Accuracy of a rapid glial fibrillary acidic protein/ubiquitin carboxyl-terminal hydrolase L1 test for the prediction of intracranial injuries on head computed tomography after mild traumatic brain injury

Acad Emerg Med. 2021 Nov;28(11):1308-1317. doi: 10.1111/acem.14366. Epub 2021 Sep 7.


Objective: The objective was to determine the accuracy of a new, rapid blood test combining measurements of both glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) for predicting acute traumatic intracranial injury (TII) on head CT scan after mild traumatic brain injury (mTBI).

Methods: Analysis of banked venous plasma samples from subjects completing the Prospective Clinical Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) trial, enrolled 2012-2014 at 22 investigational sites in the United States and Europe. All subjects were ≥18 years old, presented to an emergency department (ED) with a nonpenetrating head injury and Glasgow Coma Scale score (GCS) 9-15 (mild to moderate TBI), underwent head CT scanning as part of their clinical care, and had blood sampling within 12 h of injury. Plasma concentrations of GFAP and UCH-L1 were measured using i-STAT Alinity and TBI plasma cartridge and compared to acute TII on head CT scan.

Results: Of the 2011 subjects enrolled in ALERT-TBI, 1918 had valid CT scans and plasma specimens for testing and 1901 (99.1%) had GCS 13-15 (mTBI), for which the rapid test was intended. Among these subjects, the rapid test had a sensitivity of 0.958 (95% confidence interval [CI] = 0.906 to 0.982), specificity of 0.404 (95% CI = 0.382 to 0.427), negative predictive value of 0.993 (95% CI = 0.985 to 0.997), and positive predictive value of 0.098 (95% CI = 0.082 to 0.116) for acute TII.

Conclusions: A rapid i-STAT-based test had high sensitivity for prediction of acute TII, comparable to lab-based platforms. The speed, portability, and high accuracy of this test may facilitate clinical adoption of brain biomarker testing as an aid to head CT decision making in EDs.

Trial registration: NCT01426919.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Biomarkers
  • Brain Concussion*
  • Brain Injuries, Traumatic* / diagnostic imaging
  • Glial Fibrillary Acidic Protein
  • Humans
  • Prospective Studies
  • Tomography, X-Ray Computed
  • Ubiquitin Thiolesterase
  • Ubiquitins


  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • Ubiquitins
  • Ubiquitin Thiolesterase

Associated data