I'm Dr Teresa zeswitz I'm from University of South Florida I'm the director of the USF a taxia um Research Center and the zood Francis Ewood Parkinson's disease foundation in honor of my mother uh who died of Parkinson's disease as well and I'm so happy to be here today with you and we're going to be talking about the diagnosis and treatment of a another terrible disease called multiple system atrophy so multiple system atrophy um is a rare neurodegenerative disease it's characterized by misfolded um inclusions of what we've heard this morning is called Alpha cukan and alphascan is the abnormality that is found in Parkinson's disease and it's misfolded and it's aggregated and you heard it from Dr McFarland's talk and you know multiple system atrophy can look very similar to Parkinson's disease at first but as time goes on you know that something is not quite right and something is different these patients are different uh part of the problem is that they don't respond to leave aopa as well as a Parkinson's disease patient would and it's a clue or a red flag that hey maybe this person is dealing with something a little bit atypical it's an atypical form of parkinsonism just like Progressive superclear paly is and when I started uh or graduated 30 years ago you know we still call this by several terms shy Dreer disease strial nigral disease or all these fancy forms olop Ponto cerebell or atrophy um what they did is they referred to parkinsonism and problems with blood pressure and autonomic nervous system um and poor response to leave aopa so this disease um the his darkle roots go back to the early 20th century when two French scientists J deeran and Thomas they were neurologists at the Sal petrier Hospital in Paris described two patients with adult onset sporatic at taxia um and they called it olop Ponto cerebella atrophy and this is because there are parts of the brain that were affected so part of the brain is are the olives part of the brain are the ponds right that's the brain stem who or the cerebellum um so that's what they called it well they said all these parts of the brain that are affected we're going to call it Olive aono cerebel or atropy after the parts of the brain that are affected then in 1948 kitle and Greenfield said well you know what this is a real thing this is a real disease okay it has different names um shrager which I knew as a resident um stal nigral whatever but the the the UniFi ing concept is that these are all part of a syndrome by Grant and Graham and Oppenheimer in 1969 that they called multiple system atrophy and why is that well there's multiple systems of the brain that are affected okay it can be called multiple system atrophy P or C if it's a p you've got more Parkinson's and when we talk about Parkinson's we're saying that you are slow and stiff and have a balanc problem s when we talk about C we're talking about cerebellar disease all that means it's a part of the brain in the back called the cerebellum that is causing problems with balance and also a wide based gate and it's tough this is a tough challenging disease to diagnose uh postmortem studies show that only about 62 to 79% of patients were diagnosed accurately um and the delay there's a delayed diagnosis it's about almost 4 years before for the mean person uh is mean years until symptom onset to diagnosis and just like PSP it's rare it's 1.6 case per 100,000 over 40 and about three per 100,000 over 50 now how does that compare with Parkinson's disease which affects Millions Parkinson's disease is 120 to 180 per 100,000 this is three per 100,000 um both SE are equally affected and usually you see this in the sixth decade of life so even with Parkinson's disease um there are prod Drome symptoms and prod Drome means what are the early signs prodrome means before a lot of these patients have REM sleep behavior disorder does anyone know someone who sleeps at night and kicks and punches and calls out oh Seinfeld he was a little young but Kramer yeah so so that is one of the things that you see as a prodrome for not only multiple system atrophy but you also see this with Parkinson disease I know my mom who died of Parkinson's did this for years 20 years we would hear the calling and the crying out like what is is that a ghost or you know I don't know what that is it was REM sleep behavior disorder you know who knew and certain clinical symptoms make the diag agnosis of an atypical Parkinson's more likely so you get slow you get stiff you get early speech and balance disorder um whereas Dr McFarland said in Parkinson's disease you don't see balance for five to seven years it's kind of down the road these patients get- go early speech and balance um problems with speech problems with swallowing I'm not going to go through all that but you can see how diff difficult it can be to make the diagnosis of something like multiple system atrophy um right now we don't have a definite biomarker you know you'd have to take an autopsy or a sample of the brain but there are clinically established guidelines for what is probable multiple system atrophy I like this from verywellhealth.com these are the early signs your slow movement you may have Tremor you've got rigidity you're in coordinated impaired speech bow uh bowel problems usually bladder control issues but of note you don't usually have the decrease in downg gaze that you see with Progressive supranuclear py okay you know in the time course of this disease as well as other atypical Parkinson's much more aggressive than Parkinson's disease I had a Parkinson's disease patient this week who's had it for 30 years years that's not typical uh you know 20 years 17 years but these people by 30% of them are in a walking aid about three years after diagnosis they have to use a walker 60% may be wheelchair bound five years after diagnosis which you don't see with Parkinson's disease also have you know quarter after five years of falling daily severe speech and severe disar so uh levodopa is the gold stand for treating Parkinson's disease cinnamate and what happens with these patients is they look like they have Parkinson's disease and they come in and you try them on levadopa and it works for a little while but after about three years it doesn't work as well so it's a poor response and what do we mean when we say well we're going to give you a trial of cinnamon well it means that we're going to try you for at least a month probably higher a longer rather and high dose but the difference here is that these patients have what we call orthostatic hypotension they can pass out they have problems with orthostatic hypotension and guess what causes that levadopa so while we're trying you on high doses of levadopa we have to be very careful that we're not going to lower your blood pressure because then then we're making the disease worse um we can also do something where we bring patients in and we give you a couple of tablets while you're in the clinic with us never quite as good as giving you a full trial and there are some neuroimaging Clues again there are no definite biomarkers but there is something called the hot cross bun sign does anyone remember a hot cross bun do they make those anyway there it is I don't have a I don't have a pointer but in with the red arrow you can see in the ponds the little white cross it looks like a hot crossbone we don't see that with every multiple system atrophy patient and I think that there are other neurod degenerative uh conditions that can be marked by this as well that's what we call A sagittal uh MRI on a patient we're taking the picture of you and we're looking in your ear so we're looking sideways like this okay you could see the back of the brain the cerebellum is very very small there does anyone know what we mean by the autonomic nervous system what's the autonomic nervous system well it's the involuntary nervous system so if I have motor function I'm going to tell my arm right now I want to put my arm out and I want to move it that's voluntary right you're able to move when you want to move autonomic nervous system is involuntary this is your blood pressure and your respiration and your urination and you know bladder and bowel dysfunction you don't tell your blood pressure one to go up or down that's part of the involuntary nervous system and that is affected very um drastically in multiple system atrophy so patients have uh uh Syncopy they feel lightheaded if they get up they feel like they may pass out that is a problem because it's a leash on the patient you cannot leave someone at home if they're going to pass out um as as as our Falls this is a nice slide from osmosis and it says what are the disorders of the autonomic or the involuntary nervous system there are a lot of things that can cause it diabetes causes problems with the involuntary nervous system it's um amalo lupus but it causes you to feel weak and dizzy and and um tacac cartic and and how do you treat it well you have to diagnose it have to drink a lot of water add some salt to your diet after talking to your primary care physician and then you want to treat the underlying cause go go past that so what we do in the clinic and you may have had this done is your doctor will or healthc care provider will put you on the table and take your blood pressure after lying there for five minutes and then they'll carefully stand you and they'll ask you to wait a minute three minutes 10 minutes as long as you can of course without falling down blood pressure has two readings right what's the top one called the systolic blood pressure and the bottom is diastolic if you're dropping by 20 points when you stand that can be indicative of someone who's got this problem with autonomic nervous system issue I like this slide from the multiple system atrophy trust this is from the UK um 81% of caregivers found that it's difficult to manage problems with speech and swallowing in their loved ones 73 responders reported that multiple mle system atrophy had a severe impact on the quality of life 97% that said that they have difficulties managing basic life functions all of them have problems with movement and I think people with Progressive superclear policy would agree with those 60% are currently in a wheelchair 14% are totally dependent on a caregiver so does uh MSA interfere with quality of life yes PSP yes um we work in the neurom modulation Center which is where we put the uh wires in people's brains when they have a Tremor and I asked people you know how is the Tremor bothering you well it's bothering me I can't write anymore I can't drink I BL whatever but when I asked the multiple system atrophy patient I had one this week and I said how does this affect your quality of life and her family thought I was crazy I said of course it affects what do you mean how does it affect her quality of life it affects everything she can't walk she's falling she's dizzy she can't go to the mall she can't take care of herself she can't you know shop she can't cook she can't do anything so it's a much more severe disease these atypical Parkinson's are very severe and they affect everything they affect your quality of life and they affect your caregiver's quality of life what's the treatment for this we try Le aopa it doesn't really work it's a poor response onethird of people may get some benefit at first but the problem is it's limited it doesn't work for more than three years okay so as Dr McFarland said and we did not do our slides together but it takes a village what is it take no it takes a neurologist it takes possibly a cardiologist if you're dropping your your pressure if you're got constipation you may have a gastroenterologist if you're not sleeping there might be a sleep physician it takes a social worker you need psychological treatment possibly because these diseases are incredibly demoralizing and they're traumatic when you get them it's a trauma you're fighting a war and you need psych psych treatment to talk about this you need counselors um especially if you want to disclose this to the children your children you need support grip which thank God after covid was very useful that we at least have zoom and people who are wheelchair bound can get on a zoom call rather than having to travel right exercise medical Rehabilitation is vitally important for all of you distonia involuntary muscle contraction very painful um and this can be treated with botox and that can cause problems too if it goes in the wrong area and cause swallowing problem cerebell taxia we still don't have a treatment for it that's really gate and balance disorder physical therapy is vitally important why it's going to help your gate hopefully help your balance avoid contractures keep you mobile um help to avoid Falls and help you to avoid deconditioning it's very important if you could do a little bit every single day it's also in Parkinson's disease now we think that physical therapy um can actually slow the progression in some uh regard with Parkinson's disease um the treatments that we have for Parkinson's are symptomatic we're going to give you Le aopa it's going to help your symptoms but we can slow the progression a little bit if you exercise every day and I would recommend that you all look into that also occupational therapy um it's very important that you keep a person as to the best of your ability performing daily tasks Independence hey occupational therapy can help you maybe use a walker daily routine getting dressed brushing your teeth and occupational therapy can also come in and maybe look at your house maybe there are things that aren't safe like you have a throw rug or you need a grab bar or in the bathroom or something so that's very important and speech therapy is very important too here's just a few more things about uh multiple system atrophy but I think they're pertinent to the atypical Parkinson's as well swallowing issues swallowing can be terrible in a typical Parkinson's multiple system atrophy reduce your meal volumes eat slowly work on your posture okay there's maybe you need a Little Thicket uh drooling major problem with atypical Parkinson's as well there are anti-cholinergic drugs that you can try but they have side effects as well you can use some Botox to try to Botox the salivary gland but that can cause some uh swallowing issues and can aggravate the problem I'll go over here multiple system atrophy the orthostatic hypotension where you feel like you're going to pass out or you have these dis autonomic problems very important to drink water I know none of us want to do it why not because it makes us urinate and too much right but it is very important um many patients have a low blood pressure after a big meal it may be better if you take smaller meals more frequently so you don't drop your pressure you may need a medication to keep your pressure up but you should talk to your primary care or your neurologist about it that has to be done uh with a a health care provider okay also watch out if you have low blood pressure when we give you medication to keep the pressure up when you lie down at night your pressure will go very high it's possible so you'd have to uh sleep on a wedge almost like you have to put your bed up on blocks okay okay gate and Tremor we've talked about treatment of blad bladder is a major problem with multiple system atrophy um some patients have to catheterize themselves every day some patients have to cize themselves three or four times a day um are medications that can be tried for this um something like mric for example um that doesn't get in centrally but there are side effects to this too so it's good to ask your primary care or your neurologist about a medication for uh bladder dysfunction okay pain is one of the most more common symptoms of Parkinson's disease and also multiple system atrophy you wouldn't think it right but it occurs it there are contractures sometimes you get what we call a coat hanger pain right here and if you have a low blood pressure it's that the um blood and the oxygen is not getting to those muscles so it's important to tell your primary care or your neurologist about that we can think about some medications to try to treat the pain but parkinsonism can be a painful condition which it's not well known mood symptoms are huge anxiet depression mood Li liability Psychiatry psychology counselors mental health not only for the patient but for the caregiver and the children extremely important um there's a lot of depression and there's a lot of demoralization with this sleep symptoms extremely important if you have Strider or you have obstructive sleep apnea um you know the Strider is that noisy breathing that can occur um this necessitates a consultation with sleep uh physician sleep dysfunction can be a cause of death or a shorter uh survival time in patients with a typical Parkinson so it's very important to get to a sleep specialist um nowadays you don't really have to go and get a sleep test and go and sleep in a f in a place you can actually have the sleep test done at home constipation uh if it's Parkinson's disease or any of the parkinsonisms this is a major problem um increased water um exercise helps perhaps even a stall softener other medications and fiber can help be careful of the fiber uh it's good but it can make you feel bloated so my team and I went we're writing a paper on the research in multiple system atrophy uh mainly because I knew that I was going to come and uh had the honor of talking to you folks today and you know what we found is very interesting in the last 40 years we found 50 double blind Placebo control trials 50 not that there's not hundreds of research studies in multiple system atropy we're talking high quality double blind Placebo controlled I don't know what you're on the patient doesn't know what he's on I'm going to randomize it these are studies that would lead to a registration for a drug in multiple system atrophy um so I do have better news towards the end uh most of the studies pertain to the abnormal Alpha sunclean there was a large study that was just done that was negative very well-run study um but with the exception of two small studies that showed the intrathecal delivery of stem cell that showed some benefit most of the studies have been negative why maybe there weren't enough patients maybe we got the patients too late in the disease we don't have a biomarker we would like to do this early on in the disease rather than later now the good news is that if you go on clinical trials.gov I saw 10 new clinical trials and multiple system atrophy so clinical trials.gov no matter where you live you can look up and see if your neurologist can look at that and talk to you about wherever you live in the United States uh possibly entering a clinical trial uh some of these are from Korea they're outside the United States some of them are ja Japanese uh but many of them are European and um in the United States as well and these have to do with stem cell like oral mucosal stem cell um also monoclonal antibodies without getting into the specifics these are antibodies that Target the abnormal protein called Alpha nucleon there's at least two of those there's a another on gal cell line derived neurotropic Factor km 819 small molecule inhibitor of fast Associated Factor one which is a key regulatory protein and cell death also intrathecally administered mesenchimal stem cells and multiple system atrophy one coming up there and the last one is IO i n 464 another intal injection of what we call ASO therapy very involved we take another talk but good news is that there are about 10 of these clinical trials so even though we've had negative results so far um there's I think a lot of Hope for the future um and a lot of focus on the atypical Parkinson's in terms of of treating them well I I made it under so I want to thank the Cure PSP I want to thank you uh Dr Diaz Dr goldby uh my Floridian colleague Dr McFarland Jess curer um and all of you with cure PSP it's an amazing organization and um thank you for coming