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

Tarun Singhal, Steven Cicero, Hong Pan, Kelsey Carter, Shipra Dubey, Renxin Chu, Bonnie Glanz, Shelley Hurwitz, Shahamat Tauhid, Mi Ae Park, Marie Kijewski, Emily Stern, Rohit Bakshi, David Silbersweig, Howard L. Weiner

Research output: Contribution to journalArticlepeer-review

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 < 0.05). There was no correlation between fatigue scores and brain atrophy and lesion load in patients with MS. 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.

Original languageEnglish (US)
JournalNeurology(R) neuroimmunology & neuroinflammation
Volume7
Issue number5
DOIs
StatePublished - Sep 3 2020
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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