Question 1

Can we use in Australia?

Accepted Answer

S100; Roche Cobas - TGA approved, not incorporated into guidelines, utilised in Scandinavian and French adult TBI guidelines.

GFAP + UCH-L1: Not available in Australia yet. FDA approved for use in America, used in New Zealand. Pending approval likely in Australia.

Inflammatory Markers; These markers are available on routine pathology platforms for other indications, but none are approved, TGA-listed, or endorsed for diagnostic work-up of traumatic brain injury — paediatric or adult.

Question 2

Does the sampling timeframe fit ED workflow?

Accepted Answer

Yes. Most TBI-relevant biomarkers have rapid release kinetics and short half-lives, making them highly compatible with ED decision-making. Serum levels for S100B, GFAP, and UCH-L1 peak early and are reliably measurable within 6–12 hours, aligning well with common paediatric ED presentation windows. A minority of studies collected markers such as IL-6 up to 24 hours post-injury, but this reflects study design rather than an operational barrier.

Emerging point-of-care (POC) platforms provide results within minutes and represent a major opportunity for seamless integration into ED workflow, supporting timely imaging decisions and reducing unnecessary CT use.

Question 3

Does combining biomarkers improve diagnostic accuracy?

Accepted Answer

Yes. Multi-marker panels perform best because they track different injury pathways, such as neuronal/axonal. Additionally, they are less vulnerable to the same confounders. All tested biomarker panel combinations had higher diagnostic accuracy in all instances compared to there single marker equivalents alone.

Question 4

Are these markers affected by age in children?

Accepted Answer

Some markers, especially S100B, vary by age, which can lead to misclassification. Subgroup analysis specifically for S100B did not identify meaningful difference. Among, other markers age specific thresholds are heterogenous and not often implemented.

Question 5

Do extracranial injuries confound results?

Accepted Answer

Yes. Extracranial injury is a documented confounder in a number of biomarkers such as; S100B, Interleukins, NfL, H-FABP, NLR, NfL. It appears to have minimal/negligible influence on GFAP and UCH-L1.

Question 6

Main barrier to ED adoption?

Accepted Answer

Quantitive; heterogenous thresholds, varying specificity, emerging evidence suggesting panels superiority.

Operational; access to analysers, implementation into clinical framework.

Qualitative; Senior ED physicians report very low tolerance for missed injuries (acceptable risk 0.2–2%). They want strong evidence, near-perfect accuracy, and external validation before using biomarkers in practice.

Question 7

Integration with Australian pathways like PREDICT?

Accepted Answer

Biomarkers should support, not replace, existing CDRs. A modified PREDICT pathway that includes biomarkers could provide objective support for low-risk cases and improve consistency.

Question 8

Suitable for point-of-care use?

Accepted Answer

An FDA-approved GFAP + UCH-L1 test exists on the Abbott i-STAT system (about USD 10,000 per analyzer; USD 50 per cartridge), but widespread access is still limited.

Question 9

Impact on CT use and costs?

Accepted Answer

Biomarker-guided triage could reduce CT use by about 30%. With cranial CTs costing AUD 214 each, this could save more than AUD 10 million annually, plus reduced observation and admission costs.

Question 10

Why reducing CT scans in children?

Accepted Answer

CT exposes children to ionizing radiation, which carries a measurable cancer risk. For a 1-year-old, the lifetime malignancy risk is about 1 in 1500 per CCT, and 8-100,000 will die of fatal radiation induced changes. Most children with mTBI have normal scans (90%), making many exposures avoidable.

Question 11

What needs to happen next?

Accepted Answer

Prospective multicenter validation is essential. Future work must standardize assays, refine thresholds, and integrate biomarkers into existing decision frameworks to enable real-world adoption.

Question 12

Alternative options

Accepted Answer

Measuring S100B in urine was investigated as a highly accurate alternative, non-invasive method. One study reported a high accuracy for S100B urinary concentrations, achieving an Area Under the Curve (AUC) of 0.985 with a sensitivity of 90% and specificity of 95% for differentiating positive and normal CT scans.

Lachlan Ragg

Final-year Medical Student | University of Wollongong | BMedRadSc (Hons), Diagnostic Radiography

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