Psychological Predictors of Mental Health Difficulties after Pediatric Concussion.

Children often experience mental health difficulties after a concussion. Yet, the extent to which a concussion precipitates or exacerbates mental health difficulties remains unclear. This study aimed to examine psychological predictors of mental health difficulties after pediatric concussion. Children (aged 5 to <18 years, M=11.7, SD=3.3) with concussion were recruited in a single-site longitudinal prospective cohort study conducted at a tertiary children's hospital (n=115, 73.9% male). The primary outcomes included internalizing (anxious, depressed, withdrawn behaviors), externalizing (risk-taking, aggression, attention difficulties), and total mental health problems, as measured by the Child Behavior Checklist at two weeks (acute) and three months (post-acute) after concussion. Predictors included parents' retrospective reports of premorbid concussive symptoms (Post-Concussion Symptom Inventory; PCSI), the child and their family's psychiatric history, child-rated perfectionism (Adaptive-Maladaptive Perfectionism Scale), and child-rated resilience (Youth Resilience Measure). Higher premorbid PCSI ratings consistently predicted acute and post-acute mental health difficulties. This relationship was significantly moderated by child psychiatric history. Furthermore, pre-injury learning difficulties, child psychiatric diagnoses, family psychiatric history, lower resilience, previous concussions, female sex, and older age at injury were associated with greater mental health difficulties after concussion. Pre-injury factors accounted for 23.4-39.9% of acute mental health outcomes, and 32.3-37.8% of post-acute mental health outcomes. When acute mental health was factored into the model, a total of 47.0%-68.8% of variance was explained by the model. Overall, in this sample of children, several pre-injury demographic and psychological factors were observed to predict mental health difficulties after a concussion. These findings need to be validated in future research involving larger, multi-site studies that include a broader cohort of children after concussion.

Fatigue recovery and connected factors following paediatric concussion.

OBJECTIVE: Using a biopsychosocial framework and the three-factor fatigue model, we aimed to (1) plot recovery of fatigue over the 3 months following paediatric concussion and (2) explore factors associated with persisting fatigue during the first 3 months postconcussion. METHODS: 240 children and adolescents aged 5-18 years (M=11.64, SD=3.16) completed assessments from time of injury to 3 months postinjury. Separate linear mixed effects models were conducted for child and parent ratings on the PedsQL-Multidimensional Fatigue Scale to plot recovery across domains (General, Cognitive, Sleep/Rest) and Total fatigue, from 1 week to 3 months postinjury. Two-block hierarchical regression analyses were then conducted for parent and child ratings of fatigue at each time point, with age, sex and acute symptoms in block 1 and child and parent mental health variables added to block 2. RESULTS: There was a significant reduction in both child and parent ratings across the 3 months postinjury for all fatigue domains (all p<0.001). For both child and parent fatigue ratings, child mental health was the most significant factor associated with fatigue at all time points. Adding child and parent mental health variables in the second block of the regression substantially increased the variance explained for both child and parent ratings of fatigue. CONCLUSION: Our findings confirm that fatigue improves during the first 3 months postconcussion and highlights the importance of considering child and parent mental health screening when assessing patients with persisting postconcussive symptoms.

Examining post-concussion white matter change in a pediatric sample.

Diffusion-Weight Imaging (DWI) is increasingly used to explore a range of outcomes in pediatric concussion, particularly the neurobiological underpinnings of symptom recovery. However, the DWI findings within the broader pediatric concussion literature are mixed, which can largely be explained by methodological heterogeneity. To address some of these limitations, the aim of the present study was to utilize internationally- recognized criteria for concussion and a consistent imaging timepoint to conduct a comprehensive, multi-parametric survey of white matter microstructure after concussion. Forty-three children presenting with concussion to the emergency department of a tertiary level pediatric hospital underwent neuroimaging and were classified as either normally recovering (n = 27), or delayed recovering (n = 14) based on their post-concussion symptoms at 2 weeks post-injury.We combined multiple DWI metrics across four modeling approaches using Linked Independent Component Analysis (LICA) to extract several independent patterns of covariation in tissue microstructure present in the study cohort. Our analysis did not identify significant differences between the symptomatic and asymptomatic groups and no component significantly predicted delayed recovery. If white matter microstructure changes are implicated in delayed recovery from concussion, these findings, alongside previous work, suggest that current diffusion techniques are insufficient to detect those changes at this time.

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.

Improving subacute management of post concussion symptoms: a pilot study of the Melbourne Paediatric Concussion Scale parent report.

Aim: To pilot a modification of the Post Concussion Symptom Inventory, the Melbourne Paediatric Concussion Scale (MPCS) and examine its clinical utility. Materials & methods: A total of 40 families of concussed children, aged 8-18 years, were recruited from the emergency department. Parent responses to the MPCS in the emergency department and 2-weeks post injury determined child symptomatic status. Association between MPCS symptom endorsement and symptomatic group status was examined. Results: All additional MPCS items were endorsed by at least 25% of the parents of symptomatic children at 2 weeks. MPCS items were classified into nine symptom domains, with most falling in mood, neurological, autonomic and vestibular domains. Conclusion: The additional items and domain classifications in the MPCS have the potential to improve subacute diagnostic precision, monitoring of clinical recovery and identification of appropriate interventions post pediatric concussion.

Accuracy of Components of the SCAT5 and ChildSCAT5 to Identify Children with Concussion.

The Sport Concussion Assessment Tool 5th Edition (SCAT5) is a standardized measure of concussion. In this prospective observational study, the ability of the SCAT5 and ChildSCAT5 to differentiate between children with and without a concussion was examined. Concussed children (n=91) and controls (n=106) were recruited from an emergency department in three equal-sized age bands (5-8/9-12/13-16 years). Analysis of covariance models (adjusting for participant age) were used to analyze group differences on components of the SCAT5. On the SCAT5 and ChildSCAT5, respectively, youth with concussion reported a greater number (d=1.47; d=0.52) and severity (d=1.27; d=0.72) of symptoms than controls (all p<0.001). ChildSCAT5 parent-rated number (d=0.98) and severity (d=1.04) of symptoms were greater for the concussion group (all p<0.001). Acceptable levels of between-group discrimination were identified for SCAT5 symptom number (AUC=0.86) and severity (AUC=0.84) and ChildSCAT5 parent-rated symptom number (AUC=0.76) and severity (AUC=0.78). Our findings support the utility of the SCAT5 and ChildSCAT5 to accurately distinguish between children with and without a concussion.

Validation of the SCAT5 and Child SCAT5 Word-List Memory Task.

The Sports Concussion Assessment Tool-5th Edition (SCAT5) and the child version (Child SCAT5) are the current editions of the SCAT and have updated the memory testing component from previous editions. This study aimed to validate this new memory component against the Rey Auditory Verbal Learning Test (RAVLT) as the validated standard. This prospective, observational study, carried out within The Royal Children's Hospital Emergency Department, Melbourne, Australia, recruited 198 participants: 91 with concussion and 107 upper limb injury or healthy sibling controls. Partial Pearson correlations showed that memory acquisition and recall on delay aspects of the SCAT5 were significantly correlated with the RAVLT equivalents when controlling for age (p < 0.001, r = 0.565 and p < 0.001, r = 0.341, respectively). Factor analysis showed that all RAVLT and SCAT5 memory components load on to the same factor, accounting for 59.13% of variance. Logistic regression models for both the RAVLT and SCAT5, however, did not predict group membership (p > 0.05). Receiver operating curve analysis found that the area under the curve for all variables and models was below the recommended 0.7 threshold. This study demonstrated that the SCAT5 and Child SCAT5 memory paradigm is a valid measure of memory in concussed children.

No Evidence of a Difference in Susceptibility-Weighted Imaging Lesion Burden or Functional Network Connectivity between Children with Typical and Delayed Recovery Two Weeks Post-Concussion.

Susceptibility weighted imaging (SWI) and resting state functional magnetic resonance imaging have been highlighted as two novel neuroimaging modalities that have been underutilized when attempting to predict whether a child with concussion will recover normally or have a delayed recovery course. This study aimed to investigate whether there was a difference between children who recover normally from a concussion and children with delayed recovery in terms of SWI lesion burden and resting state network makeup. Forty-one children who presented to the emergency department of a tertiary level pediatric hospital with concussion participated in this study as a part of a larger prospective, longitudinal observational cohort study into concussion assessment and recovery. Children underwent neuroimaging 2 weeks post-injury and were classified as either normally recovering (n = 27), or delayed recovering (n = 14) based on their post-concussion symptoms at 2 weeks post-injury. No participants showed lesions detected using SWI; therefore, no group differences could be assessed. No between-group resting state network differences were uncovered using dual regression analysis. These findings, alongside previously published work, suggest that potential causes of delayed recovery from concussion may not be found using current neuroimaging paradigms.

Protocol for a randomised clinical trial of multimodal postconcussion symptom treatment and recovery: the Concussion Essentials study.

INTRODUCTION: While most children recover from a concussion shortly after injury, approximately 30% experience persistent postconcussive symptoms (pPCS) beyond 1-month postinjury. Existing research into the treatment of pPCS have evaluated unimodal approaches, despite evidence suggesting that pPCS likely represent an interaction across various symptom clusters. The primary aim of this study is to evaluate the effectiveness of a multimodal, symptom-tailored intervention to accelerate symptom recovery and increase the proportion of children with resolved symptoms at 3 months postconcussion. METHODS AND ANALYSIS: In this open-label, assessor-blinded, randomised clinical trial, children with concussion aged 8-18 years will be recruited from The Royal Children's Hospital (The RCH) emergency department, or referred by a clinician, within 17 days of initial injury. Based on parent ratings of their child's PCS at ~10 days postinjury, symptomatic children (≥2 symptoms at least 1-point above those endorsed preinjury) will undergo a baseline assessment at 3 weeks postinjury and randomised into either Concussion Essentials (CE, n=108), a multimodal, interdisciplinary delivered, symptom-tailored treatment involving physiotherapy, psychology and education, or usual care (UC, n=108) study arms. CE participants will receive 1 hour of intervention each week, for up to 8 weeks or until pPCS resolve. A postprogramme assessment will be conducted at 3 months postinjury for all participants. Effectiveness of the CE intervention will be determined by the proportion of participants for whom pPCS have resolved at the postprogramme assessment (primary outcome) relative to the UC group. Secondary outcome analyses will examine whether children receiving CE are more likely to demonstrate resolution of pPCS, earlier return to normal activity, higher quality of life and a lower rate of utilisation of health services, compared with the UC group. ETHICS AND DISSEMINATION: Ethics were approved by The RCH Human Research Ethics Committee (HREC: 37100). Parent, and for mature minors, participant consent, will be obtained prior to commencement of the trial. Study results will be disseminated at international conferences and international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12617000418370; pre-results.

Trajectories and Risk Factors for Pediatric Postconcussive Symptom Recovery.

BACKGROUND: Persistent postconcussive symptoms (PCS) are poorly understood in children. Research has been limited by an assumption that children with concussion are a homogenous group. OBJECTIVE: To identify (i) distinctive postconcussive recovery trajectories in children and (ii) injury-related and psychosocial factors associated with these trajectories. METHODS: This study is part of a larger prospective, longitudinal study. Parents of 169 children (5-18 yr) reported their child's PCS over 3 mo following concussion. PCS above baseline levels formed the primary outcome. Injury-related, demographic, and preinjury information, and child and parent mental health were assessed for association with trajectory groups. Data were analyzed using group-based trajectory modeling, multinomial logistic regression, and chi-squared tests. RESULTS: We identified 5 postconcussive recovery trajectories from acute to 3 mo postinjury. (1) Low Acute Recovered (26.6%): consistently low PCS; (2) Slow to Recover (13.6%): elevated symptoms gradually reducing; (3) High Acute Recovered (29.6%): initially elevated symptoms reducing quickly to baseline; (4) Moderate Persistent (18.3%): consistent, moderate levels of PCS; (5) Severe Persistent (11.8%): persisting high PCS. Higher levels of child internalizing behaviors and greater parental distress were associated with membership to the Severe Persistent group, relative to the Low Acute Recovered group. CONCLUSION: This study indicates variability in postconcussive recovery according to 5 differential trajectories, with groups distinguished by the number of reported symptoms, levels of child internalizing behavior problems, and parental psychological distress. Identification of differential recovery trajectories may allow for targeted early intervention for children at risk of poorer outcomes.

Child concussion recognition and recovery: a community delivered, evidenced-based solution.

Pediatric concussion is a growing health concern. Concussion is generally poorly understood within the community. Many parents are unaware of the signs and varying symptoms of concussion. Despite the existence of concussion management and return to play guidelines, few parents are aware of how to manage their child's recovery and return to activities. Digital health technology can improve the way this information is communicated to the community. A multidisciplinary team of pediatric concussion researchers and clinicians translated evidence-based, gold-standard guidelines and tools into a smartphone application with recognition and recovery components. HeadCheck is a community facing digital health application developed in Australia (not associated with HeadCheck Health) for management of concussion in children aged 5-18 years. The application consists of (I) a sideline concussion check and (II) symptom monitoring and symptom-targeted psychoeducation to assist the parent manage their child's safe return to school, exercise and sport. The application was tested with target end users as part of the development process. HeadCheck provides an accessible platform for disseminating best practice evidence. It provides feedback to help recognize a concussion and symptoms of more serious injuries and assists parents guide their child's recovery.

Use of the sport concussion assessment tools in the emergency department to predict persistent post-concussive symptoms in children.

AIM: The Sport Concussion Assessment Tool v3 (SCAT3) and its child version (ChildSCAT3) are composite tools including a symptom scale, a rapid cognitive assessment (standardised assessment of concussion (SAC)) and the modified Balance Error Scoring System (mBESS). It is unclear whether their use for the acute assessment of paediatric concussion in the emergency department (ED) may help predict persistent post-concussive symptoms (PPCS). We aim to assess the predictive value of the main SCAT3/ChildSCAT3 components for PPCS when applied in the ED. METHODS: A single-site, prospective longitudinal cohort study of children aged 5-18 years assessed within 48 h of their concussion at the ED of a state-wide tertiary paediatric hospital and followed up at the affiliated concussion clinic, between November 2013 and August 2017. PPCS was defined as ≥2 new or worsening symptoms at 1 month post-injury using the Post-Concussive Symptom Inventory. RESULTS: Of the 370 children enrolled, 213 (57.7% <13 years old) provided complete data. Of these, 34.7% had PPCS at 1 month post-injury (38.2% of children <13 years and 30.0% ≥13 years of age, P = 0.272). The adjusted ORs from multiple logistic regression models, for number and severity of symptoms, and for the SAC and mBESS performance in both the ChildSCAT3/SCAT3, were all not significant. The area under the curve of receiver operator characteristic curves for all analysed ChildSCAT3/SCAT3 components was below 0.6. CONCLUSIONS: Although SCAT3 and ChildSCAT3 are recommended tools to assist with concussion diagnosis and monitoring of patient recovery, their use in the ED does not seem to help predict PPCS.

Acute cognitive postconcussive symptoms follow longer recovery trajectories than somatic postconcussive symptoms in young children.

Objective: To investigate somatic and cognitive postconcussive symptoms (PCS) using the symptom evaluation subtest (cSCAT3-SE) of the Child Sports Concussion Assessment Tool 3 (Child SCAT) in tracking PCS up to 2 weeks postinjury.Methods: A total of 96 participants aged 5 to 12 years (Mage = 9.55, SD = 2.20) completed three assessment time points: 48 h postinjury (T0), 2 to 4 days postinjury (T1), and 2 weeks postinjury (T2). The Wilcoxon signed-rank test was used to analyze differences between cognitive and somatic symptoms over time, while the Friedman test was used to analyze differences within symptom type over time.Results: Cognitive PCS were found to be significantly higher than somatic PCS at all assessment time points and were also found to significantly decline from 4 days onwards postinjury; in contrast, somatic PCS significantly declined as early as 48 hpostinjury.Discussion: Differences between cognitive and somatic PCS emerge as early as a few days postinjury, with cognitive PCS being more persistent than somatic PCS across 2 weeks. Research in symptom-specific interventions may be of benefit in helping young children manage severe PCS as early as 2 weeks postinjury.

Trajectories and Predictors of Clinician-Determined Recovery after Child Concussion.

By age 16, 20% of children will suffer a concussion. Many experience persisting post-concussive symptoms (PCS), the cause(s) of which remain unclear. We mapped concussion recovery to 3 months post-injury and explored non-modifiable (e.g., age, sex, pre-injury factors, injury mechanism, acute PCS) and modifiable (post-acute child symptoms) predictors of persisting symptoms in order to identify opportunities for early intervention. We conducted a prospective, longitudinal study in the emergency department of a tertiary, pediatric hospital recruiting children within 48 h of concussion (T0), with follow-up at 2 days (T1), 2 weeks (T2), 1 month (T3), and 3 months (T4). Primary outcome was T2 clinician diagnosis. Clinical history, injury mechanism, acute symptoms, and physical and cognitive function were assessed. Parents rated child behavior and fatigue, and their mental health. We enrolled 256 participants, 72% males: 62 (24.3%) were symptomatic at T2. Recovered and symptomatic groups endorsed similar pre-injury PCS, but group differences were found at T1 across all PCS subscales, except Emotional, where symptoms were not evident until T2. By T2, there was significant PCS reduction, steepest in the "Recovered" group, which also had a lower rate of pre-injury psychiatric diagnoses, acute CT scans and less severe parent-rated PCS at T1 than the symptomatic group. They all demonstrated lower parent-rated PCS and less internalizing behaviors (all, p < 0.01). No differences were detected for child age, sex, injury factors, pre-injury parent-rated PCS, or acute physical and cognitive status. Our findings also highlight the importance of considering both pre- and post-injury mental health status in managing post-concussion.

Behavioral and Emotional Difficulties after Pediatric Concussion.

Pediatric concussion is a major public health concern. Despite the prevalence of behavior problems following concussion and their potential role in prolonged symptoms, little is known about how child and adolescent behavior may impact post-concussion recovery. We sought to examine change in behavioral and emotional functioning in a sample of children ages 5 to <18 years with concussion. This study reports on data collected as part of a larger single-site prospective longitudinal cohort study. Participants were recruited from the Emergency Department (ED) of a tertiary children's hospital and completed the Child Behavior Checklist (CBCL) at 2 weeks (acute; T2) and 3 months (post-acute; T4) post-injury. Children with concussion (n = 231) showed a significant reduction in internalizing (p < 0.001, d = 0.27), externalizing (p < 0.001, d = 0.23), and total behavior problems (p < 0.001, d = 0.36) at 3 months compared with 2 weeks post-injury. Multiple regression models found a significant interaction between age and sex with higher rates of internalizing (p = 0.048, ηp2 = 0.02) and total (p = 0.040, ηp2 = 0.02) behavior problems as age increased in females. The results show that pediatric concussion is associated with temporary behavioral disturbances that are likely to improve considerably in the months following injury. Nonetheless, as age increases, females may be at increased risk for experiencing ongoing internalizing problems several months after concussion and may require targeted clinical intervention.

Does a computerized neuropsychological test predict prolonged recovery in concussed children presenting to the ED?

Computerized neuropsychological tests (CNTs) are widely used internationally in concussion management. Their prognostic value for predicting recovery post-concussion is poorly understood, particularly in pediatric populations. The aim of the present study was to examine whether cognitive functioning (measured by CogSport) has prognostic value for predicting rapid versus slow recovery. This is a prospective longitudinal observational cohort study conducted at a state-wide tertiary pediatric hospital. Data were collected at 1-4, 14, and 90 days post-injury. Eligible children were aged ≥5 and <18 years presenting to the Emergency Department having sustained a concussion within 48 h. Concussion was defined according to the Zurich/Berlin Consensus Statement on Concussion in Sport. Dependent variables were reaction times and error rates on the CogSport Brief Battery. In total, 220 cases were analyzed; 98 in a rapid recovery group (asymptomatic at 14 days post-injury, mean age 11.5 [3.2], 73.5% male) and 122 in a slow recovery group (symptomatic at 14 days post-injury, mean age 12.0 [3.1], 69.7% male). Longitudinal GEE analyses modeled the trajectories of both mean log10-transformed reaction time and error rates between groups over time (1-4, 14 and 90 days). Both group main and interaction (time by group) terms for all models were non-significant (p > .05). Cognitive functioning, measured by CogSport and assessed within 1-4 days of concussion, does not predict prolonged recovery in a pediatric sample. Further, there were no significant group differences at any time point. Considering the widespread use and promotion of CNTs, it is important that clinicians understand the significant limitations of the CogSport battery.

Examining Microstructural White Matter Differences between Children with Typical and Those with Delayed Recovery Two Weeks Post-Concussion.

Delayed recovery from concussion can dramatically affect a child's social, emotional, and educational development, yet little is known about what causes some children to recover faster than others. The contribution of white matter disruption in children with delayed recovery has been hypothesized, but findings are limited by methodological issues such as: small heterogeneous samples, bias toward children with delayed recovery, and inconsistencies in timing of brain imaging, both within and between studies. The aim of the present study was to assess diffusion neuroimaging correlates of delayed recovery post-concussion in children. A prospective, longitudinal, observational cohort study was conducted at a statewide tertiary pediatric hospital. Forty-three children who presented to the emergency department (ED) with concussion (defined according to the Zurich/Berlin Consensus Statement on Concussion in Sport) underwent magnetic resonance imaging (MRI) at a 2 weeks post-injury and were classified as either normally recovering (n = 26) or delayed recovering (n = 17). Diffusion imaging comparison using voxelwise tract-based spatial statistics (TBSS) analysis found no difference between the groups in fractional anisotropy, axial diffusion, radial diffusion, or mean diffusivity metrics (p > 0.05 threshold-free cluster enhancement [TFCE] corrected). Post-hoc tract-based Bayesian analysis found evidence for the null in 11 unique white matter tracts (Bayes factor >3). These findings indicate that delayed recovery from post-concussive symptoms in children is unlikely to be caused by white matter microstructural damage.

Protocol for a prospective, longitudinal, cohort study of recovery pathways, acute biomarkers and cost for children with persistent postconcussion symptoms: the Take CARe Biomarkers study.

INTRODUCTION: The majority of children who sustain a concussion will recover quickly, but a significant minority will experience ongoing postconcussive symptoms, known as postconcussion syndrome (PCS). These symptoms include emotional, behavioural, cognitive and physical symptoms and can lead to considerable disability. The neurobiological underpinnings of PCS are poorly understood, limiting potential clinical interventions. As such, patients and families frequently re-present to clinical services, who are often ill equipped to address the multifactorial nature of PCS. This contributes to the high cost of concussion management and the disability of children experiencing PCS. The aims of the present study are: (1) to plot and contrast recovery pathways for children with concussion from time of injury to 3 months postinjury, (ii) evaluate the contribution of acute biomarkers (ie, blood, MRI) to delayed recovery postconcussion and (3) estimate financial costs of child concussion to patients attending the emergency department (ED) of a tertiary children's hospital and factors predicting high cost. METHODS AND ANALYSIS: Take C.A.Re is a prospective, longitudinal study at a tertiary children's hospital, recruiting and assessing 525 patients aged 5-<18 years (400 concussion, 125 orthopaedic injury) who present to the ED with a concussion and following them at 1-4 days, 2 weeks, 1 month and 3 months postinjury. Multiple domains are assessed: preinjury and postinjury, clinical, MRI, blood samples, neuropsychological, psychological and economic. PCS is defined as the presence of ≥2 symptoms on the Post Concussive Symptoms Inventory rated as worse compared with baseline 1 month postinjury. Main analyses comprise longitudinal Generalised Estimating Equation models and regression analyses of predictors of recovery and factors predicting high economic costs. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Royal Children's Hospital Melbourne Human Research Ethics Committee (33122). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. TRIAL REGISTRATION NUMBER: ACTRN12615000316505; Results.

Plasma Tumor Necrosis Factor Alpha Is a Predictor of Persisting Symptoms Post-Concussion in Children.

Mild traumatic brain injury (mTBI)-associated blood proteomics have become an emerging focus in the past decade, with the U.S. Food and Drug Administration recently approving the use of a blood test to determine the necessity of a computed tomography scan after adult mTBI. We now also know that the blood proteome of children is different from that of adults, and new evidence suggests that children may take longer to recover from an mTBI. Despite this, comparatively fewer studies have analyzed changes in blood protein expression after pediatric mTBI. Concussions, an mTBI subset, often go underreported, despite the potential for post-concussive symptoms to last more than one month in up to 30% of children. In the current study, we used a multiplex immunoassay to measure blood protein expression of Apolipoprotein, enolase 2, glial fibrillary acidic protein, interleukin (IL)-1B, IL-6, IL-8, IL-10, S100 calcium-binding protein B, tau and tumor necrosis factor alpha (TNFα) at admission, one to four days, two weeks, and three months post-pediatric concussion, comparing patients with normal recovery (n = 9) with those with persisting symptoms (n = 9). We identified significant differences in IL-6 (p < 0.001) and tau (p = 0.048) protein expression across time post-injury irrespective of clinical outcome and in IL-8 protein expression (p = 0.041) across time post-injury specific to children with persisting symptoms. Significantly, we have identified an increase in TNFα protein expression at one to four days post-injury (p = 0.031) in children with persisting symptoms compared with normal recovery. To our knowledge, this is the first study to identify TNFα as a potential blood biomarker for persisting symptoms post-pediatric concussion.

Blood biomarkers in paediatric mild traumatic brain injury: a systematic review.

OBJECTIVE: To summarize all current studies focusing on blood biomarkers in paediatric mild traumatic brain injury (mTBI) and to outline the possible use of blood biomarkers for diagnostic, prognostic and monitoring purposes within this setting. METHODS: A systematic review following the PRISMA guidelines was conducted using the MEDLINE, PubMed and EMBASE databases. RESULTS: A total of 21 studies were included in the review, encompassing a total of 14 different biomarkers. Seventeen (81%) of these studies found a significant association between biomarker concentration and mTBI characteristics, however results from studies to date are diverse and at times conflicting. CONCLUSION: GFAP appears to be a promising blood biomarker for the prognosis and monitoring of mTBI, whereas UCH-L1 appears more promising at mTBI diagnosis. Despite this, the overall heterogeneity in assessed biomarkers, study design and measurement tools has made drawing specific conclusions challenging. Future research will require more uniform study design and methodological approaches to allow for the comparison, corroboration and validation of blood biomarkers within the context of paediatric mTBI.