Update in Pediatric Neurocritical Care: What a Neurologist Caring for Critically Ill Children Needs to Know.

Currently nearly one-quarter of admissions to pediatric intensive care units (PICUs) worldwide are for neurocritical care diagnoses that are associated with significant morbidity and mortality. Pediatric neurocritical care is a rapidly evolving field with unique challenges due to not only age-related responses to primary neurologic insults and their treatments but also the rarity of pediatric neurocritical care conditions at any given institution. The structure of pediatric neurocritical care services therefore is most commonly a collaborative model where critical care medicine physicians coordinate care and are supported by a multidisciplinary team of pediatric subspecialists, including neurologists. While pediatric neurocritical care lies at the intersection between critical care and the neurosciences, this narrative review focuses on the most common clinical scenarios encountered by pediatric neurologists as consultants in the PICU and synthesizes the recent evidence, best practices, and ongoing research in these cases. We provide an in-depth review of (1) the evaluation and management of abnormal movements (seizures/status epilepticus and status dystonicus); (2) acute weakness and paralysis (focusing on pediatric stroke and select pediatric neuroimmune conditions); (3) neuromonitoring modalities using a pathophysiology-driven approach; (4) neuroprotective strategies for which there is evidence (e.g., pediatric severe traumatic brain injury, post-cardiac arrest care, and ischemic stroke and hemorrhagic stroke); and (5) best practices for neuroprognostication in pediatric traumatic brain injury, cardiac arrest, and disorders of consciousness, with highlights of the 2023 updates on Brain Death/Death by Neurological Criteria. Our review of the current state of pediatric neurocritical care from the viewpoint of what a pediatric neurologist in the PICU needs to know is intended to improve knowledge for providers at the bedside with the goal of better patient care and outcomes.

Recommendations for the Management of Initial and Refractory Pediatric Status Dystonicus.

Status dystonicus is the most severe form of dystonia with life-threatening complications if not treated promptly. We present consensus recommendations for the initial management of acutely worsening dystonia (including pre-status dystonicus and status dystonicus), as well as refractory status dystonicus in children. This guideline provides a stepwise approach to assessment, triage, interdisciplinary treatment, and monitoring of status dystonicus. The clinical pathways aim to: (1) facilitate timely recognition/triage of worsening dystonia, (2) standardize supportive and dystonia-directed therapies, (3) provide structure for interdisciplinary cooperation, (4) integrate advances in genomics and neuromodulation, (5) enable multicenter quality improvement and research, and (6) improve outcomes. © 2024 International Parkinson and Movement Disorder Society.

Noninvasive Neuromonitoring Modalities in Children Part I: Pupillometry, Near-Infrared Spectroscopy, and Transcranial Doppler Ultrasonography.

BACKGROUND: Noninvasive neuromonitoring in critically ill children includes multiple modalities that all intend to improve our understanding of acute and ongoing brain injury. METHODS: In this article, we review basic methods and devices, applications in clinical care and research, and explore potential future directions for three noninvasive neuromonitoring modalities in the pediatric intensive care unit: automated pupillometry, near-infrared spectroscopy, and transcranial Doppler ultrasonography. RESULTS: All three technologies are noninvasive, portable, and easily repeatable to allow for serial measurements and trending of data over time. However, a paucity of high-quality data supporting the clinical utility of any of these technologies in critically ill children is currently a major limitation to their widespread application in the pediatric intensive care unit. CONCLUSIONS: Future prospective multicenter work addressing major knowledge gaps is necessary to advance the field of pediatric noninvasive neuromonitoring.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group in the Pediatric Population.

BACKGROUND: The fundamental gap obstructing forward progress of evidenced-based care in pediatric and neonatal disorders of consciousness (DoC) is the lack of defining consensus-based terminology to perform comparative research. This lack of shared nomenclature in pediatric DoC stems from the inherently recursive dilemma of the inability to reliably measure consciousness in the very young. However, recent advancements in validated clinical examinations and technologically sophisticated biomarkers of brain activity linked to future abilities are unlocking this previously formidable challenge to understanding the DoC in the developing brain. METHODS: To address this need, the first of its kind international convergence of an interdisciplinary team of pediatric DoC experts was organized by the Neurocritical Care Society's Curing Coma Campaign. The multidisciplinary panel of pediatric DoC experts proposed pediatric-tailored common data elements (CDEs) covering each of the CDE working groups including behavioral phenotyping, biospecimens, electrophysiology, family and goals of care, neuroimaging, outcome and endpoints, physiology and big Data, therapies, and pediatrics. RESULTS: We report the working groups' pediatric-focused DoC CDE recommendations and disseminate CDEs to be used in studies of pediatric patients with DoC. CONCLUSIONS: The CDEs recommended support the vision of progressing collaborative and successful internationally collaborative pediatric coma research.

Practice Standards for the Use of Multimodality Neuromonitoring: A Delphi Consensus Process.

OBJECTIVES: To address areas in which there is no consensus for the technologies, effort, and training necessary to integrate and interpret information from multimodality neuromonitoring (MNM). DESIGN: A three-round Delphi consensus process. SETTING: Electronic surveys and virtual meeting. SUBJECTS: Participants with broad MNM expertise from adult and pediatric intensive care backgrounds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two rounds of surveys were completed followed by a virtual meeting to resolve areas without consensus and a final survey to conclude the Delphi process. With 35 participants consensus was achieved on 49% statements concerning MNM. Neurologic impairment and the potential for MNM to guide management were important clinical considerations. Experts reached consensus for the use of MNM-both invasive and noninvasive-for patients in coma with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial hemorrhage. There was consensus that effort to integrate and interpret MNM requires time independent of daily clinical duties, along with specific skills and expertise. Consensus was reached that training and educational platforms are necessary to develop this expertise and to provide clinical correlation. CONCLUSIONS: We provide expert consensus in the clinical considerations, minimum necessary technologies, implementation, and training/education to provide practice standards for the use of MNM to individualize clinical care.

Heart Rate Change as a Potential Digital Biomarker of Brain Death in Critically Ill Children With Acute Catastrophic Brain Injury.

Bedside measurement of heart rate (HR) change (HRC) may provide an objective physiologic marker for when brain death (BD) may have occurred, and BD testing is indicated in children. OBJECTIVES: To determine whether HRC, calculated using numeric HR measurements sampled every 5 seconds, can identify patients with BD among patients with catastrophic brain injury (CBI). DESIGN SETTING AND PARTICIPANTS: Single-center, retrospective study (2008-2020) of critically ill children with acute CBI. Patients with CBI had a neurocritical care consultation, were admitted to an ICU, had acute neurologic injury on presentation or during hospitalization based on clinical and/or imaging findings, and died or survived with Glasgow Coma Scale (GCS) less than 13 at hospital discharge. Patients meeting BD criteria (BD group) were compared with those with cardiopulmonary death (CD group) or those who survived to discharge. MAIN OUTCOMES AND MEASURES: HRC was calculated as the interquartile range of HR divided by median HR using 5-minute windows with 50% overlap for up to 5 days before death or end of recording. HRC was compared among the BD, CD, and survivor groups. RESULTS: Of 96 patients with CBI (69% male, median age 4 years), 28 died (8 BD, 20 CD) and 20 survived (median GCS 9 at discharge). Within 24 hours before death, HRC was lower in BD compared with CD patients or survivors (0.01 vs 0.03 vs 0.04, p = 0.001). In BD patients, HRC decreased at least 1 day before death. HRC discriminated BD from CD patients and survivors with 90% sensitivity, 70% specificity, 44% positive predictive value, 96% negative predictive value (area under the receiver operating characteristic curve 0.88, 95% CI, 0.80-0.93). CONCLUSIONS AND RELEVANCE: HRC is a novel digital biomarker that, with further validation, may be useful as a classifier for BD in the overall course of patients with CBI.

Clinical Course Associated with Aseptic Meningitis Induced by Intravenous Immunoglobulin for the Treatment of Multisystem Inflammatory Syndrome in Children.

Aseptic meningitis is a rare but potentially serious complication of intravenous immunoglobulin treatment. In this case series, meningitic symptoms following intravenous immunoglobulin initiation in patients with multisystem inflammatory syndrome were rare (7/2,086 [0.3%]). However, they required the need for additional therapy and/or readmission.

The Spectrum of Quantitative EEG Utilization Across North America: A Cross-Sectional Survey.

BACKGROUND: Continuous electroencephalography (cEEG) is commonly used for neuromonitoring in pediatric intensive care units (PICU); however, there are barriers to real-time interpretation of EEG data. Quantitative EEG (qEEG) transforms the EEG signal into time-compressed graphs, which can be displayed at the bedside. A survey was designed to understand current PICU qEEG use. METHODS: An electronic survey was sent to the Pediatric Neurocritical Care Research Group and Pediatric Status Epilepticus Research Group, and intensivists in 16 Canadian PICUs. Questions addressed demographics, qEEG acquisition and storage, clinical use, and education. RESULTS: Fifty respondents from 39 institutions completed the survey (response rate 53% [39 of 74 institutions]), 76% (37 of 50) from the United States and 24% (12 of 50) from Canada. Over half of the institutions (22 of 39 [56%]) utilize qEEG in their ICUs. qEEG use was associated with having a neurocritical care (NCC) service, ≥200 NCC consults/year, ≥1500 ICU admissions/year, and ≥4 ICU EEGs/day (P < 0.05 for all). Nearly all users (92% [24 of 26]) endorsed that qEEG enhanced care of children with acute neurological injury. Lack of training in qEEG was identified as a common barrier [85% (22 of 26)]. Reviewing and reporting of qEEG was not standard at most institutions. Training was required by 14% (three of 22) of institutions, and 32% (seven of 22) had established curricula. CONCLUSIONS: ICU qEEG was used at more than half of the institutions surveyed, but review, reporting, and application of this tool remained highly variable. Although providers identify qEEG as a useful tool in patient management, further studies are needed to define clinically meaningful pediatric trends, standardize reporting, and enhance educate bedside providers.

Neuromonitoring During ECMO Support in Children.

Extracorporeal membrane oxygenation is a potentially lifesaving intervention for children with severe cardiac or respiratory failure. It is used with increasing frequency and in increasingly more complex and severe diseases. Neurological injuries are important causes of morbidity and mortality in children treated with extracorporeal membrane oxygenation and include ischemic stroke, intracranial hemorrhage, hypoxic-ischemic injury, and seizures. In this review, we discuss the epidemiology and pathophysiology of neurological injury in patients supported with extracorporeal membrane oxygenation, and we review the current state of knowledge for available modalities of monitoring neurological function in these children. These include structural imaging with computed tomography and ultrasound, cerebral blood flow monitoring with near-infrared spectroscopy and transcranial Doppler ultrasound, and physiological monitoring with electroencephalography and plasma biomarkers. We highlight areas of need and emerging advances that will improve our understanding of neurological injury related to extracorporeal membrane oxygenation and help to reduce the burden of neurological sequelae in these children.

Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020.

Importance: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications. Objective: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021. Design, Setting, and Participants: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having multisystem inflammatory syndrome in children (MIS-C) who did not meet criteria (n = 85) were excluded. Patients (<21 years) with positive SARS-CoV-2 test results (reverse transcriptase-polymerase chain reaction and/or antibody) meeting criteria for MIS-C or acute COVID-19 were included in the analysis. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening neurologic involvement was adjudicated by experts based on clinical and/or neuroradiological features. Type and severity of neurologic involvement, laboratory and imaging data, vaccination status, and hospital discharge outcomes (death or survival with new neurologic deficits). Results: Of 2168 patients included (58% male; median age, 10.3 years), 1435 (66%) met criteria for MIS-C, and 476 (22%) had documented neurologic involvement. Patients with neurologic involvement vs without were older (median age, 12 vs 10 years) and more frequently had underlying neurologic disorders (107 of 476 [22%] vs 240 of 1692 [14%]). Among those with neurologic involvement, 42 (9%) developed acute SARS-CoV-2-related life-threatening conditions, including central nervous system infection/demyelination (n = 23; 15 with possible/confirmed encephalitis, 6 meningitis, 1 transverse myelitis, 1 nonhemorrhagic leukoencephalopathy), stroke (n = 11), severe encephalopathy (n = 5), acute fulminant cerebral edema (n = 2), and Guillain-Barré syndrome (n = 1). Ten of 42 (24%) survived with new neurologic deficits at discharge and 8 (19%) died. Among patients with life-threatening neurologic conditions, 15 of 16 vaccine-eligible patients (94%) were unvaccinated. Conclusions and Relevance: SARS-CoV-2-related neurologic involvement persisted in US children and adolescents hospitalized for COVID-19 or MIS-C in 2021 and was again mostly transient. Central nervous system infection/demyelination accounted for a higher proportion of life-threatening conditions, and most vaccine-eligible patients were unvaccinated. COVID-19 vaccination may prevent some SARS-CoV-2-related neurologic complications and merits further study.

Effectiveness of Training Programs for Reducing Adverse Psychological Outcomes in Parents of Children with Acquired Brain Injury: A Systematic Review and Meta-Analysis.

INTRODUCTION: Parental stress following critical illness in their child has the potential to impact functional outcomes and quality of life for the child and whole family. Parent emotional functioning may also be an important clinical target to optimize child outcomes. This study assessed the effectiveness of training programs for parents aimed at reducing adverse psychological outcomes in parents of children with acute brain injury (ABI). METHODS: We conducted searches of Embase, PubMed, Web of Science, and Cochrane Library to November 13, 2020. Randomized controlled trials (RCTs) that compared parent training programs with usual care, or an active comparator, and assessed psychological outcomes (depression, anxiety, stress) in parents of children with ABI were included. Two reviewers independently extracted data on study characteristics, participants, interventions, outcome measures, and results before and after intervention. Risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: Four RCTs involving 318 parents of children with ABI were eligible for review. Compared with usual care or active comparator, parent training was associated with significant reduction in parent stress (four RCTs; standardized mean difference [SMD], - 0.32 on a numerical rating scale [95% CI, - 0.60, - 0.05]; I-squared = 7.5%, p = 0.356); significant reduction in parent depression (three RCTs; SMD, - 0.43 [95% CI, - 0.72, - 0.14]; I-squared = 0.0%, p = 0.393); and significant reduction in parent anxiety (two RCTs; SMD, - 0.63 [95% CI, - 1.05, - 0.21]; I-squared = 0.0%, p = 0.629). Overall risk of bias was high for randomization process (one RCT), missing outcome data (three RCTs), measurement of the outcome (three RCTs), and selection of reported result (two RCTs). Heterogeneity between studies by country of study origin was not significant. CONCLUSIONS: Compared with usual care or an active comparator, parent training was associated with short-term reduction in stress, depression, and anxiety in parents of children with ABI. Future clinical trials of parent interventions are needed as there may be some short-term beneficial effects.

Clinical Characteristics and Outcomes of Children with Acute Catastrophic Brain Injury: A 13-Year Retrospective Cohort Study.

BACKGROUND: The purpose of this study was to describe and analyze clinical characteristics and outcomes in children with acute catastrophic brain injury (CBI). METHODS: This was a single-center, 13-year (2008-2020) retrospective cohort study of children in the pediatric and cardiac intensive care units with CBI, defined as (1) acute neurologic injury based on clinical and/or imaging findings, (2) the need for life-sustaining intensive care unit therapies, and (3) death or survival with a Glasgow Coma Scale score < 13 at discharge. Patients were excluded if they were discharged directly to home < 14 days from admission or had a chronic neurologic condition with a baseline Glasgow Coma Scale score < 13. The association between the primary outcome of death and clinical variables was analyzed by using Kaplan-Meier estimates and multivariable Cox proportional hazard models. Outcomes assessed after discharge were technology dependence, neurologic deficits, and Functional Status Score. Improved functional status was defined as a change in total Functional Status Score [Formula: see text] 2. RESULTS: Of 106 patients (58% boys, median age 3.9 years) with CBI, 86 (81%) died. Withdrawal of life-sustaining therapies was the most common cause of death (60 of 86, 70%). In our multivariable analysis, each unit increase in admission pediatric sequential organ failure assessment score was associated with 10% greater hazard of death (hazard ratio 1.10, 95% confidence interval 1.04-1.17, p < .01). After controlling for admission pediatric sequential organ failure assessment scores, compared with those of patients with traumatic brain injury, all other etiologies of CBI were associated with a greater hazard of death (p = .02; hazard ratio 3.76-10). The median survival time for the cohort was 22 days (95% confidence interval 14-37 days). Of 23 survivors to hospital discharge, 20 were still alive after a median of 2 years (interquartile range 1-3 years), 6 of 20 (30%) did not have any technology dependence, 12 of 20 (60%) regained normal levels of alertness and responsiveness, and 15 of 20 (75%) had improved functional status. CONCLUSIONS: Most children with acute CBI died within 1 month of hospitalization. Having traumatic brain injury as the etiology of CBI was associated with greater survival, whereas increased organ dysfunction score on admission was associated with a higher hazard of mortality. Of the survivors, some recovered consciousness and functional status and did not require permanent technology dependence. Larger prospective studies are needed to improve prediction of CBI among critically ill children, understand factors guiding clinician and family decisions on the continuation or withdrawal of life-sustaining treatments, and characterize the natural history and long-term outcomes among CBI survivors.

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome.

Importance: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures: Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 µg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

Multisystem Inflammatory-like Syndrome in a Child Following COVID-19 mRNA Vaccination.

A 12-year-old male was presented to the hospital with acute encephalopathy, headache, vomiting, diarrhea, and elevated troponin after recent COVID-19 vaccination. Two days prior to admission and before symptom onset, he received the second dose of the Pfizer-BioNTech COVID-19 vaccine. Symptoms developed within 24 h with worsening neurologic symptoms, necessitating admission to the pediatric intensive care unit. Brain magnetic resonance imaging within 16 h of admission revealed a cytotoxic splenial lesion of the corpus callosum (CLOCC). Nineteen days prior to admission, he developed erythema migrans, and completed an amoxicillin treatment course for clinical Lyme disease. However, Lyme antibody titers were negative on admission and nine days later, making active Lyme disease an unlikely explanation for his presentation to hospital. An extensive workup for other etiologies on cerebrospinal fluid and blood samples was negative, including infectious and autoimmune causes and known immune deficiencies. Three weeks after hospital discharge, all of his symptoms had dissipated, and he had a normal neurologic exam. Our report highlights a potential role of mRNA vaccine-induced immunity leading to MIS-C-like symptoms with cardiac involvement and a CLOCC in a recently vaccinated child and the complexity of establishing a causal association with vaccination. The child recovered without receipt of immune modulatory treatment.

Defining catastrophic brain injury in children leading to coma and disorders of consciousness and the scope of the problem.

PURPOSE OF REVIEW: Severe brain injury in children resulting in coma and disorders of consciousness (DOC) is a catastrophic event for the life and function of children and their families. The present article summarizes the recently published pediatric literature on validated diagnostic assessments, potential predictors of recovery, and outcome measures used in children with catastrophic brain injury (CBI). Literature search terms included variants of consciousness, diagnostic tests, predictors of outcome, and outcome measures. RECENT FINDINGS: Developmentally appropriate diagnostic tools, outcome predictors, and outcome measures are lacking for children with CBI leading to coma and DOC. Individual case prognosis relies on serial clinical examinations and experience. Evidence regarding optimal diagnosis of the highest level of consciousness and management of children with CBI is needed. Global efforts through the ongoing Curing Coma Campaign are aimed at: developing common data elements for information capture; streamlining the classification of coma endotypes; describing trajectories with biomarkers to monitor recovery or disease progression; and devising effective treatments for adults and children. SUMMARY: Standardized, developmentally appropriate diagnostic and outcome assessments for CBI in children are needed. Future research should use these content standards to update our understanding of children with CBI leading to coma and DOC, and evaluate effective practices using acute adjunctive and rehabilitation therapies.

A Time-Frequency Approach for Cerebral Embolic Load Monitoring.

OBJECTIVE: To enable reliable cerebral embolic load monitoring from high-intensity transient signals (HITS) recorded with single-channel transcranial Doppler (TCD) ultrasound. METHODS: We propose a HITS detection and characterization method using a weighted-frequency Fourier linear combiner that estimates baseline Doppler signal power. An adaptive threshold is determined by examining the Doppler signal power variance about the baseline estimate, and HITS are extracted if their Doppler power exceeds this threshold. As signatures from multiple emboli may be superimposed, we analyze the detected HITS in the time-frequency (TF) domain to segment the signals into individual emboli. A logistic regression classification approach is employed to classify HITS into emboli or artifacts. Data were collected using a commercial TCD device with emboli-detection capabilities from 12 children undergoing mechanical circulatory support or cardiac catheterization. A subset of 696 HITS were reviewed, annotated, and split into training and testing sets for developing and evaluating the HITS classification algorithm. RESULTS: The classifier yielded 98% and 96% sensitivity for 100% specificity on training and testing data, respectively. The TF approach decomposed 38% of candidate embolic signals into two or more embolic events that ultimately account for 69% of the overall embolic counts. Our processing pipeline resulted in highly accurate emboli identification and produced emboli counts that were lower (by a median of 64%) compared to the commercial ultrasound system's estimates. SIGNIFICANCE: Using only single-channel, single-frequency Doppler ultrasound, the proposed method enables sensitive detection and segmentation of embolic signatures. Our approach paves the way toward accurate real-time cerebral emboli monitoring.

Transcranial Doppler Ultrasound During Critical Illness in Children: Survey of Practices in Pediatric Neurocritical Care Centers.

OBJECTIVES: The scope of transcranial Doppler ultrasound in the practice of pediatric neurocritical care is unknown. We have surveyed pediatric neurocritical care centers on their use of transcranial Doppler and analyzed clinical management practices. DESIGN: Electronic-mail recruitment with survey of expert centers using web-based questionnaire. SETTING: Survey of 43 hospitals (31 United States, 12 international) belonging to the Pediatric Neurocritical Care Research Group. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A 67% (29/43) hospital-response rate. Of these centers, 27 reported using transcranial Doppler in the PICU; two hospitals opted out due to lack of transcranial Doppler availability/use. The most common diagnoses for using transcranial Doppler in clinical care were intracranial/subarachnoid hemorrhage (20 hospitals), arterial ischemic stroke (14 hospitals), and traumatic brain injury (10 hospitals). Clinical studies were carried out and interpreted by credentialed individuals in 93% (25/27) and 78% (21/27) of the centers, respectively. A written protocol for performance of transcranial Doppler in the PICU was available in 30% (8/27 hospitals); of these, two of eight hospitals routinely performed correlation studies to validate results. In 74% of the centers (20/27), transcranial Doppler results were used to guide clinical care: that is, when to obtain a neuroimaging study (18 hospitals); how to manipulate cerebral perfusion pressure with fluids/vasopressors (13 hospitals); and whether to perform a surgical intervention (six hospitals). Research studies were also commonly performed for a range of diagnoses. CONCLUSIONS: At least 27 pediatric neurocritical care centers use transcranial Doppler during clinical care. In the majority of centers, studies are performed and interpreted by credentialed personnel, and findings are used to guide clinical management. Further studies are needed to standardize these practices.

Outcomes measures in children after acute central nervous system infections and malaria.

PURPOSE OF REVIEW: Acute central nervous system (CNS) infections in children result in significant mortality and neurologic morbidity worldwide. This article summarizes the recent pediatric literature published on outcomes measures used after acute infectious meningitis, encephalitis, and cerebral malaria, and highlights ongoing research efforts to standardize outcomes measurements. Search terms were geared toward functional, cognitive, behavioral, and other outcome assessments. RECENT FINDINGS: Recent data suggest that, depending on microbiological cause, there are differences in currently used outcome measures following acute CNS infections. Outcomes assessments include a variety of formal psychological tests (structured interviews and neuropsychological tests of cognitive and motor functioning) and dichotomized or ordinal scales. Standardization of outcome measures, however, is lacking. Global efforts to standardize outcomes that encompass both the child and family are ongoing. SUMMARY: Centers worldwide can track and measure a variety of cognitive, behavioral, and functional outcomes after acute CNS infections. Standardized documentation and coding of clinically important outcomes is needed. Further research to evaluate effective practices using acute adjunctive and rehabilitation therapies will be aided by outcome measure standardization.

Fully automated, real-time, calibration-free, continuous noninvasive estimation of intracranial pressure in children.

OBJECTIVE: In the search for a reliable, cooperation-independent, noninvasive alternative to invasive intracranial pressure (ICP) monitoring in children, various approaches have been proposed, but at the present time none are capable of providing fully automated, real-time, calibration-free, continuous and accurate ICP estimates. The authors investigated the feasibility and validity of simultaneously monitored arterial blood pressure (ABP) and middle cerebral artery (MCA) cerebral blood flow velocity (CBFV) waveforms to derive noninvasive ICP (nICP) estimates. METHODS: Invasive ICP and ABP recordings were collected from 12 pediatric and young adult patients (aged 2-25 years) undergoing such monitoring as part of routine clinical care. Additionally, simultaneous transcranial Doppler (TCD) ultrasonography-based MCA CBFV waveform measurements were performed at the bedside in dedicated data collection sessions. The ABP and MCA CBFV waveforms were analyzed in the context of a mathematical model, linking them to the cerebral vasculature's biophysical properties and ICP. The authors developed and automated a waveform preprocessing, signal-quality evaluation, and waveform-synchronization "pipeline" in order to test and objectively validate the algorithm's performance. To generate one nICP estimate, 60 beats of ABP and MCA CBFV waveform data were analyzed. Moving the 60-beat data window forward by one beat at a time (overlapping data windows) resulted in 39,480 ICP-to-nICP comparisons across a total of 44 data-collection sessions (studies). Moving the 60-beat data window forward by 60 beats at a time (nonoverlapping data windows) resulted in 722 paired ICP-to-nICP comparisons. RESULTS: Greater than 80% of all nICP estimates fell within ± 7 mm Hg of the reference measurement. Overall performance in the nonoverlapping data window approach gave a mean error (bias) of 1.0 mm Hg, standard deviation of the error (precision) of 5.1 mm Hg, and root-mean-square error of 5.2 mm Hg. The associated mean and median absolute errors were 4.2 mm Hg and 3.3 mm Hg, respectively. These results were contingent on ensuring adequate ABP and CBFV signal quality and required accurate hydrostatic pressure correction of the measured ABP waveform in relation to the elevation of the external auditory meatus. Notably, the procedure had no failed attempts at data collection, and all patients had adequate TCD data from at least one hemisphere. Last, an analysis of using study-by-study averaged nICP estimates to detect a measured ICP > 15 mm Hg resulted in an area under the receiver operating characteristic curve of 0.83, with a sensitivity of 71% and specificity of 86% for a detection threshold of nICP = 15 mm Hg. CONCLUSIONS: This nICP estimation algorithm, based on ABP and bedside TCD CBFV waveform measurements, performs in a manner comparable to invasive ICP monitoring. These findings open the possibility for rational, point-of-care treatment decisions in pediatric patients with suspected raised ICP undergoing intensive care.