EpiCARE’s core programme is detailed in a work plan, work packages and delivrables. They are providing a detailed project plan, the timing of the work packages and their description.
You can find out more about EpiCARE’s core programme exploring the different work packages below:
Increasingly genetic, autoimmune and metabolic epilepsies are being recognised although few characteristic epilepsy phenotypes have been identified (i.e. PCDH19, SCN1A, NMDA encephalitis, GLUT1 deficiency) that permit prediction of which aetiology is likely involved. Progressive refinement of the phenotype will reduce the number of patients who require molecular genetics, for diagnostic purposes (with consequent financial impact, particularly for patients with poor social coverage). Neural autoantibody testing and metabolic testing can be also more targeted. Refining phenotypes requires that specific features (seizure, EEG, MRI characteristics, cognitive profile, psychiatric, movement and other possible comorbidities,) are identified accurately by physicians with appropriate expertise. Knowledge of these additional symptoms and their prediction may permit actions to reduce their impact. For given conditions, few experts have devoted time on the identification of the phenotype. Experts need to be identified from within the network so that they may contribute to this phenotypic refinement. The identification of aetiological groups throughout the EU will be able to provide appropriate genetic, metabolic and immune testing to a wider population.
Actions undertaken to promote harmonisation of best practices in neuroimaging evaluation of rare and complex epilepsies that will provide state-of-the-art procedures in the field. Creating a database of neuroimaging findings in the specific rare and complex epilepsies with further research implications.
Prague, Czech Republic
Utrecht, The Netherlands
Clinical Neurophysiology methods, especially EEG, provide valuable information for diagnosing the epilepsies, with specific patterns identified in many diseases requiring expert interpretation. Thus, integration of recent advances into EpiCARE is essential. However experience and expertise is required to recognise the advantage of accurate recording and interpretation; geographical variation requires specifically to be addressed here.
SCORE is a computer-based system for EEG assessment and reporting, which reduces the inter-observer agreement in EEG interpretation and is based on a consensus proposal by a group of European experts endorsed by the International League Against Epilepsy – Commission on European Affairs (ILAE-CEA) and the European Chapter of the International Federation of Clinical Neurophysiology (EC-IFCN). During the development process, SCORE was tested and adjusted by applying it to real, clinical data.
Electrical source imaging is part of the presurgical evaluation of patients with drug-resistant focal epilepsy. The software packages that will be used in this study have CE mark for this specific medical use. In spite of being part of the clinical standard, the evidence for the accuracy and clinical utility of these methods are derived from several smaller-scale and retrospective studies. The PROMAESIS study will provide solid evidence of the accuracy and clinical utility of automated ESI.
Danish Epilepsy Center
Behavioural and cognitive comorbidities in epilepsy are very common. They are often present already at epilepsy onset and before. Cognitive and behavioural assessments can reveal differential diagnostic indicators of epilepsy subtypes and syndromes, particularly when related to data from imaging, electrophysiology, pathology, and genetics (see other work packages). Furthermore it allows monitoring of disease dynamics (progress and control), and it can be used for the outcome and quality control of applied treatments (surgical, stimulatory, medical, behavioural comprehensive care). With the E-Neuropsych task force within the funded pilot ERN E-pilepsy an initiative was taken which aimed at the homogenization and distribution of best evidence based neuropsychological practice. The result was the availability of a core standard test battery of evidence based neuropsychological and behavioural instruments. The battery covers developmental and adult neuropsychology and addresses various cognitive and behavioural domains. The tool box was implemented in a web based E-Neuropsych platform for data entry, evaluation, collection and communication across EU reference centres for epilepsy surgery. E-Neuropsych represents one node within a diagnostic network which also comprises imaging (structural/functional), and electrophysiological (invasive/non-invasive) diagnostics and evaluation tools. E-Neuropsych, can be extended and adapted to all other questions concerning the epilepsies. Within a large network of clinics it can well be expected that for rare pathologies enough data can be collected so that their cognitive and behavioural aspects along with disease development and treatment can be defined.
Microscopic tissue diagnosis of human brain disorders remains the gold standard in modern medicine. Yet, histopathology training in epileptic disorders is difficult to obtain in many European countries. EpiCare offers, therefore, a comprehensive neuropathology service for all of their members. Currently, our workpackage addresses three activities:
1) The European Epilepsy Brain Bank is an EU-FP6/FP7 funded project collecting more than 10.000 histopathology diagnosis obtained from epilepsy surgery. This unprecedented dataset can be used for benchmark projects on disease etiologies, outcome and pathomechanisms.
2) We also offer a second diagnostic look to surgical brain samples obtained from epilepsy surgery using standardized protocols. Formalin-fixed and paraffin-embedded tissue specimens should be send to the neuropathology laboratory in Erlangen, Germany (see address below).
3) Finally, we offer an interactive, online post-surgical case-conference to discuss surgical brain specimens from various European epilepsy surgery centers. For further information, see sections below.
The European Epilepsy Brain Bank (EEBB) has enrolled more than 10.000 epilepsy surgery patients from 36 centers in 14 European countries (Blümcke et al. 2017; Lamberink et al. 2020). EEBB is a virtual database collecting a minimal data set for each (double-encoded) patient, e.g. age at epilepsy surgery, age at seizure onset, sex, location of the epileptic lesion, year of surgery, 12-24-60 month postsurgical outcome, antiseizure medication). This unprecedented databank is used for benchmark projects on disease etiologies in focal epilepsy (Blümcke et al. 2017) and post-surgical outcome (Lamberink et al. 2020). Tissue storage will help to enable future research projects, in particular addressing genetic causes of focal brain lesions and epileptogenicity.
Members of this workpackage offer the large experience in standardized neuropathological examination, i.e. establishing ILAE guidelines and classification systems. All tissue specimens will remain the courtesy of submitting centers and returned upon completion of the analysis. Guidelines for standardized tissue fixation, long-term preservation and storage have previously been published and can be downloaded through this website (Blümcke et al. 2016). Formalin-fixed and paraffin-embedded tissue specimens should be send for microscopic review to the postal address below.
Homa Adle-Biassette, Paris
Eleonora Aronica, Amsterdam
Annmaria Buccoliero, Florence
Albert Becker, Bonn
Rita Garbelli, Milano
Kristof Egervari, Geneva
Maria Thom, London
Toumas Rauramaa, Kupio
Thomas Olsson Bontell, Gothenburg
Thomas Jacques, London
We offer a monthly online discussion forum for post-surgical patients in order to review the histopathology findings. The post-surgical discussion forum is targeted for clinicians, neurosurgeons and histopathologists. Each case will be presented with the patient’s clinical history and surgical procedure. The microscopy findings will be reviewed live using our digital microscopy platform. The discussion of differential diagnosis and postsurgical outcome will conclude each case presentation. If you are interested to join this forum, or present a case please email to email@example.com.
For patient presentation, we request to obtain the patient consent using the standardized EU form.
Recognition of the epilepsies as a group of rare diseases with known aetiologies give us insight as to the underlying mechanisms involved in seizure generation, and further comorbidities such as cognitive, physical, emotional and behavioural capacities. The correct and timely diagnosis of rare forms of epilepsy is crucial for a tailored, successful treatment. For example in structural epilepsies such as subtle focal cortical dysplasias (code 269001), accurate diagnosis often requires advanced neuroimaging techniques (link to WP3) and intracranial EEG recordings (WP4), but may allow neurosurgical resection which ultimately cures the patients of epilepsy (WP8). Tuberous sclerosis (code 805) is a genetically caused structural epilepsy (WP2, 3) that can be treated surgically in some cases, but with an understanding of the gene pathway also allows the exploration of novel treatment strategies such as MToR inhibitors such as everolimus which may even, if applied in the early course of the disease, prevent the onset or at least worsening of the epilepsy. In genetically caused epilepsies, clarification of the aetiology can have an important impact on treatment strategies. For example in Dravet syndrome caused by mutations in voltage-dependent sodium channels (code 33069), the administration of sodium channel blockers may worsen seizures, and in mitochondriopathies (code 2598), the application of the anticonvulsant drug valproic acid can induce lethal liver failure. Immune-mediated epilepsies (codes 420789, 217253, 1929) require additional immunosuppressive therapies. The prognosis of some of these rare neuroinflammatory diseases appear to depend on the presence of specific antibodies in the blood or cerebrospinal fluid (WP2), but the best treatment option is currently unclear because of the rarity and lack of controlled clinical studies (WP V). All such diseases are rare and require a network multidisciplinary approach to reveal outcomes from targeted therapies.
It has been operating since January 2014. It has provided a large number of deliverables and sustained activities that have been consolidated and further developed in EpiCARE. The network initially included 28 epilepsy surgery centres but has recently grown to 52 centres. While only some epilepsy centers offer comprehensive epilepsy care and can be labelled full members of EpiCARE, it is essential that the E-pilepsy pilot network of cooperation continues to expand and ensures optimal dissemination of information, guidelines, state-of-the-art methodologies and web-based tools which help increase the effectiveness and safety of pre-surgical evaluation and epilepsy surgery.
– 1) Monthly E-Care visioconferences: These conferences, which allowed to discuss complex epilepsy surgical cases, have successfully continued under the coordination of Stefano Francione. Starting April 2021 this activity expanded to bi-monthly meetings (every 2nd and 4th Wednesday of the month from 4pm to 5H30pm CET) to increase the number of discussed surgical cases. The regularly updated agenda of EpiCARE Case discussions can be found on: https://epi-care.eu/case-discussions-epicare/
– 2) IT platform: The E-PILEPSY IT platform allowed each EpiCARE center to get access and use sophisticated neuroimaging and EEG postprocessing tools (e.g. Curry8). Maintenance includes supporting the data safety and data privacy requirements of the platform, including regular changes of each center password to access the platform via VPN (every 6 months). It will soon evolve into an expanded platform with additional functionalities, the Human Intracerebral EEG platform (HIP), thanks to the partnership established between EpiCARE and the Human Brain Project.
– 3) Epilepsy Surgery RedCap eCRF: This comprehensive eCRF aimed at collecting all relevant data from patients undergoing presurgical evaluation and epilepsy surgery. It is currently proposed to focus on patients undergoing invasive EEG recordings, but shall later expand to all patients considered for epilepsy surgery. Data can be entered on a local or central RedCap database. For those stored in their hospital of origin (local RedCap server), the Medical Informatics Platform (MIP), also developed within the framework of the Human Brain Project, can be used to federate the datasets without moving them away from their site of origin and storage.
– 4) The CogniEEG project: EpiCARE centers are core members of the CogniEEG project which aims at leveraging cognitive research performed in patients with epilepsy undergoing intracerebral EEG recordings (iEEG). Other iEEG centers from Europe, Asia and Oceania are also contributing to this project, which take advantage of the HIP platform and epilepsy surgery RedCap eCRF to collect, organise and analyse data.
– 5) The Registry: All data collected through the above activities (RedCap eCRF, CogniEEG and iEEG data in general) will feed the Epilepsy Surgery registry built to this purpose. The latter will communicate and cross-talk with the general EpiCARE registry, and will use the unique EUPID identifier for all EU patients.
Neonatal seizures are a major diagnostic challenge for clinicians because clinical presentations can be very subtle, electro-clinical correlation variable and there is generally a poor response to antiepileptic drugs. Interpretation of neonatal EEG is a highly specialised task and a thorough knowledge of the maturational changes that exist across all gestational ages is required. In addition, this expertise must be available on a 24/7 basis to meet the needs of the neonatal intensive care unit environment. Over the last number of years, we have developed the Babylink platform (G Boylan), a web based IT platform for streaming neonatal EEG on a 24 hour basis where it can be interrogated by novel neonatal seizure detection algorithms. This platform provides support to hospitals where EEG expertise is not readily available. Through the EpiCARE network we aim to scale this platform to a European population of neonates with seizures and we will identify a group of experts from the ERN centres who will be available to provide oversight for the platform
To widen awareness and availability of dietary therapies, with development of European standards and recommendations as to what, when and how dietary treatment should be applied.
Click here to download the ‘Introduction To Medical Ketogenic Dietary Therapies’ booklet.
Produced by the Matthew’s Friends charity, this booklet guides you through the first steps of Ketogenic Dietary Therapies.
The guide is an ideal supplement to this website and is extremely useful to give to patients looking to begin the diet.
We suggest that you take a look at the following publications.
Ketogenic Dietary Therapies are very low carbohydrate, high fat diets designed to encourage the body to switch its main source of fuel from carbohydrates to fats. Ketones are produced as a by-product of this increased “fat burning” process and the brain quickly adapts to using ketones as the main fuel source for energy production.
There are four ketogenic diet approaches sharing the common principle of a reduced carbohydrate (CHO) intake and an increased fat intake:
The main difference between them is the degree to which carbohydrate, fat and protein foods are weighed and counted; the Classical and MCT ketogenic diets require all foods to be measured while the Modified Ketogenic Diet and Low Glycaemic Index Treatment focuses on careful carbohydrate control and generous fat portions. The crossover between these regimes is significant and often a hybrid may be used, designed around the needs of the individual. Medical screening and monitoring is the same for ALL ketogenic therapies.
Lingfield, United Kingdom
There is much research in this area. The diet appears to “mimic starvation” by using fat as an alternative fuel source for the body, producing ketones. These ketones and the associated biochemical changes in the brain, can have an anti-convulsive effect.
The “Holy Grail” of the ketogenic diet is for a patient to be initiated on the diet, become seizure free, reduce/remove the amount of anti-epileptic medication taken, wean the diet off after a period of 2 years and STAY seizure free. This DOES happen for some, but there are also other degrees of success on the diet:
One of the aims of the EpiCARE network will be to identify the currently existing registries and databases on rare and complex epilepsies in Europe. Many institutions, networks as well as patient organizations have already developed or are in the process of developing a database with key information on patients with a specific epilepsies, at both national and European levels. Notable examples of organizations with rather well developed databases are the Dravet Syndrome European Federation, and Tuberous Sclerosis. Some organizations also gather crucial patient information through questionnaires. After identification of databases, a next step will be to look for common denominators and to merge some of the common topics across the datasets. This will allow us to better estimate and describe the true incidence of typical disease characteristics. It will for instance be possible to find common co-morbidities (such as depression, memory problems, and cognitive problems) across many rare and complex epilepsies. Efficacy and side effects of older and newer treatment options can be compared for different epilepsies. We will also determine whether the existing or newly developed guidelines by EpiCARE are also applicable for specific epilepsy syndromes. At the research level, managing the databases and registries will allow us to recognize specific patient groups for advanced diagnostic and therapeutic studies and/or for answering specific research questions.
One of the final deliverables of this work package will be to construct a common “minimum E-database” with key disease features. This electronic database will be disseminated for use in the network which finally will lead to better and more standardized patient care. The platform we will use to build this E-database is REDCap (Research Electronic Data Capture), already utilised by E-pilepsy.
The development of clinical guidelines and care pathways is crucial to improve the access to diagnosis and treatment. Guideline development was a key deliverable of E-pilepsy; such will be essential to the provision of high-quality healthcare to all patients with rare and complex epilepsies. Guidelines should also be focal points for medical training and research. We will continue to use a transparent methodology (Grading of Recommendations Assessment, Development and Evaluation; GRADE) in order to ensure implementation of all available evidence, and involvement of all stakeholders. All developments will follow the rules of the GRADE Methodology, which uses the best available evidence along with expert opinion and patient representatives to develop explicit criteria to guide clinical care. Systematic reviews of relevant evidence will thus precede all further activities in this WP and will underpin all medical information, procedures, and applications developed in EpiCARE.
The EpiCARE Guideline Development Group conducted a survey with the aim to evaluate the current state of the guidelines being used by centres of the EpiCARE network for diagnosis and treatment of rare and complex epilepsies. The guideline group is currently assessing the quality of collected documents by using the AGREE II tool. The results of the survey will be published in due course.
|SIGN 143 • Diagnosis and management of epilepsy in adults||https://www.sign.ac.uk||2015, revised 2018|
|French guidelines on stereoelectroencephalography (SEEG)||Clinical Neurophysiology||2017|
|Il trattamento dell’epilessia in eta pediatrica||2017|
|Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics||Epilepsia||2015|
|Treatment of convulsive status epilepticus in childhood: Recommendations of the Italian League Against Epilepsy||Epilepsia||2013|
|Evidence-based guideline update: Vagus nerve stimulation for the treatment of epilepsy. Report of the Guideline Development Subcommittee of the American Academy of Neurology||American Academy of Neurology||2013|
|Tuberous Sclerosis Complex Surveillance and Management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference||Pediatric Neurology||2013|
|Atteintes rénales de la sclérose tubéreuse de Bourneville : recommandations de prise en charge||Progrèsenurologie||2012|
|Treatment of Status Epilepticus in Adults: Guidelines of the Italian League Against Epilepsy||Epilepsia||2006|
|SIGN 81. Diagnosis and management of epilepsies in children and young people||https://www.sign.ac.uk||2005|
|Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Seizures||Annals of Emergency Medicine||2004|
“Epilepsies in children and young people: Investigative procedures and management” is the new guideline reflecting the most recent evidence around key issues and replaces SIGN 81.
A considerable number of educational activities and tools are already available in most EU countries, the result of either individual academic initiatives or as part of programs developed by the scientific societies (ILAE, EPNS, EAN) developed by experts from the participating centres.. What is still challenging, due to the great variety of “end-users” in the field, is the development of learning goals, preferably per “end-user”, and the establishment of priorities.
EpiCARE is an EU reference network of all disciplines involved in epilepsy care for rare and complex epilepsies. For general and specialized training in epileptology we fully adhere to the “Roadmap for a competency-based educational curriculum”, developed by the International League Against Epilepsy. In parallel, as part of a reference network of Health Care Providers for rare and complex epilepsies, the first goal of the present Working Group is to develop educational practices favouring dissemination of highly specialized knowledge and expertise within the members of the ERN and beyond, to operationalise complementarity.
With the generous contribution of experts in the corresponding fields, we developed a program of educational webinars. They offer comprehensive state-of-the-art reviews, accessible to all free of charge. At first presentation, all our webinars also offer a “meet the expert” opportunity during a live Q&A part.
Supported by a European Commission CEF Telecom program (2018 and 2021) we are also developing, in close collaboration with the ILAE Academy, a series of patient-centred interactive e-learning modules. Each of them offers a comprehensive diagnostic and therapeutic, state-of-the-art knowledge and interactive training.
Our Clinical Case Discussion weekly sessions, strictly reserved for confidentiality reasons to pre-registered health care professionals, are another source of education.
EpiCARE members regularly contribute to “Seminars in Epileptology” review manuscripts, published by the ILAE educational journal Epileptic Disorders.
Finally, HCPs members of the ERN EpiCARE in close collaboration with our Patient Advocacy Groups, regularly develop and disseminate leaflets for caregivers and patients with rare epilepsies and comprehensive patient’s journeys descriptions.
Training in clinical epileptology and related disciplines requires the physical presence of young clinicians and researchers at epilepsy reference centres. All ERN EpiCARE members and collaborating partners offer training possibilities. They can be directly contacted by those interested.
We are also partnering the Mobility Program developed and funded by the European Commission. Considering the major role of epilepsy nurses and epilepsy monitoring unit nurses we support short exchange programs between HCPs members of EpiCARE. AN EpiCARE Task Force is currently focusing upon the development of training guidelines for paramedics in epilepsy departments.
The ERN EpiCARE is one of the 3 pilot ERNs, missioned to contribute to the future development of an ERN ACADEMY and an active member of the ERNs Knowledge Generation Working Group, focusing upon the development of a joint strategy of the ERNs for training and education to overcome the gap between the increasing awareness on rare and complex diseases and the lack of a specific training in the medical curricula.
ACTIVE MEMBERS OF THE EDUCATION and TRAINING EpiCARE WG:
Arzimanoglou Alexis, France
Ingmar Blümcke, Germany (ILAE Academy Liaison)
Jansen Floor, The Netherlands
Kalviainen Reetta, Finland
Kobulashvili Teia, Austria (Liaison Guidelines WP)
Lagae Lieven, Belgium
Lesca Gaetan, France
Liakina Tatjana, Lithuania
Malenika Masa, Croatia
Openshaw-Lawrence Nicola, UK (Epilepsy Nurse liaison)
Papadopoulou Marietta, Greece
Pressler Ronit, UK (Liaison, Neonatal WP)
Specchio Nicola, Italy
Toulouse Joseph, France
Vigevano Federico, Italy
Zuberi Sameer, UK
University Hospital Centre
Research is an important component of EpiCARE. Various partners already participate in existing EU research networks; these include the ongoing NEMO (Treatment of NEonatal seizures with Medication Off-patent: evaluation of efficacy and safety of bumetanide) network on neonatal seizures that was FP7 funded to assess the role of bumetanide (grant agreement no. 241479); this network continues with further projects including Welcome funded AnSWer. Further, the FP7 project ‘DESIRE’ (Developmpent and Epilepsy – Strategies for Innovative Research to improve diagnosis, prevention and treatment in children with difficult to treat Epilepsy- grant agreement no. 602531), is now in its 3rd of 5 years duration. DESIRE studies complex and rare epileptic encephalopathies and has collected DNA and brain tissue samples, cohorts with rare syndromes, organized databases and clinical trials. The proposed clinical network EpiCARE utilising the database/registries will allow natural history studies of individual phenotypes (to include epidemiologic, phenotypic, genotypic, response to medication, natural history, comorbidity, long term outcome, existing treatments,, mortality) and determine further key areas of research priority to be addressed, as illustrated with Dravet syndrome (http://dravet.eu/ ). For those conditions whose genetic bases are still unknown, European registries will facilitate a coordinated effort for participation to worldwide consortia for genomic studies (for example Epi 25K, http://www.epgp.org/) This will facilitate applications to Horizon 2020 and E-rare calls and publications on even extremely rare disorders through manifestations of interest, following a data sharing policy we previously adopted in the Rare Epilepsy Syndromes (RES) consortium (http://epilepsygenetics.net/2013/07/03/reinventing-a-consortium-the-res-data-sharing-policy).
A large proportion of available antiepileptic drugs (AEDs) have no regulatory approval for use in children, Moreover, for most rare disabling epilepsies there are no approved treatments. There is an urgent need to collect standardized information on outcomes associated with specific treatments (individual AEDs, AED combinations, and non- pharmacological treatments such as diets, neurostimulation or surgical therapies) in epilepsy patients with well characterized rare syndromes and rare aetiologies. Moreover, there is a clear need to identify/develop novel treatments targeting specific aetiologies. Establishment of an epilepsy ERN offers unique opportunities to address these needs.