Epilepsy and functional/dissociative seizures: Dr. Wesley Kerr and Dr. Shruti Iyer

Reported by Nancy Volkers

In this Sharp Waves podcast episode “Epilepsy and Functional/Dissociative Seizures,” Wesley Kerr, MD, PhD, a statistician and epileptologist at University of Pittsburgh Medical Center, joins Shruti Iyer, MD, a third year neurology resident at University of Pittsburgh Medical Center, to discuss their recently published study on categorizing the probability of epilepsy in patients already diagnosed with functional dissociative seizures (FDS). The conversation highlights how this proposed framework may help clinicians better identify patients who could have coexisting epilepsy and improve diagnostic accuracy and treatment planning. The episode also notes that functional dissociative seizures were previously, and in some settings are still, referred to as psychogenic non epileptic seizures (PNES).

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Podcast Transcript

Host:
Welcome to Sharp Waves, a podcast from the International League Against Epilepsy. Our episodes cover epilepsy research, clinical care, career development, and issues in diagnosis and treatment from around the globe.

Wesley Kerr:
I'm Wesley Kerr. I'm a statistician and an epileptologist at University of Pittsburgh Medical Center. And I also run the functional seizure clinic or the non-epileptic seizure clinic here.

Shruti Iyer:
I'm Shruti Iyer. I'm one of the third-year neurology residents at University of Pittsburgh as well. I'm interested in epilepsy, and I'm applying to a fellowship in epilepsy this year.

Host:
Excellent. Thank you both for joining me. So we are going to walk through your study, which was recently published, and it is about... It's proposing a categorization of the probability of epilepsy in people who have already been diagnosed with functional dissociative seizures. Do I have that right?

Wesley Kerr:
You do.

Host:
Okay. Okay. And just for listeners, functional dissociative seizures previously were known as and may still be known as in some places as psychogenic non-epileptic seizures. They've also been called functional seizures, dissociative seizures. There are many names for them, but in this particular episode, we are going to refer to them as functional dissociative seizures, and I may shorten that to FDS just to reduce the number of words.

So I guess we should start by why you wanted to do this sort of study. What was the problem you were trying to solve or the issue that you were coming across that led to this paper?

Shruti Iyer:
Yeah, that's a great question. We have talked about that a lot. I think a large part, Dr. Kerr, but all of us tend to see patients with epilepsy and functional seizures. And we often see that patients are misdiagnosed in the beginning. If they do not receive a diagnosis, often placed on anti-seizure medications if there's any concern for seizures without trying to find out what type of seizures they may have.

These anti-seizure medications are not without any side effects. And a lot of these patients who may have functional seizures get exposed to these side effects that, you know, as we know, anti-seizure medications do not have any benefit in treating functional seizures. Additionally, they also, you know, because they're being treated with anti-seizure medications, do not often get the treatment that they do need to treat their underlying functional seizures.

So we were seeing a lot of patients who came to our functional clinic, which we'll talk a little more about too, who were on these anti-seizure medications and were not being treated appropriately for their functional seizures. So we were trying to develop a more structured approach to, you know, when you get a new patient, how you can think about do they have functional seizures, do they have epilepsy, and how you can think about their risk for co-occurring epilepsy and use that to manage their medications accordingly.

Host:
Excellent. Thank you. So in this study, the people in this study or the data from the study came from people who had functional seizures and you were looking at how likely was it that they also had epilepsy?

And you talked about five categories, I believe, of probability. Could you talk about those and maybe quickly walk us through them and how they're defined?

Shruti Iyer:
Sure, I can talk a little bit about them. So essentially, we tried to mirror the categories that are used for defining the certainty of functional seizures, the ILAE categories, and tried to use the same kind of way to approach developing these categories.

So we have the five categories from least likely to have co-occurring epilepsy to most likely, with it being unlikely, possible, probable epilepsy, clinically established, and documented.

So yeah, I can explain a little bit about the categories. So we came up with five categories to mirror the certainty of functional seizure categories as well, as per the ILAE.

So we have two categories out of these that are kind of in the extreme of unlikely and documented. So unlikely basically means that they are unlikely to have a risk of co-occurring epilepsy based on objective data.

And on the other end of it, we have two categories that have a higher risk of having co-occurring epilepsy, so documented and clinically established, with documented patients having an EEG documented epileptic seizure and clinically established having other objective data of an observed seizure or an EEG without video of an epileptic seizure.

We also have these intermediate categories of possible and probable, and those are based on the level of objective data that they have for epilepsy. So with possible, we go into risk factors, and with probable, we try to find any data, like whether they have EEG or imaging, that would be suggestive of co-occurring epilepsy.

Do you have anything to add?

Wesley Kerr:
I like all these things.

Host:
Excellent. Thank you. So just quickly, if you could talk about the methods of your study. So how was the data collected? Where did it come from? How many people are we talking about? And then any analysis that would be relevant?

Wesley Kerr:
Yeah. We wanted to focus on, since we're focusing on uncertainty for epilepsy, we want to be very clear about, yes, these people totally have functional seizures without a doubt.

So we included people with a really high suspicion of functional seizures, which means we've seen the seizure with an EEG and video at the same time, or a video by itself with really clear features, or an EEG by itself with really clear features.

And we at UPMC have a multidisciplinary clinic for functional seizures. And most of the patients were referrals to this multidisciplinary clinic. And there are some other sources for patients too of people who had concern for functional seizures or other indicators like ICD codes.

And we looked at all of their records to say what evidence do they have to put them in each of these categories. And we're mostly just describing what proportion of people are in each of these categories and why.

Host:
Great. So what proportion of people were in each of these categories? And were you surprised by the results or how did they relate to or compare with other data that you know of?

Wesley Kerr:
So the rates of these things have been widely varying across lots of different studies. So one of the benefits here is this structure helps us get these numbers well.

With the 480 people that were in this study, 63% of them were unlikely. So no evidence of co-occurring epilepsy. I'm not worried at all.

About 10% were yes, totally epilepsy. There's an EEG or almost as close to an EEG of totally has co-occurring epilepsy.

And then there was 16% who I'm worried about epilepsy substantially, interictal discharges, really big risk factors like MRI findings, those sorts of things.

And then the remaining like 10% are people who have subjective risk factors. Like they have nocturnal seizures during their sleep where they have shoulder dislocations, but they don't have any other objective evidence.

I was reassured about the majority of people not having co-occurring epilepsy. So that 63% was a number that I expected. And I think other people that I've talked to might be surprised by because it's a pretty high percent.

And sometimes when I talk to people, they have the false impression that almost everyone has co-occurring epilepsy.

Host:
Interesting. So you found about, well, I wouldn't say two thirds, but 63% were unlikely to have co-occurring epilepsy.

Interesting observations about the people who do have high evidence for co-occurring epilepsy?

Shruti Iyer:
Yeah, of course. I think I was, and, you know, when you were asking about the findings that were surprising, I was quite surprised that we had a fair number who were in the intermediate categories too, especially like Dr. Kerr mentioned, you know, about the patients who had, who we were a little worried about, people who had interictal discharges or MRI findings.

And if you kind of combine those with the documented patients, that brings us to a number of about 25% of the people, which was higher than I would have expected because, you know, the pathophysiology or the mechanism of having these two conditions are quite different.

So I didn't expect 25% of the people to have a high likelihood of having both these diagnoses.

Host:
So 25% is considered high, you said, or you would consider it high.

Shruti Iyer:
It was higher than I expected, but like Dr. Kerr was saying, you know, it's not the majority. So it's just something to keep in mind that we need to think about this when they come in. That doesn't mean that they all need to be treated empirically.

Host:
So these were people that were being seen at your functional seizures clinic. And there were a percentage of them who were in that middle ground where they might also have epilepsy. We're not sure.

This is not a question that I put to you, but it's a question that I thought of while listening.

Do you know anything about those people? Are most of these people on anti-seizure medications? Were they being investigated for epilepsy? Where would you take that in the clinic, I guess? If you found somebody had probable epilepsy or even possible, those are kind of the middle grounds, right? What would you do at that point?

Wesley Kerr:
That's a really good question. And that's part of the strength of this data set that we have longitudinal follow-up on these people to say what we think this might be.

With people with probable, they meet a definition of epilepsy in a lot of different ways. So generally you're asking, okay, you have seizures that might still be happening. Are these seizures epileptic? Are these seizures functional?

And trying to discuss with the patient, do we need to change medicines in response to any breakthrough seizures? And our threshold for changing medicines might be lower of like, ah, I'm tracking your nocturnal seizures. I know you have discharges. I might just treat you as if you have epilepsy for those seizures and then make sure I'm not over treating, say, daytime seizures that we know are functional.

On the other side, if possible, then you start discussing what are the things that we need to do to understand your seizures better so that we know what the right choice is. And I wouldn't be as ready to say, yeah, we totally need to treat this with seizure medicines.

I more think about, let's talk about home videos. If I can see a video of the seizure, even without EEG, I get so much information. Can I do an ambulatory EEG? Often that has EEG without video. That would add more information.

And when is the point that you have a new seizure type or a different seizure type that we need to do epilepsy monitoring unit on inpatient side and talk about what are those steps?

For some people where I'm really concerned, even if they have possible, I can start seizure medicines that have low risks before or pending that evaluation. But that's uncommon in the possible group.

It's pretty common that I will manage people with probable as I think these are epileptic, but we want to see.

Host:
Great. Thank you.

So you mentioned one of the strengths of this study was that it was longitudinal. Are there other strengths you wanted to mention or any limitations that you think are important?

Wesley Kerr:
The longitudinal is great. And the size of our study is pretty big. The 480 people with very certain functional seizures.

Our clinic started in 2023 and has a lot of referrals, which is great. So now we're up to something like 800.

Being able to describe the nuances of the population. The limitation is we are a subspecialty clinic and there's only 22 of us or somewhere around there in the United States.

So a lot of patients aren't seen by these subspecialty clinics, so they don't have clear evidence of functional seizures or there's other things going on of not being seen by a specialist or something else.

So we do need to do other studies to see how much this translates over to other specialty centers and more general neurology. This is our next steps.

Host:
Excellent. Thank you.

Yeah, you mentioned that there's only 22 of these subspecialty clinics in the United States anyway.

And I did notice in the study that people who were more likely to have epilepsy, so they had the documented, established, or probable, they had a longer time to diagnosis of functional seizures, which speculating to me says that they were diagnosed with epilepsy and it was treated as epilepsy and functional seizures was not on the table until some point in the future.

So could you discuss that and how does it tie in with these subspecialty clinics and are there other avenues for this type of functional seizure diagnosis?

Shruti Iyer:
In terms of the delay to diagnosis with these patients, I wonder if this may be because the epilepsy, you know, it depends on whether they have epilepsy first and then get the diagnosis of functional seizures.

And when these patients tend to have epilepsy first and get the diagnosis of epilepsy and get started on anti-seizure meds, any new seizure type they have is often thought to be an epileptic seizure as well without diving too deep into, you know, the semiology, whether this makes sense with their known epilepsy, if it is focal or lesional.

And I noticed that patients often empirically get increased in medications if they were having more seizures without taking a step back to stop and think, saying, hey, maybe there's a second type of pathology at play.

So that was one thing that I was wondering about when I noticed this delay in diagnosis as well.

Wesley Kerr:
To expand on that, it's hard to know when the functional seizures start when you have both. So it might look like it's longer because we're measuring the thing that started first, whether it was functional or epileptic.

And this emphasizes that if you're continuing to have seizures, probably people should be seen as a comprehensive epileptic center to understand their seizures.

We either understand their seizures as, oh, they also have functional seizures or they have entirely functional seizures. Or we should think about more modern medicines, more modern treatments like neurostimulation and epilepsy surgery.

So if someone's continuing to have seizures, we should look into them.

I was actually to think about the other side of the coin of the people with unlikely co-occurring epilepsy. I was really encouraged of the rates of people that did not start seizure medicines in the first place.

I think that's probably a big improvement over the past five or 10 years. People are identifying, ah, this person sounds like they might have functional seizures. Can I confirm that by seeing the seizure?

And we're getting shorter and shorter delay to diagnoses in those people with pretty clear functional seizures.

So that's an improvement. I think we're continuing to try to improve that overall. Those delays are still too long.

Host:
Excellent. Thanks to both of you. That's a really good point about the delay is seen as a delay from the first seizure, but I guess we are sort of assuming there that they have had functional seizures just as long as they've had epilepsy, which may not be the case.

So as far as a diagnosis of functional seizures, because you're a functional seizures clinic, can you talk a little bit about how the diagnosis is delivered and what impact that could have on the person being diagnosed as well as their family?

Wesley Kerr:
Super good question and super important.

This is our procedure. And as someone in the functional seizure clinic, I'm a little fancy in that most people have had their diagnosis delivered by someone else, so it's a general skill that all epileptologists, all people seeing people that have functional seizures need to develop.

What I think about is you understand the context that a lot of these people, they might have heard, “Oh, they're fine. Their EEG is normal. It's all in your head.”

And you need to understand that context to say, ah, validating their experience is great. What is the thing that I can hear from their story to help them understand? And how do I tailor my delivery of diagnosis to that?

An example that is super helpful is there are some people who have panic attacks and then they're like, “Oh, my panic attacks got so much better. I don't have them anymore, but I have these functional seizures.”

And then I can use the analogy that's really popular in the UK that's called “panic without panic,” where your body is in a panic attack, but the functional neurological disorder part of it is protecting you from feeling things. So you don't feel the panic in your body. It's just your body is in a panic mode.

And that is, ah, I'm validating your experience, understanding your history and saying this is how that's relevant to you.

If you're able to figure out how the patient understands it, believes it, and feels like it's a satisfactory explanation for their symptoms, you actually see lots of improvements in terms of healthcare resource utilization and reduced rates of them going to another neurologist to reevaluate this or saying, “Yeah, this neurologist didn't listen to me. They just told me I don't have epileptic seizures and go away.”

So spending time with these patients, trying to listen to them, validate their experience as much as possible helps you get them on your side, and then you can take care of them and figure out, get you the treatments you need and don't get the treatments that you don't need.

Host:
Excellent. Shruti, do you have anything to add about the diagnosis side of things?

Shruti Iyer:
That was great. I was also going to say I have seen in certain patients where just acceptance of the diagnosis in a way that they accept can itself be therapeutic, where I feel like how often they tend to have these seizures can sometimes improve just when they feel like they've been heard and if the diagnosis has been delivered in a way that they accept and find satisfactory.

Host:
Excellent. Thank you.

So my second to last question is, are there key takeaways from this research for either clinicians or people with epilepsy or people with functional seizures or people with both that you would like to share with listeners?

Wesley Kerr:
I think this is great. The most important thing I see is that most people with functional seizures do not have co-occurring epilepsy.

And being able to clearly say that, I understand your seizures well enough to know you don't have epilepsy, you don't need these other medicines for that purpose. You might need them for other purposes.

The other part is validating the other side. There are definitely people who have both. And these are the things that we're looking for. These are the objective evidence to say, yeah, I think you have both.

And in the paper, we describe this more of how do you do patient-centered decision-making of when do I need to change anti-seizure medicines? When do I need to do more diagnostics to say which one is the current problem or both?

So setting these criteria helps us have a structure, one, to talk with patients, and two, to do other studies to say, what is the burden of this in people who clearly have both epilepsy and functional seizures? What's the different outcomes for people that have no evidence for epilepsy?

So those are key things that hopefully move the field forward.

Host:
Shruti, did you want to add any key takeaways?

Shruti Iyer:
No, that was actually excellent. And yeah, I think the big takeaway is also as much as possible, if we can use this information to guide conversations and decisions to continue or discontinue medications.

So that was, I think, my key takeaway that I wanted to pass on.

Host:
Yeah, that's important. Something you mentioned at the beginning that we haven't really spoken about is that there's a percentage of people who are unlikely to have epilepsy who are taking anti-seizure medications that they don't need.

So this would be a framework sort of establishing who are those people and then working to get them off those medications.

Shruti Iyer:
Yeah, I also wanted to add, you know, I know we all know and there's been new guidelines to say that these anti-seizure medications do not treat functional seizures, but we also notice, and this is a paper we're hoping to put forward in the next couple of months, is that a lot of these patients continue these medications for other reasons.

And for example, a lot of patients remain on topiramate if they have migraines or lamotrigine if they have bipolar disorder.

So we're looking further into that to see if some of these patients who do continue their medications are the medication helpful for something else.

Host:
Great. Good point there.

Anything else that either of you wanted to add that we didn't get to?

Wesley Kerr:
I think I would highlight that there's lots of good things that we can do in this field of functional seizures versus epilepsy and highlight that Shruti is a PGY3 doing good things.

So this field is a great way to get involved and think about how do you talk with patients? How do you communicate? And there's lots of questions that we can ask and have big clinical impact and do that at any level of training.

Host:
Great. Thanks to both of you for being here. Really appreciate it.

There will be a link to the paper in the show notes and in the transcript. So you can find it if you want to read the entire paper.

And thanks again.

Shruti Iyer:
Thank you for having us.

Wesley Kerr:
Thanks for having us.