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MRI lesion activity in relapsing-remitting patients with multiple sclerosis

University of British Columbia

Multiple sclerosis (MS) is a disease of the central nervous system seen mainly in young adults in which demyelination is the most specific pathological change. Magnetic resonance imaging (MRI) is the most sensitive method for imaging MS lesions. Serial MRI can detect brain lesion activity in MS and provide an important tool for monitoring therapeutic trials. Fifty relapsing-remitting MS patients, as part of a beta-interferon trial, were examined every 6 weeks with MRI for a 2 year period in this study. The patients were randomized into three treatment arms: placebo (N=17), 1.6 mlU (N=17), and 8 mlU (N=16) beta-interferon self-administered subcutaneously every other day. Activity of MS lesions on MRI was defined as new (first appearance), enlarging (increase in size of preexisting lesion), recurrent (reappearance of lesions that had disappeared), and enhancing (lesion enhancement on Tl weighted MRI scan after a contrast agent, gadolinium, injection). Lesion activity as detected in serial MRI examination is much more common than the clinical relapse rate. Study of lesion activity is helpful in understanding MS. This thesis includes serial studies of lesion activity on MRI. The studies are (1) to detect the activity of the individual lesion in order to see if there was any characteristics that distinguished active lesions from each other and from stable ones; (2) to identify the features of enhancing and non-enhancing lesions in shape, size, and location to learn the difference between morphologically active and gadolinium enhancing lesions due to their pathological difference; (3) to describe the growth pattern of enlarging MS lesions as we believe that enlarging lesions differ pathologically from new ones; (4) to compare the sensitivity of gadolinium MRI with unenhanced serial MRI in detecting activity of lesions to see which one is the more sensitive technique for detecting active lesions. The findings from the studies disclose features of MS active lesions that provide more information in understanding the natural history of MS. To determine how much MS lesion activity information, as detected with frequent serial MRI, is lost if a less frequent scan interval is used, a study of effects of scanning frequency was carried out. Lesion activity was assessed in a blinded fashion at scan intervals of 6 weeks, 3 months, 6 months, and 1 year. We found that scanning in less than 6 week intervals detects fewer active MS lesions. Active lesions located in the corticospinal tract were studied to see any relationship between MRI activity and clinical course. The study found that there was a positive relationship between active lesions in the corticospinal tract and clinical relapses. To monitor lesion activity as an outcome to measure therapeutic trials, a study of 50 Vancouver patients was conducted. The result provides further evidence that lesion activity measurement is a useful and sensitive tool in a therapeutic trial even with small group of patients.

Thesis/Dissertation

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2009-02-12

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http://hdl.handle.net/2429/4512

Experimental Medicine

University of British Columbia

UBCV

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