Giant axonal neuropathy (GAN): cross-sectional data on phenotypes, genotypes, and proteomic signature from a German cohort.

Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease affecting the peripheral and central nervous system and is caused by bi-allelic variants in the GAN gene, leading to loss of functional gigaxonin protein. A treatment does not exist, but a first clinical trial using a gene therapy approach has recently been completed. Here, we conducted the first systematic study of GAN patients treated by German-speaking child neurologists.

Psychosocial burden in mothers with epilepsy and their caregiver: Feasibility and preliminary results of a digital screening procedure.

Objective: The present study aims to evaluate the feasibility of utilizing a digital procedure to screen for anxiety and depression as well as impairments in psychosocial aspects, such as social support, social activity and quality of life (QoL) in women with epilepsy (WWE) after childbirth. Furthermore, the study intends to digitally screen for burden of the respective caregivers in WWE compared to a healthy control group.

Materials And Methods: This comparative cross-sectional study was conducted in the post-partum period on 30 WWE and 33 healthy controls who gave birth between 01/2018 and 05/2021.

Characterization of the Epileptogenic Phenotype and Response to Antiseizure Medications in Lissencephaly Patients.

Background: Patients with lissencephaly typically present with severe psychomotor retardation and drug-resistant seizures. The aim of this study was to characterize the epileptic phenotype in a genotypically and radiologically well-defined patient cohort and to evaluate the response to antiseizure medication (ASM). Therefore, we retrospectively evaluated 47 patients of five genetic forms (, , , , ) using family questionnaires, standardized neuropediatric assessments, and patients' medical reports.

A multicenter, matched case-control analysis comparing burden of illness among patients with tuberous sclerosis complex related epilepsy, generalized idiopathic epilepsy, and focal epilepsy in Germany.

Background: Depending on the underlying etiology and epilepsy type, the burden of disease for patients with seizures can vary significantly. This analysis aimed to compare direct and indirect costs and quality of life (QoL) among adults with tuberous sclerosis complex (TSC) related with epilepsy, idiopathic generalized epilepsy (IGE), and focal epilepsy (FE) in Germany.

Methods: Questionnaire responses from 92 patients with TSC and epilepsy were matched by age and gender, with responses from 92 patients with IGE and 92 patients with FE collected in independent studies.

Effectiveness of Neuropediatric Inpatient Rehabilitation.

Aim: Inpatient rehabilitation plays an important role in treating neurological diseases in children and adolescents. However, there is a lack of current research concerning this matter. This retrospective study aims to analyze the effectiveness of neuropediatric inpatient rehabilitation, to identify influencing factors, and to examine the importance of inpatient rehabilitation programs.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Real-world data on cannabidiol treatment of various epilepsy subtypes: A retrospective, multicenter study.

Objective: Cannabidiol (CBD) is approved for treatment of Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC). Several studies suggest antiseizure effects also beyond these three epilepsy syndromes.

Methods: In a retrospective multicenter study, we analyzed the efficacy and tolerability of CBD in patients with epilepsy at 16 epilepsy centers.

Treatment of Infantile Spasm Syndrome: Update from the Interdisciplinary Guideline Committee Coordinated by the German-Speaking Society of Neuropediatrics.

Objectives: The manuscript serves as an update on the current management practices for infantile spasm syndrome (ISS). It includes a detailed summary of the level of current evidence of different treatment options for ISS and gives recommendations for the treatment and care of patients with ISS.

Methods: A literature search was performed using the Cochrane and Medline Databases (2014 to July 2020).

L-Serine Treatment is Associated with Improvements in Behavior, EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants.

Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial.

Health-related quality of life in children and adolescents with tuberous sclerosis complex and their caregivers: A multicentre cohort study from Germany.

Objective: This study aimed to measure health-related quality of life (HRQOL) in children and adolescents with tuberous sclerosis complex (TSC) and quality of life (QOL) and depressive symptoms among caregivers.

Methods: Adequate metrics were used to assess HRQOL in children and adolescents with TSC (4-18 years, KINDL) as well as QOL (EQ-5D) and symptoms of depression (BDI-II) among caregivers. Predictors for reduced HRQOL and depressive symptoms were identified by variance analysis, ordinal regression, and bivariate correlation.

Long-term efficacy, tolerability, and retention of brivaracetam in epilepsy treatment: A longitudinal multicenter study with up to 5 years of follow-up.

Objective: This study was undertaken to evaluate the long-term efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice.

Methods: A multicenter, retrospective cohort study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021.

Results: Long-term data for 262 patients (mean age = 40 years, range = 5-81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes.

Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: Compassionate use program in Germany.

Objective: Dravet syndrome (DS) is a rare but severe drug-resistant epilepsy. Before the approval of fenfluramine (FFA) for the treatment of seizures in DS, patients in Germany could receive treatment under a compassionate use program (CUP).

Methods: We conducted a multicenter, retrospective, observational study to describe the efficacy, tolerability, and retention of FFA within the CUP.

Efficacy, Retention and Tolerability of Everolimus in Patients with Tuberous Sclerosis Complex: A Survey-Based Study on Patients' Perspectives.

Background: The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder.

Objective: The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient's perspective.

Methods: A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC.

Quality of life and its predictors in adults with tuberous sclerosis complex (TSC): a multicentre cohort study from Germany.

Background: Tuberous sclerosis complex (TSC) is a monogenetic, multisystemic disease characterised by the formation of benign tumours that can affect almost all organs, caused by pathogenic variations in TSC1 or TSC2. In this multicentre study from Germany, we investigated the influence of sociodemographic, clinical, and therapeutic factors on quality of life (QoL) among individuals with TSC.

Methods: We assessed sociodemographic and clinical characteristics and QoL among adults with TSC throughout Germany using a validated, three-month, retrospective questionnaire.

Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex in children, adolescents, and caregivers: a multicenter cohort study.

Background: Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients.

Methods: A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany.

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis.

Plasticity of synaptic strength and density is a vital mechanism enabling memory consolidation, learning, and neurodevelopment. It is strongly dependent on the intact function of N-Methyl-d-Aspartate Receptors (NMDAR). The importance of NMDAR is further evident as their dysfunction is involved in many diseases such as schizophrenia, Alzheimer's disease, neurodevelopmental disorders, and epilepsies.

Direct and indirect costs and cost-driving factors in adults with tuberous sclerosis complex: a multicenter cohort study and a review of the literature.

Background: Tuberous sclerosis complex (TSC) is a monogenetic, multisystem disorder characterized by benign growths due to TSC1 or TSC2 mutations. This German multicenter study estimated the costs and related cost drivers associated with organ manifestations in adults with TSC.

Methods: A validated, three-month, retrospective questionnaire assessed the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket (OOP), and nursing care-level costs among adult individuals with TSC throughout Germany from a societal perspective (costing year: 2019).

Prescription patterns of antiseizure drugs in tuberous sclerosis complex (TSC)-associated epilepsy: a multicenter cohort study from Germany and review of the literature.

Objective: Seizures are a primary and early disease manifestation of Tuberous Sclerosis Complex (TSC). We aimed to describe the age-stratified patterns of antiseizure drug (ASD) treatments among children, adolescents, and adults with TSC in Germany. Additionally, we reviewed real-world and clinical study evidence regarding ASD utilization in patients with TSC.

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.

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years.