View complete transcript
To answer this question, we have the pleasure to have with us Dr. Svjetlana Miocinovic from the Department of Neurology at the Emory University in Atlanta, from the United States of America. Svjetlana welcome to the MDS Podcast.
[00:00:33] Dr. Svjetlana Miocinovic: Thank you and thank you for having me.
[00:00:34] Dr. Michele Matarazzo: So you are the last author of an article published in the Movement Disorder Clinical Practice titled Patients with Cognitive Impairment in Parkinson's Disease Benefit from Deep Brain Simulation: A Case-Control Study. In this study, you analyze the retrospectively 40 subjects who underwent deep brain simulation.
We, we are going to call it just DBS and this subject also had cognitive impairment at baseline. So first of all, [00:01:00] just to start understanding what the problem is, let me ask you the main question the other way around. Why should we not do deep brain simulation in people with cognitive impairment or dementia?
[00:01:12] Dr. Svjetlana Miocinovic: So the clinical guidelines for DBS have been that dementia is a contraindication for deep brain stimulation in Parkinson's disease. But in clinical practice, we oftentimes encounter patients who have maybe mild dementia or in the paper called moderate cognitive impairment.
And so, the question is what should we do with these people? And then when you look back to see where did this guideline come from? The dementia is a contraindication. This really came from some single cases very early on in the nineties and early two thousands when DBS started and they noted that these people didn't do well.
So then these people were generally excluded from further trials on DBS that eventually led to approval of this therapy.
[00:01:53] Dr. Michele Matarazzo: Great. So, I think that the good message here is that there is always a difference between clinical practice and what [00:02:00] we read in studies and research, right? So, you did end up doing DBS in people with some degree of cognitive impairment. Now can you explain to our listeners what was your main hypothesis when you started doing this analysis?
[00:02:14] Dr. Svjetlana Miocinovic: So clinical observation has been that in some cases we may operate on people who have severe motor fluctuations or severe tremors, severe dyskinesias. And they did do well, even if they had some maybe more significant cognitive impairment. So in our center we would take people on a case by case basis.
And if there was a very strong argument for potential motor improvement, we would consider surgery even if patients maybe had cognitive impairment beyond what was used in clinical trials, and so we noticed that these people oftentimes did very well, and we wanted to quantify this and share it with the community.
[00:02:49] Dr. Michele Matarazzo: And how did you do that? What did you study in your analysis?
[00:02:52] Dr. Svjetlana Miocinovic: Yeah, so this was a retrospective analysis using our clinical quality improvement DBS database that we keep at Emory. And [00:03:00] so we searched the database to find all patients who fell into this category of moderate cognitive impairment, which we kind of almost made up this category because these are people that fall between, they are beyond mild cognitive impairments, so beyond MCI, but they don't have frank dementia.
And so we found this group of people and there were 40 of them that we had operated on in the past. And then we compared their outcomes, their UPDRS and medication outcomes to a cohort that was matched to them. A cohort of patients with normal cognition, so another 40 patients with normal cognition.
[00:03:35] Dr. Michele Matarazzo: So those will be the patients that in clinical practice are kind of borderline that you will think about maybe doing DBS, but have some doubts because of this cognitive problems. So what were the key findings and the main conclusion of this analysis?
[00:03:49] Dr. Svjetlana Miocinovic: So the key findings were that number one, these patients with cognitive impairment had statistically similar improvements in UPDRS [00:04:00] scores off medications as the patients with normal cognition, so their UPDRS part three score, which is motor exam, improved just as much as the patients who were normal cognition. So your best DBS candidates and also their levodopa equivalent daily dose reduction was similar to the patients with the normal cognition. Part four, which is the dyskinesia and complications of the fluctuations, the complications of therapy were also equally improved.
So it really, in all outcomes, the two cohorts came out the same.
[00:04:31] Dr. Michele Matarazzo: And actually I think that when we think about the risk of doing DBS in these people, well we think about the safety. Were there any major safety issue in this group, especially as compared to the control group that you were using?
[00:04:43] Dr. Svjetlana Miocinovic: Right. So that is a common concern that there will be more adverse events in people who have cognitive impairments. So we then carefully looked at all adverse events in both groups. We looked at anything that we thought could be related to the surgical procedure or stimulation.[00:05:00] And so the numbers, if you just look at the absolute numbers, there were a few more complications in the cognitive impaired cohort, but statistically, this did not differ from the normal cognition cohort.
[00:05:13] Dr. Michele Matarazzo: And do you think that was a statistical power problem or that actually there is no clear difference between the two groups?
[00:05:19] Dr. Svjetlana Miocinovic: That is a good question and a reasonable concern. So while we had 44 and 40 patients, so 80 total. Power could be a consideration. And also adverse events were not that common. So again, you have few adverse events in a relatively small group of patients. So yes, absolutely.
So I wouldn't say there's absolutely no safety issues. I think we just show that the adverse events were not grossly different than the normal cohort.
[00:05:45] Dr. Michele Matarazzo: Great. Now another I think, in my opinion at least very interesting part of your article was the analysis of the different targets in the brain and also the unilateral versus bilateral staged procedure. Can you tell me a little more about that?
[00:05:59] Dr. Svjetlana Miocinovic: [00:06:00] Yeah, so this was again, fairly heterogeneous groups. So we had patients who underwent subthalamic implantation or pallidal or even thalamic the VIM target either bilateral, simultaneous or unilateral or staged. And so we wanted to see is one strategy better than another? Because in clinical practice, people oftentimes think if somebody has cognitive impairment, maybe it's better to do unilateral surgery or maybe it's better to do globus pallidus.
And so we wanted to again quantify this effect and we didn't see any differences honestly, in either target or staging. But again, that probably is because of lack of power because once you start subdividing these 40 patients into these tiny groups, I think that really comes into effect.
[00:06:44] Dr. Michele Matarazzo: Now, one thing that you say in your study, because you ended up having more STN in the cognitively normal people. And more GPi in the cognitively impaired subjects. Now you say that that's more or less a part of what you do at your center is that you tend to do [00:07:00] more GPi in people with more frail or with more cognitive impairment and more STN in younger and cognitively normal people.
Now, would you stand in that decision? I mean, do you think that's the way we should do DBS in people with PD.
[00:07:15] Dr. Svjetlana Miocinovic: It's hard to say because again our study really wasn't powered or even intended to look at this because we didn't randomize patients into one target or another. So I can't really say that this study helped answer that question. And I think my own clinical practice probably won't change because of this.
So I would still say if you're cognitively impaired, maybe stage surgery would be gentler on the brain. So I think that's still an open question.
[00:07:42] Dr. Michele Matarazzo: Okay. Well, and actually that brings me to the next question, which you started discussing a little bit about. Which is what are the implications of these findings for the clinical practice, for the management and treatment of Parkinson's disease in people with cognitive impairment?
[00:07:57] Dr. Svjetlana Miocinovic: Yes, I'm hoping that this study will [00:08:00] empower both clinicians and patients to be able to make these decisions. Oftentimes, these are, as you said, these borderline patients that we don't necessarily know what to do with. So I think, this study will help clinicians have something they can fall back on and say well, we do have a relatively large group of patients that did do well.
But again, I just want to emphasize that we very carefully screen these patients. And so we only really considered surgery in those that can have potential for meaningful motor benefit. So I think, again, I would recommend that people not be excluded from DBS, either clinical practice or even future DBS studies just based on a cutoff of a cognitive score.
[00:08:41] Dr. Michele Matarazzo: Great. Now, what further research do you think is needed in this area? And also, do you plan to do it or we should wait for someone else to do it?
[00:08:50] Dr. Svjetlana Miocinovic: Yeah, so again, this has been the largest study so far, even with only 40 patients that has reported on outcomes. But I think more is needed. Absolutely. This is only one center study. So I [00:09:00] think it would be important to replicate this on a larger cohort of patients.
There are now efforts to have a multi-center clinical outcome study, such as RAD-PD study that just concluded, where multiple centers can contribute their data. So I think an effort along those lines would be very beneficial to really answer this question, how do these people do?
And exactly what is the best approach? What is the best target? What is the best staging approach? And also clarify are the adverse outcomes, what are the exact rates.
[00:09:31] Dr. Michele Matarazzo: Perfect. Now just one extra question. I was thinking when you have these kind of patients, I think one thing that is very important is obviously to have the experience to know what to expect and how to manage also the expectation of the patients and the family and how to explain everything and also to discuss this with the neuropsychologist and with the neurosurgeon and the neurologist. To have a multidisciplinary team is quite important.
Would you agree with that or how do you manage these kind of patients?
[00:09:59] Dr. Svjetlana Miocinovic: Yes, [00:10:00] absolutely. I think having a multidisciplinary team is really critical. And, I think the number one message from the paper is the importance of this communication between the different subspecialties that are involved in the care of these patients and also the patients themselves, really having them understand what are the possible benefits, what are the possible risks, and making the decision together as a team.
[00:10:21] Dr. Michele Matarazzo: Well, perfect. Thank you very much for your time. It has been a pleasure to have you on the MDS podcast.
[00:10:26] Dr. Svjetlana Miocinovic: Thank you.
[00:10:27] Dr. Michele Matarazzo: We have had doctor Dr. Svjetlana Miocinovic, and we have discussed the article, Patients with Cognitive Impairment in Parkinson's Disease Benefit from Deep Brain Simulation: A Case-Control Study from the Movement Disorder Clinical Practice.
To know more about this intriguing research topic, please download and read the article that is available on the website of the journal. Thank you all for listening. [00:11:00]