Longitudinal trajectories of posttraumatic headache after pediatric mild traumatic brain injury.

OBJECTIVE: This prospective, longitudinal cohort study examined the trajectory, classification, and features of posttraumatic headache after pediatric mild traumatic brain injury. METHODS: Children (N = 213; ages 8.00 to 16.99 years) were recruited from two pediatric emergency departments <24 hours of sustaining a mild traumatic brain injury or mild orthopedic injury. At 10 days, three months, and six months postinjury, parents completed a standardized questionnaire that was used to classify premorbid and posttraumatic headache as migraine, tension-type headache, or not otherwise classified. Multilevel mixed effects models were used to examine posttraumatic headache rate, severity, frequency, and duration in relation to group, time postinjury, and premorbid headache, controlling for age, sex, and site. RESULTS: PTH risk was greater after mild traumatic brain injury than mild orthopedic injury at 10 days (odds ratio = 197.41, p < .001) and three months postinjury (odds ratio = 3.50, p = .030), especially in children without premorbid headache. Posttraumatic headache was more frequent after mild traumatic brain injury than mild orthopedic injury, ß (95% confidence interval) = 0.80 (0.05, 1.55). Groups did not differ in other examined headache features and classification any time postinjury. CONCLUSIONS: Posttraumatic headache risk increases after mild traumatic brain injury relative to mild orthopedic injury for approximately three months postinjury, but is not clearly associated with a distinct phenotype.

Social determinants of participant recruitment and retention in a prospective cohort study of pediatric mild traumatic brain injury.

Background: Prior studies have shown poor recruitment and retention of minoritized groups in clinical trials. Objective: To examine several social determinants as predictors of consent to participate and retention as part of a prospective, longitudinal cohort study of children 8-16 with either mild traumatic brain injury (mild TBI) or orthopedic injury (OI). Methods: Children and families were recruited during acute visits to emergency departments (ED) in two large children's hospitals in the midwestern United States for a prospective, longitudinal cohort study of children 8-16 with either mild TBI or OI. Results: A total of 588 (mild TBI = 307; OI = 281) eligible children were approached in the ED and 315 (mild TBI = 195; OI = 120) were consented. Children who consented did not differ significantly from those who did not consent in sex or age. Consent rates were higher among Black (60.9%) and multi-racial (76.3%) children than white (45.3%) children. Among the 315 children who consented, 217 returned for a post-acute assessment (mild TBI = 143; OI = 74), a retention rate of 68.9%. Participants who were multi-racial (96.6%) or white (79.8%) were more likely to return for the post-acute visit than those who were Black (54.3%). Conclusions: Racial differences exist in both recruitment and retention of participants in a prospective, longitudinal cohort of children with mild TBI or OI. Further work is needed to understand these differences to ensure equitable participation of minoritized groups in brain injury research.

Sex Differences in the Outcomes of Mild Traumatic Brain Injury in Children Presenting to the Emergency Department.

Sex differences after concussion have been studied largely in high school and college athletes, often without reference to comparison groups without concussion. This study sought to evaluate sex differences in outcomes among all children and adolescents presenting to the Emergency Department (ED) for either mild traumatic brain injury (TBI) or orthopedic injury (OI), regardless of mechanism of injury. The study involved a concurrent cohort, prospective study design with longitudinal follow-up. Participants were eight to 16 years old with mild TBI (n = 143) or OI (n = 73). They were recruited and completed an initial assessment at EDs at two children's hospitals. They returned for a post-acute assessment within two weeks of injury and for follow-up assessments at three and six months. Outcomes included child and parent proxy ratings of somatic and cognitive symptoms, and standardized tests of cognitive functioning and balance. Sex did not moderate group differences in balance, fluid or crystallized cognitive ability, or child or parent proxy ratings of somatic or cognitive symptoms. Both parents and children reported more somatic symptoms in girls than boys, but in both groups. Compared with the OI group, the mild TBI group showed significantly lower fluid cognitive ability at the post-acute assessment and significantly higher somatic and cognitive symptoms according to both child and parent proxy ratings across the first two weeks post-injury. The results suggest that sex does not moderate the outcomes of mild TBI in a pediatric ED population. Previous research pointing to sex differences after concussion may reflect the lack of comparison groups, as well as a focus on adolescents and young adults and sport-related concussion. Future research should investigate whether sex moderates the outcomes of pediatric mild TBI in adolescents but not in pre-adolescent children.

Normative and Psychometric Characteristics of the Health and Behavior Inventory Among Children With Mild Orthopedic Injury Presenting to the Emergency Department: Implications for Assessing Postconcussive Symptoms Using the Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5).

OBJECTIVE: The study sought to present normative and psychometric data and reliable change formulas for the Health and Behavior Inventory (HBI), a postconcussive symptom rating scale embedded in the Child Sport Concussion Assessment Tool 5th edition (Child SCAT5). DESIGN: Prospective cohort study with longitudinal follow-up. SETTING: Pediatric emergency departments (EDs). PARTICIPANTS: As part of 3 studies conducted in the United States and Canada between 2001 and 2019, 450 children aged 8 to 16 years with mild orthopedic injuries were recruited during ED visits and assessed postacutely (M = 9.38 days, SD = 3.31) and 1 month and 3 months postinjury. Independent variables were rater (child vs parent), sex, and age at injury. MAIN OUTCOME MEASURE: HBI ratings. METHODS: Children and parents rated children's symptoms at each time point; parents also rated children's preinjury symptoms retrospectively. Normative data (mean, SD, skewness, kurtosis, and percentiles) were computed for child and parent ratings. Internal consistency was assessed using Cronbach alpha (α), and test-retest reliability and interrater agreement were assessed with intraclass correlations (ICCs). Reliable change formulas were computed using linear regression and mixed models. RESULTS: HBI ratings were positively skewed. Mean ratings and percentiles were stable over time. Child and parent ratings demonstrated good-to-excellent internal consistency (α 0.76-0.94) and moderate-to-good test-retest reliability (ICC 0.51-0.76 between adjacent assessments). However, parent-child agreement was poor to moderate (ICC 0.31-0.69). CONCLUSIONS: The HBI demonstrates acceptable normative and psychometric characteristics. Modest parent-child agreement highlights the importance of multiple informants when assessing postconcussive symptoms. The results will facilitate the use of the HBI in research and clinical practice.

Cognitive Outcomes in Children with Mild Traumatic Brain Injury: An Examination Using the National Institutes of Health Toolbox Cognition Battery.

This study is the first to examine cognitive outcomes after pediatric mild TBI using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), a computerized cognitive test battery. The NIHTB-CB includes two complex measures of attention and executive function that allow differentiation of accuracy and response speed. We compared performance on the NIHTB-CB among children 8-16 years of age with mild TBI (n = 143) versus children with orthopedic injuries (OIs; n = 74) recruited in emergency departments and followed for 6 months post-injury. Mixed-model analyses showed that the mild TBI group showed significantly lower Fluid Cognition composite scores than the OI group at 10 days (group intercept, p = 0.018); the magnitude of group differences declined modestly over time (group × time interaction, p = 0.055). Effect sizes were d = 0.34 at 10 days post-injury, d = 0.27 at 3 months, and d = 0.10 at 6 months. No significant effects of group or time were found for the Crystallized Cognition composite. Analyses of Fluid Cognition subtests indicated that children with mild TBI displayed deficits for as long as 3 months on measures of attention and executive function (e.g., cognitive flexibility, inhibitory control), but not on measures of explicit memory, working memory, or processing speed. The poorer performance of the mild TBI group on measures of attention and executive function was attributable largely to slowed reaction time, not decreased accuracy. The findings suggest that children with mild TBI demonstrate persistent deficits in fluid cognition that are most apparent on tasks that combine demands for both speed and executive function.

Post-Acute Cortical Thickness in Children with Mild Traumatic Brain Injury versus Orthopedic Injury.

Studies of brain morphometry may illuminate the effects of pediatric mild traumatic brain injury (TBI; e.g., concussion). However, no published studies have examined cortical thickness in the early injury phases of pediatric mild TBI using an appropriate comparison group. The current study used an automated approach (i.e., FreeSurfer) to determine whether cortical thickness differed in children following a mild TBI or a mild orthopedic injury (OI), and to examine whether post-acute cortical thickness predicted post-acute and chronic post-concussive symptoms (PCS). Children ages 8.00-16.99 years with mild TBI (n = 136) or OI (n = 70) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (3-24 days post-injury) assessment, which included a 3 Tesla MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Cortical thickness was estimated using FreeSurfer. Linear mixed effects and multi-variable negative binomial regression models were used to test study aims, with false discovery rate (FDR) correction for multiple comparisons. Groups differed significantly on left parietal cortical thickness (TBI > OI) after FDR correction. Cortical thickness also varied by brain subregion and age, but not sex. Groups differed significantly on PCS post-acutely (TBI > OI), but not at 3 or 6 months. Right frontal thickness was positively related to post-acute PCS in both groups. Right cingulum thickness predicted chronic PCS in the OI group only. Results highlight the complexity of predicting outcomes of pediatric mild TBI from post-acute neuroimaging biomarkers.

Post-acute white matter microstructure predicts post-acute and chronic post-concussive symptom severity following mild traumatic brain injury in children.

INTRODUCTION: Mild traumatic brain injury (TBI) is a global public health concern that affects millions of children annually. Mild TBI tends to result in subtle and diffuse alterations in brain tissue, which challenges accurate clinical detection and prognostication. Diffusion tensor imaging (DTI) holds promise as a diagnostic and prognostic tool, but little research has examined DTI in post-acute mild TBI. The current study compared post-acute white matter microstructure in children with mild TBI versus those with mild orthopedic injury (OI), and examined whether post-acute DTI metrics can predict post-acute and chronic post-concussive symptoms (PCS). MATERIALS AND METHODS: Children aged 8-16.99 years with mild TBI (n = 132) or OI (n = 69) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (<2 weeks post-injury) assessment, which included a 3T MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from diffusion-weighted MRI using Automatic Fiber Quantification software. Multiple multivariable linear and negative binomial regression models were used to test study aims, with False Discovery Rate (FDR) correction for multiple comparisons. RESULTS: No significant group differences were found in any of the 20 white matter tracts after FDR correction. DTI metrics varied by age and sex, and site was a significant covariate. No interactions involving group, age, and sex were significant. DTI metrics in several tracts robustly predicted PCS ratings at 3- and 6-months post-injury, but only corpus callosum genu MD was significantly associated with post-acute PCS after FDR correction. Significant group by DTI metric interactions on chronic PCS ratings indicated that left cingulum hippocampus and thalamic radiation MD was positively associated with 3-month PCS in the OI group, but not in the mild TBI group. CONCLUSIONS: Post-acute white matter microstructure did not differ for children with mild TBI versus OI after correcting for multiple comparisons, but was predictive of post-acute and chronic PCS in both injury groups. These findings support the potential prognostic utility of this advanced DTI technique.

Age- and sex-related effects in children with mild traumatic brain injury on diffusion magnetic resonance imaging properties: A comparison of voxelwise and tractography methods.

Although there are several techniques to analyze diffusion-weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age- and sex-related differences. Participants were children aged 8-15 years with mTBI or mild orthopedic injuries. Imaging was obtained within 10 days of injury. We performed tract-based spatial statistics (TBSS), deterministic tractography using Automated Fiber Quantification (AFQ), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identifying group, developmental, and/or sex-related differences. Although there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy and decreases of axial, radial, and mean diffusivity with age. TBSS analyses resulted in age-related changes across all white matter tracts. AFQ and TRACULA revealed age-related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sensitivity and better tract-specific results for identifying developmental and sex-related differences within the brain.

Evaluating the Pediatric Early Warning Score (PEWS) system for admitted patients in the pediatric emergency department.

OBJECTIVES: The Pediatric Early Warning Score (PEWS) systems were developed to provide a reproducible assessment of a child's clinical status while hospitalized. Most studies investigating the PEWS evaluate its usefulness in the inpatient setting. Limited studies evaluate the effectiveness and integration of PEWS in the pediatric emergency department (ED). The goal of this study was to explore the test characteristics of an ED-assigned PEWS score for intensive care unit (ICU) admission or clinical deterioration in admitted patients. METHODS: This was a prospective 12-month observational study of patients, aged 0 to 21 years, admitted from the ED of an urban, tertiary care children's hospital. ED nurses were instructed in PEWS assignment and electronic medical record (EMR) documentation. Interrater reliability between nurses was evaluated. PEWS scores were measured at initial assessment (P0) and time of admission (P1). Patients were stratified into outcome groups: those admitted to the ICU either from the ED or as transfers from the floor and those admitted to the floor only. Clinical deterioration was defined as transfer to the ICU within 6 hours or within 6 to 24 hours of admission. PEWS scores and receiver operating characteristic (ROC) curves were compared for patients admitted to the floor, ICU, and with clinical deterioration. RESULTS: The authors evaluated 12,306 consecutively admitted patients, with 99% having a PEWS documented in the EMR. Interrater reliability was excellent (intraclass coefficient = 0.91). A total of 1,300 (10.6%) patients were admitted to the ICU and 11,066 (89.4%) were admitted to the floor. PEWS scores were higher for patients in the ICU group (P0 = 2.8, SD ± 2.4; P1 = 3.2, SD ± 2.4; p < 0.0001) versus floor patients (P0 = 0.7, SD ± 1.2; P1 = 0.5, SD ± 0.9; p < 0.0001). To predict the need for ICU admission, the optimal cutoff points on the ROC are P0 = 1 and P1 = 2, with areas under the ROC curve (AUCs) of 0.79 and 0.86, respectively. The likelihood ratios (LRs) for these optimal cutoff points were as follows: P0 +LR = 2.5 (95% confidence interval [CI] = 2.4 to 2.6, p < 0.05), -LR = 0.32 (95% CI = 0.28 to 0.36, p < 0.05); and P1 +LR = 6.2 (95% CI = 5.8 to 6.6, p < 0.05), -LR = 0.32 (95% CI = 0.29 to 0.35, p < 0.05). For every unit increase in P0 and P1 , the odds of admission to the ICU were 1.9 times greater (95% CI = 1.8 to 1.9, p < 0.0001) and 2.9 times greater (95% CI = 2.7 to 3.1, p < 0.0001) than to the floor. There were 89 patients in the clinical deterioration group, with 36 (0.3%) patients transferred to the ICU within 6 hours of admission and 53 (0.4%) patients transferred within 6 to 24 hours. In this group, an elevated P0 and P1 were statistically associated with an increased risk of transfer with optimal cutoff points similar to above; however, there were poorer AUCs and test characteristics. CONCLUSIONS: A PEWS system was implemented in this pediatric ED with excellent data capture and nurse interrater reliability. The study found that an elevated PEWS is associated with need for ICU admission directly from the ED and as a transfer, but lacks the necessary test characteristics to be used independently in the ED environment.