Multiple sclerosis (MS) has traditionally been viewed and studied as a chronic inflammatory demyelinating disorder of the central nervous system (CNS) that predominantly involves the white matter (WM). Pathology studies conducted as early as the 19th century have already recognized that MS affects not only the WM but also the gray matter (GM), which somehow got neglected over the years. However, in the last decade, substantial pathological, immunological and imaging evidence confirmed that tissue damage in the GM is a key component of the disease process in MS and that it occurs from the earliest clinical stages. During the past few years, the number of studies investigating GM damage in MS has increased exponentially. The guest editors have chosen articles which raise a number of important new questions and outline comprehensive approaches to addressing those questions in years to come. In the last decade, the use of immunohistochemistry staining methods and more advanced imaging techniques to detect GM lesions, like double inversion recovery, contributed to a surge of studies related to cortical and subcortical GM pathology in MS. It is becoming more apparent from recent biopsy studies that subpial cortical lesions in early MS are highly inflammatory. The mechanisms responsible for triggering meningeal inflammation in MS patients are not yet elucidated, and they should be further investigated in relation to their role in initiating and perpetuating the disease process. Determining the role of antigens, environmental and genetic factors in the pathogenesis of GM involvement in MS is critical. The early involvement of cortical and subcortical GM damage in MS is very intriguing and needs to be further studied. As established in numerous cross-sectional and longitudinal studies, GM damage is a better predictor of physical disability and cognitive impairment than WM damage. Monitoring the evolution of GM damage is becoming an important marker in predicting future disease course and response to therapy in MS patients. One of the primary aims of this special issue of BMC Neurology is to provide an educational update not only to general neurologists but also to MS specialists and scientists studying MS by summarizing important recent advances in our understanding of GM damage and its implications to MS pathogenesis.
Dr Istvan Pirko, Dr Robert Zivadinov