Dravet Syndrome and Lennox-Gastaut Syndrome: Perspectives from the Patient Journey - Episode 5
Kelly Knupp, MD, leads a discussion on goals of treatment for patients who are earlier in their treatment journey.
Kelly Knupp, MD: Generally, regardless of the time period that I'm seeing patients with Dravet Syndrome, I generally talk to them about all of the treatment options and really emphasize to them that it's not an issue of whether you're going to be on one of these medications. The question is when. And so, at some point in time in your child's lifespan, you are probably going to try ketogenic diet, fenfluramine, stiripentol, depakote, clobazam, Epidiolex, probably VNS, and some other seizure medications, as well. We know that, in most children with Dravet Syndrome, we don't usually get to seizure freedom, and so a lot of this is trying to find the right time to do this. I usually try to stay one or two medications ahead of where we are at, so that people are thinking ahead of time, "if this doesn't work, what are we going to do next?" So that it's an easier decision that they're not surprised by when it happens. I think it also gives both of us a little hope that we have a plan, and if this doesn't work we've got something else lined up to start next.
For that young patient who in my practice usually comes to me on Keppra, I usually talk to them about what behavior looks like now is that manageable, because Keppra can exacerbate behavior in these children who are young and are usually really, really busy to begin with, and is that manageable. And then we talk about, what next steps do we want to do. We have recently started using ketogenic diet at younger ages, in part for family preference, and it seems that we're getting a little bit more benefit at younger ages than at older ages. And so, we think about that, but I also talk about clobazam and depakote as probably our next steps, that ideally I'd like to start fenfluramine, but because of cost and insurance reasons, that doesn't usually work out well. And so, we may have to move towards the combination of clobazam, depakote and stiripentol before we move on to fenfluramine. And, then our goal is to try and find a good balance of quality of life and seizure control. While ideally we'd like to be seizure free, if we're overly sedated as we're trying to get to seizure freedom, that may not be a good balance, and that we always have to keep that balance.
Joseph E. Sullivan, MD: You've mentioned a lot of different medications there, and we'll probably maybe try to unpack each of those, but before we do so, I'd be curious: What do you consider, and this is probably going to depend on age and a lot of other factors, but what do you consider optimal control? You mentioned that it is uncommon for an unreasonable expectation to expect seizure freedom, but what is your goal? Let's start with a younger patient that's less than five years of age.
Kelly Knupp, MD: For somebody under five, my first goal is that we're having no visits to the ICU or the ED. If we're still visiting the ICU or the emergency department, we absolutely have to change something. And I think that we can often be pretty successful in reducing duration of seizures, with a combination of both a good emergency plan at home, as well as using medications. I often find in that situation, stiripentol is really helpful. I've used fenfluramine a lot, but I haven't used it as much in the younger population, and so I'm still waiting for more clinical experience to see how well will that work in avoiding the episodes of status that we see in these younger ages. I suspect that it's pretty helpful, but I think we have to keep thinking about it. I think those are the things that we think about: what is the goal? Ideally, it's seizure freedom, but if we're starting to see side effects to medication, that may not be the best goal. So, I think for each individual family, you have to discuss what the goals are, and it's often a little bit better seizure control than what you have right now.
Joseph E. Sullivan, MD: I think it takes time when we're talking about starting a new medication: these medications take time to work. There's a lot of variability just in each individual. Someone may start out with weekly seizures or a few seizures a week, or a few seizures a month, and so how I go about it is: I need to know where we are starting from. And then, yes, seizure freedom is of course our goal, but let's start medication A, at a low to medium dose and then give that some time. There have been certainly times when I've wanted to start something, because I felt like the trend was going in the wrong direction and a parent pushes back, and lo and behold, the next few months things kind of stabilized. I'm thinking this happens both on the clinician side, the provider side, but also on the parent side. There's this one group that wants to completely try to cycle through medications and squash out every seizure, and then there's another group that's like, "Oh, I'm not sure if I'm ready to move on to a new medication." So Mary Anne, I'm wondering, where do you fall in that, and maybe that's changed for you over time, but reflecting back with that first diagnosis, we didn't know as much as we know now: what were your perceptions at that time?
Mary Anne Meskis: Well, first of all, what I would qualify as the number of seizures that is acceptable has changed dramatically. I thought, after he got this diagnosis: now we're going to aim for zero seizures, and then had the stark realization that there's no real game plan. We do have first and second- and third-line treatments that we can look at and use, but it varies from patient to patient and certain combinations might work better; we have always erred more on the side of caution. I had experiences early on listening to some other parents who have older children than me that were on treatments that they were getting seizure control, they decided to mix things up, and then they weren't happy because seizures increased. And then, when they tried to go back to the original medication or combination of medications, they were never able to get back to that baseline. So, my son has been pretty much on the same treatment since age of four. we did try new medications that had come to market, but they haven't proved to be beneficial for him as much as that original combination. And so, for us, we wanted zero seizures, we're not happy with not having status seizures, and not ending up in the hospital or the ER, as Kelly said. So we continue to have one to two seizures a week, that are pretty brief and typically resolve on their own.
Transcript Edited for Clarity