Neurocognitive, behavioral, and treatment burden as key predictors of parental stress in pediatric epilepsy.

Objective: Parental stress in pediatric epilepsy is often linked to seizure-related factors. However, less is known about the contribution of child cognitive functioning, behavioral symptoms, and treatment complexity to caregiver burden. This study aimed to investigate how these variables, along with sociodemographic factors, predict perceived parental stress.

Is highly purified cannabidiol a treatment opportunity for drug-resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?

Objective: This study aimed to evaluate the efficacy and safety of adjunctive, highly purified Cannabidiol (Epidiolex®) in individuals with drug-resistant epilepsy (DRE) due to genetically determined typical Rett Syndrome (RTT) and CDKL5 Deficiency Disorder (CDD).

Methods: We recruited subjects with genetically confirmed typical RTT and CDD with drug-resistant seizures who received add-on treatment with highly purified Cannabidiol (CBD) through a national collaboration group. CBD treatment was titrated from 5 to 20 mg/kg/day; concurrent antiseizure medications (ASMs) could have been adjusted as clinically indicated.

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.

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.

Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program.

Objective: This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy.

Methods: This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency).

A Case of CDKL5 Deficiency Due to an X Chromosome Pericentric Inversion: Delineation of Structural Rearrangements as an Overlooked Recurrent Pathological Mechanism.

CDKL5 deficiency disorder (CDD) is an X-linked dominant epileptic encephalopathy, characterized by early-onset and drug-resistant seizures, psychomotor delay, and slight facial features. Genomic variants inactivating or impairing its protein product kinase activity have been reported, making next-generation sequencing (NGS) and chromosomal microarray analysis (CMA) the standard diagnostic tests. We report a suspicious case of CDD in a female child who tested negative upon NGS and CMA and harbored an X chromosome de novo pericentric inversion.

Hypothalamic Hamartoma related epilepsy: A systematic review exploring clinical, neuropsychological, and psychiatric outcome after surgery.

The post-surgical outcome for Hypothalamic Hamartoma (HH) related epilepsy in terms of seizure freedom (SF) has been extensively studied, while cognitive and psychiatric outcome has been less frequently reported and defined. This is a systematic review of English language papers, analyzing the post-surgical outcome in series of patients with HH-related epilepsy (≥5 patients, at least 6 months follow-up), published within January 2002-December 2022. SF was measured using Engel scale/equivalent scales.

Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence?

Cenobamate (CNB) is an anti-seizure medication (ASM) approved in 2021 in Europe for adjunctive treatment of focal-onset seizures in adults who were not adequately controlled with at least two previous ASMs. seizure outcome, treatment-emergent adverse events, neuropsychological profile, and blood levels of CNB and concomitant ASM were analyzed in a real world setting in two different Italian epilepsy centers in the context of CNB early access program. All patients performed a general cognitive evaluation, while 32 patients underwent the administration of a battery of neuropsychological tests at baseline and 6 months after CNB treatment.

Fenfluramine below the age of 2 years in Dravet syndrome: What about safety and efficacy?

Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy. Infants with DS are especially vulnerable to the detrimental effects of prolonged and frequent seizures on development. Fenfluramine (FFA) is approved for the treatment of DS in patients aged 2 years and older.

A real-life pilot study of the clinical application of pharmacogenomics testing on saliva in epilepsy.

Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions (ADRs). We investigated the clinical utility of salivary pharmacogenomic testing on epilepsy patients. A commercialized pharmacogenomic salivary test was performed in a cohort of epileptic patients.

Use of cenobamate for the treatment of focal epilepsy: an Italian expert opinion paper.

Introduction: Cenobamate is a new antiseizure medication (ASM) recently introduced in the USA for the treatment of adults with focal-onset seizures. In March 2021, the European Commission authorized its use for the adjunctive treatment of focal-onset seizures with or without secondary generalization (focal seizures with or without progression to bilateral tonic-clonic seizures, according to current ILAE terminology) in adults with epilepsy not adequately controlled despite the treatment with at least two ASMs.

Areas Covered: This review summarizes the mechanism of action, efficacy, and safety of Cenobamate.

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment.

Therapeutic Drug Monitoring of Quinidine in Pediatric Patients with Genetic Variants.

Quinidine (QND) is an old antimalarial drug that was used in the early 20th century as an antiarrhythmic agent. Currently, QND is receiving attention for its use in epilepsy of infancy with migrating focal seizures (EIMFS) due to potassium sodium-activated channel subfamily T member 1 () genetic variants. Here, we report the application of Therapeutic Drug Monitoring (TDM) in pediatric patients carrying genetic variants and orally treated with QND for developmental and epileptic encephalopathies (DEE).

Neurophysiological Findings in Neuronal Ceroid Lipofuscinoses.

Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of neurodegenerative diseases, characterized by progressive cerebral atrophy due to lysosomal storage disorder. Common clinical features include epileptic seizures, progressive cognitive and motor decline, and visual failure, which occur over different time courses according to subtypes. During the latest years, many advances have been done in the field of targeted treatments, and in the next future, gene therapies and enzyme replacement treatments may be available for several NCL variants.

Super-refractory status epilepticus (SRSE): A case series of 22 pediatric patients.

Background: Super-refractory Status Epilepticus (SRSE) is a rare condition in which SE persists or recurs ≥24 h after the onset of anesthesia. Although its characteristics are well defined in adulthood, only few studies on children are available.

Methods: we retrospectively analyzed the population of patients with SRSE aged <18 years treated in the Pediatric Intensive Care Unit of the Bambino Gesù Pediatric Hospital.

Is Cenobamate the Breakthrough We Have Been Wishing for?

Close to one-third of patients with epilepsies are refractory to current anti-seizure medications; however, trials with cenobamate suggest effectiveness in such patients with focal onset seizures. We searched for data published or otherwise reported on cenobamate and outlined these here. Despite being marketed in the USA, few studies are yet published in full, and trials are ongoing.

Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.

Purified cannabidiol (CBD) was administered to highly refractory patients with Dravet (DS) or Lennox-Gastaut (LGS) syndromes in an ongoing expanded access program (EAP). Herein, we report interim results on CBD safety and seizure outcomes in patients treated for a 12-month period. Thirty centers were enrolled from December 2018 to December 2019 within the open-label prospective EAP up to a maximum of 25 mg/kg per day.

New paradigms for the treatment of pediatric monogenic epilepsies: Progressing toward precision medicine.

Despite the availability of 28 antiseizure medications (ASMs), one-third of people with epilepsy fail to achieve sustained freedom from seizures. Clinical outcome is even poorer for children with developmental and epileptic encephalopathies (DEEs), many of which are due to single-gene mutations. Discovery of causative genes, however, has paved the way to understanding the molecular mechanism underlying these epilepsies, and to the rational application, or development, of precision treatments aimed at correcting the specific functional defects or their consequences.

Juvenile myoclonic epilepsy: Long-term prognosis and risk factors.

Objective: Our goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases.

Methods: We retrospectively studied a series of patients diagnosed with JME with 15 years or more of evolution.

Deciphering the premature mortality in PIGA-CDG - An untold story.

Objective: Congenital disorder of glycosylation (CDG) due to a defective phosphatidylinositol glycan anchor biosynthesis class A protein (PIGA) is a severe X-linked developmental and epileptic encephalopathy. Seizures are often treatment refractory, and patients have intellectual disability and global developmental delay. Previous reports have suggested that patients with PIGA-CDG have a high risk of premature mortality.

Impact of COVID-19 pandemic on pediatric patients with epilepsy - The caregiver perspective.

The recent COVID-19 pandemic has disrupted care systems around the world. We assessed how the COVID-19 pandemic affected children with epilepsy in Italy, where lockdown measures were applied from March 8 to May 4, 2020. We compiled an Italian-language online survey on changes to healthcare and views on telehealth.

Neuronal Ceroid Lipofuscinosis: Potential for Targeted Therapy.

Neuronal ceroid lipofuscinosis (NCLs) is a group of inherited neurodegenerative lysosomal storage diseases that together represent the most common cause of dementia in children. Phenotypically, patients have visual impairment, cognitive and motor decline, epilepsy, and premature death. A primary challenge is to halt and/or reverse these diseases, towards which developments in potential effective therapies are encouraging.