In:
Neurology - Neuroimmunology Neuroinflammation, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 1 ( 2023-01), p. e200055-
Abstract:
Immunomodulatory therapies reduce the relapse rate but only marginally control disability progression in patients with MS. Although serum neurofilament light chain (sNfL) levels correlate best with acute signs of inflammation (e.g., relapses and gadolinium-enhancing [Gd+] lesions), their role in predicting progressive biology and irreversible axonal damage is less clear. We aimed to determine the ability of sNfL to dissect distinct measures of disease severity and predict future (no) evidence of disease activity (EDA/no evidence of disease activity [NEDA] ). Methods One hundred fifty-three of 221 patients with relapsing-remitting MS initially enrolled in the Neurofilament and longterm outcome in MS cohort at the MS outpatient clinic of the University Medical Center Mainz (Germany) met the inclusion criteria for this prospective observational cohort study with a median follow-up of 6 years (interquartile range 4–7 years). Progressive disease forms were excluded. Inclusion criteria consisted of Expanded Disability Status Scale (EDSS) assessment within 3 months and MRI within 12 months around blood sampling at baseline (y0) and follow-up (y6). EDSS progression at y6 had to be confirmed 12 weeks later. sNfL was measured by single-molecule array, and the following additional variables were recorded: therapy, medical history, and detailed MRI parameters (T2 hyperintense lesions, Gd+ lesions, and new persistent T1 hypointense lesions). Results Patients experiencing EDSS progression or new persistent T1 lesions at y6 showed increased sNfL levels at y0 compared with stable patients or patients with inflammatory activity only. As a potential readily accessible marker of neurodegeneration, we incorporated the absence of persistent T1 lesions to the NEDA-3 concept (NEDA-3 T1 : n = 54, 35.3%; EDA T1 : n = 99, 64.7%) and then evaluated a risk score with factors that distinguish patients with and without NEDA-3 T1 status. Adding sNfL to this risk score significantly improved NEDA-3 T1 prediction (0.697 95% CI 0.616–0.770 vs 0.819 95% CI 0.747–0.878, p 〈 0.001). Patients with sNfL values ≤8.6 pg/mL showed a 76% risk reduction for EDA T1 at y6 (hazard ratio 0.244, 95% CI 0.142–0.419, p 〈 0.001). Discussion sNfL levels associate with severe focal axonal damage as reflected by development of persistent T1 lesions. Baseline sNfL values predicted NEDA-3 T1 status at 6-year follow-up.
Type of Medium:
Online Resource
ISSN:
2332-7812
DOI:
10.1212/NXI.0000000000200055
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2023
detail.hit.zdb_id:
2767740-0
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