Webinar: Surgical Treatment Options as Tools to Reduce the Risk of Mortality in Epilepsy

The pediatric epilepsy journey can be challenging and scary. Surgery has been less utilized but research has shown that it can be an effective treatment option, especially for those living with drug-resistant epilepsy. Surgery can reduce seizure frequency and lessen the risk of seizure-related death.

While surgery might not be an option for every patient, it is important to advocate for timely, comprehensive surgical evaluation for all people struggling with epilepsy and reduce the known disparities in access to surgical treatment options.

In this webinar, we will discuss how surgery is one of the tools available to treat epilepsy and why having a surgical evaluation is important. Attendees will also learn about how different treatment approaches can improve survival and contribute to improved healthcare outcomes.

This webinar is conducted in partnership with Partners Against Mortality in Epilepsy (PAME). The mission of PAME is to convene, educate and inspire all stakeholders – from the bereaved to those living with epilepsy, to health care professionals, advocates, clinical and basic scientists, and death investigators – to promote understanding and drive prevention of epilepsy-related mortality.  


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About the Speaker:
Sandi Lam, MD, MBA is the Division Chief of Pediatric Neurosurgery at the Ann and Robert H. Lurie Children’s Hospital. She serves as a Professor and Vice Chair in the Department of Neurosurgery at Northwestern University Feinberg School of Medicine in Chicago, IL.

Dr. Lam’s clinical focus encompasses pediatric epilepsy surgery and cerebrovascular surgery with expertise in surgical innovation, neuroendoscopy, minimally invasive surgical techniques, and development of multidisciplinary patient-centered clinical programs.

Q&A with Sandi Lam, MD, MBA

Is it an option for drug-resistant patients who have seizures as a result of FIRES? And perhaps you can explain FIRES in NORSE that are triggered across many parts of the brain. And similarly, is it helpful in the case of generalized seizures?

That’s a great question because these are very, very challenging diagnoses. So I would say from a traditional surgery standpoint, it is kind of the most straightforward when there is one area of the brain causing seizures and we can do surgery to remove that area. So that is kind of the most straightforward. And I had mentioned that we need to tailor epilepsy surgery options to the patient. And some are much more complex.

And the scenarios that you talk about, I mean generalized seizures or FIRES are really much more complex, but we actually have more options than when I first entered the field, which is we’re looking for this lesion, the one guilty area, and removing the guilty area that’s causing the seizures. And now we have neuromodulation, so vagus nerve stimulation, which is kind of a more broad way of stimulating the vagus nerve with broad projections to the brain to really kind of try to tell it to calm down.

But now we have other ways with brain stimulation, having deeper either targeted ways when we know that there’s a certain area we can put the electrodes there to do stimulation in a targeted area. Or we can actually have thalamic stimulation, which actually tries to help the whole network. And we really don’t, in those scenarios, we don’t know one area where the seizures are coming from.

It’s actually a more kind of generalized epilepsy where we’re actually targeting deep targets in the brain to actually tell the entire brain to have neuromodulation effects. So patients were not candidates for epilepsy surgery 20 years ago, or even 10 years ago or maybe even five years ago. Our thinking and our ability to do these surgeries safely and use these technologies more effectively is evolving and we’re getting better and better and we’re learning together.

At what age can you be a candidate for DBS or RNS? So deep brain stimulation or neuromodulation responsible?

From my standpoint, we don’t give up. We are always looking for is there something that we’re missing or something more that we haven’t tried or something that we haven’t thought of that could really be, that we can think of. Do we have more tools in our toolbox? So surgery is a tool, and we’ve thought about different types of surgery for patients who are even the youngest patients.

So when you think about a DBS, a deep brain stimulator or an RNS, a responsive neurostimulator, technically the US FDA approval is actually for adults, for patients 18 years old and above. We have actually implanted these device in children and even school aged children or a little bit younger. So while the companies will have to kind of stick to compliance and regulatory approvals, there are just human factors.

Where we tailor the treatment that we give to patients in a way where we decide as a whole team along with the family, if we think that there is a good chance of this helping have seizure control, then we actually consider it all together. So from a care team standpoint, there’s good precedent that at my center and actually multiple specialized centers in the country, we are doing cranial stimulation for children.

What is the frequency of DBS and RNS now? How common is it? Is it still considered exploratory or new?

That’s a good question. And I guess it depends on who you ask, right? So it is relatively new, but it has been used for… I guess when you look at the trials and onward, I would say I have seen data that’s at five years and 10 years. I would not call it experimental at this point because there have been trials and studies that are ongoing as well. I would say it would depend on the patient and the family and also your care team.

So I think that the patient and family have to be comfortable with their care team, and there has to be that trust. And also the care team has to be comfortable with what they’re offering. So they have to have that level of experience with the treatments that they’re offering. So it really is a combination of factors, but at a place that is really thinking about being innovative and really just not giving up and not taking, we don’t know or no for an answer.

And having that hope and curiosity to see are there things that we can do to help patients? That’s actually how we get better. And as I told you, when I first trained in this field and when I first started my practice, a lot of these were not actually even available. And now that they’re available, I’ve been lucky to be part of teams and centers that have been among the first to apply these technologies such as laser ablation or putting in responsive neurostimulation into children and doing endoscopic epilepsy surgeries.

And now we actually have quite an accumulated experience where my partners and I probably have one of the largest experiences among pediatric centers. So there is a certain level of comfort and experience to understand what are the tools in our toolbox. We don’t want to offer a tool that we don’t have, and we want to offer the tools that we know, right? That we know what the result is going to be and be able to really look you in the eye and work with families and say, you know what?

I believe this is going to help. And I know that in my experience I can say that I can do this safely, and I really have that hope of being able to help you. And we need the whole team to do this, and we need to be able to make those choices together.

How long did it take for RJ to recover?

RJ was at Lurie’s for one week and then we went straight over to inpatient rehab at Shirley Ryan for exactly 30 days and then we were home. We did intense PT, OT, and speech three days a week for three hours, one hour each section. And that was for about six months or so. And then we graduated to outpatient PT, OT and speech. And I would definitely say just a word of advice to those who are intense physical therapy, occupational therapy and speech therapy.

Start looking in advance because I know where I’m from, it was a long waiting list. However, like how Dr. Lam said that advocating for your child, I advocated heavily. I searched high and low, I put him on multiple waiting lists and it was first come first serve.


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 healthcare 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 healthcare professionals who are familiar with the individual’s specific health situation.

Webinar: Epilepsy with Eyelid Myoclonia (EEM), Formerly Known as Jeavons Syndrome: Diagnosis and Treatment of this Rare Photosensitive Epilepsy

Epilepsy with eyelid myoclonia (EEM), formerly known as Jeavons syndrome, is a type of rare absence epilepsy characterized by a brief but intense and repeated jerking of the eyelids. Seizures can be triggered by bright and/or flickering lights and can be associated with abnormal EEG patterns.

EEM most often starts in children aged between 6 and 8 years and is more prevalent in girls than boys.

In this webinar, attendees learn how to recognize the clinical features of EEM, as well as how to differentiate it from other epilepsy syndromes.  The webinar also reviews the consensus first-line treatments for EEM.


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About the Speaker:

Kelsey M. Smith, MD is an Assistant Professor of Neurology and epileptologist at Mayo Clinic in Rochester, MN. Her clinical and research interests include genetic generalized epilepsy syndromes including EEM, autoimmune-associated seizure disorders, and women with epilepsy. She is the first author of multiple publications that address the diagnosis and treatment of EEM.

Q&A with Dr. Kelsey M. Smith

We’ve talked about the difficulty of controlling seizures in this epilepsy syndrome. Since it is hard to treat, what level of control should be expected and how do we know when to consider a new or an additional treatment or medication?

I think that that’s a great question and it’s a question that I think should be very individualized and depends on the patient itself. So it depends on what a patient’s goals are. If the patient really wants to be driving, then we need to try to escalate therapy to the point where the patient isn’t losing awareness where that could be safe and also a risk-benefit ratio of trying a new anti-seizure medication. And so, I try and just have a discussion with my patient to see and for us to agree on that difficult question.

Does the VNS or DBS work for this syndrome?

So there’s limited data out there. In our series, we did have some patients who had VNS implanted from our 30 patients we published in 2018. I have personally seen some patients who’ve had some nice response to vagus nerve stimulation, but I would just say we don’t have enough knowledge. Deep brain stimulation as well, there’s even less knowledge on. There’s actually one case report of responsive neurostimulation to the thalamus, which is similar to deep brain stimulation. Deep brain stimulation is advancing in areas of generalized epilepsy, but there’s just not as much experience in generalized epilepsy. So that also includes epilepsy with eyelid myoclonia. It’s definitely an area of research and we should know more in the coming years.

It’s perplexing about lamotrigine. In your talk, you talk about lamotrigine works and can be prescribed, but sodium channels as a rule are not prescribed. So can you explain that dichotomy since?

I’ll try. And this is not just for epilepsy with eyelid myoclonia where there’s this dichotomy. So we know that lamotrigine works for some generalized epilepsy syndromes. We use it in multiple generalized epilepsy syndromes. It can make myoclonic seizures worse. There’s some good data for that. And there’s some debate about the eyelid myoclonia being just myoclonus of the eyes. But also, we know works usually well for the generalized tonic-clonic seizures and these generalized epilepsy syndromes. And that’s probably due to other properties than just the sodium channel blocking properties. And so, I think it’s a bit of a balance. If a patient has a lot of extremity myoclonus, that’s something to consider when starting the lamotrigine. But still typically, it’s one of our go-to medicines for generalized epilepsies despite its sodium channel, part of its action being at the sodium channel.

Have combinations of medications been trialed for effectiveness against DEM? This person has seen some better control during medication transitions when there may be multiple meds on board. Is there any evidence for that? ?

There’s no great evidence for that to, most of the studies looking at epilepsy with eyelid myoclonia are retrospective studies. And it can be hard when you look at some of that data for the confounding factors of multiple medications. It wouldn’t surprise me if there is sometimes a combination that works better balancing the eyelid myoclonia and things like that. But we just don’t have enough data to say, I would say. There’s a couple of retrospective series that puts some of the combinations together, but that data is limited and half interpreted.

So, there are some new medications available now. Is there any knowledge about how well Xcopri might work?

There was a series published actually out of Mayo by one of our fellows, Shruti Agashe, looking at Xcopri or cenobamate in generalized epilepsies. And I believe there was one patient with epilepsy with eyelid myoclonia in that. So obviously very limited data. There are studies that are hoping, my understanding is to study cenobamate or Xcopri in generalized epilepsies, and we don’t have the results from those in general. So I just don’t think we have enough knowledge at this time.


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 healthcare 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 healthcare professionals who are familiar with the individual’s specific health situation.

Webinar: Stem Cells & Epilepsy: A New Therapeutic Approach for Treating Drug-Resistant Epilepsy

Stem cells, the cells in the body that provide the blueprint for the creation of all other specialized cells (e.g., nerve, cardiac, blood cells, etc.), have generated significant interest in the research community over the past decade. Stem cells can help regenerate or repair tissues in individuals that have been affected by certain disorders and are being assessed for the ability to reduce seizures in people with epilepsy.

This webinar will discuss a pioneering neural cell therapy approach that could provide a novel treatment for drug-resistant focal epilepsy. Viewers will learn about the promising new data supporting this approach which will be presented by Dr. Robert Beach from the State University of New York (SUNY) Upstate Medical University.


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About the Speaker:
Dr. Robert Beach, MD, PhD, is an Associate Professor of Neurology and Director of the Epilepsy Program at SUNY Upstate Medical University. His clinical interests include epilepsy, epilepsy surgery, anti-seizure therapies including medical, surgical, and experimental approaches, and differential diagnosis of seizures.


Q&A with Dr. Robert Beach, MD, PhD

Will this approach only be useful for epilepsy located in the temporal lobe or any drug-resistant epilepsy? Where do you see this going?

Well, if it is successful in this well-studied area of the brain, it will probably be useful in other focal epilepsies. As long as you can localize the seizures and target them with the cells, it has the potential to be beneficial. We’re starting with the best studied and most frequently treated surgically part of the brain as a starting point because it’s far and away the best understood and the most likely to provide us with realistic estimates as how it might work elsewhere.


Do you think it will eventually help people with Lennox-Gastaut syndrome or genetic disorders?Question?

Well, most genetic disorders are not focal. Some of them, like tuberous sclerosis for example, have multiple foci, and it might be useful in that sort of setting because it’s very hard to necessarily know which is the active focus. If you’re not damaging the area as you would with surgery or something, you may be able to treat more than one focus. But many of the genetic disorders are too diffuse and not well-localized enough to likely benefit from this kind of stem cell implant.


Can stem cell therapy be used in a patient who has a deep brain stimulator?

Well, not at this point, but it could be, theoretically. Deep brain stimulation is often used for less well-localized epilepsies, and some of those probably do not have a focal area that could be treated. Some of them have multiple focal areas of which you’ve … concurrently with the responsive neurostimulator or RNS, treat two of them, but not multiple ones. This could potentially have the ability to treat these area parts epilepsies where there are more than two foci or two focus that aren’t easily addressed by the RNS.


Are the cells manipulated in any way? Are they grown to increase their number
or cultured in any way? Selected in any specific ways?

Yes, all of the above. They are put into culture and they’re differentiated using a variety of growth factors and other things that influence distill differentiation. Then they’re tested to be these inhibitory GABAergic neurons, and then they’re expanded and tested for purity, and then they’re frozen in small amounts to be used in a particular implantation, and that you have multiple samples of the cells that can be used over a longer period of time with the frozen cells.


This isn’t actually coming from the person who’s having the surgery, but these are cells that were generated some time ago?

Yes. I don’t know exactly when they were generated, but they were generated from stem cells that have been obtained from, not from an embryo or not from a fetus, I should say. I don’t know exactly where they’re obtained from. Theoretically, you might be able to generate stem cells from the individual, which would have immense advantages in terms of not needing the immune suppression. That is one of the more complicated parts of this kind of approach, and I think that that’s potentially doable. It may be that cord stem cells may be more versatile and require less immune suppression. These are things that I don’t have a lot of information on, but are potential.


So, this person has a daughter with epilepsy, but an SCN1A mutation. They have stem cells saved from birth via the cord stem cell banking, and they’ve saved it from both of their children. Do you think this type of stem cell can come in handy for treating epilepsy?

That’s a very good question. I think there probably is a potential for those stem cells for this person, but I don’t think it’s going to be necessarily this kind of stem cells delivered focally, and it may not be primarily GABAergic neurons. It may be something that might introduce a different or correction of a different deficit that would be seen in SCN1A. But at this point, I really don’t know exactly how that would work.


How long does it take to see improvement, for example, a reduction in seizures after cell implantation?

Well, we don’t know. We were pretty surprised that this person did as well as he did in terms of seizures. So, the hypothesis that we are operating under is that the benefit of the cells would come mostly after they integrated with the other cells, and form new connections and new networks, which would take time. The plan was to assess this over a year, basically, be looking at six months, but expecting to find some realistic estimate over a year. This is, being the first patient, I think it’s premature to say that this is going to be a characteristic of everybody getting these cells, but it’s very encouraging.


If somebody has a VNS and can’t have an MRI, is it still possible to be assessed for this?

Well, a person with a VNS, as long as they don’t have it slipped way down below their chest or in the lower part of their chest, can have an MRI. There’s a, you require certain things in the MRI to be able to get, in the scanner, be able to get an MRI in somebody who has a VNS. There’s an absolute area of exclusion where if it exists, you can’t do it. But for the most part, they are coils that are used that go around the head and localize the flow of the changes of magnetic fields that keep it from interfering and keep it from damage the VNS. The VNS has to be turned off during the MRI. One obvious reason is if somebody has their magnet on and they go through the MRI, they’re going to be exposed to rapidly fluctuating magnetic fields, which will trigger it on and off multiple times, which would be intolerable very quickly. But most people with a VNS can get an MRI. If they have a focal abnormality that is likely to be the source of their seizures, or a couple maybe in the future, they may be candidates, but for now we’re looking at one focus.


So, back to the GABAergic interneurons, will they only work in the hippocampus or could they work in other areas?

Well, these are neurons that come from an area of the brain that spreads out throughout the cortex. The cells are formed in the median ganglia eminence, and then they migrate to various parts of the cortex. The reason it’s being tested in the hippocampus is because it’s a well-studied model, and we know that there’s GABAergic cell loss. They should potentially work in many other areas if there is a loss of GABAergic input and they can be replaced, which if there’s a loss of GABAergic cell loss, and it’s an area that can be, well almost in the area can be accessed using stereotactic implantation. So, probably, as long as there’s a focal area that can be identified as a seizure source, and there’s a good reason to think there’s GABAregic cell loss, it does have potential again, in the future.


How long do you think it will take to get a good readout from this clinical trial and know what the next steps will be? We’re getting a lot of questions about the future of this and where it could be used, but clearly, we’ve got to complete this trial first. Talk about this trial and how long it might go.

The way the trial’s set up now is the first two patients had to be separated by I think, three months. So, second patient was implanted about three months ago, who I don’t know much about their seizure effects or side effects. But I note, they’ve had no major side effects, and the cells were implanted a very similar way as to what I demonstrated with our patient in approximately on, well, actually as of now, there’s been several things that the Data Safety Monitoring Board has allowed us to do that’s going to facilitate getting patients in faster. One of them is to open it up for additional studies in this preliminary group of patients who are really getting a low dose, and there’ll be five people in that initial cohort that should probably be all implanted within the next six months, I would hope. Approximately a year after those five people go through, we should have some idea as to whether this effect on epilepsy is real, and whether there are side effects that we haven’t yet seen that are going to be an issue.

We also may have an idea, because they’ve opened it up now, so we can do non-dominant hemisphere patients, I’m sorry, dominant hemisphere patients as well as the non-dominant hemisphere patients. We may get an idea as to whether the most important benefit for this, it may be realized, and that is if you’re treating the dominant hemisphere temporal lobe epilepsy, in somebody who has relatively normal verbal memory and function, you’re going to get a decrement on surgery, because you’re going to be taking out areas important for that. But it is very possible, and it’s been shown with the less you take out, the more likely you are to have less effect on memory and language function. It’s very likely that with this kind of approach that you’ll have even less effect, or we hope that there’s even less effect on the language and verbal memory, and that we might have some information on that within the next year. I’m not really sure.

It might take longer than that, but it’s going to take larger numbers to really get a good sense for how likely various things are. I think we’re definitely seeing some very promising results, but it’s very early to know.


So, we’ve got a question about eligibility, and you’ve been talking about unilateral mesial temporal lobe epilepsy in the non-dominant side, and you just shared that there’s been a loosening of restrictions to also now allow the dominant side. It sounds like that might be because of the lack of concern around changes in some function.

Well, it’s because there doesn’t appear to be any major risk showing up from what we’ve done so far. It’s the dominant hemisphere of patients who this is most likely to be the most attractive approach for, because of that potential for sparing language function or even getting improvement potentially. So, as long as somebody has unilateral at this point, unilateral left or right mesial temporal sclerosis and seizures coming from that area, and no progressive degenerative diseases, and various other minor or unusual restriction criteria, they would be a candidate for this. But it’s basically, think of it as somebody who might be a candidate for epilepsy surgery on one temporal lobe, may be a candidate for this. There are some details beyond that, but that’s a good starting point.


Are there any discussions about trying this in children? I know that’s a difficult question, I’m sure.

Yeah. I think there will be plans to do that, because temporal lobe epilepsy is fairly common in children. But I think that there are some differences in, I would guess that’s going to take a while before we have a good handle on anything that’s going to actually try that. If it’s very successful, maybe a no-brainer to go forward with children, but it’s a little unclear at this point.


Do immunosuppressants have any effect on seizures themselves?

Not that I know of. I mean, they have side effects that can be somewhat systemic, but I’m not aware that any of them are actually anti-convulsant. Now, there are drugs that reduce proliferation that are in some ways related to the immune suppressants that can affect development of some of the epilepsies that require things like tuberous sclerosis, where you get growth of cell populations as tubers or as giant cell astrocytomas, where they suppress that. But that’s not truly an immune suppressant. I’d have to look to see what data there is. I’m not aware of any, but there might be some data on that.


Here’s somebody who is asking about autoimmune epilepsy and its impact on the hippocampus. The autoimmune epilepsy appears to have shrunk or changed their hippocampus. So, is somebody like this a candidate?

So, autoimmune epilepsy should first be treated to reduce the impact of the molecule causing the autoimmune response and the autoimmune response itself. If that is unsuccessful, and there’s residual long-term epilepsy, then they may be a candidate for this, but autoimmune epilepsy is usually a monophasic course where if you can remove the inciting antigen, which might be in some cases related to a tumor or an abnormal cell growth, or if you can suppress the response adequately, you can get control of those seizures in most people. And, if they are treated quickly enough and aggressively enough, they’re likely to get enough of a benefit. So, long-term epilepsy is not likely to occur, but for some people it does, and I think those people, if it’s in the hippocampus, would be candidates. I don’t think they’d be candidates for this study because that’s probably a restriction, but because autoimmune is not really a clearly defined stimulus that ends at a given time, but I think that they would be candidates for this kind of approach.


So why do the cells have to be injected into the brain? Why couldn’t they be injected into the bloodstream?

So, there are immune therapies to which are largely for blood cells where there can be replacement or treatment directly into the blood, and there may be epilepsies which are widespread and without a focus that might benefit from some blood cell treatments in the future. But for the effect of the GABAergic cells to be beneficial without causing widespread suppression of activity, you want to be able to put them where the abnormality is, where the hyperexcitability is, and that requires injecting them into the brain. There might be some genetic cases where that would be different, but not at this point.


Are there any outwardly visible components of implanting stem cells in long term?

Outwardly visible? Well, I guess if you palpated their skull, you might find a small little burr hole in the back where the burr hole is made. If the person is on long-term immunosuppressants, there might be some side effects that could last over a longer period of time, and of course, being on immunosuppressants does increase the risk for infections, but that’s not really a marker. That’s just a risk, I’d say.


You’ve talked about long-term immunosuppressants. It’s likely that people would have to be on immunosuppressants for their lifetime or do we know?

Probably on some level for lifetime. The aggressive approach initially is much more, all of, I think he was at one point on three strong immunosuppressants, and is now on a single low dose of Tacrolimus, which is one of the more common immunosuppress use for tissue transplants, which is probably not causing significant side effects at this point. Does have the increased risk of possible infection though.


Do you see this being used for any other kinds of neurological disorders?

Yes. I don’t think the, there’s probably ones where I think GABAergic cells may be beneficial, but I do think that stem cell of particular kinds will be useful in some other diseases, perhaps even in something like Parkinson’s disease where we now do stimulation, there might be potential to use certain kinds of cell implants to benefit there, but that’s something that I really don’t know for sure, and it’s in the future for sure.


So, you’ve talked about, you mentioned these people who are being enrolled are on a low dose. So, is the anticipated that the next steps in the clinical trial will try different levels of stem cell infusion or different numbers of stem cell infusions?

Yeah, the plan was to try a higher dose with the second cohort, which would be after these five people have gotten adequate results, which would be roughly a year from now or maybe slightly more. I’m not sure if the results are particularly impressive with the low dose. That may be modified.


Would be useful for generalized genetic epilepsies, and generalized epilepsies in general?

Well, I think most of the generalized epilepsies don’t have a focus where we could inject GABAergics neurons and expect to get a benefit. There may be particular subtypes of GABAergic cells that might be useful in some of the generalized epilepsies, but that’s very theoretical, because you’d have to be able to figure out which subtype and where to inject it. Theoretically, with some of the generalized epilepsies, it might be in the internuclear or reticule thalamic nuclei, which is part of the relay for some of the so-called spike-wave epilepsy, which are often called primary generalized. But I think that’s highly theoretical at this point.

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 healthcare 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 healthcare professionals who are familiar with the individual’s specific health situation.

Webinar: Cutting-Edge Technologies for Treating Nano-Rare Epilepsies

Rare diseases are generally defined as those diseases that affect fewer than 200,000 people in the United States1. However, there are many diseases that are caused by genetic mutations that only impact a handful of individuals worldwide. In these cases, the small number of patients present a variety of challenges to identifying and developing effective treatment options including a long diagnostic journey, often with misdiagnosis and the high cost of clinical trial development.

This webinar will highlight the work of the n-Lorem Foundation. The n-Lorem Foundation is focused on creating free, individual treatments for people with what are termed nano-rare diseases, caused by genetic mutations that affect 30 patients or fewer in the world. 40% of n-Lorem Foundation patients suffer from epilepsy, and these individuals may benefit from more individualized genetic treatments that meet the unique needs of each person. This webinar will discuss the use of individualized antisense oligonucleotide (ASO) treatments for patients with nano-rare epilepsies. ASOs are short strands of modified deoxyribonucleic acids (DNA) that can be developed rapidly and inexpensively and can specifically target and potentially halt the development of the disease-causing proteins, thus attempting to change the course of the disease.


1  Jo, A. et al. BMJ Open 9, e027248 (2019).



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About the Speaker:
Sarah Glass, Ph.D. is the Chief Operating Officer at the n-Lorem Foundation, where she leads the implementation of the foundation’s mission to discover, develop, and provide personalized experimental medicines for patients with diseases caused by genetic mutations affecting fewer than 30 individuals worldwide. Sarah is passionate about forging partnerships to increase our collective ability to help and provide hope for people in need. She combines her professional experience as a geneticist, drug developer and clinical trialist with the urgency she has felt as the parent of a nano-rare child.


Q&A with Dr. Sarah Glass

Can you speak to families that have a diagnosis of L G S or Jevens or infantile spasms? How do they think about this technology? Is it right for them or not yet?

Honestly, it is very specific to every single mutation and I think that’s the unfortunate reality. And as much as that doesn’t help broadly speaking, and I think that’s what we’re really finding, especially in some of these cross patient groups, is like how can we actually give you a much more informative answer than that? What we have started to put in place is almost even a, we started pre-submission type of assessment, if you will, is almost even just like a triaging because we do have a lot of questions like that. So for my patient community, we have this type of mutation or this type of mutation or we have here these two which are affecting three people or five people, and what do we do? Should we find a physician? Should we submit an application? And so I think that’s the best that I can offer is that I think what we found is typically, first of all, the prevalence of the mutations is very important, obviously.

The functional consequence of the mutation. If we understand the functional consequence and if there is a realistic ability to affect the consequence of that mutation. So ultimately, for example, null mutations, ASOs aren’t able to help, those are typically going to move into the gene therapy space to some extent. We do know a hundred percent for as far as the organ system, obviously these are all C N S, but I think we get those questions a lot as, so if we want to target the muscle or if we want to target lung and things like that, those are also areas that we cannot target. So I think part of it is understanding what ASOs cannot target. So some of that also is really focused on the mutation but focused a little bit broader than that. And so I think that would be my suggestion is really in thinking about those questions is to say, the first question is what does the mutational spectrum look like for each of those areas that you mentioned, those patient groups and to say, okay, do we have some functional consequences that are well understood? Are the prevalences in these regions that would apply here? And all this is really driven by what these F D A guidance documents provide. They’re very specific, actually, refreshingly specific on the type of patients that actually qualify for these because this is a different drug discovery and development path than a commercial program. So it’s a much abbreviated path. And that’s very important for all of the patient communities to know is that these go specifically from a single G L P animal talk study right into the patient. Whereas in traditional clinical trials you go multiple animal talks, phase 1, 2, 3, et cetera. And so that’s why the F D A is very specific on what are the characteristics of patients that are actually suitable for this path. And some of those characteristics are in the genetics, it’s in the clinical manifestations, it’s in what is the other treatment landscape.

So that’s another element as well, is really just do we have a sense of, well, there are all these other treatments that are already really targeting these patient populations. So this is really focused on patients who just really and truly don’t have any other options.

How does that work get funded and if it’s not done by n-Lorem, how does that research get accomplished so that it can perhaps inform you?

It’s really variable honestly. And I think the most interesting, it’s actually fascinating, sometimes you will find a mutation that will have evidence for having gained a function consequence in some circumstances and loss in others. And some you might not necessarily very clearly be able to understand it and it could just require a little bit more research in a particular lab. Most of the research that’s happening is back into the lab of the submitting physician for the most part. So that’s only helpful, however, if one, a patient is connected with the physician who is also a lead researcher in that particular gene. And so I think what we’re working to do, and we have a couple of potential partnerships where there could enable almost a proof of concept lab to some extent, where you say, okay, this could be amenable if we have X, Y, Z data that will then get us over the ability to make that decision as far as do we have an ASO strategy or not?

And so that’s very much something that we’re working on now is to have a more centralized location. So as with a lot of rare diseases is how are we looking across diseases? So instead of saying we’re focusing on the gene, if we’re saying, well, here’s a type of study, here’s a type of experiment that is often missing, if we could only have this capability to do this for many different genes or for different patients in a more centralized type of location, I think that’s what we’re aiming to do in the future as well. That research piece is so important.

What are some of the reasons for declining an application for an ASO? And you’ve talked about some of those, but can you fill in any other information? Why would you decline an application?

Yeah, so the primary reason to decline is really around the mutation itself and the consequence of the mutation. So again, whether it’s ultimately a functional consequence that we can’t, so if it’s a null mutation, we still continue to have some of those. It also depends on the gene itself. So for example, if we’re looking at trying to upregulate, well, upregulation is not the same across the board. That’s going to be driven by specific characteristics of that particular gene itself. And so then it comes down to, well this particular gene has these different characteristics. So again, most of the decline is really related to the clinical or to the genetic, to the genotype. And so really trying to, from a technical perspective, address whether we feel at all antisense technology can help. Now there are a small, I think proportion as well where the physicians or the patients will ultimately be presented in a way that it isn’t entirely clear.

Well, the gene is the causative gene, so that we do have a handful of patients that will have maybe two mutations or more. And ultimately these are really driven towards having single mutations in a causative gene with that being very apparent. We have a number that will then creep above the 10 bus 20, 30, 40, 50 patient range. And so I think we’re not there where right now we’re really stricken directly to the guidance. I think eventually over time, one could envision that there could be a path even for if it’s an experimental ASO for almost like an intermediate population, if you will, that doesn’t exist at this stage. So that’s another reason as well. Let me think. There’s a number of patients that will be, if it’s again trying to target the muscle or cardiovascular, things like that where we don’t have a validated route of administration that we’re leveraging as part of n Lorem.

Are n-Lorem applications only available for patients that reside in the US?

Yeah, it’s an important question. And right now we only have F D A guidance to under which these patients can be treated. We have significant efforts at this point with Canada and the UK to really evaluate and try to really forge the path in partnership with those regulatory agencies, to define a path based on other partnerships in those countries. We do have a lot of patients actually starting to apply or physicians from other countries that were, I think, trying to assess on almost a case-by-case basis. But for the most part, and it’s only if we already have an ASO for that particular mutation, which is highly unlikely, but I think the goal is to help as many patients as we can, but we have to start somewhere and that’s here in the US.

What is the current cost structure for patients and what do you foresee for the future?

So ultimately the patients don’t have any obligation for the cost of these drugs and the physicians themselves. N-Lorem covers all of the costs from the point of patient acceptance through to all of the drug discovery and development and talk studies, as well as manufacturing. The physicians and the institutions are then required and obligated to support from the treatment on, and so that’s what we’re working through. So typically this should not be, and most physicians are having insurance will be billed for what can be billed and institutions will cover some of the other costs. Some others have philanthropic funds. I think the reality is that each institution is handling this differently and that every institution needs funding for it and they all should get funding for it, honestly. I think one of the biggest challenges that we continue to see with the physicians is that they’re doing this in their nights and weekends time, physicians who are entirely clinical who don’t have any research time.

And I think for someone who’s not necessarily in that space, we all cannot appreciate how busy, how many individuals, like our loved ones that they’re caring for, and then to say, okay, well, and in my own personal family time, I’m going to spend on this particular patient for n-Lorem. So I think that’s what we’re trying to really understand, and I’m personally spending a lot of time right now is trying to understand what are the costs, specifically? What does that actually entail and should this be integrated into what the cost structure could look like for these treatments moving  forward? Because ultimately the patient should not have to carry the burden for these costs. But at a minimum, I can say there is no cost for the drug itself.


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 healthcare 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 healthcare professionals who are familiar with the individual’s specific health situation.

Webinar: Advanced Imaging in Epilepsy: How MEG Can Assist in Surgery

In the United States alone, approximately 4,000 surgeries are performed each year to treat epilepsy. In comparison, an estimated 100,000-200,000 patients may benefit from epilepsy surgery . This significant gap between the number of surgeries performed and the number for whom it could reduce or eliminate seizures could be filled by procedures that can more easily identify patients who are good candidates for surgery. Magnetoencephalography (MEG) is the newest, most advanced technology that can help close this gap. MEG can pinpoint the source of abnormal brain activity and seizures 2, is painless, safe, and requires only 1.5-2 hours to perform. Ultimately, MEG can help surgeons decide whether a patient should pursue surgery. Use of MEG may allow more patients to be identified for surgery, and potentially lead to greatly reduced or no seizures.

In this webinar, viewers will learn how MEG is a key part of the epilepsy surgery evaluation, including information about the basics and safety of a MEG study, and hear about how MEG can help the surgeon by mapping key functions (speech, motor, and vision) onto their MRI for use in the operating room.

The webinar is intended for people living with epilepsy, their family members and caregivers, and anyone seeking to learn more about mental health and epilepsy.


Institute of Medicine (IOM) Epilepsy across the spectrum: Promoting health and understanding. The National Academic Press; Washington, D.C: 2012.

2 Gill MM et al. The use of PET/CT in pregnancy: A case report of malignant parathyroid carcinoma and a review of the literature. Obstet Med. 2018 Mar;11(1):45-49. doi: 10.1177/1753495X17724950. Epub 2017 Oct 9. PMID: 29636815; PMCID: PMC5888841.


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About the Speaker:
Dr. James Wheless is a neurologist and researcher whose research is focused on pediatric anti-epileptic drug development, the ketogenic diet, epilepsy surgery, and non-invasive brain mapping (TMS, MEG). Dr. Wheless is the Professor and Chief of Pediatric Neurology and the Le Bonheur Chair in Pediatric Neurology at the University of Tennessee Health Science Center (UTHSC) in Memphis. He also serves as Director of the Neuroscience Institute and the Le Bonheur Comprehensive Epilepsy Program for the Le Bonheur Children’s Hospital (LCH). Dr. Wheless is also an Adjunct Clinical Faculty Member in the Department of Pediatric Medicine at St. Jude Children’s Research Hospital.





Q&A with Dr. Wheless

Can a MEG scan identify a misconnection with a hemispherectomy?

If someone’s had a hemispherectomy, just to make sure everybody understands that, it’s a big surgery, but basically what you’ve done is you’ve disconnected, if you will, one half of the brain and parts of that brain from the other half. You may have abnormal tissue that’s still in place. It can still generate a seizure. But the way I describe it to patients, it’s kind of like it’s on an island. It can’t spread from there to the rest of the brain or to the body, so it’s not really causing a seizure, even though it may have nothing but abnormal activity. It’s been disconnected, if you will, from the rest of the brain.

Usually, the best strategy for saying are we confident that’s disconnected is to do what we call a tractography. It’s a type of MRI imaging where they actually look at the pathways from those disconnected areas and they can see have they all been cut. And that’s probably the best way to look at those, because MEG picks up abnormal electrical activity, and that abnormal electrical activity is still going to be sitting there because it hasn’t left that area. The question is, is it confined there, and that’s where the tractography helps us better.

This individual writes about having a pacemaker and also having a MEG test. One of the concerns is that the device may cause too much noise for the MEG and how well can the MEG reading be cleaned up if a device like that is present?

Yeah, that’s a great question and an area that I didn’t touch on that I probably should have for purpose of the time. But their question is great because they’ve picked up on what I was saying at the beginning that the MEG is detecting these magnetic signals and anything that’s metal generates a magnetic signal, which is why we all know if you take a magnet, you go around, you can pick up other things that are metal, right? Pacemaker nowadays, most modern pacemakers and other metal implants, if you think about dental fillings, more common than pacemakers even, as well could have an associated magnetic field with them.

The brain is small by comparison. They can overshadow, if you will, the brain. In the past, those were a huge problem. With modern software, we usually, I almost say 100%, but we usually can filter the noise out from those and still get the data that we want in patients that have those. Whereas in the past, we kind of said, “Gosh, that’s a deal breaker, unfortunately.” Nowadays, we say, “You know what? Let’s look at it. Let’s get you in the room. Let’s see what we’re recording.” Even if it’s somebody that we can just kind of… I guess you would say get in the room and try it.

We’re not doing the full recording, but just say, “Let’s make sure we’re not overwhelmed by the noise,” we can just test them, if you will, to see because it’s easy to do. You just go in the room and lie down. It’s pretty simple to do. But most of the time, nowadays with our current machines and the software improvements, we’re able to record.

Is having MEG done something that insurance will cover if a patient is not wanting surgery, but wants to identify where the seizures are coming from?

Obviously, today’s focus was on patients with surgery, but many patients get MEG that are not surgery candidates where it’s still helpful. For example, for some patients that we say, “Gosh, we think we know your seizure type, but you’re responding a little bit differently than the normal person with this.” Sometimes using the MEG with EEG really helps refine, are we on the right track for what we think is the type of seizures that they have? It’s been used there.

It’s been used some in folks that have seizures, probably mainly in childhood where the seizures also may be associated with kind of developmental or language changes that are negative to say, “Okay, let’s see if we can tease out the relationship of these two to each other.” Obviously, today’s focus was surgery, but has it been used in other aspects of epilepsy aside from surgery? Yes, as well. The question they asked about insurance, at least at our center and I think most centers, obviously like any test we do pre-approvals so somebody’s not out of pocket, a surprise. None of us like that.

I get it. I don’t like that either. Usually, that’s not a barrier. I know when we see patients, even if they’re from other centers, I mean, I didn’t mention this either, but the nice thing is the MEG data can all be kind of put on disk, if you will, or printed out in picture form. It can go back to referring neurologists, neurosurgeon, whoever, for them to pull up. We can even put it on disk so they can pull it up on their own inter-operative equipment to register in their own OR as well. It’s portable from that standpoint.

If seizures are coming from scar tissue left from a Gamma Knife surgery in middle age following an AVM removal at 15, so long time ago, could MEG be useful?

Yeah, I think MEG could be, because a couple things with that kind of surgery is, one, if it was near critically functional areas, so language, motor, vision, it could help figure out that relationship. Even if it was not in one of those areas, if around where the prior abnormality is on MRI, if all of those make dipoles line up all around that, it’s really telling you, it’s like a big arrow saying, “This is the problem. This is why you’re still having seizures.” And then obviously that’s a discussion with what are my options to get rid of that problem.

I’m amazed at the resolution that MEG has. This person is asking about the precision. I mean, clearly, it’s very precise, but is it ever inconclusive?

There are times. Just like any test, can you have an inconclusive test? Sure, you can. I would say the benefit of the MEG is that that happens. I will say I’ve not done this a lot, but we’ve done this some, we’ve had patients, their first has been inclusive. We really thought, gosh, we really need to get this data. We’ve literally brought back the patient a little while later and said, “Let’s just redo it and see for whatever reason we can get better data that day,” and we’ve got wonderful data that’s fit.

The analogy I would give folks, it’s kind of like many of our patients that have seizures have gone for EEGs and at some point in their life they say, “I have several normal EEGs or inconclusive, if you will, and then I finally got the one that showed my doc, yes, I have epilepsy. This is an abnormal EEG.” Can that happen to us? Yes, it can. But the nice thing is, especially if the person can do it without sedation or anything, is it’s an easy test to repeat.

Are you able to see the dendrites from the machine to determine damage to these after prolonged seizures?

We don’t visualize the actual structure, which is what they’re asking. We’re looking at function, if you will. We can get an idea if function has been changed in some other ways that I didn’t talk about today. There’s other ways we can use the MEG technology to look at function if it’s been altered. In the example I would give folks, again, if we look at analogies is I could give my car detail, take a picture of it, make it look great and show it to you, and then say, “Do you want to buy it?” You’d probably say, “Well, wait a minute, can I drive it first? Can I see if the air conditioning works?”

But if some of those functions weren’t quite so hot, that might change your thinking, right? They’re looking for, is there a change in structure? Whereas often what we really want to know is, is the function different in the patient, right? I mean, structure, yes, but we want to know how things are functioning.

Are there patients that cannot have MEG?

They’re rare in the modern era. The biggest ones I would say, and they’re pretty rare because the technology has shifted for a lot of our implants, I would say if a patient has had, gosh, probably like a really horrible head trauma where they had to have some kind of large bone flap that was metal plate because their head trauma was so bad and they had seizures from that. Even in the modern era, a lot of the ways that surgeons are doing that are compatible because they’ve gotten away from some of the older fashion kind of metal ones, because even with MRIs that’s a problem. They’ve kind of had to adapt for more current imaging where that’s less of an issue for us as well.

There are rare folks, to be candid. Even some of our patients that have cognitive issues that make it hard for them to understand the testing, if we can do sedation, unless they’re just behaviorally and cognitively so challenging that literally the parents tell us, the caregivers, it’s hard to even get them in a car to get to a hospital. Short of that, we can do it. There really are pretty rare exceptions in the modern world. I mean, we call patients, we kind of say, “Here’s what’s going to happen. Tell us about you,” most of those, if there’s any odd one there, we can tease it out before a patient’s driven to get a MEG or gone through the process, if you will.

Can you use prior MRI to superimpose the MEG or do you have to have sort of coincident testing done?

Prior MRI, I will say, sometimes can be used. Political answer here. The reason I say sometimes is it depends how it was done. To get the degree of resolution I showed you, we need what are called really thin cuts of the MRI to be done. Sometimes if they’re just doing what I would call a regular run-in-the-mill MRI, say you have headaches and got MRI, the cuts are much thicker. They don’t give us the details that we need to put our data on top of the structural picture.

That’s when we end up just saying we can just do part of the MRI over. We just need to do our structural part. We don’t need to do the whole 45-minute to hour MRI. It may just take us 10 minutes to do our part, for example. But if they’ve had a good structural MRI and we look at it, yeah, we can use that. Even my own patients, if they’ve had one six months, a year ago, as long as it wasn’t so long ago that we say, “Okay, things may have changed,” we can use those.


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.

“Treatment Talk”

CURE Epilepsy is proud to present our inaugural “Treatment Talk”, a social-media broadcast highlighting conditions related to epilepsy and options available for treatment of related seizures and their side effects. This “Treatment Talk” will focus on Lennox-Gastaut Syndrome (LGS), a severe form of childhood epilepsy that arises during infancy or early childhood, and the use of the drug fenfluramine to treat patients diagnosed with LGS. This talk features Dr. Michael Chez, a pediatric neurologist at Sutter Health, and Heather Bushey, a parent whose son has LGS and is a patient of Dr. Chez. Viewers will learn more about how LGS is diagnosed, common seizure types and comorbidities associated with LGS, how fenfluramine works to reduce some of these seizure types, and any risks and benefits found in recent clinical trials featuring fenfluramine.

This talk was presented in partnership with UCB.

Post-Traumatic Epilepsy and Cognitive Training: Improving Quality of Life Through HOBSCOTCH

Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by a traumatic brain injury (TBI). People diagnosed with a TBI are 29 times more likely to develop epilepsy compared to the general population1. Individuals serving in the military may be especially susceptible to PTE. In fact, over 400,000 US Military personnel were diagnosed with TBI from 2010-20192, putting them at subsequent risk for developing PTE. 

This webinar provided an overview of PTE and cognitive dysfunction, as well as some strategies to help improve the quality of life of those with PTE and their caregivers. The webinar will also provide details about HOBSCOTCH (Home Based Self-Management and Cognitive Training Changes Lives), a behavioral program designed to address memory and attention problems in adults with epilepsy and discuss a clinical trial opportunity for veterans and civilians living with PTE. 

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

1.  Herman ST. (2002) Epilepsy after brain insult: targeting epileptogenesis. Neurology 59:S21–S26. 

2. DoD Worldwide Numbers for TBI, Defense and Veterans Brain Injury Center, 2020 

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You can also learn more about the HOBSCOTCH program by watching or listening to our Seizing Life episode Learning to Manage Cognitive Challenges for People with Epilepsy featuring Dr. Elaine Kiriakopoulos.

About the Speaker:
Dr. Elaine Kiriakopoulos is an Assistant Professor of Neurology at the Geisel School of Medicine at Dartmouth College, and the Director of the HOBSCOTCH Institute for Cognitive Health & Well-Being at the Dartmouth-Hitchcock Epilepsy Center. Her research and programmatic efforts target building multisector partnerships to reduce disparities in the care of people with epilepsy, ensuring the most vulnerable populations have access to quality epilepsy care and community resources.  

Q&A with Dr. Elaine Kiriakopoulos

Could teenagers eventually participate in something like this?

I’m excited to share that we’re currently working on an adaptation for HOBSCOTCH youth, which will target adolescents between the ages of 14 and 18. We’re hoping to pilot that early in the new year as well. And so more information will come forth on that, but we feel like the program has a lot to offer adolescents as they transition to becoming adults, and helping with organizational skills, and disease management skills, as well as social skills. We’re really excited about that program. And coming along with that program is a HOBSCOTCH app, specifically for youth, targeted to youth. We think that’ll be exciting for them as well, too.

Do Georgia-based HOBSCOTCH participants need to be under the care of an Emory neurologist?

No, not at all. You can contact us, and we’ll make sure we can connect you to the team in Georgia at Emory. You can have your care with anyone in Georgia. We’re happy to have you join.

Interested in the program?



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

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

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

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

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

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

Q&A with Dr. Michael Sperling

Is this medication suitable for occipital lobe epilepsy?

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

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

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

What other medications are good to be paired with cenobamate?

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

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

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

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

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

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

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

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

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

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

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

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

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

Are there any reactions with warfarin (Coumadin)?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Does cenobamate have any synergistic effects with any other medications?

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

Does cenobamate have any reaction to warfarin (Coumadin)?

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

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

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

Will cenobamate substitute for both Vimpat and Keppra?

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

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

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

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

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

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

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

Is this suitable for epilepsies for SCN1A genes?

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

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

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

Does this medication have a prescription assistance program for patients?

Dr. Michael Sperling: Yes.

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

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

Can the drug level be checked in blood work?

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

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

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

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

Webinar: Rescue Medication Delivery Methods and Future Therapies

Seizures can be both unpredictable and unrelenting. When a seizure becomes an emergency, rescue medications provide immediate relief and help prevent the need for emergency care. While existing therapies do stop these epilepsy emergencies in many patients, some are still searching for an option that works for them.

In the second part of this two-part webinar series, gain insight from Dr. Nathan Fountain of the University of Virginia on how different rescue medications can be administered, promising research, and what rescue therapies are currently in the pipeline. His presentation includes a look at the rescue medication pipeline and the new delivery methods which may become available to patients.

Dr. Nathan Fountain, Professor of Neurology and the Director of the Comprehensive Epilepsy Program at the University of Virginia.

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Audience Q&A with Dr. Fountain

Dr. Nathan FountainIs there any reason not to use Diastat before a seizure in a child who has been seizing for five minutes? And if so, how long should you wait?

There are exceptions to every single rule. As a general principle, if you’ve been prescribed rectal diazepam gel to stop seizures, and you have – let’s say – a child who’s been seizing for five minutes, there’d be few situations in which you wouldn’t give them the rectal diazepam gel. There’s a safety concern, and there’s a treatment concern in this circumstance.

The safety concern is; imagine that you’ve already given the child other benzodiazepines, let’s say clonazepam or lorazepam, or even diazepam in a pill form an hour ago. And so, it’s already in their blood. You might be hesitant to give them more without any kind of supervision. But as a general principle, we give rescue medications and tell them, “If you actually time a seizure, five minutes is a really long time.” We do this in the epilepsy monitoring unit. We admit people to the hospital and observe their seizures to figure out where they’re coming from and so forth.

A common exercise is to ask people when we watched the seizure on the video, “How long was that?” And they almost always say, “Oh, that was five minutes.” But you know what? It’s almost always under 90 seconds – a minute and a half. The point: while you’re watching someone seize for five minutes, it’s kind of forever, especially the big convulsive seizure. For convulsive seizures or medically serious seizures, you might say, usually we would advise giving the medicine after five minutes of seizure activity.

Now, if it’s a non convulsive seizure, or if you’re not sure it’s a seizure, that’s a different situation. I suppose we could imagine a situation where you wouldn’t give them medicine. It was in five minutes because it’s a non-convulsive seizure and you think it’s not causing any harm. Let’s say it’s just a staring seizure, an absence seizure. It is unusual to have one for more than five minutes, but there are specific situations when you might. Or if you’re not sure that it’s a seizure, so if you haven’t figured that out yet, then maybe it would be okay to not give the medicine if it’s something, as in, convulsive activity.

Are there any reasons to administer rescue medications to individuals who have one tonic clonic seizure without a cluster?

That goes back to really defining what it means to have a cluster. As a casual observation, we can easily make the statement, “Sure. Give the medicine to prevent the next seizure.” But if you think about this in detail as the FDA does when they think about exactly what the medicine is used for, this starts with a careful history to determine what is a typical seizure for that individual.

If that individual has big convulsive grand mal or generalized tonic clonic seizures typically lasting three minutes, but they suddenly have three in one day or even twice in one day and you want to prevent the next seizure. Usually you’d let that seizure complete because it would almost take three minutes just to administer whatever you’re going to administer. Typically, we’d let that seizure complete itself, then give whatever medicine is appropriate to prevent the next seizure.

I’m glad that question was asked because in general, we wouldn’t treat an acute seizure unless it lasted more longer than usual or more than five minutes. Now, as I said, five minutes is a long time. By three minutes, everybody’s getting all excited and getting ready to do something – call the rescue squad or given a board of therapy or do something – because it will take your five minutes to figure all that out. But for most people with epilepsy, they don’t have a seizure that lasts longer than three minutes. In fact, if you measure it, it’s usually less than 90 seconds and a half.

If you define the typical seizures as less than five minutes, we typically wouldn’t recommend the currently available abortive therapies. Maybe that’ll change. Maybe if it turns out intranasal medications really worked very quickly and are very effective and maybe we’ll get for ongoing seizures, but at the moment we would say no.

Do you have any suggestions for rescue therapies in children younger than two,  because the FDA approved cutoff for Diastat is two years old.

That’s a situation where you really need to talk to your doctor. There are alternatives. Everyone gets nervous when treating young children. When they’re less than two, it gets a little complicated because the dosing changes as well as the method of administration.

I’d say talk to your doctor about that. For a prolonged seizure in those who are less than two years old, we have the same concerns that we have in those older than two. Although the medications are only approved down to a certain age, doctors can use them in different situations. For example, the IV form of midazolam is definitely not approved to be blown up the nose until now. Still the IV form is not, but yet we would use that in certain situations when we knew the details warranted it. Being less than two, you could still use rectal Diastat for instance, or could use some other form.

Talk to your doctor about that and what might be best in that particular situation.

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.