ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions

Epilepsia, Journal Year: 2022, Volume and Issue: 63(6), P. 1349 - 1397

Published: May 3, 2022

Abstract The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification definition of epilepsy syndromes in the neonate infant with seizure onset up to 2 years age. incidence is high this age group frequently associated significant comorbidities mortality. licensing syndrome specific antiseizure medications following randomized controlled trials development precision, gene‐related therapies are two drivers defining electroclinical phenotypes infancy. principal aim proposal, consistent 2017 ILAE Classification Epilepsies, support diagnosis emphasize importance classifying an individual both by etiology. For each syndrome, we report epidemiology, clinical course, types, electroencephalography (EEG), neuroimaging, genetics, differential diagnosis. Syndromes separated into self‐limited syndromes, where there likely be spontaneous remission developmental epileptic encephalopathies , diseases impairment related underlying etiology independent epileptiform activity encephalopathy. emerging class etiology‐specific for that clearly defined, relatively uniform, distinct phenotype most affected individuals as well EEG, and/or genetic correlates, presented. number etiology‐defined will continue increase, these newly described time incorporated classification. tables summarize mandatory features, cautionary alerts, exclusionary features common syndromes. Guidance given criteria resource‐limited regions laboratory confirmation, including MRI, testing, might not available.

Language: Английский

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Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome

JAMA Neurology, Journal Year: 2020, Volume and Issue: 77(5), P. 613 - 613

Published: March 2, 2020

Clinical evidence supports effectiveness of cannabidiol for treatment-resistant seizures in Dravet syndrome, but this trial is the first to evaluate 10-mg/kg/d dose.To efficacy and safety a pharmaceutical formulation cannabidiol, 10 20 mg/kg/d, vs placebo adjunctive treatment convulsive patients with syndrome.This double-blind, placebo-controlled, randomized clinical (GWPCARE2) recruited from April 13, 2015, November 10, 2017, follow-up completed on 9, 2018. Of 285 screened 38 centers United States, Spain, Poland, Netherlands, Australia, Israel, 86 were excluded, 199 randomized. Patients aged 2 18 years confirmed diagnosis syndrome at least 4 during 4-week baseline period while receiving 1 antiepileptic drug. Data analyzed 16 (date unblinding) December 13 final outputs), 2018, based intention treat per protocol.Patients received oral solution dose or mg/kg day (CBD10 CBD20 groups, respectively) matched equally divided doses 14 weeks. All patients, caregivers, investigators, individuals assessing data blinded group assignment.The primary outcome was change seizure frequency period. Secondary outcomes included all frequency, proportion 50% reduction activity, Caregiver Global Impression Change score.Of 198 eligible (mean [SD] age, 9.3 [4.4] years; 104 female [52.5%]), 66 CBD10 group, 67 65 190 treatment. The percentage 48.7% 45.7% 26.9% group; 29.8% (95% CI, 8.4%-46.2%; P = .01) 25.7% 2.9%-43.2%; .03) group. most common adverse events decreased appetite, diarrhea, somnolence, pyrexia, fatigue. Five discontinued owing events. Elevated liver transaminase levels occurred more frequently (n 13) than 3) affected given concomitant valproate sodium.Adjunctive mg/kg/d led similar clinically relevant reductions better tolerability profile children syndrome. Dose increases greater should be tailored individual safety.ClinicalTrials.gov Identifier: NCT02224703.

Language: Английский

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Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group

Epilepsia Open, Journal Year: 2020, Volume and Issue: 5(3), P. 354 - 365

Published: June 27, 2020

Glut1 deficiency syndrome (Glut1DS) is a brain energy failure caused by impaired glucose transport across tissue barriers. Glucose diffusion barriers facilitated family of proteins including transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide supplemental fuel, namely ketone bodies, for metabolism. The increasing complexity Glut1DS, since its original description in 1991, now demands an international consensus statement regarding diagnosis and treatment. International experts (n = 23) developed utilizing their collective professional experience, responses to standardized questionnaire, serial discussions wide-ranging issues related Glut1DS. Key clinical features signaling the onset Glut1DS eye-head movement abnormalities, seizures, neurodevelopmental impairment, deceleration head growth, disorders. Diagnosis confirmed presence these signs, hypoglycorrhachia documented lumbar puncture, genetic analysis showing pathogenic

Language: Английский

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Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants

Brain, Journal Year: 2021, Volume and Issue: 144(9), P. 2879 - 2891

Published: April 22, 2021

Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing neuroimaging can inform strategies therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years age in Scotland presenting epilepsies. used two independent sources for case identification: clinical reporting EEG record review. Capture-recapture methodology was then improve the accuracy incidence estimates. Socio-demographic details were obtained at presentation, 24 months later. Children extensively investigated aetiology. Whole offered patients drug-resistant epilepsy whom no aetiology could yet be identified. Multivariate logistic regression modelling determine associations between features, aetiology, outcome. Three hundred ninety recruited over years. The adjusted epilepsies first life 239 per 100 000 live births [95% confidence interval (CI) 216-263]. There socio-economic gradient incidence, significantly higher most deprived quintile (301 births, 95% CI 251-357) compared least (182 139-233), χ2 odds ratio = 1.7 (95% 1.3-2.2). relationship deprivation only observed group without identified suggesting that populations living areas have greater multifactorial risk epilepsy. determined 54% children, syndrome classified 54%. Thirty-one cent had an genetic cause their novel on aetiological spectrum commonly childhood. Twenty-four after 36% (DRE), 49% global developmental delay (GDD). Identification strongest determinant both DRE GDD. 82% those DRE, 75% In young epilepsy, testing should prioritized as it has highest yield any investigation is likely prognosis. 30% more common than previously reported. undetermined communities. This reflects increased within these populations.

Language: Английский

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Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 21(5), P. 417 - 427

Published: April 13, 2022

Language: Английский

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CDKL5 deficiency disorder: clinical features, diagnosis, and management

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 21(6), P. 563 - 576

Published: April 25, 2022

Language: Английский

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Cell-Selective Adeno-Associated Virus-Mediated SCN1A Gene Regulation Therapy Rescues Mortality and Seizure Phenotypes in a Dravet Syndrome Mouse Model and Is Well Tolerated in Nonhuman Primates

Human Gene Therapy, Journal Year: 2022, Volume and Issue: 33(11-12), P. 579 - 597

Published: April 18, 2022

Dravet syndrome (DS) is a developmental and epileptic encephalopathy caused by monoallelic loss-of-function variants in the SCN1A gene. encodes for alpha subunit of voltage-gated type I sodium channel (NaV1.1), primary responsible generation action potentials GABAergic inhibitory interneurons. In these studies, we tested efficacy an adeno-associated virus serotype 9 (AAV9) gene regulation therapy, AAV9-REGABA-eTFSCN1A, designed to target transgene expression neurons reduce off-target within excitatory cells, Scn1a+/− mouse model DS. Biodistribution preliminary safety were evaluated nonhuman primates (NHPs). AAV9-REGABA-eTFSCN1A was engineered upregulate levels interneurons correct underlying haploinsufficiency circuit dysfunction. A single bilateral intracerebroventricular (ICV) injection postnatal day 1 mice led increased mRNA transcripts, specifically interneurons, NaV1.1 protein brain. This associated with significant decrease occurrence spontaneous hyperthermia-induced seizures, prolonged survival over year. NHPs, delivery unilateral ICV widespread vector biodistribution throughout brain, including key structures involved epilepsy cognitive behaviors, such as hippocampus cortex. well tolerated, no adverse events during administration, detectable changes clinical observations, findings histopathology, dorsal root ganglion-related toxicity. Our results support development (ETX101) effective targeted disease-modifying approach SCN1A+

Language: Английский

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Genetic testing and counseling for the unexplained epilepsies: An evidence‐based practice guideline of the National Society of Genetic Counselors

Journal of Genetic Counseling, Journal Year: 2022, Volume and Issue: 32(2), P. 266 - 280

Published: Oct. 24, 2022

Abstract Epilepsy, defined by the occurrence of two or more unprovoked seizures one seizure with a propensity for others, affects 0.64% population and can lead to significant morbidity mortality. A majority unexplained epilepsy (seizures not attributed an acquired etiology, such as trauma infection) is estimated have underlying genetic etiology. Despite rapid progress in understanding underpinnings epilepsies, there are no recent evidence‐based guidelines testing counseling this population. This practice guideline provides recommendations approaching epilepsies using Grading Recommendations Assessment, Development Evaluation (GRADE) Evidence Decision framework. We used evidence from systematic review meta‐analysis diagnostic yield tests patients epilepsy. also compiled data other sources, including recently submitted conference abstracts peer‐reviewed journal articles. identified prioritized outcomes critical, important based our on deemed critical important. considered desirable undesirable effects, value acceptability relevant stakeholders, impact health equity, cost‐effectiveness, certainty evidence, feasibility interventions individuals Taken together, we generated clinical recommendations: (1) Genetic strongly recommended all epilepsy, without limitation age, exome/genome sequencing and/or multi‐gene panel (>25 genes) first‐tier followed chromosomal microarray, conditionally over panel. (2) It that be selected, ordered, interpreted qualified healthcare provider setting appropriate pre‐test post‐test counseling. Incorporation counselors into neurology practices referral genetics specialists both useful models supporting providers expertise implement these recommendations.

Language: Английский

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Rates of Status Epilepticus and Sudden Unexplained Death in Epilepsy in People With Genetic Developmental and Epileptic Encephalopathies

Neurology, Journal Year: 2023, Volume and Issue: 100(16)

Published: Feb. 7, 2023

Background and Objectives

The genetic developmental epileptic encephalopathies (DEEs) comprise a large group of severe epilepsy syndromes, with wide phenotypic spectrum. Currently, the rates convulsive status epilepticus (CSE), nonconvulsive (NCSE), sudden unexplained death in (SUDEP) these diseases are not well understood. We aimed to describe proportions patients frequently observed DEEs who developed CSE, NCSE, mortality, SUDEP. Understanding risks serious presentations each DEE will enable earlier diagnosis appropriate management.

Methods

In this retrospective analysis DEE, we estimated SUDEP overall SUDEP-specific mortality for diagnosis. included pathogenic variant genes SCN1A, SCN2A, SCN8A, SYNGAP1, NEXMIF, CHD2, PCDH19, STXBP1, GRIN2A, KCNT1, KCNQ2 Angelman syndrome (AS).

Results

cohort comprised 510 individuals whom CSE 47% NCSE 19%. highest proportion occurred SCN1A-associated DEEs, including 181/203 (89%; 95% CI 84–93) Dravet 8/15 (53%; 27–79) non-Dravet SCN1A-DEEs. was also notable variants KCNT1 (6/10; 60%; 26–88) SCN2A (8/15; 53%; 27–79). common SCN1A-DEEs CHD2-DEEs (6/14; 43%; 18–71) AS (6/19; 32%; 13–57). There were 42/510 (8%) deaths among cohort, producing rate 6.1 per 1,000 person-years (95% 4.4–8.3). Cases accounted 19/42 (48%) deaths. Four associated SUDEP: STXBP1. 2.8 1.6–4.3).

Discussion

showed that differ commonly encountered DEEs. estimates studied inform early management disease-specific counseling families high-risk conditions.

Language: Английский

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Developmental and epileptic encephalopathies

Nature Reviews Disease Primers, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 5, 2024

Language: Английский

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