Epilepsy Currents

Join Dr. Marawar in a conversation with Dr. Hannah Pickard and Dr. Laura Lubbers as they discuss the article, "Towards a Unified Research Agenda: International Consensus to Advance Understanding and Prevention of Sudden Unexpected Death in Epilepsy.

Click here to read the article.

This podcast was sponsored by UCB.

We'd like to acknowledge Epilepsy Currents podcast editor Dr. Adriana Bermeo-Ovalle, contributing editor Dr. Rohit Marawar, and the team at Sage.

This episode covers a 2026 Epilepsy Currents Current Review by Pickard et al., an international consensus setting out a unified research agenda for sudden unexpected death in epilepsy (SUDEP). Host Dr. Rohit Marawar speaks with Dr. Hannah Pickard of the Epilepsy Research Institute UK and Dr. Laura Lubbers of CURE Epilepsy about how two national workshops held two weeks apart converged into a single set of shared priorities, and what those priorities ask of clinicians, researchers and funders. They discuss what a neurologist can do at the next clinic visit to reduce risk, the role of medication access and adherence, how to counsel patients about seizure detection devices, why the field still cannot agree on what constitutes a SUDEP animal model, what large-scale linkage of epilepsy data across healthcare systems could reveal about time-varying risk, and why the persistent gap between SUDEP guidelines and everyday practice may be the most addressable problem of all.

Key takeaways:

1. Two independent efforts became one consensus: the Epilepsy Research Institute held a UK SUDEP workshop in 2024 and CURE Epilepsy held a parallel US workshop two weeks later, each unaware of the other. They merged their findings with the earlier Epilepsy Foundation SUDEP Summit over 12 to 18 months, with people with lived experience and bereaved families involved in every convening.

2. The agenda spans three domains: clinical (risk factors, personalized risk prediction, harmonized healthcare data, wearables, access disparities), preclinical (standardized models with common data elements, shared databases and tissue repositories, open-access collaboration), and awareness and education (clinician and public education, standardized discussion tools, registries and routine reporting, bereavement support).

3. Three things a clinician can do now, per Dr. Pickard: optimize seizure control, since generalized tonic-clonic seizure frequency remains among the strongest risk factors; raise SUDEP with every patient rather than only those who look high risk, because risk fluctuates; and use a structured tool such as SUDEP Action's SUDEP and Seizure Safety Checklist, shown to reduce individual risk factors. It should be a repeated conversation, not a one-off.

4. Medication adherence matters and poor access raises risk, but SUDEP also occurs in adherent patients. Devices should be chosen with a clinician by seizure type, may help most with nocturnal seizures, and have not yet been shown to improve survival.

5. The preclinical bottleneck is a definition problem. MORTEMUS showed people die after the seizure from respiratory and cardiac change, while lab animals usually die during the convulsion, so models may capture the wrong phase; CURE Epilepsy's common data elements aim to standardize protocols and reporting. Asked what would get us to a solution first, Dr. Lubbers chose awareness over any mechanism, noting families want to know, can act on it, and cope better with grief when informed.

Rohit Marawar, MD, FAAN, FAES (Host): One of the toughest phone calls a neurologist is likely to get is that their patient with epilepsy has suddenly passed away, likely from sudden unexpected death in epilepsy, commonly known as SUDEP. Across the general epilepsy population, SUDEP happens at a rate of roughly 1.2 per 1,000 patients per year. In developmental and epileptic encephalopathies such as Lennox-Gastaut syndrome and Dravet syndrome, among others, it is markedly higher, on the order of three to eight per 1,000 patients per year. And in that group, it accounts for roughly half of all deaths. Most of these deaths come without warning, and most happen at night.

Today, we are talking about what it would take to change those numbers and about a group of researchers, clinicians, organizations, and bereaved families on both sides of the Atlantic who sat down together to work that out.

Welcome to the Epilepsy Currents podcast, the podcast for Epilepsy Currents journal, exploring the latest research and expert commentaries from the world of epilepsy. UCB is the proud sponsor of Episode 13 of Epilepsy Currents podcast. I'm your host and Associate Editor for the podcast, Dr. Rohit Marawar. Today, we are discussing a current review published in Epilepsy Currents earlier this year, titled "Towards a Unified Research Agenda: International Consensus to Advance Understanding and Prevention of Sudden Unexpected Death in Epilepsy."

I'm joined today by two of the paper's authors. Dr. Hannah Pickard is the paper's lead author and joins us from the Epilepsy Research Institute in the UK. Welcome, Dr. Pickard. And then, we have Dr. Laura Lubbers, who is the paper's senior author and Chief Scientific Officer at CURE Epilepsy.

Welcome, Dr. Lubbers. Great to have you both with us. Before we get into the paper, I would like each of you to say a little about your organization and your own role in this work. Why don't we start with you, Dr. Pickard?

Hannah Pickard, PhD: Yeah, of course. My name is Hannah. I'm the research partnerships lead at the Epilepsy Research Institute UK. And at the Institute, our mission is to radically advance research into the causes, prevention, and treatment of epilepsy and its associated conditions. And we do this through a number of different routes by funding research, driving strategic investment, and also advocating for the research priorities of people affected by epilepsy.

And my specific role in bringing this paper together was really to manage the consensus process and bring the group together to discuss and draft our shared priorities for SUDEP. And I just want to say thank you so much for having me on the podcast. I'm really excited to join you both.

Host: Wonderful. Dr. Lubbers?

Laura S. Lubbers, PhD: Thank you, Dr. Marawar. CURE Epilepsy was founded in 1998 by parents concerned about the lack of knowledge about what causes epilepsy. They set out on a mission to fund research that would get to the root causes of epilepsy as a way to find better treatments and, one day, cures for epilepsy. Our focus on SUDEP started in 2004 when a bereaved parent named Jean Donalty challenged us all to learn more about this devastating outcome of epilepsy after she lost her son, Christopher.

In my role, I've been able to continue to build on these efforts by expanding our research portfolio focused on SUDEP, and have been honored to work closely with Dr. Pickard on the paper published earlier this year. We're excited to be here today to talk about the progress that's been made on epilepsy and SUDEP research.

Host: Thank you. Let's start with the questions. So first, a question for both of you. How did the consensus process start and develop? Were people living with epilepsy and their families involved? We can start with you, Dr. Pickard

Hannah Pickard, PhD: Perfect. Thank you so much. So, this consensus process really started all the way back in 2024 for the Epilepsy Research Institute, where we held a workshop that brought together researchers, clinicians, charities, bereaved family members, and people affected by epilepsy to discuss research priorities for SUDEP.

From this workshop, we, as the institute, began developing a paper outlining key priorities for SUDEP research in the UK, and we were working alongside researchers, bereaved family members, and the charity SUDEP Action to deliver this paper. And then, maybe I'll hand over to Laura to give a bit of a background on the different workshops that happened, and then I can touch on the consensus after.

Laura S. Lubbers, PhD: Absolutely. So simultaneously, in the US, CURE Epilepsy was developing a very similar workshop focused on SUDEP risk prevention and assessment. We held that in the fall of 2024, just two weeks after the workshop held by the Epilepsy Research Institute. Those different convenings were really developed in isolation.

But when we found out about each other, we thought, what a great opportunity to bring our learnings together and also bring in learnings from a previous workshop called the SUDEP Summit that was hosted by the Epilepsy Foundation back in 2020, 2021 timeframe. So, there were a number of convenings that had happened, but they all had a very similar outcome. And we all were coming to the same consensus.

So, we decided to join forces with the Epilepsy Research Institute and summarize the outcomes of the workshops and included our partner organizations, namely Partners Against Mortality in Epilepsy, or PAME in the US, and SUDEP Action and the Centre for Global Epilepsy in the UK, who are all interested in the same topics.

And the manuscript summarizes the convenings held by those different groups. Critically, all of the convenings did include people with lived experience, but I'll let Hannah talk more about how the consensus was developed.

Hannah Pickard, PhD: Yeah, absolutely. So, as Laura said, we were holding these workshops separately, and then Laura and her team reached out to us to discuss putting together a consensus paper that showcased some of our shared priorities across the UK and the US. And then, really, that process evolved over a 12 to kind of 18-month period starting in early 2025, where we held several meetings to discuss priorities and really reach a consensus on the recommendations which you can see outlined in the paper and we'll discuss more today

Host: Thank you. So, Dr. Lubbers, can you give an overview of the different components of this consensus document?

Laura S. Lubbers, PhD: Yes, absolutely. We synthesized the priorities into three different key domain areas: clinical research, preclinical science, and awareness and education. The clinical priorities focused on improving identification of modifiable and unmodifiable risk factors. Also, developing personalized risk prediction tools, harmonizing healthcare data systems, and expanding the use of healthcare records. Also, investment in wearable technologies and addressing disparities in access to healthcare and anti-seizure medications were part of the recommendations.

For the preclinical priorities, we emphasized uncovering the biological mechanisms underlying SUDEP through standardized animal models using common data elements, shared databases and tissue repositories, and coordinated international research efforts through open access platforms and shared infrastructure. We know that the number of groups working on SUDEP is relatively small, and we think that there is power in bringing them together.

In the area of awareness and education, we identified major gaps in communication about SUDEP between healthcare professionals, patients, and families. Solutions include education for clinicians, government agencies, caregivers, and the public, along with standardized tools to facilitate those discussions and improve reporting practices. The consensus agenda calls for better surveillance systems, stronger registries, and routine SUDEP reporting and timely support for bereaved families.

Overall, we'd like to see a more coordinated international strategy combining research, education, data sharing, and policy initiatives to accelerate SUDEP prevention, improve risk assessment, and ultimately reduce epilepsy-related deaths worldwide.

Host: Thank you. Dr. Pickard, so there is a neurologist listening to this conversation who has clinic tomorrow morning. Based on what we know about SUDEP risk, what actions could help reduce the risk for patients?

Hannah Pickard, PhD: Based on what we know about SUDEP risk and the available research evidence that we have, there are a few ways that neurologists can help reduce their patient's risk of SUDEP.

Firstly, I would say there needs to be a big focus on prioritizing seizure control. We know that one of the strongest risk factors for SUDEP is the presence and frequency of generalized tonic-clonic seizures and poor seizure control. So, neurologists should really focus on optimizing treatments where possible and improving medication adherence to reduce risk in the first instance.

Secondly, I think it's really important for neurologists to have routine conversations about SUDEP with their patients to support them to understand the risks of SUDEP, both the modifiable, as Laura mentioned earlier, and the non-modifiable risk factors that are associated with SUDEP, which go hand in hand are equally as important as each other. We know that having these conversations will help patients understand whether they might be at risk at a particular point in time, and also support them to take the steps to reduce their risk where possible.

And lastly, I would say it's incredibly important for neurologists to, where possible, use available tools that can help support meaningful conversations about risk with patients. There are several available tools out there, one of which we mention in the paper is the SUDEP Action, SUDEP and Seizure Safety Checklist. And research shows that using structured tools like this can lead to reductions in risk of SUDEP for patients.

So, these are just a few suggestions, guided by research and guided by our discussions throughout this consensus process that could really help reduce risk for patients.

Host: Dr. Lubbers, I want to ask about something less biological. So, how much of this comes down to whether a person can get access to their anti-seizure medications?

Laura S. Lubbers, PhD: Well, that's a complicated question with many facets to consider, but I'll touch on a few. So, it goes without saying, and as Hannah has already said, medication adherence is critical for reducing and hopefully eliminating seizures. A lack of medication adherence, whether it's due to lack of access to medications or other reasons, has been tied to an increased risk of SUDEP.

But research also shows that SUDEP can occur in people taking their medications. So, that alone doesn't explain entirely the occurrence of SUDEP, and more research is needed on this. But certainly, taking medications and being regularly seen by a healthcare professional are important steps. Many pharmaceutical companies have patient assistant programs to help people afford their medications if they're not able to. And if medications aren't controlling seizures, talking to their healthcare professional about other ways to control seizures, like implanted devices and other types of surgery, is recommended, as already alluded to.

Host: And as a follow-up to that question, moving from anti-seizure medications to seizure detection watches and devices, when someone wonders whether a seizure detection device will keep them safe, what can you tell them?

Laura S. Lubbers, PhD: I would say before buying a device, it's really recommended that patients speak directly with their healthcare professional and discuss their seizure type because not all seizure detection devices detect all seizures types. It's really important to do that as a part of discussing their seizure action plan. Devices may be particularly helpful for people who have seizures at night. As we know, SUDEP often occurs at night and when somebody is unattended.

There's evidence that when somebody is available to support the person having seizures, that they may be able to prevent SUDEP from occurring. Devices that are enabled to alert somebody may be particularly helpful in this circumstance, and many devices are being developed, but their effectiveness at keeping people safe is still being studied. Again, patients should talk to their doctors to ensure that they have a seizure action plan that may include the use of seizure detection devices.

Host: Thank you. Dr. Lubbers, here is something that might be surprising to many of us. After all these years, the field still cannot agree on what counts as a SUDEP model. Why is that so hard?

Laura S. Lubbers, PhD: Well, relatively speaking, the study of SUDEP is still in its relatively early stages. Science research takes a long time, and scientists are still debating what defines a SUDEP model that accurately reflects SUDEP in humans. I'll give you some background information on that.

Initially, we didn't understand what happens biologically to a person who experiences SUDEP. But one landmark study called the MORTEMUS study showed that people don't actually die during the act of convulsion, but after the seizure due to changes in breathing and cardiac function. function. However, in laboratory settings, animals almost always die during that act of seizure, which means that the model isn't capturing the right phase of the tragedy. This needs to be refined. Given the relatively small size of the MORTEMUS study, though, we are still trying to understand if the changes in respiration and cardiac function really reflect what's happening in the broader group of people who experience SUDEP.

Also, understanding and accurately modeling the biology to create relevant animal models takes time, iteration, and consensus. Compounding this, different laboratories use different methods and reporting. Some researchers use chemicals as seizure triggers, some use loud noises to trigger seizures, and others use other approaches. Because someone is starting their experiments differently, it's really hard to compare the results from different studies fairly.

The research community hasn't had a consistent way of describing their study protocols or outcomes. But recently, Cure Epilepsy conducted a project to define what are called common data elements for SUDEP to help researchers with a standardized way of reporting their studies and outcomes. And we're encouraging all researchers to use these tools to move the research along faster. Researchers can find more information on our website at cureepilepsy.org.

Host: Following up on that question, you lay out several mechanisms for prevention and treatment of SUDEP. Now, if you had to bet, which one gets us to a solution first or which one are you most excited about?

Laura S. Lubbers, PhD: This really isn't actually a research answer. It's an awareness answer, as already been touched on. I think one of the simplest solutions is to ensure that people know about the possibility of SUDEP, regardless of its rarity, and take effective steps to mitigate it. Throughout the various convenings summarized in the paper, this was a theme.

Research shows that people with epilepsy and their families want to know about SUDEP and to be able to do what they can to prevent it. This could mean taking measures to reduce and hopefully eliminate generalized tonic-clonic seizures, which Hannah has already mentioned are a significant risk, ensuring medication adherence and have seizure action plans.

Research also shows that families who are aware of SUDEP manage their grief more effectively if it does happen to their loved one.

Host: Moving on to you, Dr. Pickard. If we were able to connect epilepsy data across healthcare systems at scale, how could that transform our understanding of SUDEP risk and prevention?

Hannah Pickard, PhD: I think this is a really interesting question, and I think connecting epilepsy data across healthcare system could be incredibly transformative to what we can understand about SUDEP risk and prevention.

So firstly, I think, connecting data across these different systems at a population level. For example, data on seizures, data on medications, data on clinical history, and other risk factors, could really help us understand more about the development of personalized risk prediction tools for individuals who are at risk for SUDEP.

Understanding when an individual is at risk and how we can best prevent that from happening at that particular time, because we know risk isn't static for these individuals. It can also help us to better understand how different risk factors for SUDEP might interact with each other as well, and which patterns are associated with the highest risk at particular time points.

Another way that kind of better connected data could help us is to really understand how different factors like barriers to care, medication access, as Laura's touched on, and also socioeconomic factors like education and poverty influence SUDEP risk. Fortunately, SUDEP is a rare occurrence. And because of its rarity, it can be challenging for researchers to answer important questions about SUDEP risk and prevention. So, connecting data across different healthcare systems will be essential to help accelerate progress in research.

Host: Thank you. Dr. Pickard, only about one in five epilepsy professionals in the UK brings up SUDEP with patients, and the numbers are somewhat similar in the US, even though the guidance says that they should with every visit or every new patient. What is going on here?

Hannah Pickard, PhD: So, just to provide a little bit of background to the guidelines that are in the UK and the US. So in the UK, the guidelines state that SUDEP risk should be discussed following an epilepsy diagnosis. And I believe in the US, clinical guidelines recommend discussing SUDEP within two medical visits following diagnosis. But as we've reflected on in many conversations, in practice, this differs from state to state in the US. However, as you say, there still remains a gap between the guidelines and what happens in practice. And I think, there are several factors that could be contributing towards this.

So firstly, as we know from research, many epilepsy professionals may be understandably concerned about causing anxiety or distress by raising a topic that involves the risk of death. Despite this, it is incredibly important to have these conversations with all patients, whether they are high risk or low risk for SUDEP. As we know, and as I've mentioned before, risk can fluctuate over time.

Secondly, some epilepsy professionals may class patients as low risk because they perhaps don't exhibit the most commonly recognized risk factors for SUDEP. And as a result, the professional may feel that mentioning SUDEP isn't necessary for that particular individual. But we know that risk is not static, and an individual's circumstances can change over time, which is why ongoing conversations about SUDEP are really important for all patients as a matter of routine care.

Finally, one other kind of thing that's come out of the research is that time pressure is a big factor. So, time pressures within clinical practice can make it challenging to have detailed conversations about risk and safety with patients. And when appointments are short and multiple topics need to be addressed, discussing SUDEP may not always be prioritized by specialists.

We know, obviously, as we've mentioned in the question, there remains that clear gap between what guidelines recommend and what happens in routine practice. And I think to close that gap, we will need better training and education for healthcare professionals, which comes through all the way in our paper, and this could be through things like learning modules.

We also know that we need research to better understand the barriers that affect how risk is communicated to patients in that setting. And we also need wider use of tools that help facilitate meaningful conversations about SUDEP with patients as well.

Host: Thank you. Following up and a similar kind of a question, and you touched upon it briefly. Any suggestions on how clinicians can bring up the conversation at this point and do it well?

Hannah Pickard, PhD: Yes, absolutely. There are a couple of suggestions that have come through in a number of the meetings that we've had and the workshops that we've had as the Epilepsy Research Institute in the UK.

So, I think, to help support conversations with patients, clinicians can use tools that I've mentioned already, such as the SUDEP Actions, SUDEP and Seizure Safety Checklist, which is a robustly research tool that can support clinicians with conversations about SUDEP and risk screening. We know that using structured tools like this can make it easier to introduce the topic of SUDEP with patients. It can also help with kind of personalizing the discussion around the patient's specific risk factors that they're exhibiting. And we know that tools like this can also help with creating an action plan with patients to support them to reduce their risk outside of the clinic. And research has shown that tools like this can lead to reductions in risk. So, it's really important for clinicians to consider the available tools that they have at their hand. And if not, research the tools that they may not have seen yet or know about.

And then, kind of stepping away from the clinic setting, clinicians can also provide patients and families with leaflets and other reliable information that they can review in their own time. We know that discussions can be overwhelming, and we know that people may need more time to review and absorb information. So, providing that time and space to absorb information at home to bring questions back to the clinic is really important as well.

And I guess I just want to end on this question by saying, I think the most important thing is that discussing SUDEP should not be a one-off conversation. We know it should be revisited regularly in clinic with patients during routine reviews to make people aware of their current risk of SUDEP.

Host: Last one, and I would like to hear from you both. Everything in this consensus, what is the one thing you want to see happen in the next few years? And Dr. Lubbers, maybe we can start with you.

Laura S. Lubbers, PhD: I would like to see the research and funding communities continue to invest in understanding the factors that contribute to increased risk of SUDEP and identify ways to mitigate them. This knowledge will help foster a more accurate understanding of SUDEP, and we hope will encourage the discussions, the necessary discussions between healthcare providers and people affected by epilepsy, including their families, to understand and take steps to prevent SUDEP.

Host: Dr. Pickard?

Hannah Pickard, PhD: It's difficult to choose one thing from the paper that I would like to see happen because I think they are all equally important. But the one thing that I would like to see happen over the next few years is for the rates of SUDEP to decrease. And I think in order to do this, we're going to need more research to better understand the risk factors associated with SUDEP so that we can design better prevention strategies. We're going to need healthcare professionals to feel confident and supported in having these conversations with their patients.

And finally, we're going to need patients and families to be empowered with the information and support they need to understand and manage their risk appropriately.

Host: Thank you both for a thoughtful and, in places, a difficult conversation. For clinicians listening, the practical message is that the conversation about SUDEP is part of epilepsy care, not an optional extra, and all of us could do better. For families affected by SUDEP, stay strong. The fight against SUDEP is getting stronger.

Special thanks to our sponsor, UCB. For over three decades, UCB has been committed to people living with epilepsy and their families by leading in research, development, and treatment innovation. Past breakthroughs are only a prologue to the future as UCB reimagines how they care for patients and their families. Learn more at ucbfcompass.com.

If you found value in this episode, share it with a colleague, a trainee, or a family who might benefit from the conversation. And as always, subscribe and follow Epilepsy Currents on your favorite podcast app for insights that bridge research and real life. You can also find us on epilepsycurrents.org. Until next time, take care and keep the dialogue going.

Join Dr.Marawar in a conversation with Dr. Chalongchai Phitsanuwong and Dr. Priyamvada Tatachar as they discuss the article, "Add-on ketogenic diet versus antiseizure medications alone in children with developmental and epileptic encephalopathies: a prospective comparative cohort study" and its accompanying Epilepsy Currents commentary "Drugs, Diets, and DEEs: A Comparative Review of Medical and Dietary Treatments in Developmental and Epileptic Encephalopathies".

Click here to read the article.

This podcast was sponsored by UCB.

We'd like to acknowledge Epilepsy Currents podcast editor Dr. Adriana Bermeo-Ovalle, contributing editor Dr. Rohit Marawar, and the team at Sage.

This episode covers a 2025 Frontiers in Neurology study by Hu et al. and its accompanying Epilepsy Currents commentary on ketogenic diet therapy for developmental and epileptic encephalopathies (DEEs). Host Dr. Rohit Marawar speaks with Dr. Chalongchai Phitsanuwong and Dr. Priyamvada Tatachar about the study's findings that add-on ketogenic diet nearly doubled seizure-freedom rates versus medication adjustment alone, and produced meaningfully better developmental/cognitive outcomes. They discuss the rationale for earlier diet initiation, practical implementation (patient evaluation, dietician-led clinics, monitoring), manageable side effects, the search for response biomarkers, referral pathways for general neurologists, and the future of DEE treatment moving toward genetically targeted therapies alongside continued diet use.

Key takeaways:

1. Ketogenic diet outperformed medication adjustment alone: ~50% seizure response rate vs. ~29%, and ~20% seizure-free vs. ~10% (RR 1.73 for response, RR 1.9 for seizure freedom), consistent with prior literature (40-60% response, 10-30% freedom in DEEs).

2. Developmental gains, not just seizure control, may be the more striking finding: 36% vs. 5% showed developmental improvement on formal assessment, occurring even without medication changes, suggesting the diet has an intrinsic neuroprotective effect independent of seizure reduction.

3. Both experts argue for earlier initiation of ketogenic diet, especially in syndromes like epilepsy with myoclonic-atonic seizures (Doose syndrome, 79% response rate) and infantile epileptic spasms, rather than reserving it as a last resort after drug resistance and developmental regression are already established.

4. Side effects (mostly GI, constipation, "keto flu") are generally mild and manageable with proper monitoring (renal, bone health, lipids, micronutrients), and only ~3% discontinued therapy in the study; dedicated multidisciplinary keto clinics significantly improve feasibility and adherence.

5. No validated biomarker yet predicts individual response to the diet (early signals around acetylcarnitine levels), but resources exist for clinicians to start a program, including the Charlie Foundation, Matthew's Friends Foundation, the International Neurological Ketogenic Diet Society, and ILAE regional clinic listings.

Dr. Rohit Marawar (Host): Imagine a child whose first year of life is measured not in milestones, but in seizures, dozens a day, while medication after medication is tried and falls short, and development quietly regresses.

For children with developmental and epileptic encephalopathies, this is an all too common story. But what if one of our oldest therapies, a carefully formulated diet, could change not just the seizures, but the trajectory of a child's development?

Welcome to the Epilepsy Currents podcast, the podcast for Epilepsy Currents Journal, exploring the latest research and expert commentaries from the world of epilepsy. UCB is the proud sponsor of this episode, Episode Number 12 of Epilepsy Currents podcast. I'm your host and associate editor for the podcast, Rohit Marawar.

Today, we are discussing a prospective comparative cohort study by Hu and colleagues, published in Frontiers in Neurology in 2025, and the accompanying Epilepsy Currents commentary, Drugs, Diets, and DEEs to help us unpack what this means for clinical practice. We are joined by two expert voices in pediatric epilepsy.

First is Dr. Chalongchai Phitsanuwong, author of the commentary. Dr. Phitsanuwong is a pediatric epileptologist with a focus on ketogenic diet therapy, practicing at Bumrungrad International Hospital in Bangkok, Thailand. Welcome, Dr. Phitsanuwong.

Chalongchai Phitsanuwong, MD: Hello and good evening. Thank you very much for having me today.

Host: And then, we are also joined by Dr. Priyamvada Tatachar, a pediatric epileptologist based in Chicago with a special interest in tuberous sclerosis and who also contributed to the commentary. Welcome, Dr. Tatachar.

Priyamvada Tatachar, MBBS, MD: Good morning from Chicago, and thank you for having me on this podcast.

Host: Great to have you both with us. Let's dive in. Dr. Phitsanuwong, I'm going to start with you. To set the stage for our audience, what exactly are developmental and epileptic encephalopathies, sometimes abbreviated as DEEs, and how often are they likely to be drug resistant?

Chalongchai Phitsanuwong, MD: Thank you very much, Dr. Marawar. So, developmental and epileptic encephalopathies, or DEEs, represent some of the most severe forms of epilepsy. It's characterized by frequent seizures and abundant epileptiform activity on the EEG. It is commonly associated with developmental slowing and/or regression, like you said.

The current consensus is that both the underlying etiology and the seizures or epileptiform discharges contribute directly to this developmental stagnation or regression. DEEs carry an exceptionally high prevalence of becoming drug-resistant epilepsy, reaching up to 70% in some cohorts, by comparison to the typical 1/3 we see in general epilepsy population. So, more than double the numbers.

Host: Dr. Tatachar, from a frontline clinical standpoint, what does the day-to-day burden of a drug-resistant DEE looks like for a child and their family, and where do current medication strategies most often fall short?

Priyamvada Tatachar, MBBS, MD: I think the word overwhelming comes to mind when families face the diagnosis of developmental and epileptic encephalopathies. For most patients and parents, the initial diagnosis is basically an uncharted territory that comes with a lot of fear, uncertainty, financial and social burdens, and the day-to-day challenges of caring for a child with significant medical, social, and developmental needs. It's a very daunting situation for them.

Now, the current medical management focuses on the perspective of seizure control with several drugs added either alone or in combination for this reason. And as Dr. Phitsanuwong said, DEEs are particularly drug resistant. And based on the child's underlying diagnosis, additional challenges also need to be addressed for these families.

Host: Dr. Phitsanuwong, the Hu, et al study, which you wrote the commentary for, found around a 50% seizure response rate with add-on ketogenic diet versus around 29% with anti-seizure medication adjustment alone, and a seizure-free rate of around 20% with diet versus around 10% with ASMs alone, both of which were deemed statistically significant. Now, how meaningful is a difference of that size to you, and how does it compare with what prior studies have shown?

Chalongchai Phitsanuwong, MD: I think the result of this study is a highly meaningful context. Seizures in DEEs, like Dr. Tatachar said, are generally very difficult to control and have a high probability, of becoming drug resistant. In this prospective controlled trial, Hu and colleagues evaluated the patient with DEE who was still having seizure despite trying on an average of three anti-seizure medications already. And they found that adding ketogenic diet led to a significant higher seizure response rate. In the study, they defined as more than 50% seizure reduction, and they got the relative risk of 1.73. But what really stands out is the six-month seizure freedom rate from that.

The dietary therapy group was nearly twice as likely to achieve the complete seizure freedom compared to continued medication alone, with relative risk of 1.9, so almost double. And this finding also aligned beautifully with the historical retrospective and prospective data that we have, where we typically see the seizure response rate around 40-60% in patients with DEE alongside around 10-30% complete seizure freedom rate. So, I think that it carries quite a meaningful result.

Host: Great. Continuing with you, Dr. Phitsanuwong. So beyond seizure counts, the study also reported better EEG improvement and developmental gains in the diet group, 36% versus around 5% on formal assessment. Now, why is that developmental signal so important in this population, and how much weight should we give it?

Chalongchai Phitsanuwong, MD: This is very important question because this highlights a critical paradigm shift in how we approach the treatment of DEEs currently. Because DEEs are commonly associated with developmental stagnation and regression that can also worsen over time, our therapeutic success cannot be measured solely just by the seizure control or seizure count.

We should also focus equally on the neurodevelopmental and cognitive outcomes. While many anti-seizure medication, they are good, they can effectively reduce seizures. They frequently carry a heavy cognitive burden causing sedation, psychomotor slowing, impaired concentration, particularly in the setting of polypharmacy, which quite common in the patient with DEEs.

Ketogenic diet therapy, on the other hand, offers a distinct advantage on this point. Multiple studies has shown that it can actively promote cognitive and developmental improvement, particularly in alertness, attention, and global cognitive abilities. Interestingly, there's one landmark systematic review by van Berkel and colleagues showed that this cognitive benefit appears to be independent to seizure control, meaning even patients can experience meaningful cognitive gains even before a significant seizure reduction is achieved or apparent.

The study by Hu and colleagues strongly reinforces this, because they use formal age-appropriate assessment tools, and they documented a highly significant improvement as you showed the number, 30% to only 5% in developmental and cognitive scores in the dietary therapy group compared to the medication group.

And what makes this finding so clean is that it occurred without adjusting or reducing baseline medication during the study period. This provides a strong signal that the ketogenic diet may exert an intrinsic neuroprotective benefit that directly support development and cognition in this patient population.

Host: Dr. Tatachar, when you counsel a family about starting ketogenic diet, what are the practical realities they need to understand about feasibility, adherence, and the support a clinic has to provide?

Priyamvada Tatachar, MBBS, MD: Families and providers even usually are concerned about ketogenic diet initiation because they think it's a very complicated process. And unfortunately, this delays the initiation in many patients. It is really not that complicated if we understand the process well. Before initiating keto, a comprehensive evaluation of the child, their underlying diagnosis, specifically genetic diagnosis, the comorbidities, their metabolic health, whether they're oral or tube-fed status, and what are the social determinants of health? These are important things to assess to see if it's a feasible option for the family.

In addition, are there any food allergies, cultural or religious restrictions, any restrictive eating behaviors in that child. For example, in autism spectrum disorders. These are important parameters to assess, then we can tailor the diet for that particular family. It usually involves sitting down and going over the treatment roadmap with the family with a keto dietician and talking about the entire process with the risk and benefits discussed in a very open and transparent manner.

For this particular reason, dedicated ketogenic diet clinics are very helpful because they sit down with time, explain the rationale, initiation process, the formulas, the different types of the ketogenic diet from the most restrictive classic keto to the lesser restrictive diets, and which may also help improve adherence with the family. We have to monitor. There are surveillance labs that need to be ordered and followed up. And of course, the initial initiation part involves frequent telephone calls, telemedicine contact with the families that provides that extra layer of support and reassurance for the families that are already going through a lot. And this significantly improves adherence, and we've had families on ketogenic diet for over 10 years with really good compliance.

Host: Dr. Phitsanuwong, your commentary makes the case for considering the ketogenic diet early rather than waiting until epilepsy is firmly drug resistant. What is the argument for early initiation? And what holds clinicians back from doing it? In addition, how long should it be continued, and what are the outcomes after the diet is stopped?

Chalongchai Phitsanuwong, MD: Thank you for the series of questions. While we do not yet have a definitive and solid evidence to use ketogenic diet therapy before drug resistance develops across all the DEEs, largely because most of the literature focuses on drug-resistant cohorts. There are certain syndrome-specific DEEs where the ketogenic diet therapy can and should be deployed early.

A prime example is epilepsy with myoclonic-atonic seizures, formerly called Doose syndrome. Overwhelmingly, global evidence demonstrates that ketogenic diet therapy is one of, if not, the most effective interventions we have for this population. In a large multi-center cohort study by Nickels and colleagues showed that dietary therapy yield a striking 79% seizure respond rate and a 57% seizure freedom rate in Doose syndrome, compared to just 26% respond rate with the standard anti-seizure medications. And crucially, in the same study, the authors identified that failing ketogenic diet therapy was an independent predictor of overall treatment failure in these children.

Another compelling example that I can think of is in the infantile epileptic spasm syndrome. Data consistently shows that utilizing ketogenic diet therapy as a second-line therapy after failure of hormonal therapy or vigabatrin use, a 30% to 40% spasm-free rate along the clear EEG improvement.

However, in fact, there's a recent randomized control trial published in 2025 from India by Mahesan and colleagues compared ketogenic diet therapy directly to ACTH as a first-line treatment for infantile epileptic spasm syndrome. And they found that they both have comparable efficacy, but with a lower relapse rate and more favorable side effect profile in the ketogenic diet arm.

Giving these data points at this point and keeping in mind that we discussed earlier that the ketogenic diet also have intrinsic cognitive benefits, I believe that it's very reasonable to initiate dietary therapy early in selected patients with DEE. I don't think that we should feel compelled to wait until the epilepsy become firmly drug resistant and developmental slowing or regression is already apparent before we consider ketogenic diet therapy.

And for your next question about what holds clinician back, personally, I think that it is truly multifactorial. It often stems from structural barriers, like a lack of a specialist ketogenic dietician in your institute or limited access to a dedicated ketogenic diet center. As Dr. Thatcher mentioned that it works best when you have the multidisciplinary dedicated program. But there are also some clinical and educational hurdles. For example, a general unfamiliarity on how to initiate, monitor, and manage the diet, which naturally affects the clinician's comfort level to even offer the patient or the family the diet.

And additionally, I think that, there's still some perception of the patient's families or even clinicians that the diet are simply too difficult to implement or adhere to. And this factor leads many clinicians to hold back on starting the diet and viewing the diet therapy as an option of last resort, which is highly, highly unfortunate and not what the scientific data supports.

Your last question is how long the diet should be continued for this question, I think it's highly individualized. It depends on the epilepsy diagnosis, specific syndrome, its natural history, their response to the therapy, any perceived cognitive benefits from the diet, and ultimately, it's a family's choice.

Having said that, as a general rule of thumb, usually, we look at the landmark study from Johns Hopkins Hospital led by Dr. Kossoff, which they found that among the patients who responded remarkably well on the diet and achieved two years of seizure freedom, roughly around 80% of those patients remained seizure-free after the diet was discontinued.

This also sends us a signal that the diet may have the long-lasting benefit with the patient because even after the diet is discontinued, 80% remain seizure-free. And because of this, it has become a clinical practice that to discuss about the diet discontinuation to the patient and family after the two years of the complete seizure freedom. However, the ultimate decision usually lies on the patients and the family decision.

Host: Wonderful. Thank you for that answer. Dr. Tatachar, adverse effects in the study were mostly mild and gastrointestinal, with only about 3% discontinuing the therapy. In real-world practice, how manageable are the side effects and what monitoring do you put in place, for example, around growth, kidney stones, or bone health?

Priyamvada Tatachar, MBBS, MD: It's a great question. Initial side effects are common, especially when we are starting the diet, depending also on the age and the pre-morbid condition of the patient. We tend to do it as an inpatient setting. For that reason, it also provides us a time and opportunity to educate the caregivers.

Most commonly when we start, there is something known as the keto flu, which is a fatigue that sets in because the brain is adjusting to the alternative source of nutrition. Gastrointestinal side effects are quite common, but they are quite manageable as well. Constipation being the most common side effect of the ketogenic diet, and we use osmotic laxatives, for example, to tackle that. Improving hydration is very important as well. Now, we also have to provide education about sick days and illnesses and how to combat these illnesses, while on the ketogenic diet for the family so that they can adequately manage and not have adverse side effects from that.

Now, the long-term management and it's important to pay attention to kidney health and prompt supplementation. For example, with citrate salts, potassium citrate has been known to reduce renal stones. Surveillance is important, so we usually have labs done on these families. We also monitor fasting lipid profile as well as bone health like calcium and vitamin D and offer supplementation for trace minerals which may become deficient. For example, selenium and zinc and acetylcarnitine, for instance. These parameters are important to manage as we continue to monitor and surveil the child. It's very important also to make sure that the calorie intake is adequate for the growth of the child, and we plot their growth in an ongoing basis. For this reason, management of kids with developmental and epileptic encephalopathy is crucial in a multidisciplinary care setting, and this helps in providing a comprehensive care for that child.

Host: Wonderful. Dr. Phitsanuwong, the study could not identify any predictor of who responds to the diet. You raise a very interesting idea of a biomarker to guide therapy selection. How close are we to that, and what would it change?

Chalongchai Phitsanuwong, MD: Yeah. Thank you for the question. This is great question. So far, we do not have clear definitive biomarkers to predict an individual patient's response to ketogenic diet therapy. In clinical practice, we still rely primarily on syndrome-specific data or the underlying etiology to guide our expectations rather than individualized testing.

However, there's some interesting research looking into biochemical predictors of the response. For instance, there's a notable study by Dr. Natasha Schloeler from University College London and Great Ormond Street Hospital, published in Epilepsia, showed that the diet responder cohort has a significantly higher baseline acetylcarnitine level compared to the non-responder group. And upon their follow-up study, they found that the specific carnitine fractions show a trend. It's not statistically significant, but it show a positive trend as a positive predictor of ketogenic diet response. So, this is some signal in biochemical, study. I believe that if we can uncover reliable biomarkers, not just for the dietary therapy, but for other anti-seizure medications as well, it would completely transform our practice.

It would allow clinicians to tailor the treatments to the individual patient right from day one, and finally moving us away from the trial and error approach, that it's a good educated guess what we do, but we have to admit on some level it's a trial and error approach. So, to have biomarkers would be an ideal.

Host: Dr. Tatachar, for a general neurologist who does not run a dedicated ketogenic diet program, what is a realistic pathway to offer dietary therapy to a patient who might benefit? When to refer and what to set up locally? And is there a centralized database that provides information on which centers provide the ketogenic diet?

Priyamvada Tatachar, MBBS, MD: Yes. Especially in the last few years, there has been robust research on the ketogenic diet, notably for weight loss, but this has helped because this has brought a lot of keto-friendly food into the consumer space as well. Understanding the concepts in dietary therapy initiation by using verified online resources that are available and enlisting a keto dietician would be the first steps for a clinician who's interested in setting up a diet clinic.

In addition, there is the International Neurological Ketogenic Diet Society. Now, this society has webinars and symposia for those wanting to specialize in dietary therapies. In the United States, the Charlie Foundation for Ketogenic Diet and, in the UK, the Matthew's Friends Foundation, they have a keto college impact symposium that will help initiate people for the ketogenic diet program. And then, they can go back and set it up in their respective clinical practice. The Charlie Foundation actually has a list of all the ketogenic diet clinics in the US. And internationally, the International League Against Epilepsy, the ILAE, has a website for all the regional clinics listed around the world as well.

Now, every state has a verified center and a provider who feels that patients may benefit from the diet. It should be able to look that up and then refer patients to that center. And I think, as Dr. Phitsanuwong can attest, it is a very close-knit community. And they're always willing to help new patients or set up new programs, and they're always willing to offer assistance to any new clinician that's interested

Host: Thank you. Dr. Phitsanuwong, to close, you suggest combining modalities, diet with surgery or diet with neurostimulation. Where do you see the treatment of DEEs heading over the next few years? And what is the one message you would want a clinician or a parent to take from this discussion?

Chalongchai Phitsanuwong, MD: I personally see that the treatment of DEEs are gearing toward more and more etiologically and genetically specific therapies. With the emergence of gene editing or replacement therapy, the RNA-based antisense oligonucleotides and novel small molecules for specific genetic epilepsies. The pipeline is incredibly active and highly exciting right now.

However, because DEEs are extraordinarily heterogeneous and driven by a vast variety of etiologies, it is unlikely that we will have a specific disease-modifying therapy for every single one of them in the near future. And because of that, I still personally believe that ketogenic diet therapies would remain a highly attractive option because they offer proven efficacy in the seizure control. They can promote development and cognitive abilities, and also provide a variety of the diet types that we can tailor toward the individual patient's circumstances and needs.

If there is one message that I could leave it to other peers and the patients, it would be I would humbly but strongly encourage other peer neurologists and patients and families to employ the dietary therapy sooner rather than later for the patients with developmental and epileptic encephalopathies before the developmental regression or stagnation would become apparent.

Host: Thank you both for such a clear and practical discussion. Today, we heard that for children with developmental and epileptic encephalopathies, the ketogenic diet is more than a last resort. In this study, it roughly doubled the seizure-free rate compared with medication adjustment alone, improved EEG findings and, importantly, was linked to better developmental progress, all with side effects that were largely mild and manageable.

For clinicians listening, perhaps the takeaway is this: when a child with a DEE isn't responding to medications, dietary therapy deserves a seat at the table early, not after every other option is exhausted when development has already suffered. And for families, it's a reminder that meaningful options exist and that the right team can make this therapy feasible.

Special thanks to our sponsor, UCB. For over three decades, UCB has been committed to people living with epilepsy and their families by leading in research, development, and treatment innovation. Past breakthroughs are only a prologue to the future as UCB reimagines how they care for patients and their families. Learn more at ucbcompass.com.

If you found value in this episode, share with a colleague, a trainee, or a family who might benefit from this conversation. And as always, subscribe and follow Epilepsy Currents on your favorite podcast app for insights that bridge research and real life. You can also find us on epilepsycurrents.org. Until next time, take care and keep the dialogue going.

Join Dr. Bermeo in a conversation with Dr. Danielle Becker, Dr. Jacqueline French and Dr. Ammar Kheder as they discuss the article, "TRADEOFFS: What Are Patient-Reported Outcome Measures Missing?"

Click here to read the article.

This podcast was sponsored by UCB.

We'd like to acknowledge Epilepsy Currents podcast editor Dr. Adriana Bermeo-Ovalle, contributing editor Dr. Rohit Marawar, and the team at Sage.

The episode focuses on epilepsy outcomes that matter beyond seizure counts alone, using two 2025 papers and a related commentary to rethink how success should be measured in epilepsy care. Validation of the Seizure-Related Impact Assessment Scale by Dr. French and authors introduces a brief patient-reported tool that captures how many days are lost to seizures and how many are lost to treatment side effects. More Than Seizure Control: Multi-Dimensional Outcome Reporting in Epilepsy (MORE) as a patient-centered framework, redefining success in treatment by Dr. Kheder proposes a broader framework that combines seizure control, quality of life, and the patient's own experience of treatment. The commentary by Dr. Becker, TRADE-OFFS: What Are Patient-Reported Outcome Measures Missing?, ties these ideas together by emphasizing that better seizure control is not always a true success if it comes with worse cognition, mood, fatigue, or day-to-day functioning. The overall message is that epilepsy treatment should be judged not only by fewer seizures, but by whether life is actually better.

Key Takeaways

1. Seizure counts alone do not capture treatment success Across the discussion, a major point was that patients often care just as much, or more, about cognition, mood, side effects, independence, work, driving, and daily function as they do about seizure frequency.
2. SERIAS measures the real-life impact of seizures and side effects Validation of the Seizure-Related Impact Assessment Scale highlights a simple tool that asks how many days, or parts of days, were disrupted by seizures and separately by treatment-related adverse effects. This helps clinicians see the net impact of treatment rather than focusing only on seizure reduction.
3. MORE broadens outcome measurement beyond seizure control More Than Seizure Control: Multi-Dimensional Outcome Reporting in Epilepsy (MORE) as a patient-centered framework, redefining success in treatment proposes a structured way to combine seizure control, quality of life, and patient experience, so that meaningful improvement is recognized even when seizure reduction is modest.
4. The commentary frames these issues as trade-offs TRADE-OFFS: What Are Patient-Reported Outcome Measures Missing? emphasizes that every treatment decision should consider what is gained and what is lost. A patient may have fewer seizures but worse fatigue, worse memory, heavier medication burden, or new social and functional problems.
5. These approaches could improve both clinic care and research trials The discussion suggests that tools like SERIAS and frameworks like MORE could help with medication decisions, surgical counseling, neuromodulation follow-up, and clinical trials by capturing outcomes that matter most to patients in everyday life.

Adriana Bermeo-Ovalle, MD (Host): What if the most difficult part of living with epilepsy is not the seizures? Most people living with epilepsy report being more burdened by stigma, social limitations, and psychiatric comorbidities than by seizures themselves. So, the real question becomes: how do we measure the impact of epilepsy and the success of our treatments beyond side effects and seizure counts?

UCB is the proud sponsor of Episode 11 of Epilepsy Currents Podcast. I am the senior podcast editor for Epilepsy Currents, the official journal of the American Epilepsy Society. Today, we will be discussing the epilepsy outcomes beyond seizures with a phenomenal panel of speakers.

Let me first introduce our own Epilepsy Currents contributing editor, Dr. Danielle Becker, who's a recurrent guest in our Epilepsy Currents podcast. Dr. Becker wrote a commentary titled TRADE-OFFS: What Are Patient‑Reported Outcome Measures Missing? This commentary was published in October 2025. Dr. Becker, welcome back.

Danielle Becker, MD, MS: Thank you so much for having me.

Host: It is also my pleasure to welcome Dr. Jackie French, senior author of one of the studies which inspired that commentary published in Neurology in August 2025, titled Validation of the Seizure-Related Impact Assessment Scale. Dr. French is Professor of Neurology in the Comprehensive Epilepsy Center at NYU Grossman School of Medicine and Founder and Director of the Epilepsy Study Consortium and leader of multiple initiatives in our epilepsy community. Dr. French, welcome. It is a pleasure to have you.

Jacqueline French, MD: It's great to be here. Thanks a lot for inviting me.

Host: And last but not least, I am very happy to introduce Dr. Ammar Kheder, who wrote a second paper referenced also in Dr. Becker's commentary titled More Than Seizure Control: Multi-Dimensional Outcome Reporting in Epilepsy (MORE) as a patient-centered framework, redefining success in treatment. This article was published in epilepsy in March 2025. Dr. Kheder is Associate Professor at Emory University and Assistant Medical Director for Epilepsy and Neurodiagnostics at WellStar Health Systems in Georgia. Welcome, Dr. Kheder.

Ammar Kheder, MD: Thank you so much for having me. It's a pleasure to be here with you today.

Host: Okay. So, let's get started. Dr. Becker, how would you describe the current state of patient-reported outcomes in epilepsy? What are we still missing? What are we not capturing?

Danielle Becker, MD, MS: Thank you for this important question. I feel the current state focuses on seizure frequency and seizure freedom, but we need to acknowledge that seizure freedom may not be the number one goal of our patients or the only thing that matters. And the other question is at what costs.

So, there are other important factors: cognition, memory, mood, side effects, quality of life. And when you talk to patients, they often will focus on functional outcomes such as driving and employment and their independence. But they will also talk about the treatment-related adverse events and the unpredictability of seizures and how that individually affects their everyday lives.

So as was mentioned in the two reporting outcome papers that we'll talk about today, they call for the incorporation of individual priorities for patients' subjective experiences really to promote that patient-centered care and improvement in outcomes not only looking at seizure frequency or seizure freedom, but also at that balance or tradeoff of treatment-related adverse events. So ultimately, with where we are today, I think we need to refocus our epilepsy care on considering outcomes that are most important to each individual patient and their families, and really move to that patient-centered care of the goals that are most important to them, as well as their seizure frequency and seizure freedom possibility.

Host: Thank you for that, Dr. Becker. Very important to keep in mind what matters to each patient, what maybe to ask our patients, what really matters to you on an individualized basis. Dr. Kheder, can you please give us a quick overview of what MORE is and what it was designed to measure? And how do you envision people to use it?

Ammar Kheder, MD: Well, thank you for this question. MORE is a way for capturing what doing well in epilepsy actually means in real life. I see it as a complementary to what Dr. French has done in making impact visible over time, and to the questions Dr. Becker raises about what current outcomes don't fully capture when taken individually.

So instead of focusing only on seizures, MORE brings together three domains: seizure control, quality of life, and the patient's own experience. The idea in my mind is simple, a treatment isn't necessarily successful unless it improves how someone lives, not just how often they have seizures. For example, if you have two patients who might have the same seizure reduction, but one has gone back to work and reduced medication while the other is cognitively worse and more depressed, MORE is designed to see that difference. It's meant to be practical using structured questions that can fit into a routine clinic visit. It's less about replacing existing systems and more about bringing together dimensions that have often been measured separately.

Host: Very interesting. I'm sure we will go over how to integrate that into the clinic and what we do on a practical basis every day. Dr. French, can I ask you the same questions for the SERIAS approach? Can you give us a high-level overview of how does it measure and what does it add compared to our tracking of traditional outcomes?

Jacqueline French, MD: Absolutely. So, unlike the MORE, it really squarely focuses on whether your treatment, whatever it is, has made a positive or negative impact on an individual's life. So, it doesn't measure everything that's important to a person with epilepsy. It really focuses on has the intervention improved seizures and has the intervention, on the other hand, caused a disability because of the side effects that now have arisen?

Because often when you look at outcomes from interventions, you say, "Oh, X percent of the population had a 50% reduction or a 75% reduction in seizures. And y percent had side effects or had to drop out because of side effects," but you don't know how those two interconnect with each other. So, you don't know whether there are people who are very happy having fewer seizures and no side effects, or did everybody who got improvement in seizures have side effects.

And also, the other principle of the SERIAS is to keep it simple. So, it's just a series of five questions, and it really asks about ability, disability in regards to seizures and side effects. So, how many days or portions of days were you unable to do what you wanted to do because of seizures, and then independently because of the side effects of the medication, to see what those trade-offs are.

And the other thing that it brings to the table is that it does not only focus on the number of seizures, but the impact of the seizures. So, many of my patients tell me, "I have a seizure in the morning. And as a result of that seizure, I am dysfunctional, not only for the day that the seizure happened, but I don't really get back to my normal function until three days later for a serious seizure." And we wanted to be able to capture that if that is occurring, and that's very important to patients as well.

Host: Sure. We get a better idea of what is beyond a number of seizure, right, or a percentage of seizure. I do think the same, Dr. Kheder, we got a better idea of what doing well with epilepsy goes beyond that. But, if you don't mind, can you give us a more detailed overview of what this 40‑40‑20 split across the seizure control, quality of life, and patient experience? And why did you decide over this split? How did you and your team decide to go over a split like this and to use that as a scale or a split in the MORE scale?

Ammar Kheder, MD: Thank you. Yeah. It wasn't meant to be mathematically exact. In a way, it was more meant to be clinically honest. Seizure control still anchors epilepsy care, so it carries weight. But quality of life deserves equal importance because it often determines whether a treatment actually helps the person sitting in front of us.

The final piece is the patient's own experience, how they feel about the outcome, whether they'd recommend the treatment or choose it again. So, the 40-40-20 structure really reflects the balance, correcting the historical emphasis on seizures without dismissing them. For instance, a patient might have only moderate seizure reduction, but a big improvement in mood, daily function, medication burden. In MORE, that can still score as meaningful success. It's in some ways a starting point and something can evolve as we learn from patients and also from tools like the SERIAS.

Host: Thank you. Dr. French, you gave us an idea of how do we use the days of impact and the time loss. Can you tell us how do you use that to make decisions in the clinic? Because you can get this approach, but as Dr. Becker was telling us, it can mean different things for different patients, meaning for some people, you know, a different side effect may be okay to withstand, versus for another one, this can be really not something they can live with. So, can you help us understand that approach and how do you use that maybe to make decisions or to help patients make decisions in the clinic?

Jacqueline French, MD: By the way, I just wanted to point out that the SERIAS is based entirely on another scale in the neurology community called the MIDAS, the Migraine Disability Assessment Scale. And I think that the reason that the MIDAS has become a staple in the headache and migraine world, is because also having a headache can have many consequences and can cause disability that far outlasts just the onset of the headache or the type of headache can really be different from one to another.

And the purpose of the scale, the MIDAS scale, has gone to the point where, for example, there are many MIDAS scales that are available online to tell people what their level of disability is. And if you find that many of the days of the month are disabling or the headache is disabling, then actually that—when presented to a physician—can open the door to a higher level of care. So, it's not only saying, "This is how you were last month. This is how you are this month." But if you see that a high proportion of days for an individual are impacted by their epilepsy, then hopefully physicians will say, "This person needs to be sent for a higher level of care. This person should have access to an epilepsy center, epilepsy surgery, the more expensive medications in some cases." So, it can be used in that way as well.

But I think very importantly in the clinic, and I'm very happy to say that many people have already reached out to us to acquire the scale to be used in clinic so that we can learn more about how it helps or how it doesn't help and how it really measures things. So, I'm really interested to see what happens in those regards. But I think that if you have someone back to the clinic and you look and you see that, since you made this change in medication, they have marked many days as being disabled by side effects, that will focus your attention on that, and you will start asking questions of that individual in regards to what the side effects are and how they are impacting their ability to function.

And I did also want to mention that there's two versions of the SERIAS, and people can choose whichever one they want. One is to just verbally say how many days or portions of days, and people can fill it in. But another one, which some people find easier is the traffic light version in which people just are presented with a traffic light with a green light, meaning everything's fine for the day; a yellow light, meaning things were not as they should have been, but I was able to perform some functions; and a red light, which means that day was basically lost to me.

And I think that that really resonates with people, including parents. I've heard this a lot from parents whose children have, for example, a developmental and epileptic encephalopathy. And they put it in terms of good days and bad days. There are good days and bad days and very bad days. And if that day, the child had a series of seizures in the morning and they spent the entire day in the emergency room, that is a lost day, that's a red day, for example. You don't have to be seizing throughout the entire day for it to be a red day. And you basically can ask someone how many of your days this month were red, yellow, and green. And for some people, that is a very simple and straightforward concept, and they are able to recall over the course of the month and give you an idea of how many days they were functioning well.

And by the way, when we assessed the scale with Dr. Emma Foster in Melbourne, many, many people with epilepsy had mostly functional days. So if you do see someone where a lot of days are dysfunctional, that is not typical for a person with epilepsy. And I just want people to be aware of that.

Host: Yes, absolutely. Dr. Becker, I really like how you place this under the title of trade-offs. Like, what do we exchange for what, right? So, in real life, what are we trading for what? What examples do you find in your clinic? And how can clinicians talk about this in a way that is helpful? What kind of clinical pearls or real life scenarios come to mind? Or can clinicians talk about this? What can we learn from this? Or what do you want our listeners to remember from your commentary?

Danielle Becker, MD, MS: So, I think I like the word tradeoff because it's catchy, but it's also honest. It's what we need to be thinking about when we're talking to our patients. Seizure control at what cost? And the tradeoff is really seizure control versus the treatment-related adverse effects, especially someone who may have a seizure once a month, but has adverse effects from their anti-seizure medications every single day.

And I love the way Dr. French talked about green, yellow, red type of day. It may be that there's a day that they don't have any seizures, but it's a yellow or red day because of the side effects that they're having from their medications. And the SERIAS paper also looks at disability and what the term disability means for the patients. Also, did the disability result from the seizures or from the treatment themselves? And so, that's really what I wanted people to think about, because it's very impactful to a patient's quality of life. And we might make what we feel is an important modification to a treatment regimen that improves the patient's seizure control, but at what expense? So if we increase a medication and their seizures are reduced by half, but their tiredness is hugely increased to the point where they may not be able to function, they may not be able to go to work, that is negatively impacting their quality of life, even though their seizures have improved.

And in the SERIAS paper, they also talk about time lost. And we often think of time lost as the seizure, right? How long did you have altered awareness or altered consciousness during the seizure, but it's also time lost of when you could enjoy time with your family, your loved ones, feel fully functional at work. And so, some examples that I feel like—besides the one I just mentioned about tiredness—is also when we think about seizure freedom, right? We do this huge surgical workup and we do neuropsychological evaluations, and we're trying to predict what is the impact on their quality of life, what's the impact on their memory, on their cognition. And even if someone becomes seizure-free, if their memory or cognition is impacted to the point that they can no longer work, how will they rate their quality of life? Was that tradeoff worth it? And that's something that we can't necessarily say as providers, but patients—they are the ones that are individually living this every single day, and they are the ones that need to be involved in this conversation.

And then, one other example, I think of another patient that I sent for surgery and she became seizure-free. She had a right temporal lobectomy, but she could no longer read social cues as well, especially from her husband. And it actually created a lot of stress in the relationship, which was something that we sometimes don't know. But the point is that it's more than just seizure frequency. It's more than just seizure freedom. Each individual patient has their own goals, and we need to be addressing them and finding out what impacts their everyday lives.

Host: Yeah. That is such an important point. And the reality is that sometimes with surgery, there's so many unintended consequences, some that we really cannot truly foresee. That is a very good segue to my next question. I would like to ask Dr. Kheder, how do you see that we can use this type of beyond seizure outcomes, and these type of conversations when we talk about surgery and neuromodulation? Have you used the MORE scale or how do you think we can use these type of scales beyond pharmacological interventions?

Ammar Kheder, MD: Yeah. I think this is a great question. And in fact, the way the concept of MORE was developed, in some ways, started out with trying to capture some of the gaps in our current systems where we don't really capture harm very well. So in some of those surgical patients, for example, a patient can be seizure-free, but worse overall. And we have no structured way to reflect that.

The MORE allows that to be somewhat visible by allowing the negative score when things such as cognition, mood, or function decline or side effect perhaps are severe. So, more specifically about conversations related to surgery or neuromodulation, that matters. Because we're not just asking will the seizures improve, but also what is the overall trajectory likely to be?

For example, if a patient has corpus callosotomy and seizures are reduced to some extent, but it causes major cognitive and functional decline, the MORE score can actually fall into a negative territory, which communicates that the net impact is potentially harmful. In some ways, as we discussed trade-offs, it helps make these trade-offs more explicit and more honest, especially in situations where the surgical decision is somewhat not straightforward. So, I think that's perhaps one advantage with using something like the MORE scale.

Host: Thank you. Dr. French, how about in medication trials in which we are sometimes just so focused on seizure counts and seizure reduction? Should we use more non-seizure outcomes, and how to integrate that into medication trials?

Jacqueline French, MD: Yeah, I think that for trials, the SERIAS has a couple of benefits that we are very significantly working on. The first is that for many of the developmental and epileptic encephalopathies, the seizures are so rapid and so brief, and they come in clusters that they actually we consider them uncountable. We can't count the atypical absences, the myoclonic clusters. I usually represent this by talking about if seizures were birds and we were asking parents to count every single bird that flies over their head every day, obviously, it would be an impossible task. But if you see a flock of birds, a large flock of birds flying over, it's basically impossible to figure out how many birds are in that flock. But if you ask a question such as, "Did you see a lot of birds today? Did you see not that many or none at all?" That's a much easier question to answer. So in fact, in studies of developmental and epileptic encephalopathies, several people are now using a daily SERIAS, so a daily traffic light of red, yellow, and green, to get a sense of how the other seizures are impacting.

And also, again, back to the consequences of seizures, there have been so many attempts to do seizure severity scales to put into clinical trials. And unfortunately, they become very long, very complex. Sometimes some of the scales take up to an hour to complete, an hour of both the patient and the caregiver and observer and a coordinator. So, we needed an easier way—a simpler and easier way—to try and address whether seizures are not only becoming less frequent, but also becoming less impactful. And again, it all comes back to impact on the individual.

And finally, to your point, I think that taking into account, as Dr. Becker said, the tradeoff of, yes, your seizures went down, but have you now lost the ability to function, have you lost function because of significant side effects, and do it within an individual rather than within the entire population so you can see those trade-offs, whether people actually have more functional days overall or less functional days overall after the treatment has been initiated will be very insightful when looking at the results of clinical trials.

Host: Great. I have one more question for all of you before we finish our podcast today. If we can close with one practical message for clinicians as they are with the patients in the clinic to consider different outcomes, Dr. Becker, what would be one practical message for clinicians to do better in regard to non-seizure outcomes?

Danielle Becker, MD, MS: So, one thing I would want to bring up is drug load. We didn't talk that much about that, but we talked about treatment-related adverse events. And a lot of that is from our anti-seizure medications. And so, how does drug load or the number of medications they're on, or the doses that they're on, how does that affect our patients' everyday functioning?

And it's important to think about this outside of surgery and also post-surgery or post-neuromodulation, to remember that if we add a medication on that helps someone with better seizure control or better seizure frequency, don't forget about the other comorbidities that can develop and impact them every day. And so, think about reducing those medications. If you've added a medication or if they've had a surgery or had a neuromodulation device that improves their seizure frequency, don't forget about the other piece of the picture: At what cost? What changed? And if there were comorbidities that worsened that you need to address those just as much as the seizure frequency or potential for seizure freedom.

Host: That's a great clinical pearl. Dr. Kheder, what is your take-home message for our listeners today? What can we do better?

Ammar Kheder, MD: I think for me the simplest shift is really to ask one extra question at every visit. Are you actually doing better, not just in terms of seizures, but in terms of how are you living? Can you drive? Can you go to work? Can you go to school? Can you get on a public transport? Are you able to think clearly? Do you feel emotionally stable day to day? If we consistently ask that and take it seriously, our care starts to change.

What I like about SERIAS and what Dr. Becker's focus on trade-offs is that they push us in the same direction where we align how we measure outcomes with how patient actually experienced epilepsy.

Host: That is another wonderful message for our listeners today. Dr. French, any other pearls that come to mind?

Jacqueline French, MD: Yeah. I cannot help but remember a patient of mine who, when he came into the office after a medication change, and I said, "How are things going? My seizures are great. I'm seizure-free. I haven't had any seizures." Are you tired during the day? "No, I'm not tired during the day." And finally, I hit on the correct question only after asking many questions, and that is, "And how is your sleep?" And it turned out that he was sleeping not his usual eight hours a night, but now was requiring 12 hours a night of sleep. And if any of us can imagine life, if we needed 12 hours a night of sleep, that doesn't—you know, he was actually an attorney, which doesn't give you much time to live any life other than working and sleeping. And you can go through many questions and not necessarily hit on the one that is the important one. So, this sort of allowing people to tell you, translating it all—as Dr. Becker said—into lost time, lost function sometimes helps start that conversation that ultimately gets to what's the most important thing that has changed for that particular individual.

Host: Yes. Thank you for that. I have learned a lot. I think asking the right questions and sometimes patients want to please us, right? They want to tell us that they're doing great. Thank you all for a wonderful conversation.

I want to thank you all for joining us today for this conversation at Epilepsy Currents podcast. And I also want to thank you all our listeners. Special thanks to our sponsor, UCB. UCB, for over three decades, has been committed to people living with epilepsy and their families by leading in research development and treatment innovation. Past breakthroughs are only a prologue to the future as UCB reimagines how we can care for patients and their families. To learn more, go to www.ucbcompass.com.

Thanks to Dr. Rohit Marawar and the SAGE Podcast Production Team. We look forward to having you join our next podcast episode. Remember to subscribe to Epilepsy Currents Podcast wherever you get your podcast, and send us your feedback, suggestions, or questions through our website, epilepsycurrents.org, and follow us on X former Twitter @aescurrents. See you next time.

Join Dr. Marawar in a conversation with Dr. Danielle Becker and Dr. Martha Sajatovic, as they discuss the article, "The Impact of Perceived Epilepsy Stigma"

Click here to read the article.

This podcast was sponsored by the American Epilepsy Society through a grant from the Centers for Disease Control (CDC).

This activity is supported by the Centers for Disease Control and Prevention of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling $1,500,000 with 100 percent funded by CDC/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by CDC/HHS, or the U.S. Government.

We'd like to acknowledge Epilepsy Currents podcast editor Dr. Adriana Bermeo-Ovalle, contributing editor Dr. Rohit Marawar, and the team at Sage.

Summary

In a baseline analysis from the CDC-funded SMART self-management trial, Dr. Martha Sajatovic's team evaluated 120 adults with uncontrolled epilepsy using the 10-item Epilepsy Stigma Scale. Higher perceived stigma was not tied to seizure frequency or most demographics; instead it clustered around a short list of modifiable factors: being single, receiving little social support, scoring low on the Epilepsy Self-Efficacy Scale, and reporting poorer day-to-day functioning. Dr. Danielle Becker's accompanying commentary argues that these "big three" drivers—self-efficacy, social isolation, and depression—form a hidden clinical burden as real as any EEG abnormality and should be addressed as routine vitals in epilepsy care. Both authors highlight peer-led programs such as SMART, which blend nurse facilitation with a trained person-with-epilepsy co-leader, as a scalable way to lift self-confidence, expand support networks, and ultimately blunt stigma's impact.

Key Takeaways

1. Core Correlates of Stigma: In the SMART cohort, the strongest independent predictors of high stigma scores were low social support, low self-efficacy, and poorer functional status; seizure count and most demographic variables showed no significant link.
2. Self-Efficacy Is Central—and Modifiable: Lower confidence in managing seizures (self-efficacy) tracked closely with higher stigma. Boosting patients' belief that they can control triggers, medications, and disclosure decisions is a direct route to stigma reduction.
3. Depression Magnifies Stigma's Weight: Undiagnosed or undertreated depression deepens perceived stigma and worsens quality-of-life scores, underscoring the need for systematic mood screening and at least initial SSRI therapy while specialty referrals are arranged.
4. Peer-Led Self-Management Programs Work: Evidence-based curricula such as SMART (eight weekly Zoom sessions co-led by a nurse and a trained person with epilepsy) consistently raise self-efficacy scores, increase rescue-plan use, and shrink stigma—benefits that persist when agencies or clinics adopt the program.
5. Clinic & Policy Action Points: Ask about stigma, self-efficacy, and mood at every visit; offer a printed or electronic referral to a vetted self-management course or local support group; and advocate for payer coverage of these programs so that addressing stigma becomes as routine—and reimbursed—as ordering an MRI.

Dr Rohit Marawar (Host): [00:00:00] Picture this scenario. Two patients leave clinic on the same day. One with excellent seizure control, yet feeling ashamed to mention their diagnosis. The other with daily seizures, but surrounded by supportive friends who see them not their epilepsy. Those contrasting stories sit at the heart of today's conversation about stigma and invisible force as real as any spike and view on an EEG.

Welcome to Epilepsy Currents podcast, the podcast for Epilepsy Currents Journal, exploring the latest research and expert commentaries from the world of epilepsy. I'm your host and associate editor for the podcast, Rohit Marwar. To unpack why stigma still sticks, and more importantly, what we can do about it.

We are joined by two leading voices. First is Dr. Martha Stoic, first author of the article, clinical Correlates of Perceived Stigma Among People Living With Epilepsy, enrolled in a Self-Management Clinical Trial. Published in Epilepsy and Behavior Journal in [00:01:00] 2024. She's a professor and director of the Neurological and Behavioral Outcome Center, university Hospitals, Cleveland Medical Center in Cleveland, Ohio.

Welcome Dr. Wick.

Dr Martha Sajatovic: Thank you.

Dr Rohit Marawar (Host): Then we have Dr. Daniel Baker, whose commentary, the stigmatizing impact of perceived epilepsy stigma. Puts those findings in a broader public health frame. Dr. Becker is the division director of epilepsy and associate professor of neurology at the Ohio State University Wexner Medical Center.

Welcome, Dr. Becker.

Dr Danielle Becker: Thank you for having me.

Dr Rohit Marawar (Host): Great to have both of you on our podcast today. Let's dive in. To kick things off, Could you give us a quick elevator pitch of your study, who you enrolled, what you measure, and the takeaway finding our listeners should remember?

Dr Martha Sajatovic: Yes. Thank you. I'm happy to talk about that. So, this analysis comes from a larger parent study. That was funded by the Centers for Disease Control and Prevention, or CDC. we are part of a, network called the Managing [00:02:00] Epilepsy Well or MU Network, which has been supported by the CDC for many years.

The goal of the MU network is to develop, and test, evidence-based epileptic self-management. Curricular programs. This, analysis came from one of our randomized clinical trials that we are doing, testing a program called the Smart Epilepsy Self-Management, program. In this analysis, we focused just on baseline data.

So we weren't looking at outcomes, but we were interested in looking at the correlations or the associations between, perceived stigma. So stigma that people, perceive people with epilepsy perceive in relation to demographic and other, clinical variables. So, basically we found that, stigma was related to, not very many demographic variables, really just, not being married or, cohabiting, but we did find that, higher levels of stigma were associated with.

Less social support. So I was thinking of that in the little scenario that you gave, lower, scores [00:03:00] on a standardized rating of self-efficacy and lower functioning as well. So, there's appears to be that inverse, relationship.

Dr Rohit Marawar (Host): Dr. Becker, you call stigma a hidden burden in your commentary from your vantage point, what does the burden look like in the everyday lives of people living with epilepsy in 2025?

Dr Danielle Becker: Thank you. So I do wanna say that I think this hidden burden is not only on our patients, but also on the caregivers. Both the patients and the caregivers live with fear that a event or a seizure can happen at any time, and we know that that's associated with significant emotional burden.

This emotional burden leads to both mental and physical health. It leads to anxiety and depression. We also know that it affects opportunities for patients with employment, with education, with developing social relationships. So in all we know that it, really is impacting mental health and we really, through this commentary and through Martha's.

Paper and [00:04:00] work with the smart program. We know that when you have depression, especially undiagnosed depression, it worsens stigma and really that is a heavy burden on our patients and caregivers.

Dr Rohit Marawar (Host): Well said, Dr. Vic. We hear the terms stigma and perceived stigma to. Around, and I think you also mentioned that just now, but how do you separate the two and why did you land on the 10 item epilepsy stigma scale? To capture it,

Dr Martha Sajatovic: so that's a really excellent question. There are actually different types of stigma. if you look at the stigma literature, so there's, felt stigma, you know, if I am going to discriminate against you, sometimes called proceed stigma. there's, what we. As individuals get from our society or from those who are close to us, how do we get treated or discriminated against?

there's also a, internalized stigma. Where were people? you know, if you tell something to somebody often enough that's negative [00:05:00] about themselves, often, eventually they will start to believe that. So what we are really looking at is a standardized scale. So there aren't actually that many specific, epilepsy stigma scales around.

Rather, this was one that had already been tested and used, and we, thought would be generalizable to, the other literature. So what do people with epilepsy experience and what do they perceive?

Dr Rohit Marawar (Host): Okay, great. and I'll stay with you Dr. So. We have moved away from the term epileptic people to the more app appropriate term persons with epilepsy or people with epilepsy. I noticed that you use the term people living with epilepsy in this study, which was a first for me. Why did you use that term, and why is that wording choice important in the fight against stigma?

I.

Dr Martha Sajatovic: Thank you for noticing that and appreciate that. so the goal here is that we really want to have the language that we are using be very person centered, right? in the smart program, which we'll probably talk about in a, couple [00:06:00] minutes, but, we really stress the. The point that you are a person that's living with epilepsy, you are not epilepsy.

And epilepsy may impact your life in substantial ways often, but you are still an individual. You have stresses, you have joys. and so really anything that helps reinforce that, you are not this disease. Your person living with epilepsy is, extremely important. And over time, I think. Words matter.

If we use words in ways that are appropriate and uplift people rather than grind them down, hopefully we can eventually win this battle against stigma.

Dr Rohit Marawar (Host): Dr. Becker. thinking back to the 2012 Institute of Medicine call for action. Where have we moved the needle on epilepsy stigma and where are we still spinning our wheels?

Dr Danielle Becker: So I think we've moved the needle as far as accreditation of different epilepsy centers as far as working with mental health providers and [00:07:00] primary care as far as the foundation work that we. Done support groups, resources with epilepsy foundation, epilepsy alliance, discussion about seizure action plans and seizure rescue medications, having more acceptable routes of administration. I think we've also done a great job in increasing awareness about sudden unexpected death in epilepsy and discussing it and acknowledging that people do wanna hear about it.

I think where we still have a lot of work is still in awareness, especially workplace awareness. I have a patient right now who is fighting for her job and we filled out all the paperwork. She has a rescue plan, she has a nasal spray, and she was let go. And so I think as much as we try to increase awareness.

What we really need to do is that people are still gonna have seizures and they're gonna be unpredictable, but give them something predictable to do in that unpredictable world. Help them have action plans, help their employers with [00:08:00] education and understanding, and try to help them have a life that they want.

If it's that they wanna work, if it's that they want to be part of an organization, increase their. Resources, their support. And I think we are doing a good job, but there's still a lot that needs to be done. And while awareness and talking about that, one in 26 people have epilepsy, that does bring it to the table.

But there's more that we have to do.

The other thing that I think we are still spitting our wheels is access to care for all. We talk about the fact that there are patients in rural settings. There might only be one neurologist.

There's patients that have refractory epilepsy and may not get evaluations of comprehensive epilepsy centers. We want to be able to improve access for all treatment for patients with epilepsy and all medications.

Dr Rohit Marawar (Host): Dr. Vic, your data shows that lower self-efficacy [00:09:00] walks hand in hand with higher stigma in plain language. What is self-efficacy and why does it matter so much here?

Dr Martha Sajatovic: Yeah, so self-efficacy is very important. We did see that self-efficacy popped in our multi-variate, models as being, highly relevant. to stigma. So, self-efficacy is a term that fits in with, a model of behavioral change. We use the social cognitive model in our, evidence-based epilepsy self-management programs.

And just to kind of break it down, people have, they have to have several things that they need in order to make positive behavioral change. First of all, you have to have the knowledge. So, if I need to know what I should do and what I should try to avoid in managing my epilepsy. So I have, I mean, that's critical, but just giving people education is not enough.

Right. That's why many times we as clinicians, you know, we give people, patient printed materials or we tell them to do this and that, and, somehow it just doesn't. Materialize. So it's that self-efficacy. So they have to have the knowledge, but then they need to have [00:10:00] the confidence and the motivation so that, that's just self-efficacy.

I feel confident that if I make this behavioral change, that I will get the desired outcomes that I know what to do and I feel like I can do it. So that's self-efficacy and those are really critical. And one of the problems that we have in many clinical care settings is that. Clinicians are very busy.

When we're in there seeing patients, we have to think about, how many seizures have you had, what it could look like, what were the precipitants? I have to look at perhaps medication changes or side effects or drug levels. Right? very often the thing that gets left. By default is, how confident do you feel in managing your epilepsy?

But our data really highlights that. That's extremely important. It's a point the clinician should consider, but there are also other evidence-based practices that we can pull in to, identify, strengths or gaps and self-efficacy, and then downstream the [00:11:00] effects on epilepsy self-management.

Dr Rohit Marawar (Host): Dr. Becker, if self-efficacy, social support, and depression are the big three drivers of perceived stigma, what practical high yield steps can busy clinicians take to hit each of those targets?

Dr Danielle Becker: Well, for one, we know that depression is one of the most common mental health diagnosis in patients living with epilepsy. So first and foremost, screen for mood disorders. And not only screen for them, but I am an advocate of at least trying one medication, one SSRI. While we are putting in a referral to psychiatry, I, I do not under state or underestimate the complexity of treating depression, but I think in starting one medication while we're starting the pathway to get them to specialized psychiatry or psychological care.

I also think encouraging supportive social relationships, support groups, and also as we're talking about today, educating and making people aware that there are epilepsy, self-management support [00:12:00] groups that are taught by peer educators that can also help and give resources.

So ultimately, I think by improving education, communication and access to available resources, that helps address. Reduce the epilepsy related burden that ultimately we would be improving quality of life.

Dr Rohit Marawar (Host): Dr. Vic, I would love your input also, if you could wave a magic wand and change one everyday habit in epilepsy clinics tomorrow. To lighten the stigma load. What would you pick and why?

Dr Martha Sajatovic: my, first, choice would be to listen to Dr. Becker. That would be my first recommendation, but, I concur. epilepsy screening, and I would say, where we are not yet, so it is not a standard of care, but it should be, is that we should be able to provide evidence-based epilepsy, self-managed for everybody with epilepsy.

So my vision is, similar to what we have in, diabetes care, right? If you're diagnosed with diabetes, you, they're certified diabetes educator and you have a [00:13:00] curriculum for diabetes education that is offered and paid for by health insurers. Everywhere in the US right? Almost everybody has access to that.

So I believe we should have similar, again, this relates to Dr. Becker's access to care. Right? People should have the opportunity. I'm doing a, project now working with three epilepsy focused social service agencies where the agencies, have been trained to offer our self-management program.

what they're telling me is that sometimes people actually have to be through the course and go through the curriculum several times. Right. So, this is all a practice, right? for most of us, We become what we practice and we have to continue to practice to continue to improve. So that would be my, magic wand wish is that people should have access to evidence-based epilepsy self-management programs.

And there are a number of 'em that have been developed by the MU network. But right now, unfortunately, a standard of care is, I would say, in many clinics not access to any of [00:14:00] these evidence-based programs.

Dr Rohit Marawar (Host): A lot of the self-management management programs come down to self-motivation. Also, even if we provide the information to the patient, there needs to be that self-motivation and how can we champion that?

Dr Martha Sajatovic: So, this is where I think peer supports, and reinforcement are really important. I'm in involved in another project, another CDC funded project now. Dr. Mike Pri and Dr. Mark Gran, pri of the University of Cincinnati and Dr. Gran's from the University of Iowa. And what that project does is it filters the, electronic health record to identify people with epilepsy that might be candidates for self-management.

And then, when the patient comes to the clinic. The clinician can say, oh, there's this program, I think you might benefit from this. Right? And the patient might say, oh, I'm busy, or, I got a lot in my life right now. But you know, it comes up again and again. Right? Because we, don't see our patients just one time.

Usually we see [00:15:00] them multiple times. So it's really that opportunity, I would say, sometimes people need to hear something. Multiple times. Right. We know that when we watch, TV like commercials come on more than once. Right. And when you've heard it for the fifth or sixth or 10th time sometimes.

Oh yeah. Okay. I'll, think about that. So I would say continue to reinforce it and, you know, your, your interaction is incredibly important to your patients living with epilepsy.

They wanna hear from you about, do you recommend this? that will, I think, go a long way to increasing that motivation, increasing that, ability for to people to just give it a try.

what I like to tell, people who are thinking about. Getting into a program is that I believe our self-management programs are kind of like an excellent piece of chocolate cake. Once you have that first bite, once you get into that group and you're there with eight or 10 other people and you're talking about the same shared concerns and overlapping problem problems, and [00:16:00] solutions, it's incredibly empowering.

So it's really just hearing it again and again and continuing to offer that social support.

Dr Rohit Marawar (Host): Dr. Becker kind of flipping the lens to patients themselves, and we kind of talked about it just now, what simple strategies can people living with epilepsy use day to day to push back against perceived stigma?

Dr Danielle Becker: first and foremost, to be the driver of their own care and be their self-advocate. So Dr. Vic just talked about self-efficacy. Talk about self-efficacy with them and make them understand. Help them understand their active role in their disease journey, help them focus on what they've accomplished, help them focus on achievable goals.

Bring it up. Focus on things beyond their seizures. I think when we, as providers ask how they're doing or how they're feeling or about their mood, they are willing to tell us. But if we don't ask, they don't know, and then they don't have the resources. So. [00:17:00] Resources are provided to encourage them to partake in those resources, to participate in support groups, to show them that there are virtual support groups if they can't drive or if it's not easy to get somewhere, help them understand the available resources with the epilepsy foundation in associations in their area.

But really. Stress that there is social support, there are personal relationships, and we know that this together helps provide protection against the impact of stigma and chronic disease. So really showing them how to find the resources, how to access them and encourage them to access them. And even if they come back and say.

No, I didn't do that because let's not forget, they also have depression too. And so depression can affect motivation as we talked about. And so you be their advocate as well. You be the one that checks in with them and asks them, and even if they said no in the past that we [00:18:00] shouldn't give up and continue to empower them to know that they do have the tools to get involved, which does help reduce depression and stigma.

Dr Rohit Marawar (Host): Dr. Becker peer led programs like Smart Aim to boost self-efficacy and cut stigma. Uh. How can we as epileptologists or a typical epilepsy clinic, weave the core elements of these programs into routine care without overloading our healthcare providers?

Dr Danielle Becker: The first step is to be aware of these programs. A lot of us have epic or medical records where we can make dot phrases that actually have a bulleted synopsis of what these self-management tool or programs are. Talk to your patients about it. We know our patients have poor memory. put that dot phrase in the patient instruction so that they can go home, they can talk to their families about it.

It's not that hard for us to give the information. It's much harder to make sure that they follow up with the information. So set something up within your [00:19:00] program where you supply the information and then we have our nurses maybe check in to see if they actually enrolled. A lot of times what happens is, is that we will give the information and then we don't follow up, and so that actually can overload the staff because patients continue to have depression and.

poor self-efficacy and stigma and they will call in more. But if we initially can help set up a support system and help them learn how to manage their epilepsy by just giving a little bit of information and a way to access this, it will over time reduce load on staff and improve the quality of life for our patients.

I also, I think it's important to note that these are national virtual programs.

So even just reaching out to Dr. Vic and seeing how to get the patient's access and then supplying either the patients with the ability to enroll [00:20:00] or if there's, a trial or something like that.

making sure that the patient's willing to, and supplying their information, but basically being a partner with them to discover these different resources.

Dr Rohit Marawar (Host): Dr. S looking ahead. What study design tweaks in future studies or research advances you would like to see that would move the field forward?

Dr Martha Sajatovic: Yeah. Thank you for that. so. Currently we're in the process of, scaling up and testing and doing performance evaluation of smart being conducted within the clinical setting, using Epic. And, that is the health record that we're using to identify people. Community settings is another one, right?

Social service agencies, who wanna become smart program or other evidence-based program adopters can. So, you know, there's more than one way to skin a cat. You could get through your healthcare system, you could get through the community. I think there's some, there are some other things that we're doing.

So, we have a project now where we're tying. The smart program into, rescue medicine [00:21:00] prescribing, right? So people are prescribed, rescue medicine, but since those are self-administered meds, right, getting training and support and weaving that into the whole package of care, I think is something that, definitely needs to be investigated further.

We hope to be able to move the ball down the field. I've got a project running now in Uganda, so, epilepsy. Stigma is alive and well, unfortunately, in the US it's alive, and well globally. it definitely takes different characteristics and looks a little different, across different cultures.

So that's a another area that, is huge and needs to be addressed. and then there's another area that we, we are trying to get, support to do this, but I think it's really, really critical is. Currently our, program, the smart program, is, targeted to adults with epilepsy only. And I think where we really need to go next is looking at, adolescents and families.

we do have caregivers and care partners that sit in on our epilepsy groups, our self-management groups. But, I think we [00:22:00] need to customize it a bit more for, younger people in their developmental stages and kind of working with their family. So I would say, stay tuned.

I, hope that our team gets the opportunity to move forward. 'cause I think it's incredibly, important future need, current need that hopefully we can address in the future.

Dr Rohit Marawar (Host): So we have mentioned the smart program many times. Dr. Vic, in this recording, can you touch on it a little bit like what it is exactly?

Dr Martha Sajatovic: Yeah, yeah, yeah. I'm happy to, I'm happy to talk about the smart program till the cows come home. One of my favorite topics, but it is a remotely delivered, Program we do, we use Zoom or a similar type of video conferencing. what's unique about the program, it is as co-led by a nurse, doesn't have to be an epilepsy specialty nurse.

As a matter of fact, I tend to look for nurses that really love education rather than, necessarily going, you know, they're not prescribing or going into the medical weeds very much. But also the secret sauce is a person living with Eoli who's been trained to deliver the program. So they co-lead it.

Then you've usually got between six and [00:23:00] 10, people living with epilepsy in the group. They have eight sessions that last maybe 45 minutes to an hour. for about eight weeks. For eight weeks. sometimes we might skip a week or two if it's a holiday or our leaders, have some changes in their schedule.

But generally, it's done in. About eight to 10 weeks. So it's a relatively brief intervention. There are some brief follow-up phone calls that the nurse does, but every, session has a very specific curriculum. There's handouts, there's worksheets. I get people that say, oh, I'm already part of a self-help group.

I don't feel I need this. and what we really need to, qualify here is that this is vastly different from a self-help Groups very tightly structured. of homework. It is a commitment that somebody has to commit. We ask 'em to commit to eight hours of programming. but we tell them that we, can recommend very strongly that this will be worth your while.

And if we listen to the testimonials that we've gotten from our participants, many of them, when they're done, they say, I [00:24:00] wanna be a, peer educator. How can I become a peer educator? And to me that's the strongest endorsement that this was a valuable experience for you.

Dr Rohit Marawar (Host): Thank you. Sounds like a great program. Something I look forward to Recommending to my patients.

Dr Martha Sajatovic: We, but also, just do wanna say that smart's not the only game in town. there are a number of really excellent evidence-based epilepsy, self-management programs, and I would say, getting your patient into one of these programs is, another way for you to advance their care.

Dr Rohit Marawar (Host): Dr. Becker, we have the most challenging question for you. So imagine you've got five minutes with a health policy leader. What single policy change would you champion to shrink epilepsy stigma over the next five years?

Dr Danielle Becker: So this is a very tough question, but given the focus of this podcast, for me, it would be funding the self-management. Resource showing support and increased improved access to self-management programs that we know focus on support, [00:25:00] but are led by other individuals that have epilepsy that have. An idea of, what the patient's going through different than their caregivers or their providers, and can help guide with resources with a set curriculum and to help reduce depression, improve self-efficacy, improve social support, improve quality of life. And then as Dr. Avi just said. there's many on the market, but these self-management programs not only teach someone how to manage their epilepsy, they can teach them how to manage the repercussions of the seizures, how to manage the changes in mood, and very importantly, as she just stated, how to manage. Seizure action plans and seizure rescue, right? All of these things lend into hand improving quality of life for our patients.

I can't stress enough that epilepsy is not just about the [00:26:00] seizures. And when you look at core health related outcomes, the impact on patients' lives is just as debilitating, if not more debilitating than the seizures. So you, Mr. Congressman I ask that you help us provide financial support to continue this advocacy for our patients, for education, for support, and improve their quality of life.

Dr Rohit Marawar (Host): Thank you for answering that, and thank you both for that thoughtful tour of the science and the human side of epilepsy stigma. Today we heard that self-efficacy can be coached, social support can be built, and depression can be found and treated. That each move chips away at stigma's power. For clinicians listening, maybe the takeaway is this.

Think and ask about stigma. It's as clinically relevant as seizure count for people living with epilepsy. Remember, you're not alone. Community and self-confidence are potent medicine. I. If [00:27:00] you found value in this episode, share it with a colleague, a patient, or a policymaker who can push the conversation further.

And as always, subscribe and follow epilepsy currents on your favorite podcast app. For insights that bridge research and real life, you can also find us on epilepsy currents.org. Until next time, take care and keep the dialogue going.

Join Dr. Bermeo in a conversation with Dr. Elizabeth Gerard, and Dr. Christa Habela, as they discuss the article, " Genetic Testing in Epilepsy: Improving Outcomes and Informing Gaps in Research ".

Click here to read the article.

This podcast was sponsored by Marinus Pharmaceuticals.

We'd like to acknowledge Epilepsy Currents podcast editor Dr. Adriana Bermeo-Ovalle, contributing editor Dr. Rohit Marawar, and the team at Sage.

In episode nine of the Epilepsy Currents podcast, Dr. Adriana Bermeo discusses the evolving role of genetic testing in epilepsy with Dr. Krista Habela and Dr. Elizabeth Gerard. They explore how genetic insights are enhancing diagnosis and treatment, highlighting the rapid advancements and future potential of this field.

Key Takeaways

1. Technological Advances: Since the first epilepsy gene discovery in 1997, technological advancements such as next-generation sequencing have dramatically accelerated gene identification, enhancing genetic testing's accessibility and effectiveness.
2. Basic Genetic Concepts Clarified: Dr. Gerard explains critical genetic components—genes, chromosomes, and exomes—and their relationship to different genetic tests, providing a foundational understanding crucial for grasping how genetic variations impact epilepsy.
3. Diagnostic Yield and Personalized Treatment: Genetic testing varies in diagnostic yield based on patient-specific factors like age of onset and associated conditions. Higher yields in targeted groups underscore its role in developing precise, personalized treatment plans.
4. Impact on Patient Understanding and Future Testing: Genetic testing not only aids in diagnosis but also provides patients and caregivers with valuable explanations for the conditions, reducing uncertainty and informing better treatment choices. The future of genetic testing in epilepsy includes potential advancements in gene therapy and precision medicine, aiming to develop targeted treatments based on specific genetic profiles.
5. Overcoming Barriers to Integration: Challenges like insurance coverage, the availability of genetic counseling, and the need for provider education must be overcome as genetic testing becomes integral to standard epilepsy care. This integration promises to streamline diagnostics and potentially reduce the need for other invasive tests.

Adrianna Bermeo-Ovalle, MD (Host): Why do I have epilepsy? What causes epilepsy? Are my children or other family members at increased risk of developing epilepsy as well? These are some of the most frequent questions I hear in the clinic these days. In a healthcare environment which turns more and more towards personalized medicine, genetics presents a unique opportunity to answer some of our patients most pressing questions.

Today, we will explore the current indications and use of genetic testing in epilepsy and we'll take a peek into the future of epilepsy diagnosis and care. Marinus Pharmaceuticals is the proud sponsor of episode number nine of Epilepsy Currents podcast.

I am your host, Adriana Bermejo. I am the senior podcast editor for Epilepsy Currents, the official journal of the American Epilepsy Society. Let me first welcome Dr. Christa Habela. Dr. Habela is a Child Neurologist, Epileptologist, and the Director of the Long Term EEG Monitoring Program and the Epilepsy Genetics Clinic at the John Hopkins Hospital in Baltimore, Maryland.

Dr. Habela is the author of the review, Genetic Testing in Epilepsy, Improving Outcomes and Informing Gaps in Research. This article was published online first on March of 2024 in Epilepsy Currents. Dr. Habela, thank you for joining us today.

Christa Whelan Habela, MD, PhD: Thank you so much for having me.

Host: It is also my pleasure to welcome Dr. Elizabeth Zoe Gerard. Dr. Gerard is an Associate Professor of Neurology at the Northwestern Feinberg School of Medicine and the Founding Director of the Women in Epilepsy Program, as well as the Adult Epilepsy Genetics Clinic at Northwestern. Dr. Gerard, thank you for being with us.

Elizabeth E. Gerard, MD: Thank you so much for having me. It's my pleasure to be here.

Host: Dr. Habela, your review starts with a very nice historical perspective, a historical overview of the development of genetic testing in epilepsy. Can you please help us understand how did we get where we are today?

Christa Whelan Habela, MD, PhD: It has always been generally thought that epilepsy was a genetic disorder, even prior to any discovery of epilepsy genes. And the first gene associated with epilepsy was only discovered in 1997, and this was for the nicotinic acetylcholine receptor, and then from 1997 to 2007, only 10 more genes were discovered, and this was because we were using, very robust, but very slow and expensive Sanger Sequencing.

Early in the 2000s, the first untargeted genomic testing, came into clinical use, and this was the chromosomal microarray. This can be thought of as a very high resolution karyotype, and allowed us to look for deletions and duplications.

But it really wasn't until the development of next generation sequencing which is a much faster and a much cheaper way of sequencing our DNA; that we really began to have an explosion in gene discovery. And so, beginning with next generation sequencing, this allowed us to develop whole exome sequencing, sequencing the exomes of our genes, as well as whole genome sequencing. And these two studies allowed us to identify hundreds of genes,

up to a thousand genes from the years 2007 to present day.

Host: Wow. So it looks like our baby steps took a long time, but we are going on leaps and bounds these days. And I imagine that we will be advancing much faster, now and into the future. Dr. Gerard, let's start with the basics to orient our audience. Could you please explain the difference between a gene, a chromosome, an exome in a way that helps our listeners follow the conversation on genetics? And if you could please link that to which tests correspond to which concept?

Elizabeth E. Gerard, MD: So a gene can be thought of as a recipe for making a specific protein that's important to our body. And human genetic code contains about 20,000 recipes or 20,000 genes that make proteins. And so, as Dr. Habela was explaining, we had much faster understanding and ability to give back feedback on misspellings or typos in genes as we develop next generation sequencing.

The Sanger sequencing she referred to, could really process one gene at a time. But now with next generation sequencing, we can process and understand the genetic code of multiple genes at a time. So while single gene testing is still rarely used for very specific phenotypes, like tuberous sclerosis or neurofibromatosis, more often, patients with epilepsy, with or without neurodevelopmental disorders may need a bunch of genes sequenced at the same time to increase the diagnostic yield. And one of the ways to do that are epilepsy gene panels or neurodevelopmental gene panels, which use next generation sequencing to look at usually on the order between 200 and 500 genes all at the same time and look for errors in the genetic code that may affect how that recipe works or how it may affect how you make proteins.

So that's one commonly done tests now which are gene panels. The genes or the recipes we have are organized into chromosomes. So humans have 23 pairs of chromosomes, and you can think about these as like sort of cookbooks, that contain the recipes. So another genetic variation that can happen that can contribute to disease and contribute to epilepsy, are sort of rearrangements within that chromosome book.

So you can think about this as a missing page or half of a page missing. These are really deletions or duplications at the chromosomal level known as copy number variations. And these can include several genes or it can include just as small as part of one gene. And this stuff can be sometimes missed by gene panels or some next generation sequencing that's only focusing on certain parts of gene known as the exome, which we'll get to in a second.

So the chromosomal microarray was one of the early tests used to make diagnosis in epilepsy and neurodevelopmental disorders. I think Dr. Habela will talk about the yield of this test, but this looks specifically for deletions or duplications at the chromosomal level. As I mentioned, there are 20,000 genes or recipes in our genetic code.

And so we are moving very quickly away from these first two tests I mentioned to exomes. So whole exome sequencing, really sequences all those recipes, all the exonic parts of our recipes. We'll talk about the genetic code in our recipes, and can look at many, many, many genes at once. Even though they're looking at all of those genes in our genetic code; most exome analysis focuses on specific genes relevant to the patient's phenotype or the patient's symptoms. So this is really becoming one of the first tests that we're using in genetic testing for epilepsy and is thought by many to be one of the first two tests of choice. But there are still some things that exomes can miss.

So they can miss those copy number variants in some cases if those are not at the levels that affect whole genes. Okay, they can also miss particular disorders like expansion repeat disorders, such as seen in CSTB related progressive myoclonic epilepsy. And then the other thing that's really important to recognize is that our exome with all those 20,000 genes, is really only 1 percent of all of our genetic code.

So if you think about that recipe being made up of key components, like the ingredients that you need, that's really the exome. That set of instructions and those key factors that you need to make something or to make a recipe. But there's a lot of information on our genetic code in between the recipes or the small words within the recipe that actually tells us how to use it and how to make what we need to make.

And that's the rest of the genome. Until very recently, that's not something that we've been able to access on a clinical level, but it's becoming more affordable with advancing and sequencing techniques. And so now, genome sequencing, whole genome sequencing is becoming available at a clinical level.

And this allows us to look and learn more about the information between the genes. It also allows us in many cases, to identify with one test, those copy number variants that I talked about before. And in many cases, genome sequencing can also allow us to pick up other types of genetic anomalies like expansion repeat disorders, which are disorders where perhaps a word or a couple of letters are duplicated.

So those are some of the major tests that we're doing and many people now believe we should start for most of our patients with exome or genome sequencing. There's a few other things we haven't talked about without mitochondrial testing, which is another thing that can be added in and occasionally we should not forget to use karyotypes when these tests are not diagnostic.

Host: Thank you so much. Certainly a lot to go through, in order to get an overview of current really clinical use of genetics. Thank you for that. And I love the analogy of the recipes. Dr. Habela, can you tell us a little bit about what is the diagnostic yield of some of these tests? And also how do we determine which patients or which group of patients should take them or would benefit from one or the other?

Christa Whelan Habela, MD, PhD: I think that's one of the most important points is that the diagnostic yield of these tests really varies, depending on very specific patient factors. In general, right now, the recommendations are that if possible, if you have the resources in your clinic and the patient has the resources and can afford it, that exome or genome should be the first line, testing, but other tests may have just as high a yield.

So, chromosomal microarray, was the first sort of clinically useful and available broad spectrum testing that we used clinically, and it transformed the way that we could diagnose epilepsies, but was only giving a diagnostic yield of about three to nine percent, with the three percent being a diagnosis for somebody who had epilepsy and no other associated neurodevelopmental disorders, and the nine percent being individuals with epilepsy and intellectual disability in particular.

But at the time, that was the only test that we had available and as Dr. Gerard mentioned, sometimes we cannot pick up duplications and deletions on the exome, as sensitively as we can on a chromosomal microarray. So in general, if there has been a negative exome sequence, we would use a chromosomal microarray to confirm that there was no deletion or duplication.

Whole exome sequencing has a similarly a range of sensitivities, depending on the patient or a range of diagnostic yields depending on the patient. So, for individuals with no family history and no associated additional neurodevelopmental disorders or structural brain malformations or other congenital malformations; exome yields may only be 9%. But individuals with intellectual disability, structural brain malformations that may increase up to 50%. Similarly, estimates of diagnostic yields with the genome sequencing is around 48 to 50 percent. And then gene panels, on average have about a 19 percent diagnostic yield. But when used in specific patient populations, they can be just as highly effective as exome.

So in particular individuals who develop their epilepsy younger than the age of two, and in particularly on younger than the age of one, are most likely to benefit from a gene panel. Many of the epilepsies that develop in the first year of life are highly penetrant single gene disorders that we have already identified and are common enough that the gene testing companies have put them on their gene panels.

And so the diagnostic yield can be up to 40 percent for children who develop their epilepsy before the age of one. And for individuals who have an associated structural brain malformation, the gene panels can diagnose up to 50 percent of patients as well. And it's important to remember that when we think about doing genetic testing, that it's the age of onset, not necessarily the age of the patient. If an adult never had genetic testing as a child, doing genetic testing as an adult is just as likely to result in a diagnosis dependent on the factors of age of onset and associated developmental delays or intellectual disability, or other congenital changes.

And then finally, Dr. Gerard had mentioned a karyotype. There are certain, specific types of epilepsy caused by a ring chromosome that really a karyotype is the only test that will diagnose. So while there is not generally an indication for a karyotype in epilepsy, when you specifically suspect that syndrome, or, all other testing has been negative, that can be considered.

Host: So, for well chosen patients and populations, it looks like the yield is much higher than many of us know if we are not necessarily working on the field. Dr. Gerard, I find still that a lot of providers even are not sure of what the benefit is of doing genetic testing. Can you walk us through how do patients, caregivers, or families benefit from having genetic testing done in this day and age? And we just heard from Dr. Habela how even the yield is different when the diagnosis started at different age. So is there a difference between pediatric versus adult patients as you see mostly adult epilepsy patients in your genetics clinic?

Elizabeth E. Gerard, MD: I think the way you started off our podcast really speaks to an unrecognized power of making a genetic diagnosis through genetic testing. Since I've been working as an epileptologist, I've always been fascinated by how it's hard for patients to understand the diagnosis of epilepsy, especially if we can't give them a reason.

And so I think, as I answer the question, there's many layers to it, but I've found that one of the most powerful things about getting a genetic diagnosis is to finally have a reason, for why this epilepsy came to be. And a better understanding of it and a better individual understanding about why it affects this individual patient in a certain way.

For parents and caregivers, that understanding can also be really important. Because particularly for adult patients who have had epilepsy since childhood and have been unexplained to them because of the lack of the technology at the time and the clinical availability of these tests; oftentimes caregivers have had lots of reasons that have been suggested to them, such as birth injury or falls or all kinds of things as to why the epilepsy might have come to be when it's actually genetic.

And so it can be really powerful to have a why, and scale back some of that sort of guilt or rationalization that has happened over the years. I think, obviously, one of the hopes for genetic testing, and it certainly happens for some individuals, is the ability for the genetic testing to change treatment right now.

And I do like to say, particularly in my adult population, I wouldn't say that that is the majority of patients we test, but when it does happen, when you find a genetic diagnosis that has a specific treatment or certain specific treatment pathway; it is extremely valuable. It also is really important for people to know their genetic diagnoses now because we're at this point in medicine in general, where we're developing, as you mentioned, more specific interventions for specific genetic diagnoses.

And these include, but are not limited to, genetic targeted therapies. And so, patients who know their specific genetic diagnoses can be part of building solutions for themselves and for the future and being what we call clinical trial ready for when there are trials that are available for them.

Another really interesting phenomenon, and I think really important phenomenon, is the power of connection to other individuals or other caregivers who are going through the same experience. So when you can connect people to support groups, that are not just support groups for epilepsy in general or neurodevelopmental disabilities in general, but support groups for someone with the exact same genetic diagnosis as you, it can be really, really powerful to know that you're not alone.

And I think that the power of these specific groups, the caregivers and individuals with specific diagnoses are really moving the field forward as they help us define natural history studies for individual genetic diagnoses and connect with each other and advocate for research into specific genetic conditions.

To your point about adults versus peds, yes, I work specifically with an adult population, and there are, I believe, unique challenges to talking about genetics in 2024, to patients who are adults with epilepsy. One, we sort of have two major groups of patients. One group are patients who, if they were children nowadays, probably would have received their genetic diagnosis, and so these are patients often with earlier onset epilepsies, neurodevelopmental disabilities, and they just didn't have the testing available at the time.

And finally, I think when we are diagnosing adult patients, many of them, may have sort of milder phenotypes than the more severe phenotypes that Dr. Habela talked about. And so these can be in adults, less penetrant conditions, that we're diagnosing, and so that means that other individuals can have in the family or this individual's prospective children could inherit the genetic changes, but may or may not have symptoms and may have a variety range in their symptoms.

And so that concept is one we talk about a lot when we talk about patients undergoing testing before they want to have their own children. And that's another kind of unique challenge in the adult epilepsy clinic. Often because of these milder phenotypes, and these older diagnoses we're making, we're often saying to the patient that they're one of the oldest patients who has this specific genetic diagnosis.

And therefore, we don't have as much natural history or prognostic information to give them as well. So these are some unique challenges that we're learning about.

Host: Very interesting. We're certainly also building our knowledge and hopefully we will be able to inform other patients later on as we learn more about these adults that we're not testing as children. But we've a great possibility and opportunity. We know we face a lot of challenges. So, Dr. Habela, considering barriers like access to testing, availability of genetic counseling, training providers; how do you see we can better integrate genetics into our routine epilepsy care?

Christa Whelan Habela, MD, PhD: That is a great question. And it doesn't have an easy answer. But I think, the answer really comes from education. And in particular provider training. Even if not, every provider is able to explain genetic testing and the details of our genes and our chromosomes and how that interacts with the different types of testing, as beautifully as Dr. Gerard did; making sure that every provider who interacts with patients with epilepsy, whether it be an epileptologist or a child neurologist or, even, primary care physicians is aware that genetic testing is part of the standard evaluation of patients with epilepsy. And from a practical standpoint, including genetics and genetic testing in the curriculum of medical students and our residents and our epilepsy fellows, is extremely important.

And including a discussion of genetics into our conversations with patients, even from the time of diagnosis. Many of us were trained and think immediately of doing an EEG, depending on the type of seizures or the findings on the EEG, an MRI very quickly after diagnosing epilepsy in a patient or as part of the diagnosis of epilepsy in a patient.

And many of us include those results in our descriptions of our patients when we review notes. And I would argue that, genetic testing, whether or not it's been performed, what the findings are should be sort of part of the standard history and evaluation of our patients from diagnosis.

That doesn't mean that every clinic will be capable of sending an exome, but, understanding that it's part of the evaluation. And if we're not capable of doing it in our own clinic; knowing where we can send our patients to get that testing. And certain tests are relatively easy to send from clinic.

So our gene panels require a little bit less genetic counseling. And typically, for providers to understand the basics of genetic counseling, may allow them to send those tests on their own. So, being able to tell families and patients, what the testing is looking at, what the potential results are that we may find an answer. We may not find an answe. That we may find something that we're not sure whether or not it's related to their epilepsy yet. Those are the variants of unknown significance that are potentially the hardest answers to explain to patients, but are also the most common results that we get from genetic testing.

And being able to explain to patients that the testing may help us with medication selection, may potentially let us know about associated problems in other organ systems that come along with a genetic diagnosis. And they may or may not lead to sort of disease modifying treatment now or in the future.

Those general concepts can be talked about in a clinic visit provided the provider can make that time. But access to a genetic counselor is ideal, but not always possible.

Host: Certainly we have providers working in very, very different environments, but it is clear that genetics is part of the standard of care of epilepsy for adults and children nowadays. Now, I would like to invite both of you to try to think into the future. Where do you see the field of epilepsy genetics testing and epilepsy genetics treatment as well, in the near future, and what do you envision in the horizon for this rapidly evolving area? Dr. Gerard, I would love your thoughts first and then Dr. Habela.

Elizabeth E. Gerard, MD: There's so much there and I really think we're going to transform epilepsy care by increasing access to genetic testing. I like the analogy that Dr. Habela has used and also invite you to read her review, which is so thorough. I do think we're going to start thinking about genetic testing up there first, just like imaging.

And in many cases, if we can get a genetic diagnosis, early on, in a patient's care, that may actually preclude other expensive workups like repeated MRIs or autoimmune workups. So I think we're really going to move genetic testing as it becomes more affordable and more available, earlier and earlier into the workup of epilepsy.

We haven't touched on also, there's other genetic mechanisms such as polygenic contributions to epilepsy, which we think are underlying many of the cases that have not yet been diagnosed, including our genetic generalized epilepsies. And those polygenic risk scores may also become an early part of genetic evaluation.

There are a couple of important barriers, to reaching this goal of early integration of genetics in our workup, and a lot of those are sort of the resistance, particularly for adult patients, of insurance companies to support genetic testing, really at any level, whether you're talking panel or exomes, and so these tests are becoming more affordable, but we're going to have to advocate for them to be seen as essential by payers and people who support this testing. Because that's a lot of the bottleneck right now, for our patients, who don't see it as necessary or may not see it as necessary if their insurance company doesn't.

And I just want to make a final plug for the role of genetic counselors, as Dr. Habela mentioned. I do think we should further educate our providers about genetic testing, but nobody can provide genetic care and counseling better than genetic counselors. And I want to say my entire analogy, which I didn't get quite right, was stolen from my genetic counselor who I've been working with since 2011.

I think that we have to find a way as a neurology and epilepsy community to make sure genetic counselors are supported and are an important part of our practice.

Host: Thank you for that. And, for the advocacy plug and the plug for genetic testing. Hopefully, outlets like this one will get this message to a broader part of our community. Dr. Habela, any thoughts for the future?

Christa Whelan Habela, MD, PhD: I think that was really well summed up by Dr. Gerard. I would just second the plug for using the services of genetic counselors and advocating for more people to be trained in genetic counseling. And that I think we're really sort of just at the beginning of understanding how achieving a genetic diagnosis for our patients can, affect and improve their care going forward.

And there are multiple studies looking into genetic modification, but aside from that, understanding how particularly in polygenic genetic epilepsies, potentially how a polygenic profile may contribute to patients' tolerance of medications or how our genetic backgrounds contribute to single gene changes, affecting the severity of our symptoms from a genetic cause of epilepsy.

And then thinking about how we can apply epilepsy genetics to epilepsies that we don't always think about genetics in. So, patients with focal epilepsies who are undergoing surgical evaluations, more and more we find that there are genetic changes within the epileptic lesions, that are not necessarily discoverable by doing testing on our blood or our skin or our saliva and potentially may predict patient's surgical success or success to medications after surgery.

So, I think we're just at the beginning of understanding how we can help our patients with increased knowledge, and hopefully we can provide access to testing to the patients who need it.

Host: Wonderful. It sounds like there's still a lot to talk about in genetics, but it also sounds like the development, of this field will drive a hopeful future for our patients in testing and in treatment.

I want to especially thank both of you for participating in Epilepsy Currents podcast today. I want to thank our listeners. Today, I want to especially thank our sponsor, Marinus Pharmaceuticals. Marinus is dedicated to the development of innovative treatments for rare genetic epilepsies, including the CDKL5 deficiency disorder.

They are committed to collaborating with epilepsy experts to advance therapeutic options that support the work of physicians and make a meaningful difference in patients lives. You can learn more about their work at marinuspharma.com. That is M-A- R-I-N-U-S pharma.com. I want to thank Dr. Rohit Marwar and the SAGE podcast production team.

We look forward to having you at our next episode of Epilepsy Currents podcast. Please remember to subscribe to Epilepsy Currents podcast wherever you get your podcast and send us your feedback, suggestions, or questions through our website, epilepsycurrents.org and follow us in social media on X former Twitter at AESCurrents.

Until next time, everybody.

Join Dr. Marawar in a conversation with Dr. Anup Patel, and Dr. John Stern, as they discuss the article, "The Tell on Telehealth".

Click here to read the article.

This podcast was sponsored by Marinus Pharmaceuticals.

We'd also like to acknowledge Epilepsy Currents podcast editor Dr. Adriana Bermeo-Ovalle, and the team at Sage.

In episode eight of the Epilepsy Currents Podcast, hosted by Dr. Rohit Marawar, the focus is on telehealth's role in epilepsy care. The episode features insights from Dr. Anup Patel and Dr. John Stern, who co-authored a review article on telehealth. They discuss the evolution of telehealth services, their importance for epilepsy patients, particularly in providing access to specialized care, and the challenges and future of telehealth in clinical practice.

Brief Summary

The podcast delves into how telehealth has become integral to epilepsy care, especially during the COVID-19 pandemic which accelerated its adoption and acceptance. The experts discuss the practicalities of telehealth, including the technological advancements that have made remote healthcare more accessible and effective. They also touch on the regulatory and reimbursement changes that have facilitated its broader use. The episode emphasizes telehealth's role in overcoming geographical barriers to specialized care, making it a critical service for those with mobility restrictions or who live far from epilepsy centers.

Key Takeaways

1. Historical Context and Evolution: Dr. Patel highlights that telehealth has been around for over two decades, but significant advances in technology and the necessity brought on by the COVID-19 pandemic have greatly expanded its use. The easing of restrictions around reimbursement during the pandemic also played a crucial role in its widespread adoption.
2. Importance for Epilepsy Patients: Dr. Stern points out that beyond the convenience, telehealth is crucial for epilepsy patients due to the driving restrictions often associated with the condition. It allows patients to access specialized care regardless of geographical limitations, enhancing the quality of care they can receive.
3. Challenges in Telehealth: Despite its benefits, telehealth presents challenges such as difficulties in performing complete neurological exams, managing neurostimulator devices and managing technological issues from both patient and provider sides. These challenges necessitate a hybrid model of care where telehealth complements, but does not replace, in-person visits.
4. Patient Suitability: According to Dr. Patel, while telehealth is ideal for follow-up visits where a physical exam might not be critical, new patients or those needing detailed physical assessments might be better served by in-person visits. This distinction helps in optimizing care delivery based on patient needs.
5. Future of Telehealth: Both experts agree that telehealth will continue to be a part of the healthcare landscape. Dr. Stern speculates that future enhancements may include more integrated remote patient monitoring and possibly satellite offices that provide some in-person support functions to complement telehealth visits, which could improve the quality of remote care.

This episode effectively outlines the transformative impact of telehealth on epilepsy care, highlighting both its potential and limitations, and underscores the ongoing need to adapt and refine this mode of healthcare delivery to better serve patients' needs.

Rohit Marawar, MD (Host): What if a doctor's visit no longer meant hours of travel or long waits in a clinic? For people with epilepsy, telehealth is redefining what access to care looks like. But is this shift here to stay? Today, we're unpacking the reality of telehealth and its growing role in epilepsy. Welcome to the Epilepsy Currents Podcast, an audio accompaniment to the Epilepsy Currents Journal, where we discuss the latest in epilepsy research and care.

I'm your host, Rohit Marawar. Joining us today are Dr. Anup Patel, pediatric neurologist, and Dr. John Stern, adult neurologist, both leaders in epilepsy and co authors of the recently published Epilepsy Currents Review article, The Tell on Telehealth, which explores the evolution of telehealth, the challenges, and its impact on epilepsy patients.

before we get started, a quick thanks to Mariners Pharmaceuticals, who is proud to sponsor this episode of Epilepsy Currents Podcast.

welcome both. Thank you for joining us.

Let's get started, Dr. Patel. So I was intrigued to learn from your review article that telehealth isn't [00:01:00] actually a new concept and has been around for more than two decades. Could you give us a brief rundown of how telehealth has evolved over the years? And what led you to write this review article?

Anup D. Patel, MD: that's a really great question. I think one of the things when we, started to look into this area as an opportunity that obviously became more available during the COVID 19 pandemic, we realized that others have been using telehealth and like you said for about 20 years, but I think the evolution really exists in the technology advances that we've had to make easier for us to actually do telehealth with a video in a safe but secure environment.

I think the other big advantage obviously was the tipping point that occurred, and, during the COVID 19 pandemic. And what we recognize as an author group was that, there was not as much guidance as we needed or would want as it relates to telehealth visits, specifically The other thing is there's more than just a video [00:02:00] visit, which became obviously commonplace during the pandemic.

The other advances, obviously, because of the pandemic was like the restrictions around reimbursement were reduced. And we'll talk more later in this episode about some of the licensure changes, but it was pretty open at that time, which allowed us to be able to access this technology to help improve or continue to maintain patient care.

Rohit Marawar, MD (Host): Dr. Stern, why do you think telehealth has become such a crucial service for people with epilepsy?

John M. Stern, MD: think an obvious part of the answer is the driving restrictions that people have who don't have seizure freedom and have epilepsy. think that's really only a small part of the importance because thankfully most people with epilepsy are seizure free. And the issue really becomes a matter of access because care for epilepsy has become much more sophisticated.

It's required more specialized understanding. And Physicians who can provide that are not commonly distributed across the United States, so it's a matter of distance and access more than [00:03:00] drivability, in my mind, why it's so important, because you wouldn't want people, because of geography, to not have access to physicians with the expertise who can provide better care for them, whether or not they're seizure free.

And this, in fact, maybe is no different for other conditions. beyond epilepsy. Whereas healthcare in general is shifting with this catalyst of COVID 19 to allowing people who are not geographically well situated for expertise to not be denied those opinions.

Rohit Marawar, MD (Host): And again, Dr. Stern, when we compare outcomes for epilepsy patients who use telehealth versus those who have in person visits, what does the data show? Are there any major differences?

John M. Stern, MD: have questions about the data because it comes down to the question of the outcomes and it comes down to, as well, how do you ascertain the outcome? people like telehealth because of the convenience, and that goes for both doctors and patients, but telehealth is not, perfect, and there are definitely problems that arise with telehealth care, which [00:04:00] we'll talk about, and so if the outcome is appreciation If we can't do this without availability and ability to communicate effectively, then telehealth can do very well.

But, we need to be cognizant of telehealth being part of care delivery, and in my opinion, it's never going to replace in person visits because of the specific needs Benefits of being present with a person is two people.

Rohit Marawar, MD (Host): Dr. Patel, kind of building on that, which type of patients do you think might be better suited for in person visits rather than a telehealth visit?

Anup D. Patel, MD: Yeah, I think some of the research that we did and review of the literature showed that, you know, perhaps new patients would be better served, as being seen in person. I think that the other big thing is if there are motor and other, specific, um, Concerns around movement changes and for follow up patients, those would be better served in person.

One of the challenges that we have with video telehealth is exactly picking up some of those [00:05:00] nuances, in the exam format. But otherwise, you know, there are a lot of advantages like Dr. Stern mentioned to the telehealth visit?

and most of the epilepsy follow ups, you know, obviously the exam isn't going to be as helpful.

So in those situations, telehealth might be a little bit more ideal, but. Beyond that, you know, like Dr. Stern said, the other area that really favors inpatient is if you have a neurostimulation device, to be able to interrogate or evaluate that device, it really needs to obviously be in person in this present day.

Now that may change with some of the technological advances on the horizon, but as of now, those patients should be seen at least once a year, if not more, inpatient for that device interrogation.

Rohit Marawar, MD (Host): Makes sense. Dr. Patel, your article includes a comprehensive table on how to conduct a successful telehealth visit. Could you share some key considerations and maybe a few tips from your personal experience that have made your telehealth appointments run smoother?

Anup D. Patel, MD: Yeah, and I think [00:06:00] we've learned a lot in this area. I think that the assumptions we had made earlier, around everyone's ability to access broadband internet or at least have a stable connection is flawed. So I think one of the things I would recommend and it's like a highlight of in the table is that that's a key consideration, you know, making sure your patient and their caregivers obviously have access, that can log on.

Plan ahead. You know, I think we, assume people are going to be able to log on without any technological difficulties, but that is not necessarily always the case. So, you be prepared, for that situation by going ahead and planning ahead. I think the other things that are good key considerations that we highlighted was just really being cognizant of, how to run the examination.

So we provided some and trades of where, there's been some literature around doing a virtual exam and what are some of the pearls and opportunities in that sense. And I think the last thing is that we also highlighted was don't forget that the educational [00:07:00] materials that you would normally provide in person should also be provided some mechanism this virtual model.

And so, you know, whether that's uploading in your electronic health record and sending through the patient portal or mailing it to them, be cognizant and aware that those are some gaps. And so we'll make your visit a lot more successful.

Rohit Marawar, MD (Host): Dr. Stern, telehealth does present some barriers like challenges in completing quality scales for screening comorbidities or conducting a neurological exam. what solutions are available currently to overcome these obstacles?

John M. Stern, MD: at the risk of sounding simplistic, think the best solution is not to use telehealth, because the situations where telehealth is not optimal for the care is a situation where really there should be effort to make it an in person visit because I believe that both types of visits have definite value.

beyond what Dr. Patel just discussed, recognize more and more that the technologic obstacles are not just on the patient's side, they can be on the. Physician side, as even an [00:08:00] institution, a large hospital or university will have sometimes problems with intranet. And then as computers get updates for the operating systems, that also can create a problem.

And so, these become barriers to successful communication. It's really on our side, not the patient's side. The other part of it is, the communication. when the patient is doing well, And it's a matter of check in and reviewing a few basics. telehealth can do, serve very nicely, but when the communication has to be more nuanced and get into subtleties and much more focused toward, understanding, in person really provides a much better means for that.

And I think that's partly because of distraction. I see sometimes patients who are in telehealth, but although I get to see them in their own environment, which can be helpful, it also means all the distractions of their home environment are there. And having a room where it's just, the doctor and the patient, maybe the patient's family is a way of providing that focus, which can be really important for better understanding.

And the understanding is bilateral. My [00:09:00] understanding of the patient and the patient's understanding of me. And so when there's. Meaningful conversation that's needed sometimes in person is much better. In the same way, as an analogy, video provides better communication than just audio. I mean, the telephone encounter, my experience doesn't give the same level of communication as a telehealth video encounter and being present, adds to it as well.

think the problem can arise that sometimes one doesn't know ahead of time whether that visit really requires that level of communication. There has to be a continual attention to maybe, should the next visit be tele or should the next visit be in person as a way of paying attention to not convenience, which definitely there, but to what we're trying to achieve in making the best possible decision.

Rohit Marawar, MD (Host): Dr. Stern, can you update us on what kinds of telehealth services are currently allowed, including the type of visits, locations, and billing considerations?

John M. Stern, MD: the medical legal part of this is all [00:10:00] in flux because the world's changing. And a lot of this depends upon Medicare and federal oversight, and then it also depends on the individual states and whether the states allow for care across state boundaries. This is where we in the United States have both an advantage and a disadvantage, that we have, uh, The opportunity for different systems of care to be delivered, but then it's a question of how does that get brought together when we don't think about boundaries between states as being so important as we go about our days.

The approval for telehealth has, end dates, but it's so far been continually re approved. and extended. My expectation for what it's worth is that telehealth is here to stay for the obvious benefits that it provides, and so it's going to come down to some type of indefinite approval with more clear understanding as to boundaries among the states.

There are already arrangements across many states that allow for telehealth in terms of reciprocal arrangements, but I would say whatever I would say for today may not be true for when a [00:11:00] viewer watches this recording, and so The onus is on all of us to stay current for what's allowed and leverage the resources of our institutions to keep on top of that for us.

Rohit Marawar, MD (Host): And uh, Dr. Patel, what should physicians keep in mind regarding licensing and malpractice when providing telehealth services?

Anup D. Patel, MD: I think the biggest thing is to build on what Dr. Stern mentioned is just to stay, on top of The ever changing landscape as it relates to this subject. Use your institution or your business manager to make sure the, malpractice part is covered, which usually is and not as big of an issue.

The biggest opportunity really is understanding how your state is. There are a variety of terms that this allows for video telehealth or other forms of telehealth. Dr. Stern alluded to this that some states are a little bit more flexible in allowing patients to live in different states and access you from, you know, in a different state than they are currently living in.

But many others do not. And so, if you have a large population, percent of [00:12:00] patients who live in another state that you feel would benefit from video telehealth, consider actually getting a license to practice medicine for that state. I know that's what we've done in the Midwest And Ohio specifically because some of the borderline states we draw patients from with video telehealth.

but having a West Virginia, Indiana, or Kentucky license is definitely a benefit to many of our providers. During the pandemic, we were able to have exceptions in that regard that allowed for, again, the optimal care to be continued or even delivered. That did change. And so now don't assume that you're able to do a visit for someone who lives in a different state.

Check ahead. Be proactive, but more importantly, if you do again, have a large population, consider just getting the license for that state. It will save a lot of headaches down the road.

Rohit Marawar, MD (Host): And finally, Dr. Stern, you answered this somewhat, but what do you see as the future of telehealth in terms of legislation, compensation, and its role in clinical care, especially in epilepsy?

John M. Stern, MD: [00:13:00] expect legislation to be placed that allows for telehealth to be indefinite and a part of healthcare delivery. I expect compensation to be more nuanced for what's being delivered because that's the history of compensation is to think about what effort and risk and resources are needed to deliver the care and it's different for in person than telehealth.

But the role in clinical care, that's an exciting question because you're asking to look into the future, and although remarkable how much change has occurred in the past five years or so, those changes are all extensions of what we already had somewhat for video meetings which we've had outside of clinical care.

The question is whether clinical care might become more important. More specialized within the telecommunication world, and I wonder about two parts of this. one is we're thinking about accessing specialists, where geography is really the limitation, but access requires something more than just a meeting like we're having today.

Whether there could be satellite offices that provide [00:14:00] resources for telehealth. And I'm imagining ways of doing the exam or maybe assistants who are trained in those offices, where the physician's not there, but the person goes to a facility much closer to where they live than the actual hospital and gets something that's a bridge where it's not really at home, but nor is it going to the place of that specialist and has an encounter that Provides, a solution to some of the obstacles that are present now through the assistance of somebody, who's a, a nurse or, another trained, caregiver.

I also wonder about telehealth in, the sense of not just the encounter, but, remote patient monitoring. You know, what happens when a patient, especially with epilepsy, where the condition can fluctuate, but other conditions do the same, and world in the future is very likely to have devices that help.

So, in gathering the information that's useful for care planning, and this information might be available or should be available to the provider at a distance, where maybe [00:15:00] the telehealth is continual, not just episodic visits. And so, the telehealth in that sense of the term telehealth is the physician, maybe the epileptologist in this case, having a way of tracking how patients are doing, maybe flags come up for when changes occur, and that triggers a visit to discuss that.

And may allow for better outcomes because it's more immediate than the scheduled visit. I'm going to see you in four months, no matter what, and it's becoming, molded to the actual patient need.

Rohit Marawar, MD (Host): I think that makes great sense. that wraps up our discussion on telehealth and epilepsy care. A big thanks to Dr. Patel and Dr. Stern for sharing their insights from the review article, The Tell on Telehealth. If you enjoyed this episode, please subscribe, share, and leave a review. You can find more episodes of epilepsy currents wherever you listen to your podcasts.

Thank you to our sponsor of this episode, Marinus Pharmaceuticals. Marinus is dedicated to the development of innovative treatments for rare genetic epilepsies, including CDK five [00:16:00] deficiency disorder. The company is committed to collaborating with epilepsy experts to advance therapeutic options that support the work of physicians and make a meaningful difference in patients' lives.

Learn more at marinuspharma.com.

Join Dr. Bermeo in a conversation with Dr. Susan Arnold, and Dr. Fred Lado, as they discuss the article, "It's Current: NAEC Provides Us With the Recipe to Build a Better Epilepsy Center".

Click here to read the article.

This podcast was sponsored by the National Association of Epilepsy Centers (NAEC).

2023 Guidelines for Specialized Epilepsy Centers

We'd also like to acknowledge Epilepsy Currents podcast editor Dr. Adriana Bermeo-Ovalle, and contributing editor Dr. Rohit Marawar, and the team at Sage.

In episode 7 of the Epilepsy Currents podcast, the discussion focuses on the 2023 Guidelines for Specialized Epilepsy Centers, published by the National Association of Epilepsy Centers (NAEC). Hosted by Dr. Adriana Bermeo, the episode features insights from Dr. Susan Arnold, the senior author of the executive summary of the report, and Dr. Fred Lado, president of the NAEC and the first author of the guidelines. The guidelines aim to set comprehensive standards for epilepsy care, particularly addressing the needs of patients with drug-resistant epilepsy.

Brief Summary

The 2023 NAEC guidelines for epilepsy care are designed to elevate the standards of care provided at specialized epilepsy centers. These guidelines distinguish between best practices for patient care and accreditation standards, the latter being what centers must meet to receive NAEC accreditation. Developed through an "evidence-informed consensus" process, these guidelines include contributions from a diverse panel, including neurologists, nurses, EEG technologists, social workers, neuropsychologists, patients, and caregivers. This inclusive approach ensures that the guidelines address comprehensive needs across the spectrum of epilepsy care.

Key Takeaways

1. Guideline and Accreditation Distinction: Dr. Lado clarified the difference between the NAEC's guidelines and its accreditation process. The guidelines represent consensus on best practices in epilepsy care, while accreditation standards are specific criteria that centers must meet to demonstrate adherence to these practices. This distinction helps centers focus on gradual implementation of the guidelines without immediate pressure for compliance.
2. Inclusive Development Process: Dr. Arnold emphasized that the guidelines were developed through an evidence-informed consensus, incorporating opinions from a broad array of stakeholders, including those directly affected by epilepsy. This method helps ensure that the guidelines are comprehensive and address practical aspects of patient care.
3. Focus on Comprehensive Care: The guidelines have expanded to cover not only inpatient and surgical care but also comprehensive outpatient services, reflecting the realities of where most epilepsy care occurs. This shift acknowledges the importance of accessibility, communication, and specialized services for various patient groups.
4. Resource Considerations: Recognizing the resource-intensive nature of comprehensive epilepsy care, the guidelines provide a framework for centers to gradually adapt to higher standards without abrupt changes. This gradual implementation is intended to ease the burden on centers, allowing them time to secure necessary resources.
5. Future Directions and Improvements: The guidelines are seen as a living document, with the NAEC planning more frequent updates to keep pace with advancements in epilepsy treatment and care. This adaptive approach aims to ensure that the guidelines remain relevant and practical for implementing the latest best practices in epilepsy care.

Transcript

Adrianna Bermeo-Ovalle, MD (Host): The main purpose that brings our community together is our desire and resolve to offer people living with epilepsy the best alternatives of diagnosis and treatment; the ones that will empower them to live their best possible life. But what does that mean in practical terms? How do we put that intention into clinical practice? The National Association of Epilepsy Centers, NAEC, has taken a careful look at this question. We are delighted to have the opportunity to discuss together the 2023 Guidelines for Specialized Epilepsy Centers that will inform epilepsy care in the present and the future.

Welcome to Episode 7 of Epilepsy Currents Podcast. I am your host, Adriana Bermeo. I am the Senior Podcast Editor for Epilepsy Currents, the official journal of the American Epilepsy Society. Let me first welcome Dr. Susan Arnold. Dr. Arnold is Adjunct Professor of Pediatric Neurology at Yale University School of Medicine.

She's the Senior Author of the Executive Summary of the Report of the National Association of Epilepsy Centers, entitled Guidelines for Specialized Epilepsy Centers, which was published by the Green Journal Neurology in February of 2024. Dr. Arnold, thank you very much for joining us today.

Susan T Arnold, MD: I'm very happy to be here.

Host: It is also my pleasure to welcome Dr. Fred Lado. Dr. Lado is the president of the NAEC and professor of neurology at the Zucker School of Medicine in Hofstra University in Long Island, New York. Dr. Lado is the first author of the guidelines, which you can find linked to the Epilepsy Current site and at the NAEC home site. Dr. Lado, thank you for being with us today.

Fred A. Lado, MD, PhD: Thank you, Adriana, for the opportunity to speak with you.

Host: Great. For our listeners and our readers of Epilepsy Currents, you can also find an It's Currents commentary authored by Dr. Katherine Nichols and published in the May 2024 issue of Epilepsy Currents. So let's get this conversation started. Dr. Lado, I will start with you. Could you please explain to our listeners the role of the National Association of Epilepsy Centers in setting national standards for epilepsy care, especially for those dealing with drug resistant epilepsy?

Fred A. Lado, MD, PhD: So the NAEC was founded in 1987, and since almost the beginning, has published quality standards around the functioning and the care given in epilepsy centers. These standards have been updated approximately every 10 years. And these standards are different from the accreditation program that the NAEC runs. That accreditation program began in 2016. The guidelines have been the basis for developing accreditation standards, but for accreditation standards, centers have to provide evidence that they're meeting the guidelines. Guidelines are really focused on what is best practices. What is the best level of care that patients should be receiving?

Accreditation standards are focused on, are centers implementing these guidelines? Are they actually providing these services? Many of the recommendations that you'll find in these new guidelines are already present in prior versions of the NAEC guidelines and in the accreditation program, but many of the guidelines in the current version are new and sort of stretch the boundaries of areas that the NAEC is addressing as part of comprehensive epilepsy care.

We recognize that in sort of moving the goalpost somewhat, that in expanding the scope of guidelines, that epilepsy centers need to have adequate resources to implement. And so the process of incorporating these guidelines into accreditation is one that will unfold over the coming years, not all at once.

Host: Thank you very much for that answer. Can you just once more clarify what is the difference, how are the guidelines different from the accreditation process for the people in the epilepsy centers who may get a little bit nervous about all the new recommendations that come in the guidelines? What is the urgency for them to implement all of these recommendations into the care they provide for their patients?

Fred A. Lado, MD, PhD: Yes, this is a topic of great sensitivity in epilepsy centers. The guidelines, as we'll discuss are really the product of a consensus across sub specialists, patients, administrators, EEG techs, certainly epileptologists, about what makes a good epilepsy care, what makes a successful epilepsy center in taking care of patients.

But the guidelines are sort of a recommendation of best practices. They are not accreditation standards. Accreditation standards are what the NAEC uses to judge whether a program is meeting the requirements for NAEC accreditation, and that might involve showing reports, might involve doing a certain volume of particular cases or surgeries, it has different specific requirements.

The accreditation standards that the NAEC establishes and changes and updates from year to year, are informed by these guidelines. But the guidelines are a statement of what is considered best practice. The accreditation standards are a statement of what centers have to do to become accredited.

Host: Thank you very much for clarifying that for our listeners and our readers. Dr. Arnold, we understand that these guidelines were developed through a process that is called evidence informed consensus. Can you please elaborate on the methodology and how does it influence the recommendations provided? And if you could, how are they different from the prior guidelines published by the NAEC?

Susan T Arnold, MD: So, the idea when you're writing guidelines is really to have an evidence based process where you survey the literature, collect information, grade the evidence that you collect, and then write your recommendations based on that evidence with the level of the evidence supporting your guideline.

And that works very well for clinical treatment guidelines, where you can search the literature and find studies that compare, for example, one intervention to another. Unfortunately, for an operational guideline, such as the one we were writing for epilepsy centers, the literature doesn't have a lot of information.

And where we do have evidence, it's often not of very high quality and it has gaps. And so in that circumstance, you go to expert opinion. And so what we did is follow an evidence informed process; where we surveyed the literature, we gathered all the information, and then we went to our panel of experts. We educated them on what evidence was in the literature, discussed it as a group, and then created a consensus recommendation using the panel of experts.

What was really different, I think, this time around is that our panel of experts didn't just include the neurologists and neurosurgeons that we've included in the past, but a much broader panel of stakeholders. And so we had our neurology nurses, we had our EEG technologists, we had social workers, neuropsychologists, and most importantly, we had people with epilepsy and their caregivers, and all of that group together created the consensus recommendations for the guidelines.

Host: Thank you very much. It looks like everybody who will be affected or who has a stake in the matter was invited to participate. Dr. Lado, we will not have time in one podcast to discuss all the 52 recommendations, but, if you could walk us through the highlights of the recommendations, initially for the inpatient portion and the surgical programs, what are the items that you want our audience to remember from this podcast?

Fred A. Lado, MD, PhD: Yes, as you point out, Adriana, there are 52 recommendations in the current guidelines. Some of these are similar to our recommendations in the 2010 guidelines, but many have been updated.

With respect to inpatient services, we've always focused on resources. Do you have an EMU? Do you have the appropriate personnel?

In the current guidelines, we have a greater focus on the processes that take place. Are we providing a safe environment in the EMU? Do we have appropriate protocols for preventing escalation of seizures or acceleration of seizures in patients where medications have been reduced? And we have more emphasis on process in the multidisciplinary conferences. And this is an area that received a lot of attention in the current guidelines. We really make clear that the multidisciplinary conferences should be attended by a multidisciplinary group. And in those conferences, patients should really be considered with the full range of different surgeries that might benefit them or procedures, not just what a particular center might be best at doing, but really the full gamut.

And so, the patient can be confident when they go to an epilepsy center that they have received the most comprehensive evaluation and the recommendation of course of treatment most likely to render them seizure free. And then of course, we think that, as Dr. Arnold said, communication and informing patients throughout this process is important.

Host: Dr. Arnold, what about outpatient services? What encompasses comprehensive care for patients with epilepsy in these days and how do you see the future of epilepsy care in the outpatient setting?

Susan T Arnold, MD: Well, as Fred said, this is really the majority of epilepsy care is the outpatient care, not the inpatient areas we've focused on in the past. And so it was a very new thing for us to write guidelines addressing this very broad area. And it was really a struggle for the panel to figure out what was important and what to focus on, because of course everything is important when it addresses quality of care.

So we wrote some guidelines that address some of the American Academy of Neurology quality measures for outpatient care, and that was maybe our starting line and then we really listened to the panel, and in particular, we listened to our patients with epilepsy. We listened to, their caregivers, and we listened to the nurses and the EEG technologists who are often their advocates for us in the medical system.

And what we heard is that access to care is important, and as Fred mentioned, communication was important. And so we expanded our guidelines to those areas. We addressed centers needing to look at their access to outpatient clinic appointments and doing what they can to prioritize the sickest and the most urgent patients so that they're not waiting months for an appointment.

We addressed communication with patients, both using our electronic medical records and also using telehealth, which is something that was very new to all of us when COVID hit, but I think we've all learned a lot about managing telehealth services, since the COVID epidemic. Another thing that we looked at was screening for special needs and related complications for people with epilepsy; things like mental health needs, things like socioeconomic needs, barriers to obtaining their medication, for example. And finally, we looked at servicing special populations. Those that might have had additional needs such as neurodevelopmental difficulties, women with epilepsy and in particular patients with other mental health needs, and our patients with psychogenic non epileptic events.

Those are all patients that in the past have not really been included in the guidelines that we have written.

Host: Thank you, Dr. Arnold. It seems like between the inpatient and the outpatient updates, we will be able to see the patient in many more dimensions than we do currently, and that really makes me feel hopeful for the care that we provide. Dr. Arnold, what about pediatric epilepsy centers? Are there any specific considerations regarding pediatric epilepsy care?

Susan T Arnold, MD: Absolutely, and as a child neurologist, the pediatric population is close to my heart. And, throughout our guideline writing process, we tried to ask ourselves as we addressed each area, is there anything particular that we need to look at differently for children and for centers that treat children? And so you will see in these guidelines, really a greater emphasis, not just on adapting guidelines, emergency managment procedures to the needs of children, but also on the very specialized services that children require. Those include things such as Child Life Specialists, educational material that's focused on the needs of children and their parents. Pediatric anesthesiologists, so that when a child goes for an imaging study, they can be safely sedated, and we can have the highest quality image that we can obtain to make the best decisions for their care.

In addition, we discussed special services that are relevant for both adults and children with epilepsy, but often have a greater role in the management of children. And among those were dietary services. Dietary therapy has a very special role in certain pediatric epilepsies, in children with certain metabolic disorders, and also in children with certain very severe epilepsies.

And the guidelines anticipate that centers that serve children either will have a dietician or will be able to refer to a center that has a dietician to provide a full spectrum of therapy, including dietary therapy. Another area would be genetic services. In the last 15 or 20 years, the use of genetic testing has just exploded and has become critical in the evaluation and in the management of epilepsy, both for children and more and more recognized as being important in adults as well.

And the guidelines discussed the importance of having genetic testing available, understanding which patients will benefit most from it and how to direct the testing towards those populations that will have the most benefit. And then providing genetic counseling services and genetic specialists to manage patients with complex genetic problems.

We recognize that this is a big ask for a lot of centers. We also recognize there are a number of adult focused centers that do a very good job of offering services to older children and teenagers with epilepsy. But we really tried to put ourselves in the shoes of the parent of a child with epilepsy looking for a pediatric epilepsy center.

And for that parent and for that child, a center that advertises itself as a pediatric epilepsy center, the panel felt really had to offer a very broad range of services or have them available by referral, if not within the center.

Host: Yeah, thank you, Dr. Arnold. That really sounds like an amazing perspective of being able to include all of that in the offerings for our patients from the epilepsy centers. But as we know, managing comprehensive epilepsy care can be resource intensive. Dr. Lado, how do the guidelines address the challenges centers may face in implementing these standards, especially when you think about resource limited environments?

Fred A. Lado, MD, PhD: So we gave this lot of thought. And you're right. Some of these guidelines are resource intensive. I think it's important to recognize from the beginning that general neurologists, primary care doctors often play a role in the care of individuals with epilepsy and often offer important and excellent services to the patients with epilepsy.

So these standards are not meant to say that all care for patients with epilepsy must always check every box of these guidelines. Rather, these are to say that comprehensive epilepsy centers meet a higher level of care for patients with epilepsy, and doing so, need to have more resources.

Now, the transition from the current state to the future state, where we would like more and more of these resources to be available, can't be abrupt. There needs to be sort of an on ramp so programs can gradually develop resources where they're necessary. And so, the process of implementing the guidelines, rolling them out in the form of accreditation criteria, is a process that will unfold over several years.

It's not going to be from one year to the next. We hope that by outlining what these guidelines contain and where we're headed with accreditation standards, that epilepsy centers will have both the time as well as the facts to make the case for their hospital administration, for their administrators, to commit the resources necessary to keep the program going.

Host: Thank you very much for that answer. That would certainly be very welcome by epilepsy centers all around the country and even internationally because NAEC sets guidelines that can be used beyond our country for sure. Dr. Arnold, can you please walk us into the future? How do you see these guidelines influencing future development, future accreditation, and as you know very well the process, what areas or aspects need further refinement or further research?

Susan T Arnold, MD: As we've mentioned many times already, with the fact that the scope of these guidelines is so much broader than what we have done before, we recognize a couple of things. First of all, I'm very excited for people developing new centers, we've given them a much broader and more comprehensive list of criteria to work on to understand what an epilepsy center is and that it's more than just an epilepsy monitoring unit or a surgical program.

So I think that's key. Secondly, and we've also touched on this a little bit, the guidelines are so much broader that we can't just put all of them into the accreditation process. There's going to have to be a period of adapting our accreditation process to get its arms around the new guidelines, if you will.

As Fred mentioned, when we have guidelines, when we have something written down on paper, centers can take that to their institutions and try and get the resources they need. And our hope is that by publishing the guidelines, as we take time to phase them into the accreditation process; by the time we get there, our centers will be prepared.

They will have had the lead time to get the resources they need to meet some of these things. Looking toward the future, one of the things we learned is that 10 years is just too long to go between guideline processes. And NAEC is looking at a way to address guideline development that would be much more responsive to changes that are going on in the world of epilepsy treatment.

And so that we're not bringing a big slice of new information to the table every 10 years, but providing more real time, if you will, updates in our guideline process. And finally, there were a number of areas that we simply didn't address in the current guidelines, not because there was a lack of interest, but because either the evidence base wasn't there yet, or because we felt that we had simply gone as far as we could with one set of guideline revisions. And some of those things include looking more at outcomes because our goal for treating epilepsy is not just to have the best process within our epilepsy center, but also to have the best outcomes for epilepsy interventions. And I think that's an area that will take time to address, but eventually we'll need to look at how centers look critically at what they're doing and what their outcomes are and use that to continue to improve the care they provide to people with epilepsy.

Host: Well, it certainly feels like we are making steps into a brighter future for the care of our patients with epilepsy. I would like to invite our listeners to log in into the Epilepsy Currents website and click into the link to the National Associations of Epilepsy Centers guidelines into the original papers which are cited in our site as well.

I want to thank very much our guests and thank our listeners. I want to especially thank the National Associations of Epilepsy Centers, who is the sponsor of today's episode and came today to share these important guidelines with all of us.

I want to thank Dr. Rohit Marwar and the SAGE podcast production team. We look forward to having you join our next episode. Remember to subscribe to Epilepsy Currents podcast wherever you get your podcast and send us your feedback, suggestions, or questions through our website, EpilepsyCurrents.org, and don't forget to follow us on ex former Twitter, at AESCurrents.

Until next time, everybody.

Join Dr. Bermeo in a conversation with Dr. Jarrod E. Dalton, Dr. Bruce Hermann, and Dr. Samuel Terman, as they discuss the article, "Hiding in Plain Sight—Neighborhood Versus Individual Determinants of Psychological Outcomes in Patients With Epilepsy ".

Click here to read the article.

This podcast was sponsored by the American Epilepsy Society through a grant from the Centers for Disease Control (CDC).

These activities are supported by the Centers for Disease Control (CDC) and Prevention of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award totaling $1,500,000 with 100% funded by CDC/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor are they an endorsement, by CDC/HHS, or the U.S. Government.

We'd also like to acknowledge contributing editor Dr. Rohit Marawar, and the team at Sage.

Summary

The podcast features a discussion on how environmental conditions, specifically neighborhood deprivation, affect cognitive outcomes and mood in individuals with pharmacoresistant temporal lobe epilepsy. Dr. Hermann & Dr. Dalton's study found that patients living in more deprived areas exhibited significantly lower cognitive performance and increased levels of anxiety and depression compared to those in less deprived areas. Dr. Terman's commentary critically assesses these findings, stressing the importance of considering environmental factors alongside biological ones in understanding and treating epilepsy.

Key Takeaways

1. Impact of Neighborhood Deprivation: The study highlighted a strong correlation between increased neighborhood deprivation and poorer cognitive outcomes as well as higher levels of anxiety and depression among epilepsy patients. This suggests that external environmental factors play a crucial role in the health outcomes of individuals with temporal lobe epilepsy.
2. Role of Area Deprivation Index (ADI): The ADI is utilized to quantify neighborhood deprivation, encompassing factors like income, education, and housing conditions. It provided a robust framework for analyzing the socioeconomic conditions impacting patient outcomes, underlining the relevance of broader social determinants in health disparities.
3. Implications for Clinical Practice: These findings underscore the need for clinicians to consider the socioeconomic environment of patients when diagnosing and treating epilepsy. Addressing environmental factors could enhance therapeutic outcomes and improve quality of life for patients.
4. Study Limitations and Future Research: Dr. Terman noted limitations such as the cross-sectional nature of the study, which complicates the ability to infer causation. He advocates for longitudinal studies to better understand how and when neighborhood factors impact patient health, potentially leading to more targeted interventions.
5. Potential for Broader Implications: The discussion extends beyond epilepsy, suggesting that similar environmental influences could be significant across other neurological and psychiatric conditions. Future research might explore how modifications in social policy and urban planning could mitigate these health disparities.

[00:00:00] Adriana Bermeo (Host): It is well known that individuals living with epilepsy are at risk of experiencing cognitive decline and psychiatric comorbidities. But did you know that the individual's home address plays a significant role in the cognitive and psychiatric outcomes of people living with temporal lobe epilepsy?

[00:00:18] Welcome to episode number six of Epilepsy Currents podcast. Today, we will be talking about the role of environmental factors on cognition and mood of patients with temporal lobe epilepsy. I am your host, Adriana Bermeo. I am the Senior Podcast Editor for Epilepsy Currents, the official journal of the American Epilepsy Society.

[00:00:40] I want to first welcome contributing editor, Dr. Samuel Terman, who wrote the commentary, Hiding in Plain Sight--Neighborhood vs. Individual Determinants of Psychological Outcomes in Patients with Epilepsy. This commentary was published on the March 2024 issue of Epilepsy Currents. [00:01:00] Dr. Terman is an Assistant Professor at the University of Michigan. Dr. Terman, welcome to Epilepsy Currents Podcast.

[00:01:07] Samuel W. Terman, MD, MS: Thanks so much. Happy to be here.

[00:01:09] Host: It is also my pleasure to welcome Dr. Bruce Hermann, who is the Senior Author of the work that inspired this commentary, titled Association of Neighborhood Deprivation with Cognitive and Mood Outcomes in Adults with Pharmacoresistant Temporal Lobe Epilepsy. Their paper was published in Neurology in June 2023. Dr. Hermann is Emeritus professor of Neuropsychology at the University of Wisconsin School of Medicine and Public Health. Welcome, Dr. Hermann. Thank you for being with us.

[00:01:39] Bruce Hermann: Thank you, and good afternoon.

[00:01:41] Host: We are also joined by Dr. Jarrod Dalton, who is co-author on the original paper. Dr. Dalton is an Associate Professor and the Director of the Center for Population Health Research at the Cleveland Clinic's Lerner Research Institute. Dr. Dalton, thank you for being with us today.

[00:01:58] Jerrod Dalton, PhD: And thank you.

[00:01:59] Host: While [00:02:00] neurologists and epileptologists are familiar with the effects of the biological characteristics of the lesions causing epilepsy, the neurophysiological findings of the treatments we use in the clinic, we are much less likely to consider their patient's immediate living environment, their access to healthy foods, exposure to violence, or their access to transportation as potential modifiable variables directly affecting someone's epilepsy outcomes.

[00:02:28] Dr. Hermann. Would you mind sharing with us a snapshot of the findings from your study in a way our listeners can grasp?

[00:02:35] Bruce Hermann: Dr. Busch and I have been collaborators for quite some time, and she was able to compile an amazing cohort of 800 patients with pharmacoresistant temporal lobe epilepsy who underwent neuropsychological assessment as part of their inpatient evaluations at the Cleveland Clinic. And then, she and Dr. Dalton extracted home addresses from the EMR and binned the patients into ADI quintiles. [00:03:00] And from the neuropsychological battery that was quite extensive, as is commonly the case in preoperative evaluations, the data was reduced to seven mean cognitive domains, things such as intelligence, language, visual perception, verbal and visual memory, executive function, processing speed. And then, secondarily classified all the patients into four cognitive phenotypes that range from intact, essentially unaffected, to generalized cognitive impairment.

[00:03:32] So, the core finding and most important finding was that examination of the relationship of the Area Deprivation index was closely aligned with the cognitive scores. So as deprivation increased, cognitive scores went down. This was seen across seven of the six cognitive domain scores, and greater deprivation was associated with the more abnormal cognitive phenotype. And increasing neighborhood deprivation was also associated with [00:04:00] greater anxiety and depression. So, it really was quite a signal that we were able to observe. And as Dr. Terman pointed out in his commentary, you can just take a look at IQ. Quintile 1, the least deprived group, had a mean IQ score of 100, which is dead average. And the most deprived quintile, Quintile 5, their mean IQ was 86, which is a full standard deviation below average. So, very reliable and fairly strong signal throughout these results.

[00:04:28] Host: Yeah. Really striking findings, which seem to point out that the deprivation that patients are exposed is almost as important as the biology of the condition. And I'm sure we will discuss that in length later. Dr. Dalton, the concept of the Area Deprivation Index, or ADI, plays a central role in the study. Can you please help us understand what does this measure? How do these quintiles work? And how is this measurement different from other measurements of socioeconomic status?

[00:04:59] Jerrod Dalton, PhD: [00:05:00] Sure. Yeah, the Area Deprivation Index is a tool that we use in our research in a lot of settings. We work with clinical specialties across Cleveland Clinic and use this as one tool for understanding place-based health disparities. Essentially, the Area Deprivation Index, it's a latent variable model or a factor model that produces an index that captures correlation among 17 neighborhood-level characteristics. The ADI was established at the National Cancer Institute in 2003 by a demographer and sociologist named Gopal Singh. It was designed as scale of neighborhood socioeconomic position as opposed to socioeconomic status, which I can distinguish a little bit between the two. And it incorporates aspects of social organization, income, housing, economic inequality, and opportunity structure.

[00:05:56] So, the indicators that comprise the ADI [00:06:00] are varied, but they all speak to overall socioeconomic characteristics. So, it'll include measures of education, proportions by level of education. It includes measures of income, such as median family income, income disparities. It includes measures of housing and housing affordability, median home value, median rent, monthly mortgage amounts, and percent of households

[00:06:27] It also includes economic and employment measures such as labor force participation rates and poverty rates, family structure measures such as the percent of single-parent households among those with somebody less than 18 years of age, and a series of resources such as motor vehicle ownership, telephone ownership, and whether or not households have plumbing.

[00:06:50] Host: And those variables are related to the neighborhood where the patient is living rather than to the individual patient. Is that correct?

[00:06:57] Jerrod Dalton, PhD: That is absolutely correct. When we look [00:07:00] at these quintiles that you and Dr. Hermann were referring to, we have to be very careful not to stratify our patient populations based on observed socioeconomic position associated with their community, but rather stratify them according to the communities themselves.

[00:07:17] Host: Dr. Herrmann, it is certainly very intriguing to think that the environment can shape cognitive functions, potentially not only for patients with epilepsy, but particularly for patients with epilepsy. Can you elaborate on how factors like the person's neighborhood or community may influence their health, particularly their cognitive abilities and maybe if you can make a mechanistic idea of how does that work or what would be the factors that intervene in that relationship?

[00:07:47] Bruce Hermann: Yeah. Well from a neuropsychological standpoint, we don't have much of an understanding of how these neighborhood factors affect cognition. That, of course, was the point of the study. [00:08:00] And as you infer, in the field of neuropsychology of epilepsy, the lion's share of attention has been paid to the relationships between cognition and features of the epilepsy and its treatment.

[00:08:12] So, there are innumerable studies looking at aspects of cognition like intelligence, memory, language, and the epilepsy syndrome that the patient might have, or their age of onset, the duration, seizure frequency or severity, or the number of medications that they take. This is a classic heritage. And in addition, there's a large literature examining diverse neuroimaging correlates of cognition and psychiatric comorbidities, including depression and anxiety.

[00:08:41] But we have known for some time, just for example, through the CDC behavioral surveillance studies, that the economic, social, and lifestyle correlates of epilepsy can be punishing, and those have been documented. But how these factors relate to cognition and behavior have been less [00:09:00] well understood.

[00:09:01] Host: Dr. Terman, in your commentary, you highlight some strengths and also some limitations of the study. Would you like to share some of the specific issues that our readers may need to be aware when interpreting the findings?

[00:09:12] Samuel W. Terman, MD, MS: Yes. The study has many strengths, and like all studies, there are limitations and future directions. Some of the strengths have already been mentioned through Dr. Dalton and Hermann's discussion of the work, including a large sample size with an impressively long period of time in which patients were recruited with detailed expert cognitive assessments. Measuring the outcome well is important for any study. And while sometimes having many different domains and submeasures can raise concern for multiple comparisons when results are inconsistent, or you're not sure whether significant findings are true positives. In this case, I think it was a strength given convergence of results across multiple domains and subdomains of cognitive and neuropsychological [00:10:00] measures.

[00:10:00] But, that said, there are numerous limitations that I see. For example, as I read it, it was a cross-sectional study, which is good for hypothesis generation, but also that lack of temporal correlation, what happens over time. You can't distinguish causation from reverse causation. We can theorize what direction the relationship is going, but you can't be sure in a cross-sectional study. In other words, do neighborhoods affect people? Which is what we think from the study. Or do people non-randomly sort themselves into neighborhoods? That would be reverse causation, which is also plausible, but we can't tell.

[00:10:38] And there's some confusing relationships. For example, age was one factor in the multivariable models, and it actually was not associated with degree of cognitive impairment, which we know that aging is a very important feature of a person's cognitive health. So, future studies could address these things. For example, longitudinal data could surmount some of [00:11:00] these questions about causation versus reverse causation. There are even specialized statistical models that seek to isolate when in a person's life, what exposure matters most. For example, if a person's exposed to a neighborhood with a higher degree of deprivation earlier in life versus later in life, when does it matter most?

[00:11:21] It's also been mentioned that the mechanism by which some of the features of the ADI leads to outcome changes is unclear. And related to measurement of the ADI, a major strength is its ability to aggregate and summarize over the 17 different components that have been mentioned. But we're also left not knowing exactly quite which one is most critical when we lump rather than we split.

[00:11:45] And the ADI also, while it measures lots of things well, it also lacks potentially key measures: pollution, healthy food, social cohesion, the way a city is laid out. Also, if a high ADI neighborhood is juxtaposed next [00:12:00] to a low ADI neighborhood, there may be features that are complicated dynamics that we're not capturing here. So, we can't be sure which component of the ADI and also if there's a component in there that's just correlated with something that we haven't measured. We don't know exactly what's the driving force here.

[00:12:16] And then, two other thoughts in terms of perhaps limitations and/or future directions. The census block is an important grouping, which is how the ADI is categorized, but it's also not the only way that people are grouped. Neighborhoods in the world in which we live, we live in an online communities and a globalized society. So, just the sheer geographic location is likely important for healthy food and parks and pollution, but there's also so much more as we're connected to each other than just that specific census block.

[00:12:51] Host: Let me give you a follow up on that. Dr. Dalton, any thoughts on following these findings in a longitudinal way or including other measures of [00:13:00] deprivation or other social determinants of health.

[00:13:02] Jerrod Dalton, PhD: Yeah. I think, you know, Dr. Terman's comments are 100% right on the spot. You know, I think when I work with scientists, what I usually do is I will mention a lot of these limitations. And I will say that the ADI is just an analytic tool.

[00:13:18] A great first step in understanding social and place based health disparities in a particular, in a particular disease context, such as epilepsy. There are many issues with it. And the field of neighborhood measurement is very rapidly evolving. In terms of longitudinality, I think it's helpful for us to recall the social context under which we have place-based disparities in the United States, which was largely driven 80, 90 years ago by racial residential segregation and federal housing policy that discriminated against [00:14:00] racial and ethnic minority groups.

[00:14:01] So, in large part, we have this entrenched issue of economic deprivation in communities that disproportionately impacts those of minority race and ethnic status. And these things are very difficult to reverse. So as it relates to the question of the stability of overall measures of socioeconomic position over time, unfortunately, it's too stable. It's more stable than we would like it to be, that I personally would like it to be. And as a scientific rationale for a cross-sectional evaluation of area deprivation and relationship with outcomes, generally speaking, we have pretty stable results over time. Now, that said, there are of course issues of gentrification and neighborhood change over time that should be taken into account. And these available measures currently cross-sectionally defined. They don't accommodate in measurement [00:15:00] fashion neighborhood change.

[00:15:02] I might respond to a couple of the other good points that Dr. Terman made. Regarding the age, the age in this sample was relatively homogenous on the earlier side of the life course, around 20 to 50 years of age. So, mechanisms of cognitive decline in older adults may or may not had a large influence on the observed measures of cognition. And of course, the area deprivation and other place-based socioeconomic measures lack key mechanistic exposures like the ones that he mentioned. And like I said, it's a very active area of sociological research, and we frankly need enriched models that are more expressive than a single domain, and we've done a little bit of methodological work in our lab exploring just that.

[00:15:54] Host: Dr. Hermann, besides the cognitive outcomes, the study also highlights [00:16:00] worsening measurements of depression and anxiety in the patients with the most deprivation or the highest ADI quintile. How do you interpret these findings. And particularly, can you share with our listeners how did these findings vary when you took race into account, race and ethnicity?

[00:16:18] Bruce Hermann: Let me address this in the following way. First, we've been speaking in the abstract a little bit about deprivation and in the supplemental table of the neurology article, Drs. Busch and Dalton put together a very nice table that's informative about deprivation where people stand in these various quintiles.

[00:16:38] Let me just give you a few examples. For example, mean income. So, the mean income in the neighborhood and please correct my language if this is imprecise, Jarrod, but the mean income in the least disadvantaged quintile in that neighborhood is $118,000. The mean income in the most disadvantaged neighborhood, Quintile 5, was [00:17:00] $36,000. Huge difference. The percent of families below the poverty level in the least disadvantaged neighborhood, 1%; in the most disadvantaged neighborhood, 27%. Single parent households with youth under 18, 12% in the least disadvantaged, 68% in the most disadvantaged. And just one more, the percent of households without a vehicle, 1% in the least disadvantaged, 19% in the most disadvantaged.

[00:17:29] So in regards to the psychiatric comorbidities, there has been a long history of debate about what's important for a long time. The debate centered around where the seizure started from. So for those who had temporal lobe epilepsy, psychiatric comorbidity was driven by volumetric abnormalities in the depths of the temporal lobe and mesial regions, and/or the degree of spiking that might be shooting through limbic systems.

[00:17:58] And so, the [00:18:00] way role played by disadvantaged in social circumstances was relegated to have little role, actually. But if you think about these sorts of effects that I just mentioned, how can they not have an effect on somebody's emotional adjustment? And if you look at the general population and the relation of psychiatric comorbidities to these sorts of trends, they're quite apparent. So the most disadvantaged, and I'll start this sentence, but then ask Dr. Dalton to finish it, but in the most disadvantaged quintiles of our particular study minoritized groups were overrepresented as expected. And to address the issue of neighborhood disadvantage versus minority status, Jarrod carried out a number of analyses. And let me turn that over to you, Jarrod.

[00:18:49] Jerrod Dalton, PhD: When we look at race and ethnicity and its role in relationships with health disparities, it's important to consider the mechanisms by [00:19:00] which you would hypothesize there to be racial and ethnic differences and to study those mechanisms. And we did not hypothesize all such mechanisms associated with racial and ethnic minority status in this study. We evaluated one mechanism, which was the one I referred to earlier around racial residential segregation and the fact that in societal terms, not necessarily for a specific individual, but in societal terms, there are many barriers to economic mobility, and we have this prevalent problem of racial and ethnic minority populations residing in communities with low resources.

[00:19:42] So, there are a couple potential causal models that can be used to motivate analyses into these relationships. One would be a mediation analysis where you consider the extent to which selection into low-resource communities [00:20:00] is responsible for observed racial and ethnic disparities in your outcome. And that's exactly what we looked at here. So, we looked at models with and without adjustment for ADI and studied how the relationship between racial and ethnic minority status changed after accounting for what in technical terms would be the mediating effect of living in low-resource communities.

[00:20:28] So for our proportional odds logistic regression analysis looking at severity of cognitive phenotypes, what we found without adjustment was that minority race or ethnicity was associated with three times the risk of being in a higher or more severe cognition phenotype compared to non-minority patients. And then, after accounting for the neighborhood deprivation, that relationship was reduced to about 1.8. So in other words, [00:21:00] we do seem to have some signal of explanatory effect of ADI in terms of the racial and ethnic disparities in cognition in this patient population.

[00:21:13] Host: Thank you for that. It seems like there's so many layers to these. I would like to follow with Dr. Terman. When we study, and even from the clinic, when you see patients with medication-resistant epilepsy, how can we differentiate what is what

[00:21:27] Samuel W. Terman, MD, MS: well, it's a bit different from a research standpoint than a clinical standpoint, because there are things that you can do in one setting but can't do in another. From a research standpoint, it's a matter of measuring what matters when it matters, and we don't always have the luxury of having everything that we would like at exactly the right time points over a long period of time. But if you're trying to distinguish the effect of neighborhood deprivation versus the condition of epilepsy itself, you need to measure as many things about both of those things as accurately as you can. So, [00:22:00] variables like what anti-seizure medicines is the person on, at what doses, and what adherence, and what days did they have seizures, and were they convulsive, and how long were the seizures, and were they in status epilepticus? And you can very quickly see that, "Oh my goodness, there are so many." The world is so complicated and there's so many things that could influence the outcome. So, it's matter of what's feasible and being able capture those variables that you wish to distinguish and then you can decide, "Am I going to do a mediation or a structural equation model or some other type of model to try to tease out the effect of different potentially correlated covariates.

[00:22:40] From a clinical standpoint, sometimes if you're not sure, ultimately what you do is you manipulate what you can in the direction that you think it should be manipulated. For example, if you think a person could be having cognitive side effects due to their anti-seizure medicine and their seizures are not as problematic, then you go down. Or if you feel that their seizures are a [00:23:00] driver of their cognitive status, you go up and see if they can tolerate it better. But unfortunately, at this day and age, epilepsy care is a bit of a trial and error process.

[00:23:09] Maybe to take the next step in terms of another research avenue that people have done in socioeconomic disparities, people have even done some sorts of quasi experiments to exploit natural variation. There have been a limited number of actual randomized experiments where people were randomized to healthcare insurance versus not, or vouchers versus not, or even refugees coming out of dangerous neighborhoods or communities or countries. People were sorted new locations and people have studied these things. There're all kinds of variation, distance from a highway in terms of pollution and access to healthy food. So, there are lots of creative ways to measure the things that you would like to and the things that you think are important and would like to distinguish between. Sometimes if you can't, there are some other tricks up our sleeves using [00:24:00] clever quasi experiments or true experiments when it's ethically and practically feasible to do so.

[00:24:05] Host: Thank you very much. I will stay with that question and I would love to ask Dr. Hermann and Dr. Dalton, what's in the future? In the research arena when we consider the realm of environmental influences on neurologic conditions. In the discussion in your paper, you hint that maybe looking into how these variables affect the anatomical studies in patients with temporal lobe epilepsy may be in the works. Anything else, any future directions on where these type of studies are going or should go?

[00:24:36] Bruce Hermann: Yeah. I think an immediate applicability is with children with epilepsy, and even better, children who have new-onset epilepsies that addresses some of the points that have been raised in this discussion. So if you go and you start at the beginning with a cohort of children with epilepsy and controls in their homes of [00:25:00] origin developing over time, does epilepsy occur more often in high deprivation areas? Maybe, maybe not. What's the impact of deprivation on cognitive development going forward prospectively? What's the impact on brain development going forward? And if deprivation has an effect, how long does it last? Does it last one year, two years, three years? I mean, the literature on lifetime outcomes of youth with epilepsy generally, but not invariably, points to a somewhat difficult course in many regards as they age and grow older. And if these deprivation factors have an influence on cognition, cognitive development, brain development, then it becomes even more critical to get serious about this. And I think Dr. Terman had a very interesting point at the end of his commentary, you know, if you want to [00:26:00] intervene, do we intervene on or about? And we need to have sense, we don't have a relative ranking of the importance of deprivation versus type of epilepsy versus seizure control versus type of medication on memory, on intelligence, on depression. How much variance do these factors account for? And if you get a rank ordering, this is easy to say but hard to do, but if you can generate a rank ordering, the explanatory power correlation at the least gives you some ideas about where to go and what to do. And I think that's at least one important future for the direction, as well as getting a really good handle on exactly how is deprivation exerting its effect on a person. And one way is through imaging.

[00:26:52] Host: Thank you for that. I want to ask Dr. Terman to follow up on that, because you have some interesting [00:27:00] insight in your commentary about what can communities do besides the providers. You mentioned urban development and maybe food deserts come into mind. Any suggestions or any ideas of what can we do as providers or as a community to maybe mitigate some of these inequities.

[00:27:18] Samuel W. Terman, MD, MS: Yeah. Neighborhoods and cities are not randomly evolving entities. They are the product of planning. And so when we develop communities and neighborhoods, ideally we plan for success. Now, I'm far out of the realm of civil engineering and city planning and all this is very complicated, interfacing with politics and economics and political will. But, as Dr. Hermann mentioned, we need to understand which of these things are most critical. And after understanding which of these things are most critical, then deciding, well, if the problem is pollution, then that's a very different path than if the problem is lack of healthy food, or if the problem is crime and violence, [00:28:00] or if the problem is physical activity, or if it's truly a product of medical care. You know, these lead to very different types of solutions. Ultimately, it may be that as is often the case, that causes and effects are bidirectional and multifactorial, so it may be there is not one single solution, but a comprehensive suite of solutions to plan communities as well as we can.

[00:28:26] Host: Thank you all. I want to especially thank you for these very thought-provoking conversations. I'm sure as we go home to our own neighborhood and our own community and can imagine the communities and neighborhoods our patients are going back to after visiting us in the clinic. We may be planning in the future how to learn more about it and how can we make a difference over time.

[00:28:50] We are running out of time. I want to thank each of our guests. I want to thank our listeners. Special thanks also to the American [00:29:00] Epilepsy Society in partnership with the CDC and their initiative Disrupting Disparities: Documenting and Addressing Gaps in Epilepsy Care Through Healthcare Provider Education and Training. Their collaboration is the sponsor of today's episode.

[00:29:15] I want to thank Dr. Rohit Marawar and the SAGE podcast production team. We look forward to having all of you back on our next episode. Remember to subscribe to Epilepsy Currents podcast, wherever you get your podcast, and send us your feedback, suggestions, or questions through our website, epilepsycurrents.Org, and follow us on X, former Twitter, @aescurrents. Until next time, everybody.

Join Dr. Bermeo in a conversation with Dr. Ezequiel Gleichgerrcht, Dr. Erik Kaestner, and Dr. Peter Widdess Walsh, as they discuss the article, "More Than Meets the Eye: Human Versus Computer in the Neuroimaging of Temporal Lobe Epilepsy".

Click here to read the article.

This podcast was sponsored by the American Epilepsy Society.

We'd also like to acknowledge contributing editor Dr. Rohit Marawar, and the team at Sage Publishing.

Summary

This fantastic Epilepsy Currents podcast episode delves into a groundbreaking study on the application of artificial intelligence (AI) in differentiating temporal lobe epilepsy from Alzheimer's disease and healthy controls using MRI-based deep learning. The study, co-authored by Dr. Ezequiel Gleichgerrcht and Dr. Erik Kaestner, demonstrated AI's potential to significantly improve the accuracy of neuroimaging analysis in epilepsy. The commentary by Dr. Peter Widdess-Walsh provided a critical examination of these findings, highlighting the practical implications for clinical practice and the limitations of current methodologies. The discussion framed AI not only as a tool for enhancing diagnostic accuracy but also as a means to uncover subtle neurobiological differences between diseases, potentially leading to more personalized treatment approaches.

Key Takeaways

1. High Diagnostic Accuracy with AI: The study highlighted showed that AI, specifically convolutional neural networks (CNNs), could differentiate between temporal lobe epilepsy, Alzheimer's disease, and healthy controls with high accuracy. This demonstrates AI's capability to identify nuanced patterns in neuroimaging that may not be visible to the human eye.
2. AI Identifies Subtle Neurological Differences: The inclusion of Alzheimer's disease as a comparative group in the study was strategic to determine if the AI was recognizing temporal lobe epilepsy based on hippocampal atrophy alone or other disease-specific patterns. The findings suggest that AI can discern epilepsy-related patterns beyond the typical markers, indicating a profound potential for AI in understanding complex neurological conditions.
3. Impact on Clinical Practice: Dr. Widdess-Walsh's commentary underscores the importance of these findings for clinical practice. AI's superior detection rate compared to human analysis (90% versus 47%) suggests that AI could significantly augment clinicians' ability to diagnose temporal lobe epilepsy, potentially leading to earlier and more accurate interventions.
4. Limitations and Ethical Considerations: Despite AI's impressive capabilities, the podcast discussion acknowledges limitations, including the current inability of AI systems to interpret scans holistically, consider clinical context, or replace human decision-making. These factors highlight the need for AI to be used as an adjunct tool in clinical practice, enhancing rather than replacing the expertise of healthcare professionals.
5. Future Directions and Challenges: The episode concludes with reflections on the broader implications of AI in neurology, from predicting surgery outcomes to possibly revolutionizing epilepsy care. However, challenges such as external validation, regulatory approval, and integration into clinical workflows must be addressed to fully realize AI's potential in epilepsy diagnosis and treatment.

Transcript

Adriana Bermeo, MD (Host): Hello and welcome to episode five of Epilepsy Currents podcast. Today, we will be talking about the use of artificial intelligence and machine learning in the study of temporal lobe epilepsy. I am your host, Adriana Bermeo. I am the senior podcast editor for Epilepsy Currents, the official journal of the American Epilepsy Society.

Today, I am joined by a team of experts in this very exciting neurodiagnostic arena. I want to first welcome contributing editor, Dr. Peter Widdess-Walsh, who wrote the commentary "More Than Meets the Eye: Human vs. Computer Neuroimaging of Temporal Lobe Epilepsy." This commentary was published on December 2023 issue of Epilepsy Currents. Dr. Widdess-Walsh is a consultant neurologist and Clinical Associate Professor at Beaumont Hospital in Dublin, Ireland. Peter, welcome to Epilepsy Currents podcast. podcast.

Peter Widdess-Walsh, MD: Thank you very much, Adriana. I'm delighted to be here.

Host: Thank you for being here. It is also my pleasure to welcome Dr. Ezequiel Zeke Gleichgerrcht, who authored the work that inspired this commentary titled, "MRI Based Deep Learning Can Discriminate Between Temporal Lobe Epilepsy, Alzheimer's Disease, and Healthy Controls. Their paper was published in Nature Communications Medicine in 2023. Dr. Gleichgerrcht is an Assistant Professor of Neurology at Emory University. Zeke, welcome.

Ezequiel Gleichgerrcht, MD: Thank you. Thanks for having me.

Host: We are also joined by Dr. Erik Kaestner, co-author on the original paper and lead author on other related publications addressing the use of artificial intelligence in epilepsy. Dr. Kaestner is a postdoctoral scholar at University of California, San Diego. Erik, thanks for being with us today.

Erik Kaestner, PhD: Thank you. Excited for the conversation.

Host: Very good. I can tell you that artificial intelligence is one of the most requested topics when we ask our listeners and the epilepsy community. The challenges and opportunities presented by the use of AI in almost every aspect of our daily life, but particularly in healthcare, are intriguing, exciting, and potentially concerning to some. But before we start discussing AI, Peter, can you share with our listeners what is the added value of expanded neuroradiology in the care of patients with epilepsy?

Peter Widdess-Walsh, MD: Thanks, Adriana. And thank you for highlighting this very interesting and topical article for the podcast. And many thanks to Dr. Gleichgerrcht and Dr. Kaestner for being here with us. We know that MRI is a key tool in finding the underlying cause of focal epilepsy. However, up to 30% of MRIs are non-lesional. That is, there is no visible lesion responsible for the patient's epilepsy. We can sometimes lower this non-lesional percentage by using additional MRI techniques such as volumetry or various additional sequences or higher strength magnets. But these are not universally available or have limitations, so there's a gap there. We know that there is a focal epileptogenic network, but we cannot see it. And it is partly due to limitations of MRI technology, which are improving all the time, but it's partly due to limitations of what we can see visually with the human eye. There are also human error rates in analyzing MRI, even with skilled radiologists known as perceptual errors.

A shrunken, bright hippocampus is easier to see than subtle alterations in grey matter volumes. Particularly in surgically remediable epilepsies, finding a lesion or visualizing the epileptic network can make a huge difference in a better patient outcome after surgery. And even in non-surgical patients, it's very reassuring to have an imaging correlate of the epilepsy that you know is clinically present.

I'm not an AI expert and I wrote the commentary from the perspective of an epileptologist in clinical practice like many of our listeners. So, it was fascinating to learn more about AI and how it might fit into our daily practice in this area. The authors used the term computer vision in this article, and I'm excited to learn more about how computer vision can help us in the diagnosis of epilepsy.

Host: Thank you very much. We are certainly excited to see how we can advance our field further than what we are practicing at the moment. Zeke, could you paint the picture as for how is AI revolutionizing the field of radiology and particularly when it comes to neuroimaging analysis?

Ezequiel Gleichgerrcht, MD: Yeah, absolutely. And I think we start acknowledging that AI is becoming this true transformative force in medicine. Like you said, neuroimaging is by no means the exception. So for instance, if we think about AI and how it gives us frameworks to analyze huge amounts of imaging data, the pace and precision with which it can achieve it is unattainable by humans alone, right?

Humans not using this computer vision that Peter was mentioning. So, let's talk about neuroimaging specifically. AI algorithms can sift through MRI, CT scans, and, almost do a first pass at detecting abnormalities from brain tumors, there's applications for aneurysms, areas affected by stroke, you name it. Of course, our interest is in epilepsy, but we know how crucial early and accurate detection of some of these findings can be. So, you know, when trying to answer this question, how is it revolutionizing the field of radiology? I think it's really about how the accurate detection of these findings can be instrumental in patient care. So, AI applied to neuroimaging can help us mostly scale detection of brain diseases and have tremendous impact on outcomes.

But it's not just about detection of disease, right? AI now can support decisions about care tailoring or personalization of patient care, because if you can combine neuroimaging and health data, now you can offer insights that lead to more tailored strategies. For example, in other studies, we have shown that using AI, we can predict who becomes seizure free after epilepsy surgery based exclusively on preoperative imaging. And we found accuracies that are 30% points higher than what humans achieve just based on their combination of health data alone. You know, when I think about the revolution of AI, it's also paving the way for prediction or predictive analysis, things like forecasting disease progression or identifying when seizures will happen, for example, for a given patient. So, it's certainly a very exciting time for AI and neuroimaging and epilepsy.

Host: Wow, that's a lot of changes expected for the future in the way we practice. Erik, I want to bring it to you for those of us who are not tech wizards. Can you break down what this idea of convolutional neural network or CNN, what it is and how it could transform the way we interpret, particularly neuroimaging and MRI scans?

Erik Kaestner, PhD: So at its heart, a convolutional neural network is a way to learn patterns and data. And so for this particular project, we gave it a task. We said, "Can you differentiate patients with temporal lobe epilepsy from patients with Alzheimer's disease from healthy controls?" And we provided T1 images of the brain to do this. And so, In a lot of ways, it's very similar to what a neuroradiologist is doing. You present a neuroradiologist with an image of the brain and you ask for some sort of call on what they're seeing. So to understand what the neuroradiologist is doing, I'm going to have to defer to my colleagues in neuroscience. But it's a little more straightforward for the CNN.

So, a CNN is made up of a series of layers, and each layer basically performs a small set of computations. And so, the first layer, which is given access to the image of the brain, takes little pieces of the image, performs its calculations, passes that image on to the next layer, it performs its little calculations, passes that on to the next layer. And the number of layers is dependent on the person building it, so you decide how many layers there are. And eventually, all of this data arrives at the final layer, which makes a decision. It says, "I think this is a patient with TLE," "I think this is a patient with Alzheimer's," or "I think this is a healthy control." and so as for how this can transform how we interpret MRI scans, I've actually discovered over the last year, that this is an extremely robust debate that's kind of ongoing in the field. Because like I mentioned, there's a lot of similarities in the tasks that neuroradiologists are being asked to do and what we can ask a convolutional neural network to do.

And so, I was giving a talk recently and someone came up afterwards. A clinician came up afterwards and said, "Well, why would I trust this? You know, I have no idea what these numbers mean or where they're coming from or what the model's doing," which I think is a very fair question. Another person on the panel gave a good answer, which I'll crib from a little bit, which was, "Well, when you go to the doctor, can you really see what the doctor's brain is doing before they give you kind of their advice?" And so, I think this is a great way to think about what these networks, what these convolutional neural networks need to produce in order to gain the trust of the clinicians and of the patients. And so, in kind of a bedrock level, there's the behavior. You know, does the model get it right? Can we kind of trust it to give us the right answer over many patients? Then beyond that, we also need to think about how sure the model is. What information is it using? Is it using the proper information that we as clinicians and researchers have wanted to use? And also, we need to improve the outputs to a way that is interpretable by the human.

Host: Thank you very much. We will certainly discuss a little bit about how this difference is so remarkable and how can we trust it better. But I am curious to know why did your team decide to choose these particular control groups? What is similar or different between the Alzheimer's patients, and the relationship to healthy subjects? Dr. Gleichgerrcht, I'm curious, how did you decide to use these groups?

Ezequiel Gleichgerrcht, MD: Yeah. Thanks for the question because we thought about it a lot. And I'd say the rationale for having an Alzheimer's disease group they are competing against the TLE and the healthy controls for the machine to classify was at least twofold. On the one hand, we have literature, I would say, for the past two decades or so, showing that patients with temporal lobe epilepsy, at least at the group level, have patterns of atrophy that are widespread, right? So, it's not that we just see atrophy in the hippocampus or even in the temporal lobes. At the group level, the patterns of atrophy for TLE are sometimes extratemporal and even contralateral to the side of seizures. So, that was one side of the rationale.

On the other hand, you know, in a prior paper, I believe it was in 2021, we had already shown that AI could identify who had temporal lobe epilepsy solely from the clinical MRI. And we had that benchmark to ask ourselves this question, almost as the next natural step: Is the machine detecting TLE simply based on detecting hippocampal atrophy, or is it detecting widespread epilepsy-related patterns that the humans are not typically paying attention to? So, when we included Alzheimer's disease as a third group that offered this competing disorder with prominent hippocampal atrophy, right? That is the core of pathology in Alzheimer's disease, then we were trying to answer the question, is it, again, just the hippocampal atrophy driving the classification? And, again, hippocampal atrophy being pervasive in Alzheimer's disease, but also in so many TLE patients. And, I want to say that when we asked this question, the natural reaction was, "Well, we also have to make sure that the machine is not just detecting older versus younger brains." Because, of course, if it's detecting just age related patterns, of course, it's going to do a great job at distinguishing Alzheimer's disease from temporal lobe epilepsy, because the mean averages of those populations are so radically different.

So, a lot of our method, and I invite the audience to go and read about this, was about removing the effect of age on the brain images before we entered those images into the machine to have it classify disease. We put a lot of thought into it. And I think we had a model that can be replicated for other diseases where you're training a machine to try and detect the disease independently of all these other confounding factors like age and patterns of atrophy.

Host: So much to discern from all of these conditions that may have multiple targets in the brain. In order to go deeper a little bit into the technicalities of the study and in order to help our listeners read the paper and understand it, Erik, can you please unpack some of the jargon for our listeners? Could you explain terms like accuracy, precision, recall, the F1 score? What do they mean when someone reads the paper? How should they read these variables?

Erik Kaestner, PhD: Yeah. So, kind of in the analogy I was using earlier of how does the model gain our trust, these are kind of the bedrock elements where we're just asking, "Can you do the task? Can you get it right?" And so for something like accuracy, you're just saying, "All right, patient by patient, control by control, overall, are you able to get these accurate to some degree?" And then, we can go a little deeper and look at each individual condition, and that's where something like F1 score comes in where we can start to say, "How are you performing on patients with TLE?" How are you performing on patients with Alzheimer's?" And so, F1 score basically combines two of the other measures you mentioned, precision and recall. And precision says when the model claims that someone is a patient with TLE, is it right often? You know, is it kind of just saying this is a patient with TLE to everyone, and so we can't really trust it? Or is it being more conservative and kind of giving you a high level of accuracy within that specific patient group? And then, you have something like recall. Recall says of the patients with TLE in the cohort, Were you able to identify a large proportion of them or not? And so often these two measures, you can maximize one, but it hurts you in the other. So if you just guess patient with TLE for every single image you come across, then your recall will be quite high, because you will identify every single patient with TLE, but your precision will be quite low because, basically, every time you say it's a patient with TLE, you're going one for three. And so, F1 score is very useful because it combines these two. And so if a model is cheating in some way, it'll kind of reveal it by showing, "Okay, I don't think it's actually being quite truthful with us essentially. I don't think it's being fair." And so, like I said, once you've kind of interrogated the model's behavior in this way and said, "Okay, it seems to be doing the task quite well, then you can go on to the next step and start to interrogate it in other ways."

Host: I want to go to Peter. You know, in your commentary, you highlighted how the AI showed a success rate in detecting temporal lobe epilepsy of 90% compared to the human eyes, 47%, which is humbling. And I wonder what is your take on these AI outperforming the human eye. And how do you think AI assisted temporal lobe epilepsy detection will mean for our clinical practice?

Peter Widdess-Walsh, MB: Adriana, that's a great question. I would emphasize that we have to be careful with AI tools as to what exactly this particular AI tool used in the study, it was the carefully selected unilateral temporal lobe epilepsy and their T1 weighted MRI images. Patients with distorting structural lesions such as tumors or malformations were excluded.

Most of the scans visible to the human eye had mesial temporal sclerosis. So we see that the AI tool that the authors developed was quite a bit better at picking up these other cases that were not visible to the human eye. As I mentioned, there are limits to the human vision processing system, and we can only spontaneously analyze so many areas at once.

I gave the example in the commentary of the invisible gorilla study, an experiment where an image of an angry gorilla was placed over the lung area of a chest CT, and then radiologists looking for lung nodules missed the gorilla image 83 percent of the time due to attentive and perceptual error. So, I think AI imaging tools can help us see what we cannot see and also reduce this perceptual error.

Although I still think we'll need the radiologist or clinician to incorporate information from AI into the interpretation and clinical management of the patient. I wrote the title to be somewhat thought provoking, but perhaps a better title would have been not human versus computer, but human with computer.

AI is there to assist us in our decision making, not make the decision for us. AI tools will typically have a very specific purpose, such as in this study, to detect an MRI signature in unilateral temporal lobe epilepsy. And in its current form, it doesn't read the whole scan, or pick up unexpected findings, or incorporate the results into the whole clinical picture or with EEG or discuss it with the patient and their family.

So we're not out of a job yet, but it has the potential to enhance the delivery of care to our patients.

Adriana Bermeo, MD (Host): Thank you so much. I would love, Dr. Gleichick, to answer this question. Take on that, how do you see, the future of these, artificial intelligence, aid, in, identifying lesions in neuroimaging in patients with epilepsy? And how do you see the role of radiologists and neurologists, for the immediate future as it seems?

Ezequiel Gleichgerrcht, MD: Yeah, well, you know, as computer processing power increases, first our speed and capacity to process more data will also increase. And these advantages, or advanced computer, uh, set ups will get more affordable. In fact they are, and as they become more affordable, they also become more scalable. So we'll get almost an explosion, right, of applications across medicine.

Of course, that includes epilepsy, but I really love the way Peter described this, which is that, I really do not think of AI as a replacement for humans, but as this superpowered assistant, if you will, helping humans be more efficient and precise at their jobs. AI will direct our attention to possible subtle lesions that the human expert eyes may miss on the first pass.

We're busy clinically and our volumes are increasing across the country and so getting this super powered assistant certainly helps. And humans will be the ones vetting whether the AI detection is relevant and accurate. Like Peter said, they're integrating that into all the other elements of the clinical care the assessment.

So AI will help predict maybe clinical trajectories with greater accuracy. Clinicians are still going back and understanding what that trajectory means for their specific patient. They're having the discussions about that trajectory with the patient. And so I really want us to think about it as this super powered assistant.

Definitely not a replacement.

Adriana Bermeo, MD (Host): I like that perspective too. Peter, in your commentary, you highlight the fact that all the areas of the brain were found involved with temporal lobe epilepsy beyond temporal lobe structures. and your take on it of what it can mean for our understanding of the condition is quite, interesting and provoking. I would love it if you can elaborate on that.

Peter Widdess-Walsh, MB: Yeah, incredibly interesting to see what computer vision sees over what we see. Subtle patterns and volume and architecture probably reflect the epileptic network changes and its connections as well as the underlying epileptic substrate. We know from prior voxel based morphology studies and studies of cortical thickness, for example, from the Enigma study group, that both temporal and extratemporal structural network alterations are there in patients with temporal and extratemporal epilepsy.

This is supported by studies looking at functional connectivity, such as those from intracranial EEG. The authors have taken the next step to develop and train a model that we can plug MRI data into and get a meaningful and accurate output. Does this patient have a pattern consistent with temporal lobe epilepsy that is different from other limbic system pathologies such as Alzheimer's disease?

It would be really interesting to know if there were signature patterns within temporal lobe epilepsy such as which patients will be medication resistant, which will have more cognitive impairment, and who will have better outcomes after temporal lobectomy.

Adriana Bermeo, MD (Host): Wonderful. I have one more question for. All, which is, kind of stepping out a little bit of the paper in particular, and just thinking about the future and the use of AI in epilepsy care, even beyond radiology. Where do you think we're going? We have touched on it, a little bit briefly. Erik, we'd love to start with your take.

What is next for the use of artificial intelligence in epilepsy care?

Erik Kaestner, PhD: I mean, I think that for me personally, where my mind has been going lately is really on the question how do you get an interface between the human and the model? Because as both of the others pointed out, it really isn't that you receive kind of a definitive answer, put it in the chart and move on. You know, the clinician really has to be able to explain, not only in the chart, but also to the patient, why they think that, they're presenting with, this particular condition or another. And so having some sort of interface where the clinician can go back and forth with the model and say, Oh, really? You think this is a patient with TLE? I wasn't so sure. Like what is leading you in that direction and being able to kind of engage in that. And I think some of the large language models that we've probably all played with a little bit could be one avenue into that. But really kind of we're ending up in a, almost a, user interface set of questions.

Adriana Bermeo, MD (Host): Zeke, where are we going with AI in epilepsy?

Ezequiel Gleichgerrcht, MD: So before we move on, beyond the neuroimaging, let me just put in a plug for our group and definitely a lot of other groups that are creating a lot of applications from lateralizing side of epilepsy, detecting focal cortical dysplasia, but even cool stuff that I never even thought about. So, you know, 3TMRI is not available everywhere and there are these new portable scanners, I think they're 0.55 Tesla. So there's even AI applications now to augment those lower magnet power MRIs and try to bring them to the quality of a 3T. So there's still a lot to discover in the neuroradiology aspect. But beyond that, are a lot of algorithms trying to predict, for example, when the next seizure will happen.

Our team actually published last year, using paper seizure diaries to predict at the individual level when the next seizure will happen for a patient. And you can imagine the kinds of consequences that that would have as we get better. So, there are a lot of teams now working with wearables, chronic EEG, even chronic EGOG from systems like RNS and using those data to predict at the patient level. There are applications in development for tailored drugs and serum biomarkers, and they're all relying on AI algorithms to achieve in very short time frames things that would have taken years, just a few years ago.

So it's definitely a very exciting time for AI, well beyond neuroradiology and epilepsy.

Adriana Bermeo, MD (Host): Peter, how do you imagine your AI integrated epilepsy practice?

Peter Widdess-Walsh, MB: I think AI is here to stay. there are hurdles before it's available to the wider epilepsy community to use in clinical practice. So, for example, the AI tool used in this study was developed in house, which they typically are, and then these tools have to be validated on external data sets to ensure they generalizable.

And then there's hurdles around regulation and software development and maintenance and as they would be or can be classified as medical devices if used for clinical decision making, there is FDA or equivalent approval. So there are steps, before it's available, our desk, you know, for clinical practice, but I think AI is here to stay.

Adriana Bermeo, MD (Host): Thank you, everybody. It is certainly the picture of a hopeful future for our practice and most importantly for our patients. I want to sincerely thank our guests and thank our listeners. I want to give special thanks to the American Epilepsy Society, who's the sponsor of episode five of our podcast, and to Dr. Rohit Marawar and the SAGE production team for the podcast. We look forward to having you join our next episode, and I want to remind you as always to subscribe to Epilepsy Currents podcast wherever you get your podcast, and send us your feedback, suggestions, or questions through our website, EpilepsyCurrents.org, and don't forget to follow us, on X, formerly Twitter, @AESCurrents. See you next time, everybody.

Join Dr. Bermeo in a conversation with Dr. Page Pennell and Dr. Alison Pack as they discuss the article, "Dobbs Versus Jackson: Epilepsy, Reproductive Health, and Abortion".

Click here to read the article.

This podcast was sponsored by the American Epilepsy Society.

We'd also like to acknowledge contributing editor Dr. Rohit Marawar, and the team at Sage Publishing.

Summary: In this episode of the Epilepsy Currents podcast, Dr. Adriana Bermeo discusses the Supreme Court's decision on Dobbs v Jackson and its implications for people living with epilepsy. She is joined by Dr. Allison Pack, a professor of neurology at Columbia University, and Dr. Page Pennell, the chair of the Department of Neurology at the University of Pittsburgh School of Medicine. They discuss the key points and historical significance of the Roe v. Wade and Dobbs v Jackson rulings, the current state-by-state variation of abortion access in the United States, and the impact on women and people of childbearing age living with epilepsy. They also address the importance of contraception, the risks of anti-seizure medications during pregnancy, and the need for evidence-based care and advocacy for patients. Resources such as the Guttmacher Institute and the National Abortion Federation Hotline are mentioned for further information and support.

5 Key Takeaways:

1. The Supreme Court's decision on Dobbs v Jackson has significant consequences for persons living with epilepsy and their access to abortion.

2. The current state-by-state variation of abortion access in the United States is complex and can range from very restrictive to most protective.

3. Planned pregnancies are crucial for individuals with epilepsy to optimize outcomes for both the individual and the developing fetus.

4. Effective contraception is important for individuals with epilepsy, and options such as long-acting reversible contraception (IUDs) and birth control pills should be considered.

5. Neurologists and epilepsy specialists should advocate for their patients' rights and women's rights, ensuring that medical decisions are made by qualified practitioners based on evidence and with respect for the individual patient. Resources such as the Guttmacher Institute and the National Abortion Federation Hotline can provide information and support.

Transcript

Dr. Adriana Bermeo (00:05):

Hello and welcome to episode four of Epilepsy Currents podcast. I am your host, Adriana Bermeo. I am the senior podcast editor for Epilepsy Currents, the official journal of the American Epilepsy Society. It is my pleasure to welcome today's guest to talk about the Supreme Court's decision on Dobbs v Jackson and its consequences for persons living with epilepsy. We have two very special guests to help us understand the implications of this ruling on reproductive health and access to abortion for people living with epilepsy of childbearing potential. First, I want to welcome Dr. Pack, senior author of a commentary titled Dobbs versus Jackson Epilepsy Reproductive Health and Abortion, published online first in the May, 2023 issue of Epilepsy Currents. Dr. Pack is a professor of neurology at Columbia University. She's the Chief division of Epilepsy and sleep at New York Presbyterian, Columbia University Medical Center. I also want to especially welcome Dr. Page Pennell, who's the Henry B. Hickman Professor of Neurology and chair of the Department of Neurology at the University of Pittsburgh School of Medicine. Dr. Pennell is a global expert on the management of pregnancy-related issues in epilepsy, and she's also a past president of the American Epilepsy Society. Dr. Pack, let me start with you. Most of our listeners are familiar with Roe versus Wade and Dobbs versus Jackson Supreme Court rulings, but could you give us a quick refresher on the key points and historical significance of these two landmark cases?

Dr. Allison Pack (01:43):

Thank you very much, Adriana, and it's a pleasure to be here today and I want to thank the American Epilepsy Society for supporting this discussion as we go through our discussion today. Today we will be referring to persons with epilepsy of childbearing potential. Please recognize that we are aware that not all individuals who seek pregnancy or become pregnant identify as a woman. So I'm going to go through right now the court rulings ruling Roe v. Wade was enacted in 1973. In this ruling, the court ruled that the Constitution of the United States generally protected a right to abortion. This ruling was reaffirmed in 1992 in the ruling Planned Parenthood of Southeastern Pennsylvania versus Casey. Dobbs v Jackson was enacted on June 24th, 2022. With this ruling, the Constitution does not confer a right to abortion. Essentially, Roe v. Wade and Planned Parenthood of Southeastern Pennsylvania versus Casey were overturned. The authority to regulate abortion went back to the state and the constitutional right to abortion was eliminated.

Dr. Adriana Bermeo (03:08):

Thanks, Dr. Pack, you were mentioning how things went back to the state, and as we know, the legal landscape of these rulings then are evolving. Acknowledging this is a moving target, could you please help us understand the current state-by-state variation of abortion access in the United States, and what does this mean for the physicians practicing in the different states?

Dr. Allison Pack (03:37):

Well, I have to say understanding the state-by-state variations is quite complex. I would draw all of your attention to the Guttmacher Institute, and there's a very good website whereby you can see the map of the United States and the outline of the various regulations or the various degrees of restriction. And these vary from most restrictive occurring in over 15 states whereby abortion is banned at 12 weeks and later. There are very restrictive, which bans abortion at 12 weeks and later. Some restrictions starting at the third trimester. Protective, it's banned at fetal viability between 24 and 26 weeks, and very protective whereby it's banned at fetal viability. And then there's some other regulations that give more protections than those states that are protective and then most protective whereby there is no restriction based on gestational age. As I mentioned earlier, the most restrictive; this includes, for example, Kentucky, Texas, very restrictive, North Carolina, Georgia, some restrictions, Virginia protective, Illinois, very protective New York, and then most protective, there's only one, and that is the state of Oregon. So it is important to understand that there are varying degrees of restrictions across the United States in these different categories. And as I mentioned earlier, I would draw your attention to the website from the Guttmacher Institute, which really is very helpful for you to understand what the restrictions are or not in the state that you live.

Dr. Adriana Bermeo (05:29):

Thank you very much, Dr. Pennell. Can I turn it to you? Can you please help us understand how these rulings affect particularly women and person of childbearing age or childbearing potential living with epilepsy?

Dr. Page Pennel (05:42):

Yes. Thank you also for inviting me for this very important podcast and to sit alongside Dr. Pack who is such an expert in this area. So unplanned pregnancies in the general population are known to have a higher complication rate, but especially in persons with epilepsy, it's incredibly important to have a Planned Pregnancy and for the woman to have the best seizure control possible for her with the medication regimen and vitamin regimen that will provide the opportunity for the safety of the developing fetus. Pregnancy also carries a risk to women directly and with persons with epilepsy there are reports of elevated maternal mortality. Studies in the UK have actually shown that the elevated rates of death in persons with epilepsy are due to SUDEP or sudden unexpected death in epilepsy. So if a woman with epilepsy goes into a pregnancy unplanned and also with a high seizure burden, the chances that pregnancy will be unsafe for her and her developing fetus are much higher. And if she doesn't have the opportunity to make a decision with her clinician about what to do after that time, it can be particularly devastating.

Dr. Adriana Bermeo (07:05):

Dr. Pack, your commentary in Epilepsy Currents really makes the point that neurologists ,epileptologists and the organizations who represent their interests should care and take action in protecting patients' rights and women's rights. Can you please expand on this idea? Why should neurologists and epilepsy specialists care?

Dr. Allison Pack (07:29):

Well as individuals or practitioners who take care of persons with epilepsy of childbearing potential, we want to provide the optimal environment both for seizure control and pregnancy outcomes for the individual as well as the developing fetus. It is as the American Epilepsy Society has stated, critically important that medical decisions are made by qualified practitioners and that this be done based on evidence with respect for the individual patient. Therefore, the decisions made for the outcome or the health of the individual should be up to the practitioner and patient themselves or the person with epilepsy. Many of our anti-seizure medications may increase the risk of unplanned pregnancy. This is important. It's important that the individual has an unplanned pregnancy and are in a state whereby there are extreme restrictions. Again, as I mentioned, the decision should be left up to the provider and the person with epilepsy. As well, many anti-seizure medications, notably valproic acid, can increase the risk of adverse or negative pregnancy outcomes. As practitioners, we need to be aware of and advocate for the patients that should this occur to these individuals, that they do have options available to them to optimize their health as well as the outcome of the developing fetus.

Dr. Adriana Bermeo (09:10):

Thank you so much for that. That definitely brings the point that we're all part of the caregiving team of our patient and their family. Dr. Pennell, these rulings also bring up attention to contraception. Could you please tell us about the most contraceptive options available for persons with epilepsy of childbearing potential and how widespread the use of these methods are and how effective they are and how are they different in people with epilepsy than in other individuals?

Dr. Page Pennel (09:44):

Yeah, certainly, as Dr. Pack pointed out it is very important that we discuss actually as the person caring for our patients with epilepsy, that we have these discussions with them about how important planned pregnancies are, which begins with effective contraception. Some studies found that up to 65% of women with epilepsy had reported at least one unplanned pregnancy. So this is certainly a very important and prevalent consideration. The most effective contraception we like to encourage is under the band of long-acting reversible contraception, which are the various IUDs. This could be a copper IUD or it could be an IUD that has progestin as part of its mechanism of action. But the progestin just works in the endometrial cavity and does not depend upon blood levels for its effectiveness. So therefore, even if a woman is on an enzyme-inducing anti-seizure medication, the IUD still has a very high effectiveness rate of over 99%.

(10:50):

However, thanks to the collaborations we've had over the years with our wonderful colleagues and contraceptive gynecology made me very much aware that there are so many factors that go into decision-making. And many women in the US in particular are not open to the idea of an IUD. So our message should not be that you need to use an IUD or else nothing that's definitely should not be our message. Combined oral contraceptive pills, birth control pills are still the most commonly used form of contraception and will be very commonly used in our patients as well. So we do need to know about the interactions, but if they're on an enzyme-inducing, anti-seizure medication, we need to make them aware of that, encourage backup barrier methods, et cetera. And when we think about the enzyme-inducing medications, we also need to be aware it's not just an old-generation versus new-generation story.

(11:48):

A lot of our newer medications also can lower the hormone levels from these hormonal contraceptives. Some of those medications, some people may be surprised to know include for instance, cenobamate, rufinamide, clobazam. So we need to have the discussion if they are going to use a hormonal form of contraception such as birth control pills or the vaginal ring to just let them know that they should also consider a backup barrier method, but also give them information about the more effective types of contraception. We also like to encourage, there's a progestin implant, the brand named Nexplanon, which has a very high effectiveness rate for contraception, but again, that can be affected if they're on a strong enzyme inducer. So again, we need to consider the medications they're on in their contraceptive choices.

Dr. Adriana Bermeo (12:46):

Great. Dr. Pennell, I'm going to stay with you because following the conversation on contraceptions, we also know a lot from collaborative groups and teams that you've been part of that anti-seizure medications can pose some risks for pregnancy of children of adults living with epilepsy. Can you briefly remind us of the potential risk of congenital malformations and neurodevelopmental issues related to exposure to medications and how these risks are related to our conversation of access to abortion?

Dr. Page Pennel (13:20):

Yeah, certainly. Thank you. I do like to remind us, we can get discouraged about all the things we don't know in this field, but how far we have come because the conversation used to be that all anti-seizure medications are very teratogenic and have a high risk to the developing fetus. But now we do have a lot of information to provide evidence-based counseling and care that we do have some medications that have very low rates of major congenital malformation, also known as birth defects. And these rates are really similar to the general population. The medications that really stand out with the most abundant information supporting this are lamotrigine, levetiracetam and oxcarbazepine. But we also know other medications have very, very high rates of these major congenital malformations. And the one that has the greatest risk is valproic acid. We also now have information on some medications about the neurodevelopmental outcomes, and so that some medications have very low neurodevelopmental risk.

(14:26):

And with that we have lamotrigine and levetiracetam in that safe category. But then again, we have higher risk medications such as valproate. We now have increasing information about the concern on fetal neurodevelopment for topiramate. We also know that topiramate can lower the fetal growth and result in small-for-gestational age and also has a sort of medium rate of the malformations. So topiramate is becoming another medication that is starting to have greater restriction on it just placed in Europe and maybe coming out in the United States as well for use and persons of even reproductive potential. So it's so important to be able to get on the best medication regimen for that person and also at the right dose that will help to control their seizures the best possible. It's also important that they're taking folic acid well prior to conception. If all of those things aren't lined up, we know that the risk for the developing fetus as well as the mother is higher. And that's where if they're not in an ideal situation and not having access to making decisions about continuing the pregnancy is more devastating. Out of all the malformations, the one that certainly has such a high morbidity is neural tube defects. And so that is one in particular of the malformations that often will garner a conversation about the possibility of termination if the person is in a state, that is an option.

Dr. Adriana Bermeo (16:12):

Thank you for that answer as well. Dr. Pack, can you help us understand other specific issues or risks for people with epilepsy that neurologists and epileptologists should be mindful of when giving perinatal counseling, particularly when we consider genetic causes of epilepsy? Is there anything that you discuss with your patients, especially considering these new abortion rulings?

Dr. Allison Pack (16:39):

I think there's several issues here, and one of the things that's very important is something that Dr. Pennell touched upon earlier is that planned pregnancies are associated with better outcomes, and for individuals with epilepsy, planned pregnancies are important to optimize outcomes not only for the individual but for the developing fetus. As such, just to highlight a point that Dr. Pennell made earlier, it's important in that setting for the individual to be using effective contraception and recognize a nationwide healthcare claims database, finding that 63% of individuals with epilepsy either use no contraception or used ineffective contraception. So part of your perinatal counseling should be on the importance of planned pregnancies. There are certainly some genetic epilepsies and individuals who may have children at risk for this. That would be important within genetic counseling to have that genetic counseling done prior to pregnancy. So important points here: planned pregnancy, genetic counseling, keep in mind that that does pertain to a few individuals, not the vast majority of individuals with epilepsy.

(18:02):

And then the other piece that's important is that some of the malformations that Dr. Pennell spoke about earlier may not become evident until much later in the pregnancy. So for example, we routinely counsel that individuals get an anatomic ultrasound, which typically occurs between 16 and 20 weeks. If the individual who were pregnant with epilepsy were pregnant, were to find out that there was a malformation, the very restricted states ban abortion at 12 weeks or later. So for many of these individuals, this would be, if there a malformation was found at that anatomic ultrasound screening, this would be too late in those states. So just to summarize and go over again, it's important to emphasize that planned pregnancies will optimize the outcome both for the individual with epilepsy as well as for the developing fetus. Effective contraception is an important component of this. There are some genetic conditions whereby it would be important to have that information or have that genetic counseling prior to getting pregnant and recognize some malformations may not become evident until later in the pregnancy where in many states, abortion is not an option. Importantly, though, please understand as we go through this topic, that with planned pregnancies, with focusing on choosing optimal anti-seizure medications, as discussed by Dr. Pennell, most individuals do have normal healthy pregnancies.

Dr. Adriana Bermeo (19:47):

Dr. Pennell, are there any specific concerns related to minorities or people of color in regards to access to care, pregnancy planning, and access to abortion?

Dr. Page Pennel (20:03):

Thank you for that very important question. We know that a lot of things we're talking about when it comes to any medical care, we have to consider also how it affects our underrepresented minorities because there are differences as access to care and higher complication rates, and many of these situations just such as this one. So when you look at just access to abortion services alone, that a much higher percentage of minorities do receive abortions than are in the general population. There's a lot of reasons that come into this, whether it's economic status and ability to provide for that child after birth or whether it's that they didn't have access to good contraception and good medical counseling before. So we know that this is going to affect this population even more to not have the access to termination of pregnancy. And then when you look at the flip side, continuing the pregnancy, just again in general that the pregnancy-related death rates are over three times higher in women of color than non-Hispanic Caucasian women. So their risk during pregnancy, regardless of all the other things we've talked about today, are higher just going into a pregnancy planned, and then as we know, unplanned are probably even greater.

Dr. Adriana Bermeo (21:31):

Dr. Pack, the last question for you. How can we as neurologists effectively champion evidence-based care and protect their professional judgment in the realm of reproductive decisions for their patients? And do you know of any resources we could share with our listeners if they want to further get informed or advocate for and with their patients?

Dr. Allison Pack (21:57):

Well, I think one of the key points of all of this is that access to care, access to different therapeutic options should be, I just want to emphasize this again, up to the clinician and the individual person with epilepsy not up to the state or national rulings. Therefore, it's important for all of us to advocate for the individuals that we treat. It's important for all of us to work together so that the individuals we treat have access to optimal healthcare so that we can increase the potential for planned pregnancies as well as allow that individual access to therapeutic options to optimize their health as well as the health of the developing fetus. As such, we should all be working with the various organizations that we're involved with, including the American Epilepsy Society, the American Academy of Neurology, to really advocate that the healthcare decisions are left up to the provider and the patient themselves. If an individual were to get pregnant and have a negative outcome or potential negative outcome and is considering an abortion but lives in a restricted state, there are resources for that individual. The National Abortion Federation Hotline is available and will help that individual. It's important for us to be informed about the legislation and rulings in our individual states, and as I mentioned several times before, I would draw your attention to the Guttmacher Institute, which will guide you very clearly what the potential restrictions are in the state that you live.

Dr. Adriana Bermeo (23:56):

Wonderful. This was a very informative overview of the current landscape of reproductive health and their impact on our patients, and also neurologists and epileptologists all around the country and in the very different scenarios that each of us is navigating. I want to thank you very much. Thanks a lot to our guests and our listeners, I want to specially thank the American Epilepsy Society, who's the sponsor for episode four of Epilepsy Currents, Dr. Rohit Marawar and the SAGE Podcast production team. We look forward to having you all join our next episode, and as always, I want to remind you to subscribe to Epilepsy Currents podcast wherever you get your podcast, and send us your feedback, suggestions, or questions through our website, epilepsy currents.org, and follow us on X formerly Twitter @aescurrents. Until next time.