Okay, welcome. Welcome everybody to our talk called post-stroke movement disorders, where we will talk in depth about the upper motor neuron syndrome and talk about spasticity versus dystonia, as well as go through some patient cases. I think that this talk is a great representation of physiatry as a field because it's truly multidisciplinary. I can tell you a little bit about myself. I just completed my fellowship at TIER in Houston and am now starting my first job at UC Davis in California. We have Kelly Horstman, a physical therapist who specializes in neuro recovery, who's from TIER in Houston. And we also have the privilege of being joined by Sheng Li, who is a professor at TIER, has many years of experience treating patients with spasticity and dystonia and quite a bit of research experience as well. So let's go ahead and get started. Here are our disclosures. We have no financial disclosures, no conflicts of interest to talk about. And here's an outline of the talk. We're going to go ahead and review the upper motor neuron syndrome so that we can lay the foundation to talk about the relevant literature about post-stroke movement disorders, and then going into discussing two patient cases involving a novel therapy treatment that we wanted to discuss with you. So to get started, the upper motor neuron syndrome, this is a whole host of symptoms that's produced by having a lesion proximal to the alpha motor neuron. So having either a spinal cord or brain injury. Many diagnoses are associated with the upper motor neuron syndrome. So not just strokes, since we're going to focus on stroke today, but also traumatic brain injury, anoxic brain injury, multiple sclerosis, cerebral palsy, spinal cord injury. So just reviewing that for you. Manifestations of the upper motor neuron syndrome, we are focusing on spasticity and dystonia today, but understand that when we're talking about these positive signs of the upper motor neuron syndrome, there is weakness underlying that. So that's something that we have to be aware of when we're treating patients and trying to improve their quality of life. We have to understand that if we're treating the spasticity, that doesn't necessarily mean just because they're rigid or tight that they don't have weakness underlying. So definition of spasticity, this is not a movement disorder. So we're going to talk about movement disorders and focus on dystonia, but spasticity, even though it's part of the upper motor neuron syndrome, is its own thing. It's not a movement disorder. It's a motor disorder characterized by this velocity dependent increased resistance to passive stretch. And understand, I wanted to put a disclaimer here that we're discussing spasticity and dystonia, not spastic dystonia, which is a separate pathology manifested by spasticity when there's sustained muscle overactivity in spastic muscles. So the pathophysiology of spasticity is really a disinhibition issue where you have disinhibition effects and exaggerated stretch reflexes that result. So when the central nervous system, the brain, the spinal cord is healthy, it provides this balanced descending excitation and inhibition regulating our spinal stretch reflexes. But when you have an injury somewhere along the way involving the corticoreticulospinal tract, you get a disinhibition effect leading to this overactive stretch reflex and spasticity. And one way you can think about this is if you've ever seen a patient that's had a selective dorsal rhizotomy procedure, you can decrease that spasticity just by cutting the dorsal root ganglion, those sensory nerve rootlets. So let me go ahead and advance to the next slide here. Okay. Whereas dystonia is a sensory motor modulation issue, not that disinhibition issue. So in this case, we get sustained muscle contractions that cause these repetitive twisting movements at variable speeds leading to abnormal posture. It can be focal, segmental, or generalized. And interestingly, with this, we see a sensory and a motor component. And one way you can think about it is if you've ever seen a patient with cervical dystonia, their neck is bent to the side, they can do a sensory trick. They can sometimes take their hand and touch their chin and correct themselves towards midline. And this is temporary. And that's something that we're going to discuss a little more when we get into our patient cases and some ideas for treatment. And know that dystonia gets worse with physical activity. And it's the most common post-stroke movement disorder across men and women, hemorrhagic and ischemic strokes. And it's significant because it can cause a lot of problems for patients' quality of life and their function. We'll review the treatment options for spasticity and dystonia. So there's a lot of similarity between treatment for each pathology, therapy in both cases, really, bracing, oral medications. In dystonia, oral medications that we would use are generally slightly different than those we would use for spasticity. Thinking about anticholinergics like trihexafenadil, GABAergics like Baclofen, obviously, we use that sometimes in spasticity management. Dopaminergic agents like levodopa or tetrabenazine. But largely, patients report less than satisfactory results from the oral medication treatments. And for most patients, or for most physiatrists, we feel that neurotoxin injections are currently the best option that we have, even though the treatment options really aren't satisfactory. You can also, for dystonia, utilize things that we do in spasticity like intrathecal baclofen pumps. And then there are several cases where deep brain stimulation can be useful for dystonia. And that will be something that we discuss with one of our patients coming up. So now that we've laid the foundation to understand spasticity and dystonia, we will move into the relevant literature review where we will talk about the literature on post-stroke movement disorders. And this particular article I have highlighted is something that we're going to go in depth about and we'll bring in some other articles as well to talk about movement disorders after stroke. So with this article, this is a giant case series. So it's impressive they were able to get so many patients involved in this study to review for this study to discuss movement disorders. Many of the articles that were included in this systematic review were case reports. So again, just a giant case series, but able to derive a lot of information from this just because of the size of the population. The goal of this systematic review is to evaluate variables in post-stroke movement disorder, including the type of stroke, the location, age of the patients who have movement disorders, the time it takes for a movement disorder to develop, and then the outcomes that we see. And here on the bottom of the screen, you can see the different movement disorders that are discussed within this review. So the big picture of movement disorders after stroke, movement disorders in general from a secondary cause are only about a quarter of all movement disorders. So post-stroke movement disorders are about a quarter of all secondary movement disorders, and then they're only observed in about overall 4% of stroke patients. So the number of stroke patients, our population is so large that relatively speaking, it's a fairly small minority of all strokes. But with that said, it's still a significant impact on a patient's quality of life and their ability to function, and we want to continue to work towards getting better treatment options for these patients. Know that even though we're going to go through different areas of the brain that are associated with movement disorders, having damage to one area of the brain does not necessarily mean you're going to have a movement disorder, will see a movement disorder, and vice versa. Because there are so many association areas of the brain, there's not really a one-size-fits-all. So looking at the breakdown of movement disorders and type of stroke, we have, you know, obviously there's more ischemic strokes, much more than hemorrhagic strokes when we look at the breakdown across all types of stroke. But when we're looking at just hemorrhagic strokes versus ischemic and the type of movement disorders that develop, we're seeing that dystonia is a significant part of patients with hemorrhagic stroke and even those with ischemic stroke. So I have here noted on the bottom that dystonia and tremor were significantly higher in the hemorrhagic stroke population, but overall it's still the most common movement disorder across all types of stroke. In this slide, we're breaking down both hemorrhagic and ischemic strokes, but then within that looking at areas of the brain that have been injured because of the stroke and what, you know, whether that associates with a movement disorder. So we're seeing in hemorrhagic strokes, the posterior lateral thalamus was associated quite a bit. In ischemic strokes, it's a little more of an even distribution, but you can tell that as we would expect, the basal ganglia are often affected or involved, associated as well as the brain stem. But you can see that the frontal lobe can still result in or be associated with a movement disorder. And again, probably because there's so many association areas of the brain. Looking at age as a factor, so breaking down by age, we can see those that are above the age of 70, seeing more involvement with the putamen correlated with chorea. Those age 50 to 70, the posterior lateral thalamus being significantly associated and dystonia again being more common as well as those under the age of 50. So all of this just to again highlight the significance of dystonia as a movement disorder after stroke. This schematic is taken from the article that we're discussing and goes through different areas of the brain associated with different movement disorders. And you can see it's quite complex. And like we discussed in the very beginning or like I discussed in the very beginning, one area of the brain having damage does not necessarily mean you will have one exact movement disorder or even any movement disorder. Time to onset. This was interesting result from the systematic review that many patients actually have movement disorder developing really early after their stroke. So things like chorea appearing within 24 hours, whereas dystonia and tremor may take more time to develop. And this again, another way of talking about the time to onset patients with ischemic strokes, seeing more latency to onset of a post-stroke movement disorder versus those hemorrhagic stroke. And then looking at outcomes, more than 70% of patients with myoclonus or frontal lobe related damage, more associated with spontaneous improvement. So overall, many patients are able to improve and to recover. However, about half of the patients seen in this large case series benefited from treatment. But tremor was most likely to persist. And that was associated more with the injury to the putamen. And Parkinsonism was more likely to improve with treatment. And as you would expect in patients with Parkinson's disease, the midbrain was more affected in those patients. So why is there a poor association between a stroke location and a movement disorder? Well, movement and motor control is complex and it involves multiple areas of the brain. Damage to one area doesn't mean the others are no longer able to communicate. And another thing they found in this is that younger patients were more likely to develop a late onset post-stroke movement disorder, but know this population is more likely to recover some function versus older populations, which may be more likely to experience paresis, where you may not see a movement disorder. Okay. There were limitations to this article that we talked about. It's essentially a large case report series. So there's concerns about that. There wasn't any video provided with the article. So you question, well, was every patient truly diagnosed appropriately with a movement disorder? Didn't necessarily account for pre-existing lesions. If a patient had had a stroke previously or had had Parkinson's disease previously, and then had another stroke or had a stroke on top of their underlying disease. And then like we just mentioned the last slide, higher percentage of post-stroke movement disorders in the first week in the older population could just be due to a higher mortality. Whereas the younger patients are living longer and you may have the time to see a movement disorder develop in those patients. So we're going to go into talking about our very first case. This patient is a 63 year old female. And I have to mention, as we're talking about these patients, I'm very grateful for our patients for signing video releases and information releases so that we can share this with you for academic purposes. This patient had a left MCA stroke in 2009 and secondary to a spontaneous carotid artery dissection. Her hospital course was complicated by hemorrhagic conversion. She developed seizures after her cranioplasty, late seizures, and then was referred to our tier for spasticity management because her outside provider left her practice. So when the patient came to us, she said she was most bothered by the tone that she experienced with walking, where her right arm would lift up and extend, an example of dystonia. She was more bothered by that than she was by the tightness that she experienced due to her spasticity. And when in clinic, her husband noted that she hits herself on doorways because her arms extended and she has bruising. And it also makes it very hard to go out in public and hard to drive. So this is what we did in that initial visit. We evaluated the patient and we performed botulinum toxin injections. We're going to see video on the next slide, but for you just to review the areas that we injected to try and help with the arm abduction as well as the other areas of her spasticity. She had lower limb and upper limb spasticity. Okay, so this is her walking. We got right arm abducted, extended. Okay, and so we did injections. We brought her back for follow-up, did a very thorough neurologic examination. I wanted to put here for you that she does have aphasia. She has sensory problems. So she has pinprick absence, diminished light touch sensation. She has dysmetria, as you might expect. Her strength was actually fantastic on manual muscle testing at rest. She had excellent strength, increased reflexes, and clonus to the right ankle, as you might expect of someone with an upper motor neuron syndrome. So I'm asking her to perform these movements at rest while she's seated, and she has pretty good control over her body while she's at rest. But when she walks, her right arm abducts, she has dystonia, and it causes a lot of trouble for her. So that was comparing at rest, doing what I asked her to do, and now she's walking and she can't bring her arm down. Okay, and then I'm gonna hand the presentation at this point over to our physical therapist Kelly. Hey, so what did we do? So this is when Dr. Capizzi and Dr. Lee brought me in as a therapist to kind of see if there's a component that we could use of eSTEM, specifically sensory component, in order to bring trial this kind of device to see if this would bring help with some of her management of her dystonia. So we applied eSTEM to the right upper extremity, mostly to the median and musculocutaneous muscle groups, so your flexors. The eSTEM settings were 2 to 300 pulse width, 20 to 40 Hertz for the rate, and as far as intensity, we set it no more than 20 milliamps. So how we decided that was that the patient could, though aphasic, could indicate when she could feel it, and I also was able to take it up to where there was where the motor threshold was and basically back off from that. So that we knew that she was feeling it, but that it wasn't a motor, that the eSTEM wasn't causing a motor reaction causing her to flex. We instructed her and her husband specifically, since he was the primary kind of caretaker. This is the device that we use. This is an older picture of it. We have, it was a slightly newer device, but same thing. And she, the goal was to wear it eight hours a day, again with the electrodes placed at the proximal and distal aspects of the antecubital fossa, so at her elbow. And then she followed up with us in two weeks. So I'll progress, and then I'll pitch it back to Dr. Kapisi. Yeah, you can see the patient walking with the simulator on, the eSTEM unit on, and is bringing her arm in a little bit more. That's our feeling. And this is just after placing the unit on her flexors. So again, a little bit later, after we put the eSTEM unit on, we asked her to wear the unit for eight hours a day. We said, as much as you can, just wear the unit as much as you can to the flexors, you know, self-reported. So, you know, she came back to us for follow-up after a period of time, and told us that she was able to do about six hours a day. And initially had, was a little nervous about putting it on for that amount of time, but it was not uncomfortable for her, she said. When we followed up, she said, so this was the results of our physical exam at the next checkup. And the most significant thing that we found is that her sensation was improving after wearing the unit, compared to our initial evaluation back at the time that we had just performed the botulinum toxin injections and hadn't tried this. So this is after a couple of months, really, of her wearing the electrical stimulator unit. And she's able to walk, and you can see she is able to bring the arm in, walking down the hallway and coming back into the room on her own. And at this follow-up after that couple of months, again, she had even better sensation on her physical exam, cold sensation, light touch sensation. So still not completely normal, but has had awareness brought to those, you know, right upper limb, the right side of her face, and that's something that we had not seen previously. And this is the last follow-up, the longest amount of time after we had started the e-STEM, so we're looking at, you know, two to three months following using the e-STEM. And here's our timeline. So just to bring everything into focus for you, because I know we went through a lot of videos and a lot of physical exams and ideas of what's going on with her treatment with the e-STEM and the botulinum toxin injections. So just to show that we instructed her back in September, at the end of September, to wear the unit. We had done the botulinum toxin. She'd had significant sensory findings. She'd really not much awareness to the right side of her body. Back then in October, improvement in the sensory areas on physical exam, some improvement on dysmetria, some improvement with the ability to bring her arm in when she walks, and then finally back in November. So a couple of months after we had started, we're seeing even more improvement to the sensory areas and what we feel has been a significant change in her dystonia. So now I'm going to hand it back to Kelly to talk about our second case. Thanks, Dr. Cavesey. So our second case was this 34-year-old female. She had a TBI, secondary to a car accident that was in 2006, so like 14 years ago, resulting in spastic quadriparesis. Granted, her left side was more affected than her right, but she was globally affected. She had a seizure disorder, some cognitive deficits, though verbal and can communicate with you, just some minor cognitive issues, and then definitely significant dystonia globally, but as we'll focus on her cervical dystonia here. Previous treatment, so she's had numerous, numerous bouts of therapy, both inpatient and outpatient. I actually saw her as an inpatient back in about 2011, 2012. After she had had this DBS place, that was in 2010, she had a pump in 2013. Her current dose is around 410 micrograms per day. Again, multiple instances of Botox injections. She actually had one instance, again, back several years ago when we were inpatient, that she had difficulties with severe dysphagia after her injections, which caused her to have a PEG tube for a period of like four months, about, and then we've also trialed numerous bracing options. She has a soft collar, which she likes, but doesn't really do anything for her, and then we tried a more rigid collar, and I made a torticollis-type splint out of casting material. Again, not well-tolerated because she reports it being uncomfortable, so this is her, and then she does do a sensory trick, which Dr. Capizzi mentioned in previous slides, where she was able to touch her chin or her face, and she could bring her head up into midline, but then it was never sustained. As soon as she'd take her hand away, she'd come back into this flexed, rotated, and laterally flexed position. So she came into clinic with her parents, kind of asking for more input on how to better address her dystonia. Is there something else they could try? She again had had, they were pursuing injections, but hadn't seen a whole lot of improvement recently, so we trialed this e-stem. So again, we placed it on the right and lateral aspects of her, I mean posterior aspects of her neck. We had set the time to continuous, so it stay on with the goal of being eight hours a day. We set the pulse width again around 300, rate around 45 Hertz, and then we ramped time anywhere between two and zero and two seconds. She ended up tolerating it fine coming on, so we just kind of took the ramp time down. We left the on time for anywhere from 10 to 30 seconds, just the device requires us to put it in. It doesn't really matter because we set the off time to zero, which means that it was continuous, and then intensity was lower. She can verbally report to us when she was able to feel it between five and seven milliamps. We were, did instruct, we gave her parents, her dad specifically was the one who would apply this to her, and gave him instructions that if she desensitized to it, they could turn it up, but that they should always stay below motor threshold. We should never see the muscles activate. This was strictly to keep it sensory, and she was able to give that feedback. So we'll go to the next slide where we kind of give the time frame. So we initially saw her back in January. The picture on the left is her in January, so you can see that she's flexed forward, laterally to the left, and then rotated slightly. This is when we introduced the eStim. They didn't have that, they had a device at home, but they didn't have them with them, so I instructed them on the device I have in the clinic. They came back for a follow-up about a month later in February, when she also received injections again at that time to the SCM, the middle scalene, the splenius, the capitis, and the upper trap on the left, and this is when I re-emphasized, because dad had more questions about the eStim settings, parameters, and things like that. They were able to bring their device in. They had trialed it at home, but it was kind of hit or miss as far as how much they felt like they were doing it properly, and so I set their device up there, and so we ensured carryover again this time, and then they followed up. She followed up again in June, so five months from the initial visit, with her reporting wearing it six to eight hours a day, five days a week, again compliance with the 34-year-old patient with dystonia, reliant on her parents to put it on, but they would put it on her, and her mom confirmed, and wearing it for those long, prolonged periods of time, and the picture on the right is her in June, so as you can see, her head is more upright. She is still laterally flexed to the left, but rotation is a little bit better, and definitely more upright, and able to be in the middle longer, and not relying. She still uses her sensory trick to touch her chin a little bit, but not as much. So now I'll pitch it to Dr. Lee. Hi, so in the first, in these two cases, we, these two patients have received Botox injection, Biotoxin injection, but it did not have much success, as we would like to have, but after we add E-Stim, and for a longer period of time, as both Dr. Kabir and Henry emphasized, in both cases, and we achieved a much better outcome. So that means E-Stim does help these patients with dystonia, and the question is, how? So first, as a reminder for you, in Dr. Kabir's review, there's different areas that could be affected, and resulted in the same or different type of dystonia. So the recently proposed network model as a neurophysiology of dystonia could help us understand how E-Stim might help treat dystonia. So let's take a look at the network model. So first, as shown on the figure on the left, when there's a normal sensory motor processing and peripheral sensory information, such as tactile and perceptive information, can be appropriately processed and gated at the basal ganglia, thermos, cortical area, and the cerebellum. So as a result, smooth and coordinated movements are produced as a motor output from the system. So as we can see from on the right side, when there are sensory impairments or altered sensory gating and moderation within the system, and overt dystonic movements are produced and observed. So in a sense, the network model emphasizes that the proper dystonia is the distorted motor output as a result of altered sensory motor processing, secondary to neurological impairments, as we see in both cases, stroke and traumatic brain injury. So how does this network model of dystonia help us understand the results? As we know, it is well documented in the literature that patients with dystonia have impairments in sensory function. And this was also seen in our first patient, which Dr. Kapisi did a very thorough neurological exam. And second, when there exists sensory dysfunction, a network of motor areas that are connected to or responded to the sensory feedback are altered. And as a result, dystonia is produced and observed. So eSTIM as a neuromoderator could potentially alter the sensory motor connection and restore the sensory motor relations. So as a result, it can trigger and can treat dystonia. So for example, in a recent study with a group of 14 healthy subjects, and the subjects were instructed to imagine ankle dorsiflexion while peripheral nerve stimulation to tibial nerve was delivered. And the authors reported that cortical projections to the ankle dorsiflexor, i.e. tibialis anterior muscle were inhibited. In other words, the eSTIM to the tibial nerve strengthens the calf muscle activity and inhibits its antagonism muscle activity. So in our study, we observed that there were parallel improvements in dystonia and sensation, particularly in case one. And this observation suggests that a sensory input has a gating and or moderating effect on motor output of the sensory motor network. So our results supported the motor network hypothesis of dystonia. And furthermore, sensory restoration could be achieved through eSTIM mediated sensory motor retraining treatment. So but we would like to highlight that in both cases, a very high dose of eSTIM sensory motor retraining was used. However, the optimum dose is still unknown. So for example, in first case, it's about a cumulative about 160 hours. This is more than commonly used in the literature. So in summary, spasticity and dystonia are both part of the after motor neurone syndrome. Dystonia is poorly understood and the treatment options are less satisfactory when compared to spasticity treatment. And dystonia is the most common post stroke movement disorder. And we were well this is our case and our contribution and the eSTIM electro stimulation therapy is a low risk and a low cost. And it may be helpful option for dystonia patients. And thank you for questions. And here the email for us this Dr. Capizzi's email and we are all on Twitter. Well, here I would like to take this opportunity to thank Dr. Capizzi and Kayleigh Ostman. And this as Dr. Capizzi mentioned in the beginning is truly a teamwork between the physiatrist and therapist. And as a team we can provide a better outcome for the patient. And here's the references. Okay.

spasticity

dystonia

upper motor neuron syndrome

treatment options

e-stem therapy

sensory motor modulation

research