Hey everyone, welcome back to Brain to Bedside. I'm your host, Jamie Sessions, and we're back for another episode of making neuro practical and translating our knowledge into better bedside care. Today's episode is a bit of a continuation, or at least related to one of our previous episodes. You'll remember in our first episode we talked to Dr. Johnson about non-epileptic seizures, assessment, diagnosis, treatment, and decreasing the stigma around that diagnosis. And today we're happy to have Dr. Johnson back to discuss updates in epileptic care. So welcome back, Dr. Johnson.
Dr Brian JohnsonThanks for having me, Jamie.
Jamie Sessions MSN, RN, CENAnd as a quick intro, in case you didn't listen to our first episode, which first of all you should, but just in case Dr. Johnson is an epileptologist at the University of Utah, as well as the medical director for our Outreach TeleNeurology program.
So let's just jump right in and let's start with the basics. So I know in recent years the classification of seizures has changed. Can we do a quick rundown of seizure types?
Dr Brian JohnsonYeah, so previously you may have heard terms like grand mall or petite mall. Those are kind of the oldest terms that we use for seizures. And those were not very descriptive. They mean little bad and big bad, which doesn't tell you a lot about the seizure. And then probably in the last century or so, we started to talk about partial versus generalized seizures. That was the terminology that was previously used. And if you lost awareness during your partial seizure, we called that a complex partial seizure. So it's kind of the older terminology that we used. About 10 or 15 years ago, ILE revised the classification of epilepsies broadly into three categories: focal, generalized, or unclassified. Under focal uh seizures, you can have focal seizures, focal aware seizures, or focal impaired awareness seizures. And then those can progress to bilateral tonic clonic seizures. Previously, impaired awareness was complex partial, aware was a simple partial seizure. And then it was called secondary generalization. Under the generalized seizure categories, we have absence, my clonic, tonic clonic, clonic, tonic, and atonic seizures that are all primary generalized seizures. That's broadly how we classify seizures. Going back to focal seizures, you can further describe their onset as motor or non-motor, whatever symptom that they're having with their motor or non-motor onset. So really we've tried to move away from terms that mean nothing unless you are an epileptologist to terms that are much more descriptive and mean a little bit more than big bad and little bad.
Jamie Sessions MSN, RN, CENRight, right. It went from like really generalized, big, bad, little bad to like very focused, a huge list of different terms. And now we're kind of back generalized, focal, but at least succinct enough that it's makes a little more sense.
Okay, so taking it to the bedside as we do in this podcast, if we have a patient that we're seeing that's having an epileptic seizure, what do we do? What are our first steps? What are our next steps? Break that down for us.
Dr Brian JohnsonYeah. So if you're at the bedside and you see somebody having a tonic clonic seizure, really uh going back to the ABCs is what you need to focus on. So airway and breathing, you want to roll the patient on their side. You don't want to put anything in their mouth, don't restrain them. And then C, making sure that they're perfusing is also quite important. Most generalized tonic clonic or bilateral tonic clonic seizures will stop within three to five minutes. But if it hasn't stopped within three to five minutes, that means that the seizure is probably not going to stop on its own. And you probably need a rescue medicine. In the emergency room setting, if you have an IV, an IV benzodiazepine is really the best way to treat an acute seizure or an acute status epilepticus. That's a seizure lasting more than three to five minutes. And that's a higher dose than usually would use for other things. Most adult patients should receive four about four milligrams of IV Ativan. And then that needs to be chased by something else.
Jamie Sessions MSN, RN, CENAnd that's delivered as one dose, not like one milligram, one milligram. If that doesn't work, another milligram, like just a full dose, four milligrams.
Dr Brian JohnsonYeah, I usually deliver it in two milligram increments. Um so I push two, see if the seizure stops. If it doesn't stop within you know 30 seconds to a minute, then push a second dose of two milligrams of IV Ativan. If you're pushing more than four milligrams total, there's a good chance you're gonna run into uh an airway problem. And so make sure that you have somebody somebody there to help you manage your airway if you're pushing more than four milligrams of Ativan. If you don't have an IV, you could use intramuscular midazolam. The dose for that is 10 milligrams of intramuscular midazolam. So it can be tricky in a patient who is actively seizing to get an IV. So it's nice to have that midazolam back up.
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Jamie Sessions MSN, RN, CENAll right. So once we have the seizure acutely controlled, what are our next steps? I know I see a lot of Keppra use kind of acutely with seizures. Is that our go-to, or what are we doing next?
Dr Brian JohnsonYeah, so you always want to chase the benzodiazepine with a longer acting seizure medicine. The three that we have at our disposal are phenytoin or phosphenytoin, valproic acid or Depakote. And then uh in the past couple of years, we've been able to start using IV Keppra. And this is a very large dose of Keppra, 60 mix per kg, up to four and a half grams total, which is a lot more than you would use in a normal non non-seizure, non-status epilepticus situation. So those are those are things that you want to do. You always want to chase your benzo with a longer acting seizure medicine. And then you want to figure out, try and figure out why the patient had a seizure. If they're a known patient with epilepsy, the most frequent cause of breakthrough seizures is actually not getting their seizure medicine. And so getting a good history from somebody that knows the patient to see whether there's a chance they may have missed their seizure medicines recently for whatever reason. It's also important to look for other acute symptomatic causes. So if the patient does not have known epilepsy, it is important to obtain some sort of emergent head imaging, whether that's a CT scan or an MRI, to rule out a large stroke or tumor that may have caused their seizure. There's some basic lab work that I usually recommend. Glucose is actually the most important, and you can most places have a POC glucose, and most patients will actually roll in the door, EMS will have already obtained a point of care of glucose. Patients with diabetes, both both high and low blood sugar can cause, can cause seizures. I always get a CBC, a CMP, a Mag and a Phos, a urine drug screen. And if the patient has infectious signs or symptoms or any nuchal rigidity, I have a pretty low threshold to get a lumbar puncture to look for other causes of their epilepsy. Regarding EEG, EEG is not always necessary after a seizure. If the patient has returned to baseline, like they, you know, they might be a little bit sleepy, but they'll wake up and talk to you. You definitely don't need an EEG, but if there's any question of the patient returning to their baseline, it is quite important to get an EEG to make sure that they're not still having small seizures causing encephalopathy. If the patient comes back to baseline, you can either get an EEG to help you classify their epilepsy really within the first within the first like 10 to 12 hours is probably the most the highest yield for looking for interictal discharges. If you're not able to get that EEG within that time period, it's probably best to wait a few weeks and get that EG as an outpatient. So you definitely don't need to get an EEG in the ER every time that you see somebody with epilepsy or new onset seizures.
Jamie Sessions MSN, RN, CENGreat. So so far with our patient, we've gone down the pathway of acute treatment. We've given them the four of Ativan. We've chased it with a long-acting seizure medication and they're back to baseline. They're doing well. What would happen if we go down the other pathway where we have a patient who's not returning to baseline?
They still appear to be having seizure activity despite our Ativan and our long-acting. Yeah, so that is called refractory status epilepticus, which can be quite dangerous. It should be treated aggressively. In a patient with refractory status epilepticus, they will usually need to be intubated. With intubation, oftentimes people will receive strong GABA agonists. Etomidate is a very useful GABA agonist, and then they'll be put on a propofol drip or midazolam drip after their intubation. We treat refractory status epilepticus usually with IV anesthesia. Propofol and midazlam are the most commonly used agents, but things like ketamine or pentobarb can also be used to treat refractory status. You also want to add on another long-acting seizure medicine. So if you've already loaded them with Kepra, probably also load with uh with Depacode at that time. And then you want to make sure that you're getting an EEG with within an hour or two of intubation, because as soon as you intubate the patient, you lose your exam. And so you're you're flying blind for a little bit. So you want to get that EEG to confirm that your intervention has been successful. If you're not able to get their seizure under control with you know low dose IV anesthetics, we usually recommend escalating doses of anesthetics as the patient's able to tolerate. We used to have an aim of what's called burst suppression or a medically induced coma, where you put the brain into such low activity that all you see is a burst of activity, then it's flat for a few seconds and then a little short burst of activity. And we don't really do that very often anymore. We usually just shoot for control of the seizures. So you use the EEG and you titrate your anesthesia until you get to a point where you are not having any more electrographic seizures. So that's how we treat uh refractory status epilepticus. But it does refractory status epilepticus, it does come with a pretty high mortality rate. So it's important to treat it quickly.
Jamie Sessions MSN, RN, CENYeah, that's interesting. I remember in my ICU days doing birth suppression and keeping that for a few days. So now once once they're on the anesthetics, we have the seizure controlled, how long do you keep them sedated like that before you can trust that bringing them out won't restart the activity?
Dr Brian JohnsonSo usually we want to give them 24 hours of seizure freedom before we start to wean the IV anesthetics. There are cases where you know that first round of seizure suppression doesn't work, and then you have to try it again. And there have been some patients where we've done birth suppression or seizure suppression trials for up to a month after they initially presented. And you know, some of the patients, if they die, it's usually a complication of their ICU stay. It's not necessarily from the seizures themselves, but we have had some really good success stories of patients that we've kept trying. And eventually on the you know, seventh or eighth time that we tried seizure suppression or birth suppression, when we weaned it, they weren't seizing any longer. So, you know, those patients can wake up and go back to living their their life as before. You know, they've been in a bed for a month, so there's a lot of rehab with that, but it's not it's not a uniformly fatal medical problem.
All right. And our patients that have known epilepsy, are there things we can give them at home for that acute treatment of a seizure?
Dr Brian JohnsonYeah, that's a great question. Previously, the only things that we had available to give patients at home were rectal diazepam. And rectal diazepam works in kids, but in adults, a lot of people are not willing to give a medicine rectally. And it takes it takes a while for the medicine to be absorbed. In the past five, 10 years or so, we've had a couple of medicines the FDA approved for the treatment of status epilepticus at home or clusters of seizures. Um, and these are intranasal medicines. So there's intranasal midazolam and there's also intranasal diazepam. And those are indicated for prolonged seizures. So I usually tell my patients a tonic clonic seizure lasting more than three minutes or a cluster of seizures. So more than two or three seizures within a day for me would would indicate that maybe the patient needs a rescue, intranasal benzodiazepine. You do have to watch out with those medicines that the patient maintains their airway, especially the first time. I usually tell patients you should still call EMS after you give the medicine to make sure that their breathing's okay. But so long as they've stopped seizing and they're coming back to normal, they don't necessarily have to go to the ER. The reason it's really important to give these medicines at home is that benzodiazepines work best if you give them early. In the brain during prolonged seizures, you start to internalize your GABA receptors, and that happens actually fairly quickly. And so the longer you wait, the harder it is for your benzodiazepines to work, uh, or will have they'll have to work harder the longer that you wait to treat. So it is important to treat them as as early as you recognize that they're not going to stop seizing on their own. It's something that I I try to prescribe for all my patients who have a history of prolonged seizures or seizure clusters.
Jamie Sessions MSN, RN, CENSo we've got our patient all tidied up, we've got them back to baseline, they're discharged, and now they're seeing you in the clinic.
What h seizure medications are you reaching for to help them with long-term management?
Dr Brian JohnsonSo if you aren't sure what type of epilepsy they have, there are three that we oftentimes reach for: levetiracetam or Keppra, lamotrigine or Lamictal, and zonisamide or Zonegran. These have all been on the market for at least 20 to 30 years. They're all generic and they're fairly broad spectrum anti-seizure medicines. They treat both generalized and focal epilepsies. Levetiracetam or Keppra is a medicine that we try to avoid in patients with mood disorders. It can cause irritability and suicidality in those patients. Lamotrigine is probably the best tolerated and probably the most effective of those three for focal epilepsies. It's a mild stimulant and a mood stabilizer. You do have to watch out for Stephen Johnson syndrome, which is a dangerous, potentially life-threatening rash. And so it takes about six weeks, though, to get up to a full dose. So if your patient's having lots of seizures, that's probably not the best medicine to reach for, but it is our best tolerated and most effective. It just takes a while to get there. And lastly, zonisamide. I think about zonisamide um sort of like a newer version of Topamax or Topiramate. It's nice because it's once a day. So if you have a patient who you think uh will have problems with non-adherence, it's a good medicine for that. It does increase your risk of kidney stones. And so I always tell my patients to drink lots of water with that medicine, but it is also another great medicine. If your patient has known generalized epilepsy, specifically juvenile myoclonic epilepsy, Depakote or valproic acid has been shown to be the most effective medicine in that population. You do have to watch out for things like liver toxicity and osteoporosis with Depakote, but in your generalized epilepsies, it's probably more effective than your other medicines. In young women, I usually try to avoid Depokate if I can, especially if they're thinking about having children. It uh lowers the IQ of children born to mothers who take Depakote during pregnancy. So it is something to keep in mind if your patients wanting to have children. There is a newer seizure medicine that was released a couple years ago, Cenobamate or XCOPRI. It's specifically indicated for patients who have medication-resistant epilepsy. So they're they've tried at least two seizure medicines and are still having seizures. And it's probably the most effective seizure medicine that we have for focal epilepsies. But we do have to watch out for a dangerous, a dangerous allergy to this medicine. So it does take a couple of months to start the medicine when we started. So that the allergy is called dress syndrome, but it is is probably more effective than our other seizure medicines. So it was a pretty exciting development. A lot of places will require you to try Cenobamate before you pursue epilepsy surgery. So that's that's how effective um the medicine is.
Jamie Sessions MSN, RN, CENOkay, yeah, I was just gonna ask and you kind of answered, but in these newer anti-seizure medications that we're seeing, we're seeing better seizure control or fewer side effects, or both
Yeah, generally speaking, the newer seizure medicines are not more effective at controlling seizures, with the exception of Cenobamate. What we see is better tolerability, fewer medication interactions. The older medicines, so phenytoin, phenobarbital, and carbamazepine, those are all metabolic inhibitors. So they will increase the effective dose of other medicines. And um divalproex or Depakote is a metabolic inhibitor, and so it will increase the effective dose of other medicines. So you have to watch out for those side effects with the older seizure medicines. So that's why we reach for the newer ones usually. Fewer effects like osteoporosis, metabolic syndrome are also present with our newer seizure medicines.
Jamie Sessions MSN, RN, CENThanks for being my guest again on Brain to Bedside Dr. Johnson. We appreciate you being here. And thank you for everyone for joining us. We hope you learned something today., Again, if you enjoy this episode, please share it, subscribe, and we'll see you back here soon.