Rare Childhood Epilepsies: Dravet Syndrome and Lennox-Gastaut Syndrome - Episode 1

Childhood Epilepsies: Dravet and Lennox-Gastaut Syndromes

Elizabeth Thiele, MD, PhD, and Elaine C. Wirrell, MD, discuss the commonality of childhood epilepsies, as well as the differences between Dravet syndrome and Lennox-Gastaut syndrome.

Elizabeth Thiele, MD, PhD: Hello, and thank you for joining this Neurology Live® Peers & Perspectives® presentation titled “Rare Epilepsies: Dravet Syndrome and Lennox-Gastaut Syndrome.” I’m Dr Elizabeth Thiele, a professor of neurology at Harvard Medical School in Boston, Massachusetts. Joining me is Dr Elaine Wirrell, a professor of neurology at the Mayo Clinic in Rochester, Minnesota. Thank you so much for joining us. Let’s begin.

Elaine, the large focus of your career has been on the early epileptic encephalopathies. Can you discuss how common are childhood epilepsies with an onset during their first year of life?

Elaine C. Wirrell, MD: Looking at epidemiological studies, the most common time for epilepsy to onset is in childhood or in older adults. If we look specifically in childhood, the highest incidence is in the first year of life. At that time, the incidence is more than 1 per 1000 children. It’s a high time to have epilepsy. If we look at the types of epilepsies that begin in the first year of life, you can put them into 2 buckets. The first will be the relatively well-behaved epilepsies, the self-limited epilepsies, usually focal—supplemented focal neonatal or infantile. Those children generally have normal development, and epilepsy goes away. While seizures are a problem when they’re there, it’s not a big long-term problem for those children. The other big bucket unfortunately is the developmental and epileptic encephalopathies. Those kids have very challenging seizure disorders and high rates of drug-resistant epilepsy. There are significant comorbidities often with severe degrees of intellectual disability and sometimes movement disorders and other comorbidities. Those tend to be more long term and less likely to resolve with time.

Elizabeth Thiele, MD, PhD: Two of the epileptic encephalopathies that you and I spend a lot of time thinking about and that have been in the news recently with the clinical trials. They’re Dravet syndrome and Lennox-Gastaut syndrome [LGS]. Can you briefly give an overview of those? The similarities, the differences, and how common these are in patients we see.

Elaine C. Wirrell, MD: If we look at both conditions, they make up a significant proportion of patients we see. As with drug-resistant epilepsies, the patients continue to be followed through the epilepsy clinics. Let’s start with Dravet syndrome. There was a nice study that looked at how common it occurs. It’s about 1 in 16,000 live births, and that was a nice study that came out of Kaiser Permanente in Northern California. That’s probably a bit less frequent than for Lennox-Gastaut syndrome. For Lennox-Gastaut syndrome, there haven’t been great studies, but there was a study out of Atlanta, Georgia, that showed about 1 in 4000 persons. Lennox-Gastaut was a bit more common.

Dravet syndrome typically presents in the first year of life. Some stragglers present up to 15 months, but for most of them it’s within the first year and usually around 6 months of life. The classic presentation is often with a prolonged seizure, a hemiconvulsive seizure typically triggered by fever. It’s when the child is ill, when they’ve had their immunizations, or when they’re in a warm environment. Those children are developmentally normal at the beginning, and then over time—typically 2 to 3 years of age—you start to see plateauing of their development. They’re not gaining the skills you would expect. They continue to have recurrent and often prolonged hemiconvulsive and convulsive seizures.

Usually around 18 months to 2 years of age, they develop other seizure types, like myoclonic seizures or atypical absences, and unfortunately, that’s a lifelong seizure disorder. For Lennox-Gastaut, those children may develop seizures early in life but it’s not Lennox-Gastaut at that point. With those children it takes some time to evolve, and most children with Lennox-Gastaut aren’t developing all the criteria for Lennox-Gastaut until they’re 3 or 4 years of age. Some of those children will start having seizures later around 3 to 4 years of age and will not have early onset seizures. The characteristic seizures that we see with Lennox-Gastaut are what we call tonic seizures, or stiffening, which can often be pretty subtle, and they’re picked up only on video EEG [electroencephalogram] if you do that during sleep.

The other very problematic seizure that most kids develop are what we call atonic seizures, or drop seizures. With those, the child falls, there’s no warning when that happens and there’s significant injury. In addition, they can have absences or myoclonic seizures or tonic-clonic seizures, sometimes even focal seizures. A characteristic pattern on the EEG shows the slow spike wave in the generalized paroxysmal fast activity. Many of those children are delayed from the get-go depending on what the underlying cause is. Once those seizures start to happen frequently, sometimes you can see a regression or even more significant plateauing of the development. In the long term, most of them end up with severe to profound intellectual disability.

Elizabeth Thiele, MD, PhD: Thank you. Another big distinction between the 2—I’ve spent a lot of time explaining to families and colleagues and trainees—are the etiologies. Dravet syndrome is a genetic epilepsy. The majority of children are found to have a mutation in the SCN1A gene, or sodium channel gene, whereas Lennox-Gastaut is an epilepsy syndrome with a myriad of etiologies. It’s important to note that distinction. Sometimes it’s confusing for families. You say my kid has Lennox-Gastaut, but I thought you said that they had tuberous sclerosis complex. Explaining the etiology and them having this epilepsy syndrome that could be tuberous sclerosis complex, lissencephaly, or lots of different things. With Dravet, even though not all the kids are found to have a mutation SCN1A, and there are certainly people with SCN1A mutations who don’t have the Dravet phenotype, it’s thought to be a genetic epilepsy. LGS is not.

This transcript has been edited for clarity.