Hello, everyone. I'm Dr. Miriam Siegel, and I'm going to talk to you today about movement disorders after neurologic injury. I don't have any disclosures to make, so we'll take it from here. So before we talk about movement disorders after neurologic injury, we have to first talk about terminology. Many of us are familiar with terms like pyramidal and extrapyramidal, and while these terms are familiar, they're not really all that useful, partly because they just oversimplify the anatomic underpinnings of the phenomenon that we're observing. The terms hyperkinesia and hypokinesia are a little bit more helpful. They're more descriptive, certainly. Unfortunately, there are certain disorders that just don't fit neatly into these two boxes. So the classification systems of movement disorders more recently are termed by phenomenology, and this is thanks to a collaborative effort through the World Health Organization and the International Society for Movement Disorders, and the classifications are based on phenomenology of the disorders. So I'll give some examples of what I'm talking about in a moment. Just roughly, tremor is the most common movement disorder that we see, and so it's best described as an involuntary rhythmic movement of a body part, and it can be best described by position, posture, motor activity necessary to make it manifest, so resting tremor, postural tremor, kinetic tremors. The most common one that we talk about is intention tremor, which is the tremor that occurs before the goal of the movement is reached. So this is what the classification schema of tremor looks like, and it's on two axes. Axis one is based off of clinical features, so this is your history, physical exam, laboratory tests, and the second axis of classification is based on etiology of the tremor, and this is important and very helpful because there can be syndromes that have multiple clinical features stemming from one etiology and vice versa. There could be a single etiology that results in multiple different clinical syndromes of tremor. Another syndrome that we'll talk about is dystonia, and dystonia is best characterized by sustained pattern muscle contractions of opposite muscles, and that can result in abnormal postures of that muscle group or repetitive twisting movements, and a lot of times dystonias are misdiagnosed or under-recognized because they occur in the background of spastic weakness or other motor or movement disorders. Dystonias can happen at rest, but usually exacerbated with volitional movement, and we can talk about dystonias also in terms of where on the body they occur. They can be focal, they can be segmental, meaning a chunk of the body, generalized dystonias, hemidystonias, and similarly to tremors, we see a classification system of dystonias that involves clinical phenomenology, what's the history and the physical exam show, what is that pattern of features, and etiology, and just like with tremor, there are etiologic causes of dystonia that can result in a variety of different clinical syndromes and vice versa. Other dyskinesias that we'll be talking about are chorea, athetosis, and bolism, and this is a family of disorders, and the one common thread here with these is non-rhythmicity. So, there are a little bit different flavors of the similar thing. In athetosis, the movements are slower, writhing, and predominate in the distal limbs with alternating postures more proximally, and chorea is a little bit faster. With hemibolismus or hemibolism, it's usually unilateral, and the most obvious feature of hemibolism is that it involves the proximal limb, so the amplitude of movements is very large. We're familiar with seeing myoclonus, particularly after hypoxia, and we'll talk about that for a moment later, but in myoclonus, you see brief shock-like involuntary contractions or brief shock-like involuntary muscle relaxations or lack of muscle contractions, termed negative myoclonus, and then hypereplexia, which is a fun one, exaggerated startle, stereotypic movements, akathisia, which is motor restlessness, and the classic triad of parkinsonism, which is a combination of bradykinesia, resting tremor, and postural instability. So, in talking about movement disorders after head injury, there's a very large variability in terms of reported incidents, but most cases that are talked about in the literature are correlated with more severe injury. The first group that really talked about this was Krauss and colleagues in 1996, where he followed a large group of severe TBIs, and what he found was that generalized edema on admissions was more correlated with movement disorders, and the most prevalent movement disorder that he found in these severe TBIs was tremor, and then second was dystonia. It's important to note, however, that the overall incidence of movement disorders was relatively low, and of the movement disorders that were observed, only about half of them were persistent, which means that half of the time it went away on its own, and of those, only about half resulted in any real disability, and this is in the severe TBI. He also followed a group of mild to moderate TBIs, and what he found was that some of them had an enhanced physiologic tremor, but by and large, movement disorders in this group of patients was not disabling at all, didn't require any treatment, and it was less likely to be persistent and less likely to, like I said, result in any real disability. He stratified his patients by GCS score and furthermore found that patients with high GCS-15 were less likely to develop a movement disorder at all. So, let's talk for one brief moment about what happens in terms of the pathophysiology of brain injury that results in movement disorders. So, in primary injury, you can have an injury directly to the basal ganglia or associated pathways, and DAI has a predilection for long white matter tracts that are particularly vulnerable to rotational forces, such as the superior cerebellar peduncles, ischemia and hemorrhage, to the penetrating arteries when you have rotational forces involved can also damage the basal ganglia as well. Secondary injuries, hypoxia, hypotension, oxidative stress, toxic cytokines, all of these things can also result in damage to the aforementioned tracts. So, that's a little bit more different than the expected. So, you can have aberrant sprouting, aphaptic transmission, and alterations in neurotransmitter clearance that can result in a delayed response, a delayed effect. So, post-traumatic tremor, this is the most common post-traumatic movement disorder, and it usually doesn't happen by itself. Oftentimes, the limb that's affected will also be ataxic. And while resting tremor, like I said, physiologic tremor can happen in mild and moderate TBI and also certainly in severe TBI, the most prominent disabling tremors that we see in severe TBI are coarse postural and kinetic tremors. These can be present throughout movement. They're high, like I said, high-frequency tremor, high-amplitude tremors, and they can look jerky, which makes them tricky because they can appear irregular, giving them a myoclonic appearance to them. Predominantly, these are in the upper extremity, and they're usually associated with severe TBI. The typical classic picture is a motor vehicle accident with deceleration or a pedestrian being struck by a motor vehicle, suggesting that DAI plays a role. And like I mentioned before, sometimes these will be delayed. These are just some of the pictorial representation of the tracts that are involved and why they're so vulnerable to rotational forces. The dentatothelamic tract has been associated with post-traumatic kinetic tremor. And as you can see, it's a long white matter tract here. I won't belabor this. Post-traumatic hemidystonia is the most typical form of post-traumatic dystonia, which you'll remember is the number two most common post-traumatic dyskinesia. Age at the time of trauma in this is always pretty young, infancy or adolescence. And sometimes if the injury occurs very young, before seven, there's a longer latency compared to when it occurs later in life. Delay can be quite long and a delay of years hasn't even been reported. And so the natural history of this is initially will progress over months to years and then stabilize. So this is some of the pathoanatomy and post-traumatic hemidystonia is most often associated with basal ganglia or thalamic lesions. Hemidystonia in particular has been associated with lesions of the contralateral caudate and putamen, sometimes with palladial lesions. And these lesions correspond to specific vascular territories of the anterior lenticular striate branches of the MCA. And these are particularly vulnerable, again, to shear forces by rotational forces that occur during decelerating trauma. Moving on to chorea embolism. Hemibolism is pretty rare and can be confused for a coarse tremor sometimes, especially when there's a superimposed myoclonus involved. Post-traumatic hemibolism is associated with severe TBI and is usually more persistent than its vascular counterpart that you can see like post-stroke. It can occur also with a delay, and it's usually associated with lesions in the STM and the subthalamic nucleus. Talking about Parkinsonism, so this is, we're going to talk about two different scenarios. So Parkinsonism after a single TBI, there is usually a very difficult to prove cause and effect relationship because of the delay that occurs after injury. It's typically associated with more severe injury. And you don't usually see this, but direct lesions to the substantia nigra due to penetrating injury will show hemiparkinsonism, which is very, very unusual. Usually what you'll see is the achematic rigid symptoms, the more generalized symptoms. And there have been rare reports of hemiparkinsonism also with a chronic subdural hematoma, which is pretty amazing because with drainage of the subdural hematoma, the Parkinsonism resolves completely. When there is a substantia nigra lesion responsible Parkinsonism will respond very nicely to Sinemet, but there are no data regarding effectiveness of surgery on this because it's not that common. What's more common is Parkinsonism after a repeated head injury, even has a poster child, Muhammad Ali. Boxing is the most frequent cause of this. It's also been called pugilistic Parkinsonism, and it's directly related to the number of bouts, the number of knockouts, repeated concussions with rotational accelerating traumas to the head. Myoclonus will shift now from talking about trauma, talking about anoxic injury. When you have hypoxia, you're likely to see post hypoxic myoclonus. Myoclonus is some involuntary movements, like we said, involuntary contraction or negative myoclonus, which is lack of contraction. And it's been broken up into categories, but secondary myoclonus, there's one particular type, which is post hypoxic myoclonus. That's the one we're more familiar with. Lance Adams, Lance and Adams first described it. So we know it now as Lance Adams syndrome and it's characterized by multifocal action myoclonus. It appears after people come out of coma and it's referred to as chronic post hypoxic myoclonus. It's very disabling. It's important to separate this out from myoclonic status epilepticus, which really refers to seizure activity that happens immediately after a cardiac arrest or resuscitation. And that has a strong correlation with prognosis after cardiac arrest, but it is a separate condition from post hypoxic myoclonus that we're talking about in rehab. There are a variety of other post hypoxic movement disorders that have been reported after cerebral hypoxia in Parkinsonism, stessonia, chorea, athetosis, tremor, dystonic, achinetic, rigid syndromes alone or in combination represent a large proportion of post hypoxic movement disorders that are described in the literature. There is less epidemiologic data as of now on this as compared with traumatic post-traumatic movement disorders, but many of these are caused by hypoxic damage to the basal ganglia. So in conclusion, neurologic injury can affect motor control in many different ways. Motor disorders, movement disorders, visual vestibular deficits, oftentimes these coexist all together and coexist with cognitive deficits as well, which can interfere with motor learning. So clearly characterizing all the various phenomenon that we're seeing and utilizing a common taxonomy and lexicon provides an important framework for us to evaluate, treat, and communicate with one another for the purposes of patient care, research, and generation of literature. And also in discussing functional deficits that result from these disorders and advancement of rehab science involved. Thank you very much. I'm Dr. Kelly Crawford from Carolinas Rehabilitation in Charlotte, North Carolina, and I will be talking about the pharmacological management of movement disorders following neurological injury. So first and foremost, just to let you know that I do not have any financial disclosures and I will be talking about off-label use of medication to help off-label use of medications and procedures will be discussed. So the problem with management, specifically management of movement disorders, is that there have actually been few studies done on movement disorders. In particular, the ones that have been done have been small in number and they have not established any firm guidelines for management. The other difficulty in treatment also comes with the fact that there are a number of different locations that are affected by neurological injury and with this you have different brain lesions that can cause different brain movements or different movements after brain dysfunction. But what we do know from studies is that the basal ganglia is usually involved. And so with this I wanted to go over the basal ganglia in particular the cortex and how it works. So as you can see here to help guide management you can see that there is a cortical feedback loop which you can see signals from the cortex stimulate or relay through the striatum and then with the striatum you have some inhibitory effect on the globus pallidus and the globus pallidus has inhibitory effect on the thalamus. And so what happens is the cortex sends this excitatory impulse to the striatum and the striatum then inhibits the globus pallidus which in turn inhibits the thalamus. And as you can see the net effect at that point would be the striatum releases the thalamus from the palatal inhibition thus allowing thalamic output to excite the cortex. And so as you can see along these pathways there are different opportunities for movement disorders to develop and in addition there are different opportunities for treatment that may be options to help. So first and foremost to go over the different movement disorders as have been discussed previously is I'll go over the choria, athetose, and belismoth, dystonia, tremors, myoclonus, and parkinsonism. And just to start off with is more the choria or the hemibolism and really looking at the locations the most frequent locations for these type of movement disorders usually come in the form of the lentiform nucleus or the thalamus or the thalamus or the striatum as far as hemibolism is concerned. Now the thing about choria and belismoth is the fact that it's usually self-limited. However even though they are self-limited movement disorders can substantially increase morbidity through injury and impaired coordination and in fact in a minority of cases can significantly affect quality of life increasing the risk of falling and limiting autonomy with ADLs. And so in these patients you do truly want to step in and intervene for symptomatic treatment. And with this group of movement disorders some of the main therapy options are antidopaminergic therapy, typical and atypical neuroleptics, and catecholamine depleting agents. And looking here starting with the antidopaminergic therapy we have first and foremost tetrabenazine which is a dopamine depleting agent but with tetrabenazine not only is it a dopamine depleting agent but it also decreases monoamines such as serotonin and norepinephrine. In addition you have atypical and atypical neuroleptics and those also block dopamine receptors. Now anybody who works in neuro rehab we typically try to shy away from the typical neuroleptic agents like the halodol or the flufenazine and those are because they have a lot of cognitive inducing side effects. In addition they also have the drug-induced parkinsonism and tardive dyskinesia side effects that we don't typically like to see in our patient population or that can occur at high doses that may be needed. Also in this group is the clozapine. This is less often trialed however it is found to be successful in refractory cases but you just have to be careful because it can cause agranulocytosis so you will have to monitor for that. Another option is reserpine which we can often use but that depletes stores of catecholamines and serotonin as noted above. You have to be careful however with reserpine and tetrabenazine although they work very well in treating hemibolismus and vincoria you have to be careful because both of them do because of the depletion of the dopamine into serotonin can lead to profound depression as well as hypotension and parkinsonism so you do have to monitor for those side effects as well. And then of course there's the anti-epileptic drugs so the clonazepam sodium valproate and topiramate which have been reported to be effective in small uncontrolled number of patients. The other issue we have is refractory cases that can be used are the surgical interventions and so in this case stereotactic lesion as well as deep brain stimulation to the thalamic nuclei ventralis oralis posterior or intermedius seems to confer good control of medically refractory cases although should be considered in refractory cases you do have to consider that they are contraindicated in the very frail and elderly and anybody who does have uncontrolled hypertension. And so next we're talking about dystonia and so dystonia is the second most frequent post-stroke movement disorder after chorea. The thing with dystonia is that you often see this occur with lesions in the lenticular area lenticular lesions are the most common for this one. In addition you'll see that it's frequent delayed and onset so you won't usually see this in the acute setting and then of course treatment options may be used alone or in combination and that's really true for any of the movement disorders is a lot of times you need to start with one medication intervention but sometimes moved on the combination. And I do have that often associated with hypertonicity due to underlying spasticity so see a lot of these patients who have long acting or long occurring dystonia will also just develop some spasticity along with the dystonia. And so medications we can use are systemic medications in particular the benzodiazepines and most often for these we use the clonazepam and diazepam and that's typically used to treat focal or segmental or even generalized dystonias. Of course again with our patient population particularly those with stroke or brain injury you have to be careful because of the side effect of sedation and cognitive side effects. In addition we have baclofen and that can be used orally or intrathecally. Obviously baclofen you're limited on oral doses that are limited by sedation and drowsiness so then when you get to high doses sometimes intrathecal baclofen is a good option. But again you have to be careful of sedation and tolerance in this medication. And then you have your anticholinergic drugs and dopamine depleting agents and in particular those block the action of acetylcholine thus deactivating muscle contraction. And one of the ones we use often in that is triaxefinadil which is actually pretty well tolerated and works fairly well. Again the only problem with this medication is you have to be very careful in the elderly population because it has been known to cause confusion and constipation particularly on the higher doses that you may need to use in this case. And then again listed as an option is tetrabenazine and that is the vesicular monoamine transporter inhibitor. And again as mentioned before is that this medication does inhibit or block dopamine serotonin and norepinephrine. So you have to be careful in this case again with a profound depression but also be careful with the fact that it can actually cause dystonia at higher doses due to the extreme dopamine blockade properties. And of course there have been studies that have shown that hexafenadil and tetrabenazine can actually be an effective combination particularly in younger patients and that's because they tend to tolerate those higher doses and those side effects much better than the elderly population. Another option more for focal or segmental dystonia in particular is botulinum toxin injections and this is actually a very popular option. In that case you can kind of really focally treat the area that is dystonic or has the spasticity and you don't have to affect the patient globally. And then again there are also the surgical options specifically stereotactic lesion or deep brain stimulation. And in this case your targets are usually the globus pallidus or the thalamus when it comes to dystonia. And again as in all cases of movement disorders it's usually a good option to use a combination of the different approaches. So whether that's usually using the systemic drugs, intrathecal baclofen, deep brain stimulation, or even botox injections in combination to at least provide some partial relief. A lot of times you'll have to go to your different options of therapy to give some partial relief to patients who have this. And of course the next one is tremors. Tremors usually occur in the posterior thalamus lesions. Any lesion that really disrupts the thalamic tracts in general can lead to tremors. The unfortunate thing with post-stroke tremors is that it's actually quite refractory to pharmacological therapy. You'll see a lot of times and as we all know that propranolol and primidone are actually first-line medications when you're talking about central tremors that you have patients come to clinic or from neurology that they're on propranolol and primidone. But unfortunately these actually are not very useful when it comes to post-stroke tremors particularly the cerebral cerebellar outflow tremors. Although they can be trialed and there has been evidence that they do help in less than 30 percent of the time, these usually are rarely effective. I did want to point out one specific tremor the Holmes tremor also known as rubral tremor which we see quite often actually in our patient population just because of the skewed nature in neuro rehab. But that's a tremor that's rest it's present upon rest and action with a slow frequency tremor and it sometimes has an irregular amplitude. And the interesting thing about Holmes tremor is that it actually can develop anywhere between one to two years later after the central nervous system insult. And although it's documented as being rare and caused by focal lesions in the midbrain, I actually do see it quite often in in clinic. But like I said unfortunately some of these tremors are very difficult to to treat. And but specific treatments can be aimed as specifically at the Holmes and Pallador tremors. Specifically clonazepam and sodium falproate are options. And I think any there's very small study that showed you know there were 30 percent improvement among four patients and then 70 percent had partial improvement of 10 patients and that was done in 2004. So little studies have been done but there has been some options available especially for the Holmes and Pallador tremors. Dystonic tremors you can have that occur and those are treated just like we treat dystonia and the options we went over earlier. But really other effective options are really non-pharmacological and so those would be adding weights to the affected limbs whether those be wrists or ankles and you'll see a lot of times this will be done in therapy therapy sessions whether it's inpatient or sometimes recommending it to the outpatient therapist that you may be working with with your patients. And of course again with severe or refractory cases deep brain stimulation has also been shown to be an option and in this in this case the targets would be the thalamic nuclei, the ventralis intermedius, the oralis posterior, and in some cases the lenticular fasciculus has been targeted as well. And so moving on to myoclonus now I see a lot of this a lot of times more after anoxic brain injuries but you can see it after some some stroke or other neurological injuries as well. And so post-stroke myoclonus is usually focal or segment segmental and mainly follows lesions in the midbrain pons and thalamus. You can see some transient segmental myoclonus reported after carotid or vertebral artery abnormalities but again often they're transient. And then with pontine or bulbar strokes you can see palatable myoclonus or a palatable tremor and I also added in there for effect asterixis which we see sometimes as well and that's just a form of a negative myoclonus in which you have brief lapses of anti-gravity contractions that produce that flapping movement that you see and that typically occurs or develops in the acute phase and again is typically self-limited as the patients go through their course of recovery. And of course generalized post-stroke myoclonus has been rarely reported although we have seen it it is rarely reported. So what are some of our treatment options? So some of our treatment options and most beneficial actually come in combination and again it's always important to say start with a single agent although eventually several drugs in combination may be required for ongoing treatment. And so the first ones I have listed here are the GABAergic medications and specifically I mentioned clonazepam which has been effective in all types of myoclonus. The problem again with clonazepam and with this patient population is that it can also it can include sedation, vertigo, and sometimes some behavioral changes. So again with a patient population that's already has a neurological insult sometimes the amount you can use of this medication is limited and of course their tolerance and side effects can limit this the use of this medication as well. Then you have sodium valproate which is effective in the cortical and subcortical myoclonus and again with some similar issues has some drowsiness although a little bit usually better tolerated as far as cognitively for the patient population but unfortunately with both of them you do have to monitor hepatic function closely because they do have an element of being metabolized through the liver. And then you have your levotiracetam and paracetam. Paracetam is less sedating and can be just as effective as the levotiracetam. So both can be used as options. The only problem with these medications is you just have to make sure and look out for any renal impairment. And then you have your primidone and acetazolamide can be tried but primidone causes drowsiness, confusion, and falls and again not a very popular option in our patient population. And acetazolamide necessitates electrolyte monitoring such as potassium and sodium so those do have to be monitored regularly when using these medications. And of course another option is the botox injections and again that's more for focal or segmental myoclonus but it really helps localize the area which you're trying to treat as opposed to using a systemic medication or a medication that might affect the patient globally. And then of course last but not least going over vascular parkinsonism. So this can occur in unilateral or bilateral infarcts particularly the striatum, the lentiform nucleus, or the pons. So with this particular form it's to note that patients with true vascular parkinsonism rarely respond to conventional dopaminergic therapy that we treat our regular parkinsonism patients on. In fact again only one-third of patients show improvement with conventional therapy. So what we are really left with is some supportive therapy and in particularly we work with our therapists physical therapy and occupational therapy trying to increase strength and balance options and kind of working on safety measures in order to prevent falls. Another option we look at is making sure we're treating for the risk factors for atherosclerotic disease to arrest the progression. And particularly this might include antiplatelet agents, statins, diabetic medication, and any antihypertensives to help blood pressure and reduce stroke risk. What should be said here is that parkinsonism and idiopathic parkinson's disease can coexist. So it is worth the while to do a levodopa trial and that's because there are some people who do have them coexist and you will have some people that will respond for the to the levodopa. And what they do recommend is that you do a treatment for about one month's time with a maximum buildup dose to about 600 milligrams per day. And some people will have some response, although very minimal, and you might catch those people who have the coexisting Parkinsonism and idiopathic Parkinson's disease. However, just as important as trialing the medication is also making sure that when you start this medication and you don't see a response, that you do wean those patients who are non-responders off of the levodopa, as it is an unnecessary medication in that case. And just to go over motor cortex stimulation and deep brain stimulation, which I've mentioned a couple times throughout the presentation, although it is expensive and invasive, these are reversible treatment options for severe and refractory cases for post-stroke movement disorders. And I will say personally, I haven't had a lot of insurance companies approve it per se, but they are options when people have failed multiple medication trials and interventions. And just to throw up here, deep brain stimulation of the thalamic nuclei has been useful in more than 70% of patients with post-stroke involuntary movements. And then in clinical trials, motor cortex stimulation has been shown to help with involuntary movements when they were used for post-stroke pain. So an option, again, when severe refractory cases, that if you get to that point and treatment is absolutely needed to help with a functionality and quality of life, it is an option to consider. And then just to end with some take-home points, first and foremost, movement disorders are a rare complication. And even though a lot of us may see them more frequently, we are working with a skewed patient population and those who need us and those who do develop movement disorders may be more likely to be seen in our clinics. Just to keep in mind that they can occur with damage to many different locations. You can have the same patient with the same lesion who develops movement disorder and another patient who doesn't in different areas of the brain. But to note that it is most commonly seen in basal ganglia and thalamus lesions. Some are self-limiting, but treatment may be required in the interim just to help with quality of life and to help with risk of injury and safety. And of course, as noted several times, treatment should be started with a single agent, although eventually several medications or treatments in combination may be required. And then I'd just like to share my references. And I'd like to thank you for your time. Thank you. I'm going to show some cases of secondary dystonias or presentations of secondary dystonia. And Miriam did a wonderful job of describing the different presentations. And the other thing I'm going to say is since these are secondary, you always have to look at them in the context of what else you might be seeing in terms of movement disorders. I have a few disclosures. Basically, if it has to do with dystonia or injections or pumps, I've probably now or have been on an advisory or speaker bureau. Considerations in the treatment are, and this was already discussed somewhat, but there's a basically a motor network that is at work with the dystonias. And we don't do necessarily a great job of being able to say this is exactly where the lesion is, or that's the perfect medication for the way a particular patient presents. And what I've often said to my residents is you can't take a brain and shake it up and have disturbances throughout that brain and think, oh, it was just the basal ganglia. So factor that in as we go through some of these cases in terms of how you would consider treating patients. And as physiatrists or physiatrists, it's always important to be considering the neuroplasticity and more importantly, the function. What we're trying to create now and what we're hoping we will be able to help patients with as we go forward. So here comes some of the examples. And again, as I was saying, think about the function, think about the goals and think ahead. So this is a perfect example of why I have a bias when it comes to treating brain injury patients with neuroleptics because of the increased risk of side effects. So this patient has a psychiatric history. He also has a history of multiple traumatic brain injuries. And he self-paid to come see me when he got out of prison because he was unemployable and someone thought I might be able to help him. And he is in horrific pain and you can see his cervical dystonia. He was treated with botulinum toxin, but he had no funding for repeat injections, which is a very sad commentary on access to care. But the other thing I do want to point out about him, so as not to depress everyone, is that while he was able to access injections for his neck, he was able to bring his neck up to midline. He was able to start driving a car and he was able to become employed as a truck driver. This is another patient with cervical dystonia. She has a history of bipolar disorder, but something that's really pathognomonic in cervical dystonia is the trick maneuver. So I'm going to let her do the talking. How long can you stay like that? How long can you stay like that? Short periods of time, if I can already feel it. Oh, there we go. And it feels great. I mean, wow. It's like, oh my gosh, you know, if I could stay this way. But I really can't, very long. It'll just start to go again and then I may do this. Um, or I just found this out today that you are very good. Remind me to use this clip. And then, but most of the time it's crossing my arms and manually holding my head up. One of the things you also see in that patient is blepharospasm, which initially she was not actually aware of herself, but you very often see the dystonias start to spread depending on their etiology and the particular patient. Um, another thing to consider if you're going to be treating, let's say with injections is you always want to make sure that you're not injecting the movement that the patient uses to try to self-correct their particular dystonia. So there's one point in this where my patient looks to her right shoulder and that's basically her stretching out. But some people have misinterpreted that as that being a part of her dystonia. So this is a patient who has cerebral palsy and I had seen her for a couple of years. I inherited her and she really didn't want any interventions except oral medications. And then she fell off a horse and had increased pain. So very much like when you treat spasticity, you can see that the dystonia may get worse with essentially a noxious stimulus. What I like is for people to watch her, uh, sorry, my mouse froze for a sec and then, um, and try to figure out what you would be treating or how you would look at her, how you would try to figure out what the goals of at least an initial treatment are. And then we'll go through a little bit of what happened to her. Listen to her speech. Uh, if I, if you unhook your legs as well, are you going to fall out of the chair? You have your seatbelt on. Okay. So what happens if you reach out in front of you? Okay. And what happens when you bend your arms? And now can you move your legs out? Can you wiggle your feet up and down at all? 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 your chair? Uh, yes, but I really prefer to have my seatbelt on first. I think that's a wise idea. There isn't necessarily a correct answer to how you would treat Melissa, but I think she gives a really good example of how, as physiatrists, we kind of need to pick it apart and figure out what we're going to do and factoring in as well, um, what she's comfortable with and what she's not comfortable with. So she's lived like this a long time. And so to a degree she is comfortable. Um, but she did have a back of him pump trial because really it was very difficult to, um, to kind of get a general, more of a generalized, um, treatment plan. That was one of the aspects of her care, but here's her trial. I'm just recording because I'm not used to seeing you sit for this long in one position. And then we'll also have you sit on the edge of your feet. Okay. So she has a particular way of moving. So I'm just going to factor in, um, we can skip that. Ask me a question. So, uh, we can skip that. It's basically talking about, um, what she should expect during the actual implant. Unfortunately, Melissa did get an implant of, uh, intrathecal back with him pump. And then she had, um, a problem with her pump and eventually she had it removed. She doesn't think she wants to try it again. And she actually does not remember how she was in her trial, which is probably a good reason, a good thing that I had recorded it because we're going to review it actually next week. But here's the part of the issue is dystonia in and of itself can be a noxious stimulus. It can be painful, which can make the dystonic movements worse. Um, she has now gotten carpal tunnel from that excessive wrist flexion that she has had. So this woman who never wanted to have botulinum toxin injections now texts me, um, to try and move up her botulinum toxin injections because now she has neck pain, partly due to her developed cervical myelopathy. It is not unusual for adults with cerebral palsy to develop cervical myelopathies later on. And she has increasing issues with her bladder and her bowel. And, I guess my take-home point about Melissa is sometimes if we treat people a little bit more aggressively earlier on, we can potentially help forestall or avoid some of the complications of their longstanding movement disorder. Okay. Jeremy, this is when I first met Jeremy. Um, he had a brain tumor, uh, as an adolescent. He's in this, he's probably about mid twenties, trying to finish college. He has a very uncoordinated, no pun intended, a treatment plan where he goes out of state to get his botulinum toxin injections and he goes somewhere else to get his back lift and pump taken care of. And so a couple of years ago, um, somebody sent him to me and I want you to watch his movements in particular. So I'll probably get paid and then I'll probably get to find somebody on that end. Okay. And we're going to play it one more time. So I want you to watch his hand, his shoulder, and his foot. So I'll probably get paid and then I'll probably get to find somebody on that end. So Jeremy at that point has an ITP pump. He had been getting injected. I'm not sure with what amount. Um, and he, um, was lost to follow up eventually for about a year or so. Actually, I was lost to follow up, but, uh, he came to see me not too long ago and we had a really long conversation about where we're going with this. Uh, for those of you who are interested in his injections, he was getting, um, botulinum toxin, specifically own a botulinum toxin, a of 800 units. His father's had gotten really good insurance, initially 800 units. Um, and then they started to make it more and more difficult to, um, to get that higher dose. So now watch him. No pump right now. Let me, let me back up a little bit right now. His pump is running, um, saline because they're not sure if they want to start. What do you do with those fingers? I'm having them scanned and I'm giving you a copy. Can you put your hand down there? Let's see if it makes a cramp again. And how about that finger? Can you straighten out that finger? Does it hurt? It doesn't hurt, but it's a pain to straighten. Literally not a pain, but just annoyance. But that's a lot healthier for you than the, uh, bearing weight on all your joints thing. So how long do you think you could stay like that? There you go. Oh, and there it goes. That hurt? I'm sorry. Okay. So something to consider in terms of, um, his presentation and where you might go from here is weight bearing is a big part of treating any type of tone management, any type of tone issues, dystonia, um, or his spasticity or, or taxia, et cetera, et cetera. So just even getting his hand into a position where he can bear weight would help him with his function and help limit his ongoing, um, disability from his hands. We're gonna play this one more time or not. We'll go play. So his dad sent this to me specifically. So now it's about five years later. Um, from when you first saw him in his Texas A&M shirt, and you can see his back with the pump scar back there, and you can see how little weight he gets to put on his right. You can see the shoulder retraction on, you can see the fisting of his hand. So how do you want to approach this? And, you know, in this sort of setting, it's not like I can ask people and have you respond to me, but, um, we have dwindling, um, access to botulinum toxins and we have to treat his arm and his leg. And if you talk to Jeremy, he just wants to be comfortable and he wants to be able to use his hand more because it hurts when it claws. Uh, and I look at him and I'm a little concerned about his spine. He's starting to get knee pain. Uh, and what do we do with that foot? So this is Jeremy in May and watch him Go ahead. And this is Jeremy after he had his tendon lengthening, um, just this month. I wish you could see his shoulder on this video, but you can potentially extrapolate that it's a little better. His hand's even a little bit more open, but he will be getting injected, uh, in December in his hand. So basically all of his last botulinum toxin injection went into his upper extremity and his leg went to one of the, uh, the, uh, the, uh, the, uh, the, uh, the, uh, the, uh, his leg went to one of the, my favorite foot and ankle surgeons in Houston. Here is his foot again. Okay, so I'm going to play that one more time, because what very often happens, if you're not thinking functionally, people look at this and say, well, he really didn't get any more dorsiflexion. But watch his foot, at least he has some. And I can't tell from this if he's using his extensor hallucis longus as a weak dorsiflexor, or if it needs to have that clipped next. But the point, he does have some trace active dorsiflexion, you can see a bit now. So he hasn't been able to dorsiflex up to neutral, much less past neutral, for probably over 10 or more years. So now we first have to start working on his gait. So this is with no physical therapy postoperatively, he just got out of his cast. But his hips are already more level than they were when you saw him running in the other clips. You don't want to watch that again. Here we go. So in closing thoughts, it's really important to think about the functional implication as we go through our problem solving thought processes about how we're treating, what we're going to treat, what we're not going to treat. Other people had tended to inject Jeremy longstanding, which isn't necessarily a bad thing. It's just that we have a shrinking access to how much of any of the toxins patients are going to get. And instead of putting injections in his hand and his elbow and maybe other muscles around his shoulder from time to time, depending on his presentation and in his lower extremity, now we're just going to put all the toxin that we get in his upper extremity. And we're still going to be working on his using it more functionally over time. And as we allow him to use it more functionally over time, hopefully that becomes more of a motor plan or motor process for him. Think about what if we don't treat these patients and what they're going to look like going forward, Jeremy was starting to get knee pain. That's from a plantar flexion moment at his ankle. Now it's getting better. We do have to factor in the impact of the F word, which I mean finances and funding, the funding source, and what's the best way to utilize what patients can access. So is it insanity to do the same thing over and over again? I guess that depends on the result that we're hoping for or expecting. So I think it's important to avoid the tendency to just say to the patients, Oh, well, you're happy with what you got last time. I'll do the exact same thing this time. You really have to work through the process of what is changing and what they're hoping to accomplish. And as I very often in my talks, think about would good enough be good enough for you. Just today in my clinic, I had a conversation with somebody about if you're really satisfied with the current state of how you are, then that's fine. That is your life. But my perspective and my job essentially is to help patients understand what their process might be and the implications of whether we treat or don't treat. And with that, I'm done. And thank you. Hi. Well, now we'll shake things up and talk a little bit about my clonus. So a little bit about me. My name is Dr. Mary Russell, and I am an assistant professor at the University of Texas in Houston. And I do both inpatient and outpatient practice up in the woodlands where I have an outpatient spasticity practice. So I am on the Speakers Bureau for MERS and Allergan. I don't intend to speak about any promotional or commercial uses of any specific products that would demonstrate any conflicts of interest. So myoclonus, according to the National Institute of Neurologic Disorders and Stroke, refers to a sudden, brief, involuntary twitching or jerking of a muscle or a group of muscles. It can be caused by sudden contractions, which is positive myoclonus, or by muscle relaxation, which is negative myoclonus. So positive myoclonus is more common. Negative myoclonus can occur in hospital settings as a result of toxic or metabolic causes. Asterixis is an example of negative myoclonus. I seem to see this most with gabapentin in kidney failure and is usually a great teaching point. So I put up a picture here of Dopey because in pop culture, Dopey from Snow White and the Seven Dwarfs is postulated to have Angelman syndrome, which can result in a non-epileptic myoclonus. So myoclonus, as Dr. Siegel had said, has been classified in a number of different ways. For this presentation, I will divide it into four subsections, physiological, essential, epileptic, and symptomatic causes, just as Dr. Siegel had also mentioned. There's also a psychogenic subgroup as well that's to note. But for the physiological subgroup, there are a few conditions classified as myoclonus, which occur and are benign. For example, hypnic jerks or sleep starts when you're beginning to fall asleep would be one example. Another would be hiccups, as well as a physiologic startle, such as when you hear a loud noise. The next subgroup is essential myoclonus. These include the myoclonic dystonias, familiar, and sporadic myoclonus. But I'm not going to spend too much time on that subsection today. The third group is the epileptic myoclonus. And it's important in the myoclonus workup to make sure that there isn't any seizure activity. I think Dr. Siegel also mentioned that. So just kind of reinforcing that it's important to find out when you have a patient that's presenting with myoclonus, that it isn't also a seizure that's causing them. And then the next subgroup that we'll be focusing on primarily is the symptomatic myoclonus. And that includes such causes as the liposomal storage diseases, such as Tay-Sachs and Gauchers, spinocerebellar origin, like Friedrich's ataxia or Ramsey-Hunt syndrome, other neurodegenerative diseases, such as Wilson's disease, progressive supernuclear palsy, or Huntington's disease. Dementias can also manifest with myoclonus. Infectious or post-infectious causes, such as herpes encephalitis, HIV, Lyme disease encephalitis, those are all things that can also contribute to myoclonus. Autoimmune disorders like Hashimoto's encephalopathy or celiac disease can also present with myoclonic disorders. Metabolic causes, such as acute renal failure, dialysis syndrome, or hyponatremia, or toxic and drug-induced causes like the gabapentin. Like Dr. Segal mentioned, posthypoxic or Lance Adams syndrome is another symptomatic cause, and perineoplastic processes or focal nervous system lesions. Lance Adams syndrome, this is a rare condition that is in posthypoxic myoclonus that occurs days to weeks after successful cardiopulmonary resuscitation. It's triggered by intentional actions or external stimuli that's relieved during sleep or rest. Given that information with Lance Adams, can you identify the neurophysiological classification and possible location of the lesions? So I'm guessing judging from my question, that's going to be kind of the next thing that we're talking about. So myoclonus generally occurs at the cerebral cortex, the brainstem, or spinal. So trying to localize the lesions can include electrophysiologic testing aids. These can help in distinguishing myoclonus from other disorders and classifying them according to cortical, subcortical, or spinal origin. The classification assists in the choice of treatment. For example, levatiracetam is most effective in patients with cortical myoclonus, whereas clonazepam remains the only first-line therapeutic option in subcortical and spinal myoclonus per Espe et al. in continuum in 2013. The treatment strategy for the myoclonus is best derived from the neurophysiology classification scheme. That's the cortical, subcortical, subcortical, non-segmental, segmental, and peripheral. Per the Kojevic article in 2011, cortical myoclonus is the most common type of myoclonus. It's seen in both inpatient and outpatient settings. It mainly affects distal upper limbs and face. And if you recall the homunculus, those are the areas that have the largest cortical representation. So cortical origin myoclonus presents with an action- or movement-induced myoclonus. Focal and multifocal dirts during voluntary movements are pathognomonic for the cortical myoclonus. This type may also affect speech and gait, and they are typically sensitive to stimuli such as touch. Cortical, subcortical is demonstrated by myoclonic seizures. So the non-segmental, subcortical type have brainstem involvement. So that's seen in startle reflex or hyperepilepsia or the pathologic exaggerated startle. And the reticular reflex are classic examples of that. Spinal segmental myoclonus is usually due to an underlying lesion such as a syrinx, myelitis, trauma, or malignancy. And these can be differentiated from brainstem types due to the sparing of the face and insensitivity to auditory stimuli like the startle reflex. Peripheral myoclonus is characterized by rhythmic jerks from lesions to the nerve roots and such. Hemifacial spasms is the most common example of peripheral myoclonus. Okay, and this is a good representation of what I was just talking about. So Cavaness in 2014 noted that levotiricetam is suggested as a first-line treatment for cortical myoclonus, but valproic acid and clonazepam are also commonly used. So the cortical there is the most common. It's the most common subtype, and this is the action-induced type and affects mostly distal upper limbs and face. The cortical subcortical can be the epilepsies or Lance Adams syndrome has been suggested to be in this subtype. So per Cavaness, cortical subcortical myoclonus is the physiological classification demonstrated by myoclonic seizures. Valproic acid has demonstrated efficacy in such epileptic syndromes with other medications providing an adjunctive role. So treatment options in this group include valproic acid, levotiricetam, lamotrigine, and topiramate. Subcortical or non-segmental and segmental are the brainstem lesions, and clonazepam is used primarily for the subcortical non-segmental myoclonus, but other treatments, depending on the syndrome, have been used for this physiologic type of myoclonus. Segmental myoclonus is difficult to treat. Clonazepam and botulinum toxin have often been used. Botulinum toxin for focal examples is also used for peripheral myoclonus. Overall, though, it should be noted that myoclonus treatment commonly requires multiple medications and may be difficult. I have my references. And thank you for listening to this talk, and I hope that you found it helpful. And for any questions, I have my email there. Hi, my name is Dan Moon. Today I'll be talking about the evaluation and management of tremors and hemibiosis following stroke or brain injury. I have no financial disclosures, however, I will be discussing off-label use of medications, procedures, and surgeries. I'm also not a movement disorder specialist, but I've taken interest due to limited access to a movement disorder specialist within the inpatient rehab or the region, there can be long wait times to see them, and the devastating impact the movement disorder can have on their financial or psychological recovery following stroke or brain injury. I'll be reviewing two cases. I know this has been already gone over, but it's important to note that different movement disorders can occur following a stroke or brain injury as both the extrapyramidal and pyramidal tracts may be affected. Here's case one. This patient presents with shaking, which started three months after a brain stem stroke while being stretched in occupational therapy. Since the shaking has started, he has not slept more than 20 minutes in three weeks. You can see the shaking occurs in a segmental distribution. You may not be able to see it here, but there is some head shaking as well as left arm. It occurs at rest. However, he also has a kinetic or an action tremor and a postural tremor, and the frequency is about less than five hertz, four to five hertz. So tremor is defined as an involuntary rhythmic oscillatory movement of a body part. The Movement Disorder Society recommends classifying tremor along two axes. Axis one refers to clinical features, historical features, characteristics, associate signs, lab tests. Tremor characteristics in more detail involve body distribution, activation, and frequency. Axis two refers to etiology, which can be acquired, genetically defined, or idiopathic. For purposes of this lecture, we'll be talking about acquired. In more detail, the tremor characteristics, you can refer to our body distribution, which can be focal, segmental, or generalized. The activation characteristics, such as rest versus action, and action tremor can be kinetic. In terms of kinetic, it can be simple, intention, or task-specific. It can also be a postural tremor, which can be position-dependent or position-independent, or isometric, such as when somebody makes a fist and their hand starts to shake. Frequency is also important, as tremors less than four hertz tend to be palatal tremors of myarrhythmia. Intention and Holmes tremors are less than five hertz. Sense tremors are within the four to eight hertz frequency, however physiologic tremors are eight to 12 hertz, and primary orthostatic tremors are greater than 12 hertz. To review some tremor syndromes, the most common one is probably the enhanced physiological tremor, which you or I might experience. This is an eight to 12 hertz tremor caused by enhancement of a normal mechanical reflex. Another tremor that you may commonly encounter is the essential tremor, which usually involves the bilateral upper limb. It can be postural, kinetic, involving the head, voice, or lower limbs. Dystonic tremors can be common in our patients. This involves the tremor in the body part affected by dystonia, such as the head tremor and the cervical dystonia, where their head turns and they try to correct themselves, and you see that little head tremor. There's also, if the tremor occurs in a different body part other than the dystonia, it's called a tremor associated with dystonia. Holmes tremors can be encountered in the rehab unit. This is usually due to lesion of the brain stem, and this is why it's also called a midbrain or rubotremor. These are very problematic as they can occur at rest, postural, and intention tremors. Dr. Sivahari, whenever. Here are some other ones you can review at your leisure. The Movement Disorder Society also recommends consideration for dynamic surface electromyography recordings. This is to document the presence of a tremor, frequency, and evaluate EMG burst morphology and rhythm in a tremor from myoclonus, if it's not apparent from physical examination alone. On your right, you can see an example of a surface electromyographical recording, and in the video you can see the actual tremor occurring. You can see it's a postural tremor, and you can see the oscillatory firing of muscles associated with this. It is important to keep in mind a differential diagnosis when you see somebody with shaking of the limb. This can include clonus, muscle spasms, enhanced physiological tremor, tremor with or without dystonia, also as Mary talked about, myoclonus, as well as athetosis, choria, and or hemiplegismus. In addition, we may presume that the tremor is due to a stroke or brain injury, but it's important to consider other etiologies or contributors, such as a neurodegenerative disease underlying the pathology, infection, or inflammatory disease, medications, especially antiepileptics, antidepressants, lithium is also a common cause of tremors. In addition, endocrine and metabolic disorders, toxins, neuropathies, alcohol or drug withdrawal, or stimulant ingestion, as well as other factors such as anxiety, stress, fatigue, impaired temperature regulation, and sympathetic storming. Going back to case one, we trialed several oral medications, including Keppra, propranolol, clonazepam, permadonan, tizanidine, with limited success because he had trouble sleeping. I also tried him on zolpidem, which did not help. He saw a movement disorder specialist who trialed kecinamate, and he ended up going to the ER with increased tremors as a result of this. We also had him in physical and occupational therapy. I finally performed botulinum toxin injections. We treated his upper traps, pec major, rhomboids, peronear teres, flexor carpe radialis, flexor pollicis longus, flexor digitorum superficialis, as well as hand intrinsic muscles. We also tried baclofen at his suggestion, and this actually helped reduce his head tremor and upper limb tremor significantly, reducing botulinum toxin dosing and the number of muscles treated. And here you can see the video is playing. It does not look like it is because his tremor is surprisingly reduced following the inductions, but you can see a slight tremor in the hand and wrist. Unfortunately, the tremors returned when the effects of toxin wore off. We had to refer the patient to neurosurgery. Surgical options include surgical lesion induced by ablation using a probe of liquid nitrogen, a higher frequency generator, or radiation under stereotactic guidance. They can perform a thalamotomy. Unilateral is preferred as bilateral increases the risk of severe speech, vision, and cognitive issues. Also discussed in the literature are palidotomy, subthalamotomies, which were done for Parkinson's tremors, but these are very rarely done. Deep brain stimulation has become more common. For essential tremor, it commonly the ventralis intermedius nucleus of the thalamus is targeted, whereas for Parkinson's, it's the subthalamic nucleus or the globus pallidus internus or thalamus. Complications of deep brain stim include intracranial hemorrhage, lead migration, device failure, or battery replacement. However, in our patient, he underwent something called focused ultrasound. In this procedure, magnetic resonance guided high intensity focused ultrasound is used to create a heat coagulation based focal brain lesion. Here's a patient following, sorry, let me turn off the sound, but you can see I've not done any toxin injections on this man and following his surgery, I think this is about one month out from the surgery, you can see how much better his tremor is. Now going on to case two, case two is a patient with multiple strokes who was originally referred for stiffness in his right ankle, but also had an uncontrolled flailing of the left arm following multiple CVAs. His MRI showed acute infarctions in the left caudate head, putamen, coronary radiata, anterior left temporal lobe, anterior cortex, as well as a chronic left cerebellar infarct. You can see on his left shoulder, the ballistic movement is starting to occur, however, you also notice he has some issues going on in the right arm as well, you can see he's having difficulty with trying to open his hand, and what I'm about to do is I'm actually about to passively extend his wrist, and you can see how that really exacerbates the flailing of the left arm. So this patient has bolism, this is part of a spectrum of movement disorders ranging from athetosis, choriotabolism. Bolism is irregular high amplitude vigorous movements of the limb due to involuntary activity of the proximal limb, and associated axial muscles as Dr. Segal already reviewed. It can occur one limb, which is referred to as monobolism, one side of the body, called hemibolism, or bibolism, which is bilateral limbs, this is usually very rare and associated with metabolic abnormalities. Hemibolism was originally thought to be a poor prognosis, many people thought it led to progression of death within weeks and months due to exhaustion, however, more recent studies report high likelihood of spontaneous recovery and survival. In this patient, he has monobolism of the left arm triggered by stretching and moving of the right arm. There's also right upper and lower extremity spasticity of the wrist flexors, ankle and toe flexors. There's questionable co-contraction versus dystonic activity of the wrist and hand. He also had pain and stiffness in the ankle. My concern for this patient was if I started him on the typical treatment for hemibolism such as a dopamine blocker or a dopamine depleter, I was worried I'd exacerbate the right side symptoms, which is what he originally sought me for in the first place, therefore we trialed chemodervation. In addition, his primary care doctor put him on Suboxone and Baclofen, this resulted in reduction in his ankle pain, as well as some improvement in the hemibolism and the dystonia on the right side. Here you can see this patient post botulinum toxin injection. And you can see when I passively extend his wrist, I cause no ballistic movements on the left shoulder. He's able to actively extend flex his wrist and open close his hand without inciting ballistic movements in the left shoulder. So in review, a brain injury or stroke can lead to extrapyramidal and pyramidal tract disorder. This can cause a movement disorder, as well as hyperreflexia with clonus and spasticity. In addition to impaired strength, coordination, and motor control, it's ideal to apply a synergistic multidisciplinary model of treatment. One thing I did not mention, however it's important to note, is psychiatric management and psychological counseling, as some of these patients can become depressed or anxious. And it's important to keep in mind the effect of antidepressants and antipsychotics on the movement disorder itself. Take-home points are that post-stroke and brain injury movement disorders can be devastating. The presentation of a movement disorder in our patients can be complicated by coexisting other movement disorders and upper motor neuron syndrome. Unfortunately, the management and treatment of these movement disorders is limited by access to providers, such as movement disorder specialists and neurosurgeons who perform deep brain stem and focus ultrasound. It's important to treat these patients aggressively and start them on oral medications, even if you are referring them to a movement disorder specialist, as it may take months to see one. Unfortunately, there is lack of evidence regarding treatment, as most of the evidence is geared towards essential tremor and Parkinson's tremor. As you saw in these cases, also treatment of the coexisting species, dystonia, may also be helpful, and you may want to consider treatment with phenol, ethanol, or botulinum toxin as well. Thank you.

movement disorders

tremors

hemibolism

stroke

brain injury

differential diagnosis

surface electromyography

treatment options

multidisciplinary approach

deep brain stimulation

aggressive treatment