Rare Childhood Epilepsies: Dravet Syndrome and Lennox-Gastaut Syndrome - Episode 2

Diagnosis and Triggers for Patients With Dravet and Lennox-Gastaut Syndromes

Drs Thiele and Wirrell explain how clinicians diagnose patients with Dravet or Lennox-Gastaut syndromes and the typical triggers patients will exhibit.

Elizabeth Thiele, MD, PhD: What’s the diagnostic route, do you think? Having the gene panels and everything has really changed and expedited for many people the diagnosis of Dravet. What’s a typical patient journey for both of those to be diagnosed?

Elaine C. Wirrell, MD: That’s a good question. When we look at diagnosing a specific syndrome or a specific etiology, it’s important to take the history and find the seizure types that the child is having. Ask questions about their development, anything significant and preexisting—for example, if they had a hypoxic-ischemic brain injury at birth. The history is important and focusing on those seizure types and careful semiologies. Moving forward to an EEG [electroencephalogram], looking for changes on EEG. With Dravet syndrome most of the early EEGs are normal or may show only some postictal slowing. We often don’t see a lot of epileptiform discharges early on.

For Lennox-Gastaut syndrome [LGS], as they’re evolving and clearly becoming Lennox-Gastaut, we see those 2 characteristic features: the slow spike wave and the generalized paroxysmal fast activity. The use of genetic panels, and those are increasingly being used, has allowed a much earlier diagnosis of many of the early onset genetic DEEs [developmental epilepsies and encephalopathies], including Dravet syndrome. It’s important. It’s not every child—not every SCN1A pathogenic variant is going to be Dravet. You need to look at the gene panel, the results there, the type of variant, and what we know about that.

Does that fit with what you’re seeing clinically? If you have a young child who’s had recurrent bouts of prolonged status from about 6 months of age and has an SCN1A, that fits pretty well with Dravet syndrome. We have to be cautious about not overdiagnosing Dravet in the milder SCN1A variance. For Lennox-Gastaut, it’s a clinical diagnosis, it’s looking at the seizure semiologies, looking at the EEG. As you said, there’s different etiologies and careful neuroimaging, genetic studies, potentially some metabolic studies. That’s going to be important because as we go forward, we’re starting to see a lot of these precision therapies, so it’s going to be important to identify not only the syndrome but also the underlying etiology. Is there a specific precision therapy for that etiology as well?

Elizabeth Thiele, MD, PhD: I agree with you. A large focus of my career has been on tuberous sclerosis complex. I’ve had a slide in my talks for 15 to 20 years. It says that even if you have the most effective, best-tolerated, safest treatment, like the silver bullet, it’s only good if you make the proper diagnosis. That’s where all this genetic evolution and epilepsies are transforming the way we take care of our patients. Your comment, that not everyone with an SCN1A mutation is going to have Dravet, is really important. Especially with these gene panels, particularly in young infants, I don’t know if they’re being sent after a first seizure or after a second seizure. If a parent gets that SCN1A mutation, the sky can fall pretty quickly. It’s important to put it in context for the families that this may or may not mean this child’s going to have a Dravet phenotype. Thank you for making that point.

The other thing about the journey with LGS, I remember I was in a meeting once when someone said that especially with the gene panels, we can make some of those diagnoses early. It could take a couple of years to figure out if the child is developing or evolving into Lennox-Gastaut. As a pediatric epileptologist, it’s always in our mind. These children have infantile spasms and then develop other seizure types. Could this be evolving into LGS, which is important, especially since we’re having more FDA-approved medications that are shown to be effective.

Elaine C. Wirrell, MD: That’s true. When you look at the evolution to LGS, oftentimes we as clinicians are very concerned about that. We see a child who has infantile spasms, and those spasms are not responding, and they continue to have them. Then those spasms get a bit longer and look at it like tonic seizures. You know what’s happening, but it often takes a year before the child develops all those features where you can say absolutely LGS at this point.

Elizabeth Thiele, MD, PhD: Years ago, when topiramate had just come out, I had a patient with Down syndrome who had spasms and was evolving. I was convinced this child was going to evolve into LGS. We could do samples back then. I gave them some Topamax to take home, but they never had to use it. We’re always watchful for it, and the patient community is also knowledgeable about it, or watching as well with the change in what the child seizures look like. We talked about the seizures in these 2 syndromes, but as we all know, and the patient community definitely knows, it’s not just the seizures with these 2 disorders or many other disorders we take care of. If you look at Dravet syndrome because a particular focus of yours has been Dravet, what would you consider the main comorbidities that kids, adolescents, and adults living with Dravet face?

Elaine C. Wirrell, MD: They have terrible seizures. In addition, a lot of other issues tremendously impact their quality of life and the quality of life of the whole family. One of the biggest concerns is the intellectual disability that we see. Most of those children don’t regress. Although it’s rare, they can. But if they plateau and don’t gain the skills you would expect them to gain, part of that is related to the frequent seizures. Even if you could completely control those seizures, the underlying channelopathy has a significant impact on development as well. If you look long term at those children, most are in this severe end of intellectual disability. Even with treatments that we have right now, our best treatments to control seizures don’t address that intellectual disability. That’s a very significant issue.

Looking at some of the behavioral issues, many children with Dravet syndrome have autistic features, and that needs to be addressed. As they get into their adolescent years, sometimes we see a lot of aggression happening. Many of them have sleep problems. Many of them have a sort of a characteristic crouch gait or gait problems. These entities extend far beyond the seizures for the family. Often the comorbidities can even be more problematic to the quality of life, as you know.

Elizabeth Thiele, MD, PhD: That’s also true with the LGS population. Depending on etiology, and the spectrum of comorbidities, a lot of these children with the developmental epileptic encephalopathies have intellectual disability and behavioral issues. Often autism is an issue. Often with Dravet there’s a crouch gait. Many of them have motor issues, tuberous sclerosis, multiorgan issues, etc. These patients and families are living with a lot more than just the seizures.

Elaine C. Wirrell, MD: Yes, absolutely.

This transcript has been edited for clarity.