Hi everybody, welcome to What's Shaking. I hope that's what you want to be here for. So first off, I want to remind you that you need to turn off your cell phones or just make them silent. There are evaluation forms somewhere for you to complete and visit the pavilion. Hey everybody, so my name is Miriam Siegel from Moss Rehab and I'm gonna start by giving you guys an overview of movement disorders after acquired brain injury and we'll start by just kind of laying down a foundation in terms of terminology, classification, so that we're all kind of speaking the same language as we go through the remainder of the presentations. So speaking of terminology, I think most of us have heard movement disorders being referred to in terms of pyramidal versus extra pyramidal, right? I think that's a common terminology that's thrown around and this isn't particularly useful and it's sort of viewed as a little bit out of fashion because the pyramidal and extra pyramidal tract actually turn out to be a lot more integrated than we realized previously. And so this doesn't really kind of give you all the information that you need to make clinical decisions or even to understand the the pathology that you're seeing. And the way that I kind of explain this is if you have ever had an old-fashioned radio where you have to like turn knobs in order to tune in, right, there's like a fine adjustment and a coarse adjustment. So the coarse adjustment, I think of that as like your pyramidal system, but the so-called extra pyramidal system works as that fine tuning, that fine adjustment, or maybe that like fine adjustment on your microscope lens, right? And so those two systems work together to produce smooth, coordinated, purposeful movements. Some people also kind of talk about these disorders in terms of hyperkinesia and hypokinesia. Is there a paucity of movement? Is there excess movement? And that is somewhat useful. It's a practical way to think about it, but it's not really very descriptive. And so a number of years ago, a classification system arose through a collaboration between the World Health Organization and the International Parkinson's and Movement Disorder Society to create a more universal and consistent taxonomy. And that's more based on phenomenology. And so we'll talk about some of these disorders and where they fall. So tremor. We've all seen tremors. Involuntary, rhythmic, and oscillatory movements of a body part. And one of the ways that we describe tremor is by the part of the body that's involved and the postures necessary to make it come about, right? So there's tremor when the limb is in complete repose, when it's completely relaxed. And that's a resting tremor, a postural tremor, when the limb is, the postural muscles of the limb are activated, and kinetic tremor, which is with a movement. And sometimes it's termed intention tremor when the goal of the movement is reached and that causes an amplification. So a little bit more about classification of tremors, just so you understand like how this classification system works. There are two axes on which the movement disorders are described. The first one is clinical features. So like I said, for tremor it can be the body location, it can be activation conditions. Is it at rest? Is it postural? Is it kinetic? Historical features, clinical signs, even laboratory tests and things like that. And then the second axis is the etiology of the disorder. And the reason why it's split into these two axes is because you can have a clinical syndrome that can arise from various different etiologies. You can also have an etiology of a movement disorder that manifests as different clinical syndromes. And so this kind of covers both of those bases and accounts for that in your classification system. Oh, I did forget to mention as well that the classification system is revised and updated and kind of serves as a basis for research, for publications, and sort of, you know, creates some unification in terms of how these studies, how these disorders are discussed in the literature. So dystonia characterized by sustained muscle contractions, sometimes patterned muscle contractions, sometimes of opposing muscle groups, causing twisting movements. This is, the photo just shows like one that type of dysfocal dystonia that we have all seen before, right? The hitchhiker's toe or the striatal toe. It can occur at rest but usually exacerbated by voluntary activity, so we'll call that action dystonia. And it can also be classified based on what part of the body is involved. So focal, like the hitchhiker's toe or like a writer's cramp or something like that. Or segmental, involving, you know, connected parts of the body or of the kinetic chain. Can be generalized dystonia or hemi-dystonia. So again, the classification is on these same two axes, clinical features and etiology. Other types of disorders that, you know, we'll just talk about a little bit are, these are the fun ones, these are the dance party ones. So athetosis, so these are slow and non-rhythmic, unlike tremor, right? And the movements are often described as writhing. And the writhing movements are more in the distal limb, with the proximal limb kind of exhibiting altering postures. With chorea, again, non-rhythmic. And these are not suppressible, right? So there are some types of movement disorders that can be suppressible. These are not suppressible. Movements of the distal limbs and the face will be involved as well. And with hemibolismus, the main clinical feature is that it involves the proximal limb as well. And so that's why these movements appear ballistic, meaning that very large in amplitude because the proximal limb is involved. And so, you know, the movements will look like wild, flinging, very high amplitude movements. Some other ones that I'm putting in here for us. Myoclonus, which we've seen. These are really brief, sudden muscle contractions, positive myoclonus. And then also inhibition of muscle contraction, negative myoclonus. This is a fun one. Hyperepilepsia, an exaggerated startle response. Stereotypy, this is one that you'll sometimes see in children with autism. And these are involuntary and patterned movements. They're repetitive, they're coordinated movements, but they can be, they're purposeless, but they can look purposeful, like self-caressing. Akathisia, or motor restlessness, is something that we see a lot of in neurorehab, a lot of times as a medication issue. And Parkinsonism, which we will spend a little bit of time talking about. And that's a combination of bradykinesia, resting tremor, and postural instability. So, movement disorders that arise from brain trauma. The literature has reported a very variable incidence, and that is because I think we haven't had a common taxonomy for a long time. Most cases that you will see of clinically significant post-traumatic movement disorders are due to severe TBI. And so there's one group in 1996 that looked at a large number of severe TBIs, 398 patients, and followed them for several years, for five years. And they found that one thing that the patients with significant movement disorders had in common was generalized edema on admission CT. And the most prevalent movement disorder that they saw was tremor, followed by dystonia. And nice numbers to know here are that, so about a little over 20% of the patients had transient movement disorders, and only 10% had persistent ones, but only five had movement disorders that were disabling. The same group later on also went on to look at mild-moderate TBIs as well. And what they found was that, yes, some mild-moderate TBIs exhibited postural or intention tremor that was similar to what we call essential tremor, but those really weren't clinically significant. The movement disorders in this group tended to not be disabling at all, and did not require any therapy. A little over 7% had transient movement disorders, and a third of those were persistent. Patients that had a higher GCS score of 15 were much less likely to develop movement disorders. So what is the pathophysiology? So for patients with post-traumatic movement disorders, sometimes there are structural lesions identified on imaging, but this can be delayed. And another really important take-home message regarding post-traumatic movement disorders is that the disorders themselves can also be delayed. There can often be a significant lag from the date of injury, and so that can kind of make it a little bit difficult to tie the pathophysiology, the imaging, and the clinical presentation all together neatly. So primary injury can cause movement disorders, if there's focal injury to the basal ganglia or associated pathways. Diffuse axonal injury, for sure, especially since there are long white matter tracts that are involved in coordination of movement, like in the superior cerebellar peduncles, that are really vulnerable to shear. If you think about how they're positioned. And then ischemia and hemorrhage, especially to penetrating arteries when there are rotational forces involved. I'm going to show you some pictures that kind of depict that a little bit also. Secondary injury can definitely also create conditions for movement disorders to come about. Elevated ICP, hypoxia, deposits of hemocitrine because of bleeding, can cause oxidative stress. And then aberrant neuroplastic phenomena can also result in movement disorders. And it's been hypothesized that this is the the etiology of the delayed onset movement disorders that we see. So post-traumatic tremor. We already said that this was the most common post-traumatic movement disorder. And I think another important little take-home message from this talk is that these post-traumatic movement disorders don't occur in isolation. There are other motor disorders and other problems that coexist with them that make diagnosis and treatment more confusing. And so, okay. So while a resting tremor can, you can see that after a severe TBI, the post-traumatic tremor that tends to be more disabling are coarse postural and kinetic tremors. You can see it throughout the range of motion. And again, they're coarse and high in amplitude 10 cm or more. However, I'll show you a video, that high amplitude tremor can be masked a little bit if there is contracture or decreased available range of motion in the limb. These are predominantly in the upper extremity and usually associated with severe TBI as I've said a number of times already. A more typical setting is a motor vehicle accident with a lot of deceleration and diffuse axonal injury. And again, often can be delayed. So this is a patient of mine. And there's no volume on this, but if there were, what you would hear is that, yeah, that when she talks, the tremor becomes more apparent. And when she's quiet, you don't see it as much. So this is a postural tremor right now. She's not resting her hand. I don't know if you can see that. And it's also present with intention. And she does have pretty significant reduced available range of motion in that extremity because of contractures as well. So that it kind of auto treated her tremor because she doesn't really have that much amplitude available to her. So for post-traumatic tremor, like we have alluded to, these long white matter tracts that are vulnerable to diffuse axonal injury often result in this type of presentation. The dentatothalamic tract is implicated. And you can have pre- and post-decusational lesions in that tract where you can have ipsilateral or contralateral tremor. Post-traumatic hemidystonia is one type of dystonia that's seen. And it's the most typical form of post-traumatic dystonia. This is occurring in pediatric TBI more commonly. And when children below the age of seven are injured, the latency is much more prolonged. And so you can see up to six years of a gap between the onset, between the injury and the onset of the post-traumatic hemidystonia. The natural history of it is initial progression and eventual stabilization. The anatomy of the dystonias are a little bit different than for tremors. Again, basal ganglia and thalamic lesions, so shared circuitry, but just different location. And oftentimes these are a result of injury to the penetrating branches of the MCA, the anterior lenticulostriate branches. These are the branches that go to the basal ganglia. And they're also very vulnerable to rotational forces and shear forces. So that kind of makes sense from a mechanical perspective. Koreanbolism. Hemibolism is rare. And it can look a little confusing when superimposed on patients that have spasticity, myoclonus, other things. Post-traumatic hemibolism is really associated with severe brain injuries. And it's usually more severe, more persistent than its vascular counterpart. This can also present after a delay from the time of injury. And it's associated with lesions of the STN, the subthalamic nucleus. So let's talk about Parkinsonism, because I think this is kind of one that we do see. And so Parkinsonism is interesting because of this delay that we talk about. But in particular, we know that patients with Parkinson's disease are at risk of falls, right? And they do tend to fall and hit their heads. And so often there's like a very much a chicken-and-an-egg situation when you have patients with Parkinsonism and TBI from a fall, especially the older folks. Often post-traumatic Parkinsonism is a result of a single severe TBI. And there can be a more classic picture due to focal lesions in the substantia nigra due to penetrating injury, but that's something that's exceedingly rare. I've actually never seen that. But interestingly, and I'll show you a really interesting case, one of my favorite cases, but interestingly post-traumatic Parkinsonism has also been reported after a subdural hematoma and with remission when the subdural hematoma is drained. That's just kind of an odd thing, but it's a little bit relevant to the case I'm going to show you. And then, you know, when a substantia nigra lesion is responsible in those super rare cases, right, theoretically it should be levodopa responsive. So this is a case I'm going to tell you about. My friend Cory, he had a severe TBI after a high-speed motor vehicle accident. He had a large subdural hematoma and a craniectomy. And then he came to inpatient rehab and did really well. He was discharged and he was pretty much walking independently, you know, distant supervision. He was verbally fluent and he started outpatient therapies and things were going great. He was still wearing his helmet. He still had a craniectomy. And then while he was enrolled in our outpatient program, he began to, over the period of about a week or so, develop a functional decline in terms of his ambulation and his verbal expression. And his verbal expression tended to improve when he was supine, suggesting that maybe he had sunken flap syndrome. His flap looked really sunken externally and also on imaging. So we sent him to his neurosurgeon and he had cranioplasty. And then he came back to another inpatient course of inpatient rehab. And this is what he looked like when he came in. So you can see he's really rigid, Bradykinetic. His steps are really short. And he tends to freeze. So we didn't really recognize this right away. We didn't know what the heck was going on. He had sort of an interesting psychosocial history, some substance abuse, some psych things. And so our psychiatrist thought that maybe he had catatonia. We tried giving him IV Ativan for that. It did not do anything. And then we thought, why don't we give him some Sinemet? Because this looks like Parkinsonism. So this is after he was started on a low dose of Sinemet. This is like a week later. He's funny. Don't listen to my shriekish voice. And then the therapist was nodding in agreement. And then this is after we bumped up his dose a little, a few weeks later. So you can see, no problem with turns. So he eventually was able to come off the Sinemet actually not too long after this episode. It was weaned off completely. So I don't know if it was a syndrome similar to what one might see after a subdural is drained or something like that, maybe a more prolonged syndrome like that from his sunken flap syndrome. And it was levodopa responsive, which is also a little weird too. So Parkinsonism after repeated head injuries looks different than Parkinsonism after a single severe head injury. Boxing is the most frequent cause. It's also, you probably have heard of dementia pugilistica, Muhammad Ali is like the poster child for that. The severity of it is related to the number of bouts or the length of a boxer's career. And it's from repeated concussions involving rotational acceleration traumas to the head. As opposed to Parkinsonism that happens from a single severe injury, in Parkinsonism after a repeated injury, the tremor is more predominating and then there are other associated symptoms with it too, mainly the cognitive. Myoclonus is another type of dyskinesia that you'll see after acquired brain injury, most often after anoxia. And so sudden muscle contractions, positive myoclonus or sudden muscle relaxation, negative myoclonus. And then there are different categories of that. In 1963, Lance and Adams coined this myoclonus in patients after severe hypoxic episodes and it's been termed Lance-Adams syndrome and that's a multifocal action myoclonus that you can see after resolution of coma from anoxic brain injury. It's also now referred to as chronic post hypoxic myoclonus and it's very disabling. It's really important to distinguish this from myoclonic status epilepticus, which can happen in the immediate post-anoxic period and is a very poor prognostic indicator for neurologic recovery. There's a variety of other post hypoxic movement disorders that can happen. We kind of talked about these already, so I will leave this in the slides for you guys to review at some point. The points that I think are important to take home from this are that neurologic injury can affect motor control in a variety of ways. It can affect your motor system, can affect coordination of movement, but you also have changes in vision, changes in balance, changes in proprioception and sensory capabilities and these can all affect smooth, coordinated, purposeful movements. And so all of these things have to be looked at in context. And then it's also important to characterize the phenomena and use the appropriate terminology in order to put things into the appropriate framework in order to best evaluate and address functional deficits. Thank you. Thank you. Good afternoon. We're going to try to get through everybody in the time we have allotted, but I am Dr. Kelly Crawford. I am from Atrium Health Carolina's Rehabilitation in Charlotte and I have the distinction of being able to go over the pharmacological management of movement disorders following the neurological injury. So I'll be honest with you, I don't have any really cool videos to show about medicine, but those will come later. So this is maybe the dry part of the presentation, but I'm certain it's probably one of the most important parts because I don't know any of you who treat these disorders, this is kind of one of the problematic portions I have when I have these patients and they develop these disorders. It's very frustrating on trying to provide relief. So no disclosures. In going over the management, it's actually quite difficult. If you ever do a literature search on what medications to use in these conditions, it's actually difficult. There are very few numbers. So even though we likely see a very skewed population and we see a lot of these patients in our clinic, if you actually look at the data, only about 4, maybe 5% of those who sustain neurological injury actually have movement disorders develop. And so with that, there's not a lot of large number studies that have been done. And in fact, even in the small number studies, there'll be conflicting information. And a lot of our management actually comes from case reports or case studies. So with that, there is actually no firm guidelines that have been developed in treatment of these movement disorders. And so I will present to you kind of what we've gone through with the literature search and what has been found to be helpful in a lot of studies. The other difficulty we have is that there are a number of different locations in the brain that have been identified as areas that result in abnormal movement. So if you look to target one specific lesion or one specific area, keep in mind that movement disorders can develop after injury to multiple different areas. So that also poses a problem. But what they have found in a lot of the literature search is that the basal ganglia and the thalamus are usually most often implicated in a lot of these disorders. And so with that, if you look at the management options, I always like this schematic. It says it's the simplified diagram, which I love because it's still very confusing. And I know when I go over this with residents and medical students, to say this is simplified is kind of funny. But if you look at this, the dashed lines are the inhibitory pathways and the solid lines are the activating pathways. Breaking it down, at rest, the striatum up there is typically at rest, so it's inactive. But the globus pallidus actually has an inhibitory pattern on the thalamus. So it's inhibiting the thalamus from being active in motor movement. However, when the cortex is activated, it activates the striatum, which then inhibits the globus pallidus, thus inhibiting the inhibition of the thalamus, thus activating movement. So as you can see, with this, you also have dopaminergic pathways with the substantia nigra, and you have the subthalamic nucleus involved in the movement pattern as well. So any lesion in the brain among this pathway has the potential to cause a movement disorder. So you can imagine why there might be differences in how to treat some of these. I couldn't really go over every single movement disorder and the medications involved in treatment, so I did pick the most documented in the literature. And that has included what Dr. Segal went over, thankfully, are the acoria, athetosis, and bolismus, which are kind of upon a spectrum together, dystonia, tremors, myoclonus, and parkinsonism. And I focused more on the vascular piece, although I know the traumatic piece was more of the lesion to the substantia nigra, which we do have treatment forms for. So I'm glad Dr. Segal covered that in her portion. So starting off with, I'm just gonna kind of go along the spectrum there, the acoria and the hemibolism. And first and foremost, these typically are self-limited. So sometimes they can last for months, sometimes even years, but are typically self-limited. However, with that, keep in mind that they can be very significantly detrimental to a patient's quality of life. They can contribute to falls. It can contribute to their independence with being able to do activities of daily living. So even though these are technically self-limiting in a lot of cases, it's still very important that you treat them so that you can limit the morbidity in some of these patients and some of the risk factors that are associated with this condition, even though it may go away after some time. The pharmacological treatment involved in these patterns typically include the antidopaminergic medications, typical and atypical neuroleptics, although I hate saying that and hardly anyone uses the actual typical neuroleptics any longer, but I will mention them. And then the catecholamine-depleting agents. The antidopaminergic therapies, a lot of medications that we're not used to treating in our general population, but if anybody's used to tetrabenazine, I believe is used a lot in Huntington's disease. Not a condition I see a lot, but has been used in that patient population. So it's usually a monoamine transporter inhibitor, thus it inhibits or inhibits the release of the norepinephrine, dopamine, and serotonin. And also along with that, there's reserpine, which depletes the presynaptic stores of catecholamines, including norepinephrine and dopamine and serotonin as well. Key with these two medications, keep in mind, they do affect the serotonin. So you are looking at a patient population that is probably already at risk with developing some mood dysfunction, keeping in mind now that if you're inhibiting serotonin release, you may also be contributing to maybe some depression development as well. Typical and atypical neuroleptics block dopamine receptors, and as I mentioned, I will put on here the typical neuroleptics as your haloperidol, paraffinazine, and flufenazine. Rarely are those used anymore in our patient population, just because of the side effects from those. So we typically go through the atypical neuroleptic agents, being mostly olanzapine and quetiapine. Mostly because of the side effect profile is much less with these medications, and they have the less cause of drug-induced Parkinsonism and tardive dyskinesia, and they also have the lesser cognitive side effects that we worry about in this patient population as well. They also mention clozapine as a medication in refractory cases, which actually does have good results, you just have to be careful because it does have a high incidence of agranulocytosis. So keep that in mind if you have to use that medication as a result of a refractory case. And there are some small studies that have looked at clonazepam, sodium valproate, and topiramate with some successful controlled chorea or hemibolismus patients. Moving on, I know this is more pharmacologically based, but I have to throw in there, there are surgical interventions that have been explored in these patients as well, and they absolutely should be considered in patients that are medically appropriate and can handle such intervention, and if they are refractory to pharmacological intervention. So mostly have been mentioned the deep brain stimulation and stereotaxy-induced lesion, and the targets that have been identified with these patients have been the thalamic nuclei ventralis oralis posterior, or the intermedius. And I also, in reading through the literature, just to report that there has been improvement in chorea in patients with Moyamoya disease with the superficial temporal artery, middle cerebral artery bypass. And moving on to dystonia. So dystonia actually is the second most frequent reported movement disorder in post-stroke patients. And so I know this is probably the number one that I see in my clinic, my follow-up clinic, and it does have the frequently delayed onset, which Dr. Siegel mentioned too, can be up from one day up to six years. So keep that in mind if you're seeing a patient, just look out for that, that could be developing. Treatment options, specifically in dystonia, in all these cases you have to look, there might be some multimodal approach, or you might have to use more than one intervention. More specifically with dystonia than the others, you might have to use this combination approach of different medications and different types of interventions to help with the control of dystonia. Lenticular lesions are the most common lesions associated with dystonia, and often associated with hypertonicity due to underlying spasticity. And just of note, myoclonic dystonia seems to be particularly resistant to medications or spontaneous remissions, so those are often difficult to control. So what are some of the medications we can use for dystonia? Most of us are very familiar with these medications, however again, with the systemic medications that we use for this, keep in mind the side effect profile for these medications. So benzos are absolutely a good option, however we do know with benzos that they do have cognitive side effects and they are sedating, so you do have probably a limited ceiling on how much and what dose you can use with these medications. But the two most commonly used in this patient population are clonazepam and diazepam. And those are really successful in treating focal, segmental, and generalized dystonia, so all forms of dystonias. However as I had mentioned there, again, you have to watch out for the side effect profile in this patient population. Well, any patient population, really. And then Baclofen, always a fan favorite. Again, Baclofen, working systemically. You have a limit on the dosing with that as well, and the cognitive and sedating side effects from this medication. They also mention anticholinergic drugs and dopamine depleting and blocking agents, specifically trihexyphenidyl, which is an anticholinergic medication. But you have to be careful with that, especially in the elderly, it can cause constipation and confusion. And then tetrabenazine, which I mentioned earlier, is that dopamine depleting medication, can be used. In doing research and literature review, it looks like those two medications in particular, the anticholinergic and the antidopamine depleting agent, working together in young patients has actually been quite successful in patients with dystonia, especially the younger population. They can handle the side effects a little bit more than the elderly population, and they've had some good results in the case studies that they have done. And of course, botulinum toxin injections, we're all familiar with that. They are mostly used for the focal and segmental dystonia, and a lot of success has been seen in conjunction with the medication management with the botulinum toxin injections. And of course, surgical interventions as well. Surgical stereotactic lesions or the deep brain stimulation. They mention specific targets of the globus pallidus or the thalamus. However, in doing literature review, they really haven't come up with the most optimal location for these interventions, but these are two targets that have shown some limited success. And then again, as I mentioned earlier, when you're looking at dystonia, sometimes the multimodal approach, excuse me, including the medication and the various interventions working together will have the most success. And moving on to tremors. Tremors actually are very common. Unfortunately, there's limited success with treatment of tremors, particularly post-neurological injury tremors. So if you go back and you remember with the essential tremors, we actually have propranolol and primidone, which are the first-line treatment for essential tremors. Unfortunately, there's very limited success in using these medications with post-neurological injury tremors. Now you can try them, and I have tried them in the past with very, very limited success, but they are typically not successful with these type of tremors. The lesions usually associated with this type of tremor is posterior thalamus or any lesions that disrupt that thalamic pathway. There is specifically the Holmes tremor, or if you remember, it's called the Rubrol tremor, and it's a tremor that occurs, characterized by resting postural and movement tremor, and it sometimes can develop anywhere from one month up to two years after injury, and those are usually associated with insults to the midbrain. However, there is a little bit more success, and although it is rare, there is some more success with the treatment of the Holmes or the palatal tremor, and those studies have shown that clonazepam and sodium valproate may be more beneficial in those type of tremors compared to the posterior thalamic lesion tremors. If you have a dystonic tremor, dystonic tremor is usually treated similar to dystonia, but with our limited management with medications, what we typically focus on are alternative methods, so working with our therapists or working with our team on any assistive devices, whether that be weights, ankle weights, wrist weights, any assistive devices that might be helpful. I know we do a lot of weighted utensils with our patients as well on the inpatient unit. In severe cases where it is very life-limiting, there is the deep brain stimulation that has occurred in some patients that have demonstrated some success. Again, I have the targets listed up there, the thalamic ventralis intermedius, oralis posterior, and the lenticular fasciculus have been the best options for these patients with deep brain stimulation. And myoclonus. So myoclonus, oddly enough, so although mentioned by Dr. Siegel, in the hypoxic or post-anoxic brain injury patients, generalized myoclonus is not too uncommon. However, in the post-stroke population, generalized myoclonus is actually uncommon. So with that, you usually, with the post-stroke folks, you usually see focal or segmental myoclonus, usually mainly follows in the midbrain, the pons or the thalamus. You can also have transient segmental myoclonus reported with any carotid or vertebral artery injury. And then you have palatal myoclonus, also called the palatal tremor that I mentioned earlier, that can happen with pontine or bulbar strokes. And then, mentioned earlier, the negative myoclonus, or as we may better note it, as asterixis. And that's that negative myoclonus where you have brief lapses of anti-gravity movements and contractions when you have that outstretched limb. And those usually are self-limiting and occur more in the acute phase. And these, there's actually a lot of different options that have been explored with these medications. With this, with myoclonus in general, and various medications in conjunction with other medications working together can also be very helpful. So, first and foremost, the GABAergic medications. The most two studied and quoted in the literature have been the clonazepam, which is effective for all types of myoclonus. And sodium valproate, which is effective more in cortical and subcortical myoclonus. Keeping in mind the side effect profile for these medications, you have to be very cautious in patients who have hepatic insufficiency because they are metabolized through the liver, so you have to monitor the liver enzymes. And levotiracetam and paracetam. I know I use levotiracetam a lot in the anoxic myoclonus patients, which has been very helpful and very useful. Also been seen helpful in Lance Adams syndrome as well. The only problem with these two medications, you just have to be cautious in anyone who has renal impairment. So, you have to be cautious with hepatic impairment with those two, the first two, and then renal impairment in the second two. And then some adjunct medications that you can use in conjunction with some of these medications are primidone and acetazolamide. Acetazolamide is actually a diuretic, a carbonic anhydrase inhibitor, if I remember correctly. Also works on the GABA receptors as well. In use in conjunction with some of these other medications has actually been shown to be very helpful. The only thing you have to make sure is it is a diuretic, so you have to make sure you are monitoring the electrolytes of these patients. And then of course, my favorite again, botulinum toxin injections has also been shown to be helpful, particularly in those focal or segmental myoclonic patients. And then last but not least, I have vascular Parkinsonism. So I know we talked about the post-traumatic Parkinsonism in the substantia nigra, which does do very well with dopaminergic medications. Vascular Parkinsonism, unfortunately, does not. So if you look at vascular Parkinsonism that can develop typically with unilateral or bilateral infarcts in the striatum, lentiform nucleus, or the pons, only about 30 to 50% actually respond to dopamine medications. Now of course, 30 to 50% isn't bad, so it's worth a try. But just to keep in mind, they are typically not as responsive to your typical Parkinson's patients or those that may have had a traumatic injury to the substantia nigra. So what do we do for these patients in particularly? So we do a lot of supportive therapy. This is where we work with physical therapy and occupational therapy more to help with gait, balance, strength, and any assistive devices that might prevent injury or prevent any falls of such. And then we also wanna make sure with vascular Parkinsonism that they are looking at possible underlying causes of future vascular injury. So you wanna make sure these folks are taking their statin. And if they're at risk, they have their antiplatelet medication. If they have high blood pressure, they're having their high blood pressure treated. And if they have diabetes, that it's well controlled because our goal is to prevent further vascular injury by looking at these risk factors. Now with that, they do say that Parkinsonism and idiopathic Parkinson's disease can coexist. So the recommendation is that you should still try a levodopa trial, a minimum of at least one month to six weeks to see if these folks do actually respond to the medication. And in a lot of cases, they will, and you will continue the medication. However, of course, if they're non-responders, you wanna make sure that you wean them back off of the medication. But they do recommend that you trial at least a four to six week trial levodopa in these patients. And then just to sum up with non-pharmacological treatments, just to throw out there. As I mentioned several times, deep brain stimulation of the thalamic nuclei has actually been successful and useful in more than 70% of patients with post-stroke involuntary movements. And that's include the hemibolism, the choriad, and the apoptosis and tremor. So these are people who do fail the pharmacological treatment. These are options you can look into, again, if they are medically appropriate and can go through the stimulation. And there have been clinical trials ongoing for motor cortex stimulation in the control of post-stroke pain. But in these trials, they have also found that there has been benefits with controlling of movement disorders too. So there's more trials going on for the motor cortex stimulation as well. And then there's transcranial magnetic stimulation is another experimental approach for treatment of movement disorders that is ongoing at this time too. So other alternatives to the pharmacological management. And just wrapping up the take-home points. First and foremost, movement disorders are actually a rare complication. Again, we probably see a skewed view because of the patients we see that are referred to us. It can occur with damage to many different locations, but again, most commonly the basal ganglia and the thalamus. And some are self-limiting, but treatment may be required for symptom control and to help reduce falls or risk factors of further injury. And treatment can be started with a single agent, although eventually several medications or different treatment options in combination may be required for partial or beneficial resolution. Thank you. Okay, I'm Cindy Ivanhoe and my primary goal is to get through this lecture without coughing to death, so apologies ahead of time. I'll let you look at that. And then, so in terms of considerations and treatment, as you've all seen, I won't waste any time on this, but movement disorders, particularly in acquired brain injury, are the result of many different parts of the brain. And I always tell my residents that it's like you took a brain and you shook it up, and then you think, oh, I'm gonna fix that neurotransmitter. So sometimes all we have is to address the person in front of us. So it can be very difficult to prove the causal relationship between the particular lesion and the clinical disorder. I will own my bias about neuroleptics, whether typical or atypical, because I've seen a lot of complications that are potentially related to them longer term. Likely a network disorder. And dystonias can originate centrally or peripherally, and that's important to keep in mind, because a person can have a peripheral injury and end up with a dystonic posture as a result, often in conjunction with complex regional pain. And then remember that neuroplasticity and function are our goals as physiatrists. So as we go through these slides, you'll hear me talk a bit about treating, what is the goal of the intervention? So we're gonna go over a lot of patient examples. This was the hardest part of preparing my talk, was trying to edit all the different varieties of patients that I have a collection of. So in putting this into context for everyone here, I would like you to think about the potential cause, but very often there's very little we can do about that. Though Parkinsonism, you do need to look, particularly in your post-traumatics who've had craniectomies for hydrocephalus, because you can see Parkinsonism as a result of hydrocephalus. Think about function, think about the goals, and try to think ahead in terms of what will that patient be looking like or doing after you're through with them, however often you're gonna follow up with them. So this is one of my Wiccan patients who got out of prison where he was not only beaten several times, but has a long history of being on assorted meds for bipolar disorder. And hopefully everyone in this room is looking at him and going, what do you wanna do for that neck? Anybody? What is the primary treatment for cervical dystonia? Botulinum toxins. So his getting botulinum toxin, I won't say which one because I'm Switzerland, but he got botulinum toxin injections and it made the difference between returning to work as a truck driver or not working. Unfortunately, longer term he couldn't afford it and he couldn't get it covered, so I have no idea what happened to him longer term. Thank you. Thank you. Remind me to use this again. So what you may or may not have noted in her, so that's a trick maneuver, a gest antagoniste, where patients with dystonias in general will have a trick maneuver, something that helps suppress their abnormal posture. What never bothered her, but used to drive me crazy, was her blepharospasm. I don't know if you noticed that as well. So she has blepharospasm in cervical dystonia, but it's not functionally causing blindness, so we never treated that. So this is Melissa. You can sound with this one too, would be great. If you're not braced in the wheelchair the way you kind of wrap yourself in it, are you able to move your wheelchair by yourself, like control yourself? Uh, yeah, but every time I have to keep it on. I think that's a wise idea. And I didn't always wear it. I didn't wear it in public. So where do you want to start? It's so nice to see people's faces. I don't recognize half the people I've known for three years. Anybody want to throw it out there? I can't see that far anyway. No? So, yeah, go ahead. I'm sorry? Okay, so what do you want to do with her? She's got cerebral palsy. She's been like this for, you know, 20 plus years. Probably Botox at the start, but I think she has to do a deep brain stimulation. Okay. I know it's kind of hard to sell that to patients with brain injuries. I want to put a focal treatment in your brain that may or may not help months from now, right? So we started with toxin. I actually wanted to do a pump trial because that's a little bit easier of a sell. But the question is where do you want to inject her, and do you see goals? Because many people sort of don't. So how many people see goals? How many people don't think it's worth treating? How many people aren't going to vote this year in the elections? Come on! All right. Yeah? It depends on your therapist, right? It depends, like if you send a patient to someone who sees no goals, that patient will fulfill that expectation. But we have less and less control over where our patients go and what they can get in for how long. Obviously, she got a baclofen pump trial, so you didn't have to guess, but I want you to see, do you see a difference? So what do you see? She's still, yeah. And she's still. So she did get a pump and unfortunately had a complication, but the reason I put this up is dystonia in and of itself is a noxious stimulus, right? We always talk about spasticity and dystonia, and a noxious stimulus will make it you worse. Now I still see her. She had her pump taken out, unfortunately, I think, but I have a bias there, too. Now she has carpal tunnel, do you remember those wrists that you saw? But doesn't want to have surgery. She has a little bit of PTSD from the healthcare environment, I don't blame her. She has cervical myelopathy, not an unusual finding in adults with cerebral palsy, along with some bladder and bowel long-term issues. Neurogenic bladder and bowel. She gets migraine, so there's one injection indication, but she had her pump explanted. The reason you have this slide is, here she is doing better in therapy, outpatient, first inpatient and then transition to outpatient, but her pump wasn't working. So why is she doing better? Because she got therapy, right? Something that we don't necessarily talk about, but she got the right therapy, case in point. But it's not sustainable. It's not sustainable without an underlying intervention. So Jeremy, and I do have their permission, but Jeremy had a brain tumor when he was four years old. And he came to me, he was getting his pump managed somewhere, he was getting his injections somewhere else, and then he lived in a totally different place. Now he's all mine, took a while. But you can see the dystonia. Now at this point, he has a pump, okay? Totally low dose, has a pump, getting injected without any sort of localization technique. So now, I'm still seeing Jeremy. I think you can play the sound a little bit. So one of the things that we try to get patients to do for neuroplasticity purposes is weight bearing, right? He can't get that hand. See, watch his fingers, all right. So he's been getting injected with onobotulinum toxin since he was a little boy. Now, how many people here are injectors of toxins? OK, good. There's a lot of room for growth, guys. But how much would he need if we're going to treat his arm and his leg? We're talking onobotulinum, 400 units like insurance ones? He was getting 1,000. So I snuck him into a course I was teaching. We always did 1,000 until the FDA turned you all into weenies. But he, thank you. If he can only get so many units, how do you decide where to put that, right? You talk to him about what his expectations are and what he wants. But I snuck him in, not at three months, but two months into a course where we needed patience. Sorry. And we injected him again, and we pretended like he hadn't just been injected. And I did a frontalis test, where you inject the frontalis muscle, and you hope to see paralysis of the frontalis muscle. Nothing. He had no response to that. And because he lives in the valley, and they would report that he was, quote, better, I went with that for a while. Anyway, I switched him. He gets abobotulinum toxin. And had I not been sick, I would have included how he looks now, which is very different currently. So he's clearly one of my very few patients who has become resistant. Additionally, it is worth noting, for toxin purposes, that he was probably injected with the original, quote, Botox, which got reformulated in the late 90s. But what do you want to do, right? So I watched him. He, OK, did you see his limited dorsiflexion? That's not dystonia anymore. That's contracture. So he went for surgery, because there was really no point to my injecting him forever in his gastroxilius. And he went for surgery. And you can see he's doing better. I don't know if you can see in this slide. He has a little bit more dorsiflexion. But if you walk in high heels all day long, or for 20 years, and then we take off your high heels, you're going to find that it's really hard for you to activate the anterior compartment of your calf. So he's got some weakness now. But he has the range now. So that's kind of what we're trying to work on. My question is, did Scoliosis leave me? I mean, it's been all my life. So Sarah had a baclofen pump, did really well, was in school, believe it or not, with a communication device which she could access. And then they decided to do a scoliosis surgery and never considered during that scoliosis surgery that she had a pump in there. So I am convinced that her catheter is screwed up. But I haven't been able to wean her dose, which is ridiculously high, because she's getting something. And every time we try to decrease it too much, her mom and caregiver tell me, no, she's definitely worse. Now, she could be worse because she has megacolon. She could be worse because she has bladder dysfunction. She could be worse for who knows why. So the question becomes, what can I at least do with her toxin injections? Because of her funding, I am limited to 600 units, not four. But I want you to hear her mom as loud as you can make it. This is about a week after injections, just a week. Before the injections last week, we couldn't have done this, because she goes herself into an extension and she can't get out of it. And so is it probably because her head's forward maybe, or she's a little more tongue-controlled? It's because their alveoluses are relaxed. They normally are hypotonic. They take complete control of their body. And the Botox kills all of it. Kills is a strong word. But they can't take the time. Do you see her tongue control? Anybody know where I injected her? There's a picture I don't want. So she gets injected in her genia glossis, and in this particular injection session, she got a lot into different cervical extensors, because there's a very odd tendency for the upper cervical spine to be in hyperextension. And when you break that up and you bring a head into flexion, you can very often relax the dystonic posture, and that's an important thing to keep in mind, because that might motivate how you're going to treat her, where you're going to inject. A lot of people turn very bizarre colors when I tell them that I inject her genia glossis every three months, but it makes a big difference. She's not an oral eater, for one thing, but it's part of her whole dystonic, dyskinetic presentation. So closing thoughts, what is the functional implication of what we are treating or not treating? Particularly with the dystonias, you want to be sure that you're not... If you're injecting, that you're not injecting the antagonistic movement. In other words, patients will have a movement, like you'll see patients... Like the woman with cervical dystonia, she has a tendency to turn this way, to try... I don't know if you saw that in the video clip, but to try and get out of that lateral collis posture that she assumes. So I have to make sure I'm not injecting what's turning her head the right... This way, because then I would be taking away her compensatory movement. So that's a cautionary piece of information or factoid for when you're injecting, wherever the dystonia is. What if I do not treat? So a lot of our patients, like Jeremy is a good example, because he's what some of us might say highly functional. He went back to school after all his treatments and is trying to get a job with accommodations. Not always easy these current days, but anyway. What would happen longer term? What's going to happen long term to his knee and hyperextension, to his hip or his spine and everything up the chain from R not intervening? One of the specialties is supposed to be concerned with longer term disability. Brain injury, whatever the ideology, is a chronic disorder and we need to factor that into our treatments. The impact of the F word cannot be ignored. To me, that's funding. How we treat is really much more influenced by what we can do as opposed to what our patient's potential might be, something to consider. And is it insanity doing the same thing over and over again? Jeremy, before he came back to me, having had a hiatus for various reasons, was still getting injected in those plantar flexors. It wasn't doing anything. And so maybe because of that F word, we send patients for surgeries a little bit sooner, though you do need to factor in that sometimes dystonia can migrate a little bit. And then think about would good enough be good enough for you? Because that's something I hear over and over from patients. I very often end my talks with that because a lot of patients have come from seeing other physicians, granted I'm sort of at the end of the food chain, but who have said, you should just be glad you're still walking. And sometimes they want a little bit more than that, and we should be in a position to try and offer that to them. So with that, I will close. Thank you for coming. Thank you to those of you who wore your black t-shirts, too. So for our next five minutes, I'm going to go over a couple more videos. We're going to talk about tremors, and we're going to actually put theory to principle, as you'll see. Now I'm going to skip a lot of slides, because I think a lot of these are redundant. But we're going to go over three cases. So here is case one. This is a man who had a brainstem stroke, and three months after the stroke, he started to shake while he's been stretching OT. He blamed the OT, but I'm going to tell you, I told him clearly it's not the OT's fault. He has, you know, you see here, he has this low frequency stroke on a tremor. It's at rest. He also has it with action. And it's a home tremor, which Dr. Kelly talked about earlier today. Miriam mentioned this. I'm going to skip a lot of these slides, too, because we're going to just look at these videos. One thing I do like to do on these patients, when I do have the F word, the funding available for that, is I do like to do some dynamic electromyography studies on them. And what it consists of is you have these surface electrodes on their muscles. Here's a lady with a brain injury, and you can see she's okay right now, but then once she raises her arm up, you can see that arm oscillate back and forth, and above her is a recording, and you can see the upper trap, the deltoids, the pec major, everything is just firing. It's very rhythmic, though, and you'll notice. Now there's some more stuff you can do with these things that I don't bother to do. But anyways, when you see somebody shaking, what I hope you learn, or twisting or turning, there's so many different things that are going on. We focus at the AAP Menar so much on spasticity, but there are so many more flavors to the stuff. But in addition, when you see these people, you want to know, is there something else going on? Is it just purely the movement disorder from their brain injury, or did they have something else going on beforehand? If they're elderly, or do they have a central tremor? Sometimes with medications, I'm also very careful with neuroleptics or even SSRIs. Any of these psych meds, they can have an impact on the movement disorder is what I'm seeing. Do they have hyperthyroidism? Is that under control? Toxins, other things. Are they anxious? Are they just tired? They're so deconditioned. But anyways, so for this guy, I swear this video is actually playing right now. It looks like a picture, but it's actually playing. I don't know if you can shake a mouse over it to show that it's a video that's playing, just because I know you guys don't believe me. I tried all these meds on him that didn't really help him. I actually Botoxed him, and I saw him a month later. You can play it again, and it's a video, and he's actually still ... I did a lot of muscles. It took a lot of time to get to all of them. You see a little bit. Yeah, you may see a little bit in the hand, but it took a lot of time. What was beautiful is when you turn on the EMG machine, you can hear that coarse tremor in that machine. It is really fascinating. I also did try a little Baclofen. It also seemed to help as well. However, I kept ... The problem with Botox is that it keeps wearing off, and all the other toxins, sorry. Therefore, I referred him to neurosurgery, because there are a lot of options in that sense. You have your otomies, deep brain stem. What they did, though, is they did something called focus ultrasound first. I think it's sort of like a trial for deep brain stem, is what my understanding of it is. It's a focused lesion using ultrasound. You can see, he still has it, but it's now functional. He can use his hand to some degree. Later on, it did come back, sorry. Later on, the tremor did come back after the ultrasound, and I was doing his hand muscles and his wrist primarily, and he's now going for deep brain stem. This is to be continued as well. This is an interesting case that just came a couple months ago to our unit. This man came into our complex medical unit after he got shot in the chest twice, times two. He had a P. He was in pulseless electrical activity that had resuscitated him. It was crazy what they did. They had to do a thoracotomy. They had to go in there, do an open cardiac massage to help revive him. To see him two months later, he's actually taking these steps, but can you replay that video again? I want you to focus on his kneecaps. I don't know if you can see it, but they're like oscillating. This man came to us with a diagnosis of debility, but if you look at his history, do you see that? There you go. I don't know if you guys, but yeah, his kneecaps are oscillating. They did, I think it was more of like spastic or clonus, they used some baclofen, which did help, but I was able to do a dynamic EMG on him. If you look at his recordings, I know there's a lot going on, but if you look at the vastest rectus femoris recordings, you can see those motor units just firing constantly, and that's where the oscillation is coming from. Now we go into myoclonus, so this is a form of Lance Adams syndrome. He clearly had an anoxic brain injury that unfortunately was undocumented. Let's see, I'm going to skip a bunch of these. As you know, I like to use this dynamic EMG, it's my favorite toy. So here's another example of an anoxic brain injury, post hypoxic myoclonus, and here let me skip all those. And the key thing about this is it can be spontaneous, it can involve action, or just be stimulus-sensitive. It is multifocal, and you can have actually multiple different types of myoclonus going on in the same patient. It is fascinating and very disabling. And here's this lady, she had an overdose injury and developed an anoxic brain injury from this. And you can see she does well, and then all of a sudden she begins to develop her myoclonic jerks. Below, again, is another dynamic EMG study to demonstrate what's going on in the muscles. So this is where a lot of myoclonus can happen, and this is even, you know, can be even more unexpected. It's harder to control because you can't really predict when they happen. They tend to happen more on turns or when the patient gets anxious, but you can see as we walk this patient, you know, he's doing okay, and then all of a sudden he has a drop attack. And EMG, again, you can see there's that sudden lapse occurring in his muscle activity. However, there is hope for these patients. You know, as we talked about levotiricatum and valproic acid, Klonopin, have been used with some success. We also put a baclofen pump. So this is a patient with an intracerebral baclofen pump. And you can see... Oh, sorry, you can turn the volume down. But yeah, before, I wish I had a previous, like a pre, because he saw me a month before or a couple months before, and he was very, very shaky. And right now you can see he has fairly smooth movements until the very end, you can see a little bit of trace of myoclinus there. So I do want to mention, in addition to like doing the medications, the baclofen, a lot of therapy, he was very debilitated. And medication management, he was on, he was on primidone, he was on baclofen, he was on all these other meds. And we had to really clean up his system. We actually brought him in for inpatient rehab, because he actually was hospitalized with hyponatremia at some point, and we used that as an impetus to get him in. This is one of my favorite cases, and I will tell you, I did present this and, you know, and a case report was accepted for this, and I'll tell you, I misdiagnosed this patient. So I apologize if you guys saw this case. I want to let you know I was wrong, so going from there. So this guy, he came to me with stiffness of the right ankle. That's what they wanted me to treat. If you look at his MRI, he has lesions all over the place. And what do you see when you see him? You know, his ankle, it was definitely stiff. He couldn't move it. It was very rigid. But he also knows he's got these sort of, these proximal, and I got, you know, and this is what threw me off. They looked ballistic to me. You'll see when I stretch, and this is the other crazy thing, is when I would stretch his wrist up, you can see how they began to get really out of control. And so I thought he had, you know, botulism, and it's like they accepted it for that. I gave a talk on this a couple years ago, and, but in actuality, botulism is more continuous, right? It's not stimulus-sensitive. He actually has cortical reflex myoclonus, and the reason why I come to this conclusion is it's triggered by external stimuli, and also, if you look at where his lesions are, his lesions are all on the left side. It can be ipsilateral, whereas botulism is usually like a contralateral lesion, and it's substantia nigra. So what did I do with him? The good thing was I didn't try to put him on any of these antidopaminergics that usually use to treat botulism. I looked at the right arm, and I treated the rigidity, because that was what was inciting it. So I gave him really just botulinum toxin injection right there to the FCR. Just one muscle, and you can see how he's able to move that arm smoothly without inciting any myoclonic jerks in the left arm. So yeah. So when you look at these patients, I want you to look at them as a big picture. They have movement disorders. They're weak. They can also have clonus spasticity. You just want to sort of... If you treat some of the things you know how to treat, you can actually make a lot of improvements, and you just want to use this sort of synergistic multidisciplinary mode of treatment where you're not just treating with meds and injections, but also using... You may need a psychologist or psychiatrist to help manage their psychiatric medications. A lot of PTOT just to keep them as strong as possible, build up their endurance. And with that, I think we'll just finish off with this. I want to acknowledge my collaborators on this study, including people who couldn't be here unfortunately, and I open the floor to questions. Thank you. Thanks.

movement disorders

acquired brain injury

classification

tremor

dystonia

athetosis

chorea

myoclonus

Parkinsonism

treatment options

functional deficits