"What If?": Caregivers' Experiences Following Early Childhood Concussion.

OBJECTIVE: Little is known about the symptoms, signs, and management guidelines for children under the age of 6 years after they sustain a concussion. Caregivers of such young children may have unique concerns and encounter different challenges from those of school-age children given the distinctive developmental characteristics of the early childhood period. This study aimed to explore the experience of caregivers through semistructured interviews to inform clinical practice. METHODS: Fifty caregivers of children aged 6 months to 5.99 years were interviewed 3 months postinjury for this qualitative study to document their experience in relation to their child's accident, recovery, and healthcare provisions. RESULTS: Four main themes were identified: (1) visible changes associated with caregiver concerns, (2) a roller-coaster of emotions after the injury, (3) healthcare providers' role in addressing the need for reassurance, and (4) the need for better information after the injury. CONCLUSION: The findings provide critical insight into the unique experiences and information needs of caregivers of young children who sustain concussion. The challenges identified can inform healthcare professionals regarding the needs of caregivers after early concussion and contribute to building a knowledge base for the development of age-appropriate anticipatory guidance for caregiver mental health and child recovery.

Using Billing Codes to Create a Pediatric Functional Status e-Score for Children Receiving Inpatient Rehabilitation.

OBJECTIVE: Provide proof-of-concept for development of a Pediatric Functional Status eScore (PFSeS). Demonstrate that expert clinicians rank billing codes as relevant to patient functional status and identify the domains that codes inform in a way that reliably matches analytical modeling. DESIGN: Retrospective chart review, modified Delphi, and nominal group techniques. SETTING: Large, urban, quaternary care children's hospital in the Midwestern United States. PARTICIPANTS: Data from 1955 unique patients and 2029 hospital admissions (2000-2020); 12 expert consultants representing the continuum of rehabilitation care reviewed 2893 codes (procedural, diagnostic, pharmaceutical, durable medical equipment). MAIN OUTCOME MEASURES: Consensus voting to determine whether codes were associated with functional status at discharge and, if so, what domains they informed (self-care, mobility, cognition/ communication). RESULTS: The top 250 and 500 codes identified by statistical modeling were mostly composed of codes selected by the consultant panel (78%-80% of the top 250 and 71%-78% of the top 500). The results provide evidence that clinical experts' selection of functionally meaningful codes corresponds with codes selected by statistical modeling as most strongly associated with WeeFIM domain scores. The top 5 codes most strongly related to functional independence ratings from a domain-specific assessment indicate clinically sensible relationships, further supporting the use of billing data in modeling to create a PFSeS. CONCLUSIONS: Development of a PFSeS that is predicated on billing data would improve researchers' ability to assess the functional status of children who receive inpatient rehabilitation care for a neurologic injury or illness. An expert clinician panel, representing the spectrum of medical and rehabilitative care, indicated that proposed statistical modeling identifies relevant codes mapped to 3 important domains: self-care, mobility, and cognition/communication.

Emergency department visits for mild traumatic brain injury in early childhood.

BACKGROUND: Brain injury during early childhood may disrupt key periods of neurodevelopment. Most research regarding mild traumatic brain injury (mTBI) has focused on school-age children. We sought to characterize the incidence and healthcare utilization for mTBI in young children presenting to U.S. emergency departments (ED). METHODS: The Nationwide Emergency Department Sample was queried for children age 0-6 years with mTBI from 2016 to 2019. Patients were excluded for focal or diffuse TBI, drowning or abuse mechanism, death in the ED or hospital, Injury Severity Score > 15, neurosurgical intervention, intubation, or blood product transfusion. RESULTS: National estimates included 1,372,291 patient visits: 63.5% were two years or younger, 57.5% were male, and 69.4% were injured in falls. The most common head injury diagnosis was "unspecified injury of head" (83%); this diagnosis decreased in frequency as age increased, in favor of a concussion diagnosis. Most patients were seen at low pediatric volume EDs (64.5%) and non-children's hospital EDs (86.2%), and 64.9% were seen at a non-teaching hospital. Over 98% were treated in the ED and discharged home. Computed tomography of the head and cervical spine were performed in 18.7% and 1.6% of patients, respectively, less often at children's hospitals (OR = 0.55, 95%CI = 0.41-0.76 for head and OR = 0.19, 95%CI = 0.11-0.34 for cervical spine). ED charges resulted in $540-681 million annually, and more than half of patients utilized Medicaid. CONCLUSIONS: Early childhood mTBI is prevalent and results in high financial burden in the U.S. There is wide variation in diagnostic coding and computed tomography scanning amongst EDs. More focused research is needed to identify optimal diagnostic tools and management strategies.

Head Impact Burden and Change in Neurocognitive Function During a Season of Youth Football.

OBJECTIVE: To determine the association of repetitive subconcussive head impacts with functional outcomes in primary and high school tackle football players. SETTING: Youth football fields and an outpatient sports neurology clinic. PARTICIPANTS: A total of 112 primary school (n = 55, age 9-12 years) and high school (n = 57, age 15-18 years) football players. DESIGN: A prospective cohort study. MAIN MEASURES: Helmet-based sensors were used to record head impacts during practices and games during the 2016 football season. Impact g-forces were summed to yield a measure of cumulative impact. History of self-reported premorbid medical diagnoses was obtained preseason. Players completed assessments of a variety of outcomes both pre- and postseason: neuropsychological test performance, symptoms, vestibular and ocular-motor screening, balance, parent-completed attention-deficit hyperactivity disorder (ADHD) symptoms, and self-reported behavioral adjustment. RESULTS: Average cumulative impact was 3700 (standard deviation = 2700) g-forces for the season and did not differ between age groups (P = .594). Cumulative impact did not predict pre- to postseason change scores on any outcome measures (all P > .05). Instead, younger age group and reported history of premorbid ADHD predicted change scores on several cognitive testing measures and parent-reported ADHD symptoms, while reported history of premorbid anxiety and depression predicted change scores on symptom reporting. CONCLUSIONS: In youth tackle football, subconcussive head impacts sustained over the course of a single season may not be associated with neurocognitive functional outcomes. The absence of a significant association may reflect the relatively short follow-up interval, and signals the need for studies across multiple seasons.

Utilization of conventional neuroimaging following youth concussion.

BACKGROUND/OBJECTIVE: Conventional neuroimaging is not recommended for the routine diagnosis of concussion, but some patients with concussion undergo computed tomography (CT) or magnetic resonance imaging (MRI). The objective of this study was to explore the clinical factors that predict neuroimaging utilization in concussion. METHODS: Concussion-related CT and MRI data were analysed from 1953 patients, aged 10-19 years, who presented to a sports concussion clinic within 30 days of injury. RESULTS: The majority of CT scans (n = 193) were obtained during the acute concussion period (mean = 2.7 days post-concussion), whereas MRI scans (n = 134) were ordered later during recovery (mean = 39.4 days post-concussion). Predictors of CT utilization included loss of consciousness, amnesia and vomiting (all p < 0.001). Prior concussion (p = 0.002) and continued participation in activity after injury (p = 0.03) predicted greater MRI utilization. Neuroimaging with either CT (p = 0.024, hazard ratio = 1.2) or MRI (p < 0.001, hazard ratio = 2.75) was associated with prolonged symptoms. Only 3.1% of CTs and 1.5% of MRIs demonstrated signs of traumatic brain injury. CONCLUSION: Several clinical factors predict neuroimaging utilization in patients with concussion. CT is generally used acutely, while MRI is used in the sub-acute and chronic post-concussion periods. In a sports concussion clinic, delayed neuroimaging has limited clinical yield.

Specific Factors Influence Postconcussion Symptom Duration among Youth Referred to a Sports Concussion Clinic.

OBJECTIVE: To identify the clinical factors that influence the duration of postconcussion symptoms among youth referred to a sports concussion clinic. STUDY DESIGN: A retrospective cohort study was conducted to evaluate several potential predictors of symptom duration via a Cox proportional hazards analyses. The individual postconcussion symptom scores were highly correlated, so these symptoms were analyzed in the statistical model as coefficients derived from principal component analyses. RESULTS: Among 1953 youth with concussion, 1755 (89.9%) had dates of reported symptom resolution. The remainder (10.1%) were lost to follow-up and censored. The median time to recovery was 18 days (range 1-353 days). By 30 days, 72.6% had recovered; by 60 days, 91.4% had recovered; and by 90 days, 96.8% had recovered. Several variables in a multivariate Cox model predicted postconcussion symptom duration: female sex (P < .001, hazard ratio [HR] = 1.28), continued activity participation (P = .02, HR = 1.13), loss of consciousness (P = .03, HR = 1.18), anterograde amnesia (P = .04, HR = 1.15), premorbid headaches (P = .03, HR = 1.15), symptom components from the day of concussion (emotion, P = .03, HR = 1.08), and the day of clinic evaluation (cognitive-fatigue, P < .001, HR = 1.22; cephalalgic, P < .001, HR = 1.27; emotional, P = .05, HR = 1.08; arousal-stimulation, P = .003, HR = 1.1). In univariate analyses, greater symptom scores generally predicted longer symptom durations. Worsening of symptoms from the day of concussion to the day of clinic evaluation also predicted longer recovery (P < .001, HR = 1.59). CONCLUSIONS: Several factors help to predict protracted postconcussion symptom durations among youth referred to a sports concussion clinic.

Post-traumatic headaches correlate with migraine symptoms in youth with concussion.

OBJECTIVE: The term "post-traumatic migraine" (PTM) has been used to describe post-traumatic headaches (PTHs) that have associated migraine features, but studies of this relationship are lacking. The objective of the present study was to determine whether PTH correlates strongly with migraine symptoms among youth with concussion. METHODS: Twenty-three symptoms were analyzed from a retrospective cohort of 1953 pediatric patients with concussion. A principal component analysis (PCA) with oblique Promax rotation was conducted to explore underlying symptom relationships in the full cohort and in subcohorts stratified by the presence (n = 414) or absence (n = 1526) of premorbid headache. RESULTS: The mean patient age was 14.1 years; 63% were male. Headache was the most common postconcussion symptom, acknowledged by 69.4% of patients. When considering the full cohort, the PCA demonstrated clustering of headache with photophobia, phonophobia, nausea, dizziness, and neck pain. Similar clustering was present among patients without premorbid headaches. Repeating the analysis in the patients with preconcussion headaches led to elimination of neck pain from the cluster. CONCLUSIONS: PTH correlates strongly with other migraine symptoms among youth with concussion, regardless of premorbid headaches. This clustering of migraine symptoms supports the existence of PTM as a distinct clinical entity in some patients.

High school principals' resources, knowledge, and practices regarding the returning student with concussion.

OBJECTIVE: To determine high school principals' self-reported resources, knowledge, and practices regarding the management of students returning to school following concussion. STUDY DESIGN: A cross-sectional survey of public high school principals in the state of Ohio assessed respondent and school demographics, respondent concussion training, school resources, and monitoring and accommodation practices for students with concussion. RESULTS: Of the 695 eligible high school principals, 465 (66.9%) completed the survey. Over one-third of principals (37.2%) had some form of concussion training in the past year. Those with training were more likely to promote training of other school faculty (57.4% vs 30.6%, P < .001). Principals were asked to identify school personnel who are designated as case managers for students with concussion. Schools without a designated case manager were less likely to have an athletic trainer (P < .001) and had fewer students (median 424.5 vs 599) than schools with a case manager. Principals could list at least 1 faculty designee who communicates with health professionals more often for student-athletes than for nonathletes (P < .001). Most principals were willing to provide students with short-term academic accommodations, but 30.1% required a health professional's note prior to making any academic changes. Only 32% of principals reported providing families with a written academic plan following concussion. CONCLUSIONS: Schools differ in their resources and management strategies for students returning to school after concussion. Understanding these differences can help health professionals to overcome potential barriers in managing their school-aged patients with concussion.

How long is too long? The lack of consensus regarding the post-concussion syndrome diagnosis.

BACKGROUND/AIM: A standard definition of Post-concussion Syndrome (PCS) does not exist. The objective was to determine consensus regarding the definition of PCS among physician members of the American College of Sports Medicine (ACSM). METHODS: Physician members of the ACSM were sent an electronic survey to determine opinions regarding the PCS diagnosis. RESULTS: Five hundred and ninety-seven physicians completed the survey. When asked the minimum duration of symptoms required to diagnose PCS, respondents answered: <2 weeks (26.6%), 2 weeks to 1 month (20.4%), 1-3 months (33%) and >3 months (11.1%). Physicians who see ≥10% concussion patients in their practise, as well as physicians whose concussion population consists of >50% paediatric patients, were more likely to require >1 month of symptoms (p < 0.001). When asked the minimum number of symptoms required to diagnose PCS, responses varied: one symptom (55.9%), two symptoms (17.6%), three symptoms (14.6%) and four or more symptoms (3.2%). Respondents from the US were more likely than non-US respondents to require only one symptom for the PCS diagnosis (p = 0.01). CONCLUSIONS: There is a lack of consensus regarding the definition of PCS among physician members of the ACSM. A standard definition would improve consistency in concussion research and in clinical practise.

Comparing patient and parent recall of 90-day and 30-day migraine disability using elements of the PedMIDAS and an Internet headache diary.

AIM: The aim of this article is to compare 90-day and 30-day recall of Pediatric Migraine Disability Assessment (PedMIDAS) elements and headache frequency against daily entries from an Internet headache diary among pediatric patients and their parents. METHODS: In a prospective cohort study, patients aged 10-18 years with episodic migraine or probable migraine completed a 90-day Internet-based headache diary that incorporated PedMIDAS questions. Following the 90-day diary period, patients and parents completed modified PedMIDAS instruments to assess 90-day and 30-day recall. Intraclass correlation coefficients (ICC) were calculated to measure recall reliability. The Kruskal-Wallis and Jonckheere-Terpstra tests were used to explore recall accuracy as it relates to each participant's self-reported confidence in recall and to patient age. RESULTS: Fifty-two subjects completed 90 consecutive diary entries. Comparing 30-day to 90-day recall of PedMIDAS elements, ICC scores improved by 26.2% (patients) and 17.5% (parents). Patients had better recall than their parents for all study measures. Self-reported confidence in recall and patient age had limited and inconsistent effects on recall accuracy. CONCLUSION: The optimal recall interval to assess migraine disability must balance recall accuracy with generalizability across a range of headache frequencies. When compared to daily diary entries, recall accuracy of PedMIDAS elements and headache frequency improves at 30 days compared to 90 days. Parent report of migraine disability should not be used as a replacement for patient report.

PedMIDAS-based scoring underestimates migraine disability on non-school days.

OBJECTIVE: The aim of this study is to compare daily Pediatric Migraine Disability Assessment (PedMIDAS)-based scores for headaches occurring on school days vs non-school days and during the school year vs the summer holiday. BACKGROUND: The PedMIDAS is the only instrument validated to assess migraine disability among school-aged children. However, the PedMIDAS may underestimate disability during prolonged school holidays. METHODS: In a prospective cohort study, migraine patients aged 10-18 years completed a 90-day Internet-based headache diary. For each headache day, they answered PedMIDAS-based questions and rated their headache intensity (scale 1-10). PedMIDAS-based scores, headache intensity ratings, and relative headache frequencies were compared for school days vs non-school days and for the school year vs the summer holiday. RESULTS: Fifty-two patients completed 4680 diary entries comprising 984 headache days. The headache frequencies and intensity ratings did not differ between time periods. However, the mean headache disability scores (as measured from PedMIDAS-based questions) were significantly different for school days (0.85) compared to non-school days (0.45), P < .001, and for the school year (0.73) compared to the summer holiday (0.46), P < .016. CONCLUSION: Given similar headache intensities and frequencies, daily PedMIDAS-based scores significantly underestimate headache disability on non-school days. Accordingly, PedMIDAS scoring during the school year may not be comparable to assessments done during the summer holiday. These potential differences must be considered when using the instrument as an outcome measure for clinical trials.

Postconcussive Symptoms After Early Childhood Concussion.

Importance: Research on postconcussive symptoms (PCS) following early childhood concussion has been hindered by a lack of measures suitable for this age group, resulting in a limited understanding of their evolution in young children. Objective: To document PCS in the first 3 months after early childhood concussion using a developmentally appropriate measure. Design, Setting, and Participants: This cohort study used data collected at 3 Canadian and 1 US urban pediatric emergency departments (EDs) and 8 Canadian daycares from December 2018 to December 2022 as part of the Kids' Outcomes and Long-Term Abilities (KOALA) project, a prospective, multicenter, longitudinal cohort study. Participants included children aged 6 to 72 months with early childhood concussion or orthopedic injury (OI) or uninjured children from the community to serve as controls. Data were analyzed from March 2023 to January 2024. Exposure: Concussion sustained between ages 6 and 72 months. Main Outcomes and Measures: Primary outcomes were cognitive, physical, behavioral and total PCS assessed prior to injury (retrospectively), acutely (within 48 hours), and at 10 days, 1 month, and 3 months after injury or recruitment through caregiver observations using the Report of Early Childhood Traumatic Injury Observations & Symptoms inventory. Group comparisons were analyzed using ordinal regression models. Results: The study included 303 children (mean [SD] age, 35.8 [20.2] months; 152 [50.2%] male). Of these, 174 children had a concussion (mean [SD] age, 33.3 [19.9] months), 60 children had an OI (mean [SD] age, 38.4 [19.8] months) and 69 children were uninjured controls (mean [SD] age, 39.7 [20.8] months). No meaningful differences were found between the concussion and comparison groups in retrospective preinjury PCS. Significant group differences were found for total PCS at the initial ED visit (concussion vs OI: odds ratio [OR], 4.33 [95% CI, 2.44-7.69]; concussion vs control: OR, 7.28 [95% CI, 3.80-13.93]), 10 days (concussion vs OI: OR, 4.44 [95% CI, 2.17-9.06]; concussion vs control: OR, 5.94 [95% CI, 3.22-10.94]), 1 month (concussion vs OI: OR, 2.70 [95% CI, 1.56-4.68]; concussion vs control: OR, 4.32 [95% CI, 2.36-7.92]), and 3 months (concussion vs OI: OR, 2.61 [95% CI, 1.30-5.25]; concussion vs control: OR, 2.40 [95% CI, 1.36-4.24]). Significant group differences were also found for domain-level scores (cognitive, physical, behavioral) at various time points. Conclusions and Relevance: In this early childhood cohort study, concussion was associated with more PCS than OIs or typical development up to 3 months after injury. Given the limited verbal and cognitive abilities typical of early childhood, using developmentally appropriate manifestations and behaviors is a valuable way of tracking PCS and could aid in concussion diagnosis in young children.

Improving outcome after paediatric concussion: challenges and possibilities.

The term concussion has permeated mainstream media and household vocabulary mainly due to awareness regarding the risks of concussion in professional contact sports, yet it occurs across a variety of settings and ages. Concussion is prevalent in infants, preschoolers, children, and adolescents, and is a common presentation or reason for referral to primary care providers, emergency departments, and specialised trauma clinics. Its broad range of symptoms and sequelae vary according to multiple individual, environmental, and clinical factors and can lead to health and economic burden. More than 20 years of research into risk factors and consequences of paediatric concussion has revealed as many questions as answers, and scientific work and clinical cases continue to expose its complexity and heterogeneity. In this Review, we present empirical evidence for improving outcome after paediatric concussion. We consider work pertaining to both sports and other injury mechanisms to provide a perspective that should be viewed as complementary to publications focused specifically on sports concussion. Contemporary challenges in prevention, diagnosis, prognosis, and intervention are discussed alongside pathways and future directions for improving outcome.

Predictors of Treatment Response to Multidisciplinary Care for Persistent Symptoms after Pediatric Concussion.

PURPOSE: To assess which pediatric patients experiencing persistent post-concussive symptoms (PCS) benefit most from multidisciplinary treatment including specialists in Neurology, Neuropsychology, Physical Therapy, and Athletic Training, and to explore the effectiveness of this approach. METHODS: A retrospective chart review of 56 adolescents 10-20 years old (M = 15.0 ± 2.1) receiving multidisciplinary care for PCS (>30 days) was conducted. RESULTS: Systolic blood pressure and Body Mass Index predicted time to concussion resolution (p < .05), such that higher values were associated with slower resolution. PCS scores significantly decreased between participants' initial and final clinic visits, p < .01, and among the 25 participants for whom pre-intervention PCS scores were available, symptom severity scores significantly declined following multidisciplinary intervention compared to pre-referral values (p < .01). CONCLUSIONS: Exploratory analyses reveal that multidisciplinary treatment is a promising approach for reducing symptoms among adolescents with PCS, and that those with greater levels of physical fitness may benefit most.

Treatment of Post-traumatic Headaches in Children: A Systematic Review.

Post-traumatic headache is a secondary headache disorder beginning within 7 days of head injury. We conducted a systematic review of the evidence for treatment of post-traumatic headache in children. Of 2169 unique articles screened, 12 were included. Most studies pertained to headaches after concussion. The authors of seven studies examined the effect of medications, 4 studied nonpharmacological therapies, and 1 studied the reduction of medication usage. Much of the evidence came from retrospective chart reviews, had low level of evidence, and had fair risk of bias. High-quality randomized controlled treatment trials are needed to guide the clinical management of this condition.

Exposure to Head Impacts and Cognitive and Behavioral Outcomes in Youth Tackle Football Players Across 4 Seasons.

Importance: Repetitive head impacts have been posited to contribute to neurocognitive and behavioral difficulties in contact sport athletes. Objective: To identify associations between cognitive and behavioral outcomes and head impacts measured in youth tackle football players over 4 seasons of play. Design, Setting, and Participants: This prospective cohort study was conducted from July 2016 through January 2020, spanning 4 football seasons. The setting was a youth tackle football program and outpatient medical clinic. Players were recruited from 4 football teams composed of fifth and sixth graders, and all interested players who volunteered to participate were enrolled. Data analysis was performed from March 2020 to June 2021. Exposures: Impacts were measured using helmet-based sensors during practices and games throughout 4 consecutive seasons of play. Impacts were summed to yield cumulative head impact gravitational force equivalents per season. Main Outcomes and Measures: Ten cognitive and behavioral measures were completed before and after each football season. Results: There were 70 male participants aged 9 to 12 years (mean [SD] age, 10.6 [0.64] years), with 18 completing all 4 years of the study. At the post-season 1 time point, higher cumulative impacts were associated with lower self-reported symptom burden (ß = -0.6; 95% CI, -1.0 to -0.2; P = .004). After correcting for multiple comparisons, no other associations were found between impacts and outcome measures. At multiple times throughout the study, premorbid attention-deficit/hyperactivity disorder, anxiety, and depression were associated with worse cognitive or behavioral scores, whereas a premorbid headache disorder or history of concussion was less often associated with outcomes. Conclusions and Relevance: In this cohort of youth tackle football players, premorbid conditions, including attention-deficit/hyperactivity disorder, anxiety, and depression, were associated with cognitive and behavioral outcomes more often than cumulative impact.

Subconcussive Head Impacts and Neurocognitive Function Over 3 Seasons of Youth Football.

OBJECTIVE: To determine the association between repetitive subconcussive head impacts and neurobehavioral outcomes in youth tackle football players. METHODS: Using helmet-based sensors, we measured head impacts for 3 consecutive seasons of play in 29 male players age 9-11. Cumulative impact g's were calculated. Players completed a battery of outcome measures before and after each season, including neuropsychological testing, vestibular-ocular sensitivity, and self- and parent-reported measures of symptoms and attention-deficit hyperactivity disorder (ADHD). RESULTS: Average cumulative impact over 3 seasons was 13 900g. High-intensity hits predicted worse change for self-reported social adjustment (P = .001). Cumulative impact did not predict change in any of the outcome measures. History of ADHD, anxiety, and depression predicted worse change for self-reported symptoms and social adjustment, independent of head impacts. When players were stratified into 3 groups based on cumulative impact across all 3 seasons, differences in outcome measures existed prior to the start of the first season. These differences did not further increase over the course of the 3 seasons. CONCLUSION: Over 3 consecutive seasons of youth tackle football, we found no association between cumulative head impacts and neurobehavioral outcomes. Larger sample sizes and longer follow-up times would further assist in characterizing this relationship.

The primed ebolavirus glycoprotein (19-kilodalton GP1,2): sequence and residues critical for host cell binding.

Entry of ebolavirus (EBOV) into cells is mediated by its glycoprotein (GP(1,2)), a class I fusion protein whose structure was recently determined (J. E. Lee et al., Nature 454:177-182, 2008). Here we confirmed two major predictions of the structural analysis, namely, the residues in GP(1) and GP(2) that remain after GP(1,2) is proteolytically primed by endosomal cathepsins for fusion and residues in GP(1) that are critical for binding to host cells. Mass spectroscopic analysis indicated that primed GP(1,2) contains residues 33 to 190 of GP(1) and all residues of GP(2). The location of the receptor binding site was determined by a two-pronged approach. We identified a small receptor binding region (RBR), residues 90 to 149 of GP(1), by comparing the cell binding abilities of four RBR proteins produced in high yield. We characterized the binding properties of the optimal RBR (containing GP(1) residues 57 to 149) and then conducted a mutational analysis to identify critical binding residues. Substitutions at four lysines (K95, K114, K115, and K140) decreased binding and the ability of RBR proteins to inhibit GP(1,2)-mediated infection. K114, K115, and K140 lie in a small region modeled to be located on the top surface of the chalice following proteolytic priming; K95 lies deeper in the chalice bowl. Combined with those of Lee et al., our findings provide structural insight into how GP(1,2) is primed for fusion and define the core of the EBOV RBR (residues 90 to 149 of GP(1)) as a highly conserved region containing a two-stranded beta-sheet, the two intra-GP(1) disulfide bonds, and four critical Lys residues.

Proposal of a Functional Impairment Symptom Scale for Concussion.

Clinicians currently administer patient-reported symptom scales to quantify and track concussion symptoms. These scales are based on subjective ratings without reference to the degree of functional impairment caused by the symptoms. Our objective was to develop a concussion symptom scale based on functional impairment and compare it to a widely used concussion symptom checklist. We conducted a retrospective chart review evaluating 133 patients age 9-22 with an acute concussion who completed 2 symptom checklists at their initial visit-the Sport Concussion Assessment Tool (SCAT-3) symptom evaluation (22 symptoms, 0-6 scale) and the proposed Functional Impairment Scale (22 symptoms, 0-3 scale related to degree of functional impairment). Mean total symptom score was 27.2±22.9 for Sport Concussion Assessment Tool-3 and 14.7±11.9 for the Functional Impairment Scale. Pearson correlation between the scales was 0.98 (P < .001). Mean time from concussion to first visit was 6.9±6.2 days, and median clearance time after injury was 19 (95% CI 16-21) days. After adjusting for patient and injury characteristics, an increased score on each scale was associated with longer time to clearance (5-point increase in Sport Concussion Assessment Tool-3 hazard ratio 0.885, 95% CI 0.835-0.938, P < .001; 2.5-point increase in Functional Impairment Scale hazard ratio 0.851, 95% CI 0.802-0.902, P < .001). We propose a concussion symptom scale based on functional impairment that correlates strongly with the Sport Concussion Assessment Tool-3 scale, demonstrates a similar association with time to clearance, and may provide a more intuitive approach to monitoring how symptoms are affecting patients recovering from concussion. Future research should aim to validate this scale through a prospective longitudinal study.

Head Impact Burden Differs Between Seasons in Youth and High School US Football Players.

Retrospective estimates of head impact burden in contact sports are often used in studies assessing for correlation of head impact exposure with neurocognitive outcomes later in life. These estimations assume a consistent impact burden from year to year. We monitored head impacts in youth tackle football players in the 6th-8th grades and high school varsity players using helmet-based sensors during two consecutive seasons. Helmet-based pressure sensors were used to measure head impacts, and estimates of peak linear acceleration (g's) were then grouped and summed for cumulative impact. After each season, players estimated whether they experienced an average, below average, or above average head impact burden in relation to their teammates. Of the 98 players who participated, 54 played in both seasons and sustained a median of 102.5 impacts (2206 cumulative g's) in season 1 and 161 impacts (3682 cumulative g's) in season 2. Using pairwise comparisons, number of impacts and cumulative g's increased in the youth players from season 1 to season 2 (p = 0.0021 and p = 0.0018, respectively), but there was a trend towards a decrease in number of impacts and g's at the high school level. In an exploratory analysis, perceived cumulative head impact and measured cumulative g's weakly correlated (Pearson's correlation coefficient = 0.26 for season 1 and 0.02 for season 2). In conclusion, cumulative head impacts differ significantly from one season to the next, and players have difficulty estimating their cumulative head impacts in relation to their team mates, especially at the youth level. Retrospective estimations of head impact burden should account for this variability.