Enhancing Executive Functions in Pediatric Epilepsy: Feasibility and Efficacy of a Computerized Cognitive Training Program.

Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, significantly impacts individuals' neurobiological, cognitive, and social lives. This report presents a feasibility study investigating the effects of a computerized cognitive training program on enhancing executive functions, particularly inhibitory control, in children and adolescents with epilepsy. Employing a pre-test-intervention-post-test design, the study involved 26 participants with diverse epileptic syndromes, focusing on those without severe intellectual disabilities. The intervention, based on the CogniFit Inc. platform, consisted of personalized tasks aiming to improve participants' inhibitory skills over 16 weeks, with an average of 40 sessions completed per participant. Results indicated significant improvements in reaction times and error rates in an anti-saccade task, demonstrating enhanced inhibitory control and general performance post-intervention. These findings suggest that targeted cognitive training is a feasible approach to bolster executive functions in young individuals with epilepsy, potentially improving their academic performance, employability, and social interactions. The study underscores the importance of early cognitive interventions in epilepsy management, highlighting the potential for computerized programs to aid in mitigating cognitive deficits associated with the condition.

The psychosocial impact of caring for children with Dravet Syndrome.

This study examined the psychosocial impact on parents of children affected by Dravet Syndrome (DS), a rare drug-resistant developmental encephalopathic epileptic syndrome which affects children at an early age and that involves severe cognitive, behavioral, and motor impairments. DS has a major negative impact on caregivers, mainly on their physical and mental health, and on their social relationships and economic resources. Similarly, it has been suggested that the quality of life of caregivers and children with DS is lower compared to the general population, especially because of the severe and frequent seizures suffered by the child, leaving caregivers with heavy burdens. The main aim of the current study was to assess in detail the psychosocial impact that having a child with DS represents for their parents or caregivers. To this end, a standardized assessment tool was used, and the results were compared to those of a control group. The results highlighted critical differences in most of the areas explored, revealing a marked difference between parents caring of children with DS and parents of normotypically developing children in the psychosocial wellness. This study provides important qualitative data to help us understand and identify the complexity of DS.

Dataset on the psychosocial impact in families with children with developmental and epileptic encephalopathies.

Caring for children with developmental and epileptic encephalopathies (DEE) can be challenging for primary caregivers due to the complexity of the condition and the need to provide ongoing care. This has a psychosocial impact on their quality of life, including increased stress, anxiety, and depression, as well as an impact on their support network, work, and relationship with the affected child. It is important that caregivers receive help to manage the psychosocial impact of caring for a child with DEE and promote their long-term well-being. Besides, it is critical that policymakers receive quantitative data about this impact to adequately respond to the needs of these families. To this end, a database was developed using the Childhood Rare Epilepsy Social Impact Assessment (CRESIA) psychosocial impact measurement instrument to quantitatively assess the quality of life of caregivers.

Validation of Childhood Rare Epilepsy Social Impact Assessment (CRESIA) to Measure the Social and Family Impact of Rare Childhood Diseases with Epilepsy.

This study addresses the social relevance of low-prevalence childhood diseases and reports the process of generation and validation of a tool to assess the social impact on the direct family environment and the social context of reference. The aim of the process of construction and validation of this instrument is to provide the field with a tool with the capacity to shed light on the social consequences of suffering from a low-prevalence disease, specifically those comorbid with treatment-resistant epileptic seizures of childhood origin. The instrument here presented and called CRESIA (acronym derived from Childhood Rare Epilepsy Social Impact Assessment) provides valuable information on six specific areas framing health, economic, psychological, social, and child-related stressors, as well as family. CRESIA represents a valid and reliable instrument for family members or primary caregivers of children and adolescents with childhood rare epilepsy.

The Charlotte Project: Recommendations for patient-reported outcomes and clinical parameters in Dravet syndrome through a qualitative and Delphi consensus study.

Objective: The appropriate management of patients with Dravet Syndrome (DS) is challenging, given the severity of symptoms and the burden of the disease for patients and caregivers. This study aimed to identify, through a qualitative methodology and a Delphi consensus-driven process, a set of recommendations for the management of DS to guide clinicians in the assessment of the clinical condition and quality of life (QoL) of DS patients, with a special focus on patient- and caregiver-reported outcomes (PROs). Methods: This study was conducted in five phases, led by a multidisciplinary scientific committee (SC) including pediatric neurologists, epileptologists, a neuropsychologist, an epilepsy nurse, and members of DS patient advocates. In phases 1 and 2, a questionnaire related to patients' QoL was prepared and answered by caregivers and the SC. In phase 3, the SC generated, based on these answers and on a focus group discussion, a 70-item Delphi questionnaire, covering six topic categories on a nine-point Likert scale. In phase 4, 32 panelists, from different Spanish institutions and with a multidisciplinary background, answered the questionnaire. Consensus was obtained and defined as strong or moderate if ≥80% and 67-79% of panelists, respectively, rated the statement with ≥7. Phase 5 consisted of the preparation of the manuscript. Results: The panelists agreed on a total of 69 items (98.6%), 54 (77.14%), and 15 (21.43%) with strong and moderate consensus, respectively. The experts' recommendations included the need for frequent assessment of patient and caregivers QoL parameters. The experts agreed that QoL should be assessed through specific questionnaires covering different domains. Likewise, the results showed consensus regarding the regular evaluation of several clinical parameters related to neurodevelopment, attention, behavior, other comorbidities, and sudden unexpected death in epilepsy (SUDEP). A consensus was also reached on the instruments, specific parameters, and caregivers' education in the routine clinical management of patients with DS. Conclusions: This consensus resulted in a set of recommendations for the assessment of clinical and QoL parameters, including PROs, related to the general evaluation of QoL, neurodevelopment, attention, behavior, other comorbidities affecting QoL, SUDEP, and QoL of caregivers/relatives and patients with DS.

The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis.

INTRODUCTION: Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles. Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients' Quality of Life (QoL). Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA. METHOD: A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine's therapeutic impact on patients with DS is considered high and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of efficacy, safety and QoL when compared with available ASMs.

Analysis of endocannabinoid signaling elements and related proteins in lymphocytes of patients with Dravet syndrome.

Cannabidiol (CBD) reduces seizures in childhood epilepsy syndromes including Dravet syndrome (DS). A formulation of CBD has obtained orphan drug designation for these syndromes and clinical trials are currently underway. The mechanism responsible for CBD effects is not known, although it could involve targets sensitive to CBD in other neurological disorders. We believe of interest to investigate whether these potential targets are altered in DS, in particular whether the endocannabinoid system is dysregulated. To this end, lymphocytes from patients and controls were used for analysis of gene expression of transmitter receptors and transporters, ion channels, and enzymes associated with CBD effects, as well as endocannabinoid genes. Plasma endocannabinoid levels were also analyzed. There were no differences between DS patients and controls in most of the CBD targets analyzed, except an increase in the voltage-dependent calcium channel α-1h subunit. We also found that cannabinoid type-2 (CB 2) receptor gene expression was elevated in DS patients, with no changes in other endocannabinoid-related receptors and enzymes, as well as in plasma levels of endocannabinoids. Such elevation was paralleled by an increase in CD70, a marker of lymphocyte activation, and certain trends in inflammation-related proteins (e.g., peroxisome proliferator-activated receptor-γ receptors, cytokines). In conclusion, together with changes in the voltage-dependent calcium channel α-1h subunit, we found an upregulation of CB 2 receptors, associated with an activation of lymphocytes and changes in inflammation-related genes, in DS patients. Such changes were also reported in inflammatory disorders and may indirectly support the occurrence of a potential dysregulation of the endocannabinoid system in the brain.

The European patient with Dravet syndrome: results from a parent-reported survey on antiepileptic drug use in the European population with Dravet syndrome.

Dravet syndrome is a rare form of epilepsy largely refractory to current antiepileptic medications. The only precedents of randomized placebo-controlled trials in Dravet syndrome are the two small trials that led to the approval of stiripentol. With the arrival of new clinical trials for Dravet syndrome, we sought to determine the characteristics of the patient population with Dravet syndrome in Europe today, which has possibly evolved subsequent to the approval of stiripentol and the ability to diagnose milder clinical cases via genetic testing. From May to June 2014, we conducted an online parent-reported survey to collect information about the demographics, disease-specific clinical characteristics, as well as current and past use of antiepileptic medications by European patients with Dravet syndrome. We present data from 274 patients with Dravet syndrome from 15 European countries. Most patients were between 4 and 8years of age, and 90% had known mutations in SCN1A. Their epilepsy was characterized by multiple seizure types, although only 45% had more than 4 tonic-clonic seizures per month on average. The most common drug combination was valproate, clobazam, and stiripentol, with 42% of the total population currently taking stiripentol. Over a third of patients with Dravet syndrome had taken sodium channel blockers in the past, and most had motor and behavioral comorbidities. Our study helps define the current typical European patient with Dravet syndrome. The results from this survey may have important implications for the design of future clinical trials that investigate new treatments for Dravet syndrome.