Promising Anti-Epileptic Drugs in Development

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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.

A blond woman cradles her infant in her arms, trying to soothe them.

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.

 

An elderly woman speaks with her doctor, who is explaining the prescription.

Epilepsy’s Impact on Memory and Cognition Over Time

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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?
A young woman is speaking in an animated way to her therapist, who is listening closely.

Webinar: Anxiety and Depression Associated with Epilepsy

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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.


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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.