Figure 7. Neuropathological findings in a case with Marburg’s variant of MS (case MS-6).

Huge, active demyelinating lesions with perivascular lymphocytic cuffing (A) and infiltrating foamy macrophages phagocytosing myelin debris (B, corresponding to Figure 6A, square). Expression of Cx43 is extensively lost in this lesion (C, corresponding to Figure 6A, square). (D–I) Higher magnification view of the square area in Figure 6C. Loss of MAG is more obvious than for other myelin proteins including MBP and MOG (D–F). Numerous GFAP-positive hypertrophic astrocytes covering active lesions show patchy loss of AQP4 expression and diffuse loss of Cx43 expression (G–I). This lesion is classified as pattern A for Cx43 and pattern B for Cx47/Cx32. Nogo-A-positive oligodendrocytes are decreased and demonstrate apoptotic nuclear condensation (J, insert). Immunoreactivity for phosphorylated neurofilaments reveals degenerated, transected axons with axonal spheroids in the lesion (K). Immunoreactivity for MLC1 is specifically confirmed in perivascular foot process termini in non-affected white matter (L). This staining pattern is no longer observed in the lesion center and only cell bodies of gemistocytic astrocytes are immunopositive for MLC1 (M). Creutzfeldt astrocytes forming multiple micronuclei show a loss of Cx43 despite the preservation of GFAP and AQP4 (N–Q). Double immunofluorescence staining for Cx43 and Cx47 in an active lesion (R, S). In the unaffected white matter, Cx43 and Cx47 expression is well preserved in the perivascular space and white matter (R). Double staining for Cx43 and Cx47 shows partial juxtaposition or colocalization suggestive of GJ plaque formation around oligodendrocytes (inset). In contrast, immunoreactivity for Cx43 is markedly diminished in the perivascular space of inflamed blood vessels while immunoreactivity for Cx47 is preserved (S). Asterisks indicate vascular lumen (R, S). Scale Bar = 1 mm(A); 500 µm (B, C); 200 µm (D–I); 50 µm (J, K); 100 µm (L, M); 10 µm (N–Q); 20 µm (R); 50 µm (S).