Well, good morning everyone, thank you for joining us. My name is Joel Stein, I'm the session director for this program. You're here for Maximizing Stroke Recovery, Debating the Controversies, and it really should be an interesting and engaging presentation. Before we get started, I just want to make a few reminders that the Academy asked us to make. One is to remind you to mute your cell phones, if you haven't already done so, and that recording of the session is not allowed. There are evaluation forms online, and you can access them through the app or through the website, so please do those. And they asked me to remind you to visit the pavilion, if you haven't already, where there are snacks and people who are happy to sell you things, some of which we'll talk about here. Without further ado, I will welcome our moderator for this session, Dr. Michael O'Dell. Dr. O'Dell is Professor Emeritus at Weill Cornell Medicine, from the Department of Rehabilitation Medicine there, where he previously served as Vice Chair of the department and Chief of our clinical operations. Mike is an extremely experienced clinical trialist in stroke rehabilitation, and some of the topics we'll be discussing here are areas that, studies that he was very directly involved in, including the vagal nerve stimulator study we'll be touching on, as well as the fastest trial for lower extremity FES. So it is really a pleasure to have Mike here to moderate our session, and he will introduce the panelists, one of whom is running a few minutes late, but will be here shortly. Excellent. Thank you, Joel. Before I explain sort of the format for proceedings this morning, I do want to introduce our panelists for today. I'm actually going to start with our course director, Dr. Stein, not only because he's the most senior, but because he's the most articulate, the smartest, and the best looking, and he also happens to be my boss. Former boss. Former, and even current boss. Dr. Stein is the Physiatrist-in-Chief at New York Presbyterian Hospital in New York City, but he's also the Academic Chair at both Weill Cornell Medicine at Cornell, and he's also the Baruch Professor and Chair of the Department of Rehabilitation and Regenerative Medicine at Columbia University. To his left is Professor Vu Nguyen. He is the Robert B. Kyle Endowed Professor and Chair at the Department of Physical Medicine and Rehabilitation at the Hirsing School of Medicine at the University of Alabama at Birmingham. And running just a little bit late, and who should be joining us in just a few minutes, is Preeti Raghavan. She is the Associate Professor and Vice Chair of Research right here in Baltimore at the Johns Hopkins University School of Medicine. She's also the Sheikh Khalifa Professor and Director of the Motor Recovery Research Lab and the Center for Excellence for Treatment of Recovery and Rehabilitation at the Sheikh Khalifa Stroke Institute. Very distinguished panel. Our format this morning is going to be that I'm going to read off a short vignette of a clinical scenario, and then I will call on one of our panelists to make just some initial comments about how he or she would manage that case. We're going to spend just a few minutes among the panelists discussing perhaps agreements or disagreements about how that case would be managed. We're going to call for questions from the floor, not until the end. I will try to manage time the best I can. We have seven or eight different vignettes. I will try to move this along the best I can. We'll call for questions about whatever we're discussing, and then we'll try to pull your comments in at the end if we can. So to start out, and this will go to Dr. Wim, a 45-year-old right-handed woman has a left carotid dissection after a motorcycle accident with resulting stroke and an incomplete left MCA territory stroke. Six months have elapsed, and she has completed a usual rehabilitation with good recovery of walking ability and near resolution of her expressive aphasia, but she still has very limited use of her right dominant hand, despite the ability to open and close her hand with increasing time and effort, and some ability to extend the wrist actively. She's had very little progress recently. She has minimal spasticity. She's read about CIMT, constraint-induced motor therapy, and is asking if this is available from her current occupational therapist. She is unable to pay out-of-pocket for this therapy and needs the care locally. Dr. Vu, is CIMT feasible for this patient, and even if it's feasible, is it useful at this time? Thank you, Mike. So, just to recap, because that's a lot of history, so this is a 45-year-old woman. And CIMT is... I'm from the gym. C-I-M-T-A-S-H-E-R-Y-O-U-S-E-N-D-A-Y-O-U-S-E-N-D-A-Y-O-U-S-E-N-D-A-Y-O-U-S-E-N-D-A-Y-O-U-S-E-N-D I'm gonna save on the cons until a bit later, but just basically to answer Dr. O'Dell's question. Sorry Greg, I think it's your... I think it's your aged ears, but... Totally. So for my approach, I would basically start out with a phased approach, given the fact that she already has an occupational therapist that she's working with. So what we would want to do is we would want to utilize occupational codes, occupational therapy codes that's already in existence so that we don't have to reinvent the wheel for that. And one of the things that we have to remember is therapists typically approach therapeutic intervention in a task practice perspective. So in a task practice perspective, what they're doing is that essentially they're using a motion and focus on repetition and repeating that repetition. And that's how we... basically that's how occupational therapy approaches it. What we want to do in CIMT is we want to approach it in a shaping or behavioral shaping approach where you can utilize goals. So the patient should have an individual goal of trying to improve every single time. So once they have achieved a certain goal, they should try to basically breach that goal or break that goal at the next time. You should try to use a coach and the coach could be... doesn't necessarily have to be somebody trained. The coach could be a family member, a friend that basically can be cued in to give support and courage on the specific behavior. And then you can also utilize technologies such as a stopwatch. The reason why I said phase approaches, what we could do is that we could break it down to specific motions, right? So in this particular patient, we would want to have increased wrist extension, increased finger abduction, increased finger extension. So we can approach it with one function, time the patient and have a repetition that essentially improve over time in terms of faster and faster and faster, which is what we call behavioral shaping. Once the patient has reached a level or a threshold that we feel is appropriate for that function, then we add the other function. And then again, it's repeating of step one where essentially we continue to repeat that, which is back to what the therapist is familiar with, the task practice. And once they achieve that next function, then go on to the third function and so on. And that's how you would do a phase approach for somebody who doesn't have funding to go through a complete course of CIMT. And then the final thing is you could consider a modified constraint program that the patient could carry out at home in a similar fashion to what the occupational therapist is already doing in the gym. Dr. Stein, do you have a quick comment before we go on to the next case? Sure. So thanks. Can you guys hear me? Thanks. That was great. I think, you know, in some sense, constraint isn't controversial. I think we all recognize that the literature is pretty clear here, but the logistics of this are daunting. And so I think the questions that I ask myself is really, is constraint actually necessary to achieve the benefits here? And I think there's not really clarity on that issue. It hasn't been studied as well as it should be, but probably not. It's probably not about tying down one arm. It's probably about using the arm that is impaired. And then the other piece is, and this is sort of alluded to in Boo's sort of strategy here, is to spread it out. You know, the initial descriptions of this therapy were very intensive and very short term. And that's difficult for many patients to get through. And it's certainly difficult for us to deliver. There's a presumption that we can achieve the same or similar benefits with more distributed therapy over a longer period of time. There have been some small studies that have looked at that. It hasn't really been as well examined as it should be. But I think we mostly believe that it can be. And so the strategy here, especially since she can't pay out of pocket for a six hour a day kind of program, is to, in fact, encourage her to participate in a more spread out, distributed strategy. And I think that makes sense. Dr. Raghavan, welcome. Thank you. Thank you for letting me be fashionably late. Terrific. Thank you. Moving on. Three months later, this same patient has learned of a self-pay upper limb robotics program available at a rehabilitation hospital in the area. She really wants to try this but is worried, again, about the cost and is asking whether it's worth it. She and her spouse have equity built in their house and are willing to take out a second mortgage if need be to fund this therapy. Dr. Stein, what do you advise her? Does this type of upper extremity limb robotics therapy matter in this case? Would some robotic system be worthwhile in this scenario and others not? Sure. What I would say is come join our clinical trial. I think it's really, this comes up a lot. I think people are excited about robotics, the notion of it, doing something novel and the technology is all around us. If you walk through the exhibit hall, you'll see it. But I think it's important from my perspective, and I emphasize this with patients, that robotic aided rehabilitation is a form of exercise fundamentally. We have not yet shown convincingly that it is superior to all other forms of exercise. It is perhaps labor savings, it's certainly engaging for some patients, there's games that can be incorporated, and ultimately, I think if we're smart enough, we'll build algorithms that maybe are better than what a human therapist can do, but we're still working towards that. So I'm not convinced that she needs to take out a second mortgage on her home to get robot aided therapy, because I think the benefits motorically are probably not that dissimilar from what she could get from other forms of therapy. Most of the studies of robotic aided therapy for the upper limb have shown improvements in the upper extremity fugal mire in the range of, say, three to five points, broadly stated. And for those who aren't familiar with this scale, it's a motor impairment scale that runs from zero to 66, 66 being normal. So without knowing the details of the scale, three to five points on a 66 point scale probably isn't that big a difference, and I think that's a challenge in our motor rehab for chronic stable patients in general, but certainly in terms of spending a lot of money on robot aided therapy at this point, I'm not sure that would be worth a second mortgage. In terms of comparing robots to other forms of exercise, there have been a couple of studies that have done this pretty well. One is the study of the Armin robot. This was published in Lancet Neurology in 2014, that found that robot aided therapy was a hair better, one point better on the upper extremity fugal mire compared to regular dose-matched exercises, which I don't think is clinically meaningful. And then the Ratul study, which was a British study published in the Lancet in 2019, found that dose-matched therapy provided equivalent benefits to robotic therapy. Obviously not every robot's the same, and I think that this is not a forever statement, but this is where we are now. Voorhees, are you going to refer him to your cousin Robert, who's the mortgage broker? I don't know any financier person. So yeah, definitely I agree with Dr. Stein's comment in regards to, at this junction in medical practice, robotic therapy would not consider it to be superior to interventions that are standard with PT and OT. So stated, basically things that we could utilize is the advantages of robotics is what? The advantages of robotics is that it decreases the human intervention requirement. And so if you have the technology available and the patient doesn't have to pay out of pocket at no cost, then you can actually integrate the utilization of robotics with your therapy. So you can, again, like similar to my phase approach with CIMT, you could work on a specific function, you know, elbow flexion extension, get the patient through that phase before you develop the next section, working on wrist flexion and extension. And, you know, so that essentially saves the therapy time and manpower, which is really costs in our way. But there are now new, cost-effective, smaller robots, as you were alluding to, Dr. Woo, that, as long, the key thing I keep telling my patients is, you need to move. Anything that will facilitate that movement. rehab toys that could help patients, and I think those are worth a try. But Preeti, as in so many devices that are on the market, do we have the data? Yeah, that's a great question. She's going to lay money out, do we have the data to show that it's efficacious? Terrific. Go ahead, John. I'm sorry. In terms of the future of robotics, just to comment, you know, there is an interest in wearable devices that would allow people to use this device in the home setting, hopefully, and use it to engage in activities around their house. And that may not be any more magical than any other robot, but it might sort of cross the barrier of getting more therapy. Because that's really the big barrier. How do you get more treatment time? How do you get more exercise time? And so if we don't do that, we're not going to get anywhere. And so if we can develop robots that are easily used in a home environment, wearable, and incorporated into ADLs, then maybe we can actually get more practice time and achieve greater benefits. Please jot your questions down in the Q&A box, and we'll be happy to answer them. Thank you. Please jot your questions down. We will leave time at the end for the audience to ask questions, so jot them down so we remember them. Moving on to a new case. A 68-year-old right-handed retired electrician has a right internal capsular stroke with a pure left motor hemiplegia. Six weeks, not months, six weeks have elapsed, and he has completed inpatient rehab and is starting outpatient OT and PT. He has very limited return of movement in his left upper extremity with some shoulder abduction and flexion, elbow flexion extension, and limited finger flexion without active finger extension or individualization of the digits. He's an electrician, and naturally, he's wondering whether electrical stimulation might help with his arm recovery. His OT has tried a few sessions with the Bioness FES device, and he's wondering if he should purchase or lease one, despite the fact his insurance will not cover the cost of this device. Dr. Raghavan, how useful would this treatment be in recovering meaningful arm movement, and would you advise him to discontinue the FES device, use it only during occupational therapy sessions, or to purchase a device for use at home? Yeah, thank you. So, there's been quite a bit of... So I think, in general, the data is pointing to, number one, the patient, just giving FES alone may not be enough. The patient has to attempt to activate. So giving electrical stimulation in conjunction with therapy is better than giving electrical stimulation alone. Second is, what kind of electrical stimulation? There's EMG-triggered electrical stimulation, where the patient is trying, they get feedback from their EMG signals that they are indeed trying, and then the electrical stimulation amplifies that signal. That's been shown to promote more active muscle activation. More recently... audience. So this is, again, the idea is that you're trying, you're opening your contralateral unaffected hand and stimulating the same muscles on the affected side, right? So in some ways, you're trying to connect the activity that you have with the activity that you don't have, and we know that signals from the two sides actually can collaborate towards increasing muscle activation. But electrical stimulation, most importantly, is an adjunct to active treatment. So that's the most important takeaway. I wouldn't ask the patient to take out a mortgage to pay for the bioness or, you know, I think there are other ways. Dr. Stein, Dr. Nguyen. So, when we talk about functional electrical stimulation, I always go back to basic physics, right? For the engineers in this room, you know, V equals IR. Voltage equals impedance times resistance. And that's always a concern to me in regards to how long do you treat? We know that in order for you to drive the voltage through the resistance of tissue, you have to increase the amperage. Well, what's the problem with amperage? Amperage is what kills you when you stick your finger in the electrical socket, right? It's what burns your tissue. And so, the longer you treat, the higher intensity that you increase the amperage, the more likelihood of you having soft tissue injury. And unfortunately, at this junction in medicine, we do not have that answer yet. And so, that's another concern that I would want you to keep in mind. Well, I have to say that I'm concerned about any mention of physics. It brings back bad memories, but I got through it. So, you know, I think the commercially available devices, correct me if I'm wrong, are safe when used as appropriate. Although, I agree that obviously, if you were amped up beyond that, you could get in trouble. I guess the concern that I would have here is, is it worth it? You know, is this investment of money sort of going to provide that much benefit? This patient doesn't have a great prognosis at this point. You know, they're six weeks out. They don't really have a lot of recovery. But it's still relatively early, and you know, we can be surprised. I certainly wouldn't give up on therapy, but I would probably encourage them to either find a cheaper solution or maybe to use electrical stimulation in the therapy sessions as an adjunct, rather than to get their own expensive device. And, you know, there are leases also as another option for some of these devices. So, you know, it's an option for the patient maybe to try it for a few weeks and see. Okay. Moving on to the next case. A 57-year-old woman with obesity type 2 diabetes with mild sensory loss in her toes and both feet presumably due to diabetic peripheral neuropathy and right hemiparesis due to a stroke two years ago has difficulty adjusting to the use of an ankle foot orthosis. She'd had several different kinds of AFOs, plastic, hinged carbon fiber, but often walks without a brace despite significant foot drop. She has adopted a circumducted gait that is slower than it is with using a brace. She is managing to get around the community and has had no recent falls. She is asking about obtaining a Bioness or WalkAid electrical stimulation device as an alternative to an ankle foot orthosis and is hoping that this will improve the motor control of her leg and improve her function on a long-term basis. Dr. Stein, even if it doesn't assist with her recovery, she still thinks it would be preferable to an AFO. Her insurance will not cover the cost of this device. What do you advise her to do? Sure. Well, this is a great case. I'm sure all of you in the audience here who treat stroke survivors have patients who walk a lot better with a brace and won't use it. It used to frustrate me and now I've sort of learned to accept it. But I think here you have somebody who's willing to try something else as an alternative and assuming that she gets the right, obviously not a great response to these things, you want to try it out before you make a commitment, this is actually a potentially good candidate for this. The fastest trial that Dr. O'Dell was involved in and other clinical trials have shown that these devices provide benefits very comparable functionally to an AFO. So they are a reasonable substitute for people that like them and patient satisfaction appears to be higher. Now what drives that is hard to know and maybe it's a subtle difference in function or maybe it's just they don't like the brace and it feels less brace-like to them. But I think we've all seen in our practices patients who really like these and patients who have no interest in them and don't really benefit from them. They don't contribute to motor recovery as far as we can see and I think that's really important to clarify to any patient who's thinking about this. So they don't go in with the expectation that they'll use this and then they won't need it because their leg will get better as a result. So I think that finances obviously have to be sorted out. I can't answer that for the patient, but it's a reasonable thing to try. It would be great to try in therapy first before making a decision. I 100% agree about the neuropathy issue. You really need to make sure that it will work for her, no question. One of my favorite questions to the residents in a brace clinic is what's the greatest contraindication to a functional electrical stimulation device for gait and the answer is poverty. It really is frustrating and the fastest trial I might also add in both the AFO and the functional electrical stimulation group. These folks also walked faster over time without the device. There is a therapeutic effect to the device and AFO. For some reason, whether that is a central effect, a peripheral muscle effect, or perhaps even a cardiopulmonary effect over time because they were walking, they got a conditioning effect, these folks walked faster by use of either device over time as well, which is also an important point to keep in mind. Next case, a 74-year-old transgender man, pronouns they there, is very self-conscious about the appearance of their right arm, which is largely nonfunctional after a left MCA stroke 18 months ago. The patient is left-handed, managing their ADLs well, despite only being able to use the right upper extremity as a gross assist. They wish to find out about vagal nerve stimulation, which has recently become available at your hospital and is covered by the patient's insurance. They have type 2 diabetes and had a lower limb wound from minor trauma that took two months to heal last year. They are inquiring about the likely benefits to their parotid upper limb and the risk benefit to this therapy. Dr. Nguyen, what advice do you have for this patient? So, to recap, basically this is a 74-year-old transgender male with a left middle cerebral artery distribution infarct and a right upper extremity paresis. The patient has insurance coverage, the patient has diabetes with poor wound healing. So most physicians look at vagus nerve stimulation as basically a top-down, neck-down stimulation and erroneously think of it as a sympathetic, basically, I'm sorry, a parasympathetic situation where it's actually, what we're looking at is afferent fibers that are actually going upwards to the locus coeruleus and basically, sorry, are you not hearing at all back there? Okay, and so basically what it is, it's a down-regulating, is that better, I'm projecting much better, it's a down-regulating of the sympathetic fibers instead of an up-regulating of the parasympathetic fibers. It's useful for multiple things, basically because we're focusing on the locus coeruleus, we're stimulating adrenaline, we're stimulating serotonin, we're stimulating dopamine. There are multiple approaches, in this particular case, the hospital has a surgical approach which basically, things that you would be concerned about in this patient is the poor wound healing, the diabetes, blood sugar, glucose serum issue. But there are also transdermal type of approach where you can have magnetic, you can have electrical stimulation, and you can also have ultrasound. And so in this patient, I would recommend the use of a transdermal approach. Well study techniques that are currently presently out there right now would be a transdermal stimulation with the auricular vagus nerve stimulation and that would be, to me, would be the much safer approach rather than a cervical-surgical approach. Any other panelists? Well, I will say that I have not used... I would, you know, the paper that was, Dr. O'Dell is one of the co-authors on, so he gets the last word on this, in the Lancet that was published in 2021, found that people with vagal nerve stimulation gained about 5 points on the upper extremity fugal mire compared with exercise and sham vagal nerve stimulation, which was 2.4 points. So, statistically significant. Clinically, probably at the margin of sort of meaningfulness, you're talking about 2.5 points on the upper extremity fugal mire difference. You know, admittedly, they both improved. And so the question is, you know, risk and reward here. There's no, I don't think there's much doubt from the study that it works, but is it worth surgery? Is it worth surgery in somebody with diabetes? I'm less familiar with the non-invasive versions of vagal nerve stimulation, which have not been, as far as I know, FDA approved or probably not paid for for this indication, so I don't know how easily those could be obtained, but I think that certainly it would be nice to have a way of doing this without surgery. I'd be a little nervous about this patient, and I'm not sure it'd be, especially given this is such a new technique to us, that we don't have a lot of clinical experience with it, I'm not sure this would be the first patient I'd sign up for. Mike? I'm trying, God forbid, that I would ever do thinking for my neurosurgeons at Cornell. We have pretty conservative neurosurgeons at Cornell, and I'm trying to think through, given this scenario, would there be a scenario that they would feel comfortable doing this surgery? I mean, would they do, for example, bone scans to make sure that they're absolutely sure there was not an osteomyelitis underlying that wound? You know, what kind of preoperative clearance would they... Would there be any scenario that they would feel comfortable going in? I mean, this was a lower extremity wound. There'd be likely much better blood flow in the area they would be doing this surgery than there would the lower extremity periphery. I don't know. I think there might be a chance that our folks at Cornell would be comfortable doing this surgery. The issue of how much gain and whether it would be the risk benefit in this particular patient, I guess, is another story on that. Again, would this be the very first patient that I would take through in a vagal nerve simulation program? I'm not sure. But again, in the trial that was published in The Lancet, if you look at the gains compared to the sham group, both on the Fugl-Meyer and on the Wolf-Motor function test, there were two or three times the minimally clinically important gain in the VNS group versus the sham group. So again, I think we need to... In the setting of very few options that have been shown to be clinically effective. So again, we swim in that gray area of we have something that works in the setting of not very many options available to us. That was an appropriately vague answer, wasn't it? It was good. I will say that this is an FDA approved treatment and so the company is anxious to really spread this as a clinically available therapy. It is coming to hospitals near you. And so we'll be, I think, confronted with these decisions as clinicians in the near future. We're planning on starting up a program again for maybe patients who are a little lower risk than this with a little higher yield, we hope. But I think that it's going to become a part of rehabilitation decision making pretty soon. Next case, a 69-year-old woman has a left MCA stroke one year ago with residual right hemiparesis and expressive aphasia. She formerly worked in IT and was reading about a non-invasive brain stimulation. She was hoping she can improve both her right arm function and her expressive aphasia. She found a commercially available transcranial direct current stimulation system for sale online and is inquiring if there's any value to purchasing and using the system and if there are any significant risks. While it is not covered by insurance, the cost is really not an issue and is easily managed for her. Dr. Raghavan, what would you advise her? So, Dr. O'Dell, I think this transcranial direct current stimulation, just like electrical stimulation, is also an adjunct to therapy. The idea is that you're training, doing task-specific training and getting stimulation at the same time. The literature is all over the place on what type of stimulation, the length of stimulation. The key thing is to find a target and simultaneously deliver the therapy and the stimulation. So we have a program here at Johns Hopkins where we do have a non-invasive brain stimulation program. So there are many patients like our patient here who come to the program and some of the key factors that we look at is how much activation do they have, is there a target, and can we give them intense therapy along with the stimulation? Will they tolerate it? And the jury is out there about whether it is the stimulation per se or the therapy that is providing the most benefit. So it's hard to tell because when you look at the literature over... But as an adjunct, yes, she could use it. We need to make sure she's stimulating the right place and doing the right type of therapy at the same time. So this patient is looking at something that she's picking up online, on the internet. So as opposed to something well controlled and very standardized and regimented in a research setting. Talk to me about dosing. How does she know what she's getting? If she's picking up this thing online and whether the dose and the instruction that she's getting online is even close to reasonable. Yeah, that's a big concern, right? I wouldn't recommend that she just pick up online and go for it. The risks may be few, they may be limited, but she may not derive much benefit. That would be the biggest concern. I'm gonna ask you to commit yourself. If she's looking at the specifications of this device, are there numbers of amps that she should be looking for or time periods that she should be looking for? Well, no. I think she should find an expert. She should come to Baltimore and enroll in the Hopkins program. Other panelists? I agree with Preeti's comments and assessment of this situation. I look at this very similarly to what we're all familiar with in terms of TENS units, right? You can go on Amazon and buy a TENS unit from a gazillion different companies. There's no control in regards to the intensity, the frequency, and you know, the first thing is I definitely agree that it's not a treatment that should be used on its own. It should be a treatment that be utilized in conjunction with directed therapeutic intervention. I certainly have to agree that getting random devices off the internet and putting them on your, stimulating your brain with them is probably not a good idea. That said, you know, I think that TDCS is exciting. It's exciting because it is relatively, you know, safe and easily done. The technology is not that elaborate. So I don't think this is the right device for her, but I'd love to see her get involved in a clinical trial if we could find one for her. And I think we need to be doing more of those and maybe also some more kind of not quite, not quite research, but not quite standard clinical care, you know, options for patients who want to try cutting edge therapies because I'd much rather this was done in a supervised setting by somebody who knew what they were doing with a device we can trust than her getting something off the web. I'm not going to let you guys off the hook that easy. We said no. We said no. This is a device that's on the internet. It's, I assume, been approved by the FDA, which tells me that, so I'm an IT person now, that it's safe enough to be marketed in the United States. I can't get into your research center. I can't afford the device that my insurance company isn't going to pay for. You uppity researchers and academics are telling me that I got to come to your research center for this. I got an arm that doesn't work. You're giving me no options here. So I think... Good for you. I think first of all, you know, it's a fair point. You know, the issue, and this is very much in the weeds and maybe not a conversation I have with the patient, but the FDA has not approved these devices. They may be cleared and I think that it's important to understand a little bit sort of how devices get approved in the U.S. because really, you don't have to show efficacy and only minimal safety data to get a lot of these devices through an FDA clearance process. So just, we should all be aware, the 510K program is not really as robust, I think, as it should be for this kind of stuff, and so it is very much buyer beware. With that said, you know, some of these systems just stimulate the wrong areas. I think that, you know, Preeti was talking about this and I tried one of these systems, which is we're perhaps doing a research study on. I popped it on to see if it made me smarter. As far as I can tell, it did not. It made my skin red, but otherwise, it didn't bother me much, but it was frontal lobes. It was not, you know, going to help my motor cortex. It was in the wrong place, prefrontal cortex. So I think it's important to explain to the patient it matters where the stimulation is delivered. It's not all, the brain is not one big thing. It's got a lot of different parts. And I want to make a clarification that, Okay, fair enough. Let's up the game just a little bit. Same patient. Tries the transcranial direct current stimulation but finds no benefit. Despite combining this with home exercises, she has an opportunity to enroll in a clinical trial of a theta burst transcranial magnetic stimulation program to her injured, in other words, ipsilateral left cortex. And wants your opinion regarding the safety and likelihood of benefit. Again, Dr. Raghavan, while she has never had a seizure, she is worried because a friend has developed a seizure disorder after a stroke. What would you advise her? Well, it's good that she's trying to do something in a more controlled setting. So I would say theta burst stimulation is transcranial magnetic stimulation is high frequency repetitive transcranial magnetic stimulation. And there have been a few trials of it in stroke. And it's found to be fairly safe. You know, right at the beginning of using transcranial magnetic stimulation for stroke, there were some incidences of seizures but they've really changed the protocols and made them particularly safe. So she's never had seizures. So at this time, she can certainly be considered and seizure disorders not even if she did have a seizure. There have been other trials that have been promising. I would say, go for it. There's the risk piece. Is there enough benefit? Does the data that we have so far indicate that transcranial medics stimulation for motor recovery is effective enough to make the risk worthwhile? So the data is, again... particularly when combined with therapy. Other panelists? Well, presumably there is equipoise in the study. So I think that we don't know for sure if this works and I think it's always important to explain that to the patient that, you know, maybe it'll help, maybe it won't. We don't know. Not likely to be harmful, but the risk of seizure is not zero. It's probably low, but not zero. And I think most clinical trials of TMS have excluded people with a history of seizures. So we don't know if you can, you know, safely use this or not. The same is true with TDCS. Even though there's no evidence it causes seizures, most clinical trials exclude those patients just to keep it clean. But in any case, she's not had seizures. So I think it's, I would encourage her to seriously consider participating. It seems like a reasonable thing to try, but it's impossible to know what the likely benefits will be. Okay. All right, let's move on to our last case. I'll do some discussion. Then we're going to open it up for questions and answers from the floor, which I'm hoping we're going to get some doozies, I hope, from you guys. Last case, the same patient decided against participating in the TMS trial and is now asking if botulinum toxin might help her recover greater motor abilities. Very important point in her upper extremity. She has limited motor control and struggles to open her hand after closing it voluntarily. Her resting tone is mildly increased, approximately a two on the modified Ashford scale at the finger flexors, and minimally increased elsewhere. Her passive range of motion is full in the upper extremity, except somewhat reduced at the shoulder. She has no pain or skin lesions and does not use a hand splint. Dr. Nguyen, would botulinum toxin treatment improve the use, again I'm not asking whether it would decrease spasticity, would botulinum toxin treatment improve the use of her upper limb? So given the fact that there's a bunch of injection workshops that's going on this week, everyone in here should be able to answer this question, right? So yes, so Dr. O'Dell brings up the differential question that I always ask myself when I'm treating my patient. Am I managing the spasticity or am I managing the function? And so in this particular case, we are going after a functional improvement. And so I would say yes, the answer is a simple yes. But the questions you really have to ask is what is the patient's functional goal? What does the patient really want to get out of this function? Because it will be dependent on what, how you approach and which muscles you would approach. The second thing you want to ask is, you know, how is the patient's mobility? How are they ambulating? What's their efficiency? What's their cadence looking like? What's their balance and equilibrium look like? Because that also affects how you would approach this patient, given the fact that the patient also has involvement of the shoulder as well. Now I'm going to be a really, really... I'm going to really jump in here. Go ahead. I'd give a no. I think that this is a controversial area. And I think that it's, you know, a good topic for us to debate up here. But I think there's very little evidence that motor recovery, motor function is facilitated by botulinum toxin injections in stroke survivors with hemiparesis. It's great for spasticity. It reduces it. You know, if someone has a tightly fisted hand, you can get them to relax. You can get them to split. You know, certainly for the leg, it can be helpful with bracing. But I think the notion that it improves motor performance on a day-to-day basis is unproven. You know, our individual cases, I think most of us have seen, where we think we've seen this. So I don't say that it's never happened. But as something that I would promise or expect to see in a patient, I would say no. I don't think it's likely that she would get much function back. There's a small chance that we can sort of balance her flexors and extensors and achieve greater ability to actively extend her fingers. But even that, I have to say, I don't see happening as often as we'd like to imagine that it should. Then Dr. Stein, how do you manage that individual patient? It's one thing to quote the literature for a group and say that it doesn't work in a setting of a large group of people, but how do you manage that specific patient and that patient's expectations? Sure. Well, it's a tough question. I think given that she is able to make a fist but can't open her hand, I think it might be reasonable to try Botox once. You know, you'd say, okay, we'll see if this allows you to open your hand better. It's a 50-50 sort of thing. It may not help. It's not going to have you playing the piano. And I think that we really have to be clear about that. This is not, you know, a magical motor recovery drug. It might allow her to extend her fingers better if you take the edge off her flexors. But that's all I would offer. And one follow-up question to Dr. Winn. I'm going to be really a dirty duck. If in fact the answer to your question is yes, you do think that motor recovery or function could be improved, which toxin would you use and what doses would you use? I cannot answer that question because I signed a disclosure thing. So can I say something? You may. Well, so we talked a little bit about other options. Maybe one could try other options, you know, before we try Botox. Because she's only asked about TDCS, then... Do you mean Botox or do you mean botulinum toxin? Well, I mean electrical stimulation for hand opening. You know, I would try those before I go for toxin. Point well taken. Exactly. There are other options. And that was actually was going to be one of my counter. Essentially, we don't treat the patient in isolation in regards to our approach. Our approach has to be, you know, you start out with the daily range of motion. Why isn't this patient on a nightly splint to maintain range? And then also you could do extensor electrical stimulation while you are weakening. You don't have to knock out the flexors, but you can certainly weaken it. So that allows the patient a little bit better wrist extension, a little bit better finger extension. We have an investigator-initiated trial where basically the goal was to inject the shoulder for increased shoulder swing in order to monitor the patient's balance, equilibrium, distance of ambulation. And we used an accelerometer in order to measure their efficiency and distance. So to answer the question of is it going to be functional, oh, well, it depends on what the patient wants. And that's the reason why I go back to my question earlier. Okay. I just want to ask Dr. Raghavan what she thinks about motor recovery in this situation. What do you think? I realize you're reticent to rush to botulinum toxins, but if you were to be at that stage and trying to decide whether to proceed with it, what do you think is the opportunity for improved motor performance in this situation? I don't know exactly what you're asking, but... Would she use her hand better if you give her a shot? If I give her a shot of... Or if I give her a shot. Would she use her hand better? Yeah. Can she do more with it? Botulinum toxin or something else? Botulinum toxin. Well, you know I would give something else, right? So you're saying no. Well, for those of you... To my research... Before we move on to questions from the floor, a final question to the panelists, in every one of these fancy schmancy covered or uncovered by insurance technologies we've talked about, you've mentioned that perhaps the most important piece of this is the exercise, the therapy that goes with it. In essence, does it really not make a hill of beans difference what the technology that we use is that they're all equally the same, so long as we do something to stimulate the brain and whatever that end point is, either electrically or chemically, it doesn't really matter so long as the therapy goes along with it. True or false? False. Maybe I should explain. Could you expound? We don't know the answers, which I think is a very big difference than to say that it doesn't make a difference. Right? So we know, for example, from pretty well done clinical trials, we didn't have a case discussing this, that SSRIs, fluoxetine, Celexa, aren't particularly helpful. Right? We thought that they might be. There was some preliminary evidence suggesting that, but so in that sense, they're less effective than some of these other techniques. They're less effective than, say, vagal nerve stimulation, as one example. I think that the real question is, if you have multiple therapies that you could engage in, can they be additive, or is it a zero-sum game? We don't know the answer to that. The one thing we think we know is that exercise is part of every single strategy, that there's no substitute for experience for using the parts of the brain that you're trying to work on and improve, and so I think that's the only thing I'm confident of. But I don't know that we can say that TMS is the same as VMS, in the sense that maybe they both help a little bit, but we don't know which one's better. I think that ultimately, some will be better than others. We just haven't figured it out yet. I agree with Joel's comments. So I'll expound. I would say false as well, and the reason I say false is that, you know, there's a couple of different things here. People could do the same thing over and over and over again, and they could think that they're exercising, and they say, well, I'm not getting anywhere. How many times have we had patients come and say, I've gotten all the therapy that I could get, and I'm still in the same place? So there is a science to it, and we are still figuring it out, but I think that a few really important points have come out from the literature. Number one, you want to prevent the ill effects of immobility on the muscles per se. The muscles are the organ of disability, right? So we've got to preserve muscle length and muscle function to the extent possible, and the most recent study that came out last year on the critical period after stroke suggests that if you're giving high doses of therapy early on, that might be more beneficial than, you know, spreading the therapy out over the long term, because giving that extra 20 hours early on had benefits that were seen, you know, one year later, right? So when do you give therapy intensely is important. What therapy do you give? You know, yes, task specific, but you have to prepare the muscles to participate in the task. So, you know, there's learned non-use, right? Fleming are here, really exciting data. Again, you give it early, it helps you with secondary prevention after a stroke, and it actually. The aerobic exercise, particularly one of Joel and I's colleagues, Scott Rabuto at Columbia is looking at aerobic exercise as a treatment for ataxia in degenerative cerebellar disease and finding that perhaps aerobic exercise is a better treatment than balance training in degenerative cerebellar disease as well. So maybe a magic bullet that we've been underestimating in our exercise armamentarium. Both of these mics are ready to go. I'd love to hear some questions from the audience. Yes, ma'am. Hi, everyone. Thank you so much for a great session. I'm really excited to hear all of your perspectives. I really appreciate it. My question is threefold. I'll be brief. Number one, does anyone on the panel use biomarkers to help predict for stroke recovery? Number two, Dr. Raghavan, you mentioned some of the pathways that you use in terms of the non-invasive brain stimulation. We have to determine whether or not the pathways are even open before we even try to do that. So if you could expound on that a little bit more. And then also to piggyback on what you just mentioned, does the group feel that the next phase of this in the world of big data, precision medicine, is the world of physiatry going to move towards how do we find for each subtype of stroke, which patients will recover the best using whatever treatment modalities, be it pharmacological, non-pharmacological, and all of the tools that you mentioned above? Biomarkers, anybody? There's a lot to unpack there. Thank you for good questions. So in terms of biomarkers, the only biomarkers that I think are being used routinely are imaging and exam. And I think that probably the three of us are not doing anything beyond that, right? Are you doing TMS or? So there's the PrEP algorithm, right? Yeah. Which is interesting. It's not being used clinically. It's really just research. Yes. But it's predictive. So potentially, you could use... So the PrEP algorithm basically looks at... the safe score on the MRC, right? So then you have an excellent chance of recovery. And so the idea of the PrEP algorithm is that, you know, regardless of how they present, so you really. If they have a motor evoked potential, then they have the pathways that you mentioned. How good is this biomarker? We don't know what I know. And there was a question specifically to you from her. The pathways that you... Did I answer that? I'll just say, you know, in terms of the requirements for these biomarkers, particularly the use of TMS in the setting to really be implemented or any algorithm, you just have to be really careful that the degree of accuracy of these tests is high enough that if you're going to deny someone therapy that you are 100 or 99.9% confident that they're not going to benefit because if it's only 80% that's, you know, then you really don't want to limit treatment based on that. It's one thing to give people more treatment, but to say we're going to, oh, you have a poor prognosis, we're not going to... We don't know yet. You've got to be careful. You've got to be careful. That's the issue. And just real briefly on the last question. Let's keep going. Thank you so much. Yes? Oh, thank you. This has been really interesting. Can you comment briefly on the use of peripheral nerve stimulation? So, for shoulder pain? For pain, you mean? Well, yeah, for pain and to enhance movement, ultimately to enhance movement of the shoulder. I know that Dr. Shea would be able to give the best answer here. Dr. Shea, would you like to answer that? So I think you're referring to percutaneous peripheral nerve stimulation. So what we do know about that, it does reduce pain. The endurance is long-lasting. Whether it actually improves function of that shoulder, I think that's debatable. Dr. Richard Wilson did do a study with implantable. In fact, Dr. Vu was involved with that actually. In that group, with long-term stimulation, my impression is that they did improve function, but it was not a controlled trial. So I can't say yes or no. Thanks, John. Dr. Gittler. Thank you all. It's really exciting, and I mostly wanted to thank you for directly at one point touching on the issue of resource utilization and our responsibility as physicians to make sure that people get what they want. I'm curious if you might want to discuss a little bit about our inability to even get people the therapy they need before we start adding on the adjuncts for the therapy in terms of our trying to navigate managed Medicare plans that don't even want to give the intensity of therapy for a short time. And what is our responsibility as a community to kind of force that question? Terrific question. Thank you. It is a terrific and a difficult question. So I think that we have roles as advocates for our patients individually and then collectively as a profession. And I think it's incumbent upon us to sort of push back. When I see patients in my practice who come to me because they heard we're doing interesting research and have all these creative things, the first thing I always ask them is, well, have you had conventional therapy? Have you done the standard things? Have you had enough therapy? Because the usual answer is they haven't had enough. And so advocating for that and trying to get them that is really the foundation on which all of these other treatments needs to be built. Electrical stimulation without OT for the arm is not going to fix the problem. And I think we all know that. So that said, it's a tough situation. I don't have an easy answer to it. But we have to advocate. Definitely a difficult question to answer. You know, basically, so the question Michelle is asking is advocacy, right? So at advocacy level, that's a bigger question than all of us can answer except the fact that we all together can answer one question at a time. In the meantime, what can you do beyond advocacy? So, for instance, you can basically wield the power of your healthcare system to negotiate. For instance, our healthcare system negotiated with Blue Cross Blue Shield for improved reimbursement on therapy programming. So if you yield the force of your healthcare system, you can have some effect and some lead way into what you want to do. And other ways that you can do as an individual clinician is you can cheat the system, right? It's true, right? You know, when the patient comes back and see me, I have three months, every six months, whatever the duration is, you know, I find something new, something different to document. And then I initiate therapeutic intervention, knowing very full well that pretty much when the patient goes to therapy, they're going to get a relatively comprehensive assessment by the therapist, except this time I'm asking that therapist to answer a different question or a different focus. So my one answer is data. We need the data. We need it collectively. And we need to show the payers the data that what we're doing now will make a difference down the road in the disability, right? In how much they're going to have to pay. I mean, just imagine paying for long-term care versus being able to mitigate the disability early on so that the patient will be functional, can live in their own home with their own families, right? I think we can make a difference. The question is when and how do we get the data to prove that, you know, that more therapy early on is better? The beauty today is that there is some exciting data in research, right, from research. If we were to do a real-world trial and right, and then trying to gather the data to see if we could mitigate that long-term disability as the studies suggest. Now, doing it as part of a control study versus doing it in the real world are two different things. But if we can translate it and prove to CMS, right, that this makes a difference, it's a new approach of looking at it, it's an old approach, but it's a new structure of delivering this high-intensity, high-frequency therapy early on, then maybe they will cover it, right? I think only data can force that. I hate to do this, but I'm going to be the time mafia. For the three folks who are waiting to ask questions, if you want to, I think, probably just come straight up here and feel free to ask the panelists directly what your questions are. For the rest of you, thank you so much, panelists, for a great session. Thank you so much for coming. Have a great rest of the conference. Thank you.

therapies

interventions

stroke recovery

constraint-induced motor therapy

robotic therapy

vagal nerve stimulation

transcranial direct current stimulation

TDCS

botulinum toxin

individualized care

patient goals