The onset and progression of the lesion in multiple sclerosis

Abstract

The active established plaque in multiple sclerosis is characterized by hypercellularity at its edge and lipid phagocytosis (gitter cells). The hyperactive early plaque shows cells throughout the lesion. Active plaques seem to extend at their edges; proteolysis of myelin basic protein is perhaps an important factor in the myelin breakdown at the rim of these lesions.

The hyperactive early plaque usually shows infiltration with monocytes, lymphocytes and plasma cells around its central vein. The phagocytic element is presumably a response to myelin breakdown, but the significance of the lymphocytes in these lesions is uncertain.

Perivenular infiltrates that are predominantly composed of lymphocytes are seen around veins and venules in the vicinity of established lesions in some patients who died during an acute episode. Serial section shows that these veins are not draining the lesion, but very distant veins and venules are not involved. These lymphocyte infiltrations often show no surrounding demyelination, but not infrequently areas of inactive demyelination are seen around them. It is suggested that, if the lymphocytic infiltration is an early event, it may either proceed to a hyperactive plaque (and in the process becomes enriched with monocytes), or it may become aborted or itself aborts the pathogenic process. Areas of intense myelin pallor and oedema associated with lymphocyte cuffs might represent an intermediate stage between the simple infiltrate and the explosive hyperactive plaque.

The active perivenous lesion seems to extend along a vein and coalesces with neighbouring perivenous lesions; in this way some plaques are seen to follow the course of a vein over a considerable distance. Selective loss of basic proteins does not appear from limited evidence to be a feature around such perivenous lymphocytic infiltrates, but proteolytic activity has not yet been tested in them.