Elecsys® S100

Monitoring the cerebral status of patients with severe traumatic brain injury (TBI)

Elecsys S100
A promising marker to aid in the management of traumatic brain injury

S100 proteins are a family of small, dimeric multigenic calcium-binding proteins comprising various combinations of α and β subunits. S100 proteins most commonly occur as S100A (α – α) or S100B (α – β [S100A1B] and β – β [S100BB]) subtypes.4 S100B is predominately confined to glial and Schwann cells and is the most well-studied subtype in traumatic brain injury (TBI). Both S100A1B and S100BB have been implicated in severe TBI. 5

Severe TBI invariably results in neuronal destruction and destabilization of the blood-brain barrier (BBB). These phenomena are accompanied by a release of S100B protein into the blood. S100B is measurable within minutes of a TBI, and can be detected for an extended period in the bloodstream. S100B is removed from the serum by the renal clearance pathway, with a half-life of 20 to 25 minutes. 4

Elecsys S100
A schematic representation of the blood-brain barrier (BBB)6
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About traumatic brain injury (TBI)

In the USA alone, an estimated 1.7 million people sustain a TBI each year. Of these, 275,00 are hospitalized (16.3%), 1,365,000 are treated and released from emergency departments (80.7%) and 53,000 (3%) die.1

Patients with a severe TBI are at high risk of post-traumatic events, such as intracranial bleeding or brain edema which lead to a rise in intracranial pressure and secondary brain damage. In such cases rapid intervention is essential to relieve the intracranial pressure through medication and/or surgery (craniotomy).

Patients with severe TBI are typically treated under analgo-sedation in an intensive care unit. Although sedation provides an optimal environment for physical recovery, it limits the clinician’s options to examine the patient’s cognitive state. It is therefore common practice to monitor the stability of the patient’s neurological state using computer tomography (CT) imaging. While CT serves as a gold standard to monitor structural changes of TBI patients, two limitations restrict its usage to daily intervals or longer:

  1. The need to transport a patient for CT
  2. Exposure to high-dose radiation
S100 - Your first step to rule out mild TBI
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*Measure the S100 value within 3 hours after trauma. A negative result from a sample collected more than 3 hours after trauma should not be used. 

Monitoring progression of severe TBI with S100 assays

S100B protein is a marker that displays high clinical sensitivity for severe TBI, and the extent of S100B elevation has been found to be useful in predicting clinical outcome after brain injury.7,8

Serial daily measurements of serum S100B were found to be a useful non-invasive means for identifying brain damage and could be used for prediction of mortality.7,9 Furthermore, some studies have reported that S100B levels aboce certain thresholds might have predictive value on trauma-induced brain death.4,9,10

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Warning of secondary deteriorations

Secondary neurological events are accompanied by an elevation in the serum levels of S100B, often visible earlier than when detected with diagnostic imaging.4,15,16 S100B levels have been shown to rise hours to days before changes in intracranial pressure or onset of cerebral hypoxia.4,17 S100B levels may be used to monitor comatose intensive care patients for neurological complications such as a new infarction, new hemorrhage, or a newly developed progressive disease.16

Serial measurements using the S100 assay may therefore help a clinician to recognize the onset of a neurological complication and enable early therapeutic intervention.16 The same study has shown that this information affected patient management in 21% of severe TBI cases.16

See graph

S100B levels correlate with the severity of brain damage

S100B concentrations in serum have been shown to be representative of the extent of primary brain damage, corroborated by clinical scales of neurological status,11 subsequent CT examination,10-13 and neurological outcome.14

For example, in 60 patients with S100B measured within 24 hours of trauma, levels correlated with neurological outcome as assessed by the Glasgow Outcome Scale (GOS).14 Another study of 102 adult patients with severe TBI demonstrated that initial serum S100B concentrations correlated with the severity of brain injury on CT imaging as determined by the Marshall classification.10

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S100 levels predict short-, medium-, and long-term patient outcomes

S100B is related to outcome prognosis.7,9,18 Serial measurement of S100B accurately predicts short-term mortality, with the strongest correlation with clinical outcome seen >84 hours after trauma.18 Comparison of time courses of S100B levels in patients with favorable and unfavorable outcomes also indicate that S100B values by day 2 after admission independently predict 12-month mortality.7

In a meta-analysis of 41 studies, serum S100B concentrations measured after moderate or severe TBI were significantly associated with prognosis in the short (<3 months), medium (3–6 months) or long term (6 months), as defined by mortality or a Glasgow Outcome Score ≤3. Furthermore, this association was unaffected by concomitant traumatic injuries.19

Reducing CT use in low-risk head injuries patients

A CT scan has high sensitivity for detecting intracranial injuries in patients with head injury.20 However, the technique is costly, exposes the patient to high doses of radiation,21 and clinically relevant lesions are found in less than 10% og cases of minor head injury.2 Several studies have demonstrated that a normal S100B level reliably predicts normal CT findings after minor head injury in adults.22

In a prospective multicenter study of 1,309 patients with minor head injury, an S100B cut-off of 0.10 µg/L (the 95th percentile of healthy volunteers) identified those patients with trauma-relevant CT findings with a sensitivity of 99% and a negative predictive value of 99.68%.3

A meta-analysis of 12 studies of adults with minor head injury reported a pooled sensitivity for S100B for the prediction of CT findings of 97% (95% CI, 91-99%) and pooled specificity of 40% (95% CI, 30-51%).22 This equated to a negative predictive value of >99% (95% CI, 98-100%) at an average prevalence for intracranial findings after minor head injury of 8%.22 Omitting CT in adults with minor head injury and an S100B concentration of <0.10 μg/L would reduce the number of CTs by approximately one third.22

International guidelines advise that adult patients with mild head injury and no risk factors who have a serum S100B level <0.10 µg/L measured within 6 hours of injury may be discharged without the need for CT.23

S100B in pediatric TBI

Diagnosis of TBI in children with head injury can be more challenging than in adults, as obtaining a reliable patient history may be difficult and physical examination can be uncomfortable for the child.

Similar to studies in adult populations, S100B levels measured following TBI in pediatric populations predict CT findings24, 25 and outcomes.26, 27 In a study of 446 children who presented within 3 hours of mild TBI, S100B levels correlated with severity of TBI and predicted a poor clinical evolution with 100% sensitivity (95% CI, 84-100%).24 Furthermore, S100B levels had a 100% negative predictive value for ruling out trauma-relevant intracerebral lesions on CT. Hence, S100B determination during the first 3 hours after TBI can potentially reduce the number of CT scans in children. 

S100B CCT + CCT -  
>0.10 μg/L
92 855 PPV 10% (95% CI, 7-13%)
<0.10 µg/L
1 361 NPV 99.68% (95% CI, 99-100%)
Total 93 1216 1309
  Sensitivity: 99% (95% CI, 96-100%)
Specificity: 30% (95% CI, 29-30%)
 
Elecsys S100

Elecsys® S100

  • Assay Time

    18 minutes

  • Sample Material

    Human Serum

  • Sample Volume

    20 µL

  • Detection Limit

    0.4 pg/mL

  • Measuring Range

    15‑30000 pg/mL

References

 

  1. Bloomfield, S. M., McKinney, J., Smith, L. & Brisman, J. (2007). Reliability of S100B in predicting severity of central nervous system injury. Neurocrit Care, 6(2), 121-138.
  2. Sedaghat, F. & Notopoulos, A. (2008). S100 protein family and its application in clinical practice. Hippokratia, 12(4), 198-204.
  3. Deetjen, P. & Speckmann, E. J. (1992). Physiologie, ISBN 3-541-11751-6, Urban & Schwarzenberg, Munchen.
  4. aul, M., Xu, L., Wald, M. M., & Coronado, V. G. (2010). Traumatic brain injury in the United States: emergency department visits,hospitalizations, and deaths 2002-2006. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. http://www.cdc.gov/traumaticbraininjury/pdf/blue_book.pdf
  5. Murillo-Cabezas, F., Munoz-Sanchez, M. A., Rincon-Ferrari, M. D., Martin-Rodriguez, J. F., maya-Villar, R., Garcia-Gomez, S. et al. (2010). The prognostic value of the temporal course of S100beta protein in post-acute severe brain injury: A prospective and observational study. Brain Inj, 24(4), 609-619.
  6. Nylen, K., Ost, M., Csajbok, L. Z., Nilsson, I., Hall, C., Blennow, K. et al. (2008). Serum levels of S100B, S100A1B and S100BB are all related to outcome after severe traumatic brain injury. Acta Neurochir, 150(3), 221-227.
  7. Pelinka, L. E., Kroepfl, A., Leixnering, M., Buchinger, W., Raabe, A. & Redl, H. (2004). GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma, 21(11), 1553-1561.
  8. Korfias, S., Stranjalis, G., Boviatsis, E., Psachoulia, C., Jullien, G., Gregson, B. et al. (2007). Serum S-100B protein monitoring in patients with severe traumatic brain injury. Intensive Care Med, 33(2), 255-260.
  9. Herrmann, M., Jost, S., Kutz, S., Ebert, A. D., Kratz, T., Wunderlich, M. T. et al. (2000). Temporal profile of release of neurobiochemical markers of brain damage after traumatic brain injury is associated with intracranial pathology as demonstrated in cranial computerized tomography. J Neurotrauma, 17(2), 113-122.
  10. Raabe, A., Grolms, C., Keller, M., Dohnert, J., Sorge, O. & Seifert, V. (1998). Correlation of computed tomography findings and serum brain damage markers following severe head injury. Acta Neurochir, 140(8), 787-791.
  11. Romner, B., Ingebrigtsen, T., Kongstad, P. & Borgesen, S. E. (2000). Traumatic brain damage: serum S-100 protein measurements related to neuroradiological findings. J Neurotrauma, 17(8), 641-647.
  12. Wiesmann, M., Steinmeier, E., Magerkurth, O., Linn, J., Gottmann, D. & Missler, U. (2010). Outcome prediction in traumatic brain injury: comparison of neurological status, CT findings, and blood levels of S100B and GFAP. Acta Neurol Scand, 121(3), 178-185.
  13. Raabe, A. & Seifert, V. (1999). Fatal secondary increase in serum S-100B protein after severe head injury. Report of three cases. J Neurosurg, 91(5), 875-877.
  14. Raabe, A., Kopetsch, O., Woszczyk, A., Lang, J., Gerlach, R., Zimmermann, M. et al. (2004). S-100B protein as a serum marker of secondary neurological complications in neurocritical care patients. Neurol Res, 26(4), 440-445.
  15. Stein, D. M., Lindell, A. L., Murdock, K. R., Kufera, J., Menaker, J., Bochicchio, G. V. et al. (2012). Use of serum biomarkers to predict cerebral hypoxia after severe traumatic brain injury. J Neurotrauma, 29(6), 1140-1149.
  16. Pelinka, L. E., Toegel, E., Mauritz, W. & Redl, H. (2003). Serum S 100 B: a marker of brain damage in traumatic brain injury with and without multiple trauma. Shock, 19(3), 195-200.
  17. Mercier, E., Boutin, A., Lauzier, F., Fergusson, D. A., Simard, J. F., Zarychanski, R. et al. (2013). Predictive value of S-100beta protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis. BMJ, 346f1757.
  18. Haydel, M. J., Preston, C. A., Mills, T. J., Luber, S., Blaudeau, E. & DeBlieux, P. M. (2000). Indications for computed tomography in patients with minor head injury. N Engl J Med, 343(2), 100-105.
  19. Smith-Bindman, R. (2010). Is computed tomography safe? N Engl J Med, 363(1), 1-4.
  20. Unden, J. & Romner, B. (2010). 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, 25(4), 228-240.
  21. Unden, J., Ingebrigtsen, T. & Romner, B. (2013). Scandinavian guidelines for initial management of minimal, mild and moderate head injuries in adults: an evidence and consensus-based update. BMC Med, 11, 50.
  22. Bouvier, D., Fournier, M., Dauphin, J. B., Amat, F., Ughetto, S., Labbe, A. et al. (2012). Serum S100B determination in the management of pediatric mild traumatic brain injury. Clin Chem, 58(7), 1116-1122.
  23. Castellani, C., Bimbashi, P., Ruttenstock, E., Sacherer, P., Stojakovic, T. & Weinberg, A. M. (2009). Neuroprotein s-100B - a useful parameter in paediatric patients with mild traumatic brain injury? Acta Paediatr, 98(10), 1607-1612.
  24. Spinella, P. C., Dominguez, T., Drott, H. R., Huh, J., McCormick, L., Rajendra, A. et al. (2003). S-100beta protein-serum levels in healthy children and its association with outcome in pediatric traumatic brain injury. Crit Care Med, 31(3), 939-945.
  25. Žurek, J. & Fedora, M. (2012). The usefulness of S100B, NSE, GFAP, NF-H, secretagogin and Hsp70 as a predictive biomarker of outcome in children with traumatic brain injury. Acta Neurochir, 154(1), 93-103.