The Brain Implant That May Do More Than Reduce Seizures - Dr. Vikram Rao, UCSF Health, USA
Could a brain implant do more than reduce seizures? Dr. Vikram Rao explains how responsive neurostimulation (RNS) is changing the treatment of epilepsy, why researchers think it may work differently than first imagined, and how the technology is helping us learn more about the brain than ever before. Could it even help treat conditions beyond epilepsy in the future? Watch/listen/read here 👇!
Episode Highlights
RNS can reduce seizures by around 75-82% for many people with drug-resistant focal epilepsy.
The device may not just stop seizures - it may gradually rewire brain networks, making seizures less likely to occur over time
RNS continuously records brain activity, helping clinicians personalise treatment while advancing research into epilepsy, seizure prediction and potentially even depression and OCD.
About Vikram
Dr. Vikram Rao, MD, PhD is Chief of the Epilepsy Divisionin the Department of Neurology at the University of California, San Francisco and Professor of Clinical Neurology in the UCSF School of Medicine. His clinical and research interests include applications of neurostimulation devices for drug-resistant epilepsy, neuropsychiatric disorders, and seizure forecasting.
Full profile: Vikram Rao
Topics mentioned
seizure forecasting
responsive neurostimulation (RNS)
EEG
depression
OCD
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Responsive stimulation of the thalamus for idiopathic generalized epilepsy: Results of the randomized controlled NAUTILUS trial through 18 months - Neurology
Dileep R Nair, et al.
PMID: 32690786, PMCID: PMC7538230, DOI: 10.1212/WNL.0000000000010154Postapproval Study for Brain-Responsive Neurostimulation for Drug-Resistant Focal Epilepsy: Three-Year Efficacy and Interim Safety Results - Neurology
Dawn Eliashiv, et al.
PMID: 42030518, PMCID: PMC13112409, DOI: 10.1212/WNL.0000000000214875Responsive stimulation of the thalamus for idiopathic generalized epilepsy: Results of the randomized controlled NAUTILUS trial through 18 months - Epilepsia
Utku Uysal, et al.
DOI: https://doi.org/10.1002/epi.70321 -
Trailer
00:00 Vikram Rao
I always I tell people, you know, it's hard to predict exactly the benefit that you will get from RNS, but in every case, we learn about your epilepsy by virtue of the data. That is true in every person I've ever taken care of with RNS. But it's also true that we are learning about epilepsy as a whole, in a way that is revealing some of the fundamental underpinnings, some of the mechanisms, some of the temporal patterns, how the brain works, why seizures are generated, what makes seizures get better over time. These are things that having long-term EEG data can be very, very revealing about.
Intro
00:36 Torie Robinson
There’s an epilepsy treatment called RNS - or Responsive Neurostimulation - it’s basically a flash medtech device that detects potential seizures and zaps them before they can spread. But - it might be doing other, really cool things as well. As our guest, Dr. Vikram Rao, tells us: researchers increasingly do think it could be changing brain networks over time (in a positive way!) and in the future, similar technology might even be able help us with conditions like depression and OCD!
Meet Vikram
01:07 Torie Robinson
So Vikram, thank you for joining us today. Could you tell us just a little bit about yourself and what you do,
01:11 Vikram Rao
Yeah, sure. So I'm an epileptologist and a professor of neurology at the University of California, San Francisco. and we are a level 4 epilepsy centre. So we really offer all the treatments that are possible for people who live with epilepsy, and I've been doing this for about 14 years now.
01:27 Torie Robinson
Fantastic, and why specialise in the epilepsies?
01:29 Vikram Rao
Well, I just think that I always found seizures to be really fascinating because they're so diverse in the way that they present, and because there are so many treatments that are available for people who experience seizures. Really, I would argue maybe more treatments than most other areas of neurology. And so it's very exciting for me to try and tailor a treatment plan with all of these tools for a given person.
01:52 Torie Robinson
How things have changed over the past 20 years, eh?
01:54 Vikram Rao
Very much so. A sea change in so many ways in our field. That makes it very exciting and most importantly good for the patients themselves.
What is RNS?
02:01 Torie Robinson
So tell us about RNS or responsive neurostimulation because you are a bit of an RNS king, aren't you? An expert. So give us bit of an overview. What is it?!
02:12 Vikram Rao
Haha, yes. I forgot my crown, I suppose you could say, haha.
02:15 Torie Robinson
Haha.
02:16 Vikram Rao
Well, this is a is a really remarkable, transformative technology. It was approved by FDA in twenty thirteen, so it's been available in the US anyways for just about 13 years. still not approved elsewhere, but hopefully soon. This is an implantable device that works by delivering direct brain stimulation, electrical stimulation to the brain to reduce seizures over time. And colloquially, this is called a “pacemaker for the brain”, which I think is actually a pretty apt description. It's a device that's constantly listening to brain activity and if the brain waves are normal it doesn't do anything, but when the brain waves become abnormal, such as at the sort of a seizure, it responds by delivering some electrical stimulation to the epicentre of the seizure to try and essentially snuff the seizure out before it takes hold.
03:04 Torie Robinson
I like that "snuff the seizure out.", I haven't heard that one before. And is this an intracranial implant? I mean, how would you compare it to VNS, for instance, which, you know, is sort of shoulder to skull, that type of thing.
03:16 Vikram Rao
Quite different actually. So, VNS is totally extracranial, so the pulse generators in the chest and the lead wires in the neck on the vagus nerve. The RNS device is a cranial implant. So the device itself sits in a full thickness craniectomy, and it has 2 lead wires that have 4 electrode contacts each and those are placed inside the brain at the site or sites where seizures come from.
Surgery length and battery replacement
03:38 Torie Robinson
And how long is the surgery for this and how often do you need to have things replaced?
03:41 Vikram Rao
Yeah, the surgery takes probably around 3 hours for a typical implant and patients typically spend one night in the hospital (as they would after, you know, most brain surgeries). Most people are recovered very well the day after or maybe after 2 nights and they go home. And then we see them back a couple of weeks after surgery to check on the scalp incision and to make sure everything's looking okay. In terms of the replacements, luckily this battery that we have on the device now lasts for about almost 11 years (with average use).
04:14 Torie Robinson
Wow.
04:15 Vikram Rao
So it is not a rechargeable battery, but luckily people don't have to have it replaced too often since the battery life is quite long.
Who’s suitable for RNS?
04:21 Torie Robinson
Gosh, and so does it… give us some numbers when it comes to RNS then? Like what percentage of people with refractory epilepsy might benefit from it?
04:29 Vikram Rao
Yeah, great questions. So, RNS is best suited for people where we know where the seizures arise from (meaning which brain regions generate the seizure activity) but when those 1 or 2 foci are not amenable to surgical therapy. We like to do epilepsy surgery to remove brain tissue when we can, because that can be potentially curative for many people, but oftentimes that's not feasible because the seizure focus overlaps with a critical brain region, such as one that mediates language or movement or vision. And in those cases or cases where seizures come from more than one spot, for example, from each temporal lobe, those are cases where it's not really feasible or safe to do surgery.
Where RNS wires are placed
05:12 Vikram Rao
And those are the cases where RNS is particularly helpful because once we've pinpointed the seizures, we can place wires at those locations that start to treat the seizure foci.
05:19 Torie Robinson
So you can basically zap more than one area at one time.
05:24 Vikram Rao
You can. The device has 2 lead wires and so if there's a single focus, we can place both lead wires in the same spot and kind of double down in that area. But if seizures arise, for example, from each hemisphere independently, one wire can go on each side. So it does give you more flexibility in treating people with multiple seizure foci.
05:14 Torie Robinson
And when, maybe this is silly question, so please forgive my ignorance, but when you place it, when you do the surgery, is it usually just in one specific place or does it depend upon which part of the brain that you are trying to help the person with?
05:52 Vikram Rao
It's a wonderful question actually because the answer is it depends. Classically, I would say this the wires can be placed in many, many different brain regions and the location depends entirely on where the seizures were found to come from. So if somebody's seizures came from their hippocampus, we would put an electrode in the hippocampus. If the seizures came from their motor cortex, we would put a lead in the motor cortex. However, one treatment approach that's sort of come into vogue recently is something called thalamic RNS. The thalamus, as you know, is a structure that's sort of deep in the brain, it sits atop the brainstem, and we think of it as a hub. And that hub has spokes or connections to very diverse parts of the cortex, of the orderly cortex. And so an emerging paradigm is to place an electrode in the thalamus and to stimulate the hub and take advantage of those spokes to treat the wheel (meaning the rest of the brain, as it were). And so, in that sense, we're not putting the electrodes where the seizures come from, we're putting them at a place that talks to all the places where.
RNS: a preventative approach?
06:53 Torie Robinson
That sounds borderline more preventative rather than treating...
06:58 Vikram Rao
It it's a really interesting thought. And in fact, you know, RNS was conceived as almost like a defibrillator, if you wish, something that would detect a seizure as soon as it started and then nip it in the bud, maybe you could say, like a like a cardiac device might. But if you really think about it, maybe what you actually want is for the seizure to not begin in the first place, and to have a more, as you say, preventative approach. I actually think that is not how this was conceptualised, but it may in fact be how it actually works! We're learning that although RNS probably can terminate seizures in some cases, most of the RNS stimulation that's being applied is actually outside of seizures. And so people are now thinking that what is actually happening is the therapy over time is sort of rewiring brain circuits and engaging endogenous plasticity mechanisms to make the brain less likely to generate seizures in the first place. So to your point, more of a preventative approach.
07:47 Torie Robinson
How does it do that? Are we looking at interictal activity and like what, the things that nobody else sort of tends to see in between seizures and then faff about with that to mould the new network?
07:58 Vikram Rao
Yeah, that's right. You know, we configure the RNS device to detect abnormal activity; meaning it, you know, epileptiform discharges. And of course, we're thinking about the discharges that are present at the start of a seizure, but people have sparks in between fires, and the device also makes detections interictally (between seizures) and delivers stimulation in response to those detections. Because for all the device knows, every one of those sparks could turn into a seizure, so it's trying to treat all of them. And that's why the vast majority of stimulation typically is delivered in the interictal period; which is exactly the opposite of what you would think if this was a seizure aborting device! So not that that doesn't happen, but many of us are thinking now that actually the real action is in the interictal period and all of that chronic ongoing brain stimulation is having a therapeutic effect, which, truth be told, we don't understand fully at a mechanistic level, but we're learning.
08:49 Torie Robinson
Very exciting. What percentage of people do have a degree of seizure control?
08:52 Vikram Rao
Yeah, let's talk about efficacy first. So we have, fortunately, really high quality long-term clinical trial data to teach us how well this works on average. So the RNS long-term treatment trial was published in 2020 by Dr. Nair and colleagues. And that showed that over the course of 9 years, the median reduction in seizure frequency was around 75%. More recently, just this year actually, in the Neurology Green Journal, Dr. Elaishev and colleagues published the results of the 3-year post-approval study, which showed that in the real world, contemporary practice, people are doing even a little bit better with a median reduction in seizure frequency of 82%. It's worth noting that a minority of people treated with RNS become truly seizure-free for the long haul. So we do think of this still as a palliative therapy and not something that is likely to be curative for most people. That said, this can still be transformational in terms of improving seizure control over time.
RNS data recording benefits
09:50 Torie Robinson
And what are other potential impacts of the device?
09:53 Vikram Rao
Yeah. I would say the principal thing, maybe the most eye-opening thing for me that I didn't anticipate when we started using this, is the power of the data that is stored by the device. So even as the device is making detections of abnormal activity and stimulating in response to that, it is also storing recordings of brain activity, storing the counts of the detections of interictal discharges, for example. And patients are able to download data off the device and transmit it to an online data bank that clinicians can review. And it turns out that that that data is a treasure trove of information because this is the only way that I know of in neurology to record intracranial EEG data over years from patients who are living their lives in a natural environment, on medicine, doing all their normal activities. And it's incredibly informative what you can learn when you look at brain activity over such a long temporal scale. For example, cyclical patterns of activity in the brain, response to medicines and other therapies that we offer to patients, we can sort of quantitatively gauge those outcomes. We can, if people have 2 seizure foci, we can determine over long periods of time what the ratio of seizures coming from those 2 locations are, and that can inform future therapies. And, you know, many more things. One of my research interests is in seizure forecasting, which is the notion… like weather forecasting, of trying to give people a likelihood estimate of the chance of a seizure over some given horizon (just like you would say there's an 80% chance of rain tomorrow). And it turns out that data from RNS can be very valuable for that as well.
11:23 Torie Robinson
And that could benefit the individual as well as - assuming one is okay to share one's data - actually people, other people around and people of the future in understanding the epilepsy is better.
11:32 Vikram Rao
That's right, yes. it's really both. I always I tell people, you know, it's hard to predict exactly the benefit that you will get from RNS, but in every case, we learn about your epilepsy by virtue of the data. That is true in every person I've ever taken care of with RNS. But it's also true that we are learning about epilepsy as a whole, in a way that is revealing some of the fundamental underpinnings, some of the mechanisms, some of the temporal patterns, how the brain works, why seizures are generated, what makes seizures get better over time. These are things that having long-term EEG data can be very, very revealing about.
Suitable for focal or generalised epilepsy?
12:11 Torie Robinson
And is the device suitable for people with focal and generalised or both?
11:18 Vikram Rao
It is currently in the US approved for focal epilepsy. However, there was recently a trial that was completed called the NAUTILUS trial. It's not yet published, but it will soon be published. And that was a study that was done in people who had primary generalised epilepsy. And this was actually using that thalamic stimulation paradigm that I described earlier. And it turns out that the results of that were quite favourable, and the FDA is now mulling over whether to grant an indication for idiopathic generalised epilepsy as well. So that has not happened yet, but we're many of us are hopeful that that may come to pass because you know certainly that's a slice of the population that would be very much in need of new treatments.
Benefits for DEEs, treatment resistant depression, and OCD?
12:59 Torie Robinson
Well, totally. And I presume, given your answer just then, it's not suitable or approved yet for things like, you know, developmental epileptic encephalopathy or anything like that yet.
13:09 Vikram Rao
That's right. There are a smattering of case reports about the use of RNS off label, mind you, for things like DEEs. There is an ongoing clinical trial that we are participating in, as well as 5 other centres in the US, looking at the use of RNS for treating Lennox Gastaut Syndrome, which is a symptomatic generalised epilepsy. And there have been many other, you know, investigational uses of RNS for other things, including things that are extend beyond epilepsy, believe it or not, like treatment resistant depression, and OCD, and a lot of other things. So in a in a way, people are now starting to think that RNS really is a platform technology. This is a device, an intracranial device, that can detect activity that's of interest to you and respond with stimulation that might help to treat pathological brain activity in disease-relevant circuits. So that's a very exciting kind of high-level way to think about this device. Not how it was probably conceived originally, but we're growing into that.
14:10 Torie Robinson
I was actually just about to ask you about any potential positive or negative effects on a person's mental health because those symptoms are commonly, unfortunately come along with seizures. So it seems like you're saying that potentially it can be positive for people, for instance, with depression or OCD, or can it go the other way too?
14:09 Vikram Rao
I'm sure there's examples where it can go the other way. There are really promising early reports in a small number of patients showing that if you identify the right biomarker, for example, of mood state, you can use RNS to leverage that biomarker and treat people who have… who don't have epilepsy but have treatment-resistant depression at, you know, sometimes with really dramatically positive outcomes. It's early days, though! We are have a lot to learn about what biomarker we should be looking for and how we should be calibrating the RNS device accordingly, how we should stimulate, where we should stimulate, you know, what the time course of improvement is. But I think it's really promising for a lot of other indications even beyond epilepsy.
More information
15:15 Torie Robinson
It gives us some great realistic hope, I think. And I would encourage anybody who's interested in this to… well, what would you say for anybody who's listening, whether they be a clinician or a person with an epilepsy and they want to learn more, where should they go?
15:28 Vikram Rao
Yes. you know, one place where patients who are considering this therapy go as a first stop for some a good resource is the manufacturer is Neuropace that they have a website which is www.neuropace.com and there's a section for clinicians, there's a section for patients, and it's an it's a good place where a lot of the relevant scientific papers are published, some instructional videos and patient testimonials, and, you know, if you even... and the evidence for what we know about the mechanism, the clinical efficacy, a lot of that is housed there. There are a number of online community groups that are dedicated towards RNS and where the community of people who are treated with RNS therapy have come together to share stories and support each other and help us all learn collectively. There's only about around 9,000 people in the whole world who have RNS currently. That number is growing. But certainly the best way to learn is to pool our collective experience.
16:27 Torie Robinson
No, indeed. I think for anybody interested in the papers that you've mentioned or upcoming papers, certainly give those a read as well.
16:34 Vikram Rao
Absolutely. Yeah. There's no substitute for, you know, look at what's published and all of the studies have limitations, obviously, and strengths(!), but the best we can do is look at the data that is available, the evidence that we have, and then think about how we might want to design studies to learn even more over time. You know, I think RNS is at this really exciting place where it's largely been de-risked.
Safety and further development of RNS
16:55 Vikram Rao
You know, we didn't talk too much about this, but the safety data that we've accumulated now since the first implant in the early 2000s is really quite favourable. There are of course risks to any brain surgery and any implanted devices, but we think of RNS as a very safe therapy. And now knowing that it is not only safe but effective now really allows us to sort of liberalise our thinking and say “Well how else can we use this for what else can we use this and what does a next generation device look like.”, right? That's something that's super exciting too; we certainly are in an age where technology developments are very rapid and hardware and software are making just, you know, giant leaps all the time. Medical devices are slower because they have to go through a, you know, an understandably a long regulatory process. But there's no reason why all the hardware and engineering advances couldn't be brought to bear on a even better device in the future.
17:47 Torie Robinson
Well have to say you do make it sound like the latest iPhone or Samsung or something like that - in a good way!
17:53 Vikram Rao
Haha! In a good way, yeah! Well and just the same way that you might wish that your current iPhone has some more bells and whistles and maybe next year you'll get an iPhone that has some of those things! Those of us who use neurostimulation devices have our own wish lists and we don't get a new one every year, but we can at least look forward to the next generation and hope that, you know, the technology advancements continue and hopefully that that is accompanied by greater and greater clinical efficacy.
Closing thoughts and thanks
18:19 Torie Robinson
It’s exciting, right - to know that something which can already monitor and stimulate the brain to reduce seizures is still being developed and refined! And to not only to better control seizures, of course, but potentially to help with other conditions in the future too - including things like depression and OCD! A huge thank you to Vikram for sharing his knowledge and passion for how RNS may improve the lives of so many people with refractory focal epilepsy. Do subscribe if you haven’t already - and see you next time!