Serum Glial Fibrillary Acidic Protein in Detecting Intracranial Injuries Following Minor Head Trauma; a Systematic Review and Meta-Analysis

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.

[1]  J. Middleton UCH-L1 and GFAP Testing (i-STAT TBI Plasma) for the Detection of Intracranial Injury Following Mild Traumatic Brain Injury. , 2022, American family physician.

[2]  G. Parrish,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 , 2022, JAMA network open.

[3]  D. Okonkwo,et al.  Blood-based traumatic brain injury biomarkers – Clinical utilities and regulatory pathways in the United States, Europe and Canada , 2021, Expert review of molecular diagnostics.

[4]  P. Brennan,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 , 2021, Neurosurgical Review.

[5]  S. Vira,et al.  The Clinical Use of Serum Biomarkers in Traumatic Brain Injury: A Systematic Review Stratified by Injury Severity. , 2021, World neurosurgery.

[6]  N. Juul,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” , 2021, Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine.

[7]  K. Blennow,et al.  One-Year Prospective Study of Plasma Biomarkers From CNS in Patients With Mild Traumatic Brain Injury , 2021, Frontiers in Neurology.

[8]  T. Pawlik,et al.  MOOSE Reporting Guidelines for Meta-analyses of Observational Studies. , 2021, JAMA surgery.

[9]  M. Sharif-Alhoseini,et al.  Biofluid Biomarkers in Traumatic Brain Injury: A Systematic Scoping Review , 2021, Neurocritical Care.

[10]  M. Teixeira,et al.  Biomarkers for traumatic brain injury: a short review , 2020, Neurosurgical Review.

[11]  Adam R Ferguson,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 , 2020, Journal of Neurotrauma.

[12]  Bouvier Damien,et al.  Interest of blood biomarkers to predict lesions in medical imaging in the context of mild traumatic brain injury. , 2020, Clinical biochemistry.

[13]  A. Rubiano,et al.  Utility of biomarkers in traumatic brain injury: a narrative review , 2020, Colombian Journal of Anesthesiology.

[14]  J. Savitz,et al.  A Prospective Study of Acute Blood‐Based Biomarkers for Sport‐Related Concussion , 2020, Annals of neurology.

[15]  Adam R Ferguson,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 , 2019, The Lancet Neurology.

[16]  Celaleddin Soyalp,et al.  NRGN, S100B and GFAP levels are significantly increased in patients with structural lesions resulting from mild traumatic brain injuries , 2019, Clinical Neurology and Neurosurgery.

[17]  Sojib Bin Zaman,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 , 2019, The Lancet Neurology.

[18]  K. Blennow,et al.  Correlation of Blood Biomarkers and Biomarker Panels with Traumatic Findings on Computed Tomography after Traumatic Brain Injury. , 2019, Journal of neurotrauma.

[19]  John K. Yue,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. , 2018, Journal of neurotrauma.

[20]  J. Ornato,et al.  Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study , 2018, The Lancet Neurology.

[21]  K. Schaller,et al.  Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury , 2018, PloS one.

[22]  Saeed Safari,et al.  Thoracic injury rule out criteria and NEXUS chest in predicting the risk of traumatic intra-thoracic injuries: A diagnostic accuracy study. , 2018, Injury.

[23]  G. Iverson,et al.  Characterizing the type and location of intracranial abnormalities in mild traumatic brain injury. , 2018, Journal of neurosurgery.

[24]  M. Yousefifard,et al.  Meta-analysis of neuron specific enolase in predicting pediatric brain injury outcomes , 2017, EXCLI journal.

[25]  D. Menon,et al.  Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review , 2017, Front. Neurol..

[26]  S. Acheson,et al.  A blood-based biomarker panel to risk-stratify mild traumatic brain injury , 2017, PloS one.

[27]  Ramon Diaz-Arrastia,et al.  Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury. , 2017, Journal of neurotrauma.

[28]  S. Bixby,et al.  Ionizing radiation from computed tomography versus anesthesia for magnetic resonance imaging in infants and children: patient safety considerations , 2017, Pediatric Radiology.

[29]  A. Anell,et al.  The addition of S100B to guidelines for management of mild head injury is potentially cost saving , 2016, BMC Neurology.

[30]  F. Tortella,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 , 2016, Journal of neurotrauma.

[31]  Ewout W Steyerberg,et al.  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. , 2015, Journal of neurotrauma.

[32]  Hester F. Lingsma,et al.  Diffusion tensor imaging for outcome prediction in mild traumatic brain injury: a TRACK-TBI study. , 2014, Journal of neurotrauma.

[33]  F. Tortella,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. , 2012, Annals of emergency medicine.

[34]  Susan Mallett,et al.  QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies , 2011, Annals of Internal Medicine.

[35]  M. Gemma,et al.  Early prognosis after severe traumatic brain injury with minor or absent computed tomography scan lesions. , 2011, The Journal of trauma.

[36]  G. Guyatt,et al.  GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. , 2011, Journal of clinical epidemiology.

[37]  T. Kurki,et al.  Reliability of diagnosis of traumatic brain injury by computed tomography in the acute phase. , 2009, Journal of neurotrauma.

[38]  J. Bazarian,et al.  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. , 2009, Journal of neurotrauma.