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

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 - 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 fi lament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fi brillary acidic protein (GFAP) were assayed from serum sampled in the fi rst 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified fi ed 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 - 15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13-15 - 15 and positive CT (1.21-2.81), - 2.81), GCS 9-12 - 12 (1.16-2.02), - 2.02), GCS 3-8 - 8 (1.09-1.94). - 1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51-1.80) - 1.80) percentages of unfavourable outcome were 37-51% - 51% in the lowest quintiles of biomarker levels and reached 90-94% - 94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83-3.79), - 3.79), the percentages were 2-4% - 4% and 19-28% - 28% in the lowest and highest biomarker quintiles, respectively. Interpretation Conventional TBI severity classification fi cation 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. Copyright (c) 2024 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).