Quantitative EEG biomarkers for STXBP1-related disorders.

Objective: EEG patterns and quantitative EEG (qEEG) features have been poorly explored in monogenic epilepsies. Herein, we investigate regional differences in EEG frequency composition in patients with STXBP1 developmental and epileptic encephalopathy (STXBP1-DEE).

Methods: We conducted a retrospective study collecting electroclinical data of patients with STXBP1-DEE and two control groups of patients with DEEs of different etiologies and typically developing individuals matched for age and sex.

Unveiling variability: A systematic review of reproducibility in visual EEG analysis, with focus on seizures.

Objective: Reproducibility is key for diagnostic tests involving subjective evaluation by experts. Our aim was to systematically review the reproducibility of visual analysis in clinical electroencephalogram (EEG). In this paper, we give data on the scope of EEG features found, and detailed reproducibility data for the most studied feature.

Towards user-centered design of medical devices for SUDEP prediction and prevention: Insights from persons with epilepsy and caregivers.

Objectives: As epilepsy management medical devices emerge as potential technological solutions for prediction and prevention of sudden death in epilepsy (SUDEP), there is a gap in understanding the features and priorities that should be included in the design of these devices. This study aims to bridge the gap between current technology and emerging needs by leveraging insights from persons with epilepsy (PWE) and caregivers (CG) on current epilepsy management devices and understanding how SUDEP awareness influences preferences and design considerations for potential future solutions.

Methods: Two cross-sectional surveys were designed to survey PWE and CG on medical device design features, SUDEP awareness, and participation in medical device research.

Prodromal Phase of Idiopathic Generalized Epilepsy: A Register-Based Case Control Study.

Background And Objectives: Idiopathic generalized epilepsy (IGE) is associated with distinct behavioral traits, symptoms of frontal lobe dysfunction, and psychiatric comorbidity. Whether psychiatric symptoms are part of the IGE endophenotype or secondary to the burden of chronic disease is unknown. In this study, we aimed at describing the sequence of appearance of psychiatric and epilepsy symptoms in patients with IGE.

Fenfluramine treatment in pediatric patients with Dravet syndrome reduces seizure burden and overall healthcare costs: A retrospective and observational real-world study.

Objectives: Dravet syndrome is a developmental and epileptic encephalopathy characterized by early onset epilepsy with multiple seizure types often intractable to treatment. Randomized clinical trials have demonstrated how treatment with fenfluramine significantly reduces seizure frequency in patients with Dravet syndrome. The study aims to (1) describe the efficacy and tolerability of fenfluramine in a Danish cohort of patients with Dravet syndrome; and (2) evaluate whether treatment with fenfluramine reduces epilepsy-related hospital contacts administrated by pediatricians or epilepsy-trained nurses.

The phenotypic and genotypic spectrum of individuals with mono- or biallelic ANK3 variants.

ANK3 encodes ankyrin-G, a protein involved in neuronal development and signaling. Alternative splicing gives rise to three ankyrin-G isoforms comprising different domains with distinct expression patterns. Mono- or biallelic ANK3 variants are associated with non-specific syndromic intellectual disability in 14 individuals (seven with monoallelic and seven with biallelic variants).

Theory of mind in epilepsy.

Epilepsy is characterized by recurrent, chronic, and unprovoked seizures. Epilepsy has a significant negative impact on a patient's quality of life even if seizures are well controlled. In addition to the distress caused by seizures, patients with epilepsy (PwE) may suffer from cognitive impairment with serious social consequences such as poor interpersonal relationships, loss of employment, and reduced social networks.

Epilepsy as a Novel Phenotype of BPTF-Related Disorders.

Background: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) is associated to BPTF gene haploinsufficiency. Epilepsy was not included in the initial descriptions of NEDDFL, but emerging evidence indicates that epileptic seizures occur in some affected individuals. This study aims to investigate the electroclinical epilepsy features in individuals with NEDDFL.

Differences in manifestations of epilepsy and developmental delay in PURA syndrome and 5q31 microdeletions.

PURA is mapped to chromosome 5q31 and plays a vital role in neuronal development and synapse formation. Here, we aim to explore PURA's impact on cognitive development and epilepsy phenotype by comparing patients with single nucleotide variants (SNPs) in the PURA gene (PURA-SNP patients) to those with 5q31 microdeletions including PURA (5q31del + PURA) and those with 5q31 microdeletions not including the PURA gene (5q31del-PURA). A systematic literature search was conducted in PubMed.

Unraveling GRIA1 neurodevelopmental disorders: Lessons learned from the p.(Ala636Thr) variant.

Ionotropic glutamate receptors (iGluRs), specifically α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), play a crucial role in orchestrating excitatory neurotransmission in the brain. AMPARs are intricate assemblies of subunits encoded by four paralogous genes: GRIA1-4. Functional studies have established that rare GRIA variants can alter AMPAR currents leading to a loss- or gain-of-function.

Haploinsufficiency underlies the neurodevelopmental consequences of SLC6A1 variants.

Heterozygous variants in SLC6A1, encoding the GAT-1 GABA transporter, are associated with seizures, developmental delay, and autism. The majority of affected individuals carry missense variants, many of which are recurrent germline de novo mutations, raising the possibility of gain-of-function or dominant-negative effects. To understand the functional consequences, we performed an in vitro GABA uptake assay for 213 unique variants, including 24 control variants.

Seizure and movement disorder in CACNA1E developmental and epileptic encephalopathy: Two sides of the same coin or same side of two different coins?

Pathogenic variants in CACNA1E are associated with early-onset epileptic and developmental encephalopathy (DEE). Severe to profound global developmental delay, early-onset refractory seizures, severe hypotonia, and macrocephaly are the main clinical features. Patients harboring the recurrent CACNA1E variant p.

Spectrum of NMDA Receptor Variants in Neurodevelopmental Disorders and Epilepsy.

N-methyl-D-aspartate receptors (NMDAR) are ligand-gated ion channels mediating excitatory neurotransmission and are important for normal brain development, cognitive abilities, and motor functions. Pathogenic variants in the Glutamate receptor Ionotropic N-methyl-D-aspartate (GRIN) genes (GRIN1, GRIN2A-D) encoding NMDAR subunits have been associated with a wide spectrum of neurodevelopmental disorders and epilepsies ranging from treatable focal epilepsies to devastating early-onset developmental and epileptic encephalopathies. Genetic variants in NMDA receptor genes can cause a range of complex alterations to receptor properties resulting in various degrees of loss-of-function, gain-of-function, or mixtures thereof.

The online educational tool "Roadmap to EEGs" significantly improved trainee performance in recognizing EEG patterns.

Objective: We created a framework to assess the competency-based EEG curriculum, outlined by the International League Against Epilepsy (ILAE) through a video-based online educational resource ("Roadmap to EEGs") and assessed its effectiveness and feasibility in improving trainees' knowledge.

Methods: Ten video-based e-learning modules addressed seven key topics in EEG and epileptology (normal EEG, normal variants, EEG artifacts, interictal epileptiform discharges (IED), focal seizures, idiopathic generalized epilepsy (IGE), and developmental and epileptic encephalopathies (DEE)). We posted the educational videos on YouTube for free access.

Automated analysis and detection of epileptic seizures in video recordings using artificial intelligence.

Introduction: Automated seizure detection promises to aid in the prevention of SUDEP and improve the quality of care by assisting in epilepsy diagnosis and treatment adjustment.

Methods: In this phase 2 exploratory study, the performance of a contactless, marker-free, video-based motor seizure detection system is assessed, considering video recordings of patients (age 0-80 years), in terms of sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves, with respect to video-electroencephalographic monitoring (VEM) as the medical gold standard. Detection performances of five categories of motor epileptic seizures (tonic-clonic, hyperkinetic, tonic, unclassified motor, automatisms) and psychogenic non-epileptic seizures (PNES) with a motor behavioral component lasting for >10 s were assessed independently at different detection thresholds (rather than as a categorical classification problem).

ATP1A2-related epileptic encephalopathy and movement disorder: Clinical features of three novel patients.

Objective: Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE.

Methods: Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed.

Seizure provocation in EEG recordings: A data-driven approach.

Objective: Recording seizures on video-EEG has a high diagnostic value. However, bilateral convulsive seizures constitute a risk for the patients. Our aim was to investigate the diagnostic yield and associated risks of provocation methods in short-term video-EEGs.