title: The effect of disease-modifying therapies on brain atrophy in patients with clinically isolated syndrome: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Brain atrophy is associated with cognitive deficits in patients with clinically isolated syndrome (CIS) and can predict conversion to clinical definite multiple sclerosis. The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMDs) on brain atrophy in patients with CIS.
  
  
  METHODS
  Eligible placebo-control randomized clinical trials of patients with CIS that had reported changes in brain volume during the study period were identified by searching the MEDLINE, SCOPUS, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. This meta-analysis adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses.
  
  
  RESULTS
  Three eligible studies were identified, comprising 1362 patients. The mean percentage change in brain volume was found to be significantly lower in DMD-treated patients versus placebo-treated subgroups (standardized mean difference [SMD]: = -0.13, 95% confidence interval [CI]: -0.25, 0.01; p = 0.04). In the subgroup analysis of the two studies that provided data on brain-volume changes for the first (0-12 months) and second (13-24 months) year of treatment, DMD attenuated brain-volume loss in comparison with placebo during the second year (SMD = -0.25; 95% CI: -0.43, -0.07; p < 0.001), but not during the first year of treatment (SMD = -0.01; 95% CI: -0.27, 0.24; p = 0.93). No evidence of heterogeneity was found between estimates, while funnel-plot inspection revealed no evidence of publication bias.
  
  
  CONCLUSIONS
  DMDs appear to attenuate brain atrophy over time in patients with CIS. The effect of DMDs on brain-volume loss is evident after the first year of treatment.
authors.affiliation: Second Department of Neurology, School of Medicine, University of Athens, Iras 39, Gerakas Attikis, Athens, 15344, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsivgoulis
authors.affiliation: Second Department of Neurology, 'Attikon' Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Aristeidis H
authors.initials: AH
authors.lastname: Katsanos
authors.affiliation: Second Department of Neurology, 'AHEPA' University Hospital, Aristotelion University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
authors.affiliation: Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece.
authors.forename: Georgios M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.affiliation: Department of Neurology, Alexandroupolis University Hospital, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Heliopoulos
authors.affiliation: Department of Neurology, University of Patras Medical School, Patras, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papathanasopoulos
authors.affiliation: Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece.
authors.forename: Efthimios
authors.initials: E
authors.lastname: Dardiotis
authors.affiliation: First Department of Neurology, 'Eginition' Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Kilidireas
authors.affiliation: Second Department of Neurology, 'Attikon' Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voumvourakis
keywords: brain atrophy; brain volume; clinically isolated syndrome; disease modifying therapy