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Background: Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy that presents with frequent and prolonged seizures resistant to treatment as well as cognitive problems such as behavioral and developmental delays. However, there is a lack of scientific literature on the impact of this condition on caregivers and the family unit. Objectives: To find out the social and emotional impact of DS on the family unit, to provide a comprehensive understanding of the disease's effects on both the family and caregivers. Materials and methods: A tailored online survey was administered to Spanish DS families, collecting data on the employment, financial, emotional, and social status of patients and caregivers. Results: A total of 112 Spanish caregivers participated in the study. The mean age of the 112 parents was 46.61 years, and 77.68 % of them were mothers. The majority of caregivers had to quit their jobs or reduce their working hours to take care of their child with DS, being the most of them mothers. Most of the caregivers felt that they were not well-informed by healthcare professionals (HCPs) and the Spanish National Health System (NHS). Despite access to resources, families often face financial strain and challenges in obtaining sufficient support, highlighting the need for enhanced social, economic, and psychological backing. In addition, both sentimental and social relationships were negatively impacted in the vast majority of respondents. Conclusions: The study advocates for policy reforms, integrated social services, community programs, and multidisciplinary efforts to improve the quality of life and social integration for those affected by DS.
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BACKGROUND: Dravet syndrome (DS) is a rare and severe form of epilepsy that begins in infancy, which is primarily caused by pathogenic variants in the SCN1A gene. DS is characterized by prolonged and frequent drug-resistant seizures, as well as developmental delays and behavioral problems. The identification of these comorbidities is based on clinical interview and relies on healthcare professionals (HCPs) experience. METHODS: We assembled a group of expert HCPs and caregivers to create a screening checklist for assessing DS-Associated Neuropsychiatric Comorbidities (DANC). The checklist includes questions related to cognitive and psychiatric domains, motor skills, and the impact of DS on families' daily lives. We administered the checklist to 24 caregivers of DS patients from Belgium, France, and Spain. After piloting, we obtained feedback from expert HCPs and caregivers to refine the checklist. RESULTS: DS patients showed a wide array of neuropsychiatric symptoms related to DS. The most common cognitive domains reported were attention difficulties and multitasking problems (18/24 caregivers), and impulsivity (17/24), while the most common psychiatric symptoms were temper tantrums (14/24), mood swings (13/24) and autism spectrum disorder (12/24). Balance and coordination problem have been reported in almost all patients with a statement of only 4/23 with complete mobility. Most patients were dependent on others for self-care and eating, and presented sleeping disturbances. Caregivers reported high levels of stress in the family unit, both between siblings and parents. Results show that the main concerns of parents were the behavior and the cognition of the person with DS. The quantitative feedback results showed good-to-very good scores on usefulness, ease of completion, clarity and comprehensiveness of the checklist. CONCLUSIONS: This pilot study suggests that the DANCE checklist could be a useful screening tool in daily practice for neuropsychiatric comorbidities facilitating their diagnosis and treatment, and empowering both caregivers and patients.
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OBJECTIVES: Dravet syndrome (DS) is a rare form of refractory epilepsy that begins in the first year of life. Approximately 85% of patients have a mutation in the SCN1A gene, which encodes a voltage-gated sodium channel. The main objective of the present work was to assess the degree of knowledge of DS among Spanish primary care (PC) professionals, the communication flow between them and the pediatric neurologists (PNs), and the services available and resources offered to patients in Spain when searching for a diagnosis and adequate treatment. METHODS: Two anonymized online surveys on DS diagnosis and patient management in PC were conducted with Spanish PC pediatricians (PCPs) and caregivers of DS patients in Spain. RESULTS: Most PCPs are aware of genetic epilepsy but lack full knowledge of DS and patient advocacy groups (PAGs). Access to epilepsy treatments varies among regions, with many referrals to hospitals and pediatric neurologists. Diagnosis is often delayed, with misdiagnoses and frequent emergency room (ER) visits. Treatment involves multiple drugs, and sodium channel blockers are used, which are contraindicated in DS treatment. Improved training, resources, and communication are needed for early diagnosis. SIGNIFICANCE: To improve the care and treatment of DS patients in Spain, early diagnosis is required and, possibly, specific efforts aimed at identifying patients in adulthood, generating socio-sanitary structures that integrate social and health services to provide comprehensive care, taking into account the different features and comorbidities of the disease. PLAIN LANGUAGE SUMMARY: Dravet syndrome (DS) is a form of genetic epilepsy that starts within the first year of life. We present a study showing that, while family doctors are aware of genetic epilepsies, many don't have a complete understanding of DS. Unfortunately, getting the right diagnosis can take a long time, leading to unnecessary visits to the emergency room. Patients often need several medications, and sometimes they're given drugs that aren't recommended for DS. The takeaway is that training for doctors, more resources, and improved communication could help creating better healthcare systems and therefore give easier access to the right therapies.
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Dravet syndrome (DS) is a genetic rare disease, which is usually caused by a mutation in the SCN1A gene. DS is characterised by a drug-resistant epilepsy and by cognitive and behavioural disturbances. Thus, DS patients require both pharmacological and non-pharmacological treatments. However, there is a paucity of studies on non-pharmacological therapies and their potential benefits. The main aim of this study was to describe the non-pharmacological therapy modalities received by DS patients and their socio-economic impact on the family. Thus, we designed an online survey addressed to caregivers of DS patients. Our results indicated that up to 91.9% of the surveyed patients required non-pharmacological therapies, which were mainly directed to treat cognitive, sensory and motor impairments. In many cases, the economic costs of these therapies were borne entirely by the families. Nevertheless, patients required a deployment of resources not only at a health care level, but also at an educational level.
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Epilepsia Refractaria , Epilepsias Mioclónicas , Humanos , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/terapia , Calidad de Vida/psicología , Encuestas y Cuestionarios , Estado de Salud , Canal de Sodio Activado por Voltaje NAV1.1/genéticaRESUMEN
Dravet syndrome (Dravet) is a severe congenital developmental genetic epilepsy caused by de novo mutations in the SCN1A gene. Nonsense mutations are found in â¼20% of the patients, and the R613X mutation was identified in multiple patients. Here we characterized the epileptic and non-epileptic phenotypes of a novel preclinical Dravet mouse model harboring the R613X nonsense Scn1a mutation. Scn1aWT/R613X mice, on a mixed C57BL/6J:129S1/SvImJ background, exhibited spontaneous seizures, susceptibility to heat-induced seizures, and premature mortality, recapitulating the core epileptic phenotypes of Dravet. In addition, these mice, available as an open-access model, demonstrated increased locomotor activity in the open-field test, modeling some non-epileptic Dravet-associated phenotypes. Conversely, Scn1aWT/R613X mice, on the pure 129S1/SvImJ background, had a normal life span and were easy to breed. Homozygous Scn1aR613X/R613X mice (pure 129S1/SvImJ background) died before P16. Our molecular analyses of hippocampal and cortical expression demonstrated that the premature stop codon induced by the R613X mutation reduced Scn1a mRNA and NaV1.1 protein levels to â¼50% in heterozygous Scn1aWT/R613X mice (on either genetic background), with marginal expression in homozygous Scn1aR613X/R613X mice. Together, we introduce a novel Dravet model carrying the R613X Scn1a nonsense mutation that can be used to study the molecular and neuronal basis of Dravet, as well as the development of new therapies associated with SCN1A nonsense mutations in Dravet.
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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 2â¯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.
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Epilepsias Mioclónicas , Fenfluramina , Anticonvulsivantes/uso terapéutico , Técnicas de Apoyo para la Decisión , Epilepsias Mioclónicas/tratamiento farmacológico , Síndromes Epilépticos , Fenfluramina/uso terapéutico , Humanos , Calidad de Vida , Convulsiones/tratamiento farmacológico , España , Espasmos InfantilesRESUMEN
Dravet syndrome (DS) is a severe, rare, and complex developmental and epileptic encephalopathy affecting 1 in 16 000 live births and characterized by a drug-resistant epilepsy, cognitive, psychomotor, and language impairment, and behavioral disorders. Evidence suggests that optimal treatment of seizures in DS may improve outcomes, even though neurodevelopmental impairments are the likely result of both the underlying genetic variant and the epilepsy. We present an updated guideline for DS diagnosis and treatment, taking into consideration care of the adult patient and nonpharmaceutical therapeutic options for this disease. This up-to-date guideline, which is based on an extensive review of the literature and culminates with a new treatment algorithm for DS, is a European consensus developed through a survey involving 29 European clinical experts in DS. This guideline will serve professionals in their clinical practice and, as a consequence, will benefit DS patients and their families.
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Epilepsias Mioclónicas , Epilepsia , Síndromes Epilépticos , Espasmos Infantiles , Adulto , Epilepsias Mioclónicas/diagnóstico , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/terapia , Epilepsia/terapia , Europa (Continente) , Humanos , LactanteRESUMEN
We explored the impact of coronavirus virus 2019 (COVID-19) pandemic on patients with Dravet syndrome (DS) and their family. With European patient advocacy groups (PAGs), we developed an online survey in 10 languages to question health status, behavior, personal protection, and health services before and after lockdown. Approximately 538 European PAG members received electronic invitations. Survey ran from April 14, to May 17, 2020, with 219 answers; median age 9 year 10 months. Protection against infection was highly used prior to COVID-19, but 88% added facemask-use according to pandemic recommendations. Only one patient was tested positive for COVID-19. Most had stable epilepsy during lockdown, and few families (4%) needed emergency care during lockdown. However, behavior disorder worsened in over one-third of patients, regardless of epilepsy changes. Half of appointments scheduled prior to lockdown were postponed; 12 patients (11%) had appointments fulfilled; and 39 (36%) had remote consultations. Responders welcomed remote consultations. Half of responders were unsatisfied with psychological remote support as only few (21 families) received this support. None of the five of patient in clinical trials stopped investigational treatment. Prior adoption of protective measures against general infection might have contributed to avoiding COVID-19 infections. Protocols for the favored remote contact ought to now be prepared.