Webinar: Genetic Testing in Epilepsy: Criteria for Adults and the Promise of New Treatments

Genetic testing has long been seen by medical professionals (doctors, insurance providers, etc.) as necessary only for pediatric epilepsy patients. Despite physician reticence to prescribe genetic testing for adults with epilepsy and access challenges, it is becoming increasingly apparent that genetic testing in certain adult epilepsy patients can be beneficial.

In our last webinar, viewers learned that genetic testing can shorten a patient’s diagnostic odyssey, help tailor specific treatment options to their type of epilepsy, and aid in family risk and planning decisions. Many of these benefits also are relevant to adults with epilepsy including those who developed epilepsy as children but at a time when genetic testing wasn’t as widely available. After viewing this webinar, attendees should be able to:

  1. Identify adult epilepsy patients who would benefit from clinical genetic testing.
  2. Understand the types of clinical genetic tests available and how to interpret them.
  3. Distinguish between clinical and research genetic testing and the value of being involved in research studies.

In addition to the information above, attendees will also hear from a person living with epilepsy who underwent genetic testing as an adult to learn more about their motivation, experience, and how it was beneficial to their overall health and well-being. This webinar is the second part of a two-part series in March that reflects CURE Epilepsy’s ongoing focus on epilepsy genetics and research on rare epilepsies. Attendees will receive a link to view part one in an email to follow this webinar.


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About the Speakers:

Gemma Carvill, PhD is an Assistant Professor in the Department of Neurology at Northwestern University in Chicago, IL. Her lab uses genomic technologies, machine learning and high-throughput functional assays to define the molecular basis of epilepsy, including coding and non-coding genetic variants. Her group also uses patient-derived stem cell models to study how rare variants in genes involved in epigenetic mechanisms cause epilepsy. Dr. Carvill co-directs the Adult Epilepsy Genetics Program at Northwestern Medicine with the goal of expanding neurogenetics research and facilitating genetic diagnoses for patients. She also works with colleagues in South Africa to develop strategies for increasing access to genetic testing, and building genetic epilepsy research in sub-Saharan Africa, to ensure that precision therapies benefit all individuals affected by epilepsy.

Elizabeth Gerard, MD is an Associate Professor in the Department of Neurology at Northwestern University in Chicago, IL.  She is an adult epileptologist with clinical and research interests in the care of women with epilepsy and genetic diagnosis in adult patients with epilepsy.  She also directs the Women with Epilepsy Program at Northwestern Medicine as well as the Adult Epilepsy Genetics Clinic.  Her research interests include gene discovery and variant interpretation in adult patients with epilepsy. She also studies pregnancy and contraception in women with epilepsy and is the site-PI of the MONEAD (maternal outcomes and neurodevelopmental effects of anti-epileptic drugs) study. Finally, she is interested in the use and understanding of continuous EEG monitoring in the critically ill and is the site-PI for the Critical Care EEG Consortium.

Q&A with Dr. Elizabeth Gerard and Dr. Gemma Carvill

Will genetic testing tell you if your type of epilepsy could be passed down if you have children or if it won’t be?

Oh, thank you. That’s a great question. And I want to say that the way I got into this space in the first place was that I was counseling patients about pregnancy, which is how I started my career. And I felt like I knew everything that they wanted to know about the seizure medications and about epilepsy, and that in most cases, pregnancies are very successful. And I realized pretty early on that I wasn’t answering all of my patients’ questions because so many patients have the questions about heritability. And that’s actually how I started working with Lisa Kinsley, our genetic counselor, and this clinic grew out of that. I will say, and this is something that we want to study, we’ve been learning that answering that question for individuals is not as clear cut as it might seem, and I’ll kind of go through some of the reasons why the short.

So the first thing to know, is that if you don’t have genetic testing, depending on your epilepsy type, the chances of passing on epilepsy is not terribly high. We know that for studies of big populations of patients. That of course changes if you have many individuals in your family with epilepsy or you have specific types of epilepsy that are more likely to be genetic. So in those situations, we do recommend genetic testing to help you better understand what the cause of your epilepsy is and what the heritability of it is.

One of the reasons it’s tricky, and I want to compare and contrast this with, say for example, prenatal genetic testing you might do with an OB, is that our understanding of what’s called the penetrance of these disorders is slightly different. So we may have, in some cases we diagnose a genetic epilepsy that’s associated with a single gene and you have to have only one copy of that genetic change to be at risk for epilepsy. And those are the type of genetic changes that we often diagnose if we are diagnosing a genetic condition, and those pass to each individual 50% of the time.

However, just inheriting the variant or the genetic change doesn’t necessarily mean the individual will develop epilepsy. So we get into this probability model where it’s like, “Yes, we made the genetic diagnosis, yes, you have a 50% chance of passing this on.” And again, this is rare, it doesn’t happen often, but the likelihood that your child who inherits it will develop epilepsy can be variable, can be 60% in some of the situations that we deal with.

And so yes, it helps. It helps to understand the inheritance pattern. It helps to understand your genetic diagnosis if you have one. Another example is you may find out that your epilepsy is due to a recessive condition, and if it’s due to a recessive condition where you inherited a genetic change from mom and dad, the chances of your passing it on are very low.

But we are learning that because there’s so much uncertainty in our results, including the variance of unknown significance, including the likelihood of genetic change causes a condition, that a lot of times it’s not black and white as it is in some other forms of sort of prenatal genetic testing. So that’s why that if you’re doing genetic testing with the thought process of, “What’s the risk to my child going to be?”, that you do this very carefully with a genetic counselor and someone who understands how to explain this. And this is where I think it’s really important that your perspective partner also come to the visit as well.

Is there a way to use the Northwestern team for genetic testing if we are in another state?

Take that one, too. So, we’re very excited and we’re hoping to expand this. We do a lot of our consultations virtually now. We also do some in-person. And it’s not just me, I’m really happy to say that Dr. Scott Adney has joined me and we have other people who are hopefully going to join our team as well. I’m licensed in a few states, but not all. And if you’re not in a state where I’m licensed, then you can travel to Chicago if you’re willing to come and see us.

I will also say that interest in this type of specialized clinic is growing and there are several others throughout the country. I just want to highlight some of my colleagues at University of Pennsylvania, University of Alabama and Stanford are some of the people I work with. So if you’re in one of those regions, I’m sure there are more developing, but these are people I know and work with who are doing something very similar to us.

Would genetic testing help determine which medications will help?

So in the psychiatry space and sometimes in the neurology space, there are tests which tell people how you’re going to metabolize drugs. I think it’s important to understand that that’s different than what we’re talking about here today.

Yes, sometimes if we make a specific diagnosis of a genetic condition, there already are specific treatments, including the ketogenic diet or specific medications that you should try or not try based on your genetic diagnosis. Dr. Carvill also talked about that we’re more and more gene therapies that are developing, but in many cases, making a diagnosis does not yet lead to an immediate treatment, just like Maggie spoke about. It’s more the hope for the future.

Would genetic testing help with diagnosis with somebody with generalized seizures? And what type of genetic testing should they start with?

Do you want to try that? Still me? Okay. Actually, I don’t know if we can share or if you want, but I had in the extra slides, the sort of algorithm that’s recommended by the Genetic Counseling Society to go through testing in general. As I said, that the genetic generalized epilepsy, so I want to first make a distinction. Many patients have generalized seizures, so generalized seizures can occur in a bunch of different disorders. Sometimes we refer to the term generalized seizures just because you have a convulsion. So I don’t want to presume that having generalized seizures means generalized epilepsy. Generalized seizures occur in all genetic conditions as well. So, generalized seizures certainly don’t preclude testing.

Having what we often call a genetic generalized epilepsy or idiopathic generalized epilepsy, some of the examples of that might be, for example, juvenile myoclonic epilepsy. It’s a combination of having epilepsy usually with convulsions and certain features on your EEG, usually without developmental delays. That particular group of patients has a lower chance of having a positive result on genetic testing right now with what we have available. Doesn’t mean you shouldn’t do it, I think that’s a nuanced discussion we have with our patients, but I would put that way under 5% of getting a positive result.

Which test to do first, I think depends. So the Society of Genetic Counselors recommend for all epilepsy genetic testing now, to ideally start with either an epilepsy gene panel or an exome or genome test. That may be hard cell for the idiopathic or genetic generalized epilepsies. I also would mention that a microarray, which looks for deletions and duplications, like Maggie was describing, if you’re really questing for an answer, I’ve actually found that test to be useful in the generalized epilepsies. Again, with the implications of the results being somewhat variable

This one is related to Ring 20, and it’s recognized that it’s very rare, and in this case it’s a somatic mosaicism. Is anybody researching this specific type of epilepsy?

So, I’ll make one point while Gemma thinks about that, but I’m ultimately going to toss it to her. One point about the ring chromosomes, as I mentioned that if your testing is negative, make sure that every stone has been unturned. Ring chromosomes are extremely rare disorders, can happen in multiple different chromosomes. And there are societies for several of the ring chromosomes disorders, but that is one of the diagnoses that would not be picked up with our big test, with our exome or genome. You actually have to do a very old test called a karyotype to diagnose ring chromosome.

And Lisa and I are unfortunately finding that less and less companies are offering that because it’s not been offered as much. So we’re actually trying to make that diagnosis on a patient right now. So it’s just an interesting point, that a karyotype is the only way to diagnose ring chromosome. As to specific, we are not doing work that I know of at Northwestern on ring chromosome disorders, but there is definitely research and groups working on it. And I was now waiting for Gemma to come up with who they are.


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: Genetic Testing in Epilepsy: Understanding Results and Their Impact on Care

Genetic testing has increased our understanding of the genetic causes of epilepsy exponentially in the past two decades, specifically helping researchers identify many genes responsible for rare childhood epilepsies. Recent studies found that in addition to providing patients and their loved ones some relief in ending their often too long diagnostic odyssey, genetic testing can enable tailored treatment options and can help with long-term outcome prediction, and family risk and planning decisions. However, there are still many individuals who lack a genetic diagnosis, including adults who may not even be aware that they could benefit from genetic testing.

This webinar will help viewers understand who may want to discuss genetic testing with their doctor and then will explore the following topics following genetic testing:

  • How to read a genetic testing report.
  • What are the different types of genetic results (or variants)?
  • What are the differences between benign, pathogenic, and uncertain variants?
  • What to do after receiving a genetic diagnosis.
  • How do these results impact an epilepsy treatment plan moving forward?

This webinar is the first of two webinars in March that address CURE Epilepsy’s ongoing focus on epilepsy genetics and research in the rare epilepsies. Our second webinar will be presented by Drs. Gemma Carvill, PhD and Elizabeth Gerard, MD from Northwestern University focus on genetic testing in adults and will be held on March 22, 2024.

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About the Speakers:

Katie Angione, MS, CGC, is a neurology genetic counselor at Children’s Hospital Colorado (CHCO) in Aurora, Colorado. She provides genetic counseling for a diverse population of patients with complex neurological disorders, with a focus on developmental and epileptic encephalopathies. Katie works with patients and families with rare diseases in CHCO’s Rett Clinic, Neurogenetics Clinic, and a multidisciplinary clinic serving patients with STXBP1, SLC6A1, Ring 14, and Chromosome 8p disorders. Her primary goal as a genetic counselor is to support patients and their families through education, advocacy, and research efforts focused on understanding the natural history of these conditions, and eventually working toward precision diagnoses and treatments. 

Q&A with Katie Angione, MS, CGC

One is, this person was informed that the gene that’s been identified for Doose Syndrome has been found but not for JME. Is this the case, do you know?

So I know that Doose Syndrome or EMAS has a couple of different terms for it. It’s something that we’ve been trying for years to find the gene and there are definitely some genes that have been associated with it. There’s still multiple
different genes that can cause that presentation. Doose is a clinical presentation and so there’s not one gene, one clinical diagnosis, there is a little bit more complicated than that. JME, I know that there are some gene associations. I’m not sure off the top of my head what they are. There’s so many genes at this point to keep track of. But again, I think there’s a lot of patients who have a JME presentation who we’re not able to find a genetic cause for. So that might mean there is a genetic cause, but we don’t know the full list of genes that could cause that type of presentation yet.

What about roadblocks to insurance paying for genetic testing? Do you have any recommendations for families who face that issue?

Yeah, that can be really tricky and my experience has been that insurance providers are always changing their policies. I would say that if you work with a provider who’s comfortable with ordering genetic testing, they might be able to go to bat for you a little bit. So we often will write letters of medical necessity. A lot of our physicians will have peer-to-peer discussions with insurance companies to explain the reasoning behind doing testing. But it might be helpful if you’re seeing that testing as getting denied, you might be able to request a copy of their policy and some, sorry, I’m losing my voice, some insurance providers actually cover very limited genetic testing, so maybe single gene or a very small panel or microarray. And then very extensive genetic testing, like whole exome sequencing, but they might not cover a lot of the panels that we typically send in between.

So that’s something we struggle with a lot is wanting to send something more targeted, but then only having the option to send something really comprehensive like whole exome sequencing. So I would say have that discussion with your provider that you’re talking with about genetic testing, about what those options are and if there’s something that would make sense to send that would fit within that insurance provider’s policy. There’s also some genetic testing labs that have pretty good self-pay options and patient assistance programs. So some of the labs that we work with commonly, Gene DX and Invitae, Prevention Genetics, worked with [inaudible 00:42:31] over time depends on the tests we’re wanting to send, but a lot of those commercial labs do have really good programs for self-pay options. So that’s something else to consider. I know sometimes going through a hospital system can lead to higher costs, but going directly to the lab might be more feasible. So that’s something to look into.

I know that there have been some free testing programs. Is that still the case for our community?

Yes. So I work in neurology and with epilepsy, so that’s my bias here. Those are the things I’m most familiar with. But Invitae does have a program called Behind the Seizure that is sponsored by a bunch of different pharmaceutical companies that are working on or that have treatments for some of the genes on that panel. So that is an option for children who have epilepsy that are under the age of eight would have access to that program. I know Invitae also has a long list of other sponsored programs that is always changing over time, so I’m not sure exactly what’s on that list right now. And then Prevention Genetics definitely also has some sponsored testing options as well. I would say that that’s another thing that family groups and patient advocacy groups are good at informing their community about. So that might be a place to turn if you’re looking for a sponsored test that would work for you or for your child..

Would you recommend siblings get genetic testing?

So it depends. So if there is say a diagnosis of a rare disease in a child and their siblings are also children, so they’re under the age of 18 and they’re not expressing any symptoms of that disease, we don’t typically recommend what’s called asymptomatic or predictive testing for siblings until they’re old enough to participate in that conversation. So that doesn’t necessarily mean 18. We definitely have those conversations with teens depending on exactly what the disorder is and what their level of understanding is. But in general, we try to avoid testing minors unless there is a specific treatment or something that could really impact the course of the disease. So if a sibling, for example, is diagnosed with CLN2 disease, which is a genetic disorder that does have a gene specific treatment, we might test a newborn sibling to see if they have that same disorder because we know that it can be helpful to treat very early on and can see potentially better outcomes when treatment is started earlier. So that would be the exception to that, is if there are potential treatment implications..

If children develop epilepsies, but there’s no known history for at least two generations, is there a benefit for the parents to get tested?

I do think it is still potentially beneficial for parents to get tested. So if a diagnosis is made in a child and there’s no family history. It depends on the specific gene, but there are some disorders where someone might actually carry a mutation but not have any apparent symptoms. So that could be helpful for knowing about potential recurrence risks. I would say tuberous sclerosis is a pretty decent example of that. It has a very wide range of severity. So we sometimes see patients in clinic who have that diagnosis, they have the genetic diagnosis, there’s no apparent family history, but then we test parents and one of the parents has the same change. So for things like that where there is a wide range of presentation, I think it can be helpful if you want to know for sure.

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: Prioritizing the Role of People with Lived Experience in Epilepsy Research

The role of people with epilepsy and their support system in research has been evolving over the past couple decades as research and the corresponding care and treatment of epilepsy become more patient-centric. Involvement of people with lived experience early in the research process helps ensure that healthcare professionals treat epilepsy in a more holistic manner, not only by alleviating the impact of seizures and their debilitating side effects, but also by recognizing that everyone’s epilepsy journey is unique.

In this webinar, attendees will learn specifically about the importance and impact of people with lived experience in research of post-traumatic epilepsy (PTE). Attendees will hear about the Congressionally Directed Medical Research Programs (CDMRP), a Congressional appropriation that fills research gaps by funding high impact, high risk and high gain projects that other agencies may not fund, as well as the CDMRP’s commitment to community engagement. Additionally, people with lived experience who are deeply involved in the CURE Epilepsy mission will share their unique experiences in helping move PTE research forward.


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About the Speakers:

Melissa Miller, PhD, is a Health Sciences Program Manager with the United States Department of Defense. Dr. Miller is a biomedical science administrator with an innate sense of urgency to support research that accelerates clinical application of disease interventions. She oversees the Epilepsy Research Program (ERP) within the CDMRP and engages stakeholders across different research domains to identify and fund projects with real promise to improve the quality of life for those impacted by epilepsy. 

Jack Somers is a Captain in the United States Marines Corp (Ret.) and who served his country in Afghanistan. Jack serves on the Steering Committee of CURE Epilepsy’s latest project in PTE research. 

Patty Horan has been a long-time supporter of CURE Epilepsy and currently serves as a lived experience reviewer for the CDMRP ERP. Patty’s husband, Pat Horan, suffered a traumatic brain injury in 2007 and overcame his grave diagnosis and the devastating consequences of the corresponding PTE and now is nearly 10 years seizure-free.


Because science isn’t your background. This is all new to you. So why did you want to participate in research as a person with lived experience? What compelled you?

Jack Somers: I think the most important part to me was to serve. Ultimately, that brings me the most amount of joy. I hope that’s not a selfish response, but it is. Serving the community is the utmost importance to me. And given I do have experience, and I have so much experience over the last 14 years, the opportunity to give back, and hopefully, if it’s helping one person who has this, or helping one mother, father, wife, husband, son, daughter, anyone, a friend, who is a loved one of somebody who has PTE, then that’s, then sign me up. Anything I can do from my position is worth it. And so, service is everything to me. And so, anything I can do from my position is an obligation of mine.


Patty Horan: I guess I agree with Jack, and the fact that I’ve seen so much suffering in the veteran community is unbelievable. And if there’s anything that I can do to reduce the suffering of people in this community, they deserve it all. I mean, they deserve our attention, our focus, and anything we can do to relieve some of what they’re going through is worth it. This war is awful. But I feel like this contributes to not just veterans, but the society as a whole. Because we’re learning how to better take care of our brains, and everyone’s got a brain. And I think that it’s just a really important mission.

And I will say, I am not a scientist at all, I have a business background. And it’s very scary at first to get involved in the research. I have a little selfish reason to, just to be engaged with all these brilliant scientists, that actually can give me a better understanding of how to help my husband, how to support him. And understanding of what the broader picture of epilepsy looks like, and what’s happening out there, as far as access to care, and just the latest and greatest medications, and what’s going on in the clinics.

It is daunting without having a science background to step into a role like yours, where you are discussing with the science, with well-established researchers. What were your greatest concerns when thinking about this, when you were engaged with this? And how did you overcome those concerns?

Patty Horan: I think in the beginning it was really, it’s a totally different language. It’s like walking to a foreign country, going into like, what are they saying?

So the good thing about the ERP is, you do get some time. Each person is given five projects to evaluate, and you get a couple of weeks, look over all of these. You do have to present them and speak the language, but you have a co-presenter. So if you mess up or if you didn’t get it quite right, you have somebody else to swoop in and fix it up a little bit. But the whole panel discusses everything later too, so you’re not alone.

And I think a little of it was just ignorance, because with the first panel I sat on, I was very overwhelmed. On the first break, I went outside, and I was like, “What am I here for?” But people were so gracious, they were so nice. They were so thrilled that I was there. They felt like they thought that my opinions were valuable, which was amazing, because these are some of the smartest people in the country. So it was very scary at first. And I fumbled through presenting probably the poor researchers that got me. But I did it. And every year it gets easier, and I understand the brain a little bit more. And I’ve made some great, I’ve met some great people with CURE, and just the people on the panel are just the best people. And Melissa, and it’s been overall, a great experience.

Jack Somers: I mean, similarly to Patty, I came into it with, I would say, I was a little naive, but very excited to join this group. I didn’t know a whole lot about it, but I was okay with that. I just wanted to serve and give back, and if they were willing to let me join, that was enough. I was just so excited that they were willing to let me join.

It was really the first advisors call that, like Patty, I was just blown away by they’re going through their different milestones and what have you, and the verbiage, all of the scientific research that they had done. And I just didn’t know the level of expertise that these folks had, and I didn’t understand a lot of it, but conceptually I could get it. And so, in order to overcome it, I kind of just used that old, the acronym, keep it simple, stupid.

But I just had KISS, and I just said that the best way that I can overcome this is to just keep it simple. And when I did that, I just listened and I kept it simple, and all of a sudden, I understood what they were talking about. And it was incredible, because I learned that all of these folks, who just like Patty said, some of the most brilliant neuroscientists, and epileptologists, and folks in the world, amazing. At Cambridge, at Texas Tech, at UCA, research groups, they are trying to solve the problem that I have. And they could do whatever they’d like, but there they are, and they’re passionate about it, and they’re working on this all the time.

And it actually, it almost brought me to tears. Because I said, “Why are they doing this? Why are they working on this problem?” They could do anything in the world, and they’re trying to solve the problem. They’re trying to answer the questions that I’ve been trying to answer, and keeping it simple. Let me learn. Let me figure out just what they were trying to do. And so, I then didn’t have to worry too much about all the words that they were using. I just got to listen to generally what they were trying to do, and it blew me away. It still does, every single time I listen to them.

What do you feel is the value in sharing your voice? And what do you hope your participation achieves in doing this? So what’s to the value, and what do you hope the outcomes will be?

Jack Somers: I hope that I can use my experience to give back and help one person. I hope that I can serve again. I hope that I refuse to let my experiences be lost in translation, or be just mine. I refuse to let them go to waste.

And so, my hope is that they get leveraged, is that they’re used in ways that we are just learning how to use them, and how they were used five years ago or 10 years ago is actually just the beginning. And that we learn how to use my experiences more and more, and in more efficient, more effective ways as time goes on. That’s my goal.

Patty Horan: Well, a little bit more support for caregivers and the families. So the VA, the Veterans Administration, they need concrete evidence of what’s happening in our households. They don’t necessarily understand the toll of epilepsy in a household, on a life, especially uncontrolled epilepsy. So I feel like I contributed, at least to start looking at quality of life studies.

We have some of those in our portfolio, and I feel like I push for that. And I’m hoping that the data from those studies will be concrete evidence for the VA to actually compensate these families better, that have epilepsy. They will give them better services, better access to care, and also, home health benefits. Because some of them, and we were at this point in the beginning where I couldn’t leave Pat alone for five minutes; but we didn’t qualify for any of those services, because he’s not injured enough, or the epilepsy didn’t qualify him. So it’s interesting. So I’m hoping that out of with my voice, the value will become, will be that veterans are better supported with epilepsy by the Veterans Administration, and there’s a better understanding of the daily life.

Dr. Miller, what are your hopes and visions for the future of lived experience participation, and how we go back to how can people get involved?

Dr. Miller: So I think my greatest hope for the near future is for more researchers and people with lived experience to have the conversations that we were just having. It’s so important to have opportunities for these conversations, to force opportunities for these conversations, because without them, the researchers are doing their best, but they are not the experts in your experiences. And we need you to tell them, and guide them into what is the most important and impactful questions to be researching for policy change, for care change, for overall change. And that’s what I hope really will impact the future.

And the way that people can get involved with the ERP is just going to the CDMRP website. We have a big banner on our website that says, “Get involved.” And if people are interested in reviewing for us, in consulting on projects, let us know. We can help connect you to the necessary people. I’m sure, Laura, that your organization also has opportunities. I think there’s a lot of opportunities, and we just need people, and their generosity of time to volunteer, and we can make a really great impact in this field.

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: 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.