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BET 3: Can protein S100B add to current clinical guidelines in adult minor head injury?


A short-cut review was carried out to determine whether protein S100B either alone or incorporated into clinical guidelines could be used to identify accurately those adults with mild head injury who had significant brain trauma. Thirty-five papers were found using the reported searches, of which nine presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of those best papers are shown in table 3. It is concluded that while S100B is a sensitive test for traumatic brain injury, there is no evidence to determine whether it adds value to any current clinical guidelines.

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Report by: D Kontogeorgis, ST7 Emergency Medicine Registrar

Search checked by: D Mossop, Consultant in Emergency and Intensive Care Medicine

Institution: Royal Berkshire Hospital, Reading, UK

Clinical scenario

A 25-year-old healthy man presented to a semi-urban trauma unit with a minor head injury (MHI). After thorough assessment and following UK National Institute for Health and Clinical Excellence (NICE) guidelines, you ascertain that the patient does not require CT brain scan and can be safely discharged home. A neurosurgical colleague, having recently returned from a European conference, had adopted protein S100B sampling as a neuroimaging triage tool for the department. He suggests this is a more accurate measurement of the extent of brain injury. On following his departmental policy serum S100B sampling yielded a positive result, but subsequent neuroimaging reveals no intracranial pathology. You wonder what the clinical utility of protein S100B actually is in MHI and also whether integration of this blood test within clinical guidelines might provide improved, more cost-effective care?

Three-part question

In (adults with minor head injury) can (protein S100B alone or integrated within clinical guidelines) be used to (accurately detect those patients with significant traumatic brain injury)?

Search strategy

Week beginning 1 May 2013.

A primary literature search was conducted using key databases: the National Library for Health, MEDLINE, CINAHL and EMBASE. Secondary searches were carried out using the Cochrane Library, King's Fund Library (OVID), the National Research Register,, WHO International Clinical Trials registry platform, BestBETs ( and GoogleScholar ( Databases provided were through NLH search 2.0 CINAHL (EBSCO), EMBASE (OVID), KINGS’ FUND (OVID) and MEDLINE (OVID). The search was limited to the past 13 years.

The following search terms were used in various combinations: [Protein OR serum] AND [S100 OR S-100B OR S100B OR *S100] AND [*Minor head injury OR minor craniocerebral trauma OR minor head trauma OR mild traumatic brain injury OR acute brain injury OR acute brain damage] AND [NICE OR CT OR CT triage OR Canadian CT head rules OR New Orleans criteria].

Search outcome

Results of the primary literature search revealed 35 relevant papers. These were manually filtered after reading the article abstracts and removing duplicates. Scanning the bibliographies of identified studies and undertaking a secondary database search complemented this exercise. Overall, 21 papers were identified: 17 prospective cohorts, one prospective validation study, one invited review and two systematic reviews with meta-analytical interpretation. All 21 papers ascertained the diagnostic accuracy of protein S100B by quoting conventional measures. Twenty manuscripts were retrieved and critically appraised utilising the quality assessment of diagnostic accuracy studies checklist. Eleven of these papers were included in one or both of the published meta-analyses. No published literature explored the integration of protein S100B with UK NICE guidelines. The eight remaining papers are shown in table 3.

Table 3 Relevant papers


The published work in this field consists mostly of studies with small samples, limited to single centres and with diverse methodological quality. Patient numbers vary greatly between studies (range 50–1559) with only five studies recruiting more than 200 patients. In addition, there were marked variations in sample analysis techniques and the thresholds used to define a positive S100B result. The pooled estimate for the prevalence of intracranial injury detectable on CT was 12.6% (range 4.7–33%); this observed heterogeneity in a positive neuroimaging rate is important as the range is much wider than that reported in the MHI population.

Overall, it seems that S100B has a high sensitivity for intracranial pathology, but a poor specificity. It may have a role to play as a rule-out tool, but its poor specificity is a limiting factor because use in a low prevalence population will result in a low positive predictive value.

There is no real evidence to assess the use of S100B as an integral part of a clinical decision rule.

Clinical bottom line

S100B is a sensitive but non-specific test for traumatic brain injury. However, there is no evidence to determine whether it adds value to any current clinical guidelines.

▸ 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;25:228–40.

▸ Kotlyar S, Larkin G, Moore C, et al. S100B Immunoassay: an assessment of diagnostic utility in minor head trauma. Clin Lab Emerg Med 2010;40:285–91.

▸ Muller B, Evangelopoulos DS, Bias K, et al. Can S-100B serum protein help to save cranial CT resources in a peripheral trauma centre? A study and consensus paper. Emerg Med J 2010;28: 938–40.

▸ Leidel BA, Bogner V, Zock M, et al. Serological determination of protein S-100B: significance in emergency diagnosis of adults with mild cranio-cerebral trauma. A meta-analysis. Der Unfallchirurg 2012;115:903–12.

▸ Calcagnile O, Unden L, Unden J. Clinical validation of S100B use in management of mild head injury. BMC Emerg Med 2012;12:13.

▸ Cervellin G, Benatti M, Carbucicchio A, et al. Serum levels of protein S100B predict intracranial lesions in mild head injury. Clin Biochem 2012;45:408–11.

▸ Egea-Guerrero JJ, Revuerto-Rey J, et al. Accuracy of the S100 beta protein as a marker of brain damage in traumatic brain injury. Brain Inj 2012;26:76–82.

▸ Zongo D, Ribereau-Gayon R, Masson F, et al. S-100B protein as a screening tool for the early assessment of minor head injury Ann Emerg Med. 2012;59.