Dr. James Beck 00:00:01
Hello everyone, and welcome to the Parkinson's Foundation Expert Briefing. I'm Dr. James Beck, Chief Scientific Officer of the Parkinson's Foundation, and it's a pleasure to have you with us today. In today's briefing, we will explore the wide spectrum of motor symptoms, how they evolve and strategies for managing them. I think it's going to be a really interesting topic today.
But before we get started, we'd like to get a sense of who's joining with us today, as we always do. We're going to launch a poll. If you're joining us on Facebook Live, just be reassured, you can put a little bit about yourself in the comment section. In this poll, we're just trying to get a sense of who our audience is today. It tends to be fairly consistent, with a lot of people with Parkinson's, as we expect, but sometimes we have folks from other backgrounds who join us, and it's always nice to really understand what their connection is to Parkinson's disease. We'll leave that up for just a little while longer.
Hopefully we'll get that. I hope, wherever you are, the weather is at least somewhat nice. I'm on the East Coast, and we finally have a break in the weather. I understand, though, it's not going to last. Anyway, thanks to everyone for sharing your connection to Parkinson's disease. Let's see what we've got as a result of our poll. Great. A lot of people with PD are joining us today, as well as their loved ones, as part of the process. We have a good number of scientists and healthcare professionals, so that's great to see. Welcome, everyone. We're happy to have you here.
Before we begin our formal expert briefing, I always talk a little bit about the Foundation and remind everyone we're a nonprofit foundation dedicated to improving the lives of those living with Parkinson's by enhancing care and advancing research. It's important to remember, as we do always, our efforts are deeply rooted in the collaboration we have with the Parkinson's community. That means everything we do, we ensure is aligned with the needs and priorities of you, those people living with Parkinson's and those who support them. And so, as I've said, today's program is just another example of how we're working with you to meet those goals.
Dr. James Beck 00:02:04
One of our key initiatives that we offer through the Parkinson's Foundation is PD GENEration. This is our opportunity to offer free genetic testing and counseling to people living with Parkinson's. Any adult who wants to participate practically can. By participating, you can learn about your genetic connection to Parkinson's and contribute to research, and that will hopefully drive new treatments and one day a cure for those of us living and fighting Parkinson's disease. So we encourage, if you've already participated in PD GENEration, share this opportunity with your community.
I believe that together, we can really make a difference in tackling PD through this idea of sharing research and resources across the community. For your convenience, we're going to be, as we always do, recording our expert briefings. They'll be archived, and if you've signed up for it, you'll get an email with a link to the recording, which you can share with other individuals who may want to participate. If you've missed part of it or have to walk away, don't worry. It will be here for you to watch again and again.
Now I'd like to move on to introducing our sponsor, Light of Day, who's here to help support our PD Health @ Home series. We are very pleased to have them on board as a sponsor for us.
Dr. James Beck 00:03:07
Now I'd like to introduce Dr. Pablo Coss. He's a movement disorder specialist and assistant professor of neurology at UT Health San Antonio. Dr. Coss completed his Doctor of Medicine degree at UT Health Science Center in Houston and then went on to complete a neurology residency and movement disorder fellowship at San Antonio, where he has since stayed on as faculty in the movement disorder division.
Dr. Coss specializes in the diagnosis and treatment of a broad spectrum of movement disorders, including Parkinson's disease, and a particular focus of his is deep brain stimulation for PD and other movement disorders. He's focused on botulinum toxin injections and has an interest in Huntington's disease. Dr. Coss has a strong background in education, so we're very pleased to have him here today. He enjoys teaching neurology residents, movement disorder fellows, students and the community. He serves as the assistant movement disorder fellowship director at UT Health San Antonio.
Dr. Coss has a strong passion for serving underserved communities in South Texas and leads a movement disorder clinic in the border town of Laredo, Texas. Thank you very much for your time and for joining us today.
Dr. Pablo Coss 00:04:36
Thank you, Dr. Beck, for the introduction. I'll get started here sharing my screen.
Dr. Pablo Coss 00:05:02
Okay, great. All right, everybody. Thanks for having me. Thanks for giving me the opportunity to talk about the motor symptoms of Parkinson's disease, the tremors and all of the other symptoms that folks with Parkinson's struggle with, with regard to movement of the body. Greetings from sunny San Antonio. Hopefully everybody else is having a break from the bad weather of the winter. I have no conflicts of interest to disclose in relation to our topic today.
What I want to highlight today in terms of learning objectives is, first, to list and describe and learn the vocabulary of all of the motor symptoms that are associated with Parkinson's disease. After we've done that, we will discuss the underlying physiologic brain disorder that gives rise to these motor symptoms. Then the second half of the talk will be focused on various treatments when it comes to medications, non-pharmacological treatments and surgical treatments that are available to help the motor symptoms of Parkinson's disease.
Dr. Pablo Coss 00:06:03
Just to put it in a bit of historical context, what we're talking about when we talk about motor symptoms, we want to go back to the very first description of Parkinson's disease by Dr. James Parkinson in 1817. He wrote this essay called, he wrote a paper called, An Essay on the Shaking Palsy, based on his observations of several cases of the condition around London. He identified what would later be called the cardinal or motor symptoms of the disease, starting with a particular kind of tremor called a rest tremor, the flexed posture of many folks with Parkinson's when they walk, some of the walking changes or what they called the festinating gait, and then an insidious, progressive course.
That was in 1817. Then in the 1880s, Dr. Jean-Martin Charcot, working in Paris, further categorized the main motor symptoms of Parkinson's and highlighted the symptoms of bradykinesia and rigidity. We'll talk a little bit more about what that means in a second. He was also the first one to promote calling the condition Parkinson's disease in honor of James Parkinson for describing it 50 years earlier.
Dr. Pablo Coss 00:07:33
When we talk about the motor features, again, we're talking about symptoms that have to do with disorder of movement, of difficulty moving. That is both making your body move when your brain and your mind want it to move purposefully, and also making your body still when your brain and your mind don't want it to move, when they want it to be still. Folks with Parkinson's have difficulties with both of those issues.
First of all, they have the tremor. Most of us, when we think of somebody with Parkinson's, we think about somebody shaking, some part of the body shaking, usually the arm. We have different kinds of tremor that can affect people with Parkinson's, so we'll get into that in a little bit. Even more fundamental and defining of the condition of Parkinson's is this other motor symptom called bradykinesia. Also known as akinesia, some people call it hypokinesia, but all of that is various ways of describing slow and small movements. Folks with Parkinson's, when they're trying to move purposefully, might find that their movements are smaller or slower than they used to be in the past.
In addition to that, there's also rigidity, which most of the time we colloquially call stiffness. That's really an excess activation of muscles when they should be relaxed, which leads to this resistance to passive movement of the limbs. Then there's postural instability, which refers to loss of balance reflexes leading to stumbles and falls. We will talk about several other motor symptoms that are kind of in relation to these, but these are the four cardinal features that are actually also very important to identify, at least two of them, to make the diagnosis of Parkinson's disease.
Dr. Pablo Coss 00:09:17
Throughout the course of the presentation, I am going to be showing various videos of patients who have passed through our clinic at UT Health San Antonio. It's a very common practice in our specialty to take videos of our patients, both to track their progress over time during certain key steps, like getting a deep brain stimulator and stuff like that, and also for educational purposes for our residents and the community as well. I've blurred the faces to try to protect their privacy, but I'm very, very grateful that they allow us to take these videos and share them in these kinds of settings.
Starting with rest tremor, one of the most defining symptoms of Parkinson's is the rest tremor. Many of you who have Parkinson's probably have experienced the rest tremor. The technical definition of tremor is a rhythmic, fairly fast and continuous movement of a body part across a joint with a kind of sinusoidal wave pattern. Broadly, that's what a tremor is. But then we can subdivide that into various kinds of tremors, and the most classic form of a tremor in Parkinson's is a rest tremor.
Dr. Pablo Coss 00:10:32
That's a tremor that happens when the body part affected is relaxed or at rest, whether that's hanging at your side, your arm hanging at your side as you're walking, or resting on the lap or on top of a table. It tends to shake when the arm is relaxed, not in use. It most often affects the arms, but plenty of people have it in the legs. Plenty of people have it in other parts of their body, like their jaw or their face.
In the textbook description of somebody with Parkinson's, it is an asymmetric tremor that affects one arm more than the other or one side of the body more than the other. Often you'll hear it described as a pill-rolling tremor, which describes the way that the thumb tends to rub against the other fingers as it shakes, as if you're rolling a pill between your thumb and your other fingers. But not everybody has that quality to the tremor.
Here, we're going to see a good example of a rest tremor affecting a patient's right arm, and also you can see the right leg shaking there as well. You can see also that the tremor goes away. The arm stops shaking when he picks it up and starts to do these movements with it, and then it starts shaking again after a few seconds of him putting it back down. That's the typical rest tremor of Parkinson's disease.
Dr. Pablo Coss 00:11:36
That's not the only kind of tremor that folks with Parkinson's can have. I will say also, as many of you probably know, the rest tremor itself can be variably uncomfortable, distracting, can make oneself self-conscious in public, and can get in the way of sleep if you're trying to go to bed and some part of your body is shaking against the pillow or against the sheets. It can, of course, be a source of discomfort and disability, even if it's not intruding in the use of the hand per se.
But many folks with Parkinson's also have what we call an action tremor. An action tremor is a tremor that comes out when the hand is in use or when the body part is in use, whether that's when it's in actual motion, when it's holding a certain posture or position, or during a specific task like writing, holding a cup or using utensils. Many folks with Parkinson's have a combination of a rest tremor and an action tremor, and so we'll see both here in this video.
Dr. Pablo Coss 00:12:57
There he is. He has his hands up, and his hands are shaking even when they're up, so we call that a postural tremor. As he tries to make purposeful movements with his hand, the finger tapping and all that you're going to get used to seeing, the blurring there might get in the way, but I think you can still see the hand is still shaking even as he's trying to move it. So that's a kinetic tremor. Then even when the hands are relaxed in his lap, he's still shaking. That's the rest tremor. So he has multiple categories of tremor affecting him. You can imagine how that would get in the way of many activities of daily living and be very disabling.
Dr. Pablo Coss 00:13:39
Again, moving past the tremor and really getting to the heart of Parkinson's disease is this symptom called bradykinesia, or a slowing or shortening of voluntary movements. This can affect the whole body or various limbs and other body parts. When the facial expressions become slow and small, people develop this kind of what we classically call a masked face, as if a person is wearing a mask that doesn't make expressions. It can affect the movements of the hands, which can make it hard to accomplish fine motor tasks like ripping a bag open or unscrewing a cap or using tools, etcetera.
It can affect a person's ability to stand easily from a chair. It can affect a person's ability to walk, and we'll talk more about the specific walking changes in a second. This, for most people, translates into some amount of disability because it becomes very effortful, leads to a lot of fatigue to do your daily tasks because your body is slow to move when you want it to move. It takes longer to accomplish tasks that you used to be able to do quickly.
Dr. Pablo Coss 00:14:37
Here we have an example of bradykinesia. You can see how, when I ask him to tap his fingers, and I'm asking him to tap them as big and as fast as he can, he makes these very, very small and very slow taps. So it's a combination of the slowness and also the smallness of the movements. Here, I'm asking him to open his hand as wide as he can, and he can't really stretch the fingers very much. They're very slow movements as well.
Here he is trying to stand, and he's really not able to. This is quite a severe form of bradykinesia. I'm asking him to stand, and he's actually putting in some effort into standing, and he's not able to, so his spouse is going to come and help him stand up. He stands very slowly. He even has a bit of trouble standing, and he kind of almost wants to fall back down or sit back down quickly. Okay, so that's bradykinesia. This is a similar example, but it shows about the same thing as we just saw, so for the sake of time, I'm going to skip this one.
Dr. Pablo Coss 00:15:43
The next cardinal motor symptom that we're going to talk about is rigidity. I don't have a video to show you for this because this is not something that can be seen easily on video. It's something that has to be felt. Patients feel it as a tightening of the muscle, as an uncomfortable soreness or stiffness of the muscles. But we feel it on exam by moving the arms and legs at the different joints, at the elbows, at the wrists, at the knees, at the ankles, and seeing how much resistance there is when a person is trying to relax as much as they can to our passive movement.
Often you'll hear us describe this kind of rigidity as the limb feels like a lead pipe, like you're trying to bend a lead pipe because it's so stiff, or cogwheeling, in the sense that the limb kind of ratchets as we're trying to move it, which is probably just the rest tremor coming out as we're trying to move the limb.
Dr. Pablo Coss 00:16:45
Another aspect of Parkinson's, which very commonly affects people but is not considered a cardinal motor symptom, is something called dystonia. This is different from the rigidity we just described because when a person is rigid, their limb is relaxed and at rest. It's just when you try to move it that you feel the stiffness. In dystonia, the limb wants to assume, or the body part wants to assume, a certain abnormal position.
It very commonly affects the hand. It might make the fingers want to clench up or put themselves in a different position. It very commonly affects the leg, and the most classic form of that is a turning in of the ankle and a curling of the toes, which can be very painful. It often affects the face and, in particular, the eyes. Some people with Parkinson's might have trouble opening their eyes voluntarily because the muscles of the eyes want to close them tightly. Oftentimes, it comes along with a jerky tremor, a dystonic tremor, that can kind of overlap on the other forms of tremor of Parkinson's.
Dr. Pablo Coss 00:17:53
Here, we're going to see the typical ankle inversion or foot inversion dystonia in a patient with Parkinson's disease. You can see there, as her feet are dangling and should be relaxed and just lying gently on the ground, that left foot wants to turn in and is shaking. She's describing there to me how she likes to try to make it stop with her other foot, so she tries to rub it or put it down. But you can see how the foot turns in more and more and more as she talks. That is dystonia of Parkinson's disease. There are many other causes of dystonia as well, not just Parkinson's, but it's often a motor symptom of Parkinson's.
Dr. Pablo Coss 00:18:43
Another bothersome motor feature is vocal problems, which can come in a variety of different forms. Oftentimes it's reduced volume. The speech becomes kind of monotone, which makes it hard to put emotional expression in your speech. Articulation of specific consonants and vowels can get kind of poor, so it becomes slurred and less intelligible. Stuttering, the speech can become rushed, so that the syllables are kind of running together, which makes it harder to understand. Breaths can become shallow, so you can only speak short sentences before you have to take a breath and then continue speaking.
Here's a sound bite of a patient of mine who has particular problems speaking because of their Parkinson's. There's going to be a lot of background noise in this sound clip, but take my word that even without the background noise, it's kind of hard to understand what he's saying. Let me put the volume up for this one. Tell me the months of the year. Tell me a little bit about what it feels like when you're off in terms of your speech. How does it affect you?
Dr. Pablo Coss 00:20:28
If you're feeling the need to lean in closer so that you can understand what he's saying, that's what it feels like in the room as well. That is a combination of the reduced volume, the poor articulation, and then the rushed or festinating speech pattern.
I should say, many of you living with Parkinson's know, all of these motor symptoms affect people to a different degree. Everybody has some combination of these symptoms to different degrees. Just because I'm describing them here doesn't necessarily mean that they're going to be a part of a given person's Parkinson's disease. It's something to keep in mind.
Dr. Pablo Coss 00:21:06
Going to the walking, of course we usually think of somebody with Parkinson's as having their shoulders stooped forward, not swinging their arms very much, taking small shuffling steps where they don't pick up the foot or the toes and the foot kind of slides along the ground. We'll talk more about it later in the talk, but progressive problems with balance.
Festination, I don't have a video of the festination, but that's a sense that many of my patients describe of feeling like they're speeding up or the top half of their body is getting too far out in front of them, and they're taking these little steps to try to keep up. That might eventually lead them to fall. Then retropulsion, which is if you get knocked backwards, you take a bunch of little steps to try to catch yourself instead of just hopping back.
Dr. Pablo Coss 00:22:03
This is an example of a typical Parkinsonian gait. You can see, of course, she has the rest tremor, but on top of that, she takes these short strides. One foot is barely clearing the other as she walks. She's not picking them up very much, and she's not swinging her arms very much.
One particular problem that some people with Parkinson's run into, usually after years of having the condition, in addition to the walking issues we just described, is this other issue called freezing of gait, or freezing, where the feet feel like they get stuck, frozen or magnetized to the ground, and you have to try multiple times to take that next step, to pick the foot up to take the next step. It tends to happen often around thresholds, like narrow places, doorways or crowded areas. When a person is turning, they tend to freeze, and when they first start to walk after they get up, they tend to freeze a few times.
I understand it's very fatiguing to try to walk with freezing, and, of course, it can affect a person's center of gravity and lead to falls. Here's a man trying to walk down the hallway, and you can see how he's not really taking steps. He's just kind of picking up the feet, trying to get them to take the next step.
Dr. Pablo Coss 00:23:22
We've gone over the major motor symptoms of Parkinson's disease. The question of what underlies those symptoms, what is the brain dysfunction that causes the symptoms, it's good to go over that in a high-level overview so that we can understand the way we treat the symptoms themselves. I won't belabor this too much. Let me see if I can pull up the laser pointer.
The big picture is that whenever you want to produce a voluntary movement, say extend your arm to reach for a cup or write or anything else that you want to do with your arms, a signal from the surface of your brain called the cortex is sent down deep into the brain to a circuit of brain cells that process movement commands and allow your brain to regulate all of the voluntary movements that it makes.
That signal needs to get processed between several clusters of brain cells connected to each other deep inside the brain. If they agree with the brain signal promoting a movement, they will send an excitatory signal back through a part of the brain called the thalamus, back to the cortex, and that will excite the brain in general and produce the movement of the body that wants to be produced. Those clusters of nerve cells that do that processing deep in the brain are called the basal ganglia.
Dr. Pablo Coss 00:25:02
This is a diagram of how the basal ganglia are connected to each other. This is what medical students learn about the connectivity and the physiology of this part of the brain. I'm not going to go into much detail about it here, but suffice it to say that the signal comes from the cortex into the basal ganglia, which is this network here, this square here, into a part of the brain called the striatum, which is kind of the input nucleus for the basal ganglia that takes all of the signals from other parts of the brain for processing.
It goes through one of two pathways. It goes through a pathway that directly connects it to the GPi or goes through a pathway that takes a bit of a detour. If the signal goes through the direct pathway, that excites the brain and produces the movement. If it goes through the indirect pathway, that suppresses the signal and inhibits the movement. Both pathways are necessary in order for your brain to make your body move when you want it to move and stop it from moving when you don't want it to move. Those are regulated by dopamine cells within the striatum. Both pathways are regulated by dopamine signaling, which comes from a different part of the brain called the substantia nigra.
Dr. Pablo Coss 00:26:14
As many of you know, the problem with Parkinson's is the lack of dopamine coming out of the substantia nigra. Let's look at that a little bit in more detail. Here's another way of looking at that part of the brain. I know it's pretty complicated here. I'm going to zoom in to the basal ganglia.
Here's the substantia nigra. It's this pink nucleus here. It's a cluster of brain cells. Here in blue, here's one brain cell sending its connection, its axon, its wire, to the striatum, which is this part here. All of these brain cells that are sending out their little connections, they're producing dopamine and kind of squirting it into the striatum, and that's regulating the movement signal processing within that part of the brain.
Dr. Pablo Coss 00:26:59
Here is a picture of the substantia nigra, what it looks like actually in the brain through a brain slice of a post-mortem brain. This is the midbrain. It's in the brain stem. It's a very small part of the brain. Here, this blue purplish streak is the substantia nigra on one side of the brain and then on the other side of the brain. They're pigmented brain cells, so that's why they have that blue color. You can see, as a person with Parkinson's loses those brain cells, it also loses the pigmentation and you get this pale color. So this top brain is somebody with Parkinson's, and this bottom brain is somebody who didn't have Parkinson's, whose substantia nigra was healthy when they passed away.
Without those cells, you lose that chemical signal, that dopamine, and it makes it so that there is less traffic through the direct pathway, so less voluntary movement. There's also simultaneously more traffic through the indirect pathway. The combination of those two things makes it so the body just doesn't move as quickly and as readily as it's supposed to, and it's more tense when it's not supposed to be. That's really what underlies the rigidity, the bradykinesia and the difficulty walking of Parkinson's disease.
Dr. Pablo Coss 00:28:26
And so our answer to it is to replace the dopamine. That is the main way that we know how to help folks with Parkinson's disease. So we're going to get into treatment here. Before I get into medicines, one of the most important ways of replacing dopamine, and really the most important thing that you can do for yourself as somebody living with Parkinson's, is to exercise. There is a large body of evidence that has been building up over decades of how important and how effective regular moderate- to high-intensity aerobic exercise, really high-intensity aerobic exercise, how much of a difference that makes to folks living with Parkinson's.
It's not just, you know, when I first started treating people with Parkinson's during my fellowship and residency, I would recommend exercise as a long-term thing because the studies show that over years, folks who exercise regularly, their motor symptoms are more stable for a longer period of time than folks who don't exercise regularly. And so I was recommending it as a long-term treatment, but hardly a week goes by where my patients don't tell me that they started exercising and it makes a difference on the day that they exercise. When they exercise in the morning, they feel faster, they have more energy, less fatigue, their tremor's not as bad, and they sleep better. All of the various benefits of exercise are an immediate effect on top of the long-term benefit to the course of the disease.
Usually we're talking about aerobic exercise, like a treadmill, an elliptical, a stationary bike, a bicycle itself if it's safe and you're not going to be at risk of falling on the bike, swimming, really anything that you like to do that has an aerobic component to it, that's going to get you sweating, that's going to get you out of breath, winded a bit, and that's going to get your heart rate up. That's really the best thing that you can do. You should be doing it at least three times a week, if not more, if not every day, ideally.
There are various kinds of exercises that have been studied. Aerobic, we talked about. Strength exercises are also helpful. Balance exercises are very good to avoid falls and strengthen your leg and your core. Stretching exercises are good to help with that uncomfortable tightness or rigidity. Then functional exercises, things like dancing, boxing and martial arts, are really good for you as well.
Dr. Pablo Coss 00:31:03
Moving on from exercise, though, and you definitely need to exercise, that's the most important thing, but we do have these medications that are symptomatic treatments that are very helpful for folks with Parkinson's disease. Chief among them, central to our regimen for anybody living with Parkinson's, is this medication called carbidopa-levodopa, which I'm sure many of you, most of you, are familiar with. It was developed in the 1960s, and yet to this day, it still remains the most effective treatment that will help folks with Parkinson's.
Just for you to understand why it has this complicated name, it is two different medicines. There's the levodopa, and then there's the carbidopa. The levodopa is the active medicine that produces the clinical effect of helping Parkinson's symptoms. It crosses the blood-brain barrier, which is this specialized wall in the lining of the blood vessels within the brain that keeps a lot of stuff from coming into the brain from the blood. But it is able to cross the blood-brain barrier, and once it gets into the brain cells in the substantia nigra that make dopamine, it is metabolized into dopamine to help bolster the dopamine signaling that is going to have the good effect on that basal ganglia circuitry that we talked about.
The carbidopa, by contrast, is not active. It does not cross the blood-brain barrier. It does not get turned into dopamine. It blocks the rest of the body's metabolism of levodopa, which means that more levodopa is able to get into the brain to have its good effect. Also, it is not turned into dopamine by other parts of the body, like the GI tract, which is what causes one of the most common side effects of levodopa, which is nausea. Almost all forms of levodopa come with carbidopa because it has this benefit to the way that the levodopa affects your body.
There are various forms of carbidopa-levodopa. There's an immediate release. The old name for that is Sinemet. That's the one that most people are on when they first start to take the medicine. There's an old form called controlled release with an enteric capsule, which is used sometimes as well. Then there are the newer versions of extended-release carbidopa-levodopa, one that's called Rytary and the newest one is called Crexont, which have some innovations in the capsule and in the little microbeads inside the capsule that carry the medicine, which makes it so that it kicks in strong but also lasts longer than the regular, standard immediate-release medicine.
All of these are taken multiple times a day, unfortunately. The half-life of levodopa is such that you really have to be taking it at least two times a day, but more often three or more times a day, for it to have a continuous effect that doesn't wear off in between doses. We'll look at exactly what effect we expect from levodopa in the next slide.
Dr. Pablo Coss 00:34:14
There are also these continuous infusions. The most recent one that we're using a lot of nowadays is called Vyalev, which is a subcutaneous infusion, this pump that is connected by a thin cannula to a port that puts the medicine just right underneath the skin, so it's not very invasive. It gives a continuous infusion of the medicine 24 hours a day. There's also an inhaled version of levodopa, like an inhaler you would use for asthma, that is used kind of as needed because it kicks in very quickly. When people are feeling like the effect of the medicine is wearing off and they're not feeling good anymore, they can use the inhaler to kind of get a quick kick back in.
The possible side effects of this medicine: nausea is very common, unfortunately, but other side effects are it can make the constipation of Parkinson's worse than it already is, can make people dizzy, can contribute to low blood pressure for some people, and drowsy sometimes. Not usually something that people experience early on, but as the years go on living with Parkinson's, the medicine can contribute to the development of hallucinations, unfortunately, and these other abnormal movements called dyskinesias. We'll talk about that in a minute. It can also make some people a bit impulsive and have difficulty controlling their impulses, which is something that you should be in conversation with your doctor about.
Here is what we expect the levodopa to do, the good effect of the levodopa. You'll remember that first patient that we saw with the rest tremor on the right arm and the right leg. That was him coming off of his medicine, without taking the levodopa for 12 hours. Then we gave him the medicine, and he took it. We waited about an hour in clinic, and then we took this next video.
You can see that his tremor has gone away, both of the arm and the leg. We'll wait for him to do something with the other arm to just make sure that it's actually gone. Yeah, that tremor has gotten a lot better.
Dr. Pablo Coss 00:36:13
Now, we'll move on to this other patient. Similarly, this other patient came to the clinic in the morning without taking his first dose of the medicine. We took this video of him with the medicine worn off. Here, he never has much of a tremor, even without the medicine, but what you can see is, again, the smallness of his movements and the slowness of his movements there in the fingertips, here in the hand opening, the hand which really doesn't open very much, especially on that left side. If we could feel the tone of his arms and legs, we could probably feel that he's fairly rigid.
Now we're having him flip his hand up and down, and you can see there, again, the hand doesn't really go all the way up or all the way down. There's a reduced amplitude of that movement. Here we're having him tap his toes, or he will in a second. That right foot taps pretty good, but the left foot, you'll see, doesn't really lift very much off the ground. Now he's going to try with the left. Yeah, it gets kind of stuck. It doesn't want to come up very much.
Now we see him one hour after he took his medicine on the same day, just about an hour after that first video was taken. This is with the levodopa now kicked in. The blurring, I'm sorry, gets in the way a little bit of the video there, but the finger movements are faster than they were before. They're still kind of small, but now let's look at the hand movements. They're much bigger. It's not getting small as quickly as it was before. It's staying big, big stretching of the fingers. Similarly here, he's able to stretch them wide, whereas he wasn't able to before.
That left hand now is going to come up a lot more than it was before. It has a much bigger amplitude there of the rotation. Let's look at him tap his feet. He's also just more active in the chair. He's spontaneously moving more. The left foot also taps bigger. Does it get stuck as much?
Dr. Pablo Coss 00:38:44
I almost forgot to show on the off video. Let's watch him try to stand up. We've asked him to stand up. He's trying. He's giving it a good try there. He's going to tell us that he's not really able to on his own. So one of our nurses is going to come and help him. A single musical note plays. Now let's watch him stand after he's taken his medicine. We've asked him to stand up, and he stands up easily.
So that's what we want to see. That's why levodopa is so helpful in treating the motor symptoms of Parkinson's disease, because it really makes a big difference to the tremor, to the stiffness, to the bradykinesia, so that people can move easier and feel like they have more energy and can get things done faster and walk better and all that. If that was all there was to treating Parkinson's, and everybody enjoyed the benefits of the levodopa forever, then it would be a lot more manageable of a condition. But the problem is that as the years go on, we tend to come into a period of complications of the medicine, what we call motor fluctuations.
Here we have the textbook progression of Parkinson's disease over years. Again, I want to caution people looking at this. This is not the way that it is for everybody with Parkinson's disease. Many people have a very different course through the years of the condition than what this shows. So don't look at this and think, oh, and start the clock on these numbers, because you've got to take the condition day by day. There's a lot of variability.
Usually, most people may start to have these motor fluctuations in years three to five, in which the levodopa, the good effect that we just saw in that video, starts to wear off sooner than it used to after each dose. So if the effect of the levodopa used to last six hours, after a few years it may only last five hours or four hours. If you were only taking it two or three times a day at first, you may have to start taking it more frequently to try to pave over those periods of wearing off. Some folks might fluctuate between feeling on and feeling off throughout the day, depending on their dosing schedule.
Dr. Pablo Coss 00:41:11
On top of that, another side effect of the medicine that starts to creep in during that period is what we call dyskinesias, which are these other involuntary movements that are entirely a side effect of the medication. Setting that aside, we'll talk about this a little more at the end, many folks start to struggle more and more with walking and balance and the freezing that we talked about. So we're going to talk a little bit about what we do about those things.
First to say, this is an example of what dyskinesias look like in folks with Parkinson's disease. They can be many things for many people. Some people develop kind of a writhing movement or a wiggling movement or kind of a fidgeting of their arms and legs or their head. Some people rock side to side or back and forth when they're standing. Some people, it looks more like a dancing movement or a posturing movement, almost like a dystonia. It can affect any body part or the trunk or various body parts together. It's usually what we call a peak-dose side effect of the levodopa.
So when the levodopa is at its strongest concentration within your system, about an hour after you take the medicine, an hour to two or three hours, that's when the dyskinesias rear their heads. Then they kind of go away as the effect of the medicine is subsiding. Here's what that looks like. I won't show you the video where we see how much of a difference the levodopa makes to this gentleman's walking. It makes a huge difference. It takes away the freezing and the stutter stepping and all that. Suffice it to say that these wiggling movements of his head, that you can see through the blur effect there, and of his legs and of his trunk, kind of a side-to-side rocking, these are dyskinesias, levodopa-induced dyskinesias.
It depends on the severity of them and what body parts they affect and a person's lifestyle exactly how disabling or uncomfortable these dyskinesias are. I certainly have a lot of patients who have mild dyskinesias where they don't even notice it themselves, and it's just me or their family who picks them up when we're watching them do things. But then again, if it gets severe enough, and if it's getting in the way of a particular hobby or work, they can themselves be a very disabling part of the condition. If they stop taking their levodopa, the dyskinesias will go away, but then they will be off. So it becomes a balance of enough dose to help their symptoms, but not so much to cause the dyskinesias. That's where our advanced treatments come in.
Dr. Pablo Coss 00:44:10
I'm not going to spend very much time on this, but suffice it to say that there are various medications that are considered adjunctive treatments. I have a list here of the most commonly used ones. Suffice it to say that, in general, they are used in addition to levodopa to improve the duration and the effect of the levodopa, kind of as an additive, to reduce the amount of off periods when a person starts to wear off with the levodopa.
Some of these are used on their own. I won't get into that very much. When the symptoms of Parkinson's are mild at the beginning of the condition, in the first few years of the condition, none of these on their own are as effective as levodopa. They don't help as much as levodopa, but when a person's symptoms are mild, they may help enough that they can get by. But eventually, everybody with Parkinson's really should be on carbidopa-levodopa despite the complications that we've talked about so far.
The problem with adding more of these medicines to somebody who is already taking levodopa is that they are going to contribute to the side effects of levodopa. They will also contribute to dyskinesias. They may contribute to low blood pressure, to hallucinations, on top of the levodopa. The only one, just to point one out here, that shouldn't contribute to dyskinesias is amantadine. Amantadine is often used actually to suppress dyskinesias. It's unique among our Parkinson's medications in that it reduces the severity of dyskinesias caused by the levodopa. Oftentimes many people will be on carbidopa-levodopa and amantadine, and oftentimes the amantadine is used to suppress the dyskinesias of levodopa.
Dr. Pablo Coss 00:46:00
So what to do at the point where the motor fluctuations, the wearing off and the dyskinesias are becoming a major problem? We can't really add more medicines because that'll make the dyskinesias worse. We can't really lower the dose of the levodopa any further because then you'll feel more and more off throughout the day. So we're kind of stuck between this rock and a hard place when it comes to medications. That's where these surgical and more advanced treatments for Parkinson's come in, like deep brain stimulation.
Deep brain stimulation is a procedure that is done very, very, very commonly now. It's part of the standard of care for folks with Parkinson's disease in the U.S. and across the world. Any movement disorder center uses deep brain stimulation a lot to help folks with Parkinson's disease. It's FDA approved for the treatment of Parkinson's disease, tremor and motor fluctuations. It's also used for other movement disorders, essential tremor and generalized dystonias.
Specifically when we offer it to folks with Parkinson's, we have three main goals, three things that it's going to accomplish. We expect it to improve the motor symptoms of Parkinson's much the same way that levodopa does, with some caveats to that. We expect it to reduce the motor fluctuations, so to reduce the off periods, because it's a technology, a treatment that is going to be working consistently 24 hours a day without kicking in or wearing off the way that levodopa does. It's going to reduce the medication burden. Most people can reduce the levels of their doses of their medicines and come off of some of the extra medicines once they have a deep brain stimulator.
What a deep brain stimulator specifically is, is a set of thin wires that are implanted surgically into the brain, deep into the brain, into that same part of the brain that we called the basal ganglia that I showed you earlier, through small holes in the skull that are made by a neurosurgeon. Usually, most people with Parkinson's will have a wire in each hemisphere, on each side of the brain, left and right, to help the symptoms on both sides of the body. The wires come out through these caps in the skull, and then on the outside, they are tunneled underneath the skin, so there are no wires poking out of your head. People usually can't tell that you have one of these.
Dr. Pablo Coss 00:48:28
They go behind the ear, down the neck, and then they connect to a generator, a pulse generator, a battery that is implanted in the chest underneath the skin, much like somebody with a cardiac pacemaker would have their pacemaker on their chest. Very similarly, except for the wires go up the head and into the brain.
Here you see, in cross-section of the brain, the wire going through the white matter, the brain tissue here, and then the tip of the wire ending at the globus pallidus, which is one of the clusters of brain cells in the basal ganglia. We also sometimes put it into a different part of the brain called the subthalamic nucleus, which is also part of that same circuit. So there's some nuance about why we might do the globus pallidus for one person and the subthalamic nucleus for another person, but suffice it to say that stimulating both clusters of brain cells produces a very good effect on the motor symptoms of Parkinson's.
This is a neurosurgical procedure. So while it is very, very helpful and it makes a big positive difference to folks with Parkinson's, there are possible side effects, risks to the procedure. Like any kind of invasive procedure, there is a risk of hemorrhage. In this case, it would be within the brain, and that can be dangerous, but it's fairly rare. It's 0.5 to 2% of people who have a hemorrhage from the procedure. Then there's similarly a small risk of infection, which might mean that we need to take the device out.
There are possible side effects that are due to the stimulation itself. For some people, it may make their arm tingle, or it might cause a contraction, an involuntary contraction of a muscle, or affect a person's cognitive or mood symptoms. That kind of side effect is stimulation-dependent. There's a lot of programming that goes into making a deep brain stimulator work well. By programming it in a different way, changing the settings of the stimulation, we can often make these side effects go away and tinker with the settings until we get it working well without any of these kinds of side effects.
Dr. Pablo Coss 00:50:47
The way the DBS works, again, here we have the cap and the skull and the wire going into the brain and ending, in this case, in the subthalamic nucleus. Here we have a blown-up diagram of the tip of the wire. It has these electrodes on it. We activate individual electrodes. In this case, we're activating electrode one and electrode two. You can imagine that these are all of the brain cells connected in the tissue around the wire, even though it's not shown in this picture.
It's shown over here, actually. Here's one side of the wire, really, really zoomed up. Here are all the different kinds of brain cells in the wire's vicinity. The wire, the active electrodes create an electric field, which is depicted in this translucent blue sphere. That's the amount of tissue that is being subjected to that electric field. It changes the electric firing properties, the electric signaling properties of the brain cells in that vicinity. It snaps them out of these abnormal brain cell rhythms, these signaling rhythms that are because of the dysregulation of the lack of dopamine.
It snaps them out of those rhythms and puts them more into a normal, healthy firing rhythm. That produces this effect on the larger movement networks of the brain that produces a symptomatic benefit of the stimulator, much like the symptomatic benefit of carbidopa-levodopa, of replacing dopamine. So this is not, to be clear, to clarify a common misconception, this is not doing anything to your brain's levels of dopamine. This is only simulating the effect of the dopamine on the downstream networks with an electric signal instead of a chemical signal.
Dr. Pablo Coss 00:52:35
Here is a patient with Parkinson's disease before and after DBS. Actually, in both videos it's on the same day, but this is with the settings on the DBS turned off. So this is his symptoms without the effect of the DBS. You can see how tremulous he is, how much of a rest tremor he has there. Not just the rest tremor, but you can see even when he picks his arms up how much of a postural tremor he has in both his arms and the rest tremor in the legs. Here he is with the DBS on.
This effect happens within seconds to minutes of turning the DBS on and to the right setting, the optimum setting. You can see now he's not trembling at all, or only very mildly in one of his hands. So that's the effect of DBS, much like what we see with the levodopa on and off videos.
Here's another quick one showing how the DBS can help the walking. Here's a patient struggling with short steps, not swinging his arms very much, getting a little frozen here as he tries to turn around. His feet get kind of stuck on the turn, and he's moving very slowly. Now here he is with the DBS effect. After turning on the DBS, you can see how much wider his steps are, how much faster, how much he's swinging his arms more, and how he doesn't freeze anymore when he turns. So big, a big, big success there for DBS. It's going to make a big difference to his day-to-day activities.
One other advanced treatment that I want to talk to you about, I know I'm getting short on time here, is the focused ultrasound technique. This is newer than deep brain stimulation. Deep brain stimulation has been around for about 30 years. This has only been around for about 10 to 15 years. This is very exciting because it is, in a way, a non-invasive procedure. It's at least an incisionless procedure in which a beam of ultrasound waves is emitted into the brain. It penetrates through the skin, through the skull, through the outer layers of the brain, without any kind of hole in the skull or incision in the skin. It just penetrates through the tissues harmlessly.
The ultrasound waves focus on a small part of the brain, in the similar network of brain cells that we've been talking about. In that little cluster of brain cells where the ultrasound beams focus, it causes heat in the tissue and burns it. It cauterizes that tissue. It essentially ablates that cluster of brain cells to shut down their abnormal signaling. This has been around for about 10 years specifically to help the tremor of Parkinson's and also essential tremor.
It is now, just in the last year or so, approved and being used more in a slightly different part of the brain to help the other symptoms of Parkinson's in addition to the tremor, like bradykinesia and rigidity. It's a one-time procedure. You go in, you get the procedure done on one day, and then you go home. The effects should be long-lasting, theoretically should last years, to help the symptoms of Parkinson's. So this is definitely an alternative for a lot of people to the deep brain stimulator.
But there is a complexity and a nuance for any given person, depending on the risk profile for complications of either procedure and what we want to get out of the procedure, what the main symptoms are that we want to tackle, whether or not they're more benefited by a focused ultrasound treatment or by the deep brain stimulator. Should I keep going a little bit, or should I stop here?
Dr. James Beck 00:56:38
I think now might be a good time to stop, just to give us some time for some questions, Dr. Coss, if you don't mind. I think that's really fantastic. It's really great to see some of these videos that you presented because it really is hard to describe. As they say, a picture's worth a thousand words, and I guess a movie's maybe worth a million. So just really being able to see that, I think, is really helpful for the audience to get a basis for that as coming in.
Thank you very much for the presentation so far. I just want to remind our audience before we jump into questions, just know that our team is working to organize the questions in the back end and feed them to me so I can talk to Dr. Coss about them, and also get a variety of questions that come in. We're really going to focus on those that are going to be very directed toward our conversation today. So thank you for those. We have a helpline who can help more broadly as part of the process.
I think, when I think about this, Dr. Coss, you showed some symptoms of various people and individuals as part of this process. Tremor is often viewed as one of the key symptoms in Parkinson's disease. But is it the case that everyone develops tremor with Parkinson's disease?
Dr. Pablo Coss 00:57:49
No. Even though it's kind of what we all think of when we think of somebody with Parkinson's, somebody shaking, it's only about 70% of people with Parkinson's who have a tremor associated with their Parkinson's. For some of them, they may have the tremor, but it's kind of a relatively minor symptom of their condition, and they may struggle more with the slowness and the stiffness and the walking difficulties. So no, it is not a necessary part of Parkinson's disease for a lot of people. It's also not strictly speaking necessary for the diagnosis to have a tremor.
The most fundamental part that is required for the diagnosis is that slowing down, that bradykinesia of the movements. You saw there in various videos how we're always asking people to tap their fingers and open and close their hands. With all of those, we're always looking for that slowing and that decrement in how wide the movements are.
Dr. James Beck 00:58:48
I think that's really a good thing to bring up here because, as you can appreciate, you probably know very well professionally, a lot of people sometimes struggle getting that diagnosis of Parkinson's disease, or they get diagnosed with PD when they don't. So when is a tremor not a Parkinson's tremor? Is that something that you can briefly touch on just so that people could be aware and maybe query their physicians a bit more if there's some doubt?
Dr. Pablo Coss 00:59:15
Absolutely. You're absolutely right. There's a lot to be said about the accuracy of diagnosing Parkinson's disease and other tests that can be done to try to help with the diagnosis and all that. But Parkinson's specialists try to pride ourselves in our ability to diagnose it clinically based on what the tremor looks like, the other symptoms and what the symptoms patients describe to us are. We try to tell apart tremors based on the way they behave.
Usually, to kind of give an example, the distinction that we're almost always trying to make is between somebody with a Parkinson's tremor and somebody with an essential tremor. A Parkinson's tremor most often has a rest tremor component, so the tremor comes out when the hand or the body part is relaxed, and it's usually to some extent asymmetric. It'll affect one arm more than the other, or one leg more than the other, or just one side by itself, as we saw in the first video. Most of the time, it actually goes away when a person starts to use their hand. So if they have that very classic rest tremor, then we're probably dealing with a Parkinson's tremor.
On the flip side, if somebody has a purely action tremor, which is a tremor that only comes out when the hands are in use and goes away when the hands are relaxed, and if it's very symmetric, if it affects both hands or both sides of the body to almost the same degree or exactly the same degree, and if it affects the head, too. Most Parkinson's tremors don't affect the head. A lot of essential tremors do affect the head. Then we are more likely to call it an essential tremor or one of various other kinds of tremors.
So we do have that ability to discriminate. Most of the time, when we use these kinds of criteria, we're correct and accurate in our diagnosis. Although, there are many people who fall into a gray area where they have some component of rest tremor, some component of action tremor, and in those cases, it may be kind of hard to tell just by looking at the tremor what kind of tremor it is. Then we're also looking at, do they have bradykinesia? Do they have rigidity? That will also kind of sway us one way or the other.
We look at them walk to see if there are walking changes that look like a parkinsonian change. Then we ask them all these other questions that we haven't really talked about today about the non-motor symptoms of Parkinson's. We use that also to support a diagnosis or refute it. When we're really, really not sure for whatever reason, then we rely on these other biomarkers that many people are asked to do, like the DaTscan, that specialized SPECT scan, or nowadays these other tissue-based biomarkers. Here in our clinic, we do the Syn-One skin biopsy quite a bit to try to confirm the diagnosis when clinically it's still in question.
Dr. James Beck 01:02:14
Yeah, those are some really good things to consider. I appreciate that. I think that's a burden all people with Parkinson's disease face. It's generally not a straight line from A to B on getting that diagnosis, but thank you for laying out some of those options as part of it.
Tremors are this visible component of the disease. Some people who are still working have written in and asked about how to manage tremors, like in a speaking situation. How do you advise on that? Is this something where there's a discussion about offering some medications for people who typically get other types of anxiety for speaking? Would that type of work? What do you advise your patients?
Dr. Pablo Coss 01:03:02
Yeah, I think so. Sometimes, when they're very situational tremors, like, I know it's going to come out when I'm stressed out, like speaking publicly or at dinner eating, using my utensils, or some other aspect of a hobby or job performance. Certainly, if we can identify that it's an anxiety-driven tremor in that specific situation, then we do use medicines that can kind of control that anxiety and will also control the tremor. Depending on that medicine, those kinds of medicines, we don't like to rely on those too much.
We'll also use some of the medicines that we borrow from essential tremor. A person may have Parkinson's, but they may have an action tremor that interferes with them holding a microphone or them writing in a high-stress situation. We might give them some propranolol to help kind of relax. It has an anti-anxiety effect and also an anti-tremor effect, and they can potentially even take that as needed. But hopefully, we do a good enough job with the mainstay of the treatments like the levodopa and all that to help, so that it's really quieted down even in those situations.
I feel like if we're having to use kind of as-needed treatments, then we still haven't controlled it well enough with all of these other treatments that we've talked about. But then there are the non-pharmacologic ways. Unfortunately, I wasn't able to get to these because of time. Too many videos. But there are various devices that can help Parkinson's tremor, or an action tremor, I should say, whether it's Parkinson's or not, like a glove, the Readi-Steadi Glove that we recommend for our patients, certain kinds of electronic devices that stimulate the wrist, like the wristband that's been around now for a little while, the Cala, and various kinds of weighted utensils and stuff like that that can help with specific tremors in specific situations so that you can get things done easier without so much shaking.
It's probably best to work with an occupational therapist, and they can sort of go through those nitty-gritty details of the functional use of your hands and where the tremor's getting in the way and what you can do about it. There are neuro occupational therapists that are experienced with helping people with tremor in addition to the medicines that we prescribe in clinic.
Dr. James Beck 01:05:33
That's great to know. I think just even knowing that there are options allows people to bring this up with their clinicians to talk about as a way to move forward on it. Last question about tremors before we've got a bunch of others. As tremors get worse, does it mean that the disease is progressing necessarily? Clearly, some tremors may, as the disease goes from one side to the other side, but as a tremor just becomes more prominent with time, is that disease progression? Or could it just be these stress situations where we're seeing that?
Dr. Pablo Coss 01:06:15
It could certainly be both in different situations. What we usually will say is if your Parkinson's symptoms, be it a tremor or otherwise, suddenly get worse, like from one day to the next or one week to the next, suddenly you're very, very shaky, more so than you have been in a long time, then there's probably something underlying that worsening. Often the usual suspects are an infection like a UTI, a urinary tract infection, or maybe some change in the medicines, or maybe you forgot to take your medicines or something like that, or you've otherwise been sick, dehydrated, et cetera.
When it's a sudden worsening, we're always looking for some other cause that triggered that worsening that's not directly the Parkinson's. But unfortunately, as the years go on, we do consider, when Parkinson's is a progressive disease, that sometimes a worsening of tremor is part of that progression, or maybe a sense that the levodopa isn't helping as much as it used to. Maybe for the first couple of years it had completely stamped out your tremor, and now your tremor is kind of starting to break through again in different situations. Then, in that case, probably on a more long-term course or more gradual course, that would probably signify a progression of the condition and potentially a need for a higher dose of the medicines to help the tremor more again, or these other treatments like we talked about, like the deep brain stimulator or the focused ultrasound.
Dr. James Beck 01:07:42
Thank you for that. When we think about tremors, often it's in the extremities. Some people here described internal tremors, and then you yourself, somewhat related, talked about this issue with dystonia, often in the feet but sometimes in the face. How do you address those? Are internal tremors typically handled with carbidopa-levodopa? With the dystonia that you might see elsewhere outside of the feet, is this where botulinum toxin comes into play?
Dr. Pablo Coss 01:08:16
The internal tremor is an interesting thing. Some folks will say that they feel the tremor on the inside, that kind of an internal sensation of tremor. We look at our medicine options and we decide, maybe is it a component of anxiety that's coming out as a kind of internal sensation of tremor, and we can treat that appropriately. Or with levodopa, that can often help that internal sensation as well, or the other tremor medicines.
But specifically for dystonias, whether they come with a tremor or not, like the woman in the video that I showed, and thank you for reminding me that I should have included botulinum toxin as another treatment option, the video that I showed with the woman whose foot is turning in at the ankle, I do treat her to this day with botulinum toxin injections to the muscles of the lower leg that pull the foot in that way. It helps her quite a bit.
So actually administering botulinum toxin injections, usually Botox or one of the other brand names of the treatment, is a big part of our practice and the way that we help a lot of these dystonic symptoms of Parkinson's disease. Whether we're injecting it into the foot, to the muscles that curl the toes so that they relax and the toes don't curl as much, or whether we inject it into the muscles around the eye or the face that cause that closing of the eyes, what we call blepharospasm. Yeah, we make a lot of use of Botox, and it can be very helpful specifically for dystonic symptoms of Parkinson's.
Just before I came in here to participate in this webinar, I was doing Botox injections around the eye that have been really helpful for one of my Parkinson's patients to keep their eyes open more consistently. Before, he used to have to kind of open them manually with his hands, and he hasn't had to do that in a long time because of the Botox.
Dr. James Beck 01:10:12
Oh, that's fabulous. I'm sure that really improves quality of life, to just be able to see consistently as you navigate around in the world. You focused a fair bit on different types of treatment options. We just talked about botulinum toxin. One of the new ones out there is the subcutaneous pump Vyalev, I think that's how it's pronounced. Has it been around long enough where you've really been able to see, in your clinical experience, a real impact on controlling some of the tremors, the dyskinesias and things as far as that goes?
Dr. Pablo Coss 01:10:45
Absolutely, yeah. I think it's only been on the market for, time flies for me, so I always forget, about a year maybe. Even before that, we were part of the clinical trial, and we were getting some experience using it as well. But just in that short amount of time, many of my patients have it. Usually, they are patients who have had DBS for a number of years, and the DBS has made a big difference, but it hasn't 100% erased the dyskinesias and the fluctuations. Then we turn to the Vyalev pump.
The Vyalev pump, like I said, is a device that you carry with you 24 hours a day, usually in a little satchel or belt or a vest. It's attached to the skin through a little tiny plastic cannula, and it's infusing a constant amount of liquid levodopa into your skin. It's getting absorbed into your body 24 hours a day. It really is the best way that we can get somebody a constant level of levodopa in their bloodstream that gets a person out of the dyskinesias every time the oral dose peaks and then the wearing off every time it wears off before the next dose.
It makes a big, big difference. It really has. Actually, this patient that I injected with the Botox that I was telling you about, he also has one of those, and he was just telling me how much of a difference it's made for him to be able to walk consistently and talk consistently. Before, he was taking his medicines five, six, seven times a day, and even then, was wearing off in between and was really disabled by the difficulty walking more than anything and difficulty speaking. Now he walks and talks like you could hardly tell he has Parkinson's. So amazing. We've had really good experience with the Vyalev pump already on a number of our patients.
But the main issue that people need to know about is sometimes people have skin reactions where the cannula is infusing the medicine into the skin, and so you have to be careful about that. There's a lot of training from nurses and your doctors about how to properly manage the cannula site on the skin and how to move it every couple of days so that it's not building up all in one spot, how to be clean to avoid infections and stuff like that.
Dr. James Beck 01:13:04
I'm sorry, I didn't mean to cut you off.
Dr. Pablo Coss 01:13:07
Well, I was just going to say, even despite some of those skin issues, it helps most of my patients so much compared to the pills. It gets rid of the need to take the pills frequently throughout the day, which is an achievement on its own. They'll get good about doing the cannula cleaning and upkeep and all that stuff.
Dr. James Beck 01:13:29
That's just even something I hadn't considered, to be able to use in conjunction with DBS as part of normal care and really seeing such tremendous effects.
Dr. Pablo Coss 01:13:43
Many people will think of it as an alternative to DBS, which is not unreasonable. It's trying to accomplish the same thing, which is to get rid of the need for frequent pills and the fluctuations, which is what DBS is trying to do. But my personal opinion is that folks with Parkinson's, if they fluctuate a lot as the years go on, they're going to be benefited by having both: having the DBS producing the electric signaling that helps the symptoms, and then the subcutaneous pump that gives you a continuous chemical signal to help your symptoms.
Dr. James Beck 01:14:14
Yeah, that's interesting. Now, when you talk about DBS and other therapies, can it be used in conjunction with focused ultrasound, one or the other? Or if you go down that focused ultrasound pathway, are you locked into that?
Dr. Pablo Coss 01:14:27
No, you can do the focused ultrasound, and if it works well and it accomplishes the goals and you don't need any other advanced treatments, that's great. But if it works for a while and then maybe the disease progresses as the years go on and you need one of the other treatments, you can still get a DBS. You can still do the Vyalev pump. What you can't do is get the DBS and then try to do the focused ultrasound while the DBS is in your brain. Maybe potentially you can do it, but it's not done very often, and there are a lot of considerations that might make it not a good idea.
Dr. James Beck 01:15:01
Yeah, you don't want to heat up the wrong thing if it's blocking your way. Well, Dr. Coss, I really appreciate your time and your answers to questions as they come in. I think we're coming up to the end of our time. We've decided for the spring to make our expert briefings just a touch longer, so thank you very much for hanging in there with us and for your time today. This is a wonderful briefing on tremor, shakes and everything in between. If you want to see the full deck that Dr. Coss wasn't able to present, just know that we will be including that as part of an email that'll go out, where you can download that as part of the process.
Dr. Coss, again, thank you as part of that process. We had lots of questions come in. If you don't have an opportunity to get a response, please know that we have our helpline, Helpline@Parkinson.org, or also 1-800-4PD-INFO, which is a wonderful resource. We've got tremendous colleagues there who are really helpful at handling and answering a lot of different questions as part of the process.
Our next expert briefing is going to be hosted on April 8. We've got one down right now and are looking forward to what's going to be Inside the Science: Parkinson's Research Today. That should be a really exciting topic. I'm looking forward to that.
Also keep in mind that this is not just the complete list of our PD Health at Home series. We have a lot of things that are available on a weekly basis, Mindful Mondays, Fitness Fridays, and we even have programs in Spanish if that's your preferred language or if you have family members who are more comfortable in that as part of the process. The key thing is we're here for you. Feel free to reach out with your questions, regardless of what they may be, and know that we have people ready to respond as part of the process.
Dr. James Beck 01:16:51
Now, before you go, I just wanted to remind everyone that this is the Zoom world where it'll go black, but what will happen on your browser should be a briefing survey that comes up. Please fill out that survey. We use that tremendously and rely upon your feedback to ensure that what we're doing remains aligned with your needs and priorities. We also use it to provide feedback to our speakers. We've seen some that come in very recently, and they've really enjoyed what Dr. Coss had to say. So I appreciate those providing that kind of feedback.
We also take constructive criticism, too. We always want to figure out how to improve. If you have any feedback, please feel free to leave it for us, and we will do our best to incorporate it to ensure that we're better next time. There's always opportunity to improve as part of the process. Until April, I wish everyone a good spring, and thank you very much for your time. We'll talk again soon.
