In 2022, CURE Epilepsy initiated the SUDEP Data Standardization Project to create standardized data collection and reporting language to help preclinical researchers characterize and understand SUDEP animal models, with the aim of improving translation of animal models to the clinical setting. As a result, SUDEP common data elements (CDEs) and case report forms were developed to standardize data collection and reporting language for preclinical SUDEP research.
This webinar will help viewers understand the history and development of epilepsy CDEs with a special focus on preclinical Sudden Unexpected Death in Epilepsy (SUDEP) CDEs that have been developed in collaboration with CURE Epilepsy and the SUDEP research community. Speakers will discuss the impact CDEs can have on the translational relevance of preclinical investigations, and how the CDEs can be used in the context of daily preclinical research. There will also be a live feedback session with the speakers following the webinar. To learn more about the SUDEP CDEs and case report forms, you can preview them here. This webinar is hosted by the ILAE Young Epilepsy Section and will be moderated by Dr. Cecilie Nome.
Speakers:
Laura Lubbers, PhD, Chief Scientific Officer, CURE Epilepsy
Aristea Galanopoulou, MD, PhD, Professor, Neurology, Albert Einstein College of Medicine
Christos Lisgaras, PhD, Research Scientist, The Nathan Kline Institute for Psychiatric Research
Vicky Whittemore, PhD, Program Director, Division of Neuroscience, NINDS
Learning Objectives:
After this webinar, the participant will:
Understand the history and development of common data elements (CDEs) and use in epilepsy research.
Be able to apply practical use of SUDEP CDEs in their preclinical research, including for data collection and data analysis.
Appreciate the importance of the use of SUDEP CDEs when applying to funding agencies.
This webinar, hosted by the ILAE Young Epilepsy Section, will help viewers understand what SUDEP CDEs are, what impact they could potentially have on the translational relevance of their preclinical investigations, and how the CDEs can be used in the context of daily preclinical research.
On Wednesday, October 18 the worldwide epilepsy community will come together for SUDEP Action Day, an international event to raise awareness about Sudden Unexpected Death in Epilepsy (SUDEP). SUDEP, perhaps the most devastating possible consequence of epilepsy, occurs when a seemingly healthy person with epilepsy dies for no known or obvious reason.
This year’s theme is My Safety Matters – #mysafetymatters
Unfortunately, not everyone diagnosed with epilepsy is informed about SUDEP, the risks of SUDEP, or how to mitigate their risks. SUDEP Action Day is aimed at helping raise awareness of SUDEP and inform the epilepsy community as well as the general public about steps one can take to reduce their risks. Raising awareness, increasing education, and starting conversations are all steps needed to help bring an end to SUDEP.
As the leading private funder of SUDEP research, CURE Epilepsy is honored to support SUDEP Action Day and will be posting content each day during the week of October 16 to help increase awareness and spark important dialogues about epilepsy and SUDEP.
Research will lead us to a cure. CURE Epilepsy encourages you to share the resources below with your friends, family, and colleagues on social media using the hashtag #SUDEPActionDay2023.
Increase SUDEP Awareness and Share These Infographics
Many people are unaware of SUDEP, its risk factors, and ways to mitigate their risk for SUDEP. That’s why we created these easy to understand graphics with vital SUDEP information.
Help us spread the word and initiate critical conversations about this awful consequence of epilepsy — share these infographics with your friends and family by posting them on social media.
1 is 1 Too Many
It is estimated that over 3,000 people will die each year from SUDEP and it can happen to anyone with epilepsy. At CURE Epilepsy we are unrelenting in our mission to find a cure for epilepsy as well as see an end to SUDEP. This year, for SUDEP Action Day, CURE Epilepsy is highlighting some of the many stories of individuals who have passed due to SUDEP within our community. Visit our Facebook or Instagram on Friday, October 20 to see more individuals within our community who have passed due to SUDEP.
Webinars:
SUDEP & The Heart: A Multi-System Approach to Understanding Electrical Disturbances
In this webinar, Dr. David Auerbach, PhD, an Assistant Professor of Pharmacology at SUNY Upstate Medical University, 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.
Breathing and SUDEP: Research & the Influence of Seizures on the Respiratory System
Research suggests that respiratory dysfunction following generalized convulsive seizures is an important cause of SUDEP. Interruptions in breathing can occur during and after seizures leading to an imbalance of carbon dioxide and oxygen in the body. The ability to restore normal breathing patterns and remove excess carbon dioxide may be weakened in some people with epilepsy, potentially increasing their risk of SUDEP.
New Seizing Life Episode
In observance of SUDEP Action Day, we speak with Dr. Richard Goldstein, Associate Professor of Pediatrics at Harvard Medical School, about the program he directs conducting research into both Sudden Unexpected Death in Pediatrics (SUDP) and the grieving process of bereaved parents.
Dr. Goldstein explains how the interdisciplinary team at Robert’s Program utilizes current medical knowledge and methods to try to provide answers to bereaved families while simultaneously conducting research into the various occurrences of SUDP, such as SUDEP (Sudden Unexpected Death in Epilepsy), SIDS (Sudden Infant Death Syndrome), and SUDI (Sudden Unexpected Death in Infancy), to uncover the similarities and connections between them. He reveals some of these connections and discusses what they may mean to both epilepsy research and the larger issue of child mortality.
CURE Epilepsy Discovery on Advances in SUDEP Research
A CURE Epilepsy Discovery that focuses on new SUDEP findings thanks to research funded by CURE Epilepsy.
On Wednesday, October 19 the worldwide epilepsy community will come together for SUDEP Action Day, an international event to raise awareness about Sudden Unexpected Death in Epilepsy (SUDEP). SUDEP occurs when a seemingly healthy person with epilepsy dies for no known or obvious reason. It is perhaps the most devastating possible consequence of epilepsy.
This year, organizers are asking us to #TalkSudepNow to encourage critical conversations on epilepsy risks and SUDEP. As the leading private funder of SUDEP research, CURE Epilepsy is honored to support SUDEP Action Day and will be posting content each day during the week of October 17 to help increase awareness and spark important dialogues about epilepsy and SUDEP. Remember that through research there is hope.
Increase SUDEP Awareness by Sharing These Infographics on Social Media
Far too many people are unaware of SUDEP, its risk factors, and ways to mitigate your risk for SUDEP. That’s why we created these infographics: to make it easy for everyone to learn and share this vital information.
Help us spread the word and initiate critical conversations about this awful consequence of epilepsy — share these infographics with your friends and family by posting them on social media.
Webinar: SUDEP & The Heart: A Multi-System Approach to Understanding Electrical Disturbances
In this webinar, Dr. David Auerbach, PhD, an Assistant Professor of Pharmacology at SUNY Upstate Medical University, 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.
New Seizing Life Episode
In this new episode of Seizing Life, we welcome CURE Epilepsy Board Member Hannah Whitten to the podcast. Hannah’s older brother Dylan lived with epilepsy nearly his entire life, until he passed away from SUDEP at the age of 25. Though she was 5 years younger, Hannah was a constant companion to Dylan as they grew up and was often his main caregiver. She tells us about her brother’s attitude and determination not to let epilepsy define or limit his life, attending and graduating from college, working, and eventually living on his own. Hannah also talks about her experiences having a sibling with epilepsy and the impact that epilepsy has had on their family.
New CURE Epilepsy Discovery on Advances in SUDEP Research
A new CURE Epilepsy Discovery published on Thursday, October 20. This Discovery focuses on new SUDEP findings thanks to research funded by CURE Epilepsy.
Webinar: Breathing and SUDEP: Research & the Influence of Seizures on the Respiratory System
Research suggests that respiratory dysfunction following generalized convulsive seizures is an important cause of SUDEP. Interruptions in breathing can occur during and after seizures leading to an imbalance of carbon dioxide and oxygen in the body. The ability to restore normal breathing patterns and remove excess carbon dioxide may be weakened in some people with epilepsy, potentially increasing their risk of SUDEP.
Research will lead us to a cure. Share this video with your friends, family, and colleagues on social media using the hashtag #TalkSudepNow!
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.
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.
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.
Research suggests that respiratory dysfunction following generalized convulsive seizures is an important cause of SUDEP. Interruptions in breathing can occur during and after seizures leading to an imbalance of carbon dioxide and oxygen in the body. The ability to restore normal breathing patterns and remove excess carbon dioxide may be weakened in some people with epilepsy, potentially increasing their risk of SUDEP.
This webinar provides an introduction to basic concepts and terminology for how the respiratory system functions. It also provides evidence for breathing dysfunction caused by seizures and reviews the data for breathing dysfunction as a potential cause as well as a marker for SUDEP, and a possible means to intervene and prevent SUDEP.
Get a personal perspective on SUDEP from two mothers who each lost a son to SUDEP. Libby Boyce and Jessica Brandes discuss what they were and weren’t told about their sons’ epilepsy, and outline what should be done to build awareness of SUDEP on this episode of the Seizing Life podcast.
About the Speaker
This webinar was presented by Dr. Rup Sainju, Assistant Professor of Neurology and Medical Director of the EEG Lab at University of Iowa Health Care. Dr. Sainju is a 2016 CURE Epilepsy Award grantee, whose research found that respiratory response to high carbon dioxide levels in the blood may be weakened in some people with drug-resistant epilepsy, which puts them at an increased risk for severe breathing abnormalities and SUDEP following a generalized convulsive seizure.
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.
Audience Q&A with Dr. Sainju
Can individuals with severe intractable LGS with multiple seizures die because of SUDEP during sleep, even with no presence of clinical seizures?
This is very interesting questions. Again, if you review the risk factor, the number one risk factor for SUDEP is drug-resistant epilepsy. However, having tonic clonic or convulsive seizures seems to be in terms of types of seizure. Amongst types of seizure tonic-clonic seizure seems to be the highest in potential for causing SUDEP. But the question here is whether if the patient is having nonclinical seizure, can there be increased risk of SUDEP? I don’t think we know the answer fully but it sounds unlikely. However, we’re still learning a lot about SUDEP and SUDEP mechanism. So we still don’t know the full answer at this time. However, it sounds unlikely given the evidence so far.
What is the best type of oxygen mask to use after a seizure and are they postictal?
Number one, again, we don’t know for sure if… We don’t have strong enough evidence to suggest that we should be using oxygen as a therapy after convulsive seizure. We just have some evidence showing that it may reduce the amount of oxygen or the lowest drop in oxygen. It may prevent drop in oxygen and may recover the oxygen level a little bit faster. But that does not tells us how it changes SUDEP risk. So again, we don’t know that yet. We still need more studies addressing these questions.
What would be the risk for someone with a genetic seizure disorder to wear a mask for a work shift six to eight hours a day for three days a week? Is there any mask that would be considered safe for such long-term use? Are there any challenges with using the masks that we’re wearing today?
I don’t think I have a good answer for this question as well. Given COVID pandemic that’s going on, wearing mask is something we should all consider. One thing is for sure is it does not prevent you getting sick, it also prevents spread of disease if you are asymptomatic and still has infection. So, I don’t know that there is a good mask or what type of mask that we should be using. If you are taking care of patients, you should probably use medical grade mask, but if not, then at least using some sort of mask is still good. In relation to epilepsy, we don’t have good information to suggest what’s the best kind of mask for you if you have epilepsy.
When does SUDEP occur the most when the patient is sleeping in a safe position under monitoring, and what can parents do to lessen the chance of its occurrence?
Most witnessed death from SUDEPs reportedly happen after a convulsive seizure. So it’s not during, it’s rather after convulsive seizure. And there is good suggestion that there is something to do with sleep and if you are alone then you actually are on a really high risk of dying with SUDEP. So if you are monitored by some mechanism… Direct mechanism probably is good for a lot of people who don’t mind their privacy, but this is a very personal situation for a lot of our patient with epilepsy. So having some sort of indirect monitoring may help, but again, we don’t know for sure which monitor, whether it’s seizure detector or a video monitor or a seizure alarm like a bracelet or… There is actually FDA approved device, a watch, Empatica, that is approved to detect, an alert system after a convulsion has happened.
We don’t know, again, to the extent how much these intervention are helpful, but I want to highlight that’s why we need more research trying to get more information so we can have more intervention that is available for patients and families. What I tell my patient and their family is I would consider based on the situation, individual situation and preference, having some sort of monitoring or surveillance is reasonable thing to try. It may not have to be the video surveillance. You may just sleep next door or maybe on the same floor. So some studies suggest that when people intervene during or after convulsive seizures, sooner you go and talk to them or try to intervene in some way, recovery seems to be a little bit faster. Their oxygen recovery, as well as their arousal seems to be a little bit faster. So it’s reasonable based on the situation, but there is no single thing that is proven that we can recommend at this time.
Do you suggest that people with epilepsy have a sleep study done to monitor breathing during sleep? Is that possible?
Best thing for people with epilepsy is to take your medicine, talk to your doctor how best you can control your seizure. Because again, we don’t have a medicine to prevent SUDEP at this point given all the potential we discussed. Best approach still is try to control your seizure best. Having said that there is a good proportion of people who have epilepsy that may have obstructive sleep apnea. So if you have some of the simple symptoms of potential obstructive sleep apnea, for example, feeling fatigue, lack of energy, headaches, or people actually witnessed you snore during sleep or stop breathing during sleep, I think that would be very reasonable time to evaluate for a sleep study and get it treated because poorly controlled sleep apnea or untreated sleep apnea can worsen seizure and epilepsy control.
Does a co-morbidity of autonomic dysfunction increase SUDEP risk in epilepsy patients?
We don’t have much information about this yet and what we have is during or after convulsive seizure, some people can have really irregular heart rate or problem with blood pressure. How that translates into SUDEP risk is not clear. How common that is is also not clear at this time.
Will the pulse-ox be a helpful alarm for people while they’re sleeping?
It depends on the type of epilepsy as well as type of seizure that we’re dealing with. And if you’re talking about monitoring a child, that may be a problem putting the probe in to begin with. But if pulse oximetry is good enough to detect seizure-related drop in oxygen and alarm you, it sounds reasonable to think about it, but we don’t have a study showing that is what is very helpful. But again, I’ll circle back to the same thing. Some sort of supervision is reasonable, including pulse oximetry, but you have to think about it has a lots of false alarm that is associated. And false alarm could be because the probe is displaced while during movement or during sleep versus there are… So many different things can go wrong and give you a wrong pulse oximetry read.
A couple of people asked about examples of serotonin medications. What are those?
A very commonly prescribed group of medicine includes SSRI or selective serotonin reuptake inhibitors. These are a group of anti-depressant. Or most medicines that is often used by psychiatrists. And the studies I alluded in this talk that were included in human, part of the human studies were people taking either SSRI or similar medicine. There are a group of… Another group called SNRI is non-selective serotonin reuptake medicines. These are also antidepressant medicines. And there are some… or supplement rather that can convert into serotonin in body like tryptophan or 5-hydroxytryptophan. So these would be considered as serotonergic medicine in general, if that’s what we’re getting at.
In terms of common names, Prozac would be a common name people might recognize. Celexa or citalopram, escitalopram would be some other names.
A webinar discussing the population at risk for Sudden Unexpected Death in Epilepsy (SUDEP) and what risk factors may be involved. Dr. Elizabeth Donner explores the personal impact of SUDEP, the latest research statistics, and what resources are available to the community. Part of the CURE Leaders in Epilepsy webinar series.
What are some of the barriers that healthcare professionals have when talking about SUDEP?
One of the big issues has been the fear of healthcare providers that learning about SUDEP, that if they’re patients or parents of kids with epilepsy, learning about SUDEP, that they will actually be causing more harm than good, that the anxiety produced by learning about SUDEP will surpass any potential benefit. But there’s actually been some nice studies about this. There’s really no evidence that learning about SUDEP causes any undue anxiety or ha There has been some qualitative research done by my colleague Rajesh Ramachandran Nair at McMaster University where he’s talked to parents of children with epilepsy and people living with epilepsy about their interest in SUDEP information. They clearly have expressed a need for more information about SUDEP.
There has been a study out of Susan Duncan’s group in the UK that showed that, upon learning about SUDEP, there was no significant change in anxiety or worry related to their risk. That’s probably been the biggest barrier.
Talking about face down position, does this indicate suffocation? If so, are there things that can be done to prevent that?
I want people to think about the fact that when a person is sleeping and they’re in otherwise good health, if they roll over and their face goes into the pillow, and this probably happens to us a few times a night, what happens is, we’re not breathing well. Actually, our brain wakes us up and we roll over. You don’t suffocate while you’re sleeping because your brain has a mechanism to know when you’re not breathing well when you’re sleeping, and you wake up. What might be happening in some SUDEP cases is that, after people have a seizure, and many of you will know that often in the immediate period of time after a seizure, people can be, what we call a postictal state. Quite sedated, unresponsive like they’re in a very, very deep sleep.
It’s quite possible that the brain in that state is unable to respond to the cues that allow us to roll over when we’re breathing into our pillow. We don’t exactly call it suffocation because what’s happening is the effect of the seizure has made it such that the brain doesn’t wake up because the person is face down in their pillow. I hope that answers the question, and I recognize it’s a bit of a complicated explanation. With regards to the more practical side of the question around, well, does that mean that people would be safer if they just slept on their back all the time? There is some newer research coming out that shows that actually some SUDEP deaths people are found on their side or on their back position as well. Even if that was the case, it wouldn’t completely fix the problem, but there’s two important considerations.
One is that when we look at people who are having seizures, and we have the opportunity through our video EEG monitoring to review lots of people having seizures on videotape, we can see that most of the time in a generalized tonic-clonic seizures, the movements of the body causes the person to roll over onto their stomach. Even if you could convince the body to always stay sleeping on the back, it’s quite possible that during a seizure, a person flips over onto their stomach. The other is we move around while we’re sleeping. There are some tricks, different things you can wear and stuff that make it uncomfortable to sleep on your stomach, but even if we were to do that, it’s quite likely that the body flips over during a seizure. Unfortunately, I don’t think that’s been very well developed as a prevention technique.
Are there any wearable devices that could monitor epilepsy and that risk for SUDEP?
Something that gets a lot of attention, for sure, is the advent of all these new epilepsy monitoring devices. There are quite a few devices available to the general public that monitor for seizures. There really is no evidence that these devices actually reduce SUDEP risk. Now, of course, it’s difficult prove that because, practically speaking, you would need to give devices to so many people and then wait to see whether it reduces the risk of SUDEP. What we know about some of these epilepsy devices is that they can alert a caregiver when a seizure occurs. Then, what we need to then extrapolate from that is whether going to a person when they have a seizure, so the person who had the seizure, whether they benefit from the attention of a caregiver in the immediate post seizure period and whether that will reduce SUDEP risk.
I think it’s going to be almost impossible to prove that the devices can reduce SUDEP risk, but I definitely think that the devices have a place in alerting caregivers that a person has had a seizure, and that those can, at times, give peace of mind to caregivers. But we need to be cautious because devices can have both false positive and false negative alarms. Meaning sometimes the devices don’t pick up all the seizures and sometimes the devices pick up all sorts of movements that aren’t seizures and alarming all the time. Also, I’ll remind you that 10 of the 27 pediatric cases that I reported back in 2001, there was someone present with the child when they died. Just because there was someone there, they still are not able to save that life even if we’re alerted to seizures, it doesn’t mean we’re going to be able to save every life, unfortunately.
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