Serum Glial Fibrillary Acidic Protein in Detecting Intracranial Injuries Following Minor Head Trauma; a Systematic Review and Meta-Analysis
Archives of Academic Emergency Medicine,
Vol. 11 No. 1 (2023),
15 November 2022
Introduction: Developing novel diagnostic and screening tools for exploring intracranial injuries following minor head trauma is a necessity. This study aimed to evaluate the diagnostic value of serum glial fibrillary acidic protein (GFAP) in detecting intracranial injuries following minor head trauma.
Methods: An extensive search was performed in Medline, Embase, Scopus, and Web of Science databases up to the end of April 2022. Human observational studies were chosen, regardless of sex and ethnicity of their participants. Pediatrics studies, report of diagnostic value of GFAP combined with other biomarkers (without reporting the GFAP alone), articles including patients with all trauma severity, defining minor head trauma without intracranial lesions as the outcome of the study, not reporting sensitivity/specificity or any other values essential for computation of true positive, true negative, false positive and false-negative, being performed in the prehospital setting, assessing the prognostic value of GFAP, duplicated reports, preclinical studies, retracted articles, and review papers were excluded. The result was provided as pooled sensitivity, specificity, diagnostic score and diagnostic odds ratio, and area under the summary receiver operating characteristic (SROC) curve with a 95% confidence interval (95% CI).
Results: Eventually, 11 related articles were introduced into the meta-analysis. The pooled analysis implies that the area under the SROC curve for serum GFAP level in minor traumatic brain injuries (TBI) was 0.75 (95% CI: 0.71 to 0.78). Sensitivity and specificity of this biomarker in below 100 pg/ml cut-off were 0.83 (95% CI: 0.78 to 0.89) and 0.39 (95% CI: 0.24 to 0.53), respectively. The diagnostic score and diagnostic odds ratio of GFAP in detection of minor TBI were 1.13 (95% CI: 0.53 to 1.74) and 3.11 (95% CI: 1.69 to 5.72), respectively. The level of evidence for the presented results were moderate.
Conclusion: The present study's findings demonstrate that serum GFAP can detect intracranial lesions in mild TBI patients. The optimum cut-off of GFAP in detection of TBI was below 100 pg/ml. As a result, implementing serum GFAP may be beneficial in mild TBI diagnosis for preventing unnecessary computed tomography (CT) scans and their related side effects.
- Brain Injuries
How to Cite
Gutierre MU, Telles JPM, Welling LC, Rabelo NN, Teixeira MJ, Figueiredo EG. Biomarkers for traumatic brain injury: a short review. Neurosurg Rev. 2021;44(4):2091-7.
James SL, Theadom A, Ellenbogen RG, Bannick MS, Montjoy-Venning W, Lucchesi LR, et al. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(1):56-87.
Lingsma HF, Yue JK, Maas AI, Steyerberg EW, Manley GT. Outcome prediction after mild and complicated mild traumatic brain injury: external validation of existing models and identification of new predictors using the TRACK-TBI pilot study. J Neurotrauma. 2015;32(2):83-94.
Bouvier D, Oris C, Brailova M, Durif J, Sapin V. Interest of blood biomarkers to predict lesions in medical imaging in the context of mild traumatic brain injury. Clin Biochem. 2020;85:5-11.
Calvi MR, Beretta L, Dell'Acqua A, Anzalone N, Licini G, Gemma M. Early prognosis after severe traumatic brain injury with minor or absent computed tomography scan lesions. J Trauma Acute Care Surg. 2011;70(2):447-51.
Laalo JP, Kurki TJ, Sonninen PH, Tenovuo OS. Reliability of diagnosis of traumatic brain injury by computed tomography in the acute phase. J Neurotrauma. 2009;26(12):2169-78.
Callahan MJ, MacDougall RD, Bixby SD, Voss SD, Robertson RL, Cravero JP. Ionizing radiation from computed tomography versus anesthesia for magnetic resonance imaging in infants and children: patient safety considerations. Pediatr Radiol. 2018;48(1):21-30.
Isokuortti H, Iverson GL, Silverberg ND, Kataja A, Brander A, Öhman J, et al. Characterizing the type and location of intracranial abnormalities in mild traumatic brain injury. J Neurosurg. 2018;129(6):1588-97.
Amoo M, Henry J, O'Halloran PJ, Brennan P, Husien MB, Campbell M, et al. S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy. Neurosurg Rev. 2022;45(2):1171-93.
Nakhjavan-Shahraki B, Yousefifard M, Oraii A, Sarveazad A, Hosseini M. Meta-analysis of neuron specific enolase in predicting pediatric brain injury outcomes. EXCLI J. 2017;16:995.
Edalatfar M, Piri SM, Mehrabinejad M-M, Mousavi M-S, Meknatkhah S, Fattahi M-R, et al. Biofluid biomarkers in traumatic brain injury: a systematic scoping review. Neurocrit Care. 2021;35(2):559-72.
Wang KK, Munoz Pareja JC, Mondello S, Diaz-Arrastia R, Wellington C, Kenney K, et al. Blood-based traumatic brain injury biomarkers - Clinical utilities and regulatory pathways in the United States, Europe and Canada. Expert Rev Mol Diagn. 2021;21(12):1303-21.
Mendoza D, López K, Echeverri R, Pastor L, Rueda S, Fernández Londoño L, et al. Utility of biomarkers in traumatic brain injury: a narrative review. Revista Colombiana de Anestesiologia. 2020;48:155-61.
Al-Adli N, Akbik OS, Rail B, Montgomery E, Caldwell C, Barrie U, et al. The Clinical Use of Serum Biomarkers in Traumatic Brain Injury: A Systematic Review Stratified by Injury Severity. World Neurosurg. 2021;155:e418-e38.
Seidenfaden S-C, Kjerulff JL, Juul N, Kirkegaard H, Møller MF, Münster A-MB, et al. Diagnostic accuracy of prehospital serum S100B and GFAP in patients with mild traumatic brain injury: a prospective observational multicenter cohort study–“the PreTBI I study”. Scand J Trauma Resusc Emerg Med. 2021;29(1):75.
Middleton JL. UCH-L1 and GFAP Testing (i-STAT TBI Plasma) for the Detection of Intracranial Injury Following Mild Traumatic Brain Injury. Am Fam Physician. 2022;105(3):313-4.
Brooke BS, Schwartz TA, Pawlik TM. MOOSE Reporting Guidelines for Meta-analyses of Observational Studies. JAMA Surg. 2021;156(8):787-8.
Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529-36.
Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64(4):380-2.
Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P, Bogner-Flatz V, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17(9):782-9.
Çevik S, Özgenç MM, Güneyk A, Evran Ş, Akkaya E, Çalış F, et al. NRGN, S100B and GFAP levels are significantly increased in patients with structural lesions resulting from mild traumatic brain injuries. Clin Neurol Neurosurg. 2019;183:105380.
Clarke GJB, Skandsen T, Zetterberg H, Einarsen CE, Feyling C, Follestad T, et al. One-Year Prospective Study of Plasma Biomarkers From CNS in Patients With Mild Traumatic Brain Injury. Front Neurol. 2021;12:643743.
Gardner RC, Rubenstein R, Wang KKW, Korley FK, Yue JK, Yuh EL, et al. Age-Related Differences in Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein and Tau for Identifying Acute Intracranial Trauma on Computed Tomography: A TRACK-TBI Study. J Neurotrauma. 2018;35(20):2341-50.
Lagerstedt L, Egea-Guerrero JJ, Bustamante A, Rodríguez-Rodríguez A, El Rahal A, Quintana-Diaz M, et al. Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury. PLoS One. 2018;13(7):e0200394.
Okonkwo DO, Puffer RC, Puccio AM, Yuh EL, Yue JK, Diaz-Arrastia R, et al. Point-of-Care Platform Blood Biomarker Testing of Glial Fibrillary Acidic Protein versus S100 Calcium-Binding Protein B for Prediction of Traumatic Brain Injuries: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study. J Neurotrauma. 2020;37(23):2460-7.
Papa L, Lewis LM, Falk JL, Zhang Z, Silvestri S, Giordano P, et al. Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann Emerg Med. 2012;59(6):471-83.
Papa L, Ladde JG, O'Brien JF, Thundiyil JG, Tesar J, Leech S, et al. Evaluation of Glial and Neuronal Blood Biomarkers Compared With Clinical Decision Rules in Assessing the Need for Computed Tomography in Patients With Mild Traumatic Brain Injury. JAMA Netw Open. 2022;5(3):e221302.
Posti JP, Takala RSK, Lagerstedt L, Dickens AM, Hossain I, Mohammadian M, et al. Correlation of Blood Biomarkers and Biomarker Panels with Traumatic Findings on Computed Tomography after Traumatic Brain Injury. J Neurotrauma. 2019;36(14):2178-89.
Welch RD, Ayaz SI, Lewis LM, Unden J, Chen JY, Mika VH, et al. Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury. J Neurotrauma. 2016;33(2):203-14.
Yue JK, Yuh EL, Korley FK, Winkler EA, Sun X, Puffer RC, et al. Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study. Lancet Neurol. 2019;18(10):953-61.
Safari S, Radfar F, Baratloo A. Thoracic injury rule out criteria and NEXUS chest in predicting the risk of traumatic intra-thoracic injuries: A diagnostic accuracy study. Injury. 2018;49(5):959-62.
Meier TB, Huber DL, Bohorquez-Montoya L, Nitta ME, Savitz J, Teague TK, et al. A Prospective Study of Acute Blood-Based Biomarkers for Sport-Related Concussion. Ann Neurol. 2020;87(6):907-20.
Asken BM, Bauer RM, DeKosky ST, Svingos AM, Hromas G, Boone JK, et al. Concussion BASICS III: Serum biomarker changes following sport-related concussion. Neurology. 2018;91(23):e2133-e43.
Yuh EL, Cooper SR, Mukherjee P, Yue JK, Lingsma HF, Gordon WA, et al. Diffusion tensor imaging for outcome prediction in mild traumatic brain injury: a TRACK-TBI study. J Neurotrauma. 2014;31(17):1457-77.
Sharma R, Rosenberg A, Bennett ER, Laskowitz DT, Acheson SK. A blood-based biomarker panel to risk-stratify mild traumatic brain injury. PLoS One. 2017;12(3):e0173798.
Bogoslovsky T, Wilson D, Chen Y, Hanlon D, Gill J, Jeromin A, et al. Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury. J Neurotrauma. 2017;34(1):66-73.
Thelin EP, Zeiler FA, Ercole A, Mondello S, Büki A, Bellander BM, et al. Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review. Front Neurol. 2017;8:300.
Calcagnile O, Anell A, Undén J. The addition of S100B to guidelines for management of mild head injury is potentially cost saving. BMC Neurol. 2016;16(1):200.
Ruan S, Noyes K, Bazarian JJ. The economic impact of S-100B as a pre-head CT screening test on emergency department management of adult patients with mild traumatic brain injury. J Neurotrauma. 2009;26(10):1655-64.
- Abstract Viewed: 711 times
- pdf Downloaded: 692 times