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Changes in the amount of diseased white matter over time in patients with relapsing-remitting multiple sclerosis

From the Neuroimmunology Branch (Drs. Stone, Smith, McFarlin, and McFarland), the Biometry and Field Studies Branch (Dr. Albert), and the Epilepsy Research Branch (Dr. DeCarli), NINDS, NIH, Bethesda, MD; the Laboratory of Diagnostic Radiology Research Program (Dr. Frank), OD, NIH; and the Department of Radiology (Dr. Armstrong), Cornell University Medical Center, New York, NY.
Received May 20, 1994. Accepted in final form February 21, 1995.
Address correspondence and reprint requests to Dr. Lael A. Stone, Neuroimmunology Branch, NINDS, Building 10, Room 5B16, NIH, 9000 Rockville Pike, Bethesda, MD 20892.

MRI is a sensitive technique for assessing disease activity in MS.Diseased white matter (WM) can be identified on T_2-weighted images, and active disease is reflected by abnormalities in the blood-brain barrier (BBB) shown on T_1-weighted images after administration of paramagnetic contrast agents. Active disease may be demonstrated by contrast-enhanced MRI in patients with early, mild relapsing-remitting (RR) MS even during periods of clinical stability, which indicates that MS is an active process even during the early phase of the illness. To examine the amount of abnormal WM at frequent intervals over time, we studied seven mildly affected RRMS patients, all of whom had frequent contrast-enhancing lesions. These RRMS patients were imaged monthly for 26 to 36 months at 1.5 tesla; the area of abnormal increased WM signal was calculated by image-processing software that utilizes both the T_2- and T_1-weighted images. All patients showed fluctuations over time in amount of abnormal WM signal, which reflected factors such as the amount of BBB breakdown (measured by number or area of enhancing lesions) and measurement error. All seven RRMS patients, however, showed an overall increase in abnormal WM. Because of the fluctuations between individual measurements, the increase was most accurately reflected when the mean of the first 6 months' measurements was compared with the mean of the final 6 months' measurements, or when a linear regression model was applied. Although the accumulation of abnormal WM provides an additional tool for assessing disease activity in MS, its usefulness may be increased by the measurements obtained with additional techniques that are currently available or as yet undeveloped.

NEUROLOGY 1995;45: 1808-1814

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