Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study

Czeiter, Endre; Amrein, Krisztina; Gravesteijn, Benjamin; Lecky, Fiona; Menon, David; Mondello, Stefania; Newcombe, Virginia; Richter, Sophie; Steyerberg, Ewout W.; Vyvere, Thijs Vande; Verheyden, Jan; Xu, Haiyan; Yang, Zhihui; Maas, Andrew I. R.; Wang, Kevin; Büki, András

doi:10.1016/j.ebiom.2020.102785

Cited by 182 publications

(189 citation statements)

References 28 publications

(32 reference statements)

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“…The average intra-plate CV of samples for NfL, GFAP, tau, UCHL1 was 7, 7, 16, and 31%, respectively. These CVs are consistent with other studies utilizing this assay [ 17 , 18 ].…”

Section: Methodssupporting

confidence: 92%

Prolonged elevation of serum neurofilament light after concussion in male Australian football players

et al. 2021

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Background Biomarkers that can objectively guide the diagnosis of sports-related concussion, and consequent return-to-play decisions, are urgently needed. In this study, we aimed to determine the temporal profile and diagnostic ability of serum levels of neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP), and tau in concussed male and female Australian footballers. Methods Blood was collected from 28 Australian rules footballers (20 males, 8 females) at 2-, 6-, and 13-days after a diagnosed concussion for comparison to their levels at baseline (i.e. pre-season), and with 27 control players (19 males, 8 females) without a diagnosis of concussion. Serum concentrations of protein markers associated with damage to neurons (UCHL1), axons (NfL, tau), and astrocytes (GFAP) were quantified using a Simoa HD-X Analyzer. Biomarker levels for concussed players were compared over time and between sex using generalised linear mixed effect models, and diagnostic performance was assessed using area under the receiver operating characteristic curve (AUROC) analysis. Results Serum NfL was increased from baseline in male footballers at 6- and 13-days post-concussion. GFAP and tau were increased in male footballers with concussion at 2- and 13-days respectively. NfL concentrations discriminated between concussed and non-concussed male footballers at all time-points (AUROC: 2d = 0.73, 6d = 0.85, 13d = 0.79), with tau also demonstrating utility at 13d (AUROC = 0.72). No biomarker differences were observed in female footballers after concussion. Conclusions Serum NfL may be a useful biomarker for the acute and sub-acute diagnosis of concussion in males, and could inform neurobiological recovery and return-to-play decisions. Future adequately powered studies are still needed to investigate biomarker changes in concussed females.

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“…The average intra-plate CV of samples for NfL, GFAP, tau, UCHL1 was 7, 7, 16, and 31%, respectively. These CVs are consistent with other studies utilizing this assay [ 17 , 18 ].…”

Section: Methodssupporting

confidence: 92%

Prolonged elevation of serum neurofilament light after concussion in male Australian football players

et al. 2021

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“…Local physicians and neurosurgeons are urged to act more vigorously in treating mTBI cases and even recommending rehabilitation programs to avoid future severe physical and long-term neuropsychological disabilities. To this end, blood-based biomarkers, increasingly being used worldwide, can represent a valuable tool to enhance the diagnostic process by enabling more accurate brain injury assessment [79-81]. Moreover, their integration in clinical algorithms can improve the existing decision criteria and guide subsequent management and treatment decisions including advanced neuroimaging, hospital admission, and long-term interventions (i.e., rehabilitation programs) [82, 83].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Traumatic Brain Injury Research in the Middle East and North Africa Region: A Systematic Review

et al. 2021

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Objectives: Traumatic brain injury (TBI) represents a major health concern worldwide with a large impact in the Middle East and North Africa (MENA) region as a consequence of protracted wars and conflicts that adversely affect the general population. Currently, systematic TBI studies in the MENA region are lacking, nonetheless they are immensely needed to enhance trauma management and increase survival rates among TBI patients. This systematic review aims to characterize TBI in the MENA region to guide future policy choices and research efforts and inform tailored guidelines capable of improving TBI management and patient treatment and outcome. Furthermore, it will serve as a road map to evaluate and assess knowledge of trauma impact on regional health systems that can be adopted by health-care providers to raise awareness and improve trauma care. Methods: We conducted a comprehensive search strategy of several databases including MEDLINE/Ovid, PubMed, Embase, Scopus, CINAHL, Google Scholar, and the grey literature in accordance with the PROSPERO systematic review protocol CRD42017058952. Abstracts were screened, and selected eligible studies were reviewed independently by 2 reviewers. We collected demographics information along with TBI characteristics, mortality rates, and regional distribution. Data were extracted using REDCap and checked for accuracy. Results: The search strategy yielded 23,385 citations; 147 studies met the eligibility criteria and were included in this review. Motor vehicle accident (MVA) was the leading cause of TBI (41%) in the MENA region, followed by the military- (15.6%) and fall- (8.8%) related TBI. Males predominantly suffer from TBI-related injuries (85%), with a high prevalence of MVA- and military-related TBI injuries. The TBI mortality rate was 12.9%. The leading causes of mortality were MVA (68%), military (20.5%), and assault (2.9%). The vast majority of reported TBI severity was mild (63.1%) compared to moderate (10.7%) and severe TBI (20.2%). Patients mainly underwent a Glasgow Coma Scale assessment (22.1%), followed by computed tomography scan (8.9%) and surgery (4.1%). Conclusions: Despite its clinical, social, and economic burden, the evidence of TBI research in the MENA region is scarce. Further research and high-quality epidemiological studies are urgently needed to gain a deep understanding of the TBI burden in the region, facilitate the allocation of adequate resources, implement effective preventive and intervention strategies and advise on the TBI patient management as reflective on the TBI patterns and modes.

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“…GFAP, measured within 24 hours following mTBI, was found to improve the prediction of CT abnormalities. 18 Although the combination of GFAP and UCH-L1 did not enhance this performance, compared with GFAP alone, 18 it should be noted that GFAP and UCH-L1 were measured within 24 hours after TBI using a research-use only assay with poor agreement between replicates of biomarker assessments. No cut-off values for GFAP or UCH-L1 were obtained or predefined in the analysis.…”

Section: Discussionmentioning

confidence: 99%

“…12 14 A faster in vitro diagnostic (IVD) technique is then required for a possible use in clinical practice, together with an external validation of the diagnostic accuracy of GFAP and UCH-L1 in patients with mTBI. [15][16][17][18] Automated assays assessing serum concentrations of GFAP and UCH-L1 have been developed on the VIDAS platform (bioMérieux, Marcy l'Etoile, France). The primary objective of the study is to evaluate the diagnostic performance of the VIDAS GFAP and VIDAS UCHL-1 assays in a prospective multicentre cohort of patients with mTBI with respect to their brain CT scan findings.…”

Section: Introductionmentioning

confidence: 99%

Study protocol for investigating the performance of an automated blood test measuring GFAP and UCH-L1 in a prospective observational cohort of patients with mild traumatic brain injury: European BRAINI study

Richard

Lagares

Bondanese³

et al. 2021

BMJ Open

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IntroductionMild traumatic brain injury (mTBI) is a common cause of clinical consultation in the emergency department. Patients with mTBI may undergo brain CT scans based on clinical criteria. However, the proportion of patients with brain lesions on CT is very low. Two serum biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), have been shown to discriminate patients regarding the presence or absence of brain lesions on initial CT scan when assessed within the first 12 hours after TBI. However, the current technique for measuring serum concentrations of GFAP and UCH-L1 is manual and time consuming, which may hinder its use in routine clinical practice. This study assesses the diagnostic accuracy of an automated assay for the measurement of serum GFAP and UCH-L1 in a cohort of patients with mTBI who received a CT scan as the standard of care.Methods and analysisThis is a prospective multicentre observational study of 1760 patients with mTBI recruited in France and Spain across 16 participating sites. Adult patients with an initial Glasgow Coma Scale score of 13–15 and a brain CT scan underwent blood sampling within 12 hours after TBI. The primary outcome measure is the diagnostic performance of an automated assay measuring serum concentrations of GFAP and UCH-L1 for discriminating between patients with positive and negative findings on brain CT-scans. Secondary outcome measures include the performance of these two biomarkers in predicting the neurological status and quality of life at 1 week and 3 months after the trauma.Ethics and disseminationEthics approval was obtained by the Institutional Review Board of Sud-Ouest Outre Mer III in France (Re#2019-A01525-52) and Hospital 12 de Octubre in Spain (Re#19/322). The results will be presented at scientific meetings and published in peer-reviewed publications.Trial registration numberClinicalTrials.gov: NCT04032509.

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Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study

Cited by 182 publications

References 28 publications

Prolonged elevation of serum neurofilament light after concussion in male Australian football players

Prolonged elevation of serum neurofilament light after concussion in male Australian football players

Characterization of Traumatic Brain Injury Research in the Middle East and North Africa Region: A Systematic Review

Study protocol for investigating the performance of an automated blood test measuring GFAP and UCH-L1 in a prospective observational cohort of patients with mild traumatic brain injury: European BRAINI study

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