An update on SUDEP and SUDEP counseling: Dr. Suvasini Sharma

Reported by Dr. Emma Carter |  Edited and produced by Nancy Volkers

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Cite this article: Carter E. An update on SUDEP and SUDEP counseling: Dr. Suvasini Sharma. Epigraph 2023; 25(2): 87-94.

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Sudden Unexpected Death in Epilepsy (SUDEP) affects about one out of every 1,000 people with epilepsy. Dr. Emma Carter spoke with Dr. Suvasini Sharma about SUDEP, why it's important to inform patients and families about it, and how to manage risk factors.

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

Podcast Transcript

[00:00:00] Emma Carter: Thanks, Dr. Sharma, for being here to talk to us about SUDEP today. I was going to give you the floor and let you tell us a little bit about yourself.

[00:00:09] Suvasini Sharma: Thanks, Emma, for this invitation. I'm very happy to talk on this platform about SUDEP. My name is Suvasini. I'm a pediatric neurologist and epileptologist. I work in New Delhi, India in a common sponsored teaching hospital for children. And I have been working with children with epilepsy for the last 15 years.

And my research interests include the ketogenic diet, drug-resistant epilepsy, infantile spasms, and also SUDEP. I got involved in SUDEP in the last five or six years, when I realized that this is one topic which nobody really in India has much bothered about. I started with a family experience, which got me interested in this topic. The family wanted answers, but unfortunately we don't have any autopsies, any such systems in India, and there's really hardly any awareness even amongst neurologists. So that got me interested. 

We did a study on parental counseling of parents of children with epilepsy regarding SUDEP and how it impacts them. And we found that in fact rather than increasing anxiety, it was actually improving their confidence in managing the children and it was improving their behaviors. I'll talk about this later in detail. So that got me interested. And then I got involved in the ILAE task force. We've been working for the last almost two years now. We are involved in a number of activities for SUDEP advocacy and education. 

[00:01:43] Emma Carter: Wonderful. Thanks for sharing a little bit about you and, and your involvement with the SUDEP task force. I'll ask you a little bit more about that here too in a second. I was just going to start out and ask you if you can define sudden unexpected death in epilepsy, what we call SUDEP, for our listeners. 

[00:02:02] Suvasini Sharma: Yeah. I mean the short definition with SUDEP is that it is defined as a sudden and unexpected—we don't call it unexplained anymore, we do know that there are explanations for it—sudden and unexpected, non-traumatic and non-drowning death of a person with epilepsy without a toxicological or anatomical cause of death detected during the postmortem examination. 

This is a broad definition and there are some certain subcategories. Because not everyone gets a postmortem done, for example, especially in low-resource settings. Most postmortems we have are the medical legal ones where some foul play is suspected in a natural death. Mostly it's hardly ever done. 

So the first category is definite SUDEP.  Definite SUDEP is a sudden unexpected death witnessed or unwitnessed, non-traumatic, non-drowning death occurring in benign circumstances. It is non-suspicious circumstances in an individual with epilepsy, with or without evidence of a seizure. So seizure may or may not have occurred. But excluding documented status epilepticus, because people with epilepsy can die even because of status, but that is not considered SUDEP. And in which a postmortem examination does not reveal a cause of death. So that is definite SUDEP. 

So there is a category of probable SUDEP. Everything else is there in the definition, except that there is no autopsy evidence. But when we get a verbal autopsy and you get a whole description, and everything sounds like a SUDEP, then you call it a probable SUDEP. 

Then there are patients who may have, like when the autopsy is done, something else may be also found, not as a cause, but maybe some coronary artery disease is found, maybe some obstructive pulmonary disease. So there can be various pathologies which could also have contributed, not as the cause, but also may have been associated. These patients are said to have SUDEP plus. So definite SUDEP plus is when this is autopsy confirmed and probable SUDEP plus is when you know there's a history of some other comorbid disorder, which may have contributed.

And then there is a category of a possible SUDEP, and the competing cause of death is present. And also a category of near SUDEP or near SUDEP plus, when the patient has been revived. The whole event happened, but the patient survives with resuscitation, that is a near SUDEP.

And finally you have not SUDEP, when there's a clear cut another cause for death, then it's not SUDEP. So these are the categories, and these are used by people who adjudicate these deaths in people with epilepsy and they try and classify. But it's useful to know, especially for research purposes.

[00:04:46] Emma Carter: Wonderful. Thank you for sharing the definition, all those definitions. 

[00:04:50] Suvasini Sharma: So yeah, I will just also talk about the incidence here. So yeah, it's not very common. That's the thing we need to understand, that it's rare. So the incidence in both adults and children is 1.2 per thousand. So every year out of a thousand people with epilepsy, one person will die.

Now this risk is much less than risk of dying from, say, a road traffic accident. Or coronary artery disease. So it's rare, but it's still there, so we need to know about it. 

[00:05:18] Emma Carter: Absolutely. Very important part to include the incidence. Just wanted to jump into a little bit about the pathogenesis of SUDEP. There are many theories that are proposed such as cardiovascular etiology, respiratory control etiology, autonomic dysfunction, prone position. Those are a few of the proposed theories. Can you share your thoughts about some of these proposed mechanisms? 

[00:05:43] Suvasini Sharma: These mechanisms that you mentioned, like cardiovascular, respiratory, autonomic—they are not mutually exclusive.

So they might coexist in different people, and they might cascade as well. So it's actually a final common pathway with each death, and they're all involved in some way or the other to different degrees in different patients. I will start with the heart mechanisms. Both the seizures by themselves, the acute seizures, and chronic epilepsy can affect the heart. So acute seizures we know are associated with tachycardia and catecholamine storm. So that of course, leads to coronary artery problems and things, so acute seizures themselves are not good for the heart. But chronic epilepsy affects the heart in a number of ways.

First of all, the cortical and subcortical areas are related to cardiac function through their influence on the autonomic nervous system. And the autonomic nervous system is a final effective pathway which modulates cardiac activity. So certain structures in the brain, which are the structures which are involved in epilepsy, have the most prominent role in controlling the autonomic function. And these include posterior insula, cingulate cortex, prefrontal cortex, and the amygdala. So these are structures which are frequently involved in chronic epilepsy anyway. 

Plus with repeated seizures, each seizure would cause a heart rate and blood pressure abnormality, trans myocardial ischemia, and a lowered arrhythmia threshold. And ultimately, this repetitive catecholamine-induced injury leads to something called the formation of an epileptic heart. This epileptic heart is a terminology which is used to characterize a heart with chronic heart and coronary damage, resulting in myocardial fibrosis, accelerated atherosclerosis, systolic and diastolic dysfunction, and arrhythmias.

And of course, not to mention the problems caused by the lifestyle issues in these patients and also the anti-seizure medications. So, cardiac is actually, it's a huge part of SUDEP pathophysiology. 

In the respiratory system, people with chronic epilepsy have a high frequency of central and mixed apneas. Obstructive apneas can also occur because of laryngospasm and seizures, so this is hard to characterize. Similar to the cardiac autonomic dysfunction, the respiratory system also can have autonomic dysfunction. The seizure networks connect the cortex to the brainstem and these networks cause autonomic dysfunction. So amygdala activation has been shown to cause apnea in animal seizure models. And there's a reduced functional connectivity between the amygdala and the brainstem in patients with chronic epilepsy.

Also, post-ictal apneas occur more commonly in seizures occurring from sleep. Because in sleep there is a reduced chemoreceptor sensitivity. So the post-ictal state during sleep, there is a definite arousal deficit and post-ictal immobility. 

And the prone position is not the primary cause of death in these patients. The prone position usually occurs, it's an ictal turning prone, but once they turn prone, then of course, the recovery reflexes are not very well preserved in these patients in that post-ictal state during sleep, there is a brainstem spreading depression. And ultimately what is called the post-ictal generalized EEG suppression. So ultimately, this is called neurovegetative shutdown, shutdown of all the vital functions such as respiration and cardiac activity.

And finally, in addition to this, there's also neurotransmitter dysfunction in these patients, especially the serotonergic dysfunction in the raphe neurons of the brainstem. And the adenosine and the indigenous opioids. There might be dysfunction of these neurotransmitter pathways as well. 

[00:09:45] Emma Carter: Very comprehensive. No, thank you for going through each of the proposed mechanisms. Just wanted to jump into a little bit about SUDEP counseling and ask you about the American Academy of Neurology and American Epilepsy Society practice guidelines with SUDEP counseling.

[00:10:03] Suvasini Sharma: So these guidelines came earlier than the recent studies of the epidemiology. They mentioned five points. So first was for children, then adults. So for children, they say clinicians caring for children with epilepsy should inform parents and guardians that in one year, SUDEP will typically affect one in 4,500 children. They also clarify that means that 4,499 children will not be affected.

So give the positive message as well because we all tend to look at the negative aspect first. And similarly in adults, clinicians caring for adults with epilepsy should tell them that one in 1,000 adults will be affected per year. But again, that means that 999 will not be affected. 

The recent studies have shown that the incidence in adults as well as children is similar. So we probably should change it to say, one in 1,000 for children as well. It's not one in 4,500. 

The third point is that if a person continues to experience GTCS {generalized tonic-clonic seizures], clinicians should do active management of the epilepsy and all therapies to reduce seizures. While, of course, incorporating patient preferences and weighing the risks and benefits of any new approach. But we have to keep trying. These are the patients we need to be very aggressive about managing seizures, especially the generalized tonic seizures. So again, they have not specifically mentioned, but this obviously means surgical evaluation and maybe neuromodulation and of course keep trying drugs. This is something we need to be very aggressive about. 

And the fourth point is that, for patients who have frequent GTCS and nocturnal seizures, clinicians may advise selected patients and families, if permitted by their individualized epilepsy and psychosocial circumstances, to use nocturnal supervision or other nocturnal precautions, such as the use of a remote listening device to reduce SUDEP risk, because nocturnal supervision is the one proven modality to reduce SUDEP risk. So we have to talk to them and then of course, depending on their social circumstances and cultural issues, they decide whether they're able to do it or not. But it's our job to inform them about this. And finally, the good thing also in people with epilepsy who are seizure free, it's our job as clinicians to inform them that if you're seizure free, especially free from GTCS, then you have a definitely very low SUDEP risk. 

[00:12:35] Emma Carter: There have been some recent studies that have been published about providers’ concern with increasing patient anxiety when discussing SUDEP at a time of, or soon after the diagnosis.

However, literature supports that patients would prefer to know about SUDEP at the time of or soon after the diagnosis. In the clinical setting, when and how do you recommend SUDEP counseling be performed? 

[00:13:01] Suvasini Sharma: So again, I think it depends on different settings, amount of resources and time that the clinicians have, and if they have other support staff, like counselors and epilepsy nurses.

I usually feel that at the time of diagnosis, there's already so much information that needs to be given about the epilepsy itself, the management, the drugs, the lifestyle. So to talk about SUDEP at the very first setting itself, I think it becomes too much for the family to take in. So what I usually do is I give the diagnosis and the management of epilepsy, and then we usually give them some material, literature, to go through, that also includes a brief mention of SUDEP. And during the second or the third visit, when they're more comfortable with the diagnosis, they're more settled, that is the time I start talking about SUDEP, because I think the first visit is overwhelming at that time. 

I would not wait six months or one year. I would not wait to see if the patient is drug resistant and then talk about it. But not during the very first visit, but maybe the second or the third. 

[00:14:05] Emma Carter: Tell us, I know there are, you know, misconceptions and challenges about SUDEP counseling. What do you find in your practice, some of those most common misconceptions and challenges? 

[00:14:18] Suvasini Sharma: So the misconception amongst physicians is, they're all scared about increasing parental anxiety. So they say, on the one hand we tell them that your child is fine, they can do all the activities, some of them under supervision. We tell them that the child should lead as normal a life as possible. And on the other hand, you tell them that your child can die. So that is the physician's worry. That is one of the big challenges. 

The other challenge, especially in Indian culture, is that somehow talking about bad things, unpleasant things, is kind of taboo. It's like you talk about a bad thing and a bad thing happens. That's the thing in people's minds. So you don't want to talk about death, but when we interacted with the parents, we found that it's there in their mind all the time anyway.

So it's there in their mind and it's good to bring it out in the open and tell them that the risk is so much lower than what they feared. And then they know, they get a sense of control that some things they do can prevent it.

And we did find that once we counseled the parents about how we can prevent and what helps, we did find that compliance improved. The timing of medications improved, their frequency of hospital visits. They did not miss visits. So ultimately, it was a big factor in improving their management of epilepsy. It also gave them a sense of confidence and control. So I think what, and many major studies have shown this, that what physicians worry about, parents and families and patients really want to know. And we are more worried than we need to be when talking about it. 

The other challenge I would say definitely is the question of time. Especially in our very heavy settings. Like, I mean, in a three- to four-hour clinic, sometimes I need to see 50 patients. So it's really not possible to talk so much in detail. That's why we give them literature and now we've made short videos also, which they can see. Once they have gone through all of it, they have some idea, and then we talk about “What do you understand?” Talk, give them the risk, and that saves time. Rather than telling them everything by ourselves. But it's important to tell them. Definitely. 

[00:16:35] Emma Carter: Do you, when you see patients and you're going through SUDEP counseling, do you document or use any tools to stratify each patient's risk factors for SUDEP? 

[00:16:45] Suvasini Sharma: There are definite risk factors which are known, like frequent GTCS, comorbidities like intellectual disability or developmental delay. And more than 50 seizures per month in the past year. So there are many risk factors, but practically I don't really sit with the tool. When we see the patients, we know that we have well controlled and poorly controlled, so broad groups. And then the poorly controlled ones, we have the ones with frequent GTCS and developmental delay, which is a frequent comorbidity in children with epilepsy. So yeah, those patients definitely, I think in them we just reinforce the counseling better, like more frequently perhaps. And if we feel that there's certain preventable things the parents are missing, we can reinforce that. Like especially compliance, drug compliance and things. 

Supervision is usually not much of a problem with children, and especially in India, cosleeping is extremely common. So these children anyway would be sleeping with their parents. So that's never an issue. 

But I would say for the well-controlled patient, it would be like maybe a one-time mention and brief if they're worried about it. But the, the difficult, the high-risk patients, this counseling should be perhaps more frequent. We don't leave it with just one mention of it.

[00:17:58] Emma Carter: Do you have a sense of how many people diagnosed with epilepsy die of sudden death that may instead have had a primary cardiac problem? 

[00:18:10] Suvasini Sharma: Yeah, so this, yeah, I try to find this answer because like, you know, even normal people suddenly die. You do hear of so and so-and-so, and they say, we say they had a heart attack.

It was a, you know, they died. We assumed they must have had an MI and they died. So even people with epilepsy, in fact, they do have an increased risk of sudden cardiac deaths, as these deaths are called. The increase is like, a person with epilepsy is 2.29 times more likely to die of a sudden cardiac death than a person without epilepsy.

But this is likely because of ischemic heart disease. This is the figure that was seen in various studies but there is no data whether these patients actually had syncopal seizures or, you know, cardiac events before. This is a comorbidity, I would say, like in particular age groups, and any ischemic heart disease is also pretty common, so they may coexist with increasing age and plus of course the effects of drugs and anti-seizure medications, which also alter the lipid profile. Atherosclerosis also is more common, so this can be a comorbidity. 

[00:19:26] Emma Carter: Are there any anti-seizure medications you avoid in patients given cardiac side effects? And if they have a higher risk of SUDEP? 

[00:19:35] Suvasini Sharma: Yeah, there is a worry with the lamotrigine and sodium channel blockers because in some retrospective studies it was found, and especially animal work, that lamotrigine might be increased risk of SUDEP. And the FDA recommends that lamotrigine and sodium channel blockers should be used with caution in patients who already have an underlying structural or ischemic cardiac disease. So in a patient with a pre-diagnosed heart disease, definitely we would be very cautious with these medications and probably not use them.

But there's a very large study published from Australia wherein they followed it. They had the EMU data and followed up the patients for SUDEP risk, patients with an and lamotrigine and sodium channel blockers. And it was not found to have an increased risk. The study was a follow-up study for almost for 16 years.

And there are other population based studies which again, did not demonstrate an increase. So these are reassuring to clinicians. Because the risk of SUDEP with, just because of these medications, is likely to be low.

So ultimately, the GTCS is more likely to cause SUDEP and these medications are actually good for GTCS, right? So we need to balance the risks with the benefits . So ultimately, I think if there is an underlying heart disease, which we know about, then yes, we will not use them, but just if the patient is at high risk of SUDEP, probably to control GTCS, these medications may actually be needed, so we should not be worried about the risk and not use.

[00:21:06] Emma Carter: Wonderful. That's a very interesting article that you mentioned from Australia.

Jumping back into the questions here What should be highlighted or included about SUDEP prevention and patient counseling? 

[00:21:19] Suvasini Sharma: So I would say two major things. The compliance with the anti-seizure medications. I think that's an important risk factor because that is something which is in our hands. We cannot change the comorbidities and things. So that is one thing which we can definitely reinforce. And the other thing is nocturnal supervision, if and when possible. These are two things which can help and which are doable, which are in our control.

There are many seizure detection devices available in the market, which use different modalities like, you know, EMG active surface, EMG, ECG, and other things.

I'll not talk about particular devices, but uh, so the ILAE and IFCN, the International Federation of Clinical Neurophysiologists, have recently in 2021 given recommendations for their use and I'll talk about them.

They recommend using clinically validated wearable devices for automated detection of GTCS and focal to bilateral tonic-clonic seizures when there are significant safety concerns, so like if a patient sleeps alone, so those are the patients. And if the alarm rings and something can be done within five minutes. So both things are there. Just having this device is not going to help. Right. There's somebody, there has to be a plan in place, what to do when the alarm rings.

This recommendation is weak and conditional because we don't have any data whether wearing these devices is actually preventing SUDEP. We don't have any data regarding that. We do know that they detect seizures and there can be false alarms, there can be quality of life issues, like even for the person who sleeps in the other room, if the alarm keeps shrieking every night. And like I said, if the person's staying alone in a flat and the response time is going to be like 15, 20 minutes, it may not be of use. 

[00:23:19] Emma Carter: As a member of the International League against Epilepsy SUDEP Task Force, I know you mentioned you guys have been meeting for about the past two years. Just curious if you can share some of the activities the group is promoting globally at this time. 

[00:23:35] Suvasini Sharma: Yeah. So we are basically working on two documents. One is a consensus document on SUDEP counseling, and the other is to frame the definition and classification. Other than that, we are in the process of doing a number of educational activities on SUDEP for physicians and patients and families. We have put in proposals in various conferences to increase awareness of SUDEP for various SUDEP sessions.

Recently Dr. Rainer Surges has led a global survey of wearable seizure detection devices. And our group hopes to submit it soon. It was interesting to find that hardly any country actually has guidelines for these seizure detection devices. So there are issues that guidelines are needed to provide reimbursement and things like covering by insurance, so many things.

So these guidelines are definitely needed for national guidelines at each country level. 

[00:24:29] Emma Carter: Wonderful. Any last-minute takeaway points that you'd like to share with our listeners today, Dr. Sharma? 

[00:24:38] Suvasini Sharma: Yeah, so I will just say talk about SUDEP to patients and families.

This is highly neglected and so I think this is something which the families want and something we are not doing as much as we need to do. 

RESOURCES:

SUDEP information for families from the ILAE (ilae.org)

AAN Guidelines on SUDEP counseling (2017; reaffirmed 2020)

Directrices de la AAN en español

AES Position Statement on SUDEP counseling (2019)

Sudden Unexpected Death in Epilepsy (SUDEP) - What pediatricians need to know Garg D & Sharma S, Indian Pediatrics, 2020

Effect of counselling of parents of children with epilepsy focusing on sudden unexpected death in epilepsy Kumari S, et al., Epilepsy Research, 2022

Counseling about sudden unexpected death in epilepsy (SUDEP): A global survey of neurologists' opinions Asadi-Pooya AA, et al., Epilepsy & Behavior, 2022