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.