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
Sources
Abstract
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.
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#2Kelsey O’ConnorH-Index: 2
Last. Rohit BakshiH-Index: 79
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#1Alvino BiseccoH-Index: 17
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#1Moussa A. Chalah (University of Paris)H-Index: 14
#2Samar S. Ayache (University of Paris)H-Index: 25
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#1Tarun Singhal (Brigham and Women's Hospital)H-Index: 12
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Objective: To assess the utility of [F-18]PBR06 for noninvasive assessment of 18 kDa translocator protein (TSPO) binding in multiple sclerosis (MS). Background: [F-18]PBR06 is a second-generation PET radioligand targeting TSPO for the assessment of cerebral microglial activation. Previously used TSPO-PET tracers such [C-11]PBR28 and [C-11]PK11195 are limited due to low image counts and short radioisotope half-life. Design/Methods: Ten MS (8 RR and 2 SP, EDSS (mean±SD) 2.9±2.1, range 1.0–6.5; and...
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#1Fabien Chauveau (University of Lyon)H-Index: 17
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PURPOSE The prototypical TSPO radiotracer (R)-[11C]PK11195 has been used in humans for more than thirty years to visualize neuroinflammation in several pathologies. Alternative radiotracers have been developed to improve signal-to-noise ratio and started to be tested clinically in 2008. Here we examined the scientific value of these "(R)-[11C]PK11195 challengers" in clinical research to determine if they could supersede (R)-[11C]PK11195. METHODS A systematic MEDLINE (PubMed) search was performed...
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