What Is Dravet Syndrome? A Q&A with an Epileptologist
Medical Director of Neurology sits down for an interview on rare genetic epilepsy
Today is Dravet Awareness Day. To learn more about Dravet, we sat down with Scott Perry, M.D., medical director of Neurology and co-director of the Jane and John Justin Neurosciences Center. Dr. Perry has done multiple research studies on Dravet Syndrome and cares for more than 50 patients at Cook Children’s
What Is Dravet Syndrome?
Dravet Syndrome is a rare genetic epilepsy (1 in 25000) that begins in the first year of life with seizures in the setting of fever. Unlike typical febrile seizures, children with Dravet syndrome often seize every single time they have fevers.
They may also seize when they have mild elevations of temperature, for instance, after taking a hot bath or after being outside on a hot day. They are normal developing and healthy in that first year of life, despite the fact they have frequent febrile seizures. These seizures can be very long lasting, 30 minutes or longer.
Their initial seizures are often characterized as hemiclonic seizures, so they’ll be seizing on the right side of the body at one time and the next time they come in, it’s predominately on the left side. After the age of 1, they begin to have seizures in the absence of fever. They have multiple seizure types at that point including absence, generalized tonic clonic seizures, atonic seizures and tonic seizures. The seizure frequency often increases, their EEGs become progressively abnormal and the children themselves can have a stagnation in their development or even a decline in development as the epilepsy progresses.
In the first 10 years of life or so, seizures can be quite frequent and very difficult to control. Generally after that time the seizures slow down, but will still occur throughout life.
What are the current treatment options of Dravet?
The mainstays of treatment of Dravet syndrome are medications. The first being valproic acid (Depakote), another clobazam (Onfi), and another one called stiripentol. Beyond those three primary medicines, there are other medications that can be used with variable success in addition to dietary therapy and recently, medical cannabis or cannabidiol, has shown some promise.
Importantly, there are medications that are used to treat epilepsy that should not be used to treat children with Dravet syndrome. Those are medications that work on the sodium channels. Because the syndrome is a disorder of sodium channels, using medications that work on sodium channels actually makes these kids much much worse. Carbamazepine, Oxcarbazepine, and Lamotrigine are a few of the medicines that work on sodium channels that should be avoided in children with Dravet syndrome.
Does that happen often? That people put these kids on those medications?
Unfortunately, yes. Because those medications are typically used for focal onset seizures and when these kids first present they are having focal seizures people treating them logically say, "Well let’s put them on oxcarbazepine." When these kids get worse the next logical reaction to that is that they say, “Oh they are worse. Let’s give them some more. They must not have enough.” Then they get even worse. That’s actually one way that some of these kids get diagnosed. People recognize that these sodium channel drugs made them much worse, so maybe they have a sodium channel disorder.
I have been guilty of making this mistake. So even in my immense knowledge of this disorder, I have made this mistake.
What impact does Dravet have on the entire family?
It’s interesting that you bring that up because we actually did a project with the University of Washington in Seattle about caregiver burden of caring for Dravet Syndrome. We developed a scale that they are in the process of standardizing for clinical use. These families have difficulties caring for their other children because they can’t spend as much time on the activities of the other kids because they spend so much time focusing on the health care and safety of their kid with Dravet syndrome. Jobs, it’s difficult for both families members to hold down a job because somebody usually has to stay with the child. I imagine it’s difficult for the parents themselves to get much time with each other because one is probably up most of the night worrying about their child, while the other one is up most of the day. The amount of time lost from work and other obligations, community obligations, etc. caring for the child is pretty significant.
And it impacts the siblings too, right?
Exactly. They may not get to do all the things that they want to do. Or if they do get to do those things, if they do want to play baseball, maybe the family can’t take them to baseball all the time. So it’s your neighbors taking them. The parents can’t be there because they are at the doctor or the hospital.
What are some of the advancements that have happened in the care of patients with Dravet and what do you see for them in the future?
Dravet represents one of the best understood epilepsies since we know the genetic mutation that is the cause of the epilepsy. So that’s a really important thing. Understanding that has allowed us now to understand more about why it happens and hopefully get to a point where we understand how to treat it. People with other epilepsies or other genetic epilepsies should appreciate and support research that goes into Dravet syndrome because if you can figure out the genetic cause of one and figure out how to fix it, there’s a decent chance we might apply the same thoughts to other things and figure out how to cure other epilepsies down the road.
As far as big things that are going to come in the Dravet world … One thing is that pharmaceutical companies have increasingly recognized the importance of this syndrome, which is why you have multiple new pharmaceuticals being evaluated. Cannabidiol one. Fenfluramine, the other. Both trials we’re doing here. Some drugs being used in other syndromes are also being considered. The drug being used in muscular dystrophy that skips over the abnormality in the gene that causes the disorder to help make a more normal gene, they are looking at applying the same kinds of ideas in Dravet syndrome. If you could somehow skip over the abnormality in the SCN1A gene and make a more functional protein, might we be able to improve the disorder? Maybe? So those are some of the exciting things.
Several new drugs are probably going to be investigated in the future. They've got animal models that they can test drugs on to see which ones might be favorable and investigate it more. I mean who would have ever thought to look at fenfluramine. It was just part of a diet pill in the past. Somebody was smart enough to think, "Well maybe half that drug might be worth something. Let's go look at it." It appears to be very effective. At least in the open trials they've done.
What made you interested in Dravet Syndrome?
Really it was in training, in my residency ... I've always been fascinated with epilepsy and fascinated by the story of epilepsy. I've always been fascinated by the idea that the longer epilepsy goes on the more likely the story might actually be told. Which is why I always harp with my students that when you have a patient with intractable epilepsy, if you do not understand what's going on, you should always start from the beginning and work your way to the present because you might find a pattern and see the story as it's told over and over and over again.
Dravet is one of those things that tells a story over time. So in the beginning when it's just febrile seizures people might not quite put it together. But you take febrile seizures and then the types and how long they are and then put that you've got these new types of seizures. Now you've got developmental delay and EEG abnormalities, over time the story becomes clear.
I found so many cases of Dravet when I was in training in kids that were diagnosed with other things. There was a kid I remember when I was in training that was about to get epilepsy surgery, and this has actually happened multiple times since then, where I've seen people who were in the process of getting evaluated for epilepsy surgery and doctors are going over their history and trying to figure out if the patient was a surgical candidate. This kid sounds like he has Dravet syndrome. They are 14 or 15 years old and their family is wanting to do a surgery and then we find out, no they've got this underlying genetic epilepsy that is not surgically treatable. It's an important thing to figure out.
So over time I have encountered more and more kids with Dravet syndrome. We probably see somewhere between 40 and 50 patients. The longest distance someone came to see me was from Florida. There are a couple of spots in the US where Dravet syndrome is frequently treated and these typically develop from a doctor interested in the syndrome and word of mouth from the Dravet community. It's a very connected community. A group finds a doctor they like who understands what's going on, they share that with everybody and they end up all trying to go to the same place. It makes for a better clinic and better care when we can have that connection with our patients and they are connected with each other.
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Get to know M. Scott Perry, M.D.
Dr. Perry is the medical director, Neurology; Co-Director of the Jane and John Justin Neurosciences Center, Medical Director, Tuberous Sclerosis Complex Clinic at Cook Children's. Dr. Perry joined the Neurosciences Program of Children's in 2009 as a pediatric epileptologist, then served as the Medical Director of the Epilepsy Monitoring Unit and Tuberous Sclerosis Complex clinic before assuming the role of Medical Director of Neurology in 2016. His clinical and research interests focus on the treatment of childhood onset epilepsy, specifically those patients with uncontrolled epilepsy or those for which the cause has not been determined. Click to learn more about Dr. Perry.