Heterogeneity of cortical lesions in multiple sclerosis: Clinical and pathologic implications

Autopsy cases show that cortical lesions (CLs) in multiple sclerosis (MS) lack lymphocyte/macrophage influx, blood-brain barrier breakdown, and complement activation. However, some CLs were demonstrated to harbor activated microglia. Here, we assessed the clinical significance of microglia activation in CLs in a large autopsy sample, and we investigated possible interrelationships with other pathologic characteristics.We cross-sectionally investigated the clinicopathologic characteristics of 22 patients with MS with extensive subpial demyelination (CL group) and 19 patients with MS with only little demyelination of the cerebral cortex (non-CL group).A subset of the patients in the CL group (12 patients) showed rims of activated microglia (RAM) at the border of the CLs (RAM-CL group), whereas the other 10 patients in this group did not show microglia activation (non-RAM-CL group). A subsequent comparison between groups showed that patients with MS harboring RAM-CLs were significantly younger at the time of their death (53.5 years) than patients harboring mainly non-RAM-CLs (68.7 years; p0.05) or patients without extensive numbers of CLs (66.9 years; p0.01). In addition, a significantly shorter disease duration was found for the RAM-CL group (mean 20.9 years) than for the non-CL group (mean 34.5 years; p0.05). We also found that the presence of RAM-CLs is associated with a higher number of chronic active white matter (WM) lesions (Spearman ρ = 0.74; p0.0001).RAM-CLs were found in a subset of patients with MS who also have more active WM inflammation and a less favorable disease course.