Expert Briefing: Non-motor Symptoms: What’s New?

James Beck 00:00:00
Hi there. Welcome, everyone, to our third webinar in the Parkinson's Foundation's tenth Expert Briefing series. Today's topic is Non-Motor Symptoms: What's New? This is the first one for 2019, so I want to wish everyone a happy new year.

I'm Dr. James Beck, Chief Scientific Officer at the Parkinson's Foundation and your host for our discussion today. Welcome, everyone. I talk about this all the time, but I just cannot emphasize enough that these webinars we've created year in and year out are really based upon the feedback of the Parkinson's community. When we have surveys posted at the end of our webinar today, please fill them out. Please keep an eye out as we look to the community to come up with new ideas each year. We also work very closely with the Alliance of Independent Regional Parkinson Organizations, or AIRPO.

These are other organizations that also have roots in the community as well, so that what we present to everybody on our Expert Briefing series is what everyone's looking for. If you're looking at the presentation right now on your screen, you can see that there's a PowerPoint slide that can be downloaded from this page. If you look on the left-hand side, you can see a link that says download, and a PDF file will be made available. You can have it on your computer so you can look at it anytime after the webinar or even during it.

If you're a health professional, I've got good news. As always, you can earn one free CEU through the American Society on Aging. If you registered as a health professional and indicated you would like a CEU, then you will receive an email by the end of today with the steps on how you actually go about collecting your CEU. But remember, you only have 30 days to do so. That's until February 15 to collect that free CEU.

Now I'd like to introduce our guest speaker. Today our speaker is going to be Dr. Ronald Pfeiffer. He's at OHSU, Oregon Health & Science University in Portland. It's also a Parkinson's Foundation Center of Excellence. Dr. Pfeiffer hails from Nebraska, where he did his undergrad and medical school. He completed his neurological training at Walter Reed Army Medical Center in Washington, DC. His focus is really on three different areas of Parkinson's disease: clinical trials, genetic aspects and gastrointestinal dysfunction, which is a key non-motor feature of Parkinson's disease.

He's participated in numerous clinical trials, was chair of the movement disorder section for the American Academy of Neurology, and has authored numerous journals and books related to Parkinson's disease. He currently serves as co-editor-in-chief of the journal Parkinsonism & Related Disorders. Sorry, that's from 2008 to 2017. He remains very active within the PD community, and it's really our pleasure to have him here. Dr. Pfeiffer, welcome.

Ronald Pfeiffer 00:02:54
Thanks a lot, Jim. It's a real pleasure to be here. The topic of my talk today is going to be Non-Motor Symptoms: What's New?

These are my financial disclosures, none of which are particularly or specifically germane to what we'll be talking about today.

For about the first 150 years following James Parkinson's description of what we now call Parkinson's disease, Parkinson's disease was primarily considered to be a problem with movement, a motor disorder characterized by the triad of tremor, rigidity or stiffness, and slowness in movement, or bradykinesia, and then in the later stages also with balance impairment. But in the last 25 years or so, it's been increasingly recognized that that's just the tip of the Parkinson iceberg and that there are a host of other facets or features of Parkinson's disease that have little or nothing to do with motor function. They are now collectively called the non-motor features of Parkinson's disease.

On the right hand, if you're looking at the slides, I have grouped non-motor features into five different categories. It's a very broad topic, and I realized as I was putting this together there was no way to cover all of them. At the risk of having done a little bit of a bait and switch when it was advertised that we would talk about all of the non-motor features, I won't be talking about the ones in blue, the sleep disorders and behavioral changes in Parkinson's disease today.

However, the reason I dropped those out is not because they were not important, but because they are so important that they actually have been the topics of whole sessions in previous Expert Briefings devoted to the topics. In 2017, in June, there was a whole topic on sleep disorders, and there have been also in 2017 and 2018 sessions on depression, on cognitive changes and dementia. You can go back into the archives and review those.

Ronald Pfeiffer 00:05:21
Today I'm going to focus on some lesser-studied, lesser talked about — lesser talked about is bad English. My father, the English professor, is turning over in his grave. But we're going to be talking about some abnormalities of sensation, autonomic dysfunction and just briefly mentioning fatigue and a few other non-motor features.

First question you might be asking is: why should there be non-motor features in Parkinson's disease? To understand that, you have to understand where Parkinson's disease first makes its appearance in the brain, where the pathology starts. The work from Dr. Heiko Braak and his colleagues a number of years ago indicated that there are two areas where Parkinson's pathology first appears. The first is in the area of the olfactory nuclei that receive their innervation from the nose. The second is down at the bottom of the brainstem, specifically in a nucleus called the dorsal motor nucleus of the vagus, that is the origin of the vagus nerve that you might be familiar with.

As time goes by and the disease progresses, the pathology, particularly the pathology in the bottom of the brainstem, gradually moves up the brainstem and eventually reaches the top of the brainstem, the midbrain, which is where that nucleus called the substantia nigra resides. That's where the dopamine neurons that control or have to do with motor dysfunction or movement are located.

There's quite a lot of pathology that goes on before the motor areas of the brain are damaged. As it turns out, as the disease process moves up that brainstem, centers that are involved with gastrointestinal function, bowel function, stomach function, bladder function, sleeping and other aspects of neurological function are damaged before the motor function areas are damaged.

It shouldn't be surprising that as those areas are damaged, symptoms arise. On the slide now in front of you are some areas of non-motor dysfunction that can appear very early in the course of Parkinson's disease: impaired olfaction, of course, related to that early involvement of the olfactory nuclei; constipation; sexual dysfunction; something called REM sleep behavior disorder related to damage in centers in the lower brainstem; and then things like depression and anxiety can also occur early in Parkinson's disease for reasons that are not quite as crystal clear.

How early can non-motor features develop? For one example, Ueki and colleagues have looked at constipation. They gathered almost 100 patients, half of whom had been bothered by constipation before the motor features of Parkinson's developed. When they looked at when the constipation started in those people, they found that it was right at about 40 years of age. In those people, on average, the motor features, and therefore the diagnosis, if you will, of Parkinson's disease, wasn't made until almost 20 years later, 58 or 59 years.

Constipation had made its appearance almost 20 years before the motor features developed, and that sort of early appearance can also be seen in impaired olfaction. It can be seen with something called REM sleep behavior disorder and other non-motor features appearing years and sometimes even decades before the development of motor features.

Ronald Pfeiffer 00:09:33
How important are motor features? We tend to think of Parkinson's disease disability being due to the motor dysfunction, the stiffness and the slowness, and they certainly can and do produce motor dysfunction. But particularly as Parkinson's disease progresses, non-motor features become increasingly important as a source of disability, especially some of the behavioral changes.

Depression, and even more importantly cognitive difficulty and even dementia, can become the dominant features in advanced Parkinson's disease and can be a major cause of both hospitalization and, ultimately, institutionalization. Non-motor features are clearly a very important facet of Parkinson's disease that it's important we know about.

Let's talk about some abnormalities of sensation. I'm going to just mention three of them. There are more. We'll talk briefly about olfactory impairment, talk about visual dysfunction and then talk about pain.

Impaired sense of smell is evident in the vast majority of people with Parkinson's disease if you test for it. Anywhere from 70 to 90 percent of people with Parkinson's disease have some impairment of sense of smell. It's not that sense of smell is lost, but that it takes a stronger smell for the patient to perceive it. Another interesting facet, the explanation for which isn't entirely clear, is that not all smells seem to be affected, and some odors are more difficult for Parkinson's patients to perceive than others. I give some examples, such as licorice, coconut and banana being especially impaired.

I don't know of any treatment currently available for impaired sense of smell in patients with Parkinson's disease. The question is sometimes asked whether levodopa might help sense of smell, and I don't think there's any good evidence that it does.

Visual dysfunction is surprisingly common in people with Parkinson's disease also. Patients may describe a variety of visual symptoms. They may say they have tired eyes. They may say they have blurred vision. Double vision can occur. Usually it comes and goes intermittently. At least one study has suggested that as many as 14 percent of patients with Parkinson's disease may experience episodes of double vision. People with Parkinson's disease often say they have difficulty doing things up close, like reading. They often also will say that they have real trouble in dim lighting conditions. Driving at night might be an example of that, or just trying to read the menu in a restaurant.

Ronald Pfeiffer 00:12:26
What's particularly frustrating for people with Parkinson's disease is that they've gone to their optometrist or their ophthalmologist even, and the routine eye exam has been normal. With glasses, your visual acuity is great. You should be fine. But they're not. They have all these symptoms. If the eye docs would look further, they would actually find a variety of abnormalities.

People with Parkinson's disease tend to have what's called convergence insufficiency. When you want to look at something up close, you have to move your eyes together, get them a little cross-eyed, if you will. People with Parkinson's disease have difficulty doing that. If you test for it, people with Parkinson's disease may have impaired color perception, although that doesn't really contribute to difficulty with vision per se.

Most people with Parkinson's disease blink less frequently, and that can cause drying out of the eyes and irritation of the surface of the eye. But some people with Parkinson's disease will blink excessively. Some other people, although this is a relatively small percentage, may find that they have difficulty keeping their eyes open. The fancy word for that is apraxia of eyelid opening. Their eyes may close, and then they just can't get them open and sometimes have to actually pry them open.

Perhaps most importantly, people with Parkinson's disease may have something called reduced contrast sensitivity. The chart on the slide to the right is a little different than the usual eye chart, where that starts with the big E and then every line the letters get smaller and smaller. That standard ophthalmology chart is to look at how well you can see tiny objects.

This chart is a little different in that the letters are all the same size, but they get progressively more faint as you go down the chart. This is designed to look at how well people can see faint things. People with Parkinson's disease have difficulty perceiving the lower levels of this chart, and that's due to this problem called reduced contrast sensitivity.

Ronald Pfeiffer 00:14:43
The reason why that may occur in people with Parkinson's disease comes back once again to dopamine. This is work from Dr. Ivan Bodis-Wollner and his colleagues, and it's looking at pictures of the back of the eye, the retina. You can see that little valley or dip in the middle of the picture. That's called the fovea. In people with Parkinson's disease, there seems to be some loss of tissue, and what actually is loss of neurons around the fovea. It turns out that there are dopamine neurons in the retina, and those dopamine neurons are first damaged and then lost. That's probably the reason why people have reduced contrast sensitivity.

How do you treat the visual symptoms in Parkinson's disease? It turns out there's been one recent study, not in Parkinson's patients but in patients in general, that showed that people who play a lot of video games seem to have better contrast sensitivity than people who don't. The question might be raised: should we be looking at having Parkinson's patients with impaired contrast sensitivity play a lot of video games to see if that improves their contrast sensitivity? Unproven at this point in time, but I thought interesting.

For people who have intermittent diplopia, fitting glasses with prisms can sometimes reduce or even eliminate the double vision. For convergence insufficiency, the difficulty seeing things up close, eye-focusing exercises like pencil push-ups can be helpful. Pencil push-ups are when you take a pencil and look at a letter or writing on the pencil and then slowly bring that pencil closer and closer, trying to keep focused on the letter or the writing that you're looking at. Those are pencil push-ups.

For people who have that difficulty keeping the eyelids open, botulinum toxin injections sometimes can be helpful. There are treatments for at least some aspects of visual dysfunction in patients with Parkinson's disease, and it's important to know that and pursue that.

Ronald Pfeiffer 00:16:50
What about pain in Parkinson's disease? It doesn't get talked about very often, and neurologists are often not particularly good at dealing with pain in Parkinson's disease. It's not even clear how common it is, but in talking to a lot of patients, I would say it's quite common and can occur in a variety of forms.

Dr. Blair Ford, who's at Columbia University, a number of years ago wrote about pain in Parkinson's disease and divided it into five categories that I have listed here. Perhaps the most common of those is musculoskeletal, and this refers to problems with the muscles themselves. If muscles are tight for a long period of time, they start to hurt. If you've ever carried anything heavy, you know that it starts to hurt after a while when you're carrying it, and that can be more broadly generalized to muscles in Parkinson's disease.

One of the most common areas for pain is in the shoulder. My father was diagnosed with Parkinson's disease when I was 13 years old. But I remember in the year or so before he was diagnosed, he stopped playing catch with me in the backyard because his shoulder was hurting. He was diagnosed with bursitis and was treated with steroid injections, and they didn't help. It was only when other features became apparent that he was diagnosed with Parkinson's disease. That's a relatively common scenario for patients with Parkinson's disease, where shoulder pain may have preceded the more obvious motor features.

Because of changes with posture, and you can see this illustrated in the purple box on the slides, the propensity for nerve roots coming out of the spinal column to be pinched or compressed is higher. People with Parkinson's disease can have what's called neuropathic or radicular pain. That's often a sharp, electric shock-type pain that may go down the arm or may go down the leg.

Ronald Pfeiffer 00:19:19
Another type of pain that is relatively common in people with Parkinson's disease is due to prolonged contraction of muscles called dystonia. That most often involves the toes or the feet, causing the toes to curl under or turn up and the foot to turn in. When that goes on for a longer period of time, it can become quite painful. It tends to happen when the effect or the benefit of Parkinson medication wears off and tends to improve when the medicine turns back on again.

An uncommon cause of pain, but a very difficult cause, is when there isn't anything in the muscles or nerves or joints producing the pain, but it's due to disturbances within the brain itself. That's called central pain in Parkinson's disease. It can be very disagreeable. It can involve odd locations like the throat, genital areas, rectal areas, things like that, and can drive people to distraction.

Finally, there's this thing called akathisia, which was actually first described in people with psychiatric issues who were on antipsychotic medication, which blocks dopamine function. They develop this sense of, "I've got to move. I can't sit still. I've got to get up and walk around." It has some similarity to restless legs, but is probably a little bit different basis. People with Parkinson's disease, again, especially when they're off, can have this akathisia that can be very troublesome.

As far as treating pain with Parkinson's disease, it depends on what's producing the pain, as I just went through. If the pain is muscular in origin and it's occurring when the Parkinson medicine wears off, then adjusting Parkinson medication, taking it more frequently, increasing the dose or taking other measures may alleviate some or much of the pain. People with Parkinson's disease often ask about taking muscle relaxant medications, but my experience is that they're not usually very effective, and I tend not to prescribe them.

Physical therapy can be particularly helpful if people have a pinched nerve, but sometimes surgical correction, taking out a disc that's compressing a nerve, becomes necessary. If the person is having that constant contraction of the toes or the feet, injection of botulinum toxin into the muscles to get them to relax can be very helpful in alleviating the pain. Unfortunately, that central pain can be very resistant to treatment.

Ronald Pfeiffer 00:22:10
Let's move on and talk about the autonomic nervous system. The autonomic nervous system is the part of the brain and external or peripheral nervous system that controls things that we don't have to think about consciously. I'm talking about blood pressure, pulse rate, stomach function, intestinal function, bowel function, bladder function, sexual functioning, sweating and temperature regulation. All those are things that are controlled by the autonomic nervous system.

If you talk to people or assess people with Parkinson's disease, you will find, as we did in a study a number of years ago, that virtually all aspects of autonomic function are injured or not functioning properly in patients with Parkinson's disease. If you sum all of those up, way over on the right-hand side of that graph, you can see that autonomic symptoms are much more common in people with Parkinson's disease. I want to just talk about some of them, and we'll start with having to do with the cardiovascular system. There are three things that we'll talk about.

First of all, in patients with Parkinson's disease, the sympathetic innervation of the heart is damaged and basically gone.

Ronald Pfeiffer 00:23:30
A similar thing would be true in someone who's had a heart transplant, where the heart is transplanted and it's working just fine, but the autonomic innervation of the heart isn't there. It doesn't typically produce any symptoms, but where it can be useful is in separating Parkinson's disease from individuals with other Parkinson-plus syndromes like multiple system atrophy or even progressive supranuclear palsy. In the images that you have in front of you, on the right is a person with Parkinson's. Well, let's start on the left.

That's a person who's normal, and you can see that sort of U-shaped area of increased uptake within the blue circle. That's the heart. The bigger area over on the other side is the liver, and you can ignore that. But in a person with Parkinson's disease, you can see that uptake is essentially gone because the autonomic supply, the sympathetic supply to the heart, is gone. The reason for that is that the pathology in Parkinson's disease isn't limited to the brain. It also affects the nervous system outside the brain, the autonomic nervous system outside the brain.

If you have a person who has multiple system atrophy, for example, the pathology is primarily localized to the brain, not to the peripheral nervous system, and so they will have a normal MIBG scan, whereas a person with Parkinson's disease has an abnormal test. That can be very useful in trying to decide what process is going on. It has nothing really to do with treatment of autonomic dysfunction.

I want to talk about orthostatic hypotension, which is a fancy word that means that your blood pressure drops when you stand up. That drop in blood pressure with standing is very common in people with Parkinson's disease. Some studies suggest that about 60% of people with Parkinson's disease will have significant drops in their blood pressure when they stand up. It doesn't produce symptoms in everybody, maybe only in a third of those who have the drop in blood pressure. But for those who do develop symptoms, this can be really important.

The classic symptom that people with orthostatic hypotension have is becoming woozy or lightheaded when they stand up, and that sometimes can become so prominent that people actually faint. On the other hand, it can also produce a variety of other symptoms that are often not associated with blood pressure dropping, but should be. For example, people with orthostatic hypotension may find when they stand up that their vision becomes fuzzy, or they may find that their thinking becomes foggy.

Other people may find that they develop a pain or a headache involving primarily the back of the neck and then the shoulders, in what has been called a coat-hanger-type distribution. Other people will find that they get pain in their lower back or in their buttock region. This is a case of literally becoming a pain in the rear.

These kinds of pain are due to impaired blood flow into those muscles when the blood pressure drops. Still other people with orthostatic hypotension may just feel very fatigued or lethargic when they stand up. It's important to recognize that sense of lightheadedness when you stand up, but it's also important to realize that these other features may occur in people with orthostatic hypotension.

Ronald Pfeiffer 00:27:26
Treatment is certainly available for orthostatic hypotension, and when you're treating it, what you're trying to do is reduce the symptoms, of course, but also improve the person's ability to stand and therefore walk and ultimately prevent fainting and the falling that goes along with fainting.

The other side of the coin, though, that can happen with blood pressure regulation in Parkinson's disease is that the blood pressure can actually rise too high when people are supine, when they're lying down. You can think of this impairment of blood pressure regulation as being like a faulty thermostat. Normally, our autonomic nervous system keeps our blood pressure within a certain range that ensures that we get enough blood flowing up to the brain to prevent fainting and so on. But if the thermostat is not functioning well, it can allow the blood pressure to drop, but it also can allow the blood pressure to go too high when people are lying down.

How do you treat orthostatic hypotension? As an immediate treatment, people will find that if they drink 12 to 16 ounces of water, or even preferably ice water, that can cause a very immediate rise in blood pressure. Some people will do that before they first get out of bed in the morning, since that's a time when the tendency for the blood pressure to drop can be particularly prominent.

When a person gets woozy when they're standing up, crossing their legs, flexing their calf muscles, getting up and down on their toes, or other physical maneuvers can sometimes serve to help pump blood out of the legs, where it's pooling, up into the circulation.

More chronically, you can treat orthostatic hypotension by increasing fluid and increasing salt consumption. Elevating the head of the bed at night makes it less likely for the blood pressure to drop when you get out of bed in the morning. It also reduces the likelihood of the blood pressure getting real high while a person is sleeping.

Then there's the issue of pressure stockings. It turns out that pressure stockings that just go up to below the knee don't do enough compression to increase blood flow sufficiently. If you're going to wear pressure stockings, they really need to be at a minimum thigh-high and preferably waist-high, like pantyhose, if you will. Alternatively, some people will use an abdominal binder to compress and keep blood from pooling in the abdominal area, which is actually a much bigger vascular bed than the legs are.

There are a variety of pharmacologic treatments to boost blood pressure. The most commonly used ones are fludrocortisone, which increases salt retention and fluid retention; midodrine, which constricts blood vessels; pyridostigmine, which also can do that; and droxidopa, which imitates the effect of a transmitter called norepinephrine that, again, is involved with blood pressure and blood vessel constriction. Other medicines have been utilized, but there's much less evidence to support their efficacy.

Ronald Pfeiffer 00:30:48
It's important to remember that NOH stands for neurogenic orthostatic hypotension that we've just been talking about. That can be the major reason why blood pressure might drop in people with Parkinson's disease, but there can be other sources for this also. Medications that are used to treat Parkinson's disease, chiefly levodopa or the dopamine agonist medicines, can cause blood pressure to drop. People with Parkinson's disease often don't drink a lot of fluid because everything is slower, and they have some difficulty swallowing.

Reduced blood volume or dehydration can occur in addition to the medications on top of the neurogenic hypotension itself, and all of this can lead to increased likelihood of the blood pressure dropping.

Another area where blood pressure can drop is after eating. The fancy word for that is postprandial hypotension. You can see from the graph here that the person being looked at had a blood pressure of 130 over 80 before they ate the meal, but within 15 minutes after eating the meal, their blood pressure had dropped to like 80 over 50.

Large carbohydrate meals can trigger this. It typically develops within about 15 minutes and then may last for several hours. People may faint when they get up from the table. Occasionally, people will get lightheaded and even faint at the table. As far as dealing with this, smaller meals and lower carbohydrate loads can alleviate this problem, but sometimes I just tell people to plan on taking a nap after you eat a big meal and let it work itself out while you're sleeping.

Another issue I'm not going to say a lot about is that in people with Parkinson's disease, sometimes the blood pressure doesn't drop at night, which is the usual pattern, but instead may actually elevate. The term non-dipping has been used for this. For some people, blood pressures can get dangerously high at night, even to the point that sometimes it's necessary to use a medicine to lower blood pressure at bedtime and then use medicines to increase blood pressure during the daytime hours.

What about gastrointestinal dysfunction in Parkinson's disease? Again, it turns out it's quite common. We did some work a number of years ago that showed that these are the areas of GI dysfunction in Parkinson's disease. I want to just focus on a couple of them.

Excess saliva is very common in Parkinson's disease. Anywhere from a little over 50% to almost three-quarters of people will notice that they have too much saliva in their mouth. That may just be drooling at night, but it may get to the point that they have to carry a handkerchief around with them. I used to have a patient who would take paper napkins and roll them up to look like a cigar and keep that in his mouth like a cigar to kind of sop up the excess saliva.

Ronald Pfeiffer 00:33:50
You might think that that must mean that people with Parkinson's disease make too much saliva. They actually don't. They make less than normal, but they don't swallow their saliva as frequently, they don't swallow it as efficiently, and so it accumulates in the mouth. People with Parkinson's disease have a tendency for their mouth to be held open a little bit. When you couple that with stooped posture, that can result in drooling.

How do you treat the salivary excess? If it's just occasional, if it's embarrassing during social situations, the simplest thing is to have people chew gum or suck on hard candy because that turns the swallowing into a more conscious and more frequent action, and that reduces the amount of saliva in the mouth.

If it's more pervasive during the day, then you can look at things that might reduce saliva formation. What I tend to use initially is atropine, and those are atropine eye drops. What you have the person do is put a drop of the atropine eye drops on or under the tongue once or maybe twice a day.

There are other medicines that also can reduce saliva formation. Glycopyrrolate, or Robinul, is another example of that. If that doesn't work or isn't tolerated, the ultimate way to treat drooling in patients with Parkinson's disease is to inject the salivary glands with botulinum toxin, which reduces saliva formation. That can be very effective. In the past, surgical techniques were used, but they really should not be used, and that's why that red X is there.

On the other hand, people with Parkinson's disease sometimes find they have a dry mouth. That shouldn't be surprising because saliva production is reduced. Medications can sometimes magnify that. It's important to deal with that because not only is a dry mouth uncomfortable, but it also increases the risk of cavity formation and periodontal disease.

As far as treating dry mouth in Parkinson's disease, you can get over-the-counter artificial saliva products like Biotene, which contains xylitol and glycerin, so it's sort of a lubricant. But there also are prescription medicines that can increase saliva formation. Pilocarpine is perhaps the best known of those, but cevimeline is another one. These are medicines that are mostly used in a condition called Sjögren's syndrome, where people have a dry mouth, but I have one patient on pilocarpine currently, and it works very well.

Bad breath in Parkinson's disease is an issue you don't see written about or talked about, but it's relatively common. Multiple factors contribute to it, including dry mouth and just physical difficulty brushing and cleaning. That leads to more bacteria in the mouth and problems. How do you deal with that? Getting an electric toothbrush can make it easier to clean the mouth. Using the things we've just talked about and also mouthwashes can be helpful.

Ronald Pfeiffer 00:37:23
Impaired gastric emptying is another issue with Parkinson's disease, and it's important for the stomach to empty properly because if it doesn't, food gets stuck there, but so do medications. When food gets stuck in the stomach, it can cause reduced appetite, early fullness, even nausea, vomiting, bloating and eventually weight loss.

There are a variety of medicines, and I'm not going to go into detail on this because time is getting short, but there are a variety of medicines that can be used to try to improve gastric emptying. These are medicines that are generally administered by a gastroenterologist, but sometimes by neurologists also.

If medicines don't work and if the problem is that the pyloric sphincter at the end of the stomach isn't releasing or relaxing to let food out of the stomach, botulinum toxin injections have been used into the pyloric sphincter with some benefit. In people with diabetic gastroparesis, a pacemaker, a gastric pacemaker, has been used. I'm not aware of that being used in Parkinson's disease.

If levodopa gets stuck in the stomach because it's not emptying, you don't get a response when you take the medication. That's true with other medicines also because they're generally absorbed in the small intestine. You can get around that with some medication approaches. The intestinal infusion of levodopa would be an example. Constant subcutaneous infusion of apomorphine would be another example, or the rotigotine skin patch would be another example. That improves medicine responsiveness, but it doesn't help the treatment, the symptoms of gastroparesis itself.

The large intestine is usually covered with bacteria, trillions of them. But the small intestine typically is not. Sometimes, though, bacteria make their way from the colon into the small intestine, and that's called small intestinal bacterial overgrowth. As it turns out, a good number of people with Parkinson's disease have this small intestinal bacterial overgrowth. If it gets severe enough, it can actually impair absorption of nutrients, and I've always wondered if it might be responsible for the weight loss in Parkinson's disease.

Ronald Pfeiffer 00:40:03
It's probably related to impaired motility in the small intestine. It can produce bloating, gassiness and perhaps some other symptoms. But perhaps more importantly, what it also can do is impair absorption of medication. People with small intestinal bacterial overgrowth may find that it takes longer for their medicine to work, it may wear off more quickly, and there may be periods or times when a dose doesn't work at all. Alfonso Fasano and his group have shown that if you treat the small intestinal bacterial overgrowth with antibiotics, you can improve medication responsiveness.

The problem is that the underlying difficulty doesn't go away, and people will get the SIBO back again. I'm going to skip this slide.

I'm actually going to go briefly over constipation in Parkinson's disease. There are two parts of constipation in Parkinson's disease. One is reduced bowel movement frequency. That's pretty straightforward to treat with increased fiber and increased fluid. If that doesn't work, stool softeners can help. MiraLAX is very helpful for many people. There are other treatments that improve or increase motility through the colon.

The other aspect of bowel dysfunction, though, is when the sphincter muscles don't relax and this other muscle, called the puborectalis muscle, doesn't relax. That can result in increased straining, difficulty with defecation, painful defecation and incomplete defecation. There isn't any tried-and-true treatment for that.

Apomorphine injections may be helpful. Some people will find that they have an easier time having a bowel movement when they're on as opposed to when they're off. In Italy, a group has done botulinum toxin injections into the sphincters, but the standard treatment still remains biofeedback techniques or muscle training of the pelvic musculature. We really don't have great treatment for defecatory dysfunction, and more work needs to be done in that regard.

Ronald Pfeiffer 00:42:29
There are two aspects to bladder dysfunction in Parkinson's disease. The most common is an irritable or overactive bladder that results in frequent urination, getting up multiple times at night, having to get to the bathroom quickly, and if you can't get there quickly enough because of difficulty walking, sometimes some bladder leaking.

There are a variety of treatments for that. By and large, these are drugs that block a transmitter called acetylcholine. Older ones like oxybutynin and tolterodine work, but they also get into the brain and can cause memory problems. Newer ones like trospium, darifenacin and solifenacin either don't get into the brain or they have a more selective effect on the bladder and are probably preferable to use in people with Parkinson's disease. Then there's the recent addition, mirabegron, which doesn't work on acetylcholine at all but works on noradrenaline.

For people for whom those medicines don't work, botulinum toxin injections into the detrusor muscle in the bladder are sometimes useful. I'm going to pass on sacral nerve stimulation.

Less frequently, people with Parkinson's disease can have a lazy bladder where the fluid keeps building up and up and up. Typically, people will have difficulty initiating urination. They may have a weak urinary stream, but if the pressure builds up because there's so much fluid in the bladder, they also may develop incontinence due to overflow. It's important to remember that men can get this same problem due to an enlarged prostate gland.

The treatment of obstructive symptoms, then, is primarily aimed at reducing prostate size, and that doesn't help women with this problem. A parasympathetic agent, bethanechol, can sometimes help this in men and women, but in all honesty, if people have obstructive or lazy bladder dysfunction in Parkinson's disease, intermittent catheterization is typically needed.

Sexual dysfunction often doesn't get talked about in Parkinson's disease. It's very common. Erectile dysfunction, reduced libido or desire, and decreased ability to achieve orgasm are very common in men with Parkinson's disease. Reduced vaginal sensitivity and decreased desire or libido is very common in women.

As far as treatment, there are a variety of drugs and approaches that can be used for erectile dysfunction. If libido is diminished, desire is diminished in men, and their testosterone levels are low, then testosterone might be a useful treatment. If the problem is lubrication, lubricants can be utilized.

Temperature dysregulation is another one of these things of Parkinson's that doesn't get talked about much. I want to mention hyperhidrosis. Some studies would suggest that over 50% of people with Parkinson's have excess sweating, primarily involving the head and neck, and typically they get sudden drenching sweats. Sometimes it occurs when the medicine effect wears off. Sometimes it's when they're having a lot of dyskinesia, but sometimes it can occur for no reason whatsoever. It can be very difficult to treat. If it's occurring when medicine is wearing off, adjusting medicine may help. Same thing with dyskinesia.

Ronald Pfeiffer 00:46:08
But if it's just happening out of the blue, medicines tend not to help. There has been at least one study that suggests that subthalamic deep brain stimulation surgery may reduce hyperhidrosis. If the sweating is localized to the armpits, you can do botulinum toxin injections.

Fatigue is another unrecognized, understudied aspect of non-motor dysfunction. It's common. A surprising number of people rank it as the worst symptom of their Parkinson's and one of their most disabling symptoms. We don't really know what causes it, whether it's a problem in the brain or in the muscles, and so treatment is really not well formulated. There are some studies that suggest exercise helps. A variety of medications have been tried, with inconsistent results. In short, we really don't have good treatment for fatigue in Parkinson's disease.

Finally, I will just briefly mention that people with Parkinson's disease will sometimes say they're short of breath. What is often happening there is that rigidity in their chest wall muscles prevents full expansion of the chest, and that produces a sense of shortness of breath. Once again, trying to reduce off time or reduce dyskinesia can sometimes help. Treating anxiety can help. There is something called inspiratory and expiratory muscle strength training that has also been utilized.

With that, just a quick summary of non-motor dysfunction in Parkinson's disease. It's important we recognize it, and it's important to recognize that effective treatment may exist for at least some aspects of it. I apologize for talking a little bit windily and long here, and thank you for your attention.

James Beck 00:48:12
Thank you very much, Dr. Pfeiffer. That was fantastic. I really appreciate your approach. Having worked with you on many aspects of what the Foundation is doing to try to cover non-motor symptoms, particularly the working group on gastric dysfunction, you really have command of this material, and I appreciate you sharing that with our community today.

I want to dive into questions, recognizing we're coming up toward the top of the hour. One that came through and is a frequent topic today comes from a health professional in Canada. It's about marijuana, CBD or various forms as a treatment for pain in Parkinson's. Do you have any thoughts on that?

Ronald Pfeiffer 00:48:57
Sure. As many people may know, marijuana is legal in Oregon, so a surprising number of my patients have experimented with CBD, not THC, but CBD, and used it for a variety of things, anxiety and pain perhaps being the most common. For some people, certainly anxiety can be diminished. Insomnia can be helped. Pain is a little more inconsistent, and I think it would be fair to say that some people derive relief of their pain from the CBD, but others don't. If it's legal, I don't encourage people, but I don't dissuade them from experimenting to see whether it helps them.

James Beck 00:49:48
Yeah, absolutely. This is a topic that captured our attention as well, and we're going to be hosting a real roundtable to try to understand its utility in Parkinson's disease. It's going to be coming up this spring, appropriately enough, in Colorado with Dr. Benzi Kluger and Dr. John Stoessl, two MDs who have some thoughts and experience on this, along with many other people.

Just to provide some feedback for our community, we have over 2,200 people registered for our talk today and over 700 people listening live. Welcome, everyone, particularly from our Ohio chapter, with 23 people, and Minnesota chapter, with 27 folks who are viewing parties. Thanks, everyone, for tuning in.

When you listen to a lot of these non-motor features, it seems that the timing between the drug that people are taking, this levodopa, and when the symptoms appear is important. Would you agree?

Ronald Pfeiffer 00:50:59
If I'm understanding you correctly, for levodopa to work, it has to not only get to the stomach, which can be a problem in Parkinson's disease, it has to get through the stomach into the intestine to get absorbed. In the best of circumstances, there's going to be a delay of, say, 15 to 20 minutes before you would ever see any effect from the medicine you take.

If there's impaired gastric emptying, that can be even longer. Sometimes people won't perceive the effect of their medicine for 30 minutes, 60 minutes, and sometimes they may not get any benefit from a dose at all because of these abnormalities in getting the drug to the intestine. I don't know if that's what you're asking.

James Beck 00:51:51
Yeah, thank you for trying to rescue a poorly phrased question. I guess what I was getting at is that the timing, it seems like some of these non-motor symptoms occur as people are going off or going on. Tracking symptoms vis-à-vis the timing of when they're taking medication is important. Do you encourage people to track their symptoms in a notebook? Is that one way to help facilitate the conversation with their physician?

Ronald Pfeiffer 00:52:20
That can be very helpful for the physician if a person has been looking at this and can say, "Yeah, it's when I wear off that I get this bloating," or that this or that happens. That can be tremendously useful. I would caution people, though, not to take it to extremes. You don't need to keep a diary every day for months at a time. If you just do a few days here and there, that can be tremendously helpful for your physician.

James Beck 00:52:50
Excellent. That's good advice. For those who are on the screen, you'll notice we have our survey up there that I talked about at the top of the hour. I encourage everyone to complete that.

One non-motor symptom that can be kind of troubling for the person with Parkinson's and their loved ones around them is, I've heard about, even in non-emotional situations, sometimes people may show emotion, where they'll cry spontaneously. Is this something that you've seen a lot in Parkinson's disease? This is from someone in North Dakota who has a friend with Parkinson's disease and is witnessing this and concerned.

Ronald Pfeiffer 00:53:35
Yeah. The fancier technical term for that is pseudobulbar affect, and that certainly occurs in some people with Parkinson's disease. I don't know, it's not super common, but it does occur. There is a medication that's been specifically developed to treat that pseudobulbar affect, where people may cry when they're not particularly sad. They may laugh in inappropriate situations.

It's a combination of two drugs. If a person is having that symptom complex, mentioning it to your primary care doctor or, even more important, to your neurologist can result in getting put on effective treatment for that problem.

James Beck 00:54:24
One of the things you mentioned I thought was really good practical advice for helping to deal with orthostatic hypotension was drinking that glass of water. Another one seemed to be this idea of an abdominal binder. What is an abdominal binder, and where do you get that?

Ronald Pfeiffer 00:54:42
You can buy them at medical supply companies or probably even Walgreens, I would guess, but certainly medical supply companies. It's just a band with a Velcro stay on it that you wrap around your abdomen and cinch it tight. In essence, it's a girdle that squeezes in the abdomen.

James Beck 00:55:06
It's kind of like one of those things that people use when they're lifting heavy weights or something that helps provide that. Yeah, exactly.

Ronald Pfeiffer 00:55:13
The thing is you have to make sure that you cinch it tight enough that it's actually squeezing something. You can't just kind of put it on loosely and fool yourself.

James Beck 00:55:24
You've got to really kind of help suck in that gut, if you will. Yeah, for those who have one, like myself.

Ronald Pfeiffer 00:55:29
Yeah, my wife keeps telling me I should have one.

James Beck 00:55:34
Yes, thanks for men.

Another question that's come in, we talked about salivation and issues. It can be associated with bad breath. Oral conditions can be an issue. Is there something that you find is because swallowing can be problematic or because the issue with maybe medications making dry mouth or other issues? Have you had to troubleshoot, I guess halitosis is the fancy word for bad breath, in people with PD? Is that part of the—

Ronald Pfeiffer 00:56:12
Yeah. I think the reason why people with Parkinson's might develop bad breath has to do with the dry mouth combined with maybe impaired ability to really clean the mouth. People with Parkinson's have difficulty with back-and-forward motions, and brushing your teeth is all that.

People with Parkinson's may not be able to brush well, and food accumulates, sits there, and, in one sense, starts to break down, and that can cause smells. Treating the dry mouth, as I mentioned, and also getting an electric toothbrush, which can clean much better than a manual toothbrush, and then using mouthwash a couple times a day, three times a day, can reduce the severity, if you will, of the halitosis.

James Beck 00:57:19
Going to the other end of the body, of the GI tract, the issue regarding constipation is an issue. The flip side is, have you observed incontinence of the bowel as a problem, loss of sphincter strength for people with PD? Is that something that fluctuates?

Ronald Pfeiffer 00:57:45
Yeah. The fancy word would be fecal incontinence, and that can and does occur in people with Parkinson's disease. It's not real common, but probably more common than might be perceived. Some of it may be related to impaired sphincter control per se.

Other parts of it may be related to, again, as with bladder dysfunction, just difficulty getting to the bathroom, getting the trousers down, and getting sat down. There may just be difficulty holding it long enough, sort of an urge incontinence, if you will.

Treating fecal incontinence can be difficult. If it's a matter of getting there in time, then trying to improve motor function becomes important. If it's a problem with the sphincters, pelvic floor exercises might provide some benefit. But it can be a difficult and, of course, embarrassing problem to deal with.

James Beck 00:58:50
Another issue is skin with people with Parkinson's disease. Sometimes they have some skin problems. Is there any straightforward way to deal with it, as you encounter it?

Ronald Pfeiffer 00:59:08
Yeah. The classic abnormality is seborrheic dermatitis, where people get this flaky, oily—and how you get flaky and oily at the same time is sort of a mystery, but people with Parkinson's do—skin over the eyebrows, over the forehead, the nose and the cheeks. It's not a life-threatening problem, but it's embarrassing. How to deal with that, this is my practical answer: I send people to the dermatologist. Using their creams and ointments, they often can prescribe useful treatments in minimizing that for patients.

James Beck 00:59:49
Excellent. As we're approaching the top of the hour, I just want to remind our listeners that, as Dr. Pfeiffer is talking about, we have many fact sheets online. If you go to our website and look for Living with Parkinson's Disease, you can find our PD Library. You can search on a multitude of topics. Many of these are covered in the talk today, but you can get more information about that. You can always reach out to my colleagues at the Foundation by calling our Helpline at 1-800-4PD-INFO, and someone on the phone can help talk with you about problems you may be having and help find solutions.

I also want to give a shout-out for our next webinar, which is coming up on March 5. That's going to be Dr. Dan Gold, who's going to really cover issues regarding eye issues in Parkinson's disease. He's a professor of neurology and ophthalmology at Johns Hopkins Hospital.

If you want to go back to today's webinar and listen to it again, because of the tremendous amount of information that Dr. Pfeiffer covered, we'll have that available next Tuesday, January 22. You can find that at Parkinson.org.

One final question, if I may, Dr. Pfeiffer. For someone who's listening to your discussion today about non-motor symptoms, we often talk about how they're often the symptoms that precede Parkinson's disease. People can go back after they've been diagnosed and say, "Oh, I had this. I had that." If you are listening to this with your loved one and you've got family members affected with this, do you need to be worried about developing PD if you have some of these symptoms? What are your thoughts about it? What do you tell people?

Ronald Pfeiffer 01:01:39
Yeah. I think the thing that you have to remember is that, say, for example, constipation: a lot of people have constipation, and not everybody with constipation is going to develop Parkinson's disease. Same thing with impaired sense of smell. Probably the same thing with REM sleep behavior disorder, although that may be a little more specific.

For the most part, these non-motor features preceding the clear-cut development of what we call Parkinson's disease are suggestive, but they're not conclusive, and you can't use them to diagnose Parkinson's disease. It might increase, particularly if you have family members with Parkinson's disease, your level of alertness to developing motor features. But we still depend on the development of motor features to make a diagnosis of Parkinson's disease.

James Beck 01:02:38
Fantastic. I think, as you pointed out, many of these features, like constipation, that people deal with, there are good ways to deal with them for the general population, in addition to ways to help people with Parkinson's disease.

Ronald Pfeiffer 01:02:55
Yeah, absolutely.

James Beck 01:02:57
Dr. Pfeiffer, thank you very much for your discussion today. This was, I think, a fantastic piece of information that the community can really use. Have a good day.

Ronald Pfeiffer 01:03:08
Thanks.

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About Ronald Pfeiffer, MD