Medicinal cannabis has been of interest to the epilepsy community with greater interest fueled in 2018 by the FDA approval of a cannabidiol (CBD) extract called Epidiolex®. In fact, the marijuana or cannabis plant contains over 100 different substances, two of which specifically, CBD and tetrahydrocannabinol (THC), have been widely studied to understand their effects on the brain.
THC is the major chemical compound found in marijuana that creates a psychoactive effect when it binds to receptors in the brain. CBD binds to a different set of receptors and is not psychoactive. Epidiolex® is a purified, plant-based CBD extract used to treat seizures associated with rare genetic epilepsies. Because of its effectiveness, there is great interest in further understanding how CBD acts in the brain and also if other cannabinoids might be useful in the treatment of seizures.
In contrast, marijuana products sold in dispensaries and online are not approved or regulated by the FDA. They can vary significantly in quality, dosage, safety, and effectiveness. In some cases, commercial, nonprescription cannabis products are thought to increase seizures.
This webinar will review the basics of cannabis biology and the differences between cannabis strains. It will also explain the medical uses of medical marijuana and the recent approval of CBD to treat specific types of epilepsy.
This webinar is generously supported with funding from Jazz Pharmaceuticals.
About the Speaker:
Dr. Eric Marsh is an Associate Professor of Neurology at the University of Pennsylvania Perelman School of Medicine and the Children’s Hospital of Philadelphia (CHOP). He is the Clinical Director of the Penn Orphan Disease Center, and Director of the CHOP Rett and Related disorders clinic.
Dr. Marsh’s clinical interests include developmental and epileptic encephalopathies (DEE), neurodevelopmental disabilities, and cortical malformations. His research interests have focused on the role of intraneuronal development and altered excitability on epilepsy, analyzing intracranial EEG recordings to better localize the epileptic zone and network, and performing natural history and biomarker studies. In addition, he has studied the role of mutations in specific genes related to epilepsy such as ARX and CDKL5. Dr. Marsh has been involved in a number of clinical trials for children with the DEEs, including Dravet, Lennox Gastaut and Rett syndromes.
Rare diseases are generally defined as those diseases that affect fewer than 200,000 people in the United States1. However, there are many diseases that are caused by genetic mutations that only impact a handful of individuals worldwide. In these cases, the small number of patients present a variety of challenges to identifying and developing effective treatment options including a long diagnostic journey, often with misdiagnosis and the high cost of clinical trial development.
This webinar will highlight the work of the n-Lorem Foundation. The n-Lorem Foundation is focused on creating free, individual treatments for people with what are termed nano-rare diseases, caused by genetic mutations that affect 30 patients or fewer in the world. 40% of n-Lorem Foundation patients suffer from epilepsy, and these individuals may benefit from more individualized genetic treatments that meet the unique needs of each person. This webinar will discuss the use of individualized antisense oligonucleotide (ASO) treatments for patients with nano-rare epilepsies. ASOs are short strands of modified deoxyribonucleic acids (DNA) that can be developed rapidly and inexpensively and can specifically target and potentially halt the development of the disease-causing proteins, thus attempting to change the course of the disease.
About the Speaker:
Sarah Glass, Ph.D. is the Chief Operating Officer at the n-Lorem Foundation, where she leads the implementation of the foundation’s mission to discover, develop, and provide personalized experimental medicines for patients with diseases caused by genetic mutations affecting fewer than 30 individuals worldwide. Sarah is passionate about forging partnerships to increase our collective ability to help and provide hope for people in need. She combines her professional experience as a geneticist, drug developer and clinical trialist with the urgency she has felt as the parent of a nano-rare child.
Q&A with Dr. Sarah Glass
Can you speak to families that have a diagnosis of L G S or Jevens or infantile spasms? How do they think about this technology? Is it right for them or not yet?
Honestly, it is very specific to every single mutation and I think that’s the unfortunate reality. And as much as that doesn’t help broadly speaking, and I think that’s what we’re really finding, especially in some of these cross patient groups, is like how can we actually give you a much more informative answer than that? What we have started to put in place is almost even a, we started pre-submission type of assessment, if you will, is almost even just like a triaging because we do have a lot of questions like that. So for my patient community, we have this type of mutation or this type of mutation or we have here these two which are affecting three people or five people, and what do we do? Should we find a physician? Should we submit an application? And so I think that’s the best that I can offer is that I think what we found is typically, first of all, the prevalence of the mutations is very important, obviously.
The functional consequence of the mutation. If we understand the functional consequence and if there is a realistic ability to affect the consequence of that mutation. So ultimately, for example, null mutations, ASOs aren’t able to help, those are typically going to move into the gene therapy space to some extent. We do know a hundred percent for as far as the organ system, obviously these are all C N S, but I think we get those questions a lot as, so if we want to target the muscle or if we want to target lung and things like that, those are also areas that we cannot target. So I think part of it is understanding what ASOs cannot target. So some of that also is really focused on the mutation but focused a little bit broader than that. And so I think that would be my suggestion is really in thinking about those questions is to say, the first question is what does the mutational spectrum look like for each of those areas that you mentioned, those patient groups and to say, okay, do we have some functional consequences that are well understood? Are the prevalences in these regions that would apply here? And all this is really driven by what these F D A guidance documents provide. They’re very specific, actually, refreshingly specific on the type of patients that actually qualify for these because this is a different drug discovery and development path than a commercial program. So it’s a much abbreviated path. And that’s very important for all of the patient communities to know is that these go specifically from a single G L P animal talk study right into the patient. Whereas in traditional clinical trials you go multiple animal talks, phase 1, 2, 3, et cetera. And so that’s why the F D A is very specific on what are the characteristics of patients that are actually suitable for this path. And some of those characteristics are in the genetics, it’s in the clinical manifestations, it’s in what is the other treatment landscape.
So that’s another element as well, is really just do we have a sense of, well, there are all these other treatments that are already really targeting these patient populations. So this is really focused on patients who just really and truly don’t have any other options.
How does that work get funded and if it’s not done by n-Lorem, how does that research get accomplished so that it can perhaps inform you?
It’s really variable honestly. And I think the most interesting, it’s actually fascinating, sometimes you will find a mutation that will have evidence for having gained a function consequence in some circumstances and loss in others. And some you might not necessarily very clearly be able to understand it and it could just require a little bit more research in a particular lab. Most of the research that’s happening is back into the lab of the submitting physician for the most part. So that’s only helpful, however, if one, a patient is connected with the physician who is also a lead researcher in that particular gene. And so I think what we’re working to do, and we have a couple of potential partnerships where there could enable almost a proof of concept lab to some extent, where you say, okay, this could be amenable if we have X, Y, Z data that will then get us over the ability to make that decision as far as do we have an ASO strategy or not?
And so that’s very much something that we’re working on now is to have a more centralized location. So as with a lot of rare diseases is how are we looking across diseases? So instead of saying we’re focusing on the gene, if we’re saying, well, here’s a type of study, here’s a type of experiment that is often missing, if we could only have this capability to do this for many different genes or for different patients in a more centralized type of location, I think that’s what we’re aiming to do in the future as well. That research piece is so important.
What are some of the reasons for declining an application for an ASO? And you’ve talked about some of those, but can you fill in any other information? Why would you decline an application?
Yeah, so the primary reason to decline is really around the mutation itself and the consequence of the mutation. So again, whether it’s ultimately a functional consequence that we can’t, so if it’s a null mutation, we still continue to have some of those. It also depends on the gene itself. So for example, if we’re looking at trying to upregulate, well, upregulation is not the same across the board. That’s going to be driven by specific characteristics of that particular gene itself. And so then it comes down to, well this particular gene has these different characteristics. So again, most of the decline is really related to the clinical or to the genetic, to the genotype. And so really trying to, from a technical perspective, address whether we feel at all antisense technology can help. Now there are a small, I think proportion as well where the physicians or the patients will ultimately be presented in a way that it isn’t entirely clear.
Well, the gene is the causative gene, so that we do have a handful of patients that will have maybe two mutations or more. And ultimately these are really driven towards having single mutations in a causative gene with that being very apparent. We have a number that will then creep above the 10 bus 20, 30, 40, 50 patient range. And so I think we’re not there where right now we’re really stricken directly to the guidance. I think eventually over time, one could envision that there could be a path even for if it’s an experimental ASO for almost like an intermediate population, if you will, that doesn’t exist at this stage. So that’s another reason as well. Let me think. There’s a number of patients that will be, if it’s again trying to target the muscle or cardiovascular, things like that where we don’t have a validated route of administration that we’re leveraging as part of n Lorem.
Are n-Lorem applications only available for patients that reside in the US?
Yeah, it’s an important question. And right now we only have F D A guidance to under which these patients can be treated. We have significant efforts at this point with Canada and the UK to really evaluate and try to really forge the path in partnership with those regulatory agencies, to define a path based on other partnerships in those countries. We do have a lot of patients actually starting to apply or physicians from other countries that were, I think, trying to assess on almost a case-by-case basis. But for the most part, and it’s only if we already have an ASO for that particular mutation, which is highly unlikely, but I think the goal is to help as many patients as we can, but we have to start somewhere and that’s here in the US.
What is the current cost structure for patients and what do you foresee for the future?
So ultimately the patients don’t have any obligation for the cost of these drugs and the physicians themselves. N-Lorem covers all of the costs from the point of patient acceptance through to all of the drug discovery and development and talk studies, as well as manufacturing. The physicians and the institutions are then required and obligated to support from the treatment on, and so that’s what we’re working through. So typically this should not be, and most physicians are having insurance will be billed for what can be billed and institutions will cover some of the other costs. Some others have philanthropic funds. I think the reality is that each institution is handling this differently and that every institution needs funding for it and they all should get funding for it, honestly. I think one of the biggest challenges that we continue to see with the physicians is that they’re doing this in their nights and weekends time, physicians who are entirely clinical who don’t have any research time.
And I think for someone who’s not necessarily in that space, we all cannot appreciate how busy, how many individuals, like our loved ones that they’re caring for, and then to say, okay, well, and in my own personal family time, I’m going to spend on this particular patient for n-Lorem. So I think that’s what we’re trying to really understand, and I’m personally spending a lot of time right now is trying to understand what are the costs, specifically? What does that actually entail and should this be integrated into what the cost structure could look like for these treatments moving forward? Because ultimately the patient should not have to carry the burden for these costs. But at a minimum, I can say there is no cost for the drug itself.
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified healthcare professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified healthcare professionals who are familiar with the individual’s specific health situation.
In the United States alone, approximately 4,000 surgeries are performed each year to treat epilepsy. In comparison, an estimated 100,000-200,000 patients may benefit from epilepsy surgery 1 . This significant gap between the number of surgeries performed and the number for whom it could reduce or eliminate seizures could be filled by procedures that can more easily identify patients who are good candidates for surgery. Magnetoencephalography (MEG) is the newest, most advanced technology that can help close this gap. MEG can pinpoint the source of abnormal brain activity and seizures 2, is painless, safe, and requires only 1.5-2 hours to perform. Ultimately, MEG can help surgeons decide whether a patient should pursue surgery. Use of MEG may allow more patients to be identified for surgery, and potentially lead to greatly reduced or no seizures.
In this webinar, viewers will learn how MEG is a key part of the epilepsy surgery evaluation, including information about the basics and safety of a MEG study, and hear about how MEG can help the surgeon by mapping key functions (speech, motor, and vision) onto their MRI for use in the operating room.
The webinar is intended for people living with epilepsy, their family members and caregivers, and anyone seeking to learn more about mental health and epilepsy.
1 Institute of Medicine (IOM) Epilepsy across the spectrum: Promoting health and understanding. The National Academic Press; Washington, D.C: 2012.
2 Gill MM et al. The use of PET/CT in pregnancy: A case report of malignant parathyroid carcinoma and a review of the literature. Obstet Med. 2018 Mar;11(1):45-49. doi: 10.1177/1753495X17724950. Epub 2017 Oct 9. PMID: 29636815; PMCID: PMC5888841.
About the Speaker:
Dr. James Wheless is a neurologist and researcher whose research is focused on pediatric anti-epileptic drug development, the ketogenic diet, epilepsy surgery, and non-invasive brain mapping (TMS, MEG). Dr. Wheless is the Professor and Chief of Pediatric Neurology and the Le Bonheur Chair in Pediatric Neurology at the University of Tennessee Health Science Center (UTHSC) in Memphis. He also serves as Director of the Neuroscience Institute and the Le Bonheur Comprehensive Epilepsy Program for the Le Bonheur Children’s Hospital (LCH). Dr. Wheless is also an Adjunct Clinical Faculty Member in the Department of Pediatric Medicine at St. Jude Children’s Research Hospital.
Q&A with Dr. Wheless
Can a MEG scan identify a misconnection with a hemispherectomy?
If someone’s had a hemispherectomy, just to make sure everybody understands that, it’s a big surgery, but basically what you’ve done is you’ve disconnected, if you will, one half of the brain and parts of that brain from the other half. You may have abnormal tissue that’s still in place. It can still generate a seizure. But the way I describe it to patients, it’s kind of like it’s on an island. It can’t spread from there to the rest of the brain or to the body, so it’s not really causing a seizure, even though it may have nothing but abnormal activity. It’s been disconnected, if you will, from the rest of the brain.
Usually, the best strategy for saying are we confident that’s disconnected is to do what we call a tractography. It’s a type of MRI imaging where they actually look at the pathways from those disconnected areas and they can see have they all been cut. And that’s probably the best way to look at those, because MEG picks up abnormal electrical activity, and that abnormal electrical activity is still going to be sitting there because it hasn’t left that area. The question is, is it confined there, and that’s where the tractography helps us better.
This individual writes about having a pacemaker and also having a MEG test. One of the concerns is that the device may cause too much noise for the MEG and how well can the MEG reading be cleaned up if a device like that is present?
Yeah, that’s a great question and an area that I didn’t touch on that I probably should have for purpose of the time. But their question is great because they’ve picked up on what I was saying at the beginning that the MEG is detecting these magnetic signals and anything that’s metal generates a magnetic signal, which is why we all know if you take a magnet, you go around, you can pick up other things that are metal, right? Pacemaker nowadays, most modern pacemakers and other metal implants, if you think about dental fillings, more common than pacemakers even, as well could have an associated magnetic field with them.
The brain is small by comparison. They can overshadow, if you will, the brain. In the past, those were a huge problem. With modern software, we usually, I almost say 100%, but we usually can filter the noise out from those and still get the data that we want in patients that have those. Whereas in the past, we kind of said, “Gosh, that’s a deal breaker, unfortunately.” Nowadays, we say, “You know what? Let’s look at it. Let’s get you in the room. Let’s see what we’re recording.” Even if it’s somebody that we can just kind of… I guess you would say get in the room and try it.
We’re not doing the full recording, but just say, “Let’s make sure we’re not overwhelmed by the noise,” we can just test them, if you will, to see because it’s easy to do. You just go in the room and lie down. It’s pretty simple to do. But most of the time, nowadays with our current machines and the software improvements, we’re able to record.
Is having MEG done something that insurance will cover if a patient is not wanting surgery, but wants to identify where the seizures are coming from?
Obviously, today’s focus was on patients with surgery, but many patients get MEG that are not surgery candidates where it’s still helpful. For example, for some patients that we say, “Gosh, we think we know your seizure type, but you’re responding a little bit differently than the normal person with this.” Sometimes using the MEG with EEG really helps refine, are we on the right track for what we think is the type of seizures that they have? It’s been used there.
It’s been used some in folks that have seizures, probably mainly in childhood where the seizures also may be associated with kind of developmental or language changes that are negative to say, “Okay, let’s see if we can tease out the relationship of these two to each other.” Obviously, today’s focus was surgery, but has it been used in other aspects of epilepsy aside from surgery? Yes, as well. The question they asked about insurance, at least at our center and I think most centers, obviously like any test we do pre-approvals so somebody’s not out of pocket, a surprise. None of us like that.
I get it. I don’t like that either. Usually, that’s not a barrier. I know when we see patients, even if they’re from other centers, I mean, I didn’t mention this either, but the nice thing is the MEG data can all be kind of put on disk, if you will, or printed out in picture form. It can go back to referring neurologists, neurosurgeon, whoever, for them to pull up. We can even put it on disk so they can pull it up on their own inter-operative equipment to register in their own OR as well. It’s portable from that standpoint.
If seizures are coming from scar tissue left from a Gamma Knife surgery in middle age following an AVM removal at 15, so long time ago, could MEG be useful?
Yeah, I think MEG could be, because a couple things with that kind of surgery is, one, if it was near critically functional areas, so language, motor, vision, it could help figure out that relationship. Even if it was not in one of those areas, if around where the prior abnormality is on MRI, if all of those make dipoles line up all around that, it’s really telling you, it’s like a big arrow saying, “This is the problem. This is why you’re still having seizures.” And then obviously that’s a discussion with what are my options to get rid of that problem.
I’m amazed at the resolution that MEG has. This person is asking about the precision. I mean, clearly, it’s very precise, but is it ever inconclusive?
There are times. Just like any test, can you have an inconclusive test? Sure, you can. I would say the benefit of the MEG is that that happens. I will say I’ve not done this a lot, but we’ve done this some, we’ve had patients, their first has been inclusive. We really thought, gosh, we really need to get this data. We’ve literally brought back the patient a little while later and said, “Let’s just redo it and see for whatever reason we can get better data that day,” and we’ve got wonderful data that’s fit.
The analogy I would give folks, it’s kind of like many of our patients that have seizures have gone for EEGs and at some point in their life they say, “I have several normal EEGs or inconclusive, if you will, and then I finally got the one that showed my doc, yes, I have epilepsy. This is an abnormal EEG.” Can that happen to us? Yes, it can. But the nice thing is, especially if the person can do it without sedation or anything, is it’s an easy test to repeat.
Are you able to see the dendrites from the machine to determine damage to these after prolonged seizures?
We don’t visualize the actual structure, which is what they’re asking. We’re looking at function, if you will. We can get an idea if function has been changed in some other ways that I didn’t talk about today. There’s other ways we can use the MEG technology to look at function if it’s been altered. In the example I would give folks, again, if we look at analogies is I could give my car detail, take a picture of it, make it look great and show it to you, and then say, “Do you want to buy it?” You’d probably say, “Well, wait a minute, can I drive it first? Can I see if the air conditioning works?”
But if some of those functions weren’t quite so hot, that might change your thinking, right? They’re looking for, is there a change in structure? Whereas often what we really want to know is, is the function different in the patient, right? I mean, structure, yes, but we want to know how things are functioning.
Are there patients that cannot have MEG?
They’re rare in the modern era. The biggest ones I would say, and they’re pretty rare because the technology has shifted for a lot of our implants, I would say if a patient has had, gosh, probably like a really horrible head trauma where they had to have some kind of large bone flap that was metal plate because their head trauma was so bad and they had seizures from that. Even in the modern era, a lot of the ways that surgeons are doing that are compatible because they’ve gotten away from some of the older fashion kind of metal ones, because even with MRIs that’s a problem. They’ve kind of had to adapt for more current imaging where that’s less of an issue for us as well.
There are rare folks, to be candid. Even some of our patients that have cognitive issues that make it hard for them to understand the testing, if we can do sedation, unless they’re just behaviorally and cognitively so challenging that literally the parents tell us, the caregivers, it’s hard to even get them in a car to get to a hospital. Short of that, we can do it. There really are pretty rare exceptions in the modern world. I mean, we call patients, we kind of say, “Here’s what’s going to happen. Tell us about you,” most of those, if there’s any odd one there, we can tease it out before a patient’s driven to get a MEG or gone through the process, if you will.
Can you use prior MRI to superimpose the MEG or do you have to have sort of coincident testing done?
Prior MRI, I will say, sometimes can be used. Political answer here. The reason I say sometimes is it depends how it was done. To get the degree of resolution I showed you, we need what are called really thin cuts of the MRI to be done. Sometimes if they’re just doing what I would call a regular run-in-the-mill MRI, say you have headaches and got MRI, the cuts are much thicker. They don’t give us the details that we need to put our data on top of the structural picture.
That’s when we end up just saying we can just do part of the MRI over. We just need to do our structural part. We don’t need to do the whole 45-minute to hour MRI. It may just take us 10 minutes to do our part, for example. But if they’ve had a good structural MRI and we look at it, yeah, we can use that. Even my own patients, if they’ve had one six months, a year ago, as long as it wasn’t so long ago that we say, “Okay, things may have changed,” we can use those.
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.
Studies show that people with epilepsy are more sedentary than the general population. This is partly due to concerns about having a seizure while playing sports or exercising and the fact that healthcare professionals previously advised against physical activity. Many people with epilepsy, caregivers, and even some doctors are unaware of the research surrounding physical activity for those living with epilepsy. Unfortunately, studies have shown that up to 80% of people with epilepsy exhibit some form of cardiovascular disease 1 , and people with epilepsy have a threefold increased risk of sudden cardiac death 2. These statistics suggest the need for more physical activity among those with epilepsy, a fact that is reinforced by recent research.
This free webinar will explain the difference between exercise and physical activity, summarize the health issues faced by manypeople with epilepsy and discuss who may benefit from physical activity. Viewers will also hear the current consensus among medical professionals on the safety of different types of physical activity and exercise for people with epilepsy. Finally, viewers will learn practical tips for how to safely engage in physical activity for those living with epilepsy.
The webinar is intended for people living with epilepsy, their family members and caregivers, and anyone seeking to learn more about mental health and epilepsy.
1 Verrier RL, Pang TD, Nearing BD, Schachter SC. Epileptic heart: A clinical syndromic approach. 2021;62(8):1780-1789
2 Bardai A, Blom MT, van Noord C, Verhamme KM, Sturkenboom MC, Tan HL. Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications. 2015;101(1):17-22.
About the Speaker:
Dr. Halley Briglia Alexander is an Assistant Professor of Neurology at Wake Forest School of Medicine. She is board certified in the areas of epilepsy and clinical neurophysiology. Her research focuses on evaluating the effects of physical activity in people with epilepsy on seizure control and epilepsy-associated comorbidities. Dr. Alexander is working to develop physical activity programs that are accessible to those with epilepsy, taking into account the unique barriers to exercise that people with epilepsy may face.
Q&A with Dr. Halley Briglia Alexander
One of the most challenging obstacles to getting enough exercise and activity is the feeling of constantly being fatigued and a sense of being sedated from the antiseizure medications. Is there anything that can be done to address this issue?
One reason why we think that physical activity could be good for people with epilepsy is because of these medication side effects. And there’s been at least one study that I can think of off the top of my head that showed that people reported a reduction in their medication side effects after they started exercising. So my recommendation would be to try not to let it keep you from starting the physical activity. That’s a lot easier said than done. But I think if you can make yourself just start somewhere, like I said, a few minutes a day, you should find that increasing your physical activity, even though it’s going to be hard at first because of those side effects, will probably reduce the side effects that you’re experiencing. And then, therefore, it will kind of just get easier day after day.
The other thing that I’ll say is that it could be worth talking to your neurologist about your medications, because we don’t want anyone to have to live with side effects. And we have over 25 medications for epilepsy now. So, it’s possible that they may be willing to work with you to try adjusting medications and finding a regimen where maybe you don’t feel so fatigued.
Another question came in that relates to a very tragic event that happened very recently with regard to a surfer. This is a surfer who died potentially from seizure while surfing, and this is a very scary possibility.
The person who posed the question also enjoys surfing and has epilepsy. And generally, they feel better physically after surfing and believes that the additional ATP produced in the body might help with brain health. So, I want to get a perspective on that. What are the thoughts on ATP production from exercise? Will it help reduce seizures at all? Are there other things that the body produces during exercise that might help reduce the chances of seizures?
That’s a great question. And that’s all kind of research that we don’t have answers to right now, but they are being looked at. We do have data outside of epilepsy and some from other neurological diseases even, especially in the Alzheimer’s realm, where they’ve looked at what is actually changing in the body when people exercise and how might that be benefiting brain health. So, there are some neurotransmitters that they’ve looked at. Something that comes up a lot is BDNF, which is brain-derived neurotrophic factor, which is thought to increase plasticity of the brain, so kind of improving the health of neurons. But specifically in epilepsy, it really hasn’t been looked at. So, there’s many theories about what could be happening in the brain, different levels of different hormones, and again, neurotransmitters. And it’s probably some combination of all of those things that’s happening, but we don’t have all the answers to that right now.
Here’s a question about weightlifting, which was included in the moderate risk category, but the CDC recommends including strength training two times per week. Can you clarify or share your opinion on this?
Another good point. So, it is definitely recommended to do some weight resistance-type exercise. But of course, that is slightly increased risk in people with epilepsy because of the fact that if you’re lifting a 30-pound weight, or lifting it over your head, if you are to have a seizure, there’s a more significant risk of injury there compared to just walking or running.
And so, as far as I know, there aren’t any official guidelines or recommendations about that. But one thing that I think would be safer if you want to incorporate resistance training and you’re having frequent seizures is possibly using resistance bands, because you can get the same idea, same kind of effect on the muscles as weight lifting, but it’s a little bit safer in that you’re not lifting a weight that could drop, you’re just working with the resistance of the band.
I’m not a personal trainer, so I can’t suggest any specific exercises with the bands. And of course, I don’t know the context of this person’s specific epilepsy, but that might be somewhere to start.
So, should someone try to target a specific level of exertion or increase in heart rate? And along the same lines, can you speak to the idea of too much exercise? So, in this person’s case, they’ve always run marathons, and have become afraid of going too hard and toned it down to half marathons as a compromise, which I still think is amazing. So again, what level of exertion is reasonable?
Another good question and congratulations to that person for being so active. It’s very impressive. And afraid the answer is that there is no one level necessarily. Exercise is one of those things that the more you do it, you kind of buildup gradually. And then, the more that you’re able to do. So, for somebody who’s training to do a marathon, for them to go actually run the marathon doesn’t quite take the same amount of exertion and toll on the body as it would for somebody who hasn’t been training to go run the marathon. That could actually be disastrous for that person. So, there’s not necessarily a level of exertion that is appropriate for everyone or everyone with epilepsy.
I’m trying to think of the best way to answer the question. I think, again, it has to be individualized. But for that person, listening to their body is probably a good way to start. If they’re a marathon runner, they’re probably familiar with the feeling of a good type of hard workout and a bad type of hard workout, where hard feels too hard.
So again, I can’t give a definite answer to them, but I think that working with their neurologist and just listening to their body. But I will say, running and that type of high-intensity exercise… High intensity, so that means the intensity of the exercise in that moment was not shown to increase seizures. But when we’re talking about marathon running, we’re actually talking about low-intensity exercise over a longer period of time. And that, I don’t think has been looked at in people with epilepsy and probably won’t be. We won’t be making them run long duration to test that, so we don’t have the data there.
Are there any limitations on exercise when you have a VNS?
The reason I say that though is that some of the newer VNSs, they can be set to go off if they detect increased heart rate. The reason for that is that a lot of seizures present with increased heart rate or a fair amount of them do, so the idea is that the device can actually detect that and then go ahead and give a stimulation to help abort that seizure. So of course when you exercise, your heart rate will go up. So, in those cases, again, it still wouldn’t necessarily mean that you couldn’t exercise, but you might want to be aware of that and be prepared for the idea that your device might go off a lot more.
And if you’re somebody who wants to engage in exercise regularly, depending on your seizures and your type of epilepsy, it might be something that your neurologist could adjust. They might be willing to adjust it so that it doesn’t go off every time your heart rate increases a little bit.
So, to some of the data that were presented, on the mood graph, why didn’t exercise or activity decrease fatigue in relationship to non-exercisers? Both groups scored the same regardless of activity.
Good question. And I don’t know the answer to that, but I can offer a few points of speculation. So, it’s possible that the group that was exercising… I believe in that study it was either six weeks or 12 weeks. But when you first start an exercise regimen, you might actually be a little bit more tired because your body is working harder to adapt, which in the end is good, but in the short term could cause a little bit more fatigue. So it could be partly due to that.
Could be, again, like somebody has already mentioned, that sometimes the seizure medications are contributing to some kind of fatigue or sleepiness. And so, it might be that in that study, the exercise group, despite reporting that they had more vigor, we saw that component had gone up, that maybe that wasn’t enough to overcome… That their medications were still making them feel a little bit fatigued. And I don’t know how those two terms are perceived differently, vigor and fatigue.
So again, I’m speculating on that, but I think it could be a lot of different variables. But we do have data from other studies and from that study, showing the vigor, where people have perceived that their energy levels are increasing. And so, I didn’t show those graphs, but when we look at the quality of life scales and epilepsy, they have subdomains. So, a lot of them will look at physical function or energy level as a subdomain of the quality of life scores. And so, with exercise, in a couple of studies, people have reported improvement in the energy or the physical function domain of those subscores. So again, I can’t explain that one study, but I do think in general people have been reporting feeling improvement in their energy with exercise.
Is there a difference between physical activity indoors versus outdoors?
That’s a good question. I guess, it depends on what you’re looking at, a difference in what exactly? But being outdoors has been shown to improve mood, even if you’re not exercising. Being outdoors in the sunshine and the fresh air, that does seem to do a lot of good for a lot of people. So, I would say if the weather’s okay and you’re able to and you have the choice between the two, then going outdoors probably would have more benefits for you health-wise.
However, if we’re talking about a dangerous outdoor situation, maybe it’s not safe to walk in that neighborhood, or the weather’s bad, or being at home and doing a stationary bike means you can have family members nearby who could help you if you were to have a seizure, whereas if going outdoors, your only option is to ride the bicycle, which that was a group two sport because you’re out in traffic and everything, then looking at the difference between those two, it certainly would be safer to do the stationary bike inside. So probably depends on what you’re trying to see a difference in, but there are differences between the two. But then, at the end of the day, physical activity is physical activity. So whichever way you can safely get it would be what I would recommend doing
And just want to be clear that while some of the data focused on mesial temporal lobe epilepsy, this is broad advice for anyone with epilepsy, it’s not just restricted to mesial temporal lobe, correct?
Yes. Thank you for clarifying that. So, most of the studies looked at adults and kids, focal types of epilepsy, general type of epilepsy, some specific syndrome. So, it’s broad advice for all epilepsy.
Are there any mitochondrial effects from exercises that could be a part of the benefits to epileptics from exercise?
Yes is the short answer. They’ve looked at the mitochondrial effects of exercise in humans and a lot of other disease in the general population, in other neurological diseases. Again, as far as I know, we don’t have published data on that in people with epilepsy. But most likely, any of that, that’s affecting brain health is probably going to be beneficial for people with epilepsy.
The reason why we still need to specifically look at it in the epilepsy population, and we can’t just assume, “Oh, it’s good for brain health in Alzheimer’s, it’s probably good for epilepsy,” is that epilepsy is somewhat unique than other neurological diseases, in that it’s increased brain activity, increased signaling. And so, some of these neurotransmitters and things that might be more activating in the brain, which might help dementia or memory loss, we don’t really know necessarily the effect it would have in epilepsy.
So for example with BDNF, that increases synaptic plasticity and neurogenesis, but that’s not always beneficial in people with epilepsy. So, if you have new neuronal connections being made, it’s possible that kind of aberrant sprouting could actually be part of what could be related to the seizures themselves. So, we don’t know any of that, but that’s why we need to look at it in epilepsy, even though we’ve looked at it in other populations. And right now, we don’t have those answers.
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.
Sudden Unexpected Death in Epilepsy (SUDEP) affects approximately 1 in 1,000 people with epilepsy, regardless of age 1,2. While lack of seizure control and seizure severity are the most common concerns for increased risk of SUDEP, there is also a concern that certain genetic mutations may increase SUDEP risk.
This webinar will discuss what we know about SUDEP, specifically in the rare epilepsy community, as well as what parents and caregivers of children with rare epilepsies should know about SUDEP prevention and ways to mitigate risk. Presenters will share ideas on how to discuss SUDEP with doctors, from both the perspective of a physician and a parent of a child diagnosed with a rare genetic epilepsy who has educated themselves about SUDEP and taken steps to reduce the risk of SUDEP for their child. Attendees will have the opportunity to ask questions to all presenters. The webinar will also include a discussion about the latest advancements in basic and clinical epilepsy research focused on SUDEP risk and prevention.
The webinar is intended for people living with epilepsy, their family members and caregivers, and anyone seeking to learn more about mental health and epilepsy.
This webinar is conducted in partnership with our friends at PAME and Wishes for Elliott.
The mission of Partners Against Mortality in Epilepsy (PAME) is to convene, educate and inspire all stakeholders – from the bereaved to those living with epilepsy, to health care professionals, advocates, clinical and basic scientists, and death investigators – to promote understanding and drive prevention of epilepsy-related mortality.
Wishes for Elliott is a non-profit organization dedicated to supporting research to improve the lives and prognosis of children struggling with SCN8A mutations and similar rare epilepsies. Their collaborative DEE-P Connections project partners with more than 40 rare epilepsy groups to help educated and bring critical resources to families who have children severely affected by these disorders.
1 Sveinsson O, Andersson T, Carlsson S, Tomson T. The incidence of SUDEP: A nationwide population-based cohort study. Neurology. 2017 Jul11;89(2):170-177.
2 Keller AE, Whitney R, Li SA, Pollanen MS, Donner EJ. Incidence of sudden unexpected death in epilepsy in children is similar to adults. Neurology. 2018 Jul 10;91(2):e107-e111.
About the Speaker: Dr. Lhatoo is aneurologist and neurophysiologist with expertise in the medical and surgical management of intractable epilepsy. He has been a director for Level-IV epilepsy centers inthe UK and USA since 2006 and an instructor for the International Stereo EEG course since its inception in 2010. Dr. Lhatooserves as the head of the International League Against Epilepsy’s Task Force for Big Data in Epilepsy. He has a particular interest in the epidemiology, phenomenology, and pathogenesis of SUDEP. His published work has described potential biomarkers of SUDEP, including post-ictal generalized EEG suppression (PGES) in SUDEP cases, post-ictal hypotension, post-convulsive central apnea, and ictal central apnea.
Q&A with Dr. Lhatoo
How did you find out about SUDEP?
I’ll tell you just now is what I’ve learned about SUDEP was right here on this call with you. I didn’t think it applied to us. It wasn’t until my son’s third birthday when another one of our little buddies in our group, Emma, passed away in her sleep. She had a seizure, and they found her, I think, with her head in the pillow, and it was devastating. It was that point on that my husband and I started monitoring Lincoln, and we had a hospital grade monitor. We hooked him up every night. It used to be that we would only monitor his breathing when he was sick, when we knew that he was compromised, but from that night on, we have put Lincoln on his stat monitor every single night.
I didn’t even know that it was because of SUDEP, still. I wasn’t associating that with Emma’s passing or anything like that. We just knew we needed to monitor him. It’s not a conversation that we had with our doctors. Honestly, I thought that Lincoln has lived through so many thousands of seizures that one couldn’t possibly be the one to take him out, for lack of better terminology. I think I thought that was a non-issue. Like, “No, he’s just had lots of seizures, and he’s okay. He comes out of them.”
I’m realizing now, thanks to the doctor’s presentation, that Lincoln fits all those boxes, and we’re not going to have seizure freedom. We’re going to keep working for it, but he is very high risk. I’m comforted knowing that we’re doing what we can, and I even have questions for the doctor myself. We happened upon a solution. We can’t prevent it, but monitoring Lincoln and keeping him in our room is something that we’re comfortable with in doing what we can
Can you comment on successful ways that parents have brought this issue to your attention. I know you’re very attuned to all of this, but what recommendations do you have for parents who want to talk about this and don’t know how to bring it up?
I think the way in which patients have proactively asked me, it’s often me discussing SUDEP with patients and their carers, but every once in a while a proactive parent or a proactive carer or a patient himself or herself will bring this up to me. It’s a very direct and inoffensive question, which is, “What is the risk of something bad happening to me?” It’s a straightforward question that deserves a straightforward answer.
Most of us who have observed a grand mal seizure to occur will know that a lot of the time patients do turn a little blue around the lips and don’t breathe very well after a seizure. What does that mean to that individual? I think it’s a very important question to be asked and to be addressed. A lot of the time is the answer is reassuring. Sometimes it is okay. These are the specific things that need to look out for, and this is how you can be careful.
What do you recommend for children and teens who want to sleep alone? Is there a specific type of monitoring device, either that they wear or that is connected to the bed, that’s helpful?
That’s a very, very important question. I think there was a time when we were very careful about making overbearing recommendations because teenagers in particular have to live their lives. There’s a quality of life issue, et cetera, et cetera. But we know from recent scientific studies that one of the most powerful factors that prevents death probably is the presence of somebody else in the room; whether somebody else is in the room sleeping with that particular individual or not. There’s something to be said about that kind of observation.
Of course, as you’ve already alluded to, there’s the in between of monitoring devices and a lot of my patients do use them successfully. There are a couple of FDA approved devices that are out there on the market. I personally don’t have shares in either, but there is the Empatica, the Embrace device. There’s Brain Sentinel. They both use different approaches. What they don’t do is prevent SUDEP. What they do, do is let the designated carer or person know that a seizure is occurring or has occurred. I’m an advocate for the use of whatever technology is available for mitigating risk.
Have there been any studies with SUDEP and VNS patients? If so, are there any differences in the rate of SUDEP?
Yes. Great question. There is actually a very well-known study where several thousand patients who had had VNS devices implanted were studied over a period of time. It looked as though the rate of SUDEP over a prolonged period of time actually went down in the VNS population. Over a long period of time, it may be protective against SUDEP.
This is obviously one study, but it was sufficiently powered, I think, because there were thousands of patients who were studied to say that there is probably something there. When you couple that with the fact that VNS in some individuals reduces seizure frequency, then there’s a case to be made for doing VNS in patients who have not responded to other measures. [But] I wouldn’t say that VNS alone is completely protective.
Can a CPAP or other oxygenation aid device help those with SUDEP risk factors at night during sleep?
That’s a pretty nuanced question, I have to say. When it comes to improving sleep quality in patients with epilepsy, yes, absolutely. CPAP and those things might be useful because sleep deprivation, poor sleep quality, et cetera, et cetera. These are all linked to seizure frequency, and of course, seizure frequency is linked to SUDEP.
In somebody who’s having a seizure and may be likely to suffer from SUDEP, would CPAP prevent that? Probably not, and I say that for number reasons. Chief among those being that, in a convulsive seizure, you can have all monitoring devices, they become dislodged, there’s a lot of movement, shaking, et cetera, et cetera. So I wouldn’t rely on CPAP for preventing SUDEP directly like that.
Should electrical stimulation of the medulla, and maybe you can explain where the medulla is, be more widely used to study or to prevent SUDEP?
The medulla is part of the brain stem, the same structure that I was talking about, and medulla probably is the most important part of the brain stem for a final common pathway to controlling breathing and cardiac rhythm and blood pressure. A very important structure. It’s a very challenging part of the brain to study in humans because to stimulate the medulla, you have to put electrode into the brain stem, and that always carries a risk of bleeding hemorrhage and so forth. The outcome of bleeding in that part of the brain stem would be catastrophic, would be death. To my knowledge, nobody has done that in humans yet, but there are researchers who are looking at stimulating other parts of the brain stem; parts of the brain stem that are maybe less risky, but at the same time, likely to impact breathing and cardiac function. There’s more to come. In the next few years, I think we will hear a lot more about brain stem stimulation
For uncontrolled seizure patients, how often would you recommend doing an EMU stay? I know that the MORTEMUS study was done using patients in the EMU.
The EMU has a very specific role. We either send patients there for diagnostic assessment. Here, we’re trying to figure out if the patient has epilepsy or a related disorder. Or, we’re trying to see what kind of epilepsy it is. That’s diagnostic EMU assessment.
Then there’s the other kind of EMU assessment, which is the presurgical assessment; studying the seizure in order to do brain surgery. It’s the latter type in which we’ve become more and more practiced at assessing cardiac and breathing function, as well. There isn’t much point in repeated EMU assessments for assessing risk. Usually, if intractability or lack of control through medication surgery has been established, then one EMU assessment where cardiac and breathing function are looked at as well is probably enough.
Here’s a question related to the rare epilepsy categorization. “Is Lennox-Gastaut a part of this group of rare epilepsies that are impacted more significantly by SUDEP?
Yes. I would say that it is. It’s one of the commoner varieties of the rare epilepsies, but Lennox-Gastaut really is a syndrome. It’s not really one specific genetic condition. Within the LennoxGastaut rubric, we actually have dozens of other conditions that make up the syndrome complex that we call Lennox-Gastaut.
You’ve talked a lot about people who may have had longterm epilepsy, lots of seizures, but there are instances where after just a handful of seizures, somebody has passed due to SUDEP. We think of some more public cases like Cameron Boyce who passed away, but there are others. Is it possible to die from SUDEP without either a diagnosis of epilepsy or a first tonic clonic seizure?
Absolutely, yes. Happily, I would say that that kind of situation where it’s not uncontrolled epilepsy is extremely rare, but it does happen. As recently as two months ago, I was contacted by colleagues in another part of the country who had just such a patient who passed after a second tonic clonic seizure. We’ve come to understand that SUDEP is actually a heterogeneous phenomenon. It’s not just one thing, and there isn’t just one prototype patient that fits that mold. There’s actually a variety of types. There are tragic cases where a first ever or a second ever seizure kills, but I have to say that that is very, very rare.
You’ve talked about the cardiac disturbances, but could you talk a little bit more about that? Does that mean cardiac arrest, or what do you mean by a cardiac disturbance or arrhythmia?
By cardiac disturbance I mean cardiac rhythm dysfunction. Cardiac rhythm can be disturbed in a variety of ways during seizures. The heart can either be too fast or too slow. When it’s too fast, it can happen in a pathological fashion; conditions that we refer to as ventricular tachycardia, ventricular fibrillation, and things like that. Those are very dangerous. In the SUDEP context that seems to happen extremely, extremely rarely. What is more common is the heart beating too slow and maybe even stopping. That’s what we refer to as bradycardia and asystole. You can imagine that after a seizure, if a patient is not breathing too well and their heart’s not beating too fast either, that their blood pressure’s not going to be great. Of course, it sets a vicious spiral that can result in an unfortunate outcome
Abby, I know that you had some questions. Now that you’ve heard this discussion, as a parent, what do you think and what sorts of questions would you be coming to your physician with now?
Abby: First off, I’m like, “Wow! It’s a miracle my son is still here!” We have prolonged QTC. He has intractable epilepsy. He’s a boy. He has cluster seizures. I’m thanking God that he’s still here.
I feel like quite a few of the questions coming in were kind of along the lines of what I was thinking. My son has a VNS, so I was worried that might be a problem.
Somebody asked about the CPAP, that’s something that I have chosen not to put on my son, but I’m wondering if I should? I’m wondering if that makes a difference breathing-wise.
My question would be the sleep studies that my son had done seem like they’re separate from EKGs, like these are two different events. I’m wondering, do I need to pursue having them done together? I’m not even quite sure what my question is. It just seems that the breathing patterns that you’re looking for are maybe things my neurologist isn’t looking at. Is my neurologist looking at that, or my epileptologist, or are they just looking at seizure activity? Are they focused in on breathing patterns? How do I know if my son’s intractable epilepsy is causing breathing issues not related to just, “Oh, his SATs dropped”?
I don’t know if that was very clear cut, but that’s kind of where I’m going. How do we get everybody together on the same page to talk about this risk?
Dr. Lhatoo: If I may just make a comment, which is, I shared some of the recent research findings with you folks today, and it is always the case that clinical practice lags a little behind what comes out in research. That’s only correct because research findings need to be validated, replicated, reproduced, and so forth before they become standard clinical practice. It is not standard clinical practice in many places to routinely measure breathing. Cardiac rhythm is done. EKG is done in most places, but breathing is not routine. I believe that it should, and there are a group of us who are strong advocates for it. Over the coming months and years, you’ll see more and more folks who will begin to do it in their epilepsy monitor units. But in sleep studies, breathing is very carefully measured, so I would imagine that your child has had that done.
The questions below were answered by Dr. Lhatoo after the webinar had finished recording to answer some of the remaining questions submitted by attendees:
Why does the risk of SUDEP increase in people with nocturnal epilepsy or people who have seizures during sleep? What makes sleep or being isolated throughout the night a risk factor? Is there any recent research you could share?
Sleep onset seizures (particularly REM sleep) seem to cause more problems in animal models of SUDEP. Sleep phases may also be associated with more tendency to autonomic dysfunction [the autonomic nervous system is what controls and regulates involuntary physiologic presses such as heart rate, blood pressure, breathing, and digestion; I believe Dr. Lhatoo is saying during sleep, these processes slow down which can increase seizure severity] and post-seizure obtundation [reduced level of consciousness after a seizure]. In some people, getting tangled up in bedclothes face down may impair recovery fatally.
What are the most promising biomarkers to identify patients at SUDEP risk, and how do we implement these into clinical care (other than the biomarkers you discussed in the webinar—eg. genetic biomarkers)?
So far, there are no biomarkers that have been proven to be useful in systematic prospective studies [a study that focuses on the development of a disease and relates it to suspected risk or protection factors; usually involves watching subjects for a long period of time], but there are several for which there is some evidence of value. These include generalized convulsive seizure frequency and post convulsive [after a convulsive seizure] bradycardia/asystole [slow heartbeat/heart stops pumping entirely due to the electrical system failing] and central apnea [breathing repeatedly stops and starts because the brain doesn’t send proper signals to the muscles that control breathing]. The best way to identify these is an epilepsy monitoring unit assessment. There are several candidate genetic biomarkers but again, none with clinical utility yet.
Does SUDEP originate from specific lobes or areas of the brain (apart from the brain stem and uncontrolled epilepsy as mentioned in the webinar)? Do we know the percentage of SUDEP victims who suffered from seizures originating in these specific lobes?
There is reasonable evidence now to say that SUDEP can occur whether the seizures are of focal (any lobe) or of generalized onset, if seizures are uncontrolled.
Is the risk of SUDEP the same if a patient experiences ictal/postictal tachycardia instead of bradycardia during seizures? I understand that any cardiac arrhythmia is a risk factor for SUDEP but multiple review papers and studies have conflicting information about what type of arrhythmia is the most dangerous—could you please help clarify this??
Post-ictal bradycardia [slow heartbeat after a seizure] is likely more dangerous than tachycardia [rapid/increased heartbeat]. This is because postictal tachycardia is extremely common; the vast majority of patients who have this feature have no problems.
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.
Mental health is among the many issues that can affect both children and adults living with epilepsy. While some people may experience few mental health issues, others may suffer debilitating problems of anxiety, depression, or mood disorders. It is imperative that clinicians address and treat these psychiatric symptoms early in the individual’s epilepsy journey to reduce the negative consequences they might have on the long-term quality of life. In fact, many clinicians and patients agree that treating anxiety and depression may help improve the quality of life for people with epilepsy more than reducing seizures.
This webinar will discuss the prevalence of anxiety and depression among people with epilepsy. Viewers will learn how anxiety and depression impact people with epilepsy in different ways, and that neurologists often have multiple tools at their disposal to help alleviate these psychiatric symptoms. In some cases, the treatment of these symptoms may influence the treatment of the seizures themselves.
The webinar is intended for people living with epilepsy, their family members and caregivers, and anyone seeking to learn more about mental health and epilepsy.
About the Speaker: Dr. Heidi Munger Clary is an Associate Professor and Epilepsy Fellowship Director at Wake Forest School of Medicine. She is an adult epileptologist whose research focuses on anxiety and depression in epilepsy. The overarching goal of her work is to develop and test strategies for neurology clinic-based action to close the screening, treatment, and outcome gaps for these impactful comorbidities. Dr. Munger Clary is Chair of the American Epilepsy Society Psychosocial Comorbidities Special Interest Group, Chair of the American Academy of Neurology Epilepsy Quality Measurement Workgroup, and Co-Chair of the Integrated Mental Health Care Pathways Task Force of the International League Against Epilepsy’s Psychiatry Commission.
Q&A with Dr. Heidi Munger Clary
What are recommendations for dealing with anxiety and depression in non-verbal children?
So this is a great question, and this is a really challenging area because a lot of the work that we’ve been doing to try to address it has neglected this area. So, one of the things that needs to happen is we really do need a lot more focus and attention to this area. Now, one of the things that I have heard that can be very helpful in terms of tips from pediatric psychologists is really observing the behavior of the patient. Listening to the family, what is their intuition about how that person is doing? And then trying treatment approaches. I think it’s a real challenging area. Opening a dialogue with the neurologist can be a starting point. But it may really be that for individuals like this, if there’s a specialty clinic focused on neurobehavioral care or care of individuals with behavioral issues and developmental delay, that setting might address those patients’ needs even in an even more robust way. I will say for myself being a neurologist in practice, really trying to address these kinds of topics in a better way over time, we at our center, we’re lucky to have this excellent neuro behavioral clinic.
And I do find that once I run out of some options for potentially optimizing the seizure medications for behavioral effects, thinking about maybe a very commonly prescribed medication, sometimes an SSRI is worth considering. But getting those patients to the specialized care, I think right now is the best thing to do because this is not an area that the neurologists are really well equipped to start managing themselves, but starting the dialogue and getting the referrals and finding those resources in the community that are appropriate, I think, is the most important thing for it right now.
Can you share more about the correlation between hormonal issues and seizures?
I’m trying to think about how to focus it in the mental health area, but one of the things we commonly see in day-to-day epilepsy practices that sometimes seizures are related to the menstrual cycle in terms of the timing of seizures. This may also impact behavioral symptoms as well. I’m trying to think about what the best way to focus this response would be. But if one of the questions is a concern about seizures and hormones, doing some careful tracking of hormonal cycle related changes, whether it be the menstrual cycle or even treatment changes that might affect hormones and seizure frequency can be helpful. In terms of the way I alluded to hormones within the brain, potentially being related to mental health issues, that’s an area that’s primarily in the research zone right now, and doesn’t have a lot of everyday practical clinical implications yet from my perspective.
Do medical treatments for anxiety change for younger people, for teens compared to adults?
So this is an excellent question. So, there is more of a potential concern about whether SSRI, the most commonly prescribed antidepressant category, whether might be higher risk for suicidality in teens than in the adult population. There is a bit more of a regulatory warning associated with these medications in the teen years. So having said that if, for example, a teen is seeing an adult-focused neurologist, or maybe a pediatrician, there might be a bit more reluctance to prescribe. And so there may be more of a recommendation for specialty care. Having said that, SSRIs are used very commonly in teenage people. But I think the level of expertise to make sure that it’s safe and that it’s really the right thing to do is important.
There’s a lot of behavioral approaches, counseling, psychology-based approaches to anxiety management in children and in adolescents. And it seems that there’s a greater emphasis on that when we look at the literature and think about what kinds of treatment recommendations are out there. There also seems to be more psychology resources in many pediatric centers than I have seen in some adult centers. So, to answer the question, the approach may be different, talk to the neurologist and other care providers to see what they recommend. And it may be that more of a specialty-focused approach is appropriate in the pediatric age group.
So it may be that a pediatric neurologist may be more likely to recommend a referral to a pediatric psychologist or a psychiatrist to manage anxiety in either the teenage age group or younger age groups than so then some adult neurologists who might take on the management themselves. This may be evolving over time. Talk to the neurologist and find out what their comfort level is. There are a lot of pediatric centers that have really robust psychology resources. So that’s the potential silver lining to that question. There might be a resource there in a pediatric setting, more likely than an adult.
Does the person raise the issue or should they rely on the neurologist?
We wish that the neurologist would always bring this up. But I think that you can really help yourself, your loved one, your family member. If you have concerns in this area and you bring it up, it’s much more likely to be addressed. Some neurologists may address it as a routine. We know from survey data that sometimes they will only address if it’s raised by the patient. So do not be afraid to raise your concerns. It can really help lead to it being addressed. So I think it’s a great idea to bring it up as the patient.
Speaking on the patient, on behalf of the patient, somebody asked the question, how do you know when for somebody perhaps who’s non-verbal, when you should change a medication or try something else?
And in terms of the question, if we’re thinking about, is there a mental health side effect, a behavioral side effect from the medication, for example, observing behaviors and behavior changes as a medication has been added. For example, one of the medicines I listed as often good for anxiety, Clobazam, sometimes this causes agitation and behavioral problems, and it seems to be more common among intellectually disabled people. So if a new medicine is added, watching your loved one’s behavior and seeing, is something changing that makes me concerned? Bring it up with the neurologist and see. And then if it is the medication, medication could be reduced or taken away, and then you’ll find out if that was the cause.
Now, how do you tell if a medication specifically for mental health is working for your loved one? I think it would be similar to observing the behaviors that were the concern in the first place, and that led to prescribing that medication. Is that improving with the treatment? If it’s not, then it’s time to go back to the prescriber and think about what else could be tried to help.
Does it make sense for families to stay in touch with their provider more frequently as there’s a medication change?
I do think it’s a good idea, specifically, if you notice a change that is of concern. Sometimes people feel like they need to wait until the next visit to bring these kinds of issues. It’s important to know what’s the best way to work together with your neurologist. I do think though that most neurologists, if there’s a problem with the medicine, would rather hear about it sooner to be able to respond than not. But check with your neurologist as well to see what their recommended approach would be.
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.
This webinar provided information to help the audience understand more about autoimmune epilepsy and the different treatment options and considerations, including immunotherapy, for autoimmune related seizures and epilepsies.
Our body’s immune system is what protects our body against harmful substances. Autoimmune encephalitis is a term that refers to conditions that occur when the body’s immune system mistakenly attacks healthy brain cells, leading to inflammation of the brain. Antibodies may target different brain receptors which impact the type of autoimmune encephalitis. Symptoms may include memory loss, cognition problems, impaired speech, and seizures.1
It is important to diagnose autoimmune epilepsy because one of the hallmarks of this condition is that it does not generally respond to typical anti-seizure medications. Immunotherapy is often used to treat people with this condition, by reducing inflammation in the brain.
This webinar is intended for people living with epilepsy, their family members, and caregivers, and anyone seeking to learn more about autoimmune epilepsy and its treatments.
About the Speaker:
Dr. Stephen VanHaerents is an Assistant Professor in Neurology and Medical Education at Northwestern University Feinberg School of Medicine. His practice focuses on the medical and surgical treatment of epilepsy with particular emphasis on the treatment of medically intractable seizures. His clinical research interests include neurostimulation, identification and treatment of autoimmune-associated epilepsy, and new-onset refractory status epilepticus (NORSE). Additionally, Dr. VanHaerents is deeply invested in medical education and currently serves as the Director of Medical Student Education in Neurology. He also serves as the Co-Chair for the Neurology and Neurosurgery Health Equity, Diversity and Inclusion Committee at Northwestern University Feinberg School of Medicine and Northwestern Medicine.
Q&A with Dr. Stephen VanHaerents
There been success in diagnosing and/or treating somebody Autoimmune Epilepsy Treatment Considerations webinar Page 14 of 19 with a longer history of epilepsy and autonomic dysfunction?
Early is good. This happens where the diagnosis of an autoimmune cause is made much later than desired. And at that point, I usually do do a trial, but sometimes they don’t respond, there’s damage done, and they have persistent epilepsy for instance. And then I still look, is there any component of it that’s still immuno responsive or do they just have a structural epilepsy at this point due to damage from the brain? And so, I do try to still tease that apart to see if there’s any immuno responsive component left, but often, not often. I mean, it depends case by case, but there are many that there’s no further immune component but they do are left with a structural long term epilepsy. And then they kind of go down more of what you think of for standard epilepsy and maybe you think about epilepsy surgery or neurostimulators, things like that.
You’re clearing the blood of the bad antibodies but aren’t they going to come back. Won’t they regenerate and if so, what do you do?
This is an acute treatment that you’re doing, it’s not a long-term maintenance theory. When you’re dealing with someone like NMDA receptor encephalitis that antibody is toxic. If you take it from one mouse without NMDA receptor and encephalitis and put those antibodies in the other mouse, they will become symptomatic. And those intercellular antibodies, not so much. You want to clear the blood to get them out. And so, you clear it, but long term, often we use something called rituximab, which then is an antibody then directed at the bone marrow to stop making. So, you don’t differentiate into those plasma cells, those progenitor plasma cells so you stop making the antibody. But that’s a great question. And you also want to be sure not to give the rituximab before the plasmapheresis then you just wash out your very expensive therapy either. You wash the blood first.
Is it better to treat with carbamazepine or could we use other sodium channel blockers like lacosamide if they don’t want to use.
That is a great question. And I would not use carbamazepine in someone with hyponatremia and for the audience who doesn’t understand why that question was asked is carbamazepine or
oxcarbazepine, that family really is associated with low sodium. And so, you’re right. I would probably use something like Vimpat now keep in mind Vimpat’s not benign. Oh, sorry. I probably should use generic names, lacosamide, sorry. Lacosamide. But some of these patients have autonomic dysfunction too. And so, you do want to really monitor these patients’ parts too. Some of these sodium channel blockers a lot of them can either prolong QTC intervals, which you have four chambers of the heart, and the PR interval is how long it takes from the smaller atrium to get to the ventricles. And so essentially you want to monitor their heart too. When you’re looking at that study, you have to take it with a grain of salt. Yes, and LGI1 carbamazepine did it better, but you have to think about the patient too. And so, what’s best for them at that moment.
You’ve given us the example of this woman who’s experienced real changes in behavior, some inconsistencies, but what other things might tip off family members that might be a cause for concern for autoimmune epilepsy. How do you trigger epilepsy investigation?
That was in my first talk of kind of what are autoimmune seizures like as opposed to other seizures and keep in mind that patients with epilepsy, depending on the location of the epilepsy might have a lot of psychiatric comorbidities related to their epilepsy much higher risk of anxiety, depression, other things. Not everyone with any sort of psychiatric comorbidities autoimmune. I just want to give that kind of caveat off the bat, but the seizures of themselves are typically location-wise. And this is where talking to your doctor is important too, this kind of perisylvian, these kind of autonomic type seizures of the insula and areas and they tend to often be very brief seizures where you can have lots per day. No, when you look at this patient I just presented, she went from never having a seizure, you to having tons of seizures, tons, and they’re very short and brief, and they tend to be very medically refractory off the bat.
That’s not typical of most epilepsies, unless it’s a genetic epilepsy from a young age where they can be very refractory very early. This 27-year-old to develop that refractory of epilepsy in the course of a couple months would be very atypical. And then bilaterality too like having seizures like the guy last time I showed you, he had got left temporal seizure, right temporal seizure, left temporal, like having refractor. And he was 60 something. I forgot his exact age, but refractory epilepsy in a 60 something-year-old bilateral, that’s really hard, and older people with structural epilepsy, usually, it’s from a stroke or maybe they had a brain tumor and it’s from one spot. Maybe it propagates different so they can have different seizure types. Let’s say it’s in their parietal lobe and sometimes it will go backwards and they’ll get a visual aura or sometimes it will go forward, but they have from two different sides that refractory that should really raise your index of suspicion. Something is up here.
If somebody presents what seems like a seizure and they get put on a standard anti-epileptic drug, but then in the workup, it’s determined that, well, perhaps they actually have an autoimmune epilepsy and they go through that process. You’ve described it in your patient that you just presented to us where they titrated off of the immunotherapy and also for her off of the AEDs but that’s a very scary proposition for many to think about coming off of the anti-epileptic drug completely. How do you make those decisions and how do you work through that process??
This is how I usually do it, which is not always a hundred percent standard. And I’m glad actually now I didn’t even think about it, but those two cases, the case in the first one, he was unable to actually come off seizure meds. And I think that part of that reason I believe is that in the first case, he really presented it in September, but I didn’t meet him until March or April. So, there’s a large delay. And one rule of thumb so you do him second, we’ll talk about the patient I just presented first where she was able to come off both. Her cognitive seizure had all stopped really by about eight weeks at that point. She responded very quickly, which is awesome for her and we also got to her very quickly too.
So she really wasn’t that symptomatic without treatment very long. So essentially what I do is I never wean seizure meds and immunosuppression at the same time, because then if they have a breakthrough seizure, you don’t know is it because they have structural damage that now they have epilepsy or is it that they’re having a relapse of their autoimmune encephalitis and need immunotherapy. So, I never wean them at the same time. So, in her, I slowly wean immunotherapy while I kept her seizure medications stable. At which point when she’s off immunotherapy doing great, I usually get a follow-up EEG. Does she have any sharp waves or any epileptic potential whatsoever? At this point in her, she really can’t be driving anyways because it’s still within six months.
She wasn’t driving. And I discussed with her seizure, precautions risk. I usually give them at home rescue too, in case they do Autoimmune Epilepsy Treatment Considerations webinar Page 18 of 19 have a breakthrough seizure. And I educate the family, seizure precautions, things like that. And then we slowly wean off and then once weaned off, I usually do a follow EEG to make sure that there’s no epileptic potential in her there wasn’t, but really we don’t have a perfect marker to mark someone’s epileptogenicity and that’s an area of research that, for another webinar. But anyways, right now we have a limited approach.
I think essentially that time is really the best marker. The longer you can go without seizures. And so, in her now it’s been sixplus years without a seizure. So, she’s doing really well. The other guy, when I weaned him, actually he got off immunotherapy. He was doing great. But when we did the follow-up EEG, he still had epilepsy from discharges, from his temporal lobe. With him, we discussed any potential wean, but in him, he didn’t feel that it was worth the risk. He also took longer to recover. So, it was also over six months. And so, he
was driving again, which is also a big consideration as well. So, it’s really a case by case and discussing with them the different options. I hope that answered that question.
Can you speak to how patients have experienced any changes or flareups in autoimmune epilepsy following COVID infection and any protocols you recommend for these patients? For both presenting for the first time after COVID or they already had autoimmune disease and then got COVID).
The reality is both. I’ve seen it flare up from both. I mean, the reality is if you kick up the immune system, even with just and by no way am I anti-vax, but with the vaccine, I’ve seen upticks too. You’re activating the immune system if they make autoimmune antibodies, it makes sense. The vast majority of my patients have been totally fine, to be honest. I didn’t know how that would happen, but there are a couple notable ones that it did kick up. And in which case I’ve treated them just like I would. Anyways, I gave them steroids in those cases to bring down inflammation. I just treat it essentially. But luckily it hasn’t Autoimmune Epilepsy Treatment Considerations webinar Page 19 of 19 as bad as I initially was concerned and a lot of us were concerned about when the pandemic first started.
What’s the risk of recurrence and how do you treat it?
I took an NMDA receptor encephalitis patient off rituximab which had worked for her for years when she relapsed, I did give her steroids actually, but then I gave her rituximab to go back on it too. It depends. If there’s something that was working for them before it’s got taken them off, then you restart it.
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.
Our body’s immune system is what protects our body against harmful substances. Autoimmune encephalitis is a term that refers to conditionsthat occur when the body’s immune system mistakenly attacks healthy brain cells, leading to inflammation of the brain. Antibodies may target different brain receptors which impact the type of autoimmune encephalitis. Symptoms may include memory loss, cognition problems, impaired speech, and seizures.1
Autoimmune epilepsy is important to diagnose because one of the hallmarks of this condition is that it does not generally respond to typical anti-seizure medications. Immunotherapy is often used to treat people with this condition, by reducing inflammation in the brain.
This webinar helped viewers understand the difference between paraneoplastic and autoimmune encephalopathies and the difference between acute symptomatic seizures related to autoimmune encephalitis and autoimmune associated epilepsy. Viewers learned about the characteristics and pathophysiological mechanisms of autoimmune encephalitis, when to suspect autoimmune related seizures and epilepsy, and the algorithmic approach to the diagnosis of autoimmune encephalopathies.
About the Speaker:
Dr. Stephen VanHaerents is an Assistant Professor in Neurology and Medical Education at Northwestern University Feinberg School of Medicine. His practice focuses on the medical and surgical treatment of epilepsy with particular emphasis on the treatment of medically intractable seizures. His clinical research interests include neurostimulation, identification and treatment of autoimmune-associated epilepsy, and new-onset refractory status epilepticus (NORSE). Additionally, Dr. VanHaerents is deeply invested in medical education and currently serves as the Director of Medical Student Education in Neurology. He also serves as the Co-Chair for the Neurology and Neurosurgery Health Equity, Diversity and Inclusion Committee at Northwestern University Feinberg School of Medicine and Northwestern Medicine.
Q&A with Dr. Stephen VanHaerents
Could infections like Lyme, Babesia, or Bartonella be possible causes?
So any infection is possible. So, I actually did my training in Massachusetts, so I’ve definitely seen lots of Lyme, but Lyme, one, it’s very inflammatory. Typically, if it’s invading the spinal fluid, but post-infectious, it’s always possible. But at this point, there is no links to any bacterial-type infections.
Can you tell us about seizures that originate or localize in the brain stem?
That is more of an animal model thing, but there definitely is autoimmune encephalitis that also very much attacks the brain Identification and Treatment of Autoimmune Epilepsy Page 15 of 20 stem. I am almost like, how much time do you? The brain stem is a very content area of the brain. And so, you can have a lot of different symptoms. In one form that attacks the brain stem, they do get myoclonus, but they have a lot of sleep dysregulation as well. A lot of times when things are involving deeper areas of the brain though, seizures are not a prominent manifestation, it tends to affect more like movement disorders and coordination just because that’s what that area of the brain does more than actually seizures themselves. So, I typically actually don’t see a lot of those patients, but people tell me about them, but they tend to see my movement disorder colleagues more.
Could autoimmune epilepsy manifest itself as a focal seizure?
It’s almost always focal seizures, when they generalize it’s secondarily generalized. So as opposed to a genetic generalized epilepsy, which affects both sides of the brain at the same time, even when they have a full generalized convulsion, it’s usually secondarily generalized.
Do you see intracranial hypertension in your patients?
That’s an interesting question. There’s sort of idiopathic intracranial hypertension, which I definitely have in my clinic as well, and maybe there’s some link that they’re alluding to, but I don’t know of any link to autoimmune encephalitis, especially if they had preexisting hypertension. That being said when your brain’s inflamed, you can get rises of intracranial pressure, for sure.
How close are we to getting IVIG infusions, FDA approved?
I’m curious if this question is geared more towards to get insurance to pay for it, which is always that all that I do in my clinic. And so, there was a trial with IVIG at Mayo Clinic for LGI1 encephalitis versus placebo. So IVIG is probably more on its way than many others, but I’m not involved in the FDA process. So, I actually don’t know.
Is there a next step if immunotherapy and antiepileptic drug treatment does not work? Or do we not have anything at the moment?
I never give up, really. So, there’s lots of forms of immunosuppression. So, when we were talking about B cell and T cell mediated therapy, so for instance, it was in the newspaper and she signed a media release, but we had a patient with an NMDA receptor encephalitis who was in a coma for about five
months. And we could not get her to wake up. And we used plasmapheresis, IVIG, steroids, rituximab. She even got a chemo drug called cyclophosphamide and nothing touched her, essentially. And so, we used a newer chemo drug that she had been used in Europe, which is chemo for multiple myeloma, which is a B cell malignancy. And she woke up from that.
So there’s lots of different therapies. I didn’t talk about the ketogenic diet either, which seems to have anti-inflammatory properties to it as well.
And there’s also anti-interleukins to anti IL-6, IL-1, which gets used in those kind of NORSE and fires cases if people know what that is, but that is a whole separate lecture. So, what do I do if initial therapy doesn’t work, is I try more. But that being said, sometimes you do palliative surgeries. If one area is structurally very damaged, you could consider surgery or neurostimulation too with various nerve stimulators or even invasive neural stimulators have been used in patients that are autoimmune as well. So, you don’t give up.
Could you elaborate on musicogenic seizures in this context, any recommendations how to proceed when certain types of music are seizure triggers? And what test panels are most appropriate?
Very good question. So musicogenic seizures, there was a case series on it and some people it’s pop music and things like that, but I treat them mostly just like any other seizure, we’re trying to get their seizures under control. So, I don’t necessarily treat them any differently. It depends if somebody has a photic sensitive epilepsy as well, and there’s certain glasses you can avoid, but you can’t avoid the sunshine or something like going through trees and things. There’s certain things you just can’t avoid. And so really the answer is immunotherapy and seizure meds to try to get your seizures under control long term. It’s just more of an interesting phenomenon of reflex seizures that GAD65 seems to get.
What’s the best timing to taper off of an AED in cases of autoimmune epilepsy? How do you go about that?
So we don’t have a good answer to that. We don’t even know who needs long term therapy. So, I’ll just tell you what I do, which is what people more senior with more gray hair did. And so I just do it that way. So basically, it kind depends. I never wean seizure meds and immunotherapy at the same time. Because if you have a breakthrough seizure, you’re not going to know which one you actually need. So that’s rule number one. And so I essentially, like for instance, that guy just told you, LGI1 can be monophasic and we don’t really know who’s going to relapse and who’s not. So, in that patient I slowly wean off. For instance, I was giving him pulse steroids, so I was giving him a thousand milligrams of Methylprednisolone every week.
And I just slowly increase the time of the pulses. So, if it was every week and then every other week, and then as you’re weaning off the immunotherapy, if they relapse, then you give them something long term. So, it depends on the severity too. If they were very severe like an NMDA, I’ll often just continue immunotherapy and everything for about two years, that’s what most people do. And then try to wean after that. Now, if they get off immunotherapy, things are going well, then I’ll probably wean seizure meds too, and see if they can get off. And then I usually do a follow-up EEG and see if there’s anything epileptic as well.
Can multiple food allergies contribute to these autoimmune issues? What about the body being in a constant state of inflammation?
That’s a tough question. So, there is more, we’re learning about the gut microbiome and how it relates to the brain. I don’t think we have any specific links. There’s a lot of research that needs to be done in that, some of which is being done at Northwestern, actually with gut microbiome and effect on the central nervous system. But there’s also key things for instance, people with gluten and celiac disease, which has a very well documented neural celiac and neuro antibodies. So, I think long story short is we don’t know, I don’t know how to answer it better than that. There’s some links, but to the core autoimmune encephalitic antibodies, I am not aware of any true clear associations besides for celiac disease.
What is IVIG??
IVIG is, intravenous immune globulin, essentially when you donate blood, your blood gets divided into, it’s essentially donor antibodies, long story short. It’s concentrated donor antibodies from multiple donors and then it gets concentrated and put into an IV bag. So, when you donate blood there’s red blood cells, platelets, clotting factors, they separate it all out depending on what the patient needs. So intravenous immune globulin is really donor immunoglobulins.
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.
Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by a traumatic brain injury (TBI). People diagnosed with a TBI are 29 times more likely to develop epilepsy compared to the general population1. Individuals serving in the military may be especially susceptible to PTE. In fact, over 400,000 US Military personnel were diagnosed with TBI from 2010-20192, putting them at subsequent risk for developing PTE.
This webinar provided an overview of PTE and cognitive dysfunction, as well as some strategies to help improve the quality of life of those with PTE and their caregivers. The webinar will also provide details about HOBSCOTCH (Home Based Self-Management and Cognitive Training Changes Lives), a behavioral program designed to address memory and attention problems in adults with epilepsy and discuss a clinical trial opportunity for veterans and civilians living with PTE.
The webinar is intended for everyone, including persons with epilepsy, their friends and family, and caregivers.
1. Herman ST. (2002) Epilepsy after brain insult: targeting epileptogenesis. Neurology 59:S21–S26.
2. DoD Worldwide Numbers for TBI, Defense and Veterans Brain Injury Center, 2020
About the Speaker: Dr. Elaine Kiriakopoulos is an Assistant Professor of Neurology at the Geisel School of Medicine at Dartmouth College, and the Director of the HOBSCOTCH Institute for Cognitive Health & Well-Being at the Dartmouth-Hitchcock Epilepsy Center. Her research and programmatic efforts target building multisector partnerships to reduce disparities in the care of people with epilepsy, ensuring the most vulnerable populations have access to quality epilepsy care and community resources.
Q&A with Dr. Elaine Kiriakopoulos
Could teenagers eventually participate in something like this?
I’m excited to share that we’re currently working on an adaptation for HOBSCOTCH youth, which will target adolescents between the ages of 14 and 18. We’re hoping to pilot that early in the new year as well. And so more information will come forth on that, but we feel like the program has a lot to offer adolescents as they transition to becoming adults, and helping with organizational skills, and disease management skills, as well as social skills. We’re really excited about that program. And coming along with that program is a HOBSCOTCH app, specifically for youth, targeted to youth. We think that’ll be exciting for them as well, too.
Do Georgia-based HOBSCOTCH participants need to be under the care of an Emory neurologist?
No, not at all. You can contact us, and we’ll make sure we can connect you to the team in Georgia at Emory. You can have your care with anyone in Georgia. We’re happy to have you join.
Interested in the program?
hobscotch.org
The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.
Last year during our SUDEP Action Day webinar, we learned that there is strong evidence of the association between breathing problems and SUDEP. However, there is also equally strong data for cardiac abnormalities, particularly cardiac arrhythmias (irregular heartbeat) playing a role in SUDEP. In fact, studies have found mutations in genes associated with cardiac arrhythmias in 15% of SUDEP cases. 1
This webinar helped viewers learn how inherited neuronal or cardiac diseases may lead to electrical disturbances in both the brain and heart, how altered cardiac function may lead to SUDEP, and why it is critical for the epilepsy community to take a holistic approach to fully understand biological changes that ultimately cause SUDEP. Watch the webinar above.
The webinar is intended for everyone, including persons with epilepsy, their friends and family, and caregivers.
1. Bagnall, R.D., Crompton, D.E., and Semsarian, C. Genetic basis of sudden unexpected death in epilepsy. Neurol. 2017; 8: 348.
About the Speaker: David Auerbach, PhD, is an Assistant Professor of Pharmacology at SUNY Upstate Medical University. Dr. Auerbach leads a translational research program. Through interactions with the families of patients with severe genetic diseases, he developed the passion and determination to advance the understanding of electrical diseases of both the brain and heart. He integrates cellular, animal, and clinical recording to investigate the prevalence, risk factors, and mechanisms for dual neuro-cardiac electrical disturbances, and ultimately sudden death.
Q&A with Dr. David Auerbach
Do you know if a condition called early re-polarization could increase the risk of SUDEP? And if so, what treatments or interventions are options to reduce that risk?
Sure. So early re-polarization syndrome, also is associated with a high prevalence of cardiac arrhythmias as well. That is true, that early re-polarization syndrome can also be pathological as well. Actually, a group just 45 minutes down the road from us in Syracuse, spent many decades studying this, in fact. In terms of therapies, that field really requires the expertise of your clinical electrophysiologist, because it’s so patient-specific that it would be difficult for me to give a silver bullet therapy right now.
Please talk with your physician and see if additional consultations might be helpful. You’ve touched on some of the risk factors and some of the things that people can do. Somebody had a question about the interaction between SUDEP and sharing a bedroom. Can you tell us what that’s about?
Sure. So yes, people who have epilepsy, who share a bedroom or have nocturnal monitoring, it’s the simple hypothesis that hopefully, someone in the room will wake up when you have that seizure and help put you in a safe position. Turning you on your side, making sure that your face is not buried in the pillow, anything like that. That’s the major theory behind that.
You’ve done a lot of work with the Dravet patient population. Is it recommended that patients with Dravet syndrome receive annual cardiac screening?
I’m a firm advocate for definitely, Dravet patients getting cardiac screening. The frequency of that? I don’t think we know enough right now to say whether one time versus yearly. But I definitely would recommend if it’s a child who’s going through puberty, basically testing both before and then after puberty. Because we know that sex hormones can alter the expression of ion channels in the heart there. So in that sense, I would say getting frequent testing.
That’s great advice, because that’s a piece that we’ve not talked about, the role of puberty and hormones.
Yes.
So very important. Is there any connection between AV block and SUDEP?
Yes. Yes. When I was saying throughout conduction disturbances, AV block is an example of a conduction disturbance. In simple terms, it’s either a delay or failure of that electrical wave to travel from the upper part of the heart, the atria, down to the ventricles, the lower part. And if that lower part of the heart, the ventricles is not firing and contracting at a sufficient rate, it cannot complete its sole function of pumping blood to meet the metabolic demands of the body. So yes, AV block is associated with SUDEP there.
I think you’ve touched on this, but just to reiterate, can mutated ion channels cause seizures?
Correct. Yes. Numerous gain and loss of function of sodium channel mutations that we classically look at in the epilepsy field, are also leading to electrical disturbances in the heart, and several cardiac ion channel mutations, such as long QT syndrome, Brugada syndrome, CPVT, are all … Also, there’s numerous reports of seizures in them as well. But there’s a lot of research that’s going on, to really understand the mechanism for this association.
So more to come?
Yeah.
What should you ask a cardiologist to screen for? I know that’s a medical question, but can you comment on that?
Sure. So I’m a firm advocate for performing cardiac testing under different physiological states. And what I mean by that is, doing cardiac testing when at rest, when maybe asleep, as well as during times of increased heart rate, such as exercising. Because to me, it’s the contribution of numerous forces that ultimately lead to these unfortunate events there. So we need to be getting cardiac testing under different heart rate states there, or autonomic states.
One other thing to add to it. I talked purely about electrical abnormalities today. I could give a whole other talk on the structural abnormalities in the heart. So when talking about cardiac workup and everything, echocardiograms, looking at wall thickness, contractile function, that’s a whole other topic that there is strong associations in the epilepsy field as well.
And similarly, would vasovagal events for SUDEP be a concern?
Vasovagal events, to me, that’s more of a hemodynamic blood flow type thing where vasovagal, you pass out. But then there’s normally this, then surge of adrenaline, sympathetic activity, gets the heart pumping stronger, increases your blood pressure, and then you oftentimes wake up. So I don’t really see vasovagal events as much associated with SUDEP, but there’s a lot that we don’t know yet.
Have the VNS and the RNS been included in studies? Do they provide any protection? Do we know?
Yes. So Richard Verrier’s group at Harvard there, looked in patients with vagal nerve stimulators and showed that those with vagal nerve stimulators, there was actually improvements in the re-polarization, or their cardiac recovery process in those would VNS. In terms of seizure control, of course, there’s been a lot of research showing the efficacy of that. So hopefully, did I answer your question?
Yeah, I think so. And there’s a related question on whether patients with VNS implants should continue to get cardiac care.
Yes. The VNS is firing when there’s a sudden change in heart rate. But I was at a cardiac conference during grad school, and this quote was used many times during the conference. He showed a video of this gentleman walking through the airport, and then drop dead suddenly. And the question throughout was, why did this patient die today, not tomorrow, not yesterday, not a year ago? So even though things are under control, we still need to be monitoring these patients, and practicing with safe lifestyle habits to cut down on our risks of seizures and SUDEP.
Okay. Yeah, there are lots of related questions here. Someone commented about, should a patient who started with fainting, which lead to seizures, follow up with a cardiologist again? We started with a cardiologist and got okayed for the fainting before the seizure started. Sounds like a connection there.
Sure. I’m going to give a textbook answer. I’m sorry for saying this, but you need to get the cardiologist and the neurologist and your family practice physician sitting all at the same table to figure out which is causing which there. Too oftentimes, our patients push back and forth between specialists. And maybe I say this because I’m not a clinician, but these clinicians all need to sit down at the table together and give better team-based care. My wife’s a physician, so I can tell her that.
Is brady or tachycardia more common during the seizures leading to SUDEP?
Okay. So brady, both are reported. Oftentimes, there’s been a greater prevalence of reports of bradyarrhythmias, slow heart rates, that can be due to slow firing of the pacemaker in the heart. But also, that includes your conduction disturbances. Because even if that upper part of the heart is firing normally, that wave may not get down to the lower part of the heart. But there are many case reports and even small studies showing tachyarrhythmias as well.
If somebody is potentially at high risk, would a pacemaker make a difference? I know that’s a medical question and we’re not giving medical advice here. But are you aware of anything?
Sure. So, depends what the electrical disturbance is. A pacemaker is there as a backup. If that pacemaker in the heart, the SA node, doesn’t fire at the rate that it’s supposed to be firing, that pacemaker jumps in. Or if that electrical connection between the atria and the ventricles is not functioning properly, you can pace the lower part of the heart, the ventricles. So it contracts. It excites and then contracts at the appropriate rate. But if the electrical disturbances are not due to a rate, but due to a rhythm abnormality, the pacemaker is not the right thing. That, you need to really consult with your cardiologist to understand, what is the electrical abnormality taking place in my heart?
This comes from a family who is concerned about SUDEP in their child. Are there any over-the-counter heart monitors that could be used? I know the Apple Watch is being developed as a system. There’s the Embrace. But that doesn’t have a heart piece to it.
Right. Yep. So unfortunately, right now, there’s no alarming device. The Apple Watch will report if it detected any atrial electrical activity, abnormal atrial electrical activity. But it does not presently alarm at all, unfortunately. And the challenge with that is, as some parents could sympathize with some of these seizure-detecting watches here, the high false positive alarming is a big issue. And I see that as a big obstacle in the field, because you don’t want that Boy Who Cried Wolf scenario there, where alarm’s going off every time, it’s always been a false alarm. And then you miss that one real one. So I think we really need to have devices that have a high level of sensitivity and specificity there. But not published at all, but my lab is definitely looking into some wearables to try to detect electrical disturbances in the heart.
Somebody asked that they would like to share your research with their child’s epileptologist. Would it be possible to get information? Or even if you know of any reviews or summaries that we might pass along to help people have this conversation with their doctor?
Definitely. Definitely. Dr. Lubbers, probably the easiest thing, I can send you a PDF version of this talk, as well as a couple papers afterwards that could be made available.
Here’s a question that’s a little bit more … policy-based. There is a law called Halyn’s law, which was passed in Connecticut, which requires medical examiners to have one hour of training in SUDEP, with the goal of collecting SUDEP patient data. Do you think this would be helpful if it was more broadly applied?
Absolutely. And during the SUDEP Summit, we had a medical examiner as part of it. And I think whether it’s a medical examiner or the coroner system, it’s so critical to have them more knowledgeable and trained in identifying SUDEP cases. Because that’s the only thing that’s going to help us to get that ball rolling in terms of recognizing the prevalence and the risk of sudden death.
We’re still learning a lot in terms of the research, but we need to be at least thinking about it. Could this be due to, for this person who has epilepsy?
We see billboards all the time, about the prevalence of cancer, Parkinson’s, Alzheimer’s, all these things. But really having some hard, accurate numbers about the risk of SUDEP is so needed. It’s so needed.
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About the Speaker:
About the Speaker:
About the Speaker:
About the Speaker:
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