Diagnostic performance of S100B as a rule out test for intracranial pathology in head injured patients presenting to the Emergency Department who meet NICE CT-head criteria- A BRAIN Project Study
Authors: Rogan Alice , Sik Annabelle , Dickinson Emily , Patel Vimal , Peckler Brad , McQuade David , Larsen Peter 
Published: July 2022

Background:
Traumatic brain injury (TBI) is a common Emergency Department (ED) presentation. CT-head utilisation is escalating, exacerbating resource pressure in ED. The biomarker S100B could assist clinicians with CT-head decisions by excluding intracranial pathology. Diagnostic performance of S100B was assessed in patients meeting NICE CT-head criteria within 6 and 24-hours of injury.
Methods:
This multi-centre prospective observational study included adult patients presenting to ED with mild TBI who were able to give their own informed consent and had a CT-head scan performed as part of standard care. Patients were recruited using consecutive sampling methods. Informed consent was obtained prior to blood sampling. Serum was tested for S100B using a Cobas Elecsys S100 module; >0.1ug/ml is the validated threshold indicating a positive test. Diagnostic performance was assessed using ROC analysis as well as sensitivity, specificity, NPV and PPV calculations.
Results:
There were 265 included patients, and 35 (13.2%) had a positive CT-head. The sensitivity of S100B when performed within 24 hours of injury was 82.9% (95%CI 66.4-93.44) and specificity was 43.0% (95%CI 36.6–49.7%). NPV was 94.29% (95%CI 88.7–97.2). Within 6 hours sensitivity was 93.8% (95%CI 69.8–99.8%) and specificity was 30.8% (22.6–40.0%). NPV was 97.3% (95%CI 84.2–99.6%). Theoretically, use of S100B as a rule out test would have reduced CT scans by 37.4% within 24 hours and 27.1% within 6-hours. The risk of missing a significant injury with this approach would have been 2.3% within 24 hours and 0.75% within 6-hours.
Conclusion
Within 6-hours of injury, S100B performed well as a diagnostic test to exclude significant intracranial pathology in patients presenting with mild head injuries, with low risk of missed injury. In theory, if used in addition to NICE CT-head guidelines, CT-head request rates could reduce by one quarter and one fifth of patients could be discharged earlier from ED.
What is already known on this topic
S100B has shown promise diagnostically as an objective marker that can rule out intracranial injuries in head injured patients. S100B has a validated platform that could potentially be used to reduce CT head demand in ED. However, evidence testing the added value of biomarkers to existing clinical guidelines are limited.
What this study adds
This study demonstrates that S100B could theoretically reduce CT-head demand and enable earlier ED discharge in low-risk patients meeting NICE CT-head criteria. The included population were GCS 15, had no post traumatic amnesia and were able to consent for themselves. This low-risk population have a low yield of traumatic CT abnormalities and could be a suitable population to target biomarker use.
How this study might affect research, practice or policy
S100B has the potential to reduce CT-head demand, thereby benefitting EDs by reducing overcrowding, resource burden and healthcare costs; and from the patients’ perspective, enable shorter waits, earlier intervention and earlier discharge. Further research should focus on optimising the performance of S100B within the NICE CT-head guidelines in low-risk patients, and review real-time economic benefits.