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Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain InjuryA TRACK-TBI Study With External Validation in CENTER-TBI

Educational Objective
To determine whether different patterns of intracranial injury on head computed tomography are associated with prognosis after mild traumatic brain injury.
1 Credit CME
Key Points

Question  Are different patterns of intracranial injury on head computed tomography associated with prognosis after mild traumatic brain injury (mTBI)?

Findings  In this cohort study, subarachnoid hemorrhage, subdural hematoma, and contusion often co-occurred and were associated with both incomplete recovery and more severe impairment out to 12 months after injury, while intraventricular and/or petechial hemorrhage co-occurred and were associated with more severe impairment up to 12 months after injury; epidural hematoma was associated with incomplete recovery at some points but not with more severe impairment. Some intracranial hemorrhage patterns were more strongly associated with outcomes than previously validated demographic and clinical variables.

Meaning  In this study, different pathological features on head computed tomography carried different implications for mild traumatic brain injury prognosis to 1 year.

Abstract

Importance  A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.

Objective  To identify pathological CT features associated with adverse outcomes after mTBI.

Design, Setting, and Participants  The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale–Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.

Exposures  Acute nonpenetrating head trauma.

Main Outcomes and Measures  Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months.

Results  In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study.

Conclusions and Relevance  In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.

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Article Information

Accepted for Publication: March 3, 2021.

Published Online: July 19, 2021. doi:10.1001/jamaneurol.2021.2120

Corresponding Author: Geoffrey T. Manley, MD, PhD, Department of Neurological Surgery, University of California, San Francisco, 1001 Potrero Ave, Bldg 1, Room 101, San Francisco, CA 94110 (manleyg@ucsf.edu); and Esther L. Yuh, MD, PhD, Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry St, Bldg B, Lobby 6, Ste 350, San Francisco, CA 94107 (esther.yuh@ucsf.edu).

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Yuh EL et al. JAMA Neurology.

TRACK-TBI Investigators authors: Opeolu Adeoye, MD; Neeraj Badjatia, MD; Kim Boase, BA; Yelena Bodien, PhD; John D. Corrigan, PhD, ABPP; Karen Crawford; Sureyya Dikmen, PhD; Ann-Christine Duhaime, MD; Richard Ellenbogen, MD; V. Ramana Feeser, MD; Adam R. Ferguson, PhD; Brandon Foreman, MD; Raquel Gardner; Etienne Gaudette, PhD; Luis Gonzalez; Shankar Gopinath, MD; Rao Gullapalli, PhD; J. Claude Hemphill, MD; Gillian Hotz, PhD; C. Dirk Keene, MD, PhD; Joel Kramer, PsyD; Natalie Kreitzer, MD; Chris Lindsell, PhD; Joan Machamer, MA; Christopher Madden, MD; Alastair Martin, PhD; Thomas McAllister, MD; Randall Merchant, PhD; Lindsay Nelson, PhD; Laura B. Ngwenya, MD, PhD; Florence Noel, PhD; Amber Nolan, MD, PhD; Eva Palacios, PhD; Daniel Perl, MD; Miri Rabinowitz, PhD; Jonathan Rosand, MD, MSc; Angelle Sander, PhD; Gabriella Satris; David Schnyer, PhD; Seth Seabury, PhD; Arthur Toga, PhD; Alex Valadka, MD; Mary Vassar, RN, MS; Ross Zafonte, DO.

Affiliations of TRACK-TBI Investigators authors: University of Cincinnati, Cincinnati, Ohio (Adeoye, Foreman, Kreitzer, Ngwenya); University of Maryland, College Park (Badjatia, Gullapalli); University of Washington, Seattle (Boase, Dikmen, Ellenbogen, Keene, Machamer); Massachusetts General Hospital, Boston (Bodien); Ohio State University, Dublin (Corrigan); University of Southern California, Los Angeles (Crawford, Gaudette, Seabury, Toga); Massachusetts General Hospital for Children, Boston (Duhaime); Virginia Commonwealth University, Richmond (Feeser, Merchant, Valadka); University of California, San Francisco, San Francisco (Ferguson, Gardner, Hemphill, Kramer, Martin, Nolan, Palacios, Satris, Vassar); TIRR Memorial Hermann, Houston, Texas (Gonzalez); Baylor College of Medicine, Houston, Texas (Gopinath, Noel, Sander); University of Miami, Miami, Florida (Hotz); Vanderbilt University, Nashville, Tennessee (Lindsell); UT Southwestern Medical Center, Dallas, Texas (Madden); Indiana University, Bloomington (McAllister); Medical College of Wisconsin, Milwaukee (Nelson); Uniformed Services University, Bethesda, Maryland (Perl); University of Pittsburgh, Pittsburgh, Pennsylvania (Rabinowitz); Massachusetts General Hospital, Boston (Rosand); University of Texas at Austin, Austin (Schnyer); Harvard Medical School, Boston, Massachusetts (Zafonte).

Author Contributions: Dr Manley had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Yuh, Mukherjee, McCrea, Temkin, Diaz-Arrastia, Okonkwo, Manley, Adeoye, Corrigan, Kramer, Perl, Dikmen.

Acquisition, analysis, or interpretation of data: Yuh, Jain, Sun, Pisică, Harris, Taylor, Markowitz, Mukherjee, Verheyden, Giacino, Levin, McCrea, Stein, Temkin, Diaz-Arrastia, Robertson, Lingsma, Okonkwo, Maas, Manley, Adeoye, Badjatia, Boase, Bodien, Crawford, Duhaime, Ellenbogen, Feeser, Ferguson, Foreman, Gardner, Gaudette, Gonzalez, Gopinath, Gullapalli, Hemphill, Hotz, Keene, Kreitzer, Lindsell, Machamer, Madden, Martin, McAllister, Merchant, Nelson, Ngwenya, Noel, Nolan, Palacios, Rabinowitz, Rosand, Sander, Satris, Schnyer, Seabury, Toga, Valadka, Vassar, Zafonte.

Drafting of the manuscript: Yuh, Jain, Harris, Verheyden, Okonkwo, Noel, Rabinowitz, Vassar.

Critical revision of the manuscript for important intellectual content: Jain, Sun, Pisică, Harris, Taylor, Markowitz, Mukherjee, Giacino, Levin, McCrea, Stein, Temkin, Diaz-Arrastia, Robertson, Lingsma, Okonkwo, Maas, Manley, Adeoye, Badjatia, Boase, Bodien, Corrigan, Crawford, Duhaime, Ellenbogen, Feeser, Ferguson, Foreman, Gardner, Gaudette, Gonzalez, Gopinath, Gullapalli, Hemphill, Hotz, Keene, Kramer, Kreitzer, Lindsell, Machamer, Madden, Martin, McAllister, Merchant, Nelson, Ngwenya, Nolan, Palacios, Perl, Rosand, Sander, Satris, Schnyer, Seabury, Toga, Valadka, Zafonte, Dikmen.

Statistical analysis: Yuh, Jain, Sun, Pisică, Harris, Okonkwo, Ferguson.

Obtained funding: Mukherjee, Temkin, Diaz-Arrastia, Okonkwo, Manley, Adeoye, Corrigan, Toga.

Administrative, technical, or material support: Harris, Taylor, Markowitz, Mukherjee, Verheyden, McCrea, Diaz-Arrastia, Robertson, Okonkwo, Manley, Adeoye, Bodien, Duhaime, Ellenbogen, Ferguson, Gonzalez, Gopinath, Gullapalli, Lindsell, Martin, Merchant, Perl, Rabinowitz, Satris, Schnyer, Valadka, Vassar, Zafonte.

Supervision: Lingsma, Okonkwo, Maas, Manley, Bodien, Ferguson, Gopinath, Sander.

Other—Member of TRACK TBI Outcomes Core: McAllister.

Other—monitoring: Noel.

Other—Discussion of need for validating imaging Common Data Elements for TBI: Levin.

Other: Dikmen.

Conflict of Interest Disclosures: Dr Bodien reports grants from the National Institute of Neurological Disorders and Stroke (NINDS) during the conduct of the study. Dr Boase reports grants from NINDS and grants from the Department of Defense during the conduct of the study. Dr Diaz-Arrastia reports grants from the National Institutes of Health (NIH), Department of Defense, and Pennsylvania Department of Health. Dr Duhaime reports grants from the NIH during the conduct of the study. Dr Adeoye reports being a founder and equity holder from Sense Diagnostics Inc outside the submitted work and holding patent US13/977,689 issued, which is related to Sense Diagnostics work. Dr Giacino reports grants from NINDS, the Department of Defense, the National Institute on Disability, Independent Living and Rehabilitation Research, James S. McDonnell Foundation, and the National Football League during the conduct of the study. Dr Ferguson reports grants from the NIH (grants UG3/UH3NS106899, R01NS088475, U01NS086090), the Department of Veterans Affairs (grants I01RX002245 and I01RX002787), the Department of Energy (LLNL), and the Department of Defense (grants W81XWH-14-2-0176 and W81XWH2010245) during the conduct of the study and grants from the NIH (grants U19AR076737, R01AG056770, R01MH116156, R01CA213441, and R01NS114043), Defense Advanced Research Projects Agency (grant N660012024046), the National Aeronautics and Space Administration (grant 80NSSC19K158), the Craig H. Neilsen Foundation, and Wings for Life Foundation outside the submitted work. Dr Foreman reports grants from the NINDS, the Department of Defense, and the National Science Foundation and personal fees from UCB Pharma Inc for speaking and consulting outside the submitted work. Dr Lindsell reports grants from the NIH during the conduct of the study and grants from the NIH, Department of Defense, and US Centers for Disease Control and Prevention; research contracts to their institution from Entegrion Inc, Endpoint Health, and bioMerieux; stock options from Bioscape Digital; and grants from Marcus Foundation outside the submitted work. In addition, Dr Lindsell has a patent for risk stratification in pediatric septic shock issued to Cincinnati Children's Hospital Medical Center. Dr Levin reports grants from the NIH and the Department of Defense during the period of research for this study. Dr Maas reports a grant from European Union 7th Framework Program (grant 602150) during the conduct of the study and grants from Integra LifeSciences and NeuroTrauma Sciences and personal fees from PresSuraNeuro outside the submitted work. Dr McAllister reports grants from University of California, San Francisco research subaward for Indiana University School of Medicine for TRACK-TBI during the conduct of the study. Dr McCrea reports a research subaward from the NIH during the conduct of the study and research grants from the NINDS, Department of Defense, Centers for Disease Control and Prevention, Abbott Laboratories, National Collegiate Athletic Association, and National Football League Scientific Advisory Board outside the submitted work. Dr Mukherjee reports grants from the NIH, Department of Defense, Abbott Labs, and the National Football League Scientific Advisory Board, and patents 15/782,005 and PCT/US2020/042811 pending to the University of California Regents during the conduct of the study. Dr Nelson reports grants from NINDS during the conduct of the study and grants from the Department of Defense, Advancing a Healthier Wisconsin Research & Education Program, Medical College of Wisconsin, and the US Centers for Disease Control and Prevention outside the submitted work. Dr Machamer reports grants from the Department of Defense and grants from NINDS during the conduct of the study. Dr Madden reports grants from the NIH to TRACK-TBI during the conduct of the study. Dr Manley reports grants from NINDS to TRACK-TBI (grant U01NS086090), the US Department of Defense for the Traumatic Brain Injury Endpoints Development Initiative (grant W81XWH-14-2-0176), funding for stipends for patients in TRACK-TBI and support to clinical sites from One Mind, support for TRACK-TBI data curation efforts from NeuroTrauma Sciences LLC, support for a precision medicine collaboration from US Department of Energy, grants from US Department of Defense for TRACK-TBI precision medicine (grant W81XWH-18-2-0042), a contract from the US Department of Defense to the Medical Technology Enterprise Consortium TRACK-TBI Network (contract W81XWH-15-9-0001), and a grant from the National Football League to the TRACK-TBI LONG study (which will extend TRACK-TBI’s current 1-year follow-up for 3 additional years) during the conduct of the study. Ms Markowitz reports a grant from the US Department of Defense TBI Endpoints Development Initiative (grant W81XWH-14-2-0176), a contract from the US Department of Defense/Medical Technology Enterprise Consortium to the TRACK-TBI NETWORK (contract W81XWH-15-9-0001), personal fees from the US Department of Energy for salary support from the precision medicine collaboration, and personal fees from One Mind for salary support during the conduct of the study. Dr Okonkwo reports grants from the NIH, the Department of Defense, Abbott, One Mind, and the National Football League Scientific Advisory Board during the conduct of the study. Dr Robertson reports grants from the NIH, the Department of Defense, Abbott, and the National Football League Scientific Advisory Board during the conduct of the study. Dr Rosand reports grants from the NIH and One Mind for research during the conduct of the study and fees from Boehringer Ingelheim for consulting outside the submitted work. Dr Pisică reports a grant from European Union 7th Framework Program (EC grant 602150) during the conduct of the study. Dr Toga reports grants from the NIH during the conduct of the study. Dr Temkin reports grants from the NIH and Department of Defense during the study and other funding from the Department of Energy and University of Southern California during the conduct of the study. Dr Stein reports grants from NINDS during the conduct of the study and stock options from Oxeia Biopharmaceuticals outside the submitted work. Dr Yuh reports patents 15/782,005 and PCT/US2020/042811 pending to the University of California Regents. Dr Schnyer reports grants from the NIH and the Department of Defense during the conduct of the study. Dr Verheyden reports grants from 7th Framework Program (grant NCT02210221) during the conduct of the study. Dr Zafonte received royalties from Oakstone for an educational CD called Physical Medicine and Rehabilitation: a Comprehensive Review and Springer/Demos Publishing for serving as coeditor of the text Brain Injury Medicine; Dr Zafonte serves on the scientific advisory boards of Myomo, Oxeia Biopharma, ElMindA, and Biodirection and evaluates patients in the Massachusetts General Hospital Brain and Body–TRUST Program, which is funded by the National Football League Players Association.

Funding/Support: This Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) analysis was funded by the US Department of Defense (TBI Endpoints Development Initiative grant W81XWH-14-2-0176); TRACK-TBI was funded by the National Institutes of Health/National Institute for Neurologic Disorders and Stroke (grant U01 NS1365885), One Mind, NeuroTrauma Sciences, and Jackson Family Foundation; and Abbott Laboratories provides research support to the TRACK-TBI Network under a collaborative research agreement. Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) was funded by the European Union Seventh Framework Program (EC grant 602150) with additional funding from the Hannelore Kohl Stiftung, One Mind, the Integra LifeSciences Corporation, and NeuroTrauma Sciences. Patient travel expenses and stipends were supported by One Mind (Staglin Family and General Peter Chiarelli).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The article contents are solely the responsibility of the authors, do not necessarily represent the official views of the National Institutes of Health, and are not necessarily endorsed by the US Department of Defense or other study sponsors.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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