Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: an in vivo study with TBSS and VBM

Abstract

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.

Figure 1

TBSS results: Significant reduction in FA (voxels in red) along the bilateral corticospinal tract, the bilateral optic radiation, the bilateral corona radiate, the corpus callosum, and the left arcuate fasciculus in patients displayed on the mean FA map.

Figure 2

SPM‐VBM results: Significant reduction in grey matter in the bilateral sensory‐motor cortex, in the bilateral thalamus, in the right superior temporal gyrus, and in the left grey matter around sylvian fissure in patients displayed on the Montreal Neurological Institute template.

Figure 3

Examples of regions where anatomical (A and B) or anatomical and quantitative correlations (C) between NAWM damaged tracts (voxels in red) and GM atrophy (areas in blue) have been found in patients. This figure shows: In (A), the left corticospinal tract projecting onto the left sensory‐motor cortex (see yellow arrow); in (B), the NAWM immediately adjacent to the GM of the right superior temporal lobe (see yellow arrow); and in (C), the right corticospinal tract and the connected sensory‐motor cortex (see yellow arrow).