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.

Different trajectories of post-concussive symptom subscales after pediatric mild traumatic brain injury: Data from a prospective longitudinal study.

PURPOSE: The aim of this study was to investigate the trajectory of parent-rated post-concussive symptoms (PCS), attentional performance and participation within 6 months in children after mild traumatic brain injury (mTBI). METHODS: For this prospective longitudinal study, we included data on 64 children after mTBI and 57 healthy control children (age 8-16 years). Parents rated PCS using the Post-Concussion Symptom Inventory (PCSI) immediately (T0), 1 week (T1), and 3-6 months after injury (T2). Attentional performance (alertness, selective and divided attention) was measured using the Test of Attentional Performance (TAP) at T1 and T2 and participation was measured using the Child and Adolescent Scale of Participation (CASP) at T2. RESULTS: Friedman tests showed different trajectories of PCS subscales over time: Compared to pre-injury level, the amount of somatic and cognitive PCS was still elevated at T1, while emotional PCS at T1 were already comparable to pre-injury level. The rating of sleep-related PCS at T2 was significantly elevated compared to the pre-injury rating. Quade ANCOVAs indicated group differences in PCS subscales between patients and controls at T1, but not at T2. Patients and controls showed a similar performance in tests of attention at T1 and T2, but parental rating of participation at school was significantly reduced. Although cognitive PCS and attention were not correlated, there were significantly negative Spearman correlations between participation at home and pre-injury and concurrent PCS at T2. CONCLUSIONS: Our data imply that sleep-related PCS are still elevated weeks after injury and are thus a target for interventions after mTBI.

Gender Disparities in Neurobehavioral Symptoms and the Role of Post-Traumatic Symptoms in US Service Members Following Mild Traumatic Brain Injury.

Women are more directly involved in combat operations today than ever before, currently making up 18.6% of officers and 16.8% of enlisted personnel in the United States military. However, women continue to be under-represented in military research. Studies that do consider gender differences in traumatic brain injury (TBI) outcomes have shown that women report significantly more post-concussive symptoms than men. Conclusions for true gender differences related to TBI are hard to make without controlling for non-TBI factors. The effects previously identified in the literature may be an artifact of how men and women differ in their response to injury, unrelated to the neurological recovery process associated with TBI. The objective of this study was to examine the effects of gender specifics on mild TBI (mTBI) sequelae on injured and uninjured control groups, and to investigate the role of post-traumatic stress disorder (PTSD) on symptom reporting. It should be noted that the terms "gender" and "men/women" are used in this article in place of "sex" or "males/females" given that we are not discussing biological attributes. A total of 966 United States military service members and veterans were included in the study. Of the total sample, 455 men and 46 women were in the mTBI group, 285 men and 31 women were in the injured controls group (IC), and 111 men and 38 women in the non-injured controls group (NIC). Post-concussive and quality of life symptoms were compared for men and women while controlling for combat exposure. MTBI and IC groups were also stratified by PTSD presentation. Measures used included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist (PCL-C), Traumatic Brain Injury Quality of Life (TBI-QOL), and Combat Exposure Scale. In the mTBI group, women had worse scores on NSI total, NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety, Fatigue, and Headache scales (n2 = 0.018-0.032, small to small-medium effect sizes). When PTSD was present, women had worse scores on the NSI Somatosensory cluster only (n2 = 0.029, small-medium effect size). In contrast, when PTSD was absent, women had worse scores than men on the NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety and Headache scales (n2 = 0.032-0.063, small to medium effect sizes). In the IC group, women had worse scores on the NSI Cognitive cluster and the TBI-QOL Fatigue and Pain Interference scales (n2 = 0.024-0.042, small to small-medium effect sizes). However, group differences were no longer found when stratified by PTSD sub-groups. In the NIC group, there were no significant group differences for any analyses. We were able to identify symptoms unique to women recovering from mTBI that were not present following other forms of physical injury or in healthy controls. However, the impact of PTSD exacerbates the symptom profile and its comorbidity with mTBI equates to most of the noted gender differences.

Prefrontal Cortex Activity During Gait in People With Persistent Symptoms After Concussion.

BACKGROUND: Concussions result in transient symptoms stemming from a cortical metabolic energy crisis. Though this metabolic energy crisis typically resolves in a month, symptoms can persist for years. The symptomatic period is associated with gait dysfunction, the cortical underpinnings of which are poorly understood. Quantifying prefrontal cortex (PFC) activity during gait may provide insight into post-concussion gait dysfunction. The purpose of this study was to explore the effects of persisting concussion symptoms on PFC activity during gait. We hypothesized that adults with persisting concussion symptoms would have greater PFC activity during gait than controls. Within the concussed group, we hypothesized that worse symptoms would relate to increased PFC activity during gait, and that increased PFC activity would relate to worse gait characteristics. METHODS: The Neurobehavior Symptom Inventory (NSI) characterized concussion symptoms. Functional near-infrared spectroscopy quantified PFC activity (relative concentration changes of oxygenated hemoglobin [HbO2]) in 14 people with a concussion and 25 controls. Gait was assessed using six inertial sensors in the concussion group. RESULTS: Average NSI total score was 26.4 (13.2). HbO2 was significantly higher (P = .007) for the concussed group (0.058 [0.108]) compared to the control group (-0.016 [0.057]). Within the concussion group, HbO2 correlated with NSI total symptom score (ρ = .62; P = .02), sagittal range of motion (r = .79; P = .001), and stride time variability (r = -.54; P = .046). CONCLUSION: These data suggest PFC activity relates to symptom severity and some gait characteristics in people with persistent concussion symptoms. Identifying the neurophysiological underpinnings to gait deficits post-concussion expands our knowledge of motor behavior deficits in people with persistent concussion symptoms.

Convergence insufficiency in patients with post-concussion syndrome is accompanied by a higher symptom load: a cross-sectional study.

OBJECTIVE: To estimate the prevalence of convergence insufficiency (CI) in adult patients with post-concussion syndrome and determine the impact of CI on symptom load. METHODS: Cross-sectional study of 103 patients with neurological symptoms 2-6 months after a concussion. Symptoms were assessed with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and CI was diagnosed using near point of convergence, vergence facility, and the Convergence Insufficiency Symptom Survey. The RPQ score for patients with and without CI was compared, and sensitivity, specificity, and area under the receiver operating characteristic curve for the two visually related RPQ questions as indicators of CI were calculated. RESULTS: The proportion of patients diagnosed with symptomatic CI was 20.4% (95% confidence interval: 13.1-29.5%). The RPQ score was significantly higher for patients with symptomatic CI both before (p = .01) and after removal of the two visually related questions in the RPQ-questionnaire (p = .03). The two visually related RPQ questions were unable to detect CI. CONCLUSION: In patients with post-concussion syndrome, the load of nonvisual symptoms is higher in the presence of CI. A prospective interventional study on CI is required to study the relationship between CI and other post-concussion symptoms.

Concussion symptom presentation and clinical recovery among pediatric athletes: comparing concussions sustained during school and summer months.

OBJECTIVE: We examined post-concussion symptom presentation, exercise, and sleep among pediatric athletes who sustained concussion during the school year vs. summer months. METHODS: We evaluated athletes 6-18 years old within 21-days of concussion. They reported symptoms (Health and Behavior Inventory), with cognitive/somatic domain sub-scores calculated, and indicated if they had exercised or experienced sleep problems since injury. We grouped patients by injury season: summer months (June-August) vs. school year (September-May). RESULTS: 350 patients (14.4 ± 2.4 years old; 37% female; initial visit 8.8 ± 5.3 days post-concussion) were seen for care: 24% sustained a concussion during summer months, 76% during the school year. Lower cognitive (median = 7 [IQR = 1, 15] vs. 9.5 [4, 17]; p = 0.01), but not somatic (7 [2.5, 11] vs. 8 [4, 13]; p = 0.06), HBI scores were observed for patients injured during the summer. Groups were similar in proportion exercising (16% vs 17%) and endorsing sleep problems (29% vs 31%). After adjustments, sustaining a concussion during the summer predicted total (ß=-3.43; 95%CI = -6.50, -0.36; p = 0.029) and cognitive (ß = -2.29; 95%CI = -4.22, -0.36; p = 0.02), but not somatic (ß=-1.46; 95%CI = -2.84, -0.08; p = 0.04), symptom severity. CONCLUSION: Pediatric patients with concussion may present with greater cognitive symptoms during the school year, compared to summer months.

Cause of Concussion With Persisting Symptoms Is Associated With Long-Term Recovery and Symptom Type, Duration, and Number in a Longitudinal Cohort of 600 Patients.

It is important for patients and clinicians to know the potential for recovery from concussion as soon as possible after injury, especially in patients who do not recover completely in the first month and have concussion with persisting concussion symptoms (C+PCS). We assessed the association between the causes of concussion and recovery from C+PCS in a consecutive retrospective and prospective cohort of 600 patients referred to the Canadian Concussion Center (CCC) at Toronto Western Hospital. Data were obtained from clinical records and follow-up questionnaires and not from a standardized database. A novel method was used to assess long-term recovery, and multi-variable Cox proportional hazards models were used to assess relationships between cause of concussion and time to recovery. We examined the subsequent recovery of patients who had not recovered after at least one month from the time of concussion. Patients were grouped into the following four causes: sports and recreation (S&R, n = 312, 52%); motor vehicle collisions (MVC, n = 103, 17%); falls (n = 100, 17%); and being struck by an object including violence (SBOV, n = 85, 14%). The MVC group had the highest percentage of females (75.7%), the oldest participants (median: 40.0 [interquartile range (IQR):30.5-49.0] years), the most symptoms (median:11.0 [IQR:8.5-15.0]), and the longest symptom duration (median: 28.0 [IQR:12.0-56.00] months). In contrast, the S&R group had the highest percentage of males (58.1%), the youngest participants (median:20.0 [IQR:17.0-30.0] years), the best recovery outcome, and shortest symptom duration (median:22.0 [IQR:8.0-49.5] months). Significant differences among the four causes included age (p < 0.001), sex (p < 0.001), number of previous concussions (p < 0.001), history of psychiatric disorders (p = 0.002), and migraine (p = 0.001). Recovery from concussion was categorized into three groups: (1) Complete Recovery occurred in only 60 (10%) patients with median time 8.0 (IQR:3.5-18.0) months and included 42 S&R, 7 MVC, 8 falls, and 3 SBOV; (2) Incomplete Recovery occurred in 408 (68.0%) patients with persisting median symptom time of 5.0 (IQR:2.0-12.0) months; and (3) Unknown Recovery occurred in 132 (22.0%) patients and was because of lack of follow-up. In summary, the cause of C+PCS was associated with the type, number, and duration of symptoms and time required for recovery, although all causes of C+PCS produced prolonged symptoms in a large percentage of patients, which emphasizes the importance of concussions as a public health concern necessitating improved prevention and treatment strategies.

Optimizing the Combination of Common Clinical Concussion Batteries to Predict Persistent Postconcussion Symptoms in a Prospective Cohort of Concussed Youth.

BACKGROUND: Studies have evaluated individual factors associated with persistent postconcussion symptoms (PPCS) in youth concussion, but no study has combined individual elements of common concussion batteries with patient characteristics, comorbidities, and visio-vestibular deficits in assessing an optimal model to predict PPCS. PURPOSE: To determine the combination of elements from 4 commonly used clinical concussion batteries and known patient characteristics and comorbid risk factors that maximize the ability to predict PPCS. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: We enrolled 198 concussed participants-87 developed PPCS and 111 did not-aged 8 to 19 years assessed within 14 days of injury from a suburban high school and the concussion program of a tertiary care academic medical center. We defined PPCS as a Post-Concussion Symptom Inventory (PCSI) score at 28 days from injury of ≥3 points compared with the preinjury PCSI score-scaled for younger children. Predictors included the individual elements of the visio-vestibular examination (VVE), Sport Concussion Assessment Tool, 5th Edition (SCAT-5), King-Devick test, and PCSI, in addition to age, sex, concussion history, and migraine headache history. The individual elements of these tests were grouped into interpretable factors using sparse principal component analysis. The 12 resultant factors were combined into a logistic regression and ranked by frequency of inclusion into the combined optimal model, whose predictive performance was compared with the VVE, initial PCSI, and the current existing predictive model (the Predicting and Prevention Postconcussive Problems in Pediatrics (5P) prediction rule) using the area under the receiver operating characteristic curve (AUC). RESULTS: A cluster of 2 factors (SCAT-5/PCSI symptoms and VVE near point of convergence/accommodation) emerged. A model fit with these factors had an AUC of 0.805 (95% CI, 0.661-0.929). This was a higher AUC point estimate, with overlapping 95% CIs, compared with the PCSI (AUC, 0.773 [95% CI, 0.617-0.912]), VVE (AUC, 0.736 [95% CI, 0.569-0.878]), and 5P Prediction Rule (AUC, 0.728 [95% CI, 0.554-0.870]). CONCLUSION: Among commonly used clinical assessments for youth concussion, a combination of symptom burden and the vision component of the VVE has the potential to augment predictive power for PPCS over either current risk models or individual batteries.

Co-existence of depression and post-concussion syndrome one month after mild traumatic brain injury.

BACKGROUND: Previous studies suggest an association between Post-concussion syndrome (PCS) and depression, both highly prevalent after mTBI. OBJECTIVE: To assess the prevalence and risk-factors of depression among patients with PCS 1 month after mTBI. METHODS: We prospectively screened 372 mTBI patients admitted in two academic Emergency Departments between 2017 and 2019. One month after mTBI, we administered the Rivermead Post-concussion symptoms Questionnaire (RPQ) and the Patient Health Questionnaire (PHQ-9) questionnaires over the telephone. PCS and depression were defined by RPQ ≥ 12 and PHQ-9 ≥ 10. Multivariate multinomial regression identified baseline factors associated with PCS and depression. RESULTS: Two hundred and eight completed RPQ and PHQ-9. Forty-seven patients (22.5%) met criteria for PCS, among which 22 (46.8%) met criteria for depression (PCS+D+). Patients with PCS but without depression were less likely to present with an associated injury (Coefficient = -1.6, p = 0.047) and to report initial sadness (Coefficient = -2.5, p = 0.03). Initial sadness (Coefficient = -1.3, p = 0.047), associated injury (Coefficient = -1.9, p = 0.008), as well as initial nausea (Coefficient = -1.8, p = 0.002), and male sex (Coefficient = 1.8, p = 0.002), were associated with the absence of depression and PCS in comparison with PCS+D+ patients. CONCLUSION: Among patients with PCS 1 month after mTBI, those with depression are more likely to present with initial sadness and with an associated injury.

Emergency Department Risk Factors for Post-Concussion Syndrome After Mild Traumatic Brain Injury: A Systematic Review.

Approximately 16% of patients with mild traumatic brain injury (mTBI) develop a post-concussion syndrome (PCS) with persistent physical, neurological, and behavioral complaints. PCS has a great impact on a patient's quality of life, often decreases the ability to return to work, and henceforth has a great economic impact. Recent studies suggest that early treatment can greatly improve prognosis and prevent long-term effects in these patients. However, early recognition of patients at high risk of PCS remains difficult. The objective of this systematic review is to assess risk factors associated with the development of PCS, primarily aimed at the group of non-hospitalized patients who were seen with mTBI at the emergency department (ED). We searched PubMed/MEDLINE, Cochrane Library and EMBASE on September 23, 2022, for prospective studies that assessed the risk factors for the development of PCS. Exclusion criteria were: retrospective studies; > 20% computed tomography (CT) abnormalities, <18 years of age, follow-up <4 weeks, severe trauma, and study population <100 patients. The search strategy identified 1628 articles, of which 17 studies met eligibility criteria. Risk factors found in this systematic review are pre-existing psychiatric history, headache at the ED, neurological symptoms at the ED, female sex, CT abnormalities, pre-existent sleeping problems, and neck pain at the ED. This systematic review identified seven risk factors for development of PCS in patients with mTBI. Future research should assess if implementation of these risk factors into a risk stratification tool will assist the emergency physician in the identification of patients at high risk of PCS.

Longitudinal Associations Between Persistent Post-Concussion Symptoms and Blood Biomarkers of Inflammation and CNS-Injury After Mild Traumatic Brain Injury.

The aim of our study was to investigate the biological underpinnings of persistent post-concussion symptoms (PPCS) at 3 months following mild traumatic brain injury (mTBI). Patients (n = 192, age 16-60 years) with mTBI, defined as Glasgow Coma Scale (GCS) score between 13 and 15, loss of consciousness (LOC) <30 min, and post-traumatic amnesia (PTA) <24 h were included. Blood samples were collected at admission (within 72 h), 2 weeks, and 3 months. Concentrations of blood biomarkers associated with central nervous system (CNS) damage (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], and tau) and inflammation (interferon gamma [IFNγ], interleukin [IL]-8, eotaxin, macrophage inflammatory protein-1-beta [MIP]-1ß, monocyte chemoattractant protein [MCP]-1, interferon-gamma-inducible protein [IP]-10, IL-17A, IL-9, tumor necrosis factor [TNF], basic fibroblast growth factor [FGF]-basic platelet-derived growth factor [PDGF], and IL-1 receptor antagonist [IL-1ra]) were obtained. Demographic and injury-related factors investigated were age, sex, GCS score, LOC, PTA duration, traumatic intracranial finding on magnetic resonance imaging (MRI; within 72 h), and extracranial injuries. Delta values, that is, time-point differences in biomarker concentrations between 2 weeks minus admission and 3 months minus admission, were also calculated. PPCS was assessed with the British Columbia Post-Concussion Symptom Inventory (BC-PSI). In single variable analyses, longer PTA duration and a higher proportion of intracranial findings on MRI were found in the PPCS group, but no single biomarker differentiated those with PPCS from those without. In multi-variable models, female sex, longer PTA duration, MRI findings, and lower GCS scores were associated with increased risk of PPCS. Inflammation markers, but not GFAP, NFL, or tau, were associated with PPCS. At admission, higher concentrations of IL-8 and IL-9 and lower concentrations of TNF, IL-17a, and MCP-1 were associated with greater likelihood of PPCS; at 2 weeks, higher IL-8 and lower IFNγ were associated with PPCS; at 3 months, higher PDGF was associated with PPCS. Higher delta values of PDGF, IL-17A, and FGF-basic at 2 weeks compared with admission, MCP-1 at 3 months compared with admission, and TNF at 2 weeks and 3 months compared with admission were associated with greater likelihood of PPCS. Higher IL-9 delta values at both time-point comparisons were negatively associated with PPCS. Discriminability of individual CNS-injury and inflammation biomarkers for PPCS was around chance level, whereas the optimal combination of biomarkers yielded areas under the curve (AUCs) between 0.62 and 0.73. We demonstrate a role of biological factors on PPCS, including both positive and negative effects of inflammation biomarkers that differed based on sampling time-point after mTBI. PPCS was associated more with acute inflammatory processes, rather than ongoing inflammation or CNS-injury biomarkers. However, the modest discriminative ability of the models suggests other factors are more important in the development of PPCS.