S1 Episode 43: Facing Parkinson’s Disease

From mild resting tremors to freezing, stiffness, and loss of motor control, the symptoms of Parkinson’s disease progress relentlessly over time. Dr. Michael Kaplitt, Director of the Movement Disorders Program at Weill Cornell Medicine, along with his patient Elizabeth Larsen, explore how quality of life can erode over the years — and when it’s time for a life-changing surgical option.  

Dr. Stieg: About 1 million Americans have Parkinson’s disease and every day that number continues to grow. Right now there is no cure for Parkinson’s, but there are newer treatments helping patients achieve a much greater quality of life and scientists around the world are collaborating to find a cure. One of those neuroscientists and clinicians is Dr. Michael Kaplitt, a trailblazer in the research he spearheads to find new ways to combat this disease. Dr. Kaplitt is vice chair of research and professor of neurological surgery at Weill Cornell Medicine/NewYork-Presbyterian Hospital. I also want to welcome Dr. Kaplitt’s Parkinson’s patient, Elizabeth Larsen, who will generously share her experience with one of the most effective treatments for this disease. Mike and Elizabeth, welcome and thank you for being here. Mike, let’s start with you. How common is Parkinson’s disease, both in the United States and worldwide?

Dr. Kaplitt: Yeah, well general estimates are that 1 to 1.5 million people have Parkinson’s disease in the U S. 50,000 to a hundred thousand new patients a year are diagnosed and then live with this often for decades Worldwide, the estimates are about 10 million or more.

Dr. Stieg: I find that interesting in the sense that if we look at other diseases that are talked about every day in the news, in terms of breast cancer, the numbers are actually much bigger in Parkinson’s disease than it is for breast cancer and even for stroke and Alzheimer’s disease.

Dr. Kaplitt: Parkinson’s is a lot more common than people think. I think it’s reached a level of public consciousness that’s different now than it was when I started my practice, in part because of various celebrities and known people who’ve had the disease. I think the Michael J. Fox Foundation obviously has raised the awareness of the disease dramatically and I also think among caregivers, particularly nonspecialists in the general community, I think that there is a greater understanding of the disease. So we’re recognizing it more and so I think it is getting out there, but I agree that most people don’t realize quite how prevalent it is.

Dr. Stieg:  And as I understand it, there’s a spectrum of impact of the disease on an individual’s life.

Dr. Kaplitt: Parkinson’s disease is part of a spectrum of what are considered movement disorders. It is caused by a loss of cells in the brain that regulate movement. The brain is composed of lots and lots of circuits, very much like our computers or other things, but much more complicated obviously. But there are specific circuits in the brain that regulate movement and for reasons that we still don’t fully understand in the majority of patients, some of these cells start to die over time with age. The truth is is that these cells that make a chemical called dopamine die in all of us with age. And in fact there are estimates that if the human population lived on average to say a hundred or 110 years old, possibly 50 to 80% of us would develop Parkinson’s. So what Parkinson’s is really an acceleration of a process that already happens in most people for reasons that we are increasingly understanding but not fully understanding it.

Dr. Stieg: And then it manifests itself how?

Dr. Kaplitt: In particular for Parkinson’s are series of problems; first with movement, the most obvious that people are aware of is tremor because Parkinson’s is known as a tremor disease, so this is often what’s referred to as a resting tremor. A lot of people have tremors when they reach for a drink. That can be a very different thing which we might or might not talk about, but Parkinson’s is a tremor. When people are just sitting there not doing anything, they start to tremor and it’s a certain characteristic. Tremor. Tremor is one. Freezing where patients have difficulty actually initiating movements and then stiffness where the muscles are very stiff. Those are the three classic movement problems in Parkinson’s. It then evolves over time. People can have problems with walking where they can’t move their feet effectively. They can develop balance problems where they can start falling. Eventually they have problems with fine movements like buttoning a shirt or using utensils and then ultimately in a, in a subset of patients in in a smaller population, but a significant population of patients, they can develop other symptoms such as memory problems that can be akin to Alzheimer’s problems with blood pressure instability.

Dr. Stieg: Is it important to catch the disease early so they don’t progress to those cognitive changes?

Dr. Kaplitt: Yeah, so for many of the treatments particularly that we’re about to discuss, there is a window that is optimal for us to be able to do that precisely for the reasons that you said. When they get to that stage where there are substantial problems with cognition, with memory, depression, other things, it can create real challenges to bring in newer therapies, particularly surgical therapies or cutting edge therapies. The other reason why it’s good to recognize the disease early is that there is some evidence that even the medications that are used to treat the movement disorder and that is still the first line of treatment is medication. The medications are mostly designed to replace this lost chemical of dopamine in the brain, which then normalizes these circuits for a period of time. If you can use those medications earlier, there is some evidence that some of these medications can actually slow the disease a bit, but not by much. And obviously that’s the major research effort is to slow the disease.

Dr. Stieg: It’s become so common these days. Early on, I just want to get you to distinguish the difference between essential tremor and Parkinsonian tremor cause I, you know, last thing we want people to worry about as they got essential tremor, they’ve got this chronic debilitating disease.

Dr. Kaplitt: So it’s a fantastic point. So most tremor patients do not have Parkinson’s disease. So if you simply have a tremor, don’t immediately assume that you have Parkinson’s disease. Essential tremor is actually a tremor when people start to move. So it’s usually not at rest. It’s not a tremor that just happens. People look totally normal until they go to reach for a cup or use a spoon to eat soup and then their hand starts to tremor like crazy and then it stops when they’re, when they stop moving. Interestingly, essential tremor, which is also a disease we can help with surgery, is five times more common than Parkinson’s disease, but most people don’t know it. It is by far the most common movement disorder, one of the most common neurological diseases. But most people don’t know it because you could be having dinner or socializing with some of the essential tremor and until they did something you would never know they had the disease unlike Parkinson’s. So yes, and there are other tremors, so don’t immediately assume it’s Parkinson’s because it’s a tremor, but it is something that obviously needs investigation.

Dr. Stieg:  Elizabeth, tell me what symptoms led you to start seeking medical help?

Elizabeth Larsen: I actually have both tremors and I have herniated discs in my neck. I was having problems with my left hand and my neck was bothering me. So we started with the MRIs and we found the herniated disc in my neck and we thought that was it. And I went for physical therapy and it didn’t stop the shaking in my hand. So it wasn’t until I went to a neurologist who looked at me, I said, you know, the shaking in my hand bothers me. But when I sit down at night and I have a glass of wine, I go and it stops. He goes, you have essential tremor. So at first the essential tremor was diagnosed. After that was diagnosed, I didn’t want to think that I had Parkinson’s, but I knew there was something else going on cause I was, I was tripping. I was occasionally tripping. My balance was starting to go. My movements were slow.

Dr. Stieg: Can you describe what the slowness really felt like?

Elizabeth Larsen: It felt like I was the Energizer bunny running out of batteries because it would take, now it takes me a minute to get both my sneakers on and tie my shoes where before the surgery that I had, it was taking me 10 to 15 minutes just to put on shoes and tie them. And there were times when I just tied them just enough to get them on and I’d go to the gym and I’d be like, all right, I need to shoe tie because it’s just too much. So, and that, that’s just one. And that was everything I was doing every day was slowing down. The one thing that really got me going to my neurologist and having to admit that I had Parkinson’s was my facial expressions were like blank. And I was working with this one gentleman who knew me very well, and we worked together every day he’d be explaining something to me and he’d go, do you understand what I’m saying? I’m like, yes, I understand what you’re saying. I’m just thinking about it. He goes, all right, and every day we would go through this. And then I finally realized that my face wasn’t making any movements.

Dr. Stieg: So you lost that emotive capability to give visual contact and dialogue with your friends in addition to the normal verbal contact?

Elizabeth Larsen: Yes.

Dr. Stieg: So Elizabeth came to see you and it was obviously pretty transparent that she had this Parkinson’s disease, but for people listening to this, what should they know are the potential treatment options?

Dr. Kaplitt: When people are first diagnosed with Parkinson’s, which is often six months to two years after they’ve actually noticed things. The story that Elizabeth just said is very common, you know, before they actually come to attention. The mainstay of therapy is first medications, as I said earlier, designed to replace this lost opening in the brain. And they usually work very well to the point that if someone does not have a good response to medicine early on, it either means usually that they’re either not getting enough medicine and they need to push it or they have something more complicated going on than simple Parkinson’s. So the vast majority of routine Parkinson’s patients will respond well to medication and usually they’ll take these medicines maybe three times a day and most of their day will be just fine. What happens over time though is that first the disease continues to progress, so there’s more cells being lost and the disease worsens and the brain starts to change in response to the medicines, which is a common problem in the body to all medicines.

Dr. Kaplitt: That combination of the changing brain from the medicines and the progression of disease makes the symptoms worse and over time, after a honeymoon period of a few years usually of doing well. The symptoms worsen and people start to develop complications of medicine that we haven’t talked about yet, and that can be, for example, a thing called dyskinesia, which is an involuntary movement. People can’t sit still. They experience very strange movements, some of which can just be a social problem, but they can be bad enough that they are exhausting. It’s like running a marathon all day because they can’t stop moving. Patients can develop other problems. Because these drugs are not just going to the circuits we talked about earlier, but are going everywhere,there are other areas of the brain that are affected by dopamine that are not problematic in Parkinson’s, but that influence things like reward satisfaction, which often leads to addiction. So patients can develop real compulsive behaviors from these medicines. Even addictive behaviors can be exacerbated or worsened by these medicines.

Dr. Stieg: Addicted to the medicine or addicted to other substances?

Dr. Kaplitt: Both. So for example, patients who might, like to go to Atlantic City on occasion or Las Vegas for two days or, and, and spend maybe $500, all of a sudden they’re losing a hundred thousand dollars that they don’t have because they can’t stop gambling. You know, people who are drinking, you know, a lot of times people who are doing normal activities that have an addictive component, but they’re not addicted to it, can now all of a sudden develop these problems in addition to being a bit addicted to the medicines themselves. So they can also develop problems with um, hallucinations or with depression or anxiety or other things because they are not targeted exclusively to the areas that are controlling movement. So as patients develop these complications of medicine over time and worsening symptoms, they suddenly are taking more medicines, then they’re taking medicines to counteract the side effects of the other medicines. And it becomes this spiral for a lot of patients. And because the average age of onset is usually around mid-50s to mid-60s and because we’re doing so well at keeping people healthy in other areas with all the advances in cardiovascular medicine, et cetera, by the time these patients reach five 10 maybe 15 years into their disease, most people otherwise are still pretty healthy and have many years of life left and yet they are being terribly disabled by the inability to control these problems at that point.

Dr. Stieg: Comment a little bit about the importance of the neurologist who manages the medication component and their relationship with the surgeon and the timing of that. You indicated that you could wait too long and then I’m assuming surgery is the next option after medical management and you don’t want to get access to the patient too late in their disease process.

Dr. Kaplitt: That’s correct. I think everybody agrees that right now surgery is not the first therapy when someone first has symptoms and yet, as you said, there is a window. There is actually evidence increasingly that even earlier surgery may be beneficial to patients, but that is still an emerging concept. However, it is very important and I think that neurologists, because this has now been out there long enough, I think it is very important for neurologists to understand these windows and understand what the right timing is for patients to seek out an alternative. So for those patients who have done well with medicines, but now instead of taking it three times a day and spending most of their day doing well, when patients start taking medicines five times a day or more, and yet the medicines are still not lasting long enough. Early in the disease, patients will take medicine, they’ll kick in maybe 30 minutes after they take the medicines and it’ll last three or four hours, which is most of your morning, let’s say then you take another pill, does the same thing and so you get to each meal and you’re doing fine. Um, there’s a concept in Parkinson’s called on and off. And on is that state I just mentioned when everything’s working well. Off is when you’re very Parkinsonian and not doing well. So early in the disease, if the average person sleeps eight hours, that means out of your 16 hours of waking time, you’ll spend about 15 hours early in the disease, doing pretty well in your onstage with just little bits of time that you’re not doing great. By the time patients reach the point of considering surgery, often that is flipped. They may be taking medications five or six times a day and now it will take longer to kick in. Sometimes they won’t last as long. They’ll develop a randomness where sometimes the medicine, they’ll have a great day, they’ll have a bad day other times, and then they develop all these complications. When that starts to happen, not years after it’s happening, when that starts to happen, but they’re otherwise doing pretty well cognitively, medically. That’s really the point in which we like to see them because that’s when we can help the most.

Dr. Stieg: Elizabeth, you tell me now, did you go through medical management and then end up with surgery? What was your pathway?

Elizabeth Larsen: Kind of. I went on, I think it’s the older medicines. As you all know, exercise is important for Parkinson’s and I, because when this all started, I had those herniated discs. I’d been going to physical therapy for 10 years, so I exercise all the time and I exercise at home and I think that did help me make my medicine last a little longer because I was very stubborn and I always thought that the surgery was my last resort, not the resort coming in. And my neurologist would bring it up every time I went to see him and he’d go, Now, want to talk about it? And I would go, no, not yet. I’m not ready yet. And then eventually it got to the point where it was taken 15 minutes to put on a pair of shoes and I said, all right, what do I have to do?

Dr. Stieg: So it was a quality of life process that led you to cross that Rubicon and say, all right, it’s time for surgery.

Elizabeth Larsen: And I was diagnosed with Parkinson’s. I was an early onset, so I was like in my early forties probably when I got diagnosed.

Dr. Stieg: And give me a sense of timing between the diagnosis in your early to mid forties and when did you make the decision to consider surgical intervention?

Elizabeth Larsen: It was like eight years.

Dr. Stieg: Is that the average time that it takes?

Dr. Kaplitt: The majority of patients I see are usually between five and 10 years into the disease. So this is right in the middle of that.

Dr. Stieg: During the time period you were going through the medical management and then finally coming to terms that you needed surgery. How did you keep your spirits up?

Elizabeth Larsen: Friends and exercise. In my office at home, I have a stationary bike and I was able to work from home three days a week because I was having such a hard time when I was working.

Dr. Kaplitt: So I’d like to just say one thing about exercise because Elizabeth brings up a very important point. We all know how good exercise is for a lot of things in our body, but there’s actually really good scientific evidence from laboratory studies that show that exercise can actually increase growth factors in the brain that are, that that will specifically protect these at risk cells and slow the progression of the disease. So, in addition to all of the general health benefits and obviously the mood elevating benefits that have been shown with exercises, as you just heard, there’s actually good evidence that it can slow things down specifically for Parkinson’s disease. So it has tremendous benefits for this disorder.

Dr. Stieg: The question I have for you, was do we consider exercise just getting up and walking? Because it took you 10 minutes to put on a shoe. So what kind of exercise were you talking about?

Elizabeth Larsen: Uh, I do stationary bike, I go for golf lessons and I swing a golf club. I also box.

Dr. Stieg: And you did that pre-treatment, pre-surgery?

Elizabeth Larsen: Yes. When I loved boxing before I found out I had Parkinson’s and then when I found out it was good for Parkinson’s, it was just the perk.

Dr. Stieg: Is, is there some family history in boxing?

Elizabeth Larsen: No, the New York Sports Club had it at the time, so it was just fun.

Dr. Stieg: Let me ask, you did all these things, but it must have taken a long time to do and I’m assuming you worked eight hours a day.

Elizabeth Larsen: I did, but this boss that I had, um, he was, he didn’t care when I worked and he knew, he was like, you know what, you gotta do. You know what needs to be done, I don’t care if you work in at midnight or if you, so I mean, even when I came in the office, I couldn’t get in before 10, And there was one day I worked in One World Trade, and I used to get off the bus on Church Street and I would walk past the Oculus and you know, I’d use the blocks in the sidewalk to help me walk. And there was one day I couldn’t do it and I called him and I’m like, you got to come down. He goes, what? I go, I just, I can’t do it. And he came down and we had a chat and then he helped, you know, I held his arm and we walked back in. And I was following the blocks and he goes, “but you’re doing this so great.” I’m like, “I know I was just having a moment and you needed to come down, but—

Dr. Stieg: Everybody should have a boss like that. You, you were blessed.

Elizabeth Larsen: Yes.

Dr. Stieg: Just to put people’s mind at ease, is there a genetic component to Parkinson’s disease or an exposure factor?

Dr. Kaplitt: Yeah, that’s a great question. So there are many genes that our community has identified that can influence Parkinson’s disease. There is a small subset of maybe 10 to probably at most 15% of Parkinson’s patients that actually have an inherited form of the disease because of a specific mutation or change in a gene. Very much like other inherited diseases like cystic fibrosis, et cetera. So it can actually be inherited that way. Those tend to occur earlier. And, there are potential, um, treatments being developed for that. In fact, only two weeks ago at our center, we did a gene therapy, which has been obviously an important area of our research for many years. But we did a gene therapy for the first time in the world to correct an inherited form of Parkinson’s disease to actually fix the genetic abnormality. Um, and we’ve actually, this is the first time we’ve discussed this publicly, but that’s something that we did so the world is evolving that way, but for the vast majority of Parkinson’s patients, they don’t have an inherited form of the disease, but we still believe that many of these genes that we are identifying are important and relevant to the disease.

Dr. Kaplitt: I liken it to heart disease. Early on in understanding heart disease, there were these inherited families that had heart attacks at the age of 20 or 30. Brown and Goldstein who won the Nobel Prize for understanding the genetics of heart disease, figured all of this out through these rare families, but what they figured out about HDLs and LDLs that everybody now knows about but didn’t in 1980 were derived from what we knew about those patients. It still influences all of us even though we don’t have inherited or genetic abnormalities. And I think ultimately that’s what we are finding in Parkinson’s. That these same genes that when they’re grossly abnormal can lead to inherited forms that, in the rest of us, natural variations may predispose us to other things that are going on in the environment. Which leads to the second part of your question. That is something that we understand less about. We do know that certain pesticide exposures can actually lead to Parkinson’s. In fact, there are certain pesticides that we can use to create Parkinson’s in animal models and so some people, if they have, if they’ve lived on a farm, if they’ve had exposure to a lot of pesticides, that can actually be a risk factor. We believe that that probably extends to exposure to certain types of chemicals, et cetera. Beyond that, we don’t understand as much about environmental components, but we assume that they’re there and we just have to better understand them.

Dr. Stieg: Dr Kaplitt, thank you for explaining what Parkinson’s disease is, how it is treated and its inevitable progression and Elizabeth, it means a great deal to our listeners to understand firsthand from a patient what they experienced both physically and emotionally. For all of our listeners, I hope you will join me for part two of this conversation when Elizabeth decides to move ahead with deep brain stimulation. A state of the art neurosurgical procedure which transforms her life.