Abstract
SummaryBackgroundWe aimed to understand the relationship between serum biomarker concentration and lesion type and volume found on computed tomography (CT) following all severities of TBI.MethodsConcentrations of six serum biomarkers (GFAP, NFL, NSE, S100B, t-tau and UCH-L1) were measured in samples obtained <24 hours post-injury from 2869 patients with all severities of TBI, enrolled in the CENTER-TBI prospective cohort study (NCT02210221). Imaging phenotypes were defined as intraparenchymal haemorrhage (IPH), oedema, subdural haematoma (SDH), extradural haematoma (EDH), traumatic subarachnoid haemorrhage (tSAH), diffuse axonal injury (DAI), and intraventricular haemorrhage (IVH). Multivariable polynomial regression was performed to examine the association between biomarker levels and both distinct lesion types and lesion volumes. Hierarchical clustering was used to explore imaging phenotypes; and principal component analysis and k-means clustering of acute biomarker concentrations to explore patterns of biomarker clustering.Findings2869 patient were included, 68% (n=1946) male with a median age of 49 years (range 2-96). All severities of TBI (mild, moderate and severe) were included for analysis with majority (n=1946, 68%) having a mild injury (GCS 13-15). Patients with severe diffuse injury (Marshall III/IV) showed significantly higher levels of all measured biomarkers, with the exception of NFL, than patients with focal mass lesions (Marshall grades V/VI). Patients with either DAI+IVH or SDH+IPH+tSAH, had significantly higher biomarker concentrations than patients with EDH. Higher biomarker concentrations were associated with greater volume of IPH (GFAP, S100B, t-tau;adj r2 range:0·48-0·49; p<0·05), oedema (GFAP, NFL, NSE, t-tau, UCH-L1;adj r2 range:0·44-0·44; p<0·01), IVH (S100B;adj r2 range:0.48-0.49; p<0.05), Unsupervised k-means biomarker clustering revealed two clusters explaining 83·9% of variance, with phenotyping characteristics related to clinical injury severity.InterpretationInterpretation: Biomarker concentration within 24 hours of TBI is primarily related to severity of injury and intracranial disease burden, rather than pathoanatomical type of injury.FundingCENTER-TBI is funded by the European Union 7th Framework programme (EC grant 602150).
Highlights
Traumatic brain injury (TBI) has been described as the most complex disease in the most complex organ;[1] and much of this complexity is secondary to the large heterogeneity of lesions that may occur
We demonstrate a positive association between acute biomarker levels and intracranial lesion burden with significant positive associations between serum biomarker concentrations and volumes of intraparenchymal haemorrhage and intracerebral oedema
This study examines six biomarkers that may be released from different cell types or cell components, after TBI: glial fibrillary acidic protein (GFAP), neurofilament light (NFL), neuron specific enolase (NSE); S100 calcium protein B (S100B), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) and total tau (t-tau)
Summary
Traumatic brain injury (TBI) has been described as the most complex disease in the most complex organ;[1] and much of this complexity is secondary to the large heterogeneity of lesions that may occur. Computed Tomography (CT) remains the most commonly utilised radiological method for the diagnosis of TBI associated intracranial lesions and for determining the need for emergent management.[2] The cost and radiation burden associated with neuroimaging, in those with a mild injury, has led to increasing exploration of blood biomarkers to aid in diagnosis, detection of neuro-worsening and prognostication.[3,4] Biomarkers offer the potential to better characterise the heterogeneity of TBI. Prior literature has focused on the diagnostic ability of proteomic biomarkers for the detection of intracranial pathology.5À7 Yet the impact of intracranial injury www.thelancet.com Vol xx Month xx, 2021
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
