PMC

Panel A shows leukocortical demyelination; Panel B subpial demyelination (arrows delineate an area of cortex with preserved myelin); Panel C intracortical demyelination (arrows), with neurons in the demyelinated lesion (inset); and Panel D subpial and leukocortical demyelination in the same tissue section.

Panel A shows moderate-to-marked, diffuse meningeal inflammation (hematoxylin and eosin). Panel B shows moderate-to-marked, diffuse meningeal inflammation topographically associated with a subpial plaque (immunohistochemical staining for PLP). Panel C shows marked perivascular meningeal inflammation topographically associated with a subpial plaque (PLP staining). Neuritic loss reflects the destructive nature of the subpial plaque in Panel D (immunohistochemical staining for neurofilament). Components of the perivascular meningeal inflammatory infiltrates include CD3+ T cells in Panel E (immunohistochemical staining for CD3) and B cells in Panel F (immunohistochemical staining for CD20).

Panel A shows normal oligodendrocyte density (arrows) in nondemyelinated cortex (immunohistochemical staining for 2′3′-cyclic-nucleotide 3′-phosphodiesterase [CNPase]). Panel B shows reduced oligodendrocyte density (arrows) in demyelinated cortex (CNPase staining). In Panel C, neuronal injury is evidenced by the presence of pyknotic neurons (arrowheads) scattered among healthy neurons (arrow) (hematoxylin and eosin). Microglia in Panel D (immunohistochemical staining for KiM1P) are close to neurons, and T cells in Panel E (immunohistochemical staining for CD3) are close to oligodendrocytes.

Panel A shows the percentage of plaques with myelin-laden macrophages, according to plaque type, among 78 lesions (41 patients) with cortical demyelination. The percentage of myelin-laden macrophages in leukocortical plaques (LK) was significantly higher than the percentages in intracortical plaques (IC) (P = 0.02) and subpial plaques (SP) (P<0.001). The percentages did not differ significantly between IC plaques and SP plaques (P = 0.56). Panel B shows the percentage of plaques with mild T-cell inflammation and the percentage with moderate or severe T-cell inflammation among 71 lesions (38 patients) analyzed on the basis of CD3+ counts. The percentages of plaques that showed any inflammation did not differ significantly across plaque types (P = 0.09). I bars represent 95% confidence intervals based on logistic-regression models. Significance tests were also based on logistic-regression models.

In Panel A, myelin-laden macrophages (arrow) indicate the presence of active cortical demyelination in early multiple sclerosis (immunohistochemical staining for proteolipid protein [PLP]). In Panel B, macrophages are present in the molecular layer of the cortex at the subpial rim (immunohistochemical staining for CD68). In Panel C, myelin-laden macrophages (arrow) are also present in the subarachnoid space (PLP staining), and the inset shows the myelin-laden macrophage (arrow) at a higher magnification (PLP staining). In Panel D, marked perivascular inflammation is present in cortical plaques (PLP staining). Components of the perivascular inflammatory infiltrates include CD3+ T cells in Panel E (immunohistochemical staining for CD3) and cytotoxic T cells in Panel F (immunohistochemical staining for CD8).