Pathological Differences between White Matter and Grey Matter Multiple Sclerosis Lesions

Multiple Sclerosis (MS) is a debilitating disease and is characterized by demyelination of the central nervous system (CNS) resulting in the wide-spread formation of white matter lesions (WML) and grey matter lesions (GML). WML are pathologically characterized by the presence of immune cells that infiltrated into the CNS, whereas in GML these are hardly present. This striking pathological difference between WML and GML questions the underlying mechanism. It is known that infiltrating leukocytes contribute to the generation of WML, however, since GML show a paucity of infiltrating immune cells, their importance in GML formation remains to be determined. Here, we review pathological characteristics of WML and GML, and put forward some possible explanations for the observed pathological differences. In our view, cellular and molecular characteristics in WM and GM, and local differences residing within in WML and GML, in particular by glial cell populations and their molecules expressed, determine the pathway to demyelination. Further understanding of GML pathogenesis, considered to contribute to chronic MS, may have direct impact on the development of novel therapeutic targets to counteract this progressive neurological disorder. Marloes Prins1, Emma Schul1, Jeroen Geurts1, Paul van der Valk2, Benjamin Drukarch1 and Anne-Marie van Dam1 VU University Medical Center, Neuroscience Campus Amsterdam, 1Dept. Anatomy and Neurosciences, 2Dept. Pathology, Amsterdam, The Netherlands Annals of the New York Academy of Science 2015; Jul 22, doi: 10.1111/nyas.12841 PATHOLOGICAL DIFFERENCES BETWEEN WHITE MATTER AND GREY MATTER MULTIPLE SCLEROSIS LESIONS