PATTERNS OF OLIGODENDROGLIA PATHOLOGY IN MULTIPLE-SCLEROSIS

Patterns of inflammation, demyelination and oligodendrocyte pathology were studied in acute multiple sclerosis and during early and late exa cerbations of chronic multiple sclerosis. Cells within lesions were id entified by immunocytochemistry with markers for T lymphocytes, macrop hages, oligodendrocytes and astrocytes. In addition, in situ hybridiza tion for proteolipid protein mRNA was used to identify myelinating and myelin supporting oligodendrocytes. Degenerating cells in the lesions were detected by DNA fragmentation in cell nuclei. The inflammatory r eaction in all three types of multiple sclerosis lesions was shown to be dominated by T lymphocytes and macrophages. In late chronic multipl e sclerosis lesions, a significant increase in the number of immunoglo bulin producing plasma cells was found in infiltrates as compared with acute and early multiple sclerosis lesions. In all three types of mul tiple sclerosis, confluent plaques of demyelination were found to be p resent. In acute multiple sclerosis, demyelination was found to be ass ociated with extensive destruction of other tissue elements, including oligodendrocytes, astrocytes and axons, but even in these destructive lesions a considerable number of oligodendrocytes was preserved and a t disposal therefore, for rapid remyelination. During early exacerbati ons of chronic multiple sclerosis, selective demyelination was associa ted with almost complete preservation of oligodendrocytes in the major ity of cases. Correspondingly, a high number of remyelinating lesions was present at that stage of disease. In lesions developing late after onset of multiple sclerosis, demyelination generally accompanied exte nsive destruction and loss of oligodendrocytes. In these lesions, remy elination was sparse and restricted to lesional borders. The observed patterns of cell death suggest that in some cases oligodendrocytes, in others myelin sheaths are the primary target of the destructive proce ss. Our data indicate that the type and amount of inflammation, de- an d remyelination, and of tissue damage vary between different forms of multiple sclerosis and between different stages of the disease, possib ly reflecting different pathogenic mechanisms in a disease spectrum.