Promising Anti-Epileptic Drugs in Development

This free webinar outlines therapies in development for epilepsy and seizures, including promising therapies for patients with treatment-resistant epilepsy and children with severe epilepsy. The webinar also focuses on drugs that may not only reduce seizures, but improve treatment of the underlying disease.

The webinar is presented by Dr. Jacqueline French, a professor of Neurology in the Comprehensive Epilepsy Center at NYU Langone School of Medicine and Founder/Director of the Epilepsy Study Consortium. Dr. French’s presentation was followed by an interactive Q&A session.


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Audience Q&A with Dr. Jacqueline French

You mentioned schedule 1 and schedule 2. Can you explain these different stages a little bit further?

There are drugs that are considered to be controlled substances, which means that people can become dependent or get addicted to them. The more likelihood that there is that people will get addicted to them, the higher the level of control that the government puts on the distribution of those drugs. We all think of drugs like heroin and morphine. Heroin, in fact, is the most controlled of drugs because it is so addictive and also because it has no medicinal use. The drugs that are in the schedule 1 are considered to be highly addictive and have no medicinal use whatsoever. People are surprised to know cocaine, for example, is not schedule 1 because there is a use of cocaine for some eye diseases, so it’s actually scheduled 2.

It’s extremely difficult to even do research on schedule 1 compounds because they are so highly regulated by the government and very difficult, obviously, you can’t prescribe them because they have no medicinal use. Once a drug is known to have a medicinal use and it becomes schedule 2, then it is much more easier to move that product around to have it in pharmacies without like 10,000 locks on every door where this substance is being held and it just makes things much, much easier. Then you go down the line. For example, many of our epilepsy drugs are on the schedule of potentially addictive drugs.

You’d be surprised, drugs that perhaps people who take them would say, “I can’t imagine anybody would use these if they didn’t have to.” There is some evidence that in fact people do try and get them for recreational use and not for medicinal use and that includes drugs such as Pregabalin or Lyrica drugs such as a Vimpat or Lacosamide. Yes, those are restricted to some degree, but they’re only scheduled 4, so they’re lightly restricted. As you go up to schedule 3, schedule 2 and schedule 1, you get more and more and more restriction.

A drug such as Epidiolex and Fenfluramine and drugs that are being developed for Dravet Syndrome for instance, will they be available to others with similar seizures, but may not have the Dravet or that clinical diagnosis?

In the United States specifically, the FDA doesn’t put restrictions on doctors to say, “You can only prescribe a drug for what it has been FDA approved for and is on the FDA label.” The studies that are done and the diseases that are studied in the trials, will lead to a label that says, “This has been shown to be safe and effective in condition A, B, or C.” I could prescribed that drug for condition, D, E and F, but there are a couple of issues that I would have to have in mind as a physician.

Number one is that, there is a certain amount of liability because I am going what’s called off-label. My patient that I’m treating might say, “I came to some harm from what you did and really you weren’t doing the proper thing because the FDA didn’t say it was approved for this particular indication.” You were taking on some risk when you prescribed off-label, although many, many, many people do it. It’s done all the time.

The second thing is that, your insurance company might say, “Hey, this is a reasonably expensive drug and nobody has said that for your condition it’s effective, so why are we going to pay for it?” One or two things can happen. It may be that your doctor can then appeal to the insurance company and provide extra information and the insurance company can eventually agree to pay for it or they may just completely not agree under any circumstances. We have had that issue arise with one of our other drugs that is only approved for what we call an orphan condition and that is a Clobazam or Onfi. It’s a reasonably expensive drug and it’s only approved for Lennox-Gastaut Syndrome and sometimes I can get it for my patients and sometimes the insurance company will just completely stonewall and say, “No, you can’t have it.”

Do you know what the mechanism of action in the Cenobamate trial that you referenced earlier is?

Cenobamate, we do not specifically know the mechanism of action. However, it is in the class of drugs called carbamate. There was one other drug that was approved for epilepsy that’s in that class and that is Felbamate. We do not know its mechanism. We know that it is somewhat related. It’s a second cousin or a third cousin of Felbamate. Felbamate was a very effective drug for many people with epilepsy, but as a many of the audience may know, it is used very rarely now because it caused serious liver problems and a plastic anemia which has not been seen with this drug. If it was as efficacious as Felbamate, that would be a good thing and perhaps in some conditions it’s more and the rest remains to be seen.

Do we know whether there are targeted treatments for those epilepsies in development?

The first answer is yes. On the slide that I showed, there were a couple of genetic conditions that there are targeted treatments. Excuse me. Glut-1 deficiency is a great example where these are children who have a genetic defect that prevents their brains from turning glucose into energy. They have an energy defect in the brain and over time, that leads to seizures as well as an increase in cognitive dysfunction. There is a targeted therapy of a drug that can be used by the brain to produce energy that’s not glucose and therefore could reverse the specific problem in these children. That is one example of a treatment that is specifically targeting one genetic condition.

There is a drug called Ganaxolone that is being tried specifically in children with CDKL-5, which is another specific genetic defect. It doesn’t reverse the specific issue in CDKL-5, but there are reasons to believe it might be effective in CDKL-5. There are a number of drugs that are specifically targeting genetic defects. I think that what you may also be asking is, are we trying to reverse the genetic defect that caused the epilepsy to begin with, as was the case with the tuberous sclerosis and Everolimus? There are some attempts at that. They’re a little bit further away probably from the clinic, but, for example, there’s a drug called Endololin being tested in children with genetic code problems where there’s a certain part of the gene that’s supposed to create a protein that is very important for the development or the running of the brain. When that gene is being read, it comes upon a mutation and that whole mechanisms stops. It’s called the stop codon and that protein can’t be created.

This drug actually allows the information in the gene to be read even when that mutation is in the middle of it and that protein to be created. That would be really amazing if that works and it might actually be able to prevent the disease if it was given early enough to a child who had that genetic defect. These are the almost science fiction things that are turning into reality in clinical trials.

When you said the period of follow up is eight weeks or 12 weeks, are they on drug during those eight to 12 weeks or do they stop taking drugs and see what happens in the next eight to 12 weeks?

The way trials work is, usually, they start with what’s called the baseline period, which is just a period where we can figure out what the frequency, the typical frequency of seizures is. Let’s say an individual has four seizures a month or five seizures a month or 10 seizures a month, whatever that number is, it’s determined during an eight-week baseline. Then at the end of that baseline, they get randomized and they continue on there. During the baseline and during the study, they’re continuing to take whatever medication their physician has given them, a combination of medications that is the best control that they can get.

At that point they’re randomized to either adding the new drug or adding a sugar pill. Then for eight to 12 weeks they carry on and they see whether the seizure frequency that was determined during the baseline, is actually going to go down or go up or whatever happens. That goes on for eight to 12 weeks. Then at the end of that the randomized portion of the trial is over and they go into what’s called the open-label extension. During that time, everybody can be on the medication. The doctor knows the dosage, they know that the medication is being administered, they can manipulate it, they can change the background medications or whatever is considered to be optimal for that individual. During the double-blind they may or may not be taking the study medication, but once they get to the open-label extension, everybody is given the study medication on top of the medication that they’re already taking.

Are these drugs safe to take while a woman is pregnant?

Pregnancy, we always advise that drugs that are in clinical trials, women should not go into clinical trials if they are planning pregnancy and in fact we have significant safeguards in place. People have to sign a consent that says that during the trial, they will use appropriate birth control, so that they will not get pregnant and we make sure that they or receiving a birth control that’s likely to be effective, so that they will not get pregnant because this is not the time when you want to be experimenting to see whether this medication will adversely affect the fetus. Because, first, you want to make sure that the drug actually works, is safe and effective. Once the drug is safe and effective and is approved and is then available to the public, then over time some women will take it and will become pregnant. Only then, can we really know entirely whether the drug is safe during pregnancy.

We have many pregnancy registries that accumulate data on the drugs once they are in the clinic, but it is unfortunately a very slow process. It may take decades before there are enough women in the registries that we have really good information about whether the drug is safe in pregnancy or not. Even some of the drugs that have been around for a really long time and Lacosamide is one good example, we don’t have enough information really to say for an absolute assuredness that it is safe in pregnancy. We do have information as immediately when the drug is approved, as to whether it’s caused birth defects in animals. The label that’s put on the drug by the FDA, will say either the drug has been shown to be safe in animals, but we don’t know about humans or the drug has been shown not to be safe in animals, but we don’t know about humans or the drug has been shown to be harmful in animals and harmful in humans, so that it gives them an A, B, C or D rating.

The higher the letter, the worse it is. A class D drug would be one where it’s been shown and this is, Valproic Acid or Depakote is in this class that is both harmful in animals and also has been shown to be harmful in people during pregnancy. The A designation is almost never given where we say, “Oh we absolutely know it’s as safe as houses and anybody can take it and it’s perfectly fine. Most seizure medications are either B or C.

Where do we get more information on clinical trials?

The Epilepsy Foundation actually has a lot of information on epilepsy.com. If people want to know whether there is a trial that they could sign up for then that is an excellent place to look, there is a section of epilepsy.com where the trials that are underway describe a little bit of information about what we know about the drug and what the trial would be like if you were to enroll in it. That’s one good thing that’s on epilepsy.com and there’s also a part of epilepsy.com where there is a pipeline. You can see all of the drugs that are currently in development and what stage of development they’re in, whether they’re in early development or they’re close to the clinic.

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Diagnostic and Treatment Challenges of Infantile Spasms

This webinar focuses on the challenges of diagnosing and treating infantile spasms, and how advances in epilepsy medicine and technology have improved this process. This presentation also examines currently available treatment options.

The presenter is Dr. Shaun Hussain, Assistant Professor of Pediatrics at UCLA, Director of the UCLA Infantile Spasms Program, and inaugural recipient of the Elsie and Isaac Fogelman Endowed Chair in Pediatric Neurology. His clinical and research endeavors focus on Infantile Spasms and other forms of severe pediatric epilepsy, including Lennox-Gastaut syndrome and Dravet syndrome.


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Audience Q&A with Dr. Hussain

If an infant gains control over their infantile spasms and normalize the hypsarrhythmia, is there a greater likelihood of normal neurological development?

That’s a tough question. That is certainly the goal of therapy in the short term, and it seems to be pretty clear that if you don’t completely abolish spasms and the hypsarrhythmia, development will not turn out well. At UCLA, we follow almost 500 patients, and I can’t think of a single one who had a long-term burden of infantile spasms or long-term burden of hypsarrhythmia and did well.

In order to get a good developmental outcome, you have to abolish spasms. You have to abolish hypsarrhythmia. And you have to be a little bit lucky. You have to find that the cause of the infantile spasms is not itself something that can damage development. But in short, I would say you simply can’t tolerate any infantile spasms or hypsarrhythmia. If either of those are present, it means that you need to try different therapy.

If a gene panel doesn’t reveal a known cause genetic cause of infantile spasms, but a child has been seizure- and med-free for several years, do you recommend further genetic testing?

It’s tough. The answer to that question has to be pretty individualized, but usually the answer is no. The odds of us identifying a meaningful genetic abnormality that impacts our treatment – would tell us to begin or stop a therapy – is actually very, very low at that point.

On the other hand, if the parents are thinking about having another kid, it would be very nice to do that genetic testing and get a sense of whether there is any risk posed to the next child. There is unfortunately, very little data about the risk in general. In thinking about our cohort here at UCLA of nearly 500 patients, there have been only a couple cases in which a sibling also had infantile spasms after the first child.

Let’s say overall risk is pretty low. If it was me, I would want to do that genetic testing to figure that out. But there are also risks of genetic testing. Sometimes you might find out that a child, sibling, or parent are at risk for some other disorder associated with infantile spasms. It’s a big discussion, a difficult decision often, and you have to go into that decision-making process knowing all the risks and benefits of genetic testing.

If the first course treatment was not effective, does this equate to a delay in treatment and, therefore, a poor prognosis for future development?

We don’t actually know the answer. My sense is that the delay in finding an effective therapy probably poses some risk, but we don’t know how much. The first therapy not working probably means that the child has overall worse infantile spasms and may be at risk for bad outcomes on that basis.

The short answer is, I don’t know. But the second answer is that it doesn’t matter. If you’ve got ongoing spasms, you just got to change your treatment approach and be aggressive. Don’t be afraid of those side effects and focus on eradicating infantile spasms.

Is surgery only considered when seizures don’t respond to certain medications? Or can it also be an option when the MRI and PET scans indicate a specific portion of the brain causing abnormal EEG activity, indicating a risk of seizures, even after hypsarrhythmia has been resolved?

There is certainly no consensus in answering that, so I want point out a couple things. There are patients who have structural abnormalities – things like cortical dysplasia – who will respond to first line therapy and not need that surgery. We have multiple individuals in our cohort who responded to therapy and seemed to be doing just fine.

I will also tell you that there are patients with that exact story ; they had infantile spasms,  they had a lesion that could be removed, they responded to therapy, and we said, “Well, you don’t have hypsarrhythmia, you don’t have spasms, you seem to be doing well developmentally.” Then several years later or a decade later, we have either the return of infantile spasms, epileptic spasms, or other types of seizures. Then we have to think, “Whoa, it would have been nice to have removed that piece of brain back when that patient was an infant and when the risks and costs of surgery would have been less.”

It’s a really tough decision. I think if you asked a neurosurgeon, they would be hard pressed to remove pieces of brain in a patient who did not have ongoing infantile spasms or hypsarrhythmia. But I’m not sure that’s the right decision.

I would put it this way though: if you have ongoing spasms or hypsarrhythmia and you have identified a lesion that can be removed to potentially cure the infantile spasms, that is almost always the right path. We’ve seen that all the relapse rates are pretty high across the board, they’re much lower and those patients who are good surgical candidates and undergo a successful surgery.

You mentioned the importance of immediate diagnosis. To clarify, does that mean from the first visible spasm or from the onset of hypsarrhythmia? Could there have been hypsarrhythmia for weeks or months prior to the first visible spasm?

It refers to the interval from the first identified spasm to effective treatment. And it’s very possible that hypsarrhythmia is brewing or emerging or growing before that first spasm.

A big focus of ongoing research is to identify patients who are at risk and then sequentially check their EEG every few weeks looking for the possibility that hypsarrhythmia or infantile spasms are on the way. That might be an opportunity to treat infantile spasms when they aren’t as bad, meaning there maybe a higher opportunity to prevent them from ever happening at all.

What are the chances of stopping spasms with the combination of ACTH and vigabatrin, if the spasms have been going on for one year or more?

The odds are not great, but they’re not zero. When we look at the patients who are relatively new to the treatment combination, the response rate is in the mid-70s, about 75% is our best estimate. The odds of response after months or years of ongoing spasms – especially with ongoing hypsarrhythmia – is considerably lower. We don’t have good estimates of what that risk looks like.

But there have been plenty of patients who have had spasms for a year and failed specific therapies, like the first line therapies, but when the medications were tried a year later, they did work.

I think it’s worth consideration. Just because a therapy didn’t work a year ago doesn’t mean that it won’t work now. Infantile spasms and hypsarrhythmia are dynamic process and they’re changing. And just because it didn’t work in the past doesn’t mean that it won’t work now.

Unfortunately, the reverse is also true. You can imagine a patient who was diagnosed quickly, who responded to say ACTH and that spasms returned six months later. Just because they responded the first time doesn’t mean that they’ll respond the second time.

If a child’s spasms are brought under control, is this child more likely than the general population to develop epilepsy down the road?

It’s absolutely true. We don’t quite know the magnitude of that risk. But I would say that it’s pretty substantial. It also depends on the cause of epilepsy. For example, if a patient has one of the most common structural abnormalities that cause the infantile spasm (something like a focal cortical dysplasia), then the risk of epilepsy down the road in the absence of surgery is pretty substantial. I would say it’s probably in the neighborhood of 50 or more percent.

But it really varies. It’s hard to predict. I would just say that, yes, you’re at elevated risk. You have to be on the lookout for the return of infantile spasms or the emergence of other types of epilepsy.

You mentioned that vision loss can accompany infantile spasms. Do you have any advice if delayed speech is concerned in a child who has suffered from IS?

That is actually one of the most common concerns. To the extent that infantile spasms and hypsarrhythmia can hurt development, it seems that they disproportionately affect language. But we actually don’t know why that is.

When we conceptualized infantile spasms, they are a form of seizure and epilepsy that hijacks the entire brain, but seem to have a disproportionate impact on the temporal lobes. And the temporal lobes are very important, especially the left temporal lobe, for processing and understanding language. That seems to be a pretty big barrier for graduates of infantile spasms, including those who have responded pretty quickly to therapy.

We have a very low threshold for referring patients for speech therapy. I would say many cases, especially those which have responded robustly and quickly to therapy, are actually very good responders to speech therapy. It is something actionable, but not something too alarming. I would say that there are many, many patients who have good outcomes after infantile spasms, and many of them had some degree of speech delay.

Can other seizure types early on mask the presence of infantile spasms?

Absolutely. Another factor is that infantile spasms are sometimes subtle and don’t really register as seizures with most people. When you think about the general public, if they saw a video of a child having infantile spasms, most people would not say, “Oh, that looks like a seizure.” They would say, “I’m not sure what that is. It’s probably nothing. Maybe it’s an infant heartburn or gastroesophageal reflux.”

Infantile spasms visually don’t register and don’t register on that fear meter. But when you think about most other types of seizures, they’re rather dramatic, especially if you think about something like a generalized tonic-clonic seizure seizure, those are much scarier, much more obvious.

If you imagine a patient who’s having both generalized tonic-clonic seizures and infantile spasms, it’s pretty easy to see how everyone’s attention – parents, pediatricians, neurologists – would likely be focused on those generalized tonic-clonic seizures because they’re so dramatic. That is also probably part of the challenge. We have to keep infantile spasms in mind as part of the possibilities of seizures and infancy.

When we teach our trainees, our residents and fellows, we’re telling them, “Look, this is an infant. You need to have infantile spasms in the back of your mind, no matter what kind of seizure they’re showing you right now.”

Is vigabatrin known to cause myoclonic jerks? If these jerks are not epileptic, can you stop once the child is weaned?

It’s not exactly clear. There’s a pretty widespread rumor that vigabatrin can cause myoclonic jerks or myoclonic seizures, and that they can be classified as epileptic or nonepileptic. I would say, don’t worry about any of that.

I think it’s probably true that a minority of patients who are treated with vigabatrin have either the emergence or worsening of myoclonic seizures. These seizures are reversible after stopping vigabatrin therapy.

The big question is; if vigabatrin is working to stop the spasms, should you stop the vigabatrin to make those myoclonic jerks and myoclonic seizures better? I think that has to be considered on a case by case basis.

 

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Epilepsy’s Impact on Memory and Cognition Over Time

Cognitive deficits and memory problems are common among adults with chronic epilepsy. This webinar discusses the course of cognitive and memory aging in people with chronic epilepsy. The presentation addresses factors which contribute to healthy cognitive and brain aging, as well as what patients can do to help prevent cognitive decline.

This webinar is presented by Dr. Bruce Hermann, PhD, Director of the Charles Matthew Neuropsychology Section at the University of Wisconsin School of Medicine and Public Health. Dr. Hermann is an expert in brain and cognitive aging in people with chronic epilepsy. His research focuses on the impact of epilepsy on brain structure, cognition, and psychiatric status.

Dr. Hermann’s presentation is followed by an interactive Q&A session, where he answers questions such as:

  • Can any measures be taken to prevent or combat the cognitive decline that accompanies getting older with epilepsy?
  • Does research suggest specific therapies to help prevent memory loss associated with epilepsy?
  • Are certain individuals with epilepsy more likely to experience cognitive decline as they age than others?

For the full transcript, click the link below.


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Audience Q&A with Dr. Bruce Hermann

How did researchers differentiate between the issues caused by antiepileptic drugs, and those that are caused by seizures?

Within the epileptic drugs, the best are the controlled clinical trials, right? And there’s quite a bit of research about that, right? So, patients come in, they’re randomized to drug A or drug B, they’re tested before they’re given those medications. And there are studies that have done this with healthy controls where they’ve taken no medications, and come into the study, and take some baseline testing, then are randomized to a drug treatment trial, and no treatment control trial.

And you can figure out the specific effects of particular drugs in that fashion. And they’ve also done this with patients with epilepsy, where they’re randomized to one arm or another, and you can look at the effects of an add-on medication or a new medication. There are now, there are some very large studies where they’ve taken people at diagnosis, and randomize them into a one arm or the other. And it could be such as the childhood absence study, which was a major national study in the US that even compare the effects of seizure control as well as cognition.

If there’s marginal or no differences in their ability to control the seizures, then really clearly the more preferred compound would be the one that has fewer cognitive complications. So, quite a big literature that addresses that through the years, and it’s been worked out pretty carefully, and I can send CURE some references for that that might be useful to everyone.

Is there research done when drugs come into the market on which medications, like Keppra that may have more of an impact on memory and cognition?

Yes. I mean, nowadays it’s worked out pretty carefully. So, we have a good sense of the cognitive complications with some of these medications. It becomes clearer over time for sure, but cognition is now integrated in many of these drug development clinical trials and so on. Again, don’t forget because what happens in my career, talk about cognition or talk about behavioral issues. Generally, the first question has to do with medications, and there’s no question that it can have an effect. But these problems are present right at the get go even before any medications are given.

Can the medications exacerbate the cognitive difficulty? Sure, they can, but they are countering the effects of the seizures themselves, which have their own adverse effects. So, this research looking at new onset drug naive patients is just incredibly important. And again, there are subsets, some individuals at onset have no difficulties, and have a very uncomplicated course, whereas others from a cognitive perspective have difficulties early on, and were struggling with some issues even before the diagnosis of epilepsy, which no one fully understands, but everybody has observed that.

Is there an advantage to adults actually having genetic testing done to determine their type of epilepsy, and could that have an impact on knowing the cognitive issues, and the memory issues that may arise?

No. I mean, I think in the cognitive aging world, and especially in the Alzheimer’s disease world, there are a couple of genes. I mean, it’s a complicated business. I work with a preclinical AAD group here, and there’s a lot of interest in genetics, and the primary gene has been the ApoE4 gene. I mean, there are genes for early onset dementia, but that’s not what people are worried about. They’re worried more about must having a family.

They’re worried more about the course over the decades, and as they get older. And there are a couple of genes, but it’s very poly genetic as they say, and you can have the gene, and not have Alzheimer’s disease. You can not have the gene and have Alzheimer’s disease. So, it’s probably what’s probably most important in midlife is probably to get after all the treatable factors, and my general opinion, and the research on that, we have folks here doing exercise research.

And in at-risk patients for Alzheimer’s disease, and the exercise has positive effects on brain structure. It has positive effects on laying down of the plaques. It has positive effects on cognition going forward. So, I’ve seen a diet study using the mind diet where white matter volumes increase over time. So, I think if you look at the websites for the various organizations I mentioned, I think that’s very important to take a look at. And it’s extremely important area of research for epilepsy. It’s just critical going forward.

Is there any research being done that shows that epilepsy patients are more or less likely to develop Alzheimer’s?

This is a very hot topic right now, and there’s a lot of interest in this, if we address it from the standpoint of comorbidity studies, is there a higher incidence between epilepsy seizures, and Alzheimer’s disease? There is a higher incidence, but that’s driven in part by people who have Alzheimer’s disease, and then develop seizures as part of that disease. The really complicated question is, and not that that’s not complicated, but the question that people with chronic epilepsy have is what’s my cognitive course?

We just don’t know too much about it because our literature cuts off about age 50. We need some large population-based studies that follow people into their older years. And that, we just don’t have. We need that, and that would include imaging, and cognition, and life health history. I think that’s why the Finland data are so important. They’ve collected all sorts of health activity, personal information on these patients at midlife. And one question would be is there anything in midlife that predicts the amyloid deposition in people in their 50s?

If something can be found there, then that would have huge implications in terms of what to do, and have some… just certainly generate testable hypotheses anyway in terms of are there things we can do to reduce that risk. And, that question is, I mean, what’s the risk of Alzheimer’s disease? It’s everywhere, you pick up the paper, listen to the news, and it drives a lot of interest in cognition.

Does epilepsy actually affect long-term memory or short-term memory, more than the other?

Yeah. I think the one thing we didn’t talk about is if you think about it, the seizures, I mean I’ve always been impressed for example, by moms who will say, “We studied for the test last night, yesterday afternoon, and Johnny knew everything, and you got cold, and you’re forwards, backwards, and had it all down, and had a seizure the night, or a seizure in the evening. And then the next morning, just didn’t recall any of the information.

They weren’t postictal, but it’s erased what they had learned. And in epilepsy, the seizures, I mean memory is a process. Consolidation takes place over time, over a long time period. And if something disrupts that process, then that won’t be remembered. And episodic seizures, and probably even the spikes, if people have some clinical seizures, and they’re not aware of, these things are taking place, and are affecting the laying down of new memories.

So, it could be that if a patient and spouse say, “Well, don’t you remember that trip we took four years ago?” They may not recall that because the consolidation process had been affected by seizures, spikes, or clinical seizures. And the subclinical seizures are really a problem because you’re not sure when those things occur. You see them in the monitoring units all the time. So, long-term memory can be affected, and it is an object of study at present.

 

 

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Webinar: Anxiety and Depression Associated with Epilepsy

If you know someone with anxiety or depression and epilepsy, know they are not alone. One-third of people with epilepsy suffer from some form of psychiatric disorder, of which anxiety and depression are the most common.

This webinar discusses how anxiety and depression in people with epilepsy negatively impacts quality of life, reduces tolerance of antiepileptic medications, and increases the risk of suicidal ideation and behavior. The presentation also reviews how stress effects epileptic seizures and offers strategies patients can use to better cope with stress.

This webinar is presented by Dr. Andres M. Kanner, Chief of the Epilepsy Division in the Department of Neurology and Director of the International Comprehensive Epilepsy Center in the University of Miami Miller School of Medicine.


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Audience Q&A with Dr. Kanner

Dr. Andres KannerHow does the acceptance of an epilepsy diagnosis contribute to the development of both mood and anxiety disorders?

That’s a very important question. And this is a question that, unfortunately, we neurologists do not spend enough time discussing with patients. Because failure to accept the diagnosis of epilepsy is very frequent, a very important cause of the development of symptoms of depression and anxiety.

One of the most difficult things about dealing with epilepsy, in addition to having seizures, is the loss of the predictability of life. When you have epilepsy, you don’t know when or if you’re going to have another seizure. And that loss of predictability is very difficult to come to terms with in the beginning. It causes tremendous anxiety for the patient. It also causes tremendous uncertainty in parents of children with epilepsy. And it’s not unusual that some patients may deal with that unpredictability through denial and saying, “No, this was not epilepsy. This is not going to happen to me again.”

The emotional energy patients and families use to deny the diagnosis of epilepsy results in the opposite effect. They become more anxious and more depressed. In my experience, when a child or adolescent experiences epilepsy and senses their parent is having a very hard time accepting the diagnosis of epilepsy, the young person or child will react by denying the occurrence of the seizure disorder and will start acting out, becoming non-compliant. And it’s going to result in a vicious circle.

One of the common mistakes is that family members don’t want to upset the patients. And when they are talking about the epilepsy, they say, “No, no. Don’t worry about it. Everything is okay. We don’t want to upset you.” What needs to be done is the opposite. You need to talk openly about the diagnosis of the epilepsy, the fear of what can happen if you have epilepsy or an epileptic seizure.

And the big elephant in the room is, particularly for patients and parents, “Am I going to die if I have a convulsion?” That fear needs to be openly discussed by the patient, the family, and all family members. By coming to terms with the loss of predictability, which takes time and is equivalent to a mourning process, people come to terms with accepting the diagnosis. Then one morning, they wake up and say, “You know what? I can live with this.” But this is essential. This is a very essential part of accepting the diagnosis of epilepsy. And it prevents the development of unnecessary depression and anxiety that is a reactive process to the diagnosis.

In regard to surgery: Why can epilepsy surgery result in anxiety and depression right away? 

That’s a very interesting question, because this occurrence is not a very simple process. What we see is that about 20 to 30% of people who undergo temporal lobectomy may experience episodes of depression and anxiety during the following three to six months. After a period of 12 months, those symptoms remit completely in most of the patients, but about 10% of patients may continue to experience these symptoms.

The majority these individuals may have had depression and anxiety before epilepsy surgery, so what these episodes consist of are a reactivation of a presurgical depressive and anxiety disorder. Those depressive or anxious episodes need to be recognized before the patient goes to surgery, and the patient and family need to be educated on the possibility of these episodes recurring during the first three to six months post-surgery. The good news is, these episodes can be easily treated with low doses of antidepressant medication.

There is, however, about 15 to 20% of patients without a past history of anxiety and depression who develop these conditions after surgery. The explanation for that may lie in chemical changes that occur with a seizure disorder. That’s one of the hypotheses, but we really don’t know exactly how to explain this phenomenon.

Another interesting observation is that about 50% of patients who had a history of depression and anxiety prior to their surgery, stop experiencing those episodes after surgery. For these individuals with epilepsy, not only is the temporal lobectomy resulting in seizure improvement or remission, but also the remission of depression and anxiety disorders.

As a follow-up question, are there any studies that analyze patients pre- and post-surgery and examine their levels of anxiety and depression?

Unfortunately, there is very little in the way of formal studies that have been conducted. There were some studies done in Australia which identified that people with a previous history of depression and anxiety are more likely to experience depressive episodes after surgery. Hence why doctors could actually identify who is at increased risk of developing post-surgical episodes of depression by taking a very careful history of their psychiatric disorders before surgery.

We don’t have studies on the mechanisms that facilitate the development of the normal episodes of depression and anxiety. But hopefully, with new neuroimaging techniques and higher-solution MRI studies, we will have answers in the future.

Can you speak to the effectiveness of yoga, meditation, and homeopathic options and if patients can try these approaches before starting additional medications?

I advocate the use of yoga and relaxation techniques for people who report worsening seizures or an increase in seizure frequency when they are going through very stressful situations. In these patients, the use of these relaxation techniques – yoga in particular – can be very effective in teaching how to do self-relaxations, which in turn results in a decrease in seizure frequency.

With respect to the use of yoga and relaxation techniques for the actual treatment of depression or anxiety disorder, these practices can be beneficial, but if there is a long history of depression and anxiety disorder, it may be necessary to use additional treatment strategies. If medication is something the patient is not interested in considering, cognitive behavior therapy is a very effective form of treatment for depression and anxiety.

Cognitive behavior therapy is a form of therapy provided by psychologists. It consists of 12 sessions, one session a week, in which the psychologist teaches patients how to counteract and overcome the symptoms of depression and anxiety. The effect of this therapy is extremely impressive, and can be as good or even better than the results seen with medications. We refer our patients for cognitive behavior therapy to neuropsychologists in the community with very good results.

Is research being done to determine if cannabidiol (CBD) helps to control not only seizures, but also some mood disorders associated epilepsy?

There is no data on the use of cannabidiol on the treatment of mood and anxiety disorders in epilepsy that I’m aware of. I know there is very extensive use of marijuana by patients as a way of self-management of anxiety and depressive symptoms. The psychiatric literature on the impact of marijuana on a mood and anxiety disorder is indicative that, in the long term, it has a negative effect.

Now we’re talking about marijuana, which has a THC component. We’re not just talking about the cannabidiol extraction being used for the treatment of some epilepsy conditions. People with a history of mood and anxiety disorders have to be careful with the use, and particularly excessive use, of marijuana as a self-treatment, because in the long term it can worsen these conditions.

We don’t know cannabidiol’s effect on the treatment of depression and anxiety. This topic is one I’m sure will be investigated in the future, but today we don’t know.

Should a patient request the completion of the questionnaires you mentioned in your presentation, or are they just a normal part of the diagnosis and treatment?

Many clinics today in the United States are using those questionnaires when the patients come into the epilepsy clinic. The patient fill out these questionnaires in the waiting room, then give them to the physician. This is a nice way for the physician to screen for the presence of mood and anxiety disorders and to know to follow-up about these symptoms.

If the clinician the patient is seeing is not using those screening instruments, patients can suggest it. These instruments can be downloaded for free from the American Epilepsy Society or the Epilepsy Foundation. Or patients can email me and I’ll be happy to give them the reference of where they can obtain these instruments.

I think physicians who use the questionnaire have found it to be extremely effective. The NDDIE now has become adopted by the International League Against Epilepsy as the screening instrument for depression. In addition, it has been translated into close to 17 languages, so it’s widely used across the world.

Did the studies you referenced in your presentation account for gender differences and associated hormonal and catamenial epilepsy?

Yes, that’s a very important question. We know that women have a higher incidence of depression than men among non-epileptic patients with depression. In people with epilepsy, we’re not seeing that gender difference. The risk of depression is as high in men as it is in women. That’s an important difference we see in people with and without epilepsy.

In the case of catamenial epilepsy, which consists of seizures occurring around the time of menstrual periods, there is a change in mood during the menstrual period that women may experience. There are some women who notice they can become more easily depressed around their menstrual periods. They may have to push themselves to do things, they may become more tearful over little things, they may become irritable or cranky, they may notice their concentration is affected. So it’s like they are experiencing mini depressive episodes which last a few days every month.

Women with these conditions often have a previous history of depression or have a family psychiatric history of mood and depression disorders, as these disorders are genetically mediated. When somebody has these conditions, the next generation (first-degree relatives) have an increased risk of experiencing these psychiatric disorders, because they are linked to several genes.

That being said, the occurrence of changes in mood around the time of menstrual periods should prompt the patient to see if they have any risk factors. Patients often find out that, “Oh, my mother used to suffer from severe depression or anxiety, my grandmother….” The fact is that the sexual hormones have the same impact on seizures as on the development of symptoms of depression.

Can you summarize the main causes of mood disorders that affect epilepsy patients?

Mood and anxiety disorders have multiple causes. As previously discussed, one cause can be a reaction to the diagnosis of epilepsy and the lifestyle implications (not being able to drive, reduced independence, etc.). Also as previously mentioned, there are risk factors associated with family history of mood and anxiety disorders, including whether there’s a first or a second-degree relative who has suffered from these kind of psychiatric disorders.

A third cause is the chemical changes that happen in the brain which are associated with the seizure disorder, as well as side effects of both pharmacologic and surgical antiseizure treatments.

There are also peri-ictal psychiatric symptoms, which is when the symptoms of depression and anxiety are related to the actual occurrence of the seizure itself. This situation has to be distinguished from the causes mentioned above, because obviously those symptoms have a different mechanism of development and are not responsive to pharmacologic treatment with antidepressant medications.


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.

Webinar: Cannabidiol and Epilepsy: The Real Risks and Benefits

Recently there has been a great deal of focus on the uses and risks of marijuana in the field of epilepsy. Epidiolex, a  cannabidiol (CBD) treatment for epilepsy, gained FDA approval for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome, two rare and severe forms of epilepsy. This is the first FDA-approved plant based treatment with greater than 98% CBD.

In this webinar, learn why CBD may be an effective treatment for certain types of epilepsy, what risks can be associated with CBD, and what the FDA approval of means for the future of epilepsy research and treatment.

This webinar is presented by Dr. Anup D. Patel, Section Chief of Pediatric Neurology at Nationwide Children’s and Associate Professor of Clinical Pediatrics and Neurology at The Ohio State University College of Medicine.


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Plus, get additional research insights from CURE Chief Scientific Officer Dr. Laura Lubbers in this episode of our Seizing Life podcast.

Audience Q&A with Dr. Patel

Dr. Anup PatelHow does Epidiolex differ from the medical marijuana patients can get from dispensaries in some states?

I think the biggest difference is that the Epidiolex product must contain 98% or more CBD and very little anything else. The products you can get from dispensaries do not have that same requirements, so they may not have as much CBD. In addition, they may contain other compounds from the plant or the other chemicals I mentioned during my presentation. It cannot have any chemicals that aren’t listed, any bacterial contamination, or a higher percentage of THC. All of this is not the case with the non FDA-approved products.

There are similarities, though: CBD is CBD. If these products contain a high level of CBD, it is the same CBD that is in the Epidiolex product. CBD is a chemical structure. There is a synthetic version of CBD being concurrently studied. It is going to be a laboratory-made CBD based on the same chemical structure. That product will be 100% CBD and will not have anything else in it, but it is not plant-based.

If you’re taking a THC/CBD product purchased through a dispensary, is there a test to find out the ingredient accuracy of the product?

Yes, there are some labs, depending on your location. There are labs now that will test your products. The key thing is to find a certified lab, so that you can be sure of the integrity of the laboratory testing process.

The danger is you would have to test every bottle you get, because the content of CBD, THC, and other chemical compounds will change from bottle to bottle and month to month. To do testing well, you must test all your products every time you get a new bottle, which is really difficult and not cost effective.

Can you speak to the integrity and consistency of the Charlotte’s Web product?

There have not been a lot of good studies to show that. The company does claim to test the product and check this on a regular basis. That being said, to my knowledge this testing is done locally and not through an outside, unbiased service. Therefore it’s hard to make good, accurate information about it.

I do hope they will use what has happened with the Greenwich product Epidiolex as an example and follow the same processes to hopefully get their product potentially FDA approved. But to do that, their product will have undergo the same tests and studies that the Epidiolex product did. But I’m hopeful that this will help spur on some of that work, either through this or some similar type of group.

How can patients who have similar phenotypes to Dravet syndrome and LGS, but don’t have a specific diagnosis, access Epidiolex? If they cannot, will there be a way to in the future?

I think that’s my most important question. I’m glad somebody asked us. The reason is that we anticipated this product or medication could be of benefit outside the actual FDA label of Dravet and Lennox-Gastaut. To get ahead of that, we published a lot of the related data through our expanded access program.

Normally when a medication is FDA-approved, it’s used on label and then neurologist, pediatric epileptologist, or adult epileptologist will use it “off label”, because they just want to help patients, and not everything is known from studies. The process will lead to publications being submitted to insurance companies that they’ll then use to potentially reimburse the medication off label. In this case, we’re hopeful. I cannot guarantee it, but we’re more hopeful because actually the way this story got told was we got the off label studies published that led to the on-label studies.

We’re sitting on mountains of publications that I really encourage medical providers to submit to try to get this medication authorized by insurance companies. Unfortunately there’s no guarantee, as it really will depend on your specific insurance company. But please know that these manuscripts are out there and can be submitted to change their decisions if they choose not to authorize this and pay for it. We don’t want patients having to be burdened by medical bills. This is one way we can get ahead of that and have their medical insurances pay for it.

The company has promised to run and have run patient assistance programs, so also look towards them to help. I don’t have any details. I don’t work with them on that, so I don’t know what they’re offering, but they have told me that they’re going to have these patient assistance programs. So please, if you’re going to get this medication or prescription, get your insurance to pay for it the best way you can and use the resources that are available to try to get it compensated and paid for.

Was there an interaction with those on Onfi and Valproate who were part of the extension studies? Were the interactions in the co-treatment or were the children allowed to be in the trial while on these medications?

In the trials, we saw the same thing we saw during the Expanded Access Program trials; in some cases there was an interaction – not necessarily with clobazam, but with broken down clobazam – causing kids to be tired. I will tell you in a lot of cases the answer was not to get rid of the Epidiolex or CBD product, it was to actually lower the clobazam dosing. It’s important to work with your medical provider to either lower one or both of the products. In many cases, excessive tiredness did go away.

There is a risk for increased liver enzymes with Epidiolex or CBD products in general, even if you’re not on valproic acid or Depakote. The risk was more commonly seen in patients who were on both  CBD and Valproate during the randomized double blind placebo controlled trials. In those cases, every single one of those patients had their liver enzymes returned back to normal by doing one of three things; getting rid of the Epidiolex, getting rid of the Valproate, or lowering either medications. In those three scenarios everybody, returned back to normal. But it is going to be recommended that a patient get baseline liver enzymes before going on Epidiolex. There will also be recommendations to be monitored while you’re on this medication, because we’re not able to predict if you’re going to have this interaction or not.

While we need more data to confirm this, we do feel there may be a good pattern in kids and adults who are on both Epidiolex and clobazam, meaning that perhaps those two medicines work better in combination than either of them separately. But again more information needs to be studied with that.


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.

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.


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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?

Yes.

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.