Panamerican Journal of Trauma, Critical Care & Emergency Surgery

Register      Login

VOLUME 9 , ISSUE 2 ( May-August, 2020 ) > List of Articles


Utility of S-100B as a Potential Tool for Neuromonitoring and Prediction of Neuroworsening in Acute Phase of Traumatic Brain Injury

Alexander Rodríguez, Eliana Cervera, Gigliola Macchia, Xilene Mendoza, Walter Martínez, Osmar Pérez, Homero Sanjuán, Pedro Villalba

Citation Information : Rodríguez A, Cervera E, Macchia G, Mendoza X, Martínez W, Pérez O, Sanjuán H, Villalba P. Utility of S-100B as a Potential Tool for Neuromonitoring and Prediction of Neuroworsening in Acute Phase of Traumatic Brain Injury. Panam J Trauma Crit Care Emerg Surg 2020; 9 (2):105-113.

DOI: 10.5005/jp-journals-10030-1288

License: CC BY-NC 4.0

Published Online: 03-09-2020

Copyright Statement:  Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.


Aim: In this review, we summarize the evidence on the use of S-100B in traumatic brain injury (TBI) of all severities, its clinical significance, and its prognostic value in the different posttrauma phases. Background: Most of the published studies report the serum determination of S-100B in the context of mild TBI as a predictor of positive CT scan, which represents a valuable tool when establishing a criterion to indicate the performance of the CT and decide the medical discharge. Likewise, we have reported several studies that correlate S-100B with the clinical evolution of the patient with severe TBI, showing an excellent indicator of intracranial hypertension. However, there are few studies that report on the impact of S-100B as a predictor of neuroworsening in the acute phase in moderate TBI. Review results: Traumatic brain injury comprises a heterogeneous group of traumatic injuries that can evolve progressively. Almost 90% of head injuries that reach the hospital are mild head injuries or mild TBI, which is defined by a score of more than 12 on the Glasgow Coma Scale (GCS). Of this, a few can be accompanied by a hemorrhagic lesion that can be detected by further imaging techniques. Still, utilizing these techniques in every single patient that comes to the ER does not only take a toll on the finances of the hospital but, more importantly, also exposes the patients to unnecessary radiation. There are still difficulties to correlate the findings on imaging with secondary injury, and to predict the clinical evolution in the acute phase and in the long-term. Serum S-100B levels have shown high sensibility and negative predictive value (NPV) for intracranial complications after mild head injury. Most of the published studies report that measurement in serum of S-100B in the context of mild TBI, as a predictor of CT findings, represents a valuable tool when establishing a criterion for indication of CT and to decide medical discharge. However, there are few studies that report the impact of S-100B as a predictor of neuroworsening in the acute phase of moderate TBI, which is defined by a score between 9 and 12 on the GCS. Conclusion: Serum S-100B is a useful marker of brain damage in TBI. Its usefulness has been studied mainly as a support to evaluate the need to perform a CT scan in mild TBI, and to monitor patients with moderate-to-severe TBI, in order to predict the outcome and validate the response to treatment. This review highlights S-100B as a versatile marker whose clinical utility depends on the severity of the head trauma. In this way, S-100B would be a potential predictor of neuroworsening in the acute phase in moderate TBI. Clinical significance: Despite its valuable utility as a predictor of positive CT in mild TBI, and as a tool for neuromonitoring in established severe TBI, the greater utility of S-100B could be as a predictor of neuroworsening in the acute phase in the moderate TBI.

PDF Share
  1. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS [Internet] 2010;5(6):463–466. DOI: 10.1097/COH.0b013e32833ed177. Available from:
  2. Chau CH, Rixe O, McLeod H, et al. Validation of analytic methods for biomarkers used in drug development. Clin Cancer Res [Internet] 2008;14(19):5967–5976. DOI: 10.1158/1078-0432.CCR-07-4535. Available from:
  3. Dadas A, Washington J, Diaz-Arrastia R, et al. Neuropsychiatric Disease and Treatment Dovepress Biomarkers in traumatic brain injury (TBi): a review. Neuropsychiatr Dis Treat. 2018. 2989–3000. DOI: 10.2147/NDT.S125620.
  4. Matis G, Birbilis T. The Glasgow coma scale–a brief review. Past, Present, Future Acta Neurol Belg [Internet] 2008;108(3):75–89. Available from:
  5. Maas AIR, Menon DK, Adelson PD, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol [Internet] 2017;16(12):987–1048. DOI: 10.1016/S1474-4422(17)30371-X. Available from:
  6. Haacke EM, Duhaime AC, Gean AD, et al. Common data elements in radiologic imaging of traumatic brain injury. J Magn Reson Imaging [Internet] 2010;32(3):516–543. DOI: 10.1002/jmri.22259. Available from:
  7. Rodríguez A, Cervera E, Valencia G, et al. Revisión de tema: Biomarcadores neuronales y gliales como estrategia de clasificación cuantitativa de la severidad del trauma craneoencefálico. Rev Científica Salud Uninorte 2016;32(2):302–318. DOI: 10.14482/sun.32.2.8835.
  8. Kulbe JR, Geddes JW. Current status of fluid biomarkers in mild traumatic brain injury. Exp Neurol [Internet] 2016;275(Pt 3 03):334–352. DOI: 10.1016/j.expneurol.2015.05.004. Available from:
  9. Undén J, Bellner J, Astrand R, et al. Serum S100B levels in patients with epidural haematomas. Br J Neurosurg [Internet] 2005;19(1):43–45. DOI: 10.1080/02688690500089381. Available from:
  10. Romner B, Ingebrigtsen T, Kongstad P, et al. Traumatic brain damage: serum S-100 protein measurements related to neuroradiological findings. J Neurotrauma 2000;17(8):641–647. DOI: 10.1089/089771500415391.
  11. Haimoto H, Hosoda S, Kato K. Differential distribution of immunoreactive S100-alpha and S100-beta proteins in normal non nervous human tissues. Lab Invest 1987;57(5):489–498.
  12. Thelin EP, Nelson DW, Bellander B-M. A review of the clinical utility of serum S100B protein levels in the assessment of traumatic brain injury. Acta Neurochir (Wien) 2017;159(2):209–225. DOI: 10.1007/s00701-016-3046-3.
  13. Anderson RE, Hansson LO, Nilsson O, et al. High serum S100B levels for trauma patients without head injuries. Neurosurgery 2001;48(6):1255–1258. DOI: 10.1097/00006123-200106000-00012; discussion 1258-60.
  14. Pfortmueller CA, Drexel C, Krähenmann-Müller S, et al. S-100 B concentrations are a predictor of decreased survival in patients with major trauma, independently of head injury Kobeissy FH, ed. PLoS One [Internet] 2016;11(3):e0152822. DOI: 10.1371/journal.pone.0152822. Available from:
  15. Routsi C, Stamataki E, Nanas S, et al. Increased levels of serum S100b protein in critically ill patients without brain injury. Shock [Internet] 2006;26(1):20–24. DOI: 10.1097/01.shk.0000209546.06801.d7. Available from:
  16. Undén J, Bellner J, Eneroth M, et al. Raised serum S100B levels after acute bone fractures without cerebral injury. J Trauma [Internet] 2005;58(1):59–61. DOI: 10.1097/01.ta.0000130613.35877.75. Available from:
  17. Ercole A, Thelin EP, Holst A, et al. Kinetic modelling of serum S100b after traumatic brain injury. BMC Neurol [Internet] 2016;16(1):93. DOI: 10.1186/s12883-016-0614-3. Available from:
  18. Willoughby KA, Kleindienst A, Müller C, et al. S100B protein is released by in vitro trauma and reduces delayed neuronal injury. J Neurochem [Internet] 2004;91(6):1284–1291. DOI: 10.1111/j.1471-4159.2004.02812.x. Available from:
  19. Pandor A, Goodacre S, Harnan S, et al. Diagnostic management strategies for adults and children with minor head injury: a systematic review and an economic evaluation. Health Technol Assess (Rockv) [Internet] 2011;15(27):1–202. DOI: 10.3310/hta15270. Available from:
  20. Schulte S, Podlog LW, Hamson-Utley JJ, et al. A systematic review of the biomarker S100B: implications for sport-related concussion management. J Athl Train [Internet] 2014;49(6):830–850. DOI: 10.4085/1062-6050-49.3.33. Available from:
  21. Usui A, Kato K, Abe T, et al. S-100ao protein in blood and urine during open-heart surgery. Clin Chem [Internet] 1989;35(9):1942–1944. DOI: 10.1093/clinchem/35.9.1942. Available from:
  22. Kapural M, Krizanac-Bengez L, Barnett G, et al. Serum S-100 beta as a possible marker of blood-brain barrier disruption. Brain Res [Internet] 2002;940(1–2):102–104. DOI: 10.1016/s0006-8993(02)02586-6. Available from:
  23. Ingebrigtsen T, Romner B. Biochemical serum markers of traumatic brain injury. J Trauma [Internet] 2002;52(4):798–808. DOI: 10.1097/00005373-200204000-00038. Available from:
  24. Jackson RGM, Samra GS, Radcliffe J, et al. The early fall in levels of S-100 β in traumatic brain injury. Clin Chem Lab Med [Internet] 2000;38(11):1165–1167. DOI: 10.1515/CCLM.2000.179. Available from:
  25. da Rocha AB, Schneider RF, de Freitas GR, et al. Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males. Clin Chem Lab Med [Internet] 2006;44(10):1234–1242. DOI: 10.1515/CCLM.2006.218. Available from:
  26. Savola O, Pyhtinen J, Leino TK, et al. Effects of head and extracranial injuries on serum protein S100B levels in trauma patients. 2004;56(6):1229–1234. DOI: 10.1097/01.ta.0000096644.08735.72; discussion 1234. Available from:
  27. Pham N, Fazio V, Cucullo L, et al. Extracranial sources of S100B do not affect serum levels. PLoS One [Internet] 2010;5(9). DOI: 10.1371/journal.pone.0012691. Available from:
  28. Thelin EP, Zibung E, Riddez L, et al. Assessing bicycle-related trauma using the biomarker S100B reveals a correlation with total injury severity. Eur J Trauma Emerg Surg [Internet] 2016;42(5):617–625. DOI: 10.1007/s00068-015-0583-z. Available from:
  29. Thelin EP, Johannesson L, Nelson D, et al. S100B is an important outcome predictor in traumatic brain injury. J Neurotrauma [Internet] 2013;30(7):519–528. Available from:
  30. Thaler HW, Schmidsfeld J, Pusch M, et al. Evaluation of S100B in the diagnosis of suspected intracranial hemorrhage after minor head injury in patients who are receiving platelet aggregation inhibitors and in patients 65 years of age and older. J Neurosurg 2015;123(5):1202–1208. DOI: 10.3171/2014.12.JNS142276.
  31. Ananthaharan A, Kravdal G, Straume-Naesheim TM. Utility and effectiveness of the Scandinavian guidelines to exclude computerized tomography Scanning in mild traumatic brain injury - a Prospective cohort study. BMC Emerg Med 2018;18(1):44. DOI: 10.1186/s12873-018-0193-2.
  32. Undén J, Ingebrigtsen T, Romner B. (SNC) the SNC. scandinavian guidelines for initial management of minimal, mild and moderate head injuries in aDULTS: AN EVIDENCE AND CONSENSUS-BASED UPDATE. BMC Med [Internet] 2013;11(1):50. Available from:
  33. Unden 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(4):228–240. DOI: 10.1097/HTR.0b013e3181e57e22.
  34. David A, Mari C, Vignaud F, et al. Evaluation of S100B blood level as a biomarker to avoid computed tomography in patients with mild head trauma under antithrombotic medication. Diagn Interv Imaging 2017;98(7-8):551–556. DOI: 10.1016/j.diii.2017.03.010.
  35. Aydin I, Algin A, Poyraz MK, et al. Diagnostic value of serum glial fibrillary acidic protein and S100B serum levels in emergency medicine patients with traumatic versus nontraumatic intracerebral hemorrhage. Niger J Clin Pract 2018;21(12):1645–1650. DOI: 10.4103/njcp.njcp_431_17.
  36. Kellermann I, Kleindienst A, Hore N, et al. Early CSF and serum S100B concentrations for outcome prediction in traumatic brain injury and subarachnoid hemorrhage. Clin Neurol Neurosurg 2016;145:79–83. DOI: 10.1016/j.clineuro.2016.04.005.
  37. Egea-Guerrero JJ, Murillo-Cabezas F, Gordillo-Escobar E, et al. S100B protein may detect brain death development after severe traumatic brain injury. J Neurotrauma 2013;30(20):1762–1769. DOI: 10.1089/neu.2012.2606.
  38. Olivecrona Z, Bobinski L, Koskinen L-OD. Association of ICP, CPP, CT findings and S-100B and NSE in severe traumatic head injury. prognostic value of the biomarkers. Brain Inj [Internet] 2015;29(4):446–454. DOI: 10.3109/02699052.2014.989403.
  39. Abbasi M, Sajjadi M, Fathi M, et al. Serum S100B protein as an outcome prediction tool in emergency department patients with traumatic brain injury. Turkish J Emerg Med [Internet] 2016;14(4):147–152. DOI: 10.5505/1304.7361.2014.74317. Available from:
  40. Petzold A, Green AJE, Keir G, et al. Role of serum S100B as an early predictor of high intracranial pressure and mortality in brain injury: a pilot study. Crit Care Med 2002;30(12):2705–2710. DOI: 10.1097/00003246-200212000-00015.
  41. Andriessen TMJC, Horn J, Franschman G, et al. Epidemiology, severity classification, and outcome of moderate and severe traumatic brain injury: A prospective multicenter study. J Neurotrauma 2011;28(10):2019–2031. DOI: 10.1089/neu.2011.2034.
  42. Bouzat P, Francony G, Declety P, et al. Can serum protein S100 beta predict neurological deterioration after moderate or minor traumatic brain injury? Ann Fr Anesth Reanim 2009;28(2):135–139. DOI: 10.1016/j.annfar.2008.12.019.
  43. Korfias S, Stranjalis G, Boviatsis E, et al. Serum S-100B protein monitoring in patients with severe traumatic brain injury. Intensive Care Med 2007;33(2):255–260. DOI: 10.1007/s00134-006- 0463-4.
  44. Carney N, Totten AM, Hawryluk GWJ, et al. Guidelines for the management of severe. Traumatic Brain Injury. 4th ed., 2016.
  45. Chesnut RM, Temkin N, Carney N, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med [Internet] 2012;367(26):2471–2481. Available from:
  46. Bonow RH, Barber J, Temkin NR, et al. The outcome of severe traumatic brain injury in latin America. World Neurosurg 2018;111:2–5. DOI: 10.1016/j.wneu.2017.11.171.
  47. Chesnut RM, Temkin N, Dikmen S, et al. A method of Managing severe traumatic brain injury in the absence of intracranial pressure monitoring: the imaging and clinical examination protocol. J Neurotrauma [Internet] 2017;35(1):54–63. DOI: 10.1089/neu.2016.4472.
  48. Hendoui N, Beigmohammadi MT, Mahmoodpoor A, et al. Reliability of calcium-binding protein S100B measurement toward optimization of hyperosmolal therapy in Traumatic Brain Injury. Eur Rev Med Pharmacol Sci 2013;17(4):477–485.
  49. Shakeri M, Mahdkhah A, Panahi F. S100B protein as a post-traumatic biomarker for prediction of brain death in association with patient outcomes. Arch Trauma Res 2013;2(2):76–80. DOI: 10.5812/atr.8549.
  50. Thelin EP, Jeppsson E, Frostell A, et al. Utility of neuron-specific enolase in traumatic brain injury; relations to S100B levels, outcome, and extracranial injury severity. Crit Care 2016;20(1):285. DOI: 10.1186/s13054-016-1450-y.
  51. Doha N, Ammar A, El-Mashad M, et al. Traumatic brain injury: serum S-100B protein measurement related to neuroradiological findings. Menoufia Medical Journal 2019;32(2):417–422. DOI: 10.4103/mmj.mmj_564_17.
  52. Park SH, Hwang SK. Prognostic value of serum levels of S100 calcium-binding protein B, neuron-specific enolase, and interleukin-6 in pediatric patients with traumatic brain injury. World Neurosurgery 2018;118:e534–e542. DOI: 10.1016/j.wneu.2018.06.234.
  53. Yalcin A, Baydin A, Tuncel Ö, et al. Diagnostic values of proenkephalin and S100B protein in traumatic brain injury. Journal of Laboratory Medicine 2017;41(3):123–128. DOI: 10.1515/labmed-2016- 0045.
  54. Vos PE, Jacobs B, Andriessen TMJ, et al. GFAP and S100B are biomarkers of traumatic brain injury. Neurology 2010;75(20): 1786–1793. DOI: 10.1212/WNL.0b013e3181fd62d2.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.