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      The course of multiple sclerosis rewritten: a Norwegian population-based study on disease demographics and progression

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          Abstract

          Objectives

          Over the past few decades, there has been an improvement in the rate of disability progression in multiple sclerosis (MS) patients, and most studies relate this evolvement to the introduction of disease-modifying therapies. However, several other factors have changed over this period, including access to MRI and newer diagnostic criteria. The aim of this study is to investigate changes in the natural course of MS over time in a near-complete and geographically well-defined population from the south-east of Norway.

          Methods

          We examined disease progression and demographics over two decades and assessed the effect of disease-modifying therapies using linear mixed-effect models.

          Results

          In a cohort of 2097 patients, we found a significant improvement in disability as measured by the Expanded Disability Status Scale (EDSS) stratified by age, and the improvement remained significant after adjusting for time on disease-modifying medications, gender and progressive MS at onset. The time from disease onset to EDSS 6 in the total cohort was 29.8 years (95% CI 28.5–31.1) and was significantly longer in patients diagnosed after 2006 compared to patients diagnosed before. There are significant differences between patient demographics, as well as time to EDSS 6, in the near-complete, geographically well-defined population compared to an additional cohort from the capital Oslo and its suburbs.

          Conclusion

          The natural course of MS is improving, but the improvement seen in disease progression has multifaceted explanations. Our study underlines the importance of completeness of data, relevant timeframes and demographics when comparing different MS populations. Studies on incomplete populations should be interpreted with caution.

          Electronic supplementary material

          The online version of this article (10.1007/s00415-020-10279-7) contains supplementary material, which is available to authorized users.

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          Most cited references52

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          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          Alan Thompson, Brenda Banwell, Frederik Barkhof … (2018)
          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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            Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).

            J. Kurtzke (1983)
            One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.
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              Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

              Chris Polman, Stephen C Reingold, Brenda Banwell … (2011)
              New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use. Ann Neurol 2011
              Article 0 comments Cited 1046 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Cecilia Smith Simonsen:
                ORCID: http://orcid.org/0000-0002-9408-7199
                cecsim@vestreviken.no
                Journal
                Journal ID (nlm-ta): J Neurol
                Journal ID (iso-abbrev): J Neurol
                Title: Journal of Neurology
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 0340-5354
                ISSN (Electronic): 1432-1459
                Publication date (Electronic): 22 October 2020
                Publication date PMC-release: 22 October 2020
                Publication date (Print): 2021
                Volume: 268
                Issue: 4
                Pages: 1330-1341
                Affiliations
                [1 ]GRID grid.459157.b, ISNI 0000 0004 0389 7802, Department of Neurology, , Vestre Viken Hospital Trust, ; Dronninggata, 3004 Drammen, Norway
                [2 ]Department of Neurology, Hospital Telemark HF, Skien, Oslo, Norway
                [3 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, Department of Neurology, , Oslo University Hospital, ; Oslo, Norway
                [4 ]GRID grid.5510.1, ISNI 0000 0004 1936 8921, Institute of Clinical Medicine, , University of Oslo, ; Oslo, Norway
                [5 ]GRID grid.5510.1, ISNI 0000 0004 1936 8921, Institute of Health and Society, , University of Oslo, ; Oslo, Norway
                [6 ]GRID grid.55325.34, ISNI 0000 0004 0389 8485, Oslo Centre for Biostatistics and Epidemiology, Research Support Services, , Oslo University Hospital, ; Oslo, Norway
                [7 ]MS-Centre Hakadal, Grønvoll, Norway
                Author information
                http://orcid.org/0000-0002-9408-7199
                Article
                Publisher ID: 10279
                DOI: 10.1007/s00415-020-10279-7
                PMC ID: 7990804
                PubMed ID: 33090270
                SO-VID: e2a0088d-341f-4edf-b1d2-21133e4da03d
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 3 August 2020
                Date revision received : 13 October 2020
                Date accepted : 14 October 2020
                Funding
                Funded by: Sanofi Genzyme (US)
                Award ID: GZ-2014-11451
                Award Recipient :
                Funded by: University of Oslo (incl Oslo University Hospital)
                Open Access :

                Open Access funding provided by University of Oslo (incl Oslo University Hospital)

                Categories
                Subject: Original Communication
                Custom metadata
                issue-copyright-statement © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                ScienceOpen disciplines: Neurology
                Keywords: multiple sclerosis,disease course,natural history,epidemiology,time to edss 6
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: multiple sclerosis, disease course, natural history, epidemiology, time to edss 6

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