A5052055830- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Autism Spectrum Disorder Research
- Neuroscience and Neuropharmacology Research
- Family and Disability Support Research
- EEG and Brain-Computer Interfaces
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Chromatin Remodeling and Cancer
- Cannabis and Cannabinoid Research
- Neonatal and fetal brain pathology
- Ion channel regulation and function
- Neural dynamics and brain function
- Metabolism and Genetic Disorders
- Congenital heart defects research
- Mitochondrial Function and Pathology
- Pharmacological Effects and Toxicity Studies
- Functional Brain Connectivity Studies
- RNA regulation and disease
- Cardiac electrophysiology and arrhythmias
- Cellular transport and secretion
- Childhood Cancer Survivors' Quality of Life
- Lysosomal Storage Disorders Research
- Trauma and Emergency Care Studies
- Epigenetics and DNA Methylation
Children's Hospital of Philadelphia
2016-2025
University of Pennsylvania
2016-2025
Philadelphia University
2007-2024
Vanderbilt University Medical Center
2007-2023
University of Alabama at Birmingham
2023
Vanderbilt University
2023
RTI International
2023
Children's Hospital Colorado
2023
University of Colorado Denver
2023
Kennedy Center
2023
The Dravet syndrome is a complex childhood epilepsy disorder that associated with drug-resistant seizures and high mortality rate. We studied cannabidiol for the treatment of in syndrome.In this double-blind, placebo-controlled trial, we randomly assigned 120 children young adults to receive either oral solution at dose 20 mg per kilogram body weight day or placebo, addition standard antiepileptic treatment. primary end point was change convulsive-seizure frequency over 14-week period, as...
The contractile properties of the triceps surae (medial and lateral gastrocnemii soleus) have been studied in humans. In comparison with most other human muscles, complex had a slow twitch (mean contraction half-relaxation times 112.4 +/- 11.1 99.6 14.4 ms, respectively) low tetanus fusion frequency (60 Hz). Stretching muscle caused both to become longer. With knee bent, optimum length for torque development corresponded almost full dorsiflexion ankle. Similar results were obtained extended....
Objective Early-onset epileptic encephalopathies have been associated with de novo mutations of numerous ion channel genes. We employed techniques modern translational medicine to identify a disease-causing mutation, analyze its altered behavior, and screen for therapeutic compounds treat the proband. Methods Three tools were utilized: (1) high-throughput sequencing technology novel mutation; (2) in vitro expression electrophysiology assays confirm variant protein's dysfunction; (3)...
To advance the understanding of KCNQ2 encephalopathy genotype-phenotype relationships and to begin assess potential selective KCNQ channel openers as targeted treatments.We retrospectively studied 23 patients with encephalopathy, including 11 treated ezogabine (EZO). We analyzed in these 70 previously described patients.The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of 20 EEGs obtained within a week birth, showed burst suppression. When new types appeared infancy (15 patients), most...
Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted interim analysis of long-term efficacy and tolerability Lennox-Gastaut syndrome (LGS) or Dravet (DS) who received CBD treatment through December 2016.Children adults LGS/DS taking stable doses antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the...
Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies syndrome. In this 3 study ( https://clinicaltrials.gov identifier NCT04181723 ), females with received twice-daily oral trofinetide (n = 93) or placebo 94) for 12 weeks. For coprimary efficacy endpoints, least squares mean (LSM) change from baseline to...
A method is described for investigating the contractile properties of dorsiflexor muscles ankle. With joint in midposition tibialis anterior was found to contribute less than half maximum voluntary torque, remainder presumably being provided by long extensors toes. The mean contraction and half-relaxation times healthy young men were 81.2 +/- 7.4 (SD) ms 83.6 17.2 ms, respectively. When stretched, twitch became slower more complete fusion contractions occurred during tetanic stimulation at...
Mutations in the X-linked aristaless-related homeobox gene (ARX) have been linked to structural brain anomalies as well multiple neurocognitive deficits. The generation of Arx-deficient mice revealed several morphological anomalies, resembling those observed patients and an interneuron migration defect but perinatal lethality precluded analyses later phenotypes. Interestingly, many neurological phenotypes with various ARX mutations can be attributed, part, dysfunction. To directly test this...
Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum (ASDs), and early infantile epileptic encephalopathy. The biological function of CDKL5 its role etiology these disorders, however, remain unclear. Here we report development a unique knockout mouse model CDKL5-related demonstrate that mice lacking show autistic-like deficits social interaction, as well impairments...
Febrile infection-related epilepsy syndrome (FIRES) is a devastating affecting normal children after febrile illness. FIRES presents with an acute phase super-refractory status epilepticus and all patients progress to chronic persistent refractory epilepsy. The typical outcome severe encephalopathy or death. authors present 7 from 5 centers who had not responded antiepileptic drugs other therapies were given cannabadiol (Epidiolex, GW Pharma) on emergency expanded investigational protocols...
Recently, de novo mutations in the gene KCNA2, causing either a dominant-negative loss-of-function or gain-of-function of voltage-gated K+ channel Kv1.2, were described to cause new molecular entity within epileptic encephalopathies. Here, we report cohort 23 patients (eight previously described) with encephalopathy carrying novel known KCNA2 mutations, aim detail clinical phenotype associated each them, characterize functional effects newly identified and assess genotype-phenotype...
Transient high-frequency (100–500 Hz) oscillations of the local field potential have been studied extensively in human mesial temporal lobe. Previous studies report that both ripple (100–250 and fast (250–500 are increased seizure-onset zone patients with lobe epilepsy. Comparatively little is known, however, about their spatial distribution respect to neocortical epilepsy, or prevalence normal brain. We present a quantitative analysis rates occurrence group nine epilepsy two control no...
We sought to identify genetic causes of early onset epileptic encephalopathies with burst suppression (Ohtahara syndrome and myoclonic encephalopathy) evaluate genotype-phenotype correlations.We enrolled 33 patients a referral diagnosis Ohtahara or encephalopathy without malformations cortical development. performed detailed phenotypic assessment including seizure presentation, electroencephalography, magnetic resonance imaging. confirmed in 28 patients. Research-based exome sequencing was...
Summary Objective Patients with Lennox‐Gastaut syndrome ( LGS ) who completed 1 of 2 randomized, double‐blind, placebo‐controlled trials add‐on cannabidiol CBD GWPCARE 3, NCT 02224560 or 4, 02224690) were invited to enroll in an open‐label extension OLE study evaluating the long‐term safety and efficacy 5, 02224573). Herein we present interim analysis safety, efficacy, patient‐reported outcomes from this trial. Methods received a pharmaceutical formulation highly purified oral solution...
Abstract Temporal lobe epilepsy represents a major cause of drug-resistant epilepsy. Cognitive impairment is frequent comorbidity, but the mechanisms are not fully elucidated. We hypothesized that cognitive in temporal could be due to perturbations amyloid and tau signalling pathways related activation stress kinases, similar those observed Alzheimer’s disease. examined these pathways, as well amyloid-β pathologies hippocampus cortex patients who underwent resection (n = 19), comparison with...
Epileptic encephalopathies are a devastating group of severe childhood onset epilepsies with medication-resistant seizures and poor developmental outcomes. Many epileptic have genetic aetiology often associated de novo mutations in genes mediating synaptic transmission, including GABA
<h3>Importance</h3> Knowing the range of symptoms seen in patients with a missense or loss-of-function variant in<i>KCNB1</i>and how these correlate type will help clinicians diagnosis and prognosis when treating new patients. <h3>Objectives</h3> To investigate clinical spectrum associated with<i>KCNB1</i>variants genotype-phenotype correlations. <h3>Design, Setting, Participants</h3> This study summarized genetic information presumed pathogenic in<i>KCNB1.</i> Patients were identified...
Rett syndrome (RTT) is a severe neurodevelopmental disorder with complex medical comorbidities extending beyond the nervous system requiring attention of health professionals. There no peer-reviewed, consensus-based therapeutic guidance to care in RTT. The objective was provide consensus on best practice for addressing these concerns.Informed by literature and using modified Delphi approach, process used develop RTT professionals.Typical presents early childhood clinically recognisable...
Abstract The location of interictal spikes is used to aid surgical planning in patients with medically refractory epilepsy; however, their spatial and temporal dynamics are poorly understood. In this study, we analysed the distribution over time 20 adult paediatric (12 females, mean age = 34.5 years, range 5–58) who underwent intracranial EEG evaluation for epilepsy surgery. Interictal were detected 24 h surrounding each seizure clustered based on location. spike calculated patient effects...
Abstract Objective Recent advances in the understanding of neurodevelopmental disorders such as Rett syndrome (RTT) have enabled discovery novel therapeutic approaches that require formal clinical evaluation efficacy. Clinical trial success depends on outcome measures assess features are most impactful for affected individuals. To determine top concerns RTT and RTT-related we asked caregivers to list caregiver guide development selection appropriate these disorders. Methods Caregivers...