Current Series: Treatment Advances In Dravet And Lennox Gastaut Syndrome


Anup Patel, MD: Speaking of Lennox-Gastaut, how common is that, Elizabeth? And tell me a little bit about the symptoms and how those present.

Elizabeth A. Thiele MD, PhD: Sure. So Lennox-Gastaut, similar to Dravet, is one of our really difficult-to-treat epilepsy syndromes in childhood. And it’s quite different and distinct from Dravet. As Ian said, Dravet has a very stereotyped presentation in early childhood, and many of the kids have a result of a single gene. LGS [Lennox-Gastaut syndrome] is quite different, and the onset is usually later and the onset is not quite as stereotyped.

Typically, kids have onset of Lennox-Gastaut between 3 and 5 years of age, and many of the kids, prior to developing what we would consider Lennox-Gastaut, have other seizure types or other neurologic difficulties. And then as Lennox-Gastaut develops, the children will develop, similar to Dravet, mixed seizure types, typically tonic seizures, drop seizures which often result in injury, tonic-clonic seizures, and frequently, atypical absence seizures, which for some of my kids occupy the majority of their day. They spend just hours with atypical absence seizures. But because it’s an evolution, it can actually take longer to diagnose LGS. But LGS is wickedly common, and we think that probably about 4% of pediatric epilepsies would be consistent with LGS.

For the diagnosis, you not only need those seizure types, but really to be a purist you also want to see slow spike-and-wave on any EEG [electroencephalogram]. And that can also not be present quite at the onset. So diagnosing LGS can be a little bit more difficult and take a little bit more time. So as a pediatric epileptologist and neurologist, we need to keep stepping back and reassessing what’s going on with our patients and does this fit. Is this suggestive that this child is developing LGS?

Anup Patel, MD: Elaine, if you could comment on that triad that Elizabeth mentioned and how that changes over time, and I think Eric alluded to some of that as related to the challenges. But tell me about how that changes.

Elaine C. Wirrell, MD: I think one of the characteristic seizure types that we see in Lennox-Gastaut in young children are the drop seizures, the atonic seizures. And as you go into adulthood, those often resolve or significantly decrease. Most adults with Lennox-Gastaut will still have some degree of tonic seizures. Many of them will still have atypical absence. But also the very characteristic EEG changes that we see, the slow spike-wave, is often not there in adults. One clue though that I think that persists in most adults is still to see that generalized paroxysmal fast activity on EEG, so that’s important to look for. But the classic triad that Elizabeth mentioned, the slow spike-wave, if that’s what you’re looking for in an adult, you may not get that diagnosis.

Anup Patel, MD: Eric, as we transition and you alluded to this, from paper records to electronic records, how can we help our adult colleagues to not misdiagnose or forget the diagnosis?

Jesus Eric Pina-Garza, MD: I’ll tell you a couple of tips. One is that first, to look at Lennox-Gastaut as a great work from Dr William Lennox and Dr Henri Gastaut, but like everything, we have to update it and make it better. So they gave us like a still life, but Lennox’s study is a movie. The only 3 essential factors of Lennox-Gastaut are having an etiology for epilepsy, any of them; refractoriness early on, not forever but early on; and a childhood onset, of course. If you have those 3, you don’t have to have any gene that makes you have Lennox-Gastaut. There may be some genes that may make you more prone to development, but that’s what you need.

So this movie has a lot of different scenarios, and the good thing, even though we call it an intractable epilepsy, what we mean is an uncontrollable epilepsy because we’re treating it and it’s not controlled. But it can be controlled, so we have movies that have a good ending. We have movies where you can actually prevent the devastating effects of Lennox-Gastaut. We have movies where actually iatrogenic effect is a factor. Like someone with Dravet who never gets the correct diagnosis or treatment, you can make it go into Lennox-Gastaut. So we have a lot of different directions of this movie.

I agree with the comments earlier about how many factors can make you miss the diagnosis. We came up with something that can be used. There are many different ways of doing it, but we have a paper on epilepsy and behavior that is called “Refractory Epilepsy Screening Tool for Lennox-Gastaut.” And it’s trying to tell you that most of the patients, if you look at major and minor criteria for Lennox-Gastaut, you can look at the traditional triad, which is cognitive regression, multiple seizure types, the 2.5 Hz spike and a slow wave, and childhood onset. Those are major criteria. But you have minor criteria.

If you see an epileptic walking in your clinic with a chin laceration, very specific for Lennox-Gastaut. So you have to look at the sort of things that may tell you, hey, this is Lennox-Gastaut—helmet use, facial injuries, refractoriness to vagus nerve stimulation surgery, ketogenic diet, all these things. So, when you look at major and minor criteria, it’s a very tiny tool that if you check, most of the refractory epilepsies have 1 or 2 of the major criteria and maybe 1 or 2 of the minor. Lennox-Gastaut usually has 3 or more of the major and 3 or more of the minor. So with that simple thing that we actually check by medical students reviewing records, it’s very reliable. You don’t have to be an epileptologist to say this is possibly Lennox-Gastaut.