And without further ado, I will call Patrick Blomstedt up to the podium from Sweden to talk about new targets for deep brain stimulation and the movement disorders. Thank you. So new targets for DBS for movement disorders. Well, unfortunately, I am not aware of that many new targets. We have a few newly created targets. We have the nucleus basalis of Maynard, and we have the PPN. The nucleus basalis of Maynard was introduced as a target for DBS for Alzheimer's disease in 85 and a few cases operated later. In 2009, we saw this case report regarding DBS in a patient with Parkinsonian dementia, where it was reported that stimulation resulted in markedly improved cognitive functions. This in combination with the fact that you can reach this target and the GPI at the same time stimulated Ludwig Skrinso and others to perform a study in six patients. Unfortunately, there was no cognitive improvement, and that is also my personal experience of this target. I'm not aware of anyone using it, so it is a dead target. Then we have the PPN. The peduncle pontine nucleus was the focus of a lot of attention and a lot of hope some years ago, and a number of very heterogenic studies were published. To deem from the most anecdotal data, PPN-DBS can improve falls and freezing of gaits in some patients, but it seems as if the optimism have faded, and now it seems to be very, very seldom that anyone is using it. So perhaps it's not a dead target, but it's not really a living target either. Then we have a number of resurrected targets from the lesional era. We have the GP, we have the substantia nigra, and the posterior septalemic area. When we implant the GPI, we will typically end up with the highest contact in the GP, and it has been noted that sometimes we see beneficial effects of stimulation here, mostly regarding freezing of gait. But the target we are today using in the GPI, that of Lexel in the posterior ventral part, was only introduced by Lighten. Before, during the lesional era, people were targeting all different parts of the GPI and GP, and some avoided the GPI. So it's not a new target, and as far as I know, the GP is never targeted intentionally today. The situation is similar regarding the substantia nigra. When implanting the STN, often the deepest contact will end up in the substantia nigra, and stimulation here has been reported to sometimes improve freezing of gait. And this is not a new target either. It was used during the lesional era in isolation or in combination with other targets, such as the campotomy. And as far as I know, it's never targeted intentionally today. It would have been interesting to participate at a meeting of the Harvard Cushing Society in 1963 in Philadelphia, because much focus during this meeting was on the substantia nigra and other subthalamic targets. As you all know, Hustler introduced the thalamotomy in 54, and this naturally led to an exploration of the underlying subthalamic area, with the development of various targets, such as the substantia nigrotomy, the campotomy, and more importantly, the subthalamotomy in the posterior subthalamic area, which was introduced in 1960 by Wartheimer. This was used in thousands of patients during the coming years, and it's important when you read the old literature to understand that the term thalamotomy was often used to encompass also these subthalamotomies. A number of comparative studies were made, suggesting it to be a more effective target than the thalamotomy. It was also one of the first targets to be used for early DBS, already in 77 by Mundinger, in the 80s by Bryson McLellan, and in 83 by Orlando Andy. Then in 87 came the introduction of modern DBS by Benabid, focusing on the VIM and later on the STM, and the PSA was more or less forgotten. But I think that we are now seeing a renaissance for the PSA or caudal sona inserta. More and more people are using it around the world, and at least most departments in Scandinavia are using this target. The terminology can be quite confusing, because people are using so many different names for the target and the procedure. But when you look at the images, they seem to place the electrodes more or less in the same place. And this includes also those making tractographies for targeting. And this is hardly surprising, because it's a quite small target, and we don't have that much freedom of choice. We don't want to put the electrode in the STM, because then it's STM DBS. No one would suggest us to put it in the internal capsule or the red nucleus, or too far posterior, because then we're afraid of the middle amnesicus. And the more anterior, we have only a narrow area between the STM and the red nucleus, where we'll mostly get side effects. And eventually, if we proceed forward, we'll get the equivalent of a campotomy. So the target area is about four millimeter in diameter at this level. So what is the target, and should we target the VIM or the PSA? Well, Velasco already in 1972 said that we are probably targeting cerebellar thalamic fibers that are passing through a narrow funnel at the level of the red nucleus and STM before dispersing into the VIM. And the reason why it might be advantageous to target these fibers at the level of the red nucleus STM is that they're here more compressed, so you will reach more of them with your field of stimulation. And secondly, it might be easier to identify these fibers based on the closely related STM and red nucleus, rather than higher up in the thalamus based on the faraway anterior and posterior commissures. There are a number of studies on PSA DBS for Parkinson's disease. Many of these have been unilateral procedures or performed in patients with tremor-dominant disease, or it's working fine. It has, however, been suggested that TBS in this area might be more effective than STM-TBS also regarding rigidity and hypokinesia. For that reason, we have recently done a randomized blinded study where the patients were randomized to either immediate surgery or best medical treatment. The patients were evaluated using UPDRS-free and evaluated by two blinded evaluators. And with stimulation only, we saw an improvement of UPDRS-free total score of 42%. And this is comparable to what you see of blinded randomized studies of STM-TBS. When we look at the profile of the improvement, then we see that we have an excellent effect on tremor, but a quite modest effect on the other symptoms. We had no decrease in the medication, and no improvement in the dyskinesia score. So it seems this is a target that is best for tremor and not other symptoms. And most people that are using it today are using it for essential tremor. There are no randomized studies comparing this target with the VIM, but there are some circumstantial evidence suggesting it to be a better target than the VIM. If we look at the published literature on the PSA, then the study seems to compare favorably with the results published after VIM-DBS, both regarding tremor reduction and especially regarding energy consumption. Also, there are several studies that have analyzed the electrode location in patients with what we call VIM-DBS. And have demonstrated that often, or even most often, the best contacts in patients with so-called VIM-DBS are located below the VIM in the posterior subthalamic area. But of course, it's better if you want to be here to target indirectly than to target the VIM and just pushing the electrode down and hoping for the best. There are further two longitudinal single center studies that have demonstrated better effect in the PSA than in the VIM. And also two reports of improvement after target revision from the VIM to the PSA after failed DBS for tremor. Just to talk a little bit about my personal experience. I've operated about 114 patients in the PSA for essential tremor. It's visual anatomical targeting. We do all procedures in general anesthesia since 2011. One single electrode track. No microelectrode recording. No intraoperative stimulation. I identify the target somewhat posterior medial to posterior tip of the STN at the level of the maximal diameter of the red nucleus. And this does also coincide with the actual field of stimulation where we get the best effect on tremor in these patients. The reason why I abandoned the VIM in 2004 was that it worked quite fine in the beginning in most of our patients, but over time we saw often deteriorating effect and increasing energy consumption. When we then compared our last 34 VIM DBS with our first 34 Sona and Sarata DBS, we had a 70% improvement in hand function and tremor in the VIM and 90% in the Sona and Sarata. Also, the long-term effect of the PSA DBS after four years is maintained and there is no increase in energy consumption over time. The energy consumption is also very low from the beginning. Typically nowadays 1.9 volts, 60 microseconds and most often one single contact. So the batteries last for a long, long time. Since we can see this target, then there is really no reason to have the patients awake and since 2011 we do procedures with the patient asleep. And when we compared our last 30 patients with awake Sona and Sarata DBS for ET with our first 30 patients that were awake, we could not see any differences in the outcome. So in conclusion, in our experience, we find the Sona and Sarata to be a better alternative than the VIM for tremor and I think this is the only one of the new targets that have a bright future. If you're interested in more details regarding the PSA, then you're welcome to visit the Stereotactic Academy at stereotactic.org. Here we have more than 100 lectures and courses and several of these are focusing on the colossal Sona and Sarata. Thank you. Thank you. Questions for Dr. Bumsel. Thank you for the presentation. So I would have one question, one comment. So you said that a nucleus basalis minor is not used. I just wanted to make you aware that in Parkinson's disease, the Wurzburg group is actually in Germany is doing a trial on cognitive decline in Parkinson's disease using the nucleus basalis minor. But it's not published results, so that might be okay, what you basically said that it's not like in clinical use. My question would be for the posterior subthalamic target and the colossal Sona and Sarata or DRT, whatever you want to call that. I totally agree that with a deeper implantation, you get better efficacy and lesser amplitude and maybe even better long-term efficacy in treating the tremor. Do you have the feeling that you're running into more side effects with dysarthria and gait disturbances if you're basically stimulating that deep and even bilaterally? Yes. Thank you first for enlightening me on the German study. Concerning side effects, they are quite different in this area from what we're used to in the VIN. And I think that when we're using this in Parkinsonian patients, then we see more of gait disturbance. But we have not seen this in the patients with essential tremor, they differ quite significantly in the response to stimulation, these two groups. Often, we see patients that will get dysarthria immediately during surgery if we do intraoperative stimulation. But I guess this is because not that we are stimulating internal capsule, but because we're affecting the coordination of the speech. And here we will see a very fast adaptation. So in the long term, we don't consider this to be a problem when programming these patients. Okay. Thank you. So I use caudal ZI as a rescue target. So, you know, in that 30% or more of patients with essential tremor in whom you target VIN and then recur at, you know, a year or five years or whatever, I will take those patients back to replace the electrode into caudal ZI. You're targeting it primarily. Do you see that same escape over time or progression of tremor, I guess, over time that requires you to do something else? No. I don't see that really. I think we had a fair share of problems in the VIN. So we were very happy with the situation when we changed to the caudal zone inserta. That is not to say that we don't have any problems in the caudal zone inserta. In approximately 10% of our patients, we will see we will have a good effect in the beginning, but then we'll start to see some problems with ataxia. We haven't seen this gait ataxia that has been published. It's in the arms. But this can be a problem, and then we need to lower the stimulation, perhaps ask the patient to stimulate fewer hours a day and so on. Then often we can keep a reasonably good effect of the stimulation also in these 10%. But some of them are not good at all. I wonder if you or anybody else in the audience has any experience in this target with directional leads or segmented leads in directional stimulation, whether you can maybe capture the beneficial effect that you're seeing and maybe overcome some of these limiting side effects with directional stimulation, given it's such a compact target. Does anybody have experience with that? We've only done a couple of cases, and it makes it much better. So we target based on DTI in that region. You occasionally are too far posterior because in the DTI technology those fibers might jump to lamniscus, so then it's very nice to be just right at that junction and then steer forward to be right in that target. And it appears to be that at least in the long, you know, we're less than 12 months out, in the short term that appears to be beneficial to use directional electrodes in there. I have a similar experience. We have now implanted 20 patients with directional stimulation in this area. The first seven we started just with ring mode, and it worked fine because the electrodes were well placed. Then we started exploring the possibilities, and then we could see that in some patients the effect was better when we had directional stimulation. And what is interesting is in several patients we did not see a better effect, but when the patient got to choose, then they chose, they wanted to have directional stimulation probably because avoidance of subclinical side effects. And actually the last case we started we were saved by directional stimulation. We had a problem with, what do you call it, MRI distortion, and I should have aborted the operation when I saw the image, but I didn't think it was that bad. And how I ended up bordering on the red nucleus and we could not get a good effect in the ring mode on any contact, but in the posterior medial direction, we had an excellent effect at both levels of stimulation. So it seems to be a valuable tool. So just a question for clarification. You are getting MRI on patients with directional leads implanted? You're doing them asleep in the MRI? Yes. I do the MRI before and then I have the OR after. Okay. All right. Thank you. Thanks very much.

deep brain stimulation

movement disorders

posterior subthalamic area

essential tremor

directional leads