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Observational Study
. 2024 Sep:107:105298.
doi: 10.1016/j.ebiom.2024.105298. Epub 2024 Aug 26.

Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injury

Lindsay Wilson  1 , Virginia F J Newcombe  2 , Daniel P Whitehouse  2 , Stefania Mondello  3 , Andrew I R Maas  4 , David K Menon  2 ; CENTER-TBI participants and investigators
Collaborators, Affiliations
Observational Study

Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injury

Lindsay Wilson et al. EBioMedicine. 2024 Sep.

Abstract

Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury.

Methods: Exposure-response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates.

Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13-15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 and positive CT (1.21-2.81), GCS 9-12 (1.16-2.02), GCS 3-8 (1.09-1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) percentages of unfavourable outcome were 37-51% in the lowest quintiles of biomarker levels and reached 90-94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), the percentages were 2-4% and 19-28% in the lowest and highest biomarker quintiles, respectively.

Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity.

Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

Keywords: Blood biomarkers; GFAP; NFL; Outcomes; Traumatic brain injury; UCH-L1.

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Conflict of interest statement

Declaration of interests Data were obtained in CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA). Data for the CENTER-TBI study has been collected through the Quesgen e-CRF (Quesgen Systems Inc, USA), hosted on the INCF platform and extracted via the INCF Neurobot tool (INCF, Sweden). VFJN holds a NIHR Rosetrees Trust Advanced Fellowship, NIHR302544, which is funded in partnership by the NIHR and Rosetrees Trust. DKM reports grants, personal fees, and non-financial support from GlaxoSmithKline outside the submitted work; personal fees from Neurotrauma Sciences, Lantmannen AB, PressuraNeuro, CSL Behring, and Invex Ltd, outside of the submitted work. Dr Maas reports receiving personal fees from NeuroTrauma Sciences, and PressuraNeuro outside the submitted work. VFJN reports a grant with ROCHE Pharmaceuticals outside the submitted work, and personal fees from Integra outside the submitted work. Dr Wilson reports receiving personal fees from Novartis, Neurotrauma Sciences, and Mass General Brigham outside the submitted work. No other disclosures were reported.

Figures

Fig. 1
Fig. 1
Percentages of patients with intracranial abnormality on early CT (CT+). Biomarker concentrations are divided into quintiles within each GCS severity group (GCS 13–15 N = 1628, GCS 9–12 N = 222, and GCS 3–8 N = 629). Error bars are 95% confidence intervals for percentages.
Fig. 2
Fig. 2
Biomarker exposure–response relationships for the 6-month GOSE. Biomarker concentrations are divided into quintiles within each GCS severity group (GCS 13–15 CT− N = 868, GCS 13–15 CT+ N = 760, GCS 9–12 N = 222 and GCS 3–8 N = 629). The figure shows the four severity groups in columns and the biomarkers in rows: a NFL, b UCH-L1 and c GFAP. The graphs show percentages of patients at or below three GOSE cut-offs (<8, ≤6, ≤4) in each quintile. Error bars are 95% confidence intervals for percentages.
Fig. 3
Fig. 3
Biomarker exposure–response relationships for unfavourable outcome (GOSE ≤4) in patients with GCS 15 (N = 1243) and GCS 3 (N = 305). Quintiles for GCS 15 and GCS 3 are from the GCS 13–15 and GCS 3–12 groups, respectively. The graphs show percentages of patients at or below the GOSE cutoff in each quintile for NFL, UCH-L1 and GFAP. Error bars are 95% confidence intervals for percentages.
See this image and copyright information in PMC

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