Pallidotomy for Focal and Hemidystonia

Thank you for joining us today, Dr. Doshi.

[00:00:54] Prof. Paresh Doshi: Pleasure is mine. 

[00:00:55] Sr. Sara Schaefer: So I want to start with a little bit of background. So in this [00:01:00] study, you talk about stereotactic radiofrequency lesioning, but as we know, there are a lot of different ways to lesion the brain. So I was wondering if you might give our listeners just a, a short overview of the difference between this gamma knife radiation therapy for lesioning, focused ultrasound, and deep brain stimulation, and why you might choose this over some of those other techniques.

[00:01:27] Prof. Paresh Doshi: Radiofrequency lesioning is one of the oldest technology for lesioning in the brain. It was being used for lesioning brain targets. almost, I would say, since 1950s, since the advent of the stereotactic systems came or even before that, it is as I said, it preceded even the use of deep brain stimulation surgery.

Basically, radio frequency lesioning uses radio frequencies current. It's an alternating current which is delivered through the tip of the electrode and the tip [00:02:00] of the electrode is actually the whole electrode is insulated and the tip only is exposed and the diameter and the length of the exposed tip can define the size of the lesion.

So by the temperature control and by the width and the dimension of the tip of the electrode, you can define the size of the lesion. So it gives you an advantage of making a precise lesion. Now, as compared to that, one more point is important for the lesioning that before you lesion, you can use this electrode to stimulate that brain target.

And people doing deep brain stimulation are well aware. of intraoperative neurophysiological response and how much it helps to guide the surgical success. Because if you find side effects, you can move away from that target. If you find lesser effect, you can choose the other point in the target.

So the radiofrequency lesioning electrode helps you to actually calibrate before you actually lesion. Now, as compared to that, there are [00:03:00] other three lesioning techniques or two lesioning techniques which are very widely popularized. The third one is hardly used nowadays. I will talk about all the three.

The second is a gamma knife. Gamma knife using a focused radiation to target the lesion and it is done at certain specialized center. Gamma knife is not universally available as universally available as radio frequency lesional generator and the experience with that is restricted. There are certain centers across Europe who have greater expertise in delivering this.

The only difference between Gamma knife and a radiofrequency lesion is the lack of intraoperative neurophysiological testing. Now, that you cannot get with gamma knife. The third lesioning technique, which is very popular now, and it is getting as popular or as fancy as I would call it, is the focused ultrasound.

Because of its adaptability by the [00:04:00] Western world very fast and how it changed the scenario, we will talk about it Dr. Schaefer if we require to, in the lesioning arena over the last five years. But the focus ultrasound guided lesion uses ultrasound waves to create a focal lesion. Now, here there is an advantage that to create a lesion, which we call it in neurosurgical parlance a test lesion.

So this test lesion will provide you a similar level of improvement or assessment to tell you whether your lesion is in the right area. But because it is a test lesion, it is a reversible lesion. Now, this lesion is done usually at a temperature of 45 degrees centigrade. And we all know a thermal lesion created at a 45 degree centigrade can be reversed.

The same kind of test lesioning can be done with radio frequency lesioning also. And there is a marginal difference between [00:05:00] ultrasound guided lesion versus radio frequency lesion. Radio frequency lesion requires you to make a burr hole and insert the electrode. Now, that has an advantage and disadvantage according to me.

It helps me or helps the neurosurgeon to even record the thing the same way I would record a patient neurophysiology before doing DBS. So I can do microelectrode recording and I can do many other recordings, whereas focus ultrasound guided lesion provide some level of neurophysiological confirmation or neurophysiological feedback, but it doesn't help you to record anything intracranially. The last lesion is the cryo lesions, they were the first lesions ever made in the brain and by Irving Cooper and others. And those lesions are now hardly used because they are not very precise and they are not really calibrated. So for lesioning, the bottom line is very important.

You require a very calibrated and uniform [00:06:00] lesion, which you can assess over a period of time.

[00:06:03] Sr. Sara Schaefer: So I can imagine a table where on the left you have, you know, all of the different lesioning techniques and on the top, you might have ability to see neurophysiology invasive versus non invasive. And and ability to do a test lesion versus not do a test lesion. And you can see how all of these might fit into the different categories. So getting to your study. You looked at this radiofrequency palidotomy with dystonia patients, and importantly, only with either focal or hemidystonia patients, excluding task specific dystonia patients. What was already known about palidotomy in this patient population, and what did you hope to add to the literature with your study?

[00:06:51] Prof. Paresh Doshi: So pallidotomy is a very known surgical approach. And once again, it preceded the use of deep brain stimulation. Professor [00:07:00] Laurie Latinen and Professor Marvin Harris popularized this in 1990s for the use of Parkinson's disease. In fact it was so widely used that we, we had several centers, including centers in United States like Philip Star and other groups using this for Parkinson's disease and performing bilateral palatotomy. Some of those pallidotomies were successful and some of them were not so successful. So pallidotomy as a pallidum as a target and a pallidotomy as a surgery was not new. It was also used for dystonia because we all know that GPI globus pallidus internus is a very preferred target for most of the surgeons performing surgery for dystonia.

So, pallidotomy was known to the scientific world and to the neurosurgical fraternity. And we had been using this pallidotomy because we knew or we did not have adequate information or [00:08:00] confidence of performing bilateral pallidotomy we selected to use this for unilateral dystonia or a focal dystonia, which we know are static over two years period or more so that we know that they will not progress to become a generalized dystonia or involve opposite side of the body.

Those patients we selected for unilateral pallidotomy knowing that we will not have to revisit them again. One of the biggest advantage of the most important advantage of a lesioning surgery is that it does not require any titration, which is a disadvantage also, but it does not require a titration and it does not require to be programmed or followed up and things like that.

So it becomes very useful in certain cases where you are expecting that the disease is stable. you have a problem which can be addressed and our experience had shown that unilateral pallidotomy could be useful in hemidistonia or a focal dystonia as I explained. We [00:09:00] excluded the task specific dystonia because we had been operating task specific dystonia and we had published two big series of task specific dystonia before.

So we did not want to confound this paper with the knowledge of the literature, which already was existing and that this. So, this is going to be the reason why we published this paper on focal and hemidistonia single blinded study.

[00:09:25] Sr. Sara Schaefer: And I believe that you also mentioned in the paper that we know a lot more about short term outcomes in this type of patient population than we know about long term outcomes. So I'll rope this into the next question, which is, what did you find in your patient population both in the short term and in the long term?

And were there any differences between patients for whom this was a secondary dystonia, for example, from an encephalitis and those for whom it was a primary idiopathic dystonia?

[00:09:57] Prof. Paresh Doshi: So, that is a very interesting question. When I looked [00:10:00] at the literature, virtually I could only find one case study of a unilateral pallidotomy talking about long term outcome. especially in secondary dystonias. There were some bilateral pallidotomy series which had just been published before our paper for a primary dystonia, but that was a separate group of patients that we were talking about .

So this was a unilateral pallidotomy and there were hardly any papers to talk about the long term outcome. Short term outcome had been reported, but again as a case reports. Not any case series were there. So we thought that this would add a great value to the literature in if we publish the short term and the long term outcome.

This study was conducted over a period of 20 years. And if you can see that we hardly could collect 12 cases and out of which only 11 could be evaluated. So these are very select group of patients which can come to a high tertiary referral center. And here what we found was that the short [00:11:00] term outcome, it was uniformly positive for all patients.

What is important to note, which cannot be reflected directly in the paper, because the scores we talk about scores, we don't talk about individual issues, the individual issues, the pain was one of the most disabling features in this group of patients. And the pain was instantaneously relieved in some of the patients whom of unilateral dystonia or focal dystonia.

We did not have significant improvement. I would say 70-80 percent improvement. We only had 30-40 percent improvement. The pain did definitely get relieved. So that was our own experience which said that and that helped the quality of life of these patients. So short term outcome had uniformly improved in all patients.

Long term outcome did not improve in the total cohort of the patient. So either it did not improve to the statistically significance or we will talk about how we conducted the study later. But in the another [00:12:00] set of analysis or another group who analyze the patients, actually, it worsened. And why? When we looked at this in a little more detail, we found that three of our patients in the long term outcome group actually had progressed. And because of their progression, the overall scores reflection became skewed because we had only small numbers. If we could exclude those patients, we had almost 50 percent improvement even in the long term outcome groups.

And this was statistically significant. Coming to the primary and secondary dystonia. The blinded observers for the study did find that the primary dystonia had improvement at short term outcome and also at the long term outcome, whereas our own observations or analysis supported the short term outcome improvement, but not the long term outcome.

[00:12:51] Sr. Sara Schaefer: Okay. Yeah, you're right. I put the cart before the horse here and asked you about your results before your method. So, so tell me how [00:13:00] you underwent this analysis.

[00:13:02] Prof. Paresh Doshi: Yeah. So it was very interesting because if you look at all the lesional papers, see deep brain stimulation surgeries get funded by the industry. Why the lesional surgeries never got popularized was because there was there were never industry supports or big research grants available to analyze or study them.

And it was always perceived once the deep brain stimulation came that it is not the therapy to be adopted by the Western world or developed countries and which I don't think is right because now the entire developed world is running after MRGFUS and in Japan, the number of MRGFUS surgeries have crossed deep brain stimulation.

So, which is a developed country and in United States the essential tremor patients, I think last year or a year before last had more patients undergone MRGFUS than or a lesional surgery than DBS. So it's a question of how the world perceives a particular therapy, [00:14:00] but unfortunately radio frequency lesioning never got that attention.

So most of the case series where either case series, because obviously you can't do an RCT in this group of patients. So there were case series and observed by the observer who had operated. So we thought about that, remove the observer bias. And fortunately, over last 20 years, we had collected all the videos of patients which we could analyze in a proper manner.

So these recording videos were. Then subjected to the best, one of the best teams who are specialist in movement disorders across the globe and not in India to remove any bias. So it was evaluated by Professor Kailash Bhatia and his team in London and they evaluated in a blinded manner. And we evaluated and we put those scores together and we analyzed statistically if there was a variance between their score and our score. And you can see that in our paper, we have published blend alternate scores, which shows that all [00:15:00] the three time points, the preoperative UPI, a BFM DRS, the short term and the longterm BFM DRS, we did not have much variance between. The two team Observer A, which is us and Observer B, which is the London team.

[00:15:14] Sr. Sara Schaefer: All right. So you took patients at basically three time points. You had two different teams analyze their videos for changes in dystonia scales. And subjectively, your team also talked to the patients about their pain, which improved, which didn't make it into the paper. You did mention this small subset population that actually progressed.

And that was very interesting to me because one, you chose patients based on static disease over a couple of years prior to the radio ablation surgery. And then the other thing that was interesting about it was that some of these were actually secondary dystonia patients and, and they [00:16:00] continued to progress.

So what, how did you interpret that finding? Do you think that was a natural progression? Do you think it was a natural progression that maybe even was less of a progression than it otherwise would have been without the lesioning. Do you think that the lesioning could have caused some sort of changes to the circuitry that led to progression?

And related question, do you think that there's any way to predict who these patients might be to help us with assessing candidacy for lesioning surgeries?

[00:16:36] Prof. Paresh Doshi: Yeah, this is a very interesting question. Ourselves and our colleagues we all discuss this at great length. First of all to admit it, we had a very small number of patients to actually make any meaningful interpretation. So after even a lot of discussion, though there is a literature support which says that the patients can progress as late as up to 23 years.

[00:17:00] Lee et al had showed that it can progress after within two, three months to 23 years. And this is natural progression I'm talking about, not about post pallidotomy. What we thought was in cases of pallidotomy let me tell you a couple of things. What we had learned by during Parkinson's disease pallidotomy that if there is an inadequate lesion or a smaller lesion or suboptimal lesion, the disease can come back or disease can go miss progress.

Naturally Parkinson's disease progress. The symptoms can come back over a period off time. Now we tried to look at all these three patients who had progressed and we could not find that the lesion was not proper, but again, these are relative words we are using. Second thing was that it could have caused some changes in them, which could have led to progression.

We don't know again because it's a lesion surgery. Or it could be natural progression. I think we would require much larger number of patients [00:18:00] and keep our minds open. But as I said, this were mostly secondary dystonia patients. They were not primary. So that, and we all know that the outcome for a primary dystonia is little more favorable even for deep brain stimulation as compared to the secondary dystonia.

The same thing we have observed in lesioning also that primary dystonia patients did better with the lesioning than the secondary dystonia and which is a natural thing that we all have known. Unfortunately, we right now do not have any understanding as to why or how they would have been different here.

[00:18:31] Sr. Sara Schaefer: Yeah, of course, this is all speculative. I just wanted to see if you had any particular speculations.

[00:18:38] Prof. Paresh Doshi: We thought a lot because it was unmeaningful to make a conclusion or a assumption. So that's why we left those two thoughts open in the end of the paper saying that it could be any of this. But I think if we are aware and we are looking for it, we can always find as we progress. Yeah.

[00:18:55] Sr. Sara Schaefer: So what are the take home points after you've done all [00:19:00] these analyses and thought as hard as you have about these patients that you feel like our listeners need to walk away with and what do you think the future directions are for understanding this better?

[00:19:13] Prof. Paresh Doshi: Okay. I will take a two or three minutes more inside this because I want to also highlight the issues that might be faced because lesioning surgery, as I again keep on repeating, is getting more popular because of the MRGFUS. Unfortunately, As of today, well, while we are speaking, pallidum remains a difficult target for MRGFUS.

We cannot very easily target uniformly in all patients. So radiofrequency listening will remain the therapy of choice in my mind for pallidal listening. Now, once we know that we want to lesion a pallidum, there are many ifs and buts in this cases because sometimes when in the secondary dystonia patient, you have this areas quite atrophied.

Sometimes you have damage in this [00:20:00] area, so you might have to adjust the target. Now, as far as the take home message for the listeners is concerned the neurology part, I think if it's a unilateral focal dystonia, it is worth its try because it's a safe, effective and a successful treatment option that gives you equivalent.

If not better results than DBS without the hassles of programming and follow ups and managing these patients over a period of time.

[00:20:32] Sr. Sara Schaefer: And where do you think we can go from here?

[00:20:34] Prof. Paresh Doshi: I think if we can have larger number of groups collaborating. And putting their data together, for example, Professor Michael Okun's group is already collecting data for Tourette's syndrome. So some, some team leads the thing and collects the data. Then we may be able to have some better information or insights into that.

Otherwise, we will continue to do our work in [00:21:00] isolated area clinics and publish as case reports only.

[00:21:05] Sr. Sara Schaefer: Yeah, you're absolutely right. Global collaboration is always the answer, right?

[00:21:10] Prof. Paresh Doshi: Yeah, when the numbers are small, what do you do? Because there is no way you can collect that number of 50, 60, 70 patients to get information.

[00:21:16] Sr. Sara Schaefer: All right, well, thank you for taking the time to join us today and share your study and your thoughts on this important topic.

[00:21:25] Prof. Paresh Doshi: Thank you, Dr. Schaefer for inviting me and MDS for considering this paper as important. Thank you. [00:22:00]