| Peer-Reviewed

Insights into the Course of Illness of MS: Clinical and Radiological Aspects

Received: 10 March 2022     Accepted: 30 March 2022     Published: 9 April 2022
Views:       Downloads:
Abstract

Patients with MS manifest a high degree of variability in their disease course and at first glance the disease outcome may seem unpredictable. Here we present a framework for clinicians challenged by the management of MS patients and by highlighting important aspects of the disease to be taken into account, we review the complex relationship between inflammation and neuronal degeneration. Details of illustrative cases are here described with the goal to emphasize the involvement of the spinal cord as a key element leading to progressive phases of the disease and to underscore the utility of recent paraclinical tools including quantified MRI volumetrics. We provide insights that allow understanding the variability of disease courses of MS, assessing the rate by which the disease generates clinical and radiological burdens for individual patients, and how currently available treatments have a predictable impact on outcomes. In line with latest views on the therapeutic approach for MS, instituting an immune therapy capable of arresting the inflammatory process before the cascade of degenerative phenomena takes place is portrayed as a strategy to prevent progressive stages of the disease, increasing the chance to induce a state of permanent remission when the treatment could be discontinued.

Published in Clinical Neurology and Neuroscience (Volume 6, Issue 2)
DOI 10.11648/j.cnn.20220602.11
Page(s) 19-28
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

MS Course of Illness, Neuronal Degeneration, Disease Progression, MRI for MS, Treatment Strategies

References
[1] Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study. 1. Clinical course and disability. Brain 1989; 112: 133-146.
[2] Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of early clinical course. Brain 1989; 112: 1419-1428.
[3] Eriksson M, Andersen O, Runmarker B. Long-term follow up of patient with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis. Multiple Sclerosis 2003; 9: 260-274.
[4] Kantarci OH, Weinshenker BG. Natural history of multiple sclerosis. Neurol Clin 2005; 23: 17-38.
[5] Sayao AL, Devonshire V, Tremlett H. Longitudinal follow-up of “benign” multiple sclerosis at 20 years. Neurology 2007; 68: 496-500.
[6] Kister I, Chamot E, Salter AR, et at. Disability in multiple sclerosis. A reference for patients and clinicians. Neurology 2013; 80: 1018-1024.
[7] The International Multiple Sclerosis Genetics Consortium. Risk alleles for multiple sclerosis identified by a genomewide study. NEJM 2007; 357: 851-862.
[8] The International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium 2. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011; 476: 214-219.
[9] Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol. 2007; 61: 288-299. doi: 10.1002/ana.21117.
[10] Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: noninfectious factors. Ann Neurol 2007; 61: 504-513. doi: 10.1002/ana.21141.
[11] D’Netto MJ, Morrison KM, Ramagopalan SV, et al. Risk alleles for multiple sclerosis in multiplex families. Neurology 2009; 72: 1984-1988.
[12] De Silvestri A, Capittini C, Mallucci G, et al. The involvement of HLA Class II alleles in multiple sclerosis: a systematic review with meta-analysis. Disease Markers 2019; doi: 10.1155/2019/1409069.
[13] Lucchinetti C, Bruck W, Parisi J et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47: 707-717.
[14] Frisher JM, Bramov S, Dal-Bianco A et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 2009; 132: 1175-1189. doi.org/10.1093/brain/awp070.
[15] Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis. The 2013 revisions. Neurology 2014; 83: 278-286.
[16] McFaul D, Hakopian NN, Smith JB, Nielsen AS, Langer-Gould A. Defining benign/burnt-out MS and discontinuing disease-modifying therapies. Neurol Neuroimmunol Neuroinflamm. 2021; 8: e960. doi: 10.1212/NXI.0000000000000960.
[17] Magliozzi R, Howell O, Vora A et al. Menigeal B-cell follicles in secondary progressive multiple sclerosis associate with early osent of disease and severe cortical pathology. Brain 2007; 130: 1089-1104.
[18] Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015; 14: 183-93. doi: 10.1016/S1474-4422(14)70256-X.
[19] Tintore’ M, Rovira A, Rio J, et al. Baseline MRI predicts future attacks and disability in clinically isolated syndrome. Neurology 2006; 67: 968-972.
[20] Wattjes M, Rovira A, Miller D, et al. MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients. Nature Reviews Neurology 2015; 11: 597-606.
[21] Tintore M, Rovira A, Rio J, et al. Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain 2015: 138: 1863-1874.
[22] Bekker I, Sombekke MH, Balk LJ, et al. Infratentorial and spinal cord lesions: cumulative predictors of long term disability? Mult Scler 2020: 26: 1381-1391.
[23] Fisniku LK, Brex PA, Altmann DR, Miszkiel KA, Benton CE, Lanyon R, Thompson AJ, Miller DH. Disability and T2 MRI lesions: a 20-year follow-up of patients with relapse onset of multiple sclerosis. Brain 2008; 131: 808-817. doi: 10.1093/brain/awm329.
[24] Barkhof F. The clinical-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol 2002: 15: 239-245.
[25] Bielekova B, Kadom N, Fisher E, et al. MRI as a marker for disease heterogeneity in multiple sclerosis. Neurology 2005; 65: 1071-1076.
[26] Lavorgna L, Bonavita S, Ippolito D, et a. Clinical and magnetic resonance imaging predictors of disease progression in multiple sclerosis: a nine-year follow-up study. Mult Scler. 2014; 20: 220-226.
[27] Sastre-Garriga J, Pareto D, Rovira A. Brain atrophy in multiple sclerosis: Clinical relevance and technical aspects. Neuroimaging Clin N Am 2017; 27 (2): 289-300. doi: 10.1016/j.nic.2017.01.002.
[28] Popescu V, Agosta F, Hulst HE et al. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry 2013; 84: 1082-1091. doi: 10.1136/jnnp-2012-304094.
[29] Perez-Miralles F, Sastre-Garriga J, Tintore M et al. Clinical impact of early brain atrophy in clinically isolated syndrome. Mult. Scler 2013: 19: 1878-1886.
[30] Cole JH, Raffel J, Friede T et al. Longitudinal assessment of multiple sclerosis with brain-age paradigm. Ann Neurol 2020: 88: 93-105.
[31] Cortese R, Battaglini M, Parodi F, et al. Mild gray matter atrophy in patients with long-standing multiple sclerosis and favorable clinical course. Mult Scler 2022; 28: 154-159.
[32] Cree BA, Hollenbach JA, Bove R et al. Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol 2019; 85: 653-666.
[33] Giorgio A, Stromillo ML, Bartolozzi ML et al. Relevance of hypointense brain MRI lesions for long-term worsening of clinical disability in relapsing multiple sclerosis. Mult Scler 2014; 20: 214-219. DOI: 10.1177/1352458513494490.
[34] Dekker J, Eijlers AJC, Popescu V et al. Predicting clinical progression in multiple sclerosis after 6 and 12 years. Eur Journal Neurol 2019; 26: 893-902 doi.org/10.1111/ene.13904.
[35] Elliott C, Belachew S, Wolinsky JS et al. Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis. Brain 2019; 142: 2787-2799.
[36] Scalfari A, Romualdi C, Nicholas RS, et al. The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis. Neurology 2018; 90: e2107-e2118.
[37] Rocca MA, Valsasina P, Meani A, Gobbi C, Zecca C, et al. on behalf of the MAGNIMS Study Group. Association of gray matter atrophy patterns with clinical phenotype and progression in multiple sclerosis. Neurology 2021; 96: doi.org/10.1212/WNL.0000000000011494.
[38] Sechi E. Keegan BM, Kaufmann TJ, et al. Unilateral motor progression in MS. Association with a critical corticospinal tract lesion. Neurology 2019; 93: e628-e634.
[39] Eden D, Gros C, Badji A, et al. Spatial distribution of multiple sclerosis lesions in the cervical spinal cord. Brain 2019: 142: 633-646.
[40] Enzinger C, Fazekas F, Matthews PM et al. Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects. Neurology 2005; 64: 1704-1711.
[41] Fox RJ, Salter AR, Tyry T, Sun J, et al. Treatment discontinuation and disease progression with injectable disease-modifying therapies: findings from the north american research committee on multiple sclerosis database. Int J MS Care 2013; 15: 194-201.
[42] Hatcher SE, Waubant E, Nourbakhsh B et al. Rebound syndrome in patients with multiple sclerosis after cessation of fingolimod treatment. JAMA Neurol 2016; 73: 790-794.
[43] West TW, Cree BAC. Natalizumab dosage suspension: are we helping or hurting? Ann Neurol 2010; 68: 395-399.
[44] Goodin DS. Disease-modifying therapy in multiple sclerosis. Update and implications. Neurology 2008; 71 suppl 3: S8-13.
[45] Inojosa H, Proschmann U, Akgun K et al. The need for a strategic therapeutic approach: multiple sclerosis in check. Ther Adv Chronic Dis 2022; 13: 20406223211063032.
[46] Scalfari A, Knappertz V, Cutter G, et al. Mortality in patients with multiple sclerosis. Neurology 2013; 81: 184-192.
[47] Harding K, Zhu F, Alotaibi M, Duggan T, et al. Multiple cause of death analysis in multiple sclerosis. A population-based study. Neurology 2020: 94: e820-e829.
[48] Stankiewicz JM, Weiner HL. An argument for broad use of high efficacy treatments in early multiple sclerosis. Neurol Neuroimmunol Neuroinflamm 2020; 7: e636.
[49] Brown JWL, Coles A, Horakova D et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA 2019: 32: 175-187.
[50] Kalincik T, Diouf I, Sharmin S, Malpas C, Spelman, T, et al. Effect of disease-modifying therapy on disability in relapsing-remitting multiple sclerosis over 15 years. Neurology 2021; 96: e783-797.
[51] Burt RK, Balabanov R, Burman J, et al. Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease-modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis. A randomized clinical trial. JAMA 2019; 321: 165-174.
[52] Krieger SC, Cook K, De Nino S, Fletcher M. The topographical model of multiple sclerosis. A dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm 2016; 3: e279.
[53] Marrie RA, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer TL. Comorbidity, socioeconomic status and multiple sclerosis. Mult Scler 2008; 14: 1091-1098.
[54] Marrie RA, Rudick R, Horwitz R, Cutter G, et al. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 2010; 74: 1041-1047.
[55] Salter A, Kowalec K, Fitzgerald KC, Cutter G, Marrie RA. Comorbidity is associated with disease activity in MS. Findings from the CombiRx trial. Neurology 2020; 95: e446-e456.
[56] Poser CM. Trauma to the central nervous system may result in formation or enlargement of multiple sclerosis plaques. Arch Neurol 2000; 57: 1074-1077.
[57] Gratch D, Do D, Khankhanian P et al. Impact of cervical stenosis on multiple sclerosis lesion distribution in the spinal cord. Mult Scler Relat Disord 2020; 45: 102415. doi: 10.1016/j.msard.2020.102415.
[58] Bomprezzi R, Chen AP, Hemond CC. Cervical spondylosis is a risk factor for localized spinal cord lesions in multiple sclerosis. Clin Neurol Neurosurg 2020; 199: 106311 doi: 10.1016/j.clineuro.2020.106311.
[59] Chataway J, De Angelis F, Connick P, et al. Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised, placebo-controlled trial. The Lancet Neurology 2020; 19: 214-225.
[60] Rissanen E, Tuisku J, Vahlberg T, et al. Microglial activation, white matter tract damage and disability in MS. Neurol Neuroimmunol Neuroinflamm 2018; 5: e443. doi: 10.1212/NXI.0000000000000443.
Cite This Article
  • APA Style

    Roberto Bomprezzi, Andrew Chen, Christopher Hemond. (2022). Insights into the Course of Illness of MS: Clinical and Radiological Aspects. Clinical Neurology and Neuroscience, 6(2), 19-28. https://doi.org/10.11648/j.cnn.20220602.11

    Copy | Download

    ACS Style

    Roberto Bomprezzi; Andrew Chen; Christopher Hemond. Insights into the Course of Illness of MS: Clinical and Radiological Aspects. Clin. Neurol. Neurosci. 2022, 6(2), 19-28. doi: 10.11648/j.cnn.20220602.11

    Copy | Download

    AMA Style

    Roberto Bomprezzi, Andrew Chen, Christopher Hemond. Insights into the Course of Illness of MS: Clinical and Radiological Aspects. Clin Neurol Neurosci. 2022;6(2):19-28. doi: 10.11648/j.cnn.20220602.11

    Copy | Download

  • @article{10.11648/j.cnn.20220602.11,
      author = {Roberto Bomprezzi and Andrew Chen and Christopher Hemond},
      title = {Insights into the Course of Illness of MS: Clinical and Radiological Aspects},
      journal = {Clinical Neurology and Neuroscience},
      volume = {6},
      number = {2},
      pages = {19-28},
      doi = {10.11648/j.cnn.20220602.11},
      url = {https://doi.org/10.11648/j.cnn.20220602.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cnn.20220602.11},
      abstract = {Patients with MS manifest a high degree of variability in their disease course and at first glance the disease outcome may seem unpredictable. Here we present a framework for clinicians challenged by the management of MS patients and by highlighting important aspects of the disease to be taken into account, we review the complex relationship between inflammation and neuronal degeneration. Details of illustrative cases are here described with the goal to emphasize the involvement of the spinal cord as a key element leading to progressive phases of the disease and to underscore the utility of recent paraclinical tools including quantified MRI volumetrics. We provide insights that allow understanding the variability of disease courses of MS, assessing the rate by which the disease generates clinical and radiological burdens for individual patients, and how currently available treatments have a predictable impact on outcomes. In line with latest views on the therapeutic approach for MS, instituting an immune therapy capable of arresting the inflammatory process before the cascade of degenerative phenomena takes place is portrayed as a strategy to prevent progressive stages of the disease, increasing the chance to induce a state of permanent remission when the treatment could be discontinued.},
     year = {2022}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Insights into the Course of Illness of MS: Clinical and Radiological Aspects
    AU  - Roberto Bomprezzi
    AU  - Andrew Chen
    AU  - Christopher Hemond
    Y1  - 2022/04/09
    PY  - 2022
    N1  - https://doi.org/10.11648/j.cnn.20220602.11
    DO  - 10.11648/j.cnn.20220602.11
    T2  - Clinical Neurology and Neuroscience
    JF  - Clinical Neurology and Neuroscience
    JO  - Clinical Neurology and Neuroscience
    SP  - 19
    EP  - 28
    PB  - Science Publishing Group
    SN  - 2578-8930
    UR  - https://doi.org/10.11648/j.cnn.20220602.11
    AB  - Patients with MS manifest a high degree of variability in their disease course and at first glance the disease outcome may seem unpredictable. Here we present a framework for clinicians challenged by the management of MS patients and by highlighting important aspects of the disease to be taken into account, we review the complex relationship between inflammation and neuronal degeneration. Details of illustrative cases are here described with the goal to emphasize the involvement of the spinal cord as a key element leading to progressive phases of the disease and to underscore the utility of recent paraclinical tools including quantified MRI volumetrics. We provide insights that allow understanding the variability of disease courses of MS, assessing the rate by which the disease generates clinical and radiological burdens for individual patients, and how currently available treatments have a predictable impact on outcomes. In line with latest views on the therapeutic approach for MS, instituting an immune therapy capable of arresting the inflammatory process before the cascade of degenerative phenomena takes place is portrayed as a strategy to prevent progressive stages of the disease, increasing the chance to induce a state of permanent remission when the treatment could be discontinued.
    VL  - 6
    IS  - 2
    ER  - 

    Copy | Download

Author Information
  • Department of Neurology, University of Massachusetts Medical School, Worcester, the United States

  • Department of Radiology, University of Massachusetts Medical School, Worcester, the United States

  • Department of Neurology, University of Massachusetts Medical School, Worcester, the United States

  • Sections