Document Type
Article
Publication Date
5-2-2024
Abstract
Objective: To investigate the association between blood–brain barrier permeability, brain metabolites, microstructural integrity of the white matter, and cognitive impairment (CI) in post-acute sequelae of SARS-COV-2 infection (PASC).
Methods: In this multimodal longitudinal MRI study 14 PASC participants with CI and 10 healthy controls were enrolled. All completed investigations at 3 months following acute infection (3 months ± 2 weeks SD), and 10 PASC participants completed at 12 months ± 2.22 SD weeks. The assessments included a standard neurological assessment, a cognitive screen using the brief CogState battery and multi-modal MRI derived metrics from Dynamic contrast enhanced (DCE) perfusion Imaging, Diffusion Tensor Imaging (DTI), and single voxel proton Magnetic Resonance Spectroscopy. These measures were compared between patients and controls and correlated with cognitive scores.
Results: At baseline, and relative to controls, PASC participants had higher K-Trans and Myo-inositol, and lower levels of Glutamate/Glutamine in the frontal white matter (FWM) (p < 0.01) as well as in brain stem (p < 0.05), and higher FA and lower MD in the FWM (p < 0.05). In PASC participants, FA and MD decreased in the FWM at 12 months compared to baseline (p < 0.05). K-Trans and metabolite concentrations did not change significantly over time. Neurocognitive scores did not correlation with the increased permeability (K trans).
Interpretation: PASC with CI is associated with BBB impairment, loss of WM integrity, and inflammation at 3 months which significantly but not uniformly improved at 12 months. The loss of WM integrity is possibly mediated by BBB impairment and associated glutamatergic excitotoxicity.
Recommended Citation
Chaganti, Joga; Poudel, Govinda; Cysique, Lucette Adeline; Dore, Gregory J; Kelleher, Anthony; Matthews, Gael; Darley, David; Byrne, Anthony; Jakabek, David; Zhang, Xin; Lewis, Marrissa; Jha, Nikhil; and Brew, Bruce James, "Blood Brain Barrier Disruption and Glutamatergic Excitotoxicity in Post-Acute Sequelae of SARS COV-2 Infection Cognitive Impairment: Potential Biomarkers and a Window into Pathogenesis" (2024). Department of Medicine Faculty Papers. Paper 451.
https://jdc.jefferson.edu/medfp/451
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
38756214
Language
English
Comments
This article, first published by Frontiers Media, is the author's final published version in Frontiers in Neurology, Volume 15, 2024, Article number 1350848.
The published version is available at https://doi.org/10.3389/fneur.2024.1350848.
Copyright © 2024 Chaganti, Poudel, Cysique, Dore, Kelleher, Matthews, Darley, Byrne, Jakabek, Zhang, Lewis, Jha and Brew