This large multicentre study points to the complementary predictive value of atrophy and lesion volumes for predicting long term disability in MS.

Background: Evidence suggests that Epstein-Barr virus (EBV) plays a role in triggering or perpet-

We investigated the relationship between the damage occurring in the brain normal-appearing white matter (NAWM) and in the gray matter (GM) in patients with early Primary Progressive multiple sclerosis (PPMS), using Tract-Based Spatial Statistics (TBSS) and an optimized voxel-based morphometry (VBM) approach. Thirty-five patients with early PPMS underwent diffusion tensor and conventional imaging and were clinically assessed. TBSS and VBM were employed to localize regions of lower fractional anisotropy (FA) and lower GM volume in patients compared with controls. Areas of anatomical and quantitative correlation between NAWM and GM damage were detected. Multiple regression analyses were performed to investigate whether NAWM FA or GM volume of regions correlated with clinical scores independently from the other and from age and gender. In patients, we found 11 brain regions that showed an anatomical correspondence between reduced NAWM FA and GM atrophy; of these, four showed a quantitative correlation (i.e., the right sensory motor region with the adjacent corticospinal tract, the left and right thalamus with the corresponding thalamic radiations and the left insula with the adjacent WM). Either the NAWM FA or the GM volume in each of these regions correlated with disability. These results demonstrate a link between the pathological processes occurring in the NAWM and in the GM in PPMS in specific, clinically relevant brain areas. Longitudinal studies will determine whether the GM atrophy precedes or follows the NAWM damage. The methodology that we described may be useful to investigate other neurological disorders affecting both the WM and the GM.

Rates of progression vary widely in primary progressive multiple sclerosis. This multicenter study aimed to identify predictors of progression over 10 years. A total of 101 patients who had been imaged at baseline and 2 years were scored on the expanded disability status scale after 10 years. Ordinal logistic regression identified the following independent variables that predicted progression: male sex, shorter disease duration, and slower timed walk test at baseline (best overall predictor), and deterioration in expanded disability status scale score and reduction in brain volume over 2 years. These predictors of long-term disability provide some insight into disease progression.