Emergency treatment may be necessary after a person's first seizure or at the onset of abnormal acute repetitive (cluster) seizures; it is required for status epilepticus. Treatment for these emergencies is dictated by myriad clinical factors and informed by published guidance as well as emerging research.   In this episode, Lyell K. Jones, MD, FAAN, speaks with David G. Vossler, MD, FAAN, FACNS, FAES, author of the article “First Seizures, Acute Repetitive Seizures, and Status Epilepticus,” in the Continuum® February 2025 Epilepsy issue. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Vossler a clinical professor of neurology at the University of Washington School of Medicine in Seattle, Washington. Additional Resources Read the article: First Seizures, Acute Repetitive Seizures, and Status Epilepticus Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ  Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr Dave Vossler, who has recently authored an article on emergent seizure management, taking care of patients with the first seizure, acute repetitive seizures, and status epilepticus, which is an article in our latest issue of Continuum covering all topics related to epilepsy. Dr Vossler is a neurologist at the University of Washington, where he's a clinical professor of neurology and has an active clinical and research practice in epileptology. Dr Vossler, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Vossler: Thank you very much for the introduction, Lyell. It's a pleasure to speak with you on this podcast, and I hope to go over a lot of important new information in the management of seizure emergencies. As you said, I'm a clinical professor in neurology at University of Washington, been in medicine for many decades now and have published and done research in this area. So, I'm anxious to give you not only my academic experience, but also talk about my own management of patients with status epilepticus over the last four decades. Dr Jones: Yeah, that's fantastic. And I always appreciate hearing from experienced clinicians, and I think our readers and our listeners do appreciate that voice of clinical expertise. And I'll tell you this is a topic, you know, as a neurologist who doesn't see many patients with acute seizure emergencies in my own practice, I think this is a topic that gives many clinicians, including neurologists, some anxiety. Your article, Dr Vossler, is really chock-full of helpful and clinically relevant considerations in the acute management of seizures. So, you now have the full attention of a huge audience of mostly neurologists. What's the one most important practice change that you would like to see in the care of patients with either first or acute prolonged seizures? Dr Vossler: Without a doubt, the most important clinical takeaway with regard to the status epilepticus---and for status epilepticus, many, many clinical trials, research trials have been done over the last couple decades and they all consistently show the same thing, that by and large most patients who have status epilepticus are underdosed and undertreated and treated too slowly in the initial stages of the status epilepticus. And it's important to use full bolus dosages of benzodiazepines to prevent mortality, morbidity, and later disability of these patients. To prevent the respiratory depression, many physicians are afraid to use higher doses of benzodiazepines, even guideline-recommended doses of benzodiazepines for fear of respiratory depression. But it's actually counterintuitive. It turns out that most cases of respiratory depression are due to inadequate doses and due to the status epilepticus itself. We know there's greater mortality, we know there's greater morbidity and we know that there's greater need for higher dose, subsequent, anti-seizure medications, prolonged status, if we don't use the proper doses. So, we'll kind of go over that a little bit, but that is the one clinical takeaway that I really would like our listeners to have. Dr Jones: Let's follow that thread a little bit. Dave, I know obviously we will speak in hypotheticals here. We're not going to talk about actual patients, but I think we've all been in the clinical situation where you have a patient who comes into the emergency room usually who's actively seizing, unknown history, don't know much about the patient, don't know much about the circumstances of the onset of the seizure. But we now have a patient with prolonged convulsive seizures. How do we walk through that? What are the first steps in the management of that patient? Dr Vossler: Yeah, well, I'll try to be brief for the purposes of the podcast. We do, of course, go through all of that in detail in the Continuum article, which hopefully everybody will look at very carefully. Really in the first table, the very first table of the article, I go through the recommended guideline for the American Epilepsy Society on the management of what we call established status epilepticus. The scenario you're talking about is just exactly that: established status epilepticus. It's not sort of evolving or developing status. We're okay they're having a few seizures and we're kind of getting there. No, this patient is now having evidence of convulsive seizure activity and it's continuing or it's repeated seizures without recovery. And so, the first phase is definitely a benzodiazepine and then the second phase is then a longer-acting bolus of a drug like phosphenotoine, valproic acid or levetiracetam. I could get into the details about dosing of the benzodiazepines, but maybe I'll let you guide me on whether we wanted to get into that kind of detail right at the outset. It's going to be a little bit different. For children, its weight-based dosing, but for adults, whether you use lorazepam or you use diazepam or you use midazolam, the doses are a little bit different. But they are standardized, and gets back to this point that I made earlier, we're acting too slow. We're not getting these patients quick enough, for various reasons, and the doses that are most commonly used are below what the guidelines call for. Dr Jones: That's great to know, and I think it's fine for the details to refer our listeners to the article because there are great details in there about a step-by-step approach to the established status epilepticus. The nomenclature and the definitions have evolved, haven't they, Dr Vossler, over time? Refractory status epilepticus, new-onset refractory status epilepticus, super refractory status epilepticus. Tell us about those entities, how they're distinguished and how you approach those. Dr Vossler: That's an important thing to kind of go over. They- in 2015, the International League Against Epilepsy, ILAE, which is, again, our international organization that guides our understanding of all kinds of things epileptic in nature around the world. In 2015 they put out a definition of status epilepticus, but it used to be that patients had thirty minutes of continuous seizure activity or repetitive obvious motor seizures with impairment of awareness and they don't recover impairment between these seizures. And that goes on for thirty minutes. That was the old definition of status epilepticus. Now, the operational definition is five minutes. And I think that's key to understand that, after five minutes of this kind of overt seizure activity, you need to intervene. And that's what's called T1 in the 2015 guideline, the international guideline. There are a bunch of different axes in the classification of status that talk about semiology, etiology, EEG patterns, and what age group you're talking about. We won't really get into those in the Continuum article because that's really more detailed than a clinician really should be. Needing to think about the stages, what we call the stages of status epilepticus that you mentioned and I alluded to earlier are important. And that is sort of new nomenclature, and I think probably general neurologists and most emergency room physicians aren't familiar with those. So, it just briefly goes through those. Developing status epilepticus is where you're starting- the patient’s starting to have more frequent seizures, and it's heading essentially in the wrong direction, if you will. Established status epilepticus, as I mentioned, is, you know, this seizure act, convulsive or major, major outward overt seizure activity lasting five minutes or more, at which time therapy needs to begin. Again, getting back to my point, what doesn't happen often enough is we're not- we're intervening too late. Third is refractory status epilepticus, which refers to status epilepticus which continues despite adequate doses of an initial benzodiazepine given parenterally followed by a full loading dose of a single non-sedating anti-seizure medicine, which today includes phosphenotoine IV valproic acid or IV levetiracetam. In the United States, and increasingly around the world, people really are using levetiracetam. First, it has some advantages. There's now proof from a class one NIH-funded trial. We know that these three drugs are equivalent at the full doses that I go over in the article. You have your kind of dealer's choice on those. Phenobarbital, which we used to use and I used as a resident as long as forty years ago, is really a second choice drug because of its sedating and other side effects. But around the world in resource-poor countries phenobarbital can be used and, in a pinch, certainly is an appropriate drug. And then finally, you mentioned super refractory status epilepticus and that's status that's persisting for more than twenty four hours. Now, despite initial benzo and non-sedating anti-seizure medicine, but also lasting more than twenty four hours while receiving an intravenous infusional sedating, anesthetizing anti-seizure medicine like ketamine, propofol, pentobarbital or midazolam drips. Dr Jones: So, it sounds like the definitions have evolved in a way that improves the outcomes, right? To do earlier identification of status epilepticus and more aggressive management, I think that's a great takeaway. If we move all the way to the other end of the spectrum, let's move to the ambulatory setting and we have a patient who comes in and they've had one seizure, they're an adult; one seizure, the first seizure. The key question is, how do we anticipate the risk of future seizures? But walk us through how you talk to that patient, how you evaluate that patient to decide if and when to start anti-seizure medicines. Dr Vossler: Well, it depends a little bit if it's an adult or a child, but the decision making process and the data behind it is pretty robust now. And the decision making process is pretty similar for adults and children, with some differences which I can talk about. First of all, first seizures. I think it's really important to stress that there's been so much research in this area. I'd like to get a cross point that they're not as innocuous as I think many general neurologists might suspect. We know that there is a two- to threefold increased risk of death in children and adults following a first seizure. Moreover, the risk of a second seizure, both in kids and adults, is about 36% two years after that first seizure. It's about 46% five years after that first seizure. It's really pretty substantial. The risk of a second seizure is increased twofold. It doubled in the presence of any kind of a history of prior brain insults that could result in seizures. Could be infections, it could be a prior stroke, it could be prior significant brain trauma. It's also doubled in the presence of an EEG, which shows epileptiform discharges like spikes and sharp waves---and not just a sort of borderline things like sharply contoured rhythmic Theta activity. That's really not what we're talking about. We're talking about overt epileptiform discharges. It's doubled in the presence of lesion that can be seen on imaging studies, and it's doubled in the presence of seizures if that first seizure occurs during sleep. So, we have a number of things that double the risks, above the risk of a second seizure, above that 36% at two years and 46% at five years that I spoke about. And so those things need to be considered when you're counseling a patient about that. Should you be on an anti-seizure medicine after that first seizure? Specifically, to the point of anti-seizure medications, the guideline that was done, the 2015 guideline that was done by the American Academy of Neurology for adults, and the 2003 guideline was actually a practice parameter that was done by the Academy and the American Epilepsy Society for children, are really kind of out of date. They talk about the adverse effects of anti-seizure medications, but when you look back at the studies that were included in developing that practice parameter for kids and guidelines for adults, they are the old drugs: carbamazepine, phenytoin, phenobarbital and valproate. Well, I don't think I need to tell this audience, this well-educated audience, that we don't use those drugs anymore. We are using more modern anti-seizure medicines that have been developed since 1995; things like lamotrigine, levetiracetam, and lecosamide. Those three in particular have very low adverse events. So, the guideline that the Academy, American Academy Neurology and American Epilepsy Society put together for kids and for adults talks about this high adverse event profile. And so, you need to take a look at the risks that I talked about of a seizure recurrence and balance that against adverse effects. But I'm here to tell you that the newer anti-seizure medicines---and by newer I'm talking in the last thirty years since lamotrigine was approved in 1995---these drugs have much better side effect profiles. And I think all epileptologists would agree with that. They're not necessarily more effective, but they are better tolerated. That makes the discussion of the risk of a second seizure, the risk of mortality versus side effects of drugs, it really pushes the risk category higher on the first side and not on the side of drugs. We know that if you take an anti-seizure medicine, you reduce your risk of a second seizure by half. Now, that's not sustained over five years, but over the first two years, you've reduced it by half. In a person who's driving, needs to get to work, has to take the kids to school, whatever, most of my patients are like, yeah, okay, sign me up. These drugs are really pretty well tolerated. There's a substantial risk of a second seizure. So, I'll do that. In a kid,  a child that's, you know, not driving yet, that might be a different discussion. And the parents might say, well, I'd rather not have my son exposed, my daughter exposed to this. They're trying to go to school. They're trying to learn. We don't want to hinder that. We'll wait for a second seizure and then if they have a second seizure, which by the way is, you know, one of the definitions of epilepsy, well then they have epilepsy, then they probably will need to go on the seizure medication. Dr Jones: Great summary, Dr Vossler, and it is worth our audience being aware that the evidence has evolved alongside the improvement in the adverse effect profile. And sounds like your threshold is a little lower to treat then maybe it would have been some time ago, right? Dr Vossler: I would say that's exactly correct in my opinion. Particularly for adults, absolutely. Dr Jones: That's fantastic, Dr Vossler. I imagine there are a lot of aspects of caring for these patients that are challenging, and I imagine many scenarios are actually pretty rewarding. What do you find the most rewarding aspect of caring for patients with acute seizure management? Dr Vossler: Yes, I mean, that is really true. I would say that the most challenging things are treating refractory status epilepticus, but worse yet, new onset refractory status epilepticus and the super refractory status epilepticus, which I talk extensively about or write extensively about in the article and provide a lot of guidance on. Really, those conditions are so challenging because they can go on for such a long time. Patients are hospitalized for a long time. A lot of really good clinical guidance doesn't exist yet. There is a tremendous amount of research in that area which I find exciting, and really there's an amazing amount of international research on that, I think most of our audience probably is unaware of. And certainly, with those conditions, there is a high risk of later disability and mortality. We go through all of that in the article. The rewards really come from helping these people. When someone was super refractory status and it were non- sorry, new onset refractory status epilepticus, has been in the hospital for thirty days, it gets really hard for everybody; the family, the patient. And for us, it wears on us. Yet when they walk out the door, and I've had these people come back to the epilepsy clinic and see me later. We're managing their anti-seizure medications. They've survived. The NORSE patients often have substantial disability. They have cognitive and memory and even some psychiatric disability. But yet we can help them. It's not just management in the hospital, but it's getting to know these people, and I take them from the hospital and see them in my clinic and manage them long-term. I get a lot of great satisfaction out of that. We're hoping to do even better, stop patients’ status early and get them to recover with no sequelae. Dr Jones: What a great visual, seeing those patients who have a devastating problem and they come back to clinic and you get the full circle. And what a great place to end. Dr Vossler, thank you so much for joining us, and thank you for such a thorough and fascinating discussion on the importance of understanding and managing patients with the first seizure, acute repetitive seizures, and status epilepticus. Dr Vossler: Thank you very much, Lyell. Dr Jones: Again, we've been speaking with Dr Dave Vossler, author of an article on emergent seizure management, first seizures, acute repetitive seizures and status epilepticus in Continuum's most recent issue on epilepsy. Please check it out, and thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Genetic testing plays a key role in the evaluation of epilepsy patients. With the expanding number of choices for genetic tests and the complexity of interpretation of results, genetic literacy and knowledge of the most common genetic epilepsies are important for high-quality clinical practice. In this episode, Gordon Smith, MD, FAAN speaks Sudha Kilaru Kessler, MD, MSCE, author of the article “Epilepsy Genetics,” in the Continuum February 2025 Epilepsy issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Kessler is an associate professor of neurology and pediatrics at Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia in Philadelphia, Pennsylvania. ADDITIONAL RESOURCES Read the article: Epilepsy Genetics Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the Academy of Neurology: aan.com SOCIAL MEDIA facebook.com/continuumcme @ContinuumAAN  Host: @gordonsmithMD Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Smith: Hello, this is Dr Gordon Smith. Today I've got the great pleasure of interviewing Dr Sudha Kessler about her article on epilepsy genetics, which appears in the February 2025 Continuum issue on epilepsy. Sudha, welcome to the podcast and please introduce yourself to our audience. Dr Kessler: Oh, thank you so much. I'm Sudha Kessler. I am a pediatric epileptologist here at the Children's Hospital of Philadelphia and the University of Pennsylvania. Dr Smith: Tell us a little bit about yourself. Are you a geneticist too, or how did you get into this particular topic? Dr Kessler: Yes, I want to emphatically say that I am not a geneticist. I'm not an expert in epilepsy genetics at all. I take care of all sorts of patients with epilepsy. I actually do mostly epilepsy surgery-related care. But this part of epilepsy is, every year, increasingly important to our everyday practice. And I think it's fascinating, often a little daunting. I think I was asked to get involved with this article as a non-expert to help translate from the experts to the rest of us. Dr Smith: We're going to get there, because one of the things you do a really good job of in the article is talking about genetic concepts that are germane to everything we do. And I think you're an expert. You do it in a way that I understood. So, I'd like to get there, but- and this is a really hot area. For instance, I really loved your figure that shows the arc of discovery of genetic causes for epilepsy. It's really breathtaking, something we wouldn't have thought possible that long ago. And it's also a lot to digest. And so, I wonder if maybe we can begin by thinking about a framework and, for instance, you talk about these different groups of disorders. And one that seems to be particularly impacted by this unbelievable A-rated discovery. Our developmental and epileptic encephalopathies, or DEEs. What can you tell our listeners about that group of disorders? Dr Kessler: Sure. I think that, you know, most of what we think about in epilepsy genetics now has to do with disorders that are attributable to changes in a single gene. Genetics is obviously much more complicated than that, but that's still where we are in the stage of discovery. And the graph in the article is definitely one to take a look at because it represents the explosion that we've had in our understanding of single gene disorders leading to epilepsy and related manifestations. The DEEs are a group of disorders where any individual disorder is fairly rare, but as a group they are not that rare, and very impactful because they often cause epilepsy at a very young age. And either as a consequence of seizures or as a consequence of the underlying pathophysiology of that gene change, they are typically associated with really significant developmental impairments for a child 's entire life. Dr Smith: My understanding is that there's therapeutic development going on in this space. So, the early recognition of these genetic testing offers the promise of very impactful treatment---like we now do for SMA, for instance---early in the disease course. Dr Kessler: I think that's right. That's one of the most exciting parts of this field is that so much, just around the corner, for drug development, therapy development in this area. And as you can imagine, with a lot of these disorders, earlier intervention is likely to be much more impactful than later intervention when a lot of the developmental consequences are sort of… you know, when the cat 's already out of the bag, so to speak. Dr Smith: Yeah. So, this is really transformational and something that everyone who takes care of kids with epilepsy needs to know about, it seems. So on the other extreme, I guess, there are the self-limited epilepsies. I didn't really know about this in terms of genetic discovery, but can you talk about those disorders? Dr Kessler: Yeah, sure. I mean, I think some of these are the classic childhood epilepsy syndromes that we think about like childhood absence epilepsy or what we used to call benign romantic epilepsy and now call self-limited epilepsy of childhood with centrotemporal spikes. It's a mouthful, shortened to SeLECTS. Those are the epilepsies that occur typically in previously healthy children, that affects them for a few years and often remits so that epilepsy is just age-limited and doesn't continue for life. They clearly have genetic influences because they tend to run in families, but the genetics of them is not generally single gene associated. And so, we haven't actually explained why most of those kids actually get epilepsy. I think that'll be sort of another interesting area of discovery that will help us even understand some really fundamental things about epilepsy, like, why does this syndrome start at this age and tend to resolve by adolescence? Dr Smith: And the other thing I found interesting is disorders that I might have thought going into it would have a defined genetic cause or some of the disorders that there are not. So JME, for instance, or childhood absence, which is a little counterintuitive. Dr Kessler: It's completely counterintuitive. We call them genetic generalized epilepsies, and we know that they run in families, but we still know so little. I would say of all of the disorders that are mentioned in this article, that is the group where I think we have explained the genetic underpinnings the least well. Dr Smith: Yeah. Isn't that interesting? It's… wasn't it Yogi Berra who said, it's hard to predict things, particularly the future? So… Dr Kessler: Yes. Dr Smith: Who would have thought? So, we’ve talked a lot about kids. What about adults? You know, what role does genetic testing play in adults who have unexplained epilepsy? Dr Kessler: Yeah, I think that that is also a really important emerging area of knowledge. I think many epileptologists may think of genetic epilepsy as being solely pediatric. There are definitely not how many of these disorders can manifest for the first time in adulthood. Not only that, many of our children with childhood onset epilepsy that is due to a genetic problem grow up to become adults and will then need adult epilepsy care. In order to take care of both of those groups, it's really important for all epileptologists, including those that take care of adults, to have some knowledge of the potential impact of genetic testing. And how do you even approach thinking about it? Dr Smith: The message I guess I'm getting is if our listeners take care of patients with epilepsy, no matter how old those patients are, they need to be familiar with this. And the other message I'm getting is, it sounds like there are a lot of patients who really need genetic testing. And this came through in one aspect of your article that I found really interesting, right? So, what are the recommendations on genetic testing? So, the National Society of Genetic Counselors, as I understand it, said everyone needs genetic testing, right? Which I mean, they're genetic counselors, so. Which is great. In the International League Against Epilepsy, they recommended a more targeted approach. So, what's your recommendation? Should we be testing anyone with unexplained epilepsy, or should we be focusing on particular populations? Dr Kessler: Well, I guess I think about it as a gradation. There are certain populations that really deserve genetic testing, where it is going to be absolutely critical. You know, it's very likely that it will be critical knowledge to their care. If you diagnose somebody with epilepsy and you do imaging and that imaging does not reveal an answer, meaning you don't see a tumor or you don't see an old stroke or some other sort of acquired lesion, the next pillar of testing for understanding underlying etiology is genetic testing. That is the point at which I typically send my patients, and that's whether they're refractory or not. I think in the past some people felt that only patients with refractory epilepsy deserve or require testing. I think the reason why not to limit it to that population is that what's on a person's mind with epilepsy, or a family's mind with epilepsy, is what's going to happen to my child or to me in the future? And if genetic testing can shed some light on that, that will have a huge impact on that person's life. Dr Smith: You've got great cases in your article, which, I just want to give you a compliment. The information and entertainment, frankly, for per page: off the charts. It's not a long article, packed with useful information. And, I mean, some of your cases are great examples of patients who are heading down the surgical epilepsy path and you discovered, nope, there's a genetic cause that really impacted their care. What's the yield, right? The number of patients that you send genetic testing on for epilepsy, what percentage come back positive for a relevant sequence variant that you think is either causing or contributing to their epilepsy? Dr Kessler: That's a great question. I think that is actually still in flux because it depends on the population of patients that are being sent for testing, obviously, and then also on what testing is being done. So, I know in at least one large recent meta-analysis, the overall yield was 17%. And somebody hearing that number might think, oh, that's not very high, but it's actually very comparable to the yield for imaging. And we all do MRIs and patients that have new-onset epilepsy where the yield of MRI testing is about 20%  or so. So, quite comparable. And then with children with DEEs, the yield is much, much higher than that. Dr Smith: So, 17% is actually a really great diagnostic yield. When I think of my yield and doing genetic testing on patients who have an axonal CMT phenotype, right? I mean that's better than what I get. So, good for you. That's exciting. Dr Kessler: It's interesting. I think that maybe an assumption might be that you're working somebody up. You do a genetic test, it reveals a difference, and thus surgery is off the table. It's actually quite different than the head, which is that some results may make surgery be even more “on the table” because you might find a gene that is known to be associated with a propensity to vocal cortical dysplasia, for example. And you may take a good second look at that person's MRI imaging or do other imaging to reveal the MRI invisible vocal cortical dysplasia. Dr Smith: Outstanding point. Let's talk a little more about the genetic testing itself. So, we've got all these genes. We understand when to test. What do you do? For instance, last night I just looked at the company that we use for most of our neuromuscular testing and they have a genetic epilepsy next gen panel with, I don't know, three hundred and twenty genes, right? Do you use that kind of panel? Do you go directly to a whole EXO? What's the right approach? Dr Kessler: Yeah, I think that that is quite dynamic right now, meaning that recommendations seem to change often enough that I rely on help. I have the enormous good luck of working here at CHOP where there is a fantastic epilepsy genetics group that I can easily refer to, and I know not everyone has that resource. The current recommendation is to start with an exome if that is available and is covered by that patient's insurance. When exome is not available, then the next best thing is a gene panel. You know, in recent years there have been a lot of sponsored gene panels, meaning free to the patient, administered by a company that then, you know, has other uses for compiled or grouped genetic data. And I think that as long as all of that can be clearly explained to a patient, and- along with all of the other things so you have to explain to a patient before doing genetic testing, about the pluses and minuses of doing it, I think that you sort of go for the best test you can that's available to that patient. Dr Smith: The sponsored programs can be very, very helpful, particularly from a payer or a patient payment perspective. And so, I guess the lesson there is it's great if you got the resources and CHOP to help you decide, but better to get whatever panel you can get than to do nothing; or, of course, refer to a center if you're not comfortable. Dr Kessler: And also, just know that these things change often enough that if it's been a couple of years and you might want to recheck whether the EXO is available to that patient or whether a gene panel can be sent that includes more than they had eight years ago. Dr Smith: So, are there situations to go to the other extreme where you just do targeted sanger sequencing? Like, just sequence the specific gene of interest?  Dr Kessler: Yeah, absolutely. I'm still a big proponent of thinking clinically about a patient. If there are clues in that patient's history, exam, imaging, anything that gives you some sense of the disorder that this patient might have. And I think a classic example would be tuberous sclerosis. If you see an infant who has new onset spasms, you see hypopigmented macules on their skin and their MRI shows a tuber, you know, also known as a focal cortical dysplasia, then sure, send the targeted sequencing for the TSC1 and TSC2 genes. Dr Smith: And Rett syndrome?  Dr Kessler: And Rett syndrome would be another example. And there are many examples where, if you feel like you have a good sense of what the disorder is, I think it's completely acceptable to send the targeted testing.  Dr Smith: So, I'm going to get further down the rabbit hole and get to from easier to harder. I always get confused about things like chromosomal microarrays or, like, karyotypes and rings and stuff like that. What role do these tests play and what do our listeners need to know about them? Dr Kessler: Yeah, I think that it is really important to have at least some knowledge of what each test can't tell you. I tell my medical students at my residence that all the time. With anything in medicine, you should know what you're asking of a test and what answers a test can tell you and can't tell you. It is baseline knowledge before requesting anything. And if you don't know, then it's best to ask. So, chromosomal microarray is used when you think that there is a large-scale derangement in a bunch of genes, meaning there is a whole section of a chromosome missing---that would be deletion, or that that information is duplicated or is turned around in a, you know, in a translocation. That is what- the kinds of things that that test can tell you. I think of doing a microarray when a child has not just epilepsy and intellectual disability, but also has, for example, other organ systems involved, because sections of chromosome can include many, many, many different genes and it can affect the body in larger ways. That's often when I think about that. So, a child with multiple congenital anomalies. Karyotype, which we think of as the most old-fashioned way of looking at our genes, still has some utility because it is useful for looking at a specific situation where the ends of arm of a chromosome get cut off and get sticky and then stick to each other and make a ring. For example, ring chromosome 20 is a disorder which can cause epilepsy, particularly hard-to-treat frontal lobe epilepsy, and that sometimes doesn't show up until adolescence or even early adulthood. That's just one example of something that karyotype can tell you.  Dr Smith: And it goes without saying, but just to emphasize, these are things that you would miss completely on a next generation panel or a next genome? Dr Kessler: That's correct. Because this isn't about sequencing. This is about large structures. You know, with my patients, it's sometimes, I think, very hard to explain. It's hard enough to explain it to other physicians who aren't in genetics, but it's a whole other undertaking to explain it to families who may not have a lot of literacy about cell biology or genetics or, you know, anything related to that. So, I often rely on analogies. And one analogy I use is that if you're- all of your genetic information is like a book, that book is split into chapters and those are the chromosomes. And you can be missing entire paragraphs or have paragraphs duplicated. And that would be the kind of thing that we would be looking for with the chromosomal microarray with sequencing or, you know, with sequencing, we're looking for spelling of words, and we can look at one word at a time. That would be targeted sequencing. Or we can look at many, many words at a time. And that would be next gen sequencing.  Dr Smith: I just want to say that you are the genetic whisperer. You know, translator. I love it.  Dr Kessler: You can continue using it down to the level of explaining the possibility of a variant of unknown significance, which I think is sometimes difficult to explain. So, I often will say, I know how the word color is spelled: C O L O R. But sometimes in other places it will be spelled C O L O U R and that's still the same word, that's still color. That's just what we would call a population variant. If it is spelled C O M O R, that changes meaning; that is not a word, and that is probably a pathogenic variant. But if it gets misspelled and it’s K O L O R, then I'm not sure. Could that be a variant that means something different or not. And so that I would call that a variant of unknown significance, meaning its impact is to be determined. Dr Smith: So, I was going to ask you about variant calling, but you'd beat me to the punch. And that's a great metaphor that I will definitely remember. All right, here's another concept that I think people often find challenging, which is read depth. Can you tell us about reading depth or sequence depth?  Dr Kessler: Yes, hopefully I can. Again, not an expert here, but as I understand it, the way next gen sequencing works is that pieces of DNA are getting read. And the number of times any given nucleotide is read in this process is the read depth. It basically just translates to the number of times the processor, the machinery of doing this, pays attention to anyone site. The reason it's important is that the process by which this reading is done can sometimes result in errors. The greater your depth, the more times something is read, the less likely you are to have a mistake.  Dr Smith: In either direction. So, you're presumably less likely to have a false positive or false negative. Yep, again, very well explained. You know, I've got a lot of other questions I want to ask you, but I do want to be respectful of our listeners’ time. I wonder if we could pivot a little bit and just let's go back to where we began. Really exciting time, right? Amazing. And you've been doing this long enough. I'm sure you didn't think when you started that it was going to look like this. What does the future look like? I mean, we talked a little bit about therapeutics, but the world's changing fast. Five, ten years from now, what's your hope for that?  Dr Kessler: Oh, that's such a great question. You know, we are at the point with genetic epilepsies that gene-based therapies, either antisense oligonucleotide-based therapies or viral vector-based gene therapies, are actually now being developed and administered in trial situations to actual patients. And so, it always feels like we're on the cusp, but I think actually now we really are on the cusp of having gene-based therapies for genetic epilepsies. I think that there is still so much to sort out, both from basic scientific point and from a practical administering these things to patients and what are the potential long term consequences.For example, unlike medications, which are therapies that you can stop if there are adverse effects, often administering a gene therapy is a one-and-done thing that can't be retracted. Thinking even about the ethical framework of that and the framework of explaining to patients that we don't know the ten, twenty-year consequences of that, is part of the informed consent process, for example. So, there's still so much work that is going to be transformational, not just from the, you know, the big picture, but from developing all, you know, from going through all of these steps to really make these kinds of therapies a reality. Dr Smith: Well, it's really amazing. And, you know, we're seeing this in multiple different areas in neurology. So, well done. You run the child neurology residency program there, I understand. I try to snoop on people before I talk to them because we haven't met before this. And you're obviously a very a very good educator. Thank you so much for talking with me today. I don't spend a lot of time in epilepsy, but every time I do one of these, I kind of want to go back and do something different because it's such a neat field. Thank you.  Dr Kessler: You're welcome. It was my pleasure.  Dr Smith: Again, today I've been interviewing Dr Sudha Kessler about her article on epilepsy genetics, which is truly outstanding. This article appears in the most recent issue of Continuum on epilepsy. Be sure to check out Continuum audio episodes from this and other issues. And thank you, listeners, for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

In this insightful discussion, Dr. Christopher Skidmore, an associate professor of neurology and vice-chair at Thomas Jefferson University, shares his expertise on the pivotal role of neuroimaging in epilepsy. He emphasizes the importance of optimizing MRI protocols for accurate diagnosis and highlights various imaging techniques, including PET and fMRI, essential for surgical planning. He also delves into the nuances of identifying subtle brain malformations, illustrating how these advancements can significantly improve patient outcomes.

EEG is the single most useful ancillary test to support the clinical diagnosis of epilepsy, but if used incorrectly it can lead to misdiagnosis and long-term mental and physical health sequelae. Its application requires proper understanding of its limitations and variability of testing results. In this episode, Katie Grouse, MD, FAAN, speaks with Daniel Weber, DO, author of the article “EEG in Epilepsy,” in the Continuum® February 2025 Epilepsy issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Weber is the director of adult epilepsy and vice chair of clinical affairs at the St. Louis University in St. Louis, Missouri. Additional Resources Read the article: EEG in Epilepsy Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Guest: @drdanielweber Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Grouse: This is Dr Katie Grouse. Today, I'm interviewing Dr Daniel Weber about his article on EEG and epilepsy, which appears in the February 2025 Continuum issue on epilepsy. Welcome to the podcast and please introduce yourself to our audience. Dr Weber: Hi, thanks for having me. My name is Dan Weber and I'm an epileptologist at Saint Louis University. I direct the adult epilepsy program here and also serve as the vice chair for Clinical Affairs. Been my pleasure to work on this article. Dr Grouse: I'm so happy to have you today. I read your article. I found it to be incredibly useful as someone who often orders EEG in the general neurology clinic. So, I wanted to start with asking, what is the most clinically relevant message or takeaway from your article that you'd really like neurologists to know?  Dr Weber: Yes, when I was asked to write this article, I looked back at the previous Continuum on epilepsy and just the general literature. And there's a lot of good articles and books out there on EEG and epilepsy and sort of giving you a primer on what you might see and how to interpret it. So, we wanted to try to go a slightly different direction. This article gives you some of that gives you the background of EEG and some of the basic things that you may see, but the real thrust of it is more about the limitations of EEG in the clinical picture of epilepsy and common things you might avoid. There are some things that we get hammered into our brains in training that aren't always true and there's plenty of examples in the literature to review, and this article sort of tries to encapsulate as many of those as possible in a digestible format. The main takeaway would be that EEG is an extremely helpful tool in the diagnosis of epilepsy, is the best tool we have to help supplement your clinical acumen. But it does not make the diagnosis of epilepsy. And there are certain circumstances when it may not be as helpful as you may have been led to believe in residency. Dr Grouse: Maybe not the most comforting of messages, but certainly an important one, very important to learn more about this. So, we appreciate that. Can you tell us your decision-making process when deciding whether to order a routine EEG, an extended EEG, prolonged ambulatory EEG, or inpatient video EEG? Dr Weber: Sure. So, it's a multi-part question because each one, I think, has a different clinical scenario. In the current state, our best data for estimating risk of recurrence after an initial seizure comes with routine EEG abnormalities. So, often I will order routine EEGs in those scenarios. So new patient presentation, new patients coming in with an initial seizure who want to know what's their risk of recurrence. So, risk stratification, I use a lot of routine EEG for, often sleep deprived if possible to increase the sensitivity. If you'd like, the extended EEG does offer higher sensitivity, or you can repeat the routine EEG if the first routine EEG is nonconclusive. For generally extended EEGs, I tend to order them in my practice if patients have come to see me with a suspected diagnosis of epilepsy but haven't yet had any electrographic confirmation. Maybe they've already had routine EEGs done in the past, so we'll try to obtain just a little more data. The longer-term EEGs I tend to use in different clinical scenarios, in patients usually who already have established diagnosis or people who have become refractory and we haven't yet confirmed their diagnosis. I tend to do inpatient EEGs in those situations. Ambulatory EEGs I do more when there are certain characteristics of the patient or the patient 's presentation that may not fit well on the inpatient side. Patients who are reliant on substances who can't use while they're inpatient and may have withdrawal effects complicating the stay. Or people who have a strong activation component to their epilepsy where activity really draws it out, certain activities that they do at home that they might not do during the inpatient stay. Those are the sorts of people I'll do ambulatory EEGs on. There are a couple other scenarios as well that come up less commonly, but everything has its own little niche. Dr Grouse: That's a really helpful review as we sort of think about which way we want to go as we're working up our patients in the inventory setting. Can you tell me a little more about the difference between sensitivity of, for instance, doing maybe two routine EEGS versus prolonged ambulatory EEG? Dr Weber: Generally speaking, the longer you're recording someone's brain waves, the higher the sensitivity is going to be. So routine EEG is twenty to forty minutes at most places. One of those gives you a certain sensitivity. More of them will give you more sensitivity. And there was a recent study highlighted in the article that compared routine EEGs to initial multi-day ambulatory EEG, and the ambulatory EEG obviously, as would be expected, has a higher sensitivity than either of the routines. So, there may be some cases with that initial evaluation where an ambulatory EEG may be held and we get into that in more detail in the article. But with the caveat, a lot of this article is about limitations, and the data that we have to talk about increased risk of recurrence was based off seeing epileptic form discharges on routine EEG. So you could hypothesize that if you only have one epileptic form discharge in three days on an ambulatory EEG, that may not carry the same recurrent significance as catching one on a twenty minute EEG. But we don't have that knowledge. Dr Grouse: Getting a little bit more into what you mentioned about the limitations, when is the scalp EEG less useful or limited in the evaluation of epilepsy? Dr Weber: So, one thing I see a lot in my residence at here and other places where I've worked is, I get them very excited about EEG and they may order it a bit too much. So, if patients have a known, established diagnosis of epilepsy, electrographically confirmed, and they come in with a breakthrough seizure and they're back to their baseline, there's really not a strong reason to get an EEG. We often seem to in the emergency department as part of our evaluation, but we already know what happened to the patient. The patient's not doing poorly right now, so the EEG is not going to give you any additional information. Just like really any test, you should think, what are the possible outcomes of this test and how would those outcomes alter the care of this patient? And if no outcome is going to affect the care of the patient or give you any additional diagnostic information, then probably don't need to be doing that test. Dr Grouse: This is probably a good segue into asking, what is an area of confusion or common pitfalls that you've seen in the clinical application of EEG and epilepsy? Dr Weber: So, a lot of times on the inpatient service, we'll get longer-term EEGs for patients who are having spells that are occurrent while they're in the ICU or other places or altered in some way, encephalopathic. And these patients will have their spell, and in my report, I'll say that there is not any electrographic correlate. So, there's no EEG finding that goes along with the movement that they're doing that's concerning for a seizure. And that doesn't always mean that it's not an epileptic seizure. An EEG is not a one-hundred-percent tool. Epilepsy and seizures are a clinical diagnosis. The EEG is a helpful tool to guide that diagnosis, but it is not foolproof, so you need to take the whole clinical picture into account. Particularly focal seizures without impaired awareness often can be electrographically silent on surface EEG. If you see something that looks clinically like a seizure but doesn't show up on the EEG, there are circumstances that they get to in the paper a little bit where that can still be an epileptic seizure. And you just have to be aware of the limitations of the tests that you're ordering and always fall back on the clinical skills that you've learned. Dr Grouse: Are there any tips or tricks you can suggest to improve the clinical utility of EEG for diagnosis of epilepsy? And also thinking about the example you just gave, but maybe other cases as well? Dr Weber: Again, definitely need to incorporate EEG as part of a larger picture. The video component of EEG is incredibly helpful. You can't interpret EEG in isolation. Regardless of what the EEG shows, you can't make a diagnosis of epilepsy, but you certainly can be very suspicious of one. So, in those cases where you have a high suspicion for an epileptic seizure and the EEG has not given you any confirmatory evidence, it's really helpful to rely on any clinical expertise that you have access to. So, people who have seen lots of seizures may be helpful in that situation. Getting good recordings, good data to prove yourself one way or the other is helpful and continuing to evaluate. So usually, as I said, focal seizures that don't show up well on the EEG. People who have focal seizures will often have larger seizures if left untreated. So, you can try to admit them to an epilepsy monitoring unit where we try to provoke seizures and try to provoke a larger seizure to help confirm that diagnosis. Dr Grouse: This kind of gets into what we've already reviewed to some degree, but what is the easiest mistake to make (and hopefully avoid) when using EEG to diagnose epilepsy or make other treatment decisions? Dr Weber: I think the easiest, most common mistake I see is overreliance on the test. There's a lot of subjectivity to the interpretation of this test. There are a lot of studies out there on interrater reliability for epilepsy and intrarater reliability for epilepsy. We continue to try to make the findings more objective and get more quantified. The articles talk about our six criteria for epileptiform discharges and have reference to where that came from and the sorts of specificity that each of those criteria lead to. Just because an EEG report has said something, that does not diagnose or negate a clinical diagnosis of epilepsy. It is common for folks with non-epileptic seizures to have a history of reported epileptic form discharges on their EEG. Again, because there is some subjectivity to the test, some abnormal-looking normal variants will pop up and get interpreted as epileptiform discharges. It's important to review the whole patient, as much of the data as you can, and make the best clinical judgment you can of the overall case. Dr Grouse: What is quantitative EEG and how can it be clinically useful? Dr Weber: Now that most EEG is obtained digitally through the use of computer software, we have been able to employ computers to do a lot of the work for us. There are many different ways of looking at the EEG data, but it's all frequency bands over time. The quantitative EEG goal is really to simplify and condense what you're seeing on your normal EEG page into a more digestible format. Lets you look at a larger amount of data faster, which becomes more and more important as we're doing more of these long-term recordings, particularly in the intensive care unit. Quantitative EEG can help you assess a lot of data at a snapshot and get a general sense of what's going on with the patient over the past several hours. It does require some extra training to become familiar with it, but it's training that can be done at all levels. Again, it can help you see more, faster. Obviously, like everything, it has its own limitations. Sometimes the sensitivity and specificity may be a little off from the raw data review, and you should always go back to the raw data anytime there are questions. But it can be helpful to make things faster. Dr Grouse: Do you think you could give me a hypothetical example of a case where this would be something really nice to have?  Dr Weber: The most common example is folks with repetitive seizures in the ICU. If you're just looking at the raw data, you will get a sense of how often the seizures are happening. But if you look at the quantitative data, it sort of compresses that all down to a much smaller snapshot. So you can see much more readily, yes, these are how many seizures were happening. And here's where we gave our intervention; and look, there are fewer seizures after that intervention. So, it can help you assess response to treatment, help you assess just overall volume of seizures in a much more condensed fashion, and you can get through it much faster with the appropriate training. Dr Grouse: Can you tell us about any new developments in EEG that are on the horizon we should be aware of?  Dr Weber: Yeah. So, I think my two favorites, which I highlight in the article, are longer-term recordings---so, there's some companies that are working on subcutaneous EEG. So, implanted EEG electrodes that can stay in your body for the short, long term on the order of year or years and constantly send some EEG data. Obviously, it's not a full montage in most of those cases, but some EEG data that can help you assess long-term trends in epilepsy and long-term response to therapies. I think that's going to be really cool. I think it's very exciting and I think it'll change how we do clinical trials in the future. I think we'll be able to rely less on seizure diaries from folks and more on objective seizure data for patients who have these implanted. But with that will come an ever-increasing amount of data to be reviewed, which leads into the other exciting future trend is AI in the use of interpretations. AI is becoming more and more advanced and there are very exciting articles out on how good AI is getting at interpreting our EEGs. I think soon, in the very near future, the AI platforms will be able to dramatically reduce the amount of time it takes the experts to review an EEG. They'll be able to do a lot of the screening for us and then we can go back, just like I was talking about the quantitative EEG, go back and review segments of the raw data rather than having to review every page of every file, which is quite time consuming. Dr Grouse: Wow, that's really exciting. It certainly does seem like AI is making breakthroughs in just about every area of how we touch the practice of medicine. Exciting to hear that EEG is no exception. Dr Weber: Yeah, I'm fully excited. I think it's going to revolutionize what we're doing and also just greatly expand people's ability to access that level of expertise that the AI will offer. Dr Grouse: I wanted to transition to talking a little bit more about you and your career in neurology. How did you become interested in this area of neurology to begin with? Dr Weber: Yeah, it's sort of a roundabout fashion. So, I started out planning to be a neurointerventionalist, and then I realized that I didn't want that sort of call. For a hot minute in my PGI 3 year. I was planning to be a neuro-ICU doctor. I think that's largely because medicine is all I had been exposed to at that point and the ICU seemed like a very comfortable place. Then as I transitioned into PGI 3 we started doing more electives and outpatient rotations in my residency. And then I was planning on being a movement disorder specialist or an epileptologist, couldn't make up my mind for the longest time. And then I started to like EEG more than I liked watching videos. So, tilted myself towards epilepsy and haven’t looked back.  Dr Grouse: Well, I really appreciated you coming to talk with us today about your article. I can't recommend it enough to anyone out there, whoever treats patients with epilepsy or orders the EEGs, I just think it was just incredibly useful. And it was such a pleasure to have you. Dr Weber: Thank you very much for having me, Katie.  Dr Grouse: Again, today I've been interviewing Dr Daniel Weber about his article on EEG and epilepsy, which appears in the most recent issue of Continuum on Epilepsy. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.  

In this engaging discussion, Dr. Roohi Katyal, assistant professor of neurology and co-director of adult epilepsy at Louisiana State University Health Shreveport, shares her insights on the evolving classification of epilepsy. She explains the critical distinction between provoked and unprovoked seizures, emphasizing the role of detailed patient history. The complexities of defining resolved epilepsy and the nuanced use of EEG in medication tapering decisions are also highlighted. Listeners will learn about the unique challenges faced in epilepsy diagnosis and why patient choice matters.

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Jennifer L. Hopp, MD, FAAN, FAES, FACNS, who served as the guest editor of the Continuum® February 2025 Epilepsy issue. They provide a preview of the issue, which publishes on February 3, 2025. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Hopp is a professor in the department of neurology at the University of Maryland School of Medicine in Baltimore, Maryland. Additional Resources Continuum website: ContinuumJournal.com Subscribe to Continuum: shop.lww.com/Continuum More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Guest: @JenHopp71 Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology, clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum who are the leading experts in their fields. Subscribers to the Continuum Journal have access to exclusive audio content not featured on the podcast. If you're not already a subscriber, we encourage you to become one. For more information, please visit the link in the show notes Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, Lifelong Learning in Neurology. Today I'm interviewing Dr Jennifer Hopp, who recently served as Continuum's guest editor for our latest issue on epilepsy. Dr Hopp is a professor and executive vice chair in the Department of Neurology at the University of Maryland School of Medicine, where she's also director of the Epilepsy Center. Dr Hopp, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners?  Dr Hopp: Hi, Dr Jones. Thank you so much for having me on this podcast. I really had so much fun working with you and other authors of this issue and serving as editor. I feel like it was yesterday that I was author of an article in the past. And so, it's really a pleasure to take on this new role and create the content for the issue of Continuum for Epilepsy and really particularly to work with the stellar group of experts and authors that we were able to have us join this year.  Dr Jones: I want to thank you for, really, it's a remarkable issue. And we usually don't get into this a lot with our guest editors, but our last issue on epilepsy came out in 2022. Fantastic issue, guest edited by Dr Natalie Jette. When you were designing the table of contents and article topics for this issue, you had some great ideas. Walk us through your thought process on what was most important to convey in this issue.  Dr Hopp: Sure, I'm happy to do so. I think one of the things about Continuum that is so accessible to everybody is that it really is, to me, preeminent format of updating and educating, whether it's epileptologist, neurologist, trainees in every area of epilepsy, which is obviously an enormous task to really pull together all of these data to make updates and then to make it accessible to all of these different levels of learners as well as people like myself. I really read and always look forward to all the Continuum issues outside of my field. I use it to update my knowledge base, get ready for boards. I also read it as an educator because I want to know what my trainees are reading during their rotations and I want to be able to share materials with them. So, I really tried to go back and look at other issues and think about how we could make it fresh. So, I think one of the first challenges is just making sure that we're updating the content of each article based on the literature and the data we have. That really becomes the task of the authors. And so first of all, selecting the authors was both fun but also really important to me. But the second aspect of it to me was really the question of, how could we make this fresh this year? I think Continuum is always fresh and that it has new data, but I wanted to really think outside the box and I appreciate being able to take a few risks. One of them was really headed by Dave Clarke, who provides this incredibly thoughtful and comprehensive review of access to care and epilepsy. I think for anyone who wants a primer on the issues and language used in discussions of diversity or social determinants of health---you first of all do not have to be in the field of epilepsy to read this. So, you should check that out. But I also thought it was really critical to shed more light on these issues. So, we tried to be mindful of this in threading that through as best as we could each article, but also have a stand-alone section that he headed. And so, he addresses issues of how to think about access to care for people with epilepsy, but actually, interestingly, also thinking about the investigators, providers, and researchers, and how we think about diversity in those viewpoints as well. I think we can always do better. Dave concludes with a wonderful focus on hope in this area with next steps for our community. So, I think that that was certainly one area that I wanted to take a risk and I think it was quite successful.  Dr Jones: Totally agree. I very much enjoyed that article. We have an article on implementation of guidelines and quality measures by Dr Christina Baca. I thought that was a great choice from your perspective, not only because Dr Baca is an expert on this, but it felt very practical, right?  Dr Hopp: Exactly. Exactly. And that was the other area that I thought really is always covered so well by the Academy of Neurology. There's so much work in updating the guidelines, whether it's the guideline that just was updated on people with epilepsy of childbearing potential or others outside of the field of epilepsy. And I thought that we could use Continuum to help educate all of the readers on how to take those guidelines and measures and then really bring them into practice. I think there's a whole field of implementation science that I think shines a light on the gap between the guidelines and the measures and then really what we do with them in practice. And that's actually what's most important for our patients and for the providers. And so Christine does just an amazing job as an expert, not only walking us through the guidelines that are relevant for epilepsy, but then helping us and providing, essentially, a toolkit to take those measures and guidelines and use them in a very feasible, accessible way in day-to-day practice. And I would suggest that it's relevant for anyone from a student level resident to an epileptologist who's been in practice, like me, for many years. And so I hope that's relatable and useful to the reader.  Dr Jones: I think it will be. And let's get right into it. So, I always enjoy talking to the guest editor. You're already an expert and now you've just read a bunch of articles and edited a bunch of articles from people who are really the premier experts in their area of the field, right? They’re niche within epilepsy. So, as you've read these articles across the issue, if there were one biggest practice-changing recommendation that you would want to convey to our listeners, what would that be? Dr Hopp: I think that's a fabulous question because again, each of these articles, I think, is designed and written by the author to stand alone. But ideally, they need to all be incorporated in practice. And I think what each author was able to really successfully do is not only review the data, but really take us to the next level with practice of epilepsy. For example, I think as we embark on the next couple of decades, clearly increased technology, AI, personalized medicine are all buzzwords and taking the lead. In reality, with advances, we still have to make sure our care is personalized. And we have to remember seizures are really the symptom, but epilepsy is the disease. What I think our authors do well is make sure that our care is personalized to the patients. You could take that from the first article that Roohi Katyall writes about how to approach the patient with epilepsy, which is still, I think, the seminal way to start to think about these patients. But we need to ask issues pertaining to people with epilepsy of childbearing potential; screen for mood, other comorbidities. Mark Keezer does a great job talking about these. And then as we discussed, Christine Baca, PCU, talks about how to then incorporate those practical considerations into practice. Each author also, I think, emphasizes the need to utilize technology and testing and evaluation to make sure that our care is personalized for our patient. For example, we have a focus on certain special populations. Some patients who we see from the diagnosis of epilepsy end up not having seizures. They may have nonepileptic events. And so, Adriana Bermeo-Ovalle and her co-author talk about how to address those patients. Well, Meriem Bensalem-Owen talks about gender based issues in epilepsy as well. And, and that particular article also was updated and refreshed to really address gender and sex-based issues beyond treating the woman with epilepsy. So, I think in summary, each of them really helps us make sure that we're personalizing the care for patients by emphasizing a very thorough and individualized approach to each of our patients that we see with seizures.  Dr Jones: Now that you put it that way, that really did come across as a consistent theme essentially in every article, right? All the way from the evaluation of the patient suspected of having epilepsy to the treatment options to the context of care. Personalization is really kind of a continuous thread throughout the issue. So, I think that's a great one.  Dr Hopp: I think it's still aspirational in some sense, but hopefully practical in another. For example, we certainly are going to make a medication selection when we see each individual patient based on their comorbidities, perhaps genetic considerations, and how they may respond to medications or have risks of rash. But there are certainly still guidelines that we need to approach and think about when thinking about populations of people who have epilepsy as a whole. I think that what's interesting in the field of epilepsy is that we still don't have as much consensus as I think we could on the best way to treat, for example, a drug-resistant patient with epilepsy. One of, I think, the biggest areas of opportunity in terms of personalized medicine as we move forward is that there's such variability on patient care based on the epilepsy center, the tools that we have on how to treat these patients. And I think an aspiration is for us to, in the future, be able to see a patient who has seizures or a person who has seizures, maybe put an FDA-approved device, as Dan Friedman talks about in his article, to help detect the seizures. Use AI with EEG to detect abnormalities in their studies. And then use imaging processing and genetic or metabolic markers to really end up stratifying the risk and creating a treatment plan much akin to what's done in the world of cancer care. I think what's so exciting in epilepsy is that we have made so many advances in terms of our treatments, but I think there's so much to do to really stratify and personalize care for our patients that we really could take a lot of lessons from the world of cancer and in other fields of medicine to really be able to apply to our area of specialization.  Dr Jones: And I guess that's one of the common tensions in neurology---and medicine, really---is the pull between standardizing and protocolizing. And usually we do better when we're standardized in our care versus that personalization, doing the right thing for that individual person. And I guess expertise lies in the middle, which is why we want people to read these articles, right?  Dr Hopp: Exactly. I think you've hit the nail on the head, and I think the takeaway here is really that we need to do both. There's no question that we can't reinvent the wheel for every person who we see in the office who has epilepsy and not apply the knowledge that we've gained based on all of the research and work that's been done in the field of epilepsy. So, for example, we know that if someone is almost 25 years old, Quantum Brody published that shows that if someone does not respond to a few drugs, anti-seizure medicines, the likelihood that they're not going to respond, it is quite high. So, we need to apply data that we have to patients as a whole. But then, I think, what has changed and evolved over the past twenty-five years is our ability to potentially personalize some of that decision making. And that's where I think the field of epilepsy is right now, and hopefully where it's going to go in the next decade or so.  Dr Jones: So, what do you think the next big thing in epilepsy diagnosis or management will be? Dr Hopp: I think that technology is really going to play a role. Technology, I think, will take many forms. We hear a little bit about some of the new advances in technology in several articles in this issue. One, for example, is in the ability to manage even emergent seizures or clusters of seizures in patients. The ability to provide a nasal spray that works very quickly is so different than the tools that we had to treat seizures even 10 years ago. I think that technology will likely thread through many different areas of epilepsy care, whether it's in the treatment and availability of different medications or in the ascertainment of epilepsy itself. I think that one of the very exciting areas in technology is in pharmacogenomics and genetics, which hopefully will allow us to close the gap in selecting one of the better medications or best medication for a patient earlier in their diagnosis and in their treatment plan. If we are able to get patients treated more quickly, whether it's with medication or in selection of the best surgical treatment, hopefully we will close the gap in reducing the possibility of drug resistant epilepsy, but also have impact in quality of life and getting patients and people with epilepsy and doing that, doing the things that they want to do such as driving, going to work, getting engaged in the things that make them happy. And so, I think our ability to use technology, whether it's in using a watch to make a diagnosis of seizures or pharmacogenomics to make a good medication selection, hopefully this will allow us to speed up our algorithm in making a diagnosis and getting an effective treatment plan for patients earlier. And ultimately that's our goal. Our goal for patients is ideally to have no seizures and no side effects with a good quality of life.  Dr Jones: Yeah, the technology has really been breathtaking. You know, one of the commonalities between your practice and my practice is electrophysiology. I do neuromuscular electrophysiology, which is much simpler than what you do with cerebral electrophysiology. And whenever I sit down next to a colleague who is about to review forty-eight hours’ worth of EEG recordings, I always think what a massive amount of data and I always feel sympathy for them. What, about AI? What about automated processing tools? Is that something that our listeners should look forward to in the future?  Dr Hopp: I think so. And I hope it's a blend. I hope that---and I always actually talk about this with trainees because I love EEG so much and I love translating the principles of physics and neurophysiology when we're sitting in front of an EEG with our trainees. I am excited about AI and technology. I will admit that I hope that it doesn't replace human readers because I do think that there is an importance in threading history and semiology and thoughtfulness in a human way with the interpretation of EEG. However, you're absolutely right that the amount of data is just becoming overwhelming for epileptologists and for EEG-ers to be able to synthesize in a reasonable and feasible amount of time. So, we already are seeing the applicability of the AI to, for example, prescreen large, large amounts of EEG data and try to at least give us tools for the ability to screen EEG in a more efficient way. I think some of the more exciting areas of EEG that are coming are in the background, which is in the network analysis in high-density EEG. There are very, very smart mathematicians that currently I'm collaborating with in utilizing network analysis of EEG that will hopefully allow us to apply these algorithms to EEGs that even look normal to the naked eye, but actually may have signals that help us predict who may or may not have seizures. I agree with you wholeheartedly. I think there's so much to come and our collaboration and integration with engineers and mathematicians, I think, is going to be paramount. Dr Jones: Dr Hopp, what was your path to epilepsy?  Dr Hopp: Dr Jones, that is a great question. It was not linear and it really evolved over time, but basically went something like this. I majored in behavioral biology in college, and I was fascinated by the brain and how behavior was controlled by either physiology or anatomy or abnormalities in brain function. And as I moved along in my career and education, I really had a passion for neurology and for behavioral science. But I went to medical school and absolutely loved most of the rotations I did. And in fact, I loved OBGYN so much that I changed my entire career path with the goal of becoming an OBGYN and delivering babies. And I was really torn between two specialties of going into neurology or OB. And I went to a very sage advisor, Greg Kane up at Jefferson. And I said, I really don't know what field to go into. I love aspects of both. I like doing testing. I like making immediate impact. But I also love neurology. And he gave me some of the best advice, I think, that I have ever heard. And I try to share with our trainees all the time. He said, Jenny, I think you'll be successful at either, but which do you like reading about? And I had a relative epiphany at the time, and it was no question that I loved reading about neurology. It was very clear to me that reading about neurology and learning about the brain was just fascinating and led me to do a neurology residency where I was exposed to patients with epilepsy. And it really just continued to pique my interest to read about a field that I felt I could have such an impact. I really could help patients make a diagnosis relatively quickly and have a significant impact, maybe as I would in OBGYN but in a little bit different way. And it really has been, to me, the best choice that I could have made. And on a day-to-day basis, I still love reading about neurology. So, it was some of the best advice that I was given and I try to share that with others. Dr Jones: What a great question for a mentor to ask. And I wonder if he was really thinking, if she likes to read, she probably should be a neurologist to begin with. You like to read, don't we?  Dr Hopp: I think so. I think he was spot on. I think he knew the answer before he asked the question.   Dr Jones: Dr Hopp, thank you for joining us today. Thank you for such a thorough and fantastic discussion on caring for patients with epilepsy and our recent issue on epilepsy for Continuum. Dr Hopp: My pleasure. Thank you for having me. Dr Jones: Again, we've been speaking with Dr Jennifer Hopp, guest editor of Continuum 's most recent issue on epilepsy. Please check it out. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. Thank you for listening to Continuum Audio.

Informal care partners are essential to the care of people living with dementia, but they often experience significant burden and receive minimal training, support, and resources. Multicomponent interventions can mitigate burden and other negative consequences of caregiving. In this episode, Gordon Smith, MD, FAAN speaks with Angelina J. Polsinelli, PhD, ABPP-CN, author of the article “Care Partner Burden and Support Services in Dementia” in the Continuum® December 2024 Dementia issue. Dr. Smith is a Continuum® Audio interviewer and professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Polsinelli is an assistant professor of clinical neurology at the Indiana University School of Medicine in Indianapolis, Indiana. Additional Resources Read the article: Care Partner Burden and Support Services in Dementia Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Full interview transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Smith: This is Dr Gordon Smith. Today, I've got the great pleasure of interviewing Dr Angelina Polsinelli about her article on care partner burden and support services in dementia. This article appears in the December 2024 Continuum issue, which is on dementia. Ange, welcome to the podcast. And maybe you can begin by just introducing yourself to our audience?  Dr Polsinelli: Yeah. Well, thank you for having me. I'm very excited to be here. I'm Ange Polsinelli. I'm a neuropsychologist at Indiana University School of Medicine, where I work in the Department of Neurology. I also work with the Longitudinal Early Onset Alzheimer's Disease study that's led by Liana Apostolova. And I also do some work with the Outreach, Recruitment and Engagement Core of the Indiana Alzheimer's Disease Research Center. This topic that we're going to talk about today is extremely near and dear to my heart. Dr Smith: Well, thanks for joining me. And of course, IU is a powerhouse for Alzheimer's and basketball, in that order. So, we're really excited to have you. I'd like to get right into it. I'll emphasize, we were chatting a little bit about this, Ange, before we started recording, that your topic today is so important for all of us. And I think, you know, this is a podcast that not only neurologists listen to, but students and, and I think increasingly members of the lay public. And this conversation is going to be very important for neurologists and our neurology learners. But I lost my grandmother to Alzheimer's disease. I lost my uncle just in the last week. So, this touches all of us. So, I'm really excited. And then with that in mind, I wanted to begin with a statistic that- you can correct me if I misunderstood it, but it really blew my mind. And that is across the world, as I understand it, care partners provide one hundred and thirty three billion hours of care for people living with dementia yearly, which is pretty staggering. But what's really amazing is that by 2030 that number is expected to go to one point four trillion hours, which I couldn't grab my mind around it. So, I figured I'd try and determine how many years of person work is that and if my math is right, that's almost a hundred and sixty million person years of worth caring for people with dementia yearly across the world. One, are those numbers right? Did I get it right? And then, assuming so, can you put a human face or experience to these numbers?  Dr Polsinelli: Yeah, unfortunately those numbers are correct. And with our increasing aging population across the world, that's why you're getting that, you know, exponential increase in care per hours, compounded by the fact that the majority of the caregiving that happens is not done by doctors, physicians, but it's done by these informal care partners, these family members, these friends, these siblings, children, who are providing these really important services and unfortunately not being trained to do this, doing it largely on their own in a lot of respect. But again, these are people who are loved ones of the person living with dementia. There are a variety of kinships, as I mentioned, siblings, children, spouses, friends; and all sorts of age ranges as well. A large majority of them being spouses, and then the second largest majority being children. So, kind of a sandwich generation of people who are caring for parents with Alzheimer's or dementia and then caring for children as well. Dr Smith: Yeah, I was actually struck by the statistic that a quarter of caregivers or so called sandwich caregivers; in other words, they're taking care of a parent and a child. But listen to what you said. But just to call it out, two-thirds of care partners are women, which is a striking statistic.  Dr Polsinelli: Absolutely. Women are not only more likely to have dementia, but they are also more likely to be the care partners of somebody who has dementia. And so, the research shows, too, that if you're a care partner, you're at higher risk of developing dementia yourself. So, there's a lot of risk for women when it comes to dementia, development of dementia, but also that the burden and the majority of care needs that are that are supported by women as well. Dr Smith: Right. And there's a lot to unpack in that observation, and maybe we can come back to that. But I wonder if you might talk to us a little bit about the risk of dementia in women caregivers. That's really striking. Is there any thought regarding mechanism for that? Why is that the case? Is it a shared risk factor? Is it cause and effect? What's the story?  Dr Polsinelli: So, there are - this is kind of a dissociable or different - kind of two aspects to this, this question. There's the fact that women are at higher risk for developing dementia in general. I think the researchers feel sort of out about why exactly that is. It's not just that women are at higher risk or more likely to develop dementia because they're living longer than men, but there's probably some hormonal aspects of their higher risk factor for dementia. But then there's the other aspect of it too, is that as caregivers, caregivers are at higher risk of developing dementia. And because caregivers tend to be women, that increases or compounds the risk for women as well. We know with caregiving, particularly with someone who's living with dementia, there's more risk of developing things like depression, high stress, health problems, psychological distress, and all of these things increase somebody 's risk for developing dementia as well. Dr Smith: So, I wonder if you might talk a little more, Ange, about what you mean by burden? I think we have in our mind what that is. But in reading your article, there's a lot of- a lot more to it than may meet the eye. Dr Polsinelli: Yeah, it is a more complicated, I guess, topic or terminology that's gone through several iterations over the course of doing research into burden. But when we think about burden, it's really a kind of a combination of both objective experiences and subjective experiences. And these objective, subjective experiences fall into the categories of physical burden, emotional burden, psychological burden. So, there's a lot of different areas of life in which someone can experience burden. But really, it's a combination of factors of both the objective experience, lived experience, and the person 's perception of that experience or what they're dealing with. I should also mention that it appears to be more of that subjective experience or that perception that people have of their objective experience of stressors or burden. That really does determine the person's response to that, if whether they actually perceive their lived experience as being burdensome.  Dr Smith: One of the things I found really interesting was the societal and cultural context surrounding this, that there are different cultural expectations and societal dynamics, both in the nature of the burden care partners may feel and how they're viewed. I wonder if you could talk about that? I think it's something that it would seem all of us need to be attuned to as we're working with our patients and their families.  Dr Polsinelli: Yeah, this is a topic we could talk for a very long time on. I will try and- I will try not to kind of provide too much of a, or too lengthy of a response. But what we know now is basically that our models of stress and burden that we have typically used or historically used do not incorporate a lot of factors of cultural identity of social and structural determinants of health factors. And so, what we understand now is that stress and the way that people perceive burden is influenced by so many other factors than just kind of an experience and a perception. Because that perception is influenced by so many factors, including, as you mentioned, cultural factors that include how society's familial expectations for us, cultural expectations for us, as well as what our resources are that are determined by, again, structural and social determinants of health, what our community resources are. They're just a lot of different factors that go into how somebody perceives their ability to cope with, again, this kind of life-altering diagnosis that their loved one has received and them being the person who is caring for them through that. Dr Smith: Your article actually goes through in some detail the types of burdens and what drives the burden. And that changes over time. And so I wonder if maybe you can talk a little bit about what the specific natures of the burden are from the caregiver perspective. I mean, what  sort of tasks there are, you know, from the many of us who take care of patients, we still don't know unless we've been in the room or in the home watching this happen. So maybe you can describe that for those of our listeners who maybe haven't lived through this?  Dr Polsinelli: Yeah, absolutely. I will say upfront that the caregiving experience is going to be different for every single person. And again, kind of dependent on some of those factors that I mentioned before. So, it's going to look different for most people. It's also going to look different through the dementia journeys. The experiences and the requirements earlier on in dementia are going to be a vastly different than what occurs later on when dementia is in the more late stage, moderate or severe stages of the disease. Those care responsibilities absolutely change over the spectrum of that time as well. We know that early on the stage of disease, primary care partner might be spending forty plus hours a day. So, a full-time- or not a day. I'm sorry, a week. So, a full time job carrying it. But that number increases up to a hundred and fifty or so hours per week once the person is more advanced in their disease. So, I say that because the number of hours, I think, make all, like- putting that into perspective of somebody having a full time, multiple full time jobs, basically providing care, I think is really important. But the responsibilities of the care partner are going to range from everything from just helping the person early on in terms of managing finances or managing them, making sure they’re reminding them to take their medications, scheduling their medical appointments for them, maybe taking over all of the driving to get them to their appointments or to get them to family outings and things like that. They're going to be the ones that's going to be the most responsible for reminding people to do something: to eat, to maybe stay on track for a recipe or something that they are making. So, kind of being the eyes and ears for this person right away, basically right at the beginning, even early stages. And then that progresses over time to the person who is caregiving, who is doing potentially everything for this person. So that means helping them use the restroom when they need to, helping them shower. So, there's a physical component to the caregiving as well as that- sort of what we call instrumental support in terms of organizing medical appointments and things like that. They're just basically doing it all for that person.  Dr Smith: So, what about a busy clinician who has half an hour to see a dementia patient follow up? Kind of hard to- in these days, you know, we've got, you know, these new therapies to think about as well. What advice do you have to neurologists and other professionals caring for patients? Dr Polsinelli: Yeah. And I think neurologists, I mean, we all have limited time. And I know neurology in particular is like primary care, has even more constrained time. I think one of the biggest things that neurologists can do is really check in with the care partner. So, take a moment to check in with the care partner who's there with the person with dementia to see how are they doing. You're looking for signs of burden or stress, so things like physical complaints like headaches or stomach ache, mentioning feeling burnt out or overwhelmed, maybe feeling depressed or something like that. There's also some short kind of questionnaires that you could give care partners prior to an appointment that they could fill out. You could kind of get a sense of where is this person at this point and then help connect them potentially to some resources that might be available. And I would refer people to that article that has a list of resources in there that you could just basically print out and give to somebody.  Dr Smith: Yeah, I was going to make the same point, Ange. Your article is a treasure trove of information. And you know, I'm certainly, I keep all of these on file, as you might imagine, but I'm keeping it in hand for future use. One of the things you talk about that really hit home for me among many is the idea of self-care, and I think sometimes the best care partners are susceptible to burnout because they they're so dedicated. You made the airplane oxygen mask metaphor, which I love. So maybe you can talk about what airplane oxygen masks have to do with dementia care and what advice you have for us and helping our patient’s care partners take care of themselves? Dr Polsinelli: Yeah, absolutely. Self-care is the number one thing I tell care partners to do. It's also one of the hardest things for care partners to do. Like you mentioned, there is a deep, generally speaking, a deep love and caring for the person with who is living with dementia. And the focus becomes on them. And understandably so, the care partners sort of loses focus on themselves and making sure that they're doing okay. So I oftentimes use this oxygen airplane metaphor for people, which is basically, you know, when you're in an airplane and if there's some kind of pressure change in an airplane, they always tell you, put your oxygen mask on first before you help somebody else because you're not going to be any good to anybody if you're passed out. In the airplanes, the pressure changes, you know. You need to be available. you need to be getting what you need in order to help somebody else. So, I think that metaphor, that analogy really works well in dementia care is you need to be- the care partner needs to be caring for themselves and replenishing themselves in order to be the best care partner they can be for their loved one.  Dr Smith: Another challenge that, it strikes me as shared between people living with dementia and their care partner is that of social isolation and loneliness, right? If you're working a hundred and fifty hours a week doing anything, you don't have time to care for yourself or very hard to engage in social connections. And one of the loud messages I think I heard from your article is the power of social connectedness, both in terms of resilience and in many different ways. I wonder if you can talk a little bit about loneliness? And I just reflect that in a postpandemic world, this is probably a bigger issue than it was four years ago or four years and three months ago. Dr Polsinelli: Yeah, absolutely. Loneliness and social isolation was a big problem before, and it's even worse now is when I'm hearing from my patients. What I'm seeing in the literature is this postpandemic time is even more has been even more isolating and more problematic for people, but this social network cannot be, as you said, it cannot be overstated in terms of the importance for people. So that social network is important for not only providing potential instrumental care - so that practically care that care partners can use can lean on other people to come into the home to do things for the person living with dementia so the care partner can go practice self-care or go do those errands that need to be done - but also the emotional support as well that social networks can provide for people. And also, you know, social networks for not just the person, the care partner, but for the person living with dementia as well. We know that social engagement in particular is really good for brain health. I mean, we don't think about it, but social engagement is a very cognitive activity. And so, it helps give the brain a bit of a workout. So that social network is important for a lot of different reasons, and understandably a lot harder to maintain in this sort of postpandemic world as well. Dr Smith: As our time starts to come to- close to a close, we're not done yet, but I think we're probably going to have to start winding up. I wonder if we could pivot to something positive and then talk about the joy in this. And by that, I mean you describe and I think we've witnessed relationships and caring, caregiving situations that, as challenging as they are, provides fulfillment and the connection one has with a loved one or sort of that social aspect. Are there things that- predictive of that kind of positivity, and are there ways that we as professional caregivers for patients and their families can facilitate that? Dr Polsinelli: Yeah, there are. There are a couple of things. So, one of which is basically the quality of relationship between the care partner and the person living with dementia already. So that's the quality of that relationship. The better the quality of that relationship, the more likely it is that the care partner will experience more meaning and fulfillment and joy associated with caregiving, kind of outweighing that burden. But the additional piece of that is the more resources, the more mastery they feel about their caregiving or care partnering abilities, the more competent they feel and their ability to do good by the person, their loved one, the person living with dementia, the more likely they are to find that role fulfilling and meaningful. And I think that's where neurologists and other providers can kind of come in as helping people make sure that they have those resources that they are connecting to places where they can learn skills for giving appropriate care so that they can feel confident in what they're doing. There's the preexisting relationship piece that matters a lot. But I think that there's a lot of modifiability that neurologists have, too, in making a positive impact on the care partner and the person living with dementia. Dr Smith: That's really great advice, Ange. And I definitely will refer our listeners yet again to your article, which is a compendium of useful advice about this, both in terms of the text itself and in tables that provide lists of resources, websites, books, organizations, good case examples. It's a home run and I hope all of our listeners check it out. I'd like to wind up by talking a little bit about your work. And as I understand it, you obviously are very passionate about this topic, but you have specific interests in caregiver burden and underserved and marginalized communities. And then, we’ve touched on this, but this is a huge percentage of our population. And when you look out globally, it's even bigger than that. Tell us about what you're working on. And then maybe following that, what's the future look like? Where are we going to see advances in this in the coming years?   Dr Polsinelli: So just a really quick kind of brief history is that I've worked in dementia for almost twenty years or so now. And what I've consistently seen is when you give care partners good supports and education and resources, there are better outcomes for them and their families. The unfortunate thing is, a lot of these really great interventions and things that we have are not necessarily really accessible by a lot of people, but particularly not accessible by those living in underserved communities. The last few years in particular, I've really shifted into wanting to better understand that and better understand how do we provide culturally and socially appropriate interventions and education for these care partners and their families. With the current research project that I'm working on, we're looking at better understanding the needs of care partners of people who have early onset Alzheimer's disease, specifically from Black and African American individuals and other underrepresented groups. Again, the idea of this is to understand the needs before building an intervention for these groups, and I'm very excited about it. I know that there are lots of really great people who are working in this area, including Dr Dilworth Anderson and Kalisha Bonds Johnson, doing really fabulous work in this area. So, and building on what they're doing as well. In terms of what the future holds, one, I think we absolutely need to, we have lots of really great care partner interventions out there that have been lots of research going on, but it's not really transitioning into the clinical sphere. It's really kind of staying in that research sphere. So, I think it's really important that we get some implementation scientists who are taking those interventions and moving them into the clinical sphere, into the sort of like everyday, how do these actually work for people sphere. And then similar to some of this conversation we're having in terms of serving, making sure our interventions and making sure that our resources are appropriate and accessible for underserved communities, we really need to be taking a look at what these communities need rather than kind of saying, this is what's available. Kind of, hopefully this works for you. Speaking with these communities, engaging stakeholders and understanding what are the needs in these groups so that we can provide the appropriate resources, the appropriate interventions, the appropriate supports for care partners and people living with dementia. Dr Smith: And I'm just thinking, imagine what this looks like with effective treatments for Alzheimer's disease, that slow progression. And you know, that's going to make the caregiving even more important, it seems to me. But there's an opportunity to make it a better rewarding and a better-supported system as we develop these new therapies. So, this is a, like a Clarion call for learners listening that they should all become dementia neurologists and neuropsychologists like here. Thank you. That was outstanding. Say, Ange, I want to thank you a lot for a really engaging conversation. This fulfilled every hope I had coming into it. I was really excited to talk to you. I always love talking to neuropsychologists, but I think again, this is really useful for neurologists, learners, people who are nonneurologists everyone. And so, thank you very much. I've learned a lot and I really would encourage everyone to check out the article.  Dr Polsinelli: Well, thank you so much for having me on and giving me the opportunity to talk about the stuff that is really important to me and, I think, to most of us out there. So, hopefully people find the article and the resources in there useful and, and thanks again for having me.  Dr Smith: I'm sure they will. Again, today I've been interviewing Dr Angelina Polsinelli, whose article on care partner burden and support service in dementia appears in the most recent issue of Continuum, which is on dementia. Be sure to check out Continuum audio episodes from this and other issues. And thanks to you, our listeners, for joining us today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Dr. David Geldmacher, a leading neurologist and director of Cognitive and Behavioral Neurology at UAB, shares groundbreaking insights on Alzheimer's treatment. He discusses the impact of FDA-approved anti-amyloid therapies and their potential to alter disease progression. The importance of holistic diagnosis, personalized treatment strategies for agitation and sleep disturbances, and the critical role of caregivers in navigating care are also highlighted. Geldmacher emphasizes ongoing research's role in shaping the future of Alzheimer’s care, benefiting both patients and families.

Dr. Sonja Scholz, a senior investigator at NIH and adjunct professor at Johns Hopkins, shares her expertise in neurodegenerative dementias. She discusses the complex relationship between genetics and these diseases, emphasizing the significance of genome-wide association studies and genetic testing. The conversation also dives into advancements in biomarkers for accurate diagnostics and the future of treatments like precision medicine. Scholz highlights the need for research on atypical dementias, drawing from her clinical experiences with Parkinson's disease.

Dr. Joseph Quinn, a prominent professor at Oregon Health & Science University, dives into the groundbreaking world of fluid biomarkers for dementia diagnosis. He discusses the pivotal role of cerebrospinal fluid in clinical practice and the evolving landscape of blood tests for Alzheimer's. Quinn highlights critical trials on plasma neurofilament light and GFAP, exploring their potential in tracking treatment efficacy. The conversation also touches on exciting developments and the need for precise diagnostics to enhance early treatment strategies for neurodegenerative diseases.