The pathogenesis of tissue injury outside the white matter (WM) plaques of multiple sclerosis (MS) has not yet been clearly defined. To better understand the pathogenesis of this injury and the associated atrophy, we investigated volume loss over time in 20 WM fiber tracts. We defined two main aims: (1) to examine whether certain fiber tracts were more prone to atrophy, and to test the possible relation of tract atrophy to tract length and selected MS-specific variables; and (2) to investigate the possible relation of atrophy to lesion load (whole brain and in the specific tract). Local volume change was assessed between two distant time points for each MS patient studied. Fiber tracts were segmented automatically using a tractography-based atlas. Results demonstrate volume loss in all fiber tracts. The uncinate fasciculus and anterior-thalamic radiation had the greatest yearly percentage atrophy. Disease type, duration, median expanded disability status scale, total lesion load, and gender exhibited significant effects on atrophy in at least one tract. Together, these data are more consistent with a pathogenesis for the degeneration related to diffuse inflammation rather than the secondary effects of focal lesions.

There were two aims to this study. First, to explore how the reduction in the volume of abnormal T2-signal intensity associated with white matter (WM) lesions in multiple sclerosis (MS) relates to tissue loss resulting from focal pathology inside lesions. Second, to demonstrate that this volume of abnormal T2-signal intensity underestimates the actual size of the region to which the direct effects of lesion activity extend. For these purposes, we used deformation field analysis to quantify the evolution of local atrophy associated with a chronic peri-ventricular lesion in a patient with secondary progressive MS. This subject had particular features that may not necessarily co-exist in a group of unselected patients, which enabled interesting observations to be made. We show, quantitatively, that the focal WM lesion was associated with adjacent regional WM volume loss, which was disproportionate to concurrent diffuse atrophy in the rest of the normal appearing brain tissue, and that the loss of volume associated with the lesion was partially reciprocated by local ventricular expansion. Our observations re-emphasise the complex relationship between the change in the volume of abnormal signal intensity on magnetic resonance images and the tissue volume change directly related to lesion pathology.