Association of Subacute Mild Traumatic Brain Injury Symptoms With Long-Term Persistent Symptoms, Functional Limitations, and Quality of Life - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. 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Learn more: PMC Disclaimer | PMC Copyright Notice Neurology . 2025 Apr 1;104(8):e213427. doi: 10.1212/WNL.0000000000213427 Search in PMC Search in PubMed View in NLM Catalog Add to search Association of Subacute Mild Traumatic Brain Injury Symptoms With Long-Term Persistent Symptoms, Functional Limitations, and Quality of Life Shawn R Eagle Shawn R Eagle 1 University of Pittsburgh, PA; Find articles by Shawn R Eagle 1, ✉ , Nancy Temkin Nancy Temkin 2 University of Washington, Seattle; Find articles by Nancy Temkin 2 , Jason K Barber Jason K Barber 2 University of Washington, Seattle; Find articles by Jason K Barber 2 , Michael McCrea Michael McCrea 3 Medical College of Wisconsin, Milwaukee; Find articles by Michael McCrea 3 , Joseph T Giacino Joseph T Giacino 4 Harvard University, Cambridge, MA; and Find articles by Joseph T Giacino 4 , David Okonkwo David Okonkwo 1 University of Pittsburgh, PA; Find articles by David Okonkwo 1 , Geoffrey T Manley Geoffrey T Manley 5 University of California San Francisco. Find articles by Geoffrey T Manley 5 , Lindsay Nelson Lindsay Nelson 3 Medical College of Wisconsin, Milwaukee; Find articles by Lindsay Nelson 3 ; for the TRACK-TBI Investigators Author information Article notes Copyright and License information 1 University of Pittsburgh, PA; 2 University of Washington, Seattle; 3 Medical College of Wisconsin, Milwaukee; 4 Harvard University, Cambridge, MA; and 5 University of California San Francisco. ✉ Correspondence Dr. Eagle [email protected] Coinvestigators are listed in Appendix at the end of the article. Submitted and externally peer reviewed. The handling editor was Associate Editor Rebecca Burch, MD. ✉ Corresponding author. Received 2024 Oct 16; Accepted 2025 Feb 3; Issue date 2025 Apr 22. © 2025 American Academy of Neurology PMC Copyright notice PMCID: PMC11966525 PMID: 40168631 Abstract Background and Objectives The objective was to evaluate the association of subacute postconcussion symptoms (with the total Rivermead Post-Concussion Questionnaire [RPQ] score) with persistent symptoms, functional limitations, and quality of life at 6 months in patients with mild traumatic brain injury (mTBI). Methods This was a secondary analysis of the Transforming Research and Clinical Knowledge of Traumatic Brain Injury, which was a prospective cohort study of patients with TBI and admission Glasgow Coma Scale score between 13 and 15 at 18 US Level 1 trauma centers through 2014–2018. Participants were included in the study if presenting within 24 hours of external force trauma to the head and met the American Congress of Rehabilitation Medicine's criteria for TBI. Participants completed the RPQ, Glasgow Outcome Scale–Extended (GOSE), and Quality of Life after Brain Injury Overall Scale (QOLIBRI-OS). Primary outcomes were persistent symptoms (≥3 individual RPQ symptoms higher than preinjury level), incomplete recovery (GOSE score <8), and lower quality of life (QOLIBRI-OS score ≤51) at 6 months. Multivariable regression models were developed including RPQ clinical cutoffs at 2 weeks and 3 months and risk factors. Adjusted odds ratios (aORs) and 95% CI are reported for multivariable models. Receiver operating characteristic curves were built to identify discriminative ability of the cutoffs with area under the curve (AUC). Results The age of the study cohort (n = 2,000) was 41.1 ± 17.3 years; 33% were female (n = 669), 67% male, 57% White (n = 1,141), and 20% Hispanic (n = 408). RPQ total score ≥14 was associated with higher odds of persistent symptoms (aOR 7.25, 95% CI 5.51–9.54), incomplete recovery (aOR 4.85, 95% CI 3.69–6.39), and lower quality of life (aOR 5.31, 95% CI 3.82–7.40) at 6 months compared with patients below the cutoff. AUC for RPQ total score ≥14 at 2 weeks was 0.76–0.81 across outcomes. RPQ total score ≥12 at 3 months was associated with higher odds of persistent symptoms (aOR 18.22, 95% CI 13.09–25.35), incomplete recovery (aOR 8.44, 95% CI 6.18–11.51), and lower quality of life (aOR 7.45, 95% CI 5.40–10.26) at 6 months compared with patients below the cutoff, with AUCs of 0.80–0.88 across outcomes. Discussion Clinical cutoffs for a commonly used TBI symptom questionnaire had acceptable-to-excellent discrimination for 6-month outcomes and can be used by clinicians at 2 weeks after injury to identify patients at risk of chronic impairments and refer for targeted rehabilitation. Classification of Evidence This study provides Class III evidence that overall TBI symptoms at 2 weeks are predictive of 6-month clinical outcomes. Introduction Approximately 3 million people are treated for mild traumatic brain injuries (mTBIs) in US hospitals annually. 1 Over half of those patients report functional limitations and injury-related symptoms at 12 months after injury, which can persist much longer. 2 - 4 Even among patients with mTBI with a negative head CT scan, 56% report incomplete recovery at 6 months. 5 The recovery time line for patients with mTBI treated in emergency departments takes longer than may be expected based on previous evidence associated with this population. 2 , 6 - 9 For example, athletes with mTBI typically recover within 3–4 weeks of injury. 6 Previous research has revealed a relationship between injury-related symptoms and functional limitations after mTBI. A prior study 5 reported a dose-response relationship between higher Rivermead Post-Concussion Questionnaire (RPQ) total scores and lower Glasgow Outcome Scale–Extended (GOSE) scores in participants with mTBI with a negative head CT scan. Subacute (i.e., from 48 hours after injury up to 3 months after injury) mTBI symptoms can also precede functional limitations. 10 , 11 Another study 12 reported that higher symptoms of depression and anxiety at 2 weeks after discharge from the emergency department with mTBI were associated with subsequent functional limitations at 3 months. These studies have improved our understanding of the impact these symptoms have on overall recovery. However, there is a need to provide clinically useful guidance on how to interpret risk of poor outcome using only symptom burden scores because symptom questionnaires are highly feasible, low cost, and readily available to TBI practitioners. Previous work has suggested that only 44% of adults with mTBI follow up with a physician within 3 months of injury. 13 A valid and clinically useful cutoff for worse long-term outcomes could provide critical information for clinicians to triage patients earlier into active and indicated treatments, which may reduce symptom burden. For example, patients above the clinical cutoff for RPQ symptom score should be encouraged to consult a TBI specialist for continued monitoring because evidence suggests that they are at higher risk of persistent symptoms. 5 , 14 Conversely, patients below the cutoff for RPQ symptom score may be encouraged to continue increasing participation in activities of daily living and monitoring for any changes in status. The Transforming Research and Clinical Knowledge for Traumatic Brain Injury (TRACK-TBI) consortium's prospective cohort study from 18 Level 1 trauma center emergency departments represents an ideal data set to study the relationship between subacute symptoms and long-term prognosis. 15 TRACK-TBI included follow-up at 2 weeks and 6 months after injury allowing for the prospective assessment of 2-week and 3-month symptom burden on 6-month outcomes. The purpose of this study was to evaluate the association of a subacute RPQ total score cutoff with persistent mTBI symptoms (3+ symptoms worse than preinjury level), functional limitations (GOSE score <8), and poorer quality of life (Quality of Life After Brain Injury Overall Scale [QOLIBRI-OS] score ≤51) at 6 months after a diagnosis of mTBI in US Level 1 trauma center emergency departments. Methods Study Participants This is a secondary analysis of prospectively enrolled patients with mTBI who presented to 1 of the 18 US Level 1 trauma centers from 2013 to 2018 (n = 2,697) as part of the TRACK-TBI consortium. All centers contributed data to this data set. Participants were included in the study if they presented to the hospital within 24 hours of external force trauma to the head and met the American Congress of Rehabilitation Medicine's criteria for diagnosis of TBI. 16 The treating physician must also have ordered a head CT scan for the patient to be enrolled. Exclusion criteria included pregnancy, incarceration, nonsurvivable physical trauma, debilitating preinjury mental health disorders or neurologic disease, and non–English-speaking or Spanish-speaking primary language. This article was structured within the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Standard Protocol Approvals, Registrations, and Patient Consents Participants or their legally authorized representatives provided written informed consent to participate after being approached by a member of the research team in the hospital. Human subjects research approvals were obtained from the institutional review board or ethics committee of each site. Rivermead Post-Concussion Symptoms Questionnaire The 16-item RPQ measures severity of headaches, dizziness, and nausea as well as cognitive, mood, and sleep disturbances and other physical symptoms associated with mTBI. 17 Each item is rated on a scale of 0–4, with 0 indicating that the symptom was not experienced at all and 4 indicating that the symptom was a severe problem within the past 7 days, compared with preinjury status. 17 Because rating an item 1 indicates that the symptom was “no more of a problem,” responses of 0 and 1 were merged into a category of 0, which is consistent with previous research using the RPQ. The maximum RPQ score is 64. Clinical Outcomes Participants completed a standardized set of outcome assessments at 2 weeks, 3 months, and 6 months, including the RPQ, GOSE, and QOLIBRI-OS. The QOLIBRI-OS is a health-related quality-of-life instrument used for patients with TBI with 6 items that comprise an overall score (range 0–100, lower scores indicate worse quality of life). 18 GOSE was used to assess functional outcome specific to TBI where complete recovery was defined as GOSE score = 8 and incomplete recovery was defined as GOSE score <8. 19 These binary outcomes have been routinely used in previous studies of mTBI populations by the TRACK-TBI consortium and other authorship groups. 4 , 5 , 14 , 20 - 22 Statistical Analysis Descriptive statistics were calculated for the overall cohort. Median RPQ total scores at 2 weeks and 3 months were described based on age groups (<20, 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, 80+), sex (male/female), race/ethnicity (White, Black, Hispanic, other/unknown), baseline employment status (working/student, other/unknown, retired), psychiatric history (yes/no), TBI history (yes/no), and head CT result (positive/negative). Three binary outcomes were assessed at 6 months after injury: (1) presence of persistent symptoms, defined as 3 or more individual RPQ symptoms that have begun after injury or worsened from preinjury level (i.e., 3 or more symptoms rated 2–4); (2) incomplete functional recovery, defined as GOSE score <8; and (3) lower quality of life, defined as a QOLIBRI-OS total score ≤51. Receiver operating characteristic (ROC) analyses were conducted for RPQ total scores at 2 weeks and 3 months to determine an optimized clinical cutoff. The cutoff was determined by maximizing sensitivity plus specificity across the 3 outcome measures, 23 which is a standard methodological approach for identifying a cutoff that minimizes the sum of false negatives and false positives when both are equally important. 24 Univariable logistic regression models were built to examine the associations of age, sex, race/ethnicity, baseline employment status, psychiatric history, TBI history, and head CT result with (1) persistent symptoms, (2) incomplete recovery, and (3) lower quality of life at 6 months after injury. Clinical cutoffs for 2 weeks and 3 months were then entered into their own univariable regression models as binary (at or above threshold vs below the threshold) variables to identify odds ratios (ORs) and 95% CIs from the models in relation to the 3 outcomes. To determine whether symptom burden above the cutoff threshold is predictive of 6-month outcomes, multivariable regression models were built to evaluate the association of the 2-week and 3-month RPQ cutoffs and risk factors with (1) persistent symptoms, (2) incomplete functional recovery, and (3) lower quality of life at 6 months. Risk factors included in all multivariable models were as follows: age, sex (reference: male), race/ethnicity (reference: White), time of injury employment status (reference: working), psychiatric history (reference: no history), TBI history (reference: no history), and head CT status (reference: negative). These covariates were included in each model to control for robust predictors of worse long-term outcomes from TBI identified in previous research. 4 , 7 , 9 , 14 , 25 - 28 For each of the multivariable models, predicted probabilities were used to generate an ROC plot to compare clinical performance of the overall model with RPQ clinical cutoffs alone. Adjusted odds ratios (aORs) and 95% CIs are reported for RPQ clinical cutoffs, age, sex, race/ethnicity, time of injury employment status, psychiatric history, TBI history, and head CT status from the multivariable regression models. Statistical significance was set at 2-sided p < 0.05. Statistical analyses were conducted in R (version 4.4.1). Data Availability These data are publicly available in the Federal Interagency Traumatic Brain Injury Research online database. 29 Results Overall Cohort For the purpose of studying adult patients with “mild” TBI, who represent most of the patients seen in US emergency departments, 30 we excluded patients younger than 18 years (n = 145) and patients with Glasgow Coma Scale score <13 (n = 552). Descriptive statistics for the overall cohort (n = 2,000) are provided in Table 1 and for those included/excluded from analysis in eTable 1. The age of the study cohort was 41.1 ± 17.3 years; 33% were female (n = 669), 67% male, 57% White (n = 1,141), 16% Black (n = 324), 20% Hispanic (n = 408), and 6% other/unknown race (n = 127). Approximately 22% reported psychiatric history (n = 441), 21% reported TBI history (n = 379), and 37% had a positive head CT scan (n = 718). The median time for follow-up assessment at the 2-week time point was 15 days after injury (interquartile range = 13–17 days). Table 1. Descriptive Statistics for the Overall Cohort Along With Median 2-Week and 3-Month Total RPQ Scores by Group Total 2-wk RPQ scores Median 3-mo RPQ scores Median Participants 2,000 Age, y, n (%) Mean (SD) 41.1 (17.3) Median (IQR) 27 (25–54) <20 118 (6) 13 5 20–29 560 (28) 14 6 30–39 359 (18) 17 10 40–49 278 (14) 19 15 50–59 293 (15) 19 14 60–69 241 (12) 13 6 70–79 110 (6) 9.5 5 80+ 41 (2) 5 4 Sex, n (%) Male 1,331 (67) 12 7 Female 669 (33) 22 14 Race, n (%) Indian 6 (0) 9.5 30 Alaska Native/Inuit 2 (0) 3.5 17 Asian 68 (3) 12 4 Black 330 (17) 19.5 18 Native Hawaiian/Pacific Islander 4 (0) 6 0 White 1,531 (78) 14 8 Mixed race 34 (2) 14 5 Unknown 25 14.5 20 Hispanic, n (%) No 1,569 (79) 15 8 Yes 408 (21) 16 10 Unknown 23 16 15 Race/ethnicity, n (%) White 1,141 (57) 14 7 Black 324 (16) 19.5 18 Hispanic 408 (20) 16 10 Other/unknown 127 (6) 11.5 4 Employment status, n (%) Working now 1,357 (71) 15 9 Disabled (perm/temp) 47 (2) 29 26 Temporarily laid off 21 (1) 17 20 Keeping house 40 (2) 26 20 Looking for work (unemployed) 136 (7) 24.5 15 Student 94 (5) 13.5 6 Retired 195 (10) 11 5 Other 12 (1) 31 4.5 Unknown 98 13 5 Employment status, n (%) Working/student 1,451 (73) 15 9 Retired 195 (10) 11 5 Other/unknown 354 (18) 23 15 Psychiatric history, n (%) No 1,558 (78) 13 8 Yes 441 (22) 22 16 Unknown 1 10 — TBI history, n (%) None 1,429 (78) 14 8 ER visit 243 (13) 20 11 Hospital admit 154 (8) 21 18 Unknown 174 11 8 Initial CT, n (%) Negative 1,220 (63) 15 9 Positive/presumed positive 718 (37) 16 8 Unknown 62 20 14 Days to 2-wk assessment Mean (SD) 15.0 (2.6) Median (IQR) 15 (13–17) Unknown 389 Open in a new tab Abbreviations: ER = emergency room; IQR = interquartile range; RPQ = Rivermead Post-Concussion Questionnaire; TBI = traumatic brain injury. RPQ Clinical Cutoffs at 2 Weeks and 3 Months for Predicting 6-Month Outcomes Cutoffs and the associated area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value for RPQ total score clinical cutoffs for predicting outcomes are provided in Table 2 . The 2-week cutoff for predicting all outcomes at 6 months was ≥14. This cutoff had an AUC of 81.3% for differentiating participants with persistent symptoms at 6 months from those without (sensitivity: 75%, specificity: 72.2%). The 2-week cutoff had an AUC of 77.1% for differentiating participants with incomplete functional recovery from those with complete functional recovery at 6 months (sensitivity: 69.5%, specificity: 69.6%). The 2-week cutoff also had an AUC of 76.4% for differentiating participants with lower quality of life from those with higher quality of life at 6 months (sensitivity: 82.0%, specificity: 57.8%). Table 2. Performance of RPQ Total Score Cutoffs at 2 Weeks and 3 Months for Each 6-Month Outcome (Persistent Symptoms [Top], Incomplete Recovery [Middle], and Lower Quality of Life [Bottom]) Time point AUC Cutoff Sensitivity Specificity PPV NPV Persistent symptoms 2 wk 81.3% 14 75.0% 530/707 72.2% 428/593 76.3% 530/695 70.7% 428/605 3 mo 88.3% 12 71.5% 502/702 89.1% 513/576 88.8% 502/565 71.9% 513/713 Incomplete functional recovery 2 wk 77.1% 14 69.5% 490/705 69.6% 353/507 76.1% 490/644 62.1% 353/568 3 mo 80.4% 12 63.7% 445/699 83.0% 409/493 84.1% 445/529 61.7% 409/663 Lower quality of life 2 wk 76.4% 14 82.0% 297/362 57.8% 539/933 43.0% 297/691 89.2% 539/604 3 mo 82.2% 12 79.3% 288/363 69.8% 636/911 51.2% 288/563 89.5% 636/711 Open in a new tab Abbreviations: AUC = area under the curve; NPV = negative predictive value; PPV = positive predictive value; RPQ = Rivermead Post-Concussion Questionnaire. Raw thresholds set where the average sensitivity + specificity is maximized across the 3 measures (14 for 2 weeks, 12 for 3 months). The 3-month cutoff for predicting all outcomes at 6 months was ≥12. This cutoff had an AUC of 88.3% for differentiating participants with persistent symptoms at 6 months from those without (sensitivity: 71.5%, specificity: 89.1%). The 3-month cutoff had an AUC of 80.4% for differentiating participants with incomplete functional recovery from those with complete functional recovery at 6 months (sensitivity: 63.7%, specificity: 83.0%). The 3-month cutoff had an AUC of 82.2% for differentiating participants with lower quality of life from those with higher quality of life at 6 months (sensitivity: 79.3%, specificity: 69.8%). Univariable analyses identified that participants reporting symptom scores ≥14 at 2 weeks were associated with persistent symptoms (OR 7.77, 95% CI 6.06–9.95), incomplete recovery (OR 5.22, 95% CI 4.08–6.69), and lower quality-of-life scores (OR 6.25, 95% CI 4.64–8.42) at 6 months compared with participants below these cutoffs. Univariate analyses identified that participants reporting symptom scores ≥12 at 3 months were associated with higher odds of persistent symptoms (OR 20.44, 95% CI 15.01–27.83), incomplete recovery (OR 8.53, 95% CI 6.44–11.30), and worse quality-of-life scores (OR 8.88, 95% CI 6.64–11.88) at 6 months. RPQ Total Score Cutoffs in Relation to 6-Month Outcomes Percentages of the cohort above and below the cutoff in relation to 6-month outcomes are provided in Table 3 . For participants with a 2-week cutoff score of ≥14 (n = 695), 76% had persistent symptoms and incomplete recovery at 6 months. Nearly half (43%) had lower quality of life at 6 months. Among participants with a 3-month cutoff score of ≥12 (n = 565), 89% had persistent symptoms, 84% had incomplete functional recovery, and 51% had lower quality of life at 6 months. Table 3. Prevalence of Poor Clinical Outcome for Participants Above and Below the Clinical Cutoffs at 2 Weeks and 3 Months Persistent symptoms at 6 mo Incomplete recovery at 6 mo Lower quality of life at 6 mo 2-wk RPQ scores 0–13 177/605 (29%) 215/568 (38%) 65/604 (11%) ≥14 530/695 (76%) 490/644 (76%) 297/691 (43%) Unknown 64/94 (68%) 65/85 (76%) 40/94 (43%) 3-mo RPQ scores 0–11 200/713 (28%) 254/663 (38%) 75/711 (11%) ≥12 502/565 (89%) 445/529 (84%) 288/563 (51%) Unknown 69/116 (59%) 71/105 (68%) 39/115 (34%) Open in a new tab Abbreviation: RPQ = Rivermead Post-Concussion Questionnaire. Multivariable Modeling Results from the multivariable models are provided in Tables 4 , 5 , and 6 . After adjusting for age, sex, race/ethnicity, time of injury employment status, psychiatric history, TBI history, and head CT result, participants above the RPQ total score clinical cutoffs were associated with the highest odds of poor 6-month outcomes (persistent symptoms: aOR 7.25–18.22; incomplete recovery: aOR 4.85–8.44; worse quality of life: aOR 5.31–7.45) than any other predictor. Table 4. Univariable and Multivariable Logistic Regression Models Predicting Persistent Postconcussion Symptoms at 6 Months After Injury Univariable 2-wk multivariable model (N = 1,208) 3-mo multivariable model (N = 1,186) OR (95% CI) p Value OR (95% CI) p Value OR (95% CI) p Value Age (per +10 y) 1.06 (0.99–1.12) 0.082 1.22 (1.11–1.34) <0.001 1.05 (0.95–1.16) 0.352 Sex (female vs male) 1.62 (1.30–2.03) <0.001 1.03 (0.77–1.37) 0.843 1.25 (0.91–1.72) 0.161 Race/ethnicity — <0.001 — 0.001 — 0.042 Black (vs White) 1.82 (1.35–2.45) <0.001 1.64 (1.13–2.40) 0.010 1.36 (0.89–2.10) 0.156 Hispanic (vs White) 1.52 (1.14–2.04) 0.005 2.01 (1.39–2.92) <0.001 1.66 (1.09–2.54) 0.018 Other/unknown (vs White) 0.82 (0.52–1.29) 0.389 1.07 (0.62–1.86) 0.808 0.76 (0.40–1.42) 0.385 Work — 0.001 — 0.018 — 0.048 Other (vs working/student) 1.85 (1.33–2.57) <0.001 1.36 (0.89–2.06) 0.152 1.76 (1.11–2.81) 0.017 Retired (vs working/student) 0.92 (0.65–1.30) 0.628 0.53 (0.31–0.91) 0.021 0.90 (0.50–1.60) 0.710 Psychiatric history (vs none) 1.98 (1.52–2.57) <0.001 1.73 (1.24–2.42) 0.001 1.80 (1.24–2.61) 0.002 TBI history — 0.003 — 0.016 — 0.169 ED visit (vs none) 1.20 (0.87–1.66) 0.260 1.07 (0.72–1.58) 0.750 0.97 (0.62–1.51) 0.878 Hospital admit (vs none) 2.05 (1.34–3.14) 0.001 2.12 (1.27–3.55) 0.004 1.71 (0.97–3.02) 0.065 CT positive (vs negative) 1.15 (0.92–1.43) 0.230 1.03 (0.77–1.38) 0.822 1.61 (1.17–2.22) 0.003 2-wk RPQ score (≥14 vs not) 7.77 (6.06–9.95) <0.001 7.25 (5.51–9.54) <0.001 3-mo RPQ score (≥12 vs not) 20.44 (15.01–27.83) <0.001 18.22 (13.09–25.35) <0.001 Open in a new tab Abbreviations: ED = emergency department; OR = odds ratio; RPQ = Rivermead Post-Concussion Questionnaire; TBI = traumatic brain injury. p < 0.05 was considered statistically significant. Table 5. Univariable and Multivariable Logistic Regression Models Predicting Incomplete Functional Recovery (GOSE Score <8) at 6 Months After Injury Univariable 2-wk multivariable model (N = 1,133) 3-mo multivariable model (N = 1,114) OR (95% CI) p Value OR (95% CI) p Value OR (95% CI) p Value Age (per +10 y) 1.05 (0.99–1.12) 0.107 1.07 (0.97–1.17) 0.163 0.97 (0.88–1.07) 0.495 Sex (female vs male) 1.50 (1.19–1.91) 0.001 1.04 (0.78–1.39) 0.804 1.21 (0.90–1.64) 0.208 Race/ethnicity — 0.025 — 0.128 — 0.445 Black (vs White) 1.35 (0.99–1.84) 0.055 1.23 (0.85–1.79) 0.272 1.11 (0.74–1.66) 0.603 Hispanic (vs White) 1.22 (0.89–1.68) 0.212 1.45 (0.99–2.13) 0.055 1.14 (0.75–1.73) 0.531 Other/unknown (vs White) 0.65 (0.41–1.04) 0.071 0.80 (0.46–1.37) 0.406 0.68 (0.38–1.22) 0.198 Work — 0.350 — 0.678 — 0.308 Other (vs working/student) 1.26 (0.91–1.76) 0.169 0.85 (0.57–1.27) 0.435 0.95 (0.62–1.46) 0.830 Retired (vs working/student) 1.13 (0.78–1.63) 0.526 1.10 (0.64–1.88) 0.736 1.52 (0.88–2.65) 0.136 Psychiatric history (vs none) 1.88 (1.43–2.47) <0.001 1.61 (1.16–2.24) 0.005 1.50 (1.06–2.13) 0.022 TBI history — 0.060 — 0.227 — 0.353 ED visit (vs none) 1.38 (0.98–1.94) 0.065 1.36 (0.91–2.02) 0.133 1.35 (0.89–2.04) 0.160 Hospital admit (vs none) 1.45 (0.94–2.23) 0.090 1.29 (0.79–2.11) 0.304 1.14 (0.68–1.92) 0.616 CT positive (vs negative) 1.53 (1.21–1.94) <0.001 1.49 (1.11–1.99) 0.008 2.13 (1.57–2.89) <0.001 2-wk RPQ score (≥14 vs not) 5.22 (4.08–6.69) <0.001 4.85 (3.69–6.39) <0.001 — — 3-mo RPQ score (≥12 vs not) 8.53 (6.44–11.30) <0.001 — — 8.44 (6.18–11.51) <0.001 Open in a new tab Abbreviations: ED = emergency department; GOSE = Glasgow Outcome Scale–Extended; OR = odds ratio; RPQ = Rivermead Post-Concussion Questionnaire; TBI = traumatic brain injury. p < 0.05 was considered statistically significant. Table 6. Univariable and Multivariable Logistic Regression Models Predicting Lower Quality of Life (QOLIBRI-OS score ≤51) at 6 Months After Injury Univariable 2-wk multivariable model (N = 1,204) 3-mo multivariable model (N = 1,183) OR (95% CI) p Value OR (95% CI) p Value OR (95% CI) p Value Age (per +10 y) 1.07 (1.00–1.14) 0.040 1.22 (1.10–1.36) <0.001 1.09 (0.97–1.21) 0.136 Sex (female vs male) 1.62 (1.28–2.06) <0.001 1.02 (0.75–1.38) 0.901 1.08 (0.78–1.48) 0.649 Race/ethnicity — <0.001 — <0.001 — <0.001 Black (vs White) 2.41 (1.79–3.26) <0.001 3.03 (2.06–4.44) <0.001 2.65 (1.78–3.95) <0.001 Hispanic (vs White) 1.28 (0.93–1.76) 0.124 2.23 (1.49–3.33) <0.001 1.60 (1.04–2.46) 0.031 Other/unknown (vs White) 0.91 (0.53–1.56) 0.741 1.40 (0.72–2.70) 0.319 1.45 (0.74–2.85) 0.283 Work — <0.001 — 0.074 — 0.032 Other (vs working/student) 2.10 (1.52–2.89) <0.001 1.42 (0.95–2.12) 0.089 1.76 (1.15–2.69) 0.009 Retired (vs working/student) 1.00 (0.68–1.49) 0.987 0.66 (0.36–1.21) 0.178 1.09 (0.59–2.01) 0.781 Psychiatric history (vs no) 3.23 (2.49–4.19) <0.001 3.38 (2.42–4.73) <0.001 3.87 (2.72–5.52) <0.001 TBI history — 0.001 — 0.043 — 0.119 ED visit (vs none) 1.48 (1.05–2.07) 0.024 1.34 (0.89–2.02) 0.165 1.22 (0.79–1.88) 0.359 Hospital admit (vs none) 1.99 (1.33–2.97) 0.001 1.76 (1.08–2.85) 0.023 1.66 (1.00–2.76) 0.050 CT positive (vs negative) 0.89 (0.70–1.14) 0.368 0.91 (0.66–1.24) 0.536 1.04 (0.75–1.45) 0.810 2-wk RPQ score (≥14 vs not) 6.25 (4.64–8.42) <0.001 5.31 (3.82–7.40) <0.001 3-mo RPQ score (≥12 vs not) 8.88 (6.64–11.88) <0.001 7.45 (5.40–10.26) <0.001 Open in a new tab Abbreviations: ED = emergency department; OR = odds ratio; RPQ = Rivermead Post-Concussion Questionnaire; QOLIBRI-OS = Quality of Life after Brain Injury Overall Scale; TBI = traumatic brain injury. p < 0.05 was considered statistically significant. Classification of Evidence This study provides Class III evidence that overall TBI symptoms at 2 weeks are predictive of 6-month clinical outcomes. Discussion The results of this secondary analysis of a prospective study of 2,000 patients with mTBI indicate that higher overall symptom burden during the subacute recovery period is a robust predictor of worse 6-month outcomes. This result suggests that embedding a highly feasible symptom assessment such as the RPQ into clinical practice for subacute mTBI follow-up yields valuable prognostic information. Prognostic models in the mTBI patient population presenting to a US Level 1 trauma center have largely focused on the clinical value of demographics (e.g., biological sex and medical history) or objective findings (e.g., positive findings for intracranial trauma on head CT). After controlling for these known risk factors, total symptom score cutoffs were associated with substantially higher odds of worse 6-month outcomes compared with the next highest predictor. A 2023 report from the National Academies of Sciences, Engineering and Medicine on improving follow-up care for patients with TBI indicated that developing a list of the most effective actions clinicians can take was a top priority to improve clinical practice guidelines. 31 Previous work from TRACK-TBI has suggested that more than half of patients with mTBI do not follow up with any clinician by 3 months after injury. 13 Emphasizing the importance of serial follow-up medical care after mTBI evaluated in emergency department or acute hospital settings has potential to improve follow-up rates with a clinician who treats mTBI and potentially reduce risk of worse 6-month outcomes. 27 Furthermore, the results of this study indicate that the RPQ may represent a highly effective action for clinicians treating patients with mTBI in the subacute recovery period because the balance between time cost and clinical benefit seems beneficial for prognostication of long-term outcomes. Identification of a patient with mTBI symptoms exceeding clinical cutoffs at 2 weeks after injury could represent a clinical opportunity to refer to an indicated rehabilitation program or other targeted treatments. Future work should assess whether interventions aimed at symptom reduction improve 6-month outcomes in this population. Evidence from interventional studies in those with chronic mTBI symptoms suggests that treatments which reduce overall symptom burden improve outcomes and quality of life. One study in chronic TBI patients reported that an intervention to increase daily step count significantly reduced stress and depression symptoms. 32 Weinstein et al. 33 found a significant improvement in overall mood with moderate-to-large effect sizes after individual bouts of aerobic exercise in patients at least 6 months from their index TBI. Group-based exercise classes for outpatients with chronic mTBI issues (greater than 3 months) attending a rehabilitation clinic have also been successful in reducing symptom burden, improving overall function, and enhancing self-efficacy. 34 An observational study of 180 outpatients with persistent mTBI symptoms (greater than 3 months) found that those with persistent symptoms reported substantially less physical activity after injury compared with preinjury status. 35 Furthermore, meeting national guidelines for physical activity after injury was associated with higher quality of life and lower headache, fatigue, depression, and anxiety symptoms compared with patients who did not meet national activity guidelines. 35 These studies have made substantial contributions to our understanding of how physical activity can improve chronic mTBI symptoms, but little is known how treatment plans inclusive of physical activity may affect subacute mTBI symptoms and long-term outcomes in this population. Varner et al. 36 conducted the only known randomized controlled trial of early physical activity (initiated after 48 hours of relative rest) as an intervention in adults with mTBI. The authors reported that a prescription of 30 minutes of light exercise 5 times per week for 1 month after injury did not elicit a treatment effect compared with those with no instructions to exercise. 36 Participants in the intervention group were instructed to perform light walking or stationary cycling “at a pace that does not cause you to sweat or breathe harder.” 36 It is possible that this prescribed intensity was not strong enough to elicit a treatment effect because more vigorous forms of aerobic exercise prescribed in both adult outpatients with persistent symptoms and adolescent athletes have consistently yielded positive results. 37 , 38 Future studies should assess the efficacy of physical activity and other treatment strategies on reducing subacute symptom burden in this population because earlier reduction of post-TBI symptoms may improve long-term outcomes. These results should be interpreted in light of some limitations. The purpose of this work was to assess the clinical utility of overall symptoms in the mTBI population who presented to a US Level 1 trauma center emergency department in predicting 6-month outcomes. As such, there is limited generalizability outside this population. There could have been additional confounding variables that were not considered for this analysis. This is a secondary analysis of a prospective cohort study that was not powered to evaluate this specific research question. Symptoms are subjective and can be biased by other factors not necessarily related to the injury itself, such as other concurrent life events or medical conditions. Previous studies have shown that otherwise healthy patients (i.e., without a brain injury) with psychiatric conditions and attention deficit hyperactivity disorder, for example, have higher symptom scores on similar overall concussion symptom surveys. 39 RPQ clinical cutoffs were identified by the best-performing point for 2 weeks and 3 months, which led to 2 different cutoff values for these time points. While they are close in proximity, the lower cutoff at 3 months is likely due to a general trend of declining symptom scores over time. Regardless, using different cutoffs could affect how the multivariable models performed. Multivariable modeling identified minority race/ethnicity as a significant predictor of persistent symptoms and worse quality of life related to brain injury at 6 months. This result may reflect a sociocultural influence of being in a minoritized ethnoracial group on long-term outcomes from TBI. 25 , 40 - 42 Future work will be necessary to elucidate this multifactorial problem. In this multisite prospective cohort study of 2,000 patients with mTBI seen at the emergency department of 18 US Level 1 trauma centers, total symptom burden was the strongest predictor of persistent symptoms, incomplete functional recovery, and poorer quality of life at 6 months after injury. After controlling for known risk factors, an RPQ total score ≥14 at 2 weeks after injury was associated with 5–7 times higher adjusted odds of worse 6-month outcomes compared with patients below the cutoff. An RPQ total score ≥12 at 3 months after injury was associated with 8–18 times higher adjusted odds of worse 6-month outcomes compared with patients below the cutoff. These results reinforce the notion that triage into active follow-up care can be easily achieved with an RPQ assessment around 2 weeks after mTBI because persistently high symptoms during this stage were strongly associated with worse long-term outcomes. Clinicians who treat patients with mTBI first seen in the emergency department should consider prescription of targeted treatments with the goal of reducing overall symptom burden. Glossary aOR adjusted odds ratio AUC area under the curve GOSE Glasgow Outcome Scale–Extended mTBI mild TBI OR odds ratio QOLIBRI-OS Quality of Life after Brain Injury Overall Scale ROC receiver operating characteristic TBI traumatic brain injury TRACK-TBI Transforming Research and Clinical Knowledge for Traumatic Brain Injury Appendix. Coinvestigators Name Affiliation Role Contribution John Yue, MD University of California San Francisco Coinvestigator Critically reviewed the manuscript and approved the submitted version Sabrina Taylor, PhD University of California San Francisco Coinvestigator Contributed to data collection and integrity, critically reviewed the manuscript and approved the submitted version C. Dirk Keene, MD, PhD University of Washington Coinvestigator Critically reviewed the manuscript and approved the submitted version Christine MacDonald, PhD University of Washington Coinvestigator Contributed to data collection and integrity, critically reviewed the manuscript and approved the submitted version Ramesh Grandhi, MD University of Utah Coinvestigator Critically reviewed the manuscript and approved the submitted version Ross Zafonte, DO University of Missouri Coinvestigator Critically reviewed the manuscript and approved the submitted version Pratik Mukherjee, MD, PhD University of California San Francisco Coinvestigator Contributed to data collection and integrity, critically reviewed the manuscript and approved the submitted version Ann-Christine Duhaime, MD Harvard University Coinvestigator Critically reviewed the manuscript and approved the submitted version Amy Markowitz, JD University of California San Francisco Coinvestigator Critically reviewed the manuscript and approved the submitted version Open in a new tab Author Contributions S.R. Eagle: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data. N. Temkin: drafting/revision of the manuscript for content, including medical writing for content; analysis or interpretation of data. J.K. Barber: drafting/revision of the manuscript for content, including medical writing for content; analysis or interpretation of data. M. McCrea: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. J.T. Giacino: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. D. Okonkwo: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data. G.T. Manley: major role in the acquisition of data; study concept or design. 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Data Availability Statement These data are publicly available in the Federal Interagency Traumatic Brain Injury Research online database. 29 Articles from Neurology are provided here courtesy of American Academy of Neurology ACTIONS View on publisher site PDF (197.8 KB) Cite Collections Permalink PERMALINK Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Add to Collections Create a new collection Add to an existing collection Name your collection * Choose a collection Unable to load your collection due to an error Please try again Add Cancel Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top