Pediatric Epilepsy, a Heterogeneous Disorder

September 19, 2018

The associate chief of clinical pediatric neurology, director of the pediatric neurophysiology lab, and director at the Adolescent Epilepsy Center at UCLA spoke about therapeutic options for pediatric epilepsy.

Jason Lerner, MD

Advances have been made over the years in developing new therapeutic options for pediatric epilepsy, however, because epilepsy is such a heterogeneous disorder, there’s no one right therapy.

Jason Lerner, MD, associate chief of clinical pediatric neurology, director of the pediatric neurophysiology lab, and director at the recently opened Adolescent Epilepsy Center at UCLA, spoke with NeurologyLive in an interview to discuss the current therapeutic landscape for pediatric epilepsy from medications and devices to surgery and diet therapy.

Lerner emphasized that while it’s essential to get patients under complete seizure control, clinicians really need to be focusing on seizure freedom with the best quality of life possible for these patients.

NeurologyLive: Can you discuss the current therapeutic landscape for pediatric epilepsy?

Jason Lerner, MD: It’s a tough question because epilepsy is so heterogeneous, there’s so many different types of epilepsy, different types of seizures, all with different ways of treating. We have a few different generations of medications and even just recently over the last few months, new medications are coming out. There was a collection of older medications that they’ve created longer-acting versions of, but then just recently there’s a CBD product that was approved by the FDA that should be coming out, plus, another medication called perampanel that has been approved in Europe for a long time and is now getting approval in the United States. These are medications that are specifically used for some of the more severe types of epilepsy, I think they were approved for Dravet Syndrome and Lennox-Gastaut Syndrome, two of the most devastating forms of epilepsy and two that are essential to treat early to help improve long-term positive outcomes. There’s still a number of other medications in the pipeline from different companies and there’s always medication management and hopefully, new things coming.

Beyond that, there’s diet therapy depending on who you talk to and where you go, some places use it very early in management, and some much later—there’s a limited number of centers do diet therapy. There’s the ketogenic diet, the Modified Atkins diet, the low-glycemic index diet, and they can be used for a variety of different seizure types and there are some cases where they are the primary treatment for something like GLUT1 deficiency, and then there are a variety of other seizure types that it can be helpful with. They can be kind of difficult to use, we’ve tried to use them in some of our teen patients and even though it works really well, it’s pretty difficult for the teens to follow.

Then there are some of the devices like the vagal nerve stimulator (VNS) for certain types of epilepsies that can be very helpful for the focal epilepsies. We tend to use it in patients who we’re looking at for surgery for focal epilepsy, but surgery would require cutting through eloquent cortex affecting language or motor. The vagal nerve stimulator is a safe procedure, it’s just implanting something in the chest and then a wire to the vagus nerve in the neck, which can significantly lower seizures or get a pain seizure freedom.

Then there is surgery which a lot of people still look at as like a last-ditch effort, like you’ve tried everything now so let’s consider surgery, but here and among other big centers feel that shouldn’t be the case. The thought is after failing 2 appropriate medications with the appropriate dosing and appropriate length of time they should at least be evaluated for the possibility of surgery. There are certain situations, certain seizure types, possibly something from a focal cortical dysplasia or mesial temporal sclerosis or hemimegalencephaly encephalopathy that surgeries by far are going to be the best long-term outcome option and the sooner you do the surgery the more likely you’ll have good, positive outcomes. On that landscape, also, there’s now the responsive neurostimulation (RNS), which is a combination surgery with a VNS type of device that is implanted directly in areas of the brain that the seizures are coming from and monitors that area and then sends activity back to the brain to prevent seizures as they start to evolve. That’s where the variety of treatment that we have.

One of the biggest problems with diet therapy is the difficulty, for example, a baby who has a gastrostomy tube that's being given formula is not a problem, but it can be difficult for other people and surgery is not an option for everyone. The problem with the medications is that a lot of them have side-effects. In some newer medications that they’re developing or the newer versions of older medications the side effects do seem to be a bit better and things like cognitive outcomes and psych/behavioral outcomes do seem to be better in some of the studies from newer medications, which I think is essential because while our goal has always been seizure freedom, I think seizure freedom with the best quality of life possible is going to be really what we need to be focusing on. There are some patients that have such bad reactions to the medication that while we may be able to get their seizures under control so that they maybe have one seizure month, but to get that last seizure under control you have to give them so many medications that they’re basically out cold from all the side-effects they’re having—that’s basically an unacceptable quality of life to get them under complete seizure control.

What do we know about CBD?

JL: There really isn’t a lot of good data. We’ve participated in a few of the studies well and are still participating in a couple of them, but they’re still fairly short and we don’t have a lot of long-term data at all. The one thing you hear is that an individual has been smoking pot since he was a teenager and he’s fine, but we don’t know what’s going to happen to some of these kids who are one or two years old and how this is going to affect them. There is some concern, but there definitely are cases and the literature does back it up, that for certain types of epilepsy such as Dravet and Lennox-Gastaut, it can be very good. Now how much better than the current medications, that’s a bit questionable.

I know that everyone wants to try CBD for every single type of epilepsy, but I don’t think there’s good data for the other types of epilepsy. There’s a lot of misinformation on the Internet and there’s a lot of anecdotal evidence, but I think it’s essential and I think there’s definitely a role for it, but I definitely think it needs more research, so we can understand it better, know when to use it and what to use it with. People say it’s natural and to a degree, but things like hemlock is natural too and it can interact with a lot of medications we use frequently and can shoot the levels up.

It’s not without concern as well, but there definitely are some cases where they’re seeing some pretty impressive results from it.

Is there a stigma surrounding epilepsy?

JL: There’s a significant stigma. In studies, researchers have looked at the more common chronic disorders, and quality of life tends to be worse in epilepsy, than diabetes, juvenile rheumatoid arthritis, even once they showed it was equivalent to being HIV positive as far as the stigma.

Epilepsy is probably one of the least understood disorders out there and also one of the most feared. Seizures can be scary, and people are very hesitant when they hear about someone with seizures or they see a seizure, as many people don’t understand it. There’re still some portions of the population that think it’s an infection or think it’s something they’ve done or even bad spirits—there’s still people that think that way and a lot of it is just a lack of education.

The depictions in entertainment and the media don’t tend to be great about epilepsy. I know there’s a big controversy now about a Netflix show where the lead character has epilepsy and they call him seizure boy and people make fun of him. Depictions like that don’t help and I think it just keeps this mystery about seizures and epilepsy and keeps people scared of them.

What's the relationship between primary care physicians and neurologists?

JL: Most of the patients are seen by their primary doctor first and then they are often referred to pediatric neurologists or in some cases adult neurologists because there are not that many pediatric neurologists out there, and especially in some more rural areas there isn’t a pediatric neurologist for miles. Then after you’re at a pediatric neurologist for a while, even in those cases, some of the much more difficult cases need to be seen by pediatric epileptologists—that’s when some of the surgical cases and diet therapy tend to be more utilized.

What’s the best advice you can give to other neurologists?

JL: I would say definitely have a low threshold, as many parents are concerned about things that may be seizures. The basic EEG can be helpful but, in many cases, the best thing is usually an overnight ED to actually capture and determine whether these episodes are or are not seizures. I think the big key is to know that if you’ve been trying medications and it doesn’t work, when to call in a neurologist or epileptologist.

What else should our physician audience know?

JL: I think it’s important for primary doctors and general neurologists to find a pediatric neurologist or a pediatric epileptologist nearby that they feel comfortable with, they can talk with, and refer patients to when there’s any concerns or question.

The medications can be difficult to use sometimes because a lot of them have side effects and interactions with other medications, so it’s really important to talk to patients about the adverse effects of medications. Some of these medications cause irritability, depression, anxiety and difficulties in school and if the patients are not aware that this is a possibility, patients and parents don’t know to look for these symptoms, so it’s really important to do a lot of counseling about not only epilepsy but also the medications and treatments.

About 30%—40% of people with epilepsy have a comorbidity such as depression, anxiety, ADHD, sleep disorders, autism spectrum and they are really essential to be aware of, to think about, and to look for a diagnose. There’s plenty of studies out there that have shown treating these comorbidities actually may have a greater impact on quality of life than even giving complete seizure control.

Transcript edited for clarity.