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Purpose: Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development., Methods: A working group was formed from American Clinical Neurophysiology Society membership with expertise in neonatal cEEG and a set of priority questions developed. We performed literature searches in PubMed and EMBASE to identify relevant studies. Evidence tables were compiled from extracted data and quality assessments performed. A modification of the GRADE process was used to evaluate the body of evidence and draft recommendations., Results: Our working group identified six priority questions to evaluate the accuracy of cEEG for neonatal seizure diagnosis and the formulation of prognosis. An initial literature search yielded 18,167 results, which were distilled to a set of 217 articles. Overall, the quality of evidence for most priority questions was rated as very low and we provided conditional recommendations based on published literature and expert consensus. For each priority question, we also considered the benefits and harms of cEEG, with relative harms considered to be far less than the potential benefits across recommendations., Conclusions: We present evidence-based clinical guidelines regarding indications for cEEG monitoring in neonates. Considering resource utilization and feasibility, when cEEG monitoring results have a likelihood of altering clinical decision making, the authors felt the resource investment was justifiable., Competing Interests: C. J. Wusthoff's research is supported by NIH and the Thrasher Research Fund. She has received a stipend for serving on data safety monitoring boards for PRA Health Sciences, ICON, and the University of Utah. She is on the editorial board for Epilepsy and Behavior Reports, the Journal of Clinical Neurophysiology, and is an associate editor for Neurology. She receives royalties from Cambridge University Press. A. D. Numis's research is supported by the NIH. He is on the editorial board for Seminars in Pediatric Neurology and Frontiers in Neurology. He has served as a consultant for Ambit, Inc. R. M. Pressler is an investigator for studies with UCB. She has served as a consultant, as a speaker, and/or on advisory boards for Natus, Esai, Kephala, GW, and UCB. Her research is supported by the National Institute of Health Research (NIHR) Biomedical Research Centre at Great Ormond Street Hospital and Cambridge University Hospital, NIHR, Thrasher Research Fund, and James Bradfield Memorial Grant (via the Evelyn Trust). She is on the editorial boards of Journal of Clinical Neurophysiology, Neurophysiologie Clinique, and European Journal of Pediatric Neurology and is an associate editor for Epilepsia Open. Dr. Chu receives research support from the NIH, the Epilepsy Foundation New England, Novartis, and Biogen. She is a site investigator for a clinical trial sponsored by Neuropace. She provides consulting services to Biogen, Ionis Pharmaceuticals, Novartis, Sun Pharmaceuticals, and Ovid Pharmaceuticals. S. Massey serves as a consultant for Sun Pharmaceuticals. S. Nguyen serves as a consultant for UCB. C. D. Hahn's research is supported by NIH and CIHR. He is an associate editor for the Journal of Clinical Neurophysiology and receives royalties from Cambridge University Press. He has served as a consultant on clinical trial design to Takeda Pharmaceuticals and UCB Pharma SRL. T. N. Tsuchida's research has been supported by NIH funding and had been a seizure drug trial advisor for Xenon and Hikma Pharmaceuticals. J. J. Riviello's spouse is a section editor for UpToDate. R. A. Shellhaas' research is supported by NIH. She receives royalties from UpToDate for authorship of topics related to neonatal seizures and serves as a consultant for the Epilepsy Study Consortium. She receives a stipend for her role as president of the Pediatric Epilepsy Research Foundation. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.

Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children., Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given as the first single-dose) using a logistic regression model, adjusting for confounders such as time to ASMs. The proportion of patients receiving low first non-benzodiazepine ASM doses was calculated and a logistic regression model was used to evaluate risk factors for low dosing of the first non-benzodiazepine ASM., Results: Among 320 children, 170 (53.1 %) developed RSE, and 150 (46.9 %) responded to the first non-benzodiazepine ASM dose (non-RSE). One hundred thirty-seven (42.8 %) received a low total benzodiazepine dose, and 128 (40 %) received a low first non-benzodiazepine ASM dose. The odds of developing RSE were not higher after a low total benzodiazepine dose (OR=0.76, 95 %CI 0.47-1.23, p = 0.27) or low first non-benzodiazepine ASM dose (OR=0.85, 95 %CI 0.42-1.71, p = 0.65). Receiving a low first non-benzodiazepine ASM dose was independently associated with having received a low total benzodiazepine dose (OR=1.65, 95 %CI 1.01-2.70, p = 0.04)., Conclusion: For most patients, dosing variability in first and second-line medications for SE was not the sole clinical feature predicting progression to RSE in this cohort of benzodiazepine-resistant patients. Identification of additional modifiable clinical biomarkers that predict progression to RSE is needed. Though lower ASM doses did not predict RSE in this model, the administration of ASMs at doses likely to prevent RSE remains crucial in SE treatment., Competing Interests: Declaration of competig interest TL is part of pending patent applications to detect and predict seizures and to diagnose epilepsy. He receives research support from the NIH, the Epilepsy Research Fund, and Epitel. He received research grants from Sage, Lundbeck, Eisai, Upsher-Smith, Mallinckrodt, Pfizer, and MIKU in the past. He served as a consultant for Engage and Upsher Smith, in the past., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Parents of neonates with seizures report persistent symptoms of depression, anxiety, and posttraumatic stress. We aimed to characterize the parent experience of caring for children impacted by neonatal seizures, including longitudinal assessment across childhood., Methods: This prospective, observational, multicenter study was conducted at Neonatal Seizure Registry (NSR) sites in partnership with the NSR Parent Advisory Panel. Parents completed surveys at discharge; 12, 18, and 24 months; and 3, 4, 5, 7, and 8 years. Surveys included demographic information and open-ended questions targeting parent experience. A conventional content analysis approach was used., Results: A total of 320 caregivers completed at least one open-ended question, with the majority of respondents at discharge (n = 142), 12 months (n = 169), 18 months (n = 208), and 24 months (n = 245). We identified the following three primary themes. (1) Personal Burden of Care: Parents experienced emotional distress, financial strain, physical demands, and fears for their child's unknown outcome; (2) Managing Day-to-Day Life: Parents described difficulties navigating their parenting role, including managing their child's challenging behaviors and understanding their child's needs amid neurodevelopmental impairment; (3) My Joys as a Parent: Parents valued bonding with their child, being a caregiver, and watching their child's personality grow., Conclusions: Parents of children impacted by neonatal seizures face persistent challenges, which are interwoven with the joys of being a parent. Our findings suggest that future interventions should promote resiliency, address caregivers' psychosocial needs longitudinally, and provide enhanced support for parents caring for children with medical complexity., Competing Interests: Declaration of Competing Interest Dr. Monica Lemmon receives funding from NIH (K23NS116453). Dr. Reneé Shellhaas receives royalties from UpToDate for authorship on topics related to neonatal seizures and serves as a consultant for the Epilepsy Study Consortium. Betsy Pilon is the Executive Director of Hope for HIE. The other authors have no disclosures to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest Dr. Lemmon receives funding from NIH (K23NS116453). Dr. Shellhaas receives royalties from UpToDate for authorship on topics related to neonatal seizures and serves as a consultant for the Epilepsy Study Consortium. The other authors have no disclosures to report.

Background: Neonatal seizures are common with acute brain injury. Up to 25% of survivors develop postneonatal epilepsy. We hypothesized postneonatal epilepsy diagnosed by age 24 months would increase risk for early markers of neurobehavioral disorders than acute provoked neonatal seizures alone., Methods: Neonates with acute provoked seizures born from July 2015 to March 2018 were enrolled at nine Neonatal Seizure Registry sites. Composite scores from parent-completed standardized ratings assessed Adaptive, Social, Externalizing, Internalizing, Self-Regulation, and Sensory Seeking domains. Linear regression demonstrated relationships between composite scores for children who developed postneonatal epilepsy compared with those who did not. Results were adjusted for seizure etiology, sex, gestational age, and cerebral palsy (CP) severity., Results: A total of 151 children (n = 20, 13% with postneonatal epilepsy), 4.1 years median age, participated. Children with epilepsy had impaired adaptive (Cohen d = 1.62, P < 0.0001), social (Cohen d = 0.86, P = 0.004), and executive functioning (Cohen d = 0.56, P = 0.06) compared with children without epilepsy. Mean scores for children without epilepsy were within average range. Risk for impairment among children with epilepsy persisted after adjusting for neonatal seizure etiology, sex, and gestational age, but not when adjusting for CP severity., Conclusions: There was higher incidence of adverse neurobehavioral outcomes among preschool children diagnosed with postneonatal epilepsy compared with those without epilepsy. CP severity was associated with greater impairment; results also suggest that epilepsy is an independent predictor of adaptive functioning. Children with postneonatal epilepsy should be screened for neurobehavioral problems to facilitate early identification and developmental support., Competing Interests: Declaration of competing interest Dr. Shellhaas receives royalties from UpToDate for authorship of topics related to neonatal seizures, serves as a consultant for the Epilepsy Study Consortium, and receives a stipend for her role as president-elect of the Pediatric Epilepsy Research Foundation. The other authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether abnormal sleep is associated with adverse outcomes for children who survived acute provoked neonatal seizures, and their parents., Study Design: This 9-center study prospectively followed newborns with acute provoked seizures. When children reached age 5 years, parents completed the Children's Sleep Habits Questionnaire (CSHQ), the Pediatric Sleep Questionnaire-Sleep Related Breathing Disorders (PSQ-SRBD) subscale, the Vineland Adaptive Behavior Scales-3, and the Hospital Anxiety Depression Scale. Children were also assessed with the Wechsler Preschool and Primary Scale of Intelligence-IV (WPPSI-IV). Spearman correlations and multivariable analyses were used to evaluate risk factors for sleep problems., Results: The mean CSHQ score was 45 ± 7; 77 of 118 children (65%) had an abnormal score (above the healthy sleep threshold of 41). On the PSQ-SRBD, 32 of 119 children (27%) screened positive for sleep-disordered breathing (SDB). SDB symptoms were more common among children with cerebral palsy (42% with vs 22% without; P = .03) and epilepsy (54% with vs 24% without; P = .02). Children with lower scores on the Vineland-3 (rho = -0.25; P = .01) and WPPSI-IV (rho = -0.31; P = .004) at 5 years of age were more likely to have symptoms of SDB. Worse CSHQ and PSQ-SRBD scores were associated with higher parental anxiety (rho = 0.28 [P = .002] and rho = 0.34 [P = .0002], respectively) and depression scores on the Hospital Anxiety Depression Scale (rho = 0.16 [P = .08] and rho = 0.17 [P = .07], respectively)., Conclusions: Two-thirds of early school-aged survivors of acute provoked neonatal seizures had parent-reported sleep abnormalities and one-quarter screened positive for SDB. Early screening and effective treatment for sleep disorders could be an innovative, practice-changing approach to improve outcomes after neonatal seizures., Competing Interests: Declaration of Competing Interest Renée Shellhaas reports financial support for this study was provided by National Institute of Neurological Disorders and Stroke and the Patient-Centered Outcomes Research Institute. Renée Shellhaas reports a relationship with Pediatric Epilepsy Research Foundation that includes: board membership and employment. Renée Shellhaas reports a relationship with The Epilepsy Study Consortium that includes: consulting or advisory. Renée Shellhaas reports a relationship with UptoDate Inc that includes: royalties for authorship of topics related to neonatal seizures. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To review the available literature concerning the definition of neonatal status epilepticus (SE) and/or seizure burden., Methods: The International League Against Epilepsy Neonatal Task Force performed a scoping review of the definitions of neonatal SE. Following a systematic literature review, articles were screened and data were abstracted regarding: (1) article characteristics (author identification, publication year, journal name, digital object identifier, title, objective, and study design); (2) cohort characteristics (sample size, gestational age, seizure etiology); (3) definition of SE and/or seizure burden; and (4) the method used to identify and classify SE, including routine EEG (EEG), continuous EEG monitoring (cEEG), amplitude-integrated EEG (aEEG), or clinical features., Results: The scoping review yielded 44 articles containing a definition of neonatal SE. Studies mainly included infants with hypoxic-ischemic encephalopathy or neonates considered at risk for seizures. SE identification and classification most often relied on cEEG. The majority of studies based the definition of SE on seizure duration, including summed duration of seizures comprising ≥50% of any 1-h epoch, recurrent seizures for >50% of the total recording time, or either electrographic seizures lasting >30 min and/or repeated electrographic seizures totaling >50% in any 1-h period. Seizure burden was reported in 20 studies, and the most commonly used approach assessed total seizure burden, defined as total duration of EEG seizures in minutes. Sixteen studies assessed the relationship between seizure burden and outcomes, and most identified a significant association between higher seizure burden and unfavorable outcomes., Significance: This scoping review demonstrates a substantial variation in neonatal SE definitions across the literature. The most common definitions were based around a 30-min seizure duration criterion, but evidence was insufficient to support that 30 min was a cutoff defining prolonged seizures or that seizures exceeding this burden were more likely to be pharmacoresistant or associated with worse outcomes. As a next step, the Neonatal Task Force intends to develop a standardized approach to assessing and describing neonatal seizure burden and defining neonatal SE., Plain Language Summary: Prolonged seizures are a neurologic emergency, if untreated, can lead to permanent injury or death. In adults and children, seizures lasting longer than 30 min are believed to cause brain damage. However, it is not clear if this definition can be applied to neonates. The International League Against Epilepsy Neonatal Taskforce performed a scoping literature review which identified 44 articles containing a definition of neonatal status epilepticus. In this article, the authors reviewed the current used definitions for prolonged seizures in neonates to establish a relationship between seizure duration and neurological outcome. As a next step, the Neonatal Task Force intends to develop a standardized approach to assessing and describing neonatal seizure burden and defining neonatal SE., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Studies have shown a high prevalence of sleep-disordered breathing (SDB) among children with myelomeningocele (MMC), but there are few published data on the longitudinal care of these patients. The objective of this study was to determine the effectiveness of standard treatments for SDB in children with MMC., Methods: The authors analyzed records from three multidisciplinary spina bifida clinics to identify all patients with both MMC and SDB diagnosed by polysomnography (PSG). The primary outcome of this study was a change in apnea-hypopnea index (AHI; the number of apneic or hypopneic events per hour of sleep) before and after clinically recommended SDB treatments. Clinical and demographic variables were recorded and evaluated for possible association with posttreatment improvement of AHI. Analysis included change in AHI (a continuous variable) and whether SDB improved (defined as an AHI < 2.5 or decrease of AHI by ≥ 50% from baseline)., Results: Seventy-one eligible patients (aged 2 days-21 years, 52% male) had an initial AHI > 2.5 and had follow-up PSG after treatment for SDB. The mean AHI decreased from 20.5 (SD 21.6) at baseline to 11.6 (SD 15.7) after treatment (p = 0.0006). Children treated with supplemental oxygen and with continuous positive airway pressure had improvement on PSG (18 of 25 and 12 of 18, respectively). Children treated with adenotonsillectomy were less likely to improve (7 of 19). Forty-one patients (58%) improved from a baseline AHI > 2.5 to an AHI < 2.5 after treatment., Conclusions: Children with MMC and SDB who undergo standard SDB treatments guided by pediatric sleep medicine physicians show improvement in PSG parameters after treatment.

Objective: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy that is typically refractory to treatment. We surveyed the current landscape of LGS treatment, aiming to identify challenges to the development of efficacious therapies, and to articulate corresponding priorities toward clinical trials that improve outcomes., Methods: The LGS Special Interest Group of the Pediatric Epilepsy Research Consortium integrated evidence from the literature and expert opinion, into a narrative review., Results: We provide an overview of approved and emerging medical, dietary, surgical and neuromodulation approaches for LGS. We note that quality of care could be improved by standardizing LGS treatment based on expert consensus and empirical data. Whereas LGS natural history is incompletely understood, prospective studies and use of large retrospective datasets to understand LGS across the lifespan would enable clinical trials that address these dynamics. Recent discoveries related to LGS pathophysiology should enable development of disease-modifying therapies, which are currently lacking. Finally, clinical trials have focused chiefly on seizures involving "drops," but should incorporate additional patient-centered outcomes, using emerging measures adapted to people with LGS., Interpretation: Clinicians and researchers should enact these priorities, with the goal of patient-centered clinical trials that are tailored to LGS pathophysiology and natural history., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Sudden unexpected death in epilepsy (SUDEP) is a common cause of premature death in children and adults with epilepsy. People with epilepsy and their caregivers prefer the risk of SUDEP to be disclosed by their clinicians; however, few tools exist to support these conversations., Methods: We aimed to (1) characterize SUDEP communication preferences of clinicians and caregivers of children with epilepsy, and (2) leverage these preferences to develop a conversation guide to support the discussion of SUDEP risk. We prospectively enrolled caregivers of children with epilepsy, child neurology clinicians, and child neurology trainees to participate in virtual focus groups and/or 1:1 interviews., Results: Content was analyzed and collated into the following four domains: (1) who should participate: all participants described that the treating neurologist and/or epileptologist should lead conversations with patients and families. Caregivers preferred that clinicians disclose information about SUDEP to children only after asking permission. (2) When and where conversations should occur: most participants felt that the conversation should be discussed at the time of diagnosis and in the outpatient setting, (3) content to include about SUDEP risk: participants characterized the need to define SUDEP, what is known and unknown, as well as describe risk factors to reduce an individual child's risk, and (4) barriers and facilitators to disclosure: barriers included lack of time, limited evidence-based information regarding risk mitigation, lack of modifiable risk factors, and apprehension of causing undue stress on families. Participants shared that written material would help facilitate the discussion., Conclusions: Caregivers and clinicians emphasized the value of SUDEP risk counseling in the pediatric clinical setting. Based on these findings, neurologists caring for children with epilepsy should educate caregivers about SUDEP soon after the initial epilepsy diagnosis in an empathetic manner, revisiting the conversation longitudinally over time and highlighting actionable steps to mitigate risk. Caregiver and clinician preferences informed our novel adaptation of the SPIKES protocol for use by pediatric neurologists in the context of SUDEP risk disclosure., Competing Interests: Declaration of Competing Interest The following authors declare the following financial or non-financial interests which may be considered as potential conflicts of interest: Dr. Shellhaas serves as a consultant for the Epilepsy Study Consortium and receives royalties from UpToDate for authorship of topics related to neonatal seizures and a stipend from the Pediatric Epilepsy Research Foundation for service as president-elect. Her research is funded by NIH. Dr. Lemmon receives salary support from the NIH. Gardiner Lapham is a trustee of the BAND foundation. Apart from above, the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024. Published by Elsevier Inc.)

Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures. Continuous electroencephalographic monitoring is recommended given high rates of subclinical seizures. Prompt diagnosis and treatment of seizures may improve neurodevelopmental outcomes. International League Against Epilepsy guidelines indicate that (1) phenobarbital remains the first-line treatment of neonatal seizures and (2) early discontinuation of antiseizure medications following resolution of acute provoked seizures, and prior to discharge home, is recommended. Long-term follow-up of these infants is necessary to screen for postneonatal epilepsy and support neurodevelopment., Competing Interests: Disclosure Dr R.A. Shellhaas receives royalties from UpToDate for authorship of topics related to neonatal seizures; serves as a consultant for the Epilepsy Study Consortium; and receives a stipend for her role as president-elect of the Pediatric Epilepsy Research Foundation. Drs H.C. Glass, T. Anwar, R.L. Triplett, and A. Ahmed have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We aimed to develop a risk scoring system as a predictor of 24-month neurodevelopmental outcomes (cognitive, language, and motor) for neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE)., Methods: This was a chart review of infants with HIE treated with therapeutic hypothermia who were admitted to the Neonatal Intensive Care Unit (NICU) at the University of Michigan between 2009 and 2019 and followed in the neonatal developmental clinic until 24 months of age. We examined bivariate associations between the neonatal characteristics and Bayley-III scores. We then performed stepwise logistic regression. To create the risk scores, a participant was given one point for each of the factors included in the final model., Results: Fifty-five infants were included. The final model for Bayley cognitive abnormality included abnormal neonatal neurologic exam (p < 0.0001), white matter/watershed MRI abnormality (p = 0.01), 5-min Apgar score (p = 0.02), and EEG-confirmed seizures (p = 0.04). The model for language abnormality included abnormal neurologic exam (p = 0.0002), seizures (p = 0.007), clinical severity of HIE (p = 0.06), and basal ganglia/thalamus MRI abnormality (p = 0.17). The model for motor abnormality included seizures (p = 0.03), abnormal neurologic exam (p = 0.06) and basal ganglia/thalamus MRI abnormality (p = 0.02). The positive predictive values for the risk scores were 60 %, 85 % and 71 %, respectively, for the Bayley-III cognitive, language and motor domains., Conclusion: Our study identifies early clinical features that differentially predict domains of neurodevelopmental outcome and associated risk scores that may be of value to both clinicians and families. This novel scoring system should next be validated in a larger, prospective study., Competing Interests: Declaration of competing interest Dr. Shellhaas receives research support from the NIH. She serves as associate editor for Neurology; receives royalties from UpToDate for authorship of topics on neonatal seizures; is a consultant for the Epilepsy Study Consortium; and is president-elect of the Pediatric Epilepsy Research Consortium®. The other authors have no conflicts of interest or financial relationship relevant to this article to disclose., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates., Methods: A retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days., Results: Among 47 neonates, 98% received the first lacosamide dose in the intensive care units. During the median follow-up of 12 days, 19% of neonates died, and the crude incidence rate per 1000 patient-days (95% confidence interval) of the adverse events by diagnostic categories ranged from 2.8 (0.3, 10.2) for blood or lymphatic system disorders and nervous system disorders to 10.5 (4.2, 21.6) for cardiac disorders. Electroencephalographic seizures were observed in 31 of 34 patients with available electroencephalographic data on the index date. There was seizure improvement in 29% of neonates on day 1 and also in 29% of neonates on day 2. On day 3, there was no change in 50% of neonates and unknown change in 50% of neonates., Conclusions: The results are reassuring regarding the safety of lacosamide in neonates. Although some neonates had fewer seizures after lacosamide administration, the lack of a comparator arm and reliance on qualitative statements in electroencephalographic reports limit the preliminary efficacy results., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.R. and S.E. are employees of UCB Pharma. M.K. is an employee of Barrington James Ltd on behalf of UCB Pharma and a PhD student at London School of Hygiene & Tropical Medicine. N.F. is a former employee of UCB Pharma and current employee of Ferring SAS. RAS was an employee of University of Michigan at the time of study., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Neonates are susceptible to seizures due to their unique physiology and combination of risks associated with gestation, delivery, and the immediate postnatal period. Advances in neonatal care have improved outcomes for some of our most fragile patients, but there are persistent challenges for epileptologists in identifying neonatal seizures, diagnosing etiologies, and providing the most appropriate care, with an ultimate goal to maximize patient outcomes. In just the last few years, there have been critical advances in the state of the science, as well as new evidence-based guidelines for diagnosis, classification, and treatment of neonatal seizures. This review will provide updated knowledge about the pathophysiology of neonatal seizures, classification of the provoked seizures and neonatal epilepsies, state of the art guidance on EEG monitoring in the neonatal ICU, current treatment guidelines for neonatal seizures, and potential for future advancement in treatment., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: We investigated how diagnosis and injury location on neonatal brain MRI following onset of acute provoked seizures was associated with short term outcome., Study Design: A multicenter cohort of neonates with acute provoked seizures enrolled in the Neonatal Seizure Registry. MRIs were centrally evaluated by a neuroradiologist for location of injury and radiologic diagnosis. Clinical outcomes were determined by chart review. Multivariate logistic regression was used to examine the association between MRI findings and outcomes., Results: Among 236 newborns with MRI at median age 4 days (IQR 3-8), 91% had abnormal MRI. Radiologic diagnoses of intracranial hemorrhage (OR 3.2 [1.6-6.5], p < 0.001) and hypoxic-ischemic encephalopathy (OR 2.7 [1.4-5.4], p < 0.003) were associated with high seizure burden. Radiologic signs of intracranial infection were associated with abnormal neurologic examination at discharge (OR 3.9 [1.3-11.6], p < 0.01)., Conclusion: Findings on initial MRI can help with expectant counseling on short-term outcomes following acute provoked neonatal seizures., (© 2023. The Author(s).)

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., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Among neonates with acute symptomatic seizures, we evaluated whether inability to take full feeds at time of hospital discharge from neonatal seizure admission is associated with worse neurodevelopmental outcomes, after adjusting for relevant clinical variables., Methods: This prospective, 9-center study of the Neonatal Seizure Registry (NSR) assessed characteristics of infants with seizures including: evidence of brainstem injury on MRI, mode of feeding upon discharge, and developmental outcomes at 12, 18, and 24 months. Inability to take oral feeds was identified through review of medical records. Brainstem injury was identified through central review of neonatal MRIs. Developmental outcomes were assessed with the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) at 12, 18, and 24 months corrected age., Results: Among 276 infants, inability to achieve full oral feeds was associated with lower total WIDEA-FS scores (160.2±25.5 for full oral feeds vs. 121.8±42.9 for some/no oral feeds at 24 months, p<0.001). At 12 months, a G-tube was required for 23 of the 49 (47%) infants who did not achieve full oral feeds, compared with 2 of the 221 (1%) who took full feeds at discharge (p<0.001)., Conclusions: Inability to take full oral feeds upon hospital discharge is an objective clinical sign that can identify infants with acute symptomatic neonatal seizures who are at high risk for impaired development at 24 months., Competing Interests: Dr. Robers has no disclosures. Dr. Barks receives research support from NIH. Dr. Glass receives research support from NIH. Dr. Soul has no disclosures. Dr. Chang has no disclosures. Dr. Wusthoff has no disclosures. Dr. Chu receives research support from Biogen Inc, and from NIH. Dr. Massey has no disclosures. Dr. Abend has no disclosures. Dr. Lemmon receives research support from NIH (K23NS116453). Dr. Thomas receives research support through NIH and UCB. Dr. Guillet has no disclosures. Dr. Rogers has no disclosures. Dr. Franck has no disclosures. Mr. McCaffrey has no disclosures. Dr. Li has no disclosures. Dr. McCulloch has no disclosures. Dr. Shellhaas receives research support from NIH. She receives royalties from UpToDate for authorship of topics related to neonatal seizures, serves as a consultant for the Epilepsy Study Consortium and is president-elect of the Pediatric Epilepsy Research Foundation™.

Background: Seizures, strokes, and intracranial hemorrhage are common and feared complications in children receiving extracorporeal membrane oxygenation (ECMO) support. Researchers and clinicians have proposed and deployed methods for monitoring and detecting neurologic injury, but best practices are unknown. We sought to characterize clinicians' approach to electroencephalography (EEG) and brain imaging modalities in children supported by ECMO., Methods: We performed a retrospective observational cohort study among US Children's Hospitals participating in the Pediatric Health Information System (PHIS) from 2016 to 2021. We identified hospitalizations containing ECMO support. We stratified these admissions by pediatric, neonatal, cardiac surgery, and non-cardiac surgery. We characterized the frequency of EEG, cranial ultrasound, brain computed tomography (CT), magnetic resonance imaging (MRI), and transcranial Doppler during ECMO hospitalizations. We reported key diagnoses (stroke and seizures) and the prescription of antiseizure medication. To assess hospital variation, we created multilevel logistic regression models., Results: We identified 8746 ECMO hospitalizations. Nearly all children under 1 year of age (5389/5582) received a cranial ultrasound. Sixty-two percent of the cohort received an EEG, and use increased from 2016 to 2021 (52-72% of hospitalizations). There was marked variation between hospitals in rates of EEG use. Rates of antiseizure medication use (37% of hospitalizations) and seizure diagnoses (20% of hospitalizations) were similar across hospitals, including high and low EEG utilization hospitals. Overall, 37% of the cohort received a CT and 36% received an MRI (46% of neonatal patients). Stroke diagnoses (16% of hospitalizations) were similar between high- and low-MRI utilization hospitals (15% vs 17%, respectively). Transcranial Doppler (TCD) was performed in just 8% of hospitalizations, and 77% of the patients who received a TCD were cared for at one of five centers., Conclusions: In this cohort of children at high risk of neurologic injury, there was significant variation in the approach to EEG and neuroimaging in children on ECMO. Despite the variation in monitoring and imaging, diagnoses of seizures and strokes were similar across hospitals. Future work needs to identify a management strategy that appropriately screens and monitors this high-risk population without overuse of resource-intensive modalities., (© 2023. The Author(s).)

Background: Limited data exist regarding seizure burden, electroencephalogram (EEG) background, and associated outcomes in neonates with acute intracranial infections., Methods: This secondary analysis was from a prospective, multicenter study of neonates enrolled in the Neonatal Seizure Registry with seizures due to intracranial infection. Sites used continuous EEG monitoring per American Clinical Neurophysiology Society guidelines. High seizure burden was defined a priori as seven or more EEG-confirmed seizures. EEG background was categorized using standardized terminology. Primary outcome was neurodevelopment at 24-months corrected age using Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS). Secondary outcomes were postneonatal epilepsy and motor disability., Results: Twenty-seven of 303 neonates (8.9%) had seizures due to intracranial infection, including 16 (59.3%) bacterial, 5 (18.5%) viral, and 6 (22.2%) unknown. Twenty-three neonates (85%) had at least one subclinical seizure. Among 23 children with 24-month follow-up, the WIDEA-FS score was, on average, 23 points lower in children with high compared with low seizure burden (95% confidence interval, [-48.4, 2.1]; P = 0.07). After adjusting for gestational age, infection etiology, and presence of an additional potential acute seizure etiology, the effect size remained unchanged (β = -23.8, P = 0.09). EEG background was not significantly associated with WIDEA-FS score. All children with postneonatal epilepsy (n = 4) and motor disability (n = 5) had high seizure burden, although associations were not significant., Conclusion: High seizure burden may be associated with worse neurodevelopment in neonates with intracranial infection and seizures. EEG monitoring can provide useful management and prognostic information in this population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity., Methods: The prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression. Our primary outcome was treatment course, which considered therapy prescribed for the first and, when needed, the second IS treatment together., Results: Of 555 children, 324 (58%) were non-Hispanic white, 55 (10%) non-Hispanic Black, 24 (4%) non-Hispanic Asian, 80 (14%) Hispanic, and 72 (13%) other/unknown. Most (398, 72%) received a standard treatment course. Insurance type, geographic location, history of prematurity, prior seizures, developmental delay or regression, abnormal head circumference, hypsarrhythmia, and IS etiologies were associated with standard therapy. In adjusted models, non-Hispanic Black children had lower odds of receiving a standard treatment course compared with non-Hispanic white children (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.20-0.89; p = 0.02). Adjusted models also showed that children with public (vs. private) insurance had lower odds of receiving standard therapy for treatment 1 (OR, 0.42; CI, 0.21-0.84; p = 0.01)., Interpretation: Non-Hispanic Black children were more often treated with non-standard IS therapies than non-Hispanic white children. Likewise, children with public (vs. private) insurance were less likely to receive standard therapies. Investigating drivers of inequities, and understanding the impact of racism on treatment decisions, are critical next steps to improve care for patients with IS. ANN NEUROL 2022;92:32-44., (© 2022 American Neurological Association.)

Study Objectives: Cultural sleep practices and COVID-19 mitigation strategies vary worldwide. The sleep of infants and toddlers during the COVID-19 pandemic in the United States is understudied., Methods: Caregivers of children aged < 3 years responded to a cross-sectional survey during 2020 (divided into quarters, with the year quarter 1 being largely prelockdown). We assessed the global effect of year quarter on parent-reported total sleep time (hours) and sleep onset latency (hours) using an analysis of variance. We used multivariable linear regression to assess the adjusted effect of year quarter on total sleep time, sleep onset latency, and parental frustration. We used logistic regression to assess the adjusted effect of year quarter on nap consistency., Results: Of 594 children, the mean age was 18.5 ± 9.7 months; 52% were female. In the adjusted analyses, the reference categories were as follows: quarter 1 (year quarter), ≤ 6 months (age category), and < $25,000 (annual household income). Total sleep time was associated with age category (ages 12 to ≤ 24 months: β = -2.86; P  = .0004; ages 24 to ≤ 36 months: β = -3.25; P  < .0001) and maternal age (β = -0.04; P  = .05). Sleep onset latency was associated with year quarter (year quarter 3: β = 0.16; P  = .04), age category (ages 24 to ≤ 36 months: β = 0.28; P  < .0001), annual household income ($100,000-$150,000: β = -0.15; P  = .03; > $150,000: β = -0.19; P  = .01), and lack of room-sharing (β = -0.09; P  = .05). Parental frustration with sleep increased with age (all P  < .05) and lack of room-sharing ( P  = .01). The effect of lack of room-sharing on nap consistency approached significance (adjusted odds ratio, 1.88; 95% confidence interval, 0.95-3.72)., Conclusions: Social factors such as lower household income and room-sharing affected the sleep of U.S. infants and toddlers as opposed to the COVID-19 lockdown itself., Citation: Gupta G, O'Brien LM, Dang LT, Shellhaas RA. Sleep of infants and toddlers during 12 months of the COVID-19 pandemic in the midwestern United States. J Clin Sleep Med. 2022;18(5):1225-1234., (© 2022 American Academy of Sleep Medicine.)

Background: Children with a history of acute provoked neonatal seizures are at high risk for disability, often requiring developmental services. The coronavirus disease 2019 (COVID-19) pandemic has led to widespread changes in how health care is delivered. Our objective was to determine the magnitude of service interruption of among children born between October 2014 and December 2017 and enrolled in the Neonatal Seizure Registry (NSR), a nine-center collaborative of pediatric centers in the United States., Methods: This is a prospective cohort study of children with acute provoked seizures with onset ≤44 weeks' gestation and evaluated at age three to six years. Parents of children enrolled in the NSR completed a survey about their child's access to developmental services between June 2020 and April 2021., Results: Among 144 children enrolled, 72 children (50%) were receiving developmental services at the time of assessment. Children receiving services were more likely to be male, born preterm, and have seizure etiology of infection or ischemic stroke. Of these children, 64 (89%) experienced a disruption in developmental services due to the pandemic, with the majority of families (n = 47, 73%) reporting that in-person services were no longer available., Conclusions: Half of children with acute provoked neonatal seizures were receiving developmental services at ages three to six years. The COVID-19 pandemic has led to widespread changes in delivery of developmental services. Disruptions in services have the potential to impact long-term outcomes for children who rely on specialized care programs to optimize mobility and learning., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: In a randomized trial, we aimed to evaluate the efficacy of cosyntropin injectable suspension, 1 mg/mL, compared to vigabatrin for infantile spasms syndrome. An additional arm was included to assess the efficacy of combination therapy (cosyntropin and vigabatrin) compared with cosyntropin monotherapy. Methods: Children (2 months to 2 years) with new-onset infantile spasms syndrome and hypsarhythmia were randomized into 3 arms: cosyntropin, vigabatrin, and cosyntropin and vigabatrin combined. Daily seizures and adverse events were recorded, and EEG was repeated at day 14 to assess for resolution of hypsarhythmia. The primary outcome measure was the composite of resolution of hypsarhythmia and absence of clinical spasms at day 14. Fisher exact test was used to compare outcomes. Results: 37 children were enrolled and 34 were included in the final efficacy analysis (1 withdrew prior to treatment and 2 did not return seizure diaries). Resolution of both hypsarhythmia and clinical spasms was achieved in in 9 of 12 participants (75%) treated with cosyntropin, 1/9 (11%) vigabatrin, and 5/13 (38%) cosyntropin and vigabatrin combined. The primary comparison of cosyntropin versus vigabatrin was significant (64% [95% confidence interval 21, 82], P  < .01). Adverse events were reported in all 3 treatment arms: 31 (86%) had an adverse event, 7 (19%) had a serious adverse event, and 15 (42%) had an adverse event of special interest with no difference between treatment arms. Significance: This randomized trial was underpowered because of incomplete enrollment, yet it demonstrated that cosyntropin was more effective for short-term outcomes than vigabatrin as initial treatment for infantile spasms.

Objective: Pediatric epilepsy is often associated with diminished health-related quality of life (HRQOL). Our aim was to establish the validity of the Pediatric Epilepsy Learning Healthcare System Quality of Life (PELHS-QOL-2) questions, a novel two-item HRQOL prompt for children with epilepsy, primarily for use in clinical care., Methods: We performed a multicenter cross-sectional study to validate the PELHS-QOL-2. Construct validity was established through bivariate comparisons with four comparator measures and known drivers of quality of life in children with epilepsy, as well as by creating an a priori multivariable model to predict the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Validity generalization was established through bivariate comparisons with demographic and clinical information. Content validity and clinical utility were established by assessing how well the PELHS-QOL-2 met eight design criteria for an HRQOL prompt established by a multistakeholder group of experts., Results: The final participant sample included 154 English-speaking caregivers of children with epilepsy (mean age = 9.7 years, range = .5-18, 49% female, 70% White). The PELHS-QOL-2 correlated with the four comparator instruments (ρ = .44-.56), was significantly associated with several known drivers of quality of life in children with epilepsy (p < .05), and predicted QOLCE-55 scores in the multivariate model (adjusted R 2 = .54). The PELHS-QOL-2 item was not associated with the age, sex, and ethnicity of the children nor with the setting and location of data collection, although PELHS-QOL-Medications was significantly associated with race (worse for White race). Following both quantitative and qualitative analysis, the PELHS-QOL-2 met seven of eight design criteria., Significance: The PELHS-QOL-2 is a valid HRQOL prompt and is well suited for use in clinical care as a mechanism to routinely initiate conversations with caregivers about quality of life in children with epilepsy. The association of PELHS-QOL-Medications with race merits further study., (© 2021 International League Against Epilepsy.)

Objective: Seizures are a common neonatal neurologic emergency. Many centers have developed pathways to optimize management. We evaluated neonatal seizure management pathways at level IV neonatal intensive care units (NICUs) in the United States to highlight areas of consensus and describe aspects of variability., Methods: We conducted a descriptive analysis of 11 neonatal seizure management pathways from level IV NICUs that specialize in neonatal neurocritical care including guidelines for electroencephalography (EEG) monitoring, antiseizure medication (ASM) choice, timing, and dose., Results: Study center NICUs had a median of 70 beds (interquartile range: 52-96). All sites had 24/7 conventional EEG initiation, monitoring, and review capability. Management pathways uniformly included prompt EEG confirmation of seizures. Most pathways included a provision for intravenous benzodiazepine administration if either EEG or loading of ASM was delayed. Phenobarbital 20 mg/kg IV was the first-line ASM in all pathways. Pathways included either fosphenytoin or levetiracetam as the second-line ASM with variable dosing. Third-line ASMs were most commonly fosphenytoin or levetiracetam, with alternatives including topiramate or lacosamide. All pathways provided escalation to continuous midazolam infusion with variable dosing for seizures refractory to initial medication trials. Three pathways also included lidocaine infusion. Nine pathways discussed ASM discontinuation after resolution of acute symptomatic seizures with variable timing., Conclusions: Despite a paucity of data from controlled trials regarding optimal neonatal seizure management, there are areas of broad agreement among institutional pathways. Areas of substantial heterogeneity that require further research include optimal second-line ASM, dosage, and timing of ASM discontinuation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The International League Against Epilepsy (ILAE) seizure classification scheme has been periodically updated to improve its reliability and applicability to clinicians and researchers alike. Here, members of the Epilepsy Study Consortium propose a pragmatic seizure classification, based on the ILAE scheme, designed for use in clinical trials with a focus on outcome measures that have high reliability, broad interpretability across stakeholders, and clinical relevance in the context of the development of novel antiseizure medications. Controversies around the current ILAE classification scheme are discussed in the context of clinical trials, and pragmatic simplifications to the existing scheme are proposed, for intended use by investigators, industry sponsors, and regulatory agencies., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Enriched language exposure may benefit infants in the neonatal intensive care unit. We hypothesized that changes in neonatal electroencephalogram (EEG) coherence during sleep, in response to maternal voice exposure, predict language development., Methods: Convalescent neonates underwent 12-h polysomnography. A recording of the mother's voice was randomized to continuous playback in the first or second 6 h. We calculated the imaginary coherence (ICOH-a measure of functional connectivity) between EEG leads. Spearman correlations were computed between ICOH and 18-month Bayley-III language scores., Results: Thirty-five neonates were included (N = 18 33-to-<35 weeks gestation; N = 17 ≥ 35 weeks). Predictive value of ICOH during neonatal non-rapid eye movement (NREM) sleep was left lateralized, and varied with gestational age and voice playback. ICOH in the left-hemispheric (C3-Cz; T3-Cz) channels across multiple EEG frequency bands was associated with 18-month language scores (rho = -0.34 to -0.48). The association was driven by neonates born at 33-34 weeks gestation, and a trend suggested a possible effect of maternal voice at some EEG frequencies. Right hemisphere ICOH (C4-Cz; T4-Cz) was not associated with language outcome., Conclusions: Left-hemispheric EEG functional connectivity during neonatal NREM sleep shows early signs of physiologic asymmetry that may predict language development. We speculate that sleep analyses could have unique prognostic value., Impact: During neonatal NREM sleep, EEG functional connectivity predicts future language development. Left temporal and central EEG coherence-specifically the imaginary component of coherence-is predictive, whereas the same analysis from the right hemisphere is not. These results appear to vary according to the infant's gestational age, and a trend suggests they may be enhanced by measuring functional connectivity during exposure to the mother's voice. These findings identify early evidence of physiologic differentiation within the cerebral hemispheres and raise the possibility that neonatal NREM sleep has a role to play in language development., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Sleep comorbidities are common, and sometimes severe, for children with early-life epilepsies (ELEs). Yet, there is a paucity of data regarding the profile of these sleep disturbances and their complications., Methods: Participants registered with the Rare Epilepsy Network (REN) were queried about sleep via online questionnaires. Descriptive statistics and logistic regression were performed., Results: Median age of the 356 children was 56 months (interquartile range 30 to 99), 56% were female, and 53% (188/356) endorsed a sleep concern. Frequent nighttime awakenings (157 of 350; 45%), difficulty falling asleep (133 of 350; 38%), and very restless sleep (118 of 345; 34%) were most endorsed. Nocturnal seizures were associated with sleep concerns and were reported in 75% (268 of 356) of children. Of the children with nocturnal seizures, 56% (118 of 268) had sleep concerns. Of the children without nocturnal seizures, 43% (38 of 88) had sleep concerns. Sleep concerns were most common in dup15q syndrome (16 of 19; 84%). Children aged 4 to ≤10 years (adjusted odds ratio [aOR] 16.1; 95% confidence interval [CI] 2.0, 131.0) and 10 to <13 years (aOR 22.2; 95% CI 2.6, 188.6) had a greater odds of having a sleep concern compared with children aged ≤6 months. Female sex appeared protective for sleep concerns (aOR 0.6; 95% CI 0.4, 0.9). The association between sleep concerns and nocturnal seizures was weaker when adjusted for sex and age category in a logistic regression model., Conclusions: Reported sleep concerns are highly prevalent in children with ELEs and persist with age, in contrast to what is expected in healthy children. There may be unmet sleep-related clinical needs in children with ELEs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sleep plays a major role in neuronal survival and guiding the fetal brain's development. Preterm infants in the neonatal intensive care unit are exposed to numerous external stimuli that can severely disrupt their sleep/wake patterns. Currently, almost no behavioral classification scales are validated for preterm infants. This study aims to develop a new, easy-to-use, validated visual sleep stage classification system for preterm infants with a gestational age between 25 and 37 weeks., Methods: The Behavioral Sleep stage classification for Preterm Infants (BeSSPI) consists of four sleep-wake stages; active sleep (AS), quiet sleep (QS), intermediate sleep (IS) and wake (W), which are classified using seven items. Items include eye movements, body movements, facial movements, vocalizations, heart rate, respiratory pattern and activity level., Results: 69 preterm infants were observed (24 + 6-36 + 0 weeks GA at birth; 25 + 2-36 + 6 weeks PMA at observation; 57.3% male). Across all 69 infants, the BeSSPI was based on 10,922 min of observed behavior, with 4264 min AS (38.83%), 2873 min QS (26.16%), 2887 min IS (26.29%), and 957 min W (8.72%). For the final BeSSPI, an interrater agreement of κ = 0.80 was reached. Additionally, construct, content, face validity, and expert validity were carefully assessed and deemed satisfactory., Conclusions: We developed a method to evaluate sleep-wake stages that is simple for all neonatal healthcare providers to learn and use. The BeSSPI is of high reliability and validity. Furthermore, it can be used in all preterm age-groups. Therefore, this novel instrument may improve rigor and reproducibility for future preterm sleep research., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Prophylactic antiseizure medications (ASMs) for pediatric traumatic brain injury (TBI) are understudied. We evaluated clinical and radiographic features that inform prescription of ASMs for pediatric TBI. We hypothesized that despite a lack of evidence, levetiracetam is the preferred prophylactic ASM but that prophylaxis is inconsistently prescribed., Methods: This retrospective study assessed children admitted with TBI from January 1, 2017, to December 31, 2019. TBI severity was defined using Glasgow Coma Scale (GCS) scores. Two independent neuroradiologists reviewed initial head computed tomography and brain magnetic resonance imaging. Fisher exact tests and descriptive and regression analyses were conducted., Results: Among 167 children with TBI, 44 (26%) received ASM prophylaxis. All 44 (100%) received levetiracetam. Prophylaxis was more commonly prescribed for younger children, those with neurosurgical intervention, and abnormal neuroimaging (particularly intraparenchymal hematoma) (odds ratio = 10.3, confidence interval 1.8 to 58.9), or GCS ≤12. Six children (13.6%), all on ASM, developed early posttraumatic seizures (EPTSs). Of children with GCS ≤12, four of 17 (23.5%) on levetiracetam prophylaxis developed EPTSs, higher than the reported rate for phenytoin., Conclusions: Although some studies suggest it may be inferior to phenytoin, levetiracetam was exclusively used for EPTS prophylaxis. Intraparenchymal hematoma >1 cm was the single neuroimaging feature associated with ASM prophylaxis regardless of the GCS score. Yet these trends are not equivalent to optimal evidence-based management. We still observed important variability in neuroimaging characteristics and TBI severity for children on prophylaxis. Thus, further study of ASM prophylaxis and prevention of pediatric EPTSs is warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)