Open-label evaluation of oral trehalose in patients with neuronal ceroid lipofuscinoses.

The neuronal ceroid lipofuscinoses (NCLs) are incurable pediatric neurodegenerative diseases characterized by accumulation of lysosomal material and dysregulation of autophagy. Given the promising results of treatment with trehalose, an autophagy inducer, in cell and animal models of NCL, we conducted an open-label, non-placebo-controlled, non-randomized 12-month prospective study in NCL patients receiving oral trehalose (4 g/day). All were treated with a commercially available formulation for 6 months, followed by a 6-month washout.

Stereo-EEG around the world: State of the art in Italy.

Stereo-EEG is not just a diagnostic examination but a complex methodology, requiring an accurate synthesis of many data (anatomical, clinical, neurophysiological, cognitive, metabolic, and genetic). The implantation scheme is decided based on a hypothesis (or hypotheses) of epileptogenic zone localization. Subsequently, intracerebral electrical stimulation is used to define the extent of highly functional cortical regions and to reproduce the clinical symptoms and signs associated with seizures.

Fenfluramine treatment for Dravet syndrome: Long term real-world analysis demonstrates safety and reduced health care burden.

Objective: Fenfluramine (FFA), stiripentol (STP), and cannabidiol (CBD) are approved add-on therapies for seizures in Dravet syndrome (DS). We report on the long-term safety and health care resource utilization (HCRU) of patients with DS treated with FFA under an expanded access program (EAP).

Methods: A cohort of 124 patients received FFA for a median of 2.

Molecular and clinical Insights into KMT2E-Related O'Donnell-Luria-Rodan syndrome in a novel patient cohort.

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant neurodevelopmental disorder mainly characterized by global development delay/intellectual disability, white matter abnormalities, and behavioral manifestations. It is caused by pathogenic variants in the KMT2E gene. Here we report seven new patients with loss-of-function KMT2E variants, six harboring frameshift/nonsense changes, and one with a 7q22.

Rare dysfunctional SCN2A variants are associated with malformation of cortical development.

Objective: SCN2A encodes the voltage-gated sodium (Na+) channel α subunit Na1.2, which is important for the generation and forward and back propagation of action potentials in neurons. Genetic variants in SCN2A are associated with a spectrum of neurodevelopmental disorders.

Infantile epileptic spasms syndrome: When spasms come out of the blue.

Background: This study evaluates the electroclinical features of infantile epileptic spasms syndrome (IESS) suddenly appearing in previously normal patients, aiming to describe clinical outcomes and independent predictors.

Method: We retrospectively selected a homogeneous group of patients with IESS from two Italian centers. All patients had normal development prior to IESS onset and a follow-up period lasting at least one year.

National survey on the prevalence of single-gene aetiologies for genetic developmental and epileptic encephalopathies in Italy.

Background: We aimed to estimate real-world evidence of the prevalence rate of genetic developmental and epileptic encephalopathies (DEEs) in the Italian population over a 11-year period.

Methods: Fifteen paediatric and adult tertiary Italian epilepsy centres participated in a survey related to 98 genes included in the molecular diagnostic workflows of most centres. We included patients with a clinical diagnosis of DEE, caused by a pathogenic or likely pathogenic variant in one of the selected genes, with a molecular diagnosis established between 2012 and 2022.

Psychometric Validation of the CLN2 Quality of Life Questionnaire in Participants with CLN2 Disease Treated with Cerliponase Alfa.

Objectives: This study evaluated the psychometric properties of the ceroid lipofuscinosis type 2 Quality of Life (CLN2 QoL) questionnaire.

Methods: Data from children with CLN2 disease aged 3-16 years receiving cerliponase alfa in the BMN 190-201 and BMN 190-202 clinical studies, collected via purposive sampling, were used to assess convergent and divergent validity, internal consistency and reliability. The clinically important difference (CID) was estimated with distribution- and anchor-based methods.

Pharmacotherapeutic strategies for drug-resistant epilepsy in children.

Drug resistance is defined as the failure of adequate trials of two tolerated and appropriately chosen antiseizure medications to achieve sustained seizure freedom. In case of uncontrolled seizures, pseudo-drug-resistance (poor compliance, a worsening effect of an antiseizure medication, a diagnosis of psychogenic non-epileptic seizure) should be first ruled out in case of pediatric epilepsies. This paper discusses the process of choosing antiseizure medication and the concepts of rationale polytherapy and precision medicine.

Tonic and tonic-clonic seizures in the first year of life: Insights from electrographic features.

Objective: We studied the electrographic features of tonic seizures (TS) with bilateral contraction and tonic-clonic seizures (TCS) without focal signs occurring during the first year of life to evaluate if there is a correlation with outcome.

Methods: We retrospectively reviewed patients aged 1 to 12 months with at least one TS or TCS recorded with video-EEG between 2011 and 2021 in our Epilepsy Monitoring Unit. We analyzed the following electrographic features: seizure duration, presence and duration of focal ictal EEG onset, and post-ictal generalized EEG suppression (PGES).

The expanding field of genetic developmental and epileptic encephalopathies: current understanding and future perspectives.

Recent advances in genetic testing technologies have revolutionised the identification of genetic abnormalities in early onset developmental and epileptic encephalopathies (DEEs). In this Review, we provide an update on the expanding landscape of genetic factors contributing to DEEs, encompassing over 800 reported genes. We focus on the cellular and molecular mechanisms driving epileptogenesis, with an emphasis on emerging therapeutic strategies and effective treatment options.

Epilepsy surgery below the age of 5 years: Are we still in time to preserve developmental and intellectual functions?

Objective: The aim of this study is to describe the pre- and post-operative developmental and intellectual functions in a cohort of patients who underwent surgery for drug-resistant epilepsy (DRE) before the age of 5 years.

Method: We retrospectively reviewed the medical records and neurodevelopmental assessments of a cohort of 80 surgically treated pediatric patients with DRE. We included patients if they had at least one pre- and one post-surgical neuropsychological assessments; 27 met the inclusion criteria.

POLR3B de novo variants are a rare cause of infantile myoclonic epilepsy.

Purpose: To report on a new phenotype in a patient carrying a novel, undescribed de novo variant in POLR3B, affected by generalized myoclonic epilepsy and neurodevelopmental disorder, without neuropathy. It is known that biallelic pathogenic variants in POLR3B cause hypomyelinating leukodystrophy-8, and heterozygous de novo variants are described in association to a phenotype characterized by predominantly demyelinating sensory-motor peripheral neuropathy, ataxia, spasticity, intellectual disability and epilepsy, in which the peripheral neuropathy is often the main clinical presentation.

Methods: We collected clinical, electrophysiological and neuroimaging data from the affected subject and performed a Trio-Clinical Exome Sequencing.

Italian report on RARE epilepsies (i-RARE): A consensus on multidisciplinarity.

Objective: Rare and complex epilepsies encompass a diverse range of disorders characterized by seizures. We aimed to establish a consensus on key issues related to these conditions through collaboration among experienced neurologists, neuropediatricians, and patient advocacy representatives.

Methods: Employing a modified Delphi method, a scientific board comprising 20 physicians and 4 patient advocacy representatives synthesized existing literature with their expertise to formulate statements on contentious topics.

Movement disorder phenotype in CTNNB1-syndrome: A complex but recognizable phenomenology.

Introduction: CTNNB1 gene loss-of-function variants cause Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV, OMIM 615075). Although motor impairment represents a core feature of this condition, the motor phenotype remains poorly described. We systematically assessed a cohort of 14 patients with disease-causing CTNNB1 variants to better characterize the movement disorder phenotype.

Distinct neurodevelopmental and epileptic phenotypes associated with gain- and loss-of-function GABRB2 variants.

Background: Variants in GABRB2, encoding the β2 subunit of the γ-aminobutyric acid type A (GABA) receptor, can result in a diverse range of conditions, ranging from febrile seizures to severe developmental and epileptic encephalopathies. However, the mechanisms underlying the risk of developing milder vs more severe forms of disorder remain unclear. In this study, we conducted a comprehensive genotype-phenotype correlation analysis in a cohort of individuals with GABRB2 variants.

Effects of ganaxolone on non-seizure outcomes in CDKL5 Deficiency Disorder: Double-blind placebo-controlled randomized trial.

CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes.

Surgical and radiosurgical treatment of hypothalamic hamartoma: The Italian experience between 2011 and 2021.

Objective: To investigate the Italian experience on the surgical and radiosurgical treatment of drug-resistant epilepsy due to hypothalamic hamartoma (HH) in the period 2011-2021 in six Italian epilepsy surgery centers, and to compare safety and efficacy profiles of the different techniques.

Methods: We collected pseudo-anonymized patient's data with at least 12 months of follow-up. Surgical outcome was defined according to Engel classification of seizure outcome.