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NEUROLOGY 2005;65:1071-1076
© 2005 American Academy of Neurology

MRI as a marker for disease heterogeneity in multiple sclerosis

B. Bielekova, MD, N. Kadom, MD, E. Fisher, PhD, N. Jeffries, PhD, J. Ohayon, CRNP, N. Richert, MD, T. Howard, C. N. Bash, MD, J. A. Frank, MD, L. Stone, MD, R. Martin, MD, G. Cutter, PhD and H. F. McFarland, MD

From the Neuroimmunology Branch (Drs. Bielekova, Kadom, Ohayon, Richert, Howard, Martin, and McFarland) and Statistic Branch (Dr. Jeffries), National Institute of Neurological Disorders and Stroke, and Experimental Neuroimaging Section (Drs. Bash and Frank), Clinical Center, NIH, and Uniformed Services University of the Health Sciences (Drs. Bash), Bethesda, MD, Department of Biomedical Engineering (Dr. Fisher) and Mellen Center for Multiple Sclerosis Treatment and Research (Dr. Stone), Department of Neurology, Cleveland Clinic Foundation, OH, and Department of Biostatistics (Dr. Cutter), Birmingham, AL.

Address correspondence and reprint requests to Dr. B. Bielekova, Neuroimmunology Branch, NINDS, NIH, 10 Center Drive, Building 10, Room 5B-16, MSC 1400, Bethesda, MD 20892-1400; e-mail: bielekob{at}ninds.nih.gov

Background: Whereas recent data from imaging studies challenge the prevailing notion that multiple sclerosis (MS) is purely an inflammatory disease, pathologic studies suggest differences in the disease processes between individual patients with MS. The ability to dissect the pathophysiologic disease heterogeneity, if it indeed exists, by methodologies that can be applied in vivo is important both for the development of new therapeutics and for the ability to identify the optimal therapy for an individual patient.

Objective: To design a stratification algorithm for patients with MS based on accepted MRI measurements reflective of inflammation and axonal damage/tissue loss and to assess if such MS subgroups retain their intergroup differences long term.

Methods: Mathematical modeling was used to select three discriminatory MRI measures for clinical outcome based on the cross-sectional analysis of 71 patients with untreated MS and tested general applicability of the stratification scheme on the independent longitudinal cohort of 71 MS patients.

Results: By consecutive employment of MRI measures reflective of inflammation and tissue loss, the authors were able to separate MS patients into four clinically meaningful subgroups. The analysis of the longitudinal confirmatory cohort demonstrated persistence of the intergroup differences in selected MRI measures for 8 years.

Conclusions: The inflammatory activity and destructiveness of the multiple sclerosis process are to some degree independent of each other, and the successive evaluation of both of these variables can strengthen prediction of clinical outcome in individual patients.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the October 11 issue to find the title link for this article.

This research was supported by the Intramural Research Program of the NIH, NINDS.

The collection and analysis of the follow-up clinical and MRI data on the longitudinal confirmatory cohort were obtained as part of a separate project funded by the NMSS (grant RG3223A2/1 awarded to L.S.), in which the following authors were co-investigators: Lael Stone, MD, Henry McFarland, MD, Elizabeth Fisher, PhD, Nancy Richert, MD, and Joe A. Frank, MD.

Disclosure: The authors report no conflicts of interest.

Received March 3, 2005. Accepted in final form June 15, 2005.




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