%0 Journal Article
%T Neuroimaging assessment of facility-bound severely-affected MS reveals the critical role of cortical gray matter pathology: results from the CASA-MS case-controlled study.
%A Zivadinov R
%A Jakimovski D
%A Burnham A
%A Kuhle J
%A Weinstock Z
%A Wicks TR
%A Ramanathan M
%A Sciortino T
%A Ostrem M
%A Suchan C
%A Dwyer MG
%A Reilly J
%A Bergsland N
%A Schweser F
%A Kennedy C
%A Young-Hong D
%A Eckert S
%A Hojnacki D
%A Benedict RHB
%A Weinstock-Guttman B
%J J Neurol
%V 271
%N 8
%D 2024 Aug 17
%M 38758279
%F 6.682
%R 10.1007/s00415-024-12420-2
%X <B>BACKGROUND: </B>A subgroup of people with multiple sclerosis (pwMS) will develop severe disability. The pathophysiology underlying severe MS is unknown. The comprehensive assessment of severely affected MS (CASA-MS) was a case-controlled study that compared severely disabled in skilled nursing (SD/SN) (EDSS ≥ 7.0) to less-disabled (EDSS 3.0-6.5) community dwelling (CD) progressive pwMS, matched on age-, sex- and disease-duration (DDM).<BR><B>OBJECTIVE: </B>To identify neuroimaging and molecular biomarker characteristics that distinguish SD/SN from DDM-CD progressive pwMS.<BR><B>METHODS: </B>This study was carried at SN facility and at a tertiary MS center. The study collected clinical, molecular (serum neurofilament light chain, sNfL and glial acidic fibrillary protein, sGFAP) and MRI quantitative lesion-, brain volume-, and tissue integrity-derived measures. Statistical analyses were controlled for multiple comparisons.<BR><B>RESULTS: </B>42 SD/SN and 42 DDM-CD were enrolled. SD/SN pwMS showed significantly lower cortical volume (CV) (p < 0.001, d = 1.375) and thalamic volume (p < 0.001, d = 0.972) compared to DDM-CD pwMS. In a logistic stepwise regression model, the SD/SN pwMS were best differentiated from the DDM-CD pwMS by lower CV (p < 0.001) as the only significant predictor, with the accuracy of 82.3%. No significant differences between the two groups were observed for medulla oblongata volume, a proxy for spinal cord atrophy and white matter lesion burden, while there was a statistical trend for numerically higher sGFAP in SD/SN pwMS.<BR><B>CONCLUSIONS: </B>The CASA-MS study showed significantly more gray matter atrophy in severe compared to less-severe progressive MS.