title: Magnetic resonance imaging predictors of conversion to multiple sclerosis in the BENEFIT study.
abstract: BACKGROUND
  Several studies have confirmed the predictive value of baseline and follow-up magnetic resonance (MR) imaging variables for conversion to clinically definite multiple sclerosis (CDMS), depending on the population, follow-up duration, and treatment intervention. However, the timing of follow-up imaging and the effect of treatment intervention on the predictive value of baseline MR imaging variables require further elucidation.
  
  
  OBJECTIVE
  To assess the prognostic value of baseline MR imaging variables for conversion to CDMS over 3 years and whether this was affected by treatment intervention and (2) to assess the increased risk for conversion posed by dissemination in time on follow-up MR imaging.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Multicenter randomized clinical trial.
  
  
  METHODS
  Four hundred sixty-eight patients with a clinically isolated syndrome who had an initial clinical demyelinating event within the past 60 days who received early treatment (3 years of interferon beta-1b) or delayed treatment (placebo first, followed by > or =1 year of interferon beta-1b). Intervention Magnetic resonance imaging. Main Outcome Measure Time to CDMS.
  
  
  RESULTS
  The overall conversion rate to CDMS was 42%. Barkhof criteria with the strongest prognostic value were the presence at baseline of at least 9 T2-weighted lesions (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.15-2.33; P = .006) and at least 3 periventricular lesions (1.66; 1.14-2.41; P = .009). No specific advantage was noted in using a fixed cutoff of at least 3 Barkhof criteria (HR, 1.31; 95% CI, 0.95-1.79; P = .10). The prognostic value of all MR imaging criteria was unaffected by treatment intervention (P > or = .20 for all). Dissemination in time resulted in increased risk for CDMS only in patients without dissemination in space at baseline and was most informative at the 9-month MR imaging (HR, 2.72; 95% CI, 1.26-5.87; P = .01).
  
  
  CONCLUSIONS
  The modified Barkhof criteria showed moderate predictive value for conversion to CDMS, although all patients had received interferon beta-1b therapy for at least 1 year. The predictive value was unaffected by treatment intervention. Follow-up MR imaging was most informative after 9 months in patients without dissemination in space at baseline.
authors.affiliation: Department of Diagnostic Radiology, Multiple Sclerosis Center Amsterdam, Vrije University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands. b.moraal@vumc.nl
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Moraal
authors.forename: Christoph
authors.initials: C
authors.lastname: Pohl
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Gilles
authors.initials: G
authors.lastname: Edan
authors.forename: Mark S
authors.initials: MS
authors.lastname: Freedman
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Vivian
authors.initials: V
authors.lastname: Lanius
authors.forename: Rupert
authors.initials: R
authors.lastname: Sandbrink
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D007091:Image Processing, Computer-Assisted; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy*; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000068576:Interferon beta-1b; D016899:Interferon-beta