A quality improvement initiative to improve folic acid supplementation counseling for adolescent females with epilepsy.

OBJECTIVE: We designed a quality improvement (QI) project to improve rates of documented folic acid supplementation counseling for adolescent females with epilepsy, consistent with a quality measure from the American Academy of Neurology and American Epilepsy Society. Our SMART aim was to increase the percentage of visits at which folic acid counseling was addressed from our baseline rate of 23% to 50% by July 1, 2020. METHODS: This initiative was conducted in female patients ≥12 years old with epilepsy who were prescribed daily antiseizure medication and were seen by the 13 providers in our Neurology QI Program. Using provider interviews, we undertook a root cause analysis of low counseling rates and identified the following main factors: insufficient time during clinic visit to counsel, lack of provider knowledge, and forgetting to counsel. Countermeasures were designed to address these main root causes and were implemented through iterative plan-do-study-act (PDSA) cycles. Interventions included provider education and features within the electronic health record, which were introduced sequentially, culminating in the creation of a best practice advisory (BPA). We performed biweekly chart reviews of visits for applicable patients to establish baseline performance rate and track progress over time. We used a statistical process control p-chart to analyze the outcome measure of documented counseling. As a balancing measure, clinicians were surveyed using the Technology Adoption Model survey to assess acceptance of the BPA. RESULTS: From September 2019 to August 2022, the QI team improved rates of documented folic acid counseling from 23% to 73% through several PDSA cycles. This level of performance has been sustained over time. The most successful and sustainable intervention was the BPA. Provider acceptance of the BPA was overall positive. SIGNIFICANCE: We successfully used QI methodology to improve and sustain our rates of documented folic acid supplementation counseling for adolescent females with epilepsy.

Safety of intravenous lacosamide in hospitalized children and neonates.

OBJECTIVE: Seizures are common in critically ill children and neonates, and these patients would benefit from intravenous (IV) antiseizure medications with few adverse effects. We aimed to assess the safety profile of IV lacosamide (LCM) among children and neonates. METHODS: This retrospective multicenter cohort study examined the safety of IV LCM use in 686 children and 28 neonates who received care between January 2009 and February 2020. RESULTS: Adverse events (AEs) were attributed to LCM in only 1.5% (10 of 686) of children, including rash (n = 3, .4%), somnolence (n = 2, .3%), and bradycardia, prolonged QT interval, pancreatitis, vomiting, and nystagmus (n = 1, .1% each). There were no AEs attributed to LCM in the neonates. Across all 714 pediatric patients, treatment-emergent AEs occurring in >1% of patients included rash, bradycardia, somnolence, tachycardia, vomiting, feeling agitated, cardiac arrest, tachyarrhythmia, low blood pressure, hypertension, decreased appetite, diarrhea, delirium, and gait disturbance. There were no reports of PR interval prolongation or severe cutaneous adverse reactions. When comparing children who received a recommended versus a higher than recommended initial dose of IV LCM, there was a twofold increase in the risk of rash in the higher dose cohort (adjusted incidence rate ratio = 2.11, 95% confidence interval = 1.02-4.38). SIGNIFICANCE: This large observational study provides novel evidence demonstrating the tolerability of IV LCM in children and neonates.

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

Neuromonitoring in neonatal critical care part I: neonatal encephalopathy and neonates with possible seizures.

The blooming of neonatal neurocritical care over the last decade reflects substantial advances in neuromonitoring and neuroprotection. The most commonly used brain monitoring tools in the neonatal intensive care unit (NICU) are amplitude integrated EEG (aEEG), full multichannel continuous EEG (cEEG), and near-infrared spectroscopy (NIRS). While some published guidelines address individual tools, there is no consensus on consistent, efficient, and beneficial use of these modalities in common NICU scenarios. This work reviews current evidence to assist decision making for best utilization of neuromonitoring modalities in neonates with encephalopathy or with possible seizures. Neuromonitoring approaches in extremely premature and critically ill neonates are discussed separately in the companion paper. IMPACT: Neuromonitoring techniques hold promise for improving neonatal care. For neonatal encephalopathy, aEEG can assist in screening for eligibility for therapeutic hypothermia, though should not be used to exclude otherwise eligible neonates. Continuous cEEG, aEEG and NIRS through rewarming can assist in prognostication. For neonates with possible seizures, cEEG is the gold standard for detection and diagnosis. If not available, aEEG as a screening tool is superior to clinical assessment alone. The use of seizure detection algorithms can help with timely seizures detection at the bedside.

Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates.

Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. IMPACT: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication. For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury. Continuous multimodal monitoring as well as monitoring of sleep, sleep-wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care.

Extracorporeal Membrane Oxygenation for Neonates With Congenital Diaphragmatic Hernia: Prevalence of Seizures and Outcomes.

OBJECTIVES: We aimed to determine the prevalence of electrographic seizures and associated odds of adverse outcomes of electrographic seizures in neonates with congenital diaphragmatic hernia (CDH) receiving extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective, descriptive case series. SETTING: Neonatal ICU (NICU) in a quaternary care institution. PATIENTS: All neonates with CDH receiving ECMO undergoing continuous electroencephalographic monitoring (CEEG) and follow-up between January 2012 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All eligible neonates with CDH receiving ECMO underwent CEEG (n = 75). Electrographic seizures occurred in 14 of 75 (19%): they were exclusively electrographic-only in nine of 14, both electrographic-only and electroclinical in three of 14, and electroclinical only in two of 14. Two neonates developed status epilepticus. We identified an association between presence of seizures, rather than not, and longer duration of initial session of CEEG monitoring (55.7 hr [48.2-87.3 hr] vs 48.0 hr [43.0-48.3 hr]; p = 0.001). We also found an association between presence of seizures, rather than not, and greater odds of use of a second CEEG monitoring (12/14 vs 21/61; odds ratio [OR], 11.43 [95% CI, 2.34-55.90; p = 0.0026). Most neonates with seizures (10/14), experienced their onset of seizures more than 96 hours after the start of ECMO. Overall, the presence of electrographic seizures, compared with not, was associated with lower odds of survival to NICU discharge (4/14 vs 49/61; OR 0.10 [95% CI 0.03 to 0.37], p = 0.0006). Also, the presence of seizures-rather than not-was associated with greater odds of a composite of death and all abnormal outcomes on follow-up (13/14 vs 26/61; OR, 17.5; 95% CI, 2.15-142.39; p = 0.0074). CONCLUSIONS: Nearly one in five neonates with CDH receiving ECMO developed seizures during the ECMO course. Seizures were predominantly electrographic-only and when present were associated with great odds of adverse outcomes. The current study provides evidence to support standardized CEEG in this population.

A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus.

BACKGROUND: Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE. METHODS: Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021. RESULTS: We identified 117 study participants (28 neonates), including 79 (68%) who received midazolam and 38 (32%) who received ketamine as the first-line anesthetic infusions. Seizures terminated more often in study participants administered ketamine (61%, 23/38) than midazolam (28%, 22/79; odds ratio [OR] 3.97, 95% confidence interval [CI] 1.76-8.98; P < 0.01). Adverse effects occurred more often in study participants administered midazolam (24%, 20/79) than ketamine (3%, 1/38; OR 12.54, 95% CI 1.61-97.43; P = 0.016). Study participants administered ketamine were younger, ketamine was used more often for children with acute symptomatic seizures, and midazolam was used more often for children with epilepsy. Multivariable logistic regression of seizure termination by first-line anesthetic infusion (ketamine or midazolam) including age at SE onset, SE etiology category, and individual seizure duration at anesthetic infusion initiation indicated seizures were more likely to terminate following ketamine than midazolam (OR 4.00, 95% CI 1.69-9.49; P = 0.002) and adverse effects were more likely following midazolam than ketamine (OR 13.41, 95% CI 1.61-111.04; P = 0.016). Survival to discharge was higher among study participants who received midazolam (82%, 65/79) than ketamine (55%, 21/38; P = 0.002), although treating clinicians did not attribute any deaths to ketamine or midazolam. CONCLUSIONS: Among children and neonates with RSE, ketamine was more often followed by seizure termination and less often associated with adverse effects than midazolam when administered as the first-line anesthetic infusion. Further prospective data are needed to compare first-line anesthetics for RSE.

Quantitative electroencephalogram in term neonates under different sleep states.

Electroencephalogram (EEG) can be used to assess depth of consciousness, but interpreting EEG can be challenging, especially in neonates whose EEG undergo rapid changes during the perinatal course. EEG can be processed into quantitative EEG (QEEG), but limited data exist on the range of QEEG for normal term neonates during wakefulness and sleep, baseline information that would be useful to determine changes during sedation or anesthesia. We aimed to determine the range of QEEG in neonates during awake, active sleep and quiet sleep states, and identified the ones best at discriminating between the three states. Normal neonatal EEG from 37 to 46 weeks were analyzed and classified as awake, quiet sleep, or active sleep. After processing and artifact removal, total power, power ratio, coherence, entropy, and spectral edge frequency (SEF) 50 and 90 were calculated. Descriptive statistics were used to summarize the QEEG in each of the three states. Receiver operating characteristic (ROC) curves were used to assess discriminatory ability of QEEG. 30 neonates were analyzed. QEEG were different between awake vs asleep states, but similar between active vs quiet sleep states. Entropy beta, delta2 power %, coherence delta2, and SEF50 were best at discriminating awake vs active sleep. Entropy beta had the highest AUC-ROC ≥ 0.84. Entropy beta, entropy delta1, theta power %, and SEF50 were best at discriminating awake vs quiet sleep. All had AUC-ROC ≥ 0.78. In active sleep vs quiet sleep, theta power % had highest AUC-ROC > 0.69, lower than the other comparisons. We determined the QEEG range in healthy neonates in different states of consciousness. Entropy beta and SEF50 were best at discriminating between awake and sleep states. QEEG were not as good at discriminating between quiet and active sleep. In the future, QEEG with high discriminatory power can be combined to further improve ability to differentiate between states of consciousness.

Characteristics of Neonates with Cardiopulmonary Disease Who Experience Seizures: A Multicenter Study.

OBJECTIVE: To compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease. STUDY DESIGN: The Neonatal Seizure Registry is a multicenter, prospectively acquired cohort of neonates with clinical or electroencephalographic (EEG)-confirmed seizures. Cardiopulmonary disease was defined as congenital heart disease, congenital diaphragmatic hernia, and exposure to extracorporeal membrane oxygenation. We assessed continuous EEG monitoring strategy, seizure characteristics, seizure management, and outcomes for neonates with and without cardiopulmonary disease. RESULTS: We evaluated 83 neonates with cardiopulmonary disease and 271 neonates without cardiopulmonary disease. Neonates with cardiopulmonary disease were more likely to have EEG-only seizures (40% vs 21%, P < .001) and experience their first seizure later than those without cardiopulmonary disease (174 vs 21 hours of age, P < .001), but they had similar seizure exposure (many-recurrent electrographic seizures 39% vs 43%, P = .27). Phenobarbital was the primary initial antiseizure medication for both groups (90%), and both groups had similarly high rates of incomplete response to initial antiseizure medication administration (66% vs 68%, P = .75). Neonates with cardiopulmonary disease were discharged from the hospital later (hazard ratio 0.34, 95% CI 0.25-0.45, P < .001), although rates of in-hospital mortality were similar between the groups (hazard ratio 1.13, 95% CI 0.66-1.94, P = .64). CONCLUSION: Neonates with and without cardiopulmonary disease had a similarly high seizure exposure, but neonates with cardiopulmonary disease were more likely to experience EEG-only seizures and had seizure onset later in the clinical course. Phenobarbital was the most common seizure treatment, but seizures were often refractory to initial antiseizure medication. These data support guidelines recommending continuous EEG in neonates with cardiopulmonary disease and indicate a need for optimized therapeutic strategies.

Seizure Severity and Treatment Response in Newborn Infants with Seizures Attributed to Intracranial Hemorrhage.

OBJECTIVE: We sought to characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born term and preterm. For infants born term, we sought to compare seizure severity and treatment response for multisite vs single-site ICH and hypoxic-ischemic encephalopathy (HIE) with vs without ICH. STUDY DESIGN: We studied 112 newborn infants with seizures attributed to ICH and 201 infants born at term with seizures attributed to HIE, using a cohort of consecutive infants with clinically diagnosed and/or electrographic seizures prospectively enrolled in the multicenter Neonatal Seizure Registry. We compared seizure severity and treatment response among infants with complicated ICH, defined as multisite vs single-site ICH and HIE with vs without ICH. RESULTS: ICH was a more common seizure etiology in infants born preterm vs term (27% vs 10%, P < .001). Most infants had subclinical seizures (74%) and an incomplete response to initial antiseizure medication (ASM) (68%). In infants born term, multisite ICH was associated with more subclinical seizures than single-site ICH (93% vs 66%, P = .05) and an incomplete response to the initial ASM (100% vs 66%, P = .02). Status epilepticus was more common in HIE with ICH vs HIE alone (38% vs 17%, P = .05). CONCLUSIONS: Seizure severity was greater and treatment response was lower among infants born term with complicated ICH. These data support the use of continuous video electroencephalogram monitoring to accurately detect seizures and a multistep treatment plan that considers early use of multiple ASMs, particularly with parenchymal and high-grade intraventricular hemorrhage and complicated ICH.

Visits of concern in child neurology telemedicine.

AIM: To characterize child neurology telemedicine visits flagged as requiring in-person evaluation during the COVID-19 pandemic. METHOD: We analyzed 7130 audio-video telemedicine visits between March and November 2020. Visits of concern (VOCs) were defined as telemedicine visits where the clinical scenario necessitated in-person follow-up evaluation sooner than if the visit had been conducted in-person. RESULTS: VOCs occurred in 5% (333/7130) of visits for 292 individuals (148 females, 144 males). Providers noted technical challenges more often in VOCs (40%; 133/333) than visits without concern (non-VOCs) (28%; 1922/6797) (p < 0.05). The median age was younger in VOCs (9 years 3 months, interquartile range [IQR] 2 years 0 months-14 years 3 months) than non-VOCs (11 years 3 months, IQR 5 years 10 months-15 years 10 months) (p < 0.05). Median household income was lower for patients with VOCs ($74 K, IQR $55 K-$97 K) compared to non-VOCs ($80 K, IQR $61 K-$100 K) (p < 0.05). Compared with all other race categories, families who self-identified as Black were more likely to have a VOC (odds ratio 1.53, 95% confidence interval 1.21-2.06). Epilepsy and headache represented the highest percentages of VOCs, while neuromuscular disorders and developmental delay had a higher proportion of VOCs than other neurological disorders. INTERPRETATION: These findings suggest that telemedicine is an effective platform for most child neurology visits. Younger children and those with neuromuscular disorders or developmental delays are more likely to require in-person evaluation. WHAT THIS PAPER ADDS: It is possible to successfully flag patients who need in-person assessment. Providers can manage issues arising during telemedicine in 95% of visits. Visits flagged as concerning were likely unrelated to modality of patient care. Provider concern was independent of technical difficulties for most telehealth visits. Younger age may be correlated with need for in-person assessment.

Periodic and rhythmic patterns in critically ill children: Incidence, interrater agreement, and seizures.

OBJECTIVES: We aimed to determine the incidence of periodic and rhythmic patterns (PRP), assess the interrater agreement between electroencephalographers scoring PRP using standardized terminology, and analyze associations between PRP and electrographic seizures (ES) in critically ill children. METHODS: This was a prospective observational study of consecutive critically ill children undergoing continuous electroencephalographic monitoring (CEEG). PRP were identified by one electroencephalographer, and then two pediatric electroencephalographers independently scored the first 1-h epoch that contained PRP using standardized terminology. We determined the incidence of PRPs, evaluated interrater agreement between electroencephalographers scoring PRP, and evaluated associations between PRP and ES. RESULTS: One thousand three hundred ninety-nine patients underwent CEEG. ES occurred in 345 (25%) subjects. PRP, ES + PRP, and ictal-interictal continuum (IIC) patterns occurred in 142 (10%), 81 (6%), and 93 (7%) subjects, respectively. The most common PRP were generalized periodic discharges (GPD; 43, 30%), lateralized periodic discharges (LPD; 34, 24%), generalized rhythmic delta activity (GRDA; 34, 24%), bilateral independent periodic discharges (BIPD; 14, 10%), and lateralized rhythmic delta activity (LRDA; 11, 8%). ES risk varied by PRP type (p < .01). ES occurrence was associated with GPD (odds ratio [OR] = 6.35, p < .01), LPD (OR = 10.45, p < .01), BIPD (OR = 6.77, p < .01), and LRDA (OR = 6.58, p < .01). Some modifying features increased the risk of ES for each of those PRP. GRDA was not significantly associated with ES (OR = 1.34, p = .44). Each of the IIC patterns was associated with ES (OR = 6.83-8.81, p < .01). ES and PRP occurred within 6 h (before or after) in 45 (56%) subjects. SIGNIFICANCE: PRP occurred in 10% of critically ill children who underwent CEEG. The most common patterns were GPD, LPD, GRDA, BIPD, and LRDA. The GPD, LPD, BIPD, LRDA, and IIC patterns were associated with ES. GRDA was not associated with ES.

Early-life epilepsy after acute symptomatic neonatal seizures: A prospective multicenter study.

OBJECTIVE: We aimed to evaluate early-life epilepsy incidence, seizure types, severity, risk factors, and treatments among survivors of acute neonatal seizures. METHODS: Neonates with acute symptomatic seizures born 7/2015-3/2018 were prospectively enrolled at nine Neonatal Seizure Registry sites. One-hour EEG was recorded at age three months. Post-neonatal epilepsy and functional development (Warner Initial Developmental Evaluation of Adaptive and Functional Skills - WIDEA-FS) were assessed. Cox regression was used to assess epilepsy-free survival. RESULTS: Among 282 infants, 37 (13%) had post-neonatal epilepsy by 24-months [median age of onset 7-months (IQR 3-14)]. Among those with post-neonatal epilepsy, 13/37 (35%) had infantile spasms and 12/37 (32%) had drug-resistant epilepsy. Most children with post-neonatal epilepsy had abnormal neurodevelopment at 24-months (WIDEA-FS >2SD below normal population mean for 81% of children with epilepsy vs 27% without epilepsy, RR 7.9, 95% CI 3.6-17.3). Infants with severely abnormal neonatal EEG background patterns were more likely to develop epilepsy than those with mild/moderate abnormalities (HR 3.7, 95% CI 1.9-5.9). Neonatal EEG with ≥3 days of seizures also predicted hazard of epilepsy (HR 2.9, 95% CI 1.4-5.9). In an adjusted model, days of neonatal EEG-confirmed seizures (HR 1.4 per day, 95% CI 1.2-1.6) and abnormal discharge examination (HR 3.9, 95% CI 1.9-7.8) were independently associated with time to epilepsy onset. Abnormal (vs. normal) three-month EEG was not associated with epilepsy. SIGNIFICANCE: In this multicenter study, only 13% of infants with acute symptomatic neonatal seizures developed post-neonatal epilepsy by age 24-months. However, there was a high risk of severe neurodevelopmental impairment and drug-resistant seizures among children with post-neonatal epilepsy. Days of EEG-confirmed neonatal seizures was a potentially modifiable epilepsy risk factor. An EEG at three months was not clinically useful for predicting epilepsy. These practice changing findings have implications for family counseling, clinical follow-up planning, and future research to prevent post-neonatal epilepsy.

Assessing seizure burden in pediatric epilepsy using an electronic medical record-based tool through a common data element approach.

OBJECTIVE: Improvement in epilepsy care requires standardized methods to assess disease severity. We report the results of implementing common data elements (CDEs) to document epilepsy history data in the electronic medical record (EMR) after 12 months of clinical use in outpatient encounters. METHODS: Data regarding seizure frequency were collected during routine clinical encounters using a CDE-based form within our EMR. We extracted CDE data from the EMR and developed measurements for seizure severity and seizure improvement scores. Seizure burden and improvement was evaluated by patient demographic and encounter variables for in-person and telemedicine encounters. RESULTS: We assessed a total of 1696 encounters in 1038 individuals with childhood epilepsies between September 6, 2019 and September 11, 2020 contributed by 32 distinct providers. Childhood absence epilepsy (n = 121), Lennox-Gastaut syndrome (n = 86), and Dravet syndrome (n = 42) were the most common epilepsy syndromes. Overall, 43% (737/1696) of individuals had at least monthly seizures, 17% (296/1696) had a least daily seizures, and 18% (311/1696) were seizure-free for >12 months. Quantification of absolute seizure burden and changes in seizure burden over time differed between epilepsy syndromes, including high and persistent seizure burden in patients with Lennox-Gastaut syndrome. Individuals seen via telemedicine or in-person encounters had comparable seizure frequencies. Individuals identifying as Hispanic/Latino, particularly from postal codes with lower median household incomes, were more likely to have ongoing seizures that worsened over time. SIGNIFICANCE: Standardized documentation of clinical data in childhood epilepsies through CDE can be implemented in routine clinical care at scale and enables assessment of disease burden, including characterization of seizure burden over time. Our data provide insights into heterogeneous patterns of seizure control in common pediatric epilepsy syndromes and will inform future initiatives focusing on patient-centered outcomes in childhood epilepsies, including the impact of telemedicine and health care disparities.

Design and implementation of electronic health record common data elements for pediatric epilepsy: Foundations for a learning health care system.

OBJECTIVE: Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data-driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy. METHODS: A multiple stakeholder group (clinicians, researchers, parents, caregivers, advocates, and electronic health record [EHR] vendors) developed clinical CDEs for routine care of children with epilepsy. Initial drafts drew from clinical epilepsy note templates, CDEs created for clinical research, items in existing registries, consensus documents and guidelines, quality metrics, and outcomes needed for demonstration projects. The CDEs were refined through discussion and field testing. We describe the development process, rationale for CDE selection, findings from piloting, and the CDEs themselves. We also describe early implementation, including experience with EHR systems and compatibility with the International League Against Epilepsy classification of seizure types. RESULTS: Common data elements were drafted in August 2017 and finalized in January 2020. Prioritized outcomes included seizure control, seizure freedom, American Academy of Neurology quality measures, presence of common comorbidities, and quality of life. The CDEs were piloted at 224 visits at 10 centers. The final CDEs included 36 questions in nine sections (number of questions): diagnosis (1), seizure frequency (9), quality of life (2), epilepsy history (6), etiology (8), comorbidities (2), treatment (2), process measures (5), and longitudinal history notes (1). Seizures are categorized as generalized tonic-clonic (regardless of onset), motor, nonmotor, and epileptic spasms. Focality is collected as epilepsy type rather than seizure type. Seizure frequency is measured in nine levels (all used during piloting). The CDEs were implemented in three vendor systems. Early clinical adoption included 1294 encounters at one center. SIGNIFICANCE: We created, piloted, refined, finalized, and implemented a novel set of clinical CDEs for pediatric epilepsy.

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.

Establishing a learning healthcare system to improve health outcomes for people with epilepsy.

OBJECTIVE: To describe the organization of the Epilepsy Learning Healthcare System (ELHS), a network that aims to improve care outcomes for people with epilepsy (PWE). MATERIALS AND METHODS: Patients and family partners, providers, researchers, epidemiologists, and other leaders collaborated to recruit epilepsy centers and community services organizations into a novel learning network. A multidisciplinary Coordinating Committee developed ELHS governance and organizational structure, including four key planning Cores (Community, Clinical, Quality Improvement, and Data). Through Quality Improvement (QI) methodology grounded in the Institute for Healthcare Improvement (IHI) model, including iterative Plan-Do-Study-Act (PDSA) rapid learning cycles and other learning and sharing sessions, ELHS equipped epilepsy centers and community organizations with tools to standardize, measure, share, and improve key aspects of epilepsy care. The initial learning cycles addressed provider documentation of seizure frequency and type, and also screening for medication adherence barriers. Rapid learning cycles have been carried out on these initial measures in both clinical centers and community-based settings. Additional key measures have been defined for quality of life, screening, and treatment for mental health and behavioral comorbidities, transition from pediatric to adult care, counseling for women and girls living with epilepsy, referral for specialty care, and prevention and treatment of seizure clusters and status epilepticus. RESULTS: It is feasible to adopt a learning healthcare system framework in epilepsy centers and community services organizations. Through structured collaboration between epilepsy care providers, community support organizations, PWE, and their families/caregivers we have identified new opportunities to improve outcomes that are not available in traditional care models.

Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study.

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.

Decadron, Diamox, and Zantac: A Novel Combination for Ventricular Shunt Failure in Pediatric Neurosurgical Patients.

OBJECTIVE: Cerebral ventricular shunt failure is common and presents with symptoms that range from headaches to death. The combination of Diamox (acetazolamide), Decadron (dexamethasone), and Zantac (ranitidine) (DDZ) is used at our institution to medically stabilize pediatric patients presenting with symptomatic shunt failure before shunt revision. We describe our experience of this drug combination as a temporizing measure to decrease symptoms associated with shunt failure. METHODS: We performed a single-center retrospective chart review of patients younger than 18 years with ventricular shunt failure who underwent a shunt revision between January 2015 to October 2017 and received DDZ before surgery. The outcome variables evaluated included pre-DDZ and post-DDZ clinical symptoms, pain scores, and vital signs. RESULTS: There were 112 cases that received DDZ before shunt revision. The 4 most commonly reported symptoms were analyzed. Headache was observed in 42 cases pre-DDZ, and post-DDZ there was a 71% reduction in headache (P < 0.0001); emesis was reported pre-DDZ in 76 cases, and post-DDZ there was an 83% reduction (P < 0.0001); irritability was noted pre-DDZ in 30 cases, and post-DDZ there was a 77% reduction (P = 0.0003); lethargy pre-DDZ was observed in 60 cases, and post-DDZ 73% demonstrated improvement (P < 0.0001). Maximum pain scores significantly decreased post-DDZ (P < 0.0001). Heart rate, systolic, and diastolic blood pressures significantly decreased post-DDZ (P < 0.0001, P < 0.0001, P = 0.0002, respectively). CONCLUSIONS: The combination of Decadron, Diamox, and Zantac is a novel treatment for ventricular shunt failure that may temporarily improve symptoms in patients awaiting shunt revision. Future studies could compare efficacy with other medical treatments.

Pediatric Post-Cardiac Arrest Care: A Scientific Statement From the American Heart Association.

Successful resuscitation from cardiac arrest results in a post-cardiac arrest syndrome, which can evolve in the days to weeks after return of sustained circulation. The components of post-cardiac arrest syndrome are brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathophysiology. Pediatric post-cardiac arrest care focuses on anticipating, identifying, and treating this complex physiology to improve survival and neurological outcomes. This scientific statement on post-cardiac arrest care is the result of a consensus process that included pediatric and adult emergency medicine, critical care, cardiac critical care, cardiology, neurology, and nursing specialists who analyzed the past 20 years of pediatric cardiac arrest, adult cardiac arrest, and pediatric critical illness peer-reviewed published literature. The statement summarizes the epidemiology, pathophysiology, management, and prognostication after return of sustained circulation after cardiac arrest, and it provides consensus on the current evidence supporting elements of pediatric post-cardiac arrest care.