Written by Shannon Markus
Spoon Feed
Patients with normal blood levels of certain brain biomarkers after mild traumatic brain injury were unlikely to have intracranial lesions on CT, suggesting that biomarker testing may help reduce unnecessary CT imaging.
Testing blood to rule out a bleed?
This systematic review and meta-analysis evaluated the diagnostic accuracy of the blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) for detecting intracranial injury after mild traumatic brain injury (mTBI). Sixteen studies including 7,828 adult patients who underwent GFAP and UCH-L1 testing PLUS Head CT were analyzed.
GFAP alone demonstrated sensitivity of 94% and specificity of ~40%, while UCH-L1 alone had lower sensitivity (83%) and specificity ~51%. In contrast, GFAP and UCH-L1 combined achieved pooled sensitivity and negative predictive value of 100%, indicating excellent ability to rule out intracranial injury, though specificity remained low (~31%). Limitations include heterogeneity in sampling times and cutoff values for the biomarkers. Overall, combined biomarker testing could safely reduce unnecessary head CT in patients with minor head injuries.
How does this change my practice?
Negative results for these two brain injury biomarkers could theoretically reduce the number of head CTs in mTBI patients, as their very high sensitivity and negative predictive value suggest the test is excellent at not missing injuries. However, we also see that low specificity means the test performs poorly at confirming who actually has an injury, so many patients would still require CT imaging for a definitive rule-out. While it seems like these tests are not quite ready for primetime, brain biomarker testing is definitely generating a buzz in both neurosurgery and emergency medicine circles. I’m excited to see how this evolves!
Source
Can the Association of the Biomarkers GFAP and UCH-L1 Predict Intracranial Injury After Mild Traumatic Brain Injury in Adults? A Systematic Review and Meta-Analysis. Ann Emerg Med. 2026 Feb;87(2):167-180. doi: 10.1016/j.annemergmed.2025.03.018. Epub 2025 Apr 24. PMID: 40272329.
