Article Figures & Data
Figures
- Fig 1.
Neuropathologic assessment of cortical lesion activity. The number of active, chronic active, and chronic inactive GM lesions was evaluated with MHC class II immunostaining in 3 snap-frozen tissue blocks (A) for each of the examined 16 postmortem MS cases. A significant increased level of chronic active CL has been found compared with both active and chronic inactive CL. MOG immunostaining (B) shows an extensive chronic active subpial type III GM lesion, also reaching the WM (arrowheads). Combined MHC class II immunostaining of serial sections (C and D) demonstrates the high density of activated MHC-II+ cells close to the pial surface of the lesion (arrow in B, higher magnification in C) and toward the WM edge of the lesion (arrowheads in B, higher magnification in D). In a chronic inactive subpial CL (D), minimal density of MHC-II+ cells (E) has been found. In extensive chronic inactive lesions shown by MOG immunostaining loss (E), the lower density of MHC-II+ cells was present and scattered in all the demyelinated area, also close to the pial surface (asterisk in E, and higher magnification in F). Original magnifications ×25 (B and E),×200 (C, D, and F).
- Fig 2.
Illustration of examples of cortical lesion appearance on the quantitative susceptibility map obtained with the total generalized variation algorithm from the 3D EPI susceptibility-weighted scan. Each panel denoted by a letter is divided in 3 subpanels: 1) QSM with contoured CL (red line); 2) QSM with a superimposed CL (red), the NAGM reference tissue used in the CL classification (yellow), and NAGM obtained from the segmentation of the 3D T1 MPRAGE (cyan); 3) QSM with superimposed the 3D double inversion recovery sequence, where the CL detection and segmentation was performed. A–D, Hypointense lesions. E–H, Hyperintense lesions. The classification of CLs was performed with a 2-sided t test between QSM estimates in the lesion (with subtracted the median value of the reference QSM value in the NAGM) and a zero mean Gaussian distribution. When the t test was significant and the mean of nQSM was greater (lesser) than zero, the lesion was classified as hyperintense (hypointense).
- Fig 3.
Combined neuropathologic and MR imaging characterization of lesion activity in CLs. A–H, Immunohistochemistry staining of MOG (A–C and G) and MHC class II (D–F and H) in subpial (A–F) and leukocortical (G and H) CLs in postmortem MS brains. I–K, MR images of heterogeneous CLs in patients with MS in vivo; I, 3D double inversion recovery. J, Quantitative susceptibility mapping calculated with the total generalized variation algorithm. K, DIR superimposed on the QSM map. MOG and MHC-II immunostaining on serial sections show ongoing subpial demyelination (blue arrowheads in A, higher magnification in B) and intense pick of MHC-II+ glia activation (D, higher magnification in E) at the depth of a cerebral sulcus, resembling the QSM hyperintense signal (blue arrowheads in J) in similar regions. Concurrent complete subpial demyelination (yellow arrowheads in A, higher magnification in C) and intense peak of MHC-II+ glia activation (F) were also detected along the pial surface of the same cerebral sulcus (yellow arrowheads in A), respectively, resembling similar QSM hyperintense signal (yellow arrowheads in J). In type I leukocortical lesions, shown by MOG immunostaining (G), high occurrence and density of MHC-II+ activated microglia and macrophages (H) were observed at the GM/WM interface (green arrowheads in G and H). Higher magnification of the GM/WM interface (green arrowheads in H) reveals higher density of MHC-II+ cells mainly in proximity to inflammatory infiltrates (asterisks in G) within the WM border of the lesions, possibly corresponding to the frequent QSM hyperintense signal shown by green arrowheads in J. Original magnifications ×100 (A, D, and G), ×200 (B, C, E, F, and H).
Tables
Sex/Age at Death (yr) Postmortem Delay (hr) Age at Onset (yr) SPMS cases MS92 F/38 26 21 MS121 F/49 24 36 MS154 F/35 12 23 MS160 F/44 18 29 MS176 M/37 12 10 MS180 F/44 9 26 MS229 M/53 13 37 MS230 F/42 31 22 MS234 F/39 15 23 MS286 M/45 7 29 MS289 M/45 9 27 MS317 F/48 21 18 MS330 F/59 24 19 MS356 F/45 10 28 MS408 M/39 21 29 MS517 F/48 12 23 Control cases C14 F/64 18 C25 M/35 22 C28 F/60 13 C30 M/75 17 C36 M/68 30 C41 M/51 22 C48 M/68 10 C54 M/66 16 RRMS SPMS Whole Group No. 21 15 36 Age (yr) 36.2 ± 5.8 49.5 ± 9.2 40.5 ± 8.0 Disease duration (yr) 9.7 ± 6.3 16.9 ± 7.0 12.7 ± 7.5 Sex (F/M) 16:5 9:6 25:11 EDSS (mean) (range) 2.0 (1.0–5.5) 5.0 (4.0–7.0) 3.0 (1.0–7.0) No. of intracortical lesions (mean) Total 4.5 ± 3.6 2.1 ± 2.6 3.5 ± 3.4 QSM-hyperintense 2.8 ± 2.3 0.9 ± 1.2 2.0 ± 2.1 QSM-isointense 0.6 ± 0.7 0.1 ± 0.4 0.4 ± 0.6 QSM-hypointense 1.1 ± 1.5 0.9 ± 1.8 1.0 ± 1.6 No. of leukocortical lesions (mean) Total 2.6 ± 3.1 5.0 ± 3.5 3.6 ± 3.5 QSM-hyperintense 1.5 ± 1.8 1.9 ± 1.5 1.7 ± 1.7 QSM-isointense 0.5 ± 0.9 0.6 ± 1.3 0.5 ± 1.1 QSM-hypointense 0.5 ± 0.9 2.4 ± 2.4 1.3 ± 1.9 No. of total lesions (mean) Total 7.1 ± 5.2 7.1 ± 5.0 7.1 ± 5.1 QSM-hyperintense 4.2 ± 3.4 2.8 ± 2.3 3.6 ± 3.0 QSM-isointense 1.0 ± 1.2 0.7 ± 1.3 0.9 ± 1.3 QSM-hypointense 1.6 ± 1.8 3.3 ± 3.7 2.3 ± 2.8
