Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation

Chiarelli, Antonio Maria, Villani, Alessandro, Mascali, Daniele, Petsas, Nikolaos, Biondetti, Emma, Caporale, Alessandra, Digiovanni, Anna, Grasso, Eleonora Agata, Ajdinaj, Paola, D’Apolito, Maria, Rispoli, Marianna Gabriella, Sensi, Stefano, Murphy, Kevin ORCID: https://orcid.org/0000-0002-6516-313X, Pozzilli, Carlo, Wise, Richard G. ORCID: https://orcid.org/0000-0003-1700-2144 and Tomassini, Valentina ORCID: https://orcid.org/0000-0002-7368-6280 2022. Cerebrovascular reactivity in multiple sclerosis is restored with reduced inflammation during immunomodulation. Scientific Reports 12 (1) , 15453. 10.1038/s41598-022-19113-8

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Abstract

Cerebrovascular reactivity (CVR) reflects the capacity of the brain’s vasculature to increase blood flow following a vasodilatory stimulus. Reactivity is an essential property of the brain’s blood vessels that maintains nutrient supplies in the face of changing demand. In Multiple Sclerosis (MS), CVR may be diminished with brain inflammation and this may contribute to neurodegeneration. We test the hypothesis that CVR is altered with MS neuroinflammation and that it is restored when inflammation is reduced. Using a breath-hold task during functional Magnetic Resonance Imaging (MRI), we mapped grey matter and white matter CVRs (CVRGM and CVRWM, respectively) in 23 young MS patients, eligible for disease modifying therapy, before and during Interferon beta treatment. Inflammatory activity was inferred from the presence of Gadolinium enhancing lesions at MRI. Eighteen age and gender-matched healthy controls (HC) were also assessed. Enhancing lesions were observed in 12 patients at the start of the study and in 3 patients during treatment. Patients had lower pre-treatment CVRGM (p = 0.04) and CVRWM (p = 0.02) compared to HC. In patients, a lower pre-treatment CVRGM was associated with a lower GM volume (r = 0.60, p = 0.003). On-treatment, there was an increase in CVRGM (p = 0.02) and CVRWM (p = 0.03) that negatively correlated with pre-treatment CVR (GM: r = − 0.58, p = 0.005; WM: r = − 0.60, p = 0.003). CVR increased when enhancing lesions reduced in number (GM: r = − 0.48, p = 0.02, WM: r = − 0.62, p = 0.003). Resolution of inflammation may restore altered cerebrovascular function limiting neurodegeneration in MS. Imaging of cerebrovascular function may thereby inform tissue physiology and improve treatment monitoring.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine Physics and Astronomy Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
Date of First Compliant Deposit:	16 September 2022
Date of Acceptance:	24 August 2022
Last Modified:	10 May 2023 21:36
URI:	https://orca.cardiff.ac.uk/id/eprint/152646

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