title: Thalamic atrophy is associated with development of clinically definite multiple sclerosis.
abstract: OBJECTIVE
  To investigate the association between the development of thalamic and cortical atrophy and the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS).
  
  
  METHODS
  This prospective study was approved by the institutional review board. Informed consent was given by 216 CIS patients, and patients were treated with 30 µg of intramuscular interferon β1a once a week. They were assessed with a magnetic resonance (MR) imaging examination at baseline, 6 months, 1 year, and 2 years. Patients were evaluated within 4 months of an initial demyelinating event, had two or more brain lesions on MR images, and had two or more oligoclonal bands in cerebrospinal fluid. MR imaging measures of progression included cumulative number and volume of contrast agent-enhanced (CE) new and enlarged T2 lesions, and changes in whole-brain, tissue-specific global, and regional gray matter volumes. Regression and mixed-effect model analyses were used.
  
  
  RESULTS
  Over 2 years, 92 of 216 patients (42.6%) converted to CDMS; 122 (56.5%) CIS patients fulfilled McDonald 2005 criteria and 153 (70.8%) fulfilled McDonald 2010 criteria for MR imaging dissemination in time and space. The mean time to first relapse was 3.1 months, and mean annual relapse rate was 0.46. In mixed-effect model analysis, the lateral ventricle volume (P = .005), accumulation of CE (P = .007), new total T2 (P = .009) and new enlarging T2 lesions (P = .01) increase, and thalamic (P = .009) and whole-brain (P = .019) volume decrease were associated with development of CDMS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes (P = .009) were MR imaging variables associated with the development of CDMS.
  
  
  CONCLUSIONS
  Measurement of thalamic atrophy and increase in ventricular size in CIS is associated with CDMS development and should be used in addition to the assessment of new T2 and CE lesions.
authors.affiliation: Department of Neurology, SUNY, Buffalo Neuroimaging Analysis Center, University at Buffalo, 100 High St, Buffalo, NY 14203, USA. rzivadinov@bnac.net
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdová
authors.forename: Niels
authors.initials: N
authors.lastname: Bergsland
authors.forename: Michaela
authors.initials: M
authors.lastname: Tyblova
authors.forename: Jesper
authors.initials: J
authors.lastname: Hagemeier
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Seidl
authors.forename: Michael G
authors.initials: MG
authors.lastname: Dwyer
authors.forename: Manuela
authors.initials: M
authors.lastname: Vaneckova
authors.forename: Jan
authors.initials: J
authors.lastname: Krasensky
authors.forename: Ellen
authors.initials: E
authors.lastname: Carl
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.forename: Dana
authors.initials: D
authors.lastname: Horáková
mesh_terms: D000293:Adolescent; D000328:Adult; D001284:Atrophy / Q000453:epidemiology / Q000473:pathology; D015984:Causality; D015897:Comorbidity; D018153:Czech Republic / Q000453:epidemiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000473:pathology*; D015995:Prevalence; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013788:Thalamus / Q000473:pathology*