Abstract
Since the earliest clinical descriptions of multiple sclerosis (MS), it has been recognised that a minority of patients experience slow accumulation, or progression of disability from onset of disease [1]: this phenotype is now commonly termed primary progressive MS (PPMS). However, more commonly patients go on to develop progression only following an initial period of relapses; this is referred to as secondary progressive disease (SPMS) [2]. These two distinct phases of relapses and progression are now thought to reflect the dual pathological processes of neuroinflammation and neurodegeneration which, in part, give rise to the wide clinical phenotype of MS [3]. Although our understanding of MS has made significant advances in recent years, there remains no single definitive diagnostic test or biomarker which accurately reflects the underlying disease process or biology, and as a result our ability to identify and quantify disease progression remains limited [2]. As we enter a new treatment era for MS, including the advent of clinical trials in progressive disease, epidemiological studies remain important in providing insights into the biology and evolution of disability in primary and secondary MS and are also key to the planning of successful interventional studies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Charcot J. Lectures on the diseases of the nervous system (chapter). In: Disseminated sclerosis: its symptomatology. London: New Sydenham Society; 1877. p. 209–17.
Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278–86.
Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–17.
Andersson PB, Waubant E, Gee L, Goodkin DE. Multiple sclerosis that is progressive from the time of onset: clinical characteristics and progression of disability. Arch Neurol. 1999;56(9):1138–42.
Leray E, Yaouanq J, Le Page E, et al. Evidence for a two-stage disability progression in multiple sclerosis. Brain. 2010;133(7):1900–13.
Minderhoud JM, van der Hoeven JH, Prange AJ. Course and prognosis of chronic progressive multiple sclerosis. Results of an epidemiological study. Acta Neurol Scand. 1988;78(1):10–5.
Phadke JG. Clinical aspects of multiple sclerosis in north-east Scotland with particular reference to its course and prognosis. Brain. 1990;113(6):1597–628.
Runmarker B, Andersen O. Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain. 1993;116(1):117–34.
McDonnell G, Hawkins S. An epidemiologic study of multiple sclerosis in Northern Ireland. Neurology. 1998;50(2):423–8.
Cottrell DA, Kremenchutzky M, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study. 5. The clinical features and natural history of primary progressive multiple sclerosis. Brain. 1999;122(4):625–39.
Tremlett H, Paty D, Devonshire V. The natural history of primary progressive MS in British Columbia, Canada. Neurology. 2005;65(12):1919–23.
Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain. 2006;129(3):606–16.
Debouverie M, Louis S, Pittion-Vouyovitch S, Roederer T, Vespignani H. Multiple sclerosis with a progressive course from onset in Lorraine-Eastern France. J Neurol. 2007;254(10):1370–5.
Koch M, Mostert J, Heersema D, De Keyser J. Progression in multiple sclerosis: further evidence of an age dependent process. J Neurol Sci. 2007;255(1–2):35–41.
Maghzi AH, Etemadifar M, Saadatnia M. Clinical and demographical characteristics of primary progressive multiple sclerosis in Isfahan, Iran. Eur J Neurol. 2007;14(4):403–7.
Koch M, Kingwell E, Rieckmann P, Tremlett H. The natural history of primary progressive multiple sclerosis. Neurology. 2009;73(23):1996–2002.
Harding KE, Wardle M, Moore P, et al. Modelling the natural history of primary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014;86(1):13–9.
Jena S, Alexander M, Aaron S, et al. Natural history of multiple sclerosis from the Indian perspective: experience from a tertiary care hospital. Neurol India. 2015;63:866–73.
Piccolo L, Kumar G, Nakashima I, et al. Multiple sclerosis in Japan appears to be a milder disease compared to the UK. J Neurol. 2015;262(4):831–6.
Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) advisory committee on clinical trials of new agents in multiple sclerosis. Neurology. 1996;46(4):907–11.
Debouverie M, Laforest L, Van Ganse E, Guillemin F. Earlier disability of the patients followed in multiple sclerosis centers compared to outpatients. Mult Scler. 2008;15(2):251–7.
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(1):133–46.
Stankoff B, Mrejen S, Tourbah A, et al. Age at onset determines the occurrence of the progressive phase of multiple sclerosis. Neurology. 2007;68(10):779–81.
McDonnell G, Hawkins S. Clinical study of primary progressive multiple sclerosis in Northern Ireland. J Neurol Neurosurg Psychiatry. 1998;64(4):451–4.
Ribbons KA, McElduff P, Boz C, et al. Male sex is independently associated with faster disability accumulation in relapse-onset MS but not in primary progressive MS. PLoS One. 2015;10(6):e0122,686. published online. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122686
Simone IL, Carrara D, Tortorella C, et al. Course and prognosis in early-onset MS: comparison with adult-onset forms. Neurology. 2002;59(12):1922–8.
Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D, University of British Columbia MS Clinic Neurologists. Early onset multiple sclerosis: a longitudinal study. Neurology. 2002;59(7):1006–10.
Harding KE, Liang K, Cossburn MD, et al. Long-term outcome of paediatric-onset multiple sclerosis: a population-based study. J Neurol Neurosurg Psychiatry. 2013;84(2):141–7.
Renoux C, Vukusic S, Mikaeloff Y, et al. Natural history of multiple sclerosis with childhood onset. N Engl J Med. 2007;356(25):2603–13.
Delalande S, Seze JD, Ferriby D, Stojkovic T, Vermersch P. Late onset multiple sclerosis. Rev Neurol (Paris). 2002;158(11):1082–7.
Tremlett H, Devonshire V. Is late-onset multiple sclerosis associated with a worse outcome? Neurology. 2006;67(6):954–9.
Cossburn M, Ingram G, Hirst C, Ben-Shlomo Y, Pickersgill T, Robertson N. Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis. Mult Scler J. 2012;18(1):45–54.
Kremenchutzky M, Cottrell D, Rice G, et al. The natural history of multiple sclerosis: a geographically based study 7. Progressive-relapsing and relapsing-progressive multiple sclerosis: a re-evaluation. Brain. 1999;122(10):1941–50.
Confavreux C, Vukusic S. Age at disability milestones in multiple sclerosis. Brain. 2006;129(3):595–605.
Phadke JG. Survival pattern and cause of death in patients with multiple sclerosis: results from an epidemiological survey in north east Scotland. J Neurol Neurosurg Psychiatry. 1987;50(5):523–31.
Leray E, Morrissey S, Yaouanq J, et al. Long-term survival of patients with multiple sclerosis in west France. Mult Scler J. 2007;13(7):865–74.
Grytten Torkildsen N, Lie S, Aarseth J, Nyland H, Myhr K. Survival and cause of death in multiple sclerosis: results from a 50-year follow-up in western Norway. Mult Scler J. 2008;14(9):1191–8.
Smestad C, Sandvik L, Celius E. Excess mortality and cause of death in a cohort of Norwegian multiple sclerosis patients. Mult Scler. 2009;15(11):1263–70.
Hader WJ. Disability and survival of multiple sclerosis in Saskatoon, Saskatchewan. Can J Neurol Sci. 2010;37(1):28–35.
Kingwell E, van der Kop M, Zhao Y, et al. Relative mortality and survival in multiple sclerosis: findings from British Columbia, Canada. J Neurol Neurosurg Psychiatry. 2012;83(1):61–6.
Leray E, Vukusic S, Debouverie M, et al., 2015, Excess mortality in patients with multiple sclerosis starts at 20 years from clinical onset: data from a large-scale French observational study. PLoS One, 10(7): e0132,033. Published online. 10.1371/journal.pone.0132033
Jick SS, Li L, Falcone GJ, Vassilev ZP, Wallander MA. Epidemiology of multiple sclerosis: results from a large observational study in the UK. J Neurol. 2015;262(9):2033–41.
Sandi D, Zsiros V, Fvesi J, et al. Mortality in Hungarian patients with multiple sclerosis between 1993 and 2013. J Neurol Sci. 2016;367:329–32.
Koch MW, Greenfield J, Javizian O, Deighton S, Wall W, Metz LM. The natural history of early versus late disability accumulation in primary progressive MS. J Neurol Neurosurg Psychiatry. 2014;86(6):615–21.
Bergamaschi R, Berzuini C, Romani A, Cosi V. Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis. J Neurol Sci. 2001;189(1–2):13–21.
Eriksson M, Andersen O, Runmarker B. Long-term follow up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis. Mult Scler J. 2003;9(3):260–74.
Kremenchutzky M, Rice GPA, Baskerville J, Wingerchuk DM, Ebers GC. The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease. Brain. 2006;129(3):584–94.
Koch M, De Keyser J, Tremlett H. Timing of birth and disease progression in multiple sclerosis. Mult Scler. 2008;14(6):793–8.
Tedeholm H, Skoog B, Lisovskaja V, Runmarker B, Nerman O, Andersen O. The outcome spectrum of multiple sclerosis: disability, mortality, and a cluster of predictors from onset. J Neurol. 2015;262(5):1148–63.
Manouchehrinia A, Beiki O, Hillert J. Clinical course of multiple sclerosis: a nationwide cohort study. Mult Scler J. 2016:1352458516681197. doi:10.1177/1352458516681197. [Epub ahead of print]
Vukusic S, Confavreux C. Prognostic factors for progression of disability in the secondary progressive phase of multiple sclerosis. J Neurol Sci. 2003;206(2):135–7.
Lorscheider J, Buzzard K, Jokubaitis V, et al. Defining secondary progressive multiple sclerosis. Brain. 2016;139(9):2395–405.
Tremlett H, Zhao Y, Devonshire V. Natural history of secondary-progressive multiple sclerosis. Mult Scler J. 2008;14(3):314–24.
Skoog B, Tedeholm H, Runmarker B, Odn A, Andersen O. Continuous prediction of secondary progression in the individual course of multiple sclerosis. Mult Scler Rel Disord. 2014;3(5):584–92.
Tremlett H, Yousefi M, Devonshire V, Rieckmann P, Zhao Y. Impact of multiple sclerosis relapses on progression diminishes with time. Neurology. 2009;73(20):1616–23.
Tremlett H, Zhao Y, Devonshire V. Natural history comparisons of primary and secondary progressive multiple sclerosis reveals differences and similarities. J Neurol. 2009;256(3):374–81.
Scalfari A, Lederer C, Daumer M, Nicholas R, Ebers G, Muraro P. The relationship of age with the clinical phenotype in multiple sclerosis. Mult Scler J. 2016;22(13):1750–8.
Robertson NP, Clayton D, Fraser M, Deans J, Compston DA. Clinical concordance in sibling pairs with multiple sclerosis. Neurology. 1996;47(2):347–52.
Oturai AB, Ryder LP, Fredrikson S, et al. Concordance for disease course and age of onset in Scandinavian multiple sclerosis coaffected sib pairs. Mult Scler. 2004;10(1):5–8.
Hensiek AE, Seaman SR, Barcellos LF, et al. Familial effects on the clinical course of multiple sclerosis. Neurology. 2007;68(5):376–83.
Koch M, Zhao Y, Yee I, et al. Disease onset in familial and sporadic primary progressive multiple sclerosis. Mult Scler J. 2010;16(6):694–700.
Koch M, Uyttenboogaart M, Heerings M, Heersema D, Mostert J, De Keyser J. Progression in familial and nonfamilial MS. Mult Scler J. 2008;14(3):300–6.
Ebers GC, Koopman WJ, Hader W, et al. The natural history of multiple sclerosis: a geographically based study. 8. Familial multiple sclerosis. Brain. 2000;123(3):641–9.
IMSGC. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214–9.
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209–20.
CAMMS223 Trial Investigators, Coles AJ, Compston DAS, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–801.
Cottrell DA, Kremenchutzky M, Rice GP, Hader W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study. 6. Applications to planning and interpretation of clinical therapeutic trials in primary progressive multiple sclerosis. Brain. 1999;122(4):641–7.
Zajicek J, Ball S, Wright D, et al. Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial. Lancet Neurol. 2013;12:857–65.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this chapter
Cite this chapter
Harding, K., Robertson, N. (2018). Epidemiology of Progressive Multiple Sclerosis. In: Wilkins, A. (eds) Progressive Multiple Sclerosis. Springer, Cham. https://doi.org/10.1007/978-3-319-65921-3_2
Download citation
DOI: https://doi.org/10.1007/978-3-319-65921-3_2
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-65920-6
Online ISBN: 978-3-319-65921-3
eBook Packages: MedicineMedicine (R0)