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Robert A. Bermel, MD; Srinivas R. Puli, MD; Richard A. Rudick, MD; Bianca Weinstock-Guttman, MD; Elizabeth Fisher, PhD; Frederick E. Munschauer III, MD; Rohit Bakshi, MD

Arch Neurol. 2005;62:1371-1376.

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.

Author Affiliations: Buffalo Neuroimaging Analysis Center (Drs Bermel, Puli, Munschauer, and Bakshi), The Jacobs Neurological Institute (Drs Bermel, Puli, Weinstock-Guttman, Munschauer, and Bakshi), and Department of Neurology (Drs Bermel, Weinstock-Guttman, Munschauer, and Bakshi), School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo; The Mellen Center for Multiple Sclerosis Treatment and Research (Dr Rudick) and Department of Biomedical Engineering (Dr Fisher), Cleveland Clinic Foundation, Cleveland, Ohio; and Physicians Imaging Centers, Buffalo (Drs Munschauer and Bakshi). Dr Bakshi is currently with the Center for Neurological Imaging, Partners Multiple Sclerosis Center, and Departments of Neurology and Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

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