Exercise and epilepsy: Research and myths

In this episode, we explore the science behind exercise as an adjunct treatment for epilepsy and debunk some common myths (spoiler alert: With very rare exceptions, exercise does NOT increase seizure risk). Dr. Ayushe Sharma talked with Dr. Jane Allendorfer, Dr. Halley Alexander, and Brian Wiedmeyer, who participated in an exercise research study.

The episode refers to a 2016 report by the ILAE Task Force on Sports and Epilepsy - that report is freely available online at this link.

Some of the other research papers mentioned in the episode are listed below.

The relationship between physical activity and cognitive function in people with epilepsy: A systematic review

Effects of physical exercise in people with epilepsy: A systematic review and meta-analysis

Role of Physical Exercise as Complementary Treatment for Epilepsy and other Brain Disorders

Epilepsy and exercise: An experimental study in female rats

Effects of an exercise program on health of people with epilepsy: A randomized clinical trial

A strength exercise program in rats with epilepsy is protective against seizures

Effectiveness of Yoga Intervention in Reducing Felt Stigma in Adults With Epilepsy

Impact of exercise as a complementary management strategy in people with epilepsy: A randomized controlled trial

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

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

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

Transcript

[00:00:00] Dr. Ayushe Sharma: Hi! Welcome to the ILAE Sharp Waves podcast. I'm Ayushe Sharma, your host for today's episode, which is dedicated to understanding how exercise can serve as a powerful adjunct treatment for epilepsy.

 We have three great guests with us today. First we have Dr. Jane Allendorfer from the University of Alabama at Birmingham. She leads a lab dedicated to studying the neural and cognitive effects of exercise in people with epilepsy.

Our second guest, Dr. Halley Alexander, is an epileptologist at Wake Forest. She brings us a really valuable clinical perspective. 

And third, we have Brian Wiedmeyer, who is a patient with temporal lobe epilepsy. So in that order, would three of you mind sharing what brings you here today and how you connect with this topic?

[00:00:47] Dr. Jane Allendorfer: So like you said, Dr. Sharma, I conduct research studies in people with epilepsy, specifically exercise studies and neuroimaging studies. And I want to investigate the effects of exercise on brain chemistry, brain structure, and function. I'm especially interested in the relationships between physical activity levels of people with epilepsy and their cognitive function, specifically memory function and also how exercise training programs can help improve memory. And then the exercise induced brain changes that may subserve these beneficial effects that we see.

[00:01:27] Dr. Halley Alexander: I’m Halley Alexander, as you mentioned, I'm an epileptologist at Wake Forest University and my interest in physical activity for people with epilepsy started in when I was doing fellowship training and starting to see more epilepsy patients. I wanted to find new ways to help improve quality of life for our patients and that got me starting to think about the benefits that physical activity could provide for these patients in terms of mood, seizure frequency, maybe even reducing some medication side effects and just having an overall increased quality of life.

[00:02:05] Brian Wiedmeyer: My name is Brian Wiedmeyer; I’m epileptic. My previous knowledge before being introduced to the study I was participating in was exercise was not good for somebody with seizures, and that it would help induce a seizure in a patient. I came to find out once I got to meet Dr. Allendorfer and I talked to her a little bit about my background, she was like, “Brian, you're totally wrong. It’s actually the opposite” and I was kind of intrigued at the time and I didn't really understand exactly what she meant by that, about how it can help.

[00:02:55] Dr. Ayushe Sharma: So there are a lot of myths about exercise and epilepsy, and that's one of them, right, that exercise can actually induce seizures. I was just curious if we could talk a little bit about that. What are the most common myths about epilepsy and exercise? And why have they prevailed for so long? Especially since Drs. Allendorfer and Alexander have actually worked on the research front like this. These myths probably made it very hard to get started in research. 

[00:03:27] Dr. Jane Allendorfer: So there are specific and rare cases where exercise can cause a seizure in a person with epilepsy, but the clinical studies that we know of have found that exercise is not seizure inducing. Instead, it's actually associated with reducing these epileptiform discharges, which is the EEG marker of a seizure, both during exercise and after the post exercise period.

And then it also increases the seizure threshold. So it takes more to induce a seizure. That is actually really great news. And this is why whenever I hear people say, “I have epilepsy, I can't exercise”—that's not true. You absolutely can, and it can help.

[00:04:14] Dr. Halley Alexander: I could add, you know, some of the additional myth that's relevant to the research trajectory is that even if exercise in itself is maybe okay for people with epilepsy, there's still a myth that intense exercise should be avoided because that's really when it could trigger a seizure. That's a myth that still exists today and it isn't true. A lot of studies have shown animal and human studies that exercise—even to high intensities, exercise to exhaustion—is not something that has been shown to induce seizures. 

Another thing that I get asked a lot by patients and providers is about hyperventilation. People will say, “Well, I know I have a seizure when I hyperventilate. So then I shouldn't exercise because that causes hyperventilation.” I'd love to just talk about that for a minute because hyperventilation is actually when you're blowing off an excess of CO2. You're exhaling too quickly. It causes a respiratory alkalosis, and then it actually reduces cerebral blood flow.

But when you're exercising, you're breathing fast in order to maintain homeostasis. So your body is building up excess acid and you breathe faster to compensate, to blow off more CO2 to maintain your homeostasis. So you're actually increasing your cerebral blood flow. Hyperventilation is not the same as breathing fast during exercise and therefore is not the same as inducing a seizure.

I bring that up because that is one of the studies that was done early on when they started looking at changes with exercise. Showing, as Dr. Allendorfer had mentioned, that exercise can actually reduce interictal discharges. They did a study in the 1990s of children with absence epilepsy where they had them hyperventilate and showed that that did increase seizures, and also had them exercise and show that exercise actually reduced their seizure frequency.

[00:06:20] Dr. Ayushe Sharma: Wow. So this, that's from the 1990s. What other studies have been critical in, like, the notch point where exercise and epilepsy research is more of a burgeoning field? 

[00:06:36] Dr. Jane Allendorfer: So a lot of the studies did happen in the 1990s. Those are the very early studies that I could find. And they were in animal models of epilepsy. The majority of research studies with exercise and epilepsy actually look at whether or not it's seizure inducing. That was the question that they were trying to answer early on. If you exercise, do you cause a seizure? And so that's very, very early. 

Even now we’re still trying to answer the question that if you exercise, can you prevent a seizure or can you prevent the occurrence of epilepsy? So there's animal models that look at that. In people, it's very difficult to answer the question of if you exercise, will that help prevent you from getting epilepsy? You need a very large longitudinal study to do that. And I know of only one, in which they looked at conscripts from the military. They took all of these physical activity and physical fitness measures in these men and then they followed these individuals throughout their life and they saw that people who were moderately fit or high fit individuals early on, they had a smaller incidence of epilepsy later. That’s really the only human study that I know of that can show that [exercise] can potentially prevent epilepsy, but they do have research to that effect also in animal models of epilepsy.

[00:08:23] Dr. Ayushe Sharma: So because Brian was in your open label study, what was the structure and study design for that? 

[00:08:31] Dr. Jane Allendorfer: So that one was looking specifically at endurance training, not resistance training. So it was cardio training on either a bike or a treadmill. First we would see if a participant could potentially even engage in the exercise. So we actually did do a physical exam and I chose an epileptologist to do the physical and not just your everyday physician, I guess, because they're, they're more aware of the condition. I knew that our specialists had a good understanding of what would be appropriate for someone with epilepsy.

 And then we did exercise testing to look at their cardiorespiratory fitness level and to basically see where we would set the intensity level of the exercise program. And then they engaged in six weeks, three times a week of endurance training for about an hour, but we ramped them up to get to that level, and then we maintained them at that at that level for six weeks. And there were pre and post training assessments before and after that six-week period as well. Some people were in the control group if they couldn't do the exercise, or if they could do the exercise, they could do the control group first and then do the exercise group.

[00:09:58] Dr. Ayushe Sharma: So you talked about the importance of the epileptologist's initial screening. What sorts of factors are considered by the epileptologist like seizure control, things like that? Or what, what sorts of things would an epileptologist consider when determining if exercise is suitable? 

[00:10:18] Dr. Jane Allendorfer: They do like a whole system physical examination. We do ask them the physical activity readiness questionnaire and see if they have any heart problems or if another physician has ever told them that they shouldn't exercise. 

[00:10:39] Dr. Ayushe Sharma: Okay, so it's not like, it's not about medication seizure control. That's not necessarily a concern then. 

[00:10:54] Dr. Jane Allendorfer: It's not. And if they're not seizure free, we have them wear a helmet with a face mask. It's at a facility; It's supervised. So it's one of the safety features in my study, but if they're seizure free they’re also welcome to that if they want; we provide it for them.

[00:11:13] Dr. Halley Alexander: And so just to provide the clinical perspective, it might be a little bit different clinically, if a patient is wondering “Can I play this sport? Can I do this exercise?” And in that case, we would take things into account like their type of seizures, the severity of seizures, how frequent they are. And also, what is the probability that a seizure would occur during the activity? So if somebody only has seizures in sleep, that might be less relevant, even if they're frequent. Whether they have a warning or a prolonged prodrome that could give them time to change what they're doing if they felt a seizure coming on. what their triggers are, who's going to be supervising the activity, et cetera. 

And I do think that's relevant because I think that's part of the remaining limitations is that even if people with epilepsy want to be active, sometimes they're limited by the attitudes of the folks who would be guiding the physical activity. Like, maybe just going to the YMCA, they're not educated or they want to join the school soccer team and the coach thinks epilepsy is scary and they don't feel well equipped to deal with it. So better education of these facilitators of exercise, I think, is a helpful direction to go in.

[00:12:38] Dr. Ayushe Sharma: That's so true. Yeah, like the 2016 ILAE guidelines, the task force report on sports and exercise. It seems like that was a shift because it was actually showcasing how many different types of activities actually are safe for people with epilepsy, but then they're like limited by what you said.

And it seems like we really need these people in these positions to, not just epilepsy, there's so many there are other neurodegenerative disorders and other conditions where we really need people to the people in these positions to not be the limiting factor. 

Brian, we'll get more into the benefits of exercise and, like, your experience with that, but I'm just curious how the open label trial, how did that change what you do day to day now? 

[00:13:39] Brian Wiedmeyer: You know, you've always heard about gaining the COVID-19, weight wise. Well, I definitely did that. So I was at a moment in my life where I was ready to exercise. And so, you know, the main benefit I received was, yeah, the COVID-19 or 20 pounds, whatever you call it that I gained, I actually reduced extremely being involved in so much of the cardio effort.

 The most important aspect is what people don't know is, you know, seizure medications can be exhausting. They can be tiresome and I've been on them for going on 10, 15 years now. They are very exhausting type medications. But with exercise, that side effect is limited. 

[00:14:38] Dr. Ayushe Sharma: Really? 

[00:14:38] Brian Wiedmeyer: Yeah, absolutely. Or, I mean, with me. 

[00:14:41] Dr. Ayushe Sharma: So more energy? What, like-- 

[00:14:43] Brian Wiedmeyer: --More energy, you actually feel so much more motivated to move forward and what's interesting even more is you sleep better.And maybe what would be also even more interesting is some of my seizures occurred during my sleep and maybe since I'm sleeping better you have less risk of having a seizure. So, I don't know. 

[00:15:22] Dr. Ayushe Sharma: So, from your patient experience, it sounds like you had tremendous benefits from like sleep, to overall wellbeing, to just like general motivation and drive and energy.

I'm curious now if you could share. Dr. Allendorfer, Dr. Alexander, what you found across the board from your studies, like, what are the benefits of exercise for brain health, especially in people with epilepsy?

[00:15:47] Dr. Halley Alexander: I can say anecdotally from working with the patients and kind of interviewing them from doing our physical activity interventions, similar to what Brian's talking about, is that I see an appreciation for just how much better they feel on a day to day basis.

People have reported, you know, improved mood, improved energy, like Brian mentioned. And you know, yeah, just feeling like epilepsy isn't controlling their life as much as it was before. 

[00:17:07] Dr. Jane Allendorfer: So in terms of what we've found in my lab, we actually have found some striking improvements in verbal learning and memory for people with epilepsy who did a combined endurance and resistance training program. So the study that Brian had participated in was only endurance training, but I've also completed a small, pilot study looking at endurance and resistance or weight training, also three times a week for six weeks. And we found that those who did not exercise for those six weeks either performed the same or actually did worse on those same learning and memory tests.

So those results were very promising. And so it allowed us to conduct a larger randomized controlled trial now to really test what these effects are. Other labs who've done exercise intervention studies with in-person training have found similar improvements in attention and memory function. And this has been found in kids and adults who've participated in these exercise trials. What's interesting is those trials are usually longer, like 12 weeks, 16 weeks or longer. And we're seeing, at least in my studies, effects after just six weeks. 

[00:18:29] Dr. Ayushe Sharma: That's really cool. Your lab also uses neuroimaging. What are some of the neuroimaging findings that you're seeing that correspond to these improvements? 

[00:18:38] Dr. Jane Allendorfer: We do MRI to look at brain changes with exercise. And what we found is that the functional connectivity of brain regions that are involved in the start of seizures or the spread of seizures are actually changed with exercise and that these changes are associated with improvements in verbal learning and memory.

So one of the brain regions we focus on is the hippocampus. And we saw reduced functional connectivity between the left hippocampus and the left superior temporal gyrus and left supramarginal gyrus, which is in the parietal region. The left hemisphere of the brain is typically involved in language function, and a lot of people are dominant for language on the left hemisphere of their brain. With this decrease in functional connectivity with the left hippocampus and this left supramarginal gyrus area being associated with improvement in verbal learning and memory, that makes sense, right? In terms of, how that could work.

And it, it was interesting that it was a decrease. Usually people think that when you have a stronger connection with these brain regions, that should be better, right? And what we were seeing was it wasn't. The connection wasn't stronger after exercise. It was reduced with the hippocampus. I started thinking about why that could be. Maybe the brain is being more efficient, right? It doesn't need the stronger connection in order to perform at the same level or to actually perform better. 

We're really interested in seeing if that is also the case with just the endurance training that we're doing.

[00:20:33] Brian Wiedmeyer: It was very interesting while participating in the study, I know my biggest weakness is a short-term memory. I'm one of these people that, you know, you just give me a random number, 1,258 times 8 comes out to 10,064.

I can just do this off the top of my head. But some of my reading comprehension short term wise is very weak. It was one of those side effects that I was like, you know, I can't help it. I can't do anything about this. And that was the great thing about exercise because I felt like it does provide a little bit of strengthening towards this weakness that I can't get over and I have. 

[00:21:30] Dr. Ayushe Sharma: I'm curious, so all of these things that we're talking about, the benefits that exercise conferred to Brian and all these other patients in these studies. What's underlying it? There's a lot out there in the literature about exercise induced neuroplasticity and how does it apply in this context?

[00:22:02] Dr. Jane Allendorfer:  We don't know for certain what these mechanisms are but we are investigating them in terms of both in the animal research and animal models of epilepsy and also in human research.

So I can speak to the animal models: They see changes in brain derived neurotrophic factor. And this is a key protein molecule involved in learning and memory. And it's been associated with improvements in memory post exercise. And then there's also other studies that show that exercise can increase Gad 67 protein expression, right? And it prevents loss of these GABA-ergic inhibitory neurons. In epilepsy, right, you have an over-excitation, and that could be because maybe there's too much excitatory activity or not enough inhibitory activity, right? It's a balancing act, and so the fact that exercise can increase these inhibitory neurons or prevent the loss of the inhibitory neurons may mean that it can maintain this balance, right? This homeostasis that's needed for normal function. 

And then there's a recent study that showed that treadmill exercise in temporal lobe epilepsy animal models can induce changes in epigenetic markers. And so, you know, I think it's not just one answer. But it's multiple things going on that are helping drive these effects. 

In people with epilepsy, we can look at some of these mechanisms of action, but it's more difficult, right? In animal models, you're able to look at these very specific brain regions and look at these neurons and look at the proteins and expression.

We can't easily do that in people with epilepsy. So with my own MRI studies and the other exercise studies that I've seen, we're looking at changes in functional connectivity. There's a study in children with epilepsy, and they used EEG to look at functional connectivity in the brain regions also. And they also showed changes in different connectivity patterns that were associated with improvements in attention and also memory function in the kids with epilepsy. So now what we're trying to do with a collaborator of mine is, because they use animal model of epilepsy and they can do exercise, we're trying to look at potential markers that we can do in both animals and people. 

And that's still ongoing. So we don't have those results quite yet, but if we can see similar patterns in the animal models that we can in the humans, that gives us a better idea of what some of these mechanisms are. 

[00:25:06] Dr. Ayushe Sharma: So we've talked about the benefits of exercise in terms of like memory attention mood. What about seizure frequency and severity? Is that also something that is significantly impacted?

[00:25:20] Dr. Halley Alexander: There's been several studies looking at effects of exercise on seizure frequency, but most of them have been small. And so not really a large enough randomized controlled trials to give really high-level evidence that it can reduce seizure frequency. Although I will say, several studies have been done and none have ever shown that it's increased seizures. So we at least know it's not making them worse. Is it reducing seizures to a clinically significant extent? We don't know that yet. That's something that research is really still working on, but I will mention there was a trial that was published last year in Neurology on yoga, where they looked at almost 200 patients, it was a larger study.

They were randomized to yoga or sham yoga and the yoga group, it was not the primary outcome, but the yoga group did show a significant reduction. Like, the odds ratio for those who showed greater than a 50 percent reduction in the yoga group compared to sham yoga was over four.

So there really was evidence that the yoga was effective for seizure frequency. Sham yoga, as I understand it, and I'm not a yogi myself, was that they would do kind of the moves, but without the mindfulness and the breathing that goes along with the exercises, the position.

[00:26:55] Dr. Ayushe Sharma: That makes sense. It's like with yoga, your breath has to be coordinated with the movement. Interesting. That's, that's a really cool study. I guess that highlights a research gap for sure. I didn't even realize that was a research gap in all honesty. 

[00:27:08] Dr. Halley Alexander: I should say, though, the animal studies, you know, it's a little bit easier to do the exercise studies.

So we do have data from animal studies, including meta-analyses, showing that exercise either aerobic or resistance or combined has shown reduced seizure frequency in the animal model. We just don't have all that data in the humans yet. 

[00:27:32] Dr. Ayushe Sharma: So, like, based on these gaps, what do you think are next steps in terms of future studies that you're personally interested? Any innovative approaches? 

[00:27:50] Dr. Halley Alexander: So things that we need to understand better: Mechanisms, dosing, you know, how, how frequent, how often do you need to do it? What type is best? Yeah. Lots more to understand. And then also, you know, as a clinician, I'm interested in just how do we actually bring this into clinical care?

I mean, if you made the parallel to, you know what we know is true for exercise for cardiovascular health, but in clinical care, you still can't really prescribe exercise for your patient or help get them access to a gym. So bringing it back to the epilepsy world, even once we can really clearly delineate all the benefits, I think there's still going to be a barrier of bringing it to the patients too.

[00:28:39] Brian Wiedmeyer: Like you were saying, how do you bring it to the patient? To me, as a patient, I always felt like it was so good to hear things from another patient because they were in my shoes, Hey, if anybody who is paying attention to this that has experienced epilepsy, I'm just telling you from a patient's perspective, it helps. 

[00:29:01] Dr. Halley Alexander: There's a lot of work in the epilepsy community trying to come up with seizure prediction algorithms, like, just some ways that we can you know, using big data and things like that just to maybe someday give individualized predictions. You know, your chance of seizure today is high, your chance of seizure today is low and I think that would help a lot just in making patients feel more comfortable. 

And then, because a lot of patients with seizures have driving restrictions, something that they can do at home, ways that they can track their exercise through wearable devices and things like that.

[00:29:47] Dr. Jane Allendorfer: Like what Dr. Alexander had said, you know, it's hard for patients, especially if they have that driving restriction, to go to a gym or a lot of our patients are from a lower socioeconomic status or don't really have the means to maybe even afford a gym. So maybe coming up with a program where they can do it at home, you know, in the comfort of their own home, but also have it be something that's structured. So one of the things I found is a lot of the people with epilepsy that have done that do my trials, they have not really exercised before, you know, they're fairly sedentary for, for all the reasons that we've discussed today, in terms of not being encouraged to exercise, having fear that a seizure would occur. So they don't necessarily know how to do it, right? And so to just say, “Okay, go be more physically active and go do some exercises. It's okay for you to do that”? They may not know how to do it.

[00:30:51] Dr. Ayushe Sharma: You've really pointed out so much, like, all of the reasons why exercise is safe, the benefits, and what we know now while also considering the gaps. Based on all of the future directions and where we stand now, as we close, do you think you could give just some practical tips to our patients in the audience for how they can start exercising today, until some of these other aspects of your future directions are fulfilled?

[00:31:20] Dr. Halley Alexander: I mentioned the benefits of yoga.That's something easy, especially if somebody is a little bit still nervous about the higher intensities. And there's so many free videos on YouTube now that there really isn't a cost or a transportation barrier to just do 5 10 minutes of yoga. Just start there on a daily basis and see where that takes you.

I also start by recommending to patients to start walking for the same reasons. It's accessible. It's not expensive. You don't need to be able to go anywhere. You can do it either in your neighborhood, or if your neighborhood's not great, or the weather's not great, you know just getting to a mall or a store or around your house is always an option.

And it's you know, you can walk it at whatever intensity you like, and I do get questions a lot. You know, it's great if patients have frequent seizures, if they could go walking with a buddy so that they have somebody in case they were to have a seizure when they're a mile from their house or something but that's not always possible.

And so that has come up as a limitation for some of my patients and I advise them that there are apps that they can use. So if, say, your patient with epilepsy wants to go walk, but their family doesn't want them going out by themselves, or maybe they're nervous, you can put in a contact, you know, a phone number.

And the app will link it to the caregiver and then the caregiver can actually monitor the person's progress. You can see exactly where they are on the GPS. And also a lot of the apps will have, an emergency button you can push. So, if the patient has an aura and enough of a warning, they also, if they're out walking, they can hit that button and it sends a notification 

[00:33:09] Dr. Ayushe Sharma: I really appreciated the three of you being here today. I've learned a lot personally even though epilepsy research is what I do day to day. This is a newer arena, even though I'm very familiar with Dr Allendorfer’s work and have gotten to work on some physical activity stuff with her is really insightful to learn and also, especially having Brian's patient experience.

 Thank you all so much for being here with me today. Is there anything else you'd like to remark on any final thoughts things you'd like to share? 

[00:33:39] Dr. Jane Allendorfer: I would like to add in terms of a first step for, for someone with epilepsy, who's not really, been very active or exercise is to let their physician know. We have the 2016 guidelines from the ILAE, but there's also other resources out there like the Epilepsy Foundation, right, where there are resources that they could look at and that promote that exercise is good for people with epilepsy. Especially if someone's going to start being physically active, I think it's important for them to let their peers know, their friends, their community know that, “Hey, this is okay for me to do” so that they can maybe start to grow a support system, right, and kind of feel like this is something that they can do.

But that's hard to do if they themselves are not informed. So I think, you know, getting somebody informed is a good first step. And then seeing what they're comfortable with. Being a little bit active is better than not active at all.

[00:34:51] Dr. Halley Alexander: I was going to just kind of reiterate that because we mentioned that 2016 consensus statement on physical activity for people with epilepsy. But I just wanted to mention it again to make sure that everyone knows that there is a document that does provide some guidance for how to counsel your patients with epilepsy on what physical activity is safe, what to take into consideration. 

And then also for patients, because you might be seeing a provider who's not aware of the guidelines. So, you know, patients can also access this document and take it with them to their doctor to help make an informed decision, or to help counsel family members who are wanting to discourage them from exercise.

[00:36:04] Dr. Ayushe Sharma: Absolutely. Yeah, no, thank you so much again for bringing that report up. I really, really appreciate all of you being here. I learned a lot from each of you and thank you so much for your time.