Developmental phenotype and quality of life in SLC13A5 citrate transporter disorder.

Aim: To describe the neurodevelopment and quality of life in SLC13A5 (solute carrier family 13 member 5) citrate transporter disorder (developmental and epileptic encephalopathy 25, DEE25), a rare genetic early infantile epileptic encephalopathy caused by deficiency of a sodium-citrate transporter, characterized by heavy seizure burden in the neonatal period.

Method: We analyzed longitudinal neurodevelopmental outcomes from a prospective natural history study of DEE25, using standardized assessments of Mullen Scales of Early Learning, Peabody Developmental Motor Scales, and Vineland Adaptive Behavior Scales.

Results: There was significant global impairment across the cohort, with variable quality of life and limited genotype-phenotype correlation.

Efficacy and safety of perampanel in patients with seizures associated with Lennox-Gastaut syndrome: A randomized trial.

Objectives: The Phase 3 Study 338 (NCT02834793) assessed long-term clinical outcomes of adjunctive perampanel in patients ≥2 years of age with uncontrolled seizures associated with Lennox-Gastaut syndrome (LGS).

Methods: Eligible patients were diagnosed with LGS and receiving one to four concomitant antiseizure medications with an average of two or more drop seizures/week during baseline. The study comprised an 18-week double-blind, randomized, placebo-controlled Core Study and ≥52-week open-label Extension.

Sleep Abnormalities in SLC13A5 Citrate Transporter Disorder.

Background: SLC13A5 Citrate Transporter Disorder is a rare pediatric neurodevelopmental disorder. Patients have epilepsy, developmental disability, and impaired mobility. While sleep disorders are common in children with neurodevelopmental disorders, sleep abnormalities have not been reported in SLC13A5 patients.

The growing research toolbox for SLC13A5 citrate transporter disorder: a rare disease with animal models, cell lines, an ongoing Natural History Study and an engaged patient advocacy organization.

TESS Research Foundation (TESS) is a patient-led nonprofit organization seeking to understand the basic biology and clinical impact of pathogenic variants in the SLC13A5 gene. TESS aims to improve the fundamental understanding of citrate's role in the brain, and ultimately identify treatments and cures for the associated disease. TESS identifies, organizes, and develops collaboration between researchers, patients, clinicians, and the pharmaceutical industry to improve the lives of those suffering from SLC13A5 citrate transport disorder.

Expanding eligibility for intracranial electroencephalography using Dexmedetomidine Hydrochloride in children with behavioral dyscontrol.

Introduction: Invasive intracranial electroencephalography (IEEG) is advantageous for identifying epileptogenic foci in pediatric patients with medically intractable epilepsy. Patients with behavioral challenges due to autism, intellectual disabilities, and hyperactivity have greater difficulty tolerating prolonged IEEG recording and risk injuring themselves or others. There is a need for therapies that increase the safety of IEEG but do not interfere with IEEG recording or prolong hospitalization.

Approach, complications, and outcomes for 37 consecutive pediatric patients undergoing laser ablation for medically refractory epilepsy at Stanford Children's Health.

Objective: The objective of this study was to better understand the safety and efficacy of laser interstitial thermal therapy (LITT) for children with medically refractory epilepsy.

Methods: Thirty-seven consecutive pediatric epilepsy patients at a single pediatric center who underwent LITT ablation of epileptogenic foci between May 2017 and December 2021 were retrospectively reviewed. Patient demographics, medication use, seizure frequency, prior surgical interventions, procedural details, and pre- and postoperative seizure history were analyzed.

Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex: The PREVeNT Trial.

Objective: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months.

Characterizing a rare neurogenetic disease, SLC13A5 citrate transporter disorder, utilizing clinical data in a cloud-based medical record collection system.

SLC13A5 citrate transporter disorder is a rare autosomal recessive genetic disease that has a constellation of neurologic symptoms. To better characterize the neurologic and clinical laboratory phenotype, we utilized patient medical records collected by Ciitizen, an Invitae company, with support from the TESS Research Foundation. Medical records for 15 patients with a suspected genetic and clinical diagnosis of SLC13A5 citrate transporter disorder were collected by Ciitizen, an Invitae company.

GNAO1-related neurodevelopmental disorder: Literature review and caregiver survey.

Background: -related neurodevelopmental disorder is a heterogeneous condition characterized by hypotonia, developmental delay, epilepsy, and movement disorder. This study aims to better understand the spectrum of epilepsy associated with variants and experience with anti-seizure medications, and to review published epilepsy phenotypes in .

Methods: An online survey was distributed to caregivers of individuals diagnosed with pathogenic variants, and a literature review was conducted.

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of .

Background And Objectives: encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo variants.

Clinical Features, Neuropathology, and Surgical Outcome in Patients With Refractory Epilepsy and Brain Somatic Variants in the Gene.

Background And Objectives: The gene, located at chromosome Xp11.23, encodes for a uridine diphosphate-galactose transporter. We describe clinical, genetic, neuroimaging, EEG, and histopathologic findings and assess possible predictors of postoperative seizure and cognitive outcome in 47 patients with refractory epilepsy and brain somatic gene variants.

Limited utility of structural MRI to identify the epileptogenic zone in young children with tuberous sclerosis.

Background And Purpose: The success of epilepsy surgery in children with tuberous sclerosis complex (TSC) hinges on identification of the epileptogenic zone (EZ). We studied structural MRI markers of epileptogenic lesions in young children with TSC.

Methods: We included 26 children with TSC who underwent epilepsy surgery before the age of 3 years at five sites, with 12 months or more follow-up.

Somatic variants in diverse genes leads to a spectrum of focal cortical malformations.

Post-zygotically acquired genetic variants, or somatic variants, that arise during cortical development have emerged as important causes of focal epilepsies, particularly those due to malformations of cortical development. Pathogenic somatic variants have been identified in many genes within the PI3K-AKT-mTOR-signalling pathway in individuals with hemimegalencephaly and focal cortical dysplasia (type II), and more recently in SLC35A2 in individuals with focal cortical dysplasia (type I) or non-dysplastic epileptic cortex. Given the expanding role of somatic variants across different brain malformations, we sought to delineate the landscape of somatic variants in a large cohort of patients who underwent epilepsy surgery with hemimegalencephaly or focal cortical dysplasia.

Antiseizure medication use and medical resource utilization after resective epilepsy surgery in children in the United States: A contemporary nationwide cross-sectional cohort analysis.

Objective: Antiseizure drug (ASD) therapy can significantly impact quality of life for pediatric patients whose epilepsy remains refractory to medications and who experience neuropsychological side effects manifested by impaired cognitive and social development. Contemporary patterns of ASD reduction after pediatric epilepsy surgery across practice settings in the United States are sparsely reported outside of small series. We assessed timing and durability of ASD reduction after pediatric epilepsy surgery and associated effects on health care utilization.

An Atlas of the Quantitative Protein Expression of Anti-Epileptic-Drug Transporters, Metabolizing Enzymes and Tight Junctions at the Blood-Brain Barrier in Epileptic Patients.

The purpose of the present study was to quantitatively elucidate the levels of protein expression of anti-epileptic-drug (AED) transporters, metabolizing enzymes and tight junction molecules at the blood-brain barrier (BBB) in the focal site of epilepsy patients using accurate SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Brain capillaries were isolated from focal sites in six epilepsy patients and five normal brains; tryptic digests were produced and subjected to SWATH analysis. MDR1 and BCRP were significantly downregulated in the epilepsy group compared to the normal group.

Growth and Overall Health of Patients with Citrate Transporter Disorder.

We were interested in elucidating the non-neurologic health of patients with autosomal recessive Citrate Transporter (NaCT) Disorder. Multiple variants have been reported that cause a loss of transporter activity, resulting in significant neurologic impairment, including seizures, as well as motor and cognitive dysfunction. Additionally, most patients lack tooth enamel (amelogenesis imperfecta).

Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study.

Background: Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited.

Objective: To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients.

Methods: Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers.

A Standardized Protocol to Improve Acute Seizure Management in Hospitalized Pediatric Patients.

Background: Studies of seizure management in the pediatric inpatient setting are needed. Seizures recorded by video EEG provide an opportunity to quantitatively evaluate acute management. We observed variation in delivery of standardized seizure safety measures (seizure first aid) during epilepsy monitoring unit admissions at our hospital.

Caregivers' impression of epilepsy surgery in patients with tuberous sclerosis complex.

Epilepsy surgery is successful in the majority of patients with tuberous sclerosis complex (TSC), with high rates of postoperative seizure reduction and even seizure freedom. Epilepsy surgery is recommended after failing two appropriate antiseizure medication trials; however, this is rare in clinical practice. We hypothesized that following surgery, caregivers' perspectives on the path they took to epilepsy surgery would inform changes in clinical practice and future research to increase utilization and early use of surgery.

Epilepsy and EEG Phenotype of SLC13A5 Citrate Transporter Disorder.

Mutations in the SLC13A5 gene, a sodium citrate cotransporter, cause a rare autosomal recessive epilepsy (EIEE25) that begins during the neonatal period and is associated with motor and cognitive impairment. Patient's seizure burden, semiology, and electroencephalography (EEG) findings have not been well characterized. Data on 23 patients, 3 months to 29 years of age are reported.