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: 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.

A male doctor in scrubs analyzing brain scans on his computer.

Webinar: Transforming Data into Seizure Control with Learning Healthcare Systems

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

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

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

You can download the full transcript below.

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Dr. Zach Grinspan

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

Audience Q&A with Dr. Grinspan

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The CURE Leaders in Epilepsy Webinar Series has covered many topics related to epilepsy and innovations in research. Check out our full list of available webinars here.

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

Webinar: The ABCs of EEGs: An Evolving Tool for Epilepsy Diagnosis

This webinar explores the intricacies and advancements in a well-known diagnostic tool; an EEG.

An electroencephalogram – better known as an EEG – is a test that records electrical brain patterns from the scalp. EEGs are critical for the diagnosis of epilepsy and other neurological conditions. While this diagnostic tool has been available for nearly a century, there have been great advances in the portability and signal detection properties.

This webinar discusses how epilepsy patients have benefited from advances in EEG technology, and the role of the EEG and other neuroimaging tools in the future of epilepsy diagnosis and seizure localization.

This webinar is presented by Dr. David Burdette, Epilepsy Section Chief for Spectrum Health Medical Group in Grand Rapids, Michigan. He has been at the forefront of EEG education having served on the American Board of EEG Technologists (ABRET) and the LAB-EEG board of the American Board of EEG Technologists (ABRET).  Dr. Burdette’s clinical interests include neurotelemetry, long-term EEG trending, treatment of refractory epilepsy, treatment of status epilepticus, and electroencephalography.

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Dr. David BurdetteAudience Q&A with Dr. Burdette

How often should a patient get an EEG if a past EEG was abnormal? At what point do you elect to have a 24 hour versus a 60 minute sleep-deprived EEG?

That is an interesting question, for which there’s not necessarily a right answer or a wrong answer. First, a question: why do people get EEGs? If someone has what I would consider a prototypical seizure…. The old expression goes, “If it walks like a duck and quacks like a duck, it’s probably a duck.” And if someone has seizures that walk and quack like seizures, it’s probably seizures. And if they walk and quack like a focal seizure (what we used to call a partial seizure), then I’m going to treat it as a partial seizure. I may not even need an EEG to do that.

I’ll get an EEG, just a one off type EEG, to make sure I’m not just totally out to lunch. But that EEG may end up being normal, even though that person is probably still have seizures. So, if a patient responds to the first medication I prescribe, as arguably 47% of people do, then that’s great. There is no compelling reason in my mind to repeat that EEG. If that person doesn’t respond to the first medication, I’ll usually have a plan B, so we’ll try the plan B. If that doesn’t work, I need more information.

I need to get some insight into how a person who hasn’t responded to the second medication is doing, so I may get a sleep deprived EEG or a two hour long EEG, so that way I can see those brain waves when they’re awake, drowsy, and asleep. Often times we need that sleep in order to really see the rhythmicity of the brain and for me to figure out, “Ah I was wrong. It was walking and quacking like a partial seizure, but in fact it was a generalized seizure and I chose the wrong medication.” Ideally that doesn’t happen, but it could. So, in that instance, I would get a sleep deprived EEG or I might get an ambulatory EEG so that over 24-48 hours, I can see that waking, drowsy sleep rhythmicity and see what’s going on.

If the individual still has seizures or the EEGs are unhelpful, then I will have the person come into the epilepsy monitoring unit. The place in the hospital where the healthiest people are, and we bring them in, it’s the one time in your life we want you to have a seizure, so we crash the person off their medications, sleep deprive them every other night, and ideally record a seizure.

That being said, in children there are many genetic forms of epilepsy which may appear in childhood and be outgrown later in life. In this case, serial EEGs are necessary to identify that progression.

Regarding the rhythms you showed at the end of the presentation, are those patterns in patients with epilepsy only or do healthy patients have similar multi-day rhythms?

There will be an element of speculation to my answer because we don’t know. But I don’t think it’s too much of a leap of faith to say that multi-day variation, the diurnal variation we tend to see in seizures,  is being driven by a rhythm that is intrinsic to the brain itself. So in essence, the likelihood is that, seizures or no seizures, epilepsy or no epilepsy, we all have those rhythms. How they manifest though is difficult to say unless you have seizures.

Can you explain the subclinical seizures and EEG signatures called PLEDs, burst, and birds? This is a very detailed question about these different signatures.

Seizures are typically divided into “generalized seizures,” in which one second the brain is fine and then the next second both hemispheres are seizing, and “focal seizures,” in which seizures begin in a specific area of the brain. You’ve probably heard this notion that we only use ten percent of our brain. If we could use 90% we could do telekinesis, we could do whatever. Who knows, maybe people could develop telekinesis, I wouldn’t know. But I do know that we use our entire brains. A PET scan will light up the glucose metabolism the brain cells that are working, and we know that the whole brain lights up.

We’re using all of our brain, but we can only define what 10% of the brain does. When I do brain mapping on someone in anticipation of epilepsy surgery, in 90% of the parts of the brain I map, I can’t identify anything that happens when I stimulate it. Further, the person with epilepsy cannot identify that I’ve done anything. So, 10% of the brain is what we call “eloquent.”

If you have a seizure in eloquent cortex, it’s going to cause a symptom. If you have a seizure in a part of the brain that activates if you heard an oncoming train, then your seizure will cause an auditory hallucination of an oncoming train. But for other 90% of the brain, if the seizure starts there and stays focally there, then there’s a reasonable chance you’re going to have no symptoms. We would call that a “subclinical seizure.” In this case, we can see it on the EEG, particularly if we’re recording from directly within the brain itself. A seizure is happening, but it is subclinical – it’s causing no symptoms.

With PLEDs or LPEDs – we change the name sometimes but it’s the same phenomenon – this is a sign of an excited brain. If either some badness happens to the brain, a stroke for instance, then the area around the stroke will have excessive excitability. Or, if someone has known epilepsy and they go into status epilepticus – one seizure after another after another – the excitability of the brain really goes up in that area. The end result of this happening is that the brain keeps pushing toward a seizure, causing a burst of activity that shuts down that part of the brain for a second as it recovers, and then it happens again, boom, and then it shuts it down, and then boom…. Seizures during status epilepticus are periodic, like a metronome: fires, fires, fires, fires, it’s lateralized, it’s over one half of the brain, epileptic form discharges. So these are boom, boom, boom. This state is highly epileptogenic, but it is transient. So once you correct whatever is the underlying issue, it should resolve.

Bursts are a more descriptive term. In that case the brain is going about its business, then there’s a burst of activity, kind of like we saw earlier in my presentation where it’s burst, suppression, burst, suppression. So that is a descriptive term applied to any sudden outpouring of electrical activity within the brain. We will see bursts in a broad array of clinical situations from burst suppression to various epileptic or epilepsy related phenomena, and they are in essence this large outpouring of synchronous brain activity.

And then the final term, birds, has been applied in a few ways, but these are these brief, rhythmic discharges that are not quite seizures, but show a strong tendency towards seizures. This is a term most commonly used in neonatal EEGs. In adults, I see the brain waves going along, I see a burst of activity, looks like a spike, we call it a spike.

In the neonatal brain, development is happening really fast. Newborns get these spikes all the time and they can be normal. To differentiate abnormal bursts of activity, we use various terms to describe he specific kinds of spikes. If you see those spikes but they’re rhythmic and they last a certain period of time, then that is more worrisome for seizures. So that is most commonly how birds are used.

How sensitive are ambulatory EEGs? Is there a difference in the ability to pick up seizures between ambulatory versus in patient monitoring?

Ambulatory is more sensitive than a routine EEG. A routine EEG lasts 20 to 30 minutes. What are the odds that we’re going to pick up some abnormality in 20 to 30 minutes? It depends how active someone’s seizures are. If they’re having a seizure every five minutes, we’ll probably pick it up in a 30 minute EEG. Most people, however, are not having seizures as often as that. Most people have more widely dispersed seizures and therefore, by extension, more widely dispersed abnormal bursts of activity associated with seizures.

The longer we can record an EEG, the greater our likelihood of coming up with an answer to better inform our treatment options. A 20 to 30 minute EEG gives us some information. A 24 hour EEG gives us much more information, because we see those brainwaves in wakefulness, drowsiness, stages one, two, three, four, and REM sleep. The next step is being admitted to the epilepsy monitoring unit. If you go into an epilepsy monitoring unit and there are no medication changes made, you might as well have it done at home, because you’re less restricted at home.

But typically what we do in the epilepsy monitoring unit is evaluate situations when the ambulatory EEG didn’t give us the answers we needed. The in-patient epilepsy monitoring unit EEG allows us to take you off of medications, not necessarily to induce a seizure, but to remove your protection from seizures, so that we can record an actual seizure. That would be dangerous to do in many situations at home because there are risks of having multiple seizures. You could go into status epilepticus, you could (god forbid) have Sudden Unexpected Death from Epilepsy – it’s a scary situation. But in the hospital, it’s a monitored situation. An EEG tech is watching the screen 24-7 and when a seizure happens, they push a button, nurses come running, and they give medications to abort the seizure.

That’s the main difference – for an ambulatory EEG you’re probably on medication, and in the epilepsy monitoring unit we’re taking away the medication.

How do I know if my doctor knows the latest information about performing an EEG? Are there any questions I can ask?

I would ask if they have done an EEG or epilepsy fellowship. When someone goes into training in neurology, they do their internship right out of medical school. During that time, they get some basic training and learn more about treating patients with various maladies. Then they do a neurology residency, and focus on just brain-, spinal cord-, nerve-, and muscle-related issues. Part of that training is learning some basics of EEG, and learning the basics of taking care of a broad range of issues from Parkinson’s disease to tremors, to peripheral neuropathy to epilepsy.

Typically after someone develops seizures they will start with seeing a neurologist. And frankly, the majority of people do very well with seeing a neurologist. If, however, a person continues to have seizures, then it is time to move it up a notch. And that next notch takes the form of neurologists who did extra training for one or two years in either clinical neurophysiology, EEG, or in epilepsy (which also includes an EEG component). That by itself means that person is going to have a greater level of comfort and more in-depth knowledge of seizures and epilepsy.

In addition, you can check if your provider is board certified. Board certification will establish that a person has a minimal amount of knowledge. It doesn’t say that they’re the greatest thing since skim milk, but it assures to some degree a minimum level of competence. I tend to check if my doctor is board certified in the area in which I am seeking their opinion. That being said, some of the best epileptologists I know have never taken a board exam. Because you don’t have to take a board exam to practice in epilepsy.

If your seizures are well controlled, and by well controlled I mean you are seizure free, then your general neurologist is more than adequately capable of taking care of you. If you are still having seizures – once a month, a week, a day, a year – and adjustments are not effective, then it is time to seek the opinion of a specialist, who has done that extra training.

If that doesn’t work out, you kick it up a notch and you see someone who is in an NAEC level four epilepsy center. So that’s the National Association of Epilepsy Centers. They have a certification process whereby they evaluate who the epileptologists are, the neuropsychologists, the nurse practitioners, the entire epilepsy team, and determine if they have all of the credentials that indicate them to be highly competent in their field. If they do, those individuals will get a level three or level four (the highest level) designation. And if you’re having ongoing seizures and have tried multiple approaches, then ultimately you want to end up at an NAEC level four center.

The CURE Leaders in Epilepsy Webinar Series has covered many topics related to epilepsy and innovations in research. Check out our full list of available webinars here.

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

A Diagnostic Odyssey: Early Genetic Testing in Epilepsy

Plus, discover the latest in genetic testing advances in this episode of our Seizing Life podcast.

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Audience Q&A with Dr. Porter and Ms. Nye

We had one question that asked, ‘I am 66 and I’ve had epilepsy since I was 13. Is genetic testing important at my age? I have children age 31 and 28 who do not have epilepsy.’

Yeah. I think there’s a lot of detail that would have, to be fair, to have to determine if genetic testing would be helpful in this situation. I guess I don’t really feel confident in coming out strongly one way or the other, but I will say that genetic epilepsies are complicated. Mrs. Nye had the situation where her husband and her both have mutations in this particular gene and they’re completely healthy, and it was only when they came together that they had a child who had mutations in both copies of the gene. There’s other situations where a single mutation is new de novo in the child, and that won’t be passed on necessarily to the next child from the parents. I don’t feel very comfortable in saying that, but it’s something you can certainly talk to your epileptologist about.

What does Dr. Porter see as the major barriers to genetic testing in epilepsy?

Sometimes cost is as an issue. We have sometimes difficulty getting insurance to cover it or to cover all the testing costs, but many of the companies, including Invitae, but other ones as well are making the testing quite reasonable, meaning that there are programs for patients that are on Medicaid to help them fund the testing. Some of the companies have like a cutoff where you can’t be required to pay more than a certain amount for testing. That’s number one. I would say number two is sometimes interpreting the results. There, I’m very lucky cause I have a lot of genetics colleagues. I have a genetic counselor for just this situation, but we do come down to sometimes being not absolutely sure that the differences in the genetic testing are really causal.

I don’t think that that should deter you from testing because I think, as time goes on, it’ll become more clear whether differences are in fact causal, but costs and interpretation, I think, are still two issues that we face. The final thing though, is that there are patients that I know, I absolutely, in my heart, know have genetic epilepsy and we still cannot find a mutation. That’s why the EGI program is in existence, because if your exome sequencing, meaning the parts of the gene that make proteins don’t have a finding in them, the data can be uploaded to EGI, and it will continually be investigated.

I think in the future, some changes in certain genes that we don’t know right now cause epilepsy will be identified as causing epilepsy. So, it’s important to not think of this as a static question. Your gene testing is negative. Well, it’s negative at this moment. It doesn’t mean it’s going to be negative in a year or two.

Are there any consensus statements or practice guidelines that can be used to help support the need for early genetic testing in epilepsy when working with insurance or institutional send out labs?

Yes. I don’t know who sent that, but if you want to send me an email, I can send you a generic version of a letter that we use. I think the Lennox-Gastaut Syndrome also has some generic wording on some letters. I will not say that they’re always successful, but I think it’s a worthy cause, so it’s worth trying to do that. Feel free to just send me an email and I’ll give you our generic a letter. But again, some of the companies now have very low copays, or even an amount that you don’t have to pay over if the insurance refuses to pay for it. I think there’s ways to work around the insurance companies, to some extent, but I do have some generic letters I could send you.

If I don’t have many genetic colleagues at my institution, can I ask for guidance and testing and interpretation from the genetic testing lab?

Yes. They all have genetic counselors, at least when you say that. I’m almost positive they all have genetic counselors, at least in my experience they do. They can walk you through some of the interpretations. If that’s not fruitful, I think referring to some of the epilepsy genetics clinics that have been kind of springing up around the country, or to somebody that has more expertise in epilepsy genetics would be another reasonable option, even if it’s not at your institution. Sometimes families are willing to travel for something so important.

Do you recommend biochemical testing for metabolic disorders prior to genetic testing for epilepsy or should these be done simultaneously?

Yeah. We’ve spent a lot of time working up a protocol that we’re instituting here on how to work up a child, in this case, with suspected genetic epilepsy, including metabolic epilepsies. We have decided to kind of take a multi-pronged approach. So, we do metabolic testing, often simultaneous with the genetic testing. I would say there are certain circumstances where we might vary that slightly. It also depends a little bit on the patient’s situation. So, if it’s a very severe catastrophic epilepsy and they have features that make us highly suspect metabolic diseases, then we would definitely push for that more strongly. If the epilepsy seems to not be as severe or we think, it’s much more likely, it falls into a certain genetic syndrome, then we might skip the metabolic testing. But right now, our pathway is to do them simultaneously.

How do you broach the topic of genetic testing with a patient given that their diagnostic odyssey might already be expensive?

At our institution, MRIs are extremely expensive, especially if there’s a need for sedation. I think we just need to get our head around the fact that we don’t blink too much at the expense for that MRI, and our genetic testing is about a 10th of that. So, I agree medicine’s very expensive, but the yield from genetic testing is quite a bit higher frequently than an MRI, and I don’t really worry about the $10,000, $20,000 MRI. So, doing an exome sequencing seems like a bargain to me.

How early is too early for genetic testing in epilepsy?

If they were going to go forth and multiply again, I would guess maybe they would do testing in utero, now that they know what they’re looking for. If you don’t have a clear cut epilepsy gene that you’re looking for in a pregnancy, I don’t know that I would test the baby. That’s probably not reasonable in utero. We send genetic testing on neonates a couple of days old if we think they have a neonatal epilepsy.

Do you think it makes more sense to start with an epilepsy panel or whole exome sequencing?

So we still use epilepsy panels before we do exome. I don’t know when the tipping point is going to come when we stop doing epilepsy panels and we flip over to just doing exome, or then, now some of my patients get a whole genome if the exome has been negative. I guess for right now, anyway, I usually start with a panel because the yield is pretty high in many of my patients. But some of them that are negative, we do go on to do exome, or as I said, rarely now we’re doing whole genome.

How did you know which steps to take, to establish your foundation and work towards discovering treatment for your children’s condition?

I was really lucky to have friends that I had met along the way who also were dealing with rare diseases or had started foundations of their own. I was actually hesitant to do it. We tried triheptanoin first. We thought there was a treatment out there, and so we’ve tried the treatment before we started the foundation. It was only when it became clear that the gut instincts of treatments weren’t working that we decided to take a step back and formalize and organize everything. We continue to be close partners with other organizations. There’s a lot work to do. We certainly still work with CURE Epilepsy and other organizations that are also fighting the epilepsy battle. But I think it does just depend if you have enough patients and if there seems to be enough information to gather and enough work to do.

This is Brenda. I would just say that, of my families that I give them a diagnosis, I tell them to go out there and look. There’s almost always a Facebook page or some other group that they can meet with and start to talk about what their children have or how they’ve dealt with certain situations. So, getting together with other families that are sharing all the things that you’re going through is really important. Mrs. Nye is amazing, because she has taken it an extra step and raised money to really work on epilepsy that her children have, but even just getting together with other families is so helpful. It’s helpful to me sometimes in taking care of the kids, because the parents will say, “Oh, we talked to this family in Brazil and they tried this and it seemed to help their child. Can we talk about that?” That’s something I might not have known had they not been in contact with another family?

How do you know which epilepsy center is the best, and how do you find the best neurologist for your child near your home? How did you come to seek out epileptologists around the world?

I guess we tried to find the neurologist that had maybe seen something similar to what we thought we were dealing with. It might not be the same doctor or the same place for every family, but I tried to get an idea of what neurologists or epileptologists or geneticists might have seen something like this before.

I think seeing large numbers of patients with epilepsy and genetic epilepsies is very helpful. You start to see patterns. I can almost always pick up a kid now. Well, I shouldn’t say this, but usually I can pick up a kid with a glucose transporter, because I’ve seen enough of them over the years, fairly successfully. I think it’s a little bit just seen a lot of kids with genetic epilepsies that allows you to see patterns. People who specialize in epilepsy as opposed to some general neurologist who see some epilepsy, but maybe specialize in headache, they may not be the right person to take care of a child with really complicated epilepsy.

We would see a great doctor, that doctor would maybe have three or four ideas. We would try those three or four ideas, and then maybe it was time to seek out another opinion to see if anybody else had the next three or four ideas. As a parent, you don’t really have the option of giving up, so you just keep going and keep talking and trying to find a doctor who has an idea that hopefully moves the child’s health in the right direction.

I think also the idea that in some places there may not be a lot of specialists, but if your physician is willing to work with somebody else that’s more at a distance, that that’s always very reassuring. I certainly have people that I think of as colleagues around California, for example, or Hawaii I talk to about patients. They’ll send me some information and I’ll try to assist them as best I can. Even if your local physician may not be the world’s expert in X disease, they can certainly reach out to someone who is, and it is a collaborative environment for the most part.

How do you find support from other families if you don’t know your child’s genetic diagnosis?

I would say that there are both broad and specific diagnoses. While we went on a 10 year odyssey to find the genetic marker for the type of epilepsy that the two of my kids have, we had other diagnoses along the way. Epilepsy, in and of itself, is something of a diagnosis. So, there are certainly support groups for other families dealing with epilepsy. We seem to collect different labels. As the years went on, things like CP or ataxia or apraxia, or just developmental delay. There are support groups for all of those more clinical descriptions of what’s going on. I think families do find some comfort in those groups as well.

There are, that I know of, support groups for infantile spasms, Lennox-Gastaut Syndrome. These are all seizure types, or seizure syndromes, and all of those organizations have networks. The Lennox-Gastaut Syndrome foundation is having a meeting in Orlando next month that I’m going to. If you find the type of seizure your child has, often they’ll be a group. Then locally, the epilepsy foundation of America has local chapters all over. For instance, the one in Northern California has a very … well, I think most of them around the country have the very nice camp for kids that gives them a sense of inclusion. They have a parent support groups they help with as well.

If there’s a family history of a genetic epilepsy and another child is born with the same genetic condition, would you start antiepileptic medication before seizures begin, or do you need to wait for symptoms to become apparent?

We do not have epilepsy prevention therapies. I work on a trial right now trying to look at that in tuberous sclerosis, whether we can actually prevent the development of epilepsy and autism in children with tuberous sclerosis, treating them before they develop seizures. But for the most part, right now, we don’t have therapies focused on the prevention of epilepsy. I personally, if I know that a child is at high risk for epilepsy, I often use EEG to try to make sure I’m not missing any seizures that are subtle, or just present on the EEG, but that is a conversation you would need to have with your physician to determine whether your child would benefit from frequent EEGs.

This is also important to note that some genetic predisposition to epilepsy does not absolutely say that child will have epilepsy. There are certain mutations that it’s highly likely they will have epilepsy, and there are certain mutations where some small percentage of patients have epilepsy and others don’t. So, it really depends on the specific situation.

Do you think that technologies such as antisense oligonucleotide therapies and gene therapy using the new vectors provide hope for various types of genetic epilepsies, or will these type of advances take many more years?

They definitely provide hope. I think that the timing of when these kind of therapies will be available is much more challenging. The neuromuscular field is obviously ahead of us as far as getting across the finish line with antisense or vector-based approaches for gene therapy. I don’t think epilepsy is that far behind, but it is a little bit more complicated in some situations about how to get the protein and all the cells in the brain, how to get it early enough. There are a lot of challenges, I think it’s coming and it probably isn’t fast enough for anybody that’s on the phone with a child with epilepsy, but I don’t know when, but just take heart that it’s coming. I just don’t know when.

What would you say to a mom who’s just beginning the diagnostic odyssey for their child with epilepsy?

I would say that there’s going to be some good days and an awful lot of bad days where you want to just give up, but I just take a step back, take a deep breath, and then when I’m ready to go at it again, you just keep trying. I think that you can’t just make the diagnostic odyssey the whole goal. A diagnosis helps certain parts, but it doesn’t actually change your child. Your child is the same child the day before you receive a diagnosis, as he or she is the day after. Even though continuing this research and finding a diagnosis are really important to me, and I think they are to a lot of parents and families, the majority of my time is still spent doing physical therapies and occupational therapies and figuring out IEPs at schools, and just trying to make sure my kids have hobbies that give them something to look forward to.

I think the diagnostic odyssey or a diagnosis in general is like a piece of the puzzle, but it’s not the whole puzzle. So, try not to just completely go down that rabbit hole, and try to have fun with your kid because you don’t get these days back.

What is the yield for a multi-gene panel and for exome sequencing for a patient with epilepsy? What would the yields be if the patient has additional features?

I’ve seen papers trying to address this question, and I think it’s extremely challenging because it all comes down to the denominator like what kind of patients you include in that group. I’ve seen 30% for a panel. Again, though, it really depends on the denominator. When did the patient develop epilepsy? What kind of epilepsy do they have? Do they have some other syndrome features? Syndromic features, meaning their ears are set differently, their eyes are set differently, their MRI has an abnormality on it that’s frequently associated with a certain genetic disease. I don’t know the specific answer, but I think it’s not 1%, and it’s probably not 100% percent. It’s probably somewhere less than 50%, but in the 10s to 20s to 30%, so good we’re doing, I think.

I just wanted to say that I liked Mrs. Nye’s description of ending on this that, understanding your child’s epilepsy is so important, but having fun with your child and doing things that you and your child both can enjoy is so important. The families that I see in clinic that really take that to heart and do things with their kids that their kids can enjoy, and that they can enjoy watching their kids enjoy is so important. Maybe your child’s not going to be able to play regular soccer. I had a patient last week that is playing in the special Olympics soccer team, and he absolutely loves it. He’s so happy with it, and his parents were really enjoying it too. That is so important, to taking care of a child with special needs, is finding out what they like to do and helping them do that. It just is a nice way to end, I think.

Doctor sits with little boy in the hospital bed, showing him information on a tablet.

Panels & Exomes: Diagnostic Yield & Detection of Childhood Epilepsy


Plus, discover the latest in genetic testing advances in this episode of our Seizing Life podcast.

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Audience Q&A with Dr. Swaroop and Dr. Sullivan 

Would you wait until the patient has had at least two seizures before considering genetic testing? Or would you consider genetic testing after a single seizure?

I think you really do need to wait for that second seizure, specifically in Dravet syndrome, we’re really trying to arrive at a very early diagnosis and we’ve actually looked to see if genetic testing should be sent after a young child under the age of one has had their first episode of prolonged convulsive status. That may be an isolated situation where I think a single seizure could be argued, but other than that, I think you really need to wait for that second seizure.

The table showed a relatively high yield of TPP1, can you speak to this?

Yeah, absolutely. And this was surprising to us as well and a couple of them were actually… It turned out a couple of them were actually because of signatures that are associated with TPP1 related Neuronal Ceroid Lipofuscinosis. So there was a prior probability that we would discover it. But in several of those other ones, we actually didn’t expect those. And so it may be that as rare as this disorder is, and perhaps it is under diagnosed. And some of you may know that there’s a program that BioMarin has that is looking at these individuals with mutations in TPP1 and seeing who may be eligible for a drug therapy. And I think it appears that this disorder may not be as rare as we’ve thought before. But really, I mean, even in the quarter of 2000 children we’re seeing a number but I would really be interested in seeing a much larger cohort and seeing if this number really holds true.

How difficult has it been for you to get genetic testing approved for your patients with epilepsy?

It really does depend on the type of insurance coverage. But it also depends on the attitude of the person on the other end of the line when you’re calling in to get the prior authorization. I would say that in my practice, because we still serve about 50% of our patient population is state-insured or under-insured, Medicaid Medical, that it is still very challenging, but I know that there are a lot of companies that are working with us to try and come up with an arrangement so that those patients who could benefit the most can get testing but that’s a process in evolution right now.

Is it best to order a panel that includes deletion duplication studies performed simultaneously with the sequencing? Or does it make more sense to see what the findings of the sequencing are and then only order deletion duplication for the genes indicated based on the sequencing results?

Yeah. I think that’s a good question for a couple of reasons. One, I think it’s fair to say that we really didn’t appreciate how prevalent these exonic copy number variants are in disease genes, aside from maybe a handful like Duchenne muscular dystrophy, or some of the other ones. But where we’re really seeing this evolve to is being able to detect a much broader spectrum of variants, including single nucleotide variants, indels, exonic, copy number variants, etc, all within a single test.

And so it should be, we should all be moving towards being able to get all those pieces of information together from a single test. And we’re finding through internal analysis of our data, that the prevalence and frequency of these exonic copy number variants is actually pretty high that it accounts for almost 10% of all the pathogenic variants that we’ve ever reported from Invitae. So it’s clearly a high proportion of clinically important findings. So my opinion, is that these tests should be looking at exonic copy number variants at the same time as sequence variants so we have the most optimal clinical sensitivity of testing.

When would you recommend testing an adult patient and is that something that you need to consider with a higher concern if they have relapsed? And what would your recommendations be for them?

I’m glad that this is being asked. I think that because I commented that a lot of the early onset epilepsies have a very high diagnostic yield, if an adult being seen in an adult epilepsy practice, had an infantile onset epilepsy, and there still is not a known cause, I would say that those group of patients actually represent a very rich group where the yield could be exceedingly high. Especially if the clinician has the time to go back and take that early childhood history, I’m convinced that there are hundreds of patients sitting in an adult epilepsy clinic with SCN1A mutations that had Dravet syndrome but then when they turned into adults they have a little bit more of a nondescript phenotype and our adult epilepsy colleagues may not have that index of suspicion. But I still think that those group of patients just to summarize, are those with infantile or childhood onset who continue to have seizures and have no known cause.