Drug Resistant Epilepsy

The purpose of this study is to assess the safety and performance of the iVEAcare Neuromodulation System for the treatment of drug-resistant epilepsy. The main questions it aims to answer are: What medical problems do participants have when being implanted with and using the iVEAcare system? Does the iVEAcare neurostimulator reduce seizure frequency and severity in patients with drug-resistant epilepsy? Does the iVEAcare neurostimulator improve quality of life in patients with drug-resistant epilepsy? All participants will be implanted with an iVEAcare neurostimulator, and researchers will look at whether any medical problems are caused by the implant procedure or device, and how stimulation changes seizure frequency and severity and participant quality of life compared to when the participant enrolled. Participants will: Be implanted with an iVEAcare device. Visit the clinic 1-month, 3-months, 6-months, 1-year, 18-months and then annually through 5 years where they will be asked to answer questionnaires about their seizures and quality of life. Keep a diary of the number of seizures they have each day.

The goal of this study is to investigate the effects of a non-invasive, low intensity focused ultrasound (LIFU) stimulation on seizure frequency and the epileptogenic network in drug-resistant epilepsy. LIFU uses focused sound waves to modulate deep brain regions and to enable changes in brain network activity. Encephalography (EEG) and behavioral tasks will also be used to study how LIFU affects brain activity.

Drug-resistant focal epilepsy is a severe neurological disease that affects one-third of patients with epilepsy. Surgery is the only potentially curative treatment. Intracerebral exploration by stereo electroencephalography (SEEG) is an important step in the surgical pathway. It aims to establish the precise mapping of the epileptogenic network (EZN), including all the brain regions that generate seizures. At the end of SEEG, SEEG-guided radiofrequency thermocoagulation (SEEG RFTC) represents a therapeutic option that may be efficient as a palliative treatment in patients ineligible for resective surgery, or may lead, in some cases, to a definitive effect, avoiding open surgery. The safety and effectiveness of this approach have been established. However, the odds of remaining seizure-free after one year vary greatly between studies, ranging from 4% to 71%. This disparity in therapeutic responses could be linked to the absence of objective criteria for the selection of targets, but also to the existence of mechanisms of action outside of the direct lesional effect. A decrease in SEEG markers of epileptogenicity may predict thermocoagulation efficiency. However, no data are available regarding changes in alteration of the blood-brain barrier (BBB) connectivity, inflammation, or associated molecular changes and their relationship to prognosis. This study aims to elucidate the mechanisms underlying the clinical effect of SEEG RFTC by studying the changes in electrophysiological (SEEG), structural (ultra-high field MRI), and biological (blood biomarkers of neuro-glio-vascular damage and inflammation, molecular adaptations) markers. They will be correlated with clinical outcome in a prospective cohort of patients with drug-resistant focal epilepsy. As advantages for clinical care, this study will allow selection of RFTC targets based on scientifically validated criteria, and elaboration of predictive scores for therapeutic response in each patient. The primary objective is to study the predictive factors of response to SEEG RFTC, by correlating changes in BBB permeability with clinical response 3 months after RFTC, in a prospective cohort of patients with drug-resistant focal epilepsy.

The aim of the proposed pilot study is to investigate patient tolerability and efficacy of moderate term, repeated exposure of Pulsed Low-Intensity Focused Ultrasound (PLIFUS) in patients with drug-resistant temporal lobe epilepsy.

Epilepsy is one of the most common neurological disorders, with one of the highest morbidity rates of all diseases. Despite the development of new anticonvulsant drugs, around a third of patients suffer from drug-resistant epilepsy (RPE). The onset of RPE can be lengthy, prolonging the period during which affected patients live with seizures that have a negative impact on their quality of life. Epilepsy surgery can be a curative treatment, and can enable anticonvulsant medication to be discontinued, optimizing quality of life and cognitive development. In addition, as it has been shown that the prolonged duration of epilepsy prior to surgery has an impact on the occurrence of postoperative seizures, early surgery is increasingly being considered. Focal cortical dysplasia (FCD) is the leading cause of focal lesional epilepsy and is generally drug-resistant. Good postoperative seizure results after surgical resection are strongly linked to complete resection of the dysplastic tissue. Consequently, accurate localization and precise delineation of FCD lesions are crucial during surgery. Currently, the extent of surgical resection is based primarily on preoperative examination, as the macroscopic appearance of dysplastic tissue does not differ from normal cortex. The various intraoperative techniques available to improve the quality of excision (neuronavigation, ultrasound, intraoperative MRI and intraoperative guidance by fluorescence microscopy) all have their limitations. In this context, new intraoperative tools are needed to help the neurosurgeon delineate lesions during surgery. Intraoperative fluorescence spectroscopy is used for surgical guidance of gliomas and other brain pathologies, and has demonstrated its ability to characterize pathological tissues. DCFs exhibit metabolic differences that can also be detected by 5-amino-levulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence intraoperatively. Indeed, in some patients who underwent surgery after a diagnosis of glioma, fluorescence was observed even though histological analysis classified the excised tissue as DCF. What's more, glioma and DCF share a common feature: the mitochondria of affected cells are deficient in complex IV. Cytochrome c oxidase (CCO) is largely involved in mitochondrial complex IV, and NAD is a central metabolite involved in redox reactions within cells. Both metabolites (CCO and NAD) can be visualized intraoperatively by optical and fluorescence spectroscopy. FLUOFOCODYS is a prospective, non-comparative, single-center, human drug pilot clinical trial. 5 patients will be included.

The goal of this clinical trial is to improve non-invasive identification of epileptogenic networks in drug-resistant epileptic patient. The investigators aim to compare epileptogenic network identification with stereo-EEG (used as glod standard) with the identification of the same network using advanced MRI (rs-fMRI, microstructural analysis of white matter, ...). The main goals are to: 1. Compare the accuracy of network identification. 2. Analyse the effect of the MRI sequences on candidates selection and target identification. Participants will already have been selected for stereoEEG and will undergo a supplementary MRI (about 1h) with the additional MRI sequences. Follow-up MRI are scheduled for patient undergoing a second, therapeutic epileptic surgery.

Epilepsy is a neurological disorder affecting more than 50 million people globally, including more than 260,000 Canadians. Cannabidiol (CBD) reduces seizure frequency and improves quality of life for adults and children with Drug Resistant Epilepsy (DRE). Several uncontrolled, small, open label studies reported that CBD-enriched Cannabis Herbal Extract (CHE) resulted in a reduction of seizure frequency, but we lack critical information on efficacy, comparative effectiveness and dosing of CBD and ∆9-tetrahydrocannabinol (THC) in children and adults with DRE. CAN-DRE is an early phase, triple-blind, placebo-controlled, randomized clinical trial to answer the questions of if cannabinoids work to reduce seizures in children and adults (24 months to 55 years) with DRE and if CBD works better in an isolate or in a CBD-enriched Cannabis Herbal Extract. The primary outcome of CAN-DRE is reported monthly seizure count from baseline to maintenance phase.

The purpose of this study is to assess the safety and performance of the iVEAcare Neuromodulation System for the treatment of drug-resistant epilepsy. The main questions it aims to answer are: What medical problems do participants have when being implanted with and using the iVEAcare system? Does the iVEAcare neurostimulator reduce seizure frequency and severity in patients with drug-resistant epilepsy? Does the iVEAcare neurostimulator improve quality of life in patients with drug-resistant epilepsy? All participants will be implanted with an iVEAcare neurostimulator, and researchers will look at whether any medical problems are caused by the implant procedure or device, and how stimulation changes seizure frequency and severity and participant quality of life compared to when the participant enrolled. Participants will: Be implanted with an iVEAcare device. Visit the clinic 1-month, 3-months, 6-months, 1-year, 18-months and then annually through 5 years where they will be asked to answer questionnaires about their seizures and quality of life. Keep a diary of the number of seizures they have each day.

The goal of this clinical trial is to gauge whether overnight, non-invasive temporal interference (TI) stimulation aimed at the hippocampus can reduce abnormal brain activity linked to seizures and improve sleep in adults with drug-resistant temporal lobe epilepsy. The main questions are: Does overnight TI stimulation lower seizure-related EEG activity during sleep? Does overnight TI stimulation improve sleep quality and sleep patterns measured overnight in the lab? Researchers will compare each participant's nights without stimulation to nights with active stimulation, and will also look at a night after stimulation ends to see whether any changes last. Participants will: Stay in-lab for six days for overnight sleep and EEG monitoring Have one night of monitoring without stimulation Receive TI stimulation during sleep for several nights Have another night of monitoring without stimulation after the stimulation nights Complete brief questionnaires and thinking/memory tasks before and after the stimulation nights Be checked for side effects and comfort during the study and at follow-up

Dravet Syndrome (DS) is a severe neurodevelopmental disease, which is predominantly caused by mutations of SCN1A, the gene coding for Nav1.1 voltage-gated sodium channels. DS is characterized by infancy onset, severe cognitive deficit and drug-resistant seizures, including several generalized convulsive seizures per day and frequent status epilepticus, often triggered by fever or hyperthermia. Among the causes of premature deaths in patients with epilepsy, sudden and unexpected death in epilepsy (SUDEP) represents a major cause. SUDEP is a non-traumatic and non-drowning death in patients with epilepsy, unrelated to a documented status epilepticus. The risk of SUDEP is particularly high in patients suffering from DS, reaching about 9/1000-person-year, as compared to about 1/1000-person-year in people with epilepsy including all disease types. The main clinical risk factor of SUDEP is the frequency of convulsive seizures. Beyond improving seizure control, which we showed to mitigate the SUDEP risk, more specific preventive treatment strategies are still lacking. Experimental and clinical data suggest that most SUDEP cases result from postictal brainstem dysfunction, including central respiratory arrest There is a body of evidence suggesting involvement of serotonin (5HT) dysfunction both in the pathogenesis of epilepsy in DS and in seizure-related respiratory dysfunction. Serotonin indeed plays a key role in the regulation of respiration. Population firing of serotoninergic neurons in the medullary raphe is significantly decreased during the ictal and post-ictal periods, in association with decreased breathing and heart rate during and after seizures. Most importantly, post-mortem data in patients, including DS, showed alteration of neuronal populations in the medulla in SUDEP cases with evidence for greater reduction in neuromodulatory neuropeptidergic and monoaminergic, including serotoninergic, systems. SUDEP in DS might therefore be the result of a seizure-induced fatal apnea in a patient who has developed epilepsy-related vulnerability to central respiratory dysfunction favored by 5HT dysfunction. However, several issues remain to be addressed to identify detailed mechanisms and effective therapies. Among them, a key issue is the exact relation between the alterations of the 5HT pathway observed in DS and epilepsy-related respiratory dysfunction In the present study, the hypothesis is that adult patients with DS might demonstrate specific alterations of the 5HT pathway within the brainstem as assessed by PET imaging. The DRAPETOTINE study will thus focus on imaging 5HT brainstem pathway with PET and MRI in patients with DS to assess if abnormalities can be observed and through comparison with data collected in patients drug-resistant focal epilepsy whether these abnormalities are DS specficic or reflect the consequence on brainstem 5HT pathway of refractory seizures. This study will involve 20 adult patients, including 10 adults with established diagnosis of Dravet Syndrome and 10 patients with drug-resistant focal epilepsy. Ten healthy adults will also be included. Participants will be recruited over a period of 18 months and the duration of participation for each participant will be 2 weeks to 8 weeks

This is a multi-site registry study that aims to collect real-world clinical outcomes and device performance of the OneRF Ablation System. The study focuses on patients with refractory epilepsy who undergo, or are being considered for, sEEG-guided RF ablation using the OneRF Ablation System, as part of routine seizure diagnosis and treatment.

Epilepsy is one of the most common neurological chronic conditions with a serious burden on patients, their caregivers, and society. Drug-resistant epilepsy (DRE) heightens this burden. New approaches are thus a priority. Studies in animal models and humans have shown the link between gut microbiota (GM) and the central nervous system in health, neurological conditions, and neurodevelopmental disorders. DRE has been linked to GM dysbiosis. Preliminary findings in children with DRE showed GM modifications when responding to a ketogenic diet. The mediator role of GM has not yet been studied in DRE patients undergoing surgery/vagal nerve stimulation. CARE's central hypothesis is that the GM and its metabolic profile could contribute to clinical outcomes following these different therapeutic procedures. Identifying microbial biomarkers will enable us to deepen the knowledge of the role of gut-brain axis in epilepsy and to tailor the intervention to each patient based on GM modulation.

This will be a prospective, pilot, open-label, two-arm, parallel-group, randomized study to evaluate the efficacy and safety of low-intensity focused ultrasound (LIFU) neuromodulation using NaviFUS System in patients with drug-resistant epilepsy (DRE).

This will be a prospective, open-label, single-arm, multi-center, pilot study to evaluate the safety, tolerability, and preliminary efficacy of low-intensity focused ultrasound (LIFU) neuromodulation using NaviFUS System in patients with drug-resistant unilateral or bilateral temporal lobe epilepsy (DR-TLE).

The evaluation of neurosurgical outcomes varies from center to center, and the predictive factors that determine these outcomes are not fully known or shared. This study aims to assess outcomes and their predictors using measures agreed upon by the participating centers. Standardizing the evaluation of outcomes and predictors improves the quality of research, allows for data comparison, and facilitates a "common language" in routine clinical practice. Most importantly, it influences therapeutic decisions in various neurosurgical conditions. Clinically, the identified predictors can also be used during preoperative assessments to provide more precise guidance to patients undergoing surgery.

The goal of this observational study is to learn if magnetic resonance imaging guided focused ultrasound (MRgFUS) can treat brain lesions causing epilepsy in children with drug resistant epilepsy. The main questions it aims to answer are: Is MRgFUS safe in children with drug-resistant epilepsy due to central brain lesions? Does MRgFUS treatment reduce seizure frequency and severity and improve quality-of-life? Researchers will prospective assess outcomes following MRgFUS in children. Participants undergoing MRgFUS will complete seizure diaries and questionnaires related to seizure severity and quality-of-life.

Drug-resistant epilepsy represents roughly 40% of people with epilepsy. It is very challenging to stop seizures in this condition, and the treatment options are limited. This study aims to investigate a new treatment that involves using infra-red light. In animals, this treatment has shown promise as a possible way to reduce seizures, but it has not been tested in humans for this. The investigators are interested to know if it can reduce seizures, and how comfortable it is to be treated with this therapy.

Drug-resistant partial epilepsies are disabling diseases for which surgical treatment may be indicated. The determination of the area to be operated (or 'epileptogenic zone') is based on a bundle of clinical arguments and neuroimaging, having a direct impact on surgical success. Epileptic patients have electrical abnormalities that can be detected with surface electrophysiological examinations such as surface EEG or MagnetoEncephalography (MEG). The intracerebral source of these abnormalities can be localized in the brain using source modeling techniques from MEG signals or EEG signals if a sufficient number of electrodes is used (\> 100, so-called high EEG technique Resolution = EEG HR). EEG HR and MEG are two infrequent state-of-the-art techniques. The independent contribution of EEG HR and MEG for the localization of the epileptogenic zone has been shown in several studies. However, several modeling studies have shown that MEG and EEG HR have a different detection capacity and spatial resolution depending on the cortical generators studied. Modeling studies suggest that MEG has better localization accuracy than EEG for most cortical sources. No direct comparison of the locating value of MEG and EEG HR for the localization of the epileptogenic zone has been performed to date in a large-scale clinical study. In this prospective study, 100 patients with partial epilepsy who are candidates for epilepsy surgery, and for some of them with intracranial EEG recording, will benefit from two advanced electrophysiological examinations including magnetoencephalographic recording (MEG). ) interictal electrophysiological abnormalities and high-resolution EEG recording (128 electrodes) in addition to the usual examinations performed as part of the pre-surgical assessment, prior to cortectomy and / or intracranial EEG recording. Based on recent work conducted in humans, we postulate: * that the MEG and the EEG HR make it possible to precisely determine the epileptogenic zone, by using two approaches of definition of the epileptogenic zone (zone operated in the cured patients, zone at the origin of the crises during the intracranial recordings), but that the MEG is a little more precise than the EEG HR for the determination of the epileptogenic zone (we will try to highlight a difference of about 10%) * that the quantitative study of the complementarity between EEG HR and MEG for modeling sources of epileptic spikes will show an added value in the use of both methods compared to the use of only one of the two methods * that it is possible to determine the epileptogenic zone by determining the MEG model zone having the highest centrality value (hub) within the intercritical network by studying networks using graph theory.

A large proportion of patients (approximately 30%) with drug-resistant epilepsy are not eligible for surgical treatment. The alternatives that can be offered to reduce the frequency of seizures are neuromodulation (vagus nerve stimulation (VNS), deep brain stimulation (DBS), or transcranial direct current stimulation (tDCS)). Most of these alternatives require invasive procedures and therefore carry risks. Neurofeedback (NFB) is a potential adjunctive treatment that allows patients to self-modulate brain activity and thus reduce seizure frequency in a non-invasive manner. This technique involves measuring neurophysiological activity using a technical interface to extract a parameter of interest, which is presented in real time to the participant, who has been trained and has learned how to modify it. NFB is of interest in various neurological and psychiatric diseases and can lead to improvement in mood disorders, which are frequently associated with epilepsy. Previous NFB methods in epilepsy aimed to modulate sensorimotor rhythms or slow cortical potentials. The investigators propose an innovative EEG-NFB paradigm based on real-time estimation of EEG functional connectivity (FC) measured on the scalp EEG (NFC-FC). This paradigm was developed based on previous studies demonstrating increased functional brain connectivity during the interictal period and decreased synchrony induced by VNS and transcranial electrical stimulation as a possible anti-epileptic mechanism. This study consists of a randomized, double-blind comparison between NFB-FC and sham-NFB (control). The effect of this functional connectivity-based NeuroFeedBack (NFB-FC) will be evaluated on the number of seizures before and after treatment, as well as on their severity and on criteria related to quality of life. In this study, two healthy volunteers will be recruited in order to generate the sham sessions.

Focal epilepsy is associated with widespread alterations in structural brain connectivity, often present at the disease onset and related to learning disabilities. Whether ongoing seizure activity contributes to network pathology is a matter of debate. This study intends to measure the impact of seizures on structural connectivity on a local and on a global level. In children examined with intracerebral electrodes to evaluate whether a surgical cure can be proposed, we combine intracerebral stereotactic electroencephalography (EEG) recordings with diffusion weighted imaging of white matter fibers. On the local level, the study will quantify the number of deficient connections in the seizure onset zone. On a global level, the study will compare the white matter fibers of the left and right hemisphere to probe whether physiological language lateralization is preserved.

The goal of this clinical trial is to to obtain a significant decrease in seizure frequency in patients with refractory focal epilepsy after applying treatment of cathodal tDCS, compared to sham stimulation drug-resistant epileptic patient. The main questions it aims to answer are: * Changes in quality of life * Percent of newly reported side effects after the stimulation period * Scores in epilepsy severity. Participants will be randomized in a cross-over, and will receive 10 days of tDCS or Sham. Each day will allow 2 periods of 20 minutes stimulation separated by 20 minutes off (with 40 minutes of cathodal stimulation total).

To assess clinical outcomes in drug resistant epileptic pediatric patient by modified atkin diet with focusing on following points: 1. Control of seizures(frequency , duration and numbers of hospital admissions) . 2. Quality of life by pediatric quality of life inventory v4. 3. Cognitive function by stanford binet intelligence scale 5th edition. 4. Growth parameters ( weight, height will be combined to report BMI in kg/m\^2).

The purpose of this project is to conduct a trial to assess whether patients that receive a tablet-based waiting room priority communication tool (the "Epilepsy Visit Planner") have improved outcomes compared to patients that do not receive the tool. The project's hypotheses are: * Patients that receive the Epilepsy Visit Planner will have improved patient-provider communication compared to the non-planner group. * Patients that receive the Epilepsy Visit Planner will have improved quality of life scores. * The Epilepsy Visit Planner will score highly on process measures of feasibility and acceptability, demonstrating suitability for future larger scale study. Additionally, there is a related survey project that is not part of the clinical trial and will not be included in this registration information.

Focused ultrasound (FUS) has been shown to differentially lesion or modulate (excite and inhibit) brain circuit and neural activity across a broad range of acoustic stimulus parameters (intensity, duty cycle, pulse repetition frequency and pulse duration) for decades. From our previous study, FUS sonication may suppress the number of epileptic signal bursts observed in EEG recordings after the induction of acute epilepsy. The presence of the suppressive effect was found in terms of the number of epileptic EEG spikes from the analysis of the unfiltered and theta-band EEG activity, and further discontinue the seizure attacks. EEG activity has also been consistently reported to have a positive correlation with the level of epilepsy, and FUS-mediated reduction of epileptic EEG activity was most notably observed, no matter lesioning or modulating effects. The aims of this study are to demonstrate the safety and efficacy of FUS technology in epilepsy patients and to estimate the optimal parameters of focused ultrasound exposure that will be used in the case of epilepsy.

The goal of this observational study is to learn about the clinical and nutritional effectiveness of ketogenic diet (KD) in pediatric patients with genetic, neurological or metabolic conditions requiring KD. The main question\[s\] it aims to answer are: * does KD support adequate growth? * does KD improve clinical symptoms? * how does KD impact quality of life? Participants will be followed up as per clinical practice