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

Lindsay D Nelson; Brooke E Magnus; John K Yue; Steve Balsis; Christopher J Patrick; Nancy Temkin; Esther L Yuh; Ramon Diaz-Arrastia; Ehri Ryu; Andrew I R Maas; David K Menon; Lindsay Wilson; Geoffrey T Manley; TRACK-TBI Investigators; Daniel Kondziella

doi:10.1016/j.ebiom.2025.106001

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

Lindsay D Nelson, Brooke E Magnus, John K Yue, Steve Balsis, Christopher J Patrick, Nancy Temkin, Esther L Yuh, Ramon Diaz-Arrastia, Ehri Ryu, Andrew I R Maas, David K Menon, Lindsay Wilson, Geoffrey T Manley, TRACK-TBI Investigators, Daniel Kondziella (Medlem af forfattergruppering)

Afdeling for Hjerne- og Nervesygdomme NEU

1 Citationer (Scopus)

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.

FUNDING: This secondary analysis project was funded by the U.S. National Institute of Neurological Disorders and Stroke (Grant No. R01 NS110856).

Originalsprog	Engelsk
Artikelnummer	106001
Tidsskrift	EBioMedicine
Vol/bind	121
Antal sider	15
ISSN	2352-3964
DOI	https://doi.org/10.1016/j.ebiom.2025.106001
Status	Udgivet - nov. 2025

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10.1016/j.ebiom.2025.106001Licens: CC BY

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Nelson, L. D., Magnus, B. E., Yue, J. K., Balsis, S., Patrick, C. J., Temkin, N., Yuh, E. L., Diaz-Arrastia, R., Ryu, E., Maas, A. I. R., Menon, D. K., Wilson, L., Manley, G. T., TRACK-TBI Investigators, & Kondziella, D. (2025). Beyond mild, moderate, and severe traumatic brain injury: modelling severity from clinical, neuroimaging, and blood-based indicators. EBioMedicine, 121, Artikel 106001. https://doi.org/10.1016/j.ebiom.2025.106001

Nelson, LD, Magnus, BE, Yue, JK, Balsis, S, Patrick, CJ, Temkin, N, Yuh, EL, Diaz-Arrastia, R, Ryu, E, Maas, AIR, Menon, DK, Wilson, L, Manley, GT, TRACK-TBI Investigators & Kondziella, D 2025, 'Beyond mild, moderate, and severe traumatic brain injury: modelling severity from clinical, neuroimaging, and blood-based indicators', EBioMedicine, bind 121, 106001. https://doi.org/10.1016/j.ebiom.2025.106001

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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.FUNDING: This secondary analysis project was funded by the U.S. National Institute of Neurological Disorders and Stroke (Grant No. R01 NS110856).",

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author = "Nelson, {Lindsay D} and Magnus, {Brooke E} and Yue, {John K} and Steve Balsis and Patrick, {Christopher J} and Nancy Temkin and Yuh, {Esther L} and Ramon Diaz-Arrastia and Ehri Ryu and Maas, {Andrew I R} and Menon, {David K} and Lindsay Wilson and Manley, {Geoffrey T} and {TRACK-TBI Investigators} and Daniel Kondziella",

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doi = "10.1016/j.ebiom.2025.106001",

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T2 - modelling severity from clinical, neuroimaging, and blood-based indicators

AU - Nelson, Lindsay D

AU - Magnus, Brooke E

AU - Yue, John K

AU - Balsis, Steve

AU - Patrick, Christopher J

AU - Temkin, Nancy

AU - Yuh, Esther L

AU - Diaz-Arrastia, Ramon

AU - Ryu, Ehri

AU - Maas, Andrew I R

AU - Menon, David K

AU - Wilson, Lindsay

AU - Manley, Geoffrey T

AU - TRACK-TBI Investigators

A2 - Kondziella, Daniel

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N2 - 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.FUNDING: This secondary analysis project was funded by the U.S. National Institute of Neurological Disorders and Stroke (Grant No. R01 NS110856).

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KW - Biomarkers/blood

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KW - Adult

KW - Neuroimaging/methods

KW - Severity of Illness Index

KW - Tomography, X-Ray Computed

KW - Glasgow Coma Scale

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DO - 10.1016/j.ebiom.2025.106001

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JO - EBioMedicine

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ER -

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

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