Eliminating Tremor with HIFU: fast, effective, and non-invasive
Originally presented by Dr. Justin Sporrer on Tuesday, August 23rd at 6:00 PM.
Participants will be able to:
Identify and review the diagnosis and treatments of various tremors
Discuss focused ultrasound as a non-invasive treatment for tremors
Good evening ladies and gentlemen, my name is Michael McDermott. I'm a neurosurgeon and chief medical executive at Miami neuroscience institute. I'd like to welcome you tonight to baptist health. South florida Miami neuroscience institute. Webinar entitled eliminating tremor with high fu fast effective and non invasive. Our speaker tonight is dr Justin spore neurosurgeon and director of functional neurosurgeon at Miami neuroscience Institute and associate professor at florida International University. Before we begin, I'd like to proceed by asking the audience a few questions about essential tremor and how it's differentiated from Parkinson Ian tremor. So for the first question, approximately how many people in the United States have an essential tremor? 100,000 to 1 million or 3. 10 million. Please take a minute to answer the polling question. Second question, that is essential tremor dippers from Parkinson, Ian tremor in the following, which weighs one essential tremor is an action tremor. Whereas Parkinson ian tremor is often resting tremor To Parkinson. Ian Tremor is usually accompanied by other symptoms such as rigidity and slow movements whereas essential tremor does not. Three essential tremor is highly inheritable with 50% of patients having a family member with tremor or for all of the above. Alright, our final question is tremor can be treated with one medications, Two deep brain stimulation. Three focused ultrasound or for all of the above. All right, thank you for your participation at preliminary poll will repeat the questions at the end dr sport. Take it away. Thank you Dr McDermott for welcoming me and uh giving us this opportunity to discuss high intensity focused ultrasound for the treatment of tremor and welcome everybody who has joined and thanks for joining us this evening. Um To start out, I have no disclosures and we'll just start to talk about tremor in general. I think it's important to understand that there's different types of the most common diagnoses are listed below. The first would be essential tremor. Um And you saw in the question how many people in the in the country have this? About 10 million people in the United States. Um And for for many reasons it's probably less talked about than the next diagnosis down which is Parkinson's disease, which has about one million people with that diagnosis. In the United States there are a whole host of other types of tremor. The most common next one would probably be physiologic tremor. Uh It's interesting especially as a neurosurgeon that people think that you have perfect hands. It's not really the case. It's uh that you have good tremor management. Everybody under a microscope has a physiologic tremor. But some people have what's called an enhanced physiologic tremor where it's very noticeable and it can happen both with action and with rest and then there's other less known causes multiple sclerosis after a trauma or even after a stroke. The most common treatments of these tremors and it depends on which one it is our medication medication and medication. I list those because of course that should be the first line treatment for these for these various diagnoses. But I do want to talk about other options today. So, ultrasound um, you know, everybody's heard of ultrasound, it has existed for many decades, both diagnostically and therapeutically. Everybody's heard of a prenatal ultrasound to obtain images, but it can also be used therapeutically. And at high intensity, the energy at a focal point of ultrasonic waves increases the kinetic energy. And so I think of it as a magnifying glass. And so everybody can understand that when you put your hand right under a magnifying glass out in the sun, nothing happens. But if you bring it away so that that focal point lands right on your skin, it's burning hot. And so, um it all is about focusing that energy to a single point. We know that if you raise the kinetic energy of something that it increases the temperature of that thing. And so we can use that high temperature to kill abnormal cells. That's what that's what we call an ablation. Um we like to use that word because it's a little more uh politically correct and killing cells that people don't like to hear that, but in effect, that's what we're doing. And so one thing that people are familiar with is a cardiac ablation, to kill abnormally um firing heart cells that cause arrhythmias. And in this case you think of these cells in the brain as kind of a brain arrhythmia causing these tremors. And so for many years, we've used ultrasound to treat tumors of the abdomen, liver uterus. And that was easy because all of those things are not too far away from the external world. Um and they're only protected by a layer of skin and some fat. So there existed this brain problem. Or more accurately speaking, it was the skull problem. And so, you know, we knew that we could, you know, oblate these cells with ultrasound. But how do we get past this hard shell that surrounds and protects the brain? And how do we maintain that energy and accuracy across basically a three layered hard surface? Um And so I again, I like to use a lot of analogies, you'll see. It's not easy to hear sound through a two pane window because there's glass air and then glass again. And for every time that you change mediums um there is some absorption of that energy which lowers the total energy. And there's a refraction of energy bending. It sort of like how light bends when you go from air to water. And so how do we control all of that? And this is just kind of a close up of the skull. You can see there's an outer cortical layer of the skull. And then there's kind of a bone marrow layer which is softer and filled with bone marrow and blood. And then there's an inner cortical layer. And that was one of the challenges not to mention for a lot of it. It's a nice sphere more aptly a hemisphere, but the rest of the brain has things like sinuses and air pockets that uh further add to the complexity of the problem. And so there's another brain problem is you know, how do we know if the energy that we're inputting is actually changing the temperature inside the brain without any probes? How do we know if that change in temperature causes an ablation? Is it enough to cause an ablation? And then if there is an ablation, how do we know that an effect is actually taking place? Most importantly the effect that we want. Not an unintended side effect. And so I would say to simplify um the ultrasound machine and the computer systems that we use that determines the energy being input um that we're measuring in jewels and the M. R. I. Is able to tell us the temperature of any point in the brain, which I have to say I was not really familiar with before starting all of this and still kind of mind blowing to me. I'm just a simple neurosurgeon. But the physicists have figured out that by measuring the kinetic energy and how fast the various molecules are moving within the neurons, what the temperature of the brain is at any given point. So that's like looking at a turkey in the oven and knowing just by looking at it what the temperature is at every little point that's called thermometer tree. We use a very basic calculation really when you think about it, of temperature times time to figure out if there was an ablation. And again to use cooking as an analogy, we know that you can put something in a slow cooker for eight hours and achieve the same result as putting something at very high temperature for a few seconds. And so, you know, there are pluses and minuses to both of those when we're talking about the brain. But that's how we figure out if an ablation has taken place or not, for example, 57° at 11 2nd. That's an ablation or 54°C for three seconds. So it's a it's a simple calculation. And then lastly, the neurosurgeon myself in in this case can check for the effect by testing if there's a tremor or if there's a lack of tremor. Um And so that is how basically, you know, the workflow works. So what is this, this technology? It's called magnetic resonance guided focused ultrasound. We use high food because that's easier to say than most of us. Um But high fu is high intensity focused ultrasound. Um And so we are able to get a real time heatmap, literally a heat map of the target area and the M. R. I allows us to choose a very specific target. And so one of the first things we do is to just obtain an image which takes about 10 minutes for the patient that gives us a great picture of the brain. We choose our target, which I'll talk about in a second. And uh and then we're able to actually see the temperature of that target rising. Uh and also checking to make sure that the cells around that target are not rising. So here's the target. This is very complex. This won't, this won't be on the test, but that's a close up picture of the thalamus which is about the size of a small egg very deep inside the brain. And that egg shaped structure is then further divided into a dozen or so sub nuclei which all have projections to various parts of the brain. So I think of the thalamus is kind of like a relay station or a call center for the brain. Anything that you can think of, from, you know, your emotions and thoughts to hunger, to movements, to sensation, to tremor all have to go through there at some point. And so we know that tremor signals. Um there's lots of parts of the brain that are involved, but it has to go through this one part called the ventral is intermedia. So I think of essential tremor as the quote unquote, perfect high food disease. And why why do I say that? Um Number one, there's very few symptoms besides tremor. And so that is in contradistinction to Parkinson's disease, which has a whole host of symptoms which were only more recently, starting to understand the main ones being, you know, not only tremor but also rigidity. A Tunisia, brady Tunisia, difficulty with balance and so essential. Tremor just has the tremor. So, you know, it's easy to see whether or not this person has a central tremor or something else. Number two, the the site of the ablation is a very small, well known target in the brain called the ventral intermediate. And when I say well known, the idea of ablation is actually not new. Um for probably 40 or 50 years, we've been able to cause an ablation through various invasive means sticking an electrode into that target, heating up those cells and then killing themselves, killing those cells and taking the electrode out. But of course that's a surgery. With all the inherent risks of open surgery. And then after that we were able to develop deep brain stimulation which again, has very effective treatment of tremor. But again, involves a surgery. And then lastly central camera is a very testable symptom to look for immediate effect and if necessary to make adjustments. And so, you know, things like deep brain stimulation. Things like ultrasound have been tried and somewhat successfully in the past for things like depression. But how do you test that in real time? You know, how do you know what's your mood? Those are things that you actually have to treat and then follow over many months and then compare to kind of an amalgamation of their symptoms from previously. Whereas this is very, very straight forward. You can see that the person has tremor and literally 30 seconds later they might not if if the treatment was effective. So here is just a memory of an actual patient. Um and you can see here, it's a laser pointer here on the left is just a normal pre treatment, M. R. I. And the thalamus is in this general area, okay deep, deep in the brain. And then this is immediately after the procedure, you can see that there's this oval black area that is the ablation. And so we get immediate feedback not only with the tremor, but also with imaging to show exactly where where the ablation was. So I I call this a test drive high flow allows us to deliver low energy first and and raise the temperature of those cells little by little up to a temperature where they are stunned um stunning those abnormal brain cells but not causing permanent damage. You know, on the flip side. If you put ice on your skin, it will become numb because those neurons kind of stopped working, but they're not dead. Um and so you can do it in the opposite direction. You can heat up those neurons to a point where they're not working, but we we don't think that they have been a bladed yet. And so we go in after stunning them with a sub therapeutic temperature. And we test the tremor. Very simple things, drink from a glass, draw a spiral, write your name, put your finger to your nose. So very simple things. Um And I actually asked people you know what is your number one complaint because I want to see how that number one complaint is doing during the procedure. Um and so you can see here that is pre operative or pre procedural. I asked them to start on that dot in the center and then just to stay inside the lines here with their marker. Obviously this person had a very severe tremor and anybody who has this bad of a tremor was not able to to do basically anything with their dominant hand. You know can you imagine eating with this particular tremor or shaving your face with that tremor really not possible. And so then we were able to stun those cells And this was afterwards. So not perfect. I don't there may not be a neurosurgeon in the future but they can feed themselves and they can take care of themselves and they can write their name on a check. So a very dramatic benefit. That's the same patient, you know, only about 30 minutes later after we started. And so with that test drive ability, if there's no improvement we just move the target. Um and nothing permanent has happened yet. Whereas if we see good improvement with that stunning sarah sub therapeutic temperature, then we just increase the energy uh and cause a permanent ablation. The advantages of this, it's noninvasive, no surgery, I really can't stress that enough. And I'm a huge believer in deep brain stimulation. Uh I did all this specialized training for it. I've treated many patients with tremor with deep brain stimulation. But now that people know that this exists, it's sort of a hard sell sometimes because people don't want to have brain surgery, let alone awake brain surgery. And then secondly, besides just the day of the procedure, they're thinking about their future. There's no hardware to worry about. You know, if you have a foreign body in your, you know, in in your brain, there's always a worry about infection. Um and then if you have the brain stimulation, you have a battery that needs to be replaced every 3-5 years depending on the settings. And so it has this test drive ability um which the reason I put that up there is because even the idea of a blading something non invasively has existed with radiosurgery, stereotype radiosurgery. But once you delivered that ionizing radiation, that was it, uh you number one had to wait a few weeks to see if there was an effect or not because radiation doesn't work immediately. Um and number two, if you were wrong and you, you know, a bladed, some cells that were part of the sensory pathway, you might have some numbness and there's no going back at that point. And then lastly it's effective. So um the drawbacks a shaved head. So I say this the very first moment that the person that the patient walks into my office because I just want to make sure that there's no surprises. Um And so that's something that has to happen because it's not easy to get the ultrasound through hair and also the hair follicles hold onto air bubbles which also interrupt the flow of ultrasonic waves. I would say that it's not a quote unquote easy alternative to deep brain stimulation procedure. You know people think well you know this is non invasive so it's gotta be easier um You know you're on your back flat um and you're in an M. R. I. Machine for you know about an hour. We've gotten it down to about an hour. But um and so some of our patients, especially with back problems or older patients or respiratory problems, you know it's not that easy. Um And so I try to make sure that people, people are well prepared for that. Um And it's not modifiable after the treatment. And so once those cells are a bladed, you know there's no changing that after the fact which is different from something like deep brain stimulation which you can change the settings on after afterwards or just turn it off altogether temporary numbness of the face and hand uh temporary difficulty walking and can currently only be done on one side. So these things are because usually because of swelling or brain and Dema I tell patients, you know, we're gonna cause an ablation that's about eight in diameter. So if you can imagine putting a cigarette out on your skin at the very first moment, it would look about eight the diameter of that tip. But if you look at it the next day, it would be all red and swollen, probably several cm around. And I think that's kind of what happens in the brain. We we burn this one little area that controls, you know, that's causing the tremor. But then a demon gradually develops over the next two or three days and then it goes away. Well, those neurons surrounding the ablation, they do other things such as, you know, sensory information, balance, even a little bit of speech slowness. But knock on wood, you know, these things are 99% of the time temporary. It can currently only be done on one side. It's awaiting FDA approval for the second side. Uh And I make sure that we have a conversation about that. You know, Most people have want their dominant hand done. But if you have uh only tremor in your non dominant hand, is it worth it? And we have to have a very serious conversation about that. I think that probably this year that the FDA will approve that second side. This comes from Inside Tech, which is the company that actually makes the the only ultrasound ablation um for the brain at this time. And so here's just some quick numbers. There's a 76.5% tremor improvement at three year follow up. That's pretty good. Um you know, and that the patients are saying that their tremor is relieved and there's all these other things that come as a result of that. Um You know, I think if you ask somebody, what's your number one complaint, they'll say it's embarrassing. You know, they've come up with all kinds of ingenious ways to work around their tremor. You know, from holding their, you know, holding their razor against the wall and then just moving their face to shave, or two handed writing and all kinds of utensils for eating, but it's embarrassing to them. And so it really has a psychosocial benefit and getting them back to a normal life. And then over on the right, you can see that after treatment, the most common adverse effects, which we talked about, uh gait disturbance, 26% numbness or tingling. Third of people, headache or head paying 51% of all of those things, you know, 50% of those things had resolved within 30 days. And at three years, the most persistent ones were in balance or unsteadiness. Um, So between, you know, the 30 days and the three years, most of these people's negative side effects have gone away. Here's just a video of a before and after of somebody drinking water and I'll play it again. So you'll note that this lady's head is indeed shaved. She has those bandages on her head because we do have to place the head in a frame in order to keep the head very, very still during the procedure. Uh I just use those little tiny round band aids um to make it, you know, seem less invasive than than what than what they used here. Final points. Tremor is not just normal aging. I've had so many people come in and say, well, you know, I am 80 years old, so it's time for me to start having a tremor. You know, although the incidence is higher, it's not normal. Um and so often times, you know, I think it definitely deserves a work up because maybe they have essential tremor, maybe they have something else essential. Tremor can be treated first with medication, we didn't go into this too much, but panel law premed in those are the top two medications. What I find is it's it's can be quite effective for people at the very beginning stages, but it quickly kind of runs out or they have um side effects. They get tired or you know, kind of foggy and so they don't like the negative consequences of the medication. They'd rather have their tremor, high intensity focused ultrasound is a safe FDA approved and very effective treatment for tremor. And I added this because everybody asked it is covered by Medicare. Um that's uh, you know, different states adopted it at different times. And florida came in um just about a little over a year and a half ago. More recently. This technology is being used for Parkinson's disease. Not only tremor dominant Parkinson's disease, but also the uh non tremor symptoms with, with a pallidotomy at the different target altogether. And research is also being conducted on the second side, as well as other movement disorders and psychiatric conditions. You know, all of these things can be boiled down to an abnormal circuit in the brain. Every circuit has little bus stops along the way, that if you disrupt that circuit, that you could have a positive effect on the function of the brain. And that's it for my presentation. Thank you very much. Thanks Justin uh we've got a couple of questions from the audience. First one is with expertise in both ultrasound and physics. Does dr sport have an opinion on the risks associated with the use of ultrasound in pregnancy. Recent news in a set of men often used during pregnancy is cited as the cause of the increasing rates of autism. However, the increased risk of autism correlate more closely with increasing use of, I may point out abdominal ultrasound than in the use of a settlement during pregnant. So, so as high food contraindicated in a pregnant female. I probably would, you know because there's nothing urgent about this, I would definitely wait until the pregnancy was over. You also have to be flat on your back for uh you know at least an hour or so. And so I would probably say no, I don't know if there's an actual medical contraindications to it. Um And I'm sorry I'm not familiar with the acetaminophen effects and all of that, but I would not do it on a pregnant patient. I would wait until the baby was born. You know, I have a couple of comments at my at UCSF, we monitored uh with T. L. D. S. The dose to the abdomen in pregnant females who had malignancies and needed treatment? And the dose was well below thresholds for fetal exposures. So that proved to be safe even with ionizing radiation. And I would point out to the physician who asked the question um remember presentations um back some years ago by research neurologist pointing to an overuse of folate during pregnancy as possible uh toxin that may contribute to the increased risk of autism. So you might want to look at the more recent literature in that regard. Um 2nd question. My dad, who has tremor has also has a mitral valve replacement and therefore is on warfarin. Is there any contra indication. No, there is not. And this would be the perfect person to talk about a non invasive treatment versus an invasive treatment. And so before this existed, you know, I would you know, I might even determine that somebody was a great candidate for a deep brain stimulation from a urologic standpoint. But then we're all ready to do it and then they tell me oh but I have this cardiac valve and I have to take blood thinners or I can't breathe when I'm on, you know after after general anesthesia or whatever. And so we have had multiple patients including just patients who are kind of very frail, you know in their late 80s who can't do regular surgery, but blood thinners um anti coagulation is not a contra indication to this. Another question, why can you only do one side? Great question. So um what they have found when they've done both sides simultaneously which has been done in other countries is that the imbalance problems that I was describing are much much worse and probably like exponentially so. And the reason is because balance, like a lot of things uh that our brain controls is has got bilateral and backup systems. And so even if you negatively affect temporarily, some of the let's just call them balanced neurons on one side. The other side can compensate. Um And so if you take out both of those at the same time, even temporarily, then the person may not be able to walk. And so that's why it was not approved. The recent data which has not been approved? I'm not, I'm not saying, But is that if you separate those treatments by six months and allow the first side to recover, then the effects on balance are you know, much more mitigated, much more mild when you go to do the other side. So that was a trial that you know, has recently been completed, but the FDA has not approved it yet. Um Next question is, what is your approach to pre procedural evaluation for eligibility? And how much follow up do you offer? Post procedure? That is another fantastic question. Um for essential tremor. Um and I'm gonna kind of compare this to Parkinson's disease. Essential tremor. I see the patients directly myself oftentimes they're referred by a neurologist, but more often than that they're referred by themselves, they did their research because they were kind of desperate. There's not a whole lot of options out there And they found me um one of the reasons that I don't require them to see a neurologist is because the diagnosis is so straightforward in my opinion. You know, I asked a couple of basic questions, is it worse with action? You know, or rest, you know, is do you have any family members with it because there is a 50% inheritance. So very often somebody says, well, my mom had it and two of my daughters have it. Um and does it get better with alcohol. So this is the one time that I hope people are open and honest with me about how much alcohol they use. There's no need to be hesitant Because that is a diagnostic criteria to show whether or not it's essential tremor. And if they say yeah my mom had it, it gets better with two glasses of wine and you know, I've had it for 30 years and it's worse when I go to do something. But if I'm sitting watching TV I don't have the tremor that's essential tremor. There's really no other diagnosis that would make sense there. And so I feel confident even as the neurosurgeon um making the diagnosis to to go into treatment as far as follow up is concerned. Um I see people the next day to get a post procedure M. R. I. To see not only the ablation size but also the amount of a demon that they have. If they're having some, you know side effects imbalance or whatever. If I can look at that M. R. I. And they have more than average adama. Then you know, I reassure them and say listen this is definitely the effect of the adama, it's gonna go down and it's gonna get better and then usually I'll see them again Probably a month after that. There's there's no incisions to check, but I want to let all of that all of those effects kind of go away those 30 days. Uh some of these people are coming from pretty far away. So um I don't have to see them again but my door is always open. I tell them please call me with any questions or concerns or if they just want to come in just to show me how how well they're doing as far as the work up. I want to go back to that. I mentioned that people are coming from far away. We've done people from Louisiana and south America. Um Those people again, one of the only things I can do as a neurosurgeon over zoom or over, you know, telemedicine is this because the main things are you know hold up your hands, touch your finger to the camera and then come back, you know, draw a spiral which I could do in the office and then they just show it to me so you know, I can make the diagnosis and set everything up from another country and then they only have to come the day before the procedure, you know, get everything set up. Um So that's that's kind of the answer the question. Um The next question is are there any reports of interest cerebral hemorrhage post procedure. So that's an interesting question. Um Yes there are um you know if you sit a radiologist down and you look at the ablation, are there some punk Tate areas that could be blood? Well there's no way to really prove that because you know, how how do you differentiate that from the ablation itself plus the edema. What I would say is you know large hemorrhages. No. And the other thing is that we're raising the temperature. So it's kind of auto cauterizing at the same time. There's no major blood vessels in this area. Of course there are tiny, you know capillaries but no named blood vessels that that could cause a giant hemorrhage. And is this an outpatient procedure? It is outpatient. So um we will often see somebody like the first patient in the morning will come in at seven o'clock in the morning. Uh They're being nice now and kind of pre shaving their head. We'll just do some touch ups uh and then we'll put the head frame on, get started by maybe 8 30 or nine and then they're done before 11 and then you know we'll do two or three in a day sometimes and then they'll have lunch afterwards mostly to make sure that we can give them some soup and a glass of water. All these things to test out. You know their new hand and their lack of tremor. And then they go home they'll come back the next day just to get the M. R. I. But it's completely out patient. Thank you. Um Can you elaborate on clinical trials if any and results. So um let me go back maybe can you still see my screen or? No. So you know these were the three year clinical results. Um And it says here at the bottom, you know, the data was from, you know, the companies sponsored clinical studies. Um, but that's kind of the best that we have um, in terms of the tremor improvement and also the negative effects. You know, I don't think this is over selling. Um, I would say that of the patients that we've done probably it's it's more than this. And I would definitely say that I see, you know, less than uh, 4% of persistent, you know, imbalance and definitely less than 51% headache. I really think maybe people would say they have some pinsight pain from the frame the day after the procedure. But nobody has come back saying that they had headache for for us. Have you done high proof or Park and Sony in trimmer have um, and so it is FDA approved for tremor dominant Parkinson's disease. This is by the way, kind of influx that was as of I believe last year. So I really interview patients here because if they have all of the symptoms of Parkinson's disease, you know, bad gait disturbance. Um, if they have severe rigidity or something like that, I don't think this is the best treatment for them unless they have all of those things. But they still say, I understand, I understand I just want my tremor treated, but that's a very serious conversation. I don't want people to think that it's going to cure their Parkinson's disease or even improve most of their symptoms. But there is a subset of Parkinson's patients who have a bad resting tremor uh which is clearly Parkinson's uh and they have a positive debts can and they have a good, you know, a decent um response to dopamine allergic medication. So it's Parkinson's is not essential tremor, but really the tremor is their number one or only complaint. And so we treat them with kalamata me not pallidotomy. Now that pallidotomy has also been approved, but it's not insurance or Medicare approved yet. So you can do it. But even then, I would reserve that at this point, I would reserve that for people who cannot get dbs because it's it's um in my opinion, a more complex disease that needs a little bit more um variability and change ability after the fact, um, I've got a simple question, followed by a couple of physics questions. Simple one is our white matter lesions seen on a brain M. R. I. A contra indication to high food treatment. No. Uh And I would say that again, if that is representative of some, you know, mild cognitive impairment or if it's just they're a vascular pathetic patient, they've got bad heart or bad characters or whatever, then probably the non invasive treatment is is better. The other thing is my average patient is in their seventies and pretty much every one of them. If, you know, you sat down slice by slice, you would find some some white matter lesions. Now, if the white matter lesion is some something that is representative of something bigger, like multiple sclerosis than we should talk because this might not be the most effective treatment. All right. Um Here's the physics questions coming at you now. Um Can you comment on the desired targeted temperatures that you need to treat? What are the temperatures that are used for testing whether you're in the right spot? How long is the ultrasound applied? And can you comment, how does this temperature that you achieve compared to quote cooking? Okay. Um well, I did do a thesis in physics Georgetown, but that's not my area of expertise. It's it's neurosurgery. But I will say that the temperatures, I think I remember all these questions. 57°C for one second is what we know through, you know, previous insight to experiments. That is an ablation. That is enough temperature to kill a neuron Or 54° for three seconds. And it goes on down from there. I mean, if you kept a neuron at 51° for much, you know, many more seconds, it would be permanently damaged. Um and so that's the answer to that question. The ultrasound is applied for anywhere between 11-25 seconds at a time. And so during the procedure, this is important. I didn't put this in the presentation. People will say that they feel like a buzzing or even some warmth on their head and they'll even describe the feeling of falling backwards. Like they're doing a backflip but clearly they're not moving. So it can be very disconcerting and even nauseating. So we give anti nausea medicines for everybody Now in just as prophylaxis and I give them a lot of warning. If you know what's gonna happen then it's not scary. If I didn't say anything that would be really freaking out. And so I tell them whatever you're feeling, if you can kind of bear it for 25 seconds, just know it will be over in 25 seconds as soon as the ultrasound is turned off, that sensation goes away. Um and so if they can if they can hold on for 25 seconds, but if they can't then they just press press the ball and everything turns off so there's so many different safety checks as we go in to make sure that everything is working well As far as cooking. Um you can go up to, you know, 70, um which would cause uh what do they call it? You know, basically charring, which you do not want for a couple of reasons. One I think that the temperature increase and the temperature spread would be less controllable at that point. And two is that it creates a micro environment of little bubbles that would interfere with the next round of ultrasound, which we call a sonic ation just for clarity sake. And so the average person takes anywhere between six and eight sonic asians including the ones that are sub therapeutic to finish the treatment. Can you talk anything about dose gradients in terms of temperature outside the target volume? Um Yeah I mean there's obviously a lot of literature on this in the in the radiation um area. I don't know that there's been a specific study but using the thermometer tree you can see what the temperature is. I mean it's like, let me just say it's obviously a calculated thing but that's how we know anything with M. R. I. It's all a calculated image. Um And so what I would say is that the we have a cursor that we drag over the various areas of the brain including the area of the ablation and then the immediately surrounding area and the temperature drop off is very fast because um it's not like those cells outside of the area of the ablation are receiving that high dose of kinetic energy. That's not the focal point of the machine. And so um no there there should not be mean there should not be a large area or a penumbra of high temperature areas. There is a cumulative effect though. And so even if we don't get the temperature that we really really want that 57°, we only get up to 54 if we do that three or four times there is a cumulative effect. Um And one of the reasons we can't sometimes get to that high temperature is because the skull people's different skull densities allow various levels of ultrasound through. And so the efficiency of we talked about the efficiency of their skull. Um and how easy it is to achieve that ablation get to the energy that we want. Yeah, that was actually the next question. Was are there issues with skull thickness in terms of patient selection or ultrasound penetration? Great question. Great question. 95% of people are candidates. That's the take away 5% have a skull density ratio. It's called a skull density ratio, which is a ratio of the density of the cortical bone to their medullary bone, the bone marrow. And if that ratio, the difference is too high, then again, you have created a three pane window where your your refracting and absorbing energy through each layer. And so then that patient cannot uh effectively let the ultrasound through. It is not about skull thickness, though, I mean every man that comes to my office with his wife. The wife says that they've got a thick skull or a dent, you know, numbskull or a dense skull, it doesn't have to do with that. Uh And in fact, if you have a very hard head, that's probably better because the older you get some of that mural goes away. And then you've got this maybe thick but hard skull all the way through, that just transmits the energy, it doesn't absorb anything. You know a related question is would a cranial defect exclude the patient for consideration of life? Ooh and does a burr hole cover previously placed for dbs act as a contra indication to treatment? What we would do in that case is get the C. T. Scan ahead of time. Obviously all these things would have to be emery compatible. But most burr hole covers are I haven't seen one that's not but um and then send you know we have we send it off for analysis to get the skull density ratio but we could also loaded into the system and essentially turn off um the ultrasound transducers that are immediately overlying that defect or overlying that burr hole cover. So I don't think that that would be a contra indication. Obviously it depends on the size of these things and and the location. But um a lot of people have for example um intracranial calcifications, a rock of calcium that is going to deflect ultrasound waves. And so if you think of the ultrasound machine, like a lady's hair dryer in the salon um it's a hemisphere that has uh kind of like a planetarium 1000 ultrasound transducers, you know a raid on the inside and they're all pointing to one focal point? If there's something in the way of you know X. Y. And Z. Transducers. Then we just turn those off, There's about 1000 of them at any given time. We're only using between you know 809 50. Thank you. Um It's been said that for Parkinson's disease, deep brain stimulator treatment sometimes show worsening of cognition. Has the same been seen with high intensity focused ultrasound for Parkinson ian tremor. The answer is no. And I think the reason for that is because when we do deep brain stimulation we're in you know, we're actually introducing an electrical signal into usually the sub thalamic nucleus. Well there's parts of the sub thalamic nucleus that um you know convey information that is involved with cognition. Um And it's a very small target. So it's hard to get the target that you want and not the things that you don't want in the thalamus. Obviously there are also many nuclei but not very close to where we're doing the ablation. Um not to get into the nitty gritty of the anatomy of the micro anatomy there but you know laterally is the internal capsule. So if you get a Dema there from the ablation you're gonna get some weakness or some loss of coordination on the contra lateral side uh posterior to our target is um the vpl which is a sensory nucleus. And so if you remember that list of side effects, people say that they have tingling or paris the jys in the face or hand on the same side as the tremor relief. Oftentimes it's not a bad trade off and they're in their estimation. But those are the things that we that we worry about more than cognition or other brain functions that are not in that immediate vicinity. Question. Can you do video evaluations of patients exams? Absolutely. We we do it all the time via telemedicine um, if they're not close, but I think that's the question. Yeah. Alright, so we finished all the questions. I'd like to go back to the polling questions we had at the beginning. If I can ask the administrator to help me with this Question, Number one was approximately how many people in the United States have essential tremor if we want to try and answer that again the first time around. Um, 0% said 100,000, said one million and 57% said 10 million. So the correct answer is 10 million. For question number two. Essential tremor differs from Parkinson Ian disease because of a number of factors. 100% of the participants before your talk said all the above, which is correct And you can see the answers. Essential tremors and action. Tremors. Parkinsons arrest. Parkinson Ian Tremor is usually accompanied by other symptoms, such as rigidity and slow movements, whereas essential tremor is not central tremor is highly inheritable and 50% of patients have a family member with tremor and that's all correct. Um, When on question # three tremor can be treated with which of the following methods, 90% said all of the above 10% said medications. Um And the results of The repolling are that 73% of people said that 10 million people have Parkinson's disease Results are repolling for question # two changed a little bit Because only 88 people felt that all the above were correct. And for question # 3-related to tremor treatment. Um let's see if we can go into polling, take the pole and the results the second time around with the team. So, um I'd like to thank dr spore for his excellent presentation and response to the questions from the audience. Uh We'd like to thank the audience for their participation and we hope you have a good evening. Thank you. Thank you, everybody.