Brain, Vol. 122, No. 10, 1941-1950,
October 1999
© 1999 Oxford University Press
The natural history of multiple sclerosis: a geographically based study
7. Progressive–relapsing and relapsing–progressive multiple sclerosis: a re-evaluation
Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada
Correspondence to:
Professor G. C. Ebers, Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK E-mail: gebers{at}lhsc.on.ca
Classifications of multiple sclerosis subtypes have been largely based on clinical phenomenology. Nevertheless, definitions of relapse, remission and progression have been imprecise. Recently an international consensus group, as part of a reclassification of disease subtypes, recommended dropping the term `relapsing–progressive' (RP) and retaining the term `progressive–relapsing' (PR) multiple sclerosis. The term `RP' multiple sclerosis had been applied when the early course combined both relapses and progression and was believed to identify some patients with a worse than average outcome. The PR group consisted of patients with primary progressive disease who later in their course developed relapses. Since the terminology has been largely arbitrary, we have evaluated the validity of the terms `RP' and `PR' multiple sclerosis in the context of long-term outcome within a large population-based cohort of progressive multiple sclerosis patients seen at the London Multiple Sclerosis Clinic (Canada) between 1972 and 1984. Mean follow-up of the entire cohort was 25 years. Designation of RP multiple sclerosis did identify a more rapidly progressive subgroup. To realign these natural history data with consensus recommendations, these patients were reassigned to secondary progressive (SP) or to primary progressive (PP) multiple sclerosis, with progression defined as at least 1 year of progressive deterioration. PP multiple sclerosis patients with relapses after a year were designated as having PR multiple sclerosis. Relapses in primary progressive multiple sclerosis occurred in 27.8% of patients at some point even two to three decades after onset. In general these relapses were mild and remitting, but served to blur the distinction between progressive and relapsing–remitting disease. The long-term outcomes of time to Kurtzke disability scores (DSS) of 3, 6, 8 and 10 were compared among the progressive subtypes. Times to these disability end-points and to death were not different between PR and PP multiple sclerosis. Survival curves for progressive patients have been amended to incorporate the reassignment of PR multiple sclerosis patients into the PP group and the RP multiple sclerosis patients into the PP and SP subgroups. The time to reach DDS 3, 6, 8 and 10 for a population-based cohort of primary and secondary progressive patients resulting from the elimination of the categories of RP multiple sclerosis and PR multiple sclerosis has been established. These results provide justification for retaining only PP and SP multiple sclerosis as the subgroups of progressive disease.
relapsing progressive multiple sclerosis; progressive relapsing multiple sclerosis
DSS = Disability Status Score; PP = primary progressive; PR = progressive relapsing; RP = relapsing progressive; SP = secondary progressive
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J.-S. Wu, W. Qiu, A. Castley, I. James, F. L Mastaglia, F. T Christiansen, W. M Carroll, J. Joseph, and A. G Kermode Modifying effects of HLA-DRB1 allele interactions on age at onset of multiple sclerosis in Western Australia Multiple Sclerosis, January 1, 2010; 16(1): 15 - 20. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Koch, E. Kingwell, P. Rieckmann, and H. Tremlett The natural history of primary progressive multiple sclerosis Neurology, December 8, 2009; 73(23): 1996 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tremlett, Yinshan Zhao, and V. Devonshire Natural history of secondary-progressive multiple sclerosis Multiple Sclerosis, April 1, 2008; 14(3): 314 - 324. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Chandran, D. Hunt, A. Joannides, C. Zhao, A. Compston, and R. J.M Franklin Myelin repair: the role of stem and precursor cells in multiple sclerosis Phil Trans R Soc B, January 12, 2008; 363(1489): 171 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bergamaschi, S. Quaglini, M. Trojano, M. P. Amato, E. Tavazzi, D. Paolicelli, V. Zipoli, A. Romani, A. Fuiani, E. Portaccio, et al. Early prediction of the long term evolution of multiple sclerosis: the Bayesian Risk Estimate for Multiple Sclerosis (BREMS) score J. Neurol. Neurosurg. Psychiatry, July 1, 2007; 78(7): 757 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. O'Rourke, C. Walsh, G. Antonelli, and M. Hutchinson Predicting beta-interferon failure in relapsing-remitting multiple sclerosis Multiple Sclerosis, April 1, 2007; 13(3): 336 - 342. [Abstract] [PDF]
|
|
|
|
 |
|
 O. Gonen, T.A. Oberndorfer, M. Inglese, J.S. Babb, J. Herbert, and R.I. Grossman Reproducibility of Three Whole-Brain N-Acetylaspartate Decline Cohorts in Relapsing-Remitting Multiple Sclerosis AJNR Am. J. Neuroradiol., February 1, 2007; 28(2): 267 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Young, C. Lederer, K. Eder, M. Daumer, A. Neiss, C. Polman, L. Kappos, and on behalf of the Sylvia Lawry Centre for Multiple Relapses and subsequent worsening of disability in relapsing-remitting multiple sclerosis. Neurology, September 12, 2006; 67(5): 804 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K H Chang, R K Lyu, C M Chen, W C Hsu, Y R Wu, S T Chen, and L S Ro Clinical characteristics of multiple sclerosis in Taiwan: a cross-sectional study Multiple Sclerosis, August 1, 2006; 12(4): 501 - 506. [Abstract] [PDF]
|
|
|
|
 |
|
 G. C. DeLuca, K. Williams, N. Evangelou, G. C. Ebers, and M. M. Esiri The contribution of demyelination to axonal loss in multiple sclerosis Brain, June 1, 2006; 129(6): 1507 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kremenchutzky, G. P. A. Rice, J. Baskerville, D. M. Wingerchuk, and G. C. Ebers The natural history of multiple sclerosis: a geographically based study 9: Observations on the progressive phase of the disease Brain, March 1, 2006; 129(3): 584 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Confavreux and S. Vukusic Age at disability milestones in multiple sclerosis Brain, March 1, 2006; 129(3): 595 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Confavreux and S. Vukusic Natural history of multiple sclerosis: a unifying concept Brain, March 1, 2006; 129(3): 606 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S L Minden, D Frankel, L Hadden, J Perloff, K P Srinath, and D C Hoaglin The Sonya Slifka Longitudinal Multiple Sclerosis Study: methods and sample characteristics Multiple Sclerosis, February 1, 2006; 12(1): 24 - 38. [Abstract] [PDF]
|
|
|
|
|
|
H. Tremlett, D. Paty, and V. Devonshire The natural history of primary progressive MS in British Columbia, Canada Neurology, December 27, 2005; 65(12): 1919 - 1923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S M Leary, B Porter, and A J Thompson Multiple sclerosis: diagnosis and the management of acute relapses Postgrad. Med. J., May 1, 2005; 81(955): 302 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M J Tullman, R J Oshinsky, F D Lublin, and G R Cutter Clinical characteristics of progressive relapsing multiple sclerosis Multiple Sclerosis, August 1, 2004; 10(4): 451 - 454. [Abstract] [PDF]
|
|
|
|
|
|
F G Maggs and J Palace The pathogenesis of multiple sclerosis: is it really a primary inflammatory process? Multiple Sclerosis, June 1, 2004; 10(3): 326 - 329. [Abstract] [PDF]
|
|
|
|
|
|
A. Thompson Overview of primary progressive multiple sclerosis (PPMS): similarities and differences from other forms of MS, diagnostic criteria, pros and cons of progressive diagnosis Multiple Sclerosis, June 1, 2004; 10(1_suppl): S2 - S7. [Abstract] [PDF]
|
|
|
|
|
|
P Sundstrom, A Svenningsson, L Nystrom, and L Forsgren Clinical characteristics of multiple sclerosis in Vasterbotten County in northern Sweden J. Neurol. Neurosurg. Psychiatry, May 1, 2004; 75(5): 711 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Thompson Overview of primary progressive multiple sclerosis (PPMS): similarities and differences from other forms of MS, diagnostic criteria, pros and cons of progressive diagnosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S2 - S7. [Abstract] [PDF]
|
|
|
|
|
|
H. Bronnum-Hansen, N. Koch-Henriksen, and E. Stenager Trends in survival and cause of death in Danish patients with multiple sclerosis Brain, April 1, 2004; 127(4): 844 - 850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L M Sudlow and C. E Counsell Problems with UK government's risk sharing scheme for assessing drugs for multiple sclerosis BMJ, February 15, 2003; 326(7385): 388 - 392. [Full Text] [PDF]
|
|
|
|
|
|
H. Kalanie, K. Gharagozli, and A. R. Kalanie Multiple sclerosis: report on 200 cases from Iran Multiple Sclerosis, February 1, 2003; 9(1): 36 - 38. [Abstract] [PDF]
|
|
|
|
|
|
M-L Sumelahti, P J Tienari, M Hakama, and J Wikstrom Multiple sclerosis in Finland: incidence trends and differences in relapsing remitting and primary progressive disease courses J. Neurol. Neurosurg. Psychiatry, January 1, 2003; 74(1): 25 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O'Connor Key issues in the diagnosis and treatment of multiple sclerosis: An overview Neurology, September 24, 2002; 59(90063): S1 - 33. [Full Text]
|
|
|
|
|
|
G T Ingle, V L Stevenson, D H Miller, S M Leary, M Rovaris, F Barkhof, B Brochet, V Dousset, M Filippi, X Montalban, et al. Two-year follow-up study of primary and transitional progressive multiple sclerosis Multiple Sclerosis, April 1, 2002; 8(2): 108 - 114. [Abstract] [PDF]
|
|
|
|
|
|
X Montalban and A J Thompson Workshop on primary progressive multiple sclerosis: meeting summary Multiple Sclerosis, April 1, 2002; 8(2): 177 - 178. [PDF]
|
|
|
|
|
|
S Skurkovich, A Boiko, I Beliaeva, A Buglak, T Alekseeva, N Smirnova, O Kulakova, V Tchechonin, O Gurova, T Deomina, et al. Randomized study of antibodies to IFN-g and TNF-a in secondary progressive multiple sclerosis Multiple Sclerosis, October 1, 2001; 7(5): 277 - 284. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Confavreux, S. Vukusic, T. Moreau, and P. Adeleine Relapses and Progression of Disability in Multiple Sclerosis N. Engl. J. Med., November 16, 2000; 343(20): 1430 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Ebers, W. J. Koopman, W. Hader, A. D. Sadovnick, M. Kremenchutzky, P. Mandalfino, D. M. Wingerchuk, J. Baskerville, and G. P. A. Rice The natural history of multiple sclerosis: a geographically based study: 8: Familial multiple sclerosis Brain, March 1, 2000; 123(3): 641 - 649. [Abstract] [Full Text] [PDF]
|
|