Eight-year follow-up study of brain atrophy in patients with MS

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Eight-year follow-up study of brain atrophy in patients with MS
E. Fisher, PhD, R. A. Rudick, MD, J. H. Simon, MD PhD, G. Cutter, PhD, M. Baier, MS, J. -C. Lee, MS, D. Miller, PhD, B. Weinstock-Guttman, MD, M. K. Mass, MD, D. S. Dougherty, MD and N. A. Simonian, MD
From the Whitaker Biomedical Imaging Laboratory (Dr. Fisher), Department of Biomedical Engineering, Mellen Center for Multiple Sclerosis Treatment and Research (Drs. Rudick and Miller), and Department of Biostatistics and Epidemiology (Dr. Lee), The Cleveland Clinic Foundation, OH; Department of Radiology (Dr. Simon), University of Colorado Health Sciences Center, Denver; University of Nevada (Dr. Cutter), Reno; Center for Research Methodology and Biometrics (Dr. Baier), AMC Cancer Research Center, Denver, CO; Department of Neurology (Dr. Weinstock-Guttman), Buffalo General Hospital, NY; Department of Neurology (Dr. Mass), Oregon Health Sciences University, Portland; Department of Neurology (Dougherty), Thomas Jefferson University, Philadelphia, PA; and Millennium Pharmaceuticals, Inc. (Dr. Simonian), Cambridge, MA.

Address correspondence and reprint requests to Dr. Elizabeth Fisher, Department of Biomedical Engineering, ND20, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: fisher@bme.ri.ccf.org

Objective: To characterize whole-brain atrophy in relapsing-remitting MS (RRMS) patients over an 8-year period. The specific goals of this study were to determine if brain atrophy is related to subsequent disability status and to identify MRI correlates of atrophy progression.

Methods: A follow-up study was conducted to reassess patients from a phase III trial of interferon ß-1a (IFNß-1a) 8 years after randomization. Clinical and MRI data from 172 patients followed over 2 years in the original trial were used as baseline data. Follow-up data were obtained on 160 patients, including 134 patients with follow-up MRI examinations. Brain atrophy was estimated by automated calculation of brain parenchymal fraction. The relation between atrophy during the original trial and disability status at follow-up was determined. Correlations were also determined between lesion measurements from the original trial and the brain parenchymal fraction at follow-up.

Results: Brain atrophy was correlated with subsequent disability status. Atrophy rate during the original trial was the most significant MRI predictor of disability status at follow-up. Brain atrophy at follow-up was related to lesion volumes measured during the original trial.

Conclusions: The relation between atrophy progression and subsequent neurologic disability status suggests that atrophy progression during RRMS is clinically relevant. Therefore, atrophy progression may be a useful marker for disease progression in clinical trials. The relation between lesions and subsequent atrophy indicates that brain atrophy may be related to focal tissue damage at earlier points in time, but important predisposing or other factors contributing to atrophy remain undefined.