Non-Drug Therapies for Dravet Syndrome and LGS


Anup Patel, MD: We talked a little bit about vagus nerve treatment in Lennox-Gastaut versus corpus callosotomy versus dietary therapy. I think it’s great that we have the experts as far as dietary therapy with us today. Comment about that, Elizabeth. Where specifically do you go to dietary therapy versus when you’re going to potentially consider the vagus nerve stimulation [VNS] or corpus callosotomy?

Elizabeth A. Thiele, MD, PhD: Well as I said, I’m a self-professed zealot for dietary therapy. So we would go to dietary therapy in any child with refractory epilepsy, not just LGS [Lennox-Gastaut syndrome], not just Dravet. And we typically start thinking about the use of diet after the second medication. Some families come in and are very anti-medication, would like to go on the diet first-line, and then it’s an education of the family that you already have a child who feels different because they have epilepsy and now you’re going to totally restrict what they’re eating. So we encourage families to consider a medication, at least 1 or 2 medication trials.

Kind of educating that particularly the new medications are not poisons. They’re all well pretty well tolerated. But after the second medicine we frequently will put kids on diet. And if we have a child and we’re down to the point where they’ve been on several medications, is it diet or is it VNS, we would always; but again, we’re zealots and we have a big diet program. So that wouldn’t be universal, but we would always encourage a family to try the diet before moving on to any surgical intervention, unless the resective surgery was their next possible…if you’re talking VNS versus dietary therapy, we would always try diet first.

Ian Miller, MD: Related to the dietary therapy and medication options and the kind of opposition to medications, for whatever reason, my experience has been that families are a lot more amenable to cannabidiol than they are to chemicals, or medications, for instance. So that distinction is obviously quite arbitrary and emotional, but nevertheless, if the parents are open to it, it gives us an opportunity to use something that’s a little bit easier, in my experience. So there’s a reason we don’t do the diet first; it’s difficult.

I think it touches a little bit on something that you said earlier. Way earlier in our conversation we were talking about what medications the formulations are and how liquids are incompatible with the diet. And it’s just important to remember that cannabidiol is compatible, thankfully, with the diet. I think because of careful synthesis and choice of carrier when they formulated it.

Elizabeth A. Thiele, MD, PhD: To go back real quick to something you just said…I’m saying the diet is difficult, and the diet is difficult. But as a mother of a Dravet kid once said to me when she asked her neurologist about the diet, and the doctor said, “Oh, that’s much too difficult,” her words I will remember forever. She said, “Nothing is as difficult as watching your child have seizures.” So that’s why I agree. The diet is difficult, but that’s why I think it’s always important to offer it to families, because many families are able to do it and want the opportunity to do it. Again, because it is also more natural than many medications.

Jesus Eric Pina-Garza, MD: I absolutely agree with that one because in this area, we don’t have a good piece of evidence-based medicine that says: This option is better than that. So clearly our job is to offer all the options. In this area some of the parents are going to have a different view than what we have, so we just have to guide them. This is the plus, this is the minus of the diet. This is the plus, this is the minus of the VNS; and this is the plus and minus of the alternative new therapies that we have. And sometimes what I do is, like if it was me or it was my child, I would do this one, but it’s just a very small difference in my decision, so what do you think?

Anup Patel, MD: And I want to touch more on the surgical options. But before we do, Elaine, is there a better dietary option of all those dietary options for kids born with Lennox-Gastaut? And how do you sort this out on which dietary therapy is important?

Elaine C. Wirrell, MD: Yes, so that’s a really good question. So I think, is there a better option? And the Koreans actually did a nice study, I think if you are less than 2 years of age, and oftentimes that’s not when we’re making our diagnosis of Lennox-Gastaut, but I think in a child who’s less than 2 years of age, there is evidence that the traditional or the classic ketogenic diet is more efficacious. I think when you look at adolescents and adults there’s certainly good evidence that a modified Atkins diet or a low glycemic index is certainly much more tolerable. I think you’re kind of in the gray zone between 2 and 12, and I think really have a discussion with your families, have that dietician who you work with have that discussion with the families and work out what is the best option for that family.

Anup Patel, MD: And Elizabeth, Elaine highlighted this and you did as well. Speak a little bit about the importance of a team approach for the dietary therapy and why it’s instrumental to have a dietary team on this.

Elizabeth A. Thiele, MD, PhD: To have a team for the diet is like wicked important and crucial to make it work. We always say the most important member of the team is actually the child, working with the child to figure out what they will tolerate, what they won’t tolerate with regard to restriction.

The second most important part of the team is the family and the dietician. I think the neurologist plays an important role as well, but it’s really the dietician who works very closely with the child, particularly with the classic ketogenic diet. We’re putting those kids in a state of ketoacidosis. So if the child is not followed carefully, then that child could end up with an intercurrent illness of having a significant metabolic acidosis.

But really I think the importance of the team is not only keep this child safe and watch their growth while on the diet, but it’s really how do you work as a team to optimize the diet as a therapy for the child. If a child is eating bacon as a part of their diet and one morning wakes up and hates bacon, it’s got to be that team. Again, the family, the child, the dietician working on how can we reformulate this to make it acceptable and more palatable for the kid. I don’t think it works without having a cohesive team. We sometimes feel like we’re cheerleaders for kids on a diet, and I know the parents do as well. But the team is really important.

Anup Patel, MD: I worry that because the ketogenic diet has become more mainstream that folks are going to try to take this on their own. I don’t know if you guys have had that experience with your patient population yet. Ian, can you speak a little bit to that?

Ian Miller, MD: Yes, I’ve definitely had parents come in and say, “Oh, I read about the diet on the Internet, and so, we’re on it, right.” And so 99% of the time they’re doing their best, but realistically they’re not in ketoacidosis, if you check their urine ketones or their blood ketones. And they’re maybe doing a lot of the inconvenience part and not getting as much benefit out of it. So in those cases it kind of depends on the situation. It often isn’t super constructive to talk about that, if our goal is something else, as long as they’re tolerating it. But definitely it kind of earmarks something to come back to and revisit and try to get them on. At the very least, define what exactly it is that they’re doing and try to determine where are we in the glycemic index range versus the number of carbs versus a ketogenic ratio and identify where they are, so that if it turns out that they’re not using something completely optimally, we can revisit it in the context of the ketogenic diet clinic and then modify it a little bit to make it more effective.

Anup Patel, MD: And, Elaine, lastly I want to highlight a little bit about you have a patient who’s considering surgery, whether it’s corpus callosotomy, or the device of a vagus nerve stimulator, how do you approach that and what sort of evidence is out there as far as these therapies go for Lennox-Gastaut syndrome?

Elaine C. Wirrell, MD: Before jumping into surgery I think from my standpoint I really want to be sure that they’ve maximized medical therapies because surgery is irreversible, it’s done. Even the VNS, you’re not taking anything out but you’re putting something in. And then that’s going to be permanent…. So I think to really make sure that you’ve maximized your medical therapies.

I think for Dravet syndrome I have a lot of concern that corpus callosotomy or resective surgery should not be done in kids with Dravet syndrome. I think there is potential benefit from the vagus nerve stimulator. But I think callosotomy or resective surgery are not indicated, and many kids with Dravet syndrome may have an element of medial temporal sclerosis. Temporal lobectomies do not help them, and I think that’s an important thing to get out there.

For kids with Lennox-Gastaut syndrome, I think you’re then looking at what is their main seizure type and what is the most disabling seizure type. Corpus callosotomy can be extremely helpful and can markedly improve quality of life in children who are having recurrent drop attacks.

But I think if you have a child who has focal onset seizures, or atypical absences or things like that, that’s not a very good reason to do, and in fact that is not a reason to do a corpus callosotomy. So I think looking at what is your major seizure type, what are you hoping to achieve, callosotomy is very good if your big issue is recurrent intractable drop seizures. But I think otherwise vagus nerve stimulation is probably the road to go.

Jesus Eric Pina-Garza, MD: One point, we should not forget about felbamate. So we have all these therapies. We have a drug that is actually indicated for LGS. And the only reason we sometimes forget is because of the adverse effect profile and safety. But there’s still 1 in 10,000 fatalities from liver toxicity or aplastic anemia; it’s safer than the disease, which is 1% of the patients die every year.

So the point about Felbatol is that you should keep it at the end as one of your last choices, but possibly before surgical procedures, which also have a high mortality rate, even in the best hands.

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