A Reappraisal on cortical myoclonus and brief Remarks on myoclonus of different Origins.

Myoclonus has multiple clinical manifestations and heterogeneous generators and etiologies, encompassing a spectrum of disorders and even physiological events. This paper, developed from a teaching course conducted by the Neurophysiology Commission of the Italian League against Epilepsy, aims to delineate the main types of myoclonus, identify potential underlying neurological disorders, outline diagnostic procedures, elucidate pathophysiological mechanisms, and discuss appropriate treatments. Neurophysiological techniques play a crucial role in accurately classifying myoclonic phenomena, by means of simple methods such as EEG plus polymyography (EEG + Polymyography), evoked potentials, examination of long-loop reflexes, and often more complex protocols to study intra-cortical inhibition-facilitation In clinical practice, EEG + Polymyography often represents the first step to identify myoclonus, acquire signals for off-line studies and plan the diagnostic work-up.

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.

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.

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.

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.

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.

Developmental epileptic encephalopathy in DLG4-related synaptopathy.

Objective: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail.

Prediction tools and risk stratification in epilepsy surgery.

Objective: This study was undertaken to conduct external validation of previously published epilepsy surgery prediction tools using a large independent multicenter dataset and to assess whether these tools can stratify patients for being operated on and for becoming free of disabling seizures (International League Against Epilepsy stage 1 and 2).

Methods: We analyzed a dataset of 1562 patients, not used for tool development. We applied two scales: Epilepsy Surgery Grading Scale (ESGS) and Seizure Freedom Score (SFS); and two versions of Epilepsy Surgery Nomogram (ESN): the original version and the modified version, which included electroencephalographic data.

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model.

The phenotypic presentation of adult individuals with -related neurodevelopmental disorders.

Introduction: is one of the most common monogenic causes of epilepsy and is a well-established cause of neurodevelopmental disorders. -neurodevelopmental disorders have a consistent phenotype of mild to severe intellectual disability (ID), epilepsy, language delay and behavioral disorders. This phenotypic description is mainly based on knowledge from the pediatric population.

Vinpocetine improved neuropsychiatric and epileptic outcomes in a patient with a GABRA1 loss-of-function variant.

Vinpocetine is a synthetic derivative of the alkaloid vincamine and has been used as a dietary supplement for decades. Following a positive report of the use of vinpocetine in a patient with a loss-of-function GABRB3 variant, we here describe another patient with a loss-of-function GABRA1 variant (p.(Arg112Gln)) who benefited from vinpocetine treatment.

Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications.

Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes.

POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum.

POU3F3 variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype-phenotype correlations in individuals with POU3F3-related disorders. We recruited unpublished individuals with POU3F3 variants through international collaborations and obtained updated clinical data on previously published individuals.

IRF2BPL as a novel causative gene for progressive myoclonus epilepsy.

IRF2BPL has recently been described as a novel cause of neurodevelopmental disorders with multisystemic regression, epilepsy, cerebellar symptoms, dysphagia, dystonia, and pyramidal signs. We describe a novel IRF2BPL phenotype consistent with progressive myoclonus epilepsy (PME) in three novel subjects and review the features of the 31 subjects with IRF2BPL-related disorders previously reported. Our three probands, aged 28-40 years, harbored de novo nonsense variants in IRF2BPL (c.