Phenotypic Spectrum in Individuals With Pathogenic Loss- and Gain-of-Function Variants.

Background And Objectives: Variants in the gene encoding the γ2 subunit of the γ-aminobutyric acid type A (GABA) receptor are associated with a spectrum of epilepsy phenotypes. These range from simple febrile seizures to more severe conditions, including developmental and epileptic encephalopathies (DEEs). Despite previous analyses suggesting that pathogenic variants may lead to loss-of-function (LoF) receptors, a correlation between functional analysis and clinical phenotypic diversity remains elusive.

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.

Effectiveness of perampanel as only concomitant antiseizure medication for highly active epilepsy: insight from a real-world, multicenter retrospective study.

Introduction: Managing patients with highly frequent seizures poses significant challenges for clinicians due to their high resistance to therapy. This study aims to evaluate the 12-month efficacy, safety, and tolerability of PER as the sole add-on therapy for patients with highly active epilepsy in a real-world setting.

Methods: Data from the previous Italian retrospective, observational, multicenter "PERampanel as Only Concomitant Antiseizure Medication" (PEROC) study were analyzed, categorizing patients by baseline seizure frequency into three groups: < 5, 5-20, and > 20 seizures/month.

Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real-world study.

Objective: This real-world, retrospective, multicenter study aims to investigate the effectiveness of highly purified cannabidiol (CBD) in a large cohort of patients with epilepsy of genetic etiology due to an identified monogenic cause. Additionally, we examine the potential relationship between specific genetic subgroups and treatment response.

Methods: This study was conducted across 27 epilepsy centers and included patients with monogenic epileptic disorders (pathogenic or likely pathogenic variants) who were treated with highly purified CBD for at least 3 months.

The Interplay Between Gut Microbiota, Adipose Tissue, and Migraine: A Narrative Review.

Background: Migraine, a prevalent neurovascular disorder, affects millions globally and is associated with significant morbidity. Emerging evidence suggests a crucial role of the gut microbiota and adipose tissue in the modulation of migraine pathophysiology, particularly through mechanisms involving neuroinflammation and metabolic regulation.

Material And Methods: A narrative review of the literature from 2000 to 2024 was conducted using the PubMed database.

IL-17 in serum and cerebrospinal fluid of pediatric patients with acute neuropsychiatric disorders: Implications for PANDAS and PANS.

Background: Acute neuropsychiatric disorders are heterogeneous conditions resulting from interaction between genetic and environmental features. Among these, post infectious forms like Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are common. Preclinical studies suggest a role of CNS T-helper-17/interleukin-17 (IL-17) inflammatory mediated response in the pathogenesis of these disorders.

Management, treatment, and clinical approach of Sydenham's chorea in children: Italian survey on expert-based experience.

Sydenham's chorea (SC), an autoimmune disorder affecting the central nervous system, is a pivotal diagnostic criterion for acute rheumatic fever. Primarily prevalent in childhood, especially in developing countries, SC manifests with involuntary movements and neuropsychiatric symptoms. Predominantly occurring between ages 5 and 15, with a female bias, SC may recur, particularly during pregnancy or estrogen use.

Headache in Sturge-Weber syndrome: A systematic review.

Background: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder for which the neurological aspects, particularly headaches, remain poorly understood, despite significantly affecting morbidity. The present study aimed to elucidate the prevalence, characteristics and treatment strategies, as well as explore the pathogenesis of headaches, in SWS.

Methods: Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed observational studies, case reports and series from eight databases (Cochrane Library, EBSCO, Embase, Medline, PubMed, Science Direct, Scopus and Web of Science), published from 1978 to 2023, to investigate the prevalence, characteristics, medication response and pathogenic theories of headaches in SWS.

Exploring Headaches in Pediatric Behçet Disease: Prevalence, Clinical Impact, and Management.

Behçet's Disease (BD), also recognized as Behçet Syndrome, manifests uniquely in pediatric populations as Pediatric Behçet's Disease (PBD), characterized by multisystemic inflammatory symptoms including recurrent oral and genital aphthae, and diverse ocular, vascular, and neurological involvements. This review elucidates the prevalence, burden, and management strategies of headaches in children with PBD, focusing on both primary headaches, such as migraine and tension-type headaches, and secondary headaches linked to systemic disease manifestations. It explores the pathophysiological underpinnings specific to PBD-related headaches and discusses the intricate relationship between systemic inflammatory processes and neurological symptoms.

Depressive symptoms in children and adolescents with epilepsy and primary headache: a cross-sectional observational study.

Background: The primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels.

Methods: 68 pediatric patients aged 6-18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited.

Perampanel in post-stroke epilepsy: Clinical practice data from the PERampanel as Only Concomitant antiseizure medication (PEROC) study.

Introduction: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy. Nevertheless, there is limited evidence regarding the clinical profile of antiseizure medications (ASMs) in PSE. This study aims to evaluate the 12-month effectiveness and tolerability of perampanel (PER) used as only add-on treatment in patients with PSE in a real-world setting.

Best practices for the management of febrile seizures in children.

Febrile seizures (FS) are commonly perceived by healthcare professionals as a self-limited condition with a generally 'benign' nature. Nonetheless, they frequently lead to pediatric consultations, and their management can vary depending on the clinical context. For parents and caregivers, witnessing a seizure can be a distressing experience, significantly impacting their quality of life.

An Ultra-Rare Mixed Phenotype with Combined AP-4 and ERF Mutations: The First Report in a Pediatric Patient and a Literature Review.

The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly.

Structural brain abnormalities in Pallister-Killian syndrome: a neuroimaging study of 31 children.

Background: Pallister-Killian syndrome (PKS) is a rare genetic disorder caused by mosaic tetrasomy of 12p with wide neurological involvement. Intellectual disability, developmental delay, behavioral problems, epilepsy, sleep disturbances, and brain malformations have been described in most individuals, with a broad phenotypic spectrum. This observational study, conducted through brain MRI scan analysis on a cohort of patients with genetically confirmed PKS, aims to systematically investigate the neuroradiological features of this syndrome and identify the possible existence of a typical pattern.

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.

Ataxia Telangiectasia Arising as Immunodeficiency: The Intriguing Differential Diagnosis.

Ataxia telangiectasia (AT) is a rare disease characterized by the early onset and slow progression of neurodegenerative defects, mainly affecting the cerebellum, associated with immunodeficiency and teleangiectasias. Ataxia is the hallmark of the disease and usually its first manifestation. Overt cerebellar ataxia usually becomes evident between 16 and 18 months of age, after the onset of walking, and is characterized by frequent falls and an ataxic gait with an enlarged base.

The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications.

The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear.

Pediatric hypnic headache: a systematic review.

Introduction: Hypnic headache (HH) is a primary headache, and it is considered a rare condition in children. The underlying mechanisms of HH are not yet fully understood. This systematic review aims to provide a comprehensive description of the clinical features of all published cases of pediatric HH.

KIRREL3-related disorders: a case report confirming the radiological features and expanding the clinical spectrum to a less severe phenotype.

Background: Neurodevelopmental disorders have a multifactorial etiology, since biological, genetic, psychosocial and environmental risk factors are involved. Recent studies have been linking neurodevelopmental disorders and intellectual disability with a variety of genes, some of which encoding neuronal cell-adhesion molecules. Among these, KIRREL3 is known to play a role in CNS development, and his variants have recently been related to intellectual disability, autism spectrum disorder, childhood apraxia of speech, cerebellar hypoplasia and mild dysmorphic features.

Congenital Myopathy as a Phenotypic Expression of Gene Mutation: Case Report and Systematic Review of the Literature.

Background: Congenital myopathies are a group of clinically, genetically, and histologically heterogeneous diseases caused by mutations in a large group of genes. One of these is , which is recognized as the cause of Dihydropyridine Receptor Congenital Myopathy.

Methods: To better characterize the phenotypic spectrum of myopathy, we conducted a systematic review of cases in the literature through three electronic databases following the PRISMA guidelines.