Subcortical Deep Gray Matter Pathology in Patients with Multiple Sclerosis Is Associated with White Matter Lesion Burden and Atrophy but Not with Cortical Atrophy: A Diffusion Tensor MRI Study

Abstract

BACKGROUND AND PURPOSE:The association between subcortical deep gray matter, white matter, and cortical pathology is not well understood in MS. The aim of this study was to use DTI to investigate the subcortical deep gray matter alterations and their relationship with lesion burden, white matter, and cortical atrophy in patients with MS and healthy control patients.

Sex-Based Differences in Multiple Sclerosis (MS): Part II: Rising Incidence of Multiple Sclerosis in Women and the Vulnerability of Men to Progression of this Disease

“…There are also suggestions that white matter lesion burden may be more extensive in men with MS. The finding that deep gray matter pathology correlates more strongly with white matter lesion burden than with cortical atrophy (Cappellani et al 2014) further suggests a potential link between the more severe gray matter changes and early damage within the white matter lesions in men with MS. Certainly, further studies are required to better understand the underlying biological basis of why neurons in males may be more susceptible to damage in MS and to pinpoint whether it is because of a differential immune response or to a differential vulnerability of axons or myelin to inflammation.…”

Thalamic white matter in multiple sclerosis: A combined diffusion‐tensor imaging and quantitative susceptibility mapping study

“…Two commonly used DTI-derived parameters include fractional anisotropy (FA) and mean diffusivity (MD), which reflect the directional dependence and average magnitude of diffusion, respectively. WM in MS patients tends to be characterized by decreased FA and increased MD compared to healthy controls (HCs) (Benedict et al, 2013; Cappellani et al, 2014) but increased thalamic FA in MS patients has also been noted (Tovar-Moll, et al, 2009). Moreover, thalamic WM MD explained additional variance in cognitive status even after accounting for structural volume (Benedict, et al, 2013).…”

“…The association between increased diffusivity, within much of the WM as well as within the thalamus, and cognitive decline by other reports (Hulst, et al, 2013; Llufriu, et al, 2014) further highlights the utility of DTI in this regard. Although the exact causes of thalamic diffusivity alterations remain uncertain, WM lesions (WML) in connected WM fiber tracts play a role (Cappellani, et al, 2014). Wallerian degeneration within the thalamus following axonal transection due to WMLs likely explains this pathological aspect.…”

Longitudinal Mixed-Effect Model Analysis of the Association between Global and Tissue-Specific Brain Atrophy and Lesion Accumulation in Patients with Clinically Isolated Syndrome

“…[9][10][11] Weak-to-modest associations between the development of regional brain atrophy and changes in lesion number and lesion volume (LV) suggest that newly detected lesions, as well as progressive tissue damage in pre-existing lesions, contribute only partially to the loss of overall brain tissue. 12,13 At this time, the importance of lesion formation in relation to brain atrophy development is unclear, especially at the earliest clinical stages of MS. Against this background, the aim of the present study was to investigate the relationship between new/enlarging lesion formation and brain atrophy progression over 48 months in patients with CIS who presented with their first clinical event.…”