Sex differences in postconcussive symptom reporting in those with history of concussion: Findings from the federal interagency traumatic brain injury research (FITBIR) database.

Objective: This study investigated influence of biological sex on postconcussive symptoms (PCS) following concussion using the Federal Interagency Traumatic Brain Injury Research (FITBIR) database. Method: All studies with publicly released data as of 4/7/21 that included both males and females, enough information to determine severity of injury consistent with concussion, a measure of PCS, and objective measures of neurocognitive functioning were used. This resulted in 6 studies with a total of 9890 participants (3206 females, 6684 males); 815 participants completed the Neurobehavioral Symptom Inventory (NSI), 471 completed the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ), and 8604 completed the Sport Concussion Assessment Tool-3rd Edition (SCAT 3). Questionnaires were harmonized and the following symptom composite scores were computed: total score, somatic, cognitive, and affective. Data were analyzed using linear mixed-effects models. Results: Females endorsed higher total symptoms relative to males and that military personnel endorsed higher symptoms relative to civilians. Additionally, there was a small but significant interaction effect, such that female military personnel endorsed even higher symptoms than would be predicted by the main effects. Similar patterns were observed for somatic, cognitive, and affective symptom domains. Conclusions: Further understanding sex differences in PCS reporting is key to informing the most appropriate treatment options. Future work will need to examine whether sex differences in symptom reporting is due to sex differences in endorsement styles or genuine differences in symptom presentation, as well as the relationship between study population (e.g., military, civilian, sport) and sex on objective cognitive functioning and other functional outcomes.

White matter fiber morphology in persisting postconcussive symptoms and posttraumatic headache after pediatric concussion: a fixel-based analysis.

OBJECTIVE: Posttraumatic headache (PTH) represents the most common acute and persistent postconcussive symptom (PCS) in children after concussion, yet there remains a lack of valid and objective biomarkers to facilitate risk stratification and early intervention in this patient population. Fixel-based analysis of diffusion-weighted imaging, which overcomes constraints of traditional diffusion tensor imaging analyses, can improve the sensitivity and specificity of detecting white matter changes postconcussion. The aim of this study was to investigate whole-brain and tract-based differences in white matter morphology, including fiber density (FD) and fiber bundle cross-section (FC) area in children with PCSs and PTH at 2 weeks after concussion. METHODS: This prospective longitudinal study recruited children aged 5-18 years who presented to the emergency department of a tertiary pediatric hospital with a concussion sustained within the previous 48 hours. Participants underwent diffusion-weighted MRI at 2 weeks postinjury. Whole-brain white matter statistical analysis was performed at the level of each individual fiber population within an image voxel (fixel) to compute FD, FC, and a combined metric (FD and bundle cross-section [FDC]) using connectivity-based fixel enhancement. Tract-based Bayesian analysis was performed to examine FD in 23 major white matter tracts. RESULTS: Comparisons of 1) recovered (n = 27) and symptomatic (n = 16) children, and those with 2) PTH (n = 13) and non-PTH (n = 30; overall mean age 12.99 ± 2.70 years, 74% male) found no fiber-specific white matter microstructural differences in FD, FC, or FDC at 2 weeks postconcussion, when adjusting for age and sex (family-wise error rate corrected p value > 0.05). Tract-based Bayesian analysis showed evidence of no effect of PTH on FD in 10 major white matter tracts, and evidence of no effect of recovery group on FD in 3 white matter tracts (Bayes factor < 1/3). CONCLUSIONS: Using whole-brain fixel-wise and tract-based analyses, these findings indicate that fiber-specific properties of white matter microstructure are not different between children with persisting PCSs compared with recovered children 2 weeks after concussion. These data extend the limited research on white matter fiber-specific morphology while overcoming limitations inherent to traditional diffusion models. Further validation of our findings with a large-scale cohort is warranted.

Predictive Utility of Diffusion MRI After Mild Traumatic Brain Injury in Civilian Populations: A Systematic Review.

OBJECTIVE: A considerable number of people experience persisting symptoms and functional limitations after mild traumatic brain injury (mTBI). It is unclear whether subtle white matter changes contribute to this phenomenon. In this systematic review, the authors evaluated whether microstructural white matter indices on advanced MRI are related to clinical dysfunction among patients without abnormalities on standard brain computed tomography (CT) or MRI (uncomplicated mTBI). METHODS: A search of multiple databases was performed. Studies with individuals who experienced blast-related, sports-related, or multiple mTBIs were excluded. Diffusion tensor imaging (DTI) and susceptibility-weighted imaging (SWI) metrics and cognitive, neuropsychiatric, or functional outcome measures were extracted from each study. RESULTS: Thirteen studies were selected (participants with mTBI, N=553; healthy control group, N=438). Seven DTI studies evaluated cognitive function, with five reporting significant correlations between reduced white matter integrity and deficits in attention, processing speed, and executive function at 6-12 months after injury (three studies included only individuals with uncomplicated mTBI). Four studies found significant correlations between DTI metrics and persistent postconcussive symptoms after 3-12 months (one study included only individuals with uncomplicated mTBI). Two SWI studies reported conflicting findings regarding the relationship between the presence of microbleeds and postconcussive symptoms. CONCLUSIONS: The results revealed that indices of microstructural white matter integrity may relate to clinical presentation 3-12 months after injury in uncomplicated mTBI. However, analysis methods and brain regions studied varied across studies. Further research is needed to identify relationships between white matter indices in specific brain regions and symptom persistence beyond 12 months.

Impact of PTSD treatment on postconcussive symptoms in veterans: A comparison of sertraline, prolonged exposure, and their combination.

Many Veterans who served in Iraq and Afghanistan struggle with posttraumatic stress disorder (PTSD) and the effects of traumatic brain injuries (TBI). Some people with a history of TBI report a constellation of somatic, cognitive, and emotional complaints that are often referred to as postconcussive symptoms (PCS). Research suggests these symptoms may not be specific to TBI. This study examined the impact of PTSD treatment on PCS in combat Veterans seeking treatment for PTSD. As part of a larger randomized control trial, 198 Operation Iraqi Freedom, Operation Enduring Freedom, Operation New Dawn (OIF/OEF/OND) Veterans with PTSD received Prolonged Exposure Therapy, sertraline, or the combination. Potential deployment related TBI, PCS, PTSD and depression symptoms were assessed throughout treatment. Linear mixed models were used to predict PCS change over time across the full sample and treatment arms, and the association of change in PTSD and depression symptoms on PCS was also examined. Patterns of change for the full sample and the subsample of those who reported a head injury were examined. Results showed that PCS decreased with treatment. There were no significant differences across treatments. No significant differences were found in the pattern of symptom change based on TBI screening status. Shifts in PCS were predicted by change PTSD and depression. Results suggest that PCS reduced with PTSD treatment in this population and are related to shift in depression and PTSD severity, further supporting that reported PCS symptoms may be better understood as non-specific symptoms.

Symptom Attribution and Neuropsychological Outcomes Among Treatment-Seeking Veterans With a History of Traumatic Brain Injury.

OBJECTIVE: In this cross-sectional study, the authors aimed to examine relationships between illness perception, measured as symptom attribution, and neurobehavioral and neurocognitive outcomes among veterans with a history of traumatic brain injury (TBI). METHODS: This study included 55 treatment-seeking veterans (N=43 with adequate performance validity testing) with a remote history of TBI (80% with mild TBI). Veterans completed a clinical interview, self-report questionnaires, and a neuropsychological assessment. A modified version of the Neurobehavioral Symptom Inventory (NSI) was administered to assess neurobehavioral symptom endorsement and symptom attribution. Composite scores were calculated from standardized cognitive tests to assess specific aspects of objective cognitive functioning, including memory, executive functioning, attention and working memory, and processing speed. RESULTS: The symptoms most frequently attributed to TBI included forgetfulness, poor concentration, slowed thinking, and headaches. There was a significant positive association between symptom attribution and overall symptom endorsement (NSI total score) (r=0.675) and endorsement of specific symptom domains (NSI symptom domain scores) (r=0.506-0.674), indicating that greater attribution of symptoms to TBI was associated with greater symptom endorsement. Furthermore, linear regressions showed that symptom attribution was significantly associated with objective cognitive functioning, whereas symptom endorsement generally did not show this relationship. Specifically, greater attribution of symptoms to TBI was associated with worse executive functioning (ß=-0.34), attention and working memory (ß=-0.43), and processing speed (ß=-0.35). CONCLUSIONS: These findings suggest that veterans who routinely attribute neurobehavioral symptoms to their TBI are at greater risk of experiencing poor long-term outcomes, including elevated symptom endorsement and worse objective cognition. Although more research is needed to understand how illness perception influences outcomes in this population, these preliminary results highlight the importance of early psychoeducation regarding the anticipated course of recovery following TBI.

Quality of Life in Youth Soccer Players After Mild Traumatic Brain Injury.

CONTEXT: Pediatric mild traumatic brain injuries (mTBIs) represent an evolving field of interest in youth athletics. Although most players recover within 4 weeks, some have symptoms that last longer. Little is known about youth health-related quality of life (HRQoL) after mTBI. OBJECTIVES: To characterize youth HRQoL after soccer-related mTBI and to identify predictors of individual differences in HRQoL recovery. DESIGN: Prospective cohort study. SETTING: Youth soccer. PARTICIPANTS: Soccer players, aged 8 to 17 years, who sustained an mTBI (n = 23) or orthopaedic injury (OI, n = 24) or remained uninjured (n = 23) during a single season. MAIN OUTCOME MEASURE(S): We assessed HRQoL via the Pediatric Quality of Life Inventory, version 4.0, and postconcussive symptoms via the Health and Behavior Index. Serial assessments occurred at 24 to 48 hours, 7 days, 30 days, and 90 days postinjury via telephone interview. RESULTS: At 7 days postinjury, the mTBI and OI groups had poorer total HRQoL (F2,67 = 11.35, P < .001) than the uninjured control group. At 7 days, the mTBI group had the poorest psychosocial HRQoL, whereas the OI group had the poorest physical HRQoL. Differences between the mTBI and uninjured control groups resolved by 30 days. Within the mTBI group, players with significant postconcussive symptoms at 7 days had poorer total (F1,21 = 23.071, P ≤ .001; F1,21 = 5.798, P = .028), psychosocial (F1,21 = 16.488, P = < .001; F1,21 = 5.050, P = .039), and physical (F1,21 = 21.671, P = < .001; F1,21 = 5.119, P = .038) HRQoL at 7 and 30 days, respectively, than players with minimal symptoms; these differences resolved by 90 days. CONCLUSIONS: As a group, youth soccer players who sustained mTBI had transient impairments in HRQoL that resolved by 30 days. A subset of players with significant postconcussive symptoms at 7 days postinjury had poorer HRQoL for at least 30 days postinjury than those whose postconcussive symptoms had resolved within a week of injury. This suggests ongoing recovery in this subset at 30 days and the potential utility of HRQoL as a measure of recovery.

Utility of a Clinical Prediction Tool for Persisting Postconcussive Symptoms in a Multicenter Sample of Youth Athletes With Concussion: The Sport Concussion Outcomes in Pediatrics (SCOPE) Study.

BACKGROUND: A validated clinical risk tool has been developed to identify pediatric and adolescent patients at risk of developing persisting symptoms after concussion, but has not been prospectively investigated within a sample of athletes seen after concussion by primary care sports medicine physicians and/or athletic trainers. PURPOSE: To determine whether a validated clinical risk prediction tool for persistent postconcussive symptoms (PPCSs) predicted which patients would develop PPCSs when obtained within 14 days of concussion among a multicenter sample of adolescent athletes. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Pediatric and adolescent patients (8-18 years of age) from 7 pediatric medical centers and 6 secondary school athletic training facilities who were diagnosed with a concussion and presented ≤14 days after concussion were enrolled as part of the Sport Concussion Outcomes in Pediatrics (SCOPE) study during their initial visit and were followed until symptom resolution. Clinical risk scores (Predicting and Preventing Post-concussive Problems in Pediatrics [5P]) and total symptom severity were obtained using the Post-Concussion Symptom Inventory at the initial visit (mean, 4.9 ± 2.9 days after concussion). Participants were then compared based on symptom resolution time: PPCS group (≥28 days to symptom resolution) and no-PPCS group (<28 days). The authors assessed the odds of developing PPCSs based on the 5P risk score using a binary logistic regression model and the utility of the clinical risk prediction tool to identify total time to symptom resolution using a Cox proportional hazards model. RESULTS: A total of 184 participants enrolled, underwent initial evaluation, and were followed until symptom resolution (mean age, 15.2 ± 2.1 years; 35% female). The mean time to symptom resolution across the entire sample was 17.6 ± 3.7 days; 16% (n = 30) of participants developed PPCS. Those in the PPCS group had significantly greater mean initial total 5P risk scores than those in the no-PPCS group (7.9 ± 1.7 vs 5.9 ± 2.3, respectively; P < .001). After adjustment for initial symptom severity, time to assessment, and assessment setting, a higher initial total 5P risk score was associated with a significantly greater odds of developing PPCSs (adjusted odds ratio, 1.49; 95% CI, 1.07-2.08; P = .019). Furthermore, a higher 5P risk score was significantly associated with longer total symptom resolution time (hazard ratio, 0.80; 95% CI, 0.74-0.88; P < .001). CONCLUSION: In a multicenter sample of youth athletes seen in different outpatient health care settings, the 5P risk score accurately predicted which athletes may be at risk for developing PPCSs.

Thalamocortical coherence predicts persistent postconcussive symptoms.

The pathogenetic mechanism of persistent post-concussive symptoms (PCS) following concussion remains unclear. Thalamic damage is known to play a role in PCS prolongation while the evidence and biomarkers that trigger persistent PCS have never been elucidated. We collected longitudinal neuroimaging and behavior data from patients and rodents after concussion, complemented with rodents' histological staining data, to unravel the early biomarkers of persistent PCS. Diffusion tensor imaging (DTI) were acquired to investigated the thalamic damage, while quantitative thalamocortical coherence was derived through resting-state functional MRI for evaluating thalamocortical functioning and predicting long-term behavioral outcome. Patients with prolonged symptoms showed abnormal DTI-derived indices at the boundaries of bilateral thalami (peri-thalamic regions). Both patients and rats with persistent symptoms demonstrated enhanced thalamocortical coherence between different thalamocortical circuits, which disrupted thalamocortical multifunctionality. In rodents, the persistent DTI abnormalities were validated in thalamic reticular nucleus (TRN) through immunohistochemistry, and correlated with enhanced thalamocortical coherence. Strong predictive power of these coherence biomarkers for long-term PCS was also validated using another patient cohort. Postconcussive events may begin with persistent TRN injury, followed by disrupted thalamocortical coherence and prolonged PCS. Functional MRI-based coherence measures can be surrogate biomarkers for early prediction of long-term PCS.

Cerebral blood flow in children with persisting postconcussive symptoms and posttraumatic headache at 2 weeks postconcussion.

OBJECTIVE: Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion. The authors also investigated whether variations in CBF can explain the increased risk of acute posttraumatic headache (PTH) in female children following concussion. METHODS: As part of a prospective, longitudinal study, the authors recruited children 5-18 years old who were admitted to the emergency department of a tertiary pediatric hospital with a concussion sustained within 48 hours of admission. Participants underwent pseudocontinuous arterial spin labeling MRI at 2 weeks postconcussion to quantify global mean gray and white matter perfusion (in ml/100 g/min). Conventional frequentist analysis and Bayesian analysis were performed. RESULTS: Comparison of recovered (n = 26) and symptomatic (n = 12) groups (mean age 13.15 years, SD 2.69 years; 28 male) found no differences in mean global gray and white matter perfusion at 2 weeks postconcussion (Bayes factors > 3). Although female sex was identified as a risk factor for PTH with migraine features (p = 0.003), there was no difference in CBF between female children with and without PTH. CONCLUSIONS: Global CBF was not associated with pPCS and female PTH at 2 weeks after pediatric concussion. These findings provide evidence against the use of CBF measured by arterial spin labeling as an acute biomarker for pediatric concussion recovery.

Acute thalamic connectivity precedes chronic post-concussive symptoms in mild traumatic brain injury.

Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13-15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms and explored neurochemical associations of our findings using PET data. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of individual thalamic nuclei. Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known serotonergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.

Service Delivery Models for the Management of Pediatric and Adolescent Concussion: A Systematic Review.

Objective: To examine the current peer-reviewed literature on pediatric concussion and mild traumatic brain injury (mTBI) service delivery models (SDMs) and relevant cost analyses. Data Sources: PubMed, Embase (Elsevier), CINAHL Plus (EBSCO), APA PsycINFO (EBSCO), and Web of Science Core Collection, limited to human trials published in English from January 1, 2001, to January 10, 2022. Study Selection: Included articles that (1) were peer-reviewed; (2) were evidence-based; (3) described service delivery and/or associated health care costs; and (4) focused on mTBI, concussion, or postconcussion symptoms of children and adolescents. Studies describing emergency department-based interventions, adults, and moderate to severe brain injuries were excluded. Data Extraction: The initial search resulted in 1668 articles. Using Rayyan software, 2 reviewers independently completed title and abstract screening followed by a full-text screening of potentially included articles. A third blinded reviewer resolved inclusion/exclusion conflicts among the other reviewers. This resulted in 28 articles included. Data Synthesis: Each of the 28 articles were grouped into 1 of the following 3 categories: generalist-based services (7), specialist-based services (12), and web/telemedicine services (6). One article discussed both generalists and specialists. It was clear that specialists are more proactive in their treatment of concussion than generalists. Most of the research on generalists emphasized the need for education and training. Four studies discussed costs relevant to SDMs. Conclusions: This review highlights the need for more discussion and formalized evaluation of SDMs to better understand concussion management. Overall there is more literature on specialist-based services than generalist-based services. Specialists and generalists have overarching similarities but differ often in their approach to pediatric concussion management. Cost analysis data are sparse and more research is needed.

Responsiveness of the Post-Concussion Symptom Scale to Monitor Clinical Recovery After Concussion or Mild Traumatic Brain Injury.

Background: The Post-Concussion Symptom Scale (PCSS) is used to assess the number and intensity of symptoms after a concussion/mild traumatic brain injury. However, its responsiveness to monitor clinical recovery has yet to be determined. Purpose: To evaluate the responsiveness of the PCSS to change and longitudinal validity in patients with persistent postconcussive symptoms as well as to explore the responsiveness of other clinical outcome measures to monitor recovery of physical symptoms in patients with persistent postconcussive symptoms. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Patients with persistent symptoms after a concussion (N = 109) were evaluated using self-reported questionnaires at baseline and after a 6-week rehabilitation program. The program consisted of an individualized symptom-limited aerobic exercise program combined with education. Questionnaires included the PCSS, Neck Disability Index (NDI), Headache Disability Inventory (HDI), Dizziness Handicap Inventory (DHI), and Numeric Pain Rating Scale (NPRS) related to 1) neck pain and 2) headache. Internal responsiveness was evaluated using the effect size (ES) and standardized response mean (SRM), and external responsiveness was determined with the minimal clinically important difference (MCID) calculated using a receiver operating characteristic curve. The global rating of change was used as the external criterion. Pearson correlations were used to determine the longitudinal validity. Results: The PCSS was highly responsive (ES and SRM, >1.3) and had an MCID of 26.5 points (of 132) for the total score and 5.5 (of 22) for the number of symptoms. For longitudinal validity, low to moderate correlations were found between changes in PCSS and changes in NDI, HDI, and DHI. The NDI, HDI, DHI, and NPRS were also highly responsive (ES and SRM, >0.8). Conclusion: All questionnaires including the PCSS were highly responsive and can be used with confidence by clinicians and researchers to evaluate change over time in a concussion population with persistent symptoms.

Post-concussive symptoms mediate the relationship between sleep problems and participation restrictions among veterans with mild traumatic brain injury.

Background: Sleep problems are common among Veterans with mild traumatic brain injury (mTBI) and may contribute to participation restrictions. However, explanatory mechanisms underlying this relationship are poorly understood. Sleep problems are associated with post-concussive symptoms (e.g., headaches). In turn, post-concussive symptoms contribute to participation restrictions. We hypothesized that post-concussive symptom severity mediates the purported relationship between sleep problems and participation restrictions among Veterans with mTBI. Materials and Methods: This study was a retrospective analysis of clinical data among 8,733 Veterans with mTBI receiving Veterans Health Administration outpatient care. Sleep problems (yes/no) were identified using the sleep-related item from the Neurobehavioral Symptom Inventory (NSI). Post-concussive symptoms were measured using remaining NSI items. Participation restrictions were measured using the Mayo-Portland Adaptability Inventory Participation Index. We specified a latent variable path model to estimate relationships between: (1) sleep problems and three latent indicators of post-concussive symptoms [vestibular-sensory (e.g., headache)]; mood-behavioral [e.g., anxiety]; cognitive [e.g., forgetfulness]); and, (2) the three latent indicators of post-concussive symptoms and two latent indicators of participation restrictions (social and community participation [e.g., leisure activities]; productivity [e.g., financial management]). We examined the indirect effects of sleep problems upon participation restrictions, as mediated by post-concussive symptoms. Estimates were adjusted for sociodemographic factors (e.g., age), injury characteristics (e.g., blast), and co-morbid conditions (e.g., depression). Results: 87% of Veterans reported sleep problems. Sleep problems were associated with greater social and community participation restrictions, as mediated by mood-behavioral (ß = 0.41, p < 0.001) and cognitive symptoms (ß = 0.13, p < 0.001). There was no evidence that vestibular-sensory symptoms mediated this relationship (ß = -0.01, p = 0.48). Sleep problems were associated with greater productivity restrictions, as mediated by vestibular-sensory (ß = 0.16, p < 0.001) and cognitive symptoms (ß = 0.14, p < 0.001). There was no evidence that mood-behavioral symptoms mediated this relationship (ß = 0.02, p = 0.37). Discussion: Findings suggest that evidence-based sleep treatment should occupy a prominent role in the rehabilitation of Veterans with mTBI. Indirect effects of sleep problems differed when considering impact on social and community participation vs. productivity, informing individualized rehabilitative care for Veterans with mTBI.

Early psychological symptoms predict concussion recovery time in middle and high school athletes.

INTRODUCTION: Lingering concussion symptoms can negatively impact a child's well-being, yet variability in recovery is poorly understood. To aid detection of those at risk for prolonged symptom duration, we explored postconcussion mood and sleep symptoms as predictors of recovery time in adolescent athletes. METHOD: We utilized analyses designed to control for potentially confounding variables, such as concussion severity indicators and premorbid psychiatric history. Participants included 393 adolescent athletes (aged 12-18 years) evaluated in outpatient concussion clinics within 2 weeks after injury. Provider-documented date of symptom resolution was obtained via medical record review. Survival analysis for recovery time was conducted in the total sample, and separately for males and females using prior medical history (psychiatric disorder, prior concussion), injury-related factors (loss of consciousness, post-traumatic amnesia [PTA], concussion symptom severity), and psychological symptoms (General Anxiety Disorder-7 Item Scale, Patient Health Questionnaire-8 Item Depression Scale, Pittsburgh Sleep Quality Index) collected at initial clinic visit. RESULTS: PTA, concussion symptoms, and sleep quality were associated with recovery in the total sample (HRs = 0.64-0.99, ps < .05). When analyzed by sex, only concussion symptoms were associated with recovery for females (with females reporting greater symptom severity than males), while for males PTA and greater depression symptoms were significant predictors of recovery (HRs = 0.54-0.98, ps < .05). CONCLUSIONS: These findings identified differences in symptom presentation between sexes, particularly for mood symptoms, and suggest that assessment of postconcussive symptoms is useful in helping to identify individuals at risk for longer recovery. Continued exploration of post-injury psychological difficulties in athletes is warranted for better concussion management.

Prevalence and Correlates of Depressive Symptoms Within 6 Months After First-Time Mild Traumatic Brain Injury.

OBJECTIVE: Depressive symptoms are among the most common neuropsychiatric sequelae of mild traumatic brain injury (mTBI). Very few studies have compared correlates of depressive symptoms within the first 6 months of injury in cohorts experiencing their first TBI. The authors investigated whether the correlates of depressive symptoms (being female, older, lower education, having brain lesions, experiencing worse postconcussive symptoms, and incomplete functional recovery) that have been established in populations with moderate to severe TBI were the same for individuals with first-time mTBI within the first 6 months of recovery. METHODS: Two hundred seventeen individuals with first-time mTBI were divided into subgroups-new-onset depressive symptoms, recurrent depressive symptoms, prior depression history only, and never depressed-and compared on clinical and demographic variables and the presence of postconcussive symptoms and functional recovery at 3 and 6 months. RESULTS: New-onset depressive symptoms developed in 12% of the cohort, whereas 11% of the cohort had recurrent depressive symptoms. Both depressive symptoms groups were more likely to comprise women and persons of color and were at higher risk for clinically significant postconcussive symptoms and incomplete functional recovery for the first 6 months postinjury. CONCLUSIONS: Presence of depressive symptoms after first-time mTBI was associated with persistent postconcussive symptoms and incomplete functional recovery in the first 6 months. Adding to the existing literature, these findings identified correlates of depressive symptom development and poor outcomes after mTBI, thus providing further evidence that mTBI may produce persistent symptoms and functional limitations that warrant clinical attention.

Effect of Collaborative Care for Persistent Postconcussive Symptoms on Academic Function: A Randomized Clinical Trial.

BACKGROUND: There is limited long-term data on the course of school-related problems and academic needs for youth with persistent post-concussive symptoms (PPCS). METHODS: This was a randomized trial comparing collaborative care to usual care for 200 youth 11-18 years of age with PPCS. In this report, the main outcomes were academic functioning, GPA, school absences, date of return to school, and school days missed. RESULTS: Youth were mean age of 14.7 (SD = 1.7), 62.0% female. New or worsening academic problems occurred in half of participants in both groups at 12 months after injury. Students were most concerned about grades and falling behind. There were no significant differences by study group on school problems or GPA, but number of days missed was lower in the collaborative care group compared at 3 months (12.5 [SD = 14.5] vs 16.1 days [20.4] adjusted relative risk [aRR] 0.67 [95% CI: 0.61, 0.74; p < .001]), 6 months (14.5 [22.1] vs 19.3 [26.6] aRR 0.77 [95% CI: 0.71, 0.84; p < .001]), and 12 months (16.9 [25.4] vs 19.6 [27.7], aRR 0.68 [95% CI: 0.62, 0.74; p < .001]). CONCLUSIONS: Youth with PPCS are at high risk of school problems in the year after injury.

Atypical resting state functional connectivity in mild traumatic brain injury.

OBJECTIVES: This study aimed to investigate changes in three intrinsic functional connectivity networks (IFCNs; default mode network [DMN], salience network [SN], and task-positive network [TPN]) in individuals who had sustained a mild traumatic brain injury (mTBI). METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 27 mTBI patients with persistent postconcussive symptoms, along with 26 age- and sex-matched controls. These individuals were recruited from a Level-1 trauma center, at least 3 months after a traumatic episode. IFCNs were established based on seed-to-voxel, region-of-interest (ROI) to ROI, and independent component analyses (ICA). Subsequently, we analyzed the relationship between functional connectivity and postconcussive symptoms. RESULTS: Seed-to-voxel analysis of rs-fMRI demonstrated decreased functional connectivity in the right lateral parietal lobe, part of the DMN, and increased functional connectivity in the supramarginal gyrus, part of the SN. Our TPN showed both hypo- and hyperconnectivity dependent on seed location. Within network hypoconnectivity was observed in the visual network also using group comparison. Using an ICA, we identified altered network functional connectivity in regions within four IFCNs (sensorimotor, visual, DMN, and dorsal attentional). A significant negative correlation between dorsal attentional network connectivity and behavioral symptoms score was also found. CONCLUSIONS: Our findings indicate that rs-fMRI may be of use clinically in order to assess disrupted functional connectivity among IFCNs in mTBI patients. Improved mTBI diagnostic and prognostic information could be especially relevant for athletes looking to safely return to play, as well for individuals from the general population with persistent postconcussive symptoms months after injury, who hope to resume activity.

Persistent postconcussive symptoms in children and adolescents with mild traumatic brain injury receiving initial head computed tomography.

OBJECTIVE: The aim of this paper was to evaluate the prevalence of postconcussive symptoms and their relation to health-related quality of life (HRQOL) in pediatric and adolescent patients with mild traumatic brain injury (mTBI) who received head CT imaging during initial assessment. METHODS: Patients aged between 5 and 21 years with mTBI (Glasgow Coma Scale scores 13-15) and available Rivermead Post Concussion Questionnaire (RPQ) at 6 months of follow-up in the multicenter, prospectively collected CENTER-TBI (Collaborative European NeuroTrauma Effectiveness Research in TBI) study were included. The prevalence of postconcussive symptoms was assessed, and the occurrence of postconcussive syndrome (PSC) based on the ICD-10 criteria, was analyzed. HRQOL was compared in patients with and without PCS using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. RESULTS: A total of 196 adolescent or pediatric mTBI patients requiring head CT imaging were included. High-energy trauma was prevalent in more than half of cases (54%), abnormalities on head CT scans were detected in 41%, and admission to the regular ward or intensive care unit was necessary in 78%. Six months postinjury, 36% of included patients had experienced at least one moderate or severe symptom on the RPQ. PCS was present in 13% of adolescents and children when considering symptoms of at least moderate severity, and those patients had significantly lower QOLIBRI total scores, indicating lower HRQOL, compared with young patients without PCS (57 vs 83 points, p < 0.001). CONCLUSIONS: Adolescent and pediatric mTBI patients requiring head CT imaging show signs of increased trauma severity. Postconcussive symptoms are present in up to one-third of those patients, and PCS can be diagnosed in 13% 6 months after injury. Moreover, PCS is significantly associated with decreased HRQOL.

Invariance of the Bifactor Structure of Mild Traumatic Brain Injury (mTBI) Symptoms on the Rivermead Postconcussion Symptoms Questionnaire Across Time, Demographic Characteristics, and Clinical Groups: A TRACK-TBI Study.

This study aimed to elucidate the structure of the Rivermead Postconcussion Symptoms Questionnaire (RPQ) and evaluate its longitudinal and group variance. Factor structures were developed and compared in 1,011 patients with mild traumatic brain injury (mTBI; i.e., Glasgow Coma Scale score 13-15) from the Transforming Research and Clinical Knowledge in TBI study, using RPQ data collected at 2 weeks, and 3, 6, and 12 months postinjury. A bifactor model specifying a general factor and emotional, cognitive, and visual symptom factors best represented the latent structure of the RPQ. The model evinced strict measurement invariance over time and across sex, age, race, psychiatric history, and mTBI severity groups, indicating that differences in symptom endorsement were completely accounted for by these latent dimensions. While highly unidimensional, the RPQ has multidimensional features observable through a bifactor model, which may help differentiate symptom expression patterns in the future.

Exercise for Sport-Related Concussion and Persistent Postconcussive Symptoms.

CONTEXT: Emerging research supports the use of mild to moderate aerobic exercise for treating sport-related concussion (SRC) and persistent postconcussive symptoms (PPCS), yet the current standard of care remains to be strict rest. The purpose of this review is to summarize the existing literature on physical activity and prescribed exercise for SRC and PPCS. EVIDENCE ACQUISITION: PubMed and Embase were searched in April of 2019 for studies assessing rest or prescribed exercise for SRC and PPCS. No specific search syntax was used. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: A majority of studies show that spontaneous physical activity is safe after SRC and that subsymptom threshold aerobic exercise safely speeds up recovery after SRC and reduces symptoms in those with PPCS. Exercise tolerance can safely be assessed using graded exertion test protocols within days of injury, and the degree of early exercise tolerance has diagnostic and prognostic value. CONCLUSION: Subsymptom threshold aerobic exercise is safe and effective for the treatment of SRC as well as in athletes with PPCS. Further research is warranted to establish the most effective method and dose of aerobic exercise for the active treatment of SRC and whether early exercise treatment can prevent PPCS in athletes. STRENGTH OF RECOMMENDATION TAXONOMY: 2.