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NEXT PHASE HUMAN
Episode Transcript: Parkinson's Disease with Dr. Maheep Virdi
[Cold Open]
DR. SANDHU: Is there some symptoms that you see people commonly missing?
DR. VIRDI: Difficulty swallowing, shoulder pains, mask-like face.
[Show Intro]
Welcome to Next Phase Human, where medicine meets performance and science meets longevity. I'm your host, Dr. Rasham Sandhu, and with me is Dr. Maheep Virdi, a board-certified neurologist, and we'll talk all about Parkinson's disease today. Welcome, Dr. Virdi.
DR. VIRDI: Thank you, Dr. Sandhu, for giving me the opportunity to share pearls with our audience, and thank you for taking this initiative to start Next Phase Human.
DR. SANDHU: Thank you. All right, so let's dive right in. You see a lot of Parkinson's disease, and it looks like we are seeing more and more of this. So when we say Parkinson's disease, most of our listeners will know, but the ones who don't, what's actually happening?
DR. VIRDI: So Parkinson's disease has been there for hundreds of years, and what happens is it basically slows down the movement. You start to get rigidity in your arms and legs. It's difficult to walk, it's difficult to eat. Your face loses its expressions.
DR. SANDHU: So most people, when they think Parkinson's disease, they think shaking or tremors. Is that most of Parkinson's disease, or is there a lot more to it?
DR. VIRDI: There's a lot more to it. Shaking and tremors are a part of Parkinson's, but they are not something which we use to diagnose Parkinson's. Yes, there is a typical tremor which comes on, which is a pill-rolling tremor, but a lot of people just don't have that. It's like a pill-rolling tremor, and the more they get distracted, the more it becomes obvious. But we don't use that as a diagnostic tool. It can be used as a soft sign to say, "Hey, this could be Parkinson's," but there are a lot of patients who don't have that tremor.
The bottom line with Parkinson's is that you should have slowing down of your physical movements. There should be difficulty in walking, difficulty getting out of bed in the morning. You could be stiff in your arms and legs. And one thing which most commonly people don't actually watch out for, it's a soft sign, is they have difficulty turning to one side or the other in bed.
DR. SANDHU: Huh, interesting. And how many years on average do people have something going on before you actually see the symptoms and they come to see the doctor?
DR. VIRDI: The literature suggests that people get soft symptoms like constipation. I've been good all my life as far as my bowel movements are concerned, but one fine morning, over a period of a few weeks, without a reason, nothing has changed, diet hasn't changed, nothing else has changed, I'm starting to get more constipated than I would believe myself to be. And then people start getting shoulder pains. Both of these symptoms have antedated the diagnosis by almost six years.
DR. SANDHU: Six years, wow.
DR. VIRDI: Yeah. Constipation is very common in day-to-day life, so that alone does not mean Parkinson's. There's everything else that comes with it. You have to put it in the right context.
DR. SANDHU: Yes, it has to be put in the right perspective because it starts with constipation, then you have difficulty swallowing.
DR. VIRDI: Some people start drooling. Some people start to have difficulty walking, they start to shuffle. You cannot put one symptom as a diagnosis or say this is pointing towards it. And like you said, listeners, if somebody's constipated once in a while, they don't have to worry about it. But if you are in the right age group and there's a change in bowel habits, then it's better to get it checked sooner than later.
DR. SANDHU: Yeah, understood. So is there some symptoms that you see people commonly missing? Like, "Oh, I've had it all along, just didn't know this could be it."
DR. VIRDI: Difficulty swallowing, shoulder pains, mask-like face, intermittent shuffling of the gait. When I'm walking, I just don't feel steady enough.
DR. SANDHU: Okay. And sleep disorder, I understand, is a part of it?
DR. VIRDI: Sleep disorder is a part of it. There is a condition called REM behavior disorder. What happens is normally when we go into REM sleep, there is a disconnect between the brain and the rest of the body. The brain is working, it is consolidating all the stuff, but there's a disconnect between the brain and the rest of the body. In this condition, that disconnect is not complete. And what happens is people always come and tell you that, "I'm getting these dreams where it is persecutory in nature. Either I'm running after somebody or somebody's running after me. I'm punching, I'm kicking." And that manifests physically. I have seen patients in which their partners have been beaten blue. They have dropped things from the nightstand. They have fallen out of bed. It's not that there is some violence going on there, it is REM behavior disorder. And if you have REM behavior disorder, chances are more than likely, down the line, you may get Parkinson's.
DR. SANDHU: So just to clarify, REM behavior disorder is in our dreams, mostly the body is paralyzed, so you don't act out your dreams.
DR. VIRDI: Correct.
DR. SANDHU: And that sort of paralysis goes away and you actually act out your dreams. That would be REM behavior disorder, correct?
DR. VIRDI: Yes.
DR. SANDHU: And so someone has REM behavior disorder, or they feel like they don't smell things like they used to. What are the chances they have Parkinson's? Is it one or two things and everything stacks up quickly?
DR. VIRDI: This can be a pointer towards Parkinson's, but the percentage of people who have REM behavior disorder, it's somewhere in the range of about 10% who will develop Parkinson's down the line. Anosmia can be a pointer to a lot of other things. A lot of people who get COVID get anosmia.
DR. SANDHU: Right.
DR. VIRDI: A lot of people who have early Alzheimer's can get anosmia. And of course, with Parkinson's you can get anosmia. But this is not something — I have seen patients who, for no reason at all, have anosmia. There is something wrong with the olfactory system, doesn't mean that they will develop or have Parkinson's, but it is just one of those soft symptoms.
DR. SANDHU: Got it. And by the time you see classic motor symptoms, which is difficulty walking, rigidity, or fluid tremors, and it starts manifesting, how much neurologic change has already gone on for years? You said six years typically. But in terms of real anatomic changes, is there a lot of damage already done?
DR. VIRDI: Everybody is different. It all depends on what is your reserve in the basal ganglia circuits, and how are you programmed to further deteriorate in that. People who become symptomatic — there are people I can see walk across the hall and I can say, "Hey, this is Parkinson's," no questions asked. That happens when almost 40% to 50% of those circuits are compromised.
And there are people who — this has happened quite often — I'm asking questions, the patient is checking every box, almost every box, but when I do my physical exam, except for the tremor, the patient has got nothing going on. I wouldn't label that person as Parkinson's. I would send that patient to get a scan to see if there is any abnormality in the brain. And even when that happens, it is not the scan we are treating, because it is about 83% sensitivity and specificity. There are 17% of people who will be misdiagnosed or over-diagnosed.
DR. SANDHU: So again, coming back to, you're treating the person, not the picture.
DR. VIRDI: Not the picture.
DR. SANDHU: And suppose someone can reliably identify Parkinson's — okay, these could be very early Parkinson's — is there anything they could do differently to prevent this, or prevent this from progressing?
DR. VIRDI: There is literature, there's a lot of research being done, and I think there is something that we can talk about as a gut-to-brain kind of thing. Because in some studies, the literature suggests gut is the first brain.
DR. SANDHU: Right.
DR. VIRDI: And it is very intricately — it is not just a pipe which is processing food. There are a lot of nerves which are involved in that. You have the mesenteric plexus, you have the myenteric plexus, which is an intricate nervous system present in the gut, and then you have the biggest one, which is the vagus nerve.
DR. SANDHU: Right.
DR. VIRDI: And the vagus nerve from the gut has got a straight connection to the brain. And what happens is, one of the big things is alpha-synuclein, which is a protein, basically, that cannot be metabolized or removed. It gets deposited in the basal ganglia, and that is what causes Parkinson's. That is toxic to that part of the brain. Now, there are studies which have shown that the good bacteria and the bad bacteria in the gut — the bad bacteria, they do produce alpha-synuclein in the mucosa of the intestine, which then goes into the nerves and gets transported via the axonal system into the brain, and that causes Parkinson's.
DR. SANDHU: Interesting. And is there a way to test for that?
DR. VIRDI: Yes, there is bacterial flora which can be tested to see which ones — there are about three bacteria which are beneficial, and there are two of them which have been known to cause an increase in alpha-synuclein. You can do your endoscopy, take samples, and you can also test the stool for those bacteria. And that can help get to a better diet, and you can eliminate the risk factors for those. That may help slow down the worsening of Parkinson's.
DR. SANDHU: So there is actually a world in which you identify the bacteria, and you can act on it — maybe change the bacterial composition in your gut to slow down or stop the disease?
DR. VIRDI: Yes. There are studies which have corroborated that.
DR. SANDHU: Okay. And so we talked a little bit about gut-brain and the brain-first concept. So it used to be thought that Parkinson's is primarily a brain disease, neurodegeneration, and you don't have enough dopamine and whatnot. But now, from what I understand, it's coming from your gut, so there is a probability that the disease originates outside the brain and gets to it.
DR. VIRDI: It is multifactorial. The causation of Parkinson's is multifactorial. You cannot put one finger on one thing and say, "Hey, this is going to be Parkinson's." The majority of this is episodic and majority of this is environmental. There is a subset, about six to 12% of people, who have some genes in their body which by themselves will not cause Parkinson's, but that gene, given that you are sitting in an environmental area where there are other risk factors which will produce Parkinson's, then you will get Parkinson's early on in age.
And there are some subgroups in which they involve other different parts of the brain, which we call Parkinsonian syndromes, and that's not Parkinson's by itself, it's other parts of the brain involved. It can involve the cerebellum, it can involve your brain stem, and so on. And fortunately, they are less in frequency, but there's no treatment for them.
DR. SANDHU: Okay. So at least for Parkinson's, we have treatments.
DR. VIRDI: Yes.
DR. SANDHU: And so you just mentioned constipation precedes Parkinson's by many, many years.
DR. VIRDI: It could.
DR. SANDHU: So what could be, in your experience, the earliest signs of Parkinson's that most people don't even know about?
DR. VIRDI: A soft sign like loss of smell, that can be it. Shoulder pains have been known to antedate the diagnosis.
DR. SANDHU: What kind of shoulder pains?
DR. VIRDI: It is not associated with movement. It is just heavy shoulders and the pain is just not going away.
DR. SANDHU: And is it both shoulders or one shoulder?
DR. VIRDI: It can be either. And then also, like I said, constipation. People can have difficulty swallowing, and there can be drooling, excessive drooling. This is not the drooling patients get when sleeping, almost everybody drools when sleeping, but it is drooling when you are awake. And then difficulty swallowing — you feel that your bolus is not going the right direction. That is because of the decreased peristalsis of your GI tract. They can have coughing, it can go the wrong way and you can cough it out. So those are the kinds of things that happen.
DR. SANDHU: And could there be Parkinson's patients who don't actually have the tremor?
DR. VIRDI: Yes. They have other symptoms and just not the tremor. The diagnosis of Parkinson's is basically based on slowed movement. Watch the patient get up from a sitting position in a chair, they will have difficulty hoisting themselves onto their legs. Most of them would use their arms to push their torso out of the chair. And when they stand up, they will feel dizzy because of autonomic dysfunction — from the cardiology standpoint — is a part of this disease.
DR. SANDHU: So dizziness is a big part?
DR. VIRDI: Dizziness is a big part. There will be fluctuations in blood pressure. There will be orthostatic hypotension and the patient will not be steady. Initially they have to steady themselves, stand for maybe a minute or two before they can start walking. And another thing which they always report is that, "It's difficult for me to start walking, but once I start walking, I'm reasonably good." So that's another soft sign which a lot of people tell us.
DR. SANDHU: Got it. And you mentioned a little bit about the gut microbiome — is that a cause of Parkinson's or is it a consequence of Parkinson's? Do we know anything about that?
DR. VIRDI: It is one of the factors which contributes to Parkinson's. It is not an all-in-all by itself. It's not that if you have that microbiome which is altered, you're going to get Parkinson's. It is a combination of either the genes, your environmental factors, the way your brain is built up, or these microbiomes. It could be any or all of them.
DR. SANDHU: Any or all of them. So suppose that you have someone who has a family history of Parkinson's disease, and he or she wants to do everything to minimize their chance to go that route. What do you tell them? A worried 35, 40-year-old who does not want to go down the same way — what could they do to minimize their chances?
DR. VIRDI: Basically, keeping yourself active. Exercise plays a big role, and there have been studies now that even in people who have Parkinson's, once they are stabilized on medication, doing physical therapy and keeping yourself active with the medication works way better than either therapy alone.
DR. SANDHU: Okay.
DR. VIRDI: So keeping yourself active, doing exercise, maintaining a good, healthy lifestyle, Mediterranean diet — that is one thing which has been shown to be beneficial — and eat a lot of vegetables, more organic food.
DR. SANDHU: So fiber and fermented foods.
DR. VIRDI: Fiber and organic foods, which have as few processed chemicals in them as possible. That's the best way to do it.
DR. SANDHU: Got it. So would it be fair to say, if I want to be proactive about preventing Parkinson's disease, taking care of my gut health today and exercising are the two things that will work?
DR. VIRDI: It may not prevent it, but if you are destined to get Parkinson's, if you do these preemptively, it may give you a few more years before you get diagnosed.
DR. SANDHU: So you'll at least add quality years?
DR. VIRDI: Yes.
DR. SANDHU: Okay. So why are we seeing more and more of this?
DR. VIRDI: Like happens in medicine, it could be detection bias. Maybe we are detecting more and more people. We have the ways and means with the DaTscan, which came into vogue. Earlier it was only approved for study purposes, but about three years ago it got approved for diagnosing Parkinson's. And I have seen patients who have a positive DaTscan, but there is absolutely zero sign or symptom for those patients. And there are people who have everything in the book — it screams Parkinson's when you look at them — but the DaTscan is negative. It's 83% sensitivity and specificity, which is pretty good for a test, but it has to be taken with a grain of salt. It has to mix and match with the patient before you do anything.
And we see a lot in terms of chemicals. We live in a world full of toxic chemicals, and from what I understand, there is a link to pesticides or paraquat with this.
DR. SANDHU: How strong is that link? How big a concern is that?
DR. VIRDI: It is a very big concern, and paraquat has been known to be toxic to the basal ganglia, and that antedates Parkinson's for quite a bit. I have had so many patients who give a history of, "Hey, right now I'm in my 70s, but when I was in my 30s and 40s, I used to be a farmer way back, and we used to spray paraquat and other pesticides without any protection on us."
The other one we need to look for is TCE, trichloroethylene — that's a solvent which is used. People also used to get this from welding. They would use manganese — not magnesium, but manganese — in welding. Those fumes of manganese are toxic to the basal ganglia and can produce Parkinson's. People who get carbon monoxide poisoning, the basal ganglia gets affected, and they develop Parkinsonian symptoms.
DR. SANDHU: So just to clarify for our audience, basal ganglia are the regions of the brain which are intricately linked with movement.
DR. VIRDI: Basal ganglia is a part of the brain which is sort of a supervisor. It does not initiate movement, but what it does is two things: it filters out unwanted movement, and it gets the body to do the right movement at the right speed. So in short, the cortex, where the movement centers are, the motor cortex, sends signals to the spinal cord and to the nerves for the muscles to start moving. But before it can do that, that signal goes through the basal ganglia, which refines that signal so that the right amount and the right extent of movement happens, and there are no unwanted movements.
DR. SANDHU: Got it. And what about air pollution or contamination and toxins in well water and whatnot?
DR. VIRDI: It has been proven that well water contamination — same thing. Pesticides going into well water, air pollution, all of this contributes to Parkinson's, along with the other chemicals.
DR. SANDHU: And so sufficient to say reverse osmosis filters can help prevent it?
DR. VIRDI: It may help.
DR. SANDHU: Okay, so that should be standard for most of us, if possible.
DR. VIRDI: Yes.
DR. SANDHU: So when you talk to your patients and they've had these exposures, how do you usually go about it? "Okay, this is the reason you have Parkinson's," or, "This may have contributed, but there's a chance you may have had other reasons for Parkinson's and this just tipped you over"?
DR. VIRDI: It's a difficult conversation because I always tell patients, "Hey, I think this is what it is, but let's go ahead and do some more investigations into it." Of course, history taking is very important, but I don't usually delve into, "Hey, this could have been caused by this, by this, by that." It is likely that if you have this exposure in your history, that may have contributed to it. Because the literature is very firm on this — it is a multifactorial disease. It is not that we can put a finger on one, except for the studies about paraquat.
DR. SANDHU: So this is an environmental disease to an extent?
DR. VIRDI: Yes.
DR. SANDHU: And so is there some study — from what I was reading — that living within three miles of a golf course can increase your risk of Parkinson's? Does that hold any water? Is there data to that?
DR. VIRDI: I haven't looked at that.
DR. SANDHU: Okay. That'll be concerning.
DR. VIRDI: Yeah.
DR. SANDHU: So you mentioned a little bit about exercise, and exercise helps prevent progression, as you said. It's a part of the therapy. What kind of exercise? Is it cardio? Is it weight training? Is it high intensity? What kind?
DR. VIRDI: So the basic idea about Parkinson's is the problem is in coordination. It's not a matter of strength, it is not a matter of muscle mass, it is basically about coordination. So what has been shown is that rather than doing strengthening exercises and weight-bearing exercises to build muscle, small things like using balls in your hand — to use the small muscles of the hand so that your coordination becomes better — and doing balance training, training your brain to work with what rigidity you have in the muscles, those work better than cardio and strength training.
DR. SANDHU: So in Zone 2 exercise, that's part of low-intensity cardio — is that part of it?
DR. VIRDI: That is helpful.
DR. SANDHU: High-intensity training?
DR. VIRDI: Not so much.
DR. SANDHU: Strength training?
DR. VIRDI: Not so much. It is more of coordination — using small balls in the hand, doing those coordination movements over and over again. That helps way better.
DR. SANDHU: And from what I'm hearing, dancing or Tai Chi or boxing — they've become a part of kind of therapy, so to speak? Is it?
DR. VIRDI: That is more of the same thing, coordination. Because when you're dancing, you're trying to coordinate different muscles in a way, and that is training the brain to work with the rigidity that you have. Same as with Tai Chi, same as with dancing and so on.
DR. SANDHU: And boxing, I understand, would be the same way?
DR. VIRDI: Yes. You have to coordinate your punches and whatnot.
DR. SANDHU: And if you had to give a prescription for exercise for a week, for someone who is undergoing treatment, what is that? How much exercise a week do you suggest?
DR. VIRDI: As much as they can do without getting fatigued and without getting unbalanced. The first thing, if somebody has Parkinson's, is we get the patient stabilized on medications. We try to keep patients a tiny bit on the left side, because it's like a pendulum. If dopamine is in the middle, you're perfect, there is no Parkinson's. On the left side, you have less dopamine — that is basically Parkinson's. And you're depleting the dopamine from outside, whichever way you're doing it, it is like adding fuel to the engine. If you go a little bit beyond the midline to the opposite side, that is too much fuel in you, you will have dyskinetic movements. They are basically jerky, rhythmic movements. Most people, if you see them sitting down, they will have shoulder movements like that, they're talking to you but they'll have this kind of movement. That's dyskinesia. So when that happens, your treatment has put a little bit too much medication into the system, so what you do is you back off and it goes away.
DR. SANDHU: Okay, so there's a fine-tuning to how much you want to give.
DR. VIRDI: Yes, because there is no set dosage. For example, in hypertension, Amlodipine has to be five milligrams or ten milligrams, there's nothing in between. In this, you can mix and match, you can play around. Some people will be good with one pill three times a day, some would need one and a half in the morning, one and a half in the evening, and one in the afternoon. There are various combinations you have to do. It all depends on what the patient tells you, what the caregiver tells you — what is happening in these 24 hours to my dad or my mom — and what you see in the patient. That's how you tailor the treatment.
DR. SANDHU: And we talked about diet a little bit, so let's talk about coffee, diet, and protein supplements and whatnot. So there is some data that coffee consumption actually may reduce the risk for Parkinson's. How does that work? Where does that come in?
DR. VIRDI: There's been data behind that, and it does show that coffee has been shown to reduce the Parkinson's rate. But the quantification of how much coffee you'd drink every day to not have Parkinson's, that is a gray zone.
DR. SANDHU: And just to clarify, it's actual coffee, not energy drinks or anything else that has any data?
DR. VIRDI: Exactly.
DR. SANDHU: It's the polyphenols and everything that comes with that caffeine that's relevant to it.
DR. VIRDI: Yes, that is it.
DR. SANDHU: And you mentioned a little bit about Mediterranean diet or MIND-style diet. Is there any particular other diet that works for it?
DR. VIRDI: Out of all the kinds of diets that I have seen in the literature, it's the organic diet, and mainly the Mediterranean style of diet, that has been shown to be helpful in preventing Parkinson's.
DR. SANDHU: And is there any particular diet that increases the risk of Parkinson's?
DR. VIRDI: Processed food. Because the same way it causes anything — the basic pathway for all of this is causing inflammation in the gut, and that leads to bad bacteria being there, and that causes alpha-synuclein, and that travels to the brain. So that's the hypothesis. Good diet, reducing inflammation in the gut, that is the bottom line of this.
DR. SANDHU: Perfect. And when you give patients medications, do you tell them anything about their diet? I mean, does a high-protein diet affecting medication absorption become a concern?
DR. VIRDI: Yeah, it is a concern, because the most common medication we use for Parkinson's is carbidopa/levodopa. What happens is that the chemoreceptor trigger zone in the lower part of the brain — which is basically a part of the brain outside the blood-brain barrier — carbidopa/levodopa is a combination of two medications, and one of these gets converted into dopamine when you absorb it. When the dopamine attaches to the chemoreceptor trigger zone, it causes nausea, vomiting, and so on. So one part of carbidopa/levodopa goes and attaches to the receptors on the chemoreceptor trigger zone and blocks those receptors so that when people take the medicine, they don't get nausea. It takes about 24, 48 hours, maybe three days, for those receptors to get blocked, and then everything is fine.
Now to answer your question, this medication is actively transported across the blood-brain barrier, which means it has to use an energy-dependent receptor process to go across the blood-brain barrier.
DR. SANDHU: So just to break it down, the blood-brain barrier is a barrier that's between your brain and your blood that nature created to protect the brain.
DR. VIRDI: Exactly.
DR. SANDHU: And now to transfer or shuttle anything across, you've got to pay the currency in terms of energy to shuttle anything across.
DR. VIRDI: Yes. So what happens is the route used by carbidopa/levodopa to go into the brain is also used by proteins. So when you take a high-protein diet, or any protein diet, and you take carbidopa/levodopa with that, nature takes precedence, so the proteins get precedence over the medicine, and you will not get the required therapeutic benefits that you're looking for. So the recommendation is when you are taking carbidopa/levodopa, there should be at least an hour's difference between taking the medication and eating something.
DR. SANDHU: So the stomach has to be partially empty.
DR. VIRDI: Yes.
DR. SANDHU: And they can, after that hour or before that hour, eat proteins, because they'll need that for muscle mass.
DR. VIRDI: Yes, they can.
DR. SANDHU: So that's still totally okay. So just, if you have Parkinson's and you're taking the medicine, it's not that you shouldn't eat proteins, it should be separated from the medicine.
DR. VIRDI: Yes, exactly.
DR. SANDHU: And is there any data on things like vitamin D, fish oil, CoQ10, all those supplements?
DR. VIRDI: People have tried that, but there's no real data behind that. Of course, taking CoQ10 and vitamins and things like that, it's not harmful.
DR. SANDHU: Okay. And so the most important thing health-wise you could do for that patient — is it exercise, or is it supplements, or diet?
DR. VIRDI: Healthy diet and exercise.
DR. SANDHU: Those are the top two?
DR. VIRDI: That's the top two.
DR. SANDHU: In talking about GLP-1 medications, they are in everything now. What's their situation with Parkinson's disease? Is there an interaction? Is there a concern when people use it? What do you tell your patients?
DR. VIRDI: There is no data behind that.
DR. SANDHU: Okay.
DR. VIRDI: And there is some data with insulin signaling and Parkinson's disease, and GLPs affect that, but it's not been proven as a yes or a no.
DR. SANDHU: Is it contraindicated, is it still in the works?
DR. VIRDI: We don't just know enough yet.
DR. SANDHU: So just by improving metabolic health, if someone were to use GLP-1s, does that make a change? Does obesity play a part in Parkinson's disease?
DR. VIRDI: It may, because when you take these GLPs, you are basically decreasing the inflammatory markers in your body, and that may help indirectly prevent Parkinson's. But no clear-cut data or trial data at this point.
DR. SANDHU: And so now, obviously when we talk about it, Parkinson's concerns us — it is a lifestyle-altering disease, big time. Can we detect it before even the symptoms come?
DR. VIRDI: That scan can predate that. But doing genetic testing for this has really not panned out, because the percentage of people who have those LRRK2 genes and parkin genes — yes, they have been proven to be a cause of Parkinson's — but the percentage of the population that has those genes and develops Parkinson's is almost minuscule.
DR. SANDHU: So for people who do genetic testing and come up with those genes in their tests, they don't need to consider their fate is sealed, that they will have Parkinson's?
DR. VIRDI: Yes. It is not 100%, because the LRRK2 gene is also — there have been studies where people have tried, "Hey, we can modulate that gene, we can change or suppress that gene." But that gene is also expressed in the intestines, it is also expressed in the immune system, it is also expressed in the kidneys. So it is not something that is one-to-one directly linked, that this is only going to be responsible for Parkinson's. So yes, there have been studies, but they haven't really panned out, because of the other added risk factors — your kidneys get affected, your immune system gets affected, and so on. So it is still experimental.
DR. SANDHU: And you mentioned a few times the DaTscan. Can you tell us a little bit about what that is? How is that done?
DR. VIRDI: So DaTscan is basically done with a radioactive dye. It's a CAT scan, but done with a radioactive dye. The dye is given to you, and it takes about almost three to four hours for that dye to cross the blood-brain barrier. Normally it goes and attaches to the basal ganglia, and it attaches homogeneously, meaning you get a good picture with an equal amount of dye concentrating on both sides of the brain. And if that is patchy — if a part of that, the caudate nucleus, or the putamen, or the periphery of the putamen, is not concentrating that dye — that is because the cells in that region are not there. So because it's an active uptake, if it gives a patchy picture, then you could possibly have — we don't use, in the report, we don't say "this is Parkinson's," we use the word "dopaminergic degeneration," which could be any number of things.
DR. SANDHU: So you want to correlate it with what you're seeing in the patient?
DR. VIRDI: Yes, exactly.
DR. SANDHU: And how long does the test take?
DR. VIRDI: Five hours.
DR. SANDHU: Okay.
DR. VIRDI: Five hours is basically the time the patient is there, because you give the dye, and the patient has to wait for four hours.
DR. SANDHU: So you're not in the scanner for five hours?
DR. VIRDI: They are not in the scanner for five hours. No, no, no.
DR. SANDHU: And so we talked about treatment a little bit with the levodopa, and sometimes we used to hear patients say, or some neurologists say, "Save levodopa for later." Is there some rationale to it? Are there other therapies which should be tried first or not?
DR. VIRDI: That's a miscommunication. It has been there for a very long period of time. Starting levodopa/carbidopa today or six months down the line is not going to alter the course of the disease. Because what we are doing is the brain is producing less dopamine, we are repleting that dopamine from outside, that's all we are doing. We are not altering the course of the disease. Taking the dopamine, or the dopamine agonists, or the other medications, is not going to alter the course of the disease. So there is no rationale behind this.
DR. SANDHU: And what causes it when you're giving patients levodopa and they're starting to improve, but suddenly they're not, or they're getting worse — why does that happen?
DR. VIRDI: One is that the degeneration is continuing on its own pace, and as we are giving medications, we have to make an effort to keep up with that degeneration. So once that degeneration, or the loss of neurons, is more than what we are repleting, the patient is going to get a setback, and all we need to do is go up on the dosage of the medication.
The other caveat is that as the disease progresses, you need a certain number of those neurons in the basal ganglia for these medications to work. Once we reach that threshold, or we are reaching near that threshold, the more medication you give, there is no significant clinical improvement, but the side effects start to multiply.
DR. SANDHU: Then the side effects being?
DR. VIRDI: Dyskinesias, nausea, dizziness, blood pressure fluctuations.
DR. SANDHU: So dyskinesia is the abnormal movement that you mentioned?
DR. VIRDI: Yes.
DR. SANDHU: So then if someone gets to that point, what other options are there? Is there something like a deep brain stimulator?
DR. VIRDI: Yes. So there are two thoughts to it. Initially, when DBS came in many years ago, it used to be used for tremors, and it's got pretty good efficacy — almost 95% improvement in tremors right away. And it's very dramatic. When DBS is done, the patient is awake, and the leads are implanted, of course there's local anesthesia. Leads are implanted, and the patient gets to turn on the stimulator — tremors improve, turn it off, tremors come back again. It's that dramatic.
And then putting those leads into different parts of the thalamus also helps with Parkinson's. But this is the caveat: it helps with Parkinson's, it's not a cure. Even if you get the DBS, it is not going to be that you're not going to need any medication. The need for you to have higher dosages of medication is going to come down. Consequently, your side effects with those high dosages come down, compliance increases, and you feel better.
There used to be a rule that you only do DBS when you're reaching the last stages. Now there have been multiple studies which say that in the most appropriate patients, doing DBS early on helps.
DR. SANDHU: And so does DBS work for everyone?
DR. VIRDI: No. It's an extensive workup that needs to be done for that, because one of the most fearful side effects of DBS is suicidal ideation. So there needs to be an in-depth neuropsychological evaluation to see if there are any underlying signs of depression. Getting a DBS is not that I get somebody to do it tomorrow, it takes about six to eight months of proper planning and then doing it.
DR. SANDHU: And why suicidal ideation? Is it known, or what —
DR. VIRDI: It is known. It is thought to be because of the interplay of the thalamic nuclei.
DR. SANDHU: Okay, so that's a bit of words, but just in the simplest terms, your brain chemistry is altered in a way that —
DR. VIRDI: Yes, chemistry is altered, yes.
DR. SANDHU: So can you slow or reverse Parkinson's disease?
DR. VIRDI: Not really.
DR. SANDHU: So not even slowing?
DR. VIRDI: With diet and exercise and all that, you can probably slow it down, but there is no cure to it, there's no reversing it.
DR. SANDHU: And what you're treating is essentially dopamine deficiency.
DR. VIRDI: Yes.
DR. SANDHU: And we talked about that, and we talked about DBS. Are there any other therapies, like infusion therapies, or anything on the horizon or available?
DR. VIRDI: There are things available now — instead of taking pills, you have a liquid form of carbidopa/levodopa that comes with a device you carry, and it gets injected subcutaneously into your body. It goes on during your waking hours, fluctuations are less, off time is less, and you bypass your GI tract — with those devices, you don't have to take oral medications.
DR. SANDHU: And so is that becoming the standard of care, or is oral therapy still better?
DR. VIRDI: Oral therapy is the standard of care, but we have tried it in quite a few patients, and the results have been stunning.
DR. SANDHU: Okay, so you'll see more of that going forward, it's possible?
DR. VIRDI: Yes.
DR. SANDHU: Is there any role or any studies on stem-cell-derived dopaminergic neurons?
DR. VIRDI: No, absolutely not. Even the Michael J. Fox Foundation has done these studies, but there is no benefit, no study which shows that it is helpful at all.
DR. SANDHU: Are there any genetic modification therapies or other options for people who are struggling with this?
DR. VIRDI: People have tried LRRK2 therapies, but given the side effects — there were, I think, three studies which were done — but no tangible benefit was seen from them. So really, at this time, we cannot say that in the future there could be gene therapies that will actually fix this. People are working on it, so never say no.
DR. SANDHU: Is there anything exciting on the horizon for Parkinson's?
DR. VIRDI: There are these new devices which are coming up. One of them uses apomorphine, and the other one uses carbidopa/levodopa. They are very promising.
DR. SANDHU: So if you had to imagine a breakthrough in Parkinson's — we go flash forward 20 years — is Parkinson's still this bad, or do you think there are therapies which are going to change the course of this disease?
DR. VIRDI: It will. There's a lot of research going on. The Michael J. Fox Foundation is doing a lot of work on this. It is looking at various other risk factors and things to do. But compared to maybe 50 years ago, now there are so many other medications. There is a different pathway which is used — it is called the A2A pathway. There is a medication which is an antagonist of that pathway, and it doesn't work at all in the dopaminergic world, it works on a different pathway — working on the basal ganglia — and that has shown significant improvement. I have a patient who had early Parkinson's, we started him on that because of the less autonomic dysfunction side effects from it. Once-a-day dosage, doing amazing, works well.
DR. SANDHU: So I want to kind of get into the practical part of it. So if there's a patient, if there's a person who's near or dear to you who has signs or symptoms of Parkinson's disease, or suppose it's unfortunately one of your family members who calls you and says, "Okay, I have this tremor and shaking, and I feel I may have Parkinson's disease" — there's a series of questions that I want to go through that people have, and as a neurologist, I want to hear what you would do for your family. So what questions would you start with if someone tells you, "I think I might have Parkinson's"?
DR. VIRDI: So I usually start with the soft symptoms. The basic idea is: Do you have trouble turning to one side or the other in bed? Do you have trouble getting out of bed in the morning? Are you stiff in your arms and legs? When you get out of bed in the morning, does it take a few moments before you can start to move around? Do you feel dizzy when you get up? Do you feel, when you're walking, that suddenly your legs stand the way they are and your upper body keeps moving forward?
Another thing we commonly ask is: Do you feel, when you're walking on a flat surface, that you're walking downhill on a slope, and the longer distance you walk, the faster you go, that you cannot stop yourself? Do you start to fall forward? And the easiest way to ask that is, if there's something lying on the floor and you bend down at the back to pick something up, do you fall forward?
They would say yes. Family members can also vouch for the answer to the question, "Hey, do you think there is less emotion on the face? Is it a mask-like face?" And they will corroborate that.
DR. SANDHU: And the writing changes too?
DR. VIRDI: Writing goes smaller and smaller and smaller. And this is another thing a lot of people say, that "I go to the bank and I have to change my signature every time." And there's a test that we use — we get them to write, and the writing is very, very small. And then there's a spiral we get them to draw, and as they're going through that, the spiral becomes smaller and smaller and smaller.
DR. SANDHU: Interesting. And most people, when they worry about Parkinson's, they're going to be calling about tremors. If they don't have Parkinson's, and we went through all these soft signals, they don't — what could be the other reasons for tremors that you see?
DR. VIRDI: Tremors happen very commonly. It's basically degeneration in those circuits in the brain which are supposed to filter out unwanted movement. Anything which is going to push up adrenaline in the body is going to add fuel to the fire. If you're upset, if you're worried about something, if you're under stress, if you're concentrating on something, if you're tired, if you're trying to do some fine work — anything which is pushing adrenaline up is going to add fuel to the fire, and you will start shaking.
What happens is when you go into a certain position, the stretch of the tendons triggers a circuit in the brain, and because every joint — what is a tremor? Every joint in the body has got two muscles attached to it, antagonistic muscles. One moves it to the right, the other moves it to the left. So what that circuit does, at a different frequency, and it can vary, it starts to send those activating impulses to those antagonistic muscles. That's where you get the tremor from.
DR. SANDHU: Okay, and that's due to adrenaline?
DR. VIRDI: Some people have familial tremors — familial tremor, adrenaline, and then degeneration in the part of the brain.
DR. SANDHU: So familial tremors are not dangerous?
DR. VIRDI: No.
DR. SANDHU: How do you tell the difference between a dangerous tremor and a familial tremor?
DR. VIRDI: The only thing I would say about a dangerous tremor is if somebody has a pill-rolling tremor, which is characteristic of Parkinson's. Other than that, the recommendation is, if the tremor is not interfering with your activities of daily living, you just leave it alone. If there are no psychological issues, no self-esteem issues, if it's not getting you to drop food, you're not dropping any glass, you're eating fine, you're not having trouble writing — leave it alone.
DR. SANDHU: And so once you've gone through these steps, you've identified — and this may or may not be Parkinson's — what testing or blood work or whatnot do you order then?
DR. VIRDI: Usually it's the DaTscan that we order and see what we find. But bottom line, it's always a clinical thing. And let's say the waters are muddy — I can see something happening to the patient, I can see maybe the patient is telling me the history is pointing towards this, but the signs I'm not too sure about, or the DaTscan is equivocal, it's neither yes nor — yes, there's some abnormality, but it's not huge enough for me to say on the scan that this is what it is, or it is a false negative. Fall back on the old-fashioned way, which is basically start the patient on carbidopa/levodopa. If it is just Parkinson's disease, they should improve. If there is no improvement, even with increased dosage of carbidopa/levodopa, it is basically either one of two things: it is either Parkinsonian-plus syndrome or Parkinsonism, which is not going to be amenable to any medication, or this is not Parkinson's.
DR. SANDHU: Can you explain those Parkinsonian-plus syndromes?
DR. VIRDI: The Parkinson's-plus syndromes are the syndromes in which you have signs of Parkinson's, but it's not just the basal ganglia getting involved. There is involvement of the cerebellum, involvement of the brain stem, involvement of the cerebellar peduncles. So those add on — people will have predominant ataxia if the cerebellum is involved, they will not be able to walk straight. You can have truncal ataxia, and you can have ataxia in the arms as well — doing finger-to-nose, they will not be able to do this. So they will not pass a drunk driving test at all. That can be it. And then if the cerebellar peduncles or the brain stem is involved, you can start getting some bulbar symptoms, which is basically swallowing and speaking and so on. So those are the kinds of things that we look for.
DR. SANDHU: And what do you typically tell them about prognosis, or how life is going to unfold over the next few years?
DR. VIRDI: I always try to give them hope, in the sense that we'll try the medications, and then, if nothing works, it is all about keeping the patient comfortable.
DR. SANDHU: And do medications work in most people?
DR. VIRDI: If it is Parkinson's, yes, the majority of people will show some response to Parkinson's medication.
DR. SANDHU: And then do you combine regular exercise prescription with that, or therapy with that?
DR. VIRDI: Once a patient is stabilized to a nearly normal setup, where we try to keep them a little bit on the slower side, that is the time we send them to physical therapy and balance training.
DR. SANDHU: And do you talk to them about sleep, diet, all the lifestyle changes?
DR. VIRDI: All the lifestyle changes, yes.
DR. SANDHU: Does it impact their sleep, Parkinson's?
DR. VIRDI: Yes. One is the REM behavior disorder that happens. And as Parkinson's advances, the amount of sleep that you get becomes less and less. And there are times when you will have a change in the sleep cycle, they'll be more sleepy during the day, and the autonomic dysfunction plays a role in that. If, during the day, the blood pressure is tanking, not only because of the autonomic dysfunction, but the dopamine agonists and dopamine itself don't help blood pressure. So you've got two for one — you will have low blood pressure and fluctuating blood pressure, you will feel lightheaded and sleepy during the day.
DR. SANDHU: Got it. So I'm just going to go through a few things that come up from our day-to-day life, and we can go through just the rapid fire. Does it help, hurt, or neutral?
Coffee, we talked about that.
DR. VIRDI: It may help.
DR. SANDHU: Alcohol?
DR. VIRDI: No.
DR. SANDHU: Mediterranean diet?
DR. VIRDI: Yes.
DR. SANDHU: Strength training?
DR. VIRDI: Maybe.
DR. SANDHU: High-intensity training?
DR. VIRDI: Maybe.
DR. SANDHU: Omega-3s, fish oil?
DR. VIRDI: It won't harm you.
DR. SANDHU: Vitamin D?
DR. VIRDI: Maybe.
DR. SANDHU: Sauna?
DR. VIRDI: Maybe. Not really.
DR. SANDHU: Cold plunge?
DR. VIRDI: Not really.
DR. SANDHU: GLP-1 medication?
DR. VIRDI: No data behind that as yet.
DR. SANDHU: Artificial sweeteners?
DR. VIRDI: Oh, they should stay away from that, because they are all pro-inflammatory.
DR. SANDHU: And pesticide avoidance?
DR. VIRDI: Yes, 100%.
DR. SANDHU: Sleep tracking?
DR. VIRDI: Does help. It improves cognitive abilities in patients with Parkinson's, need to regulate the sleep cycle. If they have REM behavior disorder, that is easily treated with clonidine, and it goes away. I've had patients who had classic REM behavior disorder — 0.5 milligrams of clonidine takes it away.
DR. SANDHU: So quality sleep will help?
DR. VIRDI: Yes.
DR. SANDHU: Any wearables that can detect Parkinson's early?
DR. VIRDI: Just need to keep an eye on things. If there's a strong family history, all the things we talked about earlier in the podcast, people should keep an eye out for that. Not that they have to be looking at it like a hawk, but any small thing which comes up is well worth getting tested by a neurologist.
DR. SANDHU: And one thing everyone over 50 should do for brain health?
DR. VIRDI: Oh, they should exercise, have a healthy diet, and a good sleep cycle, keep the mind active, be involved in everything, avoid alcohol, avoid all processed food, and maintain a healthy lifestyle and Mediterranean diet.
DR. SANDHU: Excellent. So in closing, if, God forbid, you or someone, one of your loved ones, gets diagnosed with Parkinson's disease, what are the first three things you would tell that person?
DR. VIRDI: I would tell them, "Hey, we got it, but yes, there's no cure to this thing, but there is a lot of advancement in the treatment protocols that we have now. There is hope, and this is going to get better over the next years as the science advances and more research is done, and not to give up."
DR. SANDHU: And what's one thing you wish physicians would do for Parkinson's disease patients that's not typically done?
DR. VIRDI: Early diagnosis.
DR. SANDHU: Early diagnosis, refer early?
DR. VIRDI: Yes.
DR. SANDHU: Well, I think that sums it up. Anything else you would like to add from your end?
DR. VIRDI: We take care of these patients all the time, and we are very proactive in promoting a healthy lifestyle, and we are very proactive in making sure that all the ancillary services needed for the patient — be it home health, physical therapy, and so on, assisting devices, and the latest technology that can be used — we take care of that.
DR. SANDHU: Well, that's very informative. Thank you so much, Dr. Virdi.
DR. VIRDI: Thank you, Dr. Sandhu, thank you for having me.
[End of Episode]