Abstract: P489
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Post-contrast FLAIR MRI has emerged as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Autopsy studies suggest a link between cortical lesions (CLs) and meningeal inflammation.
Objective: To determine if meningeal inflammation and cortical demyelination have a true, in vivo relationship in MS.
Aim: We aimed to utilize the greater sensitivity at 7-Tesla (7T) for visualization of both leptomeningeal enhancement (LME) and CLs to explore this relationship.
Methods: Thirty-five participants with MS underwent brain MRI on a 7T scanner. Magnetization prepared 2 rapid acquisition gradient echo (MP2RAGE) and magnetization prepared fluid attenuated inversion recovery (MPFLAIR) images were acquired pre- and post-contrast. CLs were identified as hypointensities on MP2RAGE. Hyperintensities on post-contrast MPFLAIR located in the subarachnoid space, which were not present on pre-contrast images were notated as foci of LME. These were characterized as “nodular” (small spherical pial foci), “spread/fill - gyral” (contrast in the subarachnoid space from a gyrus out to dura), and “spread/fill - sulcal” (contrast filling a sulcus). Relationships were explored with Spearman correlation and Wilcoxon rank-sum analyses.
Results: Twenty-eight (80%) participants had at least one focus of LME. Only 9 (26%) participants had nodular LME, whereas 21 (60%) had spread/fill - gyral LME and 20 (57%) had spread/fill - sulcal LME. All were found to have CLs, with a median of 24 (range 9 - 79) lesions per subject. A non-significant trend was seen for a higher number of CLs in those with spread/fill - sulcal LME compared (median 27.5 (9 - 79) vs. 22 (10 - 54), p = 0.08). The number of spread/fill - sulcal foci trended towards a correlation with the number of CLs (rho = 0.26, p = 0.13). No differences were seen in the number of CLs for those with or without nodular or spread/fill - gyral LME.
Conclusions: Of the 3 patterns of LME visualized by 7T MRI in this cohort, only spread/fill - sulcal LME appeared to have any relationship with CLs. This relationship was weak; therefore, this study does not strongly support a causative relationship between meningeal inflammation and CL development. MRI identification of CLs is heavily weighted towards leukocortical CLs, which likely have a similar perivascular etiology to white matter lesions, explaining this result. Further work will be necessary to evaluate the relationship between LME and subpial demyelination.
Disclosure: Disclosures/Funding: Dr. Harrison has received research support from EMD-Serono and consulting fees from EMD-Serono, Sanofi-Genzyme, Genentech, and Biogen. Drs. Jonas and Izbudak have no financial disclosures. The study was funded in part by grants from EMD-Serono and the National Institutes of Health (NINDS 1K23NS072366-01A1).
Abstract: P489
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Post-contrast FLAIR MRI has emerged as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Autopsy studies suggest a link between cortical lesions (CLs) and meningeal inflammation.
Objective: To determine if meningeal inflammation and cortical demyelination have a true, in vivo relationship in MS.
Aim: We aimed to utilize the greater sensitivity at 7-Tesla (7T) for visualization of both leptomeningeal enhancement (LME) and CLs to explore this relationship.
Methods: Thirty-five participants with MS underwent brain MRI on a 7T scanner. Magnetization prepared 2 rapid acquisition gradient echo (MP2RAGE) and magnetization prepared fluid attenuated inversion recovery (MPFLAIR) images were acquired pre- and post-contrast. CLs were identified as hypointensities on MP2RAGE. Hyperintensities on post-contrast MPFLAIR located in the subarachnoid space, which were not present on pre-contrast images were notated as foci of LME. These were characterized as “nodular” (small spherical pial foci), “spread/fill - gyral” (contrast in the subarachnoid space from a gyrus out to dura), and “spread/fill - sulcal” (contrast filling a sulcus). Relationships were explored with Spearman correlation and Wilcoxon rank-sum analyses.
Results: Twenty-eight (80%) participants had at least one focus of LME. Only 9 (26%) participants had nodular LME, whereas 21 (60%) had spread/fill - gyral LME and 20 (57%) had spread/fill - sulcal LME. All were found to have CLs, with a median of 24 (range 9 - 79) lesions per subject. A non-significant trend was seen for a higher number of CLs in those with spread/fill - sulcal LME compared (median 27.5 (9 - 79) vs. 22 (10 - 54), p = 0.08). The number of spread/fill - sulcal foci trended towards a correlation with the number of CLs (rho = 0.26, p = 0.13). No differences were seen in the number of CLs for those with or without nodular or spread/fill - gyral LME.
Conclusions: Of the 3 patterns of LME visualized by 7T MRI in this cohort, only spread/fill - sulcal LME appeared to have any relationship with CLs. This relationship was weak; therefore, this study does not strongly support a causative relationship between meningeal inflammation and CL development. MRI identification of CLs is heavily weighted towards leukocortical CLs, which likely have a similar perivascular etiology to white matter lesions, explaining this result. Further work will be necessary to evaluate the relationship between LME and subpial demyelination.
Disclosure: Disclosures/Funding: Dr. Harrison has received research support from EMD-Serono and consulting fees from EMD-Serono, Sanofi-Genzyme, Genentech, and Biogen. Drs. Jonas and Izbudak have no financial disclosures. The study was funded in part by grants from EMD-Serono and the National Institutes of Health (NINDS 1K23NS072366-01A1).