New Advances in the Treatment of Dravet Syndrome

Trevor Resnick, MD: Lennox-Gastaut [syndrome] is an epileptic encephalopathy—[it’s] very, very difficult to control the condition—that’s characterized by an abnormal pattern on the EEG [electroencephalogram] with a slow spike and slow wave pattern of 1.5 to 2 Hz, [and it has] different seizure types. But the 1 important seizure type that you need for the diagnosis [is] the presence of tonic seizures and finally cognitive regression. So those are the 3 core criteria for Lennox-Gastaut syndrome.

It’s interesting that fulfilling criteria for Lennox-Gastaut syndrome is frequently used as a population of patients for the newer antiepileptic drugs to test their effectiveness. And the reason is because if we had a single drug that was effective for Lennox-Gastaut, we wouldn’t be able to do any of these studies. So we’re always looking for different options and effective medications in the treatment of Lennox-Gastaut syndrome.

Dravet syndrome again is another difficult-to-control epileptic encephalopathy that is characterized by initially normal kids who start having febrile seizures—often prolonged febrile seizures—in the first year of life, and then they evolve into having febrile seizures or seizures without fever, often hemiclonic seizures. And at that point, they also start having cognitive regression, [known as] ataxia. And about three-quarters of them are found to have a mutation in the SCN1A gene.

This is an interesting medication because it actually was discovered observationally to be effective in patients with Dravet syndrome a number of years ago. And more recently there have been controlled studies demonstrating its effectiveness in this population, and now randomized controlled studies [are] comparing it [with] placebo with a very gratifying benefit using the 0.8-mg dose…. I think 63% greater effectiveness,…so it works. [There is another] interesting thing that they did in the study…. As physicians, we want numbers. We want to know that there’s a median percentage reduction in seizures or a responder rate that gives us an idea of how well the medication works.

And it’s interesting that the parents’ perception of improvement was present once there was more than I think a 44% reduction in seizures. So obviously, in this study, the drug had a 63% reduction as compared [with] placebo. So it was way above that, and in that group of patients, there was a significant or really meaningful improvement in quality of life. It’s really a balance between parents’ perception or quality of life and the numbers that we’re looking at. And this study did look at both and did demonstrate that there was a gratifying improvement with this medication, especially at that 0.8-mg dose.

The syndrome is interesting because it’s mostly related to this gene mutation, and I think 1 of the important things that we learned when the gene mutation was first discovered was not what drugs to use but specifically what drugs not to use. And medications like some of the sodium channel medications, lamotrigine—these were drugs that made the patients much worse. And there was a significant improvement in how these patients did once we stopped using those drugs. So that was the first breakthrough with the discovery of this gene mutation. Subsequent to that, we looked at other kinds of therapies—such as fenfluramine in the study [and] the ketogenic diet—that have really improved these patients’ lives and morbidity.