Understanding lived experiences with KCNQ2 developmental and epileptic encephalopathy.

Background: KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE) is a rare pediatric disorder characterized by seizures and neurodevelopmental impairments. Parent- and healthcare professional (HCP)-reported outcomes regarding the impacts of seizures and neurodevelopmental impairments may guide the design of clinically meaningful KCNQ2-DEE outcome measures.

Methods: Parents of children with KCNQ2-DEE (N = 53) and HCPs with KCNQ2-DEE expertise (N = 2) participated in qualitative interviews exploring signs, symptoms, and impacts of KCNQ2-DEE, and how varying KCNQ2-DEE phenotypes affect child development.

Postneonatal epilepsy after acute provoked neonatal seizures: Incidence, predictors, and clinical burden in a multicenter cohort followed through early childhood.

Objective: Epilepsy is a known potential outcome following acute provoked neonatal seizures, but its onset, treatment patterns, and health care utilization through childhood remain poorly characterized. This study aimed to define the incidence and timing of postneonatal epilepsy, identify perinatal predictors, and describe the clinical burden of epilepsy among survivors of acute provoked neonatal seizures through early childhood.

Methods: This prospective, multicenter cohort study followed neonates with acute provoked seizures from the Neonatal Seizure Registry (NSR-II) in an extended follow-up through early childhood (Developmental Functional Evaluation).

Parent and Family Well-Being and Associated Risk Factors as Children with Neonatal Seizures Reach Preschool and School-Age: A Longitudinal Cohort Study.

Objective: To assess parent/family well-being when children with neonatal seizures reach 3-8 years of age and examine factors associated with parent/family well-being.

Methods: One parent per surviving infant in the Neonatal Seizure Registry-II was invited to complete validated surveys annually when children were between 3 and 8 years of age. Three outcomes were examined: (1) parent well-being (anxiety, depression, and quality of life); (2) parent post-traumatic stress symptoms; and (3) impact on the family.

Payer type and prediction of the time from epilepsy onset to neurosurgical intervention and from first diagnostic MRI to neurosurgical consultation in lesional drug-resistant epilepsy at a California level IV epilepsy center.

Objective: The aim of this study was to identify socioeconomic factors that underlie disparity by insurance type on time to surgery from epilepsy onset and from first diagnostic imaging identifying a structural lesion in children with drug-resistant epilepsy (DRE).

Methods: Retrospective data were abstracted from children (< 18 years) who underwent epilepsy surgery at the University of California, San Francisco (UCSF), between 2012 and 2022 with a diagnosis of DRE and structural abnormality on MRI. Univariable and multivariable Cox proportional hazard regression were used to assess associations between socioeconomic barriers (English-language speaking, ethnicity, race, single-parent household, number of parents working, number of siblings, receipt of Supplemental Security Income [SSI], distance from hospital, and practice setting of referral center) and time from epilepsy onset to surgery.

Treatment efficacy for infantile epileptic spasms syndrome in children with trisomy 21.

Background: Infantile Epileptic Spasms Syndrome (IESS) is the most common epilepsy syndrome in children with trisomy 21. First-line standard treatments for IESS include adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin. Among children with trisomy 21 and IESS, treatment with ACTH or oral corticosteroids may yield higher response rates compared with vigabatrin.

Preferred Parental Language and Neurodevelopmental Outcomes Among Infants With Acute Provoked Neonatal Seizures in the United States.

Background: Parental non-English language preference (NELP) is associated with worse pediatric health outcomes. However, little is known about its relationship with developmental outcomes in infants with neonatal seizures. This study evaluated the relationship between parental NELP and neurodevelopment in a multicenter cohort of infants with neonatal seizures.

The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates.

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.

WONOEP appraisal: Targeted therapy development for early onset epilepsies.

The early onset epilepsies encompass a heterogeneous group of disorders, some of which result in drug-resistant seizures, developmental delay, psychiatric comorbidities, and sudden death. Advancement in the widespread use of targeted gene panels as well as genome and exome sequencing has facilitated the identification of different causative genes in a subset of these patients. The ability to recognize the genetic basis of early onset epilepsies continues to improve, with de novo coding variants accounting for most of the genetic etiologies identified.

Assessing Early Severity of Hypoxic-Ischemic Encephalopathy: The Role of Electroencephalogram Background in Addition to Sarnat Exam.

Objective: To assess the relationship between the Sarnat exam, early electroencephalogram (EEG) background, and death or neurodevelopmental impairment (NDI) at age 2 years among neonates with moderate to severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

Study Design: Neonates enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy trial with EEG (n = 463) or amplitude-integrated electroencephalogram (n = 15) reports available on the first day after birth were included in this cohort study. A Sarnat exam was performed between 1 and 6 hours after birth, and neonates were classified into 3 groups of increasing severity based on the number of severe features (none, 1-2, or 3+).

Neonatal Seizures: New Evidence, Classification, and Guidelines.

Neonates are susceptible to seizures due to their unique physiology and combination of risks associated with gestation, delivery, and the immediate postnatal period. Advances in neonatal care have improved outcomes for some of our most fragile patients, but there are persistent challenges for epileptologists in identifying neonatal seizures, diagnosing etiologies, and providing the most appropriate care, with an ultimate goal to maximize patient outcomes. In just the last few years, there have been critical advances in the state of the science, as well as new evidence-based guidelines for diagnosis, classification, and treatment of neonatal seizures.

Expert opinion on use of vagus nerve stimulation therapy in the management of pediatric epilepsy: A Delphi consensus study.

Purpose: To provide consensus-based recommendations for use of vagus nerve stimulation (VNS) therapy in the management of pediatric epilepsy.

Methods: Delphi methodology with two rounds of online survey was used to build consensus. A steering committee developed 43 statements related to pediatric epilepsy and the use of VNS therapy, which were evaluated by a panel of 12 neurologists/neurosurgeons with expertise in pediatric epilepsy, who graded their agreement with each statement on a scale of 1 ("I do not agree at all") to 5 ("I strongly agree").

Machine learning for forecasting initial seizure onset in neonatal hypoxic-ischemic encephalopathy.

Objective: This study was undertaken to develop a machine learning (ML) model to forecast initial seizure onset in neonatal hypoxic-ischemic encephalopathy (HIE) utilizing clinical and quantitative electroencephalogram (QEEG) features.

Methods: We developed a gradient boosting ML model (Neo-GB) that utilizes clinical features and QEEG to forecast time-dependent seizure risk. Clinical variables included cord blood gas values, Apgar scores, gestational age at birth, postmenstrual age (PMA), postnatal age, and birth weight.

Simulation-based Inference of Developmental EEG Maturation with the Spectral Graph Model.

The spectral content of macroscopic neural activity evolves throughout development, yet how this maturation relates to underlying brain network formation and dynamics remains unknown. Here, we assess the developmental maturation of electroencephalogram spectra via Bayesian model inversion of the spectral graph model, a parsimonious whole-brain model of spatiospectral neural activity derived from linearized neural field models coupled by the structural connectome. Simulation-based inference was used to estimate age-varying spectral graph model parameter posterior distributions from electroencephalogram spectra spanning the developmental period.

Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication.

Objective: To assess among a cohort of neonates with hypoxic-ischemic encephalopathy (HIE) the association of pretreatment maximal hourly seizure burden and total seizure duration with successful response to initial antiseizure medication (ASM).

Study Design: This was a retrospective review of data collected from infants enrolled in the HEAL Trial (NCT02811263) between January 25, 2017, and October 9, 2019. We evaluated a cohort of neonates born at ≥36 weeks of gestation with moderate-to-severe HIE who underwent continuous electroencephalogram monitoring and had acute symptomatic seizures.

Simulation-based inference of developmental EEG maturation with the spectral graph model.

The spectral content of macroscopic neural activity evolves throughout development, yet how this maturation relates to underlying brain network formation and dynamics remains unknown. Here, we assess the developmental maturation of electroencephalogram spectra via Bayesian model inversion of the spectral graph model, a parsimonious whole-brain model of spatiospectral neural activity derived from linearized neural field models coupled by the structural connectome. Simulation-based inference was used to estimate age-varying spectral graph model parameter posterior distributions from electroencephalogram spectra spanning the developmental period.

A quantitative EEG index for the recognition of arterial ischemic stroke in children.

Objective: To describe and assess performance of the Correlate Of Injury to the Nervous system (COIN) index, a quantitative electroencephalography (EEG) metric designed to identify areas of cerebral dysfunction concerning for stroke.

Methods: Case-control study comparing continuous EEG data from children with acute ischemic stroke to children without stroke, with or without encephalopathy. COIN is calculated continuously and compares EEG power between cerebral hemispheres.

Association of EEG Background and Neurodevelopmental Outcome in Neonates With Hypoxic-Ischemic Encephalopathy Receiving Hypothermia.

Background And Objectives: Predicting neurodevelopmental outcome for neonates with hypoxic-ischemic encephalopathy (HIE) is important for clinical decision-making, care planning, and parent communication. We examined the relationship between EEG background and neurodevelopmental outcome among children enrolled in a trial of erythropoietin or placebo for neonates with HIE treated with therapeutic hypothermia.

Methods: Participants had EEG recorded throughout hypothermia.

Association of High-Dose Erythropoietin With Circulating Biomarkers and Neurodevelopmental Outcomes Among Neonates With Hypoxic Ischemic Encephalopathy: A Secondary Analysis of the HEAL Randomized Clinical Trial.

Importance: The ability to predict neurodevelopmental impairment (NDI) for infants diagnosed with hypoxic ischemic encephalopathy (HIE) is important for parental guidance and clinical treatment as well as for stratification of patients for future neurotherapeutic studies.

Objectives: To examine the effect of erythropoietin on plasma inflammatory mediators in infants with moderate or severe HIE and to develop a panel of circulating biomarkers that improves the projection of 2-year NDI over and above the clinical data available at the time of birth.

Design, Setting, And Participants: This study is a preplanned secondary analysis of prospectively collected data from infants enrolled in the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, which tested the efficacy of erythropoietin as an adjunctive neuroprotective therapy to therapeutic hypothermia.

The "Canopy Approach": Case Series Using Immersive Virtual Reality for Bottom-Up Target-Based Preoperative Planning in Pediatric Neurosurgery.

Background: Virtual reality (VR) is increasingly used for trajectory planning in neurosurgery.

Objective: To describe a case series showing the application of immersive VR involving both "top-down" from skull to lesion and "bottom-up" from lesion to skull approaches for trajectory planning in pediatric neurosurgical patients.

Methods: We detail the preoperative and intraoperative application of VR and clinical courses of 5 children (aged 7-14 years) with anatomically challenging intraparenchymal lesions that posed operative risks to nearby vascular anatomy and fiber tracts.

Risk of seizures in neonates with hypoxic-ischemic encephalopathy receiving hypothermia plus erythropoietin or placebo.

Background: An ancillary study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia examined the hypothesis that neonates randomized to receive erythropoietin (Epo) would have a lower seizure risk and burden compared with neonates who received placebo.

Methods: Electroencephalograms (EEGs) from 7/17 HEAL trial centers were reviewed. Seizure presence was compared across treatment groups using a logistic regression model adjusting for treatment, HIE severity, center, and seizure burden prior to the first dose.

Inequities in Therapy for Infantile Spasms: A Call to Action.

Objective: The aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity.

Methods: The prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression.

Disorders of Neuronal Migration/Organization Convey the Highest Risk of Neonatal Onset Epilepsy Compared With Other Congenital Brain Malformations.

Background: Although seizures in neonates are common and often due to acute brain injury, 10-15% are unprovoked from congenital brain malformations. A better understanding of the risk of neonatal-onset epilepsy by the type of brain malformation is essential for counseling and monitoring.

Methods: In this retrospective cohort study, we evaluated 132 neonates with congenital brain malformations and their risk of neonatal-onset epilepsy.