Profile of Trofinetide in the Treatment of Rett Syndrome: Design, Development and Potential Place in Therapy.

Trofinetide is a first-in-class pharmacological treatment proposed for patients with Rett Syndrome. It is a long half-life derivative of glycine-proline-glutamate, the tripeptide normally excided from Insulin-like Growth Factor 1 upon degradation. Due to containing glutamate and glycine in its structure, trofinetide is thought to act through NMDA receptor modulation, thus providing a normalization of neuronal activity and survival.

Simultaneous Robotic-Assisted Laser Thermal Ablation of Multiple Cortical Tubers for Drug-Resistant Epilepsy in a 17-Year-Old Patient with Tuberous Sclerosis Complex.

Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a new minimally invasive treatment for tuberous sclerosis complex (TSC)-associated epilepsy in children. This video describes a case of a 17-year-old girl with TSC-associated drug-resistant epilepsy treated with robotic-assisted MRgLITT. In our case, MRgLITT was safe and effective in simultaneous targeting of multiple epileptic tubers in 1 single procedure, leading to a marked decrease in seizure frequency.

Expanding the Mutational Landscape and Clinical Phenotype of CHD2-Related Encephalopathy.

Objectives: To present a case series of novel variants in patients presenting with genetic epileptic and developmental encephalopathy.

Background: CHD2 gene encodes an ATP-dependent enzyme, chromodomain helicase DNA-binding protein 2, involved in chromatin remodeling. Pathogenic variants in CHD2 are linked to early-onset conditions such as developmental and epileptic encephalopathy, drug-resistant epilepsies, and neurodevelopmental disorders.

Low-grade epilepsy-associated tumors: Epilepsy outcome and antiseizure medication discontinuation after lesionectomies as first-line surgical approach in pediatric population.

Objective: This study aimed to evaluate epilepsy outcome and antiseizure medication (ASM) discontinuation after lesionectomies as first surgical approach in pediatric population diagnosed with low-grade epilepsy-associated neuroepithelial tumors (LEATs).

Methods: We conducted a retrospective study. Thirty-six consecutive patients with histological diagnoses of LEATs who underwent surgery between 2018 and 2021 at our institution were included.

X-Linked Epilepsies: A Narrative Review.

X-linked epilepsies are a heterogeneous group of epileptic conditions, which often overlap with X-linked intellectual disability. To date, various X-linked genes responsible for epilepsy syndromes and/or developmental and epileptic encephalopathies have been recognized. The electro-clinical phenotype is well described for some genes in which epilepsy represents the core symptom, while less phenotypic details have been reported for other recently identified genes.

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.

Immediate and progressive neurological damage after electrical injury: A pediatric case report.

Background: An electrical injury can cause multiple consequences, especially to the nervous system, both peripheral and central. Such consequences may present immediately as well as later on.

Aims Of The Study: To report on a case of a 5-year-old boy with focal refractory status epilepticus after an electrical injury.

Mystery(n) Phenotypic Presentation in Europeans: Report of Three Further Novel Missense Variants Leading to Severe Syndromic Forms of Moyamoya Angiopathy and Literature Review.

Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy in some cases occurring in children. Incidence is higher in East Asia, where the heterozygous p.Arg4810Lys variant in (Mysterin) represents the major susceptibility factor.

The Relation of Callous-Unemotional Traits and Bullying in Early Adolescence Is Independent from Sex and Age and Moderated by Conduct Problems.

In youths, callous-unemotional (CU) traits and conduct problems (CP) are independently associated with bullying perpetration and these effects are also observed when controlling for sex. Moreover, research indicates that the co-existence of high levels of both CU and CP further increase the risk. Although several studies have examined the relationship between CU traits and traditional bullying, few have also included a measure of cyberbullying and very few of them have focused the early adolescence.

Neuroendoscopic treatment of symptomatic cyst of the septum pellucidum in children: A case series.

Background: Symptomatic cysts of the septum pellucidum (CSP) are extremely rare in children and surgical indications are not well defined. A very careful clinical and neuroradiologic evaluation is necessary to consider a patient for surgical indication.

Methods: We present a surgical series of 7 pediatric patients.

Temporal lobe malformations, focal epilepsy, and FGFR3 mutations: a non-causal association?

Temporal lobe abnormalities and focal epilepsy have been documented in FGFR3-related clinical condition, including hypochondroplasia and Muenke syndrome. FGFR3 is expressed in the brain during development and could play a role in nervous system development and hippocampal formation. These observations suggest a non-casual association between temporal malformation, epilepsy, and FGFR3 mutations.

Vitamin D deficiency is not related to eating habits in children with Autistic Spectrum Disorder.

Background And Aims: Autism Spectrum Disorder (ASD) is characterized by the impairment of communication and social interaction and by repetitive, restricted and stereotyped interests. ASD is often accompanied by comorbidities; eating disorders are frequent and imply important nutritional deficits (i.e.

Neuronal Avalanches to Study the Coordination of Large-Scale Brain Activity: Application to Rett Syndrome.

Many complex systems, such as the brain, display large-scale coordinated interactions that create ordered patterns. Classically, such patterns have been studied using the framework of criticality, i.e.

A novel RAB39B mutation and concurrent de novo NF1 mutation in a boy with neurofibromatosis type 1, intellectual disability, and autism: a case report.

Background: Mutations in RAB39B at Xq28 causes a rare form of X-linked intellectual disability (ID) and Parkinson's disease. Neurofibromatosis type 1 (NF1) is caused by heterozygous mutations in NF1 occurring de novo in about 50% of cases, usually due to paternal gonadal mutations. This case report describes clinical and genetic findings in a boy with the occurrence of two distinct causative mutations in NF1 and RAB39B explaining the observed phenotype.

Intrafamilial variability in SPTAN1-related disorder: From benign convulsions with mild gastroenteritis to developmental encephalopathy.

Mutations in SPTAN1 gene are responsible for a wide spectrum of neurodevelopmental disorders including early-onset epileptic encephalopathy with progressive brain atrophy, severe intellectual disability with cerebellar malformations, and relatively milder phenotypes with or without epilepsy. Herein, we report three affected individuals including two siblings of 13 and 8 years and their 39-year-old mother, carrying a novel pathogenic variant in SPTAN1 gene. The phenotype of the index cases and their mother was remarkable for the variable expressivity, including benign convulsions with mild gastroenteritis, intellectual disability and developmental encephalopathy with epilepsy.

Epilepsy in NF1: a systematic review of the literature.

Epilepsy is one of the possible neurological manifestations of the neurofibromatosis type 1 (NF1) that represents the most common neurocutaneous disorder. We performed a systematic review of the literature on epilepsy associated with NF1 since 1995 in order to better define prevalence and describe type and causes of seizures. Data on type, nature of studies, number of patients, gender, and inheritance of NF1 were recorded as well as data on causes, type, EEGs, brain imaging, intellectual disability (ID), surgical treatment, and outcome of epilepsy.

Neurophysiological Signatures of Motor Impairment in Patients with Rett Syndrome.

Objective: Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder due to pathogenic mutations in the MECP2 gene. Motor impairment constitutes the core diagnostic feature of RTT. Preclinical studies have consistently demonstrated alteration of excitation/inhibition (E/I) balance and aberrant synaptic plasticity at the cortical level.

Sphingolipid Metabolism Perturbations in Rett Syndrome.

Rett syndrome is a severe neurodevelopmental disorder affecting mostly females and is caused by loss-of-function mutations in the gene that encoded the methyl-CpG-binding protein 2. The pathogenetic mechanisms of Rett syndrome are not completely understood and metabolic derangements are emerging as features of Rett syndrome. We performed a semi-quantitative tandem mass spectrometry-based analysis that measured over 900 metabolites on blood samples from 14 female subjects with Rett syndrome carrying mutations.

Clinical evolution and epilepsy outcome in three patients with CDKL5-related developmental encephalopathy.

To further characterise CDKL5-related disorder, previously classified as an early-onset seizure variant of Rett syndrome, which is currently considered a specific and independent early-infantile epileptic encephalopathy. We describe the epileptic phenotype and neurocognitive development in three girls with CDKL5 mutations showing severe neurodevelopmental impairment, with different epileptic phenotypes and severity. The patients differed regarding age at epilepsy onset, seizure frequency, duration of "honeymoon periods", as well as EEG features.

Cognitive Profile, Emotional-Behavioral Features, and Parental Stress in Boys With 47,XYY Syndrome.

Objective: To describe (a) the observed cognitive, emotional, and behavioral phenotype in a cohort of male children with 47,XYY syndrome and (b) stress levels in their parents.

Methods: We conducted a cross-sectional observational study of 11 boys diagnosed with 47,XYY syndrome and compared them with 11 age-matched boys with normal karyotype (46,XY). The participants performed standardized assessments of cognitive function, emotional state, and behavioral features; the parents completed a questionnaire evaluating parental stress.