Jason Gerrard, MD, PhD, Assistant Professor of Neurosurgery and Neuroscience at Yale School of Medicine talks about the Percept device in treating epilepsy and neurological disease patients.
Can you explain what brain stimulation it is and what conditions it helps?
Dr. Gerrard: In my clinic, I often talk to patients and try to explain to them what deep brain stimulation is and what we do. It is easier to understand where it came from. For many years that preceded deep brain stimulation we were treating movement disorders like Parkinson’s disease and tremors with lesions by finding a part of the brain or brain center that if we turned it off or got rid of it, it may help with the state of the disease. We would literally go in, make a lesion, and burn that part of the brain out. Deep Brain Stimulation was thought of as a reversible lesion because we realized that over time if you stimulate neurons at an extremely high frequency, you can turn them off. So, it was thought it was a way to turn off groups of neurons, and to modulate the different activity in the brain centers rather than burning them out. It turns out it does do that. But it also does many other things while changing the way that the brain modulates itself and the way the different circuits in the brain interact with each other. Some of those things we are still trying to understand but it came to be this concept of having the ability to have what we wanted, which was a reversible lesion, and the ability to turn off certain groups of neurons to help change the way the brain circuits worked to stop tremors and to treat different symptoms of Parkinson’s disease. Now we use it to modulate a variety of different brain circuits for different neurological diseases.
How much success have patients had with implanted stimulators and now is it the preferred way to treat patients with these conditions?
Dr. Gerrard: There have been different types of brain stimulation around for many decades and the successes have been variable. Oftentimes, you have small case studies where you see this great success in a handful of patients for a certain disease and then we have a hard time generalizing that to large groups. The gold standard was to do multicenter blind studies to show that this has a significant effect. It is extremely fortunate that one of the first diseases that this was tried on were tremor and Parkinson’s diseases, where patients have a visible response, and it was highly effective. In fact, we started utilizing it without a big, multicenter blind trial and it is clearly highly effective. We have done those trials since then and it shows that it is amazingly effective. But that is not always the case. There are different neurostimulation, and neuromodulation treatments that have been tried for different therapies that have not worked. Some have worked, but not as well as we would like. About a decade ago we had a big trial because it looked like we had a very promising result in using neuromodulation to treat major depression, which is a big problem that affects a lot of people. When we tried to do a big trial to prove that it was effective, it did not pan out as well as we had hoped so we are still trying to figure out why it did not work. There are these instances where it is remarkably successful. Parkinson’s disease is the best example of that, and other times it is not quite so straightforward.
I want to talk about the Percept device.
Dr. Gerrard: This new device is something that has been under development for many years. The concept is we have electrodes that we place inside the brain to do deep brain stimulation. When we say it is an electrode, it is a bit of a misnomer in the sense that it is an electrode array. Typically, there are anywhere from four to eight electrodes on it. There are also some electrodes that are not being used for stimulation. So, one of the things we struggle with in most neurological disorders, especially Parkinson’s disease, is where the disorder itself fluctuates in its state. Biomarkers are things that tell us where the state of the disease or the brain is. So, what if we could record brain signals from the same electrodes that we are doing the brain stimulation because there are already electrodes in the brain? We do recordings of brain electrical activity for different research and in the hospital for different diseases. But it is complicated when you are trying to do that while you are sending high frequency electrical pulses because the noise from the stimulation overrides your ability to record any biological signals. So, the company Medtronic has been able to engineer a method to cancel out the stimulation and allow the device to record brain electrical activity while it is stimulating. That is the fundamental basis for this brain sense mechanism in the percept device, which has been a great breakthrough.
What is the benefit?
Dr. Gerrard: The actual benefit is still for us to understand and find out. But especially in key disorders such as Parkinson’s and tremors, where deep brain stimulation started from, we know that these diseases fluctuate. A lot of research has been done over the past several years and decades, and we can now identify certain frequency ranges in the brain activity that modulate up and down with the state of Parkinson’s disease. This device was designed to provide a readout for a biomarker or brain signals which can tell you where the disease state is in real time. So, the device is approved to record brain activity and it can record up to 60 days of activity. Then we download that information and look at the different frequency ranges at different times during the day. The patient can mark with their patient programmer, so they can push a button to say, my disease is bad right now, or my disease is doing fine right now. Then we look at the different signals during these different periods of time with the idea that eventually, the device itself will be able to know what the patient’s disease state is and change its parameters based on that state. We call that a closed loop system, where the system itself, with a device that’s doing the stimulation therapy, is actually able to change the stimulation on its own based on how the patient’s disease state is reading out. So, this is going to be extremely helpful for the patients who come in to see their neuro team. The program gets set in the device, stays there, and stimulates like that all the time or the patients will have a couple different programs, and they can change it manually. But this would be a totally different level of interface with the brain, where the device itself is changing its programming on its own as it senses the patient’s disease state.
Could explain the surgical procedure.
Dr. Gerrard: Implanting the Deep Brain Stimulation system can be done in a variety of ways. Historically and traditionally, we did this surgery with the patient in the Operating Room with a frame that is placed on the head. The frame literally gave us a frame of reference. It gave us a stereotaxis or stereotactic coordinate system that we could use to target certain parts of the brain very accurately. When we first started doing this, we did not have all the advanced imaging that we have today, so we used the brain’s physiology to confirm that we were in the right location. To do that, the patient would be under conscious sedation in the operating room. They would be given some anesthesia, so they do not need to have a breathing tube in, but they are also not awake. It is a little more comfortable to go through the procedure. But at certain points, when we are recording from the brain and stimulating the brain to get that physiology of whether we are in the correct location, the patient needs to be awake for that. So, we can wake them up quickly and do that testing. But it is not the easiest thing in the world to be awake while you are having the electrodes implanted in your brain. Over the course of time, we have developed different techniques for doing this. We still use that same technique that we have had for a while now. In some certain instances, the part of the brain that we are trying to target with the electrodes, is visible on modern high-resolution imaging and we can use direct image-guided targeting. What we mean by that is we can get a real high-resolution MRI. For instance, we have an MRI scanner that is right in our operating room on rails on the ceiling. It can come right to the OR table so patients on the table can get MRI scans. There are quite a few of these around the country at this point. It lets us do the surgery while getting the MRI scans. So, you can see the MRI scan and target where you want the electrode to go. Then place it down there while you are looking at the scan to make sure that it is going where you wanted it to go. The benefit of that technique is the patient is under general anesthesia, so they have a completely different experience. They go to sleep, wake up, and the surgery is done versus the traditional technique where they are awake, and they are doing the procedure with us. The patient is getting the feedback, be tested, and they are seeing the results and how things are working. But they must be awake for the surgery, which has its downsides.
Is it life-changing for some?
Dr. Gerrard: It has been life-changing for many patients with movement disorders. It can be effective for people who have bad tremors and have a difficult time writing, using a keyboard, cooking, cutting, just doing things we take for granted. It can reduce the amount of tremor they have by 75% to 90%, and some people will be completely tremor-free. In Parkinson’s disease, where it is best-known and had its origins from, it is extremely effective. If we think about the fluctuating state in Parkinson’s disease and there was a study done where they talked to patients and had them score whether they were doing well or whether they weren’t doing well and there was about a five or six-level score on that. They found on average, patients with Parkinson’s disease, only spend about 25% of their day in what they would call a good state. After all those patients had Deep Brain Stimulation and then Deep Brain Stimulation programming, they did the same exact study and found that they were now spending 75% of their day in a good state. So, it can be a huge improvement of quality of life. With patients a common story is if they are going to go to the grocery store, they must get there by 9 because their 8 o’clock medicine is going to kick in. If it is past 9:30, it is going to start wearing off, and they worry about getting back to the car. That is gone now because they do not wear off all the way and they have much more freedom. Many patients say, I have not gone out in years and now I go out because I do not have to worry about getting home or what is going to happen to me when I am out.
Does the patient feel a difference?
Dr. Gerrard: We have only studied the ability to use it to close the loop and change their stimulation and it seems to be promising. The hope would be that we can smooth this up and down even more, because right now, it is somewhat smooth. But again, the programming and stimulation is stable. So, patients are still taking their medications, and are making the disease state a little better and then cycling on and off. The hope is that the stimulation itself can cycle so that it keeps their symptoms stable and that the recording brain-sensing side of this device will know that their medicine is wearing off. So, I am going to turn up the stimulation to help compensate or maybe they are getting a little too much therapy right now, so we are going to turn the stimulation down. So, hopefully it will smooth out that process.
So, it is like a remote control where they control the stimulation?
Dr. Gerrard: The patients can change the program with their own device, but it is not as fluid. In other words, they can have up to five or six programs that are installed. But what you are doing is changing it from setting A to setting B, setting B to setting C, and you have to get your device connected to your stimulator and then change the program. There are people who do that, especially with essential tremors, and it can be effective for them. This can know in real time where their disease state is right now, but we do not have the ability to close that loop. But the hope is down the road we will be able to close that loop, so the patient does not have to think about it. In fact, before they know that they are wearing off, the device knows, and it can adjust the stimulation accordingly. Instead of having just five or six steps that it can jump to, it may have a full range where it can move things just a little bit over the course of time rather than making these jumps.
So, it is personalized to the individual patient?
Dr. Gerrard: Right, it would be personalized to literally that person’s brainwave activity.
For clarification, where would those readouts go?
Dr. Gerrard: Right now, the brain sense device captures the signals and stores them right on the device itself and the device has many layers of security. When they come to the clinic, and we connect to the device, we can look at and view the information that is stored on the device. You can also download the information off the device. The patient themselves do not have access to that information, but that is software-controlled, so it could be changed over the course of time as we understand these brain signals more and more. But right now, it is stored and locked on the device except for when the clinicians have what is called the clinician’s programmer and it is different than what the patient has. It can change the stimulation and to way to access the information from the device.
Was Yale one of the centers that tested this version of the Percept Device?
Dr. Gerrard: There were several centers around the country that did research leading up to the percept, and we were not one of the lead centers doing that. As I mentioned, most of that work was done in movement disorders, which is where Deep Brain Stimulation started and what the device was designed for. We were the first to take this concept and implant it into a patient with epilepsy, another neurological disorder that affects a lot of patients around the country, so we have access to the brain waves and it can be very helpful. We already have devices in epilepsy that will record the brain waves chronically. In fact, patients with epilepsy sometimes come into the hospital specifically for us to put a whole bunch of electrodes inside and around their brain, and they stay in the hospital for a period of time until we can capture enough seizures to really understand where their seizure is coming from, what parts of the brain it overlaps with, and what functions in the brain it overlaps with. This information is extremely valuable in epilepsy as well as movement disorders. What we have not done yet is identify certain biomarkers that can tell us whether the patient is more or less likely to have a seizure. So, we are hoping to lead the way in taking this technology and utilizing it in epilepsy patients as well.
Is there anything I did not ask you that you feel people should know?
Dr. Gerrard: The main thing that I like to get across especially for patients with movement disorders and epilepsy that have been on medications for a long time and are really struggling, is that there are surgical options, and sometimes that can be scary. But, with these types of technologies, we are getting better at being less invasive by offering safer and less invasive techniques for dealing with symptoms from these neurological disorders. So there are a lot of interesting options that can provide solutions or therapies for these patients and they need to spend some time and take a look at these things, and don’t just write them off because it’s brain surgery and it’s scary. And yes, there are risks involved, but it is quite safe and can be amazingly effective and I would encourage people to take time to investigate them.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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