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.

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.

De novo GABRG2 mutations associated with epileptic encephalopathies.

Epileptic encephalopathies are a devastating group of severe childhood onset epilepsies with medication-resistant seizures and poor developmental outcomes. Many epileptic encephalopathies have a genetic aetiology and are often associated with de novo mutations in genes mediating synaptic transmission, including GABA receptor subunit genes. Recently, we performed next generation sequencing on patients with a spectrum of epileptic encephalopathy phenotypes, and we identified five novel (A106T, I107T, P282S, R323W and F343L) and one known (R323Q) de novo GABRG2 pathogenic variants (mutations) in eight patients.

Neuronal networks in epileptic encephalopathies with CSWS.

Objective: The aim of our study was to investigate the neuronal networks underlying background oscillations of epileptic encephalopathy with continuous spikes and waves during slow sleep (CSWS).

Methods: Sleep electroencephalography (EEG) studies before and after the treatment were investigated in 15 patients with CSWS. To investigate functional and effective connectivity within the network generating the delta activity in the background sleep EEG, the methods of dynamic imaging of coherent sources (DICS) and renormalized partial directed coherence (RPDC) were applied.

Analysis of epileptic seizure count time series by ensemble state space modelling.

We propose an approach for the analysis of epileptic seizure count time series within a state space framework. Time-dependent dosages of several simultaneously administered anticonvulsants are included as external inputs. The method aims at distinguishing which temporal correlations in the data are due to the medications, and which correspond to an unrelated background signal.

Costs of epilepsy and cost-driving factors in children, adolescents, and their caregivers in Germany.

Objective: To provide first data on the cost of epilepsy and cost-driving factors in children, adolescents, and their caregivers in Germany.

Methods: A population-based, cross-sectional sample of consecutive children and adolescents with epilepsy was evaluated in the states of Hessen and Schleswig-Holstein (total of 8.796 million inhabitants) in all health care sectors in 2011.

Altered information processing in children with focal epilepsies with and without intellectual disability.

The aim of this exploratory study was to investigate the relationship between focal interictal epileptiform discharges (IEDs), intellectual disability and cortical information processing in children with partial epilepsy. Two groups of patients--Group 1 (n = 9 patients) with focal IEDs and normal IQ and Group 2 (n = 10 patients) with focal IEDs and intellectual disability--were compared with 14 healthy control participants. A computerized choice reaction time task (go/no-go paradigm) was performed and event-related potentials (ERPs) were recorded.

Evaluation of health-care utilization in patients with Dravet syndrome and on adjunctive treatment with stiripentol and clobazam.

Dravet syndrome (DS) is a rare, severe childhood epilepsy syndrome that imposes a substantial burden on patients and their caregivers. This study evaluated health-care utilization over a 2-year period in patients with DS at an outpatient clinic of a German epilepsy center. Data on the course of epilepsy, anticonvulsant treatment, and direct costs were recorded using the electronic seizure diary Epivista and patients' files.

Structural genomic variation in childhood epilepsies with complex phenotypes.

A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes.

Atypical vitamin B6 deficiency: a rare cause of unexplained neonatal and infantile epilepsies.

ALDH7A1 and PNPO deficiencies are rare inborn errors of vitamin B6 metabolism causing perinatal seizure disorders. The phenotypic variability, however, is broad. To assess the frequency of these deficiencies in unexplained infantile epilepsy, we screened 113 patients for mutations in both genes.

Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.

Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS). The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.

Everolimus in tuberous sclerosis patients with intractable epilepsy: a treatment option?

Background: Tuberous Sclerosis Complex (TSC) is an often severe neurodevelopmental disorder caused by overactivation of the mTOR pathway due to mutations in either the TSC1 or TSC2 genes. Seizures are the primary cause of neurologic morbidity and often refractory. The mTOR inhibitor everolimus was recently approved for the treatment of giant cell astrocytomas and renal angiomyolipomas in TSC.

EEG-fMRI in atypical benign partial epilepsy.

Atypical benign partial epilepsy (ABPE) is a subgroup among the idiopathic focal epilepsies of childhood. Aim of this study was to investigate neuronal networks underlying ABPE and compare the results with previous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies of related epilepsy syndromes. Ten patients with ABPE underwent simultaneous EEG-fMRI recording.

Variability of EEG-fMRI findings in patients with SCN1A-positive Dravet syndrome.

Purpose: Dravet syndrome (DS) or severe myoclonic epilepsy of infancy is an intractable epileptic encephalopathy of early childhood that is caused by a mutation in the SCN1A gene in most patients. The aim of this study was to identify a syndrome-specific epileptic network underlying interictal epileptiform discharges (IEDs) in patients with DS.

Methods: Ten patients with the diagnosis of DS associated with mutations in the SCN1A gene were investigated using simultaneous recording of electroencephalography and functional magnetic resonance imaging ((EEG-fMRI).

Myoclonic astatic epilepsy (Doose syndrome) - a lamotrigine responsive epilepsy?

Purpose: Myoclonic astatic epilepsy (MAE, Doose syndrome) is a difficult to treat idiopathic generalized epilepsy of early childhood. MAE frequently shows the course of an epileptic encephalopathy and may result in permanent cognitive impairment. Systematic analyses on clinical effects of different AED combinations are still needed.

Neuronal networks in west syndrome as revealed by source analysis and renormalized partial directed coherence.

West syndrome is a severe epileptic encephalopathy of infancy with a poor developmental outcome. This syndrome is associated with the pathognomonic EEG feature of hypsarrhythmia. The aim of the study was to describe neuronal networks underlying hypsarrhythmia using the source analysis method (dynamic imaging of coherent sources or DICS) which represents an inverse solution algorithm in the frequency domain.

CDKL5 mutations as a cause of severe epilepsy in infancy: clinical and electroencephalographic long-term course in 4 patients.

CDKL5 mutations cause severe epilepsy in infancy with subsequent epileptic encephalopathy. As yet, few studies report on long-term observations in patients with CDKL5-related epileptic encephalopathy. In this study, we describe the evolution of the epilepsy phenotype and the electroencephalographic (EEG) features in 4 patients during a maximum observation period of 22 years.

Concentrations of stiripentol in children and adults with epilepsy: the influence of dose, age, and comedication.

Background: Stiripentol (STP) was approved as an orphan drug in 2007 in Europe as adjunctive therapy with valproic acid (VPA) and clobazam (CLB) for Dravet syndrome. Dravet syndrome is a highly pharmacoresistant form of epilepsy, which starts in early childhood. Data about STP pharmacokinetics and interactions are still limited and in part inconsistent.

Beneficial prenatal levodopa therapy in autosomal recessive guanosine triphosphate cyclohydrolase 1 deficiency.

Objective: To report the first prenatal dopaminergic replacement therapy in autosomal recessive (AR) guanosine triphosphate cyclohydrolase 1 (GTPCH) deficiency without hyperphenylalaninemia.

Design: Case reports, literature review, and video presentation.

Setting: University of Lübeck, Lübeck, Germany.

Improving sensitivity of EEG-fMRI studies in epilepsy: the role of sleep-specific activity.

Using simultaneous recordings of EEG and functional MRI (EEG-fMRI) in patients with focal epilepsy, recent studies have revealed insufficient sensitivity and a lack of correspondence between epileptic EEG foci and activation patterns in some patients. In this study of children with focal epilepsy, we explore whether sleep-specific activity (sleep spindles, k-complexes and vertex sharp waves) may increase the sensitivity of EEG-fMRI of interictal epileptiform discharges (IED). When considering the sleep-specific activity in a statistical model, it was possible to increase the statistical significance of the activated voxels inside of the expected source of the IED and to reduce the number of activated voxels outside of it.

Valproate reduces spontaneous generalized spikes and waves but not photoparoxysmal reactions in patients with idiopathic generalized epilepsies.

Purpose: Patients with idiopathic generalized epilepsies (IGEs) often present with interictal spike-wave discharges (SWDs) at rest (spontaneous SWDs), during hyperventilation, and in response to photic stimulation (photoparoxysmal response or PPR). Valproic acid (VPA) is a first-line antiepileptic drug for therapy of patients with IGE. Herein we investigated the effect of VPA on all three types of SWDs in children and adolescents with IGE.

Serum concentrations of rufinamide in children and adults with epilepsy: the influence of dose, age, and comedication.

Rufinamide (RUF) is an orphan drug for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in persons aged 4 years and older. Several studies have investigated the pharmaconkinetics of RUF, but information about interactions is still limited and the results are in part inconsistent. The aim of our study was to analyze the effect of age, gender, daily RUF dose per body weight (mg/kg), valproic acid (VPA), and enzyme-inducing antiepileptic drugs (EIAEDs) on RUF concentration-to-dose ratio (RUF serum concentration/RUF dose per body weight), RUF clearance (RUF dose/RUF serum concentration), and RUF trough concentrations.

EEG-fMRI reveals activation of brainstem and thalamus in patients with Lennox-Gastaut syndrome.

Purpose: Even if etiologies of Lennox-Gastaut syndrome (LGS) are diverse, the multiple causes converge into a final common pathway that results in this specific epilepsy phenotype. There is little knowledge, however, about neuronal networks that may be a part of this pathway.

Methods: To investigate these networks, 11 children with LGS and 9 control children with multifocal epileptic activity were investigated using simultaneous recordings of EEG and functional MRI (EEG-fMRI) in a 3 Tesla scanner.

A retrospective study of the relation between vaccination and occurrence of seizures in Dravet syndrome.

Dravet syndrome is a severe epileptic encephalopathy starting in the first year of life. Mutations in SCN1A can be identified in the majority of patients, and epileptic seizures in the setting of fever are a clinical hallmark. Fever is also commonly seen after vaccinations and provocation of epileptic seizures by vaccinations in patients with Dravet syndrome has been reported, but not systematically assessed.