Trauma/original research
S100-B Protein as a Screening Tool for the Early Assessment of Minor Head Injury

https://doi.org/10.1016/j.annemergmed.2011.07.027Get rights and content

Study objective

A computed tomography (CT) scan has high sensitivity in detecting intracranial injury in patients with minor head injury but is costly, exposes patients to high radiation doses, and reveals clinically relevant lesions in less than 10% of cases. We evaluate S100-B protein measurement as a screening tool in a large population of patients with minor head injury.

Methods

We conducted a prospective observational study in the emergency department of a teaching hospital (Bordeaux, France). Patients with minor head injury (2,128) were consecutively included from December 2007 to February 2009. CT scans and plasma S100-B levels were compared for 1,560 patients. The main outcome was to evaluate the diagnostic value of the S100-B test, focusing on the negative predictive value and the negative likelihood ratio.

Results

CT scan revealed intracranial lesions in 111 (7%) participants, and their median S100-B protein plasma level was 0.46 μg/L (interquartile range [IQR] 0.27 to 0.72) versus 0.22 μg/L (IQR 0.14 to 0.36) in the other 1,449 patients. With a cutoff of 0.12 μg/L, traumatic brain injuries on CT were identified with a sensitivity of 99.1% (95% confidence interval [CI] 95.0% to 100%), a specificity of 19.7% (95% CI 17.7% to 21.9%), a negative predictive value of 99.7% (95% CI 98.1% to 100%), a positive likelihood ratio of 1.24 (95% CI 1.20 to 1.28), and a negative likelihood ratio of 0.04 (95% CI 0.006 to 0.32).

Conclusion

Measurement of plasma S100-B on admission of patients with minor head injury is a promising screening tool that may be of help to support the clinician's decision not to perform CT imaging in certain cases of low-risk head injury.

Introduction

The annual incidence of traumatic brain injuries ranges between 100 and 400 per 100,000 persons.1, 2, 3, 4, 5, 6 More than 90% of them are classified as minor head injuries corresponding to patients with an admission Glasgow Coma Scale (GCS) score ranging from 13 to 15.

The initial severity assessment includes GCS and clinical symptoms (loss of consciousness, amnesia, headache, vomiting), but the optimal clinical decision rule for an initial computed tomography (CT) scan is still a matter of debate7, 8, 9 because of the low power of discrimination of clinical findings.

Head CT scan is currently considered the reference diagnostic method for identifying potentially life-threatening lesions.10, 11, 12, 13 It is, however, costly and not always available, exposes the patient to high radiation doses,14 and reveals clinically relevant lesions in less than 10% of cases. Indicators that can safely identify patients for whom a CT scan can be avoided are thus needed. S100-B, a 21-kDa calcium-binding glial-specific protein mainly expressed by astrocytes, has been considered not only as an objective quantitative prognostic marker of severe head injury15, 16 but also as a potentially interesting tool for patients with minor head injury.17, 18, 19, 20, 21 The measurement of S100-B has therefore recently been proposed and evaluated as an initial screening tool for brain damage.

The result of this test can be available within an hour of blood sampling.17 Its cost is around $20.22 Its negative predictive value is promising but has so far been estimated in a limited number of patients. Further research is therefore required to establish the clinical role of S100-B in patients with minor head injury and determine the appropriate decision rules before changing clinical management procedures.

Our aim was to assess the potential role of measuring blood S100-B protein levels as a screening tool for patients with minor head injury. The main outcome was the diagnostic performance of the S100-B test compared with CT scan findings.

Section snippets

Study Design

Patients with minor head injury were consecutively included from December 2007 to February 2009 in a prospective study. Informed consent was obtained from all subjects. The protocol was approved by the regional ethics committee.

Setting

The study was conducted at an adult emergency department (ED) of a teaching hospital in Bordeaux, France, with 48,000 annual admissions, including 2,500 brain injury cases. Our study site is also the tertiary neurosurgical center in a region of more than 3 million

Characteristics of Study Subjects

The STAndards for the Reporting of Diagnostic accuracy studies (STARD chart) flow is shown in Figure 1. A total of 2,128 patients fulfilled the inclusion criteria. Twenty-one patients were excluded because complete clinical assessment showed they had associated injuries with an Abbreviated Injury Score greater than 2.

The S100-B assay was not performed for 387 patients, corresponding to short periods of high activity in the ED during which the test could not be performed. A further 95 patients

Limitations

The term minor head injury has been used in the literature with various meanings.24, 25 The question of how best to define a minor head injury still is of great importance and has been a source of confusion. Some authors have suggested that patients with a GCS score of 13 should be excluded from the minor head injury category. In our investigation, they were included because our priority was the clinical criteria that represent the typical appearance of patients with minor head injury in EDs,

Discussion

We report here the largest study ever conducted, to our knowledge, on a consecutive sample of 1,560 patients with minor head injury, comparing initial blood levels of S100-B protein with head trauma–relevant CT scan findings. Our results show that blood S100-B measurement within 6 hours of minor head injury compared with CT scan has a high negative predictive value.

Our results are consistent with those of the only other large-scale study, reported by Biberthaler et al,17 who found in a sample

References (40)

  • P.J. Yates et al.

    An epidemiological study of head injuries in a UK population attending an emergency department

    J Neurol Neurosurg Psychiatry

    (2006)
  • J. Bruns et al.

    The epidemiology of traumatic brain injury: a review

    Epilepsia

    (2003)
  • A. Fabbri et al.

    Prospective validation of a proposal for diagnosis and management of patients attending the emergency department for mild head injury

    J Neurol Neurosurg Psychiatry

    (2004)
  • T. Ingebrigtsen et al.

    Biochemical serum markers for brain damage: a short review with emphasis on clinical utility in mild head injury

    Restor Neurol Neurosci

    (2003)
  • J.L. Geijerstam et al.

    Medical outcome after immediate computed tomography or admission for observation in patients with mild head injury: randomised controlled trial

    BMJ

    (2006)
  • M.J. Haydel et al.

    Indications for computed tomography in patients with minor head injury

    N Engl J Med

    (2000)
  • S.C. Stein et al.

    The value of computed tomographic scans in patients with low-risk head injuries

    Neurosurgery

    (1990)
  • M. Smits

    External validation of the Canadian CT Head Rule and the New Orleans Criteria for CT scanning in patients with minor head injury

    JAMA

    (2005)
  • R. Smith-Bindman

    Is computed tomography safe?

    N Engl J Med

    (2010)
  • C. Woertgen et al.

    Comparison of clinical, radiologic, and serum marker as prognostic factors after severe head injury

    J Trauma

    (1999)
  • Cited by (128)

    • Plasma-based S100B testing for management of traumatic brain injury in emergency setting

      2021, Practical Laboratory Medicine
      Citation Excerpt :

      This is in line with former studies demonstrating a high linear correlation for S100B testing between serum and heparin plasma [30], and serum and citrate plasma [31], respectively. Although plasma was used for S100B measurement in few other studies [3,10], the authors did not report on verification of the tests. However, so far the comparability of test results was never demonstrated using the Elecys® S100 on a Cobas e411 test system with an analyzing time of 18 min being the fastest upon all systems currently available.

    View all citing articles on Scopus

    Supervising editor: Judd E. Hollander, MD

    Author contributions: RR-G and EL conceived and designed the study and obtained research funding. DZ, RR-G, FM, and EL supervised the conduct of the study and data collection. DM and JLB were the biologists responsible for the S100-B measurement. AM and VD were the senior radiologists supervising the CT scan interpretation. HL was the senior neurosurgeon responsible for the management of patients requiring a neurosurgery management. DZ and FM managed the data, including quality control. DZ analyzed the data. RR-G and EL chaired the data oversight committee. DZ and EL drafted the article, and all authors contributed substantially to its revision. EL takes responsibility for the paper as a whole.

    Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). This study was funded by INSERM, the Réunica Group, and the teaching hospital of Bordeaux (PHRC 2007).

    Publication date: Available online September 23, 2011.

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