Outcomes In Pediatric Traumatic Brain Injury Research Articles

A Pilot Study of Saliva MicroRNA Signatures in Children with Moderate-to-Severe Traumatic Brain Injury.

Background/Objectives: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Currently, no biological test can predict outcomes in pediatric TBI, complicating medical management. This study sought to identify brain-related micro-ribosomal nucleic acids (miRNAs) in saliva associated with moderate-to-severe TBI in children, offering a potential non-invasive, prognostic tool. Methods: A case-control design was used, enrolling participants ≤ 18 years old from three pediatric trauma centers. Participants were divided into moderate-to-severe TBI and non-TBI trauma control groups. Saliva samples were collected within 24 h of injury, with additional samples at 24-48 h and >48 h post-injury from the TBI group. miRNA profiles were visualized with partial least squares discriminant analysis (PLSDA) and hierarchical clustering. Mann-Whitney testing was used to compare miRNAs between groups, and mixed models were used to assess longitudinal expression patterns. DIANA miRPath v3.0 was used to interrogate the physiological functions of miRNAs. Results: Twenty-three participants were enrolled (14 TBI, nine controls). TBI and control groups displayed complete separation of miRNA profiles on PLSDA. Three miRNAs were elevated (adj. p < 0.05) in TBI (miR-1255b-5p, miR-3142, and miR-4320), and two were lower (miR-326 and miR-4646-5p). Three miRNAs (miR-3907, miR-4254, and miR-1273g-5p) showed temporal changes post-injury. Brain-related targets of these miRNAs included the glutamatergic synapse and GRIN2B. Conclusions: This study shows that saliva miRNA profiles in children with moderate-to-severe TBI may differ from those with non-TBI trauma and exhibit temporal changes post-injury. These miRNAs could serve as non-invasive biomarkers for prognosticating pediatric TBI outcomes. Further studies are needed to confirm these findings.

Association between social determinants of health and pediatric traumatic brain injury outcomes.

Social determinants of health (SDH) are factors that may impact outcomes following pediatric traumatic brain injuries (TBI). The purpose of this study was to investigate the relationship between race and functional outcomes in a diverse pediatric population. We further explored how this association may be modified by SDH factors, including insurance status, social vulnerability, and child opportunity. A cohort study (N = 401) of children aged 0-18 [median = 9.22 years (IQR: 3.56-13.59)] presenting to the Emergency Department at Level I and II Trauma Centers with mild to severe head injuries. Geocoded variables were used to evaluate SDH. The sample was described overall and by racial/ethnic group, which were adjusted for confounders using inverse propensity treatment weights (IPTW). Weighted and unweighted Firth logistic regression models (mortality) and generalized linear regression models (GOS-E scores) were reported without and then with potential effect modifiers. The sample is majority male (65.84%); race/ethnicity are as follows: White (52.37%), Black/African Americans (35.91%), and Hispanic (11.72%). Black (31.25%) and Hispanic (27.66%) patients had higher rates of severe TBI. 35.89% of White patients were categorized as more socially vulnerable compared to 62.68% Black and 70.21% Hispanic patients. A total 63.64% of White patients were from higher opportunity neighborhoods, compared to 25.87% of Black and 51.06% of Hispanic patients. A total 50.95% of White patients, 25.87% of Black patients, and 17.02% of Hispanic patients were privately insured. There were no differences found between racial and ethnic groups on mortality or GOS-E scores. Patients from minority backgrounds had more severe injuries, many resulting from pedestrian vs. motor vehicle accidents. Additionally, patients from minority backgrounds experience more social vulnerability and lower opportunity. Despite these discrepancies, we did not observe differences on rates of mortality or functional outcomes in either racial or ethnic groups. SDH were not found to impact outcomes. Further research is needed to determine how these complex social and environmental variables impact health outcomes.

Demography and Outcome of Pediatric Traumatic Brain Injury; Experience from a University Teaching Hospital in Nepal

Introduction: Traumatic brain injury (TBI) is one of the significant causes of disability and death. It is a common cause of emergency neurosurgical consultation. Due to differences in physiology and management strategy, outcomes of pediatric TBI are different. This study purposes to describe the demography, clinical-radiological characteristics, and outcome of patients with pediatric TBI. Methods: A retrospective study of 112 children of age up to 18 years admitted to the Neurosurgical Department in Tribhuvan University Teaching Hospital following TBI from August 2021 to July 2022 was conducted. Variables analyzed were the demographics, clinical characteristics, imaging findings, management strategies, and outcome. Results: Median age was 5.5 years. The male-to-female ratio was 2.3:1. Falls followed by road accidents (RTA) were the most common mode of injury. A significant number of patients (62, 55.3%) presented after 24 hours of injury. Vomiting (67, 59.8%) was the commonest symptom followed by loss of consciousness (60, 53.6%). Post-traumatic seizure was observed in 13 (11.6%) of the children; however, had no association with the outcome. Mild, moderate, and severe TBI were seen in 80.3%, 17.8%, and 1.7% respectively. Extra-axial hematomas (40%) were the most common findings followed by skull fractures (33.9%). Intensive care was required in 13 (11.6%) and 34 (30%) required surgery. Craniotomy (30.3%) was the most common procedure. Good outcome at discharge was seen in 107 (95.5%) of patients. Conclusion: Falls and RTAs were the commonest causes of pediatric TBI. In our study, a significant number of the patients presented after 24 hours of injury. Craniotomy was the most common managment and most of the children had good outcomes at discharge.

Generalizability of pediatric major trauma experience to severe pediatric traumatic brain injury at level 1 and 2 trauma centers

Background: To examine the volume-outcome relationship in severe pediatric traumatic brain injury (TBI) using a retrospective analysis and to determine whether volume as a measure of broader trauma experience may generalize to favor improved pediatric TBI outcomes.

Validation of CRASH Model in Prediction of 14-Day Mortality and 6-Month Unfavourable Outcome of Pediatric Traumatic Brain Injury

Background: Value of Corticosteroid Randomisation after Significant Head Injury (CRASH) prognostic model has not been assessed in children with traumatic brain injury (TBI). This study is designed to examine the value of CRASH model in prediction of 14-day mortality and 6-month unfavourable outcome of pediatric TBI. Materials and Methods: In a cross-sectional study, 738 children with TBI brought to the emergency ward of four hospitals were studied. For assessing the predictive value of the CRASH model discrimination power and calibration of CRASH basic model and CRASH CT model were examined. Results: The areas under the curve (AUC) of CRASH basic and CRASH CT models in prediction of 14-day mortality were 0.89 and 0.91, respectively. AUCs of the CRASH basic and CRASH CT models in predicting unfavourable outcome were 0.93 and 0.94. The value of two models in prediction of 14-day mortality (p=0.20), and 6-month unfavourable outcome (p=0.22) were equal. Both models had proper calibrations in predicting 14-day mortality and 6-month unfavourable outcome. Conclusion: As calculations of the basic model are easier than those of the CT model and it does not necessitate CT scanning, the CRASH basic model is suggested in the field of pediatrics.

Targeting high-mobility group box protein 1 (HMGB1) in pediatric traumatic brain injury: Chronic neuroinflammatory, behavioral, and epileptogenic consequences

High mobility group box protein-1 (HMGB1) has been implicated as a key mediator of neuroinflammation and neurodegeneration in a range of neurological conditions including traumatic brain injury (TBI) and epilepsy. To date, however, most studies have examined only acute outcomes, and the adult brain. We have recently demonstrated HMGB1 release after experimental TBI in the pediatric mouse. This study therefore examined the chronic consequences of acute HMGB1 inhibition in the same model, to test the hypothesis that HMGB1 is a pivotal mediator of neuropathological, neurobehavioral, and epilepsy outcomes in pediatric TBI. HMGB1 was inhibited by treatment with 50 mg/kg i.p. Glycyrrhizin (Gly), compared to vehicle controls, commencing 1 h prior to moderate TBI or sham surgery in post-natal day 21 mice. We first demonstrated that Gly reduced brain HMGB1 levels and brain edema at an acute time point of 3 days post-injury. Subsequent analysis over a chronic time course found that pediatric TBI resulted in short-term spatial memory and motor learning deficits alongside an apparent increase in hippocampal microglial reactivity, which was prevented in Gly-treated TBI mice. In contrast, Gly treatment did not reduce the severity of evoked seizures, the proportion of animals exhibiting chronic spontaneous seizure activity, or cortical tissue loss. Together, our findings contribute to a growing appreciation for HMGB1's role in neuropathology and associated behavioral outcomes after TBI. However, further work is needed to fully elucidate the contribution of HMGB1 to epileptogenesis in this context.

Does hypertension at initial presentation adversely affect outcomes in pediatric traumatic brain injury?

BackgroundAdults with traumatic brain injury (TBI) who present hypertensive suffer worse outcomes and increased mortality compared to normotensive patients. The purpose of this study is to determine if age-adjusted hypertension on presentation is associated with worsened outcomes in pediatric TBI. MethodsA retrospective chart review was conducted on pediatric patients with severe TBI admitted to a single system pediatric tertiary care center. The primary outcome was mortality. Secondary outcomes included length of stay, need for neurosurgical intervention, duration of mechanical ventilation, and the need for inpatient rehabilitation. ResultsOf 150 patients, 70% were hypertensive and 30% were normotensive on presentation. Comparing both groups, no statistically significant differences were noted in mortality (13.3% for both groups), need for neurosurgical intervention (51.4% vs 48.8%, p = 0.776), length of stay (6 vs 8 days, p = 0.732), duration of mechanical ventilation (2 vs 3 days, p = 0.912), or inpatient rehabilitation rates (48.6% vs 48.9%, p = 0.972). In comparing just the hypertensive patients, there was a trend toward increased mortality in the 95th and 99th percentile groups at 15.8% and 14.1%, versus the 90th percentile group at 6.7% but the difference was not statistically significant (p = 0.701). ConclusionsContrary to the adult literature, pediatric patients with severe TBI and hypertension on presentation do not appear to have worsened outcomes compared to those who are normotensive. However, a trend toward increased mortality did exist at extremes of age adjusted hypertension. Larger scale studies are needed to validate these findings. Study typeRetrospective cohort study Level of EvidenceIII

Reliability and Construct Validity of the TBI-QOL Communication Short Form as a Parent-Proxy Report Instrument for Children With Traumatic Brain Injury.

Purpose The purpose of this study was to evaluate the internal consistency and construct validity of the Traumatic Brain Injury Quality of Life Communication Item Bank (TBI-QOL COM) short form as a parent-proxy report measure. The TBI-QOL COM is a patient-reported outcome measure of functional communication originally developed as a self-report measure for adults with traumatic brain injury (TBI), but it may also be valid as a parent-proxy report measure for children who have sustained TBI. Method One hundred twenty-nine parent-proxy raters completed the TBI-QOL COM short form 6 months postinjury as a secondary aim of a multisite study of pediatric TBI outcomes. The respondents' children with TBI were between 8 and 18 years old ( M age = 13.2 years old) at the time of injury, and the proportion of TBI severity mirrored national trends (73% complicated-mild; 27% moderate or severe). Results The parent-proxy report version of the TBI-QOL COM displayed strong internal consistency (ordinal α = .93). It also displayed evidence of known-groups validity by virtue of more severe injuries associated with more abnormal scores. The instrument also showed evidence of convergent and discriminant validity by displaying a pattern of correlations with other constructs according to their conceptual relatedness to functional communication. Conclusions This preliminary psychometric investigation of the TBI-QOL COM supports the further development of a parent report version of the instrument. Future development of the TBI-QOL COM with this population may include expanding the content of the item bank and developing calibrations specifically for parent-proxy raters. Supplemental Material https://doi.org/10.23641/asha.7616534.

Using Rehabilitation along the Pediatric Trauma Continuum as a Strategy to Define Outcomes in Traumatic Brain Injury

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the pediatric population. It impacts all levels of care in our medical system. Despite numerous published guidelines and significant resources dedicated to acute management of pediatric TBI, most patients who are discharged have unrecognized or unmet needs at 6, 12, and 24 months after injury. Rehabilitation services have been developed to address the gap in both the inpatient and outpatient setting, though access to them is variable across the country. This article examines the importance of rehabilitation in the management and outcome of pediatric TBI, recognizing that there is substantial room for growth in rehabilitation services, as well as a need for further research that examines the benefits of rehabilitation on outcomes in all categories of TBI and at many time points along the continuum of care.

Depression and Depressive Symptoms in Pediatric Traumatic Brain Injury: A Scoping Review.

This scoping review aimed to summarize the existing knowledge base regarding depression and depressive symptoms in pediatric traumatic brain injury (TBI) and to identify gaps in the literature in an effort to guide future research. MEDLINE Ovid and PsycINFO Ovid databases were each searched by the authors using search terms intended to identify any original research study that examined depressive symptoms in children (ie, aged 0-18 years) with TBI. A total of 14 published studies were included in the review. The studies included examined the prevalence of depression, risk factors associated with depression, and depression as a predictor of other TBI-related outcomes. Existing research suggests that depressive symptoms are more common in a TBI population than in a healthy or orthopedically injured population. Injury-related factors such as lesions in the brain and the presence of pain, as well as noninjury factors such as older age at injury and low socioeconomic status, may be predictive of depressive symptoms. Depression is likely a secondary outcome of pediatric TBI rather than a direct result of the injury itself. Overall, a relative dearth of research exists on this topic; thus, the review concludes by proposing future research directions.

Intensive care treatments associated with favorable discharge outcomes in Argentine children with severe traumatic brain injury: For the South American Guideline Adherence Group.

ObjectiveLittle is known about the critical care management of children with traumatic brain injury (TBI) in low middle income countries. We aimed to identify indicators of intensive care unit (ICU) treatments associated with favorable outcomes in Argentine children with severe TBI.MethodsWe conducted a secondary analysis of data from patients previously enrolled in a prospective seven center study of children with severe TBI who were admitted to an ICU in one of the seven study centers. Severe TBI was defined by head AIS ≥ 3, head CT with traumatic lesion, and admission GCS < 9. Seven indicators of best practice TBI care were examined. The primary outcome was discharge Pediatric Cerebral Performance Category Scale [PCPC] and Pediatric Overall Performance category Scale [POPC]. We also examined variation in ICU care and in-patient mortality.ResultsOf the 117 children, 67% were male and 7.5 (4.3) years on average, 92% had isolated TBI. Hypotension (54%) was more common than hypoxia (28%) and clinical or radiographic signs of high intracranial pressure (ICP) were observed in 92%. Yet, ICP monitoring occurred in 60% and hyperosmolar therapy was used in only 36%. Adherence to indicators of best TBI practice ranged from 55.6% to 83.7% across the seven centers and adherence was associated with favorable discharge PCPC (aRR 0.98; 95% CI [0.96, 0.99]), and POPC (aRR 0.98; 95% CI [0.96, 0.99]). Compared to patients whose adherence rates were below 65%, patients whose adherence rates were higher between 75%-100% had better discharge PCPC (aRR 0.28; 95% CI [0.10, 0.83]) and POPC (aRR 0.32; 95% CI [0.15, 0.73]. Two indicators were associated with favorable discharge PCPC: Avoidance of hypoxia (aRR 0.46; 95% CI [0.23, 0.93]), and Nutrition started in 72 hours (aRR 0.45; 95% CI [0.21, 0.99]). Avoiding hypoxia was also associated with favorable discharge POPC (aRR 0.47; 95% CI [0.22, 0.99]).ConclusionThere is variation in Argentine ICU practice in the care of children with severe TBI. Second insults are common and hyperosmolar therapy use is uncommon. Adherence to best practice TBI care by avoiding hypoxia and providing timely nutrition were associated with significantly favorable discharge outcomes. Implementing strategies that prevent hypoxia and facilitate early nutrition in the ICUs are urgently needed to improve pediatric TBI outcomes.

Examining Emergency Department Treatment Processes in Severe Pediatric Traumatic Brain Injury.

In the treatment of pediatric traumatic brain injury (TBI), timely treatment of patients can affect the outcome. Our objectives were to examine the treatment process of acute pediatric TBI and the impact of non-value-added time (NVAT) on patient outcomes. Data for 136 pediatric trauma patients (age < 18 years) with severe TBI from 2 trauma centers in the United States were collected. A process flow and value stream map identified NVATs and their sources in the treatment process. Cluster and regression analysis were used to examine the relationship between NVAT, as a percentage of the patient's length of stay (LOS), and the patient outcome, measured by their corresponding Glasgow outcome scale. There were 14 distinct sources of NVAT identified. A regression analysis showed that increased NVAT was associated with less favorable outcomes (relative ratio = 1.015, confidence interval = [1.002-1.029]). Specifically, 1% increase in the NVAT-to-LOS ratio was associated with a 1.5% increase in the chance of a less favorable outcome (i.e., death or vegetative state). The NVAT has a significant impact on the outcome of pediatric TBI, and every minute spent on performing non-value-added processes can lead to an increase in the likelihood of less favorable outcomes.

Continuous electroencephalography in pediatric traumatic brain injury: Seizure characteristics and outcomes.

Traumatic brain injury (TBI) is a major cause of pediatric morbidity and mortality. Secondary injury that occurs as a result of a direct impact plays a crucial role in patient prognosis. The guidelines for the management of severe TBI target treatment of secondary injury. Posttraumatic seizure, one of the secondary injury sequelae, contributes to further damage to the injured brain. Continuous electroencephalography (cEEG) helps detect both clinical and subclinical seizure, which aids early detection and prompt treatment. The aim of this study was to examine the relationship between cEEG findings in pediatric traumatic brain injury and neurocognitive/functional outcomes. This study focuses on a subgroup of a larger prospective parent study that examined children admitted to a level-1 trauma hospital. The subgroup included sixteen children admitted to the pediatric intensive care unit (PICU) who received cEEG monitoring. Characteristics included demographics, cEEG reports, and antiseizure medication. We also examined outcome scores at the time of discharge and 4-6weeks postdischarge using the Glasgow Outcome Scale - Extended Pediatrics and center-based speech pathology neurocognitive/functional evaluation scores. Sixteen patients were included in this study. Patients with severe TBI made up the majority of those that received cEEG monitoring. Nonaccidental trauma was the most frequent TBI etiology (75%), and subdural hematoma was the most common lesion diagnosed by CT scan (75%). Fifteen patients received antiseizure medication, and levetiracetam was the medication of choice. Four patients (25%) developed seizures during PICU admission, and 3 patients had subclinical seizures that were detected by cEEG. One of these patients also had both a clinical and subclinical seizure. Nonaccidental trauma was an etiology of TBI in all patients with seizures. Characteristics of a nonreactive pattern, severe/burst suppression, and lack of sleep architecture, on cEEG, were associated with poor neurocognitive/functional outcome. Continuous electroencephalography demonstrated a pattern that associated seizures and poor outcomes in patients with moderate to severe traumatic brain injury, particularly in a subgroup of patients with nonaccidental trauma. Best practice should include institution-based TBI cEEG protocols, which may detect seizure activity early and promote outcomes. Future studies should include examination of individual cEEG characteristics to help improve outcomes in pediatric TBI.

Variation in Pediatric Traumatic Brain Injury Outcomes in the United States

ObjectiveTo ascertain the degree of variation, by state of hospitalization, in outcomes associated with traumatic brain injury (TBI) in a pediatric population. DesignA retrospective cohort study of pediatric patients admitted to a hospital with a TBI. SettingHospitals from states in the United States that voluntarily participate in the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. ParticipantsPediatric (age ≤19y) patients hospitalized for TBI (N=71,476) in the United States during 2001, 2004, 2007, and 2010. InterventionsNone. Main Outcome MeasuresPrimary outcome was proportion of patients discharged to rehabilitation after an acute care hospitalization among alive discharges. The secondary outcome was inpatient mortality. ResultsThe relative risk of discharge to inpatient rehabilitation varied by as much as 3-fold among the states, and the relative risk of inpatient mortality varied by as much as nearly 2-fold. In the United States, approximately 1981 patients could be discharged to inpatient rehabilitation care if the observed variation in outcomes was eliminated. ConclusionsThere was significant variation between states in both rehabilitation discharge and inpatient mortality after adjusting for variables known to affect each outcome. Future efforts should be focused on identifying the cause of this state-to-state variation, its relationship to patient outcome, and standardizing treatment across the United States.

Behavioral and Cognitive Predictors of Educational Outcomes in Pediatric Traumatic Brain Injury

Research reveals mixed results regarding the utility of standardized cognitive and academic tests to predict educational outcomes in youth following a traumatic brain injury (TBI). Yet, deficits in everyday school-based outcomes are prevalent after pediatric TBI. The current study used path modeling to test the hypothesis that parent ratings of adolescents’ daily behaviors associated with executive functioning (EF) would predict long-term functional educational outcomes following pediatric TBI, even when injury severity and patient demographics were included in the model. Furthermore, we contrasted the predictive strength of the EF behavioral ratings with that of a common measure of verbal memory. A total of 132 adolescents who were hospitalized for moderate to severe TBI were recruited to participate in a randomized clinical intervention trial. EF ratings and verbal memory were measured within 6 months of the injury; functional educational outcomes were measured 12 months later. EF ratings and verbal memory added to injury severity in predicting educational competence post injury but did not predict post-injury initiation of special education. The results demonstrated that measurement of EF behaviors is an important research and clinical tool for prediction of functional outcomes in pediatric TBI.

Towards Development of a Survival Prediction Tool for Pediatric Head Injury

Background: The ability to provide an accurate prognosis for children with traumatic brain injury (TBI) would be useful for the children’s families and the caregivers. In this study we examined whether an appropriate mathematical model can predict survival in this patient population. Methods: Data from the Children’s Hospital of Eastern Ontario (CHEO) TBI registry was analyzed. First, a series of univariate logistic regressions was performed to ascertain the significance of individual predictors, such as age, maximum Glasgow Coma Scale (GCS) score, maximum head injury Abbreviated Injury Scores (AIS) and the Injury Severity Score (ISS). Second, a multinomial logistic regression was fitted using only individually significant predictors and inmodel predictor significance, and interactions were tested. Only two significant predictors were kept in the final model. This final model was subsequently used to predict survival for each individual patient using the n-1 training set (i.e. Lachenbruch’s leave-one-out method). The receiver operating characteristics (ROC) method was used to ascertain specificity-sensitivity trade-offs at different probability cut-offs in order to predict survival. Results: Only the maximum GCS and head injury AIS remained significant, both individually and in the polynomial logistic regression. Empiric ROC curve analyses from leave-one-out survival predictions showed statistical significance (area under the curve = 0.87, Z = 6.8, p < 0.001). Only 12% of cases were misclassified using the ‘best’ cut-off. Conclusion: An outcome predictive model for pediatric TBI can be devised using an appropriate mathematical model. It may help to estimate expected outcomes in pediatric TBI more objectively.

Chapter 4. Threshold for treatment of intracranial hypertension

Chapter 4. Threshold for treatment of intracranial hypertension

Demographic and Injury-Related Moderators of Memory and Achievement Outcome in Pediatric TBI

Critical factors affecting traumatic brain injury (TBI) outcome in children and adolescents are explored with an emphasis on an examination of age at injury as a predictor of memory functioning. Age at injury and other injury-related and demographic predictors (i.e., severity, time postinjury, gender, and socioeconomic status [SES]) of memory and achievement outcome were examined in 65 children and adolescents post-TBI compared to 65 age-matched noninjured controls. Although robust findings have been found for age at injury as a general predictor of outcome, age was not found to be a significant predictor of memory functioning following pediatric TBI. Structural equation modeling suggests that the most parsimonious model of post-TBI outcome contains two causally related latent variables: one defined by gender, SES, injury severity, and age at injury, and one defined by general cognitive functioning.

Recommendations for the use of common outcome measures in pediatric traumatic brain injury research.

This article addresses the need for age-relevant outcome measures for traumatic brain injury (TBI) research and summarizes the recommendations by the inter-agency Pediatric TBI Outcomes Workgroup. The Pediatric Workgroup's recommendations address primary clinical research objectives including characterizing course of recovery from TBI, prediction of later outcome, measurement of treatment effects, and comparison of outcomes across studies. Consistent with other Common Data Elements (CDE) Workgroups, the Pediatric TBI Outcomes Workgroup adopted the standard three-tier system in its selection of measures. In the first tier, core measures included valid, robust, and widely applicable outcome measures with proven utility in pediatric TBI from each identified domain including academics, adaptive and daily living skills, family and environment, global outcome, health-related quality of life, infant and toddler measures, language and communication, neuropsychological impairment, physical functioning, psychiatric and psychological functioning, recovery of consciousness, social role participation and social competence, social cognition, and TBI-related symptoms. In the second tier, supplemental measures were recommended for consideration in TBI research focusing on specific topics or populations. In the third tier, emerging measures included important instruments currently under development, in the process of validation, or nearing the point of published findings that have significant potential to be superior to measures in the core and supplemental lists and may eventually replace them as evidence for their utility emerges.

Cerebrovascular Pathophysiology in Pediatric Traumatic Brain Injury

Traumatic brain injury (TBI) is the leading cause of traumatic morbidity and mortality in children. Although there is increasing information concerning TBI in adults and experimental animal models, relatively little is known regarding cerebrovascular pathophysiology specific to children. A review of the pertinent medical literature. Systemic and cerebral hemodynamic factors such as hypotension, hypoxia, hyperglycemia, and fever are associated with poor outcome in pediatric TBI. Similarly, cerebral autoregulation is often impaired after TBI and may adversely affect outcome, especially if systemic hemodynamics are altered. Furthermore, CO2 vasoreactivity may be altered after pediatric TBI and lead to either cerebral ischemia or hyperemia. Understanding the effect of pediatric TBI on the cerebral circulation is needed to potentially develop protocols to improve outcome in this vulnerable population. Specifically, changes in pediatric cerebrovascular physiology and pathophysiology, including CO2 vasoreactivity and pressure autoregulation, must be understood and their mechanism elucidated.