Clinical Research Directory

A Retrospective Survey-based Multicenter Study to Delineate the Molecular and Phenotypic Spectrum of Epilepsy-dyskinesia Syndromes

The Epilepsy-Dyskinesia Study aims to advance the understanding of the clinical and molecular spectrum of epilepsy-dyskinesia syndromes, monogenic diseases that cause both movement disorders and epilepsy. Addressing challenges in rare disease research -such as small, geographically dispersed patient populations and a lack of standardized protocols- the study employs a multinational retrospective survey endorsed by the International Parkinson and Movement Disorder Society. This survey seeks to collect comprehensive data on clinical features, disease progression, age of onset, genetic variants, and concurrent neurological conditions, standardizing data collection across countries to provide a unified understanding of these conditions. Through retrospective review and molecular data analysis, the study aims to identify patterns and correlations between movement and seizure disorders, uncovering genotype-phenotype relationships. The initiative\'s goals are to enhance understanding of epilepsy-dyskinesia syndromes, inform precision medicine approaches, and foster international collaboration.

A Multicenter Pediatric Deep Brain Stimulation Registry

There is limited data on outcomes for children who have undergone deep brain stimulation (DBS) for movement disorders, and individual centers performing this surgery often lack sufficient cases to power research studies adequately. This study aims to develop a multicenter pediatric DBS registry that allows multiple sites to share clinical pediatric DBS data. The primary goals are to enable large-scale, well-powered analyses of the safety and efficacy of DBS in the pediatric population and to further explore and refine DBS as a therapeutic option for children with dystonia and other hyperkinetic movement disorders. Given the current scarcity of evidence available to clinicians, this centralized multicenter repository of clinical data is critical for addressing key research questions and improving clinical practice for pediatric DBS.

Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing

This study focuses on children with Developmental and Epileptic Encephalopathy (DEE), a severe form of epilepsy that often has a genetic origin. Currently, standard diagnostic tools-known as short-read genome sequencing-fail to provide a diagnosis for over 50% of affected patients because they cannot detect certain complex DNA abnormalities. The purpose of this study is to evaluate the effectiveness of a newer, more advanced technology called Long-read Genome Sequencing (lrWGS). Unlike traditional methods, this technology analyzes very long fragments of DNA, allowing researchers to identify genetic errors that were previously "invisible." The study aims to answer whether Long-read Sequencing can successfully identify the genetic cause of epilepsy in patients who have already received a negative result from standard testing. By finding these missing answers, the research seeks to enable personalized medical treatments, improve genetic counseling for families, and advance our understanding of how these complex neurological conditions develop.

OPM MEG in Pre-surgical Mapping for Patients With Epilepsy

Magnetoencephalography, or "MEG", is a brain-scanning method which has been available for many years. It is used in the UK and worldwide to help patients with epilepsy, who need surgery to resolve their seizures. The MEG scan can help inform the surgeon about where to operate, by mapping the abnormal brain activity caused by epilepsy. During a traditional MEG recording, patients sit very still with their head in a rigid helmet which houses many tiny sensors. This can be uncomfortable, and there are additional problems if the patient is a child, because the helmet is often too big. It is not possible to record useful data from the very youngest children with a traditional MEG scanner. But there is a new generation of MEG systems, called OPM-MEG, which employ lightweight sensors housed in a kind of hat. The hat can be appropriately sized for children, and the patient can move comfortably. The new systems are also more cost-effective to run. It is important to know whether the accepted clinical protocols for using MEG in planning epilepsy surgery can be directly transferred to OPM-MEG. It is also important to understand how the patient experience compares across systems. In this project, 20 volunteer patients will be recruited from among those children already having routine pre-surgical MEG recordings Aston University. They will be invited to participate in an OPM-MEG recording in the same facility at Aston University, so that data from the new OPM-MEG device can be compared with the data from the old MEG scanner. Data analysis pipelines will be streamlined, and the accuracy of the results compared to determine whether the improved sensor arrangement for children in the OPM-MEG system leads to better localisation of epileptiform activity.

The Genetics Navigator: Evaluating a Digital Platform for Genomics Health Services

Genetic testing (GT) (including targeted panels, exome and genome sequencing) is increasingly being used for patient care as it improves diagnosis and health outcomes. In spite of these benefits, genetic testing is a complex and costly health service. This results in unequal access, increased wait times and inconsistencies in care. The use of e-health tools to support genetic testing delivery can result in a better patient experience and reduced distress associated with waiting for results and empower patients to receive and act on medical results. We have previously developed and tested an interactive, adaptable and patient-centred digital decision support tool (Genetics ADvISER) to be used for genetic testing decision making, and have now developed the Genetics Navigator (GN), a patient-centred e-health navigation platform for end-to-end genetic service delivery. The objective of this study is to evaluate the effectiveness of the GN in an RCT in reducing distress with patients and parents of patients being offered genetic testing. Results of this trial will be used to establish whether the GN is effective to use in practice. If effective, GN could fill a critical clinical care gap and improve health outcomes and service use by reducing counselling burden as well as overuse, underuse and misuse of services. These are concerns policy makers seek to address through the triple aims of health care1. This study represents a significant advance in personalized health by assessing the effectiveness of this novel, comprehensive e-health platform to ultimately improve genetic service delivery, accessibility, patient experiences, and patient outcomes.

Prognostic Value of High-resolution Electrical Source Imaging on the Success of Pediatric Focal Epilepsy Surgery

This study investigates the usefulness of high resolution electrical source imaging (HR-ESI) in the setting of presurgical evaluation of drug-resistant focal epilepsy in children. This method is based on an estimation of the intra-cerebral source that produces a signal recorded by scalp electrodes by solving the inverse problem, taking into account attenuation factors resulting from particular conductivity properties of the cerebral, peri-cerebral and cranial tissues. Electrical sources are then fused on structural magnetic resonance imaging (MRI). Scalp EEG recorded using 64 to 256 electrodes refers to as high resolution EEG (HR-EEG), leading to HR-ESI. Studies based on small population of children or on mixt population of children and adults showed that HR-ESI has accuracy values, i.e. percentage of true positives (electrical source localized in the brain area resected and success of surgery) and true negatives (electrical source localized outside the brain area resected and failure of surgery) among the total population, ranging from 50 to 80%. Discrepancies between studies could be explained by the limited number of patients included or by the mixture of pediatric and adult data. Another limitation of previously published studies is that the spatial pattern of dipole source distribution was not taken into account to determine prediction accuracy of ESI. Studies using magnetoencephalography (MEG) to perform magnetic source imaging (MSI) suggest that the spatial pattern of dipole source distribution needs to be considered, a spatially-restricted dipole distribution being associated with better post-surgical outcome when resected. To tackle these issues, the investigators aim to conduct the first large prospective multicentric study in children with focal epilepsy candidates to surgery to assess prediction accuracy of ESI based on the finding of tight clusters of dipoles. This is original as this pattern (tight versus loose cluster of dipoles) has been studied by several researchers using MEG but not using HR-EEG. The investigators make the hypothesis that HR-EEG will allow to identity good candidates for epilepsy surgery and thus to offer this underutilized treatment in more children with better post-surgical outcome. Among the secondary objectives, the investigators will address methodological issues related to the resolution of the inverse problem (methods using distributed sources models versus methods based on equivalent dipole estimation), the potential added value to model high-frequency oscillations (HFO), and the investigators will assess the cost-utility of the HR-ESI procedure.

Registry and Natural History of Epilepsy-Dyskinesia Syndromes

The Registry and Natural History of Epilepsy-Dyskinesia Syndromes is focused on gathering longitudinal clinical data as well as biological samples (blood, urine, and/or skin/tissue) from male and female patients, of all ages, who have a genetic diagnosis of epilepsy-dyskinesia syndromes. Through prospective review and molecular data analysis, the study aims to identify patterns and correlations between movement and seizure disorders, uncovering genotype-phenotype relationships. The initiative's goals are to enhance understanding of epilepsy-dyskinesia syndromes, inform precision medicine approaches, and foster international collaboration.

Effect of Sulthiame on EEG in Childhood Epilepsy Syndromes

The effect of sulthiame on EEG has been studied in epilepsy syndromes of childhood with sleep activation by comparing sleep EEG obtained at baseline and after 4 weeks of treatment. The aim of the study is to know if an effect is still identifiable after 2 weeks of treatment by performing sleep EEG recordings after 2 and 4 weeks of treatment, respectively.

Epilepsy Journey-An Executive Functioning Intervention for Teens With Epilepsy

The goal of this multi-site clinical trial is to determine the effectiveness of two components of a web-based intervention (Epilepsy Journey) to improve executive functioning in adolescents with epilepsy. The two components include web-based modules and problem-solving telehealth sessions with a therapist focused on executive functioning. This trial aims to answer the following questions: 1. Which components of Epilepsy Journey (web-based modules or telehealth sessions with a therapist) are essential for improving executive functioning in adolescents with epilepsy? 2. Which components of Epilepsy Journey (web-based modules or telehealth sessions with a therapist) are essential for improving quality of life in adolescents with epilepsy? Participants will be randomly assigned to one of four groups: 1) Epilepsy Journey web-based modules and telehealth sessions, 2) Epilepsy Journey web-based modules only, 3) telehealth sessions with a therapist only, or 4) treatment as usual. Participants will: * Independently review Epilepsy Journey web-based modules focused on executive functioning skills (\~15-30 minutes) and/or have weekly telehealth sessions (\~30-45 minutes) with a therapist for 14 weeks. * Complete measures of executive functioning (parent and teen-report) and quality of life (teen-report) at the start of the study, 14-, 26-, and 66- weeks after randomization. The NIH toolbox will be completed at the start of the study and 26-weeks after randomization. Additional measures will also be collected.

Invasive Brain-Computer Interfaces for Attention

The goal of this interventional study is to compare if the use of a brain-machine interface (BCI) therapy can improve the symptoms of attentional deficit by producing brain changes in the networks that modulate attention. The investigators intend to work with epileptic participants who do not respond to pharmacological treatment, who will undergo neurosurgery. The questions the study sets out to answer are: 1. is there an improvement of symptoms in an experimental group receiving the treatment versus a sham group receiving a simulation of the treatment? 2. does the application of the therapy before surgery reduce the recovery times of post-surgery cognitive deficits described in the literature? Making use of the information recorded from brain electrodes implanted before a participant's epilepsy surgery, the investigators will create a BCI decoder that works with the available activity sources to establish the level of attention of each participant when performing tasks. Participants: * will perform an offline phase first, which will consist of one day of evaluation, in which they will be familiarized with an attentional task. * will perform a training phase later, which will consist of several days of evaluation, where they will learn to modulate their level of attention. This modulation will be facilitated by the BCI decoder, which will classify the level of attention directly from the brain and provide visual feedback that the participant will use as a guide. If the participant is part of the experimental group (or BCI group), the feedback will work as described and should be easy to follow, but if the participant is part of the Sham group, the feedback will not work according to the brain activity of the actual participant, but according to that of another person. Because of this, a mismatch will be created between the moments a brain experiences inattention, and participants believe they are experiencing inattention. This is a randomized, double-blind study, in which the experimenters will evaluate how the effect of the attentional therapy with BCI affects an BCI group and a Sham group.

Mapping Epileptic Networks Using Multimodal Imaging

Currently, mapping the epileptogenic zone is based on a comprehensive preoperative assessment involving clinical, imaging and electrophysiological examinations. To reduce the need for invasive stereoelectroencephalography (SEEG) explorations, electrophysiological and imaging methods have been developed, such as resting-state functional MRI (fMRI) coupled with electroencephalogram and arterial spin-labeling perfusion MRI (ASL-MRI). It has been published that these new methods enable precise delineation of the epileptogenic zone and better preparation for surgery. The aim is to determine whether, in children with focal lesional epilepsy, the combination of ASL-MRI-EEG and resting-state fMRI-EEG enables precise identification of the epileptogenic zone to be defined by SEEG, the current reference examination.

Effect of Cognitive Behavioral Play Intervention and Epilepsy

The goal of this clinical trial is to assess the effectiveness of Cognitive Behavioral Play Therapy interventions in patients with epilepsy. Children with epilepsy will be randomly assigned to one of two intervention conditions: the experimental group will receive cognitive-behavioral play intervention, while the control group will engage in free play. Assessments will be done at the start (T0) and end (T1) of the intervention, measuring behaviors, coping strategies, positive thinking, problem-solving, and quality of life.

The Mosaic Brain: a New Diagnostic Approach in Focal Epilepsies

Overall, this observational cohort study aims to: 1. Improve our understanding of the genetic architecture of childhood focal epilepsies. 2. Develop a liquid biopsy of cerebrospinal fluid (CSF) and assess feasibility to detect cerebral mosaicism using cell-free DNA (cfDNA) analysis and evaluate its performance against brain tissue on the panel testing. 3. Develop a methodology to use trace tissue from Stereoelectroencephalography (SEEG) DNA and assess feasibility to detect cerebral mosaicism and evaluate its performance against brain tissue on the panel testing. 3\. Validate the use of the liquid biopsy and SEEG trace tissue for use in the English National Health Service clinical services and share with other Genomic Laboratory Hubs.

OASIS: RetrOspective Analysis on EEGs for Identifying Seizure Susceptibility in paediatrIcs Using biomarkerS

The goal of this retrospective study is to validate a set of computational biomarkers (BioEP) for seizure susceptibility on retrospective routinely collected non-contributory EEGs in paediatric participants with epilepsy. The main objectives are: Primary: To validate a set of computational biomarkers (BioEP) for seizure susceptibility on retrospective routinely collected non-contributory EEGs in paediatric participants with epilepsy. Secondary: To examine whether the use of BioEP could support a more efficient patient pathway to diagnosis (thus adding economic value), by reducing time to final diagnosis and/or the number of clinical appointments needed

The "New" Place of LEVETIRACETAM in the Management of Status Epilepticus in Children

Status epilepticus is the leading neurological emergency in children, with mortality 2-7% and significant morbidity (10-20%). It is defined as the occurrence of a crisis lasting more than 5 minutes and requiring the implementation of treatment to stop it and thus limit the immediate and long-term consequences. The research hypothesis is that LEVETIRACETAM is non-inferior to PHENYTOIN in terms of cessation and absence of recurrence of status epilepticus, with better clinical tolerance in children from 3 months to 17 years old, with or without epileptic disease, with or without a history of status epilepticus

The Incidence And Risk Factors Of Recurrent Febrile Seizures And Epilepsy Following Febrile Seizures

The goal of this observational study is to learn about the recurrence and development of epilepsy in children hospitalized with their first febrile seizures. The main questions it aims to answer are: * What is the risk of recurrence after the first febrile seizure and what are the risk factors for recurrent febrile seizures in Vietnamese children? * What is the risk of developing epilepsy later in life and what are the risk factors for developing epilepsy in Vietnamese children who have had febrile seizures?

The Effect of the Training Programme Based on the Health Promotion Model Given to Parents

This randomised controlled study evaluates the effect of a training programme based on the Health Promotion Model developed for parents of children diagnosed with epilepsy on parents' level of knowledge about epilepsy, parents' general self-efficacy level, parents' health promoting and protective behaviours and the number of hospital admissions of their children. The hypothesis of this study is that education has an effect on these.

Genetic Diagnosis in Inborn Errors of Metabolism

Inborn Errors of metabolism comprise a large number of rare conditions with a collective incidence of around 1/2000 newborns. Many disorders are treatable provided that a correct diagnosis can be established in time, and for many diseases novel therapies are being developed. Without treatment, many of the conditions result in early death or severe irreversible handicaps. The Centre for Inherited Metabolic Diseases, CMMS at Karolinska university hospital, is an integrated expert center where clinical specialists work closely together with experts in laboratory medicine, combining clinical genetics, clinical chemistry, pediatrics, neurology, and endocrinology. The center serves the whole Swedish population with diagnostics and expert advice on IEM and has a broad arsenal of biochemical investigations designed to detect defects in intermediary metabolism.