Refractory "status dyskineticus" in a child with post-herpes simplex virus 1 N-methyl-D-aspartate receptor encephalitis: a case report.

Background: Herpes simplex virus 1 (HSV-1) encephalitis may result in relapsing neurological symptoms secondary to immune-mediated processes, including anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Refractory status dyskineticus (RSD), a severe subset of status dystonicus, is characterized by a hyperkinetic movement disorder phenotype alongside dystonic features. This critical condition presents substantial challenges in neurocritical care.

Co-occurrence of childhood absence epilepsy and self-limited focal epilepsy interictal discharges: Differences from childhood absence epilepsy alone.

Objective: Some children with Childhood Absence Epilepsy (CAE) exhibit focal abnormalities similar to those observed in Self-Limited Focal Epilepsies of Childhood (SeLFEs). It remains unclear whether this subgroup of patients may present distinct clinical characteristics or prognoses compared to those with CAE and generalized discharges alone. In this study, we retrospectively evaluated the electroclinical features of patients with CAE plus focal abnormalities and compared them with those with CAE lacking focal abnormalities.

Practical management of repeated life-threatening status epilepticus in Alternating Hemiplegia of Childhood: Case report and literature review.

Background: Alternating Hemiplegia of Childhood (AHC) is a severe channelopathy that manifests before 18 months of age, primarily caused by pathogenic variants in the ATP1A3 gene. It is characterized by recurrent and disabling episodes of plegia, dystonia, dysautonomia, along with chronic neurological features and cardiac arrhythmias. About 50% of AHC patients have epilepsy, and a subset of them may develop refractory or super-refractory status epilepticus.

Derivation of the IGGi006-A stem cell line from a patient with CAPRIN1 haploinsufficiency.

CAPRIN1 gene encodes a RNA-binding protein, abundant in the brain where it plays a crucial role, regulating the transport and translation of mRNAs of synaptic proteins.CAPRIN1 haploinsufficiency causes a neurodevelopmental disorder characterized by language impairment/speech delay, intellectual disability, attention deficit, hyperactivity disorder, and autism spectrum disorder. To understand the pathogenesis of this disorder and in view of future treatment, we generated human induced pluripotent stem cells (iPSCs) from a patient carrying the c.

Autoinflammatory encephalopathy due to PTPN1 haploinsufficiency: a case series.

Background: Through the agnostic screening of patients with uncharacterised disease phenotypes for an upregulation of type I interferon (IFN) signalling, we identified a cohort of individuals heterozygous for mutations in PTPN1, encoding the protein-tyrosine phosphatase 1B (PTP1B). We aimed to describe the clinical phenotype and molecular and cellular pathology of this new disease.

Methods: In this case series, we identified patients and collected clinical and neuroradiological data through collaboration with paediatric neurology and clinical genetics colleagues across Europe (Czechia, France, Germany, Italy, Slovenia, and the UK) and Israel.

Novel De Novo RALA Missense Variants Expand the Genotype Spectrum of Hiatt-Neu-Cooper Neurodevelopmental Syndrome.

Background: RALA is a small GTPase from the RAS superfamily implicated in signal transduction and cytoskeletal dynamics. Recently, de novo variants in RALA have been associated with a neurodevelopmental syndrome characterized by intellectual disability (ID), developmental delay (DD), and seizures. So far, only < 12 patients have been reported.

Multidisciplinary, multicenter consensus for the care of patients affected with Sturge-Weber syndrome.

Background: Sturge-Weber Syndrome (SWS) is a rare, sporadic neurocutaneous disorder affecting the skin, brain, and eyes, due to somatic activating mutations in GNAQ or, less commonly, GNA11 gene. It is characterized by at least two of the following features: a facial capillary malformation, leptomeningeal vascular malformation, and ocular involvement. The spectrum of clinical manifestations includes headache, seizures, stroke-like events, intellectual disability, glaucoma, facial asymmetry, gingival hyperplasia, etc.

Subclinical rhythmic EEG discharge of adults (SREDA) in pediatric population: A case series with systematic review of the literature.

Subclinical rhythmic electrographic discharge of adults (SREDA) is one of the rarest and most challenging non-epileptic electroencephalographic variants. Although the pathogenesis of this activity is unclear, an association with vascular insufficiency and cerebral hypoxia has been proposed. SREDA usually occurs in adulthood, but there are few reports in the pediatric population.

Electro-Clinical Features and Functional Connectivity Analysis in SYN1-Related Epilepsy.

Objective: There is currently scarce data on the electroclinical characteristics of epilepsy associated with synapsin 1 (SYN1) pathogenic variations. We examined clinical and electro-encephalographic (EEG) features in patients with epilepsy and SYN1 variants, with the aim of identifying a distinctive electroclinical pattern.

Methods: In this retrospective multicenter study, we collected and reviewed demographic, genetic, and epilepsy data of 19 male patients with SYN1 variants.

Surgical treatment of cavernous malformation-related epilepsy in children: case series, systematic review, and meta-analysis.

Objective: Cerebral cavernous malformations (CCMs) are cerebral vascular lesions that occasionally occur with seizures. We present a retrospective case series from IRCCS Gaslini Children's Hospital, a systematic review, and meta-analysis of the literature with the goal of elucidating the post-surgery seizure outcome in children with CCMs.

Methods: a retrospective review of children with cavernous malformation related epilepsy who underwent surgery at Gaslini Children's Hospital from 2005 to 2022 was conducted.

Innovative LC-MS/MS method for therapeutic drug monitoring of fenfluramine and cannabidiol in the plasma of pediatric patients with epilepsy.

We present a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying fenfluramine (FFA), its active metabolite norfenfluramine (norFFA), and Epidyolex®, a pure cannabidiol (CBD) oral solution in plasma. Recently approved by the EMA for the adjunctive treatment of refractory seizures in patients with Dravet and Lennox-Gastaut syndromes aged above 2 years, FFA and CBD still do not have established therapeutic blood ranges, and thus need careful drug monitoring to manage potential pharmacokinetic and pharmacodynamic interactions. Our method, validated by ICH guidelines M10, utilizes a rapid extraction protocol from 100 µL of human plasma and a reversed-phase C-18 HPLC column, with deuterated internal standards.

A de novo frameshift variant in MED13 gene in a patient with autism spectrum disorder and magnetic resonance imaging abnormalities mimicking tuberous sclerosis.

The mediator complex subunit 13 (MED13) gene is implicated in neurodevelopmental disorders including autism spectrum disorder (ASD), intellectual disability, and speech delay with varying severity and course. Additional, extra central nervous system, features include eye or vision problems, hypotonia, congenital heart abnormalities, and dysmorphisms. We describe a 7-year- and 4-month-old girl evaluated for ASD whose brain magnetic resonance imaging was suggestive of multiple cortical tubers.

Brain and spine malformations and neurodevelopmental disorders in a cohort of children with CAKUT.

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20-30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features in children with CAKUT.

Methods: We reviewed the clinico-radiological and genetic data of 199 out of 1,165 children with CAKUT evaluated from 2006 to 2023 (99 males, mean age at MRI 6.

Novel Variant in an Adult Individual Affected by Intellectual Disability and Epilepsy: A Cold Case Solved through Whole-Exome Sequencing.

Introduction: Nowadays, whole-exome sequencing (WES) analysis is an essential part in the diagnostic pathway of individuals with complex phenotypes when routine exams, such as array-CGH and gene panels, have proved inconclusive. However, data on the diagnostic rate of WES analysis in adult individuals, negative to first-tier tests, are lacking. This is because initiatives with the aim of diagnosing rare diseases focus mainly on pediatric unsolved cases.

MYT1L variant inherited by a mosaic father in a case of severe developmental and epileptic encephalopathy.

The MYT1L gene plays a critical role in brain development, promoting the differentiation and proliferation of cells, important for the formation of brain connections. MYT1L is also involved in regulating the development of the hypothalamus, which is a crucial actor in weight regulation. Genetic variants in the MYT1L are associated with a range of developmental disorders, including intellectual disability, autism spectrum disorder, facial dysmorphisms, and epilepsy.

Acute pediatric encephalitis: etiology, course, and outcome of a 12-year single-center immunocompetent cohort.

Background: Encephalitis is an uncommon but severe disorder due to an inflammation of the brain parenchyma, usually diagnosed on clinical, laboratory, electroencephalographic, and neuroradiological features. New causes of encephalitis have been reported in recent years, so diagnostic criteria have changed over time. We report on a single-center experience of a pediatric Hospital, the hub of its region, over 12 years (2008-2021), with the evaluation of all children managed for acute encephalitis.

Genotype-phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder.

Contactin-associated protein-like 2 (CNTNAP2) gene encodes for CASPR2, a presynaptic type 1 transmembrane protein, involved in cell-cell adhesion and synaptic interactions. Biallelic CNTNAP2 loss has been associated with "Pitt-Hopkins-like syndrome-1" (MIM#610042), while the pathogenic role of heterozygous variants remains controversial. We report 22 novel patients harboring mono- (n = 2) and bi-allelic (n = 20) CNTNAP2 variants and carried out a literature review to characterize the genotype-phenotype correlation.

Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.

We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in (). MAP4K4 has been implicated in many signaling pathways including c-Jun N-terminal and RAS kinases and is currently under investigation as a druggable target for multiple disorders. Using several zebrafish models, we demonstrate that these human variants are either loss-of-function or dominant-negative alleles and show that decreasing Map4k4 activity causes developmental defects.

The phenotypic spectrum of epilepsy associated with periventricular nodular heterotopia.

Background: Periventricular nodular heterotopia (PVNH) is a congenital brain malformation often associated with seizures. We aimed to clarify the spectrum of epilepsy phenotypes in PVNH and the significance of specific brain malformation patterns.

Methods: In this retrospective cohort study, we recruited people with PVNH and a history of seizures, and collected data via medical record review and a standardized questionnaire.