Meningeal inflammation in multiple sclerosis

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Recently, immunohistochemical studies demonstrated the occurrence of extensive grey matter demyelination in MS. Mechanisms underlying the development of grey matter lesions are unknown and it has been speculated that meningeal inflammation might be involved in (sub-pial) cortical demyelination. Objective: Here, we describe the occurrence of meningeal inflammation in a large post-mortem MS dataset and correlate these data with the presence and extent of cortical demyelination. Methods: A total of 103 paraffin-embedded tissue blocks from 28 MS patients and 17 tissue blocks from nine non-neurological controls were labelled for proteolipid protein (PLP), CD3 (T-cells), CD20 (B-cells), CD68 (macrophages), Granzyme B (cytotoxic T-cells), and DC-SIGN (mature/immature dendritic cells). Cell density counts of (cytotoxic) T-cells, B-cells, macrophages and dendritic cells were performed systemically, in randomly chosen areas in the meninges not directly adjacent to cortical lesions. Separate cell counts were performed for meninges directly adjoining cortical lesions. MS tissue sections stained for PLP were measured morphometrically for the percentage of demyelinated cortex. Subsequently, the extent of meningeal inflammation was (spatially) correlated to the extent of cortical demyelination. Results: So far, analysis of a subset of our dataset revealed significantly more T-cell infiltrates in the meninges of MS patients compared with controls. However, no relation was found between the extent of global T-cell infiltration in the meninges of MS patients and the extent of cortical demyelination. Additionally, and more specifically, no differences between the extent of T-cell infiltration in the meninges directly adjacent to cortical lesions and normally myelinated cortex were found. Conclusions: The infiltration of T-cells in the meninges of MS patients does not seem to be correlated with cortical demyelination. Additional immunostainings for B-cells, cytotoxic T-cells, macrophages and dendritic cells are currently being processed. These results will be presented at the meeting.