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Lancet Neurol. 2018 Sep;17(9):782-789. doi: 10.1016/S1474-4422(18)30231-X. Epub 2018 Jul 24.

Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study.

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Department of Emergency Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Technical University of Munich, Klinikum rechts der Isar, Munich, Germany.
Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA. Electronic address:
Division of Emergency Medicine, Washington University, St Louis, MO, USA.
University of Szeged, Szeged, Hungary.
Department of Trauma Surgery, Ludwig Maximilians University, Munich, Germany.
Carilion New River Valley Hospital, The Edward Via College of Osteopathic Medicine, Blacksburg, VA, USA.
Department of Neurosurgery, The MTA-PTE Clinical Neuroscience MR Research Group, János Szentágothai Research Center, Hungarian Brain Research Program, Medical School, University of Pecs, Pecs, Hungary.
Department of Radiology, VA San Diego Healthcare System/University of California, San Diego Health System, La Jolla, CA, USA.
Department of Pathology, University of Maryland School of Medicine, University of Maryland Medical Center, Baltimore, MD, USA.
US Army Medical Research and Materiel Command, Fort Detrick, MD, USA.
University of Virginia, Charlottesville, VA, USA.
Neurosurgery, Orthopedics & Spine Specialist, Waterbury, CT, USA.
University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Charité Universitätsmedizin Berlin, Berlin, Germany.
Agility Clinical, Carlsbad, CA, USA.
Department of Neurosurgical Science, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Emergency Medicine, Virginia Commonwealth University Health System, Richmond, VA, USA.
Department of Emergency Medicine, Baylor College of Medicine, Houston, TX, USA.
US Army Medical Research and Materiel Command, Fort Detrick, MD, USA; US Army Medical Research and Material Command, Fort Detrick, MD, USA.
Department of Emergency Medicine, The University of Florida, Gainesville, FL, USA.
Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Emergency Medicine, Mount Sinai Health System, New York, NY, USA.



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.

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