Search for tag: "parkinson's disease"

Interviewer: Focused ultrasound to treat essential tremor and how to decide if it's a good option for you. Dr. Shervin Rahimpour is a neurosurgeon who specializes in the treatment of essential tremor. Who is a good candidate to get relief if they have tremor symptoms using this treatment? Let's just start there.

Dr. Rahimpour: Essential tremor is the most common movement disorder and affects upwards of 10 million people in the United States. It's characterized by this either postural tremor when you try to maintain a posture with your hands or it can be brought about when you're trying to perform some kind of physical action with your hands. And it doesn't necessarily just affect the hands. It can affect people's voice, their balance, and other extremities.

While there are effective medications for essential tremor, some patients don't either respond to these medications or have bad drug side effects, and we have good interventions to try to treat this surgically.

Interviewer: And is there somebody in particular, beyond perhaps medications don't work or they'd react badly to them, that would be a good candidate for this particular surgery?

Dr. Rahimpour: Yeah, it could be the case that the medications work but just not enough. So you could imagine if your hands are shaking, whether it's affecting your work or just even trying to feed yourself, this can be really debilitating. So if the medications make the tremor a little bit better but not quite to where you need it to be, to be functional, that's where surgical intervention can play a significant role.

Interviewer: And if somebody comes into your office, what process do you go through to determine if they're a candidate?

Dr. Rahimpour: First, we make sure that they've actually exhausted their medical options. Obviously, we don't want to perform surgery on someone that could otherwise be treated with medications.

The next step is we assess their tremor. Sometimes patients are misdiagnosed, so we want to make sure they actually have essential tremor and not some other kind of movement disorder.

Once we've confirmed that, we assess their surgical candidacy. We look at their MRI imaging to look at their brain anatomy.

And then we discuss some of the options that are available to them. Currently, we have two different treatment options for essential tremor. Historically, the mainstay of surgical management of essential tremor has been deep brain stimulation, which involves placing electrodes in the sweet spot of the brain called the thalamus where we believe is a critical area for essential tremor.

This treatment involves two stages. One is placement of the electrodes in the brain during an awake surgery to make sure that we are providing adequate tremor relief, and then a second stage, which involves connecting those wires to a battery typically in the chest pocket, like you would for a pacemaker.

Now, this therapy is not necessarily for everyone. Certainly, for patients who don't want an open surgery, and also those that may not qualify as a good surgical candidate. And that's where I think focused ultrasound can play a significant role.

Interviewer: And how does focused ultrasound work then?

Dr. Rahimpour: Yeah. So focused ultrasound . . . similar to the way a magnifying glass focuses a beam of light to a point, acoustic lenses can be used to focus sound to a point. And so we use this principle to focus sound energy to that same spot in the brain, the thalamus, to try to disrupt the circuit that's causing a patient to have tremors.

Interviewer: This is non-invasive completely?

Dr. Rahimpour: Yeah, absolutely. So it involves a couple of things. One is to shave the head entirely, and other than that, there are no incisions, and typically, patients leave the hospital the same day.

Interviewer: Wow. And what about relief from the tremors? Does that develop pretty quickly as well?

Dr. Rahimpour: Yeah. That, we expect to be immediate. The caveat currently is that we can only treat one side of the brain. So for patients who might, say, be right-handed, treating their left brain for their right hand can mean a significant improvement in their quality of life.

Interviewer: And I've heard this procedure could also be used for Parkinson's. Is that true?

Dr. Rahimpour: Yeah. So for patients who have a tremor-dominant Parkinson's disease, focused ultrasound can also be an option. And then recently, as of last year, it's also FDA approved for other symptoms of Parkinson's, not just the tremor. Other symptoms include things like bradykinesia or rigidity, so difficulties initiating movement or moving.

Interviewer: If somebody is eligible for focused ultrasound, what considerations would a patient go through to determine if that's the treatment that they want to pursue?

Dr. Rahimpour: Yeah, so similar to deep brain stimulation, we want to make sure that the patient has the appropriate diagnosis for essential tremor, again, because a lot of things can mimic this disease.

So patients have to ask themselves whether or not they are willing to undergo an open surgery, which is deep brain stimulation. And if they're not, then this gives them a nice alternative option.

Patients who undergo evaluation for focused ultrasound should also consider potential side effects from this treatment. That includes temporary ones, like having some numbness and tingling sensations on the same side as their tremor, as well as potentially a brief period of time after the procedure of poor balance.

As the swelling develops from the treatment over the course of the next several days to weeks after the procedure, sometimes these symptoms can get a little bit worse before getting better. And by three months out to a year of follow-up, we don't expect these symptoms to persist.

Interviewer: Are there any long-term type symptoms that a patient should be aware of?

Dr. Rahimpour: Very rarely can these paresthesias or the sensation of numbness and tingling persist at a year's time, and the same goes for balance and abnormal gait.

One part of our pre-procedural evaluation involves an evaluation by our physical therapist, who assesses patients' gait and balance to ensure that we have a good adequate baseline before undergoing this procedure.

Interviewer: For somebody with essential tremor, when you use the focused ultrasound to reduce their tremors, how does that impact their quality of life?

Dr. Rahimpour: Treatment with focused ultrasound to reduce tremor can have a very meaningful impact on one's quality of life. It gives them the ability to do some of the hobbies that they enjoy and certainly some basic tasks like feeding themselves.

Interviewer: After somebody has had a focused ultrasound to treat tremor and, say, the tremor starts coming back after a period of time, the three years that you mentioned, can they get the focused ultrasound again?

Dr. Rahimpour: Absolutely. We can reevaluate them in clinic to see what their options are.

Interviewer: And if at that point they've also decided, "Well, maybe I want to try the deep brain stimulation at this point," is that another option?

Dr. Rahimpour: Yes, that can also still be on the table as an option.

Interviewer: Fish that can repair their own brain up next on The Scope.

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Interviewer: I'm talking with Dr. Adam Douglass, Assistant Professor of Neurobiology and Anatomy at the University of Utah. Dr. Douglass, you have this cool result where fish basically repair their own brain. Tell me what you saw?

Dr. Douglass: In particular, we're interested in populations of neurons in the fish brain that release dopamine. So its cells that make the neurotransmitter dopamine release it into the brain and in figuring out what those cells do to behavior. Within our department, I collaborate closely with a group led by Rich Dorsky, whose lab is also interested in fish brains, but in different aspects of it, in particular, regenerative aspects of it.

The experiment that we did with Richard's lab was to ablate those neurons initially using a chemical technique that caused all of the cells, give or take a few, to disappear. What we found is that over the course of almost immediately, really, starting within a day or two of the ablation, the cells start to grow back such that by a couple of weeks after the initial insult in which we've destroyed the cell population, we have a number of neurons in the structure making dopamine that's almost identical to the number that we started with.

Interviewer: You also saw that the fish were able to regain their behavior too.

Dr. Douglass: Right. What we found is that immediately following the ablation and coincident with the loss of these dopamine neurons, the fish swim a whole lot less. If you put a group of young zebrafish, baby zebrafish into a dish, they normally swim around out pretty ruddily. They keep moving continuously and in contrast, after the ablation, the fish more or less just laid there. They could still move and, in particular, it was encouraging to see that if you startle the animals by tapping the dish or leaning over it; things that they normally don't like and try to get away from, they still swim around quite a bit. So it wasn't just a gross defect in the animal's ability to move. It seemed to be something related to its motivation to do so that was missing.

Interviewer: The fish have motivation?

Dr. Douglass: Yeah, they normally like to swim.

Interviewer: And that was able to come back over time after you . . .

Dr. Douglass: Yeah, and it came back in a way that more or less directly paralleled the regeneration of the neurons that we had killed. So while we think that there're probably other regenerative events or neurogenesis events that are ongoing in hypothalamus, some of which may have been upregulated following the ablation of these cells, the fact that the behavior comes back in a more or less proportional way relative to the number of these cells that are present makes us think that these probably are the neurons that are responsible for setting these weights, these tendencies to move or not move. And we are able to support that using other experimental techniques.

Interviewer: So you think a specific cell type regenerates and mediates this recovery. What cell type are you looking at and why is it interesting?

Dr. Douglass: The cells that we study make dopamine, this neurotransmitter which most people have heard about in the context of reward and things like addiction. It's certainly interesting in those contexts, but it turns out that dopamine does a lot of different things in human behavior as well as in fish behavior. For instance, as anybody who's learned about Parkinson's disease knows, dopamine neurons have a very important connection to locomotor behaviors, movement behaviors in every system where dopamine neurons exist.

There's also a variety of other stuff, literally dozens of different behavioral functions for this one neural transmitter. And one of the things I find interesting about this is that we have a poor ability to explain exactly how one molecule does so many different things in behavior. The answer at some level is almost certainly in the fact that there are multiple different brain regions that contain different populations of dopamine neurons. What my lab is trying to do is the relatively straightforward task of seeing what happens to behavior when you manipulate activity in these cells.

Interviewer: Do you think other cells in the brain might be able to regenerate this way as well?

Dr. Douglass: Historically, there's been this notion that brains don't grow back. Certainly the human brain . . . that its regenerative capacity that's capacity for new cell growth falls to zero following very early development. What we've come to realize over the past decades is that that's not true. It's a reasonable approximation for how the system works in the sense that neurogenesis does really fall off as you enter into adulthood and, unfortunately, cell death does increase.

But as people have looked more closely, they've realized that there are several brain areas where there's a significant amount of neurogenesis going on all the time through adulthood. That includes the area of the brain that we're studying, the hypothalamus, both in mammals and in fish exhibits lots of new cell growth.

Interviewer: Are there any implications for what this could mean for us?

Dr. Douglass: Our work is really unique in that it demonstrates not only that there's a cell population that comes back but it's a dopaminergic cell population and it's a dopaminergic cell population with a direct function in locomotor behavior. If you look at mammalian systems, unfortunately, the substantia nigra, the brain area containing dopamine neurons that are affected in Parkinson's disease, is not regenerative. That's one of the reasons that cell loss and Parkinson's ultimately leads to massive defects in locomotion and ultimately the inability to move.

Our brain area, the hypothalamus, which contains the dopamine neurons that we're studying is not functionally equivalent to the substantia nigra in a strict sense, but the fact that these neurons in fish are both connected to locomotion and have the ability to regenerate probably hold some clues as to how regeneration might be made to work in the human brain areas that are affected by neurodegenerative disease.

It's not to say that we're on the brink of having some therapeutic insight to this. That's far from the case, but I do think that it's reasonable to think that we'll learn something about how these systems work and potentially what's missing in the case of the substantia nigra dopamine neurons that makes them not able to regenerate. If you can identify those things, then that gives you potential sites for therapeutic and intervention down the line.

Announcer: Interesting, informative and all in the name of better health, this is The Scope Health Sciences Radio.

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

Announcer: Examining the latest research and telling you about the latest breakthroughs, the science and research show is on The Scope.

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.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

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