Chapters Transcript Updates on Multiple System Atrophy Dr. Di Luca provides high level updates on multiple system atrophy. So for the sake of time, I'm going to introduce our next speaker. We have Doctor Daniel DeLuca, who completed his general and chief residency in neurology at the University of Miami with Jackson Memorial Hospital in Miami, Florida. He then went on to the University of Toronto in Ontario, Canada, and completed his fellowship in movement disorder. Doctor DeLuca sees patients at the Center for Advanced Medicine. Um, at Barnes Jewish Hospital for Movement Disorders, Parkinson's disease, Parkinsonism, deep brain stimulation, tremor, essential tremor, dystonia, Huntington's disease, ataxia, multiple system atrophy, which he'll be talking about today, progressives nuclear palsy, and botulism or botulin toxin for dystonia. So some of those I can't say. I apologize. But, um, thank you so much and also Doctor DeLuca is the assistant professor of neurology with the movement disorder department at WashU. Um, so you only see patients down at the main location, correct? Yeah, it can, it's a team building mostly, yeah, yeah. OK, just wanted to make sure. So thank you so much for being with us today and, you know, educating us on um multiple system atrophy. Yeah, thank you so much, Nikki. Yeah, it's a pleasure to be here. Um, I'm usually giving talks on deep brain stimulation and focused ultrasound for Parkinson's disease and MSA, but today I'm gonna be giving a, a slightly different talk on MSA or multiple system atrophy. And part of this talk is based on our uh recently recognized Multiple System Atrophy Center of Excellence, which is a, a brand new, uh, kind of service that we have been implementing at WSU and with this designation. We thought it was a good idea to educate some of our physicians about MSA despite being a rare disease, how important it is to recognize it early. OK. I do have some disclosures including funding from this uh center of excellence that uh pays a small support and travel funding from different companies. And today I hope to um basically give a quick idea about what is multiple system atrophy that I'm gonna be calling MSA from now on. The main goal is to know when to suspect MSA and the basic approach to diagnosis and key principles in treatment. I know that most of the physicians here are probably not neurologists, so the main goal is trying to discuss the overlapping features between MSA and some other specialties. It is not uncommon for these patients to initially See an internist or see uh a cardiologist or urologist depending on their symptoms. So, uh, I think it's really important to know when to suspect MSA. I'm going to start with a clinical case for, for one of our patients. Um, I'm going to play this video and then I'll discuss her case and some of the key findings. Mhm. It Come on. Can you put your hands up again for us. OK, perfect. You can relax. That's awesome. Mhm. And I can briefly discuss this video. Um, as we can see, she has paucity of movement, so she's not moving too much. Um, uh, we call it Parkinsonian phase because she has hyponemia or lack of facial expression, and when she lifts up her hand, she has this Sort of jerky tremor. And um as we move forward a little bit, we can see that she has abnormal posture of her neck with we call intercolis. And she had hyperreflexia or brisk reflexes. Um, and she also had autonomic dysfunction, so she had orthostatic hypotension as well as a lot of urinary symptoms. Now, she had been seen for a few years in a, uh, in a different institution, uh, being treated as, uh, a different condition and misdiagnosed as ataxia, and when we saw her, we diagnosed her with, um, multiple system atrophy based on the combination of this paucity of movements, um, Autonomic dysfunction and a little bit of ataxia. Um, and she had this history for about 2 years and, uh, also associated with syncopal episodes and she had no response to our, uh, first-line treatment for Parkinson's disease, which is levodopa. Um, I like to put this picture here just to, to show this, this idea of the, uh, of the elephant in this, uh, uh, tale of, uh, blindfolded man examining different parts of an elephant and coming away of different impressions of the nature of the beast and, um, and this is a classic paper by Neil Quinn, um, just showing how MSA can look like that depending on the person who is examining them. And depending on what they see on their exam, they might feel like it's something else. Uh, so it's not uncommon again for these patients to go through cardiology and have a diagnosis of orthostatic hypotension, then go through urology and have a diagnosis of, uh, urinary incontinence and she comes see neurology who gives a diagnosis of Parkinson's and each person has a different approach because they're just looking at their own system. Without realizing that as a whole, it is, it is this uh syndrome of multiple system atrophy. Um, This was initially described in the 1900s uh in two patients that had ataxia or in coordination of symptoms with dysartria, stiffness, and brisk reflexes. And, uh, at the time, actually, it was not only a neurologist but it was a urologist that uh initially described the condition and that's because these patients had quite a lot of uh autonomic dysfunction with urinary retention. It is not a very common disorder. It is much less common than Parkinson's disease or Alzheimer's disease. We only have about 3 cases per 100,000 patients over the age of 50 with a middle age of onset in their 6th decade of life. We don't fully understand the pathophysiology of multiple system atrophy. What we know is that like in Parkinson's disease, there was an accumulation of this protein called alpha synuclein and that might be one of the triggers for multiple system atrophy. There is also a combination of perhaps environmental exposures. That over time can accumulate and cause more symptoms or more, uh, or can contribute to the, uh, beginning of the disease. Uh Uh, as opposed to Parkinson's disease, the alpha synducin is in a different part of the brain. Maybe we don't have to discuss this for, for this audience in too much detail, but I think the main idea is that there are multiple pathological processes at the same time. There is accumulation of alpha synuclein, there is inflammation, um, and there is activated microglia and also genetic factors as I mentioned before. Um, and with these changes, you might have the development of the disease that is quite fast and progressive as compared to Parkinson's disease or other forms of movement disorders. Um, the, the diagnosis of MSA is basically through a combination of autonomic dysfunction. With uh cerebellar disease, meaning ataxia or incoordination of movements or a combination of autonomic dysfunction and Parkinson's disease or Parkinsonism to be more specific. And this type is more common in the US, but in the Asian population, and I say C becomes a little more common, a little more, uh, uh, important to recognize. But we, we often see a combination of both, but definitely the, the Parkinsonian type a little more common. Um, The diagnosis is a little more challenging to be made, and we know that up to 10 patients with Parkinson's disease. In fact have MSA and they are misdiagnosed as having Parkinson's disease and the opposite as well. Uh, we have some patients with clinically diagnosed MSA who might in fact have Parkinson's disease and, uh, the main challenge is that we don't have a clinical biomarker that allows us to To basically give a diagnosis in life and we need neuropathology to look at the brain when the patients die and find this specific alpha synucle in the, uh, in the brain of patients with MSA. Now, most recently, we did have a change in the diagnostic criteria which I'm gonna discuss very briefly. Um, But I think for, for the clinicians, it's important to know when to suspect patients with MSA and when to refer them to our clinic. And sometimes that's challenging because these patients can present again with multiple symptoms and the physicians don't even know when to start and who to refer to. Um, in patients that you might believe have Parkinson's disease, but they're just not responding to the medication that we're giving them like levodopa. When they have not only uh Parkinsonism but they have severe autonomic failure at that stage of life. Uh, in fact, some patients can initially present with autonomic failure even before they have any movement disorders or any symptoms of slowness of movement. Um, and, uh, just in this point, and that's why it's important for clinicians, including internists to, to recognize the possibility that if your patient has orthostatic hypotension or if they have, uh, uh, gastroparesis or early erectile dysfunction with no clear cause that perhaps you might suspect something else. You might suspect a neurodegenerative disease causing the autonomic failure. Uh, plus patients with ataxia and Parkinsonism. By ataxia, we meaning coordination of movements. Um, As opposed to some of the conditions that we see in our clinic, multiple system atrophy has a very aggressive course. Uh, within 3 years, most patients will develop, uh, dysphagia, so trouble swallowing, some of them requiring a feeding tube, and in 3 years, those patients will also require walking aids or a wheelchair. And again, uh, it's just a more severe, more aggressive course than we usually see in Parkinson's disease. So if patients have severe disability, uh, within the first few years, uh, that's a red flag that it might be atypical Parkinsonism in this case, MSA. Um, This is just to show how broad MSA is. Uh, I'm talking here as a neurologist. Uh, so we have basically, uh, The issues including Parkinsonism, cerebellar symptoms, pyramidal signs. But often these patients again can present through urology. Uh, with, uh, Uh, early urinary symptoms, uh, erectile dysfunction at an early age that does not respond to conservative treatments and they can also have, they can present to gastroenterology and that's not uncommon. They have gastroparesis and they can have constipation, diarrhea, they can have dysphagia as well and mostly related to autonomic dysfunction. From a cardiological perspective, these patients can have syncope, uh, orthostatic hypotension, uh, which basically is a sign of autonomic dysfunction that when they lie down, they can also have, uh, basically supine hypertension with peripheral edema as well. Uh, from a sleep perspective, they have REM sleep behavior disorder. So this idea of enacting dreams and acting out while they sleep and they can also have restless leg. Uh, they can also have depression, anxiety, and from an ENT or sleep medicine perspective, these patients can have again RBD but also what we call stridor, which is a very characteristic symptom, uh, in a sleep study. OK. Just stretch and move forward. Now, this is another patient with MSA and just to show an illustration of how sometimes they can present. Bit more in the way of facial masking than it was initially. And asked to hold her arms extended in front of her. They are more unsteady, more ataxic than they were in clip 118 months previously. And you're, you're like on, you're right on. And as you can see in the video, the patient has, uh, uh, ataxia, so she has in coordination of movement and uh she has a tracheostomy. Um, she also has a feeding too, I believe. So, uh, we can see the combination of some of the severe signs of ataxia. She also has masked facia is suggestive of Parkinsonism. Um And here's a dysmetria or ataxia. So just a more severe aggressive course in this combination of autonomic dysfunction with attacks in Parkinsonism. Um, This might be a little too advanced for the audience, but just as a, uh, uh, as an understanding that we have a new diagnosis uh diagnostic criteria since 2022 and um The basic idea is that uh we don't have a way to confirm the diagnosis clinically. The only confident diagnosis is when patients die and we look at their brain. So it needs to be based on neuropathology. But we have levels of uh confidence including clinically established, clinically probable and possible prodromal MSA. Which is a research, um, description which I'm not gonna go into details, but patients with clinically established need autonomic dysfunction which we consider unexplained urinary symptoms or neurogenic orthostatic hypotension. Plus the combination of Parkinsonism that doesn't respond to levodopa or ataxia. And if they have two or more features, um, then, uh, including an MRI, then they can be, uh, diagnosed with clinically established. The clinically probable is similar, but they can have uh one of those with just one supportive clinical feature and there is no clear imaging requirement to make this diagnosis and in the prodromo, I'm gonna skip, it's a research definition but The idea being that Uh, we might be able to detect these patients even before they have the first symptoms, uh, or before they have the first neurological symptoms, and that's extremely important for research or clinical trials because potentially we might start clinical trials in therapies that can prevent the development of the first signs of MSA. Now, when we talk about supportive features, I'm talking about the fast progression, postural instability, and severe speech symptoms. Uh, they can also have this abnormal posture of the neck and head. They can have an explained Babinski sign and this jerky tremor. Uh, and they can also have a stridor, as I mentioned when they sleep, the inspiratory sights and erectile dysfunction below the age of 60 and pathological laugh crying, which we call pseudobulbar affect. Um, and here are some of the, the symptoms and signs of MSA. Um, And again, just very illustrative, uh, this is what we call PISA syndrome when patients have this posture deformity, uh, with, uh, a stooped posture, but sometimes they can have, uh, a lateral truncal deviation, uh, resembling the PISA power, so we call the PISA syndrome and panel B, we see, uh, someone with facial dystonia or just twisting and pulling of, uh, of the face. Um, we see here the colis or the neck forward. Um, here is the classic MRI imaging that we call the hot cross bun sign, um, simply because of this, uh, Kind of deformities of the, of the ponds with atrophy and resembling a hot-cross bond. We have contractures sometimes in their hands and uh I accumulation MRI brain. Um, here is also some other pictures. This includes, uh, just peripheral edema with autonomic dysfunction which can also include discolored hands and feet. And here are some videos and this patient here has uh As you can see, People are mostly pretty sure the star stuck. Yeah. Fagan. And what I mean by dystonia is his left eye closing while he talks. lived there all your life. Where did you live before? And And. Hey. And then In 199. And here's someone with uh the stridor that I mentioned. It is not a sleep apnea. It's a different type of inspiratory uh difficulty. And this strider can actually be quite uh challenging and it can be a, a risk factor for death in MSA. So, uh, many times these patients are gonna be seen by the sleep doctors first and therefore the importance of recognizing this. And here we can see this jerky tremor. It's not a rhythmic tremor that we see in Parkinson's disease. It's kind of a jerky, fast-moving, um, brief, almost like, uh, uh, shock-like movements. Yeah, and that's visual dystonia and just. The stridor and the tremor there. Um, And skip this here. And to diagnose MSA we often have to do a few things. Uh one of them is we have to try levodopa because these patients can look like Parkinson's disease and we usually give them levodopa-c carbidopa. Or Sinemet. And if patients don't have a good response to levodopa, that's a red flag that it might be a typical Parkinsonism, including MSA. Uh, they can have autonomic dysfunction which for the purposes of, uh, or the definition is a drop of more than 20, uh, in the systolic blood pressure when standing up after 2 minutes. Uh, without or with an increase of less than 0.5 beats per minute, per millimeter of mercury of systolic blood pressure, meaning that the heart is not compensating well for this drop in blood pressure. You can also have elevated post void residual volume when you do a bladder scan, for example, and, uh, usually olfaction or sense of smell is preserved in MSA while it's affected in, um, in Parkinson's disease and Also, surprisingly, uh, cognition or dementia is not a, a common feature in MSA. So you see, if you see someone with cognitive impairment, that's usually not a common sign of MSA, so it might be something else. Um, and we can do some other tests including autonomic testing including thermal regulatory sweat testing which is abnormal in MSA. When we do imaging of these patients, we can see very specific, uh, findings, uh, which we often rely on radiology, but we like to look at those ourselves so we can, uh, knowing the clinical history, identify this better. We can have the atrophy of the ponds like we see here. We can have the atrophy of the cerebellum as well. And we can have the atrophy of the middle cerebellar peduncle. And we can have the hot cross bun sign as I mentioned plus we can also have hyperintensity of the middle cerebellar peduncle. There are some other imaging findings and I'm gonna go a little quicker, uh. As not everyone here is a neurologist, but we have some hyperintensities in the putamen. We can have also some changes in the spec, also in the DT scan, which doesn't necessarily help distinguishing Parkinson's disease from MSA. Now, there are many different uh differential diagnosis and, uh, again, this is maybe a little too advanced for, for the audience, uh, but just showing how important it is for these patients to see movement disorders specialist so we can recognize some of these phenotypes and we can try to find a treatable cause for their symptoms. It might not be MSA. We might have genetic syndromes. We might have other neurodegenerative diseases including Parkinson's disease. Um, or we might have even infectious or inflammatory conditions that might look like MSA. So it's important again to find the treatable conditions that can mimic MSA. Um, we do have some future directions in terms of diagnosis including maybe looking at neurofilament light, uh, chain levels in the plasma and the spinal fluid. We also have, uh, a protein aggregation which includes alpha synuclein. And when we do alpha synuclein testing now, a lot of people have been doing skin biopsies which is not yet a full approved uh test for uh alpha synuclein, but the idea being that you can do a skin biopsy, um, And the same protein that accumulates in the brain can be accumulated in the skin of these patients. Uh, that's the same case for Parkinson's disease, so it doesn't really help us differentiating Parkinson's disease from MSA. And we also have new imaging binders that have been trying to bind to the alpha synuclein in the brain to help us diagnosing MSA, but still we're not, we're not there. Uh, unfortunately, uh, we don't have a cure for MSA and we don't have a treatment that can slow down the progression of MSA. So for the most part, we do try medications that we would commonly use for Parkinson's disease including levodopa. And we do try options for symptomatic therapy. So if patients have drooling or syorrhea, we can do Botoxin injections or Botox injections. Um, we can do physical therapies, occupational therapy, and we can symptomatically manage the orthostatic hypotension and we basically use the same drugs that, uh, someone would, uh, would use for um for patients with uh uh just uh neurogenic hypotension including midodrine, Florinef, but also the known pharmacological approaches including compression stockings, abdominal binders, increasing salt and water intake. Now, here is basically some of the treatments and the, uh, maybe for this group, this is important as well because we have uh orthostatic hypotension treatment. As I mentioned, we do the non-pharmacological symptoms first including uh compression stockings, uh, uh, we, we tell patients to eat more salt. Uh, one trick that sometimes we do in clinic, if they have very low blood pressure is to actually ask them to dissolve a bouillon cube with water and drink it as a shot. It tastes terrible but it really salty, so it brings the, the blood pressure higher up. Um, we tell patients to avoid eating large meals, uh, and the reason being that the, the blood is gonna go to the GI system. So, uh, smaller frequent meals, uh, throughout the day. Uh, and we also have medications as I mentioned, including Florinef, Midodrine, and now most recentlyroxydopa. Uh, as I mentioned, unfortunately, we don't have any disease modifying therapies for MSA. Uh, we do have some emerging therapies and that includes, uh, targeting alpha synuclein in the brain. Uh, including the expression of this specific protein. There's a lot of controversy around this topic if alpha synuclein is actually the cause of MSA or if it's just a um A marker of a cell death and if that's uh just a symptom that something else happened before. Uh, unfortunately, none of these trials with alpha synuclein have helped so far. Uh, so some groups have been doing, uh, drugs targeting their inflammation and some other groups have been doing stem cell therapy which is in the early stage but still promising. And I think most importantly is to recognize and essay and to find a specific biomarkers that allow us to diagnose these patients early. And the main reason is that to find a cure or a better therapy, we need clinical trials. And to do clinical trials for something like MSA we need a lot of patients and being rare, it's, it's very difficult and challenging to recruit patients. So we need these patients to be at a center like WashU so they can be included in research and they can be included in clinical trials. Those are patients that uh have a life-altering diagnosis that we don't have a treatment for or a disease-modifying treatment. So being able to connect them with researchers that can actually perform clinical trials and have a potential of slowing the progression of the disease, uh, is, is, uh, pivotal and it's probably the most important thing that we can do for some of those patients as well. So, that's the importance of diagnosing them early and also to finding biomarkers that allow me to tell them this is not Parkinson's, this is MSA or this is not just uh orthostatic hypotension, this might be MSA. Um We did have some uh suggestion that maybe coenzyme Q10, which is a high dose of Brenal, might actually slow the progression of the disease. Not very clear. This is a study in Japan with a lot of patients with a cerebellar type of MSA. We cannot say for sure that's helpful or not, but it's such low yield and uh not a lot of side effects. So we often, uh, I often tell patients they can try coenzyme Q10, something like 250 or 500 twice a day, uh, as a potential, uh, medication that is not gonna harm them and might provide some benefit but still unclear. Um, this is just to show that there have been lots of, uh, new drugs being tested. Those are some of the clinical trials that are ongoing or upcoming or recently terminated pending results. So quite a lot of studies around. Uh When I was in Toronto, we did, uh, perform a clinical trial looking at some of my other very big interests of deep brain stimulation and neuromodulation, and we, we tried to put some electrodes, some uh deep brain stimulation electrodes in the brain of these patients in the globus pallidus region. Uh, and looking if this would improve the disease of, uh, of these patients and, uh, unfortunately, in the 5 patients that we, uh, we inserted the DBS, uh, we did not really find a clear benefit. Um, these patients had maybe minimal improvement for a few months but then they quickly went into the same trajectory. So we We usually don't recommend. Uh, deep brain stimulation or neuromodulation, uh, surgery for patients with MSA, uh, unfortunately. And there has also been some suggestions that maybe surgery can potentially worsen patients, so. However, there's a very nice uh paper in the New England just uh, a few years ago showing a patient with uh severe orthostatic hypotension that did not improve with, uh, all medications, all therapies, and It's also neuromodulation to some degree, just not in the brain but in the spinal cord. And they placed this new device which is a uh uh an implanted system basically in the dorsal roots. Um, and with this stimulation, they were able to take this patient from severe orthostatic hypotension, unable to walk because of, uh, the severity of syncopal episodes and hypotension to being able to walk again. So, um, on the left, we have the patient before the implant and to the right patient after the implant. And you can see that before. Due to the low blood pressure, the orthostatic hypotension, she could not even stand up to take a few steps, and after the implantation of this stimulation, she was not able to walk. It's not a, a normal walk by any means, but her level of functional disability has significantly reduced. Uh, before, she used to, uh, have syncope and, uh, pass out, uh, dozens of times a day, and now with this implanted device. Uh, she is able to actually, uh, spend more time with family, to engage more, and to do more activities. Uh, This is not yet approved for clinical practice, but just to, to give you a flavor of what can be done uh in research, what can be done in MSA and how we might approach these patients in the future. Now, this takes me to kind of a little bit of the description of what we have been doing at WasU and how we, we see this uh moving forward. As you can imagine with A lot of our patients, no matter what they have, but especially with rare diseases that are many challenges in care. From the patient's perspective, uh, Rare diseases can be tough because uh they often have to travel long distances to go see a, a physician, a neurologist in this case. Uh, our medical system can be quite challenging and especially if they need multiple specialists, it is not easy to be able to manage all of that, especially when they have a, a debilitating neurological disorder. At the same time, we don't have available treatments and we don't have a cure. And for us as physicians, we also have some challenges. We, uh, as much as we would like to spend as much time with these patients, we have a limited amount of time. We all became super specialized and compartmentalized in many ways. And uh as neurologists, we have long wait lists and there is a financial pressure that is inherent to the, to the medical system. Um, often we don't have a team with experience in many of these places and I think we often have to deal with the idea that There's nothing to be done. There's nothing to do with some of these patients, so maybe it's, it's good not to refer them anywhere or why bother in a way. And I hope to change this, this, uh, perspective in the next few slides. Um. That's a publication in neurology just showing how limited is the supply of neurologists, and, and that's uh in 2013. I can bet you that's a little worse today. Uh, and as we can see here, Missouri is in, uh, Dark pink, uh, showing that we have a demand of 20% or more and these projections are just gonna, gonna worsen over time. Um, the idea of creating an MSA Center of Excellence is to provide The highest academic standard for MSA care. It's a specialized team of experts that know how to diagnose and treat MSA. Uh, with a full range of services, uh, throughout all the stages of the disease and that can also incorporate research into the care of patients with MSA. So this is the uh sponsor of the uh MSA Center of Excellence. Uh, it's uh, a foundation called Mission MSA. It is one of the, the big support groups and the big foundations for patients with multiple system atrophy, uh, along with the other, uh, society called Defeat MSA, but many other movement disorder societies including the Movement Disorder Society by itself, but also Uh, the APDA, the Parkinson's Foundations, they all to some degree help patients with MSA, but the center of excellence is driven by the mission MSA. And the idea is they would be able to connect patients to specialized. Uh, experts in MSA so these patients can have the treatment that they would need for, for their condition. Uh, so we are one of the 25 centers of excellence in the US and we basically take care of these patients and we, uh, are able to diagnose them and provide the, the care that they need. Uh, we are the only center of excellence in Missouri, um, and I think, uh, along a large catchment area including Southern Illinois in the part of Arkansas. So we do receive some of these patients coming from other states. Um, And, and the main idea and the main hope with the Centers of Excellence is that uh we would change kind of this paradigm. This is a, a, a regular um hospital visit sometimes uh that the patients are waiting for the physician uh and they're trying to navigate the system. And uh one of the, the, the very respected movement disorders neurologist, Michael Wilken has this idea that uh in some centers, the patient needs to be the sun and the doctors, physicians, other healthcare providers need to be the stars or the galaxy around the sun. Um And the idea is that we move around the patient, not the patient moving around physicians. So we facilitate their healthcare so they can have the best care they need. And we as uh providers uh make an effort to see them and to provide everything uh at an easy pace. Um, so that's the hope that, um, which, uh, has not been yet fully developed to the vision, which has many, many challenges, but the idea is that patients with MSA would have access to a broad array of, uh, of clinicians and practitioners including a neurologist, a nurse practitioner, a speech therapist, dietitian, um, occupational therapy, psychologist, social worker, and palliative care physicians. Uh, hopefully, Always in the, the BJC health system in this case. Um, Again, many challenges to do this quick, to do this the way we envisioned, but, uh, certainly, uh, what some, uh, what some patients might need from us. I'm Gonna skip this here. And the benefit of the, this clinic is that it can improve patient care, um, so patients can be seen quicker in an expedite way, uh, but also in a way that they can receive the proper care. We can also educate our residents, fellows, medical students so they know about MSA and they know about some of these rare diseases that um uh, are not that rare and rare diseases as a whole, when you sum it up together, they don't become rare anymore and they're quite common. Um, so being able to educate residents, physicians, fellows, so they go out to the community and learn how to diagnose and treaty is very important. The other idea is research development so these patients can get access to clinical trials to the latest available uh drug or to the latest available biomarker study, for example. Especially the Center of Excellence can collect data on these patients on a regular basis to later on be able to provide better treatments and better, uh, therapies. Now, probably the most likely scenario is ALS. Uh, and in ALS we do have this very classic multidisciplinary clinic where patients are, are able to see many different physicians or practitioners in the same day. And we have been able to find, to find or people have described that uh this multidisciplinary clinic actually improves survival in ALS. Uh, and it can certainly improve quality of life in ALS. And here they're showing just how survival differed in patients with ALS clinic that we're seeing in a multidisciplinary clinic versus patients that are seeing in a general neurology clinic, for example. We also have uh similar experiences with the Huntington's Disease clinic and the Washu is also privileged to be a Huntington's Disease Center of Excellence led by Doctor Alfred Dick Dunham. Uh, but there are also PSP clinics in Parkinson's net centers that also provide the Center of Excellence approach. Um, So, uh, in conclusion, I must say it's a relatively rare neurological disorder. Uh, however, they can present with, uh, a broad range of symptoms including some of those that are treated by internists, urologists, uh, and sleep doctors as well. Uh, it is a relatively challenging diagnosis as well with a high rate of, uh, misdiagnosis, the most common one being Parkinson's disease or just pure autonomic, uh, uh, failure. Um, and I hope that I was able to convey the importance of individualized care and the possibility of being part of a center of excellence and including the possibility of being part of research and education along with a tailored clinical care. which we have now been able to, to uh implement at WashU. Um, Uh, thank you for your time and uh happy to answer any questions and uh this is our movement disorders group. We have a big, uh, group of, uh, uh, physicians, uh, researchers, uh, therapists, research assistants, coordinators that work from, uh, uh, Many different disorders including Parkinson's MSA, Huntington's disease, ataxia, Botox injections all to make the quality of life of patients better. Uh, and special attention to, uh, Doctor Norris who is, uh, the, the section head for our movement disorders group. Uh, and with that, I would like to thank you for your attention and uh happy to take any questions. Thank you so much, Doctor DeLuca. OK, so there are some questions in the chat, um, which, let's see. So the first one is, in light of the iron accumulation in the brain, is the serum fertinin typically elevated? Yeah, no, thank you for, for this question. Um, And that's an important um uh consideration that uh Many, I even see that many neuroradiologists don't, don't catch this sometimes that uh many MRI's actually do not even include the sequence for iron which is the SWI or GRE. Um, so when we're suspecting MSA we, we do have to get this specific sequence which sometimes they don't get. Um, It's not a super uh sensitive finding, so it's not always there, but when it's there, it really helps us tailor the diagnosis, but we don't see serum ferritin elevated or any other changes in uh hemoglobin or, uh, or just other blood biomarkers in general. Um, unfortunately, I wish we had something like elevated ferritin to, to help us with a simple blood collection. Uh, but unfortunately that's not the case. Um. Yeah. So then the second question is, what is the typical age of onset? Is this entity familial? Is it more prevalent in certain ethnicities? Yeah, that's another good question that uh the age of onset is usually uh on the 6th decade of life, so patients in their 60s usually. Um. They can be relatively early compared to Parkinson's disease which can be in the 70s, but I may say it's in the 60s. Um So if we see someone in their 80s or 90s, that's also a red flag. Um, uh, 60s is probably the most common that we see. Um, the question of, uh, being familial, no, it's not, it's not usually, uh, familial. There's no, there's very little genetic background to MSA. Uh, all the big studies that have been done. showed some noises that maybe some genes can be associated with a higher risk, but typically we don't see uh any hereditary features. We, it's very unlikely that someone with MSA would have another family member with MSA and if that's the case, we should highly suspect a genetic disorder that is not MSA and this patient should probably be tested for something else. Um, in terms of ethnicities, not really. Uh, There is, uh, uh, predominantly this type of the cerebellar type of MSA in Japan. So, um, and, uh, if you see Japanese patients or, uh, uh, or families from, uh, from Japan or Korea, but predominantly Japan, that's a, that's a more likely diagnosis. Um, but we certainly see much more the other type of MSA, the Parkinsonian one here in the US. I think you're, uh, you're muted, Nikki. I was, thank you. So, so there is what, um, you showed the jerky tremor. Is it still a resting tremor like classic Parkinson's? Yeah. So that's uh, um, it, it's not, it can be a rest, but it becomes a little more obvious when patients are holding their hands and I can maybe see if I can go back. Um, it's easier. Uh, if we see it, and if I try to describe it. Um, but usually, um, This jerky tremor. It's predominantly when they're trying to move their hands sometimes it can certainly be seen at rest, but I think it becomes more obvious when they lift up their hands, um. And it's different than the Parkinson's tremor. The Parkinson's tremor is a We call the peel rolling tremor, right? Like this where they can have this kind of movement. Uh, and to say that something is a tremor, it usually has to be rhythmic. Uh, Like a rhythmic movement, uh, and you see here that this is not a rhythmic movement. Um, this is irregular, jerky, shock-like movement. Uh, there's a complicated name for this that some people call. Polymyoclonus or mini polymyoclonus, um, which can sometimes be seen in MSA. Uh, sometimes even if you just touch the hand of these patients, you can have a little bit of this jerky movement as well that they might call stimulus sensitive myoclonus. Uh, so it's also helpful to try to tap it and see, and see what happens there. Um. But yeah, this is sometimes what we see in, in MSA. It's a little jerky shock-like brief contractions. Yeah. OK, I think that is it for the questions that I've seen, but if you all do have questions, um, if it's OK with Dr. DeLuca, I'll leave his email address and a follow-up email with all the other speakers, or you can email me as well. So thank you so much, Doctor DeLuca. Enjoy the rest of your day. Of course, yes, feel free to share my email and uh um. We might be circulating some of the details of the clinic as well. So if you have patients that you think might be, uh, you might have a concern for, uh, again, we try to see them a little faster than our usual patients just because of how aggressive it is. So feel free to reach out to me. Created by Presenters Daniel G. Di Luca, MD, MSc Neurology View full profile
