Meningeal Inflammation is not Associated With Cortical Demyelination in Chronic Multiple Sclerosis

Cortical demyelination can be extensive in chronic multiple sclerosis (MS) patients. Cortical lesions are not associated with lymphocyte infiltration, blood-brain barrier disruption, or complement deposition; therefore, their pathogenesis is unclear. We analyzed the extent and cellular composition of leptomeningeal inflammatory infiltrates and their relationship with cortical demyelinated lesions in brain autopsy samples from 28 chronic MS patients; samples from 6 nonneurological disease control patients were also studied. Immunohistochemistry was used to detect meningeal T cells, B cells, macrophages, mature and immature dendritic cells, T-helper cells, (activated) cytotoxic T cells, and plasma cells. Quantitative analysis revealed significant meningeal inflammation in chronic MS patients; T cells were the predominant inflammatory cells. Morphometric analysis was performed on coronal hemisphere sections of the MS cases to assess subpial demyelination; no correlation between the extent of subpial demyelination and extent of meningeal inflammation was identified. Moreover, no differences were observed in the degree or cellular composition of meningeal infiltrates in areas directly adjacent to subpial lesions compared with areas adjacent to normal-appearing gray matter in the MS cases. In addition, no follicle-like structures were found in the MS samples. Our data suggest that the occurrence of cortical lesions is not related to the presence of meningeal inflammation in a large number of chronic MS patients.