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Interviewer: We're here with Dr. John Rolston, the Director of Functional Neurosurgery, and Dr. Matthew Alexander, he's an Assistant Professor of Radiology and Neurosurgery here at University of Utah Health. 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?

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Interviewer: A Link Between Methamphetamine Use and Parkinson's Disease, up Next on The Scope.''

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Interviewer: I'm talking with Dr. Glen Hanson, Interim Dean at the School of Dentistry at the University of Utah and Director of the Utah Addiction Center. You've done some researching looking at a long-term and serious side effect of meth use. What did you find?

Dr. Hanson: We were interested in the dependence on drugs, such as methamphetamine and the amphetamines, and we knew -- we've known for quite a while -- that it interacts with that part of the brain that is associated with the neurological disorder known as Parkinson's disease. And from animal studies, our findings suggested that it may lead to Parkinson's disease in humans, and that's what the study looked at. We found that there was a connection between that dependence on these compounds and Parkinson's disease.

Interviewer: So meth use increases your risk for getting Parkinson's disease. How much of an increased risk do you see?

Dr. Hanson: In the general population, it's about a threefold increase.

Interviewer: This increased risk factor for getting Parkinson's disease is one of actually many terrible side effects of meth use.

Dr. Hanson: Correct.

Interviewer: And is this really the first long-term effect that we know of?

Dr. Hanson: It is, that has looked at a neurological piece to it. We know, in human studies, there are changes in some cognitive functions in people who are long-term users, and they find that some of these neuropsych determinants or elements are still compromised in these people, things such as memory. But even these studies typically only go out two or three years, and none of them have asked the long-term question, ''What neurological diseases may happen down the road to this population of amphetamine users?'' These studies are the first ones to show that this long term, maybe ten, twenty years after you've had the amphetamine problem.

Interviewer: So maybe we can back up a second and you can remind us what Parkinson's disease is.

Dr. Hanson: Parkinson's disease is associated with a fairly select group of pathways in the brain that are involved in motor control, and so some of the earliest signs of Parkinson's are things such as tremors, usually hand tremors, the way someone walks, their posture, they tend to become stooped.

Interviewer: And so you were mentioning in the beginning that there's a particular pathway in the brain that leads to Parkinson's disease. You've also shown that, at least in an animal model, that class of drugs can also damage that part of the brain.

Dr. Hanson: So this pathway uses a chemical called dopamine, and dopamine is a big player in mobility, in behavior, in movement. So there is a selected pathway called the nigrostriatal pathway that methamphetamine or the amphetamines damage when they're used continually and they're used in high doses. So the same pathway gets damaged in Parkinson's. A general figure is that if you damage 70% of that pathway, then you start to see signs of Parkinson's disease.
In everybody, that pathway deteriorates over their lifetime, but most of us die before we reach that critical 70%, so the disease doesn't show up. However, if you take a drug like the amphetamines and it pushes you down that pathway, 20% or 30%, that means you're more likely to hit that magic 70% plateau before you die, which means you're going to have Parkinson's because you got pushed down the pathway earlier on because of your drug use.

Interviewer: Getting this information out there, what do you hope that will accomplish?

Dr. Hanson: We would hope that it would educate the population that there are long-term consequences to misusing drugs in general, not just the amphetamines, but other drugs. As we start to discuss things about, "Do we legalize this? Do we legalize that,'' oftentimes we're not asking the long-term questions. We're asking short-term questions, but we don't say, ''Might there be something showing up in 20 years or 30 years?'' Here's Parkinson's, obvious, but what about other neurodegenerative diseases? May they also be linked? Something like Alzheimer's, may that be linked, and some of these other neurological consequences? So we probably need to be looking at that more closely than what we have done in the past.
Now, we focused on the abuse side. That takes you down the road of: 'Well, what about legitimate use, therapeutic use? Are there drugs we're using for long periods of time, and for good medical reasons . . .

Interviewer: Right.

Dr. Hanson: . . . but they may be doing things, should we look at some of these databases and see is there long-term neurological or psychiatric consequences to them that we're not seeing when we just do our short-term studies?

Interviewer: Right, and you did make the point earlier, when we were talking, that methamphetamines are actually in a larger class of drugs called amphetamines, of which there are many kinds, some of which are used under clinical supervision.

Dr. Hanson: Correct. Well, methamphetamine and amphetamine are prescribed. These are Schedule II drugs. But is there consequences? Is there just the dependence situation, where you're using large doses, and maybe you're binging with it and you're injecting it versus therapeutic doses, which are smaller, you're taking them orally, and we need to look at that. My inclination would be I think that there is a difference. Some of the studies we've done in animals say that the brain responds very differently when it's done with therapeutic caution versus when it's done with abuse abandonment, but we need to make sure that that's the case when we look into our human cohorts.

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Dr. Miller: Advanced Parkinson's disease and movement disorders. We're going to talk about what to do next on The Scope radio. This is Tom Miller.

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Dr. Miller: Hi, I'm here today with Dr. Lauren Schrock. She's an assistant professor in neurology and in charge of the movement disorders program. Lauren, we're going to talk about sort of advanced Parkinson's. I think it's pretty well known that after a period of time, a lot of folks who responded to medications and treatment of their Parkinson's start not doing as well on the medications. I think the thing that we would like to talk with you about today is that there are new therapies and those involve deep brain stimulation. When should a patient maybe start thinking about this option of treatment and whom they should be working with if they're thinking about this option for treatment?

Dr. Schrock: When medications start causing complications is often the term we use in Parkinson's specialists. Basically, over time, medicines don't last as long and they wear off in between doses and people can develop dyskinesias.

Dr. Miller: Yeah, what is a dyskinesia for our listeners?

Dr. Schrock: Dyskinesia is an extra involuntary movement. It almost looks like a wiggling and a squirming. The most known person who most people have seen have this issue publicly would be Michael J. Fox. That wiggling back and forth. That is something that can be caused by a combination of both having the Parkinson's disease and also having taken Parkinson's disease medication.

Dr. Miller: Did Mohammed Ali have a deep brain stimulation device implanted? Do you know?

Dr. Schrock: No. Mohammed Ali did not, as far as I know. His Parkinson's is likely thought to be a secondary Parkinson's disease related to the multiple hits to the head. In that type of Parkinson's disease, that's caused by something else, it's not expected to respond to deep brain stimulation.

Dr. Miller: Okay. Good to know.

Dr. Schrock: Very important point about when a person is considering, "Should I have deep brain stimulation?" because there are many things that go into predicting whether someone will respond well to deep brain stimulation and how they will do afterwards.

Dr. Miller: So tell us about how someone makes the decision about inquiring on this new type of treatment.

Dr. Schrock: I'm going to actually start with one and explain what it is a little bit more. If you imagine almost like a brain pacemaker, in the same way that people have pacemakers to help their heart keep beating, in Parkinson's disease there is something called deep brain stimulation where a wire is placed deep down within the brain. When it's in place it's often not very visible. Some neurosurgeons are going to pay a lot of attention to the aesthetics of it and others put it in the way it was designed, so to speak.

With deep brain stimulation, the first thing you want to do when you're considering asking the question of whether it would be appropriate is you'd want to see a specialist in Parkinson's disease. That would be a type of neurologist who specifically has done specialized training in things like Parkinson's disease and tremors.

Dr. Miller: Both medications and in the deep brain stimulation.

Dr. Schrock: Absolutely. Yes, in medications. Because many of my colleagues, who are involved heavily in D.B.S., like myself, really will say the most important visit is the visit with the Parkinson's specialist or we call movement disorder specialist. It's not uncommon for me to be able to work with a patient and actually say, "Oh, why don't you try this medication change," and then they call and say, "Oh, cancel that neurosurgery idea," which is deep brain stimulation.

Dr. Miller: So that must mean you also have close ties to the surgeons who implant the deep brain stimulation devices. Is that correct?

Dr. Schrock: Absolutely.

Dr. Miller: So you're working with them pretty much hand in glove to design a therapy and treatment for the patient.

Dr. Schrock: Absolutely, because our goal is to have good outcomes in all patients we select. So we have special selection procedures to be able to ensure that, voiding any complications with the surgery as can happen with any type of surgery, that patients are going to do well and have improvement in the symptoms that they want to have improvement in.

Dr. Miller: Now what percentage of patients that you see will benefit from a deep brain stimulation device?

Dr. Schrock: Usually, when we think about a patient who's going to be ready for deep brain stimulation, is someone who despite optimizing their medicines is having lots of ups and downs where their medicines are wearing off and they've developed dyskinesias. They also have not developed significant problems with memory and thinking. Early on in D.B.S. most centers would say maybe 10% of their patients who were referred for deep brain stimulation would actually be candidates.

Dr. Miller: So one out of 10.

Dr. Schrock: Yeah.

Dr. Miller: One out of 10. Okay.

Dr. Schrock: However, I would say that our regional neurologists are very well educated around here and I would say that 70% of the patients who are referred to me specifically for the question of deep brain stimulation end up going on into deep brain stimulation within two years of that referral. So I really feel fortunate here. We have great neurologists in the area who really know what the indications are for the therapy.

Dr. Miller: Once this is put in you're able, just like with a pacemaker for the heart, to make adjustments in the way that you'd provide the treatment.

Dr. Schrock: Yeah, absolutely. So this is not a straight forward, like a medication sometimes can be. What you have is, with deep brain stimulation, you place this wire but it's going into a target in the brain that's about 3 by 6 by 6 millimeters. That target in the brain has several different sub areas that we have to get into. So we have to get into the little motor sub territory so any error more than 2 millimeters in our targeting is the difference between a success and a failure of surgery. So I'm dependent so much on the skills, excellent skills, of the surgeon for my ability to have great outcomes.

Dr. Miller: You say great outcomes. Tell me about that because you've got this person now that's sort of resistant to the medications. They've got the dyskinesias as you've mentioned. What do they see happening if it works?

Dr. Schrock: This only helps with what they call the motor symptoms of Parkinson's disease. So deep brain stimulation helps with tremor, slowness of movement, stiffness in the muscles as well as dyskinesias. So if you imagine a person with Parkinson's disease who's been taking medications for several years, when the medications now are only lasting every two to three hours, some people only one hour before they wear off, they can't count on any certain time. They can't go to a play and expect to be able to . . . they don't know if they're going to be able to get up and go home.

So what deep brain stimulation can do is by helping control these symptoms it can really give the person confidence in their day. That they're not going to go somewhere and get stuck. They're not going to go somewhere and start to have these wild dyskinesias that are going to be embarrassing for them. So really it's more of a smoothing out of the symptoms during the day.

Dr. Miller: How long can one expect to see that benefit from the deep brain stimulator?

Dr. Schrock: There's been growing research looking at the length of time and what symptoms are helped as time goes on. The early studies were one to three years out and showed there was very good persistence of benefits. Then we have now five-year and some 10-year studies. What they show for the symptoms that we expect it to benefit such as tremor, the dyskinesias, those continue to be well controlled even at 10 years.

Immediately after deep brain stimulation we often reduce medications anywhere from 30 to 80% but we have to gradually increase those medicines over time. What does gradually get worse is the slowness of movement. We aren't able to keep up with that as much as we are with tremor. The symptoms that D.B.S. doesn't help in the first place and those include balance, speech, freezing of gait where they get stuck and they can't keep moving, and memory and thinking issues. So all these things that D.B.S. didn't help in the beginning, at 10 years out those are the major issues.

Dr. Miller: But still, this is a great therapy to help people live a better life.

Dr. Schrock: Absolutely. As far as quality of life, all the studies that have looked at comparing optimization of medications or best medication management versus deep brain stimulation in patients with Parkinson's disease have shown much better quality of life in those with D.B.S. as compared to medicines alone. Many patients will explain to me they feel like their disease has been taken back five or 10 years.

Dr. Miller: It sounds like if you're a patient with Parkinson's or a physician's taking care of a patient with Parkinson's and they're staring to develop dyskinesias and they've been on the medications and they've been increasing the doses of the medications and things just aren't getting better, it probably is time to consider referring them to a movement disorder specialist in neurology.

Dr. Schrock: Earlier referrals are always better because we're never going to recommend surgery before it's needed and we can always provide education so you know when the time might be right.

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updated: April 16, 2019
originally published: May 13, 2014