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Subcortical volumes as early predictors of fatigue in multiple sclerosis

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Item Type:Article
Title:Subcortical volumes as early predictors of fatigue in multiple sclerosis
Creators Name:Fleischer, V. and Ciolac, D. and Gonzalez-Escamilla, G. and Grothe, M. and Strauss, S. and Molina Galindo, L.S. and Radetz, A. and Salmen, A. and Lukas, C. and Klotz, L. and Meuth, S.G. and Bayas, A. and Paul, F. and Hartung, H.P. and Heesen, C. and Stangel, M. and Wildemann, B. and Bergh, F.T. and Tackenberg, B. and Kümpfel, T. and Zettl, U.K. and Knop, M. and Tumani, H. and Wiendl, H. and Gold, R. and Bittner, S. and Zipp, F. and Groppa, S. and Muthuraman, M.
Abstract:OBJECTIVE: Fatigue is a frequent and severe symptom in multiple sclerosis (MS), but its pathophysiological origin remains incompletely understood. We aimed to examine the predictive value of subcortical gray matter volumes for fatigue severity at disease onset and after four years by applying structural equation modeling (SEM). METHODS: This multi-center cohort study included 601 treatment-naive MS patients after the first demyelinating event. All patients underwent a standardized 3T MRI protocol. A subgroup of 230 patients with available clinical follow-up data after four years was also analyzed. Associations of subcortical volumes (included into SEM) with MS-related fatigue were studied regarding their predictive value. In addition, subcortical regions that have a central role in the brain network (hubs) were determined through structural covariance network (SCN) analysis. RESULTS: Predictive causal modeling identified volumes of the caudate (s [standardized path coefficient]=0.763, p=0.003 [left]; s=0.755, p=0.006 [right]), putamen (s=0.614, p=0.002 [left]; s=0.606, p=0.003 [right]) and pallidum (s=0.606, p=0.012 [left]; s=0.606, p=0.012 [right]) as prognostic factors for fatigue severity in the cross-sectional cohort. Moreover, the volume of the pons was additionally predictive for fatigue severity in the longitudinal cohort (s=0.605, p=0.013). In the SCN analysis, network hubs in patients with fatigue worsening were detected in the putamen (p=0.008 [left]; p=0.007 [right]) and pons (p=0.0001). INTERPRETATION: We unveiled predictive associations of specific subcortical gray matter volumes with fatigue in an early and initially untreated MS cohort. The colocalization of these subcortical structures with network hubs suggests an early role of these brain regions in terms of fatigue evolution.
Keywords:Brain, Cohort Studies, Cross-Sectional Studies, Demyelinating Diseases, Fatigue, Follow-Up Studies, Gray Matter, Longitudinal Studies, Magnetic Resonance Imaging, Multiple Sclerosis, Nerve Net, Pons, Predictive Value of Tests, Prognosis, Putamen, Young Adult
Source:Annals of Neurology
Page Range:192-202
Date:February 2022
Official Publication:https://doi.org/10.1002/ana.26290
PubMed:View item in PubMed

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