Serum Neurofilament Identifies Patients With Multiple Sclerosis With Severe Focal Axonal Damage in a 6-Year Longitudinal Cohort.
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
06
06
2022
accepted:
16
09
2022
entrez:
21
11
2022
pubmed:
22
11
2022
medline:
24
11
2022
Statut:
epublish
Résumé
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]). 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). 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 sNfL levels associate with severe focal axonal damage as reflected by development of persistent T1 lesions. Baseline sNfL values predicted NEDA-3
Sections du résumé
BACKGROUND AND OBJECTIVES
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
DISCUSSION
sNfL levels associate with severe focal axonal damage as reflected by development of persistent T1 lesions. Baseline sNfL values predicted NEDA-3
Identifiants
pubmed: 36411080
pii: 10/1/e200055
doi: 10.1212/NXI.0000000000200055
pmc: PMC9679887
pii:
doi:
Types de publication
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Nat Chem Biol. 2022 Sep;18(9):925-933
pubmed: 35995862
Arch Neurol. 2008 Nov;65(11):1449-53
pubmed: 19001162
Ann Clin Transl Neurol. 2018 Oct 16;5(12):1478-1491
pubmed: 30564615
Neurol Neuroimmunol Neuroinflamm. 2020 Feb 5;7(3):
pubmed: 32024782
Stroke. 2019 Nov;50(11):3077-3084
pubmed: 31537188
Mult Scler. 1999 Aug;5(4):283-6
pubmed: 10467389
J Neurol. 2018 Mar;265(3):522-529
pubmed: 29327284
Ann Neurol. 1999 Nov;46(5):747-54
pubmed: 10553992
Neuroimage. 2012 Feb 15;59(4):3774-83
pubmed: 22119648
Cell. 2020 Mar 19;180(6):1067-1080.e16
pubmed: 32160527
Neurology. 2003 Dec 23;61(12):1720-5
pubmed: 14694036
Eur J Neurol. 2017 Jan;24(1):112-121
pubmed: 27699930
Expert Rev Neurother. 2018 Mar;18(3):203-219
pubmed: 29411688
Neurology. 2016 Sep 13;87(11):1076-84
pubmed: 27521440
Nat Neurosci. 2017 May;20(5):674-680
pubmed: 28288125
J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):93-9
pubmed: 25904813
Trends Neurosci. 2016 May;39(5):325-339
pubmed: 26987259
Neurology. 2015 Apr 21;84(16):1639-43
pubmed: 25809304
Lancet Neurol. 2018 Feb;17(2):162-173
pubmed: 29275977
EBioMedicine. 2021 Oct;72:103590
pubmed: 34571362
BioDrugs. 2021 Jan;35(1):47-60
pubmed: 33400237
Neurol Neuroimmunol Neuroinflamm. 2019 Apr 08;6(3):e555
pubmed: 31119188
Brain. 2018 Aug 1;141(8):2382-2391
pubmed: 29860296
Neurology. 2014 Jul 15;83(3):278-86
pubmed: 24871874
Mult Scler. 2020 Nov;26(13):1670-1681
pubmed: 31610732
Front Neurol. 2022 Jul 12;13:917527
pubmed: 35911894
JAMA Neurol. 2019 Nov 01;76(11):1359-1366
pubmed: 31403661
Eur J Neurol. 2017 May;24(5):703-712
pubmed: 28261960
JAMA Neurol. 2018 Jul 1;75(7):781-782
pubmed: 29800951
Brain. 2009 May;132(Pt 5):1175-89
pubmed: 19339255
Acta Neurol Scand. 2014 Aug;130(2):81-9
pubmed: 24571714
Mult Scler. 2016 Oct;22(12):1550-1559
pubmed: 26754800
Neurol Neuroimmunol Neuroinflamm. 2020 Feb 4;7(3):
pubmed: 32019769
Neurol Neuroimmunol Neuroinflamm. 2019 Aug 08;6(5):e598
pubmed: 31516913
Nat Rev Neurol. 2018 Oct;14(10):577-589
pubmed: 30171200
Eur J Neurol. 2015 Aug;22(8):1169-75
pubmed: 25324032
Prog Neurobiol. 2019 Nov;182:101663
pubmed: 31374243
JAMA. 2019 Jan 15;321(2):175-187
pubmed: 30644981
Nat Rev Neurosci. 2018 Oct;19(10):599-609
pubmed: 30158590
Neurology. 2017 Feb 28;88(9):826-831
pubmed: 28148632
Ann Neurol. 2001 Jun;49(6):793-6
pubmed: 11409432
Mult Scler. 2016 Sep;22(10):1297-305
pubmed: 26585439
Mult Scler. 2021 Jan;27(1):52-60
pubmed: 31961243
Neurology. 2020 Sep 8;95(10):436-444
pubmed: 32675076
Brain. 2021 Nov 29;144(10):2954-2963
pubmed: 34180982
Neurology. 2017 Nov 28;89(22):2230-2237
pubmed: 29079686
Brain. 2016 Sep;139(Pt 9):2395-405
pubmed: 27401521
Mult Scler. 2020 May;26(6):659-667
pubmed: 30912689
Lancet Neurol. 2019 Jun;18(6):573-586
pubmed: 30981640
EBioMedicine. 2020 Jun;56:102807
pubmed: 32460167
Ann Neurol. 2017 Jun;81(6):857-870
pubmed: 28512753
Acta Neurol Scand. 2010 Jul;122(1):1-8
pubmed: 20003089
Mult Scler. 2019 Apr;25(5):678-686
pubmed: 29542376
J Neurol Neurosurg Psychiatry. 2016 Feb;87(2):126-9
pubmed: 25716934