The natural history of primary progressive multiple sclerosis
Abstract
Background: Primary progressive multiple sclerosis (PPMS) carries the worst prognosis of the multiple sclerosis (MS) subtypes and is currently untreatable. A previous analysis of the British Columbia MS database challenged the view that disability progression is rapid in PPMS, but identified few predictors of disease progression. Here, we extend previous analyses in an updated PPMS retrospective cohort study of prevalent cases.
Methods: We used Kaplan-Meier survival analyses and Cox regression models to investigate the influence of gender, age at onset, and onset symptoms on time to and age at Expanded Disability Status Scale (EDSS) 6.0 in patients with PPMS.
Results: Of 5,779 patients with definite MS, 552 (10%) had PPMS. Median time to EDSS 6.0 was 14.0 years (95% confidence interval [CI] 11.3–16.7), reached at a median age of 58.6 years (95% CI 56.8–60.3). Sensory onset symptoms were associated with a longer time to and an older age at EDSS 6.0 (multivariable hazard ratios 0.55 [95% CI 0.35–0.87] and 0.54 [0.35–0.85]). Younger age at disease onset was associated with a longer time to but a younger age at EDSS 6.0. Gender and other onset symptoms were not associated with these outcomes. Fifty patients with PPMS (9%) fulfilled criteria for benign MS (EDSS ≤3.0 after 10 years' disease duration).
Conclusions: We identified 2 predictors of a slower disease progression in primary progressive multiple sclerosis. Sensory onset symptoms were associated with both a longer time to and a higher age at Expanded Disability Status Scale (EDSS) 6.0. A younger age at disease onset was associated with a longer time to EDSS 6.0, but patients with an early disease onset reached EDSS 6.0 at a younger age.
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REFERENCES
1.
Miller DH, Leary SM. Primary-progressive multiple sclerosis. Lancet Neurol 2007;6:903–912.
2.
Runmarker B, Andersen O. Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 1993;116:117–134.
3.
Confavreux C, Vukusic S. Natural history of multiple sclerosis: a unifying concept. Brain 2006;129:606–616.
4.
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;122:625–639.
5.
Tremlett H, Paty D, Devonshire V. The natural history of primary progressive MS in British Columbia, Canada. Neurology 2005;65:1919–1923.
6.
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;254:1370–1375.
7.
Wolinsky JS, Narayana PA, O'Connor P, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 2007;61:14–24.
8.
Sweeney VP, Sadovnick AD, Brandejs V. Prevalence of multiple sclerosis in British Columbia. Can J Neurol Sci 1986;13:47–51.
9.
Sadovnick AD, Ebers GC, Wilson RW, Paty DW. Life expectancy in patients attending multiple sclerosis clinics. Neurology 1992;42:991–994.
10.
Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227–231.
11.
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;46:907–911.
12.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444–1452.
13.
Kurtzke JF. A new scale for evaluating disability in multiple sclerosis. Neurology 1955;5:580–583.
14.
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;122:1941–1950.
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Published online: December 7, 2009
Published in print: December 8, 2009
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