Robert Zivadinov

There is a growing interest in studying the extent of cortical and subcortical deep gray matter pathology (SDGM) starting from the earliest clinical stages of multiple sclerosis (MS). The relationship between the appearance of white matter (WM) lesions and SDGM atrophy in patients with MS is not well-understood.  A number of independent studies have shown that volume loss of SDGM occurs in the early stage of MS. However, an important question is whether the WM damage contributes to the abnormalities in gray matter (GM) regions through a disconnection mechanism or whether GM and WM tissue alterations are affected independently. The aim of our study was to quantify SDGM alterations by examining associations between diffusion tensor imaging (DTI) parameters, structural volume, and lesion measurements in the brain parenchyma of patients with clinically isolated syndrome (CIS), and to compare them with healthy controls. Our findings suggest that diffuse DTI alterations of GM structures, not associated with lesion formation, are present in patients with CIS.

Current guidelines have recognized the benefits of early treatment with disease-modifying therapies (DMTs) in patients with MS. The efficacy of early treatment with DMTs for delaying the conversion of CIS to clinically definite MS has been evaluated in several studies; however, there are a number of barriers for implementing early MS treatment. Our results suggest that microstructural alterations are present in the SDGM of patients with CIS, underscoring the importance of starting early treatment of MS, as the delay may result in poorer response to DMTs and more severe neurological disability.

In the future, it will be very important to introduce nonconventional MRI techniques as part of standardized protocols in clinical trials and standard clinical routine, to better evaluate the efficacy of DMTs, not only concerning the accumulation of lesion burden and progression of atrophy of the central nervous system but also the recognition of microstructural damage of different brain structures and the pathology outside of the focal WM and GM lesions.

To further establish the relationship between SDGM atrophy and WM lesions, future longitudinal studies are needed in order to assess the structural WM and GM alterations combining different nonconventional MRI techniques in patients with CIS.

Read this article at AJNR.org . . .