Performance of serum neurofilament light chain in a wide spectrum of clinical courses of amyotrophic lateral sclerosis-a cross-sectional multicenter study.
amyotrophic lateral sclerosis (ALS)
long disease duration
sNfL Z score
serum neurofilament light chain (sNfL)
tracheostomy invasive ventilation (TIV)
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
15
01
2023
received:
29
11
2022
accepted:
06
03
2023
medline:
8
5
2023
pubmed:
11
3
2023
entrez:
10
3
2023
Statut:
ppublish
Résumé
The objective was to assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of progression, duration and tracheostomy invasive ventilation (TIV). A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations were age adjusted using sNfL Z scores expressing the number of standard deviations from the mean of a control reference database and correlated to ALS duration and ALS progression rate (ALS-PR), defined by the decline of the ALS Functional Rating Scale. In the total ALS cohort (n = 1378) the sNfL Z score was elevated (3.04; 2.46-3.43; 99.88th percentile). There was a strong correlation of sNfL Z score with ALS-PR (p < 0.001). In patients with long (5-10 years, n = 167) or very long ALS duration (>10 years, n = 94) the sNfL Z score was significantly lower compared to the typical ALS duration of <5 years (n = 1059) (p < 0.001). Furthermore, in patients with TIV, decreasing sNfL Z scores were found in correlation with TIV duration and ALS-PR (p = 0.002; p < 0.001). The finding of moderate sNfL elevation in patients with long ALS duration underlined the favorable prognosis of low sNfL. The strong correlation of sNfL Z score with ALS-PR strengthened its value as progression marker in clinical management and research. The lowering of sNfL in correlation with long TIV duration could reflect a reduction either in disease activity or in the neuroaxonal substrate of biomarker formation during the protracted course of ALS.
Sections du résumé
BACKGROUND AND PURPOSE
The objective was to assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of progression, duration and tracheostomy invasive ventilation (TIV).
METHODS
A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations were age adjusted using sNfL Z scores expressing the number of standard deviations from the mean of a control reference database and correlated to ALS duration and ALS progression rate (ALS-PR), defined by the decline of the ALS Functional Rating Scale.
RESULTS
In the total ALS cohort (n = 1378) the sNfL Z score was elevated (3.04; 2.46-3.43; 99.88th percentile). There was a strong correlation of sNfL Z score with ALS-PR (p < 0.001). In patients with long (5-10 years, n = 167) or very long ALS duration (>10 years, n = 94) the sNfL Z score was significantly lower compared to the typical ALS duration of <5 years (n = 1059) (p < 0.001). Furthermore, in patients with TIV, decreasing sNfL Z scores were found in correlation with TIV duration and ALS-PR (p = 0.002; p < 0.001).
CONCLUSIONS
The finding of moderate sNfL elevation in patients with long ALS duration underlined the favorable prognosis of low sNfL. The strong correlation of sNfL Z score with ALS-PR strengthened its value as progression marker in clinical management and research. The lowering of sNfL in correlation with long TIV duration could reflect a reduction either in disease activity or in the neuroaxonal substrate of biomarker formation during the protracted course of ALS.
Substances chimiques
Biomarkers
0
Neurofilament Proteins
0
Types de publication
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1600-1610Informations de copyright
© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Références
Turner MR, Hardiman O, Benatar M, et al. Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurology. 2013;12:310-322.
Hardiman O, Al-Chalabi A, Chio A, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017;3:17071.
Chiò A, Logroscino G, Hardiman O, et al. Prognostic factors in ALS: a critical review. Amyotroph Lateral Scler. 2009;10:310-323.
Bianchi E, Pupillo E, de Feudis A, Enia G, Vitelli E, Beghi E. Trends in survival of ALS from a population-based registry. Amyotroph Lateral Scler Frontotemporal Degener. 2021;23:1-9.
Benatar M, Zhang L, Wang L, et al. Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Neurology. 2020;95:e59-e69.
Feneberg E, Oeckl P, Steinacker P, et al. Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology. 2018;90:e22-e30.
Steinacker P, Feneberg E, Weishaupt J, et al. Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. J Neurol Neurosurg Psychiatry. 2016;87:12-20.
Thouvenot E, Demattei C, Lehmann S, et al. Serum neurofilament light chain at time of diagnosis is an independent prognostic factor of survival in amyotrophic lateral sclerosis. Eur J Neurol. 2020;27:251-257.
Vacchiano V, Mastrangelo A, Zenesini C, et al. Plasma and CSF neurofilament light chain in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study. Front Aging Neurosci. 2021;13:753242.
Ashton NJ, Janelidze S, Al Khleifat A, et al. A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. 2021;12:3400.
Behzadi A, Pujol-Calderón F, Tjust AE, et al. Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics. Sci Rep. 2021;11:22128.
Dreger M, Steinbach R, Gaur N, et al. Cerebrospinal fluid neurofilament light chain (NfL) predicts disease aggressiveness in amyotrophic lateral sclerosis: an application of the D50 disease progression model. Front Neurosci. 2021;15:651651.
Poesen K, de Schaepdryver M, Stubendorff B, et al. Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease. Neurology. 2017;88:2302-2309.
Zhang L, Ji T, Wu C, et al. Serum neurofilament light chain levels may be a marker of lower motor neuron damage in amyotrophic lateral sclerosis. Front Neurol. 2022;13:833507.
Thompson AG, Gray E, Verber N, et al. Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain. Brain Commun. 2022;4:fcac029.
Verde F, Otto M, Silani V. Neurofilament light chain as biomarker for amyotrophic lateral sclerosis and frontotemporal dementia. Front Neurosci. 2021;15:679199.
Poesen K, van Damme P. Diagnostic and prognostic performance of neurofilaments in ALS. Front Neurol. 2018;9:1167.
Miller TM, Cudkowicz ME, Shaw PJ, et al. Phase 1-2 trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med. 2020;383:109-119.
Miller TM, Cudkowicz ME, Genge A, et al. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med. 2022;387:1099-1110.
Huang F, Zhu Y, Hsiao-Nakamoto J, et al. Longitudinal biomarkers in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2020;7:1103-1116.
Verde F, Steinacker P, Weishaupt JH, et al. Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2019;90:157-164.
Steinacker P, Huss A, Mayer B, et al. Diagnostic and prognostic significance of neurofilament light chain NF-L, but not progranulin and S100B, in the course of amyotrophic lateral sclerosis: data from the German MND-net. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18:112-119.
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453-1457.
Shefner JM, Al-Chalabi A, Baker MR, et al. A proposal for new diagnostic criteria for ALS. Clin Neurophysiol. 2020;131:1975-1978.
Gordon PH, Cheng B, Katz IB, et al. The natural history of primary lateral sclerosis. Neurology. 2006;66:647-653.
Fürstenau D, Klein S, Vogel A, Auschra C. Multi-sided platform and data-driven care research. Electron Markets. 2021;31:811-828.
Meyer T, Kettemann D, Maier A, et al. Symptomatic pharmacotherapy in ALS: data analysis from a platform-based medication management programme. J Neurol Neurosurg Psychiatry. 2020;91:783-785.
Khalil M, Pirpamer L, Hofer E, et al. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat Commun. 2020;11:812.
Benkert P, Meier S, Schaedelin S, et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurology. 2022;21:246-257.
Cedarbaum JM, Stambler N, Malta E, et al. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS study group (phase III). J Neurol Sci. 1999;169:13-21.
Kimura F, Fujimura C, Ishida S, et al. Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS. Neurology. 2006;66:265-267.
Rossi D, Volanti P, Brambilla L, Colletti T, Spataro R, La Bella V. CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis. J Neurol. 2018;265:510-521.
Hviid CVB, Knudsen CS, Parkner T. Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults. Scand J Clin Lab Invest. 2020;80:291-295.
Tortelli R, Copetti M, Ruggieri M, et al. Cerebrospinal fluid neurofilament light chain levels: marker of progression to generalized amyotrophic lateral sclerosis. Eur J Neurol. 2015;22:215-218.
Steinacker P, Verde F, Fang L, et al. Chitotriosidase (CHIT1) is increased in microglia and macrophages in spinal cord of amyotrophic lateral sclerosis and cerebrospinal fluid levels correlate with disease severity and progression. J Neurol Neurosurg Psychiatry. 2018;89:239-247.
Gong Z-Y, Lv G-P, Gao L-N, Lu Y, Guo J, Zang D-W. Neurofilament subunit L levels in the cerebrospinal fluid and serum of patients with amyotrophic lateral sclerosis. Neurodegener Dis. 2018;18:165-172.
Scarafino A, D'Errico E, Introna A, et al. Diagnostic and prognostic power of CSF tau in amyotrophic lateral sclerosis. J Neurol. 2018;265:2353-2362.
Spittel S, Maier A, Kettemann D, et al. Non-invasive and tracheostomy invasive ventilation in amyotrophic lateral sclerosis: utilization and survival rates in a cohort study over 12 years in Germany. Eur J Neurol. 2021;28:1160-1171.
Wicks P, Massagli MP, Wolf C, Heywood J. Measuring function in advanced ALS: validation of ALSFRS-EX extension items. Eur J Neurol. 2009;16:353-359.
Kettemann D, Funke A, Maier A, et al. Clinical characteristics and course of dying in patients with amyotrophic lateral sclerosis withdrawing from long-term ventilation. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18:53-59.
Nishihira Y, Tan C-F, Toyoshima Y, et al. Sporadic amyotrophic lateral sclerosis: widespread multisystem degeneration with TDP-43 pathology in a patient after long-term survival on a respirator. Neuropathology. 2009;29:689-696.
Ito J, Shimada T, Tada M, et al. Clinicopathologic features of two patients with sporadic amyotrophic lateral sclerosis who maintained communication ability for over 30 years. J Neuropathol Exp Neurol. 2018;77:981-986.
Mochizuki Y, Hayashi K, Nakayama Y, et al. ALS patients with ability to communicate after long-term mechanical ventilation have confined degeneration to the motor neuron system. J Neurol Sci. 2016;363:245-248.
Wurster CD, Steinacker P, Günther R, et al. Neurofilament light chain in serum of adolescent and adult SMA patients under treatment with nusinersen. J Neurol. 2020;267:36-44.