Hans Lassmann, Brain Research Institute, University of Vienna, Austria

In multiple sclerosis a chronic inflammatory process in the central nervous system is associated with primary demyelination and a variable degree of secondary axonal loss. The composition of inflammatory infiltrates is consistent with a T-cell mediated immune reaction, which leads to profound activation of microglia cells and secondary recruitment of hematogenous macrophages. In chronic disease this inflammatory process is global, affecting not only the classical demyelinated plaques, but also the "normal" white and gray matter. Although most intense in actively demyelinating lesions significant inflammation is also present in all inactive demyelinated and even in remyelinated plaques. Demyelination is accomplished by various different immunological mechanisms, involving cytokines and products of activated macrophages or microglia cells as well as demyelinating antibodies. In other lesions signs of oligodendrocyte dystrophy are seen, which are comparable with either virus induced or metabolic disturbances of this cell population. These different mechanisms of demyelination are reflected in distinct patterns of demyelination, which are heterogenous between MS patients, but homogenous in multiple active lesions arising in a single patient at a given time point of the disease. Our data indicate that demyelination in multiple sclerosis is a complex event and its immunological mechanisms differ between patients and within single patients between different stages of the disease. This pathogenetic heterogeneity of multiple sclerosis lesions may be a reflection of the highly polygenic background of this disease.