Advances in understanding gray matter pathology in multiple sclerosis: Are we ready to redefine disease pathogenesis?

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 [1]. 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 [2-5]. During the past few years, the number of studies investigating GM damage in MS has increased exponentially.This special issue of BMC Neurology includes four review articles. One of the primary aims 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. The authors and topics of the articles have been chosen by the guest editors to provide a state-of-the-art review of this rapidly emerging field in MS. The article by Lucchinetti and Popescu focuses on pathology, [4] the article by Walker and colleagues on immunology, [3] by Hulst and colleagues on imaging [2] and by Horakova and colleagues on clinical [5] features of GM involvement in patients with MS.In the last decade, advanced tissue processing and immunohistochemistry methods, including staining for myelin basic protein (MBP) and proteolipid protein (PLP), [6-8] and more advanced magnetic resonance imaging (MRI) techniques to detect GM lesions, like double inversion recovery (DIR), [9-11] contributed to a surge in studies investigating cortical and subcortical GM pathology in MS.Although it has been shown that cortical lesions could occur secondary to WM damage in relation to Wallerian degeneration, [12] recent hi