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Observational Study
. 2025 Oct 1;32(5):351-358.
doi: 10.1097/MEJ.0000000000001234. Epub 2025 Apr 9.

Exclusion of intracranial lesions in mild traumatic brain injury using glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1: a European multicenter study

Lara Milevoj Kopcinovic  1   2 , Nora Nikolac Gabaj  1   3 , Ivana Lapić  3   4 , Dunja Rogić  3   4 , Oana Roxana Oprea  5 , Minodora Dobreanu  5 , Jakub Nożewski  6 , Mariusz Sieminski  7   8 , Ewelina Stępniewska  7   8 , Małgorzata Dąbrowska  8 , Barbara Mroczko  9 , Marzena Wojewódzka-Żelezniakowicz  10 , Rakesh Jalali  11   12 , Marcin Baluch  11   12 , Joanna Malinowska  11   12 , Jerzy Romaszko  13 , Evgenija Homšak  14   15 , Gregor Prosen  15   16 , Matej Strnad  15   16 , Helena Ferreira da Silva  17 , Martina Pavletić  18 , Vesna Šupak-Smolčić  19   20 , Lidija Bilić-Zulle  19   21 , Ana Tancabel Mačinković  22   23 , Mate Lerga  18   23 , Dušan Dobrota  24 , Daniel Čierny  24 , Štefan Sivák  25 , Egon Kurča  25 , Martina Martiníková  26
Affiliations
Observational Study

Exclusion of intracranial lesions in mild traumatic brain injury using glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1: a European multicenter study

Lara Milevoj Kopcinovic et al. Eur J Emerg Med. .

Abstract

Background: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are blood biomarkers that able to aid in the assessment of mild traumatic brain injury (mTBI) patients and reduce computed tomography (CT) overuse.

Objectives: The aim of this study was to evaluate the predictive performance of individual biomarkers and their combination (i.e. mTBI assay) in detecting clinically significant intracranial injuries in mTBI. Furthermore, the influence of older age on the predictive performance of individual biomarkers and their combination was investigated.

Methods: This prospective multicenter study was conducted in 12 European healthcare centers. Adults with suspected mTBI presenting to the emergency department (ED) of each participating healthcare center within 12 h of head trauma were enrolled. GFAP and UCH-L1 were determined in blood samples collected from each participant. Head CT was considered as reference standard for the presence of intracranial injury.

Results: The mTBI assay yielded the highest sensitivity [95.5%, 95% confidence interval (CI): 89.9-98.5] and the highest negative predictive value (NPV) value (97.3%, 95% CI: 93.9-98.9) for the exclusion of intracranial lesions in mTBI. The sensitivities and NPVs of individual biomarkers were lower compared with the mTBI assay. In adults over 65 years, the individual biomarkers and the mTBI assay displayed the weakest diagnostic performances. After optimizing cutoff values for the mTBI assay for older adults, the following diagnostic accuracy measures were obtained: sensitivity 87.7%, 95% CI: 77.2-94.5 and NPV: 94.4%, 95% CI: 89.6-97.0 ( P < 0.001).

Conclusion: The mTBI assay yielded high sensitivity and NPV for the exclusion of significant intracranial injuries in mTBI patients presenting to the ED within 12 h from injury, performing better than individual biomarkers. A significant age-dependent influence on the predictive performances of the individual biomarkers and the mTBI assay was demonstrated.

Keywords: biomarkers; computed tomography; glial fibrillary acidic protein; mild traumatic brain injury; ubiquitin C-terminal hydrolase L1.

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References

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