Regional microglial activation in the substantia nigra is linked with fatigue in MS.

Published on Sep 3, 2020in Neuroimmunology and Neuroinflammation7.724
· DOI :10.1212/NXI.0000000000000854
Tarun Singhal12
Estimated H-index: 12
Steven Cicero1
Estimated H-index: 1
+ 12 AuthorsHoward L. Weiner164
Estimated H-index: 164
Objective The goal of our study is to assess the role of microglial activation in MS-associated fatigue (MSAF) using [F-18]PBR06-PET. Methods Fatigue severity was measured using the Modified Fatigue Impact Scale (MFIS) in 12 subjects with MS (7 relapsing-remitting and 5 secondary progressive) and 10 healthy control participants who underwent [F-18]PBR06-PET. The MFIS provides a total fatigue score as well as physical, cognitive, and psychosocial fatigue subscale scores. Standardized Uptake Value (SUV) 60–90 minute frame PET maps were coregistered to 3T MRI. Voxel-by-voxel analysis using Statistical Parametric Mapping and atlas-based regional analyses were performed. SUV ratios (SUVRs) were global brain normalized. Results Peak voxel-based level of significance for correlation between total fatigue score and PET uptake was localized to the right substantia nigra (T-score 4.67, p = 0.001). Similarly, SUVRs derived from atlas-based segmentation of the substantia nigra showed significant correlation with MFIS (r = 0.76, p = 0.004). On multiple regression, the right substantia nigra was an independent predictor of total MFIS (p = 0.02) and cognitive MFIS subscale values (p = 0.007), after adjustment for age, disability, and depression. Several additional areas of significant correlations with fatigue scores were identified, including the right parahippocampal gyrus, right precuneus, and juxtacortical white matter (all p Conclusion Substantia nigra microglial activation is linked to fatigue in MS. Microglial activation across key brain regions may represent a unifying mechanism for MSAF, and further evaluation of neuroimmunologic basis of MSAF is warranted.
#1Anthony L. Komaroff (Brigham and Women's Hospital)H-Index: 69
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#1Tarun SinghalH-Index: 12
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#2Jan J.A. van den Dorpel (EUR: Erasmus University Rotterdam)H-Index: 2
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#2Charles R.G. Guttmann (Brigham and Women's Hospital)H-Index: 70
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#1Fabien Chauveau (University of Lyon)H-Index: 17
#2Guillaume Becker (University of Lyon)H-Index: 4
Last. Hervé Boutin (University of Manchester)H-Index: 26
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