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Clinical and Demographic Predictors of Long-term Disability in Patients With Relapsing-Remitting Multiple SclerosisA Systematic Review
Annette Langer-Gould, MS, MD;
Rita A. Popat, PhD;
Stella M. Huang, MS;
Kristin Cobb, PhD;
Paulo Fontoura, MD;
Michael K. Gould, MS, MD;
Lorene M. Nelson, PhD
Arch Neurol. 2006;63:1686-1691.
Objective To identify clinical and demographic factors associated with long-term disability in patients with relapsing-remitting multiple sclerosis.
Data Sources We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO computerized databases, and reviewed reference lists of retrieved articles.
Study Selection We included studies that examined predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. We excluded studies that did not distinguish relapsing-remitting multiple sclerosis from primary progressive multiple sclerosis, enrolled fewer than 40 subjects, observed subjects for less than 5 years, or collected follow-up information in less than 80% of the inception cohort.
Data Extraction Two reviewers assessed study quality in 4 domains: cohort assembly, definitions and assessments of prognostic factors and outcomes, and statistical methods. One reviewer extracted data on the direction, magnitude, precision, and statistical significance of the effect of each predictor on prognosis.
Data Synthesis Heterogeneity of study designs precluded us from pooling the results of 27 eligible studies. Study quality was limited by cross-sectional design, enrollment of prevalent cases from referral centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3-3.3), and a short interval between the first and second attack (hazard ratio, 1.6-1.9) were most strongly and consistently associated with poor prognosis. Other factors widely believed to be of prognostic importance, including sex and age at onset, demonstrated inconsistent or weak effects on prognosis.
Conclusions The most robust predictors of long-term physical disability in relapsing-remitting multiple sclerosis are sphincter symptoms at onset and early disease course outcomes. These factors can be used to guide treatment decisions for drugs with significant toxicities.
Author Affiliations: Department of Health Research and Policy, Stanford University School of Medicine (Drs Langer-Gould, Popat, Cobb, Gould, and Nelson and Ms Huang), and Department of Neurology, Stanford University (Dr Langer-Gould), Stanford, Calif; Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal (Dr Fontoura); and VA Palo Alto Health Care System, Palo Alto, Calif (Dr Gould). Ms Huang is now with Touro University College of Osteopathic Medicine, Vallejo, Calif.
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