Neurophysiologic Features Reflecting Brain Injury During Pediatric ECMO Support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides lifesaving support to critically ill patients who experience refractory cardiopulmonary failure but carries a high risk for acute brain injury. We aimed to identify characteristics reflecting acute brain injury in children requiring ECMO support. METHODS: This is a prospective observational study from 2019 to 2022 of pediatric ECMO patients undergoing neuromonitoring, including continuous electroencephalography, cerebral oximetry, and transcranial Doppler ultrasound (TCD). The primary outcome was acute brain injury. Clinical and neuromonitoring characteristics were collected. Multivariate logistic regression was implemented to model odds ratios (ORs) and identify the combined characteristics that best discriminate risk of acute brain injury using the area under the receiver operating characteristic curve. RESULTS: Seventy-five pediatric patients requiring ECMO support were enrolled in this study, and 62 underwent neuroimaging or autopsy evaluations. Of these 62 patients, 19 experienced acute brain injury (30.6%), including seven (36.8%) with arterial ischemic stroke, four (21.1%) with hemorrhagic stroke, seven with hypoxic-ischemic brain injury (36.8%), and one (5.3%) with both arterial ischemic stroke and hypoxic-ischemic brain injury. A univariate analysis demonstrated acute brain injury to be associated with maximum hourly seizure burden (p = 0.021), electroencephalographic suppression percentage (p = 0.022), increased interhemispheric differences in electroencephalographic total power (p = 0.023) and amplitude (p = 0.017), and increased differences in TCD Thrombolysis in Brain Ischemia (TIBI) scores between bilateral middle cerebral arteries (p = 0.023). Best subset model selection identified increased seizure burden (OR = 2.07, partial R2 = 0.48, p = 0.013), increased quantitative electroencephalographic interhemispheric amplitude differences (OR = 2.41, partial R2 = 0.48, p = 0.013), and increased interhemispheric TCD TIBI score differences (OR = 4.66, partial R2 = 0.49, p = 0.006) to be independently associated with acute brain injury (area under the receiver operating characteristic curve = 0.92). CONCLUSIONS: Increased seizure burden and increased interhemispheric differences in both quantitative electroencephalographic amplitude and TCD MCA TIBI scores are independently associated with acute brain injury in children undergoing ECMO support.

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.

Early Electroencephalographic Features Predicting Cerebral Physiology and Functional Outcomes After Pediatric Traumatic Brain Injury.

BACKGROUND: We investigated whether early electroencephalographic features predicted intracranial pressure (ICP), cerebrovascular pressure reactivity, brain tissue oxygenation, and functional outcomes in patients with pediatric traumatic brain injury (TBI). METHODS: This was a retrospective analysis of a prospective data set of 63 patients with pediatric TBI. Electroencephalographic features were collected in the first 24 h of recording to predict values of ICP, pressure reactivity index (PRx), and brain tissue oxygenation (PbtO2) through the initial 7 days of critical care monitoring, in addition to Glasgow Outcome Scale Extended-Pediatric Revision (GOSE-Peds) scores at 12 months. Electroencephalographic features were averaged over all surface electrodes and included seizures, interictal epileptiform discharges, suppression percentage, complexity, the alpha/delta power ratio, and both absolute asymmetry indices and power in beta (13-20 Hz), alpha (8-13 Hz), theta (4-7 Hz) and delta (0-4 Hz) bands. Demographic data and injury severity scores, such as the Glasgow Coma Scale (GCS) and Pediatric Risk of Mortality III (PRISM III) scores, at presentation were also assessed. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that best explain variability in ICP, PRx, PbtO2, and GOSE-Peds values, and best fit models were applied to pediatric age strata. We hypothesized that suppression percentage and the alpha/delta power ratio in the first 24 h of recording predict ICP, PRx, PbtO2, and GOSE-Peds values. RESULTS: Best subset model selection identified that increased suppression percentage and PRISM III scores predicted increased ICP (R2 = 79%, Akaike information criterion [AIC] = 332.30, root mean square error [RMSE] = 6.62), with suppression percentages < 5% (slope = - 5687.0, p = 0.0001) and ≥ 45% (slope = 9825.9, p = 0.0000) being predictive of dose of intracranial hypertension. When accounting for age and GCS score, increased suppression percentage predicted increased PRx values, suggestive of inefficient cerebrovascular pressure reactivity (R2 = 53%, AIC = 3.93, RMSE = 0.23), with suppression percentages ≥ 5% (p = 0.0033) and ≥ 45% (p = 0.0027) being predictive of median PRx values ≥ 0.3. Lower GCS scores, the presence of seizures, and increased suppression percentages each were independently associated with higher GOSE-Peds scores (R2 = 52%, AIC = 194.04, RMSE = 1.58), suggestive of unfavorable outcomes, with suppression percentages ≥ 5% (p = 0.0005) and ≥ 45% (p = 0.0000) being predictive of GOSE-Peds scores ≥ 5. At the univariate level, no electroencephalographic or clinical feature was associated with differences in PbtO2 values. CONCLUSIONS: Increased electroencephalographic suppression percentage on the initial day of monitoring may identify patients with pediatric TBI at risk of increased ICP, inefficient cerebrovascular pressure reactivity, and unfavorable outcomes.

Common Data Elements for Disorders of Consciousness: Recommendations from the Electrophysiology Working Group.

BACKGROUND: Electroencephalography (EEG) has long been recognized as an important tool in the investigation of disorders of consciousness (DoC). From inspection of the raw EEG to the implementation of quantitative EEG, and more recently in the use of perturbed EEG, it is paramount to providing accurate diagnostic and prognostic information in the care of patients with DoC. However, a nomenclature for variables that establishes a convention for naming, defining, and structuring data for clinical research variables currently is lacking. As such, the Neurocritical Care Society's Curing Coma Campaign convened nine working groups composed of experts in the field to construct common data elements (CDEs) to provide recommendations for DoC, with the main goal of facilitating data collection and standardization of reporting. This article summarizes the recommendations of the electrophysiology DoC working group. METHODS: After assessing previously published pertinent CDEs, we developed new CDEs and categorized them into "disease core," "basic," "supplemental," and "exploratory." Key EEG design elements, defined as concepts that pertained to a methodological parameter relevant to the acquisition, processing, or analysis of data, were also included but were not classified as CDEs. RESULTS: After identifying existing pertinent CDEs and developing novel CDEs for electrophysiology in DoC, variables were organized into a framework based on the two primary categories of resting state EEG and perturbed EEG. Using this categorical framework, two case report forms were generated by the working group. CONCLUSIONS: Adherence to the recommendations outlined by the electrophysiology working group in the resting state EEG and perturbed EEG case report forms will facilitate data collection and sharing in DoC research on an international level. In turn, this will allow for more informed and reliable comparison of results across studies, facilitating further advancement in the realm of DoC research.

International Prevalence and Mechanisms of SARS-CoV-2 in Childhood Arterial Ischemic Stroke During the COVID-19 Pandemic.

BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2. METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 years, numbers of incident AIS cases among children (29 days to <18 years), frequency of SARS-CoV-2 testing for children with AIS, and numbers of childhood AIS cases positive for SARS-CoV-2 June 1 to December 31, 2020. Two stroke neurologists with 1 neuroradiologist determined whether SARS-CoV-2 was the main stroke risk factor, contributory, or incidental. RESULTS: Sixty-one centers from 21 countries provided AIS data. Forty-eight centers (78.7%) provided SARS-CoV-2 hospitalization data. SARS-CoV-2 testing was performed in 335/373 acute AIS cases (89.8%) compared with 99/166 (59.6%) in March to May 2020, P<0.0001. Twenty-three of 335 AIS cases tested (6.9%) were positive for SARS-CoV-2 compared with 6/99 tested (6.1%) in March to May 2020, P=0.78. Of the 22 of 23 AIS cases with SARS-CoV-2 in whom we could collect additional data, SARS-CoV-2 was the main stroke risk factor in 6 (3 with arteritis/vasculitis, 3 with focal cerebral arteriopathy), a contributory factor in 13, and incidental in 3. Elevated inflammatory markers were common, occurring in 17 (77.3%). From centers with SARS-CoV-2 hospitalization data, of 7231 pediatric patients hospitalized with SARS-CoV-2, 23 had AIS (0.32%) compared with 6/971 (0.62%) from March to May 2020, P=0.14. CONCLUSIONS: The risk of AIS among children hospitalized with SARS-CoV-2 appeared stable compared with our earlier estimate. Among children in whom SARS-CoV-2 was considered the main stroke risk factor, inflammatory arteriopathies were the stroke mechanism.

Pediatric Acute Stroke Protocols in the United States and Canada.

OBJECTIVE: To describe existing pediatric acute stroke protocols to better understand how pediatric centers might implement such pathways within the context of institution-specific structures. STUDY DESIGN: We administered an Internet-based survey of pediatric stroke specialists. The survey included questions about hospital demographics, child neurology and pediatric stroke demographics, acute stroke response, imaging, and hyperacute treatment. RESULTS: Forty-seven surveys were analyzed. Most respondents practiced at a large, freestanding children's hospital with a moderate-sized neurology department and at least 1 neurologist with expertise in pediatric stroke. Although there was variability in how the hospitals deployed stroke protocols, particularly in regard to staffing, the majority of institutions had an acute stroke pathway, and almost all included activation of a stroke alert page. Most institutions preferred magnetic resonance imaging (MRI) over computed tomography (CT) and used abbreviated MRI protocols for acute stroke imaging. Most institutions also had either CT-based or magnetic resonance-based perfusion imaging available. At least 1 patient was treated with intravenous tissue plasminogen activator (IV-tPA) or mechanical thrombectomy at the majority of institutions during the year before our survey. CONCLUSIONS: An acute stroke protocol is utilized in at least 41 pediatric centers in the US and Canada. Most acute stroke response teams are multidisciplinary, prefer abbreviated MRI over CT for diagnosis, and have experience providing IV-tPA and mechanical thrombectomy. Further studies are needed to standardize practices of pediatric acute stroke diagnosis and hyperacute management.

Factors associated with long-term outcomes in pediatric refractory status epilepticus.

OBJECTIVE: This study was undertaken to describe long-term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE. METHODS: We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients. RESULTS: Follow-up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow-up duration was 1.6 (.9-2.7) years. The in-hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty-six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1-134.5] h vs. 4 [1.6-16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008-1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale-Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion. SIGNIFICANCE: About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow-up, with longer electroclinical RSE duration as a predictor.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

OBJECTIVE: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). METHODS: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ASM. RESULTS: We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997-.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73-3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40-6.03, p < .0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01-2.06, p = .04). Forty-seven percent of patients (n = 94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival. SIGNIFICANCE: Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.

Implementation of Multimodality Neurologic Monitoring Reporting in Pediatric Traumatic Brain Injury Management.

BACKGROUND/OBJECTIVE: Multimodality neurologic monitoring (MMM) is an emerging technique for management of traumatic brain injury (TBI). An increasing array of MMM-derived biomarkers now exist that are associated with injury severity and functional outcomes after TBI. A standardized MMM reporting process has not been well described, and a paucity of evidence exists relating MMM reporting in TBI management with functional outcomes or adverse events. METHODS: Prospective implementation of standardized MMM reporting at a single pediatric intensive care unit (PICU) is described that included monitoring of intracranial pressure (ICP), cerebral oxygenation and electroencephalography (EEG). The incidence of clinical decisions made using MMM reporting is described, including timing of neuroimaging, ICP monitoring discontinuation, use of paralytic, hyperosmolar and pentobarbital therapies, neurosurgical interventions, ventilator and CPP adjustments and neurologic prognostication discussions. Retrospective analysis was performed on the association of MMM reporting with initial Glasgow Coma Scale (GCS) and Pediatric Risk of Mortality III (PRISM III) scores, duration of total hospitalization and PICU hospitalization, duration of mechanical ventilation and invasive ICP monitoring, inpatient complications, time with ICP > 20 mmHg, time with cerebral perfusion pressure (CPP) < 40 mmHg and 12-month Glasgow Outcome Scale-Extended Pediatrics (GOSE-Peds) scores. Association of outcomes with MMM reporting was investigated using the Wilcoxon rank-sum test or Fisher's exact test, as appropriate. RESULTS: Eighty-five children with TBI underwent MMM over 6 years, among which 18 underwent daily MMM reporting over a 21-month period. Clinical decision-making influenced by MMM reporting included timing of neuroimaging (100.0%), ICP monitoring discontinuation (100.0%), timing of extubation trials of surviving patients (100.0%), body repositioning (11.1%), paralytic therapy (16.7%), hyperosmolar therapy (22.2%), pentobarbital therapy (33.3%), provocative cerebral autoregulation testing (16.7%), adjustments in CPP thresholds (16.7%), adjustments in PaCO2 thresholds (11.1%), neurosurgical interventions (16.7%) and neurologic prognostication discussions (11.1%). The implementation of MMM reporting was associated with a reduction in ICP monitoring duration (p = 0.0017) and mechanical ventilator duration (p = 0.0018). No significant differences were observed in initial GCS or PRISM III scores, total hospitalization length, PICU hospitalization length, total complications, time with ICP > 20 mmHg, time with CPP < 40 mmHg, use of tier 2 therapy, or 12-month GOS-E Peds scores. CONCLUSION: Implementation of MMM reporting in pediatric TBI management is feasible and can be impactful in tailoring clinical decisions. Prospective work is needed to understand the impact of MMM and MMM reporting systems on functional outcomes and clinical care efficacy.

Association of Outcomes with Model-Based Indices of Cerebral Autoregulation After Pediatric Traumatic Brain Injury.

BACKGROUND: We investigated whether model-based indices of cerebral autoregulation (CA) are associated with outcomes after pediatric traumatic brain injury. METHODS: This was a retrospective analysis of a prospective clinical database of 56 pediatric patients with traumatic brain injury undergoing intracranial pressure monitoring. CA indices were calculated, including pressure reactivity index (PRx), wavelet pressure reactivity index (wPRx), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Each CA index was used to compute optimal cerebral perfusion pressure (CPP). Time of CPP below lower limit of autoregulation (LLA) or above upper limit of autoregulation (ULA) were computed for each index. Demographic, physiologic, and neuroimaging data were collected. Primary outcome was determined using Pediatric Glasgow Outcome Scale Extended (GOSE-Peds) at 12 months, with higher scores being suggestive of unfavorable outcome. Univariate and multiple linear regression with guided stepwise variable selection was used to find combinations of risk factors that can best explain the variability of GOSE-Peds scores, and the best fit model was applied to the age strata. We hypothesized that higher GOSE-Peds scores were associated with higher CA values and more time below LLA or above ULA for each index. RESULTS: At the univariate level, CPP, dose of intracranial hypertension, PRx, PAx, wPRx, RAC, percent time more than ULA derived for PAx, and percent time less than LLA derived for PRx, PAx, wPRx, and RAC were all associated with GOSE-Peds scores. The best subset model selection on all pediatric patients identified that when accounting for CPP, increased dose of intracranial hypertension and percent time less than LLA derived for wPRx were independently associated with higher GOSE-Peds scores. Age stratification of the best fit model identified that in children less than 2 years of age or 8 years of age or more, percent time less than LLA derived for wPRx represented the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and dose of intracranial hypertension. For children 2 years or younger to less than 8 years of age, dose of intracranial hypertension was identified as the sole independent predictor of higher GOSE-Peds scores when accounting for CPP and percent time less than LLA derived for wPRx. CONCLUSIONS: Increased dose of intracranial hypertension, PRx, wPRx, PAx, and RAC values and increased percentage time less than LLA based on PRx, wPRx, PAx, and RAC are associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. Reducing intracranial hypertension and maintaining CPP more than LLA based on wPRx may improve outcomes and warrants prospective investigation.

Multimodal Assessment of Cerebral Autoregulation and Autonomic Function After Pediatric Cerebral Arteriovenous Malformation Rupture.

BACKGROUND: Management after cerebral arteriovenous malformation (AVM) rupture aims toward preventing hemorrhagic expansion while maintaining cerebral perfusion to avoid secondary injury. We investigated associations of model-based indices of cerebral autoregulation (CA) and autonomic function (AF) with outcomes after pediatric cerebral AVM rupture. METHODS: Multimodal neurologic monitoring data from the initial 3 days after cerebral AVM rupture were retrospectively analyzed in children (< 18 years). AF indices included standard deviation of heart rate (HRsd), root-mean-square of successive differences in heart rate (HRrmssd), low-high frequency ratio (LHF), and baroreflex sensitivity (BRS). CA indices include pressure reactivity index (PRx), wavelet pressure reactivity indices (wPRx and wPRx-thr), pulse amplitude index (PAx), and correlation coefficient between intracranial pressure pulse amplitude and cerebral perfusion pressure (RAC). Percent time of cerebral perfusion pressure (CPP) below lower limits of autoregulation (LLA) was also computed for each CA index. Primary outcomes were determined using Pediatric Glasgow Outcome Score Extended-Pediatrics (GOSE-PEDs) at 12 months and acquired epilepsy. Association of biomarkers with outcomes was investigated using linear regression, Wilcoxon signed-rank, or Chi-square. RESULTS: Fourteen children were analyzed. Lower AF indices were associated with poor outcomes (BRS [p = 0.04], HRsd [p = 0.04], and HRrmssd [p = 0.00]; and acquired epilepsy (LHF [p = 0.027]). Higher CA indices were associated with poor outcomes (PRx [p = 0.00], wPRx [p = 0.00], and wPRx-thr [p = 0.01]), and acquired epilepsy (PRx [p = 0.02] and wPRx [p = 0.00]). Increased time below LLA was associated with poor outcome (percent time below LLA based on PRx [p = 0.00], PAx [p = 0.04], wPRx-thr [p = 0.03], and RAC [p = 0.01]; and acquired epilepsy (PRx [p = 0.00], PAx [p = 0.00], wPRx-thr [p = 0.03], and RAC [p = 0.01]). CONCLUSIONS: After pediatric cerebral AVM rupture, poor outcomes are associated with AF and CA when applying various neurophysiologic model-based indices. Prospective work is needed to assess these indices of CA and AF in clinical decision support.

Intracranial Electroencephalography in Pediatric Severe Traumatic Brain Injury.

OBJECTIVES: Electroencephalography is used in neurocritical care for detection of seizures and assessment of cortical function. Due to limited resolution from scalp electroencephalography, important abnormalities may not be readily detectable. We aimed to identify whether intracranial electroencephalography allows for improved methods of monitoring cortical function in children with severe traumatic brain injury. DESIGN: This is a retrospective cohort study from a prospectively collected clinical database. We investigated the occurrence rate of epileptiform abnormalities detected on intracranial electroencephalography when compared with scalp electroencephalography. We also investigated the strength of association of quantitative electroencephalographic parameters and cerebral perfusion pressure between both intracranial and scalp electroencephalography. SETTING: This is a single-institution study performed in the Phoenix Children's Hospital PICU. PATIENTS: Eleven children with severe traumatic brain injury requiring invasive neuromonitoring underwent implantation of a six-contact intracranial electrode as well as continuous surface electroencephalography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Visual detection of epileptiform abnormalities was performed by pediatric epileptologists. Association of intracranial and scalp electroencephalography total power, alpha percentage, and alpha-delta power ratio to cerebral perfusion pressure was performed using univariate dynamic structural equations modeling. Demographic data were assessed by retrospective analysis. Intracranial and scalp electroencephalography was performed in 11 children. Three of 11 children had observed epileptiform abnormalities on intracranial electroencephalography. Two patients had epileptiform abnormalities identified exclusively on intracranial electroencephalography, and one patient had seizures initiating on intracranial electroencephalography before arising on scalp electroencephalography. Identification of epileptiform abnormalities was associated with subsequent identification of stroke or malignant cerebral edema. We observed statistically significant positive associations between intracranial alpha-delta power ratio to cerebral perfusion pressure in nine of 11 patients with increased strength of association on intracranial compared with scalp recordings. CONCLUSIONS: These findings suggest that intracranial electroencephalography may be useful for detection of secondary insult development in children with traumatic brain injury.

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.

Multimodal neuromonitoring in the pediatric intensive care unit.

Neuromonitoring is used to assess the central nervous system in the intensive care unit. The purpose of neuromonitoring is to detect neurologic deterioration and intervene to prevent irreversible nervous system dysfunction. Neuromonitoring starts with the standard neurologic examination, which may lag behind the pathophysiologic changes. Additional modalities including continuous electroencephalography (CEEG), multiple physiologic parameters, and structural neuroimaging may detect changes earlier. Multimodal neuromonitoring now refers to an integrated combination and display of non-invasive and invasive modalities, permitting tailored treatment for the individual patient. This chapter reviews the non-invasive and invasive modalities used in pediatric neurocritical care.

Reversal of Cerebral Arteriopathy Post-Hematopoietic Stem Cell Transplant for Sickle Cell Disease.

Sickle cell disease (SCD) is a chronic hematologic disorder which causes progressive cerebral arteriopathy beginning in childhood. As a result, arterial ischemic stroke is a major cause of morbidity and mortality in SCD, and SCD is a leading cause of childhood stroke worldwide. Allogenic hematopoietic stem cell transplant (HSCT) may be curative for individuals with SCD. Long-term outcomes and effects are currently being studied. In this report, we describe a child with SCD who presented with arterial ischemic stroke at 6 years of age and was found to have a severe form of cerebral large vessel arteriopathy by catheter-directed angiography. The patient initially underwent revascularization surgery by indirect superficial temporal artery to middle cerebral artery bypass, and 1 year later, he underwent curative HSCT. Approximately 3 years after HSCT, repeat catheter-directed angiography revealed a striking reversal of cerebral large vessel arteriopathy. This article reveals a previously unrecognized and potentially beneficial effect of HSCT that may ameliorate cerebral large vessel arteriopathy and improve cerebrovascular health for children with SCD.

Changes in autonomic function and cerebral and somatic oxygenation with arterial flow pulsatility for children requiring veno-arterial extracorporeal membrane oxygenation.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) carries variability in arterial flow pulsatility (AFP). Research question: What changes in cerebral and somatic oxygenation, hemodynamics, and autonomic function are associated with AFP during VA-ECMO? Methods: This is a prospective study of children on VA-ECMO undergoing neuromonitoring. AFP was quantified by arterial blood pressure pulse amplitude and subcategorized: no pulsatility (<1 mmHg), minimal pulsatility (1 to <5 mmHg), moderate pulsatility (5 to <15 mmHg) and high pulsatility (≥15 mmHg). CVPR was assessed using the cerebral oximetry index (COx). Cerebral and somatic oxygenation was assessed using cerebral regional oximetry (rSO2) or peripheral oxygen saturation (SpO2). Autonomic function was assessed using baroreflex sensitivity (BRs), low-frequency high-frequency (LF/HF) ratio and standard deviation of heart rate R-R intervals (HRsd). Differences were assessed across AFP categories using linear mixed effects models with Tukey pairwise comparisons. Univariate logistic regression was used to explore risk of AFP with brain injuries. Results: Among fifty-three children, comparisons of moderate to high pulsatility were associated with reductions in rSO2 (p < 0.001), SpO 2 (p = 0.005), LF/HF ratio (p = 0.028) and an increase in HRsd (p < 0.001). Reductions in BRs were observed across comparisons of none to minimal (P < 0.001) and minimal to moderate pulsatility (p = 0.004). Comparisons of no to low pulsatility were associated with reductions in BRs (p < 0.001) and ABP (p < 0.001) with increases in SpO2 (p < 0.001) and HR (p < 0.001). Arterial ischemic stroke was associated with higher pulsatility (p = 0.0384). Conclusion: During VA-ECMO support, changes toward high AFP are associated with autonomic dysregulation and compromised cerebral and somatic tissue oxygenation.

Quantitative Electroencephalographic Changes Associated With Brain Tissue Hypoxia After Pediatric Traumatic Brain Injury: A Retrospective Exploratory Analysis.

PURPOSE: Brain tissue hypoxia is associated with poor outcomes after pediatric traumatic brain injury. Although invasive brain oxygenation (PbtO 2 ) monitoring is available, noninvasive methods assessing correlates to brain tissue hypoxia are needed. We investigated EEG characteristics associated with brain tissue hypoxia. METHODS: We performed a retrospective analysis of 19 pediatric traumatic brain injury patients undergoing multimodality neuromonitoring that included PbtO 2 and quantitative electroencephalography(QEEG). Quantitative electroencephalography characteristics were analyzed over electrodes adjacent to PbtO 2 monitoring and over the entire scalp, and included power in alpha and beta frequencies and the alpha-delta power ratio. To investigate relationships of PbtO 2 to quantitative electroencephalography features using time series data, we fit linear mixed effects models with a random intercept for each subject and one fixed effect, and an auto-regressive order of 1 to model between-subject variation and correlation for within-subject observations. Least squares (LS) means were used to investigate for fixed effects of quantitative electroencephalography features to changes in PbtO 2 across thresholds of 10, 15, 20, and 25 mm Hg. RESULTS: Within the region of PbtO 2 monitoring, changes in PbtO 2 < 10 mm Hg were associated with reductions of alpha-delta power ratio (LS mean difference -0.01, 95% confidence interval (CI) [-0.02, -0.00], p = 0.0362). Changes in PbtO 2 < 25 mm Hg were associated with increases in alpha power (LS mean difference 0.04, 95% CI [0.01, 0.07], p = 0.0222). CONCLUSIONS: Alpha-delta power ratio changes are observed across a PbtO 2 threshold of 10 mm Hg within regions of PbtO 2 monitoring, which may reflect an EEG signature of brain tissue hypoxia after pediatric traumatic brain injury.

Corrigendum: Post-discharge outcomes of hospitalized children diagnosed with acute SARS-CoV-2 or MIS-C.

[This corrects the article DOI: 10.3389/fped.2024.1340385.].