A growth chart of brain function from infancy to adolescence based on EEG.

BACKGROUND: In children, objective, quantitative tools that determine functional neurodevelopment are scarce and rarely scalable for clinical use. Direct recordings of cortical activity using routinely acquired electroencephalography (EEG) offer reliable measures of brain function. METHODS: We developed and validated a measure of functional brain age (FBA) using a residual neural network-based interpretation of the paediatric EEG. In this cross-sectional study, we included 1056 children with typical development ranging in age from 1 month to 18 years. We analysed a 10- to 15-min segment of 18-channel EEG recorded during light sleep (N1 and N2 states). FINDINGS: The FBA had a weighted mean absolute error (wMAE) of 0.85 years (95% CI: 0.69-1.02; n = 1056). A two-channel version of the FBA had a wMAE of 1.51 years (95% CI: 1.30-1.73; n = 1056) and was validated on an independent set of EEG recordings (wMAE = 2.27 years, 95% CI: 1.90-2.65; n = 723). Group-level maturational delays were also detected in a small cohort of children with Trisomy 21 (Cohen's d = 0.36, p = 0.028). INTERPRETATION: A FBA, based on EEG, is an accurate, practical and scalable automated tool to track brain function maturation throughout childhood with accuracy comparable to widely used physical growth charts. FUNDING: This research was supported by the National Health and Medical Research Council, Australia, Helsinki University Diagnostic Center Research Funds, Finnish Academy, Finnish Paediatric Foundation, and Sigrid Juselius Foundation.

'Baby Liberation' - Developing and implementing an individualised, developmentally-supportive care bundle to critically unwell infants in an Australian Paediatric Intensive Care Unit.

BACKGROUND: Infants requiring high acuity care within a Paediatric Intensive Care Unit are at multifactorial risk of neurological injury to the immature brain, resulting in long-term developmental difficulties. In 2020, Queensland Children's Hospital implemented an individualised family-centred developmental care program, 'Baby Liberation', to address an identified service gap for critically unwell infants, aimed at optimising early neuroprotective strategies and minimising risk of suboptimal developmental outcomes. AIM: To implement Baby Liberation for infants admitted to a quaternary paediatric intensive care referral centre. Secondary aims were to describe environmental changes, enablers and limitations related to implementation. STUDY DESIGN: A single-centre, prospective implementation pilot study investigated the feasibility of implementing Baby Liberation. Subjects included infants less than six months of age admitted to Queensland Children's Hospital Paediatric Intensive Care Unit. OUTCOME MEASURES: Primary measures comprised data collected during the implementation period, including number of eligible patients and number of developmental care plans provided. Environmental audit data were collected pre and post implementation to inform secondary outcomes. RESULTS: Baby Liberation was feasibly implemented into the Queensland Children's Hospital Paediatric Intensive Care Unit. During implementation, 181 individualised care plans were provided to 313 eligible infants (57.8 %). Environmental audits showed improvements in all areas of developmental care, with greatest improvements noted in pain and stress management (+95 %) and staff support and development (+83.3 %). CONCLUSION: Implementation of Baby Liberation was feasible within a large quaternary paediatric intensive care unit and has potential to be expanded into other clinical areas providing acute infant care.

Tenecteplase in Pediatric Stroke: Ready or Not.

BACKGROUND: Intravenous thrombolysis with tissue plasminogen activator is used for off-label treatment of acute childhood stroke. Tenecteplase (TNK) is used to treat acute stroke in adults at many institutions, although there are extremely few data about TNK use in children. We aimed to characterize pediatric stroke experts' experience and preferences with regard to TNK use in children with stroke. METHODS: Online survey distributed to members of the International Pediatric Stroke Organization in April 2023. RESULTS: We received 33 responses. Most (81.2%) respondents reported only being "a little familiar" or "somewhat familiar" with TNK. Only six (18%) respondents reported being "familiar" or "very familiar" with TNK. Seventy percent of respondents were willing to treat pediatric stroke with TNK, at least in some situations. In a hypothetical scenario of a child in an outside emergency room with only TNK available, 81.8% would consider recommending treatment with TNK. However, only three (9.1%) respondents had TNK in their stroke protocol and seven (21.2%) had TNK on formulary at their hospital. Two respondents reported direct awareness of a child treated with TNK. CONCLUSIONS: The majority of pediatric stroke neurologists responding to this survey reported a willingness to consider TNK use in children. However, data on TNK use in children, provider experience, and pediatric hospital preparedness are limited.

Implementing paediatric appropriate use criteria for endotracheal suction to reduce complications in mechanically ventilated children with respiratory infections.

BACKGROUND: Endotracheal suction is used to maintain endotracheal tube patency. There is limited guidance to inform clinical practice for children with respiratory infections. OBJECTIVE: The objective of this study was to determine whether implementation of a paediatric endotracheal suction appropriate use guideline Paediatric AirWay Suction (PAWS) is associated with an increased use of appropriate and decreased use of inappropriate suction interventions. METHODS: A mixed-method, pre-implementation-post-implementation study was conducted between September 2021 and April 2022. Suction episodes in mechanically ventilated children with a respiratory infection were eligible. Using a structured approach, we implemented the PAWS guideline in a single paediatric intensive care unit. Evaluation included clinical (e.g., suction intervention appropriateness), implementation (e.g., acceptability), and cost outcomes (implementation costs). Associations between implementation of the PAWS guideline and appropriateness of endotracheal suction intervention use were investigated using generalised linear models. RESULTS: Data from 439 eligible suctions were included in the analysis. Following PAWS implementation, inappropriate endotracheal tube intervention use reduced from 99% to 58%, an absolute reduction (AR) of 41% (95% confidence interval [CI]: 25%, 56%). Reductions were most notable for open suction systems (AR: 48%; 95% CI: 30%, 65%), 0.9% sodium chloride use (AR: 23%; 95% CI: 8%, 38%) and presuction and postsuction manual bagging (38%; 95% CI: 16%, 60%, and 86%; 95% CI: 73%, 99%), respectively. Clinicians perceived PAWS as acceptable and suitable for use. CONCLUSIONS: Implementation of endotracheal tube suction appropriate use guidelines in a mixed paediatric intensive care unit was associated with a large reduction in inappropriate suction intervention use in paediatric patients with respiratory infections.

Optimization of time series features to estimate brain age in children from electroencephalography.

Functional brain age measures in children, derived from the electroencephalogram (EEG), offer direct and objective measures in assessing neurodevelopmental status. Here we explored the effectiveness of 32 preselected 'handcrafted' EEG features in predicting brain age in children. These features were benchmarked against a large library of highly comparative multivariate time series features (>7000 features). Results showed that age predictors based on handcrafted EEG features consistently outperformed a generic set of time series features. These findings suggest that optimization of brain age estimation in children benefits from careful preselection of EEG features that are related to age and neurodevelopmental trajectory. This approach shows potential for clinical translation in the future.Clinical Relevance-Handcrafted EEG features provide an accurate functional neurodevelopmental biomarker that tracks brain function maturity in children.

Continuous electroencephalography in the intensive care unit: A critical review and position statement from an Australian and New Zealand perspective.

Objectives: This article aims to critically review the literature on continuous electroencephalography (cEEG) monitoring in the intensive care unit (ICU) from an Australian and New Zealand perspective and provide recommendations for clinicians. Design and review methods: A taskforce of adult and paediatric neurologists, selected by the Epilepsy Society of Australia, reviewed the literature on cEEG for seizure detection in critically ill neonates, children, and adults in the ICU. The literature on routine EEG and cEEG for other indications was not reviewed. Following an evaluation of the evidence and discussion of controversial issues, consensus was reached, and a document that highlighted important clinical, practical, and economic considerations regarding cEEG in Australia and New Zealand was drafted. Results: This review represents a summary of the literature and consensus opinion regarding the use of cEEG in the ICU for detection of seizures, highlighting gaps in evidence, practical problems with implementation, funding shortfalls, and areas for future research. Conclusion: While cEEG detects electrographic seizures in a significant proportion of at-risk neonates, children, and adults in the ICU, conferring poorer neurological outcomes and guiding treatment in many settings, the health economic benefits of treating such seizures remain to be proven. Presently, cEEG in Australian and New Zealand ICUs is a largely unfunded clinical resource that is subsequently reserved for the highest-impact patient groups. Wider adoption of cEEG requires further research into impact on functional and health economic outcomes, education and training of the neurology and ICU teams involved, and securement of the necessary resources and funding to support the service.

CSF neopterin and quinolinic acid are biomarkers of neuroinflammation and neurotoxicity in FIRES and other infection-triggered encephalopathy syndromes.

OBJECTIVE: Infection-triggered encephalopathy syndromes (ITES) are potentially devastating neuroinflammatory conditions. Although some ITES syndromes have recognisable MRI neuroimaging phenotypes, there are otherwise few biomarkers of disease. Early detection to enable immune modulatory treatments could improve outcomes. METHODS: We measured CSF neopterin, quinolinic acid, kynurenine and kynurenine/tryptophan ratio using a liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) system. The CSF of 18 children with ITES were compared with acute encephalitis (n = 20), and three control groups, namely epilepsy (n = 20), status epilepticus (n = 18) and neurogenetic controls (n = 20). RESULTS: The main ITES phenotypes in 18 patients were acute encephalopathy with biphasic seizures and late restricted diffusion (AESD, n = 4), febrile infection-related epilepsy syndrome (FIRES n = 4) and other ITES phenotypes. Influenza A was the most common infectious trigger (n = 5), and 50% of patients had a preceding notable neurodevelopmental or family history. CSF neopterin, quinolinic acid and kynurenine were elevated in ITES group compared to the three control groups (all p < 0.0002). The ROC (area under curve) for CSF neopterin (99.3%, CI 98.1-100) was significantly better than CSF pleocytosis (87.3% CI 76.4-98.2) (p = 0.028). Elevated CSF neopterin could discriminate ITES from other causes of seizures, status epilepticus and febrile status epilepticus (all p < 0.0002). The elevated CSF metabolites normalised during longitudinal testing in two patients with FIRES. INTERPRETATION: CSF neopterin and quinolinic acid are neuroinflammatory and excitotoxic metabolites. This CSF metabolomic inflammatory panel can discriminate ITES from other causes of new onset seizures or status epilepticus, and rapid results (4 h) may facilitate early immune modulatory therapy.

Tenecteplase in Acute Stroke: What About the Children?

Tenecteplase is replacing alteplase as the fibrinolytic agent of choice for the acute management of ischemic stroke in many adult stroke centers due to practical and pharmacokinetic advantages in the setting of similar outcomes. Although thrombolytic use is increasing for acute childhood stroke, there is very limited experience with tenecteplase in children for any indication, and importantly, there are no data on safety, dosing, or efficacy of tenecteplase for childhood stroke. Changes in fibrinolytic capacity over childhood, pediatric pharmacological considerations such as age-specific differences in drug clearance and volume of distribution, and practical aspects of drug delivery such as availability in children's hospitals may impact decisions about transitioning from alteplase to tenecteplase for acute pediatric stroke treatment. Pediatric and adult neurologists should prepare institution-specific guidelines and organize prospective data collection.

Consensus-Based Evaluation of Outcome Measures in Pediatric Stroke Care: A Toolkit.

Following a pediatric stroke, outcome measures selected for monitoring functional recovery and development vary widely. We sought to develop a toolkit of outcome measures that are currently available to clinicians, possess strong psychometric properties, and are feasible for use within clinical settings. A multidisciplinary group of clinicians and scientists from the International Pediatric Stroke Organization comprehensively reviewed the quality of measures in multiple domains described in pediatric stroke populations including global performance, motor and cognitive function, language, quality of life, and behavior and adaptive functioning. The quality of each measure was evaluated using guidelines focused on responsiveness and sensitivity, reliability, validity, feasibility, and predictive utility. A total of 48 outcome measures were included and were rated by experts based on the available evidence within the literature supporting the strengths of their psychometric properties and practical use. Only three measures were found to be validated for use in pediatric stroke: the Pediatric Stroke Outcome Measure, the Pediatric Stroke Recurrence and Recovery Questionnaire, and the Pediatric Stroke Quality of Life Measure. However, multiple additional measures were deemed to have good psychometric properties and acceptable utility for assessing pediatric stroke outcomes. Strengths and weaknesses of commonly used measures including feasibility are highlighted to guide evidence-based and practicable outcome measure selection. Improving the coherence of outcome assessment will facilitate comparison of studies and enhance research and clinical care in children with stroke. Further work is urgently needed to close the gap and validate measures across all clinically significant domains in the pediatric stroke population.

Ventilator weaning and extubation practices in critically ill children: An Australian and New Zealand survey of practice.

OBJECTIVES: We aimed to (i) describe current weaning and extubation practices in children (protocols to identify weaning candidates, spontaneous breathing trials, and other aspects of care such as sedation weaning) and (ii) understand responsibilities for ventilation weaning decisions across Australia and New Zealand (ANZ). METHODS: A cross-sectional survey of ANZ intensive care units who routinely intubate and ventilate children (<18 years) was conducted. We worked with the Australian and New Zealand Intensive Care Society Paediatric Study Group to identify units and potential respondents (senior nurse representative per unit) and to administer questionnaires. Survey questions (n = 35) examined current protocols, practices, unit staffing, and decision-making responsibilities for ventilation weaning and extubation. Open-ended questions examined respondents' experiences of weaning and extubation. RESULTS: A senior nursing respondent from 18/22 intensive care units (82%) completed the survey. Across units, most used sedation assessment tools (88%), and less often, sedation weaning tools (55%). Spontaneous awakening protocols were not used; one unit (5%) reported the use of a spontaneous breathing protocol. Two respondents reported that ventilation weaning protocols (11%) were in use, with 44% of units reporting the use of extubation protocols. Weaning and extubation practices were largely perceived as medically driven, with qualitative data demonstrating a desire from most respondents for greater shared decision-making. CONCLUSION: In ANZ, ventilation weaning and extubation practices are largely medically driven with variation in the use of protocols to support mechanical ventilation weaning and extubation in children. Our findings highlight the importance of future research to determine the impact of greater collaboration of the multidisciplinary team on weaning practices.

Brain-Directed Care: Why Neuroscience Principles Direct PICU Management beyond the ABCs.

Major advances in pediatric intensive care (PICU) have led to increased child survival. However, the long-term outcomes among these children following PICU discharge are a concern. Most children admitted to PICU are under five years of age, and the stressors of critical illness and necessary interventions can affect their ability to meet crucial developmental milestones. Understanding the neuroscience of brain development and vulnerability can inform PICU clinicians of new ways to enhance and support the care of these most vulnerable children and families. This review paper first explores the evidence-based neuroscience principles of brain development and vulnerability and the impact of illness and care on children's brains and ultimately wellbeing. Implications for clinical practice and training are further discussed to help optimize brain health in children who are experiencing and surviving a critical illness or injury.

Pediatric Moyamoya Biomarkers: Narrowing the Knowledge Gap.

Moyamoya is a progressive cerebrovascular disorder that leads to stenosis of the arteries in the distal internal carotid, proximal middle cerebral and proximal anterior cerebral arteries of the circle of Willis. Typically a network of collaterals form to bypass the stenosis and maintain cerebral blood flow. As moyamoya progresses it affects the anterior circulation more commonly than posterior circulation, and cerebral blood flow becomes increasingly reliant on external carotid supply. Children with moyamoya are at increased risk for ischemic symptoms including stroke and transient ischemic attacks (TIA). In addition, cognitive decline may occur over time, even in the absence of clinical stroke. Standard of care for stroke prevention in children with symptomatic moyamoya is revascularization surgery. Treatment of children with asymptomatic moyamoya with revascularization surgery however remains more controversial. Therefore, biomarkers are needed to assist with not only diagnosis but also with determining ischemic risk and identifying best surgical candidates. In this review we will discuss the current knowledge as well as gaps in research in relation to pediatric moyamoya biomarkers including neurologic presentation, cognitive, neuroimaging, genetic and biologic biomarkers of disease severity and ischemic risk.

Closing the Gap in Pediatric Hemorrhagic Stroke: A Systematic Review.

Pediatric hemorrhagic stroke (HS) accounts for a large proportion of childhood strokes, 1 of the top 10 causes of pediatric deaths. Morbidity and mortality lead to significant socio-economic and psychosocial burdens. To understand published data on recognizing and managing children with HS, we conducted a systematic review of the literature presented here. We searched PubMed, Embase, CINAHL and the Cochrane Library databases limited to English language and included 174 studies, most conducted in the USA (52%). Terminology used interchangeably for HS included intraparenchymal/intracranial hemorrhage, spontaneous ICH, and cerebrovascular accident (CVA). Key assessments informing prognosis and management included clinical scoring (Glasgow coma scale), and neuroimaging. HS etiologies reported were systemic coagulopathy (genetic, acquired pathologic, or iatrogenic), or focal cerebrovascular lesions (brain arteriovenous malformations, cavernous malformations, aneurysms, or tumor vascularity). Several scales were used to measure outcome: Glasgow outcome score (GOS), Kings outcome score for head injury (KOSCHI), modified Rankin scale (mRS) and pediatric stroke outcome measure (PSOM). Most studies described treatments of at-risk lesions. Few studies described neurocritical care management including raised ICP, seizures, vasospasm, or blood pressure. Predictors of poor outcome included ethnicity, comorbidity, location of bleed, and hematoma >2% of total brain volume. Motor and cognitive outcomes followed independent patterns. Few studies reported on cognitive outcomes, rehabilitation, and transition of care models. Interdisciplinary approach to managing HS is urgently needed, informed by larger cohort studies targeting key clinical question (eg development of a field-guide for the clinician managing patients with HS that is reproducible internationally).

Real-time seizure detection in paediatric intensive care patients: the RESET child brain protocol.

INTRODUCTION: Approximately 20%-40% of comatose children with risk factors in intensive care have electrographic-only seizures; these go unrecognised due to the absence of continuous electroencephalography (EEG) monitoring (cEEG). Utility of cEEG with high-quality assessment is currently limited due to high-resource requirements. New software analysis tools are available to facilitate bedside cEEG assessment using quantitative EEG (QEEG) trends. The primary aim of this study is to describe accuracy of interpretation of QEEG trends by paediatric intensive care unit (PICU) nurses compared with cEEG assessment by neurologist (standard clinical care) in children at risk of seizures and status epilepticus utilising diagnostic test statistics. The secondary aims are to determine time to seizure detection for QEEG users compared with standard clinical care and describe impact of confounders on accuracy of seizure detection. METHODS AND ANALYSIS: This will be a single-centre, prospective observational cohort study evaluating a paediatric QEEG programme utilising the full 19 electrode set. The setting will be a 36-bed quaternary PICU with medical, cardiac and general surgical cases. cEEG studies in PICU patients identified as 'at risk of seizures' will be analysed. Trained bedside clinical nurses will interpret the QEEG. Seizure events will be marked as seizures if >3 QEEG criteria occur. Post-hoc dedicated neurologists, who remain blinded to the QEEG analysis, will interpret the cEEG. Determination of standard test characteristics will assess the primary hypothesis. To calculate 95% (CIs) around the sensitivity and specificity estimates with a CI width of 10%, the sample size needed for sensitivity is 80 patients assuming each EEG will have approximately 9 to 18 1-hour epochs. ETHICS AND DISSEMINATION: The study has received approval by the Children's Health Queensland Human Research Ethics Committee (HREC/19/QCHQ/58145). Results will be made available to the funders, critical care survivors and their caregivers, the relevant societies, and other researchers. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) 12621001471875.

The Paediatric AirWay Suction (PAWS) appropriateness guide for endotracheal suction interventions.

BACKGROUND/OBJECTIVE: Endotracheal suction is an invasive and potentially harmful technique used for airway clearance in mechanically ventilated children. Choice of suction intervention remains a complex and variable process. We sought to develop appropriate use criteria for endotracheal suction interventions used in paediatric populations. METHODS: The RAND Corporation and University of California, Los Angeles Appropriateness Method was used to develop the Paediatric AirWay Suction appropriateness guide. This included defining key terms, synthesising current evidence, engaging an expert multidisciplinary panel, case scenario development, and two rounds of appropriateness ratings (weighing harm with benefit). Indications (clinical scenarios) were developed from common applications or anticipated use, current practice guidelines, clinical trial results, and expert consultation. RESULTS: Overall, 148 (19%) scenarios were rated as appropriate (benefit outweighs harm), 542 (67%) as uncertain, and 94 (11%) as inappropriate (harm outweighs benefit). Disagreement occurred in 24 (3%) clinical scenarios, namely presuction and postsuction bagging across populations and age groups. In general, the use of closed suction was rated as appropriate, particularly in the subspecialty population 'patients with highly infectious respiratory disease'. Routine application of 0.9% saline for nonrespiratory indications was more likely to be inappropriate/uncertain than appropriate. Panellists preferred clinically indicated suction versus routine suction in most circumstances. CONCLUSION: Appropriate use criteria for endotracheal suction in the paediatric intensive care have the potential to impact clinical decision-making, reduce practice variability, and improve patient outcomes. Furthermore, recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research.

Appropriate use criteria for endotracheal suction interventions in mechanically ventilated children: The RAND/UCLA development process.

OBJECTIVES: Endotracheal suction is an invasive airway clearance technique used in mechanically ventilated children. This article outlines the methods used to develop appropriate use criteria for endotracheal suction interventions in mechanically ventilated paediatric patients. METHODS: The RAND Corporation and University of California, Los Angeles Appropriateness Method was used to develop paediatric appropriate use criteria. This included the following sequential phases of defining scope and key terms, a literature review and synthesis, expert multidisciplinary panel selection, case scenario development, and appropriateness ratings by an interdisciplinary expert panel over two rounds. The panel comprised experts in the fields of paediatric and neonatal intensive care, respiratory medicine, infectious diseases, critical care nursing, implementation science, retrieval medicine, and education. Case scenarios were developed iteratively by interdisciplinary experts and derived from common applications or anticipated intervention uses, as well as from current clinical practice guidelines and results of studies examining interventions efficacy and safety. Scenarios were rated on a scale of 1 (harm outweighs benefit) to 9 (benefit outweighs harm), to define appropriate use (median: 7 to 9), uncertain use (median: 4 to 6), and inappropriate use (median: 1 to 3) of endotracheal suction interventions. Scenarios were than classified as a level of appropriateness. CONCLUSIONS: The RAND Corporation/University of California, Los Angeles Appropriateness Method provides a thorough and transparent method to inform development of the first appropriate use criteria for endotracheal suction interventions in paediatric patients.

Evaluation of an educational video providing key messages for doctors to counsel families following a first afebrile seizure.

AIM: The aim was to evaluate an educational video in educating doctors on the key messages and follow-up pathways following a first afebrile seizure presentation. A multidisciplinary expert team developed the video (http://www.pennsw.org.au/families/resources/first-seizure-pack-and-video) based on available evidence and best-practice. It contains a role-play between the parent/child and physician. It addresses: key messages to impart following a first seizure, seizure first aid, safety messages including necessary precautions post-discharge, contents of the First Seizure Pack for families, follow-up pathway and issues for discussion with the paediatrician at a later appointment. METHODS: Paediatric/Emergency department (ED) trainees across three Australian sites were recruited during terms 1 and 2, 2019. A repeated measures design was used. Multilevel modelling analyses were performed. The primary outcome was clinician knowledge. Secondary outcomes were confidence in answering questions and counselling families. Qualitative data on the utility, strengths and weaknesses of the video were evaluated. RESULTS: A total of 127 participants consented, one withdrew prior to commencing. A total of 126 baseline surveys, 115 follow-up surveys and 45 1-month follow-up surveys were returned. Viewing the video significantly improved knowledge of key messages at immediate follow-up (P < 0.001) and 1-month follow-up (P = 0.048). Likewise, confidence was significantly improved; 96.5% of responders found the video useful, 90.3% were likely to use the resource in the future and 82% would change their approach to counselling. Most liked aspects of the resource were clarity/conciseness of the information (n = 70) and comprehensiveness (n = 38). CONCLUSION: This education video significantly improved clinician knowledge and confidence in counselling families following first seizure.

Predicting Neurological Recovery after Traumatic Brain Injury in Children: A Systematic Review of Prognostic Models.

Predictive modeling is foundational to treatment and long-term management of children with traumatic brain injury (TBI). Assessment of injury severity in the acute-care setting enables early stratification of patients based on their risk of death, lifelong disability, or unfavorable outcome. This review evaluates predictive models that have been developed or validated for pediatric TBI patients. The predictive accuracy of these models, the outcomes and time points predicted, and the variables and statistical methods utilized in model development were compared. Embase, Scopus, MEDLINE®, and Web of Science were searched for studies that developed statistical models for predicting patient outcomes following pediatric TBI. Studies were excluded if they focused on adults or non-traumatic brain injury, or if they did not assess classification accuracy. A total of 4538 entries were identified and screened, with 7 studies included for analysis. This included five studies in which adult predictive models were validated for use in the pediatric setting, and two in which new models were derived from a pediatric cohort. Trials of adult prediction tools in pediatric cohorts, including the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) and Corticoid Randomisation After Significant Head Injury (CRASH)-TBI models, showed comparable accuracy between classification of adults and children. Models derived from pediatric cohorts showed improved accuracy. Most studies solely focused on clinical variables, with two studies incorporating biochemical and imaging variables. Predictive models for pediatric TBI are primarily based on methods and variables identified in adult studies. Although adult models have proven effective in select pediatric cohorts, they may be suboptimal when compared with models derived or adjusted for children.

Acute Hemorrhagic Leukoencephalopathy: Pathological Features and Cerebrospinal Fluid Cytokine Profiles.

BACKGROUND: Acute hemorrhagic leukoencephalopathy is a rare encephalopathy of unknown etiology, causing fulminant, hemorrhagic central nervous system demyelination with high mortality. It is unclear whether acute hemorrhagic leukoencephalopathy is an entirely distinct entity from acute disseminated encephalomyelitis. PATIENTS AND METHODS: We report two patients with rapidly progressive neurological illness resulting in raised intracranial pressure and coma, with biopsy-proven acute hemorrhagic leukoencephalopathy (perivascular hemorrhages and demyelination, predominantly neutrophil infiltrates). RESULTS: Acute cerebrospinal fluid showed pronounced T cell-associated cytokine elevation (interleukins 6, 8, and 17A) and CCL2 or CCL3, higher than in patients with acute disseminated encephalomyelitis, but no B cell-associated cytokine elevation. CONCLUSION: Improved understanding of the immune process may provide rationale for use of anticytokine biologic agents.