The Relation between Meningeal Inflammation, Cortical Demyelination and White Matter Lesional Activity in Chronic Multiple Sclerosis: a Pilot Study (P5.228)

OBJECTIVE: To carry out a pilot investigation of the relationship between meningeal inflammation, cortical demyelination and white matter lesional activity in multiple sclerosis (MS) donors with progressive disease.BACKGROUND: Cortical demyelination (particularly subpial demyelination) is an important component of MS pathology, being associated with disease progression and cognitive impairment. There have been variable reports on the association of such cortical demyelination with meningeal inflammation. Some studies have reported relative paucity of meningeal immune cells or lack of correlation with cortical injury; other studies report substantial meningeal inflammation that topographically relates to subpial demyelination. It is also not known whether, and to what extent, meningeal inflammation may be associated with white matter lesional activity.DESIGN/METHODS: Using immunohistochemistry on well-characterized post-mortem tissue collected at the Netherlands Brain Bank during rapid-autopsy, we analyzed the presence and extent of meningeal inflammation and its topographic association with subpial demyelination in progressive MS donors with high (81-95[percnt];n=4) or low (10-35[percnt];n=4) white matter lesional activity, derived by the analysis of PLP and HLA staining of all diagnostic tissue blocks available per donor (up to 30 blocks containing up to 132 lesions). Density and morphology of B cells (CD20+) and T cell (CD3+) were analyzed in 8 tissue blocks, containing meninges and 29 subpial cortical lesions.RESULTS: Meningeal immune cells were observed in all samples, though to variable degree. Meninges adjacent to subpial cortical lesions appeared to have higher density and enlarged morphology of CD20+ and CD3+ cells, particularly in donors with high white matter lesional activity compared to low activity donors, and compared to meninges adjacent to normal appearing grey matter.CONCLUSIONS: In this pilot study, progressive MS donors with a high white matter lesional activity appear to have obvious meningeal inflammation, which seemed associated with cortical demyelination. Quantification studies are currently underway to extend these observations. Disclosure: Dr. Ramaglia has received personal compensation as a co-inventor of a patent that describes the use of inhibitors of the terminal complement pathway for therapeutic purposes. Dr. Michailidou has nothing to disclose. Dr. Touil has nothing to disclose. Dr. van Eden has nothing to disclose. Dr. Huitinga has nothing to disclose. Dr. Gommerman has nothing to disclose. Dr. Bar-Or has received research support from Amplimmune, EMD Serono, and Novartis.