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From the Departments of Diagnostic Radiology (Drs. van Walderveen, Barkhof, and Valk) and Neurology (Drs. van Walderveen and Polman), Free University Hospital, Amsterdam; the Department of Epidemiology and Biostatistics (H. Tobi), Free University, Amsterdam; and the Institute of Neurology (Drs. Hommes and Frequin), Nijmegen, The Netherlands.
Received August 8, 1994. Accepted in final form February 3, 1995.
Address correspondence and reprint requests to Dr. Frederik Barkhof, Department of Diagnostic Radiology, Free University Hospital, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
Magnetic resonance imaging (MRI) is being used as an outcome criterion in therapeutic trials in multiple sclerosis (MS) on the assumption that it, as a sensitive marker of biologic disease activity, could serve as a surrogate marker of disability.We evaluated the relation between MRI findings and disability in a quantitative follow-up study of 48 MS patients. Median duration of follow-up was 24 months (range, 10 to 42 months). Computer-assisted volume measurements employing a seed-growing technique yielded a standard error of measurement of 0.275 cm2. The median total area of the hyperintense lesions on the initial T2-weighted images was 8.4 cm2. The median increase was 0.76 cm2/yr (9%). In a subgroup (n equals 19) with short-TR/short-TE spin-echo (SE) images, we measured the hypointense lesion load. The median total area of the lesions at entry was 0.70 cm2, with a median increase of 0.28 cm2/yr (40%). The total area of the hyperintense lesions on the initial T2-weighted images showed a weak correlation with the Expanded Disability Status Scale score at entry (Spearman rank correlation coefficient [SRCC] equals 0.30; 0.02 less than p less than 0.05). The increase in disability showed a positive correlation (SRCC equals 0.19) with the increase in hyperintense lesion load on the T2-weighted SE images, but this correlation did not reach statistical significance (p equals 0.09), probably because of lack of clinical progression. The number of active lesions detected by visual analysis of the T2-weighted SE images correlated significantly (SRCC equals 0.40; 0.001 less than p less than 0.01) with the number of relapses during the interval between the initial and follow-up imaging examinations. The subgroup with short-TR/short-TE SE images (whose disease was clinically more active than the group as a whole) showed a significant correlation of increased disability with increase in hypointense lesion load (SRCC equals 0.74; p less than 0.002). Our results, and those from previous follow-up studies, suggest a positive correlation between MRI and clinical activity, but extended follow-up studies are needed to confirm the appropriateness of quantitative MRI as a surrogate marker of disability in MS. Short-TR/short-TE SE images seem to be more relevant than T2-weighted SE images in identifying the lesions that cause disability.
NEUROLOGY 1995;45: 1684-1690
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