OBJECTIVES: Current research affirms that sufficiently high knowledge about epilepsy is crucial for reducing stigmatization and improving the quality of life for people with epilepsy. While educational interventions targeting older children, adolescents, and adults are relatively common, there is a notable lack of approaches suitable for preschool children. Building on our previous research, which focused on educational interventions using a game and a story, this study aims to evaluate the effectiveness of two video-based interventions, Campi the Seahorse and Adventure While Fishing, in children aged 5-6 years with no prior knowledge about epilepsy. METHODS: A total of 199 children participated in two intervention studies. Knowledge about epilepsy was assessed through interviews using an 11-item test that had been successfully employed in our previous intervention studies, demonstrating satisfactory internal consistency and construct validity. The level of knowledge was evaluated immediately after each intervention and one month later. Additionally, satisfaction with the intervention and its potential impact on epilepsy-related stigma were measured using a smiley-face scale. RESULTS: The Adventure While Fishing intervention demonstrated notable effectiveness compared to our previously developed intervention using an educational story. Its impact was also significant when compared to the level of knowledge observed in children aged 9-11 years with no prior exposure to epilepsy-related interventions. In contrast, the outcomes of the Campi the Seahorse intervention were significantly poorer across all comparisons, likely due to its insufficient coverage of key aspects of the topic. CONCLUSIONS: The results indicated that the Adventure While Fishing intervention was an effective approach to establishing basic knowledge about epilepsy within the targeted age group. In contrast, the Campi the Seahorse intervention would require further extension and/or modification to achieve sufficient effectiveness for this purpose.
- Klíčová slova
- Educational video, Intervention, Knowledge about epilepsy, Preschool,
- MeSH
- audiovizuální záznam MeSH
- dítě MeSH
- epilepsie * psychologie terapie MeSH
- lidé MeSH
- předškolní dítě MeSH
- vzdělávání pacientů jako téma metody MeSH
- zdraví - znalosti, postoje, praxe * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Despite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator using chemogenetics, it also becomes an "on-demand" treatment. Here, we evaluate a targeted and specific chemogenetic therapy, the PSAM/PSEM system, which holds promise as a potential candidate for clinical application in treating drug-resistant epilepsy. We show that the inert ligand uPSEM817, which selectively activates the chloride-permeable channel PSAM4-GlyR, effectively reduces the number of depolarization-induced action potentials in vitro. This effect is likely due to the shunting of depolarizing currents, as evidenced by decreased membrane resistance in these cells. In organotypic slices, uPSEM817 decreased the number of bursts and peak amplitude of events of spontaneous epileptiform activity. Although administration of uPSEM817 in vivo did not significantly alter electrographic seizures in a male mouse model of temporal lobe epilepsy, it did demonstrate a strong trend toward reducing the frequency of interictal epileptiform discharges. These findings indicate that PSAM4-GlyR-based chemogenetics holds potential as an anti-seizure strategy, although further refinement is necessary to enhance its efficacy.
- MeSH
- akční potenciály účinky léků MeSH
- chemogenetika MeSH
- epilepsie temporálního laloku * terapie genetika MeSH
- epilepsie * terapie genetika MeSH
- genetická terapie * metody MeSH
- hipokampus * metabolismus patofyziologie účinky léků MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Epilepsy is the most common chronic neurological disease, affecting nearly 1%-2% of the world's population. Current pharmacological treatment and regimen adjustments are aimed at controlling seizures; however, they are ineffective in one-third of the patients. Although neuronal hyperexcitability was previously thought to be mainly due to ion channel alterations, current research has revealed other contributing molecular pathways, including processes involved in cellular signaling, energy metabolism, protein synthesis, axon guidance, inflammation, and others. Some forms of drug-resistant epilepsy are caused by genetic defects that constitute potential targets for precision therapy. Although such approaches are increasingly important, they are still in the early stages of development. This review aims to provide a summary of practical aspects of the employment of in vitro human cell culture models in epilepsy diagnosis, treatment, and research. First, we briefly summarize the genetic testing that may result in the detection of candidate pathogenic variants in genes involved in epilepsy pathogenesis. Consequently, we review existing in vitro cell models, including induced pluripotent stem cells and differentiated neuronal cells, providing their specific properties, validity, and employment in research pipelines. We cover two methodological approaches. The first approach involves the utilization of somatic cells directly obtained from individual patients, while the second approach entails the utilization of characterized cell lines. The models are evaluated in terms of their research and clinical benefits, relevance to the in vivo conditions, legal and ethical aspects, time and cost demands, and available published data. Despite the methodological, temporal, and financial demands of the reviewed models they possess high potential to be used as robust systems in routine testing of pathogenicity of detected variants in the near future and provide a solid experimental background for personalized therapy of genetic epilepsies. PLAIN LANGUAGE SUMMARY: Epilepsy affects millions worldwide, but current treatments fail for many patients. Beyond traditional ion channel alterations, various genetic factors contribute to the disorder's complexity. This review explores how in vitro human cell models, either from patients or from cell lines, can aid in understanding epilepsy's genetic roots and developing personalized therapies. While these models require further investigation, they offer hope for improved diagnosis and treatment of genetic forms of epilepsy.
- Klíčová slova
- drug‐resistant epilepsy, genetic testing, in vitro human cell culture, legal and ethical aspects, precision medicine,
- MeSH
- buněčné kultury * MeSH
- epilepsie * genetika terapie MeSH
- indukované pluripotentní kmenové buňky MeSH
- lidé MeSH
- neurony metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: The use of patient-reported outcomes (PRO) in clinical practice is gaining increasing attention. This study aimed to provide a critical assessment of the current state-of-the-art and beliefs about the use of PRO in the management of people with epilepsy across some European countries. METHODS: Structured interviews were conducted with European experts to collect insights about (I) the personal experience with PRO; (II) the value and impact of PRO in the decision-making process at the national level; and (III) the interest for and use of PRO by national health authorities. RESULTS: Nine neurologists (Austria, Belgium, Czechia, Denmark, France, Greece, Italy, Poland, and United Kingdom), three health economists (Portugal, Romania, and Sweden), and one epidemiologist (Slovakia) participated. They all stated that PRO are collected at their own countries in the context of clinical trials and/or specific projects. During everyday clinical practice, PRO are collected routinely/almost routinely in Austria and Sweden and only at the discretion of the treating physicians in Czechia, Denmark, France, Greece, and Portugal. There was complete consensus about the favorable impact that the PRO can have in terms of clinical outcomes, healthcare resources utilization, and general patient satisfaction. Only participants from Portugal and Sweden answered that the PRO are perceived as very important by the National Health Authorities of their respective countries. CONCLUSIONS: Differences exist in attitudes and perspectives about PRO in epilepsy across Europe. An active plan is warranted to harmonize the measurement of PRO and ensure they can be relevant to people with epilepsy and health services.
Epilepsy is a common neurological disorder, with one third of patients not responding to currently available antiepileptic drugs. The proportion of pharmacoresistant epilepsies has remained unchanged for many decades. To cure epilepsy and control seizures requires a paradigm shift in the development of new approaches to epilepsy diagnosis and treatment. Contemporary medicine has benefited from the exponential growth of computational modeling, and the application of network dynamics theory to understanding and treating human brain disorders. In epilepsy, the introduction of these approaches has led to personalized epileptic network modeling that can explore the patient's seizure genesis and predict the functional impact of resection on its individual network's propensity to seize. The application of the dynamic systems approach to neurostimulation therapy of epilepsy allows designing stimulation strategies that consider the patient's seizure dynamics and long-term fluctuations in the stability of their epileptic networks. In this article, we review, in a nontechnical fashion suitable for a broad neuroscientific audience, recent progress in personalized dynamic brain network modeling that is shaping the future approach to the diagnosis and treatment of epilepsy.
- Klíčová slova
- brain stimulation, computational modeling, dynamic systems, epilepsy treatment, surgery,
- MeSH
- antikonvulziva terapeutické užití MeSH
- epilepsie * terapie farmakoterapie MeSH
- lidé MeSH
- mozek MeSH
- záchvaty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antikonvulziva MeSH
Deep brain stimulation (DBS) is an established method in the treatment of not only Parkinson's disease motor complications but also dystonia and tremor, and there are data supporting the efficacy of DBS in epilepsy and some psychiatric problems. The alleviation of the neurologic problems may enable females of childbearing age to consider pregnancy because of being able to take care of their child. The aim of the study is to provide a review of the data available on the effect of DBS on the course of pregnancy and delivery in patients suffering from diseases amenable for DBS treatment (Parkinson's disease, dystonia, obsessive compulsive disorder, Tourette's syndrome, epilepsy). Although data available in the literature on pregnancy and childbirth in patients with an implanted active DBS system are limited to small case series and case reports, the number of younger patients implanted with DBS systems will potentially require more attention beyond specialized DBS centers. In emergency deliveries, general obstetricians and neurosurgeons should be provided with a protocol to prevent injuries to the implanted system with potentially devastating consequences for the patient.
- MeSH
- dítě MeSH
- dystonie * terapie MeSH
- epilepsie * terapie MeSH
- hluboká mozková stimulace * metody MeSH
- lidé MeSH
- Parkinsonova nemoc * terapie MeSH
- těhotenství MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: To review the therapeutic effects of deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) and the predictors of its effectiveness, safety, and adverse effects. METHODS: A comprehensive search of the medical literature (PubMed) was conducted to identify relevant articles investigating ANT-DBS therapy for epilepsy. Out of 332 references, 77 focused on focal epilepsies were reviewed. RESULTS: The DBS effect is probably due to decreased synchronization of epileptic activity in the cortex. The potential mechanisms from cellular to brain network levels are presented. The ANT might participate actively in the network elaborating focal seizures. The effects of ANT-DBS differed in various studies; ANT-DBS was linked with a 41% seizure frequency reduction at 1 year, 69% at 5 years, and 75% at 7 years. The most frequently reported adverse effects, depression and memory impairment, were considered non-serious in the long-term follow-up view. ANT-DBS also has been used in a few cases to treat status epilepticus. CONCLUSIONS: We reviewed the clinical literature and identified several factors that may predict seizure outcome following DBS therapy. More large-scale trials are required since there is a need to explore stimulation settings, apply patient-tailored therapy, and identify the presurgical predictors of patient response. SIGNIFICANCE: A critical review of the published literature on ANT-DBS in focal epilepsy is presented. ANT-DBS mechanisms are not fully understood; possible explanations are provided. Biomarkers of ANT-DBS effectiveness may lead to patient-tailored therapy.
- Klíčová slova
- Anterior thalamic nuclei, Deep brain stimulation, Focal epilepsy,
- MeSH
- epilepsie parciální * terapie MeSH
- epilepsie * terapie MeSH
- hluboká mozková stimulace * MeSH
- lidé MeSH
- nuclei anteriores thalami * MeSH
- záchvaty terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
There is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device provides constrained brain sensing power within a frequency band (power-in-band [PIB]), recorded in 10-min averaged increments. Here, four patients with temporal lobe epilepsy were implanted with an investigational device providing full bandwidth chronic intracranial electroencephalogram (cEEG) from bilateral ANT and hippocampus (Hc). ANT PIB-based seizure detection was assessed. Detection parameters were cEEG PIB center frequency, bandwidth, and epoch duration. Performance was evaluated against epileptologist-confirmed Hc seizures, and assessed by area under the precision-recall curve (PR-AUC). Data included 99 days of cEEG, and 20, 278, 3, and 18 Hc seizures for Subjects 1-4. The best detector had 7-Hz center frequency, 5-Hz band width, and 10-s epoch duration (group PR-AUC = .90), with 75% sensitivity and .38 false alarms per day for Subject 1, and 100% and .0 for Subjects 3 and 4. Hc seizures in Subject 2 did not propagate to ANT. The relative change of ANT PIB was maximal ipsilateral to seizure onset for all detected seizures. Chronic ANT and Hc recordings provide direct guidance for ANT DBS with brain sensing.
- Klíčová slova
- chronic brain recordings, deep brain stimulation, neuromodulation, seizure detection,
- MeSH
- epilepsie * terapie MeSH
- hipokampus diagnostické zobrazování MeSH
- hluboká mozková stimulace * MeSH
- lidé MeSH
- nuclei anteriores thalami * fyziologie MeSH
- thalamus MeSH
- záchvaty diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
OBJECTIVE: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. METHODS: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. RESULTS: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. SIGNIFICANCE: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers.
- Klíčová slova
- Dravet syndrome, autoimmune encephalitis, orphan disease, progressive myoclonic epilepsy, targeted therapies, tuberous sclerosis complex,
- MeSH
- antikonvulziva terapeutické užití MeSH
- dospělí MeSH
- encefalitida imunologie terapie MeSH
- epilepsie myoklonické terapie MeSH
- epilepsie patofyziologie terapie MeSH
- everolimus terapeutické užití MeSH
- kohortové studie MeSH
- kojenec MeSH
- konsensus MeSH
- křeče u dětí * terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- průzkumy a dotazníky MeSH
- tuberózní skleróza * terapie MeSH
- vzácné nemoci * MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- antikonvulziva MeSH
- everolimus MeSH
INTRODUCTION: Vagus nerve stimulation is a palliative treatment for patients with refractory epilepsy to reduce the frequency and intensity of seizures. A bipolar helical electrode is placed around the left vagus nerve at the cervical level and is connected to the pulse generator placed in a subcutaneous pocket, most commonly in the subclavian region. METHODS: Between March 1998 and October 2019, we performed 196 procedures related to the vagal nerve stimulation at the Neurosurgery Department in Motol University Hospital. Of these, 126 patients were vagal nerve stimulator implantation surgeries for intractable epilepsy. The cases included 69 female and 57 male patients with mean age at the time of the implantation surgery 22±12.4 years (range 2.158.4 years). RESULTS: Nine patients (7.1%) were afflicted by complications related to implantation. Surgical complications included postoperative infection in 1.6%, VNS-associated arrhythmias in 1.6%, jugular vein bleeding in 0.8% and vocal cord paresis in 2.4%. One patient with vocal cord palsy also suffered from severe dysphagia. One patient (0.8%) did not tolerate extra stimulation with magnet due to a prolonged spasm in his throat. The extra added benefit of vagus stimulation in one patient was a significant reduction of previously regular severe headaches. CONCLUSION: Vagus nerve stimulation is an appropriate treatment for patients with drug-resistant epilepsy who are not candidates for focal resective surgery. Implantation of the vagus nerve stimulator is a relatively safe operative procedure.
- Klíčová slova
- VNS − complications, epilepsy − epilepsy surgery − vagus nerve stimulation,
- MeSH
- epilepsie terapie MeSH
- lidé MeSH
- nervus vagus MeSH
- neurochirurgické výkony MeSH
- pooperační komplikace MeSH
- předškolní dítě MeSH
- vagová stimulace škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
