EpiCARE: The European Reference Network for Rare and Complex Epilepsies

A network of more than 60 expert epilepsy teams across Europe: That's EpiCARE. The network aims to improve care for rare and complex epilepsies and reduce inequalities in access to the best diagnostic and treatment practices and investigational tools. Sharp Waves talked to EpiCARE coordinator Dr. Alexis Arzimanoglou about what EpiCARE is, what it isn't, and how it may contribute to changes in epilepsy care across the region and beyond.

For more information:

EpiCARE website

EpiCARE on Instagram (@ern_epicare)

EpiCARE webinars

Patient and caregiver resources

EpiCARE position paper: Areas of research priorities in epilepsy (Epilepsia Open, Jan 2026)

The Declaration on the European Innovation and Care Ecosystem for Rare and Complex Diseases (Dec 2025)

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Let us know how we're doing: podcast@ilae.org.

The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

Transcript

[00:00:00] 

Dr. Alexis Arzimanoglou: I am Professor Alexis Arzimanoglou. I'm a child neurologist in training. I come from Greece. I worked for many years in France, and since 2023 at the Barcelona Children's Hospital, Sant Joan de Deu in Barcelona. And I am the coordinator of the European Reference Network for Rare and Complex Epilepsies since 2019. 

Nancy Volkers: Since 2019. So the network, we’re going to abbreviate that as EpiCARE. This one of, I think, 24 European reference networks. They're all aimed at tackling rare and complex diseases. Can you talk a little bit about how it was established and how it got started? 

Dr. Alexis Arzimanoglou: Yes. So EpiCARE is one of the 24 European [00:01:00] Reference Networks for rare diseases.

They were first launched by the European Commission in 2017. And they cover 24 different areas of diseases, as we said, mainly for rare and complex diseases. The European Commission is funding the management of the networks, not the members of the networks themselves. The members of the networks are, in fact, mainly university hospitals that have quite large expertise, the main aim being cross-border health within the European Union. 

In 2017, EpiCARE was coordinated by Professor Helen Cross who was also, as we know, the current past president of the ILAE. And following Brexit, of course a non-EU country could not coordinate the network, and this is where my peers honored me with the election of replacing Helen to the [00:02:00] coordination of the network. 

The network has today 60 medical teams across Europe, which are accredited following a grant call by the European Commission, and to be members, they need to also be validated by their own member states. So one cannot apply individually. It has to come after a call from the European Union to apply for membership. And then there are a number of criteria that are evaluated both by us as a network and of course by the board of member states, which are the representatives of the health authorities. 

EpiCARE has some particularities compared to other ERNs. For example, there is another ERN on rare neurological disorders where they structured the network per subgroups of diseases, ataxia, dystonia, and so on. With the epilepsies, we are facing the usual challenge. The epilepsies are at the [00:03:00] same time, a symptom of many neurological diseases, epileptic seizures, or there are diseases per se, epileptic syndromes, epilepsy syndromes. So it would be practically impossible to structure the network per disease because there are more than 160 rare forms of epilepsy, without mentioning those that are rare diseases with only seizures as a symptom.

So we took the decision, my colleagues of the executive committee, which represent the centers, to structure it, I would say, in 20 different working groups. Ten of them focus more on best practices in care, neuroimaging, neurophysiology, genetics, neonatal epilepsies, and the other 10 focus more on transversal issues like education, clinical trials, how to integrate the overall network with the national networks in [00:04:00] the countries that the members belong to, and so on. 

So this is our basic structure. We also have a very specific working group trying to involve nurses and EEG technicians. It is more difficult to make it grow mainly because of language barriers, because every, all the nurses do not speak necessarily English.

And there is another one which has a clear role of patient empowerment because one of the obligations of the ERNs is to work very closely with patient advocacy groups. So we have a specific working group for patient advocacy groups, and we collaborate with patients or patient associations across the European region and beyond.

This is the main work. Now, if you ask in terms of daily basis, the working groups are independent. They are coordinated by project managers who are funded by the European Commission. In fact, EpiCARE has [00:05:00] seven project managers across Europe that I coordinate and they act as a liaison with each of the working groups.

There is an executive committee, mainly composed of the leaders of the working groups and the historical people that created EpiCARE some years back, and there is an obligatory board of network members meeting three times a year, one of them being face-to-face, which are the representatives of each of the 50 60 centers that are accredited members of the network.

Nancy Volkers: Excellent. Thank you. So you mentioned one of the aims of EpiCARE was patient involvement and being involved with advocacy groups. Could you talk about some of the other main goals of EpiCARE and how those are being addressed? 

Dr. Alexis Arzimanoglou: One of the main missions of EpiCARE as a European network is to share expertise [00:06:00] across borders. The main direct impact for the patients is that when a medical team has a complex case in terms of diagnosis, in terms of treatment, in terms of investigations, there is a secure platform funded by the European Commission where the clinical case is uploaded. The network invites its experts to specific sessions where the case is presented by the medical team who requests some support. And the discussion, of course, the final decision remains with the treating medical team, but the patient benefits from input from all over Europe and beyond, because when we need experts coming from other countries, of course we are open to invite them. We cannot fund people outside of the European Union, because the budget comes from the European Union. But our working groups and our expertise is open [00:07:00] to those who wish or have time to offer to EpiCARE. 

To give you a concrete example, we have three case discussion sessions per month in which we usually discuss two or three cases. Two of them are surgical cases, indications for surgery, indications of pre-surgical evaluation, and the third one is on clinical cases in terms of diagnosis or treatment decisions. This is one level. 

Now beyond the direct impact to the patients, which means we discuss, let's say 50 to 70 very complex cases per year, at the same time, you need to see the dynamics of this. The fact that the members of the network are on a regular basis in contact between them facilitates enormously, I would say, unofficial discussions of cases with other people that we meet during the work of EpiCARE, being at [00:08:00] congresses or being because we collaborate on a research project and so on. So it is not only the official ones, it's also, I would say, the unofficial case discussions. 

Now beyond the direct discussion of clinical cases, all the ERNs and EpiCARE particularly have an obligation to knowledge generation. So we are producing, we are working on specific guidelines, usually in collaboration with the ILAE, with the European Academy of Neurology, with the European Pediatric Neurology Society, but they are initiated by EpiCARE and we have methodologists and project managers that follow those projects until they are published as updated or new guidelines.

There is a specific working group on clinical trials and targeted therapies where we discuss new treatments to come.

We also disseminate all the calls for collaborative research. I mean, small [00:09:00] centers that wish, for example, they discovered one mutation and they want to find other centers that have patients with a similar clinical or genetic profile. The network puts them in contact to collect as much data as possible, because we are dealing with rare diseases and the patients are quite few. But this allows a quite comprehensive description of new diseases or a better description of already-known diseases, both in terms of diagnosis and of treatment.

Two more concrete examples, which are more, I would say, how a network like this, once it is structured, may act very rapidly are one, the COVID pandemic. During the COVID pandemic, for example, because the network was already there, in practically three or four weeks, all centers were contacted with guidelines on how to replace a drug that is in shortage, or what to avoid or what to do in terms [00:10:00] of treatment of the epilepsy for a patient having COVID symptoms and so on. And this went on during the whole COVID pandemic and goes on for the war in Ukraine, in fact, in collaboration again with the ad hoc task force of the ILAE, because we always work together and under our scientific society. 

Nancy Volkers: Excellent. Those are some really important examples. There's also a registry. Can you discuss that a little bit? 

Dr. Alexis Arzimanoglou: Yes. So EpiCARE indeed created a registry called EpiReg, which is now driven by the University of Leuven in Belgium.

Our decision was that this will remain a registry, meaning that we only introduce the data that allows us to identify a specific diagnosis of where the patients are, to which center they are followed. It is not a database that is regularly updated with the [00:11:00] everyday information for each patient, but what it helps is that when a new treatment appears, or if we want to do a natural history study to understand the evolution of a disease, because all our centers use exactly the same template and collect exactly the same data, it is very easy for someone who wants to launch a research project or a clinical trial or a natural history study to ask the register to provide him where he or she can find the patients to get the information. 

It took quite a time to have the data sharing agreement for the protection of the data of the patients, but this is now also in place. The data is fully anonymized and it allows, again, for the patients to benefit from the knowledge coming from other patients having exactly the same disease or a similar disease. So now the network very recently is fully operational, [00:12:00] and each of the centers can send data and information. 

In addition, we created the registry in a way that if a research project, for example, once is launched for a given period of time, five years, six years, this project, the common data elements can go and clip to the main registry to feed it up with new information about patients. And even if the project, the research project finishes, the localization of the patients or the medical teams that treat those patients still remain within the main registry, which is sustainable and can be used for a different trial or for a different study in the future.

Nancy Volkers: So in your years with EpiCARE, what impacts have you, have you personally seen? What are two or three things that really stand out for you?

Dr. Alexis Arzimanoglou: Well. First of all, [00:13:00] regarding the patients, I think that it is extremely reassuring for them to know that experts from all over Europe may discuss a very difficult case. Of course, the patient is informed that his data will be presented to such a panel and they agree to it, and then they benefit from information that avoids them having to travel across Europe to find a solution.

But if a given treatment or a given surgical technique was not available in one country, the consortium, the network edited an official letter saying that this patient needs to go to another country for this treatment, which helps a lot with local administrative issues and funding from the National Security systems across Europe.

Second point, again, concerning the patients, the experts, together with the patient associations, produce what we call patient leaflets and patient journeys, which are documents that have two pages explaining the disease to the [00:14:00] caregiver, and two pages for the general practitioner, the family doctor, and those are done together, experts and patient associations, to take in consideration their needs. They're public, they're on the website. They can be uploaded by anyone in the world, no matter if they are in the European Union or not. And very recently, with the help of our local members and patient associations, they are translated in six, seven languages with validated medical data.

So the idea is a patient with a given disease, first, his family can know more about the disease. Second, the second part of the leaflet gives to the family doctor what he or she needs to do to help with the regular follow-up of the patient. And we produce regularly up to say, six, seven patient leaflets per year at least, and it is increasing in numbers with time.

At the initiative of the patient [00:15:00] advocates, they are translated. And again, in that case, the translation is double checked by a clinician working in that country to make sure that there are no misunderstandings or false information.

Nancy Volkers: So moving to research. Are there any basic or clinical research projects within EpiCARE that you want to discuss? 

Dr. Alexis Arzimanoglou: This is a very good question. Again, as I said at the beginning, the ERNs were created mainly for cross border care, so there was no research. Their role is as a network is not research, but on the other hand, I would say by definition or by nature, because the members are the biggest reference hospitals in Europe, they do perform research, so the role of the network is to foster research activities as much as possible.

We are not performing the [00:16:00] research as a network, but we promote the research projects to our members that can take the lead, including either members of the European Union or depending on the applications, on the grant applications from the European health program, countries that are outside Europe and they can fully participate.

And again, because of the dynamic of this process during the last five, six years, we participated one way or another in at least 85 research projects, which in that case, the medical teams that lead them are also beneficiaries of the grant. It is not the network. The network supports the infrastructure, but the grant itself is managed by the medical team that leads the research project or the other beneficiaries of the grant project. So in that aspect, it helps a lot. 

And the other way the network is helping our members and beyond, we have a dedicated project manager [00:17:00] that reviews the grant applications for research every month, and there is a new newsletter which is public, summarizing which of the calls that could be interesting in the epilepsy field so people can study them, can apply, and when they want to write the project, we propose also some help. Of course we cannot write it but we can help. 

And the third, which is a very recent, I would say, success story of EpiCARE, is that two months ago at a meeting we had in Rome, we launched for the first time what is now called EpiSPARK, which is a group of young mid-career experts in epilepsy that are also involved in research. EpiCARE supported their venue in a brainstorming session so they can tell us what they see as future research projects to be done in the years to come. And the good news [00:18:00] is that the position paper of EpiCARE on research priorities was accepted for publication in Epilepsia Open. It was a collaborative work created by the network group. So the network supports a number of activities of research being at the management level or connecting the medical teams or supporting them to better define a research question or develop a research project.

Nancy Volkers: So have there been any challenges or unforeseen roadblocks that you have dealt with or are currently dealing with? 

Dr. Alexis Arzimanoglou: Well, I would say yes and no. I mean, the motivating story with the ERNs is that those that are doing the work for the ERNs, EpiCARE in particular and the European Commission, we are building up the whole project while it is in process. The [00:19:00] general frame came out in 2017. To be honest, nobody knew exactly at that time how this would evolve. 

What are the caveats, what are the difficulties? So one of the difficulties, for example, is that because it was initially integrated within the classical European calls for research, it was a time-limited grant of five years, but such a network may need 25 years to develop. This, we discovered in process and together with the European Commission, and we tried and we still try to make the grant provided by the European Commission more sustainable because you cannot replace a management team every five years. You have to retrain everyone to find the doctors again.

Second difficulty was to establish a fair evaluation process of the members themselves because they do have to deliver. It is not just having the accreditation and they are [00:20:00] not evaluated on what they do at the national level. This is the job of the Ministries of Health. They are evaluated on what they do offer or not, and I insist offer to the network because again, they are not funded by the network. The time experts will spend at a case discussion is for free at the level of the network, and it is their own personal time or their hospital time or when they review a leaflet and so on.

This needs to be evaluated at a regular basis, first of all, because it is a request from the European Commission to justify the budget. And I can give a very precise idea. The management of an ERN, like EpiCARE, the European Commission spends something like 800,000 euro per year to fund the project managers, the different infrastructures and so on. So this needs to be justified.

Last week we had a very important meeting at the European Parliament [00:21:00] initiated by us. There was a declaration of priorities and one of those was ring fencing the needs and the structure of the ERNs and at the same time facilitate their link with the national networks because it remains true that the patient is better investigated near his home or in his own country than across Europe.

Our role is to share the expertise, not to share the patients. So we need to have strong links with the national networks. We know that there are inequalities in Europe that the network tries to study and identify. For example, genetic testing across the European countries is quite different. Some countries have a full panel of screening. Others have only one or two tests. Same for newborn screening. Reimbursement of genetic screening in some countries is fully [00:22:00] reimbursed, and at others, not at all. And we are trying to highlight and find solutions for these issues so that all patients in Europe have, I would say, equal access to care, to expertise, to treatments.

Some people say yes, but this is only for rare and complex diseases. First of all, we are talking about millions of people. People with rare diseases in Europe are estimated to be between 36 and 40 million people. So yes, each disease taken separately is rare, but the patient is a patient. The other thing that we are also trying to see with that process is that whatever EpiCARE is producing unavoidably shapes also the healthcare system as a whole, in the sense that you have a rare disease only if someone made the diagnosis, but you still have the symptoms before. It might be a common disease, no doubt, [00:23:00] but someone has to make sure it is a common disease and not a rare disease.

So whatever actions we take with patient advocates, by identifying the needs of reference hospitals, by identifying the best treatments or the best practices, unavoidably also shape the global healthcare system across Europe and beyond, not only the ones for rare diseases. 

Nancy Volkers: Yeah, that's a very good point. And you said that within Europe there are as many as 40 million people.

Dr. Alexis Arzimanoglou: Forty million people, all rare and complex diseases taken together. And here we are talking only about the patients, but we know that a patient with a severe rare disease impacts the whole family, the brothers, the sisters, the parents, the grandparents. So there are many millions of people suffering from those diseases.

The advances in recent years are huge, but they also have an economic high cost. [00:24:00] Precision medicine, genetic treatments need one to be discovered; two, to be developed in collaboration with industry, and then to be implemented or administered to the patients. Networks with such expertise can tomorrow be a source of information on priorities, a source of information for the regulatory agencies. Which are the drugs that need to be funded first compared to others? Where should be the centers that have the expertise to provide this treatment? Because these are complex treatments. They cannot be done in every city, in every village, but this means, again, a public health policy that needs to be developed in each country and at the level of Europe.

So all of those outputs, we discovered them ourselves progressively. We didn't think it would be that large, but it is. And that makes it of interest also for the patients at least.

Nancy Volkers: Do you have an estimate [00:25:00] of how many people in Europe have a rare or complex epilepsy? 

Dr. Alexis Arzimanoglou: Oh, 3 million at least. And again, you know that at least our community knows that an epileptic seizure can end up being a rare disease or a common epilepsy or a self-limited epilepsy.

But again, someone has to do the diagnosis as early as possible because, and it'll be more and more like this because of the new treatments, because of earlier access to surgery. Particularly for children, it is not the same thing to do the diagnosis, to have the diagnosis when they are two years old or they are 20.

So all this changes with time and I think that networks like this help a lot, all medical teams independently if they are reference centers or not. And above all, of course, the patients.

Nancy Volkers: Is there anything else you wanted to mention? 

Dr. Alexis Arzimanoglou: Well, what [00:26:00] I would like to mention is I would say a thank you to the epilepsy community, because we are one of the ERNs with a very large contribution of our experts to all what the network is doing. It is not the case in all medical disciplines. It is in ours. The collaboration with patient advocates is excellent, and the collaboration or the input of the experts and the medical teams is really impressive. 

We have, if a rough estimation, if you take the 60 medical centers, it's something like 1,400 experts without counting the nurses and so on working, being interested in these diseases. And we regularly have our working groups with 20, 30, 40, or 50 participants from different countries and each one has something to offer, to input. And the same applies, of course, to the case discussions. [00:27:00] So I think that we need to acknowledge that our community works in a very solid way, I would say, with very good collaboration between our members.

Nancy Volkers: Great. Thank you so much for joining me. This was very illuminating.

Dr. Alexis Arzimanoglou: thank you. 

Nancy Volkers: It sounds like you're probably doing about five or six jobs right now. 

Dr. Alexis Arzimanoglou: More or less? Yes. More or less. Yeah. Because at the same time we created, we helped ILAE Europe to create, I mean it was there, but now it is launched, a European consortium for epilepsy trials, for example. The idea is to support and to develop and to have earlier access to clinical trials in Europe for patients with drug resistant epilepsies. And this network was also something that was created within the process of, and the dynamics of a network like EpiCARE.

What happens often with our US colleagues is that when they listen or [00:28:00] read this, they say, “Wow, this is incredible. We should do the same in the US.” The problem is that the difference in social healthcare is completely different between the two. As I said, most of us do this pro bono here in Europe. In the US the structure is completely different. I mean, the patient that is discussed at nine o'clock at night by a panel of 15 experts pays zero euros. 

I would say theoretically, for a case to be discussed at the level of the network, the patient needs to be seen in one of our member centers to make sure that at least the basics are done and well done. We do not forget that if the information provided to a panel of experts who do not examine the patients is the wrong information, the advice will be the wrong advice. So we need to make sure [00:29:00] that what is presented is solid data done by people that know the job to secure the patient and the answers given. So that's why even within the EU to present the case at the level of the network the patient has to be seen by one of the teams in his own country, which explains why the number of patients discussed at the level of the network, one could say it's relatively small. Seventy patients a year is not that much. But the difference is that each of the centers sees 2,000 or 3,000 patients with rare diseases. So of course at the end, what we discuss at the level of the network are the more complicated and difficult to treat patients or diagnoses. 

[00:30:00]