Comprehensive Management of Dravet Syndrome - Episode 6

Dravet Syndrome: Management of Treatment

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Joseph Sullivan, MD, and Elaine C. Wirrell, MD, discuss the management of seizures for Dravet syndrome with different approved therapies.

Joseph Sullivan, MD: I’m wondering, how do you approach that? You have a patient who comes to you on 4 medications, do you try to rock the boat a little bit?

Elaine C. Wirrell, MD: Definitely, especially if their seizures are not well controlled. We don’t often now see kids on contraindicated medications, but you still need to look at that. So if they’re on a sodium channel agent or they’re on lamotrigine, those are medications that I tend to try and get rid of because we know that those actually can exacerbate seizures. For the other medications, each child is individual. You may have one child where valproic acid was super effective, and then another child where it really did squat. What I often will do is I’ll say, “Look, your child’s on 4 medicines—rate them. Which one do you think the child is responding to the best?” Get them to rank them 1 to 4. Then [ask], “Which one do you think is causing the most side effects?” By doing that, I think it’s helpful because you get the family’s perspective on what they feel has worked best for their child and I think that’s much more helpful info than you can get from looking through reams and reams of medical records. Then you can make a decision on which one you want to try and get rid of.

Joseph Sullivan, MD: Absolutely. I find if you just mention one, you’ll often get a reaction— “No, don't take that one away.” “That one was life-changing for us.” As opposed to others, they’ll just be like, “Yeah, and in retrospect, I don’t think that did squat.” Then I know that if the families really can’t tell, which again most of them can, then what I personally do is I try to look at the potential side effect profile and eliminate the one that may. Again, maybe they’re tolerating it, but a lot of these kids have been on these medicines for many years and so it’s hard to know what “Johnny” looks like without sodium valproate, for example. We keep bringing up sodium valproate, valproic acid, you and I, and some of our colleagues, work together on consensus guidelines to try and put some months of order supported by the data if it existed in terms of how we should approach the treatment of these patients. I recall having our few calls and at that time meeting in person to discuss this project. I think we were surprised that a lot of what we were doing was really not rooted in much data. Valproic is a very broad-spectrum anti-seizure medication. As you’d already mentioned, [with] all these different seizure types that unfortunately occur in this patient population, it seems to make sense to pick a broad-spectrum medicine. We came to the conclusion that valproic acid and clobazam were sort of the first-line syndrome specific treatments. I quantify it in that way because these patients don’t come in saying, “I have Dravet syndrome.” They come in with their prolonged seizure. Maybe they’re diagnosed with febrile seizures. Maybe they’re diagnosed with epilepsy and put on levetiracetam, and then the genetic testing is done and it’s, “Oh, you have a truncating mutation, the SMC1A gene and you have Dravet syndrome.” In my opinion, at least. It doesn’t mean they need to be immediately switched to valproic acid or clobazam as soon as you have this Dravet diagnosis if they’re doing well on levetiracetam. Are you going a few months seizure-free? Are you not having episodes of status? Then that’s OK. You can keep them on levetiracetam but unfortunately, we know from the natural history that it’s highly likely that seizures are going to pick up again in the setting of levetiracetam, and then we would reach for something like valproic acid or clobazam. Then along that same exercise, as we learned from our search, there’s often these often suboptimal [treatments]. Could you go through the second-line treatments that we sort of came to the conclusion in that consensus?

Elaine C. Wirrell, MD: Sure. Just a comment on the first-line treatment. The responder rates for both of those medications was between 25% and 50%, so they were certainly not cureless for most kids. Second-line, we had a ketogenic diet that was reasonable, and I think many people still use that pretty early on in treatment. I’ve certainly had good success with that in kids with Dravet syndrome. Topiramate also; there’s limited data to suggest that that might be efficacious. Then stiripentol, although it wasn’t available in the U.S. yet. It is now for a prescription, but it wasn’t then. Many of us were using it anyways, and we’re finding that it was beneficial second-line for Dravet syndrome. Particularly with reducing status epilepticus.

Joseph Sullivan, MD: Absolutely. I know we have some colleagues to whom we really need to pitch the ketogenic diet in a nonjudgmental way. Don’t get me wrong. We know it’s difficult. It changes how someone eats and already, you may have a child who is a picky eater and is difficult to care for, so limiting their diet even more just may sound like a crazy idea, but certainly, it is much easier today in 2021 than it was 10 years ago with all the availability of these low carbohydrate products that are still healthy and well-balanced for their overall growth and development. Certainly, families need to give them the benefit of the doubt. I think if they do it and it works, they will say, “Why didn’t I do this sooner?”

Elaine C. Wirrell, MD: We have phenomenal dieticians who can be very creative and make this easier as well for the child and family.

Joseph Sullivan, MD: I should mention, this should not be done on your own. It really should be done with guidance and expertise of an epilepsy dietician that can really help you with this.

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Transcript Edited for Clarity