title: Predictors of disability worsening in clinically isolated syndrome.
abstract: OBJECTIVE
  To assess demographic, clinical, magnetic resonance imaging, and treatment exposure predictors of time to 3 or 12-month confirmed disability worsening in clinically isolated syndrome (CIS) and early multiple sclerosis (MS).
  
  
  METHODS
  We utilized the MSBase Incident Study (MSBasis), a prospective cohort study of outcome after CIS. Predictors of time to first 3 and 12-month confirmed expanded disability status scale worsening were analyzed using Cox proportional hazards regression.
  
  
  RESULTS
  About 1989 patients were analyzed, the largest seen-from-onset cohort reported to-date. A total of 391 patients had a first 3-month confirmed disability worsening event, of which 307 were sustained for 12 months. Older age at CIS onset (adjusted hazard ratio: aHR 1.17, 95% 1.06, 1.30), pyramidal (aHR 1.45, 95% CI 1.13, 1.89) and ambulation (HR 1.60, 95% CI 1.09, 2.34) system dysfunction, annualized relapse rate (aHR 1.20, 95% CI 1.18, 1.22), and lower proportion of observation time on treatment were associated with 3-month confirmed worsening. Predictors of time to 12-month sustained worsening included pyramidal system dysfunction (Hazard ratio: aHR 1.38, 95% CI 1.05, 1.83), and older age at CIS onset (aHR 1.17, 95% CI 1.04, 1.31). Greater proportion of follow-up time exposed to treatment was associated with greater reductions in the rate of worsening.
  
  
  CONCLUSIONS
  This study provides class IV evidence for a strong protective effect of disease-modifying treatment to reduce disability worsening events in patients with CIS and early MS, and confirms age and pyramidal dysfunction at onset as risk factors.
authors.affiliation: Department of Medicine (RMH), The University of Melbourne Parkville, Australia.
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authors.initials: VG
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authors.affiliation: Department of Neurology, Royal Melbourne Hospital Parkville, Australia.
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authors.affiliation: Department of Medicine (RMH), The University of Melbourne Parkville, Australia.
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authors.forename: Cavit
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authors.affiliation: Ospedale di Macerata Macerata, Italy.
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authors.affiliation: Amiri Hospital Kuwait City, Kuwait.
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authors.affiliation: Flinders University and Medical Centre Adelaide, Australia.
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authors.affiliation: Department of Neurology University of Florence Florence, Italy.
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authors.affiliation: Melbourne EpiCentre, University of Melbourne and Melbourne Health Melbourne, Australia.
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authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Bari, Italy.
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authors.lastname: Paolicelli
authors.affiliation: Department of Medicine (RMH), The University of Melbourne Parkville, Australia ; Department of Neurology, Royal Melbourne Hospital Parkville, Australia.
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authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Bari, Italy.
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