THE CONTROVERSY SURROUNDING THE PATHOGENESIS OF THE MULTIPLE-SCLEROSIS LESION

The main issues in multiple sclerosis research revolve around four fun damental questions, (1) What initiates the disease-that is, autoimmune T cells, a virus, or a toxin? (2) Is the inflammatory response primar y to the development of demyelination, or is it a secondary response t o injury? (3) Is the oligodendrocyte, the myelin-producing cell, the p rimary target? (4) How can myelin repair be promoted? This review focu ses on the controversies revolving around these important questions, A lthough many investigators believe that T-cell receptors on CD4(+) cel ls interact with myelin antigens to initiate an inflammatory cascade t hat leads to myelin destruction, others maintain that a viral agent ma y have a direct or indirect role in the pathogenesis of multiple scler osis. The concept that the immune system contributes to the tissue des truction in multiple sclerosis is generally accepted; however, the deb ate about cause versus consequence of the pathologic process remains u nresolved, as does the identification of the initial event or focus of the damage. Electron microscopic studies have disclosed evidence of r emyelination (albeit often incomplete) in lesions of multiple sclerosi s. Enhanced understanding of the factors limiting remyelination could help formulate strategies to promote repair. By innovative experimenta l design and application of available molecular techniques, the answer s to these questions may provide insights on how to prevent or treat m ultiple sclerosis.