Evo Terra (Host): This is Check-up Chat with EvergreenHealth. I'm Evo Terra. And with me today is Dr. Thomas Bullock, an epileptologist, and neurosurgeon Dr. Ryder Gwinn. They're here to share how they are using responsive neurostimulation, RNS, to treat epilepsy. Doctors, welcome to the show.

Ryder Gwinn, MD: Thank you for having us.

Tom Bullock, MD: Thanks for having us.

Host: Dr. Gwinn, I'll start with you. What is epilepsy and how common is it?

Ryder Gwinn, MD: Right. Yeah. Epilepsy is a condition in which people have unprovoked seizures. So, I think most people know what a seizure is. They can come in different varieties. But if you have one seizure, that doesn't mean you have epilepsy. If you get in a car crash or you have a really high fever, people can have a one-off seizure. That does not mean they have epilepsy. But if you then start to have seizures after that, that aren't associated with any trauma or any insult to the brain, now you have epilepsy. And it is extremely common. It still has a stigma to it today. So, people don't really talk about it if they have epilepsy or if their family members do.

It tends to not be as obvious. But a lot of people have it. Over 150,000 people are diagnosed every year in the United States. Almost 4% of the population will have epilepsy at some point in their lives, and one in 10 people will have a single seizure or more in their lives. So, it's actually more common than cerebral palsy, multiple sclerosis, and Parkinson's disease combined. So, very, very common condition.

Host: Dr. Bullock, I'll switch to you and ask how common is drug-resistant epilepsy and why is there such thing as drug-resistant epilepsy?

Tom Bullock, MD: Yeah. Thank you for the question. Drug-resistant epilepsy is when the therapies we would first choose to treat someone's seizures aren't working, and the patient continues to have seizures despite taking an adequate trial of medicines. In fact, in order to qualify for medication-refractory epilepsy, we need to have tried at least a couple, and they continue to have seizures.

We've studied this population over time. And unfortunately, the chances that the third, the fourth, the fifth seizure medicine really have a meaningful improvement in their seizures becomes progressively lower with each try. These people have a network problem with their epilepsy, where they're not able to have the medicine benefit them and control their seizures. It's frustratingly common. If you were to take a group of epileptics, I think about one-third of them would have medication-refractory epilepsy unfortunately.

And with that, they are facing greater challenges than people who have controlled seizures. They have a higher risk of death from sudden unexplained death in epilepsy. They have a lot of more increased incidence of physical injuries. They're facing cognitive and memory decline, mental health struggles, given the ongoing nature of this disease, and facing a lower quality of life due to the restrictions in their activity. These are often people who can't drive, have difficulty maintaining work and contributing to their families that they need to provide for.

Host: Definitely a challenge, for sure. Dr. Gwinn, I assume that's why we're here talking about RNS. So, how does RNS help these patients who are resistant to epilepsy medication?

Ryder Gwinn, MD: Sure. Yeah. Well, the short answer is that it helps by reducing the number of seizures that they have. And it does that through a mechanism where we place electrodes either on the surface of the brain or actually below the surface of the brain. And those electrodes constantly kind of read the information that they're seeing from the brain, and we train it to recognize when there's abnormal activity.

So, if this device then sees that a seizure is starting or any kind of abnormal activity, it then stimulates through those same electrodes. And the goal is to kind of either abort a seizure before it spreads to other parts of the brain, or probably more likely what we're doing is we're retraining the brain.

We're kind of squashing down that abnormal activity often enough and for long enough that the brain just focuses on other activity and kind of forgets to continue to have seizures. That's fairly simplistic, and this is a very complicated disease that, you know, has abnormalities maybe focally in one part of the brain, but also, as Dr. Bullock was saying, the whole network within a brain could be altered. So, it's a big challenge to be able to treat patients using neurostimulation, but it is a very reversible, and programmable therapy that is increasingly effective as time goes on.

Host: I'm fascinated by these devices. I know you and I have talked in the past about using deep brain stimulation for Parkinson's patients, and this seems like it's right or very similar to that. Dr. Bullock, I want to ask you about how this RNS device actually learns someone's brain functions over time. What does that mean?

Tom Bullock, MD: Oh. Well, given that we're able to record the electrical activity in their brain intracranially, we're getting a very detailed picture of the seizure onset zone. Working with Dr. Gwinn, we're able to place those electrodes really at the main problem centers of the seizure. And as we watch their seizures happen after the electrodes are in, we can get a really good pattern every time they have a seizure. We can review the seizure pattern and refine the ability of the machine to detect it earlier and faster. We can train it to give electrical signals when it would most benefit the seizure and interrupt it from snowballing into a larger symptom. And every month, I review those electrodes, their seizure correlates, and find a new way to try to make the RNS work better and better. That's why we've noticed that this machine works best with experienced centers and with ongoing use over time as we continue to refine it. They'll come in, they'll tell us their symptoms are regularly on a clinic basis, and we can adjust the machine together to try to get a better sweet spot for their seizure control.

Host: A question for you, Dr. Gwinn. How does this RNS measure up against other epilepsy treatments in terms of efficacy, risks, and maybe even side effects?

Ryder Gwinn, MD: Sure. Yeah. Good question. Obviously, the first line of treatment for epilepsy is medication. And as Dr. Bullock said, about two-thirds of patients will be well-controlled with the medication. But that other third, they're candidates for a whole other host of potential interventions. And the number of interventions are kind of across a continuum in terms of both the likelihood of controlling seizures and in terms of the invasiveness and potential risk and side effects associated with it.

So, for example, there's a device called a vagus nerve stimulator that we don't have to do anything to the brain. We stimulate the nerve in the neck, and that can reduce patient seizures up to by half or so. It's not perfect, but it's less invasive than some of the other things.

Deep brain stimulation is another method that we kind of talked about. We can place electrodes in the brain. That's a little bit more invasive, has a little more risk. If there's bleeding or infection, there can be problems. But it's more effective than the vagus nerve stimulator.

RNS or responsive nerve stimulation is kind of the next level up above that. It's a little bit more effective, has a little bit fewer side effects from deep brain stimulation. We don't know exactly why, but I think a lot of it is because that it's not always stimulating. It's listening for abnormal activity. And then, when it sees it, it stimulates, whereas deep brain stimulation is kind of always stimulating areas that maybe don't need to be stimulated. It might be interfering with their normal function if you're always stimulating.

So, RNS is sort of this sweet spot where it's minimally invasive, but still highly effective. We can reduce seizures by 80% or more, and there are people that even go for a year or more without any seizures from this therapy. So, it's really elegant in terms of how we can apply it to interrupt seizures and reduce them from happening. And it has a very good safety profile.

After RNS, there are more invasive things we can do. We can try to find out where seizures are coming from in the brain with intracranial electrodes or MRIs that identify abnormalities. And then, we can try to physically remove that area, either with a laser fiber or directly with instruments.

That has a very good chance many times of curing the epilepsy altogether, but it can have a lot of functional consequences at times as well. It really depends on where in the brain we're talking about. So, people, you know, if they have seizures coming from near where their motor areas are or their language areas are, we may want to take that area out to get them seizure-free, but we don't want to because we'd interrupt a very important function. So, those are really good candidates for this RNS therapy.

There are other interventions called disconnection therapies. They generally are kind of what we call palliative, meaning that they don't cure epilepsy, but they can stop seizures from spreading and becoming bigger. Not used as much. So, you can see there's a whole continuum of different therapies for epilepsy. And RNS, in my view, kind of sits in that middle sweet spot where we have really good safety profile and still a pretty good degree of effectiveness.

Tom Bullock, MD: A lot of times, when we get to meet people in clinic, we don't know what they're going to ultimately need. This is the beginning of a relationship as we try to solve their medication-refractory epilepsy. And so, we'll educate them on all the opportunities, including resection, laser ablation, and neuromodulation.

But until we've really determined where that problem center is and whether that problem center is also used for essential neurological function, it's hard for us to decide, does this person best benefit from a destructive treatment or from a neuromodulatory treatment? Having this whole comprehensive approach to surgical epilepsy, that allows us to take care of anybody who comes to our door.

Host: And I know this RNS therapy, just from what you two have told me about today, is it sounds life-changing. And that to me means I know you both have had some patient outcomes that are just mind-blowing to you as well, even though you're a doctor. Can you provide me some examples of what you've seen after activating the RNS device? And, Dr. Bullock, we'll start with you.

Tom Bullock, MD: Well, yeah. This is a privilege and a pleasure to talk about, fortunately, with working with Dr. Gwinn and localizing the onset of seizure zones, our treatment with RNS has been highly effective. The data about RNS suggests that even in the short-term period, some patients notice more than a 50% to 60% reduction in their seizures, which is a meaningful change in their seizure control. That's already associated with a higher quality of life. Working with them for one to three years, the RNS it has been shown to reduce seizures by up to 67% to 82% percent over that one to three-year time gap.

And the nice thing is, as we continue to refine it, continue to make it work better, and use the patient's experience and the intracranial recordings to refine the picture, we can do even better. We've now been seeing the results of these studies at nine years of follow-up and are reporting up to a 75% reduction, with some of them, about a third reporting greater than 90% reduction in their seizures. This is something that'll really allow people to change the story about how their seizures affect their lives and allow them to pursue things that previously weren't available.

Ryder Gwinn, MD: Yeah. I've been in this field for a while now, over 20 years. And before the RNS was available, I would talk to a lot of patients who we know where their seizures are coming from. I have one patient in particular that was coming from the occipital lobe, which is where our vision is served, and we knew the seizures were coming from there. And in the past, we would basically say to patients, "Look, we can either allow you to continue to have seizures, or we can remove this area. But unfortunately, your half of your vision will go as part of that therapy." And one patient, you know, years ago, we presented that to, and they were like, "No, I don't want to do that. I'd rather continue to have seizures than lose half my vision."

And then, we were involved in the study that got this RNS approved, and we were able to then offer him a solution where we could put electrodes into the occipital lobe where the vision is and stimulate that area. And occasionally, he'd see a flash of light or something when that stimulator's going off, but he had effective control of his seizures and still maintained his vision. And this happens over and over again. We no longer have to have these critical decisions where it's like, "Okay, either you lose this really critical function, or you're just going to continue to have seizures." Now, we have a really good option that's, like, much better than one or the other

Host: And to wrap things up here, Dr. Bullock, I'll ask you, you know, I've heard about this talk of providers talking about getting people seizure freedom, which, you know, usually means no seizures for at least a year. Is that possible with RNS?

Tom Bullock, MD: Fortunately, yes. While the RNS system is really meant to reduce seizure frequency and severity, when you're talking about controlling seizures, you're really monitoring for seizure-free intervals. And the longer those seizure-free intervals persist, the greater autonomy and opportunity a patient has.

We've now been following patients long enough that we're noticing about one in five patients can experience one full year of continuous seizure freedom, using the RNS machine. And even 30% to 40% percent are having six-month gaps in their seizures, which again is correlated with a meaningful improvement in the quality of their life and their risks.

Ryder Gwinn, MD: Yeah, we like to, I think, underpromise and overdeliver generally. So, we don't generally tell people, "Look, you're going to be seizure-free after we put this device in." But it is fundamentally different than something like medication. You know, as Dr. Bullock was saying, if we've tried two or three medications with somebody already, we know if we give them a third or a fourth, they might be seizure-free for three months or even six months, but it's very likely that those seizures will start again at some point in the future.

Whereas with the RNS, we actually know that the likelihood of stopping their seizures gets better every year for the first four or five years after it's implanted. So, this is a very unique therapy that only gets better with time, whereas everything that we deal with with medications, we generally find that things get a little worse over time.

So, it's so exciting to be able to offer something that does continue to overdeliver as time goes on. Not everybody's seizure-free, but we love it when we see that, and there are patients who get back to driving and, you know, get on their job and have very meaningful lives because of this.

Host: Dr. Bullock, Dr. Gwinn, thank you so much. I always love chatting about these life-changing procedures.

Ryder Gwinn, MD: Thank you very much for having us

Tom Bullock, MD: Yeah. It's been exciting to share this with you. Thank you.

Host: And that wraps up this episode of Check-up Chat with EvergreenHealth. Head over to our website at evergreenhealth.com for more information and to connect with one of our providers. Please remember to subscribe, rate, and review this podcast and all the other EvergreenHealth podcasts. For more health tips and updates, follow us on your social channels. I've been your host, Evo Terra. Thanks for watching this episode of Check-up Chat with EvergreenHealth.