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Griffiths et al. Neuroimmunol Neuroinflammation 2020;7:51-67 I http://dx.doi.org/10.20517/2347-8659.2019.21 Page 59

Figure 4. Defining a cohort of cortical High grey matter lesion MS. Nine progressive MS cases with the greatest relative area of subpial
cortical demyelination were labelled as Cortical High GML MS and the remaining cases as Cortical Low GML MS (A). Cortical High
GML MS had a greater area of demyelinated deep grey matter and hippocampus (B), but unchanged white matter lesion areas (C). The
density of CD68+ microglia/macrophages was increased in both normal appearing GM (NGM) and GML of cortical High GML MS (D)
but was only different in the underlying normal appearing WM (NWM) (E). Semi-quantitative evaluation of meningeal inflammation
revealed cortical High GML MS to have increased inflammation of the leptomeninges (F). Examples of CD68+ microglia of a subpial GM
lesion (G) and CD68+ microglia/macrophages in a white matter lesion (H). Examples of 1-3 rated inflammatory infiltrates (“+” to “+++”)
of the forebrain meninges [I-N with (L-N) being higher power images of (I-K), respectively]. Please note that infiltrates (I, L, K, N) are
near partially de/re-myelinated cortex of cortical High GML Case MS257. Cx: cortical; GML: grey matter lesion; NGM: normal appearing
grey matter; NWM: normal appearing white matter; PLP: proteolipid protein immunohistochemistry; WML: white matter lesion. (G-K)
Scale bar = 100µm; (L-N) Scale bar = 25 µm