Atrophy in white matter fiber tracts in multiple sclerosis is not dependent on tract length or local whitematter lesions

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.