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.

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Read the article: First Seizures, Acute Repetitive Seizures, and Status Epilepticus

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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.