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The outcome spectrum of multiple sclerosis: disability, mortality, and a cluster of predictors from onset

Journal article
Authors Helen Tedeholm
Bengt Skoog
Vera Lisovskaja
Björn Runmarker
Olle Nerman
Oluf Andersen
Published in Journal of Neurology
Volume 262
Issue 5
Pages 1148-1163
ISSN 0340-5354
Publication year 2015
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Department of Mathematical Sciences, Mathematical Statistics
Pages 1148-1163
Language en
Keywords Multiple sclerosis, Natural history, Prediction, Prognosis, Gender, Age
Subject categories Neurosciences


Interest in the long-term natural history of multiple sclerosis (MS) is being revived, as disability endpoints become increasingly important with the advent of highly efficacious long range but potentially harmful drugs. MS had an increasingly benign course, probably due to better assessment and changing diagnostic criteria. Incidence cohorts reduce inclusion bias, capturing both extreme benign and severe cases. We conducted a 50-year follow-up of an incidence cohort of Gothenburg residents with MS onset in 1950-1964 (n = 254; 212 with an initial relapsing-remitting course and 42 with a monophasic course, diagnostic criteria according to Poser). Patients were followed longitudinally until censoring, death, or study termination in 2012 and evaluated using Kaplan-Meier estimates and Cox regression analysis. Median time to secondary progression was 15 years. Median time to EDSS6 and EDSS7 was 26 and 48 years (n = 254), respectively. The cumulative risk of reaching EDSS6 was 50 % at 55 years of age and 80 % at 80 years of age (n = 212). A score based on a cluster of clinical features at onset predicted secondary progression, EDSS6, EDSS7, and EDSS10 (hazard ratio 1.6-2.3 per score unit for women, 0.99-1.49 for men). This score predicted the disease course during five decades indirectly, by predicting time to secondary progression. Age at onset predicted the course in men, with 3-6 % yearly increase in the risk of reaching disability milestones. The present incidence cohort provided hard outcome data in untreated patients over several decades.

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