Efficacy and safety of corticosteroids and ACTH in epileptic syndromes beyond Infantile Epileptic Spasms Syndrome (IESS): A systematic review and meta-analysis.

We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti-seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates.

Mutations in plasticity-related-gene-1 (PRG-1) protein contribute to hippocampal seizure susceptibility and modify epileptic phenotype.

The Phospholipid Phosphatase Related 4 gene (PLPPR4,  *607813) encodes the Plasticity-Related-Gene-1 (PRG-1) protein. This cerebral synaptic transmembrane-protein modulates cortical excitatory transmission on glutamatergic neurons. In mice, homozygous Prg-1 deficiency causes juvenile epilepsy.

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.

EEG-Findings during long-term treatment with everolimus in TSC-associated and therapy-resistant epilepsies in children.

Aim: This prospective observational study evaluated the long-term EEG changes in children treated with everolimus (EVO) for refractory TSC-associated epilepsy. Changes in EEG-abnormalities were related to developmental outcomes.

Methods: Thirteen children treated with EVO were examined for EEG-recorded seizures and interictal epileptic discharges (IED) during a 72-hour-video-EEG-monitoring, which was performed at baseline and repeated at follow-up intervals of at least 9 months.

Neuronal networks underlying ictal and subclinical discharges in childhood absence epilepsy.

Childhood absence epilepsy (CAE), involves 3 Hz generalized spikes and waves discharges (GSWDs) on the electroencephalogram (EEG), associated with ictal discharges (seizures) with clinical symptoms and impairment of consciousness and subclinical discharges without any objective clinical symptoms or impairment of consciousness. This study aims to comparatively characterize neuronal networks underlying absence seizures and subclinical discharges, using source localization and functional connectivity (FC), to better understand the pathophysiological mechanism of these discharges. Routine EEG data from 12 CAE patients, consisting of 45 ictal and 42 subclinical discharges were selected.

Intrathecal application of ethosuximide is highly efficient in suppressing seizures in a genetic model of absence epilepsy.

Systemic drug application is the main approach in epilepsy treatment. However, the central nervous system (CNS) is a challenging target for drug delivery as the blood-brain barrier (BBB) restricts the transfer of drugs into the brain. Accordingly, there is a general interest in developing new therapeutic strategies to improve CNS drug accessibility.

Long-term treatment with everolimus in TSC-associated therapy-resistant epilepsies.

Purpose: To investigate the efficacy and tolerability of long-term treatment with Everolimus (EVO) in patients with tuberous sclerosis complex (TSC) and therapy-resistant epilepsy in a compassionate use trial.

Methods: After a 3-month baseline, patients were treated with EVO. Treatment was divided into treatment phases each lasting at least 9 months.

Differentiating ictal/subclinical spikes and waves in childhood absence epilepsy by spectral and network analyses: A pilot study.

Objective: Childhood absence epilepsy (CAE) is a disease with distinct seizure semiology and electroencephalographic (EEG) features. Differentiating ictal and subclinical generalized spikes and waves discharges (GSWDs) in the EEG is challenging, since they appear to be identical upon visual inspection. Here, spectral and functional connectivity (FC) analyses were applied to routine EEG data of CAE patients, to differentiate ictal and subclinical GSWDs.

Source imaging of deep-brain activity using the regional spatiotemporal Kalman filter.

Background And Objective: The human brain displays rich and complex patterns of interaction within and among brain networks that involve both cortical and subcortical brain regions. Due to the limited spatial resolution of surface electroencephalography (EEG), EEG source imaging is used to reconstruct brain sources and investigate their spatial and temporal dynamics. The majority of EEG source imaging methods fail to detect activity from subcortical brain structures.

Developmental outcomes in children/adolescents and one adult with tuberous sclerosis complex (TSC) and refractory epilepsy treated with everolimus.

This prospective observational study focuses on developmental outcomes in the treatment of tuberous sclerosis complex (TSC) with everolimus (EVO). Fourteen children/adolescents aged 1.7-13.

Neurogeriatrics-a vision for improved care and research for geriatric patients with predominating neurological disabilities.

Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g.

SVD Square-root Iterated Extended Kalman Filter for Modeling of Epileptic Seizure Count Time Series with External Inputs.

In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate.

Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial.

Importance: Fenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens.

Objective: To determine whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were taking stiripentol-inclusive regimens.

Design, Setting, And Participants: This double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted in multiple centers.

A multicenter, matched case-control analysis comparing burden-of-illness in Dravet syndrome to refractory epilepsy and seizure remission in patients and caregivers in Germany.

Objective: To compare direct and indirect costs and quality of life (QoL) of pediatric and adult patients with Dravet syndrome (DS), with drug-resistant epilepsy (DRE) and in seizure remission (SR), and their caregivers, in Germany.

Methods: Questionnaire responses from 93 DS patients and their caregivers were matched by age and gender with responses from 93 DRE and 93 SR patients collected in independent studies, and were compared across main components of QoL, direct costs (patient visits, medication use, care level, medical equipment, and ancillary treatments), and indirect costs (quitting job, reduced working hours, missed days).

Results: Mean total direct costs were highest for DS patients (€4864 [median €3564] vs €3049 [median €1506] for DRE [excluding outliers], P = 0.

Quality of life and correlating factors in children, adolescents with epilepsy, and their caregivers: A cross-sectional multicenter study from Germany.

Purpose: To identify factors correlating with poorer quality of life (QoL) in children and adolescents with epilepsy and regarding QoL and depression of their caregivers in Germany.

Method: A cross-sectional multicenter study on QoL and depression was performed in two representative German states (Hessen and Schleswig-Holstein). Variance analysis, linear regression, and bivariate correlation were used to identify correlating factors for poorer QoL and symptoms of depression.

Linking pre-existing biorepositories for medical research: the PopGen 2.0 Network.

The significance of human biorepositories for modern medical research, particularly for comprehensive population-based genetic analyses, is constantly growing. While large and centralized institutions are usually considered best suited to meet the increasing demand for high-quality "biobanks," most medical research institutions still host rather heterogeneous and fragmented biobanking activities, undertaken by clinical departments with oftentimes rather different scientific scope. Undoubtedly, most clinicians and medical researchers would appreciate infrastructural support in terms of the storage and handling of their biosamples, but they are also likely to expect access to their samples avoiding extensive formal requirements.

Pipeline for Forward Modeling and Source Imaging of Magnetocardiographic Recordings via Spatiotemporal Kalman Filtering.

the aim of this proof-of-concept work was to apply the spatiotemporal Kalman filter (STKF) algorithm to magnetocardiographic (MCG) recordings of the heart. Due to the lack of standardized software and pipelines for MCG source imaging, we needed to construct a pipeline for MCG forward modeling before we could apply the STKF method. In the forward module, the finite element method (FEM) solvers in SimBio software are used to solve the MCG forward problem.

Multifocal epilepsy in children is associated with increased long-distance functional connectivity: An explorative EEG-fMRI study.

Objective: Multifocal epileptic activity is an unfavourable feature of a number of epileptic syndromes (Lennox-Gastaut syndrome, West syndrome, severe focal epilepsies) which suggests an overall vulnerability of the brain to pathological synchronization. However, the mechanisms of multifocal activity are insufficiently understood. This explorative study investigates whether pathological connectivity within brain areas of the default mode network as well as thalamus, brainstem and retrosplenial cortex may predispose individuals to multifocal epileptic activity.

Variants in the ATP1A3 Gene Mutations within Severe Apnea Starting in Early Infancy: An Observational Study of Two Cases with a Possible Relation to Epileptic Activity.

Mutations in the gene are known to cause alternating hemiplegia of childhood (AHC) and rapid-onset dystonia parkinsonism (RDP). Both conditions are childhood-onset neurological disorders with distinct symptoms and different times of onset. has also been associated with CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss).

Mutations in PMPCB Encoding the Catalytic Subunit of the Mitochondrial Presequence Protease Cause Neurodegeneration in Early Childhood.

Mitochondrial disorders causing neurodegeneration in childhood are genetically heterogeneous, and the underlying genetic etiology remains unknown in many affected individuals. We identified biallelic variants in PMPCB in individuals of four families including one family with two affected siblings with neurodegeneration and cerebellar atrophy. PMPCB encodes the catalytic subunit of the essential mitochondrial processing protease (MPP), which is required for maturation of the majority of mitochondrial precursor proteins.

Source reconstruction via the spatiotemporal Kalman filter and LORETA from EEG time series with 32 or fewer electrodes.

The clinical routine of non-invasive electroencephalography (EEG) is usually performed with 8-40 electrodes, especially in long-term monitoring, infants or emergency care. There is a need in clinical and scientific brain imaging to develop inverse solution methods that can reconstruct brain sources from these low-density EEG recordings. In this proof-of-principle paper we investigate the performance of the spatiotemporal Kalman filter (STKF) in EEG source reconstruction with 9-, 19- and 32- electrodes.

Spatial projection as a preprocessing step for EEG source reconstruction using spatiotemporal Kalman filtering.

The reconstruction of brain sources from non-invasive electroencephalography (EEG) or magnetoencephalography (MEG) via source imaging can be distorted by information redundancy in case of high-resolution recordings. Dimensionality reduction approaches such as spatial projection may be used to alleviate this problem. In this proof-of-principle paper we apply spatial projection to solve the problem of information redundancy in case of source reconstruction via spatiotemporal Kalman filtering (STKF), which is based on state-space modeling.