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Aging and Epilepsy: Consequences and Comorbidities to Consider in Older Individuals


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Epilepsy is the third-most common neurological disorder in people age 65 and older after stroke and dementia, conditions which themselves increase seizure risk.1

This webinar discusses the relationship between epilepsy, dementia, and stroke, and discuss whether people with epilepsy have an increased chance of developing dementia as they age. Viewers will also learn about strategies that people with epilepsy can implement to reduce their risk for these conditions.

  1. World Health Organization. “Epilepsy: A Public Health Imperative.” Date: 2019. Date accessed: May 3, 2021. https://www.who.int/mental_health/neurology/epilepsy/report_2019/en/ 

About the Speaker
Dr. Alice Lam is Assistant Professor of Neurology at Harvard Medical School and the Massachusetts General Hospital. As a physician, Dr. Lam takes care of patients in both the subspecialty Epilepsy Clinic as well as the Memory Disorders Unit. Her clinical and translational research program explores the interface between epilepsy, the neurodegenerative diseases, and cognition, using a combination of neurophysiology, neuroimaging, artificial intelligence approaches and cognitive outcomes.


Q&A with Dr. Alice Lam

It is well-documented that AED side effects are more pronounced in the elderly because metabolism is slower. How should this be communicated to neurologists? Are they aware, and how often and what age do you recommend that dosages be lowered because of this?

Dr. Lam: That’s a great question. The answer to that is a little complicated, but you’re definitely right that as people get older our metabolism slows. Our liver slows down the metabolism, our kidneys slow down eliminating medications from the bloodstream. But that’s also highly variable from individual to individual and as you know people have different body weights and there’s a lot of different variability person to person. I think if you’re aware of that and you think that this may be something that affects you I think it’s important to talk to your doctor about that.

And one thing that your doctor can check, they can look at the level of seizure medicine that’s actually in your blood and that will give for you… That basically tells you how your body is metabolizing the amount of medication your doctor is prescribing for you. And it might turn out that maybe your doctor was unaware or your level was actually a lot higher than they thought it was and you might be able to reduce your dose of seizure. But that’s one objective way you can decide whether you’re on too much seizure medication as you get older.

Can Dilantin affect balance over time and do you have any comments on this or suggestions about what to do about it? There’s an article published in Future Medicine entitled Antiepileptic Drugs and Their Impact on Balance, and this person hopes that you can comment on that.

Dr. Lam: I haven’t read that article but I can say that Dilantin can definitely affect your balance and it can do that in a few different ways. One, if you’re on too high a dose of Dilantin you can actually have this Dilantin toxicity where you’re off balance and you’re wildly… Some people describe it as this feeling of being drunk without having had anything to drink. And so if your dose is too high you might notice that, and if that were the case you’ll probably notice it usually about the hour or two after you take your medicine. That’s one way it can affect dizziness.

But long-term it can also affect a dizziness in a number of different ways. Sometimes people can develop what we call a neuropathy that’s associated with long-term Dilantin use. That means that the nerves that go from your spinal cord down to your feet and help your brain know where your feet are and what they’re feeling on the ground below, those nerves can get damaged and you might not be able to feel your feet as well. And we also know that Dilantin over time can affect the cerebellum. That’s a structure in your brain that controls balance and coordination, things like that. So, yeah, I think that there is a fair amount of evidence that Dilantin can affect your balance but again it can do that in different ways.

Is there anything that can be done about that?

Dr. Lam: If you’re on too high a dose of Dilantin then obviously reducing the dose or trying to adjust how you take those doses or maybe even changing the medicine if it’s not the right medicine for you would be one way to do it. Obviously Dilantin is an older seizure medicine and I tend to avoid using it in older adults for a number of reasons. It tends to be older adults who are on it because if they were diagnosed with epilepsy years ago that’s what was available years ago and a lot of people are very comfortable staying on that medicine if it was working for their seizures, and so that’s often the case of patients who come to see me who are on Dilantin already.

But there’s a lot of newer seizure medications that may not have those kinds of adverse effects, for one. Dilantin also, the way it’s metabolized is a little interesting and there can be interactions with a lot of other medications, not even just seizure medications but other common medications that you might take for other conditions. In an older adult if you’re running into these problems you might think about switching off of Dilantin for that reason, the medication interactions and these long-term effects that we know can happen with it.

If a person is over 80 and has had no seizure activity in 15 years, do you think medication dosages could be lowered?

Dr. Lam: This is something that’s very individual and I can’t answer that without knowing more details of what happens to you when you’re having a seizure or what risk for injury might you incur if you did have a breakthrough seizure because you lowered your dose. But these are tricky questions. Even if I did know more about this person it’s not something that I could answer concretely, it’s something that really depends on the risk benefit ratio for each person and how willing they are to take a risk like that. I think you have to think about what would happen if you had a breakthrough seizure versus how bad it is to be on the level of medicine that you’re on right now. Are you having a lot of side effects from it or not? You just feel you want to be on a lower dose. The good thing is to discuss with your neurologist.

I think about the risk of falls, and as we get older we have greater propensity to break bones and so we want to avoid falls as well for those reasons so it is trickier. Here’s a bit of a different question and you sort of answered it I think during your talk but let’s just review. So a rupture of an arterial venous malformation maybe has led to development of tonic-clonic seizures and many cognitive issues, including problems with memory. Is there a greater risk of this person acquiring dementia as they age?

Dr. Lam: We can think about this in terms of this whole cognitive reserve a thing that I talked about. And so having this brain injury and having these cognitive issues that result you’re now at a lower cognitive reserve than you would have been before this AVM ruptured. And so I would say that, yeah, if you were to develop the kind of changes in your brain from Alzheimer’s disease you might be more susceptible to having dementia earlier from that than you would have had you not had this brain injury. But it doesn’t mean that you shouldn’t still try to reduce your risk for that.

A person wants to know if their seizures increase with age. And at what point, and this I think is really relevant for those independent older people around, driving. At what point in time do you start having the discussion about driving or not driving?

Dr. Lam: The first question with the seizures increase with age, again, I’d have to say it depends but it’s not something that I typically see or counsel my patients like, “Oh, we better worry that your seizures are going to get worse as you get older.” It’s not something that… I would say I don’t think that there’s a lot of evidence that that occurs but again it depends on each individual.

The second question about driving, that’s a great question. And this is a question that I deal with with people with epilepsy and I take care of people with Alzheimer’s disease as well so it always comes up then. I think that sometimes people have awareness or insights to know when they feel it’s not safe for them to be driving. But it’s a really hard thing to actually make this assessment in my clinic, in my office, because I’m seeing somebody, I’m talking with them but I have no idea when they get behind the wheel how they would react to things. I don’t know, what would they do? Would they be able to stop in time if a kid ran out in front of the car to run after a ball or something like that? What would they do if a car swerved into their lane all of a sudden, how would you react to that? These kinds of things are really hard to gauge in a clinic.

One thing I’ll often do is sometimes I think it becomes pretty clear that someone shouldn’t be driving. They’re either getting into accidents or they’re getting lost while they’re driving, things like that. And those cases are a little bit more straightforward and often families will take away their loved one’s keys before even asking me about it. But when it gets a little grayer, when things aren’t quite working as well as you want to in your brain, but a lot of you’ve been driving your whole life, it’s an automatic thing almost, you don’t have to think about it so much.

What I’ll often do is I’ll recommend that people undergo a formal driving assessment. And so there are different centers that do this. There’s occupational therapists who are trained in assessing people’s safety in driving, and often this kind of driving assessment it may involve pen and paper tests first and if you do fine on that then you would do a behind the wheel on the road test where someone will be with you and assessing how you’re able to react to different things that happen. And so I often lean fairly heavily on these kinds of assessments to make a good assessment of that. It’s again, as I said, it’s really hard to know from just talking to someone in my office how they would actually do on the road.

Sometimes it’s actually more helpful for family members who don’t want their loved ones to be driving but their loved ones won’t listen to them. And so and if they won’t listen to me I’ll say, “Well, if you want to drive you need to have a formal driving evaluation.” And then it’s an objective, it’s not just someone judging or wanting to take away their independence it’s an objective. You either passed or you didn’t pass the test.

Are some epilepsy medications worse for dementia?

Dr. Lam: Let me answer that a different way, or let me pose the question differently. Maybe one way to ask it would be, are some epilepsy medications worse for cognition, not necessarily dementia? But I guess if they’re worse for cognition then they’re not going to help if you have dementia either. So if I ask my question, are some medicines worse for cognition? There are some medicines that we know have a worst cognitive profile compared to others.

Now, again my patients can respond very differently to seizure medicines. Again, there’s a lot of inter-individual variation, but generally there are some medicines that are thought to be relatively neutral or relatively… That they don’t really affect cognition too much. And those medicines that people often use in that case are levetiracetam or Keppra and lamotrigine or Lamictal. Those are thought to have relatively benign cognitive effects.

But then there are medicines that we know can definitely worsen cognition. These tend to be some of the older ones, so phenobarbital has been shown to have poor effects on cognition. Dilantin even can do that as well and carbamazepine. Some of these older medicines may have more of those more pronounced effects. But, yeah, I think, again, as in that slide where I looked at what kinds of things can affect memory in someone with epilepsy, choice of seizure medication can definitely do that. Topiramate, that’s another one that tends to affect cognition pretty badly.

How about zonisamide?

Dr. Lam: Again, it really varies from individual to individual. Zonisamide wouldn’t be on my top list for someone who’s having cognitive problems already, it would a bit further down the list. But I would say it’s not entirely neutral but it’s not as bad necessarily as some other ones. But everyone is… Again, I can have one patient who’s on a whopping dose of a medication, has no idea it’s in their system. And have another patient who’s on the same medication on a really tiny dose and is falling over because the side effects are so bad. So it’s really hard to predict that unless you actually just try it and see how you feel on it.

If somebody is feeling a cognitive impact and it’s possibly because of their medication, are those changes reversible if patients switch medications?

Dr. Lam: Some of them can be. Again, if it tends to be a, “I just started this medicine a couple of months ago and I and my family are all noticing that I’m a lot slower on forgetting conversations.” Then yeah, in general come off that medicine. I would expect those side effects to get better as you’re off the medicine. But some of these older medicines like phenobarbital, Dilantin, if you’ve been on them for years and years and now you’re coming off them it may not be as great a benefit because there are some long-term changes from those medicines. So you might not notice as great a benefit but it might still be worth trying to come off them to see if you do get a benefit.

Can testing neuropsych evals tease out declines in cognition based on AED side-effects versus declines resulting from regular aging? Can testing determine the source of the cognitive decline?

Dr. Lam: I use neuropsychological testing actually pretty frequently in my patients with epilepsy and memory problems. I think that there’s a number of things that can be helpful with it and often I do use it for the purposes that you’re talking about to try to tease apart what is actually causing this person’s cognitive impairments. Because one thing that neuropsych testing allows you to do is it really… I mean, if any of you have ever done neuropsych testing it’s a several hour-long cognitive test. You never knew that there are many tests for your learning and for your memory and things like that. So it’s very detailed and it can get in very good detail what parts of your thinking are working well and what parts of your thinking aren’t working well?

A lot of patients will say, “My memory is bad.” But actually it’s not their memory that’s bad, it may actually be their executive function, their ability to plan and organize things that’s more affected than their memory. And so neuropsych testing allows you to tease apart some of those things. And depending on what cognitive domain, whether it’s memory, executive function, language, any of those things, depending on which domains are affected, that can often help us hone in on what might be causing those changes.

And so sometimes that can help me distinguish between whether it’s someone’s longstanding epilepsy that’s causing their cognitive troubles or whether it might be something new or different, maybe they’ve developed dementia or maybe they’ve developed depression late in life. Trying to tease apart some of those factors, neuropsych testing can be helpful for that.

Is the ketogenic diet a heart-healthy diet?

Dr. Lam: I know that people who are on the ketogenic diet get monitored frequently. They have their cholesterol levels checked, they have a lot of these metabolic things checked. But I don’t know what the data is in terms of long-term, if it actually predisposes you to having heart attacks because of the high-fat content or not.

Does chronic microvascular ischemic change get worse with time and does it make epilepsy worse?

Dr. Lam: For those who don’t know what is chronic microvascular ischemic change, the best way I can describe it is let’s say you have an MRI that’s done. What it looks like on an MRI are these little white spots actually, these little white spots that you don’t normally see but you do tend to see them more as people get older. And what we think of these little white spots is that it’s reflecting damage to really small blood vessels in the brain. It’s showing you that there’s some disease of the small blood vessels, they’re affected somehow. And sometimes that can be due to the kinds of vascular risk factors that we’ve been talking about, high blood pressure can definitely do that. People who smoke definitely you’ll see a lot more of these microvascular changes in the brain.

There have been studies that been done recently looking at what are the risk factors for people who develop late-onset epilepsy. And it turns out that people who have these chronic microvascular ischemic changes, again think of them almost silent changes. Most people don’t know that they’re there, it’s something that you see on MRI, on brain imaging when you do the imaging but they’re silent. Think of it as silent cerebrovascular disease. It tells you that your blood vessels are not as healthy as we’d like them to be.

But anyhow, if you have those kinds of changes in mid-life in your 40s and 50s, that is actually a risk factor for developing late-onset epilepsy. Whether if you already have epilepsy that kind of change will worsen your epilepsy. I’m not sure if we know that or not, but again, in terms of this vascular risk I’ve been talking about, think about this chronic microvascular change as another sign that maybe things aren’t as healthy as you want them to be.

Are there different outcomes on epilepsy in other areas of the brain, for example, parietal lobe? Has this been studied or has it just been focused on temporal lobe epilepsy (TLE)?

Dr. Lam: A lot of the studies on cognition and epilepsy have been done in people with temporal lobe epilepsy. It’s the most common focal epilepsy so there’s a lot more people that have it compared to things like parietal or occipital or frontal lobe epilepsy, that’s probably one of the reasons. But also we know that temporal lobe epilepsy affects the temporal lobes and we know that those are really important for memory as well. I think that historically that’s been the case and it’s hard to do… You need really big studies in order to make these kinds of observations or to get these kinds of insights you need a lot of patients over time too.

So you’re looking at thousands of patients in that study in that graph that I showed. I think it can be challenging maybe to find enough people with certain kinds of epilepsy to be able to do those studies and to be able to make these kinds of clear inferences. But it’s an area that we definitely need to work more on to understand better.


The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.

a lime green ribbon with the text "Mental Health Awareness Month"

Mental Health Awareness Month

May is Mental Health Awareness Month, an opportunity for the epilepsy community to raise awareness and challenge stigma about mental health concerns specific to people with epilepsy.

One-third of people with epilepsy suffer from some form of psychiatric disorder, of which anxiety and depression are the most common.

To learn more about epilepsy and mental health, watch or listen to the Seizing Life episode “Epilepsy and Mental Health: What You Should Know featuring Dr. Andres Kanner” or the webinar “Anxiety and Depression Associated with Epilepsy.”

 

Siblings and Severe Childhood Epilepsy: The Impact of Seizures on the Family’s Mental Health

Siblings of children diagnosed with a severe childhood epilepsy known as a developmental and epileptic encephalopathy (DEE) often play an integral role in the care of their brother or sister. While they may learn patience and compassion at an early age, the mental health impact on these siblings can be enormous and often overlooked.

Children who have a sibling with a DEE may experience very strong emotions such as guilt, anger, sadness, fear, anxiety, and depression. The Siblings Voices Study, which included siblings in a variety of age ranges, was created to help families understand more about the impact of having a brother or sister with severe epilepsy and how these siblings adapt.1

This webinar discusses some of the key research findings of the Siblings Voices Survey, including some strategies to help improve the mental well-being and social development of siblings and resources that are available for families.

  1. Psychosocial impact on siblings of patients with developmental and epileptic encephalopathies. Laurie D. Bailey, Lauren Schwartz, Tracy Dixon-Salazar, Mary Anne Meskis, Bradley S. Galer, Arnold R. Gammaitoni, Carla Schad, Epilepsy & Behavior, 2020, Volume 112, 107377 


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To hear from two college students about their experiences growing up with a sibling who has epilepsy, watch or listen to the Seizing Life episode Growing Up Alongside a Sibling with Epilepsy featuring Emma Cardwell & Nathan Bliss.


About the Speaker
Dr. Kelly Knupp is Associate Professor of Pediatrics and Neurology at the University of Colorado. Dr. Knupp practices medicine at Children’s Hospital Colorado in Aurora, Colorado and is the Associate Research Director of Neuroscience Institute and Director of the Dravet Program. Her interests are epileptic encephalopathies including Dravet Syndrome and infantile spasms. Dr. Knupp is also a member of CURE Epilepsy’s Scientific Advisory Committee.


Q&A with Dr. Kelly Knupp

For siblings of children who have frequent seizures or other types of associated unpredictable, visible medical things that need urgent care like respiratory events, is there a language, or are there tips to make this easier on the sibling?

Dr. Knupp: I think it’s really important to meet the siblings where they’re at. But I do think it’s important to talk to them about it. You may have some local resources with child life who may be able to come up with some very age appropriate terminology to discuss that. I know at my institution, our child life personnel are available to talk to siblings just as much as they are to talk to patients and are really good at figuring out how to turn that terminology into something that’s child-friendly. So ideas like having an IV that goes into your blood vessels paints a very different picture for a five-year-old than it does for a 15-year-old. So it’s really important to think about the words you’re using and how you describe it.

But I think as a parent, what’s also important is to ask clarifying questions to see if the sibling has really understood what you are trying to describe, or if they came up with something scarier in their head. That’s more often what happens, is we use words and children may misinterpret that as something scarier than what’s really happening. But I think knowing your resources and trying to find help with that can be really helpful. There are a number of books out there that can help with some of these specific things as well. And usually child life is aware of those books, or if there’s a family library at your hospital, they often have a number of these books around that can help describe those things.

Are there other helpful literature or resources in general to share with families who are struggling?

Dr. Knupp: Again, I would probably go back to the child life specialists and the family library. They often have sort of the best group of books, the… We actually turned to our epilepsy foundation to provide those books about epilepsy. So I think… I wish I knew of a great resource that listed all of those books. And maybe if somebody has a good idea of those resources, they can post them in the chat to share them with us, that really would be an amazing resource for families if there was a website that they could go to and find those.

One person notes that she believes that there’s a list of books on epilepsy.com. As a sibling myself, I pay attention to this space and there are lots of great books that span the age ranges. I was just reading one over the weekend that was really targeted to the younger set to talk about a sibling with disability. In this case it was somebody with autism, but clearly many of the context are the same. This particular book also had a workbook like a coloring book where a child could express their emotions.

Dr. Knupp: Along that line, one of the things I didn’t mention, I’ve had a number of siblings who have used an art therapist, which has been really helpful. It’s been really impressive to me to see some of the artwork that comes out of that.

What is most impressive to me is that oftentimes what the children think is going on is far worse than what’s really happening. particularly when our patients are going through things like epilepsy surgery, we have found that it’s really important for those siblings to be able to come into the hospital and see what’s happening to their sibling because otherwise what they picture when they hear about things like intracranial electrodes and surgery is so much worse than what’s really happening. It’s really important for them to see the real thing and know that their siblings are safe, but art therapy can be particularly powerful and helpful.

This person has found that her parents were also emotionally impacted, what resources are available for them?

Dr. Knupp: Yes. Parents definitely can be emotionally impacted by this. I think that every parent who has a child with a chronic illness really has to go through the whole grieving process. I think it can be really helpful to talk to other parents. I think it’s helpful to have a good social support network and it may require therapy. It may be that they really do need to sit down with a counselor or a therapist to work through some of that, and also have some insight of whether they may have some underlying anxiety or depression that could be contributing to this as well. And grieving is something that everybody does in different ways. So some people move through the grieving process fairly quickly, some people stall at one of the stages. So I think trying to get help to continue to move through that process and come to a place of acceptance can be really helpful for everybody in the family.

To your point, Kelly, I think we are recognizing it as a community that this is not post-traumatic stress, this is traumatic stress and chronic stress and that process starts very early and it’s good to start addressing it early for all members of the family. So here is a question. There are so many ways a severe epilepsy divides a family in an effort to maintain some normalcy for siblings versus keeping the child with epilepsy safe. How do families accept the new normal and not allow it to divide a marriage?

Dr. Knupp: Boy, that’s a challenging question. That’s a very complicated question and we know that divorce rates are higher in families with chronic illness. I think the more parents are aware of that, the more they are open to receiving some support and help through that. I think it’s also important for parents to recognize that their own individual processes are going to be different between the two of them just like it is with any other crisis or trauma that they have to deal with. And some families really do better when they’re apart than when they’re together, which is hard to say but that is the reality sometimes. But I think trying to intervene and trying to find some time to focus on yourselves as a couple can be very helpful.

That’s where extended family and friends often come in. It can often be very difficult to receive help from people outside your immediate nuclear family but I think that can be really helpful. Many of those people want to help you, they just don’t know how to help you. And so trying to establish that communication so that you can be clear with them of it doesn’t help me when you come empty my dishwasher, but it’s really helpful if you can take the kids for three hours so that we can go for a walk together and try to reconnect and trying to find ways to maintain your relationship that way. But I don’t think that there’s a perfect answer to this. Honestly, there are families with healthy children who struggle with this as well. So it’s not something unique to children with chronic illness, it’s just something that we see more often in children with chronic illness.

Can you discuss strategies for talking about risks of death for our eight-year-old with severe DEE has been near death multiple times and is in a hospice program? While those high risks for imminent death have been less frequent recently, should we still be open about discussing the risk with a five-year-old sibling?

Dr. Knupp: Boy, that’s tough. And I think this is where things child life can be really helpful. I mean, this is what child life does, is helps you have these difficult conversations. I think for the five-year-old, it’s really important to ask them where they’re at. And I would keep in mind that many siblings do worry about this and they may be afraid to talk to you about it. And so it may be helpful to say, “Hey, when you think about your brother or your sister, what worries you are you? Are you worried that he can’t run? Are you worried that he eats different food? Are you worried he’s going to die someday?” And try to figure out where that five-year-old’s at so that you can answer their questions in the place that they’re at. And I do think it’s important to talk about it and also to let them know that it’s not their fault. Particularly for a five-year-old the world still sort of revolves around them and so things that are not their fault still feel like their fault. And I think that’s really important to talk about that.

So here is sort of the intermediate age. The siblings in our family showed previous unspoken anxiety and concerns as they began planning their own families, thoughts about this.

Dr. Knupp: That’s very real, right? The question that comes up is will this be what my family looks like and do I have to worry about my children having this epilepsy? I think we’re in a better place now answering those questions than we were 20 years ago, because we know so much more about genetics. But I think having open honest discussions about that … I know that in my practice I’ve met a number of families who had sort of stopped looking for the cause of epilepsy for several years because it was exhausting, it was disappointing, it’s expensive, and it didn’t make a difference in the day-to-day care of their child. But when siblings started to approach sort of family planning age, it took on a new significance to reach out and have genetic testing done to figure out what were those risks really. So I think as much as you can provide information that usually is helpful.

I think also having open discussions about expectations of whether who will care for this child as parents get older. Oftentimes it’s very surprising because many times siblings will say, “That’s what I’ve always planned to do.” And the parents say, “Boy, I don’t want you to have this burden.” So it’s really important to have that discussion so that there’s a clear plan and clear expectations. Because more often than not, that’s the way that discussion goes: Parents are trying to find a way to reduce the burden and the siblings are saying, “No, no, no, I want to do this.”

Our focus was on our child with epilepsy and the therapy for coping with his diagnosis. How do we introduce this with his older sibling after the fact and make sure we didn’t neglect their feelings during this entire process of learning and understanding?

Dr. Knupp: Well, first of all, I would give yourself a break because you can’t undo the past. So if you think that you may have neglected something, what’s done is done and you can’t undo that. I think it’s important to focus on the here and now and moving forward and checking in with them and asking them, how are they feeling? Maybe if they’re older, talk to them about how you’re feeling and what it felt like in those times in the past that you felt like you had to do everything you can, and all of your energy had to focus on that and now you want to move forward. But I think it’s really important to be forward-looking with this. We’re not perfect, none of us are perfect and we’ve all had those moments where you really can’t undo that. But what’s important is to recognize the situation you’re in now and try to find the best path forward.

Just to clarify that child life is usually services at hospitals. Is that the case?

Dr. Knupp: Child life is usually services at hospitals, the vast majority of children’s hospitals have both inpatient and outpatient child life experiences. At my hospital they are able to meet with people before procedures, before appointments, they’re able to meet with siblings to talk about things like this. We actually have our child life specialists come up to our epilepsy camp to help out there. So child life specialists are usually open to a broad range of supports that they’re able to provide.

So somebody is asking for ideas for affordable counseling for parents. It’s definitely chronic anxiety and stress that would be lifelong. Is there anything available through hospitals for the parents?

Dr. Knupp: I think that’s hospital dependent. Here in my state, we would usually refer somebody to the Epilepsy Foundation for that as opposed to the hospital because we’re a children’s hospital. But I do think reaching out, and this again comes to sort of knowing your local resources. There often are sliding scale offerings for counseling available in a variety of places, and so it would be very helpful to start talking to your providers to see if they’re able to identify those. Interestingly, usually your primary care provider has the best knowledge of what those resources are. So it may not be your neurologist, it may actually be your family practice doctor, your internal medicine doctor or your pediatrician who may be able to identify those resources for you.

I wanted to learn more about the BLC, basic life support. Where does one find more about that? Is that something that might be available through hospital resources or hospice communities? But families are so burdened with all they have to do, how can we get them there quickly?

Dr. Knupp: Basic life support is usually offered through Red Cross. It can also be offered through your local fire departments, your hospital. So there’s lots of different resources for basic life support. As I have started mentioning this to families, it’s something that teenagers have really been open to taking. For many girls who may be taking babysitting courses or things like that, basic life support is usually part of that. But it’s a very systematic approach to what to do when somebody is in trouble and really can go a long way to alleviate some anxiety of what will I do if my sibling runs into trouble. I’ve been really surprised that many of the sisters may have already taken it with their babysitting courses and things like that, but many of the brothers have been really excited to take these courses and really do think that it helps a little bit in alleviating anxiety.

Here is less of a question, more of a statement, but I think it’s important to just share these things. So this person says that they have twins and a severely medically refractory child with severe SCN1A epilepsy and his needs completely consume me. I’m home schooling too to keep them healthy. I feel like I’m just meeting everyone’s needs and not spending quality time with my medically fragile child along with the twins. I feel guilty.

Dr. Knupp: I acknowledge that. I don’t have a way to fix that. I think that the truth is parents feel guilty all the time because we can’t be everything to everybody all the time. And that sounds like a particularly stressful situation. I think the first step is recognizing that you feel guilty and if you’re able to find ways to get some help so that you are able to first take care of yourself. Because if we’re not able to take care of ourselves, it’s really hard to take care of our loved ones. We sometimes forget that because we’re so busy taking care of our loved ones. But even if it’s taking a 20 minute walk, taking a break for a cup of coffee, taking those moments.

I really do encourage families to reach out to your friends and family for that type of help. They oftentimes want to help you and they just don’t know how. And that’s something that’s fairly simple, that maybe you just go sit in the backyard. So sometimes I know it’s hard to be away from your child with epilepsy because nobody else knows their seizures as well as you do and nobody else manages their seizures as well as you do. But if you can just get 20 minutes in the backyard to catch your breath, now they would probably be more than willing to help you with that and to identify those resources so that you can take care of yourself in that situation. I think parents always feel guilty and I’ll be the first to admit, I don’t have any children with chronic illness and I still have many, many moments of guilt for my parenting.

Thank you for that realism. But here’s an interesting point. While many families are able and want to help, this question is how do you get in-laws or extended family to believe that your child is having seizures and not faking it?

Dr. Knupp: I’ve encountered this. And I think oftentimes in that situation, it’s really helpful to invite them if you’re willing to, to visit with your neurologist so that your neurologist can help out with this. I’ve seen this come up not just with are these seizures really happening, but is this the management that really needs to happen? Sometimes we see this with ketogenic diet management where grandparents just don’t understand why they can’t slip a scoop of ice cream to the child and why that would be so detrimental. And so in those situations, it can be really helpful to enlist some help. I would definitely recommend that you give your provider a heads up that that’s what you want to discuss and what the concerns are so that they know to specifically address that during the visit. But that can be a really helpful way to manage that.

Here is one. It’s actually coming from a sibling and it’s actually a medical question, so I just want to change gears but sometimes it’s hard for siblings to get this information and so I do want to pose this question. Why would increasing dosage of medication be the go to answer when seizure frequency increases? Thank you in advance, worried older sibling.

Dr. Knupp: Often our thought when we’re doing that is if the medicine’s helping at a lower dose, it may help more at a bigger dose. We always have to be cautious though, because sometimes our medicines have the opposite effect. Sometimes our medicine can trigger seizures instead of helping with seizures. But we always want to make sure we maximize the medication before we move on to another medication. Usually that is our go-to, is to increase medications. The other thing that can contribute to that is particularly in our pediatric population, is that kids are growing. We may have to keep adjusting doses because the kids are getting bigger and so they need more medication to account for that bigger body size.

Thank you. As a sibling myself, I found it helpful to also go to medical appointments and learn more. So I encourage all siblings to do that, ask those questions. You may be taking on more responsibility and it’s just helpful to have that relationship with the medical provider and be able to go to them with these questions.

Dr. Knupp: Now I was just realizing at epilepsy camp, we have an Ask the Doc session where the patients, the campers who have epilepsy get to ask physicians questions because more often than not in the visit, their parents are doing the talking and not the kids. And I’m just realizing… and I had made a note to myself that we probably need to do a sibling ask the doc so that siblings have an opportunity to ask questions as well without everybody else interfering.

Thank you Dr. Knupp for spending your time and your expertise with us and answering so many great questions.


This webinar is supported with funding from Zogenix
Zogenix

The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.

Women’s Health: Complex Interactions of Epilepsy, Medications, and Hormones

People with epilepsy may experience changes in their seizure patterns at times of hormonal fluctuation; for example, epilepsy in some individuals either develops or subsides during puberty. However, the connection between hormones and seizures is not well understood. This relationship is particularly challenging to understand in women, whose hormone levels change according to their menstrual cycles and during pregnancy. Seizures associated with a women’s menstrual cycle are referred to as “catamenial seizures.”

This webinar discusses how epilepsy and anti-seizure medications can affect hormones and reproductive health, how sex steroid hormones can affect anti-seizure medications and seizure control, and how the menopausal transition can affect epilepsy. Viewers will also learn about potential treatment options for catamenial epilepsy.


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About the Speaker
Page B. Pennell, MD is Professor of Neurology at Harvard Medical School, Vice-Chair of Academic Affairs in the Department of Neurology, and Director of Research for the Division of Epilepsy at Brigham and Women’s Hospital, with a secondary appointment in the Division of Women’s Health. She is a clinician investigator with a focus on sex-specific outcomes in epilepsy. Dr. Pennell’s current clinical studies focus on the effects of hormones on seizure provocation, pharmacokinetic changes of AEDs with exogenous hormones or differing reproductive phases, and maternal and fetal outcomes during pregnancy in women with epilepsy.


Q&A with Dr. Page B. Pennell

Here’s a question regrading a rare epilepsy. This person has noted clustering. The question is about PCH 19, and the person has noted clustering with menstrual period being a trigger for seizures. What’s the best treatment for stopping the period to keep the hormones from triggering the seizures in somebody like this?

Dr. Pennell: I actually had a slide about that and took it out. That is a very specific syndrome that is predominantly in females, and is very much related to this topic. There are some treatments that are currently in investigation and actually Dr. Lubbers, you might know more about the most recent, but really acts on that allopregnanolone basis. There’s a synthetic allopregnanolone called Ganaxolone. So there was a treatment trial specifically for this. Then also allopregnanolone, it’s only in infusion is a problem. But that’s being used in post-partum depression, so that hopefully will also get to the point that it can be used directly and developed as not just an infusion. But do you know the latest on the trial results?

That’s a great question. I know that it’s still under study for some specific rare diseases, including tuberous sclerosis. I don’t think the results have been reported yet, but that’s a great thing to pay attention to, as those trials are progressing, and thinking about it in the context of not just general seizure control, but seizure control in women. Great point. Here’s a question for you. Are there any known interactions between hormone changes and epilepsy devices, such as the vago-neural stimulator?

Dr. Pennell: Yes. There’s no known interactions between that. There have been not so much publications, but some investigators have looked to make sure that it has no effect on the reproductive axis hormones. Now in addition to VNS, of course we have RNS now. I guess technically, it’s a good question. If it’s in an area that’s going to cause a change in firing to the hypothalamus maybe. But I don’t know that any studies yet. That gives us another great idea to try to get funding, and just to make sure, maybe in those people who have it in an area that’s likely to cause hormonal change to look at the effect. But nothing reported to my knowledge.

How does elevated testosterone in polycystic ovary syndrome figure into the progesterone/estrogen balance? And particularly, the influence of Estradiol on seizure activity?

Dr. Pennell: Polycystic ovarian syndrome can potentially increase seizure frequency by first of all having more anovulatory cycles. Going back in the slides, I don’t know if you remember, but a C3 pattern, when you have anovulation, you don’t get the rise in progesterone, so you can have increased seizures because of that. Then as mentioned, it also causes hyper-androgynism, and testosterone levels. Back in the slide, I don’t know if I can go back, there is a metabolite, of testosterone, DH, which is an androgen, DHEAS. Which can be excitatory. Those are two ways it could contribute potentially to increased seizures. DHEA sulfate is actually from, you can see here’s the androgen and testosterone. Those don’t directly have an effect on seizures. They do have an effect on the brain, but not on seizures that we know of. But also, the androgen can maybe decrease the DHEA sulfate, which could increase seizures.

Does supplementing progesterone have an impact on the elevated testosterone?

Dr. Pennell: Not that I know of. Supplementing progesterone, yes. Not that I know of. Good question though.

Why do you prescribe progesterone lozenges for the C1 group rather than birth control?

Dr. Pennell: The lozenges that were used in the study are actually pretty high dose compared to the progesterone you would get in any of the birth control options. But more importantly, in the birth control options are synthetic progestins. They’re not quite this progesterone. The synthetic progestins do not metabolize to allopregnanolone. You really need natural progesterone and it is not easily taken as a pill, and actually gotten into the blood system through GI absorption. There’s two ways to give it, which is a lozenge, which it gets through the mucosa into the bloodstream. Or as an actually vaginal suppository. There is a micronized progesterone that can be taken as something you swallow, so that is another option.

Can medication become less effective post-menopause?

Dr. Pennell: So post-menopause, often seizures get better, and the medications are still effective. It is possible to have some seizure worsening during the menopause transition. It can actually take quite a while. It can be anywhere from two years to seven years. I have worked with our gynecology specialists on suppressing that erratic hormone phase through other hormones to try to stabilize that. In rare instances, we’ve even gone to suppression of the hormone axis with things that are such as used in in vitro fertilization techniques to completely shut down the hypothalamus, pituitary, ovarian axis. But again, I only do that in concert with reproductive endocrinology specialists.

We have a listener who makes the point that there’s still too many doctors who dismiss the issue in women. And I agree. Do you have any advice? Actually now we have these transcripts, and people can take transcripts of these recordings to their doctor. But what would you advise somebody who’s faced with a situation like that?

Dr. Pennell: It’s unfortunate. I certainly got into women’s health issues and epilepsy because of a lot of the stigma that was there, that is actually often present in women’s health across all disorders, but especially epilepsy. We just didn’t have information, scientific data to be able to discuss it and that also pertains to a lot about pregnancy issues. I think the best way is still to bring information to them with some of the studies that show that a third of women with epilepsy have this pattern, and there are considerations as far as different strategies that could be added on to the primary strategy for controlling seizures that can be a benefit.

If the doctor or PA or nurse practitioner doesn’t listen then, then find a new doctor. I know it’s not that easy. There’s a lot of areas in the country there are not enough neurologists, never mind epileptologists. But certainly, I’ve had patients move to other areas of the country where they didn’t have the same resources, and that they brought the information to the doctor and it was really actually very, very effective.

Does Epidiolex, or CBD, have positive or negative effects on catamenial seizures? Or do we know?

Dr. Pennell: I don’t know. It’s also a good question. I do know that Epidiolex has a lot of interactions. The first question I would have is how does it affect these pathways? I haven’t seen anything with it yet. But obviously it’s still not as commonly used in women of reproductive age as some of the other populations. So I don’t have any information yet.

If you are thinking about getting pregnant, what is the safest way to get off of a medication? For example, Trokendi RX, or XR, beforehand.

Dr. Pennell: The question is really, really important. We know that 50% of pregnancies are unplanned, and then we have that extra in the United States, and then we have that extra problem we talked about, about interactions and causing lower efficacy of some birth control options. The best thing to do is yeah, if you can plan the pregnancy, and to speak with your neurologist hopefully about how to get onto the safest medication regimens. We have several medications which are very safe during pregnancy. It really should be the exception to stay on a medicine that’s not as safe, because you’ve already tried the other medications and they don’t work for your epilepsy.

Topiramate is one that is in the middle, where it does have some increased risk, especially for small progestational aged births, or low birth weight, and a slightly increased risk of cleft lip and cleft palette. But it’s also not one of the most dangerous ones. If the other medications were tried, and they weren’t effective, certainly it would be possible to move ahead with a pregnancy on it. But as far as how to switch over, that is so individualized according to seizure types, seizure frequency, background, what’s been tried, side effects, so many things that it’s not one size fits all, but hopefully it’s a good partnership with your neurologist to get to that point.

Have you heard of seizures destabilizing in males as it they go through puberty? Does aromatization of testosterone to estrogen play any role?

Dr. Pennell: I did mention how some seizures begin around puberty. I should’ve mentioned that there are certain epilepsy types that the seizures get better as someone moves through puberty, or even goes away. The obvious is childhood absence epilepsy, or benign rolandic epilepsy. But I don’t know, yeah, if it’s been studied beyond that. Actually at the end, we were talking about the menopause transition and how we need more studies on it. But likewise, the pubertal transition is another thing that definitely is understudied.

As a woman with epilepsy who’s hoping to become pregnant, how can I find out about research studies I might be able to qualify for when I do become pregnant?

Dr. Pennell: There’s a few ways. There’s our pregnancy registries, which have provided such incredibly helpful information to know a lot more about the risk versus benefits of many different medications, medication combinations. In North America, there’s the North American AED pregnancy registry, which can be found pretty easily through the website. I encourage everyone to enroll in. It’s only a few phone calls, it doesn’t take much time. Likewise, there’s international ones such as EURAP. Then for other studies that are very active, you can look under ClinicalTrials.gov has a listing and search by epilepsy, and that gives information about trials that are ongoing. We have a very large study going on across the country, in case anyone also participate in that. It’s called MONEAD, Maternal Outcomes and Neurodevelopmental Effects of Anti-Epileptic Drugs. It’s 20 sites across the country.

But we are fortunately in the latter stages of it, because so many people volunteered time, and for their families. We’re not enrolling new families at this time, but believe me, we are always looking for funding to continue the quest to get all the answers. Likewise, there could be something new that’s happening at that time. You could also check with your local Epilepsy Foundation Chapter. But again, if there’s any study that involves humans, we have to actually register on ClinicalTrials.gov. That’s always a good place to look. Then you might have something through CURE Epilepsy, Dr. Lubbers, as a resource?

We would also guide people to ClinicalTrials.gov. It’s the biggest resource, most accessible, for the most current studies. How frequent do women with epilepsy develop preeclampsia? Will preeclampsia worsen the woman’s epilepsy?

Dr. Pennell: I know it’s frustrating to get mixed messages. But there were some studies that suggested that preeclampsia was more likely to occur in women with epilepsy, and those were studies that looked at hospital records, which is coding. They’re not as pure. Because whatever is coded for insurance reasons. It’s not very specific. In the MONEAD study that I just mentioned, we actually had a primary aim of looking at obstetric complications, and there were actually no increased rates of preeclampsia, eclampsia, in women with epilepsy versus the general population.

But obviously, women with epilepsy could still develop preeclampsia. It doesn’t seem to make her underlying seizures worse. But of course, if she goes on to eclampsia, she can develop seizures because of the other vascular effects of eclampsia. It doesn’t seem to be an increased risk in women with epilepsy.

Can repeat seizures lead to loss of libido in women of childbearing age?

Dr. Pennell: We think that’s possible, as we mentioned, the medications can cause decreased libido, depression can, and the treatments for depression can. A lot of the medications that are used for depression can also cause decreased libido. It’s multifactorial. We did want to look at this really specifically in WEPOD, that study I mentioned where we had women track their sexual intercourse according to their menstrual cycle and their medications, but we had a collaborator who’s an OB-GYN, and she was so helpful to remind us of these basic things that we don’t think about as neurologists, which is that once a person is trying to get pregnant, sexual intercourse has very little to do with libido. Its primary goal is very different. She did not feel that we could use our diary data to address libido whatsoever.

There is some nice work by Martha Morell to go back and look at, that does show some interactions with types of epilepsy and also medications. But untangling all those things, such as frequency of seizures, isn’t completely clear. But I think it probably is linked to frequency of seizures to some degree.

This person mentions the start of seizures that included tonic-clonic and absence seizures starting around 12 years of age. Depakote and Onfi has been offered as the best seizure control so far, and it seems like growth has slowed drastically. This brings in another hormonal paradigm, with a delay in menarche at about 16, at almost 16. Can medications or the seizures be responsible? I think particularly around the growth issue? And what would be good treatments for people to keep in mind?

Dr. Pennell: Around the growth, I’m not sure. First of all, I should say I’m an adult epileptologist. That’s where a lot of my hesitation is. Because although I’ll see someone who’s 16 because they have a hormonal problem or a concern, hormonal concern, or they become pregnant, I don’t practice during that earlier phase. Now, that valproate in particular has actually also been shown to cause lower androgens and lower sperm count in men with epilepsy. She said it could be affecting other hormones. You’ll have to ask a pediatric epileptologist.

Is there an over-the-counter way to check progesterone and estrogen levels for somebody who might want to track what’s happening with their cycles?

Dr. Pennell: Not over the counter for progesterone. But what you can do, is very effective, is do LH test kits. Luteinizing hormone is the hormone that’s released right before ovulation, and it causes the egg to be released. Then after the egg is released, then the corpus luteum stays behind and that releases progesterone. You can use LH test kits. They’re most commonly used for fertility, when someone’s trying to get pregnant, to see if they’re ovulating. You can actually get batches of them cheaper, such as through Amazon or some other source, if you are going to be doing it on a regular basis. It’ll tell you where to being. Usually around day 10, you do a urine sample every day. Then it’ll tell you if you’re having the LH surge. It is very accurate, as to whether a person’s ovulating or not.

Although it won’t give you the progesterone level if you’re not ovulating, it means the progesterone level’s low. The other thing we do in research settings are check day 21 progesterone level, because if they’re ovulating, that’s where the progesterone should be at the level we want. Then sometimes I’ll do it before starting the progesterone lozenge treatment. Then after I start progesterone lozenges, I check it again, and I want to make sure it gets above 20 nanograms per milliliter. If you’re going to check it, check it at day 21. Or if you want to see it over several cycles, if there’s ovulation occurring, then you can use the LH test kits.

Learn More

Seizing Life® Episode #20 – What to Expect When You’re Expecting … as a Woman with Epilepsy featuring Caroline McAteer

In this episode of Seizing Life, mother Caroline McAteer speaks to her experience bringing her daughter Nora into the world. Caroline discusses how she approached the topic of pregnancy with her husband, her epileptologist, and her OB-GYN, as well as how she managed her epilepsy and medication changes throughout the process to reduce the risk of having seizures while pregnant.


The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE Epilepsy strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.

International Disparities in Epilepsy Care: Social & Economic Effects of Epilepsy in Sub-Saharan Africa

More than 65 million people around the world are affected by epilepsy and its effects can be much more profound in underserved populations worldwide. For example, epilepsy in sub-Saharan Africa is more common than in the US and seizure disorders in Africa are associated with a high risk of early death from seizure-related injuries and status epilepticus. In addition, the epilepsy treatment gap, meaning the number of people with a chronic, active seizure disorder who are not on treatment, is 50-90+% in most African communities.

This webinar details the complex challenges to epilepsy care in sub-Saharan Africa at the community, clinician, and health facility levels. It also discusses potential interventions aimed at prevention of some common causes of epilepsy in Africa, including prenatal brain injuries, high automobile-related injuries due to poor transportation infrastructure, and cerebral malaria.


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Plus, learn more about the global impact of epilepsy and how advocates combat the epilepsy health crisis in the developing world in this episode of the Seizing Life podcast.

About the Speaker
Gretchen L. Birbeck, MD is the Edward A. and Alma Vollersten Professor in Neurology, Research Director, Epilepsy Division at the University of Rochester. Dr. Birbeck has served as a physician, medical educator, and researcher in sub-Saharan Africa since 1994. Her overarching professional goal is to understand common neurological disorders in the region. She also seeks to identify modifiable risk factors for these conditions and their secondary comorbidities so that feasible, affordable, evidence-based interventions aimed at preventing or reducing neurologic injury can be evaluated and broadly implemented.


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.


Q&A with Dr. Gretchen Birbeck

This question is about cerebral malaria. Is it more likely to cause seizures than neurocysticercosis?

Dr. Gretchen Birbeck: I don’t know that there’s been a head-to-head study. Neurocysticercosis in many ways is more heterogeneous, so people can have lesions in different places and the risk of subsequent epilepsy is probably based upon the location of the parasitic lesion. So I think it would be hard to do a head-to-head study. I think the location may matter as well, so obviously there’s limited cerebral malaria in, say, some areas of Latin America that have quite a lot of cysticercosis. We actually do have plenty of cysticercosis in Africa as well, so I think it’s probably just safe to say both are really contributing to the burden any time you get into low resource settings.

Why do you believe that stigma reduction interventions cannot be streamlined? Can you give examples of what hasn’t worked in the past?

Dr. Birbeck: So, if you examine the outcomes of the mass social marketing campaigns–not what they did but rigorous assessments evaluating whether they actually impacted stigmatizing attitudes. First of all, they weren’t terribly well studied, and when they were looked at usually the benefits were very short-lived. Those are very expensive things to do, and so they’re not really very sustainable.

My own group had looked at focused interventions in terms of epilepsy focused, epilepsy stigma reduction, but we identified power groups. So we worked very closely with people with epilepsy and came to recognize that rather than trying to decrease stigmatizing attitudes in the general population we might benefit the lives of people with epilepsy more if we targeted individual groups of people who have a big impact on the lives of people with epilepsy. We decided or determined that that would include people like teachers, clerics, healthcare workers, police officers because in areas where there’s no 911 if someone has a public seizure the police officer may be the person coming to the scene, and employers.

We did interventions with those groups and some interventions were successful, some were not. Some were even being scaled up, but again, the cost of these interventions and the cost of sustaining them really, really quite high. We’re trying to think about what could be sustainable if we could partner with other common stigmatizing conditions, the models of the stigma, the driving forces of the stigma being shared, and work with those conditions to do sort of broad interventions, I think the sustainability would be more likely. So yes, you can do focused interventions that are effective, but the question is sustainability and scalability. So to do them in one country really isn’t enough, we want to do them everywhere.

I can provide this after the talk, but we did an article, there was a whole series from the Fogarty International Center on stigma and this was published in Nature, and we really tried to make the argument about what these would look like, these sort of broader stigma reduction interventions that epilepsy could be one of the conditions that’s looked at. I do think if such interventions were sort of developed say by the World Health Organization or the World Bank and scaled up, those interventions would almost always include epilepsy amongst the conditions of interest because it is very well recognized I think even outside of the epilepsy world, that when you think about health related stigmatizing conditions, epilepsy is unfortunately the top of the pile.

On a related note, one of our audience members noted that there’s an advocate’s toolkit for making epilepsy a priority in Africa, and that can be found at epilepsyafrica.org. That’s a great resource, and it sounds like we’ve got other resources that we can gather and share with this audience.

So another question. Can you tell us a bit more about the traditional healing methods that are used and if any of these have been researched?

Dr. Birbeck: I have to say we have been very fortunate where I work in that we have developed I think a very effective partnership with our healers in the rural areas. One of the things we discovered, it was actually in the setting of the ChEAFS study, that was the febrile seizure study which was requiring a cohort, a group of children that we would follow through home visits over several months was actually three years follow up, and in trying to determine what would perhaps undermine those follow ups, it was pointed out to us that if the traditional healers in the village didn’t want children to continue to be in our study they simply would pull out or be unavailable.

That was our original motivating factor to bring in the traditional healers and speak to them about what we wanted to do and take advantage of that situation to talk to them about how they conceptualize seizure disorders and epilepsy, et cetera, and it ended up being a very positive foundational way to work with this group.

The way they described their understanding, and again, this is one region of Africa, so I cannot claim that this is generalized, most of these rural traditional healers were from the communities, they had had some life event that had led them to be chosen to be a healer or believed to be a healer, and they have a very strong bond to their community, and I would say that they have a very strong therapeutic relationship with their population. That may be very different than some of the real scoundrels that kind of come through to make a bunch of money and leave.

With that group of individuals they really viewed a seizure as a problem. They would intervene and the seizure would stop, as seizures usually do, and then some people would go on to have more seizures, so we would call those persons who now have epilepsy, and those patients they really didn’t want to take care of because they didn’t think they could help them. So what they viewed their role as was to take care of acute symptomatic seizures, which are usually brief and usually go away, so they were usually successful. Then when people developed chronic seizure disorders they really didn’t think that they could help them, and they in fact once the therapeutic door was open they became very happy to refer those patients to us.

For the group that I’ve worked with, they actually don’t believe that they’re particularly effective at taking care of epilepsy. We do see them try and many of them will tell you that trying to refer patients to help centers and hospitals are difficult because of the cost to the patients and because often they will get to a health center and find there are no drugs anyway, so they traveled all that way.

The healers take excellent case history, so I’ll often see a patient come who has localization related epilepsy with sort of focal onset in one limb. That limb will already have tattooing or scarification. The healer who has actually obtained the history, they give sometimes rather magical explanations that make sense to patients. So if a patient has sort of an aura that is a rotten egg smell they will decide that the cause of the seizures was witchcraft and that eggs were used in the magic. So there’s a lot of reasons why their explanations and their management are sort of contextually very valid to patients.

What I find most reassuring is that when I work with healers closely, most of them are very happy to refer chronic seizure disorders to us because they feel like their intervention is with the acute symptomatic seizure, which again, is usually brief, is usually going to resolve, and many of those people won’t go on to have a second seizure or at least won’t have one for some time.

There are some healers that have particular herbs that they use and we have seen situations, usually in families that already have a family member with epilepsy and they have some traditional herbal teas is the household that are being given to that individual, where somebody with an acute symptomatic seizure will receive those. That can be problematic if sort of a hot tea is orally administered to some child in the midst of a febrile seizure because then you have oral burns, aspiration pneumonia, et cetera.

So, for those sort of mismanagement, which I might say is actually the family taking a therapy for somebody else and administering it to the child without the healer’s input, we have tried to do some public education about that to decrease the oral injuries and the aspirations that we’ve occasionally seen. But in general in the rural healers in Zambia what I found is once the therapeutic door is open they will continue in the community to manage acute symptomatic seizures that aren’t epilepsy, but refer epilepsy quite happily for care to the hospital.

Along the same lines, do religious leaders can they decrease stigma and reduce that evil spirit ideology?

Dr. Birbeck: It’s interesting. We did some early work trying to look at what the drivers of stigmatizing attitudes were in different important groups of people, power entities, and you heard me say that clerics are power entities, teachers are power entities. Each of the power entities we looked at–and we looked at teachers, police officers, clerics and healthcare workers–each of those groups had different factors driving stigmatizing attitudes.

You’ve asked about clerics. The clerics’ driver was whether or not they recognized epilepsy to be a stigmatizing condition–I’m sorry, to be a biomedical condition. So for healers who recognized that epilepsy was a brain disorder, it’s like having TB or a broken leg, you need to take this to the hospital. For healers who recognize epilepsy as a brain disorder and not being bewitched and not being possessed, those healers actually had pretty good attitudes. They were not stigmatizers. It was the clerics who were unaware of the biomedical basis of epilepsy who were stigmatizing.

It would seem that the ideal intervention would be to improve their knowledge. Now, that is one of the lines of investigation and intervention we did, so we did a series of intervention programs with clerics in a large swath of Zambia, and we were able to improve knowledge. Yet we didn’t improve attitudes and we didn’t change how they were handling people with seizure disorders in their congregations.

We went back to the drawing board and spoke to them in structured interviews and in-depth interviews to understand this better, and we’d fail most because they felt like they had to respond to seizure disorders in the way that their congregation expected and not necessarily congruent with their new knowledge. So, that is a group we actually failed miserably with.

Let me give you the success stories, since we’ve been talking about stigma reduction. So we were able to improve clerics’ knowledge but we could not change their behavior. They felt compelled to behave in a certain way based on congregational expectations.

On the other hand, for teachers we found that one of the primary, actually the primary driver was teachers are educated, they knew that seizures were a biomedical disorder. Whether or not they stigmatized, and I should state they stigmatize much less than the clerics, but their stigmatizing attitudes in terms of throwing kids out of the classroom, not wanting them in the classroom, thinking that they were not capable of some of the work was really driven by whether they had any personal proximity to somebody with epilepsy. So did they have a friend or a neighbor with epilepsy? And if they did, then they were much more accepting of the condition.

So our intervention with teachers was an educational program that took place over some days in a seminar center where people were attending the seminars full time and eating communally, pre-COVID, eating communally and staying in accommodations next to each other and coming to know each other, and the instructors were people with epilepsy, the teachers found this out at the end of the intervention. So much as the intervention looked like an educational intervention, it was actually a personal proximity intervention, and that was worryingly successful in terms of not only changing teachers’ attitudes and changing what they were doing, but actually also there was a knockoff effect with other teachers in their school sort of changing attitudes over time as well based upon interactions and education from that other teacher.

So we failed miserably with clerics, I’m afraid, but we did have more luck with some groups such as teachers, healthcare workers and police officers.

There’s a couple questions along this line: What are the best ways for nonprofit organizations outside of Africa to support African organizations to narrow treatment gaps and what areas are most helpful to approach first, is it diagnostics, medication, advocacy?

Dr. Birbeck: I think here your local partners have to really inform you because it’s really the situation on the ground, and it can be very different from country to country, it can even be very different from regions within the same country. Coming in from the outside I don’t think that we can really hope to understand what that is. I think that sometimes we come in with a list of what we think people could need, and the more open we can be to really allowing the true needs to come forward from the community that’s advocating on the ground the better. Sometimes the asks, the things they may need, might seem very unusual, but if you get the full details of what they’re dealing with it’ll be clearer. So I really think in these situations local partners have to guide us because you just can’t know from the outside.

Is there a line in Western medicine that people need to be aware of? Do we need to be more accepting and understanding of the traditional healing? Can we be wrong in our Western approaches or our Big Brother mindset?

Dr. Birbeck: I think we have to at least be open to what the healers bring in. I think I’ve had a different experience than many people because of my sort of home base and work really originating in rural areas. So, I really believe in the rural areas the vast majority of healers who come they are from the community, they originate there, they live there, and they really very much view themselves as being responsible for trying to improve the health of their community. They often get very little in terms of personal income or gain, but they get a lot of status in their community. I’ve learned over time most of those people have all the best intentions, and I don’t think I’m incorrect in that.

On the other side, in the urban settings, I’ve seen plenty of charlatans coming through and they’ll whip into a city and they’ll set up a clinic, and they’ll appear from nowhere, they’ll make outlandish promises, they’ll charge huge amounts of money, and as soon as they make enough trouble for themselves they sort of disappear quietly overnight with everything that they’ve made.

I think we have to just be open-minded about who we’re dealing with. I’d be very careful about sort of painting any group of people that are claiming at least to be trying to help individuals with seizure disorders as being bad just because of sort of a label they have. I think it’s healthy to have some skepticism and to learn more. I wouldn’t recommend sort of suddenly trying to support unknown groups that are providing traditional medicines, but there’s a lot to be said for the therapeutic benefit to the family.

Let’s say somebody has their first seizure. It’s a brief, unprovoked seizure, they may well go on to develop epilepsy. This is an intensely traumatic event for anybody anywhere, first seizure, right? It means a lot to that patient that their family seeks care for them, and it doesn’t matter that that care may be garnered from the traditional healer in the community as opposed to a primary care clinic 12 miles away, that they may not even know the nurse or clinical officer there.

There’s a lot of importance in the family unit and just people’s responses to such an acute traumatic event, of just the simple care seeking process and having healers in the community makes that possible. So I think we have to be open-minded and sort of willing to learn a bit more about what an individual is actually doing, what are their motivations for being in that community before we sort of decide that they’re either all good or all bad.

Is there a difference for children or adults with the first onset seizure? Is one or the other more likely to be referred for care?

Dr. Birbeck: It depends. So we have some data sadly to suggest that females in general are less likely to be sent for care in the African setting, and I think actually sadly they’re seeing this in the Nigerian study that I cited as well. So that sort of your value in the community, your value within your family probably determines how hard or how many resources are going to be expended to get care for you. So if you are a prime age adult male you’re going to do a lot better in terms of resource seeking and the family investing in that than sort of say a young female. So yeah, it goes along power differentials. The family wealth itself obviously makes a difference, but if you control for that, less valued individuals.

This becomes problematic if you think about let’s say somebody with comorbid cerebral palsy or some comorbid condition that may be playing a role in their seizure disorder. Somebody who is disabled may be very much devalued by their community. So maybe very unlikely to have care sought for them because that requires resources that even within the family nobody wants to invest. So yeah, unfortunately there’s differential care access, even at the family level.

What can people watching this webinar do? How can they support the cause? In fact, one person was interested in learning more about how to join research efforts and even your group.

Dr. Birbeck: There are groups like CURE Epilepsy, right? I mean, there you go. There are organizations that are already partnering with local organizations in communities doing important work. I think your best bet is to identify groups whose values and approach kind of resonate with yourself, because the more what they’re doing sort of seems in line with how you feel about the condition and what the priorities should be, I think the more positive feedback that you’re going to feel in your engagement.

Then think about what you do. I mean, I see some people on the line here, and there are EEG technicians, and people with those skills who sort of volunteer. There are people who give money there, people who give support to educational activities that are ongoing to try to build local expertise. I think there’s a lot of opportunities out there if you tap into everything that groups like CURE Epilepsy and ILAE and World Federation. If you have a particular location in the world that you have some connection to you might make some inquiries and say, “What’s going on in your community for epilepsy care?” And you may be astonished to find there’s a small group there, some grassroots group trying to advocate for or do something, and then you can do something more personal.

We’ve done things for Christmas gifts just within my university, where people can gift a goat. I know that’s a thing that some of the bigger organizations do, but we’ve been able to do it on a small basis, and yet it has a big impact locally because of the revenues that then support some of our patients who are really on the most dire end of poverty and really can’t afford medicine. So I think you have to kind of look for what works for you, but I think even a brief internet search and you will find lots of opportunities to get involved. Then I would just look hard for the ones that resonate most with you so that you can have maximal enthusiasm for following through and engaging.


Learn More

Seizing Life® Episode #34 – Acting Globally to Fight Epilepsy featuring Gardiner Lapham

On this episode, former CURE Board Chair and BAND Foundation trustee Gardiner Lapham speaks with current Board Chair Stacey Pigott about the the global impact and complex challenges of epilepsy and tells us how the foundation is helping combat the epilepsy health crisis in the developing world.

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

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


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


The information contained herein is provided for general information only and does not offer medical advice or recommendations. Individuals should not rely on this information as a substitute for consultations with qualified health care professionals who are familiar with individual medical conditions and needs. CURE strongly recommends that care and treatment decisions related to epilepsy and any other medical condition be made in consultation with a patient’s physician or other qualified health care professionals who are familiar with the individual’s specific health situation.


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

Q&A with Dr. Michael Sperling

Is this medication suitable for occipital lobe epilepsy?

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

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

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

What other medications are good to be paired with cenobamate?

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

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

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

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

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

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

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

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

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

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

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

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

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

Are there any reactions with warfarin (Coumadin)?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Does cenobamate have any synergistic effects with any other medications?

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

Does cenobamate have any reaction to warfarin (Coumadin)?

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

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

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

Will cenobamate substitute for both Vimpat and Keppra?

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

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

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

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

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

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

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

Is this suitable for epilepsies for SCN1A genes?

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

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

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

Does this medication have a prescription assistance program for patients?

Dr. Michael Sperling: Yes.

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

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

Can the drug level be checked in blood work?

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

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

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

Disparities in Epilepsy: Overcoming Barriers to Improve Care and Treatment Outcomes

Our health is shaped by a combination of many factors such as the conditions in which we are born, work, and live, as well as broader forces and systems influencing the conditions of daily life. The differences in these social determinants across societies result in inequalities (disparities) in both health status and access to health resources, such as health care. Disparities in epilepsy have been identified based on factors such as socioeconomics, race and ethnicity, and address. Increasing awareness and knowledge of social factors in epilepsy is the first step to eliminating disparities and improving care and outcomes for all people living with epilepsy.

This webinar helps viewers define the social determinants of health and health disparities, how these translate to the epilepsy community, and how to identify strategies that can address disparities in epilepsy care.


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Hear from a mother about how her personal experience with healthcare disparities has impacted her daughter with special needs, and their experience with health care, in this episode of Seizing Life: Seeing the Whole Person: Disability, Race, and Healthcare featuring Sherri Brady.

About the Speaker
This webinar is presented by Dr. Magdalena Szaflarski, a medical sociologist and health disparities researcher. Her research focuses on barriers to optimal health for vulnerable populations including racial and ethnic minorities, low-income groups, and people living with chronic conditions. Dr. Szaflarski is joined by her research collaborator and spouse, Dr. Jerzy Szaflarski, an adult epileptologist and Director of the University of Alabama at Birmingham Epilepsy Center, for the Q&A portion of the webinar in an effort to address questions related to clinical treatment and care.


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.

Q&A with Drs. Szaflarski

Has there been research that shows evidence on the most effective types of awareness campaigns? I think we all know that we need to increase awareness of epilepsy, but one of the best strategies for doing that?

Dr. Magdalena Szaflarski: So first of all, I believe, based on my experience, that to develop any campaigns or any educational programs, it is necessary to have different groups represented. These types of interventions programs are most effective if they’re put together by different stakeholders working together, right? Because we researchers have our own perspective about how to do this, but we need to listen to the patients and families, what they respond to, and what is important to them. The same thing include healthcare providers and just lay people without epilepsy as well and see where the gaps in knowledge are and awareness and develop programs that work best. For example, in this day and age, in this year in particular, maybe webinars are way to go for some groups and some communities.

And we have health departments across the country doing different webinars for groups of stakeholders but also expanding some of these town hall meetings to whole communities and then people can communicate in that. But I think the essential part is to not only pull together evidence that would be presented to a community, but also have the stakeholders to weigh in on what is the most important information and how it is the best to present this information to others.

Dr. Jerzy Szaflarski: I wanted to add one thing from the clinical perspective, is important to recognize that most of the centers around the country, epilepsy centers, have patients symposia and patients are invited to come, clinicians meet with patients, present the most recent epilepsy data, but these symposia are also designed to listen to patients, to hear their concerns, hear what they need to learn from us so we can in many ways provide better education to our patients.

Can you help us better understand the reasons for regional differences in care and outcomes, for example, in the northeast versus the south?

Dr. Magdalena Szaflarski: So from the research perspective, we know there’s evidence that there is a growing number of cases of epilepsy, and specifically uncontrolled epilepsy in the south. So the term the epilepsy belt has been borrowed from the term the stroke belt in the south. So looking at the regions where there is a high prevalence of neurological disorders and looking at the reasons for it, and in the south, it is the whole area has been plagued by very high rates of health problems, including neurological disorders, but also we have higher rates of poverty and we have high numbers of minorities living in this area. This, and also access issues, can be compiled to contribute to both, I think, the occurrence of epilepsy, but also the trajectory for people with epilepsy to get into care and treatment. I’ll let Jerzy elaborate a little bit farther because he, with his colleagues, also did different additional research on this so-called epilepsy belt.

Dr. Jerzy Szaflarski: So I think the most important factor is that the risk factors for developing epilepsy are very similar to risk factors for developing stroke. So there will be overlap, but we are recognizing now… And I think first time I saw the term stroke belt… I’m sorry, epilepsy belt, was about seven or eight years ago in one of the papers from my colleagues. The risk factors are in many ways similar and access to care is limited, hence what we see is that the conditions in some ways get… maybe not the best word is neglected, but certainly don’t receive as much attention as other conditions, like for example cancer. And access to care is another reason why there is increasing disparity in the care that patients with epilepsy receive.

I actually made that comment a few days ago that the change to telehealth and telemedicine that I’ve been promoting in Birmingham for the last five or six years has actually made access to care better and we see that the participation of patients in their care is much, much better from what we saw about 30% of no-show rates to now about maybe 5% no-show rates. So we are actually providing more care now than we were providing before, which is one of the very few positive things of this pandemic. So that’s certainly is something that we see. However, what we also looked at was the disparities in the care the elderly receive, so Medicare beneficiaries. The interesting part was that although the care that the Medicare beneficiaries receive is very similar across all racial groups, actually the existence of comorbidities drives that the cost of care, especially in patients of African-American descent. So that creates another disparity that we have observed here in Alabama at least.

What should be the role of government, health providers, and pharma industry in trying to equip liberate equal or similar access to health? What about providing health education? Which one do you believe is more important or more probable to reach the target population and have positive impacts to ameliorate these disparities?

Dr. Magdalena Szaflarski: Let me start with maybe the partnership between government, health agencies, federal agencies, and pharmaceutical industry. This relationship is very important. So Jerzy and I come from Europe where there is much higher occurrence of negotiation between the government and pharmaceutical industries and basically the prices of drugs are lower than in the United States where the pharmaceuticals are more independent, I think, and they can dictate the prices of drugs. So somehow you look at the models around the world, it would be important at implementing developing models for the United States, where there’s a closer relationship, where there is more regulation basically on pricing of drugs and I think that really helps. The United States has a long way to go, but we have seen these efforts, I think, at the federal level, the government trying to negotiate the prices of drugs in the United States.

And it’s possible, other countries have done it, so we just have to learn about those models and try to implement some here. But for that, we need public advocacy, right? We need to encourage our government to do this kind of activity and work on our behalf to reduce the prices of drugs. So that’s one way to address this question.

There are two, I think, ways of looking at [improving health education]. One is education of patients and families and then the second is educating the wider public about epilepsy. So on the first front, I think healthcare providers as well as advocacy groups, organizations, provide a great platform for educating patients about new treatments and having this relationship between providers and researchers, epilepsy centers, and organizations like CURE and others, epilepsy foundation, and so on, to create the platform for dissemination of information. While the information for patients and families could be more specific in terms of treatments and also any axillary maybe services available to patients and families within a healthcare setting is important, then on the public level, we’ve seen educational campaigns through the media educating about what epilepsy is and maybe what to do in case somebody sees a person seizing with epilepsy and so on, right?

Knowing more about epilepsy and its source, that it is… in some cultures, it’s still considered… the source of epilepsy is not well known and so there are maybe these spiritual beliefs about epilepsy that exists in certain communities and there is a taboo in terms of talking about epilepsy and also isolating individuals with epilepsy from the larger community. So the more the public knows about what epilepsy is and how to respond and how to improve the treatment of people… treatment, I’m talking about the social relations with patients affected by it and families. So that kind of education is also very important and can be done both by the health agencies, public health agencies, but also private foundations and advocacy groups.

Who is an international organization? Is there a US agency or office that oversees and/or coordinates initiatives to address epilepsy healthcare disparities?

Dr. Jerzy Szaflarski: I think that the most international organization that addresses these issues is International League Against Epilepsy and the American Epilepsy Society is part of the International League Against Epilepsy. International League Against Epilepsy provides not on the education at the provider level but also at the patient level. So it can be accessed through multiple resources, either through webinars or through lectures or through other resources that are available on the International League Against Epilepsy webpage.

But within the US government, there really isn’t an agency that oversees this?

Dr. Jerzy Szaflarski: Not that I’m aware of.

Dr. Magdalena Szaflarski: The Centers for Disease Control and Prevention, the CDC, has a small division of mostly researchers but also public health workers that focus on epilepsy, and there are some research funding opportunities and intervention development opportunities through the CDC. They’ve done a nice job trying to garner some funding and also they are a source of very great data in epilepsy. We can find it on the web, at the cdc.org and look for epilepsy information and their statistical information. There’s basic information about epilepsy, what it is as a disease, but then also statistical information about how many people are affected and some additional things about healthcare and treatment. So the CDC is a good source. Then at the local public health departments level, in some areas geographically, there is some focus on epilepsy as well, and there could be a small sources of local epilepsy data through health departments around the country.

Okay. Terrific. I know the CDC group is very interested in raising awareness and ensuring that it continues to be funded to do this important work.

Dr. Magdalena Szaflarski: Right. I see a comment there from Sarah Franklin here at the Epilepsy Foundation, Alabama, that obviously the Epilepsy Foundation has done tremendous work as well to educate and to disseminate information.

Right. Absolutely right. Yes, the advocacy groups play important roles. So a question; in terms of disparities, many people with epilepsy also have intellectual and cognitive challenges, are there studies that have looked at the particular challenges and opportunities for this population?

Dr. Jerzy Szaflarski: There are number of studies that look at the challenges, especially controlling the seizures but also creating a safe environment for patients with epilepsy who have intellectual disabilities, whether this is home environment, whether this is a group home environment, whether this is institutional environment. I’m not aware of any studies that look specifically for other opportunities outside of providing better care and better seizure control for these patients that I may be able to say more about that.

Dr. Magdalena Szaflarski: I would say that evidence is limited, they’re small studies, and it’s sometimes hard to extrapolate to larger populations. However, I think where we need to pay most attention is we have this large population of patients with uncontrolled seizures and there are many cases among those where there could be improvement if only the right treatment was applied. So one of the issues is that people don’t always have the access to the best maybe advanced epilepsy care. If we can improve the care and improve the outcomes in terms of seizure control especially, then I think the people who have additional comorbidities or intellectual disabilities, mental health issues and so on, their additional problems could be better addressed as well.

It’s been suggested in the literature, but again, the studies are limited on multi-disciplinary groups, teams, at medical centers and healthcare settings working together, so that you can have epileptologists working together with a mental health specialist, with a psychologist, with a social worker, and that their referral system is easy through the healthcare setting to help these patients and families. I think there’s much more work to be done to understand how these systems of multidisciplinary teams is working and where the gaps are and how to maybe expand that area to provide better overall holistic care to these patients.

Dr. Jerzy Szaflarski: One important aspect that I wanted to add is the transition of care, so something that we see more and more emphasis on when pediatric patients are transitioned to adult epilepsy care. And that is really in every aspect of medicine, we see expansion of the transition of care programs because there are very unique needs that the pediatric patients have, and when they are transitioning to adult care, their needs may not necessarily be changing if they have multiple handicaps. And that is very important. It’s very strongly supported in epilepsy care by the American Academy of Pediatrics in collaboration with the American Academy of Neurology and there are multiple centers around the country that are investigating the most adequate or the best pathways for transition of care. I think that’s an important aspect of that discussion.

Dr. Magdalena Szaflarski: I would like to add one more thing. Sometimes we usually think about the patients, persons affected by a disease such as epilepsy, but I think more work need to be done to understand the situation and experiences of the family, especially the caregivers. We have recently done a nice study of caregivers of people with treatment resistant epilepsy and to understand how they are fairing, and they do not fare so well. Some things that they indicated they would like to see is more support for the caregivers to have places where maybe you can provide care even for an hour or two for a patient so that the caregiver can have an hour or two for themselves to basically recoup and try to relax and so on. So giving more attention to the caregivers as well, especially in those severe cases of epilepsy is important and improve their quality of life as well.

How is patient satisfaction or rating of neurologists factored into the research? Patients without neurologists may have negative experiences with providers and some people give up. So how is that factored in as a social determinant?

Dr. Magdalena Szaflarski: Again, there’s very little systematic research on this, but I think what’s important is to think how much we have to go in terms of changing the culture among healthcare providers somewhat to address specifically social determinants of health, such as different social statuses that their patients may have to be more aware of their socioeconomic status and race and gender playing a role. And I think that education of medical trainees in this area is very important and I think medical schools are actually doing it more and more these days to produce neurologists and other medical doctors who are more compassionate and who understand the barriers that patients may have, also to understand their own biases they bring to the profession and to the care being from different social backgrounds.

And the self-reflection is very important because that is something that could influence the relationship between the provider and the patient and the family and strengthen both not only each other’s understanding, but then having better communication about treatments and also empowering the patients on this treatment journey. So there are some factors there to consider for sure. In terms of just neurologists, I’m not sure in terms of rating neurologists and how people feel about it. But what we know, for example in terms of race, generally in medicine, that patients prefer to have a provider that is from the same racial and ethnic background, right? They have a better understanding if the provider is similar to who they are. I mean, we are lacking a minority neurologists in this country.

There are very few racial ethnic minorities that go into this specialty and so we need to focus on how to attract people from different racial ethnic groups into the profession because then we can serve the patients better through this.

Is there information about disparities in participation in epilepsy support groups across the country? Is there some strengthening that can be done there?

Dr. Magdalena Szaflarski: I have seen many studies on social support groups, and in specific programs in specific healthcare settings, they seem to be working well. What I have not seen is research across different healthcare settings and how social support groups across different healthcare settings work. Also, you have social support groups outside of the healthcare system, right? So you may have them through advocacy groups and more and more so through social media and networking. You have social media outlets where groups of people with different types of health problems can get to get together and help each other. Right? So there are support groups forming online these days as well. But there is no systematic research, there are small studies here and there, so there’s a lot to be done in terms of gathering evidence and to see where maybe improvements can be made and how. And we can have different groups, we can have families with patients, we can have those patients who can communicate well with others, could participate separately, and then you can have caregiver groups as well or maybe providers and patients together. So there are different types of models, I think. It could be thought through and some of them I’m sure are already implemented and used in different settings. But there’s a little systematic evidence about that except to say that they are working well in specific settings.

Dr. Jerzy Szaflarski: I think it’s a very important comment about patients working with patients. I used to practice in Cincinnati now I practice in Birmingham, but I see… and patients ask the question many times, “Doctor, you are advocating for me to have epilepsy surgery. That’s great, is there a patient I could talk to?” And in both centers, we had groups of patients we could refer to patients to. They wanted to be informed, they wanted to hear from other patients who had questions and explain their experiences with epilepsy surgery. And that’s actually very successful. Many patients who are very hesitant, after they talk to others and have better understanding from the patient’s side, they are much more willing to undergo the evaluation and then eventually epilepsy surgery, there are candidates.

So patient-to-patient discussions are very important. 20 years ago, there was no Facebook, so this was okay. “Here is the phone number of so-and-so, please call them if you’re interested.” Today, there are Facebook groups, there are multiple other venues where patients meet and discuss these things. We know about it because we hear from the patients or we hear from people who run these groups, whether this is Epilepsy Foundation, whether this is other group of people taking cannabis for the treatment of seizures who want to learn more. There are multiple groups like that where patients get information and they come to us then to verify it or say, “Well, you said this, but they said this. What are we supposed to do?” Then of course we are in the middle answering questions, but that’s great because that also forces us to address the patient needs and their questions in more detail.

In your opinion, why do African Americans have less advanced treatments?

Dr. Magdalena Szaflarski: Multiple factors are at play. One is that trust between the provider and the patient seems to be an issue for racial and ethnic minorities. One explanation is, of the past treatment of minorities in medical research, we know that there have been abuses of patients in clinical trials, the syphilis Study, for example, the Tuskegee Experiment. So within African American community specifically, there is still some mistrust after all these years of the medical profession, of medical treatments and so on. So medical centers specifically have been doing a lot and building trust in the community, especially in large urban centers where there are large populations from racial ethnic minorities. Outreach efforts are underway in those big cities trying to educate minorities and give them opportunities to be more active in seeking healthcare and to even collaborate and partner with medical centers and community health interventions.

So mistrust is a problem. The other thing is that some research shows that African Americans have lower levels of knowledge about medical treatments. And we don’t know exactly why that is. It could be that they have less contact overall maybe in terms of the temporal dimension, not spending enough time with your physician to actually learn, to increase their health literacy through interactions with providers, and maybe it’s the provider that are at fault a little bit not being forthcoming with information about advanced treatments thinking maybe that they’re not maybe appropriate for these specific groups or something else. So there are definitely patient level and provider level factors that have been identified from mistrust to lack of information and other things that we need to work on from different angles within the healthcare setting on the provider side, but also engaging communities in their health more as well to increase trust.

Epilepsy can be viewed as a spectrum disorder with a broad range of impact on patients depending on severity, ability to gain seizure control for example. How did the studies and figures on quality of life elucidate how disease severity impacts quality of life?

Dr. Magdalena Szaflarski: I’ll let Jerzy answer it. He spent most of his life studying quality of life in epilepsy.

Dr. Jerzy Szaflarski: Thank you for putting me on the spot. Yeah. So, this is actually a very important question. However, we know that there are multiple aspects of epilepsy care that affect quality of life, whether this is seizure control or lack of control, whether this is medication side effects or not having side effects, whether this is some other factors like mood, for example, that definitely affects quality of life as well. There’s a lot of interplay between them. We know from epilepsy surgery studies that quality of life of patients who achieve seizure freedom after epilepsy surgery improves. No question about it. We also know that with improved seizure frequency, there is improvement in quality of life, and when patients go back to driving and when patients go back to full employment their quality of life improves.

So as we are treating our patients, we’re focusing not only on, “Here’s the pill,” or, “Here is the treatment that you should have,” but how we affect their quality of life, their mood, their ability to live independently, their ability to go back to a full employment or to be employed. Those are very important aspects of epilepsy care and questions that we are asked and answer every day.

Dr. Magdalena Szaflarski: Sometimes this balance has to be achieved between what kind of quality of life I can provide with this treatment or another treatment. So if there are severe side effects in the case of one treatment, then what do we recommend and also what patient prefers, right? So patient preferences are very important to consider in the treatment decisions about what they’re willing to maybe give up or accept in order to improve their quality of life. And just to keep in mind, we always just say quality of life in general, health-related quality of life, but it is a complex construct, right? We are looking at different dimensions of life, of functioning, of mental health, social health, and so on, and when we’re starting quality of life, we’re actually looking at these different dimensions and how treatment effects the different dimensions of quality of life.

Breathing and SUDEP: Research & the Influence of Seizures on the Respiratory System

Research suggests that respiratory dysfunction following generalized convulsive seizures is an important cause of SUDEP. Interruptions in breathing can occur during and after seizures leading to an imbalance of carbon dioxide and oxygen in the body. The ability to restore normal breathing patterns and remove excess carbon dioxide may be weakened in some people with epilepsy, potentially increasing their risk of SUDEP.

This webinar provides an introduction to basic concepts and terminology for how the respiratory system functions. It also provides evidence for breathing dysfunction caused by seizures and reviews the data for breathing dysfunction as a potential cause as well as a marker for SUDEP, and a possible means to intervene and prevent SUDEP.


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Get a personal perspective on SUDEP from two mothers who each lost a son to SUDEP. Libby Boyce and Jessica Brandes discuss what they were and weren’t told about their sons’ epilepsy, and outline what should be done to build awareness of SUDEP on this episode of the Seizing Life podcast.

Dr. Rup Sainju, Assistant Professor of Neurology and Medical Director of the EEG Lab at University of Iowa Health CareAbout the Speaker
This webinar was presented by Dr. Rup Sainju, Assistant Professor of Neurology and Medical Director of the EEG Lab at University of Iowa Health Care.  Dr. Sainju is a 2016 CURE Epilepsy Award grantee, whose research found that respiratory response to high carbon dioxide levels in the blood may be weakened in some people with drug-resistant epilepsy, which puts them at an increased risk for severe breathing abnormalities and SUDEP following a generalized convulsive seizure.


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.

Audience Q&A with Dr. Sainju

Can individuals with severe intractable LGS with multiple seizures die because of SUDEP during sleep, even with no presence of clinical seizures?

This is very interesting questions. Again, if you review the risk factor, the number one risk factor for SUDEP is drug-resistant epilepsy. However, having tonic clonic or convulsive seizures seems to be in terms of types of seizure. Amongst types of seizure tonic-clonic seizure seems to be the highest in potential for causing SUDEP. But the question here is whether if the patient is having nonclinical seizure, can there be increased risk of SUDEP? I don’t think we know the answer fully but it sounds unlikely. However, we’re still learning a lot about SUDEP and SUDEP mechanism. So we still don’t know the full answer at this time. However, it sounds unlikely given the evidence so far.

What is the best type of oxygen mask to use after a seizure and are they postictal?

Number one, again, we don’t know for sure if… We don’t have strong enough evidence to suggest that we should be using oxygen as a therapy after convulsive seizure. We just have some evidence showing that it may reduce the amount of oxygen or the lowest drop in oxygen. It may prevent drop in oxygen and may recover the oxygen level a little bit faster. But that does not tells us how it changes SUDEP risk. So again, we don’t know that yet. We still need more studies addressing these questions.

What would be the risk for someone with a genetic seizure disorder to wear a mask for a work shift six to eight hours a day for three days a week? Is there any mask that would be considered safe for such long-term use? Are there any challenges with using the masks that we’re wearing today?

I don’t think I have a good answer for this question as well. Given COVID pandemic that’s going on, wearing mask is something we should all consider. One thing is for sure is it does not prevent you getting sick, it also prevents spread of disease if you are asymptomatic and still has infection. So, I don’t know that there is a good mask or what type of mask that we should be using. If you are taking care of patients, you should probably use medical grade mask, but if not, then at least using some sort of mask is still good. In relation to epilepsy, we don’t have good information to suggest what’s the best kind of mask for you if you have epilepsy.

When does SUDEP occur the most when the patient is sleeping in a safe position under monitoring, and what can parents do to lessen the chance of its occurrence?

Most witnessed death from SUDEPs reportedly happen after a convulsive seizure. So it’s not during, it’s rather after convulsive seizure. And there is good suggestion that there is something to do with sleep and if you are alone then you actually are on a really high risk of dying with SUDEP. So if you are monitored by some mechanism… Direct mechanism probably is good for a lot of people who don’t mind their privacy, but this is a very personal situation for a lot of our patient with epilepsy. So having some sort of indirect monitoring may help, but again, we don’t know for sure which monitor, whether it’s seizure detector or a video monitor or a seizure alarm like a bracelet or… There is actually FDA approved device, a watch, Empatica, that is approved to detect, an alert system after a convulsion has happened.

We don’t know, again, to the extent how much these intervention are helpful, but I want to highlight that’s why we need more research trying to get more information so we can have more intervention that is available for patients and families. What I tell my patient and their family is I would consider based on the situation, individual situation and preference, having some sort of monitoring or surveillance is reasonable thing to try. It may not have to be the video surveillance. You may just sleep next door or maybe on the same floor. So some studies suggest that when people intervene during or after convulsive seizures, sooner you go and talk to them or try to intervene in some way, recovery seems to be a little bit faster. Their oxygen recovery, as well as their arousal seems to be a little bit faster. So it’s reasonable based on the situation, but there is no single thing that is proven that we can recommend at this time.

Do you suggest that people with epilepsy have a sleep study done to monitor breathing during sleep? Is that possible?

Best thing for people with epilepsy is to take your medicine, talk to your doctor how best you can control your seizure. Because again, we don’t have a medicine to prevent SUDEP at this point given all the potential we discussed. Best approach still is try to control your seizure best. Having said that there is a good proportion of people who have epilepsy that may have obstructive sleep apnea. So if you have some of the simple symptoms of potential obstructive sleep apnea, for example, feeling fatigue, lack of energy, headaches, or people actually witnessed you snore during sleep or stop breathing during sleep, I think that would be very reasonable time to evaluate for a sleep study and get it treated because poorly controlled sleep apnea or untreated sleep apnea can worsen seizure and epilepsy control.

Does a co-morbidity of autonomic dysfunction increase SUDEP risk in epilepsy patients?

We don’t have much information about this yet and what we have is during or after convulsive seizure, some people can have really irregular heart rate or problem with blood pressure. How that translates into SUDEP risk is not clear. How common that is is also not clear at this time.

Will the pulse-ox be a helpful alarm for people while they’re sleeping?

It depends on the type of epilepsy as well as type of seizure that we’re dealing with. And if you’re talking about monitoring a child, that may be a problem putting the probe in to begin with. But if pulse oximetry is good enough to detect seizure-related drop in oxygen and alarm you, it sounds reasonable to think about it, but we don’t have a study showing that is what is very helpful. But again, I’ll circle back to the same thing. Some sort of supervision is reasonable, including pulse oximetry, but you have to think about it has a lots of false alarm that is associated. And false alarm could be because the probe is displaced while during movement or during sleep versus there are… So many different things can go wrong and give you a wrong pulse oximetry read.

A couple of people asked about examples of serotonin medications. What are those?

A very commonly prescribed group of medicine includes SSRI or selective serotonin reuptake inhibitors. These are a group of anti-depressant. Or most medicines that is often used by psychiatrists. And the studies I alluded in this talk that were included in human, part of the human studies were people taking either SSRI or similar medicine. There are a group of… Another group called SNRI is non-selective serotonin reuptake medicines. These are also antidepressant medicines. And there are some… or supplement rather that can convert into serotonin in body like tryptophan or 5-hydroxytryptophan. So these would be considered as serotonergic medicine in general, if that’s what we’re getting at.

In terms of common names, Prozac would be a common name people might recognize. Celexa or citalopram, escitalopram would be some other names.

Fenfluramine for Dravet: An Old Drug with a New Purpose

Epilepsy research has given the once-popular weight loss drug fenfluramine a new  purpose. Fenfluramine (Fintepla®) is now FDA-approved to treat Dravet syndrome, a rare, catastrophic form of  pediatric epilepsy. In this webinar, you will learn why doctors explored fenfluramine as a possible therapeutic option for epilepsy, and why it is safe and effective treatment for epilepsy in children with Dravet, as well as the potential side effects caregivers should know.

Our webinar presenter is leading-expert Dr. Joseph Sullivan, pediatric neurologist and Director of the UCSF Pediatric Epilepsy Center. He specializes in evaluating and treating children with epilepsy, particularly for those with epilepsies that do not respond to medications. In addition, he runs a specialized Dravet/PCDH19 clinic, where he cares for a large cohort of children with these types of genetic epilepsies.


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Audience Q&A with Dr. Sullivan

Can you talk about other syndromes or epilepsy types that Fintepla might be useful for or is being tested for?

There is a completed Phase 3 study with published results in Lennox-Gastaut syndrome, which also showed efficacy compared to placebo. It wasn’t as dramatic as what was seen in Dravet syndrome, but Lennox-Gastaut syndrome is a very different syndrome than Dravet syndrome. My understanding is that Zogenix will be submitting for labeling for the use of Fenfluramine in Lennox-Gastaut syndrome. I think that it definitely warrants additional study in terms of whether there are other epilepsy syndromes that this could be effective for. My colleague Elizabeth Dr. Thiele has a small study in sunflower syndrome that has also shown efficacy.

Those are three very different epilepsy syndromes. It’s very possible that fenfluramine could be a broad spectrum antiepileptic drug with sort of these favorable or more enriched responder rates in some of these syndromes. It’s our job as the clinical pediatric epilepsy community to try and figure out what would be the next target syndrome to go after.

Are there medications that help kids who have seizures related to heat or rapid body temperature changes?

We definitely know that patients with Dravet syndrome and who have SCN1A mutations do have temperature sensitivity. That’s been well documented in animal models. Interestingly, this temperature sensitivity does tend to wane over time. Adults tend not to be as temperature sensitive.

In my opinion, fenfluramine is not necessarily being effective in just those patients that have temperature sensitivities. I think this may be something where, again, there’s that enriched responder rate for Dravet syndrome, but that’s independent of this temperature sensitivity, but it’s an interesting question to ask as to whether or not there are other temperature-sensitive seizure syndromes that may be a target.

In my practice, when Dravet patients actually have a fever, even though we have no evidence to support this, we do try temperature reduction reducing measures, and for some kids we even try to give sort of benzodiazepines for 24 to 48 hours to bridge them through their fever. Again, isolated patients say, “Yes, that’s effective for my child,” but that’s not something that I recommend with every patient and certainly don’t have any scientific data to support those recommendations that I’m making.

Do you have any concerns recommending this treatment for kids with minor cardiac regurgitation after study Fintepla? My child couldn’t get into the clinical trial because of this issue.

Even in the placebo group, we saw this regurgitation. This actually created some anxiety for some of our patients who were left wondering, “Oh, no. Does my child need to see a cardiologist?” The answer is no and we’ve asked cardiologists this all across the country. Your child’s heart is normal if they have trace regurgitation, and that should not be a precaution for starting Fenfluramine now in the post-studies commercialization phase.

We don’t really see any signal to suggest that trace regurgitation – again, because it’s a normal physiologic finding – would be a risk factor for the development of valvulopathy. That finding going to be followed over time and is why I feel very comfortable that this REMS program is going to allow us to start this drug in more patients and follow that safety signal over time.

Could this drug be used in a child who is weaning off phenobarbital?

Our goal is seizure control and minimizing side effects and maximizing quality of life. I think you’d have to ask yourself, how is your child or your patient doing on phenobarbital? Phenobarbital certainly gets a bad reputation, but it does work for some patients. I would say if the patient is doing whatever you determine is okay, then I would not rock the boat. Go with what you know because while fenfluramine was effective in the majority of patients, there are some patients it’s not necessarily going to work for.

I said my new bar is 75% reduction of seizures. If the child is still having a high seizure burden and you’re questioning whether or not they are phenobarbital-related side effects, I think it would certainly be the right next step to add fenfluramine to that regimen. If the patient improves, then very, very slowly taper off some of the background drugs, That’s true for phenobarbital and that’s true for valproic acid. It’s true for any background drug.

If I’m adding a second or a third or a fourth drug to a regimen, I’m acknowledging that drugs one, two, and three are not getting that person to where they want to be. We see dramatic improvement after taking the new drug, we then have to ask ourselves, “Is the majority of that improvement all being realized from the additional drug? Can I reduce background drugs?” Unfortunately, I showed you that list of drugs that were in the Phase 3 trials. Even though there were only four to five drugs that were the most commonly used, we cannot tease out whether or not there’s like a combination that was more effective than others and I think we’ll just sort of have to realize that as more patients get started on these over time.

Are patients on Fintepla also on Epidiolex?

Epidiolex was not yet FDA-approved during our Phase III program, and any other investigational drug was not allowed in the double-blind placebo-controlled trials. Even on the open label extension, for the first six months, we really couldn’t make any changes to background medications – specifically adding of drugs because then that actually really confounds the open label extension data. Then, it just happened to align that as once Epidiolex was approved and we had more patients in the open label extension, and again, even if you were considered one of those super responders and had a 75% reduction of seizures, if you were still having seizures, the investigators did have the ability to ask the medical monitor for permission to start the drug.

In the expanded access program, I certainly have a handful of patients who are on both. It’s still been a relatively short period of time for me to be able to say with confidence how that combination working. It seems at first glance to be well tolerated. There does not seem to be significant drug-to-drug interactions, but ask me that question a year from now and I think it’s going to be exciting to report back whether or not we can see these incremental benefits of two drugs that have good Phase III controlled data to support their use in these patients.


This webinar is supported with funding from Zogenix
Zogenix
A male doctor in scrubs analyzing brain scans on his computer.

Webinar: Transforming Data into Seizure Control with Learning Healthcare Systems

“Learning healthcare systems” is a method of improving clinical outcomes in patients by collecting and analyzing privatized electronic health data, then rapidly disseminating findings to change medical practices.  This approach is highly collaborative, bringing together patients, families, doctors, and researchers from institutions around the country and even globally.

Two learning healthcare system initiatives are actively working towards this goal specifically for people with epilepsy, one focused on care for adults and one focused on care for children.

This webinar will discuss the progress and potential impact of the Pediatric Epilepsy Learning Healthcare System to epilepsy patients, their families, and to the entire epilepsy research community. At the end of the presentation, audience viewers asked Dr. Zach Grinspan questions on how data and collaboration is being used to improve patient care and outcomes.

You can find a transcript of the audience Q&A below.

Dr. Zach Grinspan

This webinar is presented by Dr. Zach Grinspan, Associate Professor of Population Health Sciences and Pediatrics, and Director of Pediatric Epilepsy at Weill Cornell Medicine.  He is primary investigator of the Pediatric Epilepsy Learning Healthcare System project and the Rare Epilepsies in New York City project, and currently serves as chair of the steering committee for the Pediatric Epilepsy Research Consortium.

Audience Q&A with Dr. Grinspan

From a digital perspective, what are your biggest data-gathering needs at this point?

Let me be a little wordy with my response. We’ve had many conversations with IT groups around the country about how do we standardize process of getting electronic health records. Other groups have done that and I think we need to get better at that.

Right now, it’s a lot of phone calls and a lot of specifications. It works. We’re getting there, but we could certainly be more efficient. We have a good system to transfer the data. Now that we have the data, we’re starting to run into some bottlenecks with the processing. We have one analyst working through it. As we scale up, we’ll need more people processing the data and getting it ready. A lot of the technology is free, so we have a good pipeline to get the reports out.

We have electronic health record system questionnaires deploying over the next few months. Epic is going to release our questions this month. Cerner is not far behind, and someone has already built the questionnaires in Athena. We’ll want to expand to other electronic health record vendors, because we really want to be vendor agnostic. Then, we’d like to bring more data in.

Data from EEGs, MRIs, devices, and patient-reported outcomes would be amazing. People who wear devices are walking around collecting data moment to moment with an RNS or a VNS, and so we want to explore partnering or working together to include that data. Some of it is humanware. I think technology is relatively straightforward. It’s just a matter of all of the conversations and figuring out how to get the data out, move it, and link it.

Have advancements in implants, watches, and other devices helped you understand more about medication efficacy for patients? Has this new data increased the whole picture of an epilepsy patient’s day and changed the way you view potential versus multi-drug prescription regimens?

It’s a great question, because what it gets at is that, in the digitized world, you have people who are creating oceans of data, begging the question, “Can we do anything with it?” For some patients, the answer is absolutely. Certain kinds of data, like VNS and RNS data, can help doctors make very targeted changes. The question is, how do we scale that process and how do we learn from it? And the question is very compelling. We are not there yet, because we don’t quite know how to do this yet at scale. It’s a long-term goal of ours.

Can the collected, aggregated data be individualized? Or can that data be available to doctors and patients for a fee? For example, if RNS data is collected, would somebody need to pay in order to see their own data?

I’ve never had anyone ask me for a copy of their VNS or RNS data. It’s certainly doable and the data is, after all, coming from the patient. I don’t see any obstacle to that.

Other learning health systems use identified data, so their databases know your name, date of birth, everything. These systems actually do provide as the questioner poses direct services. “Here is a patient-level report about how your patient is doing.”

We shied away from that for privacy reasons. Data breaches can be devastating for so many reasons, so we opted to use less personalized data. We don’t know anyone’s name, date of birth… we do know zip codes, but we don’t know where patients live or their medical record number. That was intentional.

Our thought process here is that we can send information to individual centers, which can identify the patient. The report might say, “Patient ABC had this happen.” Then the center has the ability to say, “ABC is actually John Smith.” They have to do that extra step. I don’t know it’s John Smith. I know it’s ABC.

This method helps make the data more secure, but we’re very much about data sharing, and so we have promised all of our collaborators that they can have their own data with no questions asked. We’ll just give it back to them. We’ve crunched it and processed it a little bit because we want to promote your new faculty, we want to promote residents, and fellows who do research projects. Then, for the network, if one investigator says, “I have an idea. It works on my own data. Can I do it on everyone else’s data?” Then, we have a very straightforward process to allow that to happen, too. We really all want to learn together.

You’ve talked about data sharing. Will data sets be made publicly available?

I don’t think we’ve thought about that really. The data sets we have qualify as limited protected health information (PHI), so we can’t share information like dates of birth and zip codes. But the full data sets… I mean, theoretically we could. I think we’d have to talk and think a bit more about that.

A lot of networks want to make sure that patient data is used for a purpose that’s aligned with the mission of the organization, so there’s often a process. We don’t have such a process in place right now, but if that became something of interest to the community, there’s no reason we couldn’t start planning.

How have you had to overcome the barriers of institutions not wanting to share their data with other institutions?

I thought that was going to be a huge problem, but it doesn’t seem to be an issue. Everyone’s so happy to share. It’s really nice. As much as I’d like to say I’m a pioneer, I’m not. People have been working on this in other fields for more than a decade, so the ground has really shifted and we’re in a new world.

The Pediatric Hospital Inpatient System has data from roughly 45 centers, including data from Cornell, Columbia, NYU… and you can walk from one to the next in an hour. I think that the culture, particularly in pediatric hospitals, is very mission-driven, so these potential issues of competition and “you can’t have my data” has just not been a problem.

What are you doing to monitor and measure the impact of diet on seizure control?

It’s not easy to figure out who is on an epilepsy-related diet and who isn’t from the data we have. I showed you that one question about the seizure frequency, but we built in some questions also about diet. It’s pretty epilepsy-specific, so the options we list are the ketogenic diet and modified Atkins, low glycemic index, or other. That’ll give us some high-level information about who’s on what diet, if it’s working, and similar information. More detailed information about specific foods and specific exposures would mean a whole different level of data collection.

Are you familiar with the Observational Health Data Sciences and Informatics (OHDSI)?

Let me nerd out for a bit! One of the major questions we’ve had is, “What does a tables look like in the database?” A lot of people have spent whole careers thinking about that for health data. The Patient-Centered Outcomes Research Institute, has advocated use of PCORnet, the PCORnet Common Data Model.

Our data looks a little bit more like PCORnet mixed with the OMOP model. Currently, our data model is our own, which could be sort of seen as a simplified version of OMOP and PCORnet. What we told our sites is, “If you have the data in PCORnet or if you have the data in OMOP, just send that. Don’t reinvent the wheel.” No one’s taken us up on the offer, so it seems like operationally, a lot of the sites are finding it easier just to kind of make a custom extract for us and just sending us what we want, which we’ve been fine with.

Would it be beneficial for a healthcare provider to have the PELHS questions answered before the visit versus during the visit?

Yes and no. We really want curated data reviewed by a clinician. The workflow that this question proposes is a good one, in which the parents or the young adult enters the data in prior to the visit, and then the clinician and the family review it together. That would be totally okay!

We’ve spoken with Rob Moss, who runs SeizureTracker, and he’s very excited about this idea. He’s been working to link his application with Epic, which is one of the electronic health record vendors. What we’ve asked is, “If you get that workflow there, can the SeizureTracker data populate the learning healthcare system data?” We’re agnostic on how the data gets into the system. If the data gets in there and the clinician vouches for it, then we’re good.

Are patients and their families aware you are collecting these data? How do they feel about participating?

We’ve been very deliberate from the beginning in maintaining communication with advocacy groups and including parents and people with epilepsy at the highest levels involved in developing this system, so there are representatives. That being said, if a parent bring their child to one of the centers involved in this project, they wouldn’t know that the information from that visit is being brought into our Learning Healthcare System.

The reason we forgo getting patient and caregiver consent is that the labor required is too much work for the kind of data we’re gathering. The way electronic health record data is used for research in this country tends to support that. Institutional review boards granted us an exemption from the federal regulations from HIPAA, which allows us to look at the data without getting explicit permission from a hundred thousand people.

We’re comfortable with because we feel the good things we’re going to learn far outweighs the risk to loss of privacy. We’ve been quite intentional, as I said, about making sure that the data that we have doesn’t have a lot of personal information – no names, no addresses. We have dates of birth, but lots of people share same dates of birth. When we’ve spoken to advocacy groups, most people are in agreement that the labor required is too much work to get those consents. We’d spend all of our effort doing that and the groups would rather us do the learning . We got all of the approvals. We have data use agreements. We have all of the legal and ethical infrastructure, but it’s true that you wouldn’t know that your data is going to be in there necessarily.

How have you involved patients in designing this system, the process, and the governance? Are differences between the Pediatric Epilepsy Learning Healthcare System and the other system that you mentioned in your presentation?

Both systems are quite deliberate and have made a big effort. The ELHS, the Epilepsy Learning Healthcare System, is run out of the Epilepsy Foundation, which at its heart is an advocacy organization. I think the DNA there I think is much more about patients’ perspectives. We were aware of that. We wanted to make sure we were listening and including that voice, which is why we bring everyone on the calls.

As a example, when we put our forms together, we wanted to have a scale like, “How often are you having seizures?” In the original scale, the most you could say was multiple per day. A couple of parents were like, “My kid has more than that.”

“What do you mean?” we asked. “Multiple per day, that’s it.” Parents said, “Yeah. I can’t even count because there’s so many.”

We said, “Oh, okay. We missed something important.” Now the highest level is “too many to count.”

Is there the possibility for an international collaboration? Could it be even better with hundreds or thousands in the wider group?

I love that. Whoever wrote that question, we are like mind melded. We’ve had some conversations about collaborating internationally. Building the questionnaire into the healthcare records vendors’ system, then all of their customers internationally can then use the form. Then, if you get a collaborator, then the data’s already there. The collaborator just has to send it.

How do I encourage my neurologist to participate in The Pediatric Epilepsy Learning Healthcare System?

Tell them to email me. We have some funding and we were provided 20 participating centers some seed funding. That money has run out, but some sites are willing to join with internal resources. At present, if there are sites that are enthusiastic, they can just find me and I can have a conversation with them.

The other thing is that 54 of the US Pediatric Epilepsy Centers are part of PERC, and I am pitching and giving updates on this through all of our PERC calls. We just had our annual meetings last week and we have calls every other month. Find out if your center is part of PERC, find out who the PERC representative is, and then having that person reach out to me.


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.