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Clinical guidance on outpatient follow-up of children hospitalized with acute neurologic complications of SARS-CoV2 infection is needed. We describe the clinical infrastructure of our pediatric neurology post-Covid clinic, including our clinical evaluation and cognitive testing battery specific to this patient population, and a case series of our initial patient cohort. Our findings demonstrate cognitive sequelae in all 4 of our patients months following acute SARS-CoV2 infection with neurologic complications including acute disseminated encephalomyelitis, posterior reversible encephalopathy syndrome, viral encephalitis, and gait difficulties. Verbal and executive function domains were predominantly affected in our cohort, even in patients who did not endorse symptomatic or academic complaints at follow-up. Our recommendations include systematic clinical follow-up for children following hospitalization with SARS-CoV2 infection with a comprehensive cognitive battery to monitor for cognitive sequalae and to assist with developing an individualized education plan for the child as they return to school.

OBJECTIVES Survivors of the PICU face long-term morbidities across health domains. In this study, we detail active PICU follow-up programs (PFUPs) and identify perceptions and barriers about development and maintenance of PFUPs. METHODS A web link to an adaptive survey was distributed through organizational listservs. Descriptive statistics characterized the sample and details of existing PFUPs. Likert responses regarding benefits and barriers were summarized. RESULTS One hundred eleven respondents represented 60 institutions located in the United States (n = 55), Canada (n = 3), Australia (n = 1), and the United Kingdom (n = 1). Details for 17 active programs were provided. Five programs included broad PICU populations, while the majority were neurocritical care (53%) focused. Despite strong agreement on the need to assess and treat morbidity across multiple health domains, 29% were physician only programs, and considerable variation existed in services provided by programs across settings. More than 80% of all respondents agreed PFUPs provide direct benefits and are essential to advancing knowledge on long-term PICU outcomes. Respondents identified “lack of support” as the most important barrier, particularly funding for providers and staff, and lack of clinical space, though successful programs overcome this challenge using a variety of funding resources. CONCLUSIONS Few systematic multidisciplinary PFUPs exist despite strong agreement about importance of this care and direct benefit to patients and families. We recommend stakeholders use our description of successful programs as a framework to develop multidisciplinary models to elevate continuity across inpatient and outpatient settings, improve patient care, and foster collaboration to advance knowledge.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.

BACKGROUND: Neuromonitoring is the use of continuous measures of brain physiology to detect clinically important events in real-time. Neuromonitoring devices can be invasive or non-invasive and are typically used on patients with acute brain injury or at high risk for brain injury. The goal of this study was to characterize neuromonitoring infrastructure and practices in North American pediatric intensive care units (PICUs). METHODS: An electronic, web-based survey was distributed to 70 North American institutions participating in the Pediatric Neurocritical Care Research Group. Questions related to the clinical use of neuromonitoring devices, integrative multimodality neuromonitoring capabilities, and neuromonitoring infrastructure were included. Survey results were presented using descriptive statistics. RESULTS: The survey was completed by faculty at 74% (52 of 70) of institutions. All 52 institutions measure intracranial pressure and have electroencephalography capability, whereas 87% (45 of 52) use near-infrared spectroscopy and 40% (21/52) use transcranial Doppler. Individual patient monitoring decisions were driven by institutional protocols and collaboration between critical care, neurology, and neurosurgery attendings. Reported device utilization varied by brain injury etiology. Only 15% (eight of 52) of institutions utilized a multimodality neuromonitoring platform to integrate and synchronize data from multiple devices. A database of neuromonitoring patients was maintained at 35% (18 of 52) of institutions. Funding for neuromonitoring programs was variable with contributions from hospitals (19%, 10 of 52), private donations (12%, six of 52), and research funds (12%, six of 52), although 73% (40 of 52) have no dedicated funds. CONCLUSIONS: Neuromonitoring indications, devices, and infrastructure vary by institution in North American pediatric critical care units. Noninvasive modalities were utilized more liberally, although not uniformly, than invasive monitoring. Further studies are needed to standardize the acquisition, interpretation, and reporting of clinical neuromonitoring data, and to determine whether neuromonitoring systems impact neurological outcomes.

Background In patients with acute neurological injury, abrupt temperature change exacerbates increased intracranial pressures and negatively affects perfusion pressure and cerebral blood flow. Critical care nurses must provide coordinated and effective interventions to maintain normothermia without precipitating shivering immediately after acute neurological injury in pediatric patients. Objective To improve hyperthermia management in a 40-bed pediatric intensive care unit, an interdisciplinary pediatric critical care team developed, implemented, and evaluated a targeted temperature management protocol. Methods The project was guided by the organization’s plan-do-study-act quality improvement process. Quality improvement was assessed retrospectively using electronic medical records of patients meeting eligibility criteria. Samples of pediatric patients who received temperature interventions were compared before and after protocol implementation. The protocol included environmental, pharmacological, and body surface cooling device interventions, as well as use of a bedside shivering assessment scale and stepwise interventions to prevent and control shivering. Results Before implementation of the targeted temperature management protocol, 64% of patients had documented temperatures higher than 37.5 °C, and body surface cooling devices were used in 10% of patients. After protocol implementation, more than 80% of patients had documented temperatures higher than 37.5 °C, and body surface cooling devices were used in 62% of patients. Four patients (6%) before and 5 patients (31%) after protocol implementation were treated with body surface cooling without requiring use of neuromuscular blockade. Conclusions Creation and implementation of a targeted temperature management protocol increased nurses’ documented use of body surface cooling to manage hyperthermia in pediatric intensive care unit patients with acute neurological injury.

Aim To clarify the extent to which medical comorbidities and goals-of-care decisions influence death among individuals with childhood-onset hydrocephalus. Method This was a retrospective cohort study of 1705 individuals (759 males, 946 females, mean age 11y 5mo, SD 6y 6mo, range 0-37y 7mo at last follow-up) with childhood-onset hydrocephalus, of whom 88 (5.2%) were deceased. Existing medical records, death records, and publicly available internet sources were analyzed. We estimated hazard ratios for putative risk factors through Cox regression based upon 10 529 person-years of data and quantitatively and qualitatively analyzed the circumstances surrounding each death. Results Mortality did not differ statistically by demographic factors, although higher proportions of non-White and Hispanic individuals were deceased. Most deaths were related to medical comorbidities rather than hydrocephalus itself. Of the 14 deaths directly related to hydrocephalus, seven were caused by shunt complications and four occurred after decisions to forgo treatment, apparently in response to poor outcomes predicted by the medical team. Half the deaths were preceded by shifts to comfort-based care; however, these decisions appeared to substantially change the patient's clinical trajectory only half the time. Interpretation Children are more likely to die with, rather than from, hydrocephalus. Our results emphasize the complexities of medical decision-making and the influence of clinicians in guiding these choices.

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.

The coronavirus disease 2019 (COVID-19) pandemic has affected mortality and morbidity across all ages, including children. It is now known that neurological manifestations of COVID-19, ranging from headaches to stroke, may involve the central and/or peripheral nervous system at any age. Neurologic involvement is also noted in the multisystem inflammatory syndrome in children, a pediatric condition that occurs weeks after infection with the causative virus of COVID-19, severe acute respiratory syndrome coronavirus 2. Knowledge about mechanisms of neurologic disease is scarce but rapidly growing. COVID-19 neurologic manifestations may have particularly adverse impacts on the developing brain. Emerging data suggest a cohort of patients with COVID-19 will have longitudinal illness affecting their cognitive, physical, and emotional health, but little is known about the long-term impact on affected children and their families. Pediatric collaboratives have begun to provide important initial information on neuroimaging manifestations and the incidence of ischemic stroke in children with COVID 19. The Global Consortium Study of Neurologic Dysfunction in COVID-19-Pediatrics, a multinational collaborative, is working to improve understanding of the epidemiology, mechanisms of neurological manifestations, and the long-term implications of COVID-19 in children and their families.

Febrile‐infection related epilepsy syndrome (FIRES) is a devastating neurological condition characterized by a febrile illness preceding new onset refractory status epilepticus (NORSE). Increasing evidence suggests innate immune dysfunction as a potential pathological mechanism. We report an international retrospective cohort of 25 children treated with anakinra, a recombinant interleukin‐1 receptor antagonist, as an immunomodulator for FIRES. Anakinra was potentially safe with only one child discontinuing therapy due to infection. Earlier anakinra initiation was associated with shorter duration of mechanical ventilation, ICU and hospital length of stay. Our retrospective data lay the groundwork for prospective consensus‐driven cohort studies of anakinra in FIRES.

BACKGROUND/OBJECTIVE: Optimizing blood pressure is an important target for intervention following pediatric traumatic brain injury (TBI). Existing literature has examined the association between systolic blood pressure (SBP) and outcomes. Mean arterial pressure (MAP) is a better measure of organ perfusion than SBP and is used to determine cerebral perfusion pressure but has not been previously examined in relation to outcomes after pediatric TBI. We aimed to evaluate the strength of association between MAP-based hypotension early after hospital admission and discharge outcome, and to contrast the relative strength of association of hypotension with outcome between MAP-based and SBP-based blood pressure percentiles. METHODS: We examined the association between lowest age-specific MAP percentile within 12 hours after pediatric intensive care unit admission and poor discharge outcome (in-hospital death or transfer to a skilled nursing facility) in children with severe (Glasgow Coma Scale score

ObjectiveTo identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation.MethodsThis was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation.ResultsWe included 289 patients (55.7% male) with a median age of 4.3 (1.3–9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18–3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05–1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23–3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24–3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57–0.95).ConclusionBZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation.Classification of evidenceThis study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.

Objective To describe the characteristics of pediatric intensive care neurologists and their practice in the United States and Canada. Methods We performed a survey-based study of child neurologists who self-identify as ‘intensive care neurologists’. The survey included questions about demographics, training, pediatric neurocritical care service and job structure, teaching, academics, challenges, and views on the future of pediatric neurocritical care. Results We analyzed 55 surveys. Most respondents were 31-50 years of age with ≤10 years of practice experience. Fifty-four percent identified as female. Most completed subspecialty training after child neurology residency. The majority practice at highly resourced centers with >45 intensive care unit beds. Respondents cover a variety of inpatient (critical and noncritical care) services, at times simultaneously, for a median of 19.5 weeks/y and work >70 hours/wk when on service for pediatric neurocritical care. The top 3 challenges reported were competing demands for time, excess volume, and communication with critical care medicine. Top priorities for the “ideal pediatric neurocritical care service” were attendings with training in pediatric neurocritical care or a related field and joint rounding with critical care medicine. Conclusion We report a survey-based analysis of the demographics and scope of practice of pediatric critical care neurologists. We highlight challenges faced and provide a framework for the further development of this rapidly growing field.

Objective: To characterize the risk of hemorrhagic transformation following cardioembolic stroke in childhood, and whether anticoagulation impacts that risk. Methods: Ninety-five children (1 month-18 years) with cardioembolic arterial ischemic stroke between January 1, 2009, and December 31, 2019, at 2 institutions were identified for retrospective chart review. Neuroimaging was reviewed to assess for hemorrhagic transformation. Results: There were 11 cases of hemorrhagic transformation; 8 occurred within 2 days of stroke diagnosis. Risk of hemorrhagic transformation did not differ in patients with and without anticoagulation use (15% vs 9%, estimated risk difference 5%; CI –9%, 19%). Stroke size did not predict hemorrhagic transformation (OR 1.004, 95% CI 0.997, 1.010). Risk of hemorrhagic transformation was higher in strokes that occurred in the inpatient compared with the outpatient setting (16% vs 6%). Conclusion: Hemorrhagic transformation occurred in 11% of pediatric cardioembolic ischemic stroke, usually within 2 days of stroke diagnosis, and was not associated with anticoagulation or stroke size.

Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C).Multicenter, cross-sectional study of neurological manifestations in children aged18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed.Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P 0.05.In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.

CONTEXT Acute neurologic dysfunction is common in critically ill children and contributes to outcomes and end of life decision-making. OBJECTIVE To develop consensus criteria for neurologic dysfunction in critically ill children by evaluating the evidence supporting such criteria and their association with outcomes. DATA SOURCES Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020, by using a combination of medical subject heading terms and text words to define concepts of neurologic dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION Studies were included if the researchers evaluated critically ill children with neurologic injury, evaluated the performance characteristics of assessment and scoring tools to screen for neurologic dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies with an adult population or premature infants (≤36 weeks' gestational age), animal studies, reviews or commentaries, case series with sample size ≤10, and studies not published in English with an inability to determine eligibility criteria were excluded. DATA EXTRACTION Data were abstracted from each study meeting inclusion criteria into a standard data extraction form by task force members. DATA SYNTHESIS The systematic review supported the following criteria for neurologic dysfunction as any 1 of the following: (1) Glasgow Coma Scale score ≤8; (2) Glasgow Coma Scale motor score ≤4; (3) Cornell Assessment of Pediatric Delirium score ≥9; or (4) electroencephalography revealing attenuation, suppression, or electrographic seizures. CONCLUSIONS We present consensus criteria for neurologic dysfunction in critically ill children.

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

BACKGROUND Optimized benzodiazepine (BZD) dosing decreases morbidity and mortality in children with status epilepticus (SE), but previous studies have documented widespread underdosing. Prior interventions have focused on in-hospital SE treatment, although more than 75% of pediatric patients with SE are initially treated by emergency medical services (EMS). Our goal was to assess whether an EMS-focused, collaboratively developed dosing resuscitation aid (Medic One Pediatric [MOPed] cards) and training could improve BZD dosing and pediatric SE outcomes. METHODS We conducted a retrospective review of patients aged 12 years and younger treated by EMS for SE and transferred to Seattle Children's Hospital during the 1 year before and immediately after MOPed card training. The primary outcome was the percentage of patients receiving underdosed BZD treatment. Secondary outcomes included time to second-line antiseizure medication (ASM), intubation, and intensive care unit (ICU) admission. RESULTS The 44 children before and 33 after MOPed implementation were similar with respect to age, gender, and pre-existing epilepsy diagnosis. The percentage of children receiving underdosed BZDs fell from 52% to 6% after MOPed implementation (P

OBJECTIVES To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients. DESIGN Retrospective cohort study with prospectively collected data between June 2011 and January 2019. SETTING Seventeen academic hospitals in the United States. PATIENTS We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We identified 281 patients (157 males) with a median age of 4.1 years (1.3-9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55-491.5 min] vs 62 min [33.3-120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5-1,255 min] vs 150 min [90-318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58-368 hr] vs 3 hr [1.4-5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5-40 d] vs [1.8-8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments. CONCLUSIONS Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.

We aimed to determine whether clinical EEG reports obtained from children in the intensive care unit with refractory status epilepticus could provide data for comparative effectiveness research studies.We conducted a retrospective descriptive study to assess the documentation of key variables within clinical continuous EEG monitoring reports based on the American Clinical Neurophysiology Society's standardized EEG terminology for children with refractory status epilepticus from 10 academic centers. Two pediatric electroencephalographers reviewed the EEG reports. We compared reports generated using free text or templates.We reviewed 191 EEG reports. Agreement between the electroencephalographers regarding whether a variable was described in the report ranged from fair to very good. The presence of electrographic seizures (ES) was documented in 46% (87/191) of reports, and these reports documented the time of first ES in 64% (56/87), ES duration in 72% (63/85), and ES frequency in 68% (59/87). Reactivity was documented in 16% (31/191) of reports, and it was more often documented in template than in free-text reports (40% vs. 14%, P = 0.006). Other variables were not differentially reported in template versus free-text reports.Many key EEG features are not documented consistently in clinical continuous EEG monitoring reports, including ES characteristics and reactivity assessment. Standardization may be needed for clinical EEG reports to provide informative data for large multicenter observational studies.

BackgroundNew-onset headache after stroke is common among adult stroke survivors. However, pediatric data are limited. The primary aim of this study was to investigate the prevalence of new-headache after pediatric ischemic stroke. Secondary outcomes were to describe the characteristics of patients experiencing poststroke headache and the association between poststroke headache and stroke recurrence.MethodsWe conducted a single-center retrospective study on children aged 30 days to 18 years with a confirmed radiographic diagnosis of arterial ischemic stroke (AIS) from January 1, 2008, to December 31, 2016. Patients were identified from an internal database, with additional data abstracted from the electronic medical record. Poststroke headache (occurring >30 days after stroke) was identified through electronic searches of the medical record and confirmed by chart review.ResultsOf 115 patients with confirmed AIS, 41 (36%) experienced poststroke headache, with headache developing a median of 6 months after stroke. Fifty-one percent of patients with poststroke headache presented to the emergency department for headache evaluation; 81% of the patients had an inpatient admission for headache. Older age at stroke (odds ratio [OR] 21.5; p = 0.0001) and arteriopathy (OR 8.65; p = 0.0029) were associated with development of poststroke headache in a multivariable analysis. Seventeen patients (15%) had a recurrent stroke during the study period. Poststroke headache was associated with greater risk for stroke recurrence (p = 0.049).ConclusionsRemote poststroke headache is a common morbidity among pediatric stroke survivors, particularly in older children. Headaches may increase health care utilization, including neuroimaging and hospital admissions. We identified a possible association between poststroke headache and stroke recurrence.

Severe Traumatic Brain Injury in Infants, Children, and Adolescents in 2019: Some Overdue Progress, Many Remaining Questions, and Exciting Ongoing Work in the Field of Traumatic Brain Injury ResearchIn this Supplement to Pediatric Critical Care Medicine, we are pleased to present the Third Edition o

Background and Purpose: Focal cerebral arteriopathy (FCA) of childhood with unilateral stenosis of the anterior circulation is reported to account for up to one-quarter of childhood arterial ischemic stroke, with stroke recurrence in 25% of cases. Limited knowledge regarding pathophysiology and outcome results in inconsistent treatment of FCA. Methods: Children with arterial ischemic stroke due to FCA between January 1, 2009, and January 1, 2019, were retrospectively identified at our institution which serves the US Pacific Northwest region. Electronic health record data, including neuroimaging studies, were reviewed, and the Pediatric Stroke Outcome Measure at 1 year was determined as the primary clinical end point. Results: Fifteen children were diagnosed with FCA, accounting for 19% of children with cerebral arteriopathies (n=77). Among children with FCA, the median age at the time of stroke was 6.8 years (Q1–Q3, 1.9–14.0 years). Four (20%) patients had worsening stroke, 3 of whom had concurrent infection. Three (20%) FCA cases were treated with steroids, one of whom had worsening stroke. Median Pediatric Stroke Outcome Measure at 1 year was 1.0 (Q1–Q3, 0.6–2.0). Variability in arteriopathy severity was observed within many patients. Patients with more severe arteriopathy using the Focal Cerebral Arteriopathy Severity Score had larger strokes and were more likely to have worsening stroke. The most common long-term neurological deficit was hemiparesis, which was present in 11 (73%) patients and associated with middle cerebral artery arteriopathy and infarcts. Conclusions: FCA may be less common than previously reported. Neuroimaging in FCA can help identify patients at greater risk for worsening stroke.

Background Time to treatment in pediatric refractory status epilepticus is delayed. We aimed to evaluate the influence of weekends and holidays on time to treatment of this pediatric emergency. Methods We performed a retrospective analysis of prospectively collected observational data of pediatric patients with refractory status epilepticus. Results We included 329 patients (56% males) with a median (p25 to p75) age of 3.8 (1.3 to 9) years. The median (p25 to p75) time to first BZD on weekdays and weekends/holidays was 20 (6.8 to 48.3) minutes versus 11 (5 to 35) minutes, P = 0.01; adjusted hazard ratio (HR) = 1.20 (95% confidence interval [CI]: 0.95 to 1.55), P = 0.12. The time to first non-BZD ASM was longer on weekdays than on weekends/holidays (68 [42.8 to 153.5] minutes versus 59 [27 to 120] minutes, P = 0.006; adjusted HR = 1.38 [95% CI: 1.08 to 1.76], P = 0.009). However, this difference was mainly driven by status epilepticus with in-hospital onset: among 108 patients, the time to first non-BZD ASM was longer during weekdays than during weekends/holidays (55.5 [28.8 to 103.5] minutes versus 28 [15.8 to 66.3] minutes, P = 0.003; adjusted HR = 1.65 [95% CI: 1.08 to 2.51], P = 0.01). Conclusions The time to first non-BZD ASM in pediatric refractory status epilepticus is shorter on weekends/holidays than on weekdays, mainly driven by in-hospital onset status epilepticus. Data on what might be causing this difference may help tailor policies to improve medication application timing.

Researchers from the National Pediatric Hospital in Buenos Aires, Argentina, describe their experience with therapeutic plasma exchange (TPE) for refractory inflammatory central nervous system (CNS) attacks in children over the course of the last 15 years.

Objective To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review. Methods We performed a retrospective analysis of a prospectively collected dataset from June 2011 to September 2019 on pediatric patients (1 month-21 years of age) with rSE. Results We studied 328 patients (56% male) with median (25th-75th percentile [p(25)-p(75)]) age of 3.8 (1.3-9.4) years. There were no differences in the median (p(25)-p(75)) time to first benzodiazepine (BZD) (20 [5-52.5] vs 15 [5-38] minutes,p= 0.3919), time to first non-BZD antiseizure medication (68 [34.5-163.5] vs 65 [33-142] minutes,p= 0.7328), and time to first continuous infusion (186 [124.2-571] vs 160 [89.5-495] minutes,p= 0.2236). Among 157 patients with out-of-hospital onset whose time to hospital arrival was available, the proportion who received at least 1 BZD before hospital arrival increased after publication of evidence of delays (41 of 81 [50.6%] vs 57 of 76 [75%],p= 0.0018), and the odds ratio (OR) was also increased in multivariable logistic regression (OR 4.35 [95% confidence interval 1.96-10.3],p= 0.0005). Conclusion Publication of evidence on delays in time to treatment was not associated with improvements in time to treatment of rSE, although it was associated with an increase in the proportion of patients who received at least 1 BZD before hospital arrival., This study and consortium were funded by the Epilepsy Research Fund, the Epilepsy Foundation of America (EF-213583, Targeted Initiative for Health Outcomes), by the American Epilepsy Society/Epilepsy Foundation of America Infrastructure Award, and by the Pediatric Epilepsy Research Foundation.

Background and Purpose— Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)—a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke—was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes. Methods— Data on children treated with intravenous tPA for neuroimaging-confirmed arterial ischemic stroke were collected retrospectively from 16 former TIPS sites to establish preliminary safety data. Participating sites were required to report all children who were treated with intravenous tPA to minimize reporting bias. Symptomatic intracranial hemorrhage (SICH) was defined as ECASS (European Cooperative Acute Stroke Study) II parenchymal hematoma type 2 or any intracranial hemorrhage associated with neurological deterioration within 36 following tPA administration. A Bayesian beta-binomial model for risk of SICH following intravenous tPA was fit using a prior distribution based on the risk level in young adults (1.7%); to test for robustness, the model was also fit with uninformative and conservative priors. Results— Twenty-six children (age range, 1.1–17 years; median, 14 years; 12 boys) with stroke and a median pediatric National Institutes of Health Stroke Scale score of 14 were treated with intravenous tPA within 2 to 4.5 hours (median, 3.0 hours) after stroke onset. No patient had SICH. Two children developed epistaxis. Conclusions— The estimated risk of SICH after tPA in children is 2.1% (95% highest posterior density interval, 0.0%–6.7%; mode, 0.9%). Regardless of prior assumption, there is at least a 98% chance that the risk is

OBJECTIVES Early resuscitation may improve outcomes in pediatric traumatic brain injury (TBI). We examined the association between timely treatment of hypotension and hypoxia during early care (prehospital or emergency department locations) and discharge outcomes in children with severe TBI. METHODS Hypotension was defined as systolic blood pressure less than 70 + 2 (age in years), and hypoxia was defined as PaO2 less than 60 mm Hg or oxygen saturation less than 90% in accordance with the 2003 Brain Trauma Foundation guidelines. Timely treatment of hypotension and hypoxia during early care was defined as the treatment within 30 minutes of a documented respective episode. Two hundred thirty-six medical records of children younger than 18 years with severe TBI from 5 regional pediatric trauma centers were examined. Main outcomes were in-hospital mortality and discharge Glasgow Outcome Scale (GOS) score. RESULTS Hypotension occurred in 26% (60/234) during early care and was associated with in-hospital mortality (23.3% vs 8.6%; P = 0.01). Timely treatment of hypotension during early care occurred in 92% (55/60) by use of intravenous fluids, blood products, or vasopressors and was associated with reduced in-hospital mortality [adjusted relative risk (aRR), 0.46; 95% confidence interval, 0.24-0.90] and less likelihood of poor discharge GOS (aRR, 0.54; 95% confidence interval, 0.39-0.76) when compared to children with hypotension who were not treated in a timely manner. Early hypoxia occurred in 17% (41/236) and all patients received timely oxygen treatment. CONCLUSIONS Timely resuscitation during early care was common and associated with lower in-hospital mortality and favorable discharge GOS in severe pediatric TBI.

BACKGROUND AND PURPOSE: To assess whether initial imaging characteristics independently predict one-year neurological outcomes in childhood arterial ischemic stroke (AIS) patients. METHODS: We used prospectively collected demographic and clinical data, imaging data, and one-year outcomes from the Vascular effects of Infection in Pediatric Stroke (VIPS) study. In 288 patients with first-time stroke, we measured infarct volume and location on the acute magnetic resonance imaging (MRI) studies, and hemorrhagic transformation on brain imaging studies during the acute presentation. Neurological outcome was assessed with the Pediatric Stroke Outcome Measure (PSOM). We used univariate and multivariable ordinal logistic regression models to test the association between imaging characteristics and outcome. RESULTS: Univariate analysis demonstrated that infarcts involving uncinate fasciculus, angular gyrus, insular cortex, or that extended from cortex to the subcortical nuclei were significantly associated with poorer outcomes with odds ratios ranging from 1.95 to 3.95. All locations except the insular cortex remained significant predictors of poor outcome on multivariable analysis. When infarct volume was added to the model, the locations did not remain significant. Larger infarct volumes and younger age at stroke onset were significantly associated with poorer outcome, but the strength of the relationships was weak. Hemorrhagic transformation did not predict outcome. CONCLUSION: In the largest pediatric AIS cohort collected to date, we showed that larger infarct volume and younger age at stroke were associated with poorer outcomes. We made the novel observation that the strength of these associations was modest and limits the ability to use these characteristics to predict outcome in children. Infarcts affecting specific locations were significantly associated with poorer outcomes in univariate and multivariable analyses, but lost significance when adjusted for infarct volume. Our findings suggest that infarcts which disrupt critical networks have a disproportionate impact upon outcome after childhood AIS. NON-STANDARD ABBREVIATIONS AND ACRONYMS: Acute Ischemic Stroke (AIS); Vascular effects of Infection in Pediatric Stroke (VIPS); Pediatric Stroke Outcome Measure (PSOM); Percentage Infarct Volume (PIV)

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

Objective Super-refractory status epilepticus (SRSE) is a life-threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multicenter, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE-547 Injection), a proprietary, aqueous formulation of the neuroactive steroid, allopregnanolone. Secondary objectives included pharmacokinetic assessment and open-label evaluation of brexanolone response during and after anesthetic third-line agent (TLA) weaning. Methods Patients receiving TLAs for SRSE control were eligible for open-label, 1-hour brexanolone loading infusions, followed by maintenance infusion. After 48 hours of brexanolone infusion, TLAs were weaned during brexanolone maintenance. After 4 days, the brexanolone dose was tapered. Safety and functional status were assessed over 3 weeks of follow-up. Results Twenty-five patients received open-label study drug. No serious adverse events (SAEs) were attributable to study drug, as determined by the Safety Review Committee. Sixteen patients (64%) experienced ≥1 SAE. Six patient deaths occurred, all deemed related to underlying medical conditions. Twenty-two patients underwent ≥1 TLA wean attempt. Seventeen (77%) met the response endpoint of weaning successfully off TLAs before tapering brexanolone. Sixteen (73%) were successfully weaned off TLAs within 5 days of initiating brexanolone infusion without anesthetic agent reinstatement in the following 24 hours. Interpretation In an open-label cohort of limited size, brexanolone demonstrated tolerability among SRSE patients of heterogeneous etiologies and was associated with a high rate of successful TLA weaning. The results suggest the possible development of brexanolone as an adjunctive therapy for SRSE requiring pharmacological coma for seizure control. Ann Neurol 2017;82:342–352

To examine the frequency of and factors associated with emergency department (ED) intracranial pressure (ICP) monitor placement in severe paediatric traumatic brain injury (TBI).Retrospective, multicentre cohort study of children18 years admitted to the ED with severe TBI and intubated for48 hours from 2007 to 2011.Two hundred and twenty-four children had severe TBI and 75% underwent either ED, operating room (OR) or paediatric intensive care unit (PICU) ICP monitor placement. Four out of five centres placed ICP monitors in the ED, mostly (83%) fibreoptic. Nearly 40% of the patients who received ICP monitors get it placed in the ED (29% overall). Factors associated with ED ICP monitor placement were as follows: age 13 to18 year olds compared to infants (aRR 2.02; 95% CI 1.37, 2.98), longer ED length of stay (LOS) (aRR 1.15; 95% CI 1.08, 1.21), trauma centre designation paediatric only I/II compared to adult/paediatric I/II (aRR 1.71; 95% CI 1.48, 1.98) and higher mean paediatric TBI patient volume (aRR 1.88;95% CI 1.68, 2.11). Adjusted for centre, higher bedside ED staff was associated with longer ED LOS (aRR 2.10; 95% CI 1.06, 4.14).ICP monitors are frequently placed in the ED at paediatric trauma centres caring for children with severe TBI. Both patient and organizational level factors are associated with ED ICP monitor placement.

Purpose of review Cardiac arrest in childhood is associated with a high risk for mortality and poor long-term functional outcome. This review discusses the current evidence for neuroprotective therapies and goals for postarrest care in the context of the pathophysiology of hypoxic-ischemic injury, modalities for neurologic prognostication in these children and potential future monitoring paradigms for maximizing cerebral perfusion in the postarrest period. Recent findings The recent publication of the in-hospital and out-of-hospital Therapeutic Hypothermia After Cardiac Arrest trials demonstrated a lack of statistically significant benefit for the use of postarrest therapeutic hypothermia. As a result, targeted normothermic temperature management has become standard of care. Continuous electroencephalographic monitoring during the acute postarrest period provides useful additional data for neurologic prognostication, in addition to its value for detection of seizures. Ongoing research into noninvasive monitoring of cerebrovascular autoregulation has the potential to individualize blood pressure goals in the postarrest period, maximizing cerebral perfusion in these patients. Summary Therapeutic strategies after cardiac arrest seek to maximize cerebral perfusion while mitigating the effects of secondary brain injury and loss of autoregulation. Future research into new monitoring strategies and better long-term outcome measures may allow more precise targeting of therapies to these goals.

Objectives The role of sleep architecture as a biomarker for prognostication after resuscitation from cardiac arrest in children hospitalized in an ICU remains poorly defined. We sought to investigate the association between features of normal sleep architecture in children after cardiac arrest and a favorable neurologic outcome at 6 months. Design Retrospective review of medical records and continuous electroencephalography monitoring. Setting Cardiac and PICU of a tertiary children's hospital. Patients All patients from 6 months to 18 years old resuscitated from cardiac arrest who underwent continuous electroencephalography monitoring in the first 24 hours after in- or out-of-hospital cardiac arrest from January 2010 to June 2015. Interventions None. Measurements and main results Thirty-four patients underwent continuous electroencephalography monitoring after cardiac arrest. The median age was 6.1 years (interquartile range, 1.5-12.5 yr), 20 patients were male (59%). Most cases (n = 23, 68%) suffered from in-hospital cardiac arrest. Electroencephalography monitoring was initiated a median of 9.3 hours (5.8-14.9 hr) after return of spontaneous circulation, for a median duration of 14.3 hours (6.0-16.0 hr) within the first 24-hour period after the cardiac arrest. Five patients had normal spindles, five had abnormal spindles, and 24 patients did not have any sleep architecture. The presence of spindles was associated with a favorable neurologic outcome at 6-month postcardiac arrest (p = 0.001). Conclusions Continuous electroencephalography monitoring can be used in children to assess spindles in the ICU. The presence of spindles on continuous electroencephalography monitoring in the first 24 hours after resuscitation from cardiac arrest is associated with a favorable neurologic outcome. Assessment of sleep architecture on continuous electroencephalography after cardiac arrest could improve outcome prediction.

Spectral electroencephalogram analysis is a method for automated analysis of electroencephalogram patterns, which can be performed at the bedside. We sought to determine the utility of spectral electroencephalogram for grading hepatic encephalopathy in children with acute liver failure.Retrospective cohort study.Tertiary care pediatric hospital.Patients between 0 and 18 years old who presented with acute liver failure and were admitted to the PICU.None.Electroencephalograms were analyzed by spectral analysis including total power, relative δ, relative θ, relative α, relative β, θ-to-Δ ratio, and α-to-Δ ratio. Normal values and ranges were first derived using normal electroencephalograms from 70 children of 0-18 years old. Age had a significant effect on each variable measured (p0.03). Electroencephalograms from 33 patients with acute liver failure were available for spectral analysis. The median age was 4.3 years, 14 of 33 were male, and the majority had an indeterminate etiology of acute liver failure. Neuroimaging was performed in 26 cases and was normal in 20 cases (77%). The majority (64%) survived, and 82% had a good outcome with a score of 1-3 on the Pediatric Glasgow Outcome Scale-Extended at the time of discharge. Hepatic encephalopathy grade correlated with the qualitative visual electroencephalogram scores assigned by blinded neurophysiologists (rs = 0.493; p0.006). Spectral electroencephalogram characteristics varied significantly with the qualitative electroencephalogram classification (p0.05). Spectral electroencephalogram variables including relative Δ, relative θ, relative α, θ-to-Δ ratio, and α-to-Δ ratio all significantly varied with the qualitative electroencephalogram (p0.025). Moderate to severe hepatic encephalopathy was correlated with a total power of less than or equal to 50% of normal for children 0-3 years old, and with a relative θ of less than or equal to 50% normal for children more than 3 years old (p0.05). Spectral electroencephalogram classification correlated with outcome (p0.05).Spectral electroencephalogram analysis can be used to evaluate even young patients for hepatic encephalopathy and correlates with outcome. Spectral electroencephalogram may allow improved quantitative and reproducible assessment of hepatic encephalopathy grade in children with acute liver failure.