ID: BE2019666
                Funded by: Natural Science Foundation of Jiangsu Province , doi 10.13039/501100004608;
                Award ID: BK20211075
                This work was funded by Key Research and Development Plan of Jiangsu Province grant BE2019666; Natural Science Foundation of Jiangsu Province , doi 10.13039/501100004608; grant BK20211075.
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                April 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.0 mode:remove_FC converted:17.04.2024

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