Dravet Syndrome and Lennox-Gastaut Syndrome: Perspectives from the Patient Journey - Episode 14
Joseph E. Sullivan, MD, leads a discussion on treatment options for the management of patients with LGS and considers the impact of treatment on quality of life.
Joseph E. Sullivan, MD: Thankfully despite the sobering statistics that Kelly you said about seizure freedom we do have a lot of treatment options for Lennox Gastaut. Go back into the late 90s, medications topiramate, lamotrigine, and then more recently somewhat renewed interest in Lennox Gastaut patients with cannabidiol and fenfluramine also and then Kelly you had mentioned surgical options for these patients whether that be vagus nerve stimulator or something that maybe barbaric but corpus callosotomy but can be very, very helpful for some of these patients. Acknowledging Tracy like these are thousands of seizures a week sometimes and we have these sobering statistics of 20 to 30% reduction in seizures. Kelly, during our prior conversation trying to minimize polypharmacy. You can see there are lot of moving parts here, so you’re starting out at a baseline of thousand seizures a month let’s just say and we are going to get 30% reduction with the first medication. Tracy, if you’re meeting me for the first time we are going to get Savannah down to 700. Is that just like don’t go there or is that the best you can, or I’ll take it?
Tracy Dixon-Salazar, PhD: It has to be a conversation in a larger picture, going from a thousand seizures a month to 700 does not have a huge improvement on quality of life. But we know that not doing anything – if we know not trying that next treatment, we have zero percent chance of responding and we know that patients who are in placebo arm of epilepsy clinical trials are more at risk of SUDEP. For many reasons, we don’t want to let these seizures go out of control plus they are causing these brain changes and these damages. In the context of this bigger picture, we want to be fighting back against the seizures even if we may not achieve seizure freedom is the way that I would approach it with families and I do think if you look longitudinally and this is a little hand waving when you look at the data but if you look at older studies on LGS it was like 95% of patients continued to have seizures into adulthood. If you look now, it’s somewhere between 85% and 90%. They are still having seizures, but I think it’s slowly going down and while we don’t have the data I do think LGS is living longer. We are moving in the right direction and we are finding treatments that are specific for LGS. You can say yes maybe the numbers are dismal, but you can also flip it and say in the cannabidiol trial 8% were seizure free. And this percentage – I don’t know the percentage of the top of my head has 75% reduction because I will tell you that there have been some studies on this and there is something like 65% reduction in seizures is the tipping point for quality of status. I don’t know I mean it has not been replicated but there is a number there and certainly at 75% reduction and higher in seizures. But framing it that way is more attractive than we are going to get you down from 1000 to 700 seizures. It’s like we need to fight back against these because they are not OK. We are not going to normalize seizures. They are not good for your brain. They are a sign that something is wrong, and we are going to fight back or if they don’t like the fight language you can say we are going to push back, we are going to do everything we can to get them to the lowest number possible.
Joseph E. Sullivan, MD: So glad you said that. It was almost like a softball. I was hoping because when we read these clinical trials for the purposes of reporting the paper and for getting regulatory approval, they look at 250 patients and look at the median reduction in seizures and they come up with the number. Statistically significant and placebo but then you look at some of the subsets and even though it may not reach statistical significance we are all scientists here and yes we know that there is chance and what not. But if 8% of patients have seizure freedom or 75% reduction in seizures, does it matter if it’s a chance. That’s like I’ll be a little bit flippant.
Kelly Knupp, MD: We won’t know if that could be you unless you’ve tried.
Joseph E. Sullivan, MD: Exactly. That’s where I use these studies in my counseling to say this is what we can hopefully expect. We can set our bar at this, but this is the bell curve, we are hoping that you are going to do a little better, I appreciate you doing this. I am curious Kelly you were going to say something then.
Kelly Knupp, MD: I just wanted to make sure we circle back a little bit to talk about epilepsy surgery because for providers who maybe listening in and for families to think about this. When you look at the overall data in patients with Lennox Gastaut the intervention that is most likely to make somebody seizure free is resective surgery and certainly not all patients are candidates for that. But as an epileptologist it is sometimes challenging to think about doing a receptive surgery in somebody with Lennox Gastaut because it’s a network disorder and what we see on our EEG are just charges everywhere. That causes us to pause to say boys is it worth this surgery in this patient who has focal lesion on their MRI, has a combination of different seizure types, some of which are focal coming from that lesion because we see abnormalities in other places and is it worth it to take this patient to surgery, are we going to see improvement. But the data suggest that we do see improvement in those patients. I think it’s an important thing for people to keep in mind that in a patient with Lennox Gastaut who has a lesion on their imaging and has some of their seizures coming from that lesion that they are – that intervention is more likely to lead to seizure-freedom than additional medications. I think it’s worthwhile at least mentioning that and think about it a little bit.
Joseph E. Sullivan, MD: Absolutely. And as a plug for pediatric epilepsy specialist who just because we are aware of this and we may not feel that it’s going to be half of our patients but if we know about the lesion, if we know that this is a network disorder even if the EEG is not necessarily congruent we know that these patients actually and it takes a little bit of leap of faith but I see discharges everywhere but there is just one right frontal lesion, we are going to go after that. But I agree those are the cases that can be life changing. Tracy, you wanted to say something about surgery.
Tracy Dixon-Salazar, PhD: I absolutely agree. We have to stop thinking about it as a last resort. I mean by the time you get an LGS patient, I love the way you said this Kelly is that you don’t see new-onset epilepsy. By the time you have LGS diagnosis, these families have been through it. You’re coming in at a much higher level in the conversation and whole tone of the conversation changes and now it’s time to bring surgery to the forefront. Surgery is more and more data is coming out on deep brain stimulation, on responsive neuro stimulation, on corpus callosotomy, and on resective surgery which has great numbers. There are some great papers out there showing that if you remove the focus that you can normalize the generalized EEG by removing the focus in LGS patient.
Kelly Knupp, MD: That’s the network.
Tracy Dixon-Salazar, PhD: Yes, it’s huge. You’re disrupting the network. Of course, none of us are lining about the door for brains surgery for our young children but I would rather have been presented with brain surgery early on and then like we need to move forward on this knowing what I know now about LGS. Knowing how devastating LGS is, it’s like you need to be aggressive a little bit earlier but you need to be aggressive smartly. We were aggressive with polytherapy. My kids were she was on 8 treatments and most LGSers are on 4 to 5 treatments on average if you take a poll. You maybe not as smart about that but being smart and aggressive in the beginning we know if we can make an impact earlier in the onset of this disease that it can have lasting consequences and often when you do get an improvement like that patient who was an adult who had resective surgery missed it, he has a lot of cognitive damage from the years of seizures but if we had intervened on that earlier he would have been much better. I think being smart about it and offering that to families and having an honest conversation and cancer never cuddles, they are like you have 3% chance of living. If you add radiation then that gives you an extra 3- 6 months. By the time you get LGS we should just be honest and presenting the data to our families, presenting the options and having the conversation with them so that they can make the best possible decision for their loved one. It’s a brutal thing to consider brain surgery and to do it and to have done one that wasn’t successful but it’s also brutal never have been given that option.
Joseph E. Sullivan, MD: Yes, you have to be willing to ask the question as a provider just as much as we are expecting parents to consider trying one of these medications to give you a better chance like you said if you don’t try it, it’s 0%. At least if you try you will get something and you can make that decision whether or not that’s worth it for your child and your family but I think with surgery if we are not offering people aren’t usually coming in saying what about brain surgery, although sometimes they do.
Transcript Edited for Clarity