Heterogeneity of cortical lesions in multiple sclerosis
Clinical and pathologic implications
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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.
GLOSSARY
- ANOVA=
- analysis of variance;
- BSA=
- bovine serum albumin;
- CL=
- cortical lesion;
- HLA=
- human leukocyte antigen;
- MS=
- multiple sclerosis;
- PBS=
- phosphate-buffered saline;
- PLP=
- proteolipid protein;
- PP=
- primary progressive;
- PR=
- progressive relapsing;
- RAM=
- rim of activated microglia;
- SP=
- secondary progressive;
- WML=
- white matter lesion.
Footnotes
Study funding: E.-J.K. and the Multiple Sclerosis Center Amsterdam are supported by the Dutch Multiple Sclerosis Research Foundation (grants 02–498MS, 06–587MS, and 09–358c).
- Received January 23, 2012.
- Accepted May 8, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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