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Background: Neonatal seizures (NS) represent an important clinical manifestation among critically ill infants and are often the first sign of underlying brain injury. Early recognition and treatment are essential to reduce morbidity and mortality. The present study investigated the NS management and treatment approaches employed by level II/III neonatal intensive care units (NICUs) across the United States to identify areas of consensus and variability., Methods: Personnel associated with level II/III NICUs were directly surveyed with an electronic questionnaire. Access to neurology specialists, on-site electroencephalography (EEG) monitoring, and use of antiseizure medications was directly queried. A total of 51 NICUs participated in this survey., Results: Twenty-five percent of the surveyed NICUs reported having an established clinical practice pathway available for treating NS. Twenty-four percent endorsed having written guidelines that provided a formal definition for the concept of "neonatal seizures." Although the majority of NICUs reported having phenobarbital available for rapid seizure management, most NICUs lacked access to additional antiseizure medications for treatment escalation. Twenty-four percent of the surveyed NICUs had no access to EEG monitoring available to them on-site. Daytime and overnight access to neurology consultants was limited and variable., Conclusions: Findings were consistent with a lack of equitable access for NS treatment. Areas of potential improvement include development and implementation of a protocol for rapidly treating NS that emphasizes enhanced access to EEG and rapid neurology consultation, acknowledging and improving upon resource limitations. These developments may eventually provide earlier detection, evaluation, and treatment of seizures in newborns, contributing to improved long-term outcomes., Competing Interests: Declaration of competing interest The authors declare no known conflicts of interest associated with this publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study aims to understand diagnosis communication experiences and preferences of youths with functional seizures and their parents., Methods: Semistructured interviews with youths and their parents from a tertiary care children's hospital were conducted separately. We confirmed the diagnosis of functional seizures with the youth's treating providers. All interviews were audio recorded and professionally transcribed. Two coders performed thematic analysis and determined themes., Results: Thirteen youths (aged 12 to 18) and 13 parents completed interviews separately. Themes included the following: (1) both parents and youths reported substantial fear about their symptoms, diagnosis, prognosis, and treatment options; (2) good communication skills highlighted included providing reassurance, listening, and allowing time for questions, with different preferences between youths and parents in the mode of communication; (3) poor communication for both youths and parents included use of medical jargon, brevity of communication especially with the youth, minimization of youth's symptoms, lack of apparent compassion, and lack of written materials to supplement discussions; (4) perspectives on the role of mental health in functional seizures were heterogeneous, yet concrete treatment plans were desired including access to behavioral therapy; and (5) youths and parents wanted practical guidance including plans for school and how to respond to functional seizures in all settings., Conclusions: Youths and parents provided concrete recommendations for optimal diagnosis communication. Study findings will inform the future development of an educational intervention to improve communication and create a supportive environment for youths with functional seizures., Competing Interests: Declaration of Competing Interest Dr. Kerr writes paid review articles for Medlink Neurology on topic; is a paid consultant for SK Lifesciences, Biohaven Pharmaceuticals, Cerebral Therapeutics, UCB, EpiTel, and the Epilepsy Study Consortium; and has collaborative or data use agreements with Eisai, Janssen, Radius Health, GlaxoSmithKline (GSK), Johnson & Johnson, and Jazz Pharmaceuticals. The remaining authors have no conflicts of interest to declare. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The presented evidence-based clinical practice guideline (CPG) is proposed as a National CPG where we adapted the international recommendations for the emergency management of seizures in children beyond the neonatal period to suit the health care in Egypt. The quality of evidence and the strength of recommendations are indicated. This study aimed to standardize the treatment of acute epileptic seizures and to provide an easy-to-apply acute treatment protocol that will allow immediate and appropriate seizure control., Methods: This is part of a larger program by the Egyptian Pediatric Clinical Practice Guidelines Committee (EPG) in collaboration with the staff of pediatric departments of 15 Egyptian universities and the National Research Centre. EPG was affiliated later to the Supreme Council of the Egyptian University Hospitals aiming to define the topics of, assign authors to, and assist in the adaptation of pediatric evidence-based CPGs according to a national strategic plan (http://epg.edu.eg). The committee is guided by a formal CPG adaptation methodology: the "Adapted ADAPTE.", Results: The Egyptian Childhood Seizure Group (ECSG) reviewed the results of the Appraisal of Guidelines for Research and Evaluation II assessment and decided to adapt the recommendations of three source CPGs: American Epilepsy Society, Italian League Against Epilepsy, Neurocritical Care Society, and Neurologic & Psychiatric Society of Zambia. Eight implementation tools were included. A comprehensive set of multifaceted CPG implementation strategies was provided for the clinicians, patients, nurses, and other relevant stakeholders contextualized to the national settings., Conclusions: Our experience with this adaptation methodology provides useful insight into its national utilization in Egypt., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To compare seizure burden between newborn infants treated with therapeutic hypothermia (TH) and those that were not and to compare the need for antiseizure medications (ASM) in a cohort of infants who were diagnosed with neonatal hypoxic-ischemic encephalopathy (HIE)., Methods: This was a retrospective cohort study on infants born after 35 weeks' gestation, diagnosed with moderate to severe HIE, monitored with amplitude-integrated electroencephalography (aEEG) and eligible for TH. Infants born before the implementation of TH in 2008 were compared with infants born thereafter who received TH. Seizure burden was assessed from aEEG as total time in minutes of seizures activity per hour of recording. Other clinical and demographic data were retrieved from a prospective local database of infants with HIE., Results: Overall, 149 of 207 infants were included in the study: 112 exposed to TH and 37 not exposed. Cooled infants had a lower seizure burden overall (0.4 vs 2.3 min/h, P < 0.001) and were also less likely to be treated with ASM (74% vs 100%, P < 0.001). In multivariable regression models, not exposed to TH, having a depressed aEEG background, and having higher Apgar scores were associated with higher seizure burden (incidence rate ratio: 4.78 for noncooled infants, P < 0.001); also, not exposed to TH was associated with a higher likelihood of multidrug ASM (odds ratio: 4.83, P < 0.001)., Conclusions: TH in infants with moderate to severe HIE is associated with significant reduction of seizure burden and ASM therapy., Competing Interests: Declaration of competing interest 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 paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Significant knowledge gap exists on vagus nerve stimulation (VNS) efficacy and tolerability in medically refractory absence seizures (MRAS). This retrospective review of patients with MRAS aims to narrow this knowledge gap by comparing ultra rapid duty cycling ([URDC] ON time seven seconds, OFF time 0.2 minutes) with less frequent stimulations of rapid duty cycling (RDC, OFF time <1.1 minutes) and normal duty cycling (NDC, OFF time ≥1.1 minutes)., Methods: Patients with MRAS aged less than 21 years who underwent VNS implantation were identified. Patient demographics, antiepileptic medications, seizure types, frequency, VNS parameters, outcomes of seizure reduction rate (SRR), and seizure freedom were extracted and compared among NDC, RDC, and URDC patient cohorts., Results: Thirty-six patients with MRAS were identified. After a mean follow-up of 32.6 months, responder rate ([RR], SRR ≥50%) for URDC was 80% for absence seizures and 80% for all seizure types versus 66.67% and 66.77% for NDC and 78.57% and 57.14% for RDC, respectively. Six of 10 patients (60%) on URDC achieved complete seizure freedom. A higher rate of subjective improvement in academic performance, attention, and developmental gain was noted in the URDC group. Patients on URDC tolerated higher output current (mean 3.025 mA) with minimal side effects but required a battery change sooner., Conclusions: VNS is a safe and effective nonpharmacologic management choice in patients with MRAS. The data presented demonstrate that the combination of URDC and high output current provides better RR and seizure freedom. Apart from a reduced battery life, this parameter modality seems to be well-tolerated., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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: 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.)

Background: Parents of neonates with seizures are at risk of mental health symptoms due to the impact of illness on family life, prognostic uncertainty, and the emotional toll of hospitalization. A family-centered approach is the preferred model to mitigate these challenges. We aimed to identify strategies to promote family-centered care through an analysis of parent-offered advice to clinicians caring for neonates with seizures., Methods: This prospective, observational, and multicenter (Neonatal Seizure Registry) study enrolled parents of neonates with acute symptomatic seizures. Parents completed surveys about family well-being at 12, 18, and 24 months corrected gestational age. Parents were asked open-ended questions eliciting their advice to clinicians caring for neonates with seizures. Responses were analyzed using a conventional content analysis approach., Results: Among the 310 parents who completed surveys, 118 (38%) shared advice for clinicians. These parents were predominantly mothers (n = 103, 87%). Three overarching themes were identified. (1) Communicate information effectively: parents appreciate when clinicians offer transparent and balanced information in an accessible way. (2) Understand and validate parent experience: parents value clinicians who display empathy, compassion, and a commitment to parent-partnered clinical care. (3) Providesupportand resources: parents benefit from emotional support, education, connection with peers, and help navigating the health care system., Conclusions: Parents caring for neonates with seizures appreciate a family-centered approach in health care encounters, including skilled communication, understanding and validation of the parent experience, and provision of support and resources. Future interventions should focus on building structures to reinforce these priorities., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Sturge-Weber syndrome (SWS) is a sporadic, neurocutaneous syndrome involving the skin, brain, and eyes. Because of the variability of the clinical manifestations and the lack of prospective studies, consensus recommendations for management and treatment of SWS have not been published., Objective: This article consolidates the current literature with expert opinion to make recommendations to guide the neuroimaging evaluation and the management of the neurological and ophthalmologic features of SWS., Methods: Thirteen national peer-recognized experts in neurology, radiology, and ophthalmology with experience treating patients with SWS were assembled. Key topics and questions were formulated for each group and included (1) risk stratification, (2) indications for referral, and (3) optimum treatment strategies. An extensive PubMed search was performed of English language articles published in 2008 to 2018, as well as recent studies identified by the expert panel. The panel made clinical practice recommendations., Conclusions: Children with a high-risk facial port-wine birthmark (PWB) should be referred to a pediatric neurologist and a pediatric ophthalmologist for baseline evaluation and periodic follow-up. In newborns and infants with a high-risk PWB and no history of seizures or neurological symptoms, routine screening for brain involvement is not recommended, but brain imaging can be performed in select cases. Routine follow-up neuroimaging is not recommended in children with SWS and stable neurocognitive symptoms. The treatment of ophthalmologic complications, such as glaucoma, differs based on the age and clinical presentation of the patient. These recommendations will help facilitate coordinated care for patients with SWS and may improve patient outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has an extensively studied classical role in neuronal growth, differentiation, survival, and plasticity. Neurotrophic, from the Greek neuro and trophos, roughly translates as "vital nutrition for the brain." During development, BDNF and its associated receptor tyrosine receptor kinase B are tightly regulated as they influence the formation and maturation of neuronal synapses. Preclinical research investigating the role of BDNF in neurological disorders has focused on the effects of decreased BDNF expression on the development and maintenance of neuronal synapses. In contrast, heightened BDNF-tyrosine receptor kinase B activity has received less scrutiny for its role in neurological disorders. Recent studies suggest that excessive BDNF-tyrosine receptor kinase B signaling in the developing brain may promote the hyperexcitability that underlies refractory neonatal seizures. This review will critically examine BDNF-tyrosine receptor kinase B signaling in the immature brain, its role in the emergence of refractory neonatal seizures, and the potential of targeting BDNF-TrkB signaling as a novel antiseizure strategy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The burden and characteristics of unplanned readmission after epilepsy-related discharge in children in the United States is not known., Methods: We undertook a retrospective cohort study of children aged one to 17 years discharged after a nonelective hospitalization for epilepsy, sampled from the Healthcare Cost and Utilization Project's 2013 and 2014 Nationwide Readmissions Database. Descriptive statistics and logistic regression models were used to examine the characteristics of initial hospitalization and risk factors for readmission., Results: A total of 42,873 admissions for unique patients were identified, with 4470 (10.4%) leading to readmission within 30 days. The most common readmission diagnosis was epilepsy (24.9%). Neurodevelopmental diagnoses including cerebral palsy, intellectual disability, and developmental delay were associated with increased odds of readmission. Longer hospitalization, gastrostomy, and tracheostomy were also associated with readmission, but continuous electroencephalography use was not. Children insured by Medicare had a readmission rate of 34.4%, whereas there were no associations of readmission with other sociodemographic characteristics such as neighborhood, income, and sex., Conclusions: Seizures are among the most frequent reasons for hospitalization in children. Establishing a benchmark readmission rate for pediatric epilepsy of 10.4% may be useful to health systems designing quality improvement efforts. Clinical factors were more strongly associated with readmission than demographic characteristics. Interventions to reduce pediatric epilepsy readmissions may have the highest yield when targeting children with neurodevelopmental comorbidities., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To determine whether the use of rapid sequence magnetic resonance imaging (rsMRI) is associated with improved efficiency of care when managing infants with suspected neonatal onset seizures., Methods: We conducted a preintervention and postintervention study of the use of rsMRI in term infants with suspected neonatal onset seizures without evidence of hypoxic ischemic encephalopathy. Study patients were collected from a contemporary cohort from 2016 to 2017 and were compared with a historical cohort from 2014. The primary outcome was hospital length of stay. Secondary outcomes included use of other imaging modalities (head ultrasound, computed tomography [CT], and MRI), use of antiseizure medications at the time of discharge, and cost of hospitalization. Continuous variables were compared using the Mann-Whitney U test and categorical variables using the Fisher's exact or χ 2 tests. A two-tailed P < 0.05 was considered statistically significant., Results: Ninety-five patients met inclusion criteria, 47 in the preintervention and 48 in the postintervention group. Incorporation of the protocol-guided rsMRI in the evaluation of patients with neonatal seizures was associated with decreased use of CT scans (34% vs 10%, P = 0.007) and full MRIs (85% vs 62%, P = 0.019). Use of head ultrasound, length of stay, and costs were not different between groups., Conclusions: In patients with neonatal seizures, rsMRI was not associated with a reduced hospital length of stay. The use of rsMRI resulted in fewer neonates receiving CT scans during their hospitalization. rsMRI may hasten the identification of stroke or hemorrhage in neonates with seizures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Rapid, effective treatment for status epilepticus reduces associated morbidity and mortality, yet medication delivery remains slow in many hospitalized patients. We utilized quality improvement (QI) methodology to improve treatment times for hospitalized children with status epilepticus. We hypothesized rapid initial seizure treatment would decrease seizure morbidity., Methods: We utilized QI and statistical process control analysis in a nonintensive care setting within a tertiary care pediatric hospital. We performed Plan-Do-Study-Act cycles including (1) revising the nursing process for responding to seizures, (2) emphasizing intranasal midazolam over intravenous lorazepam, (3) relocating medications and supplies, (4) developing documentation tools and reinforcing correct processes, (5) developing and disseminating an online education module for residents and nurse practitioners, and (6) completing standardization to intranasal midazolam., Results: Seventeen months after starting the project, 66 seizures had been treated with a benzodiazepine in a median (p 25 -p 75 ) time of 7.5 minutes (5 to 10), decreased from a baseline of 14 minutes (8-30) (P = 0.01). The proportion of patients receiving a benzodiazepine in 10 minutes or less improved from 39% to 79%. The proportion of patients transferred to intensive care decreased from a baseline of 39% to 9% (P < 0.005), resulting in an estimated $2.1 million in mitigated hospital charges. Significant harm did not occur during the implementation of these interventions., Conclusions: Children with status epilepticus were treated with benzodiazepines more rapidly and effectively following implementation of QI methodology. These interventions reduced utilization of critical care and mitigated hospital charges., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Neonatal seizures due to acute brain injury are associated with high rates of death, disability, and epilepsy. Our objective was to examine incidence of and risk factors for epilepsy among survivors of acute symptomatic neonatal seizures who were cared for by a neonatal neurocritical care service., Methods: Neonates with acute symptomatic seizures who were admitted to UCSF Benioff Children's Hospital Neuro-Intensive Care Nursery from July 2008 to June 2014 were considered for inclusion., Results: A total of 144 children with acute symptomatic seizures met study criteria and 37 (26%) died before age one. Eighty-seven children (85% of eligible survivors) were followed up to one year or longer. Epilepsy was diagnosed in eight children at median age 4.9 (interquartile range 1.7, 6.1) years. The cumulative incidence risk of epilepsy at one year was 2% (95% confidence interval 0.6% to 9%) and at five years was 7% (95% confidence interval 3% to 20%). Cerebral palsy was diagnosed in 21%. Bayley-III cognitive subscale less than 85 was present in 13%. Children with epilepsy were more likely to be preterm, have brain injury, and be discharged home on antiseizure medication, although the results were not significant after adjusted analysis., Conclusions: The risk of epilepsy was lower and age at onset was older than in previous reports, which may be related to multiple factors including a neurocritical care approach, treatment of hypoxic-ischemic encephalopathy with hypothermia, high rate of neonatal transition to palliative care, and the exclusion of neonatal onset epilepsies. Continuation of antiseizure medications in infancy did not decrease the risk of epilepsy. Long-term, multicenter studies are needed to understand whether neonatal seizure management can alter the risk of epilepsy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to characterize hypoxic-ischemic injury and seizures in abusive head trauma., Methods: We studied 58 children with moderate or severe traumatic brain injury due to abusive head trauma. Continuous electroencephalograms and magnetic resonance images were scored., Results: Electrographic seizures (51.2%) and hypoxic-ischemic injury (77.4%) were common in our cohort. Younger age was associated with electrographic seizures (no seizures: median age 13.5 months, interquartile range five to 25 months, versus seizures: 4.5 months, interquartile range 3 to 9.5 months; P = 0.001). Severity of hypoxic-ischemic injury was also associated with seizures (no seizures: median injury score 1.0, interquartile range 0 to 3, versus seizures: 4.5, interquartile range 3 to 8; P = 0.01), but traumatic injury severity was not associated with seizures (no seizures: mean injury score 3.78 ± 1.68 versus seizures: mean injury score 3.83 ± 0.95, P = 0.89). There was a correlation between hypoxic-ischemic injury severity and seizure burden when controlling for patient age (r s =0.61, P < 0.001). The ratio of restricted diffusion volume to total brain volume (restricted diffusion ratio) was smaller on magnetic resonance imaging done early (median restricted diffusion ratio 0.03, interquartile range 0 to 0.23 on magnetic resonance imaging done within two days versus median restricted diffusion ratio 0.13, interquartile range 0.01 to 0.43 on magnetic resonance imaging done after two days, P = 0.03)., Conclusions: Electrographic seizures are common in children with moderate to severe traumatic brain injury from abusive head trauma, and therefore children with suspected abusive head trauma should be monitored with continuous electroencephalogram. Severity of hypoxic-ischemic brain injury is correlated with severity of seizures, and evidence of hypoxic-ischemic injury on magnetic resonance imaging may evolve over time. Therefore children with a high seizure burden should be reimaged to evaluate for evolving hypoxic-ischemic injury., (Published by Elsevier Inc.)

Background: Seizures may cause added harm in neonates with hypoxic-ischemic encephalopathy (HIE). Specific recommendations about seizure treatment in this context are lacking. We sought to determine the scope of practice regarding management of non-status epilepticus electrographic-only seizures in this setting., Methods: A case-based survey was distributed to members of the Child Neurology Society. Providers were asked about their preferred management strategy for sequential clinical scenarios., Results: A total of 177 child neurologists responded to the survey. Seventy-seven percent of providers would treat 20 seconds or less of electrographic seizure activity. In a neonate with mild HIE and an electrographic-only seizure, there was no agreement among providers regarding whether to start maintenance therapy in addition to a one-time anti-seizure drug load. In a neonate with moderate HIE on phenobarbital for early electro-clinical seizures, most providers would escalate treatment for ongoing electrographic-only seizures by increasing phenobarbital dosing. In a neonate with severe HIE complicated by status epilepticus on phenobarbital who subsequently develops recurrent electrographic-only seizures, providers varied substantially in their management preferences. For all three cases, 75% to 85% of providers would not change their management preferences based on the absence of a clinical correlate with the electrographic seizure., Conclusions: We found marked variability among providers regarding preferred management of non-status epilepticus electrographic-only seizures after HIE. Our results identified specific aspects of electrographic-only seizure management in neonatal HIE where there is limited consensus. These discrepancies may serve as opportunities for future investigation., (Copyright © 2017. Published by Elsevier Inc.)

Background: The severity of the initial encephalopathy in neonatal hypoxic-ischemic encephalopathy correlates with seizure burden. Early electroencephalograph (EEG) background activity reflects the severity of encephalopathy. Thus, we hypothesized that early EEG background would be predictive of subsequent seizures in neonatal hypoxic-ischemic encephalopathy., Methods: This study included infants undergoing therapeutic hypothermia at St. Louis Children's Hospital between January 2009 and April 2013. Two pediatric epilepsy specialists independently characterized EEG background qualitatively using amplitude-integrated EEG trends. Total EEG power in the 1-20 Hz frequency band was calculated for quantitative EEG background assessment. Seizures were identified on conventional full montage EEG. Statistical analysis was performed using logistic regression., Results: Seventy-eight of the 93 eligible infants had artifact-free EEG data; 23 of 78 infants (29%) developed seizures, and of these, 11 developed status epilepticus. The best predictors of subsequent seizures during the first hour of EEG recording were a flat tracing pattern on amplitude-integrated EEG (sensitivity 26%, specificity 98%, likelihood ratio 13, positive predictive value 85%) and the total EEG power less than 10 μV 2 (sensitivity 52%, specificity 98%, likelihood ratio 30, positive predictive value 92%)., Conclusions: Early EEG biomarkers predict subsequent seizures in infants with hypoxic-ischemic encephalopathy. Compared with the qualitative amplitude-integrated EEG background, total EEG power improves our ability to identify high-risk infants from the first hour of EEG recording. Infants with a total EEG power of less than 10 μV 2 have a 90% risk of subsequent seizures. Quantitative EEG measures could stratify cohorts while evaluating novel neuroprotective strategies in neonatal hypoxic-ischemic encephalopathy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: SCN8A mutations are rare and cause a phenotypically heterogeneous early onset epilepsy known as early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558). There are currently no clear genotype-phenotype correlations to help guide patient counseling and management., Patient Description: We describe a patient with EIEE13 (de novo heterozygous pathogenic mutation in SCN8A - p.Ile240Val (ATT>GTT)) who presented prenatally with maternally reported intermittent, rhythmic movements that, when observed on ultrasound, were concerning for fetal seizures. Ultrasound also revealed abnormal developmental states. With maternal administration of levetiracetam, the rhythmic fetal movements stopped. After birth, the patient developed treatment-refractory multi-focal epilepsy confirmed by electroencephalogram. Neuroimaging revealed restricted diffusion in the superior cerebellar peduncles, a finding not reported previously in EIEE13., Conclusion: This is the first report of EIEE13 associated with clinical prenatal-onset seizures. Ultrasonography can be useful for identifying fetal seizures, which may be treatable in utero. Ideally, the clinical approach to fetal seizures should involve a multidisciplinary team spanning the pre- and postnatal course to expedite early diagnosis and optimize management, as illustrated by this patient., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The diagnosis and management of psychogenic nonepileptic seizures (PNES) is often challenging and fraught with discord and disagreement between patients, parents, and physicians. Furthermore, there are ethical challenges when making the diagnosis, communicating this information, and instituting management., Methods: We reviewed the current body of knowledge regarding the characteristic differences between epileptic seizures and PNES, and the high incidence of psychiatric comorbidities. An ethical analysis was made of diagnosis and management based on ethical principles, virtue ethics, and the social contract that health professionals have with patients., Results: Key distinctions between PNES and epilepsy lie in both patient and seizure characteristics. Long duration, eye closure, asynchronous movements, frequent recurrence in the same context, intra-ictal awareness, and lack of post ictal state are useful in helping establish the diagnosis. Psychiatric comorbidities, history of abuse, cognitive impairment, and multiple non specific somatic complaints are some salient patient features that should increase suspicion for the diagnosis of PNES. However, definitive diagnosis rests on capturing the events on video EEG., Conclusion: Effective diagnosis and management of PNES requires the use of video EEG and an early collaborative approach between pediatricians, neurologists, psychiatrists, nursing staff, and other professional colleagues. Ethical questions that may arise should be addressed with the virtues of competence, courage, compassion, prudence, and honesty; and the principles of respect beneficence, and the avoidance of unnecessary harm., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The aims of this study were to evaluate sleep difficulties in children with neuronal ceroid lipofuscinosis and to determine the association between the sleep difficulties and the onset of seizures and loss of vision., Method: We recruited individuals with a confirmed diagnosis of neuronal ceroid lipofuscinosis. We obtained information from the caregiver using the validated Children's Sleep Habits Questionnaire which is a sleep instrument for both behaviorally and medically based problems. Additional information was collected including onset of symptoms, treatment trials, and screen for restless leg syndrome symptoms., Results: In our cohort of 54 individuals, 96.3% had sleep scores consistent with a sleep disturbance. Sleep subscale analysis provided additional insight into the characteristics of the sleep disturbance. Fifty two of the 54 patients had at least one abnormal sleep subscale. The onset of sleep disturbance was associated with the onset of both seizures (ρ = 0.5834, P < 0.0001) and loss of vision (ρ = 0.3840, P = 0.0084). Restless leg syndrome symptoms were reported in 35.2%., Conclusion: Children with neuronal ceroid lipofuscinosis have a high burden of sleep disturbances. Using the results of a sleep disturbance screening tool can help to identify the most disturbing symptoms. Targeted treatment of sleep disturbance may improve the quality of life for the patient and family., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Paroxysmal nonepileptic events are common in children. Events with a psychological basis, historically referred to as pseudoseizures, are a large subset of paroxysmal nonepileptic events., Methods: A review of the relevant pediatric and adult literature was performed., Results: It was found that these events have many semioloigc features similar to epileptic events and can be challenging to correctly identify. The use of a detailed history in combination with video encephalography and knowledge of psychogenic paroxysmal nonepileptic events will facilitate making the correct diagnosis. Paroxysmal nonepileptic events are important to identify as comorbid disorders such as depression, anxiety disorder, family discord, and school issues are frequent. In addition, prior sexual, emotional, and/or physical abuse may be present., Conclusions: Pediatric patients with paroxysmal nonepileptic events need to be recognized in order to avoid unnecessary antiepileptic drugs and emergency department or hospital visits and to facilitate appropriate psychological intervention to address the underlying etiologies. This review will focus on evaluation and identification of paroxysmal nonepileptic events, in addition to reviewing the various comorbidities, effective treatments, and outcomes for pediatric patients. The key differences between pediatric and adult patients with paroxysmal nonepileptic events are addressed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The direct charges for emergency department visits resulting from recurrent seizures are significant, and home intervention with abortive medications can be cost-saving. Over a 1-year period, we evaluated children with seizures who were seen in the emergency department, stabilized, and released. The information is necessary to assess the pharmacoeconomic advantages of at-home interventions for seizure emergencies., Methods: We did a retrospective chart review of 90 patients and divided them into febrile versus nonfebrile seizures and existing versus new-onset seizure disorder. The hospital accounting department performed a charge analysis., Results and Conclusion: The total charges for all 90 patients treated for seizures in the emergency department were $219,945. The minimum was $370, for a patient with no history of febrile seizures. The maximum was $17,126, for a patient with a nonfebrile seizure and a history of seizures. This information allows a comparison with the cost of preventive medications, such as diazepam rectal gel or intranasal midazolam., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Paroxysmal nonepileptic events of psychogenic etiology in children and adolescents are common. Patients and their parents are often confused by the terminology used to describe these events. This can lead to frustration and may result in the failure to obtain the necessary nonpharmacologic treatment. Various terms are used to describe such events, some of which might be considered offensive to some individuals. Surveys from 146 parents or guardians of patients identified from a general pediatric clinic, a general neurology clinic, and a pediatric epilepsy monitoring unit were completed with the aim of determining which words and phrases were least offensive. It was determined that nonepileptic events, functional seizures, and nonepileptic attack disorder were the least offensive labels; whereas "it is all in his or her head," hysterical seizures, and psychogenic seizures were the most offensive terms. This is the only study of its type in the pediatric population. Although each child and family requires individualized communication, we hope that this article will provide useful information to guide the practicing pediatric neurologist in informing families that their children are having events of nonepileptic etiology., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We report the case of an adolescent girl with anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis who presented with focal seizures and hemichorea, followed by agitation, speech disturbance, mutism, and autonomic dysfunction. The institution of immunotherapy and removal of an ovarian cystadenofibroma led to full resolution of her symptoms with disappearance of serum NMDAR antibodies. This is the first report linking ovarian cystadenofibroma to anti-NMDAR encephalitis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Neonatal seizures are common, and often comprise the first clinical indicator of central nervous system dysfunction. Although most neonatal seizures are secondary to processes such as hypoxic-ischemic injury, infection, or cortical malformations (which are readily identifiable through routine testing and imaging), seizures secondary to inborn errors of metabolism can be much more difficult to diagnose, and thus a high index of suspicion is required. The early diagnosis of inborn errors of metabolism is crucial, considering that many can receive effective treatment (e.g., dietary supplementation or restriction) with favorable long-term outcomes. This review emphasizes the importance of considering inborn errors of metabolism in the differential diagnosis of neonatal seizures, discusses red flags for inborn errors of metabolism as a cause of neonatal seizures, and provides an overview of diagnoses and treatments of inborn errors of metabolism most commonly associated with neonatal seizures., (Copyright © 2011 Elsevier Inc. All rights reserved.)

There is a pressing need for consistent, evidence-based guidelines in the management of neonatal seizures by pediatric neurologists and neonatologists. Israeli pediatric neurologists and neonatologists completed a 20-item, self-administered questionnaire on choices of antiepileptic drugs, treatment of intractable neonatal seizures (unremitting seizures after 3 medications), treatment duration, and recommended workup. The responding 36/55 (65%) neurologists and 66/112 (59%) neonatologists made similar antiepileptic drug choices (phenobarbital as first line, phenytoin as second line, and benzodiazepines as third line). Antiepileptic treatment duration was similar for both groups, but varied considerably within them (range, 1-52 weeks). Neurologists tended to recommend longer treatment for seizures secondary to asphyxia or hemorrhage. Neurologists and neonatologists recommended different antiepileptic drugs for intractable neonatal seizures: valproic acid and topiramate by neurologists, vs lidocaine and benzodiazepines by neonatologists (P = 0.0023). Fewer neurologists recommended continuous electroencephalography monitoring after asphyxia than neonatologists (40% vs 70.5%, P = 0.013). These responses reflect both similarities and inconsistencies of the two groups in diagnosing and treating neonatal seizures. Our findings call for controlled clinical trials to establish protocols for (1) diagnosing neonatal seizures, (2) studying the efficacy and safety of new-generation antiepileptic drugs, and (3) determining optimal duration of drug administration.

Little is known about acute recurrence of seizures, and children with unprovoked seizure tend to be admitted for observation on the basis of the risk factors known for epilepsy. The purpose of this study is to define the clinical profile of pediatric seizure patients who are likely to be admitted and to analyze the incidence and the risk factors of acute recurrence of seizures in the admitted patients within 24 hours after admission. A retrospective chart review was performed on pediatric patients who arrived to the Schneider Children's Hospital Emergency Department because of an unprovoked seizure who were not on antiepileptic medication. Fifty-nine percent of children who arrived to the emergency department were admitted. Emergency department physicians tend to admit children with younger age (P<0.01), multiple seizures (P<0.001), and children who were treated in the emergency department (P<0.001). Twenty percent of admitted patients had one or more seizures within 24 hours. Multiple seizures before the emergency department arrival was a significant risk factor for acute recurrence (33%, P<0.05). Based on our findings that 20% of admitted children had one or more seizures within 24 hours, we think it is justified to admit and observe the children with seizures who are not on antiepileptic medications if the follow-up cannot be ensured.

There are four unresolved clinical issues at bedside with respect to the recognition, differential diagnosis, prognosis, and treatment of infants who present with seizures. There is also an overriding fifth question which bridges these four clinical issues, based on a laboratory researcher's perspective at the "bench". Given the increasing understanding of the neurobiologic and pathophysiologic explanations for seizures in animal models, one must consider the question of whether neonatal seizures cause brain injury or are a surrogate of injury resulting from other etiologies.