Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity

Arch Neurol. 2005 Sep;62(9):1371-6. doi: 10.1001/archneur.62.9.1371.


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.

Design: Post hoc analysis.

Setting: 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.

Main outcome measures: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Brain Diseases / drug therapy
  • Brain Diseases / etiology*
  • Brain Diseases / pathology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Disability Evaluation
  • Female
  • Gadolinium
  • Humans
  • Image Enhancement / methods
  • Image Processing, Computer-Assisted / methods
  • Interferon beta-1a
  • Interferon-beta / therapeutic use
  • Magnetic Resonance Imaging / methods*
  • Male
  • Multiple Sclerosis / complications*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology*
  • Predictive Value of Tests


  • Interferon-beta
  • Gadolinium
  • Interferon beta-1a