Jeffrey J Bazarian, Peter Biberthaler, Robert D Welch, Lawrence M Lewis, MD, Pal Barzo, Viktoria Bogner-Flatz, P Gunnar Brolinson, Andras Büki, James Y Chen, Robert H Christenson, Dallas Hack, J Stephen Huff, Sandeep Johar, J Dedrick Jordan, Bernd A Leidel, Tobias Lindner, Elizabeth Ludington, David O Okonkwo, Joseph Ornato, W Frank Peacock, Kara Schmidt, Joseph A Tyndall, Arastoo Vossough, Andy S Jagoda’ Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurology. 24 July 2018. https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(18)30231-X.pdf
More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI.
This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9–15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT.
Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931–0·995) and an NPV of 0·996 (0·987–0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative.
These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted.
Banyan Biomarkers and US Army Medical Research and Materiel Command.
"We see this test not as a substitute for head CT scan, but as an accurate and objective way to help emergency care providers decide which patients really need one," Jeffrey Bazarian, MD, MPH, professor, Department of Emergency Medicine, University of Rochester Medical Center, New York, told Medscape Medical News.
"Our results suggest that this blood test holds potential for ruling out the need for head CT scan among head-injured patients presenting to EDs, in whom a head CT scan is felt to be clinically indicated; in fact, up to a third of head CT scans done in the acute setting of TBI could be avoided, with very low false-negative rates," he said…
The "diagnostic modality of choice" in evaluating patients for traumatic intracranial injuries is a head CT scan, which accounts for approximately 20 million CT scans performed annually in the United States.
"[T]he widespread use of head CT scanning has been questioned due to potential adverse effects of radiation exposure, unnecessary [ED] resource use, and cost," the authors state.
Moreover, the prevalence of CT-detected intracranial injury in patients with mild TBI is typically less than 10%.
Previous research has suggested the potential for blood-based brain injury biomarkers to predict the absence of intracranial injury after TBI and aid in reducing unnecessary head CT scans….
S100B, a well-established biomarker for TBI, is already in clinical use in Europe; however, to date, no blood-based brain biomarker tests have been approved by the US Food and Drug Administration for clinical use in the United States…
Two novel brain proteins that have been advanced are UCH-L1 and GFAP, but preliminary investigations into these "promising" biomarkers have been limited by small cohort sizes, variability in blood sample acquisition timing, and retrospective determination of cutoff values…
When the researchers conducted a sensitivity analysis comparing the diagnostic accuracy of the combined biomarker test with each protein individually, they found that the combination of both proteins outperformed each marker separately on the primary outcomes…
"We were pleasantly surprised to see that 97.6% of patients with a CT-detected intracranial injury, like hemorrhage, tested positive, and 99.7% of patients with a negative test had a normal head CT scan," he said.