Improved correlation between scores on the expanded disability status scale and cerebral lesion load in relapsing-remitting multiple sclerosis. Results of the application of new imaging methods

Abstract

We hypothesized that a better correlation between MRI and clinical measures of neurological disability using the expanded disability status scale (EDSS) in multiple sclerosis could be obtained by assessing lesion load only in and around the corticospinal tracts, since the EDSS is weighted towards motor and ambulatory deficits. Multiple sclerosis lesions in cerebral MRIs from 39 patients with relapsing-remitting multiple sclerosis were manually painted using a three-dimensional computer display tool and mapped into a standardized three-dimensional coordinate space. Total lesion load was then measured. A mask to expose only the corticospinal tract was extracted from an MRI atlas and used to measure lesion load in the corticospinal tract. To account for the residual anatomical variability among the different MRI volumes after stereotaxic transformation, the corticospinal tract mask was dilated to various degrees and the lesion load remeasured. Spearman's rank correlation coefficient was used to calculate the correlation between the EDSS and total lesion load and corticospinal tract lesion load and between the EDSS subscores and total lesion load and corticospinal tract lesion load. Spearman's rank correlation coefficient between the EDSS and total lesion load was 0.6, probably reflecting the rather broad EDSS range represented in the study. The highest correlation of 0.67 was between the EDSS and corticospinal tract lesion load, dilated with a blurring kernel of 8-10 mm. The pyramidal subscore alone showed a weaker correlation with total lesion load, and with corticospinal tract lesion load, than did the overall EDSS, possibly reflecting the narrow range of disability in these subscores in patients with EDSS scores of 1-6.5. The imperfect correlation between the EDSS and corticospinal tract lesion load suggests that factors other than cerebral T2-weighted lesion volume are important determinants of disability.

‘Importance sampling’ in MS: Use of diffusion tensor tractography to quantify pathology related to specific impairment

“…The lack of correlation between pyramidal tract T 2 lesion load and pyramidal FSS has been observed previously [14] and may reflect the fact that the T 2 measure lacks specificity and takes no account of the subtle pathology known to occur in the NAWM that contributes to disability [3]. However, in a previous study [40], which used a standard brain atlas to identify the pyramidal tracts, EDSS was found to correlate with the T 2 lesion volume in the pyramidal tracts, although only marginally better than with the global T 2 lesion volume.…”

T 1 relaxation time mapping of white matter tracts in multiple sclerosis defined by diffusion tensor imaging

“…This suggests that pathology located within specific functional pathways may be a more significant factor than the overall disease burden in determining disability, and probably reflects the fact that the EDSS is heavily weighted towards motor and ambulatory deficits [15]. A previous study in which both the global and intra-pyramidal tract T 2 lesion loads correlated with the EDSS, showed only a marginally improved correlation coefficient for the intra-pyramidal tract T 2 lesion volume [29]. This was partly attributed to the lack of histopathological specificity of T 2 lesions and partly to changes in the NAWM, which were not measured.…”

“…This has previously been demonstrated by DT imaging of cerebrovascular disease [38]. There are other methods for determining the location of anatomical regions of interest, such as the use of a standardized brain atlas defined in stereotaxic space [29]; however, these may be affected by anatomical variability.…”

Clinical correlations of brain lesion distribution in multiple sclerosis

“…As long as we continue to include asymptomatic lesions in the total lesion burden, we may not reach stronger correlations between MRI and clinical observation than are currently reported (4). In an attempt to split symptomatic lesions from asymptomatic ones, one study related the lesional burden in the corticospinal tract to disability (11). This improved correlations between MRI lesion burden and measures of disability, but only moderately so.…”