DISTINCT PATTERNS OF MULTIPLE-SCLEROSIS PATHOLOGY INDICATES HETEROGENEITY IN PATHOGENESIS

Multiple sclerosis is an inflammatory demyelinating disease of the cen tral nervous system. The hallmark of its pathology is the demyelinated plaque with reactive glial scar formation. However, a detailed analys is of the patterns of demyelination, oligodendroglia cell pathology an d the reaction of other tissue components suggests that the pathogenes is of myelin destruction in this disease may be heterogeneous. In this review we present a new classification scheme of lesional activity on the basis of the molecular composition of myelin degradation products in macrophages. When these criteria are used, different patterns of d emyelination can be distinguished, including demyelination with relati ve preservation of oligodendrocytes, myelin destruction with concomita nt and complete destruction of oligodendrocytes or primary destruction or disturbance of myelinating cells with secondary demyelination. Fur thermore, in some cases a primary selective demyelination may be follo wed by secondary oligodendrocyte loss in the established lesions. Fina lly, some extraordinarily severe conditions may result in destructive lesions with loss of myelin, oligodendrocytes, axons and astrocytes. T his heterogeneity of plaque pathology is discussed in the context of r ecent experimental models of inflammatory demyelination, which show th at different immunological pathways may lead to the formation of demye linated plaques that reveal the diverse structural aspects described a bove. Our data indicate, that the demyelinated plaques of multiple scl erosis may reflect a common pathological end point of a variety of dif ferent immunological mechanisms of myelin destruction in this disease.