title: Volumetric MRI markers and predictors of disease activity in early multiple sclerosis: a longitudinal cohort study.
abstract: OBJECTIVE
  To compare clinical and MRI parameters between patients with clinically isolated syndrome and those converting to clinically definite multiple sclerosis within 2 years, to identify volumetric MRI predictors of this conversion and to assess effect of early relapses.
  
  
  METHODS
  The SET study comprised 220 patients with clinically isolated syndrome treated with interferon beta (mean age, 29 years; Expanded Disability Status Scale, 1.5). Three patients with missing data were excluded from the analysis. Physical disability, time to clinically definite multiple sclerosis and volumetric MRI data were recorded for 2 years.
  
  
  RESULTS
  Patients reaching clinically definite multiple sclerosis showed impaired recovery of neurological function, faster decrease in corpus callosum cross-sectional area, higher T2 lesion volume and more contrast-enhancing lesions. Six-month decrease in corpus callosum cross-sectional area (≥ 1%) and baseline T2 lesion volume (≥ 5 cm(3)) predicted clinically definite multiple sclerosis within 2 years (hazard ratios 2.5 and 1.8, respectively). Of 22 patients fulfilling both predictive criteria, 83% reached clinically definite multiple sclerosis (hazard ratio 6.5). More relapses were associated with poorer recovery of neurological function and accelerated brain atrophy.
  
  
  CONCLUSIONS
  Neurological impairment is more permanent, brain atrophy is accelerated and focal inflammatory activity is greater in patients converting to clinically definite multiple sclerosis. Six-month corpus callosum atrophy and baseline T2 lesion volume jointly help predict individual risk of clinically definite multiple sclerosis. Early relapses contribute to permanent damage of the central nervous system.
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. tomas.kalincik@unimelb.edu.au
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.forename: Manuela
authors.initials: M
authors.lastname: Vaneckova
authors.forename: Michaela
authors.initials: M
authors.lastname: Tyblova
authors.forename: Jan
authors.initials: J
authors.lastname: Krasensky
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Seidl
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003337:Corpus Callosum / Q000473:pathology; D018153:Czech Republic; D003711:Demyelinating Diseases / Q000175:diagnosis* / Q000188:drug therapy; D018450:Disease Progression; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000473:pathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012008:Recurrence
chemical_list: D016899:Interferon-beta