Search

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.)

Summary: Cochlear implants to aid sensorineural hearing loss are becoming commonplace. In this study, we describe two cases that showed artifacts related to the cochlear implant device during scalp EEG recording. To our knowledge, cochlear implant artifacts have not been reported previously. Recognizing cochlear implant artifacts will avoid misinterpretation and resultant inappropriate treatment., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Purpose: In 2011, the authors conducted a survey regarding continuous EEG (CEEG) utilization in critically ill children. In the interim decade, the literature has expanded, and guidelines and consensus statements have addressed CEEG utilization. Thus, the authors aimed to characterize current practice related to CEEG utilization in critically ill children., Methods: The authors conducted an online survey of pediatric neurologists from 50 US and 12 Canadian institutions in 2022., Results: The authors assessed responses from 48 of 62 (77%) surveyed institutions. Reported CEEG indications were consistent with consensus statement recommendations and included altered mental status after a seizure or status epilepticus, altered mental status of unknown etiology, or altered mental status with an acute primary neurological condition. Since the prior survey, there was a 3- to 4-fold increase in the number of patients undergoing CEEG per month and greater use of written pathways for ICU CEEG. However, variability in resources and workflow persisted, particularly regarding technologist availability, frequency of CEEG screening, communication approaches, and electrographic seizure management approaches., Conclusions: Among the surveyed institutions, which included primarily large academic centers, CEEG use in pediatric intensive care units has increased with some practice standardization, but variability in resources and workflow were persistent., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 by the American Clinical Neurophysiology Society.)

Objective: Responsive neurostimulation (RNS) is a US FDA-approved form of neuromodulation to treat patients with focal-onset drug-resistant epilepsy (DRE) who are ineligible for or whose condition is refractory to resection. However, the FDA approval only extends to use in patients with one or two epileptogenic foci. Recent literature has shown possible efficacy of thalamic RNS in patients with Lennox-Gastaut syndrome and multifocal epilepsy. The authors hypothesized that RNS of thalamic nuclei may be effective in seizure reduction for patients with multifocal or regionalized-onset DRE., Methods: The authors performed a retrospective chart review of all patients who had an RNS device managed at Texas Children's Hospital between July 2016 and September 2023, with at least one active electrode in the thalamic nuclei and ≥ 12 months of postimplantation follow-up. Information conveyed by the patient or their caregiver provided data on the change in the clinical seizure frequency, quality of life (QOL), and seizure severity between the preimplantation baseline visit and the last office visit (LOV)., Results: Thirteen patients (ages 8-24 years) were identified with active RNS leads in thalamic nuclei (11 centromedian and 2 anterior nucleus). At LOV, 46% of patients reported 50%-100% clinical seizure reduction (classified as responders), 15% reported 25%-49% reduction, and 38% reported < 25% reduction or no change. Additionally, 42% of patients reported subjective improvement in QOL and 58% reported improved seizure severity. Patients with focal cortical dysplasia (FCD) responded strongly: 3 of 5 (60%) reported ≥ 80% reduction in seizure burden and improvement in seizure severity and QOL. Patients with multifocal epilepsy and bilateral thalamocortical leads also did well, with all 3 reporting ≥ 50% reduction in seizures., Conclusions: RNS of thalamic nuclei shows promising results in reducing seizure burden for patients with multifocal or regional-onset DRE, particularly in a bilateral thalamocortical configuration or when addressing an underlying FCD.

Medical and surgical advancements have improved survival in children with acquired and congenital heart disease (CHD), but the burden of neurological morbidity is high. Brain disorders associated with CHD include white matter injury, stroke, seizure, and neurodevelopmental delays. While genetics and disease-specific factors play a substantial role in early brain injury, therapeutic management of the heart disease intensifies the risk. There is a growing interest in understanding how to reduce brain injury and improve neurodevelopmental outcomes in cardiac diseases. Pediatric neurologists serve a vital role in care teams managing these complex patients, providing interpretation of neuromonitoring and imaging, managing neurologic emergencies, assisting with neuro prognostication, and identifying future research aims., 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 © 2024. Published by Elsevier Inc.)

Neuromonitoring is used to assess the central nervous system in the intensive care unit. The purpose of neuromonitoring is to detect neurologic deterioration and intervene to prevent irreversible nervous system dysfunction. Neuromonitoring starts with the standard neurologic examination, which may lag behind the pathophysiologic changes. Additional modalities including continuous electroencephalography (CEEG), multiple physiologic parameters, and structural neuroimaging may detect changes earlier. Multimodal neuromonitoring now refers to an integrated combination and display of non-invasive and invasive modalities, permitting tailored treatment for the individual patient. This chapter reviews the non-invasive and invasive modalities used in pediatric neurocritical care., 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 © 2024. Published by Elsevier Inc.)

Tumor-related epilepsy (TRE) is a frequent and major consequence of brain tumors. Management of TRE is required throughout the course of disease and a deep understanding of diagnosis and treatment is key to improving quality of life. Gross total resection is favored from both an oncologic and epilepsy perspective. Shared mechanisms of tumor growth and epilepsy exist, and emerging data will provide better targeted therapy options. Initial treatment with antiseizure medications (ASM) in conjunction with surgery and/or chemoradiotherapy is typical. The first choice of ASM is critical to optimize seizure control and tolerability considering the effects of the tumor itself. These agents carry a potential for drug-drug interactions and therefore knowledge of mechanisms of action and interactions is needed. A review of adverse effects is necessary to guide ASM adjustments and decision-making. This review highlights the essential aspects of diagnosis and treatment of TRE with ASMs, surgery, chemotherapy, and radiotherapy while indicating areas of uncertainty. Future studies should consider the use of a standardized method of seizure tracking and incorporating seizure outcomes as a primary endpoint of tumor treatment trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Non-sleep related apnea (NSA) has been observed in alternating hemiplegia of childhood (AHC) but has yet to be characterized., Goals: Investigate the following hypotheses: 1) AHC patients manifest NSA that is often severe. 2) NSA is usually triggered by precipitating events. 3) NSA is more likely in patients with ATP1A3 mutations., Methods: Retrospective review of 51 consecutive AHC patients (ages 2-45 years) enrolled in our AHC registry. NSAs were classified as mild (not needing intervention), moderate (needing intervention but not perceived as life threatening), or severe (needing intervention and perceived as life threatening)., Results: 19/51 patients (37 %) had 52 NSA events (6 mild, 11 moderate, 35 severe). Mean age of onset of NSA (± Standard Error of the Mean (SEM)): 3.8 ± 1.5 (range 0-24) years, frequency during follow up was higher at younger ages as compared to adulthood (year 1: 2.2/year, adulthood: 0.060/year). NSAs were associated with triggering factors, bradycardia and with younger age (p < 0.008 in all) but not with mutation status (p = 0.360). Triggers, observed in 17 patients, most commonly included epileptic seizures in 9 (47 %), anesthesia, AHC spells and intercurrent, stressful, conditions. Management included use of pulse oximeter at home in nine patients, home oxygen in seven, intubation/ventilatory support in seven, and basic CPR in six. An additional patient required tracheostomy. There were no deaths or permanent sequalae., Conclusions: AHC patients experience NSAs that are often severe. These events are usually triggered by seizures or other stressful events and can be successfully managed with interventions tailored to the severity of the NSA., Competing Interests: Declaration of competing interest Dr. Mohamad Mikati reports that he has intellectual property interest in gene therapy of ATP1A3 related disease., (© 2023 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Purpose: Delayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE)., Methods: Retrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020. We selected pediatric patients (one month-21 years) with RCSE initiated outside the hospital and transported to the hospital by EMS., Results: We included 91 patients with a median (percentile 25 -percentile 75 ) age of 3.0 (1.5-7.3) years. The median time from seizure onset to hospital arrival was 45 (30-67) minutes, with a median time cared for by EMS of 24 (15-36) minutes. Considering treatment by caregivers and EMS before hospital arrival, 20 (22%) patients did not receive any anti-seizure medications (ASM) and 71 (78%) received one to five doses of benzodiazepines (BZD), without non-BZD ASM. We provided the prehospital treatment flow path of these patients through caregivers and EMS including relevant time points. Patients with a history of SE were more likely to receive the first BZD in the prehospital setting compared to patients without a history of SE (adjusted HR 3.25, 95% CI 1.72-6.12, p<0.001)., Conclusion: In this multicenter study of pediatric RCSE, prehospital treatment may be streamlined further. Patients with a history of SE were more likely to receive prehospital rescue medication., Competing Interests: Declaration of Competing Interest M.A.G. was supported by Fundación Alfonso Martín Escudero and the Epilepsy Research Fund. I.S.F. was supported by Fundación Alfonso Martín Escudero, the HHV6 Foundation, and the Epilepsy Research Fund. R.A. receives research support from NIH NINDS R01 NS115929 and Procter Foundation (Procter Scholar Award 2018–2021). C.B.A. was supported by Fundación Alfonso Martín Escudero. J.N.B. has served as a consultant for Novartis. T.A.G. is funded by NIH grants 2U01-NS045911, U10-NS077311, R01-NS053998, R01-NS062756, R01- NS043209, R01-LM011124, and R01-NS065840. He has received consulting fees from Supernus, Sunovion, Eisai, and UCB. He also serves as an expert consultant for the US Department of Justice and has received compensation for work as an expert on medico-legal cases. He receives royalties from a patent license. E.J.N. is a professional advisory board of the Epilepsy Foundation of America and served on Advisory Board for Zogenix. J.J.R. is a member of a data safety monitoring board for GW Pharmaceuticals. His-spouse is an editor for Uptodate. D.T. receives research funding from Children's Miracle Network Hospitals and has previously received consultation fees from Gerson Lehrman Group, Guidepoint, IQVIA, and bioStrategies Group. M.S.W. serves as a scientific consultant and on the clinical advisory board for Sage Pharmaceuticals. A.W. receives research funding from Novartis, Eisai, Pfizer, UCB, Acorda, Lundbeck, GW Pharma, Upsher-Smith, and Zogenix and receives publication royalties from Up to date. T.L. is part of pending patent applications to detect and predict seizures and diagnose epilepsy. He receives research support from the NIH, the Epilepsy Research Fund, the Epilepsy Foundation of America Epilepsy Venture Fund (Shark Tank Award), MIKU, and Epitel. He received device donations from Epitel, MIKU, Empatica, and neuroelectrics. In the past, he received research grants from Sage, Lundbeck, Eisai, Upsher-Smith, Proximagen, UCB, Mallinckrodt, Pfizer, and Empatica. In the past, he served as a consultant for Engage and Upsher Smith. The remaining authors have no disclosures relevant to this manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Background: We describe a cohort of children with severe myelin oligodendrocyte glycoprotein (MOG)-IgG-associated cerebral cortical encephalitis (CCE), manifesting with bilateral cortical cytotoxic edema and critical neurological illness., Methods: We retrospectively reviewed our pediatric MOG antibody-associated disease (MOGAD) database and identified patients with specific radiographic pattern of bilateral, multifocal cortical cytotoxic lesions. We collected demographic, clinical, and outcomes data from these patients and compared select variables with radiographically distinct cerebral MOGAD syndromes (case-control analysis). We assessed the correlation of quantitative clinical variables with severity/outcomes measures using simple linear regression., Results: Sixty-five of 88 total MOGAD cases had cerebral disease, and six of 88 met inclusion criteria for fulminant CCE (f-CCE). Age range was 2 to 7 years; five of six were male. Six of six were critically ill with severe encephalopathy and seizures, two of six required barbiturate coma, and two of six required invasive intracranial pressure monitoring. Six of six required treatment escalation beyond steroids. Four of six had favorable outcome; two of six had moderate-severe disability. Compared with other cerebral MOGAD cases (n = 59), children with f-CCE were more likely to have critical illness and poor neurological outcomes scores. Neurofilament light chain and treatment latency positively correlated with intensive care unit length of stay and outcomes scores; cerebrospinal fluid (CSF) white blood cell count and neutrophil-to-lymphocyte ratio did not., Conclusions: Pediatric CCE with bilateral cytotoxicity is associated with more fulminant disease and worse outcomes than other cerebral MOGAD syndromes., Competing Interests: Declaration of competing interest V.K. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. V.K., A.J.S., T.A.E., J.M.Y., A.A., V.A.H., N.M.S., S.R.R., K.K.M., and K.F. have no financial disclosures or conflicts of interest. T.E.L. has received personal compensation in the range of $5,000 to $9,999 for serving as an Expert Witness for Department of Justice VICP. T.E.L. has received research support from NIH, National MS Society, Sarepta Therapeutics, PTC Therapeutics, and Avexis. T.E.L. has received publishing royalties from a publication relating to health care. J.J.R. has received speaking fees from Wayne State University, Drexel University, and Children's Healthcare of Atlanta. Y.-C.L. has received funding support from the NIH/NINDS and is a member of the Medical and Scientific Advisory Board of the NORSE Institute., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: To review seizure outcomes in children with tuberous sclerosis complex (TSC) and drug-resistant epilepsy (DRE) treated with the responsive neurostimulation (RNS) System., Methods: We retrospectively reviewed children (<21 years old) with TSC implanted with the RNS System at Texas Children's Hospital between July 2016 and May 2022., Results: Five patients meeting the search criteria were identified (all female). The median age of the RNS implantation was 13 years (range: 5 to 20 years). The median epilepsy duration before the RNS implantation was 13 years (range: 5 to 20 years). Surgeries before RNS implantation included vagus nerve stimulator placement (n = 2), left parietal resection (n = 1), and corpus callosotomy (n = 1). The median number of antiseizure medications tried before RNS was 8 (range: 5 to 12). The rationale for the RNS System implantation included seizure onset in eloquent cortex (n = 3) and multifocal seizures (n = 2). The maximum current density for each patient ranged between 1.8 and 3.5 μC/cm 2 , with an average daily stimulation of 2240 (range: 400 to 4200). There was an 86% median seizure reduction (range 0% to 99%) at a median follow-up duration of 25 months (range: 17 to 25 months). No patient experienced implantation or stimulation-related complications., Conclusions: We observed a favorable improvement in seizure frequency in pediatric patients with DRE secondary to TSC treated with the RNS System. The RNS System may be a safe and effective treatment for DRE in children with TSC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage-gated K + channel subunit K V 1.1. So far, loss-of-function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain-of-function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4-aminopyridine. Clinical use of 4-aminopyridine was associated with reduced seizure burden, enabled simplification of co-medication and prevented rehospitalization., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

In a retrospective case series of 10 children with cryptogenic FIRES, we sought to describe the early clinical course and potential biomarkers following anakinra initiation. Six children achieved anesthetic withdrawal within 3 weeks of therapy and one in week four. Of the available cEEG (six children), CRP (10 children), and serum cytokine (six children) studies, there were temporal changes in highly epileptiform bursts (observed in three children), CRP, IL-6, and IL-10 levels that might parallel clinical progression. These observations may represent candidate biomarkers for monitoring clinical progression and therapeutic interventions including anakinra, which merits further investigation in future studies., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objectives: To describe adherence to continuous electroencephalogram (cEEG) monitoring as part of a pediatric neurocritical care (PNCC) program for status epilepticus (SE)., Design: Retrospective review of pre- and postintervention cohorts., Setting: A pediatric referral hospital., Patients: Children admitted to the PICU for SE., Interventions: We restructured the care delivery model to include a pediatric neurointensive care unit (neuro-ICU) and expanded the cEEG capacity. We created a criteria-based cEEG pathway. We provided education to all providers including the nursing staff., Measurements and Main Results: The main outcomes were: 1) the percentages of children meeting American Clinical Neurophysiology Society (ACNS) criteria who underwent cEEG monitoring and 2) the time interval between PICU arrival and cEEG initiation. PICU admissions with the diagnosis of SE from May 2017 to December 2017 served as the baseline, which was compared with the same periods in 2018 to 2020 (PNCC era).There were 60 admissions in the pre-PNCC period (2017), 111 in 2018, 118 in 2019, and 108 in 2020. The percentages of admissions from each period that met ACNS criteria for cEEG monitoring were between 84% and 97%. In the pre-PNCC era, 22 of 52 (42%) admissions meeting ACNS criteria underwent cEEG monitoring. In the PNCC era, greater than or equal to 80% of the qualified admissions underwent cEEG monitoring (74/93 [80%] in 2018, 94/115 [82%] in 2019, and 87/101 [86%] in 2020). Compared with the pre-PNCC era, the neuro-ICU had a shorter interval between PICU arrival and cEEG initiation (216 min [141-1,444 min] vs 138 min [103-211 min])., Conclusions: The implementation of a PNCC program with initiatives in care delivery, allocation of resources, and education was associated with increased adherence to best care practices for the management of SE., Competing Interests: Dr. Riviello received funding from BioMarin; he disclosed that his spouse is the section editor for UptoDate. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: There has been a growing impetus for developing pediatric neurocritical care (PNCC) programs to improve care delivery for children with critical neurological conditions. We sought to develop a unique PNCC program using the concept of Community of Practice (CoP)., Methods: This is a process improvement project in an academic Children's Hospital. Using CoP framework (domain, community, practice), we created a domain of PNCC with a stated vision and formal organizational structure, a core community of intensivists and neurologists interested in PNCC, and a standardized practice approach by establishing core competencies for PNCC and implementing practice guidelines., Results: We evaluated the program through the Four-Frame Model of Organizational Theory and Behavior (structural, human resource, political, symbolic) and by the Neurocritical Care Society's (NCS's) standards for a Level I Neurocritical Care Unit (Neuro-ICU). Structural frame included opening a pediatric Neuro-ICU, identifying PNCC leaders across specialties, and developing a multidisciplinary care delivery model. Human resource frame included forming physician and nurse groups with a primary role in PNCC and ongoing education through workshops, lecture series, and certification. Politically, program implementation was tailored to each department gaining institution-wide support for program initiatives. Symbolically, the PNCC program highlighted the vision to advance knowledge and best practices. Our program met 232 of 252 (92%) proposed NCS standards., Conclusions: The CoP as the foundation for program development has enabled us to achieve the majority of standards proposed by NCS for a Level I Neuro-ICU. The generalizability of these frameworks may facilitate the development of a PNCC program for other institutions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pediatric neurocritical care (PNCC) is a rapidly growing field. Challenges posed by the COVID-19 pandemic on trainee exposure to educational opportunities involving direct patient care led to the creative solutions for virtual education supported by guiding organizations such as the Pediatric Neurocritical Care Research Group (PNCRG). Our objective is to describe the creation of an international, peer-reviewed, online PNCC educational series targeting medical trainees and faculty. More than 1600 members of departments such as pediatrics, pediatric critical care, and child neurology hailing from 75 countries across six continents have participated in this series over a 10-month period. We created an online educational channel in PNCC with over 2500 views to date and over 130 followers. This framework could serve as a roadmap for other institutions and specialties seeking to address the ongoing problems of textbook obsolescence relating to the rapid acceleration in knowledge acquisition, as well as those seeking to create new educational content that offers opportunities for an interactive, global audience. Through the creation of a virtual community of practice, we have created an international forum for pediatric healthcare providers to share and learn specialized expertise and best practices to advance global pediatric health.

Objective: This study aimed to assess the clinical outcome and outcome predictive factors in pediatric epilepsy patients evaluated with stereo-electroencephalography (SEEG)., Methods: Thirty-eight patients who underwent SEEG implantation at the Pediatric Epilepsy Center in New York Presbyterian Hospital between June 2014 and December 2019 were enrolled for retrospective chart review. Postoperative seizure outcomes were evaluated in patients with at least 12-months follow up. Meta-analysis was conducted via electronic literature search of data reported from 2000 to 2020 to evaluate significant surgical outcome predictors for SEEG evaluation in the pediatric population., Results: In the current case series of 25 postsurgical patients with long-term follow up, 16 patients (64.0%) were seizure free. An additional 7 patients (28.0%) showed significant seizure improvement and 2 patients (8.0%) showed no change in seizure activity. Patients with nonlesional magnetic resonance imaging (MRI) achieved seizure freedom in 50% (5/10) of cases. By comparison, 73% (11/15) of patients with lesional MRI achieved seizure freedom. Out of 12 studies, 158 pediatric patients were identified for inclusion in a meta-analysis of the effectiveness of SEEG. Seizure freedom was reported 54.4% (n = 86/158) of patients at last follow up. Among patients with nonlesional MRI, 45% (n = 24) achieved seizure freedom compared with patients with lesional MRI findings (61.2%, n:= 60) (p = 0.02). The risk for seizure recurrence was 2.15 times higher [95% confidence interval [CI] 1.06-4.37, p = 0.033] in patients diagnosed with nonlesional focal epilepsy compared to those with lesional epilepsy [ 1.49 (95% CI 1.06-2.114, p = 0.021]., Conclusion: Evaluation by SEEG implantation in pediatric epilepsy is effective in localizing the epileptogenic zone with favorable outcome. Presence of a non-lesional brain MRI was associated with lower chances of seizure freedom. Further research is warranted to improve the efficacy of SEEG in localizing the epileptogenic zone in pediatric patients with non-lesional brain MRI., (Copyright © 2021. Published by Elsevier B.V.)

Purpose of Review: This review provides guidance for acute spinal cord injury (SCI) management through an analytical assessment of the most recent evidence on therapies available for treating SCI, including newer therapies under investigation. We present an approach to the SCI patient starting at presentation to acute rehabilitation and prognostication, with additional emphasis on the pediatric population when evidence is available., Recent Findings: Further studies since the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS) demonstrated a potential functional outcome benefit with ultra-early surgical intervention ≤ 8 h post-SCI. Subsequent analysis of the National Acute Spinal Cord Injury Study (NASCIS) II and NASCIS III trials have demonstrated potentially serious complications from intravenous methylprednisolone with limited benefit. Newer therapies actively being studied have demonstrated limited or no benefit in preclinical and clinical trials with insufficient evidence to support use in acute SCI treatment., Summary: Care for SCI patients requires a multi-disciplinary team. Immediate evaluation and management are focused on preventing additional injury and restoring perfusion to the affected cord. Rapid assessment and intervention involve focused neurological examination, targeted imaging, and surgical intervention when indicated. There are currently no evidence-based recommendations for pathomechanistically targeted therapies., Competing Interests: Conflict of InterestThe authors did not receive support from any organization for the submitted work. The authors have no relevant financial or non-financial interests to disclose. Open access of this publication was supported by the Texas Children’s Hospital Young Investigator Endowment., (© The Author(s) 2022.)

Background: Patients with brain tumor-related epilepsy (BTRE) are at a higher risk of significant morbidity, lower quality of life, and increased risk of mortality. We surveyed providers regarding anti-seizure medication (ASM) management in pediatric BTRE to determine if practices are standard or markedly variable., Methods: An anonymous voluntary online survey was sent to members of the Child Neurology Society. Providers were asked specific questions regarding initiation and wean of ASMs and if this was dependent on multiple factors. Demographic information was collected., Results: Fifty-one providers responded to the survey. Ninety-four percent of providers would start an ASM after a second seizure. Eighty-four percent chose levetiracetam as the preferred ASM. Management was variable when based on tumor location, extent of surgical resection, pathology, and tumor prognosis. Statistically significant differences in responses regarding management were identified when comparing neurologists and epileptologists, providers with formal neuro-oncology or epilepsy training, providers at large institutions, and years of experience. For patients who underwent a gross total resection of the tumor, neuro-oncology and epilepsy-trained providers were more likely to wean off ASMs (p < 0.049). Providers without formal training in neuro-oncology or epilepsy were more likely to get an EEG prior to making a decision about weaning off ASMs (p < 0.016)., Conclusion: These results suggest that ASM management in BTRE varies greatly according to sub-specialty and experience. Further studies and potential development of guidelines are needed to identify the most appropriate management of ASMs for BTRE., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients., Design: Retrospective cohort study with prospectively collected data between June 2011 and January 2019., Setting: Seventeen academic hospitals in the United States., Patients: We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups., Interventions: None., Measurements and Main Results: We identified 281 patients (157 males) with a median age of 4.1 years (1.3-9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55-491.5 min] vs 62 min [33.3-120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5-1,255 min] vs 150 min [90-318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58-368 hr] vs 3 hr [1.4-5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5-40 d] vs [1.8-8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments., Conclusions: Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus., Competing Interests: Dr. Vasquez’s, Dr. Arya’s, Ms. Clark’s, Dr. Peariso’s, Dr. Sands’s, and Dr. Loddenkemper’s institutions received funding from Epilepsy Research Fund, American Epilepsy Society/Epilepsy Foundation of America, and Pediatric Epilepsy Research Foundation, and they disclosed off-label product use of nonapproved status epilepticus treatments; these are part of general treatment algorithms. Dr. Amengual-Gual was funded by “Fundación Alfonso Martín Escudero” and she disclosed work for hire. Dr. Sánchez Fernández is funded by the Epilepsy Research Fund and was funded by Fundación Alfonso Martín Escudero and the Human Herpes Virus 6 (HHV-6) Foundation. Dr. Brenton has served as a consultant for Novartis. Dr. Chapman disclosed that he received grant funding to support enrollment of patients via different funding mechanisms over the years. Drs. Gaillard’s and Morgans’s institution received funding from Pediatric Epilepsy Research Foundation. Drs. Glauser’s and Piantino’s institutions received funding from Boston Children’s Hospital. Dr. Glauser received funding from Supernus, Neurelis, Eisai, UCB Pharma, Myriad Genetics, and WedMD; he received support for article research from the National Institutes of Health (NIH); and he disclosed off-label product use of an anticonvulsant in status epilepticus. Dr. Goodkin received funding from UptoDate, Elsevier, and NIH grant support. Dr. Novotny is on the professional advisory board of the Epilepsy Foundation of America. Dr. Riviello is a consultant with Biomarin, and Early Neuronal ceroid lipofuscinosis 2 (CLN2) Signs North American Advisory Board, and he disclosed off-label product use of seizure medications. His spouse is an editor for Uptodate. Dr. Tchapyjnikov receives research funding from Children’s Miracle Network Hospitals and has previously received consultation fees from Gerson Lehrman Group, Guidepoint, IQVIA, and bioStrategies Group. Dr. Wainwright is a member of Clinical Advisory Board Sage Therapeutics. Dr. Wilfong’s institution received funding from Zogenix, Marinus, and OVID, and he received funding from UptoDate, Medtronic (data and safety monitoring board member of Stereotactic Laser Ablation for Temporal Lobe Epilepsy national trial), LivaNova, UCB, and Greenwich. Dr. Loddenkemper serves on the Council of the American Clinical Neurophysiology Society, as founder and consortium principal investigator (PI) of the pediatric status epilepticus research group, as an Associate Editor for Wyllie’s Treatment of Epilepsy 6th edition and 7th editions (Elsevier), and as a member of the New Onset Refractory Status Epilepsy Institute and Critical Care EEG Monitoring Research Consortium, and is coinventor of the TriVox Health technology. He served as an Associate Editor of Seizure (Elsevier) and served on the Laboratory Accreditation Board for Long Term (Epilepsy and Intensive Care Unit) Monitoring, and American Board of Clinical Neurophysiology in the past. He is part of patent applications to detect and predict clinical outcomes, and to detect, manage, diagnose, and treat neurological conditions, epilepsy, and seizures. Dr. Loddenkemper and Boston Children’s Hospital might receive financial benefits from this technology in the form of compensation in the future. He received research support from the Epilepsy Research Fund, NIH, Center for Integration of Medicine & Innovative Technolody/Department of Defense, Patient-Centered Outcomes Research Institute, the Epilepsy Foundation of America, the American Epilepsy Society, the Epilepsy Therapy Project, the Pediatric Epilepsy Research Foundation, the Danny Did Foundation, Cure, and the HHV6 Foundation, and received research grants from Lundbeck, Eisai, Upsher-Smith, Mallinckrodt, Sunovion, Sage, Empatica, Acorda, and Pfizer, including past device donations from various companies, including Empatica, SmartWatch, and Neuro-electrics. In the past, he served as a consultant for Eisai, Lundbeck, UCB, Amzell, Sunovion, Upsher Smith, and Zogenix. He performs video electroencephalogram long-term and ICU monitoring, electroencephalograms, and other electrophysiological studies at Boston Children’s Hospital and affiliated hospitals and bills for these procedures and he evaluates pediatric neurology patients and bills for clinical care. He has received speaker honorariums/Grand Round travel support from national/international societies and national/international academic centers. Some of Dr. Loddenkemper’s trainees received salary support from international foundations/societies and academic centers while working in his laboratory. His wife, Dr. Stannard, is a pediatric neurologist and she performs video electroencephalogram long-term and ICU monitoring, electroencephalograms, and other electrophysiological studies and bills for these procedures, and she evaluates pediatric neurology patients and bills for clinical care. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objective: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE)., Methods: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ASM., Results: We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997-.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73-3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40-6.03, p < .0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01-2.06, p = .04). Forty-seven percent of patients (n = 94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival., Significance: Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Medical care has become more complex as the scientific method has expanded medical knowledge. Medicine is also now practiced across different medical systems of varying complexity, and creating standard treatment guidelines is one way of establishing uniform treatment across these systems. The creation of guidelines ensures the delivery of quality medical care and improved patient outcomes. Evidence-based medicine is the application of scientific research to produce these treatment guidelines. This article shall focus on the current treatment guidelines used for inpatient pediatric neurology., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Neonatal cerebral sinus venous thrombosis (CSVT) causes high morbidity and mortality. Factors associated with either favorable or unfavorable long-term outcomes have not been clearly established. This study aimed to determine the factors involved in long-term neurological outcomes in patients with neonatal CSVT., Methods: This was a retrospective cohort study of patients with neonatal CSVT at a single institution. Clinical factors associated with long-term neurological outcomes were examined., Results: A total of 67 patients met study inclusion criteria for radiologically confirmed neonatal CSVT. The mean patient follow-up duration was four years (range one week to 16 years, median six years). We observed a favorable neurological outcome defined by a pediatric stroke outcome measures (PSOM) score of 0 to 0.5 in 26 (53%) of osurviving patients at follow-up. An unfavorable neurological outcome as defined by PSOM score >0.5 was observed in 23 survivors (47%). Death was reported in 18 (27%) patients, of which 10 patients died due to direct complications of CSVT. Congential heart disease and genetic disease were associated with significantly increased odds for all-cause death. Cardiorespiratory failure and altered mental status during the initial neurological examination were significantly associated with increased odds of death due to CSVT. Among surviving patients, higher PSOM scores were associated with premature birth (i.e., gestational age < 37 weeks), traumatic birth, site of thrombosis in the straight sinus, site of thrombosis in the internal cerebral veins, and hemorrhagic infarct. In contrast, lower PSOM scores were associated with a normal neurological examination at presentation, thrombosis in only superficial sinuses, and hemorrhage without infarct. There was no statistically significant association between the type and duration of CSVT treatment., Conclusions: The major factors influencing outcome of neonates following CSVT included comorbid medical conditions, abnormal neurological examination at presentation, location of venous thrombosis, and type of cerebral injury. These results can help guide further studies in neonatal CSVT aiming to decrease morbidity and mortality with the goal of improving long-term neurological outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The goal of neurocritical care (NCC) is to improve the outcome of patients with neurologic insults. NCC includes the management of the primary brain injury and prevention of secondary brain injury; this is achieved with standardized clinical care for specific disorders along with neuromonitoring. Neuromonitoring uses multiple modalities, with certain modalities better suited to certain disorders. The term "multimodality monitoring" refers to using multiple modalities at the same time. This article reviews pediatric NCC, the various physiologic parameters used, especially continuous electroencephalographic monitoring., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Hypothalamic hamartoma is rarely associated with epileptic spasms. We describe epileptic spasms in a large cohort of hypothalamic hamartoma patients., Methods: We performed a retrospective chart review between March 2011 and March 2020 to identify patients with hypothalamic hamartoma and epilepsy., Results: We identified 114 patients with hypothalamic hamartoma and epilepsy, only 3 male patients (2.6%) also had epileptic spasms. The epileptic spasms developed between 6 and 18 months of age. Epileptic spasms resolved with oral prednisolone in 1 and with vigabatrin in the second patient. The third patient continued epileptic spasms despite multiple antiepileptic drugs and partial resection of hypothalamic hamartoma. All 3 patients underwent laser-ablation of hypothalamic hamartoma at the age of 14, 29, and 63 months. The seizure burden decreased by 100%, 84%, and 93% at follow-up (3-47 months)., Conclusions: Epileptic spasms are rare in hypothalamic hamartoma patients and early laser-ablation could potentially treat epileptic spasms and all other seizure types associated with hypothalamic hamartoma.

Febrile infection-related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL-1 receptor antagonist that blocks biologic activity of IL-1β) are recommended., Competing Interests: Sookyong Koh applied and received unrestricted educational grant from Sobi to hold FIRES Workshops. 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., (© 2020 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

SV2A encodes a neuronal synaptic vesicle glycoprotein essential for neurotransmitter release. Altered SV2A function leads to epilepsy in animal models, yet only two reports of human variants have linked SV2A to syndromic drug-resistant epileptic encephalopathies and epilepsy. SV2A is also the binding site for the commonly used antiseizure medication levetiracetam (LEV). However, information about how rare SV2A variants influence LEV response is lacking. Here, we report a two-year-old child with new-onset epilepsy found to have a de novo heterozygous rare variant in SV2A (NM&#95;014849.5:c.1978G>A;p.Gly660Arg) who developed refractory status epilepticus after escalation of LEV treatment for initial baseline seizure control. This report provides additional evidence that monoallelic pathogenic SV2A variants cause epilepsy and that genetic variation in SV2A could lead to paradoxical seizure worsening when treated with LEV., (© 2021 The Author(s).)

Objective: To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation., Methods: This was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation., Results: We included 289 patients (55.7% male) with a median age of 4.3 (1.3-9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18-3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05-1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23-3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24-3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57-0.95)., Conclusion: BZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation., Classification of Evidence: This study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation., (© 2020 American Academy of Neurology.)

Purpose: To evaluate whether the onset of pediatric refractory status epilepticus (rSE) is related to time of day., Method: We analyzed the time of day for the onset of rSE in this prospective observational study performed from June 2011 to May 2019 in pediatric patients (1 month to 21 years of age). We evaluated the temporal distribution of pediatric rSE utilizing a cosinor analysis. We calculated the midline estimating statistic of rhythm (MESOR) and amplitude. MESOR is the estimated mean number of rSE episodes per hour if they were evenly distributed. Amplitude is the difference between MESOR and maximum rSE episodes/hour, or between MESOR and minimum rSE episodes/hour. We also evaluated the temporal distribution of time to treatment., Results: We analyzed 368 patients (58% males) with a median (p 25 - p 75 ) age of 4.2 (1.3-9.7) years. The MESOR was 15.3 (95% CI: 13.9-16.8) and the amplitude was 3.2 (95% CI: 1.1-5.3), p = 0.0024, demonstrating that the distribution is not uniform, but better described as varying throughout the day with a peak in the morning (11am-12 pm) and trough at night (11 pm-12 am). The duration from rSE onset to application of the first non-benzodiazepine antiseizure medication peaked during the early morning (2am-3 am) with a minimum during the afternoon (2 pm-3 pm) (p = 0.0179)., Conclusions: The distribution of rSE onset is not uniform during the day. rSE onset shows a 24-h distribution with a peak in the mid-morning (11am-12 pm) and a trough at night (11 pm-12am)., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Patients with medically refractory localization-related epilepsy (LRE) may be candidates for surgical intervention if the seizure onset zone (SOZ) can be well localized. Stereoelectroencephalography (SEEG) offers an attractive alternative to subdural grid and strip electrode implantation for seizure lateralization and localization; yet there are few series reporting the safety and efficacy of SEEG in pediatric patients., Methods: The authors review their initial 3-year consecutive experience with SEEG in pediatric patients with LRE. SEEG coverage, SOZ localization, complications, and preliminary seizure outcomes following subsequent surgical treatments are assessed., Results: Twenty-five pediatric patients underwent 30 SEEG implantations, with a total of 342 electrodes placed. Ten had prior resections or ablations. Seven had no MRI abnormalities, and 8 had multiple lesions on MRI. Based on preimplantation hypotheses, 7 investigations were extratemporal (ET), 1 was only temporal-limbic (TL), and 22 were combined ET/TL investigations. Fourteen patients underwent bilateral investigations. On average, patients were monitored for 8 days postimplant (range 3-19 days). Nearly all patients were discharged home on the day following electrode explantation. There were no major complications. Minor complications included 1 electrode deflection into the subdural space, resulting in a minor asymptomatic extraaxial hemorrhage; and 1 in-house and 1 delayed electrode superficial scalp infection, both treated with local wound care and oral antibiotics. SEEG localized the hypothetical SOZ in 23 of 25 patients (92%). To date, 18 patients have undergone definitive surgical intervention. In 2 patients, SEEG localized the SOZ near eloquent cortex and subdural grids were used to further delineate the seizure focus relative to mapped motor function just prior to resection. At last follow-up (average 21 months), 8 of 15 patients with at least 6 months of follow-up (53%) were Engel class I, and an additional 6 patients (40%) were Engel class II or III. Only 1 patient was Engel class IV., Conclusions: SEEG is a safe and effective technique for invasive SOZ localization in medically refractory LRE in the pediatric population. SEEG permits bilateral and multilobar investigations while avoiding large craniotomies. It is conducive to deep, 3D, and perilesional investigations, particularly in cases of prior resections. Patients who are not found to have focally localizable seizures are spared craniotomies.

Objective: The purpose of this study is to describe the pharmacokinetics of phenytoin in pediatric patients receiving fosphenytoin., Design: Retrospective, population pharmacokinetic analysis., Setting: Emergency department or PICU of a large tertiary care children's hospital., Patients: Patients less than 19 years old who received fosphenytoin in the PICU or emergency center for treatment of seizures from January 2011 to June 2017 were included., Interventions: Population pharmacokinetic analysis was performed with NONMEM v7.3 (Icon Plc, Dublin, Ireland). Simulation was performed to determine optimal loading dose and maintenance dosing regimens., Measurements and Main Results: A total of 536 patients (55.4% male; median age, 3.4 yr [interquartile range, 0.92-8.5 yr]) met study criteria. Fosphenytoin was administered at median 15.1 mg/kg/dose (interquartile range, 6.3-20.7 mg/kg/dose). Mean serum concentrations of 17.5 ± 7.8 mg/L were at a median 4.2 hours (interquartile range, 2.5-7.8 hr) after a dose. A pharmacokinetic model with two compartments, allometrically scaled fat-free mass on all parameters, and serum creatinine and concomitant phenobarbital use on clearance had the best fit. Simulation demonstrated that a 20 mg/kg loading dose followed by 6 mg/kg/dose every 8 hours had the greatest percentage of concentrations in the 10-20 mg/L range, with reduced doses to achieve therapeutic in patients with reduced kidney function., Conclusions: A loading dose of 20 mg/kg followed by 6 mg/kg/dose every 8 hours based on fat-free mass is a reasonable empiric strategy for attainment and maintenance of therapeutic trough concentrations. Concomitant phenobarbital use may increase clearance of phenytoin and fosphenytoin dose reductions should occur in patients with reduced kidney function.

Objective: Phenobarbital is frequently used in pediatric patients for treatment and prophylaxis of seizures. Pharmacokinetic data for this patient population is lacking and would assist in dosing decisions., Methods: A retrospective population pharmacokinetic analysis was designed for all pediatric patients <19 years of age initiated on phenobarbital at our institution from January 2011 to June 2017. Patients were included if they were initiated on intravenous or enteral phenobarbital for treatment or prophylaxis of seizures and had a serum phenobarbital concentration monitored while an inpatient. Data collection included the following: age, weight, height, gestational age, core body temperature, serum creatinine, blood urea nitrogen, aspartase aminotransferase, alanine aminotransferase, urine output over the prior 12 hours, phenobarbital doses and serum concentrations, and potential drug-drug interactions. Descriptive statistical methods were used to summarize the data. Pharmacokinetic analysis was performed with NONMEM and simulation was performed for doses of 10, 20, 30, and 40 mg kg -1  dose -1 , iv, followed by enteral doses of 3, 4, 5, and 6 mg kg -1  d -1 ., Results: A total of 355 patients (50.3% male, median gestational age 39 weeks (interquartile range [IQR] 35, 40), median age 0.28 years (IQR 0.06, 0.82). Median phenobarbital dose was enteral = 2.6 (IQR 1.9, 3.9) mg kg -1  dose -1 ; intravenous = 2.6 (IQR 2.2, 4.9) mg kg -1  dose -1 ) and mean serum concentration was 41.1 ± 23.9 mg/L at median 6.5 (IQR 2.9, 11.1) hours after a dose. A one-compartment proportional error model best fit the data where clearance and volume of distribution were allometrically scaled using fat-free mass. Significant covariates included serum creatinine, postmenstrual age, and drug-drug interactions on clearance, and age in years on volume of distribution., Significance: Phenobarbital dosing of 30 mg kg -1  dose -1 ,iv, followed by 4 mg kg -1  d -1 had the highest probability of attaining a therapeutic concentration at 7 days. Postmenstrual age and drug-drug interactions should be incorporated into dosing decisions., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objective: We report a case series of 10 patients with γ-aminobutyric acid (GABA)-transaminase deficiency including a novel therapeutic trial and an expanded phenotype., Methods: Case ascertainment, literature review, comprehensive evaluations, and long-term treatment with flumazenil., Results: All patients presented with neonatal or early infantile-onset encephalopathy; other features were hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth. EEGs showed burst-suppression, modified hypsarrhythmia, multifocal spikes, and generalized spike-wave. Five of the 10 patients are currently alive with age at last follow-up between 18 months and 9.5 years. Treatment with continuous flumazenil was implemented in 2 patients. One patient, with a milder phenotype, began treatment at age 21 months and has continued for 20 months with improved alertness and less excessive adventitious movements. The second patient had a more severe phenotype and was 7 years of age at initiation of flumazenil, which was not continued., Conclusions: GABA-transaminase deficiency presents with neonatal or infantile-onset encephalopathy including hypersomnolence and choreoathetosis. A widened phenotypic spectrum is reported as opposed to lethality by 2 years of age. The GABA-A benzodiazepine receptor antagonist flumazenil may represent a therapeutic strategy., (© 2017 American Academy of Neurology.)

Ongoing investigation from the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) study hopes to examine the long-term effect on cognitive and language development of a single anesthetic exposure in children undergoing inguinal hernia repair. The fifth PANDA Symposium, held in April 2016, continued the mission of previous symposia to examine evidence from basic science and clinical studies on potential neurotoxic effects of anesthetics on developing brain. At the 2016 Symposium, a panel of specialists from nonsurgical pediatric disciplines including anesthesiology, radiology, neurology, gastroenterology, oncology, cardiology, and critical care reviewed use of anesthesia in their practices, including how concern over possible neurodevelopmental effects of early childhood anesthetic exposure has changed discussion with patients and families regarding risks and benefits of imaging studies and interventional procedures involving sedation or anesthesia. This paper summarizes presentations from nonsurgical pediatric specialists at the 2016 PANDA Symposium.

The important question that often emerges in the clinic is how aggressive the therapy for nonconvulsive status epilepticus and electrical status epilepticus in sleep ought to be and how continuous the discharges in each of these 2 entities should be before therapy is aimed at them. Additionally, as the use of electroencephalographic monitoring continues to expand to include the clinic and intensive care unit populations, it is important to identify epileptiform patterns that warrant identification and treatment. This review will present the state-of-the-art data and suggest algorithms to manage these conditions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Patients with prolonged or rapidly recurring convulsions lasting more than 5 min are in status epilepticus (SE) and require immediate resuscitation. Although there are relatively few randomized clinical trials, available evidence and experience suggest that early and aggressive treatment of SE improves patient outcomes, for which reason this was chosen as an Emergency Neurological Life Support protocol. The current approach to the emergency treatment of SE emphasizes rapid initiation of adequate doses of first-line therapy, as well as accelerated second-line anticonvulsant drugs and induced coma when these fail, coupled with admission to a unit capable of neurological critical care and electroencephalography monitoring. This protocol will focus on the initial treatment of SE but also review subsequent steps in the protocol once the patient is hospitalized.

Introduction: Critical Care Continuous EEG (CCEEG) is a common procedure to monitor brain function in patients with altered mental status in intensive care units. There is significant variability in patient populations undergoing CCEEG and in technical specifications for CCEEG performance., Methods: The Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society developed expert consensus recommendations on the use of CCEEG in critically ill adults and children., Recommendations: The consensus panel recommends CCEEG for diagnosis of nonconvulsive seizures, nonconvulsive status epilepticus, and other paroxysmal events, and for assessment of the efficacy of therapy for seizures and status epilepticus. The consensus panel suggests CCEEG for identification of ischemia in patients at high risk for cerebral ischemia; for assessment of level of consciousness in patients receiving intravenous sedation or pharmacologically induced coma; and for prognostication in patients after cardiac arrest. For each indication, the consensus panel describes the patient populations for which CCEEG is indicated, evidence supporting use of CCEEG, utility of video and quantitative EEG trends, suggested timing and duration of CCEEG, and suggested frequency of review and interpretation., Conclusion: CCEEG has an important role in detection of secondary injuries such as seizures and ischemia in critically ill adults and children with altered mental status.

Introduction: Critical Care Continuous EEG (CCEEG) is a common procedure to monitor brain function in patients with altered mental status in intensive care units. There is significant variability in patient populations undergoing CCEEG and in technical specifications for CCEEG performance., Methods: The Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society developed expert consensus recommendations on the use of CCEEG in critically ill adults and children., Recommendations: The consensus panel describes the qualifications and responsibilities of CCEEG personnel including neurodiagnostic technologists and interpreting physicians. The panel outlines required equipment for CCEEG, including electrodes, EEG machine and amplifier specifications, equipment for polygraphic data acquisition, EEG and video review machines, central monitoring equipment, and network, remote access, and data storage equipment. The consensus panel also describes how CCEEG should be acquired, reviewed and interpreted. The panel suggests methods for patient selection and triage; initiation of CCEEG; daily maintenance of CCEEG; electrode removal and infection control; quantitative EEG techniques; EEG and behavioral monitoring by non-physician personnel; review, interpretation, and reports; and data storage protocols., Conclusion: Recommended qualifications for CCEEG personnel and CCEEG technical specifications will facilitate standardization of this emerging technology.

Background: Intracarotid amobarbital procedure (IAP) is acknowledged as the gold standard test for language lateralization. EEG is performed routinely during IAP to monitor the anesthetization of a brain hemisphere. Here, we studied the correlation between the early EEG changes using envelope trend and the clinical outcome of IAP., Method: Fifty consecutive patients underwent IAP at Texas Children's Hospital (2004-2009). Intracarotid amobarbital procedure was considered "complete" or "incomplete" based on the outcome if the procedure was completed or aborted due to behavior changes. Envelope trend was used to calculate the median EEG amplitude changes within the first 60s of IAP. Statistical analysis was performed to determine the role of EEG changes and clinical features on the procedure outcome., Results: Only 30 IAP-EEG files were available for review. Amobarbital was administered at the dose of 60-150mg (mean: 110±20). The intracarotid amobarbital procedure was recorded as complete in 23 patients and incomplete in 7 patients. EEG changes occurred within the first few seconds following amobarbital injection. Following amobarbital injection, focal slowing was present in the ipsilateral frontal region or both ipsilateral and contralateral frontal regions. Elapsed time to the first EEG change or duration and change in median EEG amplitude in the ipsilateral frontal regions were indifferent between the complete and incomplete groups (p>0.05). However, the median amplitude changes between the ipsilateral and contralateral frontal regions within each group were found significant only in the complete group (p<0.05), suggesting ipsilateral without contralateral frontal slowing. Other than age at the time of IAP (p=0.03), none of the other clinical features correlated with the clinical outcome of IAP (p>0.05)., Conclusion: Early EEG changes during IAP using envelope trend may predict successful completion of the IAP test. Younger children are at risk of behavioral changes during IAP., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Pediatric neurocritical care (NCC) has emerged as a defined subspecialty in child neurology and requires a collaborative effort among child neurologists, pediatric critical care medicine specialists, and pediatric neurosurgeons. Pediatric NCC has evolved differently in children than in adults, and its delivery depends on the local resources available for pediatric care. This article reviews the current practice of pediatric NCC by child neurologists: where it is practiced, how it is practiced, the disorders encountered (that differ from adult NCC), the training required to care for these disorders, and what is needed for the future of pediatric NCC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study aimed to identify the indications in which electroencephalography in the pediatric emergency department is most useful. We retrospectively reviewed the influence that the results of the emergent electroencephalogram had on the eventual disposition of patients at our pediatric emergency department. Sixty-eight children (mean age, 7.3 years; 32 males) underwent 70 emergent electroencephalograms. Fifty-seven emergent electroencephalograms were performed for the suspicion of ongoing seizures or status epilepticus. Thirteen of the 22 children (59.1%) discharged from the emergency department were sent home mainly based on the results of the emergent electroencephalogram, which prevented an admission. In particular, 11 of 38 children with frequent and recurrent paroxysmal events concerning for seizures and 2 of 19 children with suspected ongoing status epilepticus were discharged after excluding an epileptic disturbance. The emergent electroencephalogram provided meaningful clinical information that influenced disposition, especially in patients with ongoing events in which the clinical picture was clarified by a rapidly acquired electroencephalogram.

Purpose: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG)., Methods: A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network., Results: The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome., Conclusion: The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Generalized periodic epileptiform discharges (GPDs) are a specific periodic EEG pattern, reported as having a poor clinical outcome. The incidence and clinical implications of this EEG pattern in children are not known. In this study, we examined the clinical features of children with GPDs., Methods: EEG-video monitoring reports of children with critical illness in the intensive care unit were retrospectively reviewed to detect GPDs. The clinical history, hospital course and seizure characteristics were reviewed and outcome was based on the clinical findings at hospital discharge., Results: Twenty one children (age 2-18 years) were identified with GPDs. The most common underlying etiology was encephalitis (N=11). At the time of EEG, a continuous intravenous infusion (cIV) of an anticonvulsant drug was used to treat refractory status epilepticus (RSE). Non-convulsive seizures (NCS) were identified in 15, and clinical seizures in 13 children after GPDs were detected. GPDs occurred after a dose reduction in the cIV in 43%. Neuroimaging done in 16 children showed an acute change in 13/16 (81%) and chronic changes in 2/16 (13%). Five children (23%) died. Seven (33%) children had a favorable outcome, whereas the remaining children had a moderate to severe disability at the time of hospital discharge., Conclusion: GPDs are seen during the course of RSE in critically ill children and are associated with seizure recurrence. A lower mortality rate occurs in children with GPDs compared to adult counterparts, likely related to different etiologies. Although the significance of GPDs must be determined within the context of the clinical situation, GPDs suggest a still active epileptic process., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: To describe current continuous EEG monitoring (cEEG) utilization in critically ill children., Methods: An online survey of pediatric neurologists from 50 US and 11 Canadian institutions was conducted in August 2011., Results: Responses were received from 58 of 61 (95%) surveyed institutions. Common cEEG indications are altered mental status after a seizure or status epilepticus (97%), altered mental status of unknown etiology (88%), or altered mental status with an acute primary neurologic condition (88%). The median number of patients undergoing cEEG per month per center increased from August 2010 to August 2011 (6 to 10 per month in the United States; 2 to 3 per month in Canada). Few institutions have clinical pathways addressing cEEG use (31%). Physicians most commonly review cEEG twice per day (37%). There is variability regarding which services can order cEEG, the degree of neurology involvement, technologist availability, and whether technologists perform cEEG screening., Conclusions: Among the surveyed institutions, which included primarily large academic centers, cEEG use in pediatric intensive care units is increasing and is often considered indicated for children with altered mental status at risk for nonconvulsive seizures. However, there remains substantial variability in cEEG access and utilization among institutions.