Robert Gross, MD, PhD, Neurosurgeon at Emory School of Medicine talks about targeting tremors.
Interview conducted by Ivanhoe Broadcast News in 2024.
The first question is about Parkinson’s. Do they all experience tremors?
Gross: No, Parkinson’s disease is characterized by tremors, rigidity, akinesia, and some walking problems. However, not all patients have tremors, many do. It can be amongst the most incapacitating aspects of it. The thing about tremors for Parkinson’s disease is sometimes the other symptoms are well treated. However, the tremor can be completely refractory to medical treatment and thus be a disabling feature of the disease.
We’ll talk about that bit about the debilitation of it. What exactly causes the tremors?
Gross: We don’t completely know for sure, but we all have some degree of tremor. It’s called physiological tremor. There are parts of our brain that are involved in coordination that allow us to have a feedback system whereas you’re moving, your body knows- your brain knows exactly where your hand is. If we get some abnormal signals going through the brain during that period, it doesn’t quite know exactly where your hand is. You might have it go a little bit farther than you wanted, or a little bit less and it leads to this oscillation going back and forth because of a lack of tuning of the system that helps us move from one spot to the other.
Talk about how it can be debilitating.
Gross: We’re going to talk about two disorders, Parkinson’s disease and essential tremor which have opposite types of tremors. In Parkinson’s disease which you asked about, the tremor is a rest tremor. At rest, you’re trying to be relaxed and as you relax, the tremor then starts to come out and makes it very impossible to relax. You have this shaking. Imagine if every time you sit quietly, you are not able to relax. It also can impair your movement of course. Now in Parkinson’s disease, the movement will suppress the tremor for a moment. As you’re sitting there at rest and then you go to move, but then when you get to that point where you’re at, it starts to tremor again. Essential tremor, which we’ll talk about a little bit more is the opposite. There is no tremor at rest, so you’re fine. Then when you go to try to do something like grab a cup, then it comes out. They’re both disabling in a very different way, but it’s really hard to go about your normal activities such as drinking and buttoning your shirt and feeding yourself when you have this type of tremor affecting your movement.
What is traditionally out there to help control the tremors as medications and things that?
Gross: For Parkinson’s disease, the standby is Sinemet. In Parkinson’s disease, the brain has lost its dopamine neurons that are in the motor circuit. We try to boost up dopamine by giving the precursor for it called L dopa, which is what Sinemet is. Because it boosts those normal levels, it can restore your function. Early in Parkinson’s disease, that may be very effective, but as we start to lose the neurons, that precursor doesn’t have any place to go for all intents and purposes. It becomes more and more difficult for the medication to work.
Now talking about this noninvasive way to control these.
Gross: When patients reach the end point of their medical therapy where the medicines are still working but they’re not working as well as you need them to be. You have periods when you have tremors or when you have other symptoms of Parkinson’s disease. It’s at that stage that surgical therapies are considered, and fortunately, are effective. Now, we have been doing for years, deep brain stimulation, which involves putting electrical wires into your brain and a pacemaker. It works great. But not all patients like to have that hardware and the associated tuning that’s required as well as sometimes replacing the battery. There’s another way to go about this, and that’s instead of putting an electrical wire in, which essentially jams the circuit, we can just create a small thermal lesion. We essentially burn out the area that’s involved. Now this has been being done by me and my colleagues and predecessors since the 1950s, but now we have a new way to go about that. The old way involved putting an electrode into the brain invasively to create that burned lesion. Now we can do this non-invasively using sound waves that get through the brain and create that thermal heating in the area where we’re trying to negate the activity.
What is ultra-focused ultrasound and how does it specifically work?
Gross: It’s MRI-guided high-frequency or high-intensity focused ultrasound. First, it’s guided by an MRI scan. We can now see the area in the brain that we know is the therapeutic target within an area called the thalamus. We’re trying to create a small hole in the thalamus, and we call that thalamotomy. This is an MR-guided focused ultrasound thalamotomy. Focused ultrasound refers to the fact that we take sound waves that are normally used in diagnostic ultrasound. You’re familiar with them because you might have had kidney stones or during pregnancy, you can see the beating heart. That’s a diagnostic ultrasound that sends sound waves into the brain and looks at their reflection. In this case, instead of taking one single ultrasound transducer, we take 1,000 ultrasound transducers. They’re arranged around the head in a helmet. We focus those 1,000 beams such that as they’re going through, they don’t do very much heating at any trajectory through the brain. But they all meet at a certain point, which is exactly where we want to create that lesion. That small amount of heating from each ultrasound wave will summate at that target and create an amount of heating that is sufficient to create a lesion- a thermal lesion in that spot. It’s a high-intensity focused ultrasound guided by MRI imaging.
Does it work, do you have any success stories? Is it working?
Gross: Yeah, it’s working great. We’ve known for years that thalamotomy, creating that hole in my thalamus is effective. It just required us to go through the brain and through the head with an invasive electrode. This novel way it’s not that novel. It’s been being developed for decades, but now we have the hardware that allows us to do it in an almost turn-key approach and we can do it in different centers. This means of doing thalamotomy is very effective and it’s noninvasive. Patients love the ability to be able to come in and have the procedure, not have surgery as we know it, and go out just a few hours later. For its degree of effectiveness, it’s associated with a greater than 50 percent decrease in tremor and it’s longstanding as well. We have data going out now, two to five years and beyond that shows that it’s a very sustained effect, keeping at about 50 percent with some little bit of decrease as time goes by.
Is this an ongoing treatment or is it a one-time thing?
Gross: One-time treatment takes about two to three hours really in the whole experience. Let’s say you’re the first case in the morning. You come in, start at 7:30, 10:30 you’re walking out the door and on your way. Usually, our patients go to a restaurant and eat soup, which for them is an ecstatic experience.
This is not all new technology, it’s all just a combination of many different layers of technology. Is that true?
Gross: Yeah. The first conception of this and the forerunner of this was back in the 1940s. But it’s a technically difficult problem to solve. There have been iterations every 10, 15 years going through the decades to the point now where our technologies have advanced. For example, MRI imaging technology has advanced, and the hardware has advanced such that just in the last decade, we’ve had access to this type of technology that can be now installed in multiple centers around the world.
Is it FDA-approved?
Gross: It is FDA-approved. The FDA approved the use of MR-guided focus ultrasound for the treatment of tremors, from essential tremors and from Parkinson’s disease in what we call tremor-dominant Parkinson’s patients. It’s been further approved for treating the other symptoms of Parkinson’s disease as well, such as excessive movements that come from taking medications, slowness of movement, and rigidity. In that technique, we do what’s called a pallidotomy rather than a thalamotomy. Essentially the same technology, making a hole in the brain, but instead of making that hole in the thalamus for those other symptoms of Parkinson’s disease, we make the hole in the palladium.
What does this mean for a patient?
Gross: It’s been remarkable to get on this journey. I’ve been treating patients with surgery for 25 years. It’s not a tremendous surgery, but you must come into the hospital, you must go to the operating room, you stay overnight, and you’re discharged the next day. There’s pain associated with incisions and so forth, and really, it’s game-changing for these patients. They come in in the morning, your first case comes in in the afternoon. If you’re the second case, you hardly get out of your civvies, your regular street clothing. We have patients lying on the MRI table in their sneakers. It’s not trivial to go through, there’s a frame that gets affixed to the head. There’s a four-point restraint on your head and there’s some discomfort associated with that. There’s some discomfort associated with the procedure itself, some heating up of the skull, but people get through it. After about an hour, hour, and a half, we finish up, take another MRI scan, you’re back into your regular street clothes, and walk out the door. It’s as close to drive-through neurosurgery as you can get. I have appreciated how meaningful that is in patients’ lives because, at that point, it’s one and done. They don’t have to come back for adjustment of the device, battery changes, and so forth, and wait for the effect to come in from the adjustment of a deep brain stimulator. They see the effect right away; they hold their hands up. We might drink champagne or eat a piece of cake with the patient right then, and they see the effect right then and there, and it’s meaningful for them.
Let’s talk about Mr. McDonald. He’s the first person to have done here through Emory. Can you tell me about him? What was his life before, and then what about after?
Gross: As with all our essential tremor patients, he had essential tremors. Essential tremor is not Parkinson’s disease. There are four symptoms of Parkinson’s disease, tremors, rigidity, slowness of movement, and walking problems. With essential tremor, there’s one symptom, that tremor that happens not at rest, but when you go to try to do something. It’s a sick joke of a disease. You’re fine when you’re just sitting there. People can look at you and say you have no problem, but as soon as you try to do something, which is what we as humans do, we do things, that’s when it interferes with your ability to get dressed in the morning, to eat a bowl of cereal, to drink your coffee, to button your shirt yourself, to sign a check. You can’t go out or you find difficulty in going out to restaurants because you’re sitting there having a conversation, the food comes and now you start to shake it all over the place. People walk around with big sippy cups with straws because that’s the only way they can drink things. It can get to the point where you can be a recluse, essentially, that you’re even afraid to go out and do those social things. It gets worse with the years so that when you’re in the twilight of your career, you’re enjoying your retirement, you want to do woodworking, you want to do artwork, sports, golf, it interferes with all those activities. Mr. McDonald was in that category, retired and ready to enjoy the things that he wanted to do daily and maintain his independence, and he couldn’t do that. He was never willing to come in for a brain stimulator because there’s a lot involved in that for just this one symptom that is getting in the way of your life. He was eager to join in and even though he was our first patient, not our first surgery patient, but our first focused ultrasound patient, he just said from the beginning, I have total confidence we’re going to get it done and it’s going to work and I’m not going to get hurt. He was courageous to do that. He came in, we had to do a little head shave. The device needs to have good contact between the ultrasound and your skin, so we must shave your head. For me, that’s not so much of a problem but for other people it is. He had his head shaved and he looked great, his wife liked the way he looked as well. Then he laid down, we put the frame on, got him in the MRI scanner. Just a courageous person throughout that whole thing had a little bit of discomfort during it. When we finished, he got up and we literally, it was our first patient, so we got a bottle of champagne and we toasted together. he held that as firm as could be, went out to our restaurant, had soup.
Was it instant results for him?
Gross: Yeah. Once that hole is burned in your brain, and we do it progressively, we do a little bit of heating, a little test heating, see that we’re in the right place, that we’re getting the results, that we’re not getting adverse effects, and then we turn it up a little bit more and then we cinch it in. Once we’re done with burning that hole, it’s done. We’ve done the operation, it’s as good as it gets, and so you have immediate results, and we see that on the table. We have people sign their name and draw spirals and when we see they’re able to do that for the first time, then we know we’re done. Usually, there’s a little bit of a tear shed from our patients at that point. It’s been years since they’ve been able to do this basic human act of signing your name and that creates a little bit of an emotional experience, and I understand it. Sometimes we shed a tear too.
What’s his life like now?
Gross: He’s enjoying it. We’ve seen him, now it’s been, I guess it was about, not quite a year ago and we’ve seen him six months, at three months, and he’s off doing things and traveling. I’ve been struck by how many people go on cruises afterward.
Do you think this is the future of treating tremors?
Gross: Yes, already in its short several years since its introduction, it has surpassed the use of deep brain stimulation for treating essential tremors. Now, Parkinson’s disease is more complicated because it’s only some patients that have this tremor-dominant form of Parkinson’s disease. This thalamotomy only treats the tremor so we use it less in tremor-dominant Parkinson’s disease. But again, there’s another type of therapy we can use. But for essential tremor, there’s no going back from this. It’s not the right surgery for everybody with essential tremor, some patients still get deep brain stimulation, but just in the decades since its introduction, it has surpassed the use of deep brain stimulation because it doesn’t tether people to their doctor, they don’t have to have this device come in, have it always tuned up. They get this procedure and off they go and don’t have to come back for all intents and purposes.
Do you think that this could help with other illnesses that cause tremors?
Gross: Yeah, other things cause tremor. Some people have multiple sclerosis as a cause of tremor. Some people have damage to their cerebellum from a stroke or an injury. Thalamotomy in general works sometimes not quite as good, but it is the best therapy for some of those disorders as well. We certainly see that on the horizon. Also, focused ultrasound as a technology can be used to burn holes in the brain for other reasons that are therapeutic, like epilepsy, for example. We’re even able to use a slightly different version, low intensity or a low-frequency focused ultrasound that doesn’t create holes in the brain but modulates brain function. That’s being explored for other things like even brain tumors, Alzheimer’s disease, and addiction, and I think there will be several other disorders that will be in our crosshairs in the coming years.
Has this just even shocked you as a doctor?
Gross: Yes. Having done thalamotomies in the past, I did not see this as being all that revolutionary in terms of I can do a thalamotomy, I just must drill a hole in your brain and put it in, for me, that’s not a big deal.
END OF INTERVIEW
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