Structural brain network lateralization across childhood and adolescence.

Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub-nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development. Further, we investigated BC and CC in seven functionally defined networks. Our cross-sectional study consisted of 211 participants between the ages of 6 and 21 years with 93% being right-handed and 51% female. Global efficiency, HC, and CC demonstrated a leftward lateralization, compared to a rightward lateralization of BC. The sensorimotor, default mode, salience, and language networks showed a leftward asymmetry of CC. BC was only lateralized in the salience (right lateralized) and dorsal attention (left lateralized) networks. Only a small number of metrics were associated with age, suggesting that topological organization may stay relatively constant throughout school-age development, despite known underlying changes in white matter properties. Unlike many other imaging biomarkers of brain development, our study suggests topological lateralization is consistent across age, highlighting potential nonlinear mechanisms underlying developmental specialization.

A Pilot Randomized Controlled Trial of Cognitive-Behavioral Therapy for Insomnia in Adolescents With Persistent Postconcussion Symptoms.

OBJECTIVE: Cognitive-behavioral therapy for insomnia (CBT-I) is an effective insomnia treatment but has yet to be applied to adolescents with sleep disruption following concussion. This pilot study evaluated CBT-I to improve insomnia in adolescents with protracted concussion recovery. SETTING: Tertiary pediatric hospital. PARTICIPANTS: Participants (N = 24) were 12 to 18 years old (M = 15.0, SD = 1.4), 15.1 weeks (SD = 9.2) postinjury, and presenting with sleep disruption and persistent postconcussion symptoms. DESIGN: A single-blind, parallel-group randomized controlled trial (RCT) design comparing 6 weeks of CBT-I and a treatment-as-usual control group. Outcomes were measured before treatment, at treatment completion, and 4 weeks after completion. MAIN MEASURES: Primary outcome was Insomnia Severity Index. Secondary outcomes included Pittsburgh Sleep Quality Index, Dysfunctional Beliefs and Attitudes about Sleep Scale, 7-night sleep diary, PROMIS Depression, PROMIS Anxiety, and Health and Behavior Inventory. RESULTS: Adolescents who received CBT-I demonstrated large and clinically significant improvements in insomnia ratings at posttreatment that were maintained at follow-up. They also reported improved sleep quality, fewer dysfunctional beliefs about sleep, better sleep efficiency, shorter sleep-onset latency, and longer sleep time compared with those with treatment as usual. There was also a modest reduction in postconcussion symptoms. CONCLUSION: In this pilot RCT, 6 weeks of CBT-I produced significant improvement in sleep in adolescents with persistent postconcussion symptoms. A larger trial is warranted.

N-Acetyl-Aspartate in the Dorsolateral Prefrontal Cortex Long After Concussion in Youth.

OBJECTIVE: Despite increasing interest in the neurobiological effects of concussion in youth, a paucity of information is available regarding outcomes long after injury. The objective of this study was to determine the association between a history of concussion and the putative neuronal marker N-acetyl-aspartate (NAA) in the dorsolateral prefrontal cortex (DLPFC) in youth. SETTING: Outpatient clinic in a children's hospital. PARTICIPANTS: Youth with concussion (N = 35, mean = 2.63, SD = 1.07 years postinjury) and youth with a nonconcussive orthopedic injury (N = 17) participated. DESIGN: A cross-sectional proton magnetic resonance spectroscopy (H-MRS) study. MAIN MEASURES: The primary outcome measure was NAA concentration in the right and left DLPFCs. RESULTS: We observed lower levels of NAA in the right DLPFC in youth with past concussion (F = 3.31, df = 4,51, P = .018) than in orthopedic controls but not in the left DLPFC (F = 2.04, df = 4,51, P = .105). The effect of lower NAA concentrations in the right DLPFC was primarily driven by youth with a single prior concussion versus those with multiple concussions. NAA in the left DLPFC, but not in right DLPFC, was associated with worse emotional symptoms in youth with concussion. CONCLUSION: The presence of lower levels of DLPFC NAA suggests potential association of concussion in youth, although further investigation is needed, given that the result is driven by those with a single (and not multiple) concussion. Exploration of applying MRS in other brain regions is also warranted.

Functional magnetic resonance imaging study of working memory several years after pediatric concussion.

PRIMARY OBJECTIVE: The neurophysiological effects of pediatric concussion several years after injury remain inadequately characterized. The objective of this study was to determine if a history of concussion was associated with BOLD response differences during an n-back working memory task in youth. RESEARCH DESIGN: Observational, cross-sectional. METHODS AND PROCEDURES: Participants include 52 children and adolescents (M = 15.1 years, 95%CI = 14.4-15.8, range = 9-19) with past concussion (n = 33) or orthopedic injury (OI; n = 19). Mean time since injury was 2.5 years (95%CI = 2.0-3.0). Measures included postconcussion symptom ratings, neuropsychological testing, and blood-oxygen-dependent-level (BOLD) functional magnetic resonance imaging (fMRI) during an n-back working memory task. MAIN OUTCOMES AND RESULTS: Groups did not differ on accuracy or speed during the three n-back conditions. They also did not differ in BOLD signal change for the 1- vs. 0-back or 2- vs. 0-back contrasts (controlling for task performance). CONCLUSIONS: This study does not support group differences in BOLD response during an n-back working memory task in youth who are on average 2.5 years post-concussion. The findings are encouraging from the perspective of understanding recovery after pediatric concussion.

Cerebral blood flow in children and adolescents several years after concussion.

OBJECTIVES: The long-term effects of concussion in youth remain poorly understood. The objective of this study was to determine the association between history of concussion and cerebral blood flow (CBF) in youth. METHODS: A total of 53 children and adolescents with a history of concussion (n = 37) or orthopaedic injury (OI; n = 16) were considered. Measures included pseudo-continuous arterial spin labelling magnetic resonance imaging to quantify CBF, post-concussion symptoms, psychological symptoms, and cognitive testing. RESULTS: Participants (mean age: 14.4 years, 95% CI = 13.8-15.4, range = 8-19) were on average 2.7 years (95% CI = 2.2-3.1) post-injury. Youth with a history of concussion had higher parent-reported physical, cognitive, anxiety, and depression symptoms than children with OI, but the groups did not differ on self-reported symptoms (post-concussive or psychological) or cognitive testing. Global CBF did not differ between groups. Regional CBF analyses suggested that youth with a history of concussion had hypoperfusion in posterior and inferior regions and hyperperfusion in anterior/frontal/temporal regions as compared to those with OI. However, neither global nor regional CBF were significantly associated with demographics, pre-injury functioning, number of concussions, time since injury, post-concussive symptoms, psychological symptoms, or cognitive abilities. CONCLUSIONS: Youth with a history of concussion demonstrate differences in regional CBF (not global CBF), but without clear clinical expression.

Incorporating a Computerized Cognitive Battery Into the Emergency Department Care of Pediatric Mild Traumatic Brain Injuries-Is It Feasible?

OBJECTIVES: The use of computers to test cognitive function acutely after a concussion is becoming increasingly popular, especially after sport-related concussion. Although commonly performed in the community, it is not yet performed routinely in the emergency department (ED), where most injured children present. The challenges of performing computerized cognitive testing (CCT) in a busy ED are considerable. The aim of this study was to evaluate the feasibility of CCT in the pediatric ED after concussion. METHODS: Children, aged 8 to 18 years with mild traumatic brain injury, presenting to the ED were eligible for this prospective study. Exclusion criteria included the use of drugs, alcohol, and/or physical injury, which could affect CCT performance. A 30- or 15-minute CCT battery was performed. Feasibility measures included environmental factors (space, noise, waiting time), testing factors (time, equipment reliability, personnel), and patient factors (age, injury characteristics). RESULTS: Forty-nine children (28 boys; mean age, 12.6; SD, ± 2.5) participated in the study. All children completed CCT. Mean testing times for the 30- and 15-minute battery were 29.7 and 15.2 minutes, respectively. Noise-cancelling headphones were well tolerated. A shorter CCT was more acceptable to families and was associated with fewer noise disturbances. There was sufficient time to perform testing after triage and before physician assessment in over 90% of children. CONCLUSIONS: Computerized cognitive testing is feasible in the ED. We highlight the unique challenges that should be considered before its implementation, including environmental and testing considerations, as well as personnel training.

Cognition in the Emergency Department as a Predictor of Recovery after Pediatric Mild Traumatic Brain Injury.

Cognitive abilities can be acutely disrupted in children and adolescents who sustain a mild traumatic brain injury (mTBI), with the potential that these disruptions may be predictive of recovery. The objective of this study was to determine if cognitive abilities in the emergency department (ED) can differentiate and predict poor symptom recovery following a pediatric mTBI. Participants included 77 male and female youth with a mTBI (mean age=13.6; SD=2.6). All participants completed computerized cognitive testing (four subtests from the CNS Vital Signs) when they presented to the ED. Symptom measurement occurred in the ED (for pre-injury), at 7-10 days, 1 month, 2 months, and 3 months post-mTBI using the post-concussion symptom inventory (PCSI). Recovery was determined using reliable change scores for symptom ratings from 28 orthopedic injury controls (mean age=13.9 years; SD=2.1). Significantly worse Reaction Time scores (i.e., rapid information processing) in the ED were found in those who remained symptomatic at 1 month. Performances on the Reaction Time and Cognitive Flexibility domain scores were predictive of symptom outcome at 1 month for youth (above and beyond sex and baseline symptom burden). Youth with low scores on Reaction Time and/or Cognitive Flexibility were nearly 15 times (95% CI=1.8-323.5) more likely to remain symptomatic at 1 month post-mTBI. No significant group differences were found at 7-10 days, 2 months, or 3 months post-injury. Rapid computerized cognitive testing in the ED following a mTBI may help clinicians predict which youth may or may not remain symptomatic at follow-up.

A Systematic Review of Psychiatric, Psychological, and Behavioural Outcomes following Mild Traumatic Brain Injury in Children and Adolescents.

BACKGROUND: Evidence regarding longer-term psychiatric, psychological, and behavioural outcomes (for example, anxiety, mood disorders, depression, and attention disorders) following mild traumatic brain injury (mTBI) in children and adolescents has not been previously synthesized. OBJECTIVE: To conduct a systematic review of the available evidence examining psychiatric, psychological, and behavioural outcomes following mTBI in children and adolescents. MATERIALS AND METHODS: Nine electronic databases were systematically searched from 1980 to August 2014. Studies selected met the following criteria: original data; study design was a randomized controlled trial, quasi-experimental design, cohort or historical cohort study, case-control study, or cross-sectional study; exposure included mTBI (including concussion); population included children and adolescents (<19 years) at the time of mTBI, as well as a comparison group (for example, healthy children, children with orthopaedic injuries); and included psychiatric, psychological, or behavioural outcomes (for example, anxiety, mood disorders, depression, attention disorders). Two authors independently assessed the quality and level of evidence with the Downs and Black (DB) criteria and Oxford Centre of Evidence-Based Medicine (OCEBM) model, respectively, for each manuscript. RESULTS: Of 9472 studies identified in the initial search, 30 were included and scored. Heterogeneity in methodology and injury definition precluded meta-analyses. The median methodological quality for all 30 studies, based on the DB criteria, was 15/33 (range 6 to 19). The highest level of evidence demonstrated by all reviewed studies was level 2b based on OCEBM criteria, with the majority (28/30 studies) classified at this level. Based on the literature included in this systematic review, psychological and psychiatric problems in children with a history of mTBI were found to be more prevalent when mTBI is associated with hospitalization, when assessment occurs earlier in the recovery period (that is, resolves over time), when there are multiple previous mTBIs, in individuals with preexisting psychiatric illness, when outcomes are based on retrospective recall, and when the comparison group is noninjured healthy children (as opposed to children with injuries not involving the head). CONCLUSIONS: Overall, few rigorous prospective studies have examined psychological, behavioural, and psychiatric outcomes following mTBI. In the absence of true reports of preinjury problems and when ideally comparing mild TBI to non-TBI injured controls, there is little evidence to suggest that psychological, behavioural, and/or psychiatric problems persist beyond the acute and subacute period following an mTBI in children and adolescents.

QTc Prolongation in Acute Pediatric Migraine.

OBJECTIVES: Migraine headache is common in pediatrics and is frequently assessed in emergency departments. Altered cardiac conduction, including prolongation of the QTc interval on electrocardiogram, has been observed in adults during migraine headache and resolves interictally. Prolonged QTc is associated with life-threatening arrhythmia, and many acute and prophylactic therapies for migraine can further prolong the QTc interval. It is the objective of this prospective cohort study to examine whether the QTc interval prolongs significantly during periods of acute migraine headache in children. METHODS: Patients ages 6 to 17 years presenting to the emergency department with acute migraine headache were recruited prospectively. Exclusion criteria included the use of QTc-prolonging medications and medical illnesses, including cardiovascular abnormalities, infection, or head injury. Paired, one-tailed Student t tests compared QTc intervals with and without headache and evaluated for QTc prolongation of 30 ms or longer during headache. RESULTS: Thirteen patients with migraine (mean age, 11.6 ± 2.6 years) were evaluated. Mean QTc interval during headache was significantly longer than the QTc interval in the absence of headache (437.9 ± 27.7 ms compared with 419.3 ± 29.9 ms; p = 0.04). Three patients (23%) had unequivocal prolongation of the QTc (>460 ms) during the migraine, two of which normalized with headache resolution. The mean increase in QTc during headache did not reach or exceed 30 ms (p = 0.86) CONCLUSIONS: This study is the first to illustrate a connection between QTc prolongation and acute migraine headache in children. If confirmed in future studies, children should be monitored for QTc prolongation during the acute treatment of migraine in the emergency department when using medications that can lengthen the QTc interval.

The role of serotonin receptor alleles and environmental stressors in the development of post-concussive symptoms after pediatric mild traumatic brain injury.

AIM: To determine whether post-injury depressive symptoms, and pre-injury major life stressors and genetic factors (HTR1A C(-1019)G alleles; rs6295) are more common in children with mild traumatic brain injury (mTBI) who develop postconcussion syndrome (PCS) symptoms compared with children with asymptomatic mTBI. METHOD: This was a cross-sectional study of 47 symptomatic children (32 males, 15 females; mean age 14y [SD 3y 3mo]) who experienced post-concussive symptoms for 7 or more days and 42 asymptomatic children (26 males 16 females; mean age 13y 6mo [SD 3y 1mo]) after mTBI. Outcome measures were the Postconcussion Symptoms Inventory (PCSI), the Children's Depression Inventory (CDI), standard questionnaire of previous life events, and buccal DNA analysis to determine genotype and allele frequencies for the HTR1A C(-1019)G polymorphism. RESULTS: Depressive symptoms were uncommon. CDI scores did not differ between groups. Allelic and genotypic frequencies for HTR1A C(-1019)G were similar in both groups. Symptomatic children continued to have elevated PCS scores compared with asymptomatic children 1.72 (SD 0.69) years later and had experienced significantly more life stressors (Wald (1)=8.51, p=0.004). INTERPRETATION: HTR1A polymorphisms do not differ in children with PCS. Children who have experienced more significant life stresses are more likely to develop PCS symptoms after mTBI.

Absence of differences between male and female adolescents with prior sport concussion.

OBJECTIVE: Sex differences following concussion are poorly understood. The purpose of this study was to examine whether male and female adolescent athletes with prior concussions differ regarding neurocognitive function and symptom reporting. SETTING: Community-based hockey teams. PARTICIPANTS: Participants included 615 elite hockey players 13 to 17 years old (mean = 15.5, 95% confidence interval [CI] = 15.4-15.6). There were 517 males and 98 females. Players with English as a second language, attention or learning problems, a concussion within 6 months of baseline, or suspected invalid test profiles were excluded from these analyses. DESIGN: Cross-sectional. MAIN MEASURE: Domain scores and symptom ratings from the ImPACT computerized battery. RESULTS: There were no significant neurocognitive differences between males and females with (F5,227 = 1.40, P = .227) or without (F5,376 = 1.33, P = 0.252) a prior history of concussion. Male and female athletes with a history of concussion reported higher raw symptom scores than those without a prior concussion; however, sex differences disappear when symptom scores are adjusted for known sex differences in controls (total score, F2,230 = 0.77, P = .46; Cohen d = 0.01 or domain scores (F4,227 = 1.52, P = .197; Cohen d = 0.07-0.18). CONCLUSIONS: Although those with prior concussions report more symptoms (but do not differ on neurocognition), this study does not support sex differences with cognition or symptoms in adolescent athletes with prior concussions.

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.

Attention Please! Unravelling the Link Between Brain Network Connectivity and Cognitive Attention Following Acquired Brain Injury: A Systematic Review of Structural and Functional Measures.

Traumatic brain injury (TBI) and stroke are the most common causes of acquired brain injury (ABI), annually affecting 69 million and 15 million people, respectively. Following ABI, the relationship between brain network disruption and common cognitive issues including attention dysfunction is heterogenous. Using PRISMA guidelines, we systematically reviewed 43 studies published by February 2023 that reported correlations between attention and connectivity. Across all ages and stages of recovery, following TBI, greater attention was associated with greater structural efficiency within/between executive control network (ECN), salience network (SN), and default mode network (DMN) and greater functional connectivity (fc) within/between ECN and DMN, indicating DMN interference. Following stroke, greater attention was associated with greater structural connectivity (sc) within ECN; or greater fc within the dorsal attention network (DAN). In childhood ABI populations, decreases in structural network segregation were associated with greater attention. Longitudinal recovery from TBI was associated with normalization of DMN activity, and in stroke, normalization of DMN and DAN activity. Results improve clinical understanding of attention-related connectivity changes after ABI. Recommendations for future research include increased use of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to measure connectivity at the point of care, standardized attention and connectivity outcome measures and analysis pipelines, detailed reporting of patient symptomatology, and casual analysis of attention-related connectivity using brain stimulation.

Pediatric Sport-Related Concussion: Recommendations From the Amsterdam Consensus Statement 2023.

The 6th International Consensus Conference on Concussion in Sport, Amsterdam 2022, addressed sport-related concussion (SRC) in adults, adolescents, and children. We highlight the updated evidence-base and recommendations regarding SRC in children (5-12 years) and adolescents (13-18 years). Prevention strategies demonstrate lower SRC rates with mouthguard use, policy disallowing bodychecking in ice hockey, and neuromuscular training in adolescent rugby. The Sport Concussion Assessment Tools (SCAT) demonstrate robustness with the parent and child symptom scales, with the best diagnostic discrimination within the first 72 hours postinjury. Subacute evaluation (>72 hours) requires a multimodal tool incorporating symptom scales, balance measures, cognitive, oculomotor and vestibular, mental health, and sleep assessment, to which end the Sport Concussion Office Assessment Tools (SCOAT6 [13+] and Child SCOAT6 [8-12]) were developed. Rather than strict rest, early return to light physical activity and reduced screen time facilitate recovery. Cervicovestibular rehabilitation is recommended for adolescents with dizziness, neck pain, and/or headaches for greater than 10 days. Active rehabilitation and collaborative care for adolescents with persisting symptoms for more than 30 days may decrease symptoms. No tests and measures other than standardized and validated symptom rating scales are valid for diagnosing persisting symptoms after concussion. Fluid and imaging biomarkers currently have limited clinical utility in diagnosing or assessing recovery from SRC. Improved paradigms for return to school were developed. The variable nature of disability and differences in evaluating para athletes and those of diverse ethnicity, sex, and gender are discussed, as are ethical considerations and future directions in pediatric SRC research.

The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.

Characteristics of post-traumatic headaches in children following mild traumatic brain injury and their response to treatment: a prospective cohort.

AIM: Post-traumatic headaches (PTHs) following mild traumatic brain injury (mTBI) are common; however, few studies have examined the characteristics of PTHs or their response to treatment. The aims of this study were (1) to describe the clinical characteristics of PTH in a prospective cohort of children presenting to a paediatric emergency department with mTBI, and (2) to evaluate the response of PTH to treatment. METHOD: The emergency department cohort was obtained from a prospective longitudinal cohort study of symptoms following mTBI (n=670; 385 males, 285 females) and a comparison group of children with extracranial injury (n=120; 61 males, 59 females). A retrospective chart review of a separate cohort of children from a brain injury clinic (the treatment cohort) treated for PTH was performed (n=44; 29 females, 15 males; mean age 14 y 1 mo, SD 3 y 1 mo). The median time since injury was 6.9 months (range 1-29 mo). The mean follow-up interval after treatment started was 5.5 weeks (SD 4.3 wks). RESULTS: Among the emergency department cohort (n=39; 20 males, 19 females; mean age 11 y 1 mo, SD 4 y 3 mo) 11% of children were symptomatic with PTHs at a mean of 15.8 days (SD 11.6d) post injury. Three months post injury, 7.8% of children complained of headaches; of those, 56% had pre-existing headaches and 18% had experienced migraine before the injury. Although headache type varied, 55% met the criteria for migraine. A family or past medical history of migraine was present in 82% of cases. Among the treatment cohort, medications included amitriptyline, flunarizine, topiramate, and melatonin, with an overall response rate of 64%. CONCLUSION: This is the first prospective cohort study to describe the clinical characteristics of PTHs following mTBI in children. Migraine was the most common headache type seen; other headaches included tension-type, cervicogenic, and occipital neuralgias, and 64% responded to treatment. Referral to a headache specialist should be considered, especially when the features are not typical of one of the primary headache disorders.

Health care impact of implementing a clinical pathway for acute care of pediatric concussion: a stepped wedge, cluster randomised trial.

OBJECTIVES: To test the effects of actively implementing a clinical pathway for acute care of pediatric concussion on health care utilization and costs. METHODS: Stepped wedge, cluster randomized trial of a clinical pathway, conducted in 5 emergency departments (ED) in Alberta, Canada from February 1 to November 30, 2019. The clinical pathway emphasized standardized assessment of risk for persistent symptoms, provision of consistent information to patients and families, and referral for outpatient follow-up. De-identified administrative data measured 6 outcomes: ED return visits; outpatient follow-up visits; length of ED stay, including total time, time from triage to physician initial assessment, and time from physician initial assessment to disposition; and total physician claims in an episode of care. RESULTS: A total of 2878 unique patients (1164 female, 1713 male) aged 5-17 years (median 11.00, IQR 8, 14) met case criteria. They completed 3009 visits to the 5 sites and 781 follow-up visits to outpatient care, constituting 2910 episodes of care. Implementation did not alter the likelihood of an ED return visit (OR 0.77, 95% CI 0.39, 1.52), but increased the likelihood of outpatient follow-up visits (OR 1.84, 95% CI 1.19, 2.85). Total length of ED stay was unchanged, but time from physician initial assessment to disposition decreased significantly (mean change - 23.76 min, 95% CI - 37.99, - 9.52). Total physician claims increased significantly at only 1 of 5 sites. CONCLUSIONS: Implementation of a clinical pathway in the ED increased outpatient follow-up and reduced the time from physician initial assessment to disposition, without increasing physician costs. Implementation of a clinical pathway can align acute care of pediatric concussion more closely with existing clinical practice guidelines while making care more efficient. TRIAL REGISTRATION: ClinicalTrials.gov NCT05095012.

ABSTRAIT: OBJECTIFS: Mettre à l'essai les effets de la mise en œuvre active d'une voie clinique pour le traitement aigu des commotions cérébrales chez les enfants sur l'utilisation et les coûts des soins de santé. MéTHODES: Essai randomisé en grappes d'une voie clinique, échelonné, mené dans cinq services d'urgence en Alberta, au Canada, du 1 février au 30 novembre 2019. Le cheminement clinique mettait l'accent sur l'évaluation normalisée du risque de symptômes persistants, la fourniture de renseignements uniformes aux patients et aux familles, et l'aiguillage vers un suivi externe. Les données administratives dépersonnalisées ont permis de mesurer six résultats : visites de retour à l'urgence; visites de suivi en clinique externe; durée du séjour à l'urgence, y compris le temps total. le temps entre le triage et l'évaluation initiale du médecin, et le temps entre l'évaluation initiale du médecin et la décision; et le nombre total de demandes de remboursement du médecin dans un épisode de soins. RéSULTATS: Un total de 2878 patients uniques (1164 femmes, 1713 hommes) âgés de 5 à 17 ans (médiane 11,00, IQR 8, 14) répondaient aux critères de cas. Ils ont effectué 3009 visites aux 5 sites et 781 visites de suivi aux soins ambulatoires, ce qui représente 2910 épisodes de soins. La mise en œuvre n'a pas modifié la probabilité d'une visite de retour à l'urgence (RC 0,77, IC à 95 %, 0,39, 1,52), mais a augmenté la probabilité de visites de suivi en clinique externe (RC 1,84, IC à 95 %, 1,19, 2,85). La durée totale du séjour à l'urgence est demeurée inchangée, mais le temps écoulé entre l'évaluation initiale du médecin et la décision a diminué considérablement (changement moyen : -23,76 minutes, IC à 95 %, -37,99, -9,52). Le nombre total de demandes de règlement de médecins a augmenté de façon significative à seulement 1 site sur 5. CONCLUSIONS: La mise en œuvre d'un cheminement clinique à l'urgence a augmenté le suivi des patients externes et réduit le temps entre l'évaluation initiale du médecin et son élimination, sans augmenter les coûts des médecins. La mise en œuvre d'un cheminement clinique peut harmoniser davantage les soins de courte durée en cas de commotion cérébrale pédiatrique avec les lignes directrices de pratique clinique existantes tout en rendant les soins plus efficaces. ENREGISTREMENT D'ESSAI: ClinicalTrials.gov NCT05095012.

Cerebral Blood Flow Predicts Recovery in Children with Persistent Post-Concussion Symptoms after Mild Traumatic Brain Injury.

Persistent post-concussion symptoms (PPCS) following pediatric mild traumatic brain injury (mTBI) are associated with differential changes in cerebral blood flow (CBF). Given its potential as a therapeutic target, we examined CBF changes during recovery in children with PPCS. We hypothesized that CBF would decrease and that such decreases would mirror clinical recovery. In a prospective cohort study, 61 children and adolescents (mean age 14 [standard deviation = 2.6] years; 41% male) with PPCS were imaged with three-dimensional (3D) pseudo-continuous arterial spin-labelled (pCASL) magnetic resonance imaging (MRI) at 4-6 and 8-10 weeks post-injury. Exclusion criteria included any significant past medical history and/or previous concussion within the past 3 months. Twenty-three participants had clinically recovered at the time of the second scan. We found that relative and mean absolute CBF were higher in participants with poor recovery, 44.0 (95% confidence interval [CI]: 43.32, 44.67) than in those with good recovery, 42.19 (95% CI: 41.77, 42.60) mL/min/100 g gray tissue and decreased over time (ß = -1.75; p < 0.001). The decrease was greater in those with good recovery (ß = 2.29; p < 0.001) and predicted outcome in 77% of children with PPCS (odds ratio [OR] 0.54, 95% CI: 0.36, 0.80; p = 0.002). Future studies are warranted to validate the utility of CBF as a useful predictive biomarker of outcome in PPCS.