Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter May 5, 2022

Evaluation of serum neurofilament light in the early management of mTBI patients

Samy Kahouadji, Jean-Baptiste Bouillon-Minois, Charlotte Oris, Julie Durif, Bruno Pereira, Jérémy Pinguet, Agathe Rozand, Jeannot Schmidt, Vincent Sapin and Damien Bouvier

Abstract

Objectives

Serum S100B allows a one-third reduction of computed tomography (CT) scans performed for mild traumatic brain injury (mTBI) patients. In this study, we evaluated the diagnostic performance of serum NF-L in the detection of intracranial lesions induced by mTBI.

Methods

One hundred seventy-nine adult mTBI patients presenting to the emergency department of Clermont-Ferrand University Hospital with a Glasgow Coma Scale (GCS) score of 14–15 were included. S100B assays were performed for clinical routine while NF-L samples were stored at −80 °C until analysis. CT scans were performed for patients with S100B levels above the decision threshold of 0.10 μg/L. Later, NF-L and S100B levels were compared to CT scan findings to evaluate the biomarkers’ performances.

Results

The area under the ROC curve (AUC) evaluating the diagnostic ability in the prediction of intracranial lesions was 0.72 (95% CI; 0.58–0.87) for S100B and 0.58 (95% CI; 0.45–0.71) for NF-L, the specificities (at a threshold allowing a 100% sensitivity) were 35.7% for S100B, and 28% for NF-L (p=0.096). AUCs of NF-L and S100B for the identification of patients with neurological disorders were statistically different (p<0.001). The AUCs were 0.87 (95% CI; 0.82–0.93) for NF-L and 0.57 (95% CI; 0.48–0.66) for S100B. There was a poor correlation between NF-L and S100B, and NF-L levels were correlated to patients’ age (Spearman coefficient of 0.79).

Conclusions

NF-L showed poor performances in the early management of mTBI patients. NF-L levels are strongly correlated to neurodegeneration, whether physiological, age-related, or pathological.


Corresponding author: Pr. Damien Bouvier, Service de Biochimie et Génétique Moléculaire, Centre de Biologie, CHU Gabriel Montpied, 58 Rue Montalembert, Clermont-Ferrand, 63000, France, Phone: +33 473754882, Fax: +33 473751855, E-mail:

  1. Research funding: None declared.

  2. Author contributions: SK and CO analyzed and interpreted the data. SK wrote the initial version of the manuscript. DB and VS designed the study and assisted with interpretation of the data and writing of the manuscript. JBBM and JS supervised the trial and data collection. SK, JD, AR, and JP carried out assays. BP provided statistical advice for the study design and analyzed the data. All the authors contributed to revision of the manuscript before submission. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: This research complied with the tenets of the Helsinki Declaration (as revised in 2013), and has received approval by the French Patient Protection Committee (CPP Ile-de-France X) (Reference 52–2019).

References

1. Cassidy, JD, Carroll, L, Peloso, P, Borg, J, von Holst, H, Holm, L, et al.. Incidence, risk factors and prevention of mild traumatic brain injury: results of the who collaborating centre task force on mild traumatic brain injury. J Rehabil Med 2004;36:28–60.https://doi.org/10.1080/16501960410023732.Search in Google Scholar

2. Tagliaferri, F, Compagnone, C, Korsic, M, Servadei, F, Kraus, J. A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien) 2006;148:255–68.https://doi.org/10.1007/s00701-005-0651-y.Search in Google Scholar

3. Mutch, CA, Talbott, JF, Gean, A. Imaging evaluation of acute traumatic brain injury. Neurosurg Clin 2016;27:409–39.https://doi.org/10.1016/j.nec.2016.05.011.Search in Google Scholar

4. Vos, PE, Alekseenko, Y, Battistin, L, Ehler, E, Gerstenbrand, F, Muresanu, DF, et al.. Mild traumatic brain injury: mild traumatic brain injury. Eur J Neurol 2012;19:191–8.https://doi.org/10.1111/j.1468-1331.2011.03581.x.Search in Google Scholar

5. Sapin, V, Gaulmin, R, Aubin, R, Walrand, S, Coste, A, Abbot, M. Blood biomarkers of mild traumatic brain injury: state of art. Neurochirurgie 2021;67:249–54.https://doi.org/10.1016/j.neuchi.2021.01.001.Search in Google Scholar

6. Stiell, IG, Wells, GA, Vandemheen, K, Clement, C, Lesiuk, H, Laupacis, A, et al.. The Canadian CT head rule for patients with minor head injury. Lancet 2001;357:1391–6.https://doi.org/10.1016/s0140-6736(00)04561-x.Search in Google Scholar

7. Perotte, R, Lewin, GO, Tambe, U, Galorenzo, JB, Vawdrey, DK, Akala, OO, et al.. Improving emergency department flow: reducing turnaround time for emergent CT scans. AMIA Annu Symp Proc 2018;2018:897–906.Search in Google Scholar

8. Jehlé, E, Honnart, D, Grasleguen, C, Bouget, J, Dejoux, C, Lestavel, P, et al.. Traumatisme crânien léger (score de Glasgow de 13 à 15) : triage, évaluation, examens complémentaires et prise en charge précoce chez le nouveau-né, l’enfant et l’adulte. Ann Fr Médecine Urgence. 2012;2:199–214.10.1007/s13341-012-0202-4Search in Google Scholar

9. Bouvier, D, Oris, C, Brailova, M, Durif, J, Sapin, V. Interest of blood biomarkers to predict lesions in medical imaging in the context of mild traumatic brain injury. Clin Biochem 2020;85:5–11. https://doi.org/10.1016/j.clinbiochem.2020.08.001.Search in Google Scholar PubMed

10. Allouchery, G, Moustafa, F, Roubin, J, Pereira, B, Schmidt, J, Raconnat, J, et al.. Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients. Clin Chem Lab Med 2018;56:1897–904. https://doi.org/10.1515/cclm-2018-0471.Search in Google Scholar PubMed

11. Biberthaler, P, Linsenmeier, U, Pfeifer, K-J, Kroetz, M, Mussack, T, Kanz, K-G, et al.. Serum S-100B concentration provides additional information for the indication of computed tomography in patients after minor head injury: a prospective multicenter study. Shock 2006;25:446–53. https://doi.org/10.1097/01.shk.0000209534.61058.35.Search in Google Scholar PubMed

12. Bouvier, D, Oddoze, C, Ben Haim, D, Moustafa, F, Legrand, A, Alazia, M, et al.. Intérêt du dosage sérique de la protéine S100B dans la prise en charge du patient après traumatisme crânien léger. Ann Biol Clin 2009;67:425–31. https://doi.org/10.1684/abc.2009.0347.Search in Google Scholar PubMed

13. Undén, J, Romner, B. Can low serum levels of S100B predict normal CT findings after minor head injury in adults? an evidence-based review and meta-analysis. J Head Trauma Rehabil 2010;25:228–40.10.1097/HTR.0b013e3181e57e22Search in Google Scholar PubMed

14. Anderson, RE, Hansson, LO, Nilsson, O, Dijlai-Merzoug, R, Settergren, G. High serum S100B levels for trauma patients without head injuries. Neurosurgery 2001;48:1255–8. discussion 1258-1260. https://doi.org/10.1227/00006123-200106000-00012.Search in Google Scholar

15. Kahouadji, S, Salamin, P, Praz, L, Coiffier, J, Frochaux, V, Durif, J, et al.. S100B blood level determination for early management of ski-related mild traumatic brain injury: a pilot study. Front Neurol 2020;11:856. https://doi.org/10.3389/fneur.2020.00856.Search in Google Scholar PubMed PubMed Central

16. Savola, O, Pyhtinen, J, Leino, TK, Siitonen, S, Niemelä, O, Hillbom, M. Effects of head and extracranial injuries on serum protein S100B levels in trauma patients. J Trauma 2004;56:1229–34. discussion 1234. https://doi.org/10.1097/01.ta.0000096644.08735.72.Search in Google Scholar PubMed

17. Undén, J, Romner, B. Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: an evidence and consensus-based update. BMC Med 2013;11. Available from: http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-50.10.1186/1741-7015-11-50Search in Google Scholar PubMed PubMed Central

18. Hoffman, PN, Cleveland, DW, Griffin, JW, Landes, PW, Cowan, NJ, Price, DL. Neurofilament gene expression: a major determinant of axonal caliber. Proc Natl Acad Sci U S A 1987;84:3472–6. https://doi.org/10.1073/pnas.84.10.3472.Search in Google Scholar PubMed PubMed Central

19. Friede, RL, Samorajski, T. Axon caliber related to neurofilaments and microtubules in sciatic nerve fibers of rats and mice. Anat Rec 1970;167:379–87. https://doi.org/10.1002/ar.1091670402.Search in Google Scholar PubMed

20. Yuan, A, Rao, MV, Veeranna, Nixon, RA. Neurofilaments and neurofilament proteins in health and disease. Cold Spring Harbor Perspect Biol 2017;9:a018309. https://doi.org/10.1101/cshperspect.a018309.Search in Google Scholar PubMed PubMed Central

21. Perrot, R, Berges, R, Bocquet, A, Eyer, J. Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration. Mol Neurobiol 2008;38:27–65. https://doi.org/10.1007/s12035-008-8033-0.Search in Google Scholar PubMed

22. Lépinoux-Chambaud, C, Eyer, J. Review on intermediate filaments of the nervous system and their pathological alterations. Histochem Cell Biol 2013;140:13–22.10.1007/s00418-013-1101-1Search in Google Scholar PubMed

23. Disanto, G, Barro, C, Benkert, P, Naegelin, Y, Schädelin, S, Giardiello, A, et al.. Serum Neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol 2017;81:857–70. https://doi.org/10.1002/ana.24954.Search in Google Scholar PubMed PubMed Central

24. Gauthier, A, Viel, S, Perret, M, Brocard, G, Casey, R, Lombard, C, et al.. Comparison of SimoaTM and EllaTM to assess serum neurofilament-light chain in multiple sclerosis. Ann Clin Transl Neurol 2021;8:1141–50. https://doi.org/10.1002/acn3.51355.Search in Google Scholar PubMed PubMed Central

25. Lu, C-H, Macdonald-Wallis, C, Gray, E, Pearce, N, Petzold, A, Norgren, N, et al.. Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 2015;84:2247–57. https://doi.org/10.1212/wnl.0000000000001642.Search in Google Scholar PubMed PubMed Central

26. Maggi, P, Kuhle, J, Schädelin, S, van der Meer, F, Weigel, M, Galbusera, R, et al.. Chronic white matter inflammation and serum neurofilament levels in multiple sclerosis. Neurology 2021;97:e543–53. https://doi.org/10.1212/WNL.0000000000012326.Search in Google Scholar PubMed PubMed Central

27. Mattsson, N, Andreasson, U, Zetterberg, H, Blennow, K, Alzheimer’s Disease Neuroimaging Initiative. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol 2017;74:557–66. https://doi.org/10.1001/jamaneurol.2016.6117.Search in Google Scholar PubMed PubMed Central

28. Laribi, S, Kansao, J, Borderie, D, Collet, C, Deschamps, P, Ababsa, R, et al.. S100B blood level measurement to exclude cerebral lesions after minor head injury: the multicenter STIC-S100 French study. Clin Chem Lab Med 2014;52:527–36. https://doi.org/10.1515/cclm-2013-0621.Search in Google Scholar PubMed

29. Oris, C, Bouillon-Minois, J-B, Pinguet, J, Kahouadji, S, Durif, J, Meslé, V, et al.. Predictive performance of blood S100B in the management of patients over 65 years old with mild traumatic brain injury. J Gerontol Biol Med Sci 2021;76:1471–9. https://doi.org/10.1093/gerona/glab055.Search in Google Scholar PubMed

30. Portela, LVC, Tort, ABL, Schaf, DV, Ribeiro, L, Nora, DB, Walz, R, et al.. The serum S100B concentration is age dependent. Clin Chem 2002;48:950–2.https://doi.org/10.1093/clinchem/48.6.950.Search in Google Scholar

31. Steiner, J, Schiltz, K, Walter, M, Wunderlich, MT, Keilhoff, G, Brisch, R, et al.. S100B serum levels are closely correlated with body mass index: an important caveat in neuropsychiatric research. Psychoneuroendocrinology 2010;35:321–4. https://doi.org/10.1016/j.psyneuen.2009.07.012.Search in Google Scholar PubMed

32. Polyakova, M, Sander, C, Arelin, K, Lampe, L, Luck, T, Luppa, M, et al.. First evidence for glial pathology in late life minor depression: S100B is increased in males with minor depression. Front Cell Neurosci 2015. http://doi.org/10.3389/fncel.2015.00406.10.3389/fncel.2015.00406Search in Google Scholar

33. Gazzolo, D. Pediatric concentrations of S100B protein in blood: age- and sex-related changes. Clin Chem 2003;49:967–70. https://doi.org/10.1373/49.6.967.Search in Google Scholar

34. 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;80:291–5. https://doi.org/10.1080/00365513.2020.1730434.Search in Google Scholar

35. Ray, P, Le Manach, Y, Riou, B, Houle, TT. Statistical evaluation of a biomarker. Anesthesiology 2010;112:1023–40. https://doi.org/10.1097/aln.0b013e3181d47604.Search in Google Scholar

36. Blomquist, S, Johnsson, P, Lührs, C, Malmkvist, G, Solem, JO, Alling, C, et al.. The appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgery: a possible marker for cerebral injury. J Cardiothorac Vasc Anesth 1997;11:699–703. https://doi.org/10.1016/s1053-0770(97)90160-9.Search in Google Scholar

37. Shahim, P, Gren, M, Liman, V, Andreasson, U, Norgren, N, Tegner, Y, et al.. Serum neurofilament light protein predicts clinical outcome in traumatic brain injury. Sci Rep 2016;6:36791. https://doi.org/10.1038/srep36791.Search in Google Scholar PubMed PubMed Central

38. Millecamps, S, Gowing, G, Corti, O, Mallet, J, Julien, J-P. Conditional NF-L transgene expression in mice for in vivo analysis of turnover and transport rate of neurofilaments. J Neurosci 2007;27:4947–56. https://doi.org/10.1523/jneurosci.5299-06.2007.Search in Google Scholar PubMed PubMed Central

39. Thelin, EP, Zibung, E, Riddez, L, Nordenvall, C. Assessing bicycle-related trauma using the biomarker S100B reveals a correlation with total injury severity. Eur J Trauma Emerg Surg 2016;42:617–25. https://doi.org/10.1007/s00068-015-0583-z.Search in Google Scholar PubMed

40. Carpenter, CR, Banerjee, J, Keyes, D, Eagles, D, Schnitker, L, Barbic, D, et al.. Accuracy of dementia screening instruments in emergency medicine – a diagnostic meta‐analysis. Acad Emerg Med 2019;26:226–45.Search in Google Scholar

41. Rockwood, K. Acute confusion in elderly medical patients. J Am Geriatr Soc 1989;37:150–4. https://doi.org/10.1111/j.1532-5415.1989.tb05874.x.Search in Google Scholar PubMed

Received: 2022-02-25
Accepted: 2022-04-20
Published Online: 2022-05-05
Published in Print: 2022-07-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Scroll Up Arrow