Focused ultrasound: Effective treatment for Parkinson’s disease and essential tremor

Transcript

Scott Webb (Host): Focused ultrasound is an innovative, non-invasive treatment for tremor caused by essential tremor or Parkinson’s disease. Neurosurgeon and Chief of Neurosurgery at Prisma Health Richland in Columbia, South Carolina, and Clinical Professor with the USC School of Medicine, Dr. Erwin Mangubat joins us today to talk about this new treatment option, offering minimal risk and maximum precision.

This is Flourish, the podcast brought to you by Prisma Health. I’m Scott Webb. ​Doctor, truly nice to have you here today. I was mentioning to you that I want to learn more about focused ultrasound. I’m sure listeners do as well. But before we get there, I don’t want to get too far ahead of ourselves here. Let’s start with maybe the most obvious one. What is Parkinson’s disease and do we know what causes it?

Dr. Erwin Mangubat: Parkinson’s disease is a progressive neurodegenerative disorder that affects movement, but also can cause some cognitive and other non-motor symptoms. But classically, the motor features are tremor at rest, having bradykinesia or slowness of movement, muscle rigidity, and having some postural instability or imbalance.

Other features that are more non-motor are things like depression. Patients can have issues like sleep problems, other things like constipation, loss of smell. And, you know, unfortunately things like cognitive decline, dementia are pretty, unfortunately, common things that patients with Parkinson’s can experience. And typically, these symptoms can gradually worsen over time.

So, the cause of it, the hallmark is a loss of dopamine-producing neurons and deep brain structures, specifically called the substantia nigra. And this dopamine is used for smooth, coordinated muscle movement. Why this happens, it’s not really fully understood, but it’s a combination of a number of things. We’re starting to understand that genetics do play some role that can predispose some folks to developing Parkinson’s disease, but doesn’t absolutely say that they’re going to for sure develop it. More and more studies are showing that the environment, such as exposure to certain toxins, pesticides, heavy metals, that sort of thing, head injuries. And the strongest risk factor is aging. But still the most common reason for or cause of Parkinson’s disease is it’s more sporadic. So, around 90% of patients with Parkinson’s, there’s no clear genetic link. There isn’t any clear combination of any environmental exposures or anything like that. So in the end, unfortunately, for the most part, it’s just unfortunate luck.

Host: So, you went through some of the symptoms there, and I guess it makes me wonder do folks sometimes attribute these symptoms to something else, right? And they don’t automatically default to Parkinson’s. Does that maybe slow them going in to see a provider or speak with somebody? And are there any, let’s say, rare symptoms that people should be on the lookout for?

Dr. Erwin Mangubat: The rare things that can be seen: patients can have trouble with movement of their eyes, particularly with looking up. It’s called slow saccades or difficulty tracking things with their eyes. Folks can have freezing of their gait or they move and they stop moving suddenly. That can happen when turning or approach things like doorways. They can develop things like dystonia, which can be painful, like toe curling or their foot getting inverted and that sort of thing. And then, more of the non-motor things like hallucinations. Folks can also have some impulse control disorders, even some pain syndromes. And then, some other red flags are early falls, dementia, again, problems with their gaze, may suggest things not just Parkinson’s, but more atypical Parkinson’s syndromes.

Host: In preparing for this, I was reading about essential tremor or ET and wondering if you could break that down for us. What does that mean? What is essential tremor?

Dr. Erwin Mangubat: So essential tremor, it can be confused with Parkinson’s because Parkinson’s has that tremor component. It’s one of the cardinal features. But essential tremor is actually the most common movement disorder. It’s characterized by involuntary, rhythmic shaking. It can affect the hands and arms, also can affect the head and the jaw and actually, the voice and legs and so forth.

The difference between the tremor, between essential tremor and Parkinson’s, is the Parkinson’s tremor is at rest. So if their hand is resting on their lap or something, that you can see that tremor. Essential tremor is more action-related or postural. So, you know, when you get tested with coordination at the doctor’s office, bringing your finger to the doctor’s finger and back to the nose and that sort of thing. At that end point, from the patient’s nose to the doctor’s finger, you see a lot of waving and that sort of thing. These patients have a lot of difficulty, things like writing, eating, doing normal activities of daily living and that sort of thing.

Host: Okay. So, it really sounds like even though folks with Parkinson’s have tremors, it’s a sort of different manifestation, if you will. And essential tremors sounds like it’s really it’s own medical condition, right?

Dr. Erwin Mangubat: Yeah, that’s right. It’s thought to be understood. There’s a certain circuit in the brain called the cerebello-thalamo-cortical circuit, So again, with Parkinson’s, it’s more of a neurodegenerative disorder of loss of certain neurons in the brain. This is more of a dysfunction in itself of a certain circuit.

Host: Okay. So, let’s then talk about some of the treatment options, how do you treat Parkinson’s essential tremor, and is there such thing as a cure for these or is it really managing these diseases or conditions?

Dr. Erwin Mangubat: The most important thing is getting a correct diagnosis of one or the other, because the treatment can be different. First off though, after getting that correct diagnosis, most likely initially through a primary care physician, but even more further so through a neurologist that sees and treats movement disorders. But the first form of treatment is generally medication with essential tremor. It’s things like beta-blockers or like propanolol or certain antiseizure medication called primidone is first tried. Parkinson’s, it’s physical therapy, medication, things like Sinemet.

And also, both pathologies, you know, other things that you can do are more lifestyle changes. We know using sort of weighted instruments like weighted cups and weighted forks and spoons to feed themselves can help with those things for daily living. If the diseases progress, we have these certain tools, either deep brain stimulation or what you brought me on to also discuss was MRI-guided focused ultrasound.

For deep brain stimulation, it’s very well-studied. You know, in my opinion, and I think a lot of other surgeons’ opinions, is that it’s still the gold standard. And the reason why is that it is a reversible type of treatment. Essentially, it is creating an electric field in the brain to neuromodulate certain circuits in the brain. For essential tremor and tremor-predominant Parkinson’s disease, we actually treat the thalamus where we put a lead into the brain, into the thalamus, where we create an electric field to disrupt those abnormal circuits.

It is reversible, especially with diseases like Parkinson’s, where again, it’s a neurologically progressive disease. Nice thing with having something programmable is that as the disease progresses the stimulation can be turned up to hopefully give more of a treatment. The downsides with deep brain stimulation, a lot of reasons why people go away from it is because it is a surgical procedure. It is placing a lead in the brain. It can be scary. There are risks. There’s like a 1% risk of causing bleeding in the brain. There’s a pacemaker that goes in the chest that regulates the electric stimulation that goes in the brain that needs to be either charged and/or replaced every few years, that’s just more surgery.

The other option is MRI-guided focused ultrasound. And this has been FDA approved specifically for essential tremor since 2016. Same target, it’s the thalamus, so specifically the ventral intermediate nucleus of the thalamus. And it has been shown to be very effective in treating tremor over a period of five years. Longest studies have shown that the patients have had a reduction in their tremor, pretty durable reduction in their tremor over five years by 50-70%.

Host: Wow. Yeah. That’s pretty amazing. I want to dig in and roll up my sleeves here. You roll up your sleeves too. But how exactly does that work? How does focused ultrasound work, the sort of technology, if you will?

Dr. Erwin Mangubat: I don’t ever want to say it’s not invasive because it is invasive in a sense, because we are causing or creating a lesion in the brain. The thing is it’s a controlled lesion. But it is incisionless. It’s an incisionless surgical technique. I think that’s a bit more of an honest description of it.

So, it uses specifically the device that’s out there, it’s made by Insightec. It uses 1,024 different apertures installed in a helmet that delivers a small amount of ultrasonic energy. With those different apertures, it meets at one center, if you can imagine a center in the helmet. And so, in that center, it converges and it’s very precise and very hot. Again, so each individual beam passes harmlessly through the skin and the skull, and then combines to generate enough heat. So in the brain to create a lesion, our goal is to develop heat at about 55 to 60 degrees Celsius to injure – and specifically what the terminology is ablate – a tiny area of brain tissue, so that will be that part of that thalamus.

The entire procedure is done in the MRI scanner. We can very, very precisely target where the lesion will be created. And then, also, we can see what that temperature is through MRI thermography or measurement of the temperature through MRI. The beautiful thing with this technology is that, although in the end it’s going to create a lesion, a permanent lesion, we can actually, before we create that lesion, heat up the tissue to a point where it’s not injured, but causes more paresis or a temporary kind of paralysis. What we want to see is obviously symptom relief, meaning reduction in the tremor specifically for something like essential tremor. And we want to avoid seeing anything like weakness or numbness in the fingers or difficulty speaking and that sort of thing.

So, if we see any unwanted side effects, what we do is we let the brain cool down, we readjust our target, we test again. And then, if we’re happier with that, that’s when we create a permanent lesion. In the end it has a good, balance, with deep brain stimulation where we can test things out before we permanently put something. But also, we’re able to create a lesion such that it gives a pretty one durable lesion that reduces symptoms, and then without having the other downsides of deep brain stimulation, like having to be programmed again, charging a battery, or getting batteries replaced and that sort of thing.

Host: Yeah. So definitely different, as you say, deep brain stimulation perhaps still the gold standard, but focused ultrasound maybe catching up, of course. And I guess it makes me wonder, is there a right candidate for focused ultrasound? Is it a matter of qualifying? What’s the right terminology and how does one receive that treatment?

Dr. Erwin Mangubat: Yeah. The big thing, I think, is first off is patient preference. It’s always good for a center to give options to a patient. If you look at the grand scheme of things, even with focused ultrasound, the amount of deep brain stimulations that’s in the country has stayed pretty stable, but the amount of focused ultrasound has exponentially increased since the FDA approval of this device just because patients, for a lot of reasons, would prefer not having an implantable device in the body.

So, the biggest contraindications for focused ultrasound would be for any reason a patient can’t have an MRI. They either have a metal implant or pacemakers that are not safe, or even if they have like severe claustrophobia, because oftentimes patients who have claustrophobia only can get through MRIs with anesthesia. But it’s very important for patient participation for this to be done right and safely where they have to participate in the exams and making sure that we deliver the energy to create that lesion in a safe spot. They have to be able to participate.

So, another thing is the patient’s skull and the thickness and any irregularities can play a big part in this procedure. About half of the energy that is absorbed from this device is absorbed at the skull. And in order for the device to calculate, to predict how much energy is needed to raise that temperature, having a uniform skull thickness and pretty smooth thickness, it’s important to have something called good skull density ratio so that we can have good predictability of the amount of energy that gets to the target.

And then, again, in terms of being able to participate, any cognitive impairment or unstable psychiatric diseases or anything like that would make it difficult for a patient to lie flat for a period of time in the MRI suite and that sort of thing would limit having focused ultrasound.

Host: Yeah. Wondering is it an outpatient procedure, and roughly how long does it take?

Dr. Erwin Mangubat: Yeah. So, it’s an outpatient procedure. It takes anywhere from 45 minutes to an hour and a half. A lot of that just depends on the thickness of the skull and just the efficiency of the team. But again, it is less than deep brain stimulation. This is a same-day procedure, generally in and out about 45 minutes to an hour.

Host: And is there much preparation, if you will, for patients? And then, on the other end, is there long recovery period?

Dr. Erwin Mangubat: As far as preparation goes, before the treatment day, it’s meeting someone like myself, a surgeon, obviously working with a neurologist or their primary care physician who’s adept at treating things like essential tremors is important.

Before the treatment day, we generally get that CT scan to make sure that the skull is appropriate for treatment. I generally get a pre-planning MRI so that I can plan on the MRI before the procedure. So, there’s not necessarily too much in terms of on-the-fly planning. It’s more just taking our plan and carrying it out.

And then, the day of the procedure, there’s a couple things that we need to do. So, we do a preoperative test. We have the patient draw a few spirals as a baseline, draw a few lines and that sort of thing as a baseline study. And then, we’ll have the patient also do that same thing during treatment, and we give a grade in terms of their improvement in their mobility and their tremor relief.

Also, we have to give them a special haircut. We got to shave the head pretty close to the skin. The reason for that is, again, with that ultrasonic ultrasound delivery, we don’t want any things like bubbles which can be at the level of the hair that can cause deflection of the ultrasonic wave. So, having a very close shaved haircut is going to be very important that we would do. Then, after that, we would place a frame, it’s like a halo that is attached. Using a lot of local medication, patients tolerate it pretty well. It’s just a lot of that is just mostly coaching. And then, after that we place a little diaphragm around the head because, again, with that ultrasonic energy that’s delivered, it would cause some thermal injury to the scalp. to avoid that, there’s this diaphragm around the head within this helmet. We place circulating cooled deionized water to prevent any bubbles, to prevent any thermal injury of the scalp.

And then, as far as recovery, patients recover about an hour within just to make sure that they’re doing okay, okay to go home after the procedure. And then, usually, around two or three days, patients are back to normal daily living.

Host: Yeah. It’s just so remarkable. I want to have you give listeners and myself a sense of the effectiveness of focused ultrasound on the treating of tremors.

Dr. Erwin Mangubat: Yeah. Both for essential tremor and a tremor-predominant Parkinson’s disease, it’s a very durable procedure. In the longest studies that we have over a period of five years, it was around 73% patients reported reduction in their tremor. So, it’s pretty durable, it’s very effective.

Host: Durable and effective, I love hearing that. Are there any disadvantages or side effects to focused ultrasound?

Dr. Erwin Mangubat: Yeah. There are some risks. And I think we’re getting better at avoiding those risks. But one risk, especially if both sides are treated, patients could have some gait disturbances or imbalance with walking. I think with the changes in where we’re targeting, we’ve changed the targeting a bit from classic treatment with deep brain stimulation where we actually treat a little about two millimeters above a previous targeting. we’ve been able to or reduce the chances of patients having gait disturbances.

Obviously, we do our best in terms of reducing things, and that’s why the live testing, the intraprocedural testing, to avoid any weakness or the paraesthesia or numbness in the hand and that sort of thing, but it still can happen. Unfortunately, we are creating a lesion, although I do feel and I think most people feel that it is still a very controlled injury, but still sometimes that injury can grow a little bit and it can cause some dysfunction to some of the adjacent structures. The chance of that is pretty low these days. And honestly, it is temporary. And it’s usually not debilitating. The most common is the paresthesias in the hand or in the fingers. Patients would report that, but they wouldn’t say that it was disabling or anything like that.

Host: Yeah. Really fascinating stuff. I just want to finish up, you said you’ve used the term durable a few times, so it makes me wonder naturally, how long do the benefits last of focused ultrasound? Does it last forever? Do they have to come back in, you know, again, after five years or 10 years, how does that play out?

Dr. Erwin Mangubat: That’s still a question. I mean, the reason why we say five years right now is because that’s the longest study that’s out there. I would say that it could last a lifetime. A lot of the cases though, there is some reduction in effectiveness. But the nice thing with this procedure is that it doesn’t burn bridges, meaning, one, we could consider deep brain stimulation later, or we could more commonly talk about retreating with focused ultrasound.

Host: Right, re-treatment. Yeah. Well, It’s amazing stuff. We’ve come so far in the treatment of Parkinson’s and essential tremor. And it’s just great to have your time and your expertise today. Thank you so much.

Dr. Erwin Mangubat: Thank you, sir.

Host: And for more information, go to prismahealth.org/news. For more information and other podcasts just like this one, head on over to prismahealth.org/flourish. This has been Flourish, a podcast brought to you by Prisma Health. I’m Scott Webb. Stay well.

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