0:08 Hello, I’m Jim Ausman.
0:11 I'm the creator and producer of SNI. Digital.
0:16 Ah, If you didn't hear my introductory lecture on your finish with this, go back and listen to that or an annual gives you some idea of what we're trying to accomplish in this session
0:29 In this session. I think this is one of the best set of lectures I've I've heard given by Antonio de Salas. He's from the Neuro Sapiens group which he founded in Brazil, Sao Paulo, Brazil, and he's an emeritus professor of neurosurgery radiation oncology at U, C L A, and Los Angeles,
0:53 Alessandra, or glows the second speaker, who run Sir, the postgraduate program in the Neurosurgeons Institute of Education, Research and saw Paulo, she also worked.
1:07 Add to U. C L A and functional neurosurgery.
1:12 This is a talk that they're going to give Tony's going to give the first time our center is the second one It's about treating mental disorders like depression probably shouldn't call them mental disorders. Other diseases of the nervous system and Toni's going to talk about functional neurosurgery where we came from past present, and where we're going in then. After
1:39 eighty years in the future of neurosurgery he'll talk to you about her neurosurgery is going to change. We. We neurosurgeons like to operate like to clip aneurysms, but technology has advanced and we had the interventional treatments, putting coils and aneurysms and now probably over eighty percent of the aneurysms are being treated that way.
2:02 A B M's used to be resected. Now they can be treated. Both were set with surgery. What radiation surgery, which can induce thrombosis in the blood vessels and the avian Ah, and, and also by interventional treatment by end of embolism,
2:22 so there are a number of techniques and new technologies that have affected are especially their more, and Tony's going to talk to you about that He's going to talk to you about genetic surgery. How do we change? If the Dna? How do we? I operate on the molecular structure of the cell?
2:43 He's going to talk about
2:46 some major diseases in the world,
2:49 diseases like addiction affecting two billion people, or seven point, eight billion people in the world,
2:55 or depression. Alexandra is going to talk about that or obesity, almost a billion people
3:03 or chronic pain. Anxiety, obsessive, compulsive disorder. These are all diseases of the nervous system. I really mental disorders and diseases of the nervous system. They are functional diseases, and now we're beginning to understand them were beginning to know how to treat them. Tony's going to tell you about that.
3:27 There's there's a lot of technology that he's going to mention that you're aware of.
3:33 We had deep brain stimulation, initially stereo, tactically placed to stimulators or emulate certain ablation, techniques, destructive techniques of certain nuclei,
3:46 Ah, but now we've gone to using a fiber optic cables to stimulate with light cells to cause them to discharge, so we can work. And cells, and not on large areas,
4:07 we've Also seen interstitial neuro therapy.
4:11 It's it's not as precise and relax, but it's function. It works in certain kinds of diseases. High frequency ultrasound of of working on specific nuclei, specific ourselves. Somebody's reviews radio surgery to to be focused on targets to treat trigeminal neuralgia, and they can treat certain targets in the brain. We're also using techniques to stimulate the brain and and using neuromodulation techniques move an extremity or get a person or understand how a person's thinking amazing discoveries.
4:53 So there's a world of opportunity out there. There's there's diseases affecting millions, if not billions of people costing billions of dollars waiting for you to come and to find solutions. And you're the only one who can do this Because your neurosurgeon you can do craniotomy. You can open the dura stimulate the cortex. Remove a tumor stimulating the surrounding tissue and find out what they were. They're sensitive fiber tracts. We got fiber tract imaging that tells us where we are great advances,
5:31 Aware of all the identify more targets in the brain because we have 'em our technology.
5:36 Initially started with point five, then it was one point five nights, three point. O. It's up to seven point. Oh, or you should see the detail you can see where some point, Oh Tesla amazing detail
5:48 beyond what we now see most in most hospitals around the world. So many technological advances have been made that are going to help us be able to treat people better, but in the central nervous system, the diseases can be treated. You can put viral vectors. In the brains, and introduce in tactically into certain cells, and you can
6:12 alter the genetic code or alter with the metabolism, the region it, so those are the things you can do. That's going to turn out to be genetic surgery.
6:22 So there are many many things that can be done done is going to tell you about them. I'm not going to take time to go through all that. Actually. I had to listen to his lecture. I've listened to it more than why I've listened to it five times. Six types every time you listen to it, See it. I get more out of it. He covers an immense amount of material
6:45 all about the future of neurosurgery.
6:50 All the other specialties are changing neurosurgery is changing the other specialties outside the surgery, or going into molecular treatments or surgery, and surgery are still stuck in technical advancements. That's our neurosurgery is going to be.
7:06 This is one of the areas It's going to be. We're going to need to know the molecular causes of osteoarthritis
7:15 and some of the other disease retreat.
7:18 That's where neurosurgery is going to go,
7:21 so Tonio tell you about that, He'll tell you how amazing ways that have things and discover how they're getting there.
7:30 How they've seen diminish fiber tracts that are put in patients who have autistic disorder.
7:37 As an example of what's happening in brain tracks that we couldn't visualize before,
7:46 so that'll be the first talk. It said talk not only about functional neurosurgery. Future, it's about where you're going to be in the next eighteen.
7:56 Alessandro is going to give a talk about depression. I've already told you to majors disease in the world.
8:05 People. Though not a treat at
8:08 the end of her talk, she's going to come to the point where she talks about treating those people who failed drug therapy pharmacological therapy. They failed and stimulation.
8:24 Stimulation of the brain, extra cranial stimulation of the brain bagel nerves, Stimulation. They fail. That what do you do for these people? She is going to show how they stimulated, bilateral, the super orbital nurse, super armor, The nerves going to the trigeminal nerve,
8:42 and they been able. They designed a certain frequency and pattern. They been able to alter these people's behavior with depression, and I found something interesting is that. After a while, the treatment fades doesn't work as well, but they found if they keep it up, and eventually begins to work in a high percentage of people. Very very important discovery
9:07 Gonna change the field of
9:11 Cns disorders,
9:14 functional diseases,
9:17 So these are two very important talks. I think you'll enjoy them. Konstantin Slavin is one of the commentators. He sits University of Illinois in Chicago, and he. He has worked in pain. For many many years, is an expert in that subject.
9:34 You all know that. With
9:37 that. If if somebody has a limb that they've removed, the brain is reorganized, brain reorganizes itself plasticity.
9:47 It's it's how you get central pain, painful neuromas.
9:52 And Sergio can Vero is also a pain specialist is also worked on repairing the spinal cord, so this ought to be a terrific session. I suggest. If you, if if you hear it, you're probably gonna wanna see it because their slides are really very informative and very helpful, Ah, while you hope you enjoy it a comment to me a James Ousmane at Baghdad Com, if you've got any suggestions. Comments criticism we want to hear mood can do better. Thank you. Very much.
10:27 First of all I would like to present to you at the surf full session. I was asked to organize it, and that the idea is a very futuristic view of where functional neurosurgery is going to start a little bit from the past and go to the future, and I present to you results of a future. Application, such as depression, Dr, that guru, who will present the results of a stimulation, for instance, for depression, the idea is to bring to you all the technologies that are being developed at this point and functional neurosurgery. Why they are being developed in how we got there, we. I feel that the function for research is really a bad mood of his future cents an orientation is really used. It last technology possible. This is really the mindset of the neurosurgeon that the chooses to do functional neurosurgery and using all this technology has just started treat the diseases that that we were not able to treat. The before, and even now we are still developing, so I will talk about this technology is here and talk about the radio biology a little bit because we modify the gene here, and we will talk about the importance of imaging in several diseases that I will mention. Throughout my lecture today, we have a very very large group of people working with us. You know this technologists. One example of what this to a disruptive technology and that there's a very morphological, is, for instance, the treatment of aneurysms, The treatment of phone to honor his, was dominated nearest surgery for many many years, since the seventies all the way to the late eighties, the young neurosurgeon wanted to put a clipping in realism, and I, this was the top. Surgery that we could do in my time and I then came the cat that there is an hassles, designers was today, or even more, are treated with the with a interventional radiology, and his lips out of neurosurgery so we need to to be sure that we are aware of these as sad neurosurgeons mainly as functional neurosurgeons foreign ancestry, we already starting to think about using. At treating these lesions with radio surgery, so pretty soon, I, this and these. These will not be a pain in the ass knife up rearm. I will talk a little bit about this. Just disruptive technologies. Robotics up their genetic. They have the old ones radio frequency and laser, and a high frequency, ultrasound, low frequency or something and. Go through, I just feel diseases at just to recognize the people that taught me and helped me. I'm the main part of my professional life at U. C L A I, the grupo in the lab or a laboratory, and at the group of radiation from them, I learned quite a bit and actually Doctor Bergoglio. That to be speaking here, we'd asked at the start of a lot of the as scientific A. Work we did, and now all cindy administration of neuroscience, and that we are developing Ad to take about thirty percent of their neurosurgery and look at this, thirty percent of the Department of neurosurgery at U, C. L. A was treated with radiosurgery at the time I was there, and this was nineteen and two thousand and fourteen, from nineteen, ninety, to two thousand and fourteen functional neurosurgery very little
14:37 if we look. At a neurosurgery and in general, what we see, we are around here now our neurosurgery, but before and in the seventeen, hundreds of people used to buy, when they were thirty five, you know Mozart died, but thirty five great man. They were all die around here, a few of them the dove and got the sixties, but in general they died early on. And until we found the antibiotics anesthesia x -rays a see, the surgeries became possible, great quality surgery, including the aneurysm surgery I mentioned to you before, and we arrived here to sixty, when the cardiologist game, and they were able to transplant the heart three better strokes, food, proper food, proper, limitation, proper proper care of. The boy exercising, we are arriving to eighty nineties, and now they almost Ips is running to the future. We should go beyond ninety years old, But for that we need to understand our gentle. Understand and manipulate the dna. They aren't any here Scofield killing millions of people throughout the world, and because we don't understand yet quite a bit, our Jr a gene or genome. And I'm talking here with you a little bit about the high level techniques for radio, Because we can modify this molecule as ocean to you.
16:13 I call it genetic surgery. Now we can't. We need now to arrive to add the gene. We need to modify his diseased marechal, and disease to add Dna and bring it to a normal a good Dna, And how do we do that we can. In several ways, definitely with conventional surgery, have only mechanical energy now when you have heat, have biological stem cells. Growth factors. All of these skin indeed start to change the way we did surgery in the best, but photos and brought tones in viral vectors will be able to reach this molecule in the best way possible, so we take a a disease. And more local a disease and martha, Dna, and we bring it address through gene therapy to something that is becoming normal. How the which techniques can do that when we're looking at the brain, The brain is a. It's a major forest that that of cells that we need to choose each one of them in a way that we can be selective. Because
17:29 when we. What large probs here, such as for instance a Dbs, we are stimulating out the cells at once. What is the technique that can be a little bit more selective, so that begin, suppress or again is stimulate his specific cells in the brain, and if we go to the microbial world, we learned that there several of this at primitive animals. They were able to at at through Rhodopsin for dancers to open and close the channels, and with this have an action vacation, so he's for your light, and they are at opening, depending on the light. That's shiny. So if you like with China blue light, we opened a channel when we get the action potential If you shine a orange light than you suppress the channel. So we bring one molecule of Dna of that kind, You know Animo and report them in the newer one and now it multiplies as a viral vector, and that we have. Now those mala goes over, adopts in in the Wo, have a newer one U N Ur in here now with light stimulation, We can open this channels and have now a action petition, So here we are. Is stimulating this Sl? So this is very bored then developed at Mit by that I add Boyd, and and he has a thought us about this, and that and not a way of changing his doctor. Adler is putting a lot of effort than this. He is trying to change them moloch of Dna, with proper precise Ma, and images, Ap, and radiosurgery, White folk was good. Did he developed at some point Cyberknife and Gamma Knife is the gold standard of this and this is the precision that we need in all this app technology is bringing us to that level. Well this concept I developed in that twenty years ago, This isn't two thousand when one. We're modifying the molecule of Dna with radiation radiosurgery, with a three millimeter, call him later in the monkey brain. We were able to produce tyrosine hydroxylase, which is the precursor of dopamine, So this is extremely important in terms of treatment, so when you break that moloch of dna, we can add really great certainty disease that we were unable to street before, so what we need to do is harness this energy in a way that we can modify this monocles and in this way. We can indeed to start to treat diseases. We didn't tweet before producing and neurotransmitters psychiatric diseases. Neuropharmacology streaming extremely important. Here we have a lot of side effects in neuropharmacology Because they medication bolster the whole body can act. We changed neurotransmitter specific areas of the brain. We need to do that than L. L. L proposed to you that I'll be able to show. Insert certain disease that I will discuss with you. I obviously irradiation is used in cancer. Widely the validation of multiplication of cells breaking a chromosomes, making them unable to produce a myth, a myth, as he and he does not to divide to sell well, electricity, Dbs for Federal nervous stimulation, Tms light, and high, high food, local, able also to modify. Function in the brain look where we are in terms of functional notice surgery when we are using a full tones, coming from a gun, a knife, that is precise enough for us to do functional neurosurgery. We have down here, obviously tumors and malformations, Vascular malformations are important diseases to three. Morphological diseases that we can treat the. We just acknowledge that. That's why this technology progressed so fast from nineteen eighty six. When I started worth it this in at Harvard. We are now in two thousand and nineteen are almost a thirty to forty years there, and we already using Gamma knife, Cyberknife and I drank to use this zap. The new technology here are the three patients, and we have been developing this machines over the years. Ian, why we were so excited and we think this is so important because the price of medicine can fall ten times with this disease. Neurosurgery is a very expensive
22:31 technology. Right The to bring a patient to the operating room. Until the day he he. I see you, We spend a lotta money with that, so this is extremely important that began three, three machines, not invade. The brain not bring the patient into the last to let the patient working, instead of making them recover from a major surgery that will take two to three months. Maybe lose the job, or maybe even not been able to return to the job if we have a complication. In neurosurgery.
24:09 Exemple of modification of cell function here. We are a vasculature that you can obstruct because we are producing now college in type. For that accumulates around his best friend. Three. It's an arteriovenous malformation. You can modify the function of a hypothalamic karma dharma, and three to add seizures, bringing patients that are extremely as epileptic. The position of a good angle classification, and actually treating pain in the case of the middle innovation, we can see that I think this monkey in this is treating swine model that'd be developed for treating pain not only in the in the brain but also the spine, and can now study this this lesions and learn how we can get serotonin tyrosine hydroxylase glutamate. Jsc be, so we can indeed modify the function of these cells when we are focused, and your at precise, Wherever you want to get well, we can reach, because of the imaging Mri in the nineties a Nobel prize showing the importance of this technology for us to see details in the brain and three, the diseases that that were not treated before without opening to head in that. Waking the patient were high risk, and there we go epilepsy. We can modify the function of the cells and it did obtain control of the diseases marching into psychiatric diseases. Extremely bored. Then I hear this patient suffered extremely weekend, treated capsulotomy, Capsulotomy is a known,
26:05 yeah. Surgery for obsessive compulsive disorders and we are showing here that we can do this If you believe the Dbs group. If you're doing deletion group began have a little less expensive, and moreover, we in the long -term we can get a better result, so it's important not only to focus in one technology but use all of them knowing. Which one will be more effective for the population in general in the world? As we see here, it's a huge problem, addiction obesity, and chronic pain, this iron depression that we'll discuss a little bit later post traumatic disorder. These are diseases that cost a lot the society and cost a lot to the people that saw me to extremely important clinical well. We can destroy the novel concept that I'm presenting here at the manipulation of the Dna with their radiation, so this as well known in the literature, we are drifting between Terry tumors, myth, that is, is we are treating epilepsy trigeminal neuralgia, so this is a very
27:21 very versatile technique in neurosurgery and when you see here now a little bit of movement disorders, a drama. The most common and restless
27:33 legs syndrome, Parkinson's disease you looked here is half of are both still one that gives most expensive in the hospital. Right If you look at the movement disorders, arriving into hospital. The one third of Parkinson's disease dystonia look at this and grammar. His last is alas, a it difficult diseases to three, well we have already. I dominated quite a bit of the electrical stimulation in the brain. Here we have a patient that is completely independent and grammar with the her son, that helps her quite a bit, and there's two weeks after the treatment. We can see that the she recovered from that position. It's dancing now in the middle of the pandemic. She is a exercising heavy, a quite normal life. And now we see that that we can do that, but several technologies, electrical stimulation
28:36 transcranial, doppler, and in several stimulation ways of doing this, a long term, long term results already in the literature, two thousand, and at twenty one, fifteen years after, took the Olympic nucleus stimulation, which was we did what this woman received, so this is published by Atlanta. Mauro. That has a lot of experience with this in where we aren't going right where we are going Medication. Yeah, we have walls with this extremely important side effects do happen. And when we need to move on from here. Why do you want is really cure Disease is right. We want to do. We try to read the cell transplantation for Parkinson's disease. But the technology is not quite there yet I can lie And what about electricity? When can we do this? With success, yes, we can write a book. Because we are learning very fast in the past. We used to learn. We die
29:37 comparing animals autopsies, electrical stimulation during surgery, very difficult to learn. Here we were landing nineteen eighty seven injecting horseradish peroxidase, to see what we see now with the anthrax dog or a fee and undesired therapy. Where we can start to see really, I did the the target step we want, and what they would they do in the brain. When this spreads through the whole brain as C app, your amateur track measure it to do their. Though I'm Autumn is properly with the radio radiosurgery, and Dbs is extremely important. We do this for Bain will do this for Dystonia. And so envy actually see clearly what is happening when we are treating this patient, sir, with the track dog or a few, so we have a group of our young neurosurgeons South fellows with us, trying to you study this pathways for us to be able to treat not only pain, but also patients with stroke to see what we can do to happen. Effect of that fear is happening is helping us to understand for. Is this all just how can we do some plasticity to improve these? The marshmallow study at Stanford has shown that who has a good app prefer onto a striatum at tracked. This spacious can do much about this. People can do much better in life than the ones that don't have this pathways White dwell. So there's this study is are becoming extremely important for us to treat diseases that that we couldn't do before like a Ram's horn is doing a great job where we can even entered inside of the brain virtually and learn how to do things start to, stood Morrow in motivation in the brain with this technology is start to do
31:46 this to help dementia and start to understand diseases that we don't even there. Terrible diseases that bid cannot read. Then we don't know what to do with them, and actually, even in a forensic up E area of neuroscience is just starting to enter. We know that the person that's lying, take much more brain than a person that's telling the truth that Because you have to think how we gonna lie about the truth. What about the crossroad of our brain, The The the hypothalamus Here, we have two of our young guys, Daniel. And Tiago that have helped us in business studies, we brought to Brazil, the possibility of three things obesity. I'm running a little bit, so I don't get too much time here. We also are thinking about that they studies that we did that injecting here viral vectors for growth factors in this region trying to treat the Alzheimer's disease. Ptsd with electrical stimulation, All this at these people suffer quite a bit. Then what about the disorders of of eating disorders that that I will discuss with your wrapped up in the actually the psychiatric diseases, so Dr. Gregorio helped us in this clinical trial. We did it together. We planted six patients, and here is the child that they're the best patient with one hundred and seventy that the arrive to one hundred. He lost his say his stimulator went off. He gained weight again and we are changing his stimulator now For next week, actually ain't planting the electrode in the medial hypothalamus. He was better in his asleep is better than his humor in sexual function and also better in his blood pressure and you'll see his sir, saying that yes. I got better. I had tried everything before. And about the personality of his people that can accept this type of treatment is important, psych, yet the business, a psychiatric diseases that do have to add to treat. We can increase the metabolism, but that's not enough to make people lose weight sweating as if he was exercising his smiling, as if it was with the sardonic smiling of a jelastic seizures, and sweating very fast. Heavy heat sensations. What about that? Getting to the brain from outside? Yes, it can get to the brain from outside and a doctor. Will you discuss with you a little bit about the trigeminal nerve, but we know we know that that fatal nervous stimulation is important. He can even treat inflammatory diseases, so this at the brain is really the next step and. Oregon, that be have been vandal and not be able to treat diseases that we don't know how to treat until today and this is possible Foreigners. This doctor is Lavon. Is one is specialist in stimulating for forests as the occipital region for pain. They study that will be presented to you by doctor. Go to Google shows, And really? How does this stimulation goes to the brain. You can implant that we can do from outside? And it's important to think that that from outside we will be able really to treat a lot of these diseases with the Dms for instance, and it gets out of the rearm of functional neurosurgery Imaging is helping us to understand in targeting pathways for treatment that the diseases and symptoms we didn't have able to treat before a neuro stimulation is helping, already proved the principle. And we can move this on to several diseases that we still don't threat. Mainly. The psychiatric diseases are still without treatment. The in largely with a lot of side effects radiation radiosurgery, a weekend at reached the moloch of Dna optogenetics as well and we will treat the diseases that we didn't threaten the best, and we are trying to teach here the late people that that we need to treat this disease. At the, because the technology is out there, the group that worked with us in San Paulo, The group that there is a spread throughout Brazil, of them Part of neuroscience. That's just our group. A working together. Thank you very much.
36:33 I would like to introduce Dr. Gregorio or Doctor is laughing, is already in the room. It will make the introduction.
36:44 Yes, that that that was wonderful presentation that Antonio did sites very impressive How you were able to fit so much information was in forty minutes of talk. This is this beautiful overview of all the current and future situation, and I think I think that's that's that's how we're going to be developing. I look forward to here Alessandra Stalker, and it's it's a great pleasure to introduce Alexandra. And it's nice to see you all the way from Brazil looking so great. And the moderator do to where I see them online As well. He looked great, too
37:18 alright, Thank you very much. It's it's a great thing, y'all and I look forward to hear all listen to Stoke, and then maybe we can have some time to discuss them as well.
37:27 Okay, Ah, thank you, Oh, all right, I'm trying to share it. Thanks for the invitation to be here. It's really a pleasure to be here. And to be part of the summit, I know Ah, Professor Ousmane is always very very proactive on fostering knowledge throughout the world, and the I know Dr. Epstein is also doing a lot of effort to to keep up with the The objectives here, so thank you very much for it. We decided his doctorate is lobbying. Doctor cannot afford a vacation, so I'll try then
38:14 he might talk a within the allotted time, and that the idea here is to discuss with you and hopefully convince you that there is the surgical removal. In depression treatment, I know this is not the most difficult to convince the audience that, but I think it's important to discuss about this, so we know this is the most common psychiatric disorder and we have about one hundred sixty three meeting people with this disease and deaths according to the most recent of demographics of India, percentage of depressed. People have actually increased even though life got better throughout the centuries. For some reason, environmental or stress, whatever depression rates are really growing up into the population and we know that thirty to thirty five percent of these patients are treatment resistant, and debt accounts for fifty percent of the expenditure according to American and European. His statistics on their money spending the movies Disney, so it's it is a heavy burden, terms of suffering terms of number of people, ending terms of costs with the disease, so we have to think and we know that depression is way more complicated to think from the neurosurgical standpoint in comparison to other functional diseases that we treat moving away from tremor that. Relatively be steam beer, even though it's not that simple towards a disease that we can't really focus on one year and was near on one target one at work, and we know that are many many other. If genetic factors that play an important role, so this is. I think it's very important to keep in mind what we currently have as a standard for treatment of depression and that was. I'm my opinion as a neurosurgeon, the most important trial that was sponsored by the Nih That was the stated to beat him into the to do the stages, treatment alternatives that for a depression, and that trialing, rolled over three thousand patients, using really recruiting criteria from the average population patients, and very. Complicated design to get it here, but basically they started with one medication and the patient didn't respond. They move. They moved on four different types of antidepressants antidepressants, and also with augmentation therapies, and they kept on continuing at four levels, for just patience in what they found out. It's actually very similar to the results from it left the medication trials if you give one drug. And you have your a better shot on getting this patients to respond. If you try the second drug, then you still have a good chance. But then when we start adding more and more medications, three, four in one, the patient therapies the percentage gain that you get for that is very very modest, and also maintenance, and for for the control of the depression is also. War as you add more layers of treatment, and that's an important point because we we are searching, so we accept that, but we have the task to convince the nations that we don't see surgery as the last resource we should think about identifying in a very clever way earlier on who are going to be. The refractory cases for medication, and we should consider offering other types of treatments, or the or one of his lead, that are all the issues regarding proper selection, etc, but as surgery doesn't mean a much higher risk, if when you compare all the side effects of Bali therapy and lack of the.
42:44 At the rainsy to to the treatment, we have drop out rates, ranging the literature from thirty percent to fifty percent when the the prescribers, so we are thinking we are tweaking his patients, but actually they are left to luck until they are. You know labeled as very very resistant and can have another access to other types of treatments. Also, it's very important to think when we called senior to our success. Criteria our trials there today's a huge difference in the long -term punctual between re meters and responders. So we are talking really about as the gold standard about achieving remission of depression. If you see, hear the different levels of maintenance of success of the therapy. This is one year of relapse. This is one year. And maintenance, so. When are you compare? You have relapses rate, that are pretty much almost double in there ones that were responders, but we're not read. Ingredients. Should, So what about the letter of if therapy? A date is very interesting because it was given to patients before the development of the drugs, so he should look at the old literature. We have been throwing them out fifty to seventy percent of the cases sixty five, but asked obviously. Medication treatment got better. We do have a electroconvulsive therapy been indicated only in patients who are refractory or treatment resistant depression, and then Yeah, we have a dropping the success rates, and it is this steal a very effective treatment, so we do have fifty percent of acute response, even for this very difficult to treat. Population, however, it is a short list of therapy, so we have among the fifty percents responders. We had thirty seven percent of recurrences six months and fifty percent at one year, So it idiot. It is helpful, but we need to having lying debt does is not a definitive treatment. It it is helpful, but we need to add something to keep. His patient functioning, and then we have to think from and in, I'm going to not to discuss Tms or a T. D C 's because I don't have find here, but now let's move afford to eat less invasive surgical procedure, taking into account pretty sure stimulation, so the vagus nerve stimulation has been going on for all now almost twenty years for depression, and it didn't lounge in. Why did any lounge? Besides the issues with payment
45:39 there, there were two negative Rct trials and problems with the design dining to evaluate really the results, but if we look at the author, the open label trials in also. Indeed, Vms in the setting of his target trial, so as a alternative, a surgical alternative for those who are resistant to the four levels of treatment, the results are way more in.
56:33 It is I read online with better outcomes that we could expect. Obviously does this one single center Chios mall, simple size. In terms of complications. It was very well tolerated, so acutely the all of them had paying, and swearing, and long time to adapt to the presence of the stimulator, Hear the generator here, but. They all get along. Go along with this, but we didn't need to reposition the leading three patients. Because it was a little bit pointed towards different, and we were able to keep the medications is stable and I. This is a one of the patients is just a
57:15 She until she fell, she casually have been encouraged to see. A diamond she quit as he was a year to buy that suit down for animals. In these footnote. The sleeves. She doesn't want British academy. The boys still really see a walk or a medical usefulness, and that is talked about 'em behavior, learning, she said, singing the damage to the famous was assumed that.
57:46 Please was the data so explicit kinds of feeding silly born. She seemed to go the past year.
57:56 Oh, I will just skip the conclusions by the F of his knee, Neat was very very. Positive in terms of improvement in patient and out, but we didn't address mechanism of action in August. We need a larger sample and cease. I have one minute and a half hour. Just touch upon decrease the relation. I don't need to review the literature for this audience, but I movie from less -invasive to war invasive, and four Dbs. We have amounted to a Gulf, targets and easier. It's really fair to think that one target will be the best. I'm on the champion. Among all of them bore me to thinking a more
58:40 personalized way. So basically we had two targets that took the The Dbs to the faced with trials. One was the Cbs
58:51 from the group
58:54 in Cleveland, and that when they went to the randomized trial. Unfortunately, he didn't. Truth, so that was sponsored by Red twenty, and then a lot of teachers under power, blanket Face was too short, only bipolar settings, very very rigid protocol, so majority toward men, So probably it didn't help
59:18 Italy. There was a rush to move to Phase two and the thing happened with the single singular. Targeted that was proposed by me bored, and when you go to a larger multi stage trick, even though it wasn't for the lies that was the study sponsored by centered again, he didn't come through so again, a lot of issues, and but very cook at between the crowds, so she started to looking out for the position. Then I thought not comical position of the target, The decline activity, and she needs a small perspective and and she. He got written respectively, analyzing only the successful cases, and then she did April a prospective small child showing a much better response rate among Uh dissertations, So that's a different way. If we look at the The review of the literature in Dbs. We see that overall the trials are very short duration of stimulation, and then you'll cross over, and then we'd show the hour trial that does is too short. It's did to make your wash out or change targets, so adapting designs are coming up. This is more interesting to allow us to take advantage of that child. That's extremely expensive and hard to recruit and we need to be a little bit more flexible to get the best out of this opportunity, so we need to have a serious registry on this in order to make comparisons and we are moving towards personalized Dbs so. We are refining. Queen is the best target we network in when we should, says that network, according to distinct symptom of the patient and I, we in obviously does is very very elegant, but it's also very very complex, so it's very expensive and I, I think we will actually come up with different approaches different surgeries to different levels of patients with. It, but I think I said, does not a. The Dps is Peter. Two periods here on nerve stimulation, or does is superior to Tms. I think it is the broad range, as an showed him crystallites. He did show that we need to think big, and take advantage of all the opportunities and energies and targets and treme who are the best candidates for which the treatment in maybe. At Pdc nerve stimulation may be a step or offered for patients before they go to Bs, or you will find markers that will predict it esteemed peers to perform for short, it beach south to a broader area in the brain, but we need to see. I. I think the main purpose here is really to take this patients earlier on for a faith in surgical. The Hoxton
1:02:20 so we can really cruel the depression care overall, so thank you very much. This is my email here. In case anybody would retell textured electric. This was wonderful. This was wonderful, etc once again, I think you, you, you and and Antonio. Are you sure you show the wonderful overview of what's going on in functional neurosurgery. The, The depression is obviously frontier for us and the fact that we are able to offer this patience. Multitude of treatments even hypothetically or theoretically as approach, That's already very promising, but you know, I remember. Maybe fifteen years ago we were talking about getting rid of stereotactic frames, and thus switching to frameless approach and I in surgery and radiosurgery, and people were discussing it, and you know beating each other, and in the next question is will was still continue invasive interventions in the future, do you think based on your experience and based on what you see? Is there still room for neurosurgery in the future or are we going to go away? Was that was invasive interventional approaches altogether and switch to something transcutaneous or the remote, and will have some kind of bluetooth receiver in our in our head or next to trigeminal nerve, and you be simulating it from across the room and where do you think we stand on that based on what you read and seen and done in this field That how far do you think we are from? Eliminating the invasiveness
1:03:49 Cohen's doing a ghost The first state.
1:03:53 Yeah, I can. I think I. I pushed that quite a bit. I think that's why Costa in fail to offended by what I'm seeing Because he's a surgeon and I am as well, so we don't want to lose our job, but the reality Constantine is that the patient doesn't let us. What they want is something that's non invasive. They want to suffer less, and they want to pay less and they want to be well, so we need to be very aware of that and offered to them therapies that are are less and less invasive to them. In the future. It's true it's going to happen. It's happening, right the patient before they arrived, was there having Pms. And they're having all kinds of transcranial electrical stimulation. It wasn't New England journal, so we have to be quite aware that The. Our our field is decreasing in size. However, I can tell you that we still have a very important function because we are the only ones that. In arrive inside of the brain and change function of cells and destroy tumors, or wherever you wanted to do, a neurosurgeons are the ones that have the door we can enter, so we just needed to accept that our our talent is being disrupted, run and and I'm very happy to see that, because you know I've got back to that. We are the biggest protectors of patients and we wanted to be as as less invasive as possible. Yes, now I want to touch upon little bit what Alexandra mentioned in the very end of her speech. There the presence of biomarkers. I think It's It's still quite barbaric that we use the same procedure for everybody you know people have tremor. Which is go for one target Doesn't matter what kind of tremor. It is. You will have Parkinson's, despite old variability or presentations were going for one target with depression. We have multiple targets, but we still using them. Indiscriminately it's either somebody gets one stargate than one stand there. Somebody get another target another center and the papers that you showed with published within the last few years about biomarkers and personalized treatments. I think they, they, they kind of have paved the way towards a future individualized approaches now based on what you've seen in your practice and read the literature. How far do you think were from very practical and easy to stamp markers for our treatments in functional neurosurgery. I e, for well, I'll I'll focus on depression. First. I think there are diseases that rear closer to get to this, but depression. In my opinion, it's not one of them and the reason why I Ii net. If you look at the picture, the psychiatrists had been looking for this intensively for the past fifteen twenty years. I mean they try to classify the cell types of depressions. Nothing came out. Now that are all these huge initiatives of the brain mapping, send all this data getting pulled together, aiming to see the width of gray matter, white matter, D T I data, but depression is so complicated and you know each child leads to a different conclusion, so I think that's the way, and now he have all these trials coming up in inserting ten. Seven ten fifty roads and trying to record and try to find her. You know whatever electrophysiological marker for this, but I think it is a really did deeds these itself. It's a mixed pool, so I think we'll reach out to this earlier on. Maybe he knows Cd even though we treat the symptoms. We don't treat disease, so, but but I think the O C D population Mr clean your population to get to some conclusions in comparison to the depression population. But I think it's the only way we'll get to this. I mean they tried to inflammatory markers, then gulf chronological markers of a. They tried all the demographics that you can. I mean if you look at the psychiatric literature. These people have done a tremendous job trying to find something, but I think probably the knowledge will come from our our side of things. I think at the functionality of the the brain of the the brain. The dorms. We we will end up finding something,
1:08:54 thank you very much, that was wonderful, very educational, and very very very futuristic, thank you. It very much, thank you.
1:09:02 Was nice seeing you all.