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. 2023 Sep 5;6(9):e2335804.
doi: 10.1001/jamanetworkopen.2023.35804.

Longitudinal Recovery Following Repetitive Traumatic Brain Injury

Leila L Etemad  1   2 , John K Yue  1   2 , Jason Barber  3 , Lindsay D Nelson  4   5 , Yelena G Bodien  6   7 , Gabriela G Satris  1   2 , Patrick J Belton  1   2 , Debbie Y Madhok  8 , J Russell Huie  1   2 , Sabah Hamidi  1   2 , Joye X Tracey  1   2 , Bukre C Coskun  1   2 , Justin C Wong  1   2 , Esther L Yuh  2   9 , Pratik Mukherjee  2   9 , Amy J Markowitz  1   2 , Michael C Huang  1   2 , Phiroz E Tarapore  1   2 , Claudia S Robertson  10 , Ramon Diaz-Arrastia  11 , Murray B Stein  12 , Adam R Ferguson  1   2   13 , Ava M Puccio  14 , David O Okonkwo  14 , Joseph T Giacino  6   7 , Michael A McCrea  4   5 , Geoffrey T Manley  1   2 , Nancy R Temkin  3 , Anthony M DiGiorgio  1   2   15 ; TRACK-TBI Investigators
Collaborators, Affiliations

Longitudinal Recovery Following Repetitive Traumatic Brain Injury

Leila L Etemad et al. JAMA Netw Open. .

Abstract

Importance: One traumatic brain injury (TBI) increases the risk of subsequent TBIs. Research on longitudinal outcomes of civilian repetitive TBIs is limited.

Objective: To investigate associations between sustaining 1 or more TBIs (ie, postindex TBIs) after study enrollment (ie, index TBIs) and multidimensional outcomes at 1 year and 3 to 7 years.

Design, setting, and participants: This cohort study included participants presenting to emergency departments enrolled within 24 hours of TBI in the prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years, February 2014 to July 2020). Participants who completed outcome assessments at 1 year and 3 to 7 years were included. Data were analyzed from September 2022 to August 2023.

Exposures: Postindex TBI(s).

Main outcomes and measures: Demographic and clinical factors, prior TBI (ie, preindex TBI), and functional (Glasgow Outcome Scale-Extended [GOSE]), postconcussive (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]), psychological distress (Brief Symptom Inventory-18 [BSI-18]), depressive (Patient Health Questionnaire-9 [PHQ-9]), posttraumatic stress disorder (PTSD; PTSD Checklist for DSM-5 [PCL-5]), and health-related quality-of-life (Quality of Life After Brain Injury-Overall Scale [QOLIBRI-OS]) outcomes were assessed. Adjusted mean differences (aMDs) and adjusted relative risks are reported with 95% CIs.

Results: Of 2417 TRACK-TBI participants, 1572 completed the outcomes assessment at 1 year (1049 [66.7%] male; mean [SD] age, 41.6 [17.5] years) and 1084 completed the outcomes assessment at 3 to 7 years (714 [65.9%] male; mean [SD] age, 40.6 [17.0] years). At 1 year, a total of 60 participants (4%) were Asian, 255 (16%) were Black, 1213 (77%) were White, 39 (2%) were another race, and 5 (0.3%) had unknown race. At 3 to 7 years, 39 (4%) were Asian, 149 (14%) were Black, 868 (80%) were White, 26 (2%) had another race, and 2 (0.2%) had unknown race. A total of 50 (3.2%) and 132 (12.2%) reported 1 or more postindex TBIs at 1 year and 3 to 7 years, respectively. Risk factors for postindex TBI were psychiatric history, preindex TBI, and extracranial injury severity. At 1 year, compared with those without postindex TBI, participants with postindex TBI had worse functional recovery (GOSE score of 8: adjusted relative risk, 0.57; 95% CI, 0.34-0.96) and health-related quality of life (QOLIBRI-OS: aMD, -15.9; 95% CI, -22.6 to -9.1), and greater postconcussive symptoms (RPQ: aMD, 8.1; 95% CI, 4.2-11.9), psychological distress symptoms (BSI-18: aMD, 5.3; 95% CI, 2.1-8.6), depression symptoms (PHQ-9: aMD, 3.0; 95% CI, 1.5-4.4), and PTSD symptoms (PCL-5: aMD, 7.8; 95% CI, 3.2-12.4). At 3 to 7 years, these associations remained statistically significant. Multiple (2 or more) postindex TBIs were associated with poorer outcomes across all domains.

Conclusions and relevance: In this cohort study of patients with acute TBI, postindex TBI was associated with worse symptomatology across outcome domains at 1 year and 3 to 7 years postinjury, and there was a dose-dependent response with multiple postindex TBIs. These results underscore the critical need to provide TBI prevention, education, counseling, and follow-up care to at-risk patients.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Yue reported grants from the Neurosurgery Research and Education Foundation and the Bagan Family Foundation Research Fellowship during the conduct of the study. Dr Nelson reported grants from the National Institute of Neurological Disorders and Stroke, US Centers for Disease Control and Prevention, the US Department of Defense, Medical Technology Enterprise Consortium, and Medical College of Wisconsin Advancing a Healthier Wisconsin Endowment outside the submitted work. Dr Bodien reported grants from the National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr Yuh reported grants from the National Institutes of Health and the Department of Defense during the conduct of the study. Dr Mukherjee reported grants from the National Institutes of Health during the conduct of the study and has a patent for USPTO 62/269778 issued. Dr Markowitz reported grants from the Department of Defense TBI Endpoints Development Initiative during the conduct of the study. Dr Robertson reported grants from the National Institutes of Health, Department of Defense, and National Football League during the conduct of the study. Dr Diaz-Arrastia reported grants and personal fees from BrainBox Solutions and holds stock options in BrainBox Solutions outside the submitted work. Dr Stein reported personal fees from atai Life Sciences, BigHealth, Biogen, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Roche/Genentech, Sage Therapeutics, and Sumitomo Pharma and holds stock options in Oxeia Biopharmaceuticals and EpiVario outside the submitted work. Dr Ferguson reported grants from the National Institutes of Health, Veterans Affairs, Craig H. Neilsen Foundation, and Wings for Life Foundation during the conduct of the study; grants from Santa Clara Valley Medical Center; personal fees from Neuronasal and Spine X; and nonfinancial support from DataRobot outside the submitted work. Dr Giacino reported grants from the Department of Defense and National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr McCrea reported grants from the National Institutes of Health during the conduct of the study; grants from the National Institutes of Health, Centers for Disease Control and Prevention, Deptartment of Defense, National Collegiate Athletics Association, and National Football League; and has served as a consultant for NeuroTrauma Sciences outside the submitted work. Dr Manley reported grants from the Department of Defense, National Institutes of Health, National Football League, and US Department of Energy during the conduct of the study and has received support from NeuroTrauma Sciences and One Mind outside the submitted work. Dr Temkin reported grants from the US Federal Government and the National Football League Foundation during the conduct of the study. Dr DiGiorgio reported grants from Mercatus Center at George Mason University, DePuy Synthes, and AO Spine as well as personal fees from the National Football League outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. CONSORT Flow Diagram
TBI indicates traumatic brain injury.
Figure 2.
Figure 2.. Unweighted Mean Outcome Scores by Group Status at 1 Year and 3 to 7 Years
The diamond indicates the mean; midline, the median; box, the IQR; whiskers, the range; and data points, outliers. BSI-18 indicates Brief Symptom Inventory-18; GOSE, Glasgow Outcome Scale–Extended; PCL-5, PTSD Checklist for DSM-5; PHQ-9, Patient Health Questionnaire-9; QOLIBRI-OS, Quality of Life After Brain Injury–Overall Scale; RPQ, Rivermead Post-Concussion Symptoms Questionnaire; TBI, traumatic brain injury.
See this image and copyright information in PMC

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