Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_6A4C8678004D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis.
Journal
Neurology
Author(s)
Maggi P., Kuhle J., Schädelin S., van der Meer F., Weigel M., Galbusera R., Mathias A., Lu P.J., Rahmanzadeh R., Benkert P., La Rosa F., Bach Cuadra M., Sati P., Théaudin M., Pot C., van Pesch V., Leppert D., Stadelmann C., Kappos L., Du Pasquier R., Reich D.S., Absinta M., Granziera C.
ISSN
1526-632X (Electronic)
ISSN-L
0028-3878
Publication state
Published
Issued date
10/08/2021
Peer-reviewed
Oui
Volume
97
Number
6
Pages
e543-e553
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
To assess whether chronic white matter inflammation in patients with multiple sclerosis (MS) as detected in vivo by paramagnetic rim MRI lesions (PRLs) is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuroaxonal damage.
In 118 patients with MS with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathologic evaluation was performed in 25 MS lesions from 20 additional autopsy MS cases.
In univariable analyses, participants with ≥2 PRLs (n = 43) compared to those with ≤1 PRL (n = 75) had higher age-adjusted sNfL percentiles (median, 91 and 68; p < 0.001) and higher Multiple Sclerosis Severity Scale scores (MSSS median, 4.3 and 2.4; p = 0.003). In multivariable analyses, sNfL percentile levels were higher in PRLs ≥2 cases (β <sub>add</sub> , 16.3; 95% confidence interval [CI], 4.6-28.0; p < 0.01), whereas disease-modifying treatment (DMT), Expanded Disability Status Scale (EDSS) score, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRLs (n = 30; β <sub>add</sub> , 30.4; 95% CI, 15.6-45.2; p < 0.01). Subsequent multivariable analysis revealed that PRLs ≥2 cases also had higher MSSS (β <sub>add</sub> , 1.1; 95% CI, 0.3-1.9; p < 0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center: p = 0.004 and p = 0.0002, respectively).
Chronic white matter inflammation was associated with increased levels of sNfL and disease severity in nonacute MS, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.
Keywords
Adult, Axons/pathology, Female, Humans, Inflammation/blood, Inflammation/diagnostic imaging, Inflammation/pathology, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis/blood, Multiple Sclerosis/diagnostic imaging, Multiple Sclerosis/pathology, Multiple Sclerosis/physiopathology, Neurofilament Proteins/blood, Severity of Illness Index, White Matter/diagnostic imaging, White Matter/pathology
Pubmed
Web of science
Open Access
Yes
Create date
15/06/2021 15:08
Last modification date
21/11/2022 8:31
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