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

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 μg/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 (R²=0.23; P=.002) and 2-year (R²=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.