Daniel G. Di Luca, MD, MSc presents on how to recognize the applications of FUS in essential tremor and evaluating FUS in Parkinson Disease and Movement Disorders.
Uh Thank you so much, Nicole. Um And thanks for having me today. Uh I will be discussing the application of uh focus ultrasound and movement disorders, but predominantly essential tremor. And uh I would try to be relatively brief and have this for maybe 40 minutes or so, which would give us enough time to answer questions or concerns anyone might have. Should say that I have no relevant disclosures. Uh Meaning that I also don't get any sort of financial incentive from any of the companies involved in focus ultrasound or in other technologies for advanced therapies like deep brain stimulation. Um In this uh lecture, I'm gonna try to discuss the basic principles of focus ultrasound uh to recognize how we can apply focus ultrasound in essential tremor, but also in other movement disorders like Parkinson's disease. And to discuss the advantages and limitations of focused ultrasound, but also the future directions and some of the innovations associated with focused ultrasound. Uh I should start by discussing that o ultrasound is a relatively novel and minimally invasive ablative procedure. Um And basically what that means is it's similar to a cardiac ablation, but in this case, you're using ultrasound energy to increase the energy in a part of the brain, increasing the temperature, which causes necrosis of that part of the brain is, is a term onc roses which can interrupt certain pathways and improve symptoms of tremor. Um It has been FDA approved for essential tremor since 2016 when they had one of the pivotal studies for essential tremor published in the New England Journal of Medicine and then for Parkinson's disease later on in 2018 and 2021 when I say that it is a novel therapy, I'm not uh very accurate. In fact, we know that this technology has been around uh at least since the fifties in very different ways. This is uh one of the first publications of uh ultrasound being used to uh destroy part of the brain. Uh uh and that's work done by the Fry Brothers. And since then, multiple groups have tried to use focus ultrasound as a therapeutic option for many neurological disorders. But most recently, this has been uh evolving and growing in our uh sort of um uh uh possibilities for for therapy. He was just a graph showing the number of publications by the year. And as you can see here in the nineties, it's quite a slow silent uh uh period for focused ultrasound. And later on uh with the publication of the trials and essential tremor, it becomes quite popular and the number of publications has been uh growing and growing each year and most recently with other indications like A LS uh depression and other psychiatric disorders as well. Um I would just like to discuss more about the mechanism of action of focused ultrasound. And it's based in two different principles, the principles that you can a blade part of the brain to improve a certain neurological symptom. And you can do that by uh increasing the temperature in that part of the brain by using ultrasound waves. So basically, you are destroying a part of the brain by using ultrasound beams in a way, each ultrasound beam individually does not increase the temperature of the brain. However, when you put thousands of ultrasound beams in one confluent spot, you can increase the temperature in that a blades that part of the brain. So it creates literally a lesion in the brain. Um The way they do it is by placing this helmet around the head which delivered these thousands of uh ultrasound beams. We don't know exactly why this helps with tremor. But our understanding is that there is an abnormal circuit of the brain, uh one circuit or pathway that creates the tremor almost like a highway in the brain. And when you disrupt this abnormal circuit, you can somehow improve the symptoms and improve the tremor. Um What I like to tell patients when I'm explaining, which might make it easier to understand is almost like when you're a kid and you get uh this uh mirrors to reflect the energy and kill a bug or make a hole in a leaf. That's sort of the same idea that you're using this energy to burn uh a hole inside the brain. In this case, that is therapeutic. I'm gonna discuss the approved indications for focus ultrasound, which include essential tremor but also Parkinson's disease, especially the tremor, predominant Parkinson's disease, essential tremor as uh probably all of you know, is uh the most common movement disorder. It affects meetings of patients in the US. And we we only have a few drugs that can be effective. Uh And I'm sure that in your practice, you see patients with essential tremor, you probably treat those patients initially before sending to us. So we have propranolol primidone, gabapentin, topiramate. And when those medications don't work, we consider the possibility of advanced therapies classically, uh V I MD BS or deep brain stimulation of the thalamus. Like you can see in this picture has been considered highly effective in the main strategy for treating these tremors that the these patients that don't respond to medication. Uh deep brain stimulation has been around since the nineties. It's very effective. However, it is an invasive brain surgery that you have to open the skull and you have to place this electrode with the hardware that you have to change over time. The use of ultrasound has been uh uh started in 2013 in this randomized control trial and followed by the New England Journal of Medicine publication in 2018, which was the uh the, the sort of pivotal study that led to the FDA approval of this therapy. I just wanted to show you a video of how this technology works and this is not from WU, but it gives us a sense of the technology that you have a um a radiologist or a neurosurgeon. Uh In our case, as a neurosurgeon, Doctor Willie, who is going to the um to the MRI, they find the thalamus and uh the patient is inside the MRI awake and they find this area, they target this area. And at the same time, they test the patient to see how much improvement they have while having this uh procedure done. And here is the testing during the MRI procedure. I think in general there was a lot of misconception about how the focused ultrasound works. A lot of patients believe that it is like a pregnancy ultrasound that you just get a transducer, put a gel and you just put on top of your head. And uh we can do this in clinic and then you go home, but that's really not how it works. Uh These patients have to come here one morning and they can go home the same day, but it is a little uh a little more invasive than we make it sound or how the name suggests. Uh uh we do have to shave the head of these patients completely, which for some patients might be an issue, especially for women. And that's probably one of the most common reasons why patients do not wanna go for the procedures that they have to shave their heads. Um And once they go in the MRI uh there are still risks of side effects that we, we should discuss in the next few few slides here. Um Here is the, the sort of people who study that I was discussing the New England Journal of Medicine showing that focus ultrasound, thalamotomy or the focus ultrasound targeting the thalamus can be effective for treating tremor. And they compare here, the sham group versus thalamotomy in the tremor rating scale, which is the scale that we use to assess patients with essential tremor. And you can see how there is a big drop in their main scores which has been consistent over time. And that also leads to improvement in several 80 albums including eating, drinking, writing and dressing. Now, as I was mentioning, uh focus ultrasound can have some complications or you can have adverse events because we are lesioning a part of the brain and this part of the brain is connected to other circuits like the cerebellar temic uh circuit, you can have some complications including gate disturbance. And in these trials, the numbers were uh maybe around uh 5 to 10% later on. But initially a lot of patients can have quite a lot of the side effect, up to 30% of the patients because of the swelling of the brain. And it is expected that over time, the symptoms would go away as the swelling goes down. So basically, um as we can see here, this is a highly selective cohort of patients for this trial. But still 30% of them had uh symptoms of gait disturbance which improved. But at the end of the uh 12 months, some patients still had persistent gait disturbance. Um probably the most concerning uh a diverse event would be weakness would mean uh basically lesioning the corticospinal tract which would lead to uh a hemiplegia involving that side. Uh But that's quite rare and uh less than 2% of patients are just one patient in this specific study. Uh But as I mentioned before, this adverse events, especially numbness, tingling, paresthesia, but also dear or slurred speech can be quite common, especially in the immediate post op period. And that uh the statistics is that up to 80% can have some sort of a 80% of people can have some sort of adverse event uh soon after the procedure. But most of this adverse events would go down and disappear after the swelling goes down. Now, we still have a lot of difficulty understanding uh which patients might be at a high risk for ga imbalance. Um As I mentioned, this uh has been a highly selective trial including patients who are otherwise healthy. Uh But this is study here that at the Mayo Clinic was sort of a real life uh kind of study very pragmatic looking at the 45 patients that had focused ultrasound and uh about 45% of patients had gait decline after the procedure which remain persistent in about 30% of patients. And what is interesting is that uh patients who had a history of neuropathy were more likely to have gate decline. And the idea is that uh we have all these systems in our body that allows us to, to uh to have a good sense of balance, including our vision, our vib system, our preserved uh sensory system. And if you have some sort of disruption in this network like a neuropathy, if you do another hit, like the focus ultrasound, which disrupts some of these other mechanisms of balance, you can do even worse. So we really try to be careful in selecting patients for focused ultrasound. And if someone already has a history of neuropathy or gaining balance, requiring a walker or a cane, we really try to advise them that gaining balance can be a possibility. Most procedures are done uh in just one side. So it's a unilateral procedure which after nine months can be done on the second side. So we usually start with the dominant hand. So if someone is right-handed, we would usually target the left thalamus to control the right hand tremor. And after nine months, if you're doing well into the second side, meaning the right side of the brain controlling the left hand. However, we don't have a lot of experience with bilateral procedures. Most patients feel that just one side is enough to treat their symptoms or their disability. But if we decided to do that, we have to be very careful. There are safety concerns that by doing bilateral procedure, you can have even worse and gain in stability, uh which can be quite AAA major symptom for these patients. Now, here is the long term outcome of uh focus ultrasound in patients with essential tremor. And the largest uh or the longest study that we have is about five years, which is not very long for this type of study as well. So we have here patients that uh still had some persistent benefit of uh their tremor control after five years. But as you can see, it goes up slightly over time, it is not as bad as it was initially, but we have certainly seen patients that have experienced a return of the tremor after focus ultrasound. And here's the main change from baseline. And again, you can see how initiative is around 54%. But by the end of five years, um there is a main change to baseline of 40% still a great benefit and really uh a big improvement in their overall quality of life. However, we should always discuss with patients the possibility that after a few years, they might experience some return of the tremors. And I should also say that this study, despite being the longest one also had quite a lot of limitations, including uh uh a large number of patients uh dropping out or uh losing follow up. As you can imagine, it's quite difficult to follow patients for such a long time. So the numbers might not be completely accurate when we're discussing these uh long term outcomes. By far, the most common indication for focus ultrasound is essential tremor. However, we can still use part of focus ultrasound in Parkinson's disease. It is a little more challenging and that's because Parkinson's disease is not only tremor. Uh Parkinson's disease comes with slowness of movement, dyskinesia, uh rigidity, but also non motor symptoms. They can have cognitive impairment. They can have depression, anxiety, apathy, they can have um constipation, urinary symptoms and uh just focusing on the tremor of Parkinson's disease does not necessarily provide the large improvement in the quality of life that these patients are expecting. However, if you have someone with tremor, predominant Parkinson's disease, meaning the tremor is the most wome feature for these patients. If you cannot control with medications, then you can consider something like focus ultrasound. Uh This was the initial indication, but most recently, we can also target other areas to treat motor fluctuations in wearing off in Parkinson's disease. But what I should also mention is that for Parkinson's disease, most of these studies included patients with a highly asymmetric or mostly unilateral disease, which is not what we see in clinical practice very often. Plus these patients with Parkinson's disease tend to get worse over time. It's a progressive disorder. So having a deep brain stimulator with a battery that you can adjust over time and it can change the energy and the settings. The simulation is probably the most straightforward uh way for those patients. The focus ultrasound is a one time hit that it cannot necessarily fine tune over time. So in Parkinson's disease, it gets a little more, more tricky and difficult to, to discuss or make sense of the the indication. However, there have been several studies for Hokus ultrasound in Parkinson's disease. Here's the gemma publication of uh focus ultrasound thalamotomy. So targeting the same part of the brain, the thalamus for tremor. And as you can see, they had a significant improvement in their tremor scale um which did improve and persist over one year. Um However, this is not discussing the other aspects of the Parkinson's disease, the rigidity, the uh bradykinesia, the walking difficulties, simply the tremor over the subsequent years, they also had publications of a different part of the brain, the glomus pallidus. So they were doing a pallidotomy. So targeting the glomus pallidus in patients with Parkinson's disease who had motor fluctuations and wearing off. So after a while, as, as you know, Parkinson's disease patients can have trouble with their medications and they start having a lot of ups and downs and when they have these ups and downs, we might consider something like deep brain stimulation. In this case, they did the ultrasound ablation or the focus ultrasound ablation in the glo spats. And patients did have an improvement in their dyskinesia but also in their motor symptoms as suggested by the N DS UPS, which is the scale we use to track uh how fast they move and how stiff they are. Um Again, this is uh predominantly unilateral and uh uh we don't have a long follow up for those patients. It's just one year and we don't have head to head comparisons with deep brain stimulation, but it led to the approval of this therapy for Parkinson's disease, which can be used. However, as I mentioned before, it is not as straightforward as a deep brain stimulation. Few patients had desire to add visual disturbance, facial weakness. Um Most recently, they also had the long term follow up study of patients with Parkinson's disease, predominantly unilateral who underwent sub thalamotomy. So including the subthalamus or STN, which is a classic target for deep brain stimulation. And I know that we're probably getting to a lot of details, but I just wanted to show videos of how those patients might look and showing that there is quite a lot of applications for focus ultrasound in different parts of the brain, especially in Parkinson's disease. And as you can see, this patient uh had significant uh rigidity tremor, bradykinesia, which has improved after high intensity focused ultrasound and that persisted after a few years. And that's what the authors are showing in this study. You can have persistent benefits after three years, as we can see by the scores uh of the M DS CPD S um part three. And again, you can see from the video that this patient had a significant improvement of their symptoms. Just wanna show the initial part that he has significant tremor. That following focus ultrasound is, is basically resolved. We also had Brady kinesia on the left which has also improved. Now, there are some limitations to focus ultrasound. Um There is a cost related with focus ultrasound, although it does not seem to be as um expensive and compared to the brain stimulation which requires uh the battery placement, the charging, the replacement of the battery, you require uh a larger group including anesthesia. Uh Although we have a diverse uh range of possibilities for focused ultrasound, we cannot put the ultrasound everywhere in the brain. We have to choose the specific parts of the brain that might might not completely resolve all of the symptoms of the patients. It is not for everyone. Um We should get this uh specific type of CT that we call skull density ratio. So we have to measure the thickness of the skull. And if they have a number that is out of this range, we might not be able to perform the procedure simply because of technical aspects of how the ultrasound beams would penetrate in their skull. As I mentioned, patients do have to shave their head completely, which for some patients is a deal breaker and they definitely don't want to go ahead with it. And there is also a side effect profile that might include gaining balance and potentially Persia. Um There has also been some other indications for um high intensity focused ultrasound. And I just wanted to show you um some of the other things that can be potentially done. In this case, they did thalamus uh ultrasound for musicians, dystonia, which is a type of uh involuntary movement that affects a certain body part related to task specific movements like playing the piano, playing the guitar or maybe writing. And I just wanted to play these videos with sound so you can hear how it sounds before and after focus ultrasound. But knowing that this is more a um uh a research prospect as of now, you don't really hear the music or the piano. So you could see how this patient before the procedure could barely play the piano because of this dystonia of his hands. And this patient was a professional uh pianist. And after the procedure, um they were able to perform in a much uh a much more accurate way. And here's someone with a focal dystonia and trying to write and that's a Japanese study. So, um, you're gonna see different letters there and the patient can. All right. And after the procedure, you're gonna see how there is an improvement of, of his symptoms. Again, not an FDA approved indication, but it shows you how, how it can be quite a powerful procedure in that sense. Now, the focus ultrasound has also been used in research for other conditions and uh I'm just showing this. So you can have a sense of how much we can do with this type of technology. And what is the, what the future looks like? Um They have been using focused ultrasound, for example, for Alzheimer's disease. They also have trials for O CD and major depressive disorder. Uh They have trials for A LS for paying and they can even use it to perform modulation of the visual cortex in a group of patients. Um So really a lot that can be done and a lot has been studied in this sense. One more interesting aspect of focused ultrasound, which again is still research. But I think it's interesting uh at least uh uh knowing about is that um it can open the blood brain barrier. So we are now talking about low intensity focused ultrasound before when we were talking about the brain lesions. That's a high intensity focused ultrasound. However, you can use low intensity focused ultrasound to open this blood brain barrier. And as you know, the blood brain barrier is a tight space that doesn't allow toxins, but also medications or any sort of compounds, uh, uh, that have a certain type of characteristic or size to cross to the brain. And that's a protective mechanism that we all have that, um, that is quite helpful for the brain to preserve its homeostasis. However, uh, it's a major challenge for drug development as some of the drugs that have been now attempted to be using in clinical trials are quite large and heavy and they cannot cross the blue barrier. So it's a, it's a major limitation for those studies. So they realize that if you give this drug and at the same time, you put um the focus ultrasound in the specific part of the brain, let's say the basal ganglia, you can open this tight space to allow the drug to leave the blood vessel for uh a few hours, which would allow them to go exactly where you want them to go in the brain. And then when you remove the focused ultrasound, this blood brain barrier closes again. Um And this has been quite uh interesting to study in conditions like Parkinson's disease, for example. And they have now clinical trials going on where they're putting this, they're giving this drug and opening the blood brain barrier at the same time. So the drug can go exactly where you want it to go. Um The future directions of po ultrasound is precision is trying to make it even more accurate. So you have less side effects and less swelling of the brain. It is potentially combining the focus ultrasound with other techniques or other neuromodulation techniques, maybe including even deep brain stimulation and uh exploring other targets in the brain to treat a broad range of disorders, including psychiatric disorders and other neurological conditions. If I could just summarize in one slide, because um a lot of people might have this question of when is indicated to have deep brain stimulation or MRI guided focused ultrasound. And what I should say is that this is a discussion that we, we have with our patients when they come to clinic and we can definitely have this discussion. It's not uh the job of the primary care physician, but it might be helpful to know what it can be done. Um um When you discuss both procedures at the same time now, so deep brain stimulation is a much uh older procedure that has been around for now 30 years. And uh MRI gotta focus on it's much newer for the past seven years. And DPS allows us to have this fine tuning so I can turn it off. I can even remove the lead if I want to. But the MRI guided focused ultrasound is irreversible because you are burning a part of the brain. Uh So you cannot have fine tuning over time. And if you have an undesired side effect, then unfortunately, you're probably gonna have to live with him. Um On the other hand, deep brain stimulation is more invasive because you need to uh make a brain incision. And it also requires general anesthesia. And that's not the case for focused ultrasound patients can be awake, they can come in and go the same day. Um In the case of D BS, they have to stay in the hospital for at least two nights, one before and one after. And they have to carry this device with them like a pacemaker at all times. And this pacemaker many times needs to be charged or potentially needs to be replaced after a few years. And we focus ultrasound as a one time procedure. You do have to shave your head completely with MRI guided focused ultrasound in D BS. That might not be the case with MRI. Got it focused ultrasound. You have an immediate benefit. They come in the morning, they go home in the afternoon with no tremor. And for D BS, you still need to do programming, you still need for the swelling to come down to turn it on. So this whole process might take up to a few months, maybe even six months. So you, you have an optimized tremor control. So it's not um they're not competing technologies, but rather they complement each other and it's at the end of the day sort of a personal decision of risks and benefits and how patients see that and how they would like to proceed before choosing the brain stimulation or MRI guided focused ultrasound. But we're quite happy to be offering this procedure for our patients. There has been a growing interest and uh we have seen a surge of uh uh patients coming to our clinic trying to learn more about focused ultrasound. Uh And we're happy to offer this uh uh education opportunities for them to make the, the the best informed decisions. And now in the next few minutes, I'm gonna um try to discuss our experience and how we have been uh using the focus ultrasound. Here was you. Um We have done our first case in December of 2023 and to my knowledge, we have seven cases date. Um maybe we have done the, the eight case in the next, in the last month. Um uh And the reason for, for having not more cases is that, but some people have a, a different impression of what bocas ultrasound is. And when they come here, we explain to them that it is a little more uh invasive because you have to burn a part of your brain. When you have side effects, they, they might refuse to have the procedure and instead they might have deep brain stimulation. Um The way we do it is that they come to our clinic or their evaluation, we confirm their diagnosis and we make sure that there is no other medication we can try or there's not a, there's not a lasting faces of possibility for those patients if still they have a lot of disability related to their symptoms, especially tremor. We refer them for uh Doctor Willie from neurosurgery who's going to, to perform the procedure before that they need to get a pre op world cup. And what is important is that they need the school density ratio, as I mentioned before. And uh it's maybe in about uh 5 to 10% of patients, they don't have an appropriate code density that would allow us to perform this procedure. Um If they are eligible, they come to the hospital and uh uh they don't have to be admitted to the hospital. They actually come in the morning and go home in the afternoon. Um They shaved their head completely. They didn't send the MRI they do the sonication, which basically means increasing the temperature in that part of the brain. So you heat it up and you burn that part of the brain during this procedure. Doctor Willy is monitoring the response in terms of tremor. So here is someone who had the tremor coming in in a few minutes later. After the ultrasound is used, we can see how they can now draw and it's much better and we then see them in clinic in about 136 and 12 months. Uh evaluating their benefit and any potential side effects. I just wanted to show the case of one of our patients who uh had this procedure done in August of this year. So this is the pre uh procedure drawing done uh in the morning, I think sometime around 8 a.m. or so. And uh a few hours later, that's probably around noon. You can see how his tremor is basically gone and he can now ride and he can draw. Um this is uh our first patient actually. And uh I just wanted to show you his scale, that's his um uh baseline scale, the tremor rating scale. And you can see that, that the gray one is uh is probably the most important one that relates to disability and how it it slowed down and came much lower over the past the next few months. And his drawing before surgery compared to after surgery. And uh he had a, a bilateral hand tremor that was quite severe. And you can see in the video that we treated his right hand only, which was very similar to the left hand. Uh So you can kind of have a sense of how his right hand is now very steady compared to his left hand. And this patient has been quite happy about his results and his tremor control uh before he couldn't write, uh he couldn't feed himself and he couldn't hold a cup of water. And after the focus ultrasound, he's now able to use his right hand to perform these activities and to be independent for AD LS. And we haven't treated his left side yet because, uh, um, it has been less than nine months and we, we have been discussing, but, uh, considering the risk of gaining balance with bilateral procedures, it is very likely that he's quite happy with just the right hand being treated. So that's probably gonna be the case. And as you can see, his balance has been quite stable, he hasn't noticed any significant worsening of his uh of his balance. And just again, showing the kind of a very drastic improvement of his right hand tremor, which was very similar to the left hand, if not worse. Um uh in terms of side effects, uh at least two patients had some uh minimal gait imbalance after the procedure, but none of them uh require a walker or wheelchair after this procedure. And I would say that probably most patients have been quite satisfied with the with the treatment. At least one patient experienced difficulty with fine motor movements, which is predominantly just playing his guitar, um which we uh we're probably describing as an issue with proper reception. Uh but it's, it's not a very common sort of side effect, but he has experienced this and yeah, thought it was worth mentioning. So if um um as uh physicians that was you or BJC or even outside, you are interested to refer patients to our clinic for evaluation of focus ultrasound. Uh you can do so by referring to the movement disorder section. Our approach is that uh these patients would first come to us in the movement disorder. So we can uh we can assess their diagnosis and make sure that there is nothing else that we can try, that is less invasive. And uh if that's the case, we'll refer him to or her to doctor Willie for the focused ultrasound. What I would suggest is, uh if, if you do make a referral, just make sure to include focused ultrasound or surgery advanced therapies, the reason for referral because that makes us see these patients faster as you know, we have quite a long wait list. Um uh However, we have reserved slots for patients who require these advanced therapies, uh which might be a little more urgent. So we can often screen them faster and see them relatively fast in probably uh a few months or less. If we have this as a reason for referral. If they come as just a movement disorders, referral, sometimes they might wait for, for quite a long time. So I would encourage uh making it quite clear that uh the patient or the physician are interested in having the focus ultrasound evaluated. Um So in conclusion, um the focus ultrasound, this is too invasive. Um um because you're burning a part of the brain, but it is less invasive because there is no incision, but it's a minimally invasive procedure with fewer surgery related complications, uh which does not require a hardware implantation uh and does not require the uh programming like D BS does and which can be quite an effective therapy to treat tremor but also other movement disorders like Parkinson's disease. It is still a relatively new procedure with a short modern history over the past uh seven years or so with less long term data of maybe five years or so. And that we still need a lot of research to understand side effects um potential long term complications and long term uh efficacy of these procedures. However, uh it can be used as uh quite a um what a fantastic treatment for uh this uh movement disorders, especially essential tremor. And uh with that, I'll conclude my presentation and have uh a few minutes for, for questions or uh concerns and I'm happy to, to uh answer any, any other questions from the audience. Thank you so much. So, there is a question if insurance approves, what is general copay for patients? Is there a general range of cost if it, if it's not covered? Yeah, in my experience, um it is quite similar to deep brain stimulation that it's a very straightforward approval process and uh uh neurosurgery especially has a great uh uh support system. Um I've never had any issues with uh related to, to copay. I think it's, it's simply um whatever is their terms with the insurance and they just have their fixed copay, whatever goes beyond it. It's, it's covered by insurance. So it's, it's relatively straightforward. It's uh uh they just, they just have their regular copay and the rest is covered by insurance. It's an FDA approved indication. So, uh they, we, we never had any issues related to, to that specifically. What are the rules of the team members that help decide if the procedure is appropriate. Um And I guess that's probably related to the, the flow of the, of the clinic and the, and the team members. And, um, um, um, I think from an initial perspective, if these patients uh are coming from outside, uh, maybe you as the physician, um, are probably thinking that, uh, you have limited abilities or resources and you have a question about it. You can feel free to refer them to one of us and we can discuss with them if they are eligible or if there is anything else that we can do. Uh And often we do see a lot of patients that just want to learn more about the procedures and we're happy to, to do that. We're happy to see patients just to answer questions, even if they're not ready for it or even if they're not good candidates. Now, we can, we can at least, uh uh have a, an open discussion, very educational about what the procedure can be done. And we usually have a longer appointment time. So we, we spend uh as the neurologist evaluating those patients, usually around one hour and a half, uh making sure they have the right diagnosis and uh uh making sure they are eligible that they have no uh potential uh uh uh contraindications. And if so we refer them to uh through the uh CT or the skull density ratio evaluation. If that's OK. They go see Doctor Willie, who is the neurosurgeon and the neurosurgeon, uh, approaches it from a very technical perspective as well. Um If they agree with our assessment of the contraindications and the potential benefits, uh, he discusses the technical aspects and make sure there's, he make sure there's nothing else. Uh, there might be an issue and, uh, and refers or does not refer a patient for, for surgery. Um, I hope that answers your question. And then let's see. Have you seen recurrence of tremors in patients treated at wash U so far? Um, we have not, um, the first patient that I showed here. Um, and I can maybe go back. Um, so this is just before surgery. This is the day after surgery and that's six months, as you can see in six months, maybe it is a slightly worse. So the tremor has perhaps, uh, uh, worsened a little bit, uh, but it's definitely not the same as it was before and the patient remains quite happy. And again, what we care about is not necessarily the drawing but the disability related to the tremor for most of these patients. Uh uh They have not uh had more significant disability related to tremors. They might have had maybe a slightly higher amplitude as compared to the day of the procedure. But uh but nothing as compared to to before the procedure. Um And as we, as we move forward, we, we gain more experience in this procedure too, especially doctor uh Doctor Wheeley, which is a very, it's a very technical procedure as well. So, um uh we understand more about specific target, the specific amount of energy that needs to be used. And that also increases the efficacy of the procedure with less side effects. But we have not seen a uh a dramatic worsening of the tremor. Uh We have certainly seen patients from uh uh other institutions uh that I can recall that have had this procedure done years ago. Uh And they came to us because they, they had uh uh recurrence of tremor. But again, we're not sure about how was the technique. Um uh it's uh the amount of sonication, the temperature, the location. Uh So we cannot answer on that. But so far, things have been quite, quite stable and relatively uh uh relatively good from an efficacy standpoint here, not seeing any other questions right now in the chat or Q and A. So, um thank you so much. I appreciate it. And then in the follow up email. I will also have an information sheet for um movement disorder and f focus ultrasound and at the front bottom right corner of that sheet, it will also reiterate kind of what um Doctor Deli was saying about how to put those patients in or refer those patients to make sure that they're seen quickly um for this specific uh either procedure or just for patients with the essential tremors. Yeah. Yeah. Thank you. Thank you Nicole. And I'm happy to, to answer any questions if you want to send me an email or if you have questions about, um, is this appropriate or not? But we, uh, we, we usually, uh, are quite open to seeing those patients. Uh, we can, so we can, uh, so we can try to make their symptoms better. I'll put your email in the follow up email as well. So, thank you so much. Um, it looks like it's 250. Um, our next speaker is not on yet. So why don't we take a quick bio break and come back at three o'clock? Thank you so much, everybody. Thank you so much. Thank you. I appreciate it. Enjoy the rest of your day. Thank you too. Take care. Bye bye. All right. You too. Bye.
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