Large, nonplateauing relationship between clinical disability and cerebral white matter lesion load in patients with multiple sclerosis.

OBJECTIVE To better characterize the relationship between cerebral white matter lesion load (CWM-LL) and clinical disability by (1) covering the entire range of the Kurtzke Expanded Disability Status Scale (EDSS), (2) minimizing nonbiological sources of variability, and (3) increasing pathologic specificity by studying CWM lesions that are hypointense on T1-weighted magnetic resonance imaging. DESIGN Cross-sectional, retrospective study. SETTING Hospital-based multiple sclerosis (MS) clinic. Patients  A total of 110 patients with untreated MS were recruited and studied from June 1, 1997, through June 30, 2003. MAIN OUTCOME MEASURES Cube-rooted CWM-LL and EDSS-measured clinical disability scores. RESULTS We found a large, nonplateauing relationship between cube-rooted CWM-LL and concurrent EDSS scores, more so for T1-hypointense than T2-hyperintense lesions (r = 0.619 vs 0.548). Correlations between the EDSS scores and CWM-LL diminished when, as typically done in clinical trials, only those patients with EDSS scores of 0 to 6.0 were studied (n = 92; r = 0.523 for T1-hypointense lesions and r = 0.457 for T2-hyperintense lesions); more important, a series of boot-strapped correlations suggested that this decrease was not simply due to smaller sample size, and these relationships remained even after correcting for disease duration. CONCLUSION A large, nonplateauing relationship exists between CWM-LL and EDSS-measured clinical disability when patients with MS are studied to examine the entire range of disability, minimize nonbiological sources of variability, and increase pathologic specificity.