Beyond mild, moderate, and severe traumatic brain injury: modelling severity from clinical, neuroimaging, and blood-based indicators

Citation

Nelson LD, Magnus BE, Yue JK, Balsis S, Patrick CJ, Temkin N, Yuh EL, Diaz-Arrastia R, Ryu E, Maas AI, Menon DK, Wilson L, Manley GT, Track TBI Investigators & CENTER-TBI Participants and Investigators (2025) Beyond mild, moderate, and severe traumatic brain injury: modelling severity from clinical, neuroimaging, and blood-based indicators. eBioMedicine, 121, Art. No.: 106001. https://doi.org/10.1016/j.ebiom.2025.106001

Abstract
Background The conventional clinical approach to characterising traumatic brain injuries (TBIs) as mild, moderate, or severe using the Glasgow Coma Scale (GCS) total score has well-known limitations, prompting calls for more sophisticated strategies. Methods We used item response theory (IRT) to develop a new method for quantifying TBI severity using 24 clinical, head computed tomography, and blood-based biomarker variables familiar to clinicians and researchers. IRT uses individuals’ response patterns across indicators to estimate relationships between the indicators and a latent continuum of TBI severity. Model parameters were used to assign severity scores in two large cohorts, and associations with traditional GCS categories and 6-month functional outcomes (Glasgow Outcome Scale-Extended [GOSE]) were tested with correlational and logistic regression analyses. Findings In the prospective Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) cohort (N = 2545), modelling showed the 24 indicators index a common latent continuum of TBI severity. IRT enabled us to identify the relative contribution of these features to estimate an individual's TBI severity. Finally, within both the TRACK-TBI derivation sample and an external validation sample (Collaborative European NeuroTrauma Effectiveness Research in TBI [CENTER-TBI]), TBI severity scores generated using this novel IRT-based method incrementally predicted functional (GOSE) outcome better than classic clinical (mild, moderate, severe) or International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) classification methods. Interpretation Our findings directly inform ongoing international efforts to refine and deploy new pragmatic, empirically-supported strategies for characterising TBI, while illustrating a strategy that may be useful to improve staging systems for other diseases.

Keywords
Traumatic brain injury; Severity; Classification; Blood-based biomarkers; Neuroimaging; Item response theory

Journal
eBioMedicine: Volume 121

• Beyond mild, moderate, and severe traumatic brain injury: modelling severity from clinical, neuroimaging, and blood-based indicators