Episode 97: Understanding Bradykinesia and Dyskinesia

Dan Keller 0:08

Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller. At the Parkinson's Foundation, we want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research—the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow.

People often think of Parkinson's disease as involving tremors, but while tremors may or may not be present, the defining symptom is bradykinesia, a slowing of movement. For a diagnosis of PD to be considered, bradykinesia must be present in conjunction with either tremor or rigidity. The flip side of bradykinesia is dyskinesia—involuntary, erratic, writhing movements of the face, arms, legs, or trunk. They may be fluid, possibly dance-like, or jerky. Whereas bradykinesia is a symptom of PD, dyskinesia is a side effect of certain anti-Parkinson drugs.

I spoke with Dr. Benjamin Walter about what can be done to help alleviate them and what is in development. He said that while both may occur in any one person with PD, they are two different forms of movement disturbance.

Dr. Benjamin Walter 1:43

There are really two sides of a coin. Bradykinesia refers to slow movements, but it's a little bit more than that. And dyskinesia, the term itself just means abnormal involuntary movement, but really, when we're talking about Parkinson's disease, we're talking about increased movements that are involuntary that happen typically in the presence of dopaminergic medications or medications that promote movement in patients with Parkinson's disease.

Dan Keller 2:11

So, bradykinesia is a feature of the disease, but dyskinesia results from medication. Is that right?

Dr. Benjamin Walter 2:19

That's correct, except that we couldn't see dyskinesia as a result of medication in somebody who does not have Parkinson's disease in the first place. So, for example, if somebody who did not have Parkinson's took a Parkinson's medication over time, they would never develop dyskinesia. So, it really requires the presence of a low dopamine state where the brain's not making enough dopamine in the first place, and then over an extended period of time, the brain may change in some people where they develop dyskinesia as a response to the medication.

Dan Keller 2:50

How common are each in PD, and at what stages?

Dr. Benjamin Walter 2:55

Bradykinesia is really ubiquitous in Parkinson's disease. Every patient, really, by definition, has to have some bradykinesia in order to meet the diagnosis of Parkinson's by the criteria that are really followed today. That is the most cardinal of the cardinal symptoms. They may have other symptoms and should have other symptoms in order to make the diagnosis, things such as resting tremor, a change in posture, a change in walking with shuffling, or even freezing, but all patients essentially have bradykinesia with Parkinson's disease. Dyskinesia is not as common, and it may be in 20% or so of early patients up to 40, 50% as the disease progresses.

Dan Keller 3:41

What are some examples of bradykinesia, and what parts of the body are most affected? How do they manifest?

Dr. Benjamin Walter 3:48

One of the first things we do is look at overall spontaneous movements, and with Parkinson's disease, you'll see that patients don't blink their eyes as much, they don't move as much spontaneously, there's less expression in their face. But when we look at hand movements, in particular, we'll look at finger tapping, or opening and closing of the hands, and that's where you really see some of the key features of bradykinesia, where we can also be more clear in our minds that this is Parkinson's disease.

There's a feature of bradykinesia that we see called a decremental response, so when a patient taps their fingers together several times in succession with Parkinson's disease, the amplitude not only slows but gets smaller over time, the more times they tap. And that decremental response, or a decreasing movement over time, is a classic feature of Parkinson's disease, and one that really tells us—I think our understanding of this is that patients with Parkinson's disease have abnormalities in scaling of movement. They don't make movements as big as they should or as fast as they should. There's really a misperception in the brain of the extent of how big their movements are, and so over time, without the proper feedback, their movements actually get smaller and smaller because of that abnormal perception.

Dan Keller 5:09

How troubling is bradykinesia in terms of function, daily life activities of daily living, quality of life?

Dr. Benjamin Walter 5:17

I think bradykinesia has a big impact on the quality of life for people with Parkinson's disease. They may express it in different ways, because sometimes it's hard to put into terms without necessarily understanding what is underlying, but patients find that it's hard to find tasks with their hands, it's hard for them to write, which is something that people complain a lot about, their movements are small and slow, it takes longer to do things, it takes longer to eat. This may translate to losing weight, because when they sit down for a meal with their family, it takes a lot longer to eat, and everybody else is done eating. They may stop as well, without having as large of a meal as they normally would have. They may impair work if they're still working because they're not getting their tasks done. It's hard to complete what's in front of them.

Early morning activities, I think, are very difficult for patients, particularly if they have a lot of bradykinesia before their medications begin to work for them. And so, getting ready for work, or getting ready for an appointment, getting ready to go out, becomes a daunting task for many patients.

Dan Keller 6:21

Is bradykinesia always predictable, or can it come upon someone suddenly, or not at a typical time? They would get it some other time.

Dr. Benjamin Walter 6:30

Initially, bradykinesia typically is predictable. In fact, early on, the medications, when patients go on them, may work more or less all the time, and they may have just a little slowing overall compared to what they had before the diagnosis of Parkinson's. But as they begin to wear off more and they progress with the disease, they get wearing off between doses that initially is predictable, and then over time that may become unpredictable, where it really can happen at any given time, and that becomes a much greater challenge for patients. Because now they can't plan, they can't go out, and even at times when they feel they have the capability of doing things, some patients may unfortunately give up and choose not to do the things that they would like to do, or things that would give them improved quality in their life, because they're afraid that they'll have unpredictable wearing off and they'll have bradykinesia and other Parkinson's symptoms set in and not be able to comfortably progress through whatever they're trying to do if they're out and about and try to do things. And so they give up and just kind of not engage in activities.

Dan Keller 7:41

In terms of both bradykinesia and dyskinesias, is it helpful for a person with Parkinson's to keep a record or a diary to report to their movement disorder specialist?

Dr. Benjamin Walter 7:53

A diary can be very helpful in understanding these patterns of how the medications are working and how patients are having bradykinesia, which occurs in off-time, or when the medications are working, which we refer to as on-time. So many times we will ask patients to keep a diary for usually just a couple days. It doesn't have to be forever, but particularly three or four days prior to an appointment, or when a decision is going to be made on therapy. If a patient is able to keep track of when they're on and that their medications are working, when they're off, where their medications are not working, where they have more bradykinesia... We would also want to know what times they're asleep, in which case the effect of medication would be unknown. And then with that, we'd also want to know the timing of their medication on that given day in relation to that. With that, we can start to see the pattern of when patients are experiencing on-time or dyskinesia and bradykinesia.

Dan Keller 8:56

Are patient reports really the main thing, or is there any use to using things like wearable sensors, or even Apple Watch, or Fitbit, those sorts of things?

Dr. Benjamin Walter 9:07

More and more, these technologies are being developed where you can get accurate readings from wearables that can tell whether a patient is on with dyskinesia—so they have those extra, sometimes bothersome involuntary movements—or when they're off and more bradykinetic. Yes, these technologies are available now. Some of them are being developed into the commercially available consumer market devices. Apple Watch and Android watches have some capability of monitoring these things with the accelerometers that are built in, and there are some applications that are built for that. And then there are some specialized companies that have developed both applications for these platforms and standalone, more sophisticated devices that are able to monitor whether a patient is on, having more tremor when they're off, or having dyskinesia, all the different states that we may see. And this can be very helpful, because now instead of having to think about it, a patient can wear one of these devices for a little while and gather some of that information again, so we can see the patterns of when the medications are working and when they're not, or when they're working too well, and the patients are having dyskinesia.

Dan Keller 10:16

Are dyskinesias painful? They look like they might be.

Dr. Benjamin Walter 10:20

Dyskinesias can be painful for many patients. Dyskinesias may be mild and not bothersome if they aren't too excessive. The movements have different characteristics. One is what we call a choreiform movement, which is kind of a dance-like movement. Some patients also have dystonic movements with their dyskinesia, where they have much more severe twisting and turning of their muscles, where muscles will contract against each other and distort the posture of a joint, and when you have a lot of dystonia, those muscle pullings can actually be uncomfortable and cause problems for patients.

Also, if the dyskinesia is choreiform and it's very severe, where there's a lot of thrashing about, that over time can be uncomfortable as well, or cause structural damage to joints and cause significant problems. I guess, in a more severe case, I've had one patient who actually developed a fracture of a bone because the dyskinesia was so bad they shook their arm apart, essentially. And that's an extreme example, that's not typically the case. Some patients more commonly have mild dyskinesia, and they're not so much bothered by it, but the more dystonic twisting and turning can be uncomfortable for patients.

Dan Keller 11:31

What can be done to lessen both bradykinesia or dyskinesia?

Dr. Benjamin Walter 11:38

There are a number of different ways to treat dyskinesia with medications, particularly a class of medications that works on NMDA receptors—amantadine being the main one, or rimantadine, which is similar, may suppress dyskinesia. So that's probably the main strategy with receptors, is through NMDA. The different dopamine receptors—D1, D2, D3—may be activated by levodopa to some degree, but also different dopamine agonists, which are medications that are similar to dopamine but aren't actually dopamine and may selectively hit some of these dopamine receptors a little bit differently than levodopa, can be used to give long-term benefit with them. Their bigger advantage is probably more in that a lot of these medications, not all of them, are longer-acting—they're not metabolized as quickly as levodopa, so they can give a smoother benefit, and we're able to more precisely tune the level of stimulation that they need without excessive amounts, so they don't develop the dyskinesia.

But in general, these medications aren't typically as potent as levodopa, and so they may give a degree of benefit, but for patients that are more severe, we're still using levodopa, we're still having issues with those medications going too high and too low, getting dyskinesia when the medications are high and bradykinesia when it's low. And then the strategies may be using longer-acting forms of levodopa. So, we've got a long-acting form called Rytary. There's something that is also being developed called IPX203, that's a long-acting form that's being researched as well. People are looking at subcutaneous infusion therapies that put levodopa basically in in a continuous fashion, and there's also an approved therapy called Duopa, which is an 16-hour continuous infusion through essentially a feeding tube in the stomach—it's called a PEG-J tube, where the patients get continuous levodopa that way. And with all these more continuous levodopa or dopaminergic therapies, patients tend to have less dyskinesia because they're not getting the highs and the lows, and they're more precisely tuned. If the medications are adjusted properly, they're more precisely tuned in what we call the therapeutic window, where they're not having bradykinesia, and they're not too high, where they're having dyskinesia. Another approach to this are the surgical therapies, so deep brain stimulation can be done, which gives a pacemaker that gives patients continuous stimulation of these same areas where the medications work.

Dan Keller 14:13

Is it worthwhile trying music therapy, exercise, dance, boxing, these physical movements? Does that help either of these?

Dr. Benjamin Walter 14:23

There's a number of different exercise therapies that are very helpful for people with Parkinson's disease. These are a few of them. Dance is helpful. Some people found that fast-paced cycling—and there's some data behind that—can be beneficial to the symptoms of Parkinson's, and some of these symptoms are benefited for a prolonged period of time, but eventually the benefit goes away if you stop regularly engaging in exercise. But exercise for sure has beneficial effects for a lot of the symptoms in Parkinson's disease.

Dan Keller 14:53

Which healthcare professionals deal with these conditions? Is it mainly the movement disorders neurologist, or are there other members of the team?

Dr. Benjamin Walter 15:02

There's a number of different healthcare professionals that are involved in any multidisciplinary approach, for sure. As far as the primary decision making with these particular medications for controlling motor symptoms, typically it's a neurologist or a neurologist that's trained specifically in movement disorders. And as maybe sensed from this conversation, I think not only is this a very complex area, complex to treat, but it's also constantly changing, and that we do have a lot of very new therapies, so patients are probably best served by a movement disorders neurologist to treat their motor symptoms.

But in addition to that, with Parkinson's disease, there's a whole another area of issues that we focus on, and that are the non-motor symptoms, and this is a much bigger conversation, but depression, anxiety, sleep problems, blood pressure control, hallucinations, and psychosis, in some cases memory problems can all be part of Parkinson's disease as well. And this is something that we really need multiple specialists—we need psychologists, physical therapists, speech therapists, occupational therapists, sometimes sleep specialists involved to help patients really get around and wrap their arms around all the different problems that are affecting our patients with Parkinson's disease, so we can give them good quality of life, and certainly all these different features kind of feed into those types of problems.

Dan Keller 16:27

In terms of the movement disorders, especially the bradykinesia and dyskinesia, do you see anything that's particularly caught your eye for the future?

Dr. Benjamin Walter 16:37

I think that there's a lot of excitement in my mind, for I guess two areas. One is that our continuous dopaminergic therapies are getting better and better as we get more technologies, more continuous levodopa preparations, or other medications, and then also the surgical therapies, particularly with the different technologies that are being deployed with deep brain stimulation, are getting much more sophisticated very quickly.

There's now the ability with a new device for the Medtronic DBS system, where the device actually senses signals in the brain, and we know that these signals may correlate with bradykinesia, and there are signals that correlate with dyskinesia that we can pick up from the same stimulating wire that is creating the pacing therapy that controls the symptoms. And the hope is that in the near future we'll be able to tie those signals to the way that patients are programmed, so that their stimulation actually can adjust up and down depending on whether they're more bradykinetic or more dyskinetic, and keep them in that sweet spot more of the day, and really responding to how their brain is responding to the therapy. That technology is basically available right now in what's available, and we're really just waiting for some of the applications to be worked out, but it should be usable this way in the near future. In the meantime, the technology is available for clinicians to have a much better monitor of how a patient is responding to their therapy, so that we can adjust their deep brain stimulation a little bit more in an evidence-based fashion, based on data that we're getting from the device that they have implanted.

Dan Keller 18:18

Is there anything important we've missed or interesting to add?

Dr. Benjamin Walter 18:23

I think you covered a lot of it.

Dan Keller 18:25

Okay.

Dr. Benjamin Walter 18:26

Very good questions.

Dan Keller 18:28

I appreciate all the help.

For more on managing motor symptoms in PD, please join us on February 9 for the first in our winter-spring 2021 series of expert briefing webinars titled Symptom Management: Is it PD, Medication, or Aging? Michael S. Okun, National Medical Director of the Parkinson's Foundation, and occupational therapist Lisa Warren will be talking about co-managing motor symptoms. You can find information on the expert briefing series at parkinson.org/eb.

A past expert briefing with Dr. Hubert Fernandez covers a variety of medications and side effects, as does a recent podcast with Dr. Irene Richard called PD Medications and Side Effects. In it, she discusses various classes of anti-Parkinson's drugs, the adverse effects that may accompany them, and potential ways to minimize these unwanted effects. You can also search our library or call our helpline to download or get a free copy of our book on medications. Of course, you can find a wealth of information on bradykinesia and dyskinesia by searching our website, parkinson.org, or our library on those terms.

If you have questions about today's topic or anything else having to do with Parkinson's, our information specialists can provide answers in English or Spanish. You can reach them at 1-800-4PD-INFO. News and updates about future events and resources are available by joining our email list at the bottom of our website's homepage. If you want to leave feedback on this podcast or any other subject, you can do it at parkinson.org/feedback. If you enjoyed this podcast, be sure to subscribe and rate and review the series on Apple Podcasts or wherever you get your podcasts.

At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life today. To that end, we'll be bringing you a new episode in this podcast series every other week. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO, that's 1-800-473-4636. Thank you for listening.

Dr. Benjamin Walter is the head of the Section of Movement Disorders and medical director for deep brain stimulation at Cleveland Clinic in Ohio, a Parkinson’s Foundation Center of Excellence. Prior to this role, he held the Penni and Stephen Weinberg Chair in Brain Health at University Hospitals and was an associate professor of neurology and biomedical engineering at Case Western Reserve University School of Medicine.

He is board-certified in neurology. Special interests include DBS, dystonia, functional magnetic resonance imaging (MRI), intrathecal baclofen, the mechanism of effect of DBS, movement disorders, Parkinson’s disease and tremors.

He earned his medical degree from MCP-Hahnemann School of Medicine in Philadelphia. He completed his internship in internal medicine and residency in neurology at Emory University Hospital, as well as fellowship training in movement disorders with an emphasis on intraoperative mapping and deep brain stimulation.

In his research laboratory, Dr. Walter uses functional MRI to study mechanisms underlying changes in Parkinson’s disease and dystonia, participating in several projects funded by the National Institutes of Health (NIH). He is currently an investigator on an NIH-funded project exploring intracortical control of arm and hand function restored by functional electrical stimulation in people with spinal cord injury (Brain Gate). He has also served as an investigator on the Enhanced Exercise Study for Patients with Parkinson’s Disease (EXCEED) study of how exercise and education affects people with Parkinson’s disease and depression, as well as on an NIH-funded project to develop an “intelligent” bicycle for rehabilitation in Parkinson’s patients.

Dr. Walter is the author of more than 20 articles in peer-reviewed medical journals, as well as five book chapters. He has presented posters and abstracts at more than 20 international and national peer-reviewed medical conferences.

In addition, Dr. Walter has served as an invited lecturer/instructor at national and international medical education conferences and colloquia. He is grant reviewer for the NIH and the American Association for the Advancement of Science and also reviews manuscripts for several prominent medical journals. He is a member of the Organization for Human Brain Mapping, Society for Neuroscience, American Academy of Neurology and the Movement Disorder Society.