title: Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity.
abstract: BACKGROUND
  Gray matter magnetic resonance imaging T2 hypointensity, a marker of iron deposition, is associated with clinical impairment and brain atrophy in cross-sectional studies of multiple sclerosis. Treatment with intramuscular interferon beta-1a limits brain atrophy in the second year of treatment.
  
  
  OBJECTIVE
  To test whether T2 hypointensity predicts brain atrophy and whether interferon affects this relationship.
  
  
  METHODS
  Post hoc analysis.
  
  
  METHODS
  A multicenter treatment trial conducted at tertiary care comprehensive multiple sclerosis centers. Patients Patients with multiple sclerosis who took part in a 2-year clinical trial in which they received intramuscular interferon beta-1a (30 mug/wk) or placebo.
  
  
  METHODS
  Deep gray matter T2 hypointensity, brain parenchymal fraction (BPF), and total T2, gadolinium-enhancing, and T1 lesion volumes.
  
  
  RESULTS
  T2 hypointensity in various gray matter areas correlated with baseline BPF (r = 0.19-0.39; P = .001-.03). In placebo-treated patients (n = 68), baseline T2 hypointensity predicted the change in BPF in the first year and throughout 2 years (r = 0.26-0.42; P<.001-.03). T2 hypointensity was chosen in regression modeling as the best predictor of BPF change at the 1-year (R(2) = 0.23; P = .002) and 2-year (R(2) = 0.33; P<.001) time points after accounting for all magnetic resonance imaging variables. In the interferon group (n = 65), no relationship existed between baseline T2 hypointensity and BPF change.
  
  
  CONCLUSIONS
  Gray matter T2 hypointensity predicts the progression of brain atrophy in placebo- but not interferon beta-1a-treated patients. This predictive effect is seen as early as the first year. We hypothesize that interferon beta may exert its effect on brain atrophy in part by reducing a cascade of events that involve iron deposition as a mediator of neurotoxicity or as a disease epiphenomenon.
authors.affiliation: Buffalo Neuroimaging Analysis Center, University at Buffalo, State University of New York, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bermel
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Puli
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fisher
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Munschauer
authors.forename: Rohit
authors.initials: R
authors.lastname: Bakshi
mesh_terms: D000328:Adult; D001927:Brain Diseases / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D005260:Female; D005682:Gadolinium; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D011237:Predictive Value of Tests
chemical_list: D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a