Survey of the distribution of lesion size in multiple sclerosis: implication for the measurement of total lesion load.

OBJECTIVES Quantitative measurement of lesion load on proton density or T2 weighted brain MRI in multiple sclerosis is a widely used marker of disease progression in treatment trials and natural history studies. However, it has proved difficult to obtain highly reproducible measurements. Several factors account for this, one of which is uncertainties in lesion identification, particularly very small white matter abnormalities. This paper aims to ascertain the significance of very small white matter abnormalities in the measurement of lesion load in multiple sclerosis. METHODS All visible lesion areas identified by an experienced observer on proton density weighted spin echo brain MRI with 5 mm thick slices were measured by using a contouring technique in 15 patients with secondary progressive multiple sclerosis (SPMS) and 13 with relapsing remitting multiple sclerosis (RRMS). The size distribution of these lesions was analysed. RESULTS 80% of the number of the lesions were smaller than 80 mm2. Lesions that were smaller than 10 mm2 (equivalent diameter <3.5 mm) made up nearly 20% of all lesions; their relative contribution to the total lesion load varied from 0.0-5.7% (mean=1.1%, median=0.65%) in individual patients, and was larger when the total lesion load was smaller (r = -0.65, P<0.001). Median lesion size was significantly smaller in the SPMS group than the RRMS group. CONCLUSIONS The results suggest that it is prudent to identify and measure small lesions in evaluating treatment effects, and that measures are undertaken (for example, using thinner slices such as 3 mm) to improve their detection.