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
Summary
Background
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.
Methods
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.
Findings
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.
Interpretation
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.
Funding
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.
https://www.medscape.com/viewarticle/899859
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