NES Webinar Seizures

Non-epileptic Seizures: Diagnosis, Treatment, and Management Strategies for Patients and their Families

An epilepsy diagnosis usually occurs after an individual has suffered several unprovoked seizures. The diagnosis is then confirmed by a test known as an electroencephalogram (an EEG for short). However, there are cases in which individuals experience symptoms similar to those of an epileptic seizure without any of the unusual electrical activity detected in the brain. This phenomenon is known as a non-epileptic seizure (NES). While the physical signs and symptoms of NES may be similar to epileptic seizures, these patients do not respond to anti-epileptic drugs and therefore require different treatment options. Up to 20% of those diagnosed with epilepsy actually have NES.1

This webinar educated viewers on how to recognize the signs, symptoms, and history associated with the presentation and diagnosis of NES, how to discuss the diagnosis of NES with patients and families to enable acceptance of treatment, and identify the management options available for patients with NES and their families.  

The webinar content is intended for everyone, including persons with epilepsy, their friends and family, and caregivers.

1. Krumholz A, Hopp J. Psychogenic (nonepileptic) seizures. Semin Neurol. 2006;26:341-350. 

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Professor Curt LaFrance JR Speaker Non Epileptic seizures NESAbout the Speaker: 
W Curt LaFrance Jr., MD, MPH, is Director of Neuropsychiatry and Behavioral Neurology at Rhode Island Hospital and Professor of Psychiatry and Neurology at Alpert Medical School, Brown University. He is a staff physician at the Providence VA Medical Center, and Clinical Lead for the VA National Telemental Health Center Tele-Seizures clinic. His research focuses on developing new biomarkers and treatments for neuropsychiatric aspects of epilepsy, TBI, and more. 

Q&A with Dr. Curtis LaFrance Jr.

It seems like epileptic seizures may come and go, based on the experience of our audience. If none-epileptic seizures reoccur, are epileptic seizures are also likely to reoccur? There seems to be an interest in understanding that connection, if there is one.

Dr. Curtis LaFrance: So we follow people over the course of time, and what we found, interestingly, is there can be periods… what we call periods of quiescence, or quiet periods, where there’s no seizures. This can be for epilepsy or for non-epileptic seizures. In taking the history, in talking with people, we’ll say… They’ll come back, and they’ll say, oh, I just had a flurry of seizures again. This could be epileptic or non-epileptic seizures. The question is, anything different recently?

More times than not, what we’ll hear is, well, actually, I was getting ready for a final, and I pulled an all-nighter. And then after the final, I had the seizures again. This could be for epileptic or for non-epileptic seizures. As you’re aware, sleep deprivation is one of the ways that we actually induce seizures, whether epileptic or non-epileptic seizures. So I’ll see what we’ll call environmental changes. That can be after a period of a quiet period, and then a flurry again, or recurrence, sometimes environmental. Sometimes it can be physiologic changes in the person.

I see this from kids, to adolescents, to adults, I see this with other medications being added, bodily changes happening, all kinds of things. And then the physiology changes, and that has an effect on the way that the medications that the individual is taking is processed, what we call the pharmacokinetics and pharmacodynamics in the in the system. So a few different ways that seizures might recur.

Could there be age-related factors, from childhood to adulthood, that can induce more non-epileptic seizures? There was also a question about whether trauma, for example, having wisdom teeth taken out, can that induce? That’s a pretty big stressor in a young person’s life. So it sounds like that, yes, those certainly can influence the occurrence of non-epileptic seizures.

Dr. Curtis LaFrance: Yes. You said a very important word there, you said stressors in their life. So I’ll hear this from some people, they’ll say, but doc, I wasn’t even stressed, and I had the seizure. So I’m not talking about stress-induced seizures, I’m talking about life stressors contributing to the formation. What I mean by that is, sometimes it’s not in the ramped up period, where a lot of things are happening in life, or somebody just had a procedure, or a surgery, or something like that. They do happen postoperatively. I’ve seen them coming out of anesthesia, non-epileptic seizures. But also, after procedure, like wisdom teeth extraction… But it also happens in what I call the letdown period. What I mean by that is, I’m on the beach, and I’m with my family, and it’s wonderful, and I had a seizure there. What’s that all about doctor? So sometimes people, when they’re in the ramped up stage, they’ve got their defenses up, and then they’re when they’re in the letdown stage, then their defenses are down, and that’s where the seizure may occur. So there’s not a one-to-one relationship of, I was stressed out, I had a seizure. It could be in different types of environments. So I refer to life stressors, life events… we’ve all got life events.

One thing that people hear, is that we’re not seeing an EEG signature, but it’s because the the seizure is occurring deep in the brain, and we just can’t pick it up. How would you respond to that?

Dr. Curtis LaFrance: I would say there are some seizures that… There are some locations, or foci, in the brain that elude scalp EEG signal. So what I mean by that is if you’ve got a what we call mesial temporal, or some frontal lobe seizures, epileptic seizures, they actually… you can have the epileptic seizure, and the scalp EEG is not going to pick up that abnormal brain cell firing, epileptiform activity. So in that case, it’s not that it’s not epilepsy, it’s that the focus eluded the scalp electrode. So we’ve got a clue there, though.

Just because you haven’t had a normal EEG doesn’t mean it’s not epileptic seizures. We’ve got a clue, though, and we use the term semiology, ictal semiology, and all that means is the physical characteristics of the seizure. There are certain ways that frontal lobe epileptic seizures present, characteristically, that differ from psychogenic non-epileptic seizures. Even though both of those might have scalp negative EEG, we can look at the ictal semiology, the physical characteristics of the seizure, and we can make a comparison.

That’s why you heard me say earlier, the right history, with the right witnessed seizure, with the right EEG, those are the ways that we get the documented… That’s how we get documented non-epileptic seizures. If we have the seizure characteristics, even though it’s a scalp negative EEG we may say, hmm, this looks more like frontal lobe epilepsy than it does psychogenic non-epileptic seizure, just because I’m watching the seizure myself. That’s the importance of the video EEG.

How do we find providers were trained to provide these therapies in our states or regions?

Dr. Curtis LaFrance: I would say start with your local epilepsy center, send them an email and say, do you have people who are trained in treatment for non-epileptic seizures? Now, that doesn’t mean that they were trained with taking control of your seizures workbook, they may have their own approach. What I showed you was just one of a number of approaches. So this is not the be all and end all for everybody. There may be places around the country, who say yeah, we’ve got somebody who’s been treating people for 20 years, and they use this approach.

I would say start with your local epilepsy center, your local epileptologist. If there’s a neuropsychiatry department, sometimes they’ll do overlap brain and behavior, and you can contact them. Those are the main resources… I would say start locally. And then, sometimes people will email and they’ll say, do you have somebody trained in Michigan? Oh, yes. Well, there’s actually Dr. Baim, who’s trained in Michigan, and this person’s in Stanford, and this person… If you’re talking about treatment with the workbook, then that’s how that’s listed.

To start with the epilepsy center and move on from there. Of course, CURE Epilepsy is also helpful, willing to try to help find resources as well, if we can make connections. We know that this is an area of great struggle for people, and less identified providers. Another question is, are non-epileptic seizures ever a diagnosis that can be removed from a patient’s problem list? This is something that needs to be on the radar now and indefinitely.

Dr. Curtis LaFrance: I view seizures, whether epileptic or non-epileptic seizures, as a chronic medical illness.

I’m thinking now of the International League Against Epilepsy’s more recent definitions for epilepsy. Before, there wasn’t a great definition for resolved, but now there’s a category for resolved epilepsy. So just as there’s a category for resolved epilepsy, you can have a category for non-epileptic seizures. That’s not official from the ILA per se, but I’m thinking, in parallel, what’s been done for the new diagnostic criteria for epilepsy and terminology, that could also be done for non-epileptic seizures.

Here’s what I will say. Life events are still going to keep happening, life is going to keep happening. Somebody is going to get sick in the family, a bill is going to come due that you didn’t expect, the car is going to break on the day that you don’t want it. That’s always going to keep happening. The treatment that we… The tools that patients get with the workbook, they have to keep applying those tools.

The way that I demonstrate that to patients is, if they have readers, then at the end of the treatment, I’ll say, okay, read this sentence, and they’ll read it. And I’ll say, now take off your glasses and read the next sentence, and they can’t read the sentence. And I’ll say, the glasses didn’t cure you. You have to have the glasses on for you to be able to read, you have to keep using the tools for you to be able to address the stressors, the ongoing life stressors.

So people can go for extended periods… I’ve had this and people who’ve been in our prior studies. They’ve come back two or three years later, and they’ve said, the stuff came back. And I said, how are you doing with this, what’s going on in life, and how are you using the tools? And they said, life has gotten a lot harder, I just had two kids, and I’m not using the tools. I forgot about. So there’s a little booster, and that booster is the thing that helps them to get back on track to use the tools again to address life events that are going to keep happening.

People have asked about the role of psychogenic seizures, non-epileptic seizures, and post traumatic stress. I think you’ve already touched on this a bit. It’s not just the current life events that are happening, but the sequelae, as well, and using these tools to address that. Correct?

Dr. Curtis LaFrance: Yeah. So people will refer to the various comorbidities or co-occurring illnesses. I didn’t put the slide in, but you’re probably already familiar. We’re talking about epilepsy now. Anywhere from a third to a half of patients with epilepsy also have depression. Anywhere from 20 to 40% of individuals with epilepsy also have anxiety. Anywhere from a third to a half have cognitive issues with epilepsy. So, these are comorbidities, neuropsychiatric comorbidities that occur with epilepsy, very similar in non-epileptic seizures.

So you’ve got about half of the people have comorbid depression with non-epileptic seizures, about half have anxiety. 40% of civilians, and up to 70% of veterans have PTSD, as you would expect, with non-epileptic seizures. So a lot of comorbidities. So it’s not just about treating the seizure. That’s why I was saying earlier, you’ve really got to treat the whole patient.

Can there be a false diagnosis of non-epileptic seizures? Why and how?

Dr. Curtis LaFrance: The answer is yes, and it can go either way. You can be diagnosed with non-epileptic seizures, and it can be epilepsy, or you can be diagnosed with epilepsy, and it can be non-epileptic seizures. I’ve seen both of those. I’ve mentioned with one of my early distance mentors was Orrin Devinsky, and he said early on, Curt, you have to approach a patient with seizures with humility, because you can be fooled either way. So people can say, oh, well, I’ve seen that ictal semiology, I’ve seen the physical characteristics of that seizure, and that’s got to be a pseudo seizure, they said in a dismissive manner.

You know what? Number one, it’s not a pseudo procedure, and number two, it was actually a very odd manifestation of a frontal lobe epileptic seizure. Conversely, you can have somebody it’s like, wow, that’s a story for epilepsy, I’m going to treat them for two or three years with anti-seizure medications for presumed epilepsy. Nope. This was not epileptic seizures. The AED’s are not going to help the individual.

It keeps you honest as a clinician. You can’t go and say, I’ve got the answers. I wrote a textbook on it, and still sometimes I’m scratching my head saying, hmm, I wonder about this. Let’s take a tincture of time. Let’s use a tincture of time to try and figure out, let’s see what you’ve got. That sometimes is the best medicine.

Do none-epileptic seizures present during sleep?

Dr. Curtis LaFrance: The answer is yes. The devils in the details here. So, epileptic seizures can arise out of physiologic sleep. Non-epileptic seizures can occur during the nighttime, when a person is sleeping. Those are two different statements. The way that we figure that out is if both of them can occur at night, both of them can occur while people are sleeping. But what I mean by that is, we look at the tracing on the EEG. As many of the individuals know, the EEG changes when we’re in sleep and out of sleep stages.

So what happens is, we’re watching somebody, and then there’s an arousal, so they become awake, out of sleep, and then they have their non-epileptic seizure. That’s how we see that. But we really need the EEG that corresponds to the video to be able to say, oh, you know what, there was an arousal, so they were awake, even though it was at nighttime, when they were sleeping, and it was a non-epileptic seizure, as opposed to literally coming out of physiologic sleep and treated to a seizure. More times than not, it’s going to be epilepsy.

Do you have to have regular events in order for them to be classified as non-epileptic seizures, or can very infrequent events still be characterized as such?

Dr. Curtis LaFrance: I’ve seen people who have them once a year, and I’ve seen people who have 30 in a day. So I wish it was that simple, it would make my job a lot easier. But no, it’s never that simple. So we really have to pay attention to how often are these occurring? When are they occurring? In the workbook, we have a thing called a seizure log, and that’s where the individual really pays attention to their symptoms. So every day, they’re documenting, I had one seizure at 12:00 PM, 12 noon, in the kitchen, after I was preparing breakfast, and it had this effect on me. So we get them to start paying attention, whether it’s an epileptic or non-epileptic seizure.

And then when they start to pay attention to what’s happening, and what might be a precipitant to the seizures, then they can use some of the tools to go back and say, when I have my aura, number one, I want to get to a safe place, first thing, I want to let somebody know, if I can, if I have the ability to do that, and then I want to use some of the tools that I’ve been learning to apply, to, hopefully prevent the progression of the seizure into the full blown seizure. We’ve seen people with epilepsy and with non-epileptic seizures be able to take that approach.

There’s a project called Project Uplift. Is this is something that’s similar or different to the workbook?

Dr. Curtis LaFrance: Yeah. So Project Uplift is a great self-management tool that was created by the Managing Epilepsy Well Network, some of my colleagues and collaborators, who were funded by the CDC, the Center for Disease Control and Prevention. So Project Uplift addresses depression and epilepsy. This addresses the seizures and the comorbidities. So it’s an inverse of the approach. They can both affect quality of life and improve quality of life, but the approach is a little bit different with Uplift, as it is with ours.

The other thing that I say with our workbook is, it’s not a self-help book. So it’s to be done in concert with a clinician who knows how to treat people with seizures. So Uplift, you can get trained… or rather the clinician can get trained, and then be able to work with individuals with epilepsy. That’s for Uplift. They’ve got a number of other things that Managing Epilepsy Well network uses, whether it’s Hopscotch, which is used for cognition or thinking problems that can be associated with epilepsy. Yeah, a number of great resources that the MEWN has through the CDC.

So eye movement desensitization reprocessing therapy. Tell us about this.

Dr. Curtis LaFrance: Now, EMDR is the acronym for that. People with histories of trauma can use EMDR to reduce some of their trauma-related symptoms. There are some case series that have been done for EMDR in individuals with non-epileptic seizures that showed a reduction in seizures. Those weren’t controlled studies, so we can’t attribute causation to say, well, that’s what made it go down.  I’ve got a number of patients with trauma histories, who say that EMDR was the thing that really helped me.

Vastly, I’ve had people say, you know what, I started doing it, and it didn’t really help. Nothing that we do in medicine is 100% effective, but I can say that some of my patients have anecdotally said, this has really helped me.

Do these programs work for kids, as well? How do you include family members in this process?

Dr. Curtis LaFrance: Yep. It has not been studied in children 18 and younger, or rather, under 18. All of our clinical trials have been in 18 and older. So I’m only speaking from the published data. What I can say is, anecdotally, I’ve had a number of people say, yeah, I used the workbook with my 16-year-old, and it was fine. So when you say kids with epilepsy, are you talking about neonates, are you talking about 18-year-olds? That kind of thing.

When people ask me, hey, can it be used with kids? I say, it can be used for kids who have some self-awareness, and who have some maturity. For those who might be in their tweens, they might not be ready for some of the ideas or the concept. But I’ve had some adolescents, who were very mature and had a lot of insight. So there’s not a statement about it, it can only be used from this age to this age. There are people who do want to do a clinical trial in kids using the workbook, but that hasn’t been done yet.

If there’s nobody in the area in somebody’s region that’s an epilepsy specialist, what can they do? What can this person do? How can they find either remote resources, or is that possible? There are there lots of people in rural areas, or unable to get to an epilepsy center and see a specialist. What do they do?

Dr. Curtis LaFrance: They keep being an advocate for themselves.

Here’s what I mean by that. I tell people, my patients and family members, you are your best advocate. I’ll hear statements like doctor, can you write me a letter, I’ll say I can, but I want you to write the letter, and I want you to write the letter to your doctor, your hospital, your congressman. I want you to write letters to the licensing boards. The reason why I say this is because I live in two different worlds on a number of fronts, so in neurology and psychiatry. I live in two different worlds at the same time. In the VA and in the civilian world, I live in two different worlds at the same time.

So interestingly, with the VA system, being trained in telemedicine, I can treat veterans around the country. I go to my office in Providence, Rhode Island, and I see veterans all around the country, because the VA is a national system. So, one of the reasons that people can’t treat across state lines is because for me to treat somebody in Georgia or Arizona, I have to have a license in the state of Arizona, and I’m not going to get 50 licenses to be able to do that. So that’s why I’m saying, lobby. Go to the boards and say, you know what, telehealth has been helping people around the country and around the world, let’s make sure that people who have specialties can treat people, or people who are primary care can treat across state lines, and not have that burden of the system that exists in the civilian world. That would be a way to really push the envelope, which I’m a big fan of.

So that’s what I would say, keep being an advocate for yourself, but also keep asking around. A lot of times people will say, well, I’ve got a local clinician, they’re familiar. I view us in medicine as eternal students. So some people will say, I’ll see you, and I’ll read the workbook, and we’ll work through this together. That’s another option, is have the local people, whoever it is, to get equipped using the resources that are available. But I would say, like we’ve talked about earlier, Epilepsy Foundation, CURE Epilepsy, American Epilepsy Society, CDC, those are all places that have information. Sometimes you’ll see websites that will say, here, local clinicians. Keep advocating for yourself, is what I would say.

Are non-epileptic seizures less dangerous to the brain than epileptic seizures?

Dr. Curtis LaFrance: People will ask, am I going to get brain damage from these? What I will say is that the effects of recurrent epileptic seizures… Sometimes people who have certain types of epileptic seizures, they can drop their oxygen level, and they can become hypoxic, and that can actually affect the brain, as you’re aware, we don’t see those same oxygen level drops in people who have generalized tonic-clonic non-epileptic seizures. So over time, we don’t see the same brain energy risks that may be associated with some types of epileptic-seizures that we do with non-epileptic seizures.

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.

Cenobamate: A New Treatment Option for Partial-Onset (Focal) Seizures

Approximately 30% of epilepsy patients have epilepsy that is considered refractory, or resistant to current treatment options. Therefore, it is critical that new and improved anti-epileptic drugs be developed. Cenobamate (XCOPRI®) is an FDA-approved drug made available to patients in 2020 and is approved for the treatment of partial-onset (also referred to as “focal”) seizures. Learn what is known about how cenobamate reduces seizure activity, and why it is a safe and effective treatment of partial seizures. Also discussed are the potential side effects that patients and caregivers should be aware of when considering this treatment option.

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About the Speaker
This webinar is presented by Dr. Michael Sperling, the Baldwin Keyes Professor of Neurology and Vice Chairman for Clinical Affairs in the Department of Neurology at Thomas Jefferson University in Philadelphia, PA. He is the Director of the Jefferson Comprehensive Epilepsy Center and the Clinical Neurophysiology Laboratory at Thomas Jefferson University Hospital. His primary research interests include surgical treatment of epilepsy, mortality in epilepsy, epilepsy genetics, and clinical neurophysiology.

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.

This webinar is supported with funding from SK Life Science
SK Life Sciences

Q&A with Dr. Michael Sperling

Is this medication suitable for occipital lobe epilepsy?

Dr. Michael Sperling: It is approved and has been studied in all of the focal epilepsies. So, if you have occipital, or parietal, or frontal, or temporal, evidence exists that it works for focal epilepsy and occipital is a focal epilepsy. Is it good for generalized epilepsy, if you have Lennox-Gastaut syndrome, for example, or Dravet syndrome? Is it good if you have an idiopathic generalized epilepsy like juvenile myoclonic epilepsy or childhood absence epilepsy, or juvenile absence, or just generalized epilepsy with tonic-clonic seizures? It has not been studied in that. Studies need to be done.

There was a similar question somebody is asking about frontal lobe epilepsy.

Dr. Michael Sperling: Frontal lobe epilepsy is a focal epilepsy, absolutely appropriate.

What other medications are good to be paired with cenobamate?

Dr. Michael Sperling: I am not a huge fan of pairing medicines. I do it more than I should, as do many doctors. But in the best of all possible worlds, you would be on only one drug because then you have less side effects. If you’re going to pair it, however, drugs that work via a similar mechanism are probably not ideal because you’re more likely to get side effects. If you take a drug that’s a sodium channel blocker already, and then a new drug is added, which also blocks sodium channels, you’re more likely to have side effects. So you have to discuss with your doctors what’s suitable for what you have. But drugs like lacosamide (brand name Vimpat), carbamazepine, which is Tegretol but basically Trileptal, and some others, like lamotrigine also (Lamictal brand name) are sodium channel blockers.

When you add cenobamate you’re more likely to get side effects. You can pair it but I routinely have people start lowering their other drugs somewhat–usually by 50 or 100 milligrams a day, depending on how much they’re taking when they’re starting–to try to block side effects. I tell them that if you start seeing side effects, you can start lowering it sooner. Drugs with a different mechanism of action–so levetiracetam (which is Keppra), brivaracetam (which is Briviact), perampanel (which is Fycompa)–they’re probably going to be a bit less likely. There haven’t been great studies on that. Some analyses have been done looking at side effects and there have been some formal studies, but that’s a general rule that one can follow. The details of the studies are almost irrelevant in some sense, because it’s the dose that you’re on that makes a difference more than anything.

You’ve mentioned felbamate and that this is possibly viewed as a newer version of felbamate, but how does the effectiveness of cenobamate compare to felbamate?

Dr. Michael Sperling: Felbamate was studied in Lennox-Gastaut syndrome. There aren’t formal studies in focal epilepsy so we can’t really compare it quite as well. Now, many people, myself included, used it in focal epilepsy somewhat, but then felbamate was discovered to cause potentially fatal liver reactions and bone marrow reactions where people became profoundly anemic within a year of its appearance. So people use it very infrequently these days and mostly it’s used in Lennox-Gastaut. So we don’t have a good idea. We all thought that felbamate was a strikingly effective agent, however.

You mentioned the issues with felbamate and liver toxicity. There is no worry about cenobamate in liver toxicity in this case?

Dr. Michael Sperling: You can do the numbers: 930 plus 1,339. We have over 2,200 people and there’s been no significant abnormalities of liver reported with this. Does that mean that a less rare or less common reaction might not happen? It’s possible. So, felbamate in the trials looked, say, for liver abnormalities also. It wasn’t until it started being prescribed that liver problems resulted.

Keep in mind that when you start a new drug that just came out, we have reasonable evidence about it being effective. We have really modest evidence about safety. There’s nothing gross and horrible, but if one person out of 5,000 has a serious liver reaction and a serious bone marrow reaction, you have to have 25,000 people get the drug before you can be reasonably confident that the rate is at least 1 in 5,000. If the rate’s 1 in 50,000, a quarter of a million people have to have it. When drugs are approved after only 2,000 and 3,000 have had it, we know the risk is not large, it’s going to be small, but it doesn’t mean that there couldn’t still be a 1 in a 1,000 or 1 in 5,000 or 1 in 10,000 reaction. Time will tell.

We don’t routinely order liver function tests when starting people on this drug. We just ask them how they feel and keep an eye on things. We don’t order any blood tests with regularity because it’s not that the blood tests really predict it. And if you have what’s known as an idiosyncratic reaction, there’s no evidence that monitoring in advance actually makes a difference. The body’s exposed to it, something happens, and whether you take it for an extra one day or seven days probably doesn’t make a difference. What’s going to be is going to be at that point. And it’s when people don’t feel well that then we have to investigate more.

In terms of metabolic pathways, does cenobamate share a pathway with CBD? We know a lot of people are on CBD, whether it’s the approved version, the FDA version, or medications or substances that are purchased at dispensaries. Is there any known interaction with CBD?

Dr. Michael Sperling: A lot of people are taking it with CBD and products that contain CBD. Medical marijuana has many chemicals, one of which is presumably CBD. The enzymes in the liver that metabolize cenobamate also will metabolize CBD and other marijuana constituent chemicals. Does cenobamate alter the metabolism of CBD? Cenobamate does inhibit one of the enzymes within the liver that helps metabolize some compounds. It’s a 2C-19 compound. There’s a potential for an effect on that. How significant is it? We don’t know, and there really haven’t been great studies in people. In all those studies that were done, there’s not a whole lot of measurement of CBD that we can know. This is one of the things that needs to be studied. I’m sure there will be data that’s out there. In fact, I wouldn’t be surprised that there’s a paper or two published addressing this that I haven’t noticed yet. In practice, we start a new drug, and if there are side effects that start to develop, it’s common to start learning about other drugs and other medications.

Again, for focal epilepsy, I would point out that there is no scientific evidence in humans that CBD has benefit. There’s no data. People can try it. I have many patients who have given it a try, so give it a try see if it helps. But there’s actually no scientific data that it works. What the effect of CBD in people with focal epilepsy who have this drug is still needs further information and a large tail cross of people. Because they’re not just on CBD, they’re on usually one or two other drugs, or sometimes three other drugs. And it’s the whole mixture of the gemisch that we need to understand that adding one more drug into the mix may not enlighten us as much as we’d like.

Do you know if there are any studies on tuberous sclerosis and cenobamate, or if there’s anything in the works?

Dr. Michael Sperling: Many seizures in tuberous sclerosis are focal. So I would expect that for focal seizures in tuberous sclerosis this will be beneficial. I don’t think there are any formal randomized controlled trials like I showed you, but I’m certain that some people in tuberous sclerosis centers are starting to use this drug and tracking how their patients are doing. I would expect that we’ll see some results relatively soon.

Are there any reactions with warfarin (Coumadin)?

Dr. Michael Sperling: None that have been significant and been reported to date. I would still be cautious in the sense of checking the INR in people on warfarin when starting any new drug that can interact with liver enzymes because you can always be unpleasantly surprised. I would hope that most of the time we would be pleasantly surprised that it shouldn’t make a difference with warfarin. But it’s one of those things we want to keep an eye on.

Do you have any recommendations for patient compliance in a digital world where there are virtual visits?

Dr. Michael Sperling: For encouraging compliance, we talk to each other and we can talk to each other through computers or phones, which is how most of my patient visits are done during the pandemic. The vast majority are done that way. I think it’s the same conversation we have. One of the things that we, as doctors, have to do is understand our patient’s motivations.

In my experience, there are three main reasons people don’t take their drugs. The most common is it bothers them. They have side effects from it so they’ll skip a dose now and then because they don’t feel well. If doctors don’t ask about that, we don’t know, and then we don’t adjust. Or you don’t tell me that you’re skipping it every now and then because it bothers you because you don’t want to disappoint me. You’re not disappointing me. I want to know if you’re having a problem; let me know and I’ll adjust your doses. We want you to feel well. The idea is to take the pill, but otherwise not notice that it’s there. In my experience, I think a lot of it has to do with the drugs causing people not to feel well. They don’t want to embarrass their doctors by making them feel bad that I gave them a drug that makes them feel bad. It’s fine. I won’t feel bad. I want you to feel well. Tell me. That’s one reason.

The second reason, unfortunately, is affordability. We live in practically the only advanced country in the world–advanced economy, I should say–advanced economy where healthcare and drugs aren’t covered and drugs can be very expensive. Insurance companies have learned that your copay can be $10 a month for the generic, and they can make it $200 a month or a $100 a month if you’re on the brand. If drugs are on brand, suddenly it’s too expensive and people wind up skipping doses or taking less than they should. So, cost makes it different. Again, have a conversation with a doctor. If it’s too expensive, you need to be on a different drug. Some of the companies have programs to provide drugs for free for people who have certain income qualifications who otherwise couldn’t afford it. We need our health system fixed where people with chronic conditions don’t have to pay money to take drugs. Right now, I have patients who are on atorvastatin (Lipitor) for cholesterol lowering. If you’re on a generic, there’s no copay at all. If you have epilepsy, you really shouldn’t have a copay. There should be no barriers. So, that’s the barrier.

The third barrier–which I’ve been guilty of too–is that every once in a while, people forget, right? We all forget. We stay up late. We were out late in the pre-pandemic world more than now, but we’re out late, we’re doing something and we go to bed and we forget our medicine. We wake up in the morning, we’re rushing, we’re late for work. We have to go somewhere. We forget our medicine.

That, you can try to do something about. I always encourage people to brush their teeth twice a day and keep your medicine with your toothbrush next to the toothbrush. It’s there in the morning, it’s there at night, if you’re doing it once a day or twice a day. Set an alarm on your phone to ring. Set two alarms. One, if you’re supposed to take your medicine at 10:00 at night, have it ring at 10:00 and then have it ring at five after 10:00 to nag you. You’ll get in the habit and then you won’t need the alarm anymore. It just becomes automatic. So there are a few techniques could be done. Most important, frankly, is to make sure that the drug doesn’t bother you.

Additional Q&A not included in webinar, but answered by our webinar expert:

What are the similarities and differences between cenobamate and felbamate? How does the effectiveness of cenobamate compare to felbamate? The risks of felbamate were not discovered until after trials. The trial numbers don’t seem particularly large to identify issues either. How can we be confident about the safety issues? Would a patient change from felbamate to cenobamate and how would one do that (e.g, taper felbamate while starting Cenobamate)?

Dr. Michael Sperling: We do not yet fully understand the differences between felbamate and cenobamate, but the drug response seems different. We will not have full information about risks of any new drug until at least 50,000 to 100,000 people have been treated with that drug. That is why brand new drugs are often best reserved for people who have not responded to at least several other medications. It is possible to consider transitioning from felbamate to cenobamate, but there is no evidence about how this would work yet as it has not been reported.

With consideration to your comment on “needing new more effective drugs,” what are the ways to increase awareness of new drug adoption by doctors as well as patients, with Xcopri as an example?

Dr. Michael Sperling: The best way to increase awareness is by offering lectures at professional meetings to educate physicians and other health care providers about new treatments. Patient education is equally important as they can ask their physicians about new medications.

Were the patients in the placebo group taking other anti-seizure medications (ASMs)? If yes, what do you think was the effect of these other ASMs? How was that controlled for?

Dr. Michael Sperling: People in the placebo group were all taking their baseline ASMs. Improvement in seizure control occurs in some patients in the placebo arm during trials, and may relate to both more careful adherence to medication regimens and positive psychological effect.

Since cenobamate alters flow of sodium into neurons, are there side effects or precautions athletes should keep in mind, such as changes to the amount or type of fluid they should drink during a workout (water, Gatorade, etc.)?

Dr. Michael Sperling: There are no established precautions for athletes. There’s no need to alter the amount of fluid or type of liquids.

Does cenobamate have any synergistic effects with any other medications?

Dr. Michael Sperling: There may be synergistic effects, but this has not been studied enough to know.

Does cenobamate have any reaction to warfarin (Coumadin)?

Dr. Michael Sperling: Cenobamate does not appear to interact with warfarin/coumadin and doses do not appear to need to be changed in the preliminary studies. However, INR should be closely monitored as these preliminary studies are limited.

How does this interact with onfi (Clobazam)? I am experiencing major side effects and wonder if a large part is withdrawal from onfi.

Dr. Michael Sperling: People taking onfi may become more sleepy and the onfi dose may need to be lowered.

Will cenobamate substitute for both Vimpat and Keppra?

Dr. Michael Sperling: Cenobamate might be substituted for either of these drugs, carefully reducing their dose after the drug is started.

Are there any drug interactions with Vimpat, Banzel or Oxtellar?

Dr. Michael Sperling: There are potential interactions with oxcarbazepine (Oxtellar). Studies are needed for rufinamide (Banzel) but there is probably no interaction. There is probably no effect on Vimpat levels.

Will doctors have information on how to dose this drug? Is there a concern about a patient who already takes four medications adding this to the regimen?

Dr. Michael Sperling: If someone is on four medications, adding a fifth is usually problematic. It is best to be on fewer drugs before trying to add in cenobamate or any other drug.

Does this work better than polypharmacy with a combination of a sodium channel blocker and GABA modulator?

Dr. Michael Sperling: This is not better with polypharmacy. It probably works as well by itself but has not been tested that way. However, there is no reason to think that it would not work well if given by itself.

Is this suitable for epilepsies for SCN1A genes?

Dr. Michael Sperling: That’s not known at this time.

Can you explain drug reaction with eosinophilia and systemic symptoms (DRESS) for the skin rash reaction?

Dr. Michael Sperling: DRESS is a serious, potentially life threatening allergic reaction with inflammation in multiple organs, rash, and fever. The chance that it will occur is reduced by starting at a low dose and gradually increasing the dose over two to three months.

Does this medication have a prescription assistance program for patients?

Dr. Michael Sperling: Yes.

I also have hypothyroidism. Is there any risk in taking this drug?

Dr. Michael Sperling: No, there’s no problem for hypothyroidism.

Can the drug level be checked in blood work?

Dr. Michael Sperling: Yes, but the therapeutic range is not well characterized, so checking the level is not terribly helpful.

What kinds of blood work or other testing is required or recommended prior to starting cenobamate? An EKG to check for long QT syndrome, for example?

Dr. Michael Sperling: No blood work is required. An EKG is not required either. It has the potential to slightly shorten the QT, so having long QT should not be an issue. If long QT syndrome is present, however, then pre-treatment and post-treatment EKG is advisable.

The New Way to Describe Your Seizure Types

Managing epilepsy can be a challenge, but understanding the most up-to-date medical terms can help.

Learn the International League Against Epilepsy’s (ILAE) new ways to organize and describe seizures and epilepsy types. Becoming familiar with this new language can enable you and your doctor to better communicate about your treatment options, triggers to avoid, and what to expect in the future.

The webinar is presented by Dr. Robert S. Fisher, who led the task force responsible for the ILAE’s new classification system.

Download Full Transcript

Audience Q&A with Dr. Fisher on Seizure Types

Dr. Robert FisherWhy is this new classification system important to me?

So, how does it matter to you? Well, over the many years of working with people with epilepsy, I have found there is a great desire for them to know what their seizure types are called. The studies examining the correspondence between what people with epilepsy think their seizures are called compared to what their doctor thinks the seizures are called show there is often not a very good correspondence.

To be clear, I’m not implying that the people with epilepsy are wrong. Often the doctors are not really very accurate about what the seizure type is, and when I see that, it means that the names are too complicated. This reclassification is a streamlining. It should help you communicate to other patients and family members, if you go on online to share common experiences and help you to communicate to your medical team accurately and clearly.

Secondly, the new classification system is going to be useful for people whose seizure types just didn’t exist in the previous classification. We can never classify every seizure type, but now, it includes more than it did before.

To your knowledge, are the new classifications being commonly used by doctors now?

Not yet, but bear in mind that there’s a diffusion timeline here. Doctors and other healthcare providers will start to use the new terms over time. Research articles on epilepsy are now required to use the new terms by journal editors, so doctors will be reading articles using the new term with familiarity. Those of us who were involved in the reclassification give a lot of talks to a lot of different groups as well. I also think insurance companies will likely start using the new terminology soon.

There is also the International Classification of Diseases (ICD), which always lags behind the specialty organizations in naming things, but the next version, the ICD-12 will incorporate the new terminologies.

Are the new terms for seizure types localized into other languages?

Fortunately, the “I” in ILAE stands for international! The committee was 19 people, and while all of them spoke English, most were not from the United States. There was great representation of other languages during the reclassification process, and the terms have been translated into many other languages.

Is it still okay to use old terminology, such as grand mal and petit mal?

I’ve worked very hard not to be the terminology police. We’re a year into switching to this classification system, when I read my clinic notes, I’m still going to the extra trouble of using the old terms and the new terms every time I classify a seizure in writing, putting one of them in parentheses.

There are several generations of this reclassification we’re dealing with. It’s not just a new an old classification because if we go back to the 1950s, the terms that people were using were petit mal, grand mal, psychomotor seizure, and sometimes focal motor seizures. Ultimate, these terms are not that bad. I think we’ve improved it a little, but those were not that bad. Then in 1981, we started saying simple partial, complex partial, secondarily generalized, and so on.

If you’re enamored with an old term, you can use it, but here’s the thing that causes confusion: a lot of my patients talk about petit mal and grand mal seizures when they’re all in effect, focal impaired awareness seizures. The petit mals might be the smaller ones that aren’t as intense. The grand mal, they say, are the ones that cause a patient to have a feeling of dread or doom or something that.

The danger is that, if you’re using an old term that isn’t the right term for your seizure type, it may make it confusing when you are speaking with people who have other seizure types when or it may even mislead some doctors.

But otherwise, no, I’m not opposed to using the old terms, if you do so correctly and consistently.

Is petit mal the exact same thing as what is now called an absence seizure?


Can a person have more than one type of seizure?

Absolutely, you can have more than one type of seizure. There are two different baskets I would put that occurrence into. One basket is having one seizure focus (one place in your brain where seizure starts) which the abnormal electricity stays in. In the second basket, the seizure spreads a bit farther sometimes and a lot farther other times.

For example, you might have a focal aware seizure with a sense of déjà vu, or strange familiarity. That may be all that happens in some seizures, and then you might call it an aura, which is an old term for a small seizure that could lead into a larger seizure. So, if the abnormal electricity then spreads to both sides of the brain, you’re not going to be able to lay down and remember memory traces.

Now, in this example, say you have a focal aware seizure which progresses to a focal impaired awareness seizure. If the activity then spreads to the whole brain, you’ll completely lose consciousness. You’ll fall, you’ll stiffen, you’ll have tonic activity, you’ll shake, and you have a focal to bilateral tonic-clonic seizure. In a way, although we call this experience three different seizure types, there’s really one seizure starting place and three different seizure types, because the abnormal activity may spread to different extents. So, the second basket is where you really have two completely different seizure types that don’t overlap. That’s much less common than the first basket.

By the way, seizure medications may keep a seizure from spreading and may turn focal to bilateral tonic-clonic seizures into just focal aware seizures. That would be a good thing.

Can you clarify if tonic-clonic seizures are exclusively generalized (as opposed to focal)?

Generalized tonic-clonic seizures are always generalized. Focal to bilateral tonic-clonic are not exclusively generalized. Patients can have both varieties. That being said, there is no defined seizure type “focal tonic-clonic seizures.” It does exist if you look hard in the literature, but this occurrence is so rare we decided not to include it in the classification.

What’s the practical import of this? If you have a tonic-clonic seizure – tonic stiffening, clonic jerking – your doctor should definitely investigate if you have a focal aura or an onset warning, because that indicates that the seizure is a focal to bilateral tonic-clonic seizure. Your neurologist ought to pay attention to what’s wrong with that focal part of your brain where the seizure starts.

Is there a definition or description for autonomic seizures? And if so, what would that be called, and what would be the most common characteristics of that seizure type?

It’s called “focal autonomic seizures.” It could be “focal aware autonomic” or “focal impaired awareness autonomic seizures.” The autonomic nervous system is comprised of your sympathetic system and your parasympathetic system. Sympathetic is your fight-or-flight system. It involves sweating, the hair on your arms rising up on end, pupil dilation, increased heart rate, etc.. Parasympathetic is your more internal system, like your digestive processes, slowing the heart rate down, slowing breathing, and pupil constriction.

If you have seizures which play into the brain structures that control the sympathetic or the parasympathetic system, you may get heart racing, gastrointestinal symptoms, a sense of heat flushing, hair rising. These are autonomic symptoms. If these are the first symptoms you have, then you have a focal autonomic seizure.

How often is jerking associated with a loss of consciousness and impaired awareness?

The majority of the time. You can have focal clonic seizures with jerking, or focal myoclonic seizures. Remember, myoclonic is irregular twitching, whereas clonic is rhythmical, sustained jerking. If the seizure just stays in the motor center of the brain, the patient is not going to have loss of consciousness or loss of awareness as a marker of consciousness, but if it spreads to both sides of the brain, then the patient will probably going to have loss of consciousness.

If a person tells me they’re experiencing their entire body jerk, but they’re awake, aware, alert, remembering – they see they’re jerking, they report it to me afterwards – then I wonder, “Was this really an epileptic seizure, or was it and imitators?” This is because generalized jerking should not be associated with loss of consciousness.

There are two exceptions I want to mention; generalized myoclonic seizures and generalized atonic seizures. Some seizures, even when generalized, are so brief that you can’t even tell if someone lost consciousness. The classic example of that is generalized myoclonic seizures. These seizures may look like a subtle jerk in the hands, head, and legs.  This jerking could be a generalized myoclonic seizure. We could see spikes on the EEG that match the jerks, and it would be impossible to tell whether the person lost consciousness. The other exception could be a generalized atonic seizure, during which you suddenly go limp and drop to the ground, but as soon as you hit the ground, the seizure is over and you’re awake and alert.

Is there a definition of cluster seizures?

Cluster seizures mean seizures happen one right after the other. The term implies that if you have one seizure, you’re going to have another one in a fairly short order. We haven’t been able to agree on exactly what time parameters those are because there is a lot of variability.

If a person has only one seizure a year, then having three seizures in a month might be a cluster for them. But someone who has seizures every day might require having a whole bunch of seizures together in one day in order to call it a cluster. We have to relate the cluster to how frequent an individual’s normal seizure frequency.

We do care about clusters, and there are rescue medications now that caregivers can spray in the nose to disrupt clusters of seizures. Many patients prone to seizure clusters will carry recuse medicines in their purse or pocket to use as a cluster-buster after one seizure.

There’s also the marketed rectal diazepam medicine that can be used to break up clusters of seizures. And that’s approved and it’s been used for many years.

Do individuals who have been diagnosed with an epilepsy syndrome, such as Doose syndrome, have a specific seizure classification?

An epilepsy syndrome describes a combination of many different features, including various types of seizures. You may have a constellation of seizure types together in your clinical picture. Epilepsy syndromes are extremely important, because they are what doctors are really treating, rather than seizures in isolation.

An individual’s syndrome determines prognosis and treatment options, and the seizure types are the building blocks we use to classify the syndrome and epilepsy type. Syndromes are things like Lennox-Gastaut syndrome, Dravet syndrome, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, etc.. Infantile spasms are both a seizure type, with West syndrome being a synonym for Infantile Spasms.

How do doctors differentiate between a dystonic storm and a seizure?

Dystonia means a sustained abnormal posture and can be a symptom of seizures that have spread to the basal ganglia and the motor centers of the brain. Often in a focal impaired awareness seizures, some dystonic posturing.

Dystonia can also exist without a seizure, instead caused by a movement disorder, hereditary condition, medications, and so on. You can’t really tell just by looking or talking to the person, but if a patient is losing awareness, then you know it’s a seizure. Loss of awareness is not part of movement disorder dystonia. If dystonia has turned into a tonic-clonic seizure at any point in your history, then that’s a seizure and not dystonia.

Making the distinction can sometimes require a video EEG to record brainwave activity during the attack. A seizure will show abnormal brain activity and the movement disorder will not. I recommend consulting a team with expertise both in epilepsy and movement disorders to make the distinction.

Do certain classifications of seizure onset put individuals at a higher risk for Sudden Unexpected Death in Epilepsy (SUDEP)?

Yes, unfortunately. Generalized tonic-clonic seizures, especially frequent ones.

We know that many children outgrow their seizures. How do neurologists determine if a pediatric patient has outgrown seizures if they are on a daily medication?

Before I answer, I am not encouraging anybody to stop their medicines to see if they have outgrown seizures. Doctors all have ways of safely checking to see if reducing or stopping medications is appropriate. Please, do not just stop your epilepsy medication to see if you need it.

With that said, you cannot claim that your epilepsy is resolved so long as you are still taking seizure medicines since you don’t know what would happen if you stop. A neurologist will determine whether there have been seizures in recent years, as sometimes people aren’t even aware that certain types of daydreaming or fumbling or automatic activity may be seizures. If those symptoms exist, we certainly don’t want patients to stop medication. Neurologists need a careful history and likely an EEG to make the determination.

From the patient’s perspective, they have to be comfortable with the risk of having a seizure by withdrawing from medications. Personally, I ask my patients not to drive for a period of time, because we don’t want to find out that the medicines were needed while the person is on the highway. That can be a deal breaker for stopping medications for some patients.

The CURE Leaders in Epilepsy Webinar Series has covered many topics related to epilepsy and innovations in research. Check out our full list of available webinars here.

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.