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.

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.

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.

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.

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.

Temporal Changes in Fixational Eye Movements After Concussion in Adolescents and Adults: Preliminary Findings.

Concussions often involve ocular impairment and symptoms such as convergence insufficiency, accommodative insufficiency, blurred vision, diplopia, eye strain, and pain. Current clinical assessments of ocular function and symptoms rely on subjective symptom reporting and/or involve lengthy administration time. More objective, brief assessments of ocular function following concussion are warranted. The purpose of this study was to evaluate changes in fixational eye movements (FEMs) and their association with clinical outcomes including recovery time, symptoms, cognitive and vestibular/ocular motor impairment. Thirty-three athletes (13-27 years of age; 54.5% female) within 21 days of a diagnosed concussion participated in the study. A tracking scanning laser ophthalmoscope (TSLO) evaluated FEMs metrics during fixation on a center and corner target. Participants completed symptom (Post-Concussion Symptom Scale [PCSS]), cognitive (Immediate Post-concussion Assessment and Cognitive Testing [ImPACT], and Vestibular/Ocular Motor Screening (VOMS) evaluations. All measures were administered at the initial visit and following medical clearance, which was defined as clinical recovery. Changes in FEMs were calculated using paired-samples t tests. Linear regression (LR) models were used to evaluate the association of FEMs with clinical recovery. Pearson product-moment correlations were used to evaluate the associations among FEMs and clinical outcomes. On the center task, changes across time were supported for average microsaccade amplitude (p = 0.005; Cohen's d = 0.53), peak velocity of microsaccades (p = 0.01; d = 0.48), peak acceleration of microsaccades (p = 0.02; d = 0.48), duration of microsaccade (p < 0.001; d = 0.72), and drift vertical (p = 0.017; d = -0.154). The LR model for clinical recovery was significant (R2 = 0.37; p = 0.023) and retained average instantaneous drift amplitude (ß = 0.547) and peak acceleration of microsaccade (ß = 0.414). On the corner task, changes across time were supported for drift proportion (p = 0.03; d = 0.43). The LR model to predict clinical recovery was significant (R2 = 0.85; p = 0.004) and retained average amplitude of microsaccades (ß = 2.66), peak velocity of microsaccades (ß = -15.11), peak acceleration of microsaccades (ß = 12.56), drift horizontal (ß = 7.95), drift vertical (ß = 1.29), drift amplitude (ß = -8.34), drift proportion (ß = 0.584), instantaneous drift direction (ß = -0.26), and instantaneous drift amplitude (ß = 0.819). FEMs metrics were also associated with reports of nausea and performance within the domain of visual memory. The FEMs metric were also associated with PCSS, ImPACT, and VOMS clinical concussion outcomes, with the highest magnitude correlations between average saccade amplitude and VOMS symptoms of nausea and average instantaneous drift speed and ImPACT visual memory, respectively. FEMs metrics changed across time following concussion, were useful in predicting clinical recovery, and were correlated with clinical outcomes. FEMs measurements may provide objective data to augment clinical assessments and inform prognosis following this injury.

Acute psychological symptom profiles in high school football players following sport-related concussion.

OBJECTIVE: In a cohort of high school football athletes, the authors sought to 1) describe the proportion of those with acute psychological symptoms postconcussion, 2) determine predictors of more acute psychological symptoms postconcussion, and 3) determine if acute psychological symptoms impact recovery. METHODS: A retrospective cohort study of high school football athletes (14-18 years of age) who sustained a sport-related concussion between November 2017 and April 2022 and presented to a multidisciplinary concussion center was performed. Based on their Post-Concussion Symptom Scale (PCSS) scores at the initial clinic visit, their total psychological symptom cluster score was calculated by summing their scores for the four affective symptoms (irritability, sadness, nervousness, and feeling more emotional). The psychological symptom ratio was defined as the ratio of the psychological symptom cluster score to the total initial PCSS score. Primary outcomes included time to return to learn (RTL), symptom resolution, and return to play (RTP). Uni- and multivariable regression analyses were performed controlling for demographic factors, learning disabilities, attention-deficit/hyperactivity disorder, and personal and/or family history of psychological diagnoses and migraine. RESULTS: A total of 195 male football players (mean age 16.2 ± 1.2 years) were included in the study. About one-third of the sample (n = 70, 35.9%) reported at least one psychological symptom. Of these 70 athletes, their psychological symptom scores were 1 (10.3%), 2 (7.7%), and ≥ 3 (17.9%). Irritability was the most endorsed psychological symptom (25.1%), followed by nervousness (15.9%), feeling more emotional (12.8%), and sadness (11.8%). The multivariable regression model showed that a positive psychological history (B = 2.66, 95% CI 0.74-4.58, p = 0.007) and family psychological history (B = 2.43, 95% CI 0.98-3.88, p = 0.001) were significant predictors of a higher psychological symptom cluster score. Multivariable linear regression analysis showed that a higher psychological symptom cluster score was associated with a longer time to RTP (B = 1.22, 95% CI 0.17-2.264, p = 0.023) but not with time to symptom resolution or RTL. The psychological symptom ratio was not a significant predictor. CONCLUSIONS: In a cohort of male football players, 36% reported at least one psychological symptom, with irritability being most commonly reported. Athletes with a personal and/or family history of psychological disorders experienced more acute psychological symptoms following a sport-related concussion. A higher psychological symptom cluster score was associated with delayed time to RTP but not time to RTL or symptom resolution.

Evidence of Ongoing Cerebral Microstructural Reorganization in Children With Persisting Symptoms Following Mild Traumatic Brain Injury: A NODDI DTI Analysis.

Approximately 300-550 children per 100,000 sustain a mild traumatic brain injury (mTBI) each year, of whom ∼25-30% have long-term cognitive problems. Following mTBI, free water (FW) accumulation occurs in white matter (WM) tracts. Diffusion tensor imaging (DTI) can be used to investigate structural integrity following mTBI. Compared with conventional DTI, neurite orientation dispersion and density imaging (NODDI) orientation dispersion index (ODI) and fraction of isolated free water (FISO) metrics may allow a more advanced insight into microstructural damage following pediatric mTBI. In this longitudinal study, we used NODDI to explore whole-brain and tract-specific differences in ODI and FISO in children with persistent symptoms after mTBI (n = 80) and in children displaying clinical recovery (n = 32) at 1 and 2-3 months post-mTBI compared with healthy controls (HCs) (n = 21). Two-way repeated measures analysis of variance (ANOVA) and voxelwise two-sample t tests were conducted to compare whole-brain and tract-specific diffusion across groups. All results were corrected at positive false discovery rate (pFDR) <0.05. We also examined the association between NODDI metrics and clinical outcomes, using logistical regression to investigate the value of NODDI metrics in predicting future recovery from mTBI. Whole-brain ODI was significantly increased in symptomatic participants compared with HCs at both 1 and 2 months post-injury, where the uncinate fasciculus (UF) and inferior fronto-occipital fasciculus (IFOF) were particularly implicated. Using region of interest (ROI) analysis in significant WM, bilateral IFOF and UF voxels, symptomatic participants had the highest ODI in all ROIs. ODI was lower in asymptomatic participants, and HCs had the lowest ODI in all ROIs. No changes in FISO were found across groups or over time. WM ODI was moderately correlated with a higher youth-reported post-concussion symptom inventory (PCSI) score. With 87% predictive power, ODI (1 month post-injury) and clinical predictors (age, sex, PCSI score, attention scores) were a more sensitive predictor of recovery at 2-3 months post-injury than fractional anisotropy (FA) and clinical predictors, or clinical predictors alone. FISO could not predict recovery at 2-3 months post-injury. Therefore, we found that ODI was significantly increased in symptomatic children following mTBI compared with HCs at 1 month post-injury, and progressively decreased over time alongside clinical recovery. We found no significant differences in FISO between groups or over time. WM ODI at 1 month was a more sensitive predictor of clinical recovery at 2-3 months post-injury than FA, FISO, or clinical measures alone. Our results show evidence of ongoing microstructural reorganization or neuroinflammation between 1 and 2-3 months post-injury, further supporting delayed return to play in children who remain symptomatic. We recommend future research examining the clinical utility of NODDI following mTBI to predict recovery or persistence of post-concussion symptoms and thereby inform management of mTBI.

Post-Concussion Symptoms in Women With Head Injury Due to Intimate Partner Violence.

Limited research has examined the symptom sequelae of head injuries in women survivors of intimate partner violence (IPV), despite this community being at increased risk for neurotrauma due to partner abuse. The current study compared post-concussion symptom severity between women with and without IPV-related head injuries. Women were recruited from court jurisdictions in Kentucky, USA, after receiving a protective order for partner abuse. The sample included 268 women with no prior head injuries (age: M[standard deviation (SD)] = 31.8[9.8], 77.2% White) and 251 women with lifetime IPV-related head injuries (age: M[SD] = 31.8[9.8], 88.0% White). Women with IPV-related head injuries were slightly older (t = 2.46, p = 0.014) with lower education (χ2 = 5.81, p = 0.016), were more frequently unemployed (χ2 = 9.23, p = 0.002), and had a higher likelihood of residing in a rural setting (χ2 = 30.16, p < 0.001). Women with IPV-related head injuries were also more often White (χ2 = 10.47, p = 0.001), but this group difference was almost entirely related to rural versus urban residence. Women with IPV-related head injuries reported a higher severity of lifetime physical IPV (t = 7.27, p < 0.001, d = 0.64, 95% confidence interval [CI]: [.46, .82]) and sexual IPV (t = 4.65, p < 0.001, d = 0.41 [0.24, 0.59]). A three-factor model of post-concussion symptoms, inclusive of cognitive, physical, and emotional symptoms, fit well (χ2 = 368.99, p < 0.0001, comparative fit index [CFI] = 0.974, Tucker-Lewis index [TLI] = 0.968, root mean square error of approximation [RMSEA] = 0.079 [0.071, 0.087]), and showed evidence for strong measurement invariance across women with and without IPV-related head injuries. The subscale and total scores each had acceptable reliability: cognitive (ω = 0.88 [0.86, 0.90]), physical (ω = 0.74 [0.70, 0.77]), and emotional (ω = 0.88 [0.86, 0.89]), and total score (ω = 0.93 [0.92, 0.95]). Women with IPV-related head injuries reported all individual post-concussion symptoms at a significantly higher frequency, with medium group differences in cognitive (t = 7.57, p < 0.001, d = 0.67 [0.50, 0.85]) and physical symptoms (t = 7.73, p < 0.001, d = 0.68 [0.51, 0.86]) and large group differences in emotional (t = 8.51, p < 0.001, d = 0.75 [0.57, 0.93]) and total symptoms (t = 9.07, p < 0.001, d = 0.80 [0.62, 0.98]). All sociodemographic characteristics were independently associated with post-concussion symptoms, as were physical IPV (total score: r = 0.28 [0.19, 0.35], p < 0.001) and sexual IPV severity (total score: r = 0.22 [0.13, 0.30], p < 0.001). In hierarchical regression analyses, controlling for sociodemographic characteristics (i.e., age, race/ethnicity, education, unemployment, and rural/urban residence) and physical and sexual IPV severity, IPV-related head injury was independently significant and accounted for significant additional variance when predicting cognitive (ΔR2 = 0.05, p < 0.001), physical (ΔR2 = 0.03, p < 0.001), emotional (ΔR2 = 0.07, p < 0.001), and total symptoms (ΔR2 = 0.06, p < 0.001). Negative-binomial regression resulted in similar findings. This study demonstrates that multiple sociodemographic and IPV history variables are related to post-concussion symptom severity, but IPV-related head injury was independently associated with greater symptom severity. Women with IPV-related head injuries may be at increased risk for unaddressed health problems spanning cognitive, physical, and emotional domains. Future research is needed to psychometrically evaluate assessment instruments for this population and to assess efficacy of interventions to address their unique health care needs.

Lifetime Traumatic Brain Injury and Risk of Post-Concussive Symptoms in the Millennium Cohort Study.

Traumatic brain injury (TBI) is prevalent among active duty military service members, with studies reporting up to 23% experiencing at least one TBI, with 10-60% of service members reporting at least one subsequent repeat TBI. A TBI has been associated with an increased risk of cumulative effects and long-term neurobehavioral symptoms, impacting operational readiness in the short-term and overall health in the long term. The association between multiple TBI and post-concussive symptoms (PCS), however, defined as symptoms that follow a concussion or TBI, in the military has not been adequately examined. Previous studies in military populations are limited by methodological issues including small sample sizes, the use of non-probability sampling, or failure to include the total number of TBI. To overcome these limitations, we examined the association between the total lifetime number of TBI and total number of PCS among U.S. active duty military service members who participated in the Millennium Cohort Study. A secondary data analysis was conducted using the Millennium Cohort Study's 2014 survey (n = 28,263) responses on self-reported TBI and PCS (e.g., fatigue, restlessness, sleep disturbances, poor concentration, or memory loss). Zero-inflated negative binomial models calculated prevalence ratios (PRs) and 95% confidence intervals (CIs) for the unadjusted and adjusted associations between lifetime TBIs and PCS. A third of military participants reported experiencing one or more TBIs during their lifetime with 72% reporting at least one PCS. As the mean number of PCS increased, mean lifetime TBIs increased. The mean number of PCS by those with four or more TBI (4.63) was more than twice that of those with no lifetime TBI (2.28). One, two, three, and four or more TBI had 1.10 (95% CI: 1.06-1.15), 1.19 (95% CI: 1.14-1.25), 1.23 (95% CI: 1.17-1.30), and 1.30 times (95% CI: 1.24-1.37) higher prevalence of PCS, respectively. The prevalence of PCS was 2.4 (95% CI: 2.32-2.48) times higher in those with post-traumatic stress disorder than their counterparts. Active duty military service members with a history of TBI are more likely to have PCS than those with no history of TBI. These results suggest an elevated prevalence of PCS as the number of TBI increased. This highlights the need for robust, longitudinal studies that can establish a temporal relationship between repetitive TBI and incidence of PCS. These findings have practical relevance for designing both workplace safety prevention measures and treatment options regarding the effect on and from TBI among military personnel.

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.

Interdisciplinary rehabilitation for persisting post-concussion symptoms after mTBI: N=15 single case experimental design.

BACKGROUND: Despite clinical guidelines recommending an interdisciplinary approach to persisting post-concussion symptom (PPCS) management, evaluations of interdisciplinary interventions remain scant. OBJECTIVES: This pilot study aimed to explore the feasibility and preliminary efficacy of an interdisciplinary intervention for PPCSs. METHOD: A single-case experimental design with randomisation to multiple baselines (2, 4, or 6 weeks) was repeated across 15 participants (53% female) with mild traumatic brain injury (mean age 38.3 years, SD 15.7). The 12-week treatment incorporated psychology, physiotherapy, and medical interventions. Feasibility outcomes included recruitment and retention rates, adverse events, treatment adherence and fidelity. Patient-centred secondary outcomes included the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), assessed 3 times per week during the baseline and treatment phases, and at the 1- and 3-month follow-ups. Other secondary outcomes included measures of mood, sleep and fatigue, physical functioning, health-related quality of life, illness perceptions, and goal attainment. Changes in PPCSs were evaluated using systematic visual analysis and Tau-U. Clinically significant changes in secondary outcomes were explored descriptively. RESULTS: 16/26 individuals assessed for eligibility were enroled (61% recruitment rate); 15 completed the post-treatment follow-ups, and 13 completed the 1- and 3-month follow-up assessments (81% retention rate). High treatment adherence and competence in delivering treatments was observed. Moderate-large effect sizes for reducing PPCSs were observed in 12/15 cases, with 7/15 reaching statistical significance. Improvements were maintained at the 1- and 3-month follow-ups and were accompanied by reductions in fatigue, sleep difficulties, and mood symptoms, and changes in illness perceptions. All participants had clinically significant improvements in at least 1 outcome, with 81% of individual therapy goals achieved. CONCLUSIONS: This pilot study provided preliminary support for a subsequent randomised controlled trial (RCT), with satisfactory recruitment, retention, treatment compliance, and treatment fidelity. Improvement was evident on participant outcomes including symptom reduction and goal attainment, suggesting that progressing to a phase-II RCT is worthwhile. Findings highlight the potential benefit of individualized interdisciplinary treatments.

Lack of association between four biomarkers and persistent post-concussion symptoms after a mild traumatic brain injury.

Approximately 15 % of individuals who sustained a mild Traumatic Brain Injury (TBI) develop persistent post-concussion symptoms (PPCS). We hypothesized that blood biomarkers drawn in the Emergency Department (ED) could help predict PPCS. The main objective of this project was to measure the association between four biomarkers and PPCS at 90 days post mild TBI. We conducted a prospective cohort study in seven Canadian EDs. Patients aged ≥ 14 years presenting to the ED within 24 h of a mild TBI who were discharged were eligible. Clinical data and blood samples were collected in the ED, and a standardized questionnaire was administered 90 days later to assess the presence of symptoms. The following biomarkers were analyzed: S100B protein, Neuron Specific Enolase (NSE), cleaved-Tau (c-Tau) and Glial Fibrillary Acidic Protein (GFAP). The primary outcome measure was the presence of PPCS at 90 days after trauma. Relative risks and Areas Under the Curve (AUC) were computed. A total of 595 patients were included, and 13.8 % suffered from PPCS at 90 days. The relative risk of PPCS was 0.9 (95 % CI: 0.5-1.8) for S100B ≥ 20 pg/mL, 1.0 (95 % CI: 0.6-1.5) for NSE ≥ 200 pg/mL, 3.4 (95 % CI: 0.5-23.4) for GFAP ≥ 100 pg/mL, and 1.0 (95 % CI: 0.6-1.8) for C-Tau ≥ 1500 pg/mL. AUC were 0.50, 0.50, 0.51 and 0.54, respectively. Among mild TBI patients, S100B protein, NSE, c-Tau or GFAP do not seem to predict PPCS. Future research testing of other biomarkers is needed to determine their usefulness in predicting PPCS.

Characterizing the profiles of patients with acute concussion versus prolonged post-concussion symptoms in Ontario.

Identifying vulnerability factors for developing persisting concussion symptoms is imperative for determining which patients may require specialized treatment. Using cross-sectional questionnaire data from an Ontario-wide observational concussion study, we compared patients with acute concussion (≤ 14 days) and prolonged post-concussion symptoms (PPCS) (≥ 90 days) on four factors of interest: sex, history of mental health disorders, history of headaches/migraines, and past concussions. Differences in profile between the two groups were also explored. 110 patients with acute concussion and 96 patients with PPCS were included in our study. The groups did not differ on the four factors of interest. Interestingly, both groups had greater proportions of females (acute concussion: 61.1% F; PPCS: 66.3% F). Patient profiles, however, differed wherein patients with PPCS were significantly older, more symptomatic, more likely to have been injured in a transportation-related incident, and more likely to live outside a Metropolitan city. These novel risk factors for persisting concussion symptoms require replication and highlight the need to re-evaluate previously identified risk factors as more and more concussions occur in non-athletes and different risk factors may be at play.

Does earlier vestibular therapy after sport-related concussion lead to faster recovery?

OBJECTIVE: Many patients experience vestibular dysfunction following a sport-related concussion (SRC). Vestibular rehabilitation therapy has recently become more well established. In a cohort of athletes with SRC, the authors sought to 1) assess the relationship between symptoms at the initial clinic visit and time to referral for vestibular therapy, and 2) evaluate whether earlier referral to vestibular therapy was associated with faster recovery, as defined as days to return to learn (RTL), symptom resolution (SR), and return to play (RTP). METHODS: A retrospective cohort study was conducted using a regional multidisciplinary concussion center's database. Patients aged 12-23 years diagnosed with SRC who received vestibular rehabilitation therapy between October 2017 and October 2021 were included. Demographics and Post-Concussion Symptom Scale (PCSS) scores were extracted. The independent variable of interest was time to vestibular therapy referral. The three outcome variables were RTL, SR, and RTP. Spearman's rho correlation (rho) was used to evaluate the relationship between total PCSS score and individual symptoms (balance problems, blurred vision, and dizziness) and time to referral for vestibular therapy. Multivariable linear regression was performed to determine the impact of time to vestibular therapy on the three outcomes of RTL, SR, and RTP. Covariates included initial symptom burden, age, and prior concussions. RESULTS: Forty-two concussed athletes were referred for vestibular therapy (mean age 16.8 ± 2.7 years; 54.8% female). The mean time from concussion to the initial clinic visit was 22.4 ± 20.2 days, and the mean time from the initial clinic visit to vestibular therapy referral was 4.9 ± 11.3 days. Initial total PCSS scores (rho[37] = 0.05, p = 0.78) and individual symptoms, including balance problems (rho[33] = -0.004, p = 0.98), blurred vision (rho[34] = -0.17, p = 0.33), and dizziness (rho[33] = 0.07, p = 0.67), were not correlated with time to referral for vestibular therapy. Multivariable linear regression analysis found that earlier vestibular therapy referral was predictive of shorter days to SR (p = 0.002) and RTP (p = 0.02) but not RTL (p = 0.59). CONCLUSIONS: In athletes with SRC referred for vestibular therapy, earlier vestibular therapy referral was significantly associated with faster time to RTP and SR. Future investigations should focus on identifying common postconcussive signs and symptoms that serve as indications for referral to vestibular therapy.

The importance of screening for functional neurological disorders in patients with persistent post-concussion symptoms.

BACKGROUND: Functional neurological disorder (FND) may commonly co-occur with persistent symptoms following a psychological trauma or physical injury such as concussion. OBJECTIVE: To explore the occurrence of FND in a population with persistent post-concussion symptoms (PPCS) and the associations between FND and depression as well as anxiety in participants with PPCS. METHODS: Sixty-three individuals with PPCS presenting to a specialized brain injury clinic completed the following questionnaires: screening for somatoform disorder conversion disorder subscale (SOM-CD), Rivermead post-concussion symptom questionnaire (RPQ), patient health questionnaire-9 (PHQ-9), and generalized anxiety disorder questionnaire- 7 (GAD-7). Both multiple linear regression and logistic regression were conducted to evaluate the relationship between questionnaires and adjust for covariates. RESULTS: We found that total RPQ score (߈= 0.27; 95% CI = [0.16, 0.38]), GAD-7 score (߈= 0.71; 95% CI = [0.50, 0.92]) and PHQ-9 score (߈= 0.54; 95% CI = [0.32, 0.76]) were positively associated with SOM-CD score individually, after consideration of other covariates. Participants meeting the criteria for severe FND symptoms were 4.87 times more likely to have high PPCS symptom burden (95% CI = [1.57, 22.84]), 8.95 times more likely to have severe anxiety (95% CI = [3.31, 35.03]) and 4.11 times more likely to have severe depression symptom burden (95% CI = [1.77, 11.53]). CONCLUSION: The findings of this study indicate an association between FND and post-concussion symptoms as well as an association between FND and symptoms of depression and anxiety in patients with PPCS. Patients with PPCS should be screened for FND to provide a more targeted treatment approach that includes somatic-focused interventions.

Patterns of post-traumatic stress symptoms in mild traumatic brain injury and their relationship with outcomes: a latent profile analysis.

INTRODUCTION: Post-traumatic stress symptoms (PTSS) are known to contribute to postconcussion symptoms and functional status following mild traumatic brain injury (mTBI). Identifying symptom cluster profiles provide an opportunity to better understand PTSS and their influence on these outcomes. In this study, latent profiles of PTSS following mTBI were identified, and their association with mTBI outcomes was examined. The predictive role of demographic and injury related variables on profile membership was also explored. METHOD: Adults (N = 252) completed self report measures of PTSS and mTBI outcomes (post-concussion symptoms and functional status) within three months of mTBI. These measures were re-administered six months later (N = 187). Latent profile analysis (LPA) was used to ascertain the latent class structure of PTSS, and regression analysis to examine predictors of profiles. ANCOVA, with general psychological distress as a covariate, revealed the relationship between profiles and mTBI outcomes. RESULTS: LPA identified a four-profile model to best describe PTSS at baseline. This included a resilient (49.6%), moderate (30.6%), moderate with high intrusion/avoidance (14.3%) and a highly symptomatic profile (5.6%). A secondary school education or less and/or unemployment before mTBI was significantly more likely in the highly symptomatic profile, as well as sustaining an mTBI due to an assault or motor vehicle accident. PTSS latent class membership was significantly associated with mTBI outcomes even when controlling for general psychological distress. The resilient group had significantly better outcomes at baseline and six-month follow-up. However, no significant differences in mTBI outcomes emerged between the moderate, moderate with high intrusion/avoidance and the highly symptomatic profiles. CONCLUSION: The current study provides novel information on the symptom profiles of PTSS in mTBI, predictors of profile membership and their relationship with mTBI outcomes. Although future research using this approach is needed, the current study offers a more in-depth understanding of PTSS in mTBI to inform clinical care.

Investigation of long-term symptoms and influencing factors in patients with mild traumatic brain injury: A cross-sectional study.

BACKGROUND: Traumatic brain injury is the leading cause of death and disability in individuals under the age of 45, which places a heavy disease burden on patients and society. However, the prevalence of long-term symptoms in individuals who suffered from mild traumatic brain injury and how psychosocial factors affect their long-term symptoms remain unclear. OBJECTIVE: To determine howpsychosocial factors influence long-term symptomsin individuals who suffered from mild traumatic brain injury as well as the prevalence of long-term symptoms. METHODS: A demographic characteristics questionnaire, adapted self-report questionnaire of family relationship quality, revised Chinese version of the disease perception questionnaire, Rivermead postconcussion syndrome symptom questionnaire, Glasgow Outcome Scale-Extended, and Brief Symptoms Inventory 18 were used to collect data anonymously. Psychosocial factors associated with long-term symptoms in individuals who suffered from mild traumatic brain injury weremeasuredusingmultiple linear regression. RESULTS: More than half of individuals who suffered from mild traumatic brain injury showed at least 1 long-term symptom after injury. Our results indicated that family relationship quality, disease perception, and demographic characteristics were related to the long-term symptoms of individuals who suffered from mild traumatic brain injury. CONCLUSIONS: Our study shows that theprevalence of long-term symptomsfollowingmild traumatic brain injuryishigh. Psychosocial factors are related to patients' long-term symptoms. The findings indicate that healthcare administrators ought to adopt a robust health promotion strategy that prioritizes familial support and health education of diseases to ameliorate long-term symptoms in individuals who suffered from mild traumatic brain injury.