title: Heterogeneity of cortical lesions in multiple sclerosis: clinical and pathologic implications.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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; p < 0.05) or patients without extensive numbers of CLs (66.9 years; p < 0.01). 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; p < 0.05). 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; p < 0.0001).
  
  
  CONCLUSIONS
  RAM-CLs were found in a subset of patients with MS who also have more active WM inflammation and a less favorable disease course.
authors.affiliation: Department of Pathology-Neuropathology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: Kooi
authors.forename: Eva M M
authors.initials: EM
authors.lastname: Strijbis
authors.forename: Paul
authors.initials: P
authors.lastname: van der Valk
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000473:pathology*; D006801:Humans; D008297:Male; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000145:classification / Q000401:mortality / Q000473:pathology*; D013997:Time Factors