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Interviewer: We're here with Dr. John Rolston, the [former] director of functional neurosurgery, and Dr. Matthew Alexander, he's an assistant professor of radiology and neurosurgery here at University of Utah ÐÇ¿Õ´«Ã½. Let's start with just kind of talking about essential tremors. What is an essential tremor and what does that mean for patients that have it?

What Is an Essential Tremor?

Dr. Rolston: So essential tremor is the most common movement disorder that anyone in the world has. So it's a movement disorder characterized by uncontrolled tremors or movements of typically the hands, but sometimes the voice and head too. These movements are pretty common around eight times per second when they happen, and they can start disrupting people's lives. So with a really bad tremor, it's hard to do things like sign your name, write checks, hard to eat or drink from a glass, hard to eat soup with a spoon. It can become so disabling that people are unable to do these activities at all. And that's when they start to, and before them, when they start to approach us for medical treatment or surgical treatment.

Interviewer: And so you're saying eight times a second? Is that all day long?

Dr. Rolston: All day long, all the time, except when you're asleep when it goes away. But when you're doing any sort of activity, it's there and prevents you from doing all these normal things you used to do like talk on the phone or type on a keyboard.

Essential Tremor Causes

Interviewer: And what causes it?

Dr. Rolston: We don't really know yet. So even though it's the most common movement disorder, the amount of research that's been done for it is far dwarfed by the amount that's been done with other diseases like Parkinson's. So we're still trying to find out the underlying mechanisms for what causes it. But we do know that it's definitely involving circuits in the brain. We know this because changing how these circuits function can improve the tremor, which is the basis of our surgical therapies for a tremor.

Interviewer: And Dr. Alexander, when someone comes with an essential tremor, how do you diagnose it? What do you look for? What do you . . .

Dr. Alexander: So it's fairly obvious to us by the time they get to us, but it's usually a progressive disease that has gone over the course of decades. There can be familial variants. So some people experience this starting their 20s, 30s. I've heard of some people even in their teens. Most people, it's, you know, middle-aged folks start to notice it. And it's usually just kind of a tremor that they have in their hands. They might notice it gets a little worse with intentional movements. But it's a progressive disease. And so they'll notice over years that it gets worse and worse and worse. And so by the time they get to us, because we only treat the most advanced cases, it's a pretty easy diagnosis to make. And it's often been made by someone in the community, either a primary care physician or someone in neurology that that patient has been referred to.

Essential Tremor Treatment: Medications Used

Interviewer: And Dr. Rolston, after you have the diagnosis, you're seeing these people, they have this really debilitating tremor in their lives, what is the way that it's typically treated or used to be treated?

Dr. Rolston: Sure, that's a great question. So the way we typically start treating these patients is with medications. So there's only one FDA-approved medication for essential tremor, and that's propranolol. The brand name is Inderal. So many patients are prescribed this if they can tolerate it, if they're not forced out by the side effects of low pulse, dizziness, lightheadedness. Then, they can go and take this medication, and it might reduce the either frequency of the tremor or the amplitude of the tremor, so basically how much it's affecting them.

There's other drugs when that one doesn't work. There's another drug called Primidone, which is very common. It's actually an anti-seizure drug. This one also has a lot of side effects, so dizziness, tiredness, that a lot of people can't tolerate. Once those two medications have failed, there's a lot of other more experimental drugs people try. But when the first two primary drugs fail, the chances of one of these third or fourth-line therapies working is pretty low. And that's when surgical therapy becomes more of an indication.

Essential Tremor Surgery

Interviewer: What is the typical way of doing the surgery? I mean, we're talking brain surgery, right?

Dr. Rolston: Yeah. So they've known since the 1950s that if you go to these small little parts inside the brain . . . they're called the ventral intermediate nuclei of the thalamus. So there's two of these. They're both pea-sized little pieces of tissue deep inside the brain, kind of toward the middle of the brain. There's one on the left and one on the right.

If we damage either one of these . . . We noticed, back in the '50s again, that there was a substantial improvement in the tremor on the opposite side of the body. So if you injure or get rid of this left-sided one, you can see an improvement in the tremor on the right side and vice versa. The way we used to do that was with an open brain surgeries. We would make a hole in the skull, insert a fine needle, heat up the tip of the needle, and burn out this small little pea-sized area. This worked great, but it involves a hole in the head, which is a big deterrent for a lot of people to seek this therapy.

Interviewer: Understandably.

Dr. Rolston: Yeah. In the 1990s, they developed a deep brain stimulation, which puts a wire in the same location, but instead of damaging that part of the brain, it stimulates it electrically with a pacemaker that sits in the chest. And that's very effective. And that's what we've been mostly doing for the past couple of decades now.

New Treatment for Essential Tremors: Focused Ultrasound

Interviewer: But it's my understanding there's this new ultrasound-assisted . . . what is it called?

Dr. Alexander: MR-guided focused ultrasound. The MR is for magnetic resonance, so like an MRI machine, which is actually where we perform the surgery.

Interviewer: Inside the big tube?

Dr. Alexander: Yes.

Interviewer: Wow. Okay.

How It Works

Dr. Alexander: So they go in an even smaller tube, the thing goes inside that big tube. So this utilizes the opportunity of ultrasound to be able to deliver energy to tissues in the body. So we normally think of ultrasound when it comes to diagnostic imaging, so maybe for like an obstetrical ultrasound, to look at a fetus, or maybe if somebody has gallstones, they look at the gallbladder that way. And that involves a diverging set of little sound waves that are sent out from a probe. And then, that bounces back and gets interpreted and spit out by a computer on a screen to look at an image inside the body.

We've known for a long time that each of those little sound waves can cause a little bit of energy to be deposited in the tissues. In those diagnostic scenarios, it's very safe. Again, they're diverging and it's a small amount of energy. We know that we can focus these beams much like using a magnifying glass with the sunlight. And we can use that to actually effect change. We deposit enough energy that we raise the temperature and burn that little pea-sized area just as they did back in the '50s but without actually making an incision.

Ultrasound, it's the same technology that underlies those imaging studies that people get, but it's a different way to harness that energy to use over 1,000 elements to deliver a bunch of very small things. And so you get them all converged at one area. It actually delivers a fair amount of energy. And so we go through several steps of imaging to map out where this VIM nucleus of the thalamus is using an MRI. And then, we also have a CT scan that kind of maps the skull, and then we overlay that with the MRI. And using that CT of the skull, we can direct the ultrasound to make sure that we target it precisely where we need to get.

How Long Does a Focused Ultrasound Take?

Interviewer: Wow. And how long does the whole process take?

Dr. Alexander: So the whole process is probably about three to four hours. Part of that is spent shaving the head, getting the frame on. The actual part where they're in the scanner is probably anywhere from an hour and a half to three hours. Probably more often on the hour-and-a-half range though at this point.

Interviewer: And then what? Do you just send them home? Are they stuck in the hospital for a while or . . .

Dr. Alexander: We observe them for a little bit, make sure there are no side effects. They've gotten some of those medications. And then, there will be a little bit of swelling in the brain that makes them a little uneasy, a little wobbly. So we observe them for an hour or two, but it's an outpatient procedure. They go home that day.

Focused Ultrasound Effectiveness

Interviewer: Dr. Rolston, how long have you guys been doing this?

Dr. Rolston: So we've been doing this for about a year now. It's been FDA-approved for slightly longer than that. So we're the only place that does it in this time zone in the United States, so the only center in this region. We've had a great experience. So the patients that we've done have had fantastic outcomes.

When they did the randomized control trial to prove that this was effective, they had about, on average, a 50% improvement in the tremor. But that included patients that . . . The way they designed the study was called an intention to treat. So there were some people that didn't actually get treated that are included in that 50%. So the results, they were probably a little bit better than that. We're seeing results that are better than that still. So more like 75% or better improvement in the tremor for all the patients we've treated.

Best Candidates for a Focused Ultrasound

There's some thoughts and considerations we put into selecting patients. We want to make sure that they obviously have essential tremor before we do this procedure. But there's also a consideration for how dense the skull is. The skull is a big component of how we do the therapy. We try to do the therapy through the skull with the ultrasound, but sound waves travel really well through solid, dense things, but less well through kind of mushy, less solid things. So you can kind of imagine knocking on a table, and that has a nice loud echo, but if you knock on a pillow, you don't get much sound through that.

So we need to make sure the patient's skull is very dense and able to conduct these sound waves to cause the changes we're looking for. And we do this with a preoperative CT. So we get a CT scan the day before or a month before. And we measure the density of the skull to make sure that we can actually have a successful therapy. And there's some people, especially with bad osteoporosis, where we can't get the result we're looking for. So those patients, you could perform the procedure, but you might not get enough temperature increase to cause a permanent change.

Non-Invasive Treatments for Essential Tremor Patients

The most important thing about this is we've had good surgical treatments for tremor for a long time, but many people are understandably worried about doing any invasive surgery, any sort of incision anywhere. Now that we have this non-invasive treatment, even though there are some limitations based upon skull density, some limitations on the kind of person to be best for, even though we have that, it's a wonderful new opportunity to bring people in for a treatment that otherwise would never consider any sort of invasive therapy. So there's a large population of patients that would never be able to be treated that can now be treated, which is why we have such a tremendous response to this and so many patients that are interested.

The Future of Focused Ultrasounds

Interviewer: This seems like a technology that could be used in a lot of potential ways. What do you think the future is for this?

Dr. Alexander: Absolutely.

Dr. Rolston: Yeah.

Dr. Alexander: So it's a fantastic new tool, and we're looking for ways to apply this tool. So there are new trials that are currently underway for other things such as Parkinson's disease, mood disorders, things like that that will be on the horizon in the coming years. But then, in addition to that, and part of what's exciting to be doing this at the University of Utah, is we're looking to further expand indications. So we are working with some of our basic science and translational researchers here on campus to use animal models to try to develop new methods, new things that we can use this to tackle. And so it's a really exciting opportunity, both to be able to offer this new, really effective treatment, but also be able to try to expand the horizons so that we could offer it for, you know, a lot more people for a lot different diseases.