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. 2021 Apr 1;4(4):e213046.
doi: 10.1001/jamanetworkopen.2021.3046.

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study

Harvey S Levin  1   2 , Nancy R Temkin  3   4 , Jason Barber  3 , Lindsay D Nelson  5   6 , Claudia Robertson  2 , Jeffrey Brennan  1 , Murray B Stein  7 , John K Yue  8 , Joseph T Giacino  9   10 , Michael A McCrea  5   6 , Ramon Diaz-Arrastia  11 , Pratik Mukherjee  8 , David O Okonkwo  12 , Kim Boase  3 , Amy J Markowitz  8 , Yelena Bodien  9   10 , Sabrina Taylor  8 , Mary J Vassar  8 , Geoffrey T Manley  8 ; TRACK-TBI Investigators; Opeolu Adeoye  13 , Neeraj Badjatia  14 , M Ross Bullock  15 , Randall Chesnut  3 , John D Corrigan  16 , Karen Crawford  17 , Sureyya Dikmen  18 , Ann-Christine Duhaime  19 , Richard Ellenbogen  3 , V Ramana Feeser  20 , Adam R Ferguson  8 , Brandon Foreman  13 , Raquel Gardner  8 , Etienne Gaudette  17 , Luis Gonzalez  21 , Shankar Gopinath  1 , Rao Gullapalli  14 , J Claude Hemphill  8 , Gillian Hotz  15 , Sonia Jain  7 , C Dirk Keene  3 , Frederick K Korley  22 , Joel Kramer  8 , Natalie Kreitzer  13 , Chris Lindsell  23 , Joan Machamer  3 , Christopher Madden  24 , Alastair Martin  8 , Thomas McAllister  25 , Randall Merchant  20 , Amber Nolan  8 , Laura B Ngwenya  13 , Florence Noel  1 , Eva Palacios  8 , Ava Puccio  13 , Miri Rabinowitz  12 , Jonathan Rosand  10 , Angelle Sander  1 , Gabriella Satris  8 , David Schnyer  26 , Seth Seabury  17 , Xiaoying Sun  7 , Arthur Toga  17 , Alex Valadka  20 , Kevin Wang  27 , Esther Yuh  8 , Ross Zafonte  28
Affiliations

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study

Harvey S Levin et al. JAMA Netw Open. .

Abstract

Importance: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients.

Objective: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI.

Design, setting, and participants: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021.

Exposures: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls.

Main outcomes and measures: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales).

Results: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02).

Conclusions and relevance: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Temkin reported receiving grants from the US federal government during the conduct of the study. Dr Nelson reported receiving grants from National Institute of Neurological Disorders and Stroke (NINDS) Support for the research during the conduct of the study, grants from the Department of Defense Funding for unrelated research, and grants from the Medical College of Wisconsin Advancing a Healthier Wisconsin Endowment Funding for unrelated research outside the submitted work. Dr Robertson reported receiving grants from the National Institutes of Health (NIH) and from the Department of Defense during the conduct of the study. Dr Stein reported receiving stock options from Oxeia Biopharmaceuticals outside the submitted work. Dr Giacino reported receiving a subcontract from the University of California, San Francisco during the conduct of the study. Dr McCrea reported receiving grants from the US Department of Defense and research funding to the Medical College of Wisconsin during the conduct of the study. Dr Diaz-Arrastia reported receiving grants from the NIH/NINDS, the US Department of Defense, and BrainBox Solutions during the conduct of the study; receiving stock options from Nia Therapeutics; and receiving personal fees from Pinteon Therapeutics and Ischemix Inc outside the submitted work. Dr Mukherjee reported receiving a pending patent for 15/782,005 University of California, San Francisco. Dr Boase reported receiving grants from the US federal government during the conduct of the study. Dr Markowitz reported receiving grants from the US Department of Defense Traumatic Brain Injury Endpoints Development Initiative (no. W81XWH-14-2-0176), a contract from the US Department of Defense/Medical Technology Enterprise Consortium TRACK-TBI Network (no. W81XWH-15-9-0001), personal fees from the US Department of Energy, and salary support from Precision Medicine Collaboration and One Mind during the conduct of the study. Dr Vassar reported receiving grants from NINDS and the US Department of Defense during the conduct of the study. Dr Adeoye reported receiving grants from NIH/NINDS and being a founder and equity holder of Sense Diagnostics Inc outside the submitted work; in addition, Dr Adeoye reported receiving a patent related to Sense Diagnostics work. Dr Corrigan reported receiving grants from the NIH during the conduct of the study. Dr Dikman report receiving grants from the US federal government during the conduct of the study. Dr Ferguson reported receiving grants from the NIH/NINDS (grant no. U01NS086090, UH3NS106899, R01NS088475), the US Department of Defense (grant no. W81XWH-14-2-0176), the Veterans Administration (grant no. I01RX002787, I01RX002245), the Craig H. Neilsen Foundation Special Project, the Wings for Life Foundation Special Project, and the US Department of Energy Lawrence Livermore National Laboratory during the conduct of the study. Dr Foreman reported receiving speaking and consulting fees from Union Chimique Belge (UCB) Pharma and grants from the NIH/NINDS, the US Department of Defense, and the National Science Foundation outside the submitted work. Dr Lindsell reported receiving grants from the National Center for Advancing Translational Sciences, the NIH, the US Centers for Disease Control and Prevention, and the US Department of Defense; receiving institutional contracts for clinical trial coordination and data coordination from Entegrion, Endpoint Health, and bioMerieux outside the submitted work; in addition, Dr Lindsell reported having a patent for risk stratification in sepsis and septic shock issued during the conduct of the study. Dr Machamer reported receiving grants from the US federal government during the conduct of the study. Dr McAllister reported receiving grants from the University of California, San Francisco, and support for participating in the TRACK-TBI Outcomes Core during the conduct of the study. Dr Rosand reported receiving grants from the NIH and personal fees from Boehringer Ingelheim outside the submitted work. Dr Sander reported receiving grants from the NIH during the conduct of the study. Dr Schnyer reported receiving grants from the NINDS during the conduct of the study. Dr Toga reported receiving grants from the NIH during the conduct of the study. Dr Yuh reported receiving grants from the NIH and the US Department of Defense during the conduct of the study. Dr Zafonte reported receiving royalties from Oakstone for an educational CD, “Physical Medicine and Rehabilitation: a Comprehensive Review,” and from Springer/Demos Publishing for serving as coeditor of the text Brain Injury Medicine. Dr Zafonte also reported serving on the scientific advisory boards of Myomo, Oxeia Biopharma, ElMINDA, and Biodirection. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Postconcussion Symptoms Questionnaire (RPQ) Cognitive (A), Emotional (B), and Somatic (C) Cluster Scores Plotted by End Points for Women and Men with Traumatic Brain Injury (TBI) and Controls With Orthopedic Trauma (OTC)
Figure 2.
Figure 2.. Postconcussion Symptoms Questionnaire (RPQ) Cluster Scores for Cognitive (A), Emotional (B), and Somatic (C) Clusters Plotted by End Points for Subgroups of Women With Traumatic Brain Injury and Controls With Orthopedic Trauma Aged 17-34 Years, 35-49 Years, and Older Than 50 Years
See this image and copyright information in PMC

Comment in

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