Failed transition to independence in young adults with epilepsy:the role of loneliness

\u3cp\u3ePurpose: Many young adults with epilepsy are still living with their parents (‘failed transition to independence’) despite reaching the adult age. This study evaluated patient-related variables and measures of loneliness correlated to ‘failed transition to independence’ in adults, 25–30 years of age, with (childhood-onset) epilepsy. Methods: Patients with (childhood-onset) epilepsy and 25–30 years of age were recruited from Epilepsy Center Kempenhaeghe. Inclusion criteria were: diagnosis of (childhood-onset) epilepsy, and an (estimated) IQ > 70. Patients were sent one questionnaire and informed consent was obtained from all participants. Questions included the patient's level of functioning and satisfaction on three transitional domains (medical status, educational/vocational status, independence/separation from their parents), satisfaction with their friendships, and the validated De Jong-Gierveld Loneliness Scale. ‘Transition to independence’ was defined and categorized in a continuum with scores ranging from 0 (‘Failed transition’) to 4 for all patients. A Bivariate Correlation analysis was used to compute correlations between patient characteristics and failed transition to independence. Results: 59 patients were included in the analysis, of which 19 (32.2%) had a failed transition to independence. A statistically significant correlation was found between transition to independence and the social loneliness scale (p = 0.047) and the total loneliness scale (p = 0.04), and for the patients self-reported satisfaction with their independence/separation from parents (p = 0.01) and friendships (p = 0.04). Conclusions: Adults with epilepsy with a failed transition to independence experience loneliness and are not satisfied with their current developmental and social situation.\u3c/p\u3

Behavioral side-effects of levetiracetam in children with epilepsy:A systematic review

\u3cp\u3ePurpose Children with epilepsy are more likely to have behavioral problems compared to children without epilepsy. Literature suggests that levetiracetam leads to behavioral side-effects in children with epilepsy. The objective of this study is to provide a better overview of the frequency and variety of behavioral side-effects, which can be initiated by levetiracetam therapy in children with epilepsy. Method Electronic databases used in the search were PubMed, Medline, Cochrane and Embase. Studies were eligible for inclusion when they included children from one month to 18 years of age with a diagnosis of epilepsy, used levetiracetam, had other AEDs on a stable regimen for at least two months, reported about behavioral side-effects and had a follow-up of at least two weeks. Quality assessments and data collection were carried out for all eligible studies. Results Thirteen studies, including 727 patients using levetiracetam, were included in this systematic review. Three randomized controlled trials showed a total of 62 behavioral side-effects in 203 patients, effects which led to discontinuation of levetiracetam in only two of 102 patients (2.0%). Hostility, nervousness and aggression were reported mostly. Meta-analysis showed a statistically significant relative risk of 2.18 for the total number of behavioral side-effects for levetiracetam versus placebo. Observational studies showed mixed results with both behavioral deteriorations and improvements following levetiracetam. Conclusion Based on the findings in this systematic review, children using levetiracetam have a risk of developing several behavioral side-effects such as aggression, hostility and nervousness compared to children who do not use levetiracetam.\u3c/p\u3

Functional network abnormalities consistent with behavioral profile in autism spectrum disorder

\u3cp\u3eAutism spectrum disorder (ASD) is a neurodevelopmental disorder in which the severity of symptoms varies over subjects. The iCAPs model (innovation-driven co-activation patterns) is a recently developed spatio-temporal model to describe fMRI data. In this study, the iCAPs model was employed to find functional imaging biomarkers for ASD in resting-state fMRI data. MRI data from 125 ASD patients and 243 healthy controls was selected from the online ABIDE data repository. Following standard fMRI preprocessing steps, the iCAP patterns were fitted to the data to obtain network time series. Furthermore, specific combinations of iCAPs were mapped to behavioral domain time series. To quantify to which extent the time series contribute to the fMRI dynamics, their (temporal) standard deviation was calculated and compared between patients and controls. Abnormalities were found in networks involving subcortical and limbic areas and default mode network regions. When mapping the network dynamics to behavioral domain time series, abnormalities were found in emotional and visual behavioral subdomains, and within the ASD spectrum were more pronounced in subjects with autism compared to Asperger's syndrome. Also a trend towards impairment in networks facilitating social cognition was found. The functional imaging abnormalities are consistent with the behavioral impairments typical for ASD.\u3c/p\u3

A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy

\u3cp\u3eObjective: To evaluate the efficacy and tolerability of the ketogenic diet (KD) during the first 4 months of a randomized controlled trial (RCT) in refractory epilepsy patients aged 1–18 years. Methods: Children and adolescents with refractory epilepsy, not eligible for epilepsy surgery, were included. Following 1 month at baseline, patients were randomized to either the KD or to care as usual (CAU).Primary outcome is the proportion of patients with at least 50% reduction in seizure frequency at 4 months. Secondary outcomes are mean percentage of baseline seizures, seizure severity, and side effects. Results: Fifty-seven patients were randomized; nine dropped out, leaving 48 for analysis (i.e., 26 KD, 22 CAU). In an intention-to-treat analysis, 13 patients (50%) treated with the KD and four patients (18.2%) of the CAU group were responders.Mean seizure frequency at 4 months compared to baseline, after removal of two outliers in the KD group, was significantly lower (P = 0.024) in the KD group (56%) (95% CI: 36–76) than in the CAU group (99%) (95% CI: 65–133%).Twice as many patients in the KD group had a relevant decrease in seizure severity score (P = 0.070).Patients treated with the KD had a significantly higher score for gastrointestinal symptoms (P = 0.021) without an increase in the total score of side effects. Conclusions: This trial provides class I evidence that the KD is an effective therapy in children and adolescents with refractory epilepsy compared with CAU. Most often reported side effects are gastrointestinal symptoms.The study has been registered with the Netherlands Trial Registry (NTR2498).\u3c/p\u3

A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy

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Transition to adult medical care for adolescents with epilepsy

Introduction\u3cbr/\u3eDuring transition to adult medical care, the adolescent with epilepsy is especially prone to emotional, mental, physical, and social developmental difficulties, leading to stigma and poor psychosocial and socioeconomic outcome in the long term.\u3cbr/\u3eObjectives\u3cbr/\u3eThe aim of this review is twofold: to describe the psychosocial and medical transition from adolescence to adulthood and to evaluate the most effective model for transitional services in adolescents with epilepsy.\u3cbr/\u3eMethods\u3cbr/\u3eWe searched PubMed for quantitative and qualitative data about transition from adolescence to adulthood in patients with epilepsy.\u3cbr/\u3eResults\u3cbr/\u3eA total of 49 articles were retrieved. We reviewed personal, psychosocial, and medical issues during transition and their long-term individual and societal consequences. Identifying risk factors for poor transition can lead to appropriate interventions for patients and their family. Although the concept of multidisciplinary transition care for adolescents with epilepsy is widely recognized, only a few transition clinics have been established. There is lack of evidence for their quality and cost-effectiveness.\u3cbr/\u3eConclusion\u3cbr/\u3eIn addition to medical problems, more attention should be paid to the risk of psychosocial problems during transition from pediatric to adult care. The implementation of transition care for adolescents with epilepsy is considered beneficial; however, its effectiveness should be further investigated.\u3cbr/\u3

Neu\u3csup\u3e3\u3c/sup\u3eCA-RT:a framework for real-time fMRI analysis

\u3cp\u3eReal-time functional magnetic resonance imaging (rtfMRI) allows visualisation of ongoing brain activity of the subject in the scanner. Denoising algorithms aim to rid acquired data of confounding effects, enhancing the blood oxygenation level-dependent (BOLD) signal. Further image processing and analysis methods, like general linear models (GLM) or multivariate analysis, then present application-specific information to the researcher. These processes are typically applied to regions of interest but, increasingly, rtfMRI techniques extract and classify whole brain functional networks and dynamics as correlates for brain states or behaviour, particularly in neuropsychiatric and neurocognitive disorders. We present Neu\u3csup\u3e3\u3c/sup\u3eCA-RT: a Matlab-based rtfMRI analysis framework aiming to advance scientific knowledge on real-time cognitive brain activity and to promote its translation into clinical practice. Design considerations are listed based on reviewing existing rtfMRI approaches. The toolbox integrates established SPM preprocessing routines, real-time GLM mapping of fMRI data to a basis set of spatial brain networks, correlation of activity with 50 behavioural profiles from the BrainMap database, and an intuitive user interface. The toolbox is demonstrated in a task-based experiment where a subject executes visual, auditory and motor tasks inside a scanner. In three out of four experiments, resulting behavioural profiles agreed with the expected brain state.\u3c/p\u3

Wavelet entropy of BOLD time series:an application to Rolandic epilepsy

\u3cp\u3ePurpose: To assess the wavelet entropy for the characterization of intrinsic aberrant temporal irregularities in the time series of resting-state blood-oxygen-level-dependent (BOLD) signal fluctuations. Further, to evaluate the temporal irregularities (disorder/order) on a voxel-by-voxel basis in the brains of children with Rolandic epilepsy. Materials and Methods: The BOLD time series was decomposed using the discrete wavelet transform and the wavelet entropy was calculated. Using a model time series consisting of multiple harmonics and nonstationary components, the wavelet entropy was compared with Shannon and spectral (Fourier-based) entropy. As an application, the wavelet entropy in 22 children with Rolandic epilepsy was compared to 22 age-matched healthy controls. The images were obtained by performing resting-state functional magnetic resonance imaging (fMRI) using a 3T system, an 8-element receive-only head coil, and an echo planar imaging pulse sequence (T\u3csub\u3e2\u3c/sub\u3e \u3csup\u3e*\u3c/sup\u3e -weighted). The wavelet entropy was also compared to spectral entropy, regional homogeneity, and Shannon entropy. Results: Wavelet entropy was found to identify the nonstationary components of the model time series. In Rolandic epilepsy patients, a significantly elevated wavelet entropy was observed relative to controls for the whole cerebrum (P = 0.03). Spectral entropy (P = 0.41), regional homogeneity (P = 0.52), and Shannon entropy (P = 0.32) did not reveal significant differences. Conclusion: The wavelet entropy measure appeared more sensitive to detect abnormalities in cerebral fluctuations represented by nonstationary effects in the BOLD time series than more conventional measures. This effect was observed in the model time series as well as in Rolandic epilepsy. These observations suggest that the brains of children with Rolandic epilepsy exhibit stronger nonstationary temporal signal fluctuations than controls. Level of Evidence: 2. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2017;46:1728–1737.\u3c/p\u3

Cost-effectiveness of the ketogenic diet and vagus nerve stimulation for the treatment of children with intractable epilepsy

\u3cp\u3ePURPOSE: The objective of this study was to estimate the expected cost-utility and cost-effectiveness of the ketogenic diet (KD), vague nerve stimulation (VNS) and care as usual (CAU), using a decision analytic model with a 5-year time horizon.\u3c/p\u3e\u3cp\u3eMETHODS: A Markov decision analytical model was constructed to estimate the incremental costs, quality-adjusted life years (QALYs) and successfully treated patient (i.e. 50% or more seizure reduction) of the treatment strategies KD, VNS and CAU, from a health care perspective. The base case considered children with intractable epilepsy (i.e. two or more antiepileptic drugs had failed) aged between 1 and 18 years. Data were derived from literature and expert meetings. Deterministic and probabilistic sensitivity analyses were performed.\u3c/p\u3e\u3cp\u3eRESULTS: Our results suggest that KD is more effective and less costly, and thus cost-effective compared with VNS, after 12 months. However, compared to CAU, neither KD nor VNS are cost-effective options, they are both more effective but also more expensive (€346,899 and €641,068 per QALY, respectively). At 5 years, VNS is cost-effective compared with KD and CAU (€11,378 and €68,489 per QALY, respectively) and has a 51% probability of being cost-effective at a ceiling ratio of €80,000 per QALY.\u3c/p\u3e\u3cp\u3eCONCLUSIONS: Our results suggest that on average the benefits of KD and VNS fail to outweigh the costs of the therapies. However, these treatment options should not be ignored in the treatment for intractable epilepsy in individual or specific groups of patients. There is a great need for high quality comparative studies with large patient samples which allow for subgroup analyses, long-term follow-up periods and outcome measures that measure effects beyond seizure frequency (e.g. quality of life). When this new evidence becomes available, reassessment of the cost-effectiveness of KD and VNS in children with intractable epilepsy should be carried out.\u3c/p\u3

The cognitive profile of ethosuximide in children

\u3cp\u3eIntroduction: Although ethosuximide is one of the oldest antiepileptic drugs (AEDs), little information is available about the cognitive side effects of ethosuximide. Objective: The aim of this study was to investigate the cognitive profile of ethosuximide. Methods: In this cross-sectional study, we used an extensive neuropsychological test battery in patients with epilepsy aged 6–16 years who were treated with monotherapy ethosuximide. We evaluated the efficacy of the drug by seizure frequency (seizure free or not). Results: We included 61 patients with a mean age of 9.4 years [standard deviation (SD) 2.7] who used on average 686 mg/day (SD 245) ESM as monotherapy. ESM was effective in the majority of the patients (70 % were seizure free for at least 6 months at moment of inclusion). The total study population showed impairments of intelligence, visuomotor, and attentional function including activation/alertness. Comparisons between the well-controlled patients and patients who were not in remission showed significantly lower intelligence values and lower performance on the visual-perceptual and attentional tasks for the group with ongoing seizures. Our results suggested that the higher order cognitive dysfunctions (such as intelligence and visual-perceptual functions) may be regarded as seizure or aetiology effects and that the impaired fluid cognitive functions, such as activation/alertness, sustained auditory attention and attentional control or switching, were due to ESM. Conclusion: This study suggests the attentional dysfunction resulting in psychomotor slowing and alertness deficits may be regarded as effects of ethosuximide. Although no untreated baseline assessment was available, these effects are comparable to those of other AEDs, and ethosuximide may therefore be considered an AED with only mild effects on cognition. As ethosuximide is a first-line therapy for absence seizures in childhood, and drug-induced cognitive impairment may interfere with development, learning, and academic achievement, these findings are of interest to clinicians who prescribe this drug, especially when informing parents.\u3c/p\u3