Children with MOG-IgG positive bilateral optic neuritis misdiagnosed as fulminant idiopathic intracranial hypertension.

Background: Fulminant idiopathic intracranial hypertension (IIH) is characterized by headache, rapid decrease of vision and elevated CSF-opening pressure.

Objective: To delineate a subgroup of MOGAD mimicking fulminant IIH.

Methods: In this case series children with MOGAD with vision loss, optic disc swelling and elevated CSF opening pressure, initially diagnosed with fulminant IIH, were included.

Upregulation vs. loss of function of NTRK2 in 44 affected individuals leads to two distinct neurodevelopmental disorders.

Introduction: Heterozygous pathogenic variants in NTRK2 (HGNC: 8032) have been associated with global developmental delay. However, only scattered cases have been described in small or general studies. The aim of our work was to consolidate our understanding of NTRK2-related disorders and to delineate the clinical presentation METHODS: We report extended cohort of 44 affected individuals, of whom 19 are from the literature and 25 were previously unreported.

Expression of mGluR5 in Pediatric Hodgkin and Non-Hodgkin lymphoma-A Comparative Analysis of Immunohistochemical and Clinical Findings Regarding the Association between Tumor and Paraneoplastic Neurological Disease.

Autoantibodies targeting the neuronal antigen metabotropic glutamate receptor 5 (mGluR5) have been identified in patients with Ophelia syndrome, which describes a co-occurrence of paraneoplastic limbic encephalitis and Hodgkin lymphoma (HL). Little data exist regarding frequency and function of mGluR5 in HL and its potential role in causing seropositive paraneoplastic disease. We studied a representative cohort of pediatric HL and NHL patients (n = 57) using immunohistochemistry and fluorescence staining to investigate mGluR5 expression.

Pediatric de novo movement disorders and ataxia in the context of SARS-CoV-2.

Objective: In the fourth year of the COVID-19 pandemic, mortality rates decreased, but the risk of neuropsychiatric disorders remained the same, with a prevalence of 3.8% of pediatric cases, including movement disorders (MD) and ataxia.

Methods: In this study, we report on a 10-year-old girl with hemichorea after SARS-CoV-2 infection and immunostained murine brain with patient CSF to identify intrathecal antibodies.

Hodgkin Lymphoma Cell Lines and Tissues Express mGluR5: A Potential Link to Ophelia Syndrome and Paraneoplastic Neurological Disease.

Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression.

Autoimmune Encephalitis with Autoantibodies to NMDAR1 following Herpes Encephalitis in Children and Adolescents.

Herpes simplex virus (HSV) type 1 is a frequent pathogen causing infectious encephalitis (HSVE). Early treatment with intravenous acyclovir has led to a significant decrease in mortality. However, especially in children, deterioration during or after HSVE may occur without any evidence of HSV reactivation or improvement following repeated antiviral therapy.

Temporal Dynamics of MOG Antibodies in Children With Acquired Demyelinating Syndrome.

Background And Objective: The spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking.

Modified Zipper Method, a Promising Treatment Option in Severe Pediatric Immune-Mediated Neurologic Disorders.

Objective: To introduce and evaluate a modified version of the "zipper method"-a treatment strategy alternating intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) first reported for 9 pediatric cases of Guillain-Barré syndrome in 2018-for treatment of severe immune-mediated neurologic disorders in children.

Methods: The modified zipper method comprised longer intervals between PLEX-IVIG cycles (48hours instead of 24hours), more cycles (7-10 instead of 5), a consistent plasma volume exchange (instead of the original multistep approach), and variable infusion times for IVIGs (4-8hours). The modified zipper method was applied as an individual treatment approach once standard therapy failed.

A New Mechanism in THRA Resistance: The First Disease-Associated Variant Leading to an Increased Inhibitory Function of THRA2.

The nuclear thyroid hormone receptors (THRs) are key mediators of thyroid hormone function on the cellular level modulation of gene expression. Two different genes encode THRs ( and ), and are pleiotropically involved in development, metabolism, and growth. The THRA1 and THRA2 isoforms, which result from alternative splicing of , differ in their C-terminal ligand-binding domain (LBD).

Novel bi-allelic variants expand the SPTBN4-related genetic and phenotypic spectrum.

Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND, OMIM #617519) is an autosomal recessive disease caused by homozygous or compound heterozygous variants in SPTBN4 coding for type 4 βIV-spectrin, a non-erythrocytic member of the β-spectrin family. Variants in SPTBN4 disrupt the cytoskeletal machinery that controls proper localization of ion channels and the function of axonal domains, thereby generating severe neurological dysfunction. We set out to analyze the genetic causes and describe the clinical spectrum of suspected cases of NEDHND.

Presence of anti-neuronal antibodies in children with neurological disorders beyond encephalitis.

Background: Anti-neuronal autoantibodies have been reported as the cause of several neurologic disorders other than encephalitis. Unfortunately, data are mostly based on serum analysis. Predictions about pathogenicity are thus limited.

Clinical and Magnetic Resonance Imaging Outcome Predictors in Pediatric Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Objective: To evaluate disease symptoms, and clinical and magnetic resonance imaging (MRI) findings and to perform longitudinal volumetric MRI analyses in a European multicenter cohort of pediatric anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) patients.

Methods: We studied 38 children with NMDARE (median age = 12.9 years, range =1-18) and a total of 82 MRI scans for volumetric MRI analyses compared to matched healthy controls.

Fulminant cerebral venous thrombosis associated with the m.3243A>G MELAS mutation: A new guise for an old disease.

MELAS-syndrome (mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes) is a multisystem disorder with various presentations. Common clinical manifestations include stroke-like episodes, encephalopathy with seizures, muscle weakness, recurrent headaches and vomiting, hearing impairment, and short stature. Uncommon clinical presentations like cerebral venous thrombosis, which is almost unprecedented for MELAS-syndrome, impede correct diagnosis.

MutationDistiller: user-driven identification of pathogenic DNA variants.

MutationDistiller is a freely available online tool for user-driven analyses of Whole Exome Sequencing data. It offers a user-friendly interface aimed at clinicians and researchers, who are not necessarily bioinformaticians. MutationDistiller combines MutationTaster's pathogenicity predictions with a phenotype-based approach.

Phenotero: Annotate as you write.

In clinical genetics, the Human Phenotype Ontology as well as disease ontologies are often used for deep phenotyping of patients and coding of clinical diagnoses. However, assigning ontology classes to patient descriptions is often disconnected from writing patient reports or manuscripts in word processing software. This additional workload and the requirement to install dedicated software may discourage usage of ontologies for parts of the target audience.

CSF reactivity in GABA receptor antibody encephalitis - Immunocytochemical distribution in the murine brain.

The y-aminobutyric acid A receptor (GABAR) participates in most neurophysiological processes. Mutations cause epilepsy and neuropsychiatric pathologies. Recently a severe encephalitis with refractory seizures and antibodies against GABARs has been described.

Variants in EXOSC9 Disrupt the RNA Exosome and Result in Cerebellar Atrophy with Spinal Motor Neuronopathy.

The exosome is a conserved multi-protein complex that is essential for correct RNA processing. Recessive variants in exosome components EXOSC3, EXOSC8, and RBM7 cause various constellations of pontocerebellar hypoplasia (PCH), spinal muscular atrophy (SMA), and central nervous system demyelination. Here, we report on four unrelated affected individuals with recessive variants in EXOSC9 and the effect of the variants on the function of the RNA exosome in vitro in affected individuals' fibroblasts and skeletal muscle and in vivo in zebrafish.

Severe GABA receptor encephalitis without seizures: A paediatric case successfully treated with early immunomodulation.

Background: Autoimmune-mediated processes are the driving force behind many neurological diseases. Autoimmune encephalitis, a group of syndromes, mediated by or at least associated with autoantibodies against neuronal tissue, have gained increasing importance especially in paediatric neurology. Since the first NMDAR encephalitis was described a growing number of patients with encephalopathy, seizures and psychiatric symptoms were found to suffer from treatable autoimmune disorders.