A5036362648- Epilepsy research and treatment
- Pharmacological Effects and Toxicity Studies
- Neuroscience and Neuropharmacology Research
- Neonatal and fetal brain pathology
- Metabolism and Genetic Disorders
- Genetics and Neurodevelopmental Disorders
- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Genomics and Rare Diseases
- Cerebral Palsy and Movement Disorders
- Mitochondrial Function and Pathology
- EEG and Brain-Computer Interfaces
- Cardiac electrophysiology and arrhythmias
- Neurological disorders and treatments
- Biotin and Related Studies
- Neurogenetic and Muscular Disorders Research
- Diet and metabolism studies
- Pharmaceutical studies and practices
- Drug Transport and Resistance Mechanisms
- Genomic variations and chromosomal abnormalities
- Infectious Encephalopathies and Encephalitis
- ATP Synthase and ATPases Research
- Cerebrospinal fluid and hydrocephalus
- Memory and Neural Mechanisms
- Hemoglobinopathies and Related Disorders
Duke University
2016-2025
Duke University Hospital
2015-2024
Duke Medical Center
2015-2024
Children's Hospital of Philadelphia
2015-2023
University of Pennsylvania
2015-2023
University of Cincinnati Medical Center
2015-2023
Cincinnati Children's Hospital Medical Center
2015-2023
Duke University Health System
2017-2022
Boston Children's Hospital
1998-2021
Harvard University
1993-2021
We report 2 patients with drug‐resistant epilepsy caused by KCNT1 mutations who were treated quinidine. Both manifested gain of function in vitro, showing increased current that was reduced One, had infancy migrating focal seizures, 80% reduction seizure frequency as recorded diaries, and partially validated objective evaluation on EEG. The other, a novel phenotype, severe nocturnal secondary generalized seizures starting early childhood developmental regression, did not improve. Although...
Treatment delay for seizures can lead to longer seizure duration. Whether treatment is associated with major adverse outcomes, such as death, remains unknown. To evaluate whether untimely first-line benzodiazepine unfavorable short-term outcomes. This multicenter, observational, prospective cohort study included 218 pediatric patients admitted between June 1, 2011, and July 7, 2016, into the 11 tertiary hospitals in United States within Pediatric Status Epilepticus Research Group. Patients,...
<b><i><i>Background:</i></i></b> Long-term antiepileptic drug (AED) use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described institutionalized patients. The objective is to determine the effect of AED on vitamin D levels density ambulatory patients compare effects enzyme-inducing -noninducing single vs therapy density. <b><i><i>Methods:</i></i></b> A cross-sectional evaluation was conducted 71 (42 adults 29 children/adolescents)...
Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of deletions, as well other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation 3812 patients a diverse spectrum syndromes 1299 neurologically-normal controls. Large deletions (> 100 kb) were observed 23 patients, whereas no control had deletion greater than 16 kb. Patients, even those...
Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which association-studies successfully revealed variants associated with disease risk, role of variation in partial has not yet been explored well-powered study. We undertook genome-wide association-study identify influence risk epilepsy shared amongst syndromes, 3445 patients and 6935 controls European ancestry. did any significant...
Mutations in the gene ATP1A3 have recently been identified to be prevalent patients with alternating hemiplegia of childhood (AHC2). Based on a large series AHC, we set out identify spectrum different mutations within and further establish any correlation phenotype. Clinical data from an international cohort 155 AHC (84 females, 71 males; between 3 months 52 years) were gathered using specifically formulated questionnaire analysed relative mutational for each patient. In total, 34 detected...
Abstract Cerebral palsy (CP) is a condition affecting young children that causes lifelong disabilities. Umbilical cord blood cells improve motor function in experimental systems via paracrine signaling. After demonstrating safety, we conducted phase II trial of autologous (ACB) infusion with CP to test whether ACB could (ClinicalTrials.gov, NCT01147653; IND 14360). In this double-blind, placebo-controlled, crossover study single intravenous 1–5 × 107 total nucleated per kilogram ACB, ages 1...
Objective Somatic variants are a recognized cause of epilepsy‐associated focal malformations cortical development (MCD). We hypothesized that somatic may underlie wider range epilepsy, including nonlesional epilepsy (NLFE). Through genetic analysis brain tissue, we evaluated the role variation in with and without MCD. Methods identified through high‐depth exome ultra–high‐depth candidate gene sequencing DNA from surgery specimens leukocytes 18 individuals NLFE 38 Results observed 5 cases...
To describe the time elapsed from onset of pediatric convulsive status epilepticus (SE) to administration antiepileptic drug (AED).This was a prospective observational cohort study performed June 2011 2013. Pediatric patients (1 month-21 years) with SE were enrolled. In order timing AED during all stages SE, we restricted our population who failed 2 or more classes needed continuous infusions terminate SE.We enrolled 81 (44 male) median age 3.6 years. The first, second, and third doses...
Defective primary ciliogenesis or cilium stability forms the basis of human ciliopathies, including Joubert syndrome (JS), with defective cerebellar vermis development. We performed a high-content genome-wide small interfering RNA (siRNA) screen to identify genes regulating as candidates for JS. analyzed results supervised-learning approach, using SYSCILIA gold standard, Cildb3.0, centriole siRNA and GTex project, identifying 591 likely candidates. Intersection this data whole exome from 145...
Variants in KCNQ2 encoding for Kv 7.2 neuronal K+ channel subunits lead to a spectrum of neonatal-onset epilepsies, ranging from self-limiting forms severe epileptic encephalopathy. Most pathogenic variants cause loss-of-function, whereas few increase activity (gain-of-function). We herein provide evidence new phenotypic and functional profile KCNQ2-related epilepsy: infantile spasms without prior neonatal seizures associated with gain-of-function gene variant. With use an international...
Summary Objective To analyze whether KCNQ 2 R201C and R201H variants, which show atypical gain‐of‐function electrophysiologic properties in vitro , have a distinct clinical presentation outcome. Methods Ten children with heterozygous, de novo or variants were identified worldwide, using an institutional review board ( IRB )–approved patient registry database. We reviewed medical records and, where possible, interviewed parents treating physicians structured, detailed phenotype inventory...
<h3>Objective</h3> To update a 1996 American Academy of Neurology practice parameter. <h3>Methods</h3> The authors systematically reviewed literature published from January 1991 to March 2020. <h3>Results</h3> long-term (24–60 months) risk seizure recurrence is possibly higher among adults who have been seizure-free for 2 years and taper antiseizure medications (ASMs) vs those do not ASMs (15% 7% per the 1 Class I article addressing this issue). In pediatric patients, there probably no...
Abstract Post-zygotically acquired genetic variants, or somatic that arise during cortical development have emerged as important causes of focal epilepsies, particularly those due to malformations development. Pathogenic variants been identified in many genes within the PI3K-AKT-mTOR-signalling pathway individuals with hemimegalencephaly and dysplasia (type II), more recently SLC35A2 I) non-dysplastic epileptic cortex. Given expanding role across different brain malformations, we sought...
We report 7 children who received gabapentin (GBP) as adjunctive medic ation and subsequently developed behavioral side effects. These changes consisted of intensification baseline behaviors well new problems. Behaviors that parents considered most troublesome were tantrums, aggression directed toward others, hyperactivity, defiance. All reversible managed by dose reduction or discontinuation GBP. had attention deficit hyperactivity disorder developmental delays.
<b>Objective:</b> To investigate the long-term effects of two widely used antiepileptic medications, valproate and phenobarbital, on learning behavior in kainic acid (KA) model epilepsy. <b>Background:</b> Prior clinical animal studies have demonstrated that phenobarbital administered during development may result subsequent cognitive impairment. It is unclear whether these adverse extend to other drugs. <b>Methods:</b> A convulsant dose KA was rats postnatal day (P) 35. From P36-75 received...
Abstract To investigate the potential role of drug therapy in preventing or exacerbating seizure‐related brain injury prepubescent brain, we administered kainic acid to rats at postnatal day 35. Therapy with daily phenobarbital was started directly before 1 after administered, and continued through 153. Rats receiving had therapeutic concentrations during most 24‐hour dosing period, but also experienced supratherapeutic peak concentrations. The animals were subsequently tested using water...
<b>Objective: </b> To investigate the effects of two doses vitamin D given over 1 year on bone density in ambulatory patients long-term antiepileptic drug (AED) therapy. <b>Methods: We conducted parallel, randomized, controlled trials 72 adults (18 to 54 years old) and 78 children adolescents (10 18 years) AED They received either low-dose 400 IU/day or high-dose 4,000 (adults) 2,000 (children/adolescents). Bone mineral (BMD) was measured using dual-energy x-ray absorptiometry. <b>Results:...
Idiopathic generalized epilepsy (IGE) is a complex disease with high heritability, but little known about its genetic architecture. Rare copy-number variants have been found to explain nearly 3% of individuals IGE; however, it remains unclear whether moderate effect size and frequencies below what are reliably detected genome-wide association studies contribute significantly risk. In this study, we compare the exome sequences 118 IGE 242 controls European ancestry by using next-generation...