The histologic appearance of the lesion depends on its age. Relatively recent lesions show a partial or complete destruction and loss of myelin throughout a zone formed by the confluence of many small, predominantly perivenous foci; the axons in the same region are relatively spared or less affected. There is a variable but usually slight degeneration of oligodendroglia (see further on), a variable astrocytic reaction, and perivascular and para-adventitial infiltration with mononuclear cells and lymphocytes as discussed in detail further on. Later, large numbers of microglial phagocytes (macrophages) infiltrate the lesions and astrocytes in and around the lesions increase in number and size. Long-standing lesions, are composed of thickly matted, relatively acellular glial tissue, with only occasional perivascular lymphocytes and macrophages; in such lesions, a few intact axons may still be found. In old lesions with interruption of axons, there may be descending and ascending wallerian degeneration of long fiber tracts in the spinal cord. Partial remyelination is believed to take place on undamaged axons and to account for incompletely demyelinated “shadow patches” (Prineas and Connell). A few of the most severe older lesions will have undergone cavitation, indicating that the process has affected not only myelin and axons but also supporting tissues and blood vessels. All gradations of histopathologic change between these two extremes may be found in lesions of diverse size, shape, and age.
The relatively ineffective remyelination of the MS plaque leaves in its wake denuded axons that are thinly myelinated, creating the just mentioned shadow plaques. Histologic evidence suggests that some oligodendrocytes are destroyed in areas of active demyelination but also that remaining ones have little ability to proliferate. Instead, there is an influx of oligodendroglial precursor cells, which mature into oligodendrocytes and provide the remaining axons with new myelin. Probably the astrocytic hyperplasia in regions of damage and the persistent inflammatory response account for some of the inadequacy of the reparative process (see Prineas et al).
Most data suggest that antibody and complement-mediated myelin phagocytosis are the dominant mechanism of demyelination in MS. An insight into the complexity of the immunopathologic process can be appreciated in the analyses by Lucchinetti and colleagues (2000) of autopsy and brain biopsy specimens from patients with MS. They separated the lesions into four histologic subgroups: inflammatory lesions made up of T cells and macrophages alone (pattern I); an autoantibody lesion mediated by immunoglobulin and complement (pattern II); those characterized by apoptosis of oligodendrocytes and absence of immunoglobulin or complement, and partial remyelination (pattern III); and those showing only oligodendrocyte dystrophy and no remyelination (pattern IV). Two features are of interest here. First, each case demonstrated only 1 pattern of pathology, suggesting that perhaps different pathophysiologic processes operated in each patient. Moreover, the last 2 histopathologic types were considered to represent a primary oligodendroglial cell degeneration. Some confirmation of a primary process in oligodendrocytes is the material from newly symptomatic lesions reported by Barnett and Prineas, in which there was loss of these cells. In addition, early lesions have been found to contain areas of demyelination within the cerebral cortex and these are often in contiguity with meningeal inflammatory infiltrates, or lymphoid follicles (Lucchinetti et al, 2011; Howell et al).
The overall implication is that the pathologic characteristics of the chronic progressive type of MS may differ from those of the typical relapsing type (see further on).