Holistic!™ - Atypical Parkinsonism: Doc, why don't I have PD? - Irene Litvan

<Transcrript 0 we'll uh turn the floor over to our amazing uh neurologist host facilitator dr suber 0:06 manian hi everyone welcome it's almost the weekend uh and uh i hope everyone's staying safe 0:13 and doing well and we are still physically unfortunately distanced but socially 0:19 connecting through this virtual modality and thank you to the pmd alliance for hosting and um it's with great pleasure that i um 0:26 bring you a fellow colleague who also is based here in southern california dr lipban 0:33 and i'll be introducing her in a minute she has been in a number of parts of the u.s before 0:38 and i have a lot of close friends that have worked with her before and she just brings such a wealth of information and it's been just nice to 0:45 collaborate with her down here um and it's this is a talk that's uh from a lot of what people have asked for 0:52 um through the series so they've been asking for an understanding of if it's not parkinson's disease 0:58 what else could it be and so we'll be covering some of the atypical parkinson's syndromes or um you know 1:04 there's parkinson's so there's many ways that we talk about this umbrella of parkinsonism and 1:09 dr lipvan will be telling us a little bit about that she has a really interesting background she's sort of 1:14 been all over the world she is originally from uruguay and then she did her medical degree there and then 1:22 did some training in georgetown university in washington dc and also spent time in 1:28 barcelona um did a fellowship in barcelona spain um and so it's just a real wealth of 1:35 information that she brings and she's really been heading up a huge number i was looking at her cv she just has such a wealth of 1:42 research talents and um has really been bringing together people uh to study many of the disorders 1:48 that she'll be talking about today so i wanted to um introduce you and welcome you dr litvan and 1:54 learn a little bit about your journey maybe you could tell us a little bit about how you started in uruguay ended up in barcelona and now in sunny 2:01 southern california what brought you to medicine originally maybe what inspired you as a neurologist 2:06 and also what made you interested in specifically these sorts of disorders 2:13 well i love to help out and so i always felt that being a physician was 2:20 kind of something that i wanted to do or being a nurse either one and as i grew up i started look at the 2:27 brain and i was fascinated with the idea that there were different areas in the brain 2:33 and that each one would have different functions and that when there would be a problem a lesion 2:41 then the person would not have that function and i thought that was important and more importantly i thought 2:48 well perhaps we can do something to make things better and that's kind of 2:54 how i got into research so yes i was born in uruguay and i did 3:02 finish my medical school but there was a dictatorship that came in so i moved to spain but in spain 3:10 um they just were coming out of another dictatorship that was franco and so there was a lot of uh 3:18 revolution in some ways um and eventually everything came 3:24 uh you know it was well and i had a wonderful time uh being a 3:31 fellow over there and do my first obviously doing my residency and then 3:37 doing my fellowship in the best hospital in spain in barcelona 3:44 so when i finished i realized that i wanted to do research and i thought that 3:49 the u.s was the right place so i came to the national institutes of health and i spent many many years there uh 3:56 working and it came to a point that they told me you know if you really want to grow 4:02 further you have to go to academia and so i there was a position in kentucky 4:10 and i thought okay i'm gonna go there and start something i had no idea where kentucky 4:16 was i have to admit uh so it was a whole new thing for me 4:22 and so i end up in louisville at the university of louisville and uh there i established a whole 4:30 woman disorder center and uh and i just very well to the city i was 4:35 really very happy and the people from the university of california told me why 4:42 don't you come and establish the same here and i thought oh i'm not sure i want to 4:48 start all over again but they said just come and see once i 4:53 came here and i saw san diego i said yes i'm coming here i love it 5:00 so i came back to san diego and established a whole movement disorder 5:06 center that i'm very happy because now is a parkinson's foundation center of 5:11 excellence it is a cure psp center of care it is a 5:19 a research center for dementia with louis bodies it is a huntington's cc center we work on dystonia so it is a 5:27 whole uh whole thing of um things happen that we were able to grow 5:35 and uh be successful and i'm really happy with my patients that gave me the 5:41 strength to move forward and all the inspiration that makes me move towards 5:49 doing more research so i can help more that's amazing i think you could go to 5:54 mars and start a center and you'd have [Laughter] humans and every other so you could just 6:03 it's we've had a really great run of powerful women in movement disorders and um i'm proud 6:09 to say that you're one of them we had claudia trunk welder on earlier for world brain day and um she talked 6:14 about the movement disorder society which i know you're a fellow in as well and so we applaud the work and 6:20 and it is a lot of work um to succeed in this field and and put together these things but i'm inspired by your inspiring story 6:27 and it sounds like we're all really inspired by our patients so i think without further ado we will let you 6:33 teach us a little bit about this field i know you put together some slides and we can kind of start there and take some 6:39 questions as we go and learn a little bit more about you know what you do thank you 6:44 so i'll talk about why don't i have pd that is a question that some of my patients ask 6:51 um they said i'm slow i'm stiff i have tremors so why is it that i don't have pd 6:58 um these are my disclosures uh we're just going to share the screen right 7:04 we have to put up the slides oh i thought that i'm sorry i thought that 7:12 that is some you disconnected me from the slides i thought so i thought i was sharing them again 7:19 yeah you just have to go at the bottom and show the screen yeah i'm doing that there you go perfect yeah we got it 7:24 okay all right lovely so hold on a second 7:34 so this is lovely san diego um so these are my disclosures um 7:40 i most of them are related to research and really or therapeutic trials 7:48 and very little is related to industry 7:53 so the key points of today are let's define what parkinsonism is 8:00 so we can understand what the parkinsonian disorders are and let's see how we can classify these 8:07 disorders let's also talk on about a typical parkinsonian disorders and 8:14 differentiate parkinson's from all the typical parkinsonian disorders 8:20 i'll give a few examples at the end if i go too long you let me know okay 8:30 so the most important aspect or the most important feature of 8:37 parkinsonism is slowness or slow loss of amplitude of the movement um 8:44 that you'll see an example in in a second uh it is also the presence of 8:52 either stiffness or tremor and uh this is the patient 8:58 that is doing the finger tapping than many of you may have done and you can 9:06 see that there is slowness and at times that is kind of hard to see 9:13 okay let me let me go from the beginning here these ones are starting on their own so 9:19 this is a patient that has a rest tremor and you can see it here and when he's moving his arms that is 9:26 going to disappear and that is typical of parkinsonism 9:33 the slowness can be also shown as we walk and so this is a person that is 9:38 very slow and it is also having 9:43 uh no movements of the arms and the steps are kind of small 9:50 and that is a little bit of what parkinsonian gait is 9:58 so all these disorders that are parkinsonian disorders have something in common and what they 10:05 have in common is like in the back of the brain you may have heard about some something 10:11 that is called the substantia that is what produces the chemical 10:17 dopamine that makes the motor circuit work dopamine is like gas for a car without 10:24 it it doesn't work well so what happens is a dopamine goes to these 10:31 areas of the brain and then makes it uh the whole 10:38 circuit in order to be able to allow us to walk well 10:45 and you may have heard of that scans and so some people say okay if i get at 10:50 that scan will i be able to know what i have well you would know 10:57 that you have parkinsonism but it doesn't really tell you what disease you have so 11:04 as you see these areas in the brain the nuclei 11:10 sorry you can see here the same thing and this is a normal uh 11:18 coded that is the deep area in the brain and this one is an abnormal one you can 11:25 see that there is something that is missing here 11:31 that is related to lack of chemical dopamine that comes to the brain 11:40 so what are the parkinsonian disorders well these are diseases in which we have 11:47 parkinsonism and we basically divide them in two major groups 11:54 secondary secondary to a cause that we can identify and that's why we ask you what are your 12:01 medications have you had a little stroke have you had some infections 12:07 etc etc because these kind of help us figure out if there is something that 12:13 we can identify and treat right away but if there is nothing like that 12:21 and the disease is kind of presents gradually and slowly pretty much 12:27 is what happens when we have a neurodegenerative disease it's a big fancy name to basically say 12:36 that cells in the brain die and die much earlier 12:42 when they should as we age so all these diseases that are 12:48 neurodegenerative can be divided into uh main ones parkinson's disease and these 12:55 ones that are called atypical parkinsonian disorders and there are many there are 13:03 sporadic diseases diseases that don't have family members within with a illness um and that 13:10 is progressive supernuclear policy psp uh that is something more 13:18 more known as psp multiple system atrophy msa cortical basal degeneration cbd 13:26 dementia with lewy bodies dlb or lewy body disease and then there are 13:32 familial uh diseases like frontotemporal dementia with parkinsonism 13:39 this is just to let you know it's not that you need to learn all these all these fancy names 13:47 so the important aspect here of knowing what disease is is 13:53 what allows us to know what is the protein that deposits into the brain 14:00 the the protein that deposits into the brain in parkinson's disease in multiple 14:06 system atrophy and in lewy body dementia is called alpha nuclei this protein 14:14 is very important but what is more important is that it allows us to diagnose a 14:22 disease if we do newer studies that are to look at the spinal fluid and 14:30 measure alpha nuclei this is still not um available 14:38 for commercial but it is in research and likely is going to go uh into the market 14:45 but in addition and more importantly is that we can develop and we are 14:51 developing treatments to try to slow all these diseases that have alpha 14:57 nuclei so if we know that is one of these three diseases 15:03 perhaps we can try to find eventually a 15:08 treatment that can slow or stop the illness the other protein that deposits in psp 15:16 and in cbd is called tau tau is another protein that is kind of 15:22 what forms the walls of the cells that the walls of the pipes that 15:29 nourish the cells and if it's not functioning well 15:36 of course the cell is gonna die and that is pretty much what happens and again 15:42 we're having multiple treatments that are being looked at to try to see if any of them 15:51 can help slow these diseases 15:56 there are these other ones several other ones that i'm not going to mention because i'm not going to discuss them 16:02 and that have other proteins and we don't have treatments for those yet experimentally 16:12 so what is anatypical parkinsonism so while we can define 16:20 parkinson's disease as having the slowness with or without tremor or rigidity 16:29 the typical parkinsonian disorders have more than that they have early on 16:36 problems with walking problems with balance and in addition they have problems that 16:43 do not occur in people that have parkinson's disease 16:49 so i'm gonna tell you what are the differences between one and another uh although i'm not 16:56 gonna be able to go over all the differences uh but i'm gonna go into several so you can get a sense of what's 17:04 going on so if we give a person that has parkinson's 17:11 levodopa or requip or pramipex or whatever it is that you that you administer 17:19 it makes all these motorcycles that i told you 17:26 work because it's replacing that dopamine that we normally have so the patients 17:33 respond beautifully because that is a major aspect of the motor problems that 17:39 patients with parkinson's have they don't have so many other problems regarding motor uh motor problems there 17:48 are other problems without any any doubt and as the disease progresses 17:53 some of the things that happens in a typical parkinsonian disorders may happen in parkinson's 18:01 but one thing that does not happen is what happens in the typical parkinsonian disorders 18:07 there is lack of benefit there is no benefit the person stays about the same 18:14 initially may respond minimally or mildly but not a major major benefit as 18:21 we see with parkinson's disease another difference is that while in 18:29 parkinson's the diseases progresses in a slow way uh 18:34 this does not happen with the typical parkinsonian disorders for 18:40 example early on we can have problems with balance 18:46 people that just fall without knowing why they fall uh because there is not 18:53 that they had an accident it's not that they didn't see something or have other clearly 19:01 problems such as having problems with the knees or the the hip or 19:09 something that would explain that fall 19:14 then um those people may have what we call one of the symptoms of the 19:21 typical parkinsonian disorders in parkinson's on the other hand as you 19:27 saw in that patient that i showed you earlier they may walk slowly may have slow steps 19:34 but there are no problems with balance or fall for many many years 19:44 so here you can see a patient of mine who actually was not working so bad 19:52 but she has an abnormal posture and also she has no balance as i minimally 19:59 touch her she falls and she cannot recover she also has uh the skin with a red 20:07 color that if she puts the legs 20:12 horizontally that disappears that is those are the symptoms that have to 20:20 do uh this one in particular with the autonomic system and i'll talk about that later on 20:29 what are the differences so 20:35 another difference is that patients with the other parkinsonian disorders may 20:42 walk like if they were inaugurated uh this is not the one i wanted to show 20:48 you so let me show you the one i want to show you i'll go back to the to the other one so you can see that 20:54 this person is unstable but also on when the legs are really separated 21:01 from each other at times it's hard to see but but you clearly can see that overall 21:07 the legs are separated um and that is not something that we see in 21:13 parkinson's disease let me go backwards now 21:23 freezing can occur in parkinson's disease usually does not occur early but this 21:30 patient had freezing for many many years and ended up having 21:35 another disease that is psp so it is a different 21:41 story altogether because freezing walking was her major problem she didn't 21:48 have any other problem freezing was it 21:57 so we talked about the rapid progression so one of the things that could happen is 22:03 that we can see a patient early on coming in a wheelchair 22:09 um and having like a fracture and that kind of let us know that this 22:15 patient does not have in parkinson's uh so we already know as the patient 22:21 comes in into the office that this is not parkinson's disease 22:27 again there is a slow progression in parkinson's dc so 22:34 we don't see many people walking with uh going into a wheelchair and if they do 22:41 is when the disease is quite advanced and they may come in a wheelchair but 22:46 then they leave walking normally um because now the 22:51 levodopa is working or the another medication that makes the motor circle work 23:03 so in this a typical parkinsonian disorders there 23:09 are problems moving the eyes it could be up and down it could be horizontally 23:16 um there is also a clear difficulty with reading that is beyond what we have as we age 23:25 and that doesn't happen in parkinson's disease and i'm going to show you a little bit of a patient that had psp 23:33 um and he was able to follow horizontally that pen 23:40 but you're going to see that he's unable to follow it in the vertical direction and that 23:48 is um why the disease is called supranuclear policy 23:55 because there are lesions that are above of where the uh the nuclei the areas 24:02 for the nerves that go to the eye are and make both eyes not being able to 24:09 to move appropriately and we can confirm it because if we move 24:16 the head up and down we can see that the eyes move like a you will see in adults 24:24 and that is what we call the doll's head maneuver 24:30 he wants to see his watch but he's unable to do so and the same uh perhaps move in the eyes 24:38 but not really like that because they go up but in any case um moving his his arm is how he's going 24:45 to truly see it there could be that 24:52 the person has a stiffness i may say that they have tremor when not 25:00 doing anything as we saw tremor at rest in the patient with parkinson's disease being slow 25:08 but in the typical parkinsonian disorders there may be a lack of ability to use 25:16 a hand or a leg or uh there could be a 25:23 difficulty having special abnormal postures 25:30 and here actually this patient of mine was a policeman who had 25:36 lost the ability of using his gun and that was his first symptom and then 25:43 he developed these abnormal movements that you saw 25:48 and there are several here um the the difficulty that he has extending 25:56 his arms and how he has his fingers and also that little jump 26:02 that he has none of that we usually see in parkinson's however i'm gonna clarify something 26:10 in people that have young parkinson's disease at times we do see uh this abnormal posture 26:18 what we call dystonia and that improves uh with the levodopa the dopamine 26:27 agonist but this one that this patient has does not improve with anything 26:33 so it's a different one it could be that patients may have 26:40 dementia early on they may see things that are not there 26:46 they may have problems talking may find a significant difficulty 26:53 saying words and that is not what happens in parkinson's in 26:59 parkinson's recognition in in general is normal 27:05 there may be some difficulties multitasking or perhaps planning there can be some 27:11 depression some anxiety but unless they have 27:16 some medications they don't have hallucinations the hallucinations that we see in 27:24 typical parkinsonian disorders are hallucinations without 27:29 any medication whatsoever or any reason whatsoever is that scary for you in some 27:36 ways that's sort of interesting okay what are the interesting things you 27:44 see oh faces and colors things that are attractive people that 27:52 you know yeah sometimes and other times 28:00 okay so you saw that uh this was a patient that had dementia 28:06 with lewy bodies and we'll talk about that briefly later and hallucinations early on without any 28:13 medication or any reason occur may occur early on 28:20 so on the other hand here we have that in parkinson's disease people 28:28 act out the dreams normally when we sleep we don't move when we 28:35 dream but what happens in parkinson's is that 28:42 we can act out the dreams and if the dreams are really bad then we're trying to defend ourselves 28:49 uh because we don't want to be attacked and then we can either hurt someone or fall to this the floor or hurt 28:57 ourselves in in different ways that is not usually present 29:02 in the typical parkinsonian disorders and i'm going to show you this because 29:08 actually this is one of the early signs of parkinson's disease 29:14 this may not happen on everybody but may happen many many years 29:20 before someone developed parkinson's disease 29:26 so he's having a bad dream and obviously he's trying to defend himself so this 29:33 is why he's doing this at times the patient may awake and at times continue sleeping and in this case 29:40 also continue sleeping so now let me summarize a little bit 29:49 and give you a little bit of a glimpse of what is some what what are the features 29:57 of some of these disorders and i'm starting with psp because it's the most common one 30:05 so these patients present with early balance problems and falls that is extremely 30:12 common they may have this parkinsonism the slowness the stiffness but usually 30:20 instead of being a lot of the limbs as in parkinson's is more on the 30:26 axial areas it's more in the walking is more uh related to the neck areas 30:33 that are completely different in addition as i mentioned these patients unfortunately do not 30:40 benefit from the dopamine medication and they don't benefit because 30:47 not only that lesion that i show you initially was present the substantia 30:53 lesion that leads to not having dopamine but there are also 30:58 lesions in other uh areas of the brain that are part of that motor uh 31:05 circle therefore uh if we give dopamine it's not good enough 31:12 and this would be like you know the problem is that you don't have gas and you don't have 31:18 oil you can put gas but if there is no oil the car is not going to work and here is 31:25 something like that the only problem is that we don't know what are the other chemicals that we 31:32 would need to use in this case as the patient that i 31:38 showed you before there is difficult to move difficulty moving the eyes and at times this is the 31:45 first problem but most of the patients don't have that 31:50 and there is problems with speech it's like um it comes difficult uh 31:57 in enunciate the words and there may be problems swallowing and at times 32:05 there is a more significant and that is common actually to have much more difficulty with 32:13 what we call the frontal lobe that is the areas in the brain that pretty much 32:19 coordinate the rest of the brain it's kind of the conductor of the brain 32:24 and so that's why these functions are called executive because it is like an 32:31 executive uh functioning that is problems planning 32:37 problems uh multitasking so these things that an executive would do 32:46 your main problems well i fall out and i lose my balance 32:54 and i don't have any speech and i write terrible what was the first problem you 33:01 had falling so that's kind of the typical 33:06 history of a patient with psp so now a glimpse of multiple system 33:13 atrophy so the major problem in this disease is the autonomic system 33:21 that is having lesions and the autonomic system is pretty much the nerves that go 33:28 to the different organs so that's why the urine is one of the same 33:35 the the function of the urinary system is one of the problems and so there could be some urgency and 33:42 eventually incontinence or retention of urine without having any prostate problems 33:50 there could be erectile dysfunction and they could be as well a drop of the blood pressure 33:58 when standing and that can be very very significant 34:03 and gives a lot of problems being extremely fatigued 34:08 having pain in the back of the neck feeling like you're gonna faint 34:13 or fainting having a single event so if in addition we have the other 34:21 features that we talk about parkinsonism then this is multiple system atrophy 34:27 with parkinsonism msap is called and it has all the features that we just went over 34:36 on the other hand if they have cerebellar problems that is that inhibited walk 34:43 being extremely coordinated and in coordinated and having problems with 34:50 speech then we have a multiple system atrophy with cerebellar symptoms and i'm going 34:57 to show you a little bit of this problems with incontinence uh 35:02 impotence was that a problem also 35:09 feeling woozy that's not been much of a problem your 35:16 blood pressure was when you were lying down 167 over 79 35:22 but then when you when you got up your blood pressure came to be 95 or 59 so it really the reason 35:29 fluctuated a lot so people think oh it's fluctuations but reality is 35:35 that the blood pressure drops in significant ways and that's why not enough blood goes to the brain and 35:43 so the person has all these symptoms 35:54 so that is kind of a speech that is different that occurs in cerebellar disorders and this patient 36:02 in four years went from walking to being wheelchair bound 36:10 so this patient has the incoordination that i was trying to tell you that is a little bit different than the 36:17 tremor itself if you see there is a little bit of difficulty that goes beyond 36:25 and it's difficult at times for her to find where is that that finger that is 36:31 different than a real tremor 36:37 so what happens with dementia with lewy bodies well the major problem is the dementia that 36:43 could be just what we said before having problems that are executive 36:51 having fluctuations like one day i'm functioning beautifully and the other day i'm so confused that 36:58 it's really hard seeing things that are not there not related to medication 37:05 having parkinsonism and here is also enacting the dreams 37:13 so in summary parkinsonism is a combination of slowness stiffness tremor 37:21 and balance problems but persons with atypical parkinsonian 37:26 disorders have that parkinsonism plus other problems that patients with 37:34 parkinson's do not have and i briefly pointed the problems 37:41 that persons with psp msa and dlb that are the most frequent a 37:48 typical parkinsonian disorders have so thank you very much 37:57 thank you that was great um so let's uh maybe just um we can stop 38:02 sharing those uh slides and we can reconnect that's perfect so we have a number of questions um 38:09 irene uh i think uh it was a really thorough um presentation and just so i can summarize a little bit um so it 38:16 sounds like you know the ways that we can approach parkinson's patients so there's this umbrella of people that look like parkinsonians so 38:23 they're stiff and sometimes um you know slow and sometimes have a tremor but then there's 38:29 these other things that kind of are red flags as doctors that should point us in 38:34 a direction that might be different than parkinson's disease one of them is that the response to medications um 38:41 with classic parkinson's is quite robust many symptoms do respond um 38:46 really really well to levodopa and that response lasts for many many years with the atypical 38:52 parkinson's um it sounds like that's not the case when we can some of the questions ask about 38:57 the response to leave it over so we'll clarify then there's a number of things i wrote down that kind of are 39:02 red flags like you said the wide base gate early on eye movement issues early on where we 39:08 can't look up especially or down when the hand gets dystonic or tight 39:14 early on um and not responsive to medications early cognitive changes 39:20 early hallucinations that are early like in the first couple of years of the parkinson's early 39:27 falling so if somebody presents to a doctor and they're falling like one of your patients on the video 39:32 right at the beginning then we start questioning is this actually regular parkinson's disease and then it sounds like early speech 39:39 problems and swallowing problems so these are usually not things we see in classic idiopathic 39:45 parkinson's disease early on so if you have these things and you're seeing a doctor 39:50 and you're not really responding to medication and you're feeling like you might have got the diagnosis of parkinson's disease 39:56 maybe revisit that and maybe try to see some you know expert maybe like a movement disorder specialist or definitely a 40:02 neurologist if you're not seeing one um so that you can get a little bit more guidance does that sound about 40:07 right absolutely yes and i see some of the questions yeah i can kind of i i can sort those 40:14 out don't worry about those um so one of the questions um just to clarify because there were some words i think early on um one of the 40:22 questions was um does where do things like dopa responsive dystonia fit 40:27 in the classification another question was about vascular parkinsonism where does that 40:33 fit um in in this sort of stuff and then one one of the questions was also um about clarifying what 40:40 familial is because it was on one of your slides so maybe we can um find out about dope responsive and 40:46 vascular parkinsonism where would those fit so in parkinson's disease particularly 40:53 early on you may have an abnormal posture of the hand and you may have 40:59 an abnormal posture of the leg when you walk 41:04 and at times is when you walk a lot at times it's only when you're running 41:09 and eventually when we adjust the medications that abnormal posture 41:17 goes away the majority of the times um it could be that some 41:23 people may not but in general it goes away and the person has many 41:29 many years doing very very well that by the way 41:34 the dopamine response in parkinson's is forever 41:41 it may well be that because this certain medications such 41:48 as cinnamon doesn't last long then initially 41:55 it may happen that we have other neurons that are storing 42:03 the dopamine and so it may last many many hours but because 42:10 the levodopa lasts normally as in cinema uh 42:17 an hour and a half um when the disease progresses then 42:24 the medication lasts less but this is not a problem that the disease 42:30 makes it not to work the problem in the majority of the situations is that 42:37 the medication doesn't last enough so there are nowhere medications that last 42:43 longer such as right tariff for example and then that happens much 42:50 much later because the retiree lasts five hours 42:55 as an example so that i wanted to mention because many people reading the 43:02 internet that oh you try livodopa and then it goes you know you you end up 43:09 not functioning it doesn't work yes it always works it just happens to 43:15 be that it works for less amount of time so that was related to 43:21 and related to what i was asked the first one was the dystonia and what was the second one 43:28 um vascular so there was dope dopa responsive dystonia and then vascular okay so the dopa the 43:36 uh response estonia is what i just explained before that is the dystonia 43:42 that responds to cinnamon or libodopa uh or dopamine agonists like requip 43:50 pramipexo all right so 43:55 vascular parkinsonism is in fact one of the secondary uh 44:02 disorders because we have a cause and the cause is the multiple strokes 44:09 that lead to that parkinsonism so as i mentioned before there are 44:16 certain areas of the brain that lead to a function so if we have a 44:22 stroke in the area that has to do with language we may not be able to speak well 44:29 here if we have little strokes in the areas that had to do with the 44:35 motor circle then we may not be able to function 44:43 as normally and we would become having vascular parkinsonism the vascular 44:50 parkinsonism i didn't talk but the person walks with 44:57 a wide back wide gate with the legs separated as i show 45:03 you before in the inaugurated there is postural instability and the problems 45:12 are mostly in the legs the arms are pretty pretty good that is 45:17 very different than in parkinson's that the arm and the leg or the in the 45:23 typical parkinsonian disorders that eventually the arm and the leg are 45:28 affected so that goes for vascular parkinsonism 45:35 we can diagnose that based on the history based on mris uh when we do an mri of 45:43 the brain okay and the treatment is mostly physical therapy 45:48 just in case go ahead okay perfect um there's just a clarification or two about um other syndromes this is a very 45:55 educated bunch so um they've been watching a lot of these videos um just you know so they were 46:01 just asking about rem behavior disorder because um we had a speaker just speaking about that and they they they know that it's also sometimes 46:08 seen and you mention this also in lewy body disease um and there's also a question about whether that can be seen in multiple 46:14 system atrophy as well yes absolutely i'm sorry i think i was misleading you on that one and that was 46:21 my error because i was thinking mostly on psp and in cortical basal degeneration where 46:27 that does not occur but certainly in dementia with your bodies and in multiple systematrophy 46:35 those are uh also that are the diseases that have problems with 46:43 um deposits of alphas in nuclear in all those diseases ram behavior 46:49 disorder occurs that is the enacting of the dreams perfect and you showed us that beautiful 46:55 video that's so interesting um so there's been a few questions about um sort of 47:00 early on in in in presentation whether sometimes cinematic is added and sometimes people 47:06 can have a response and then maybe they lose that response um the question is you know 47:11 is there actually response is there a placebo effect should people get off the levodopa if 47:16 after some time if they end up feeling like you know maybe they didn't end up having parkinson's sort of what's your sense of 47:23 that well what happens is that when we give the levodopa and someone 47:30 does beautifully this is because we're giving the 47:35 chemical that is needed to make the motor circle work um 47:41 so if we take it away the motor circle is not going to work 47:47 this is like you know saying well is gas for a car a placebo effect no it isn't if you 47:54 don't put gas it doesn't work period and here it is the same 47:59 we have a decrease on the amount of of dopamine and the levodopa converts 48:07 into dopamine so it is very important to continue the 48:13 medication it is like uh for type people that have diabetes 48:19 they have to when they use insulin in general particularly those that have diabetes 48:25 when they are kids uh or very young they have to use insulin all their lives 48:33 so there are certain things that you feel great but you're feeling great 48:41 because you're taking medication which is uh really a blessing to be able to do 48:48 well with medication okay that sounds good so there's a question about um i guess 48:54 it's sort of more like a biomarker question um we've had actually chuck adler came 49:00 on and talked about some of his studies with parkinson's and even the brain donation he gave a really nice talk for us 49:06 there's been a question about whether um skin biopsies and other biopsies in the parkinson's plus disorders might be 49:14 helpful not yet these are things that are being experimental 49:20 and are being used uh but still we don't have uh real good ways of making diagnosis in 49:28 that way however uh while we cannot do 49:33 that i mean the problem is that the typical parkinsonian disorders there are different proteins it's not 49:40 just one as in parkinson's and so you can generalize uh but in some 49:46 of the parkinsonian disorders such as psp and cortical basal degeneration 49:52 there are ligands that bind to the proteins in the brain that have 49:58 tau and we can see those in pet scans as we can see the amyloid 50:07 in alzheimer's disease so it is still a question of 50:14 being exploratory and in research but more and more there are 50:21 better uh ligands that are allowing us to see much better the brain 50:28 so eventually we may be able to diagnose early these two diseases by using a pet scan 50:36 not yet okay that doesn't occur for parkinson's or msa go ahead 50:43 um so a question just i think there's been an interest in learning a little bit about research and 50:48 um what are your most exciting kind of prospects in terms of the research that's happening 50:54 in this area for patients with atypical parkinson's syndromes so the most 51:00 exciting thing for me is to see that we are starting to have treatments for patients 51:08 that have the typical parkinsonian disorders so we are doing a lot of treatments 51:15 for patients that have psp because we can diagnose them very very well 51:21 it may take us a little bit to diagnose them uh it will be better once we have the pet 51:27 scan with that ligand for tau but we can diagnose them well 51:32 so industry instead of using so much all these 51:38 efforts in treating alzheimer's disease realize that in psp 51:45 there is only one protein that deposits into the brain and it may well be much easier to find a 51:53 solution than an alzheimer that has two proteins tau and beta amyloid so 52:02 there are many studies and one of them uh we're we're doing we just finished two of them 52:08 that unfortunately didn't work but we're having a third one that is coming up 52:13 um that is antibodies against that the tau uh so i don't know if you 52:20 went over some of these things or not but the disease uh progresses going from 52:26 one cell to another did you go over all that because i don't want to 52:31 no not about the atypicals but in parkinson's we have talked with dr lang came on and talked about this 52:37 you know the um alpha nuclean type antibody treatments and then alberto 52:42 gave a very complicated talk on you know how a lot of the pathology may not have anything to do with ashley the way that 52:49 we've had a lot of different people that have talked about things but if you'd like to describe that for a minute or two we 52:54 have about five minutes left so happy to have you you know teach us a little bit about that so what happens 53:01 in psp as in parkinson's disease is that several studies in animal models 53:09 have shown that if you put the brain of a person that had the 53:15 disease and you put that that's those areas that were affected into a mouse 53:21 uh the mouse develops the exact same lesion that occurs in in the human person and also 53:30 starts to uh go from one cell to another and that is and spreads so 53:37 it became clear then that the disease goes from one cell to another 53:42 how does that happen so what happens is that the protein 53:49 kind of falls in abnormal shapes and because of that 53:56 uh the functions change in the cell and they start to bind to each other and 54:02 when they bind to each other eventually they go with 54:07 and because they still communicate they are sick but not dead the 54:14 proteins can go from one neuron to another neuron um 54:20 so the idea of antibodies is to use the antibodies to try to 54:27 rescue or actually to take uh to get rid of to rescue to get rid of 54:35 all these abnormal proteins that deposit into the brain and get them out of course not all of 54:41 them are going to be gone but the important part here 54:47 is that we take away the part of the protein that is abnormal 54:54 and is the one that leads to the spread and apparently 55:01 the antibodies that we just finished using that fail unfortunately 55:08 went to the part of the tao protein that actually was not the 55:14 responsible of moving from one cell to another 55:20 okay so it sounds like there's clumping there's proteins that are folding weirdly they clump together then they 55:26 affect the cells near them to make them also fold weirdly and clump abnormally so we're trying to attack 55:32 some part of the protein that is responsible for this spreading and bad clumping but we 55:38 haven't quite found exactly where to attack um and we're looking for the right place for the antibody to 55:44 be attacking and so you have some hope that um we can do this in in not only 55:50 possibly parkinson's like dr lang was talking about but also in things that affect the other protein 55:56 which is the tau protein like in psp so that's really exciting so so i think we have two minutes um irene 56:02 uh i was hoping to um just have you give some hope and sort of a message of closure um 56:08 for our group here there's a lot of activists a lot of people who want to get involved in research um and so maybe you 56:14 could just tell us about you know what you think would be sort of the best way for them to to kind of improve their um outcome well i think 56:22 research is the best thing that can happen uh and particularly at this 56:27 time is in particular in parkinson's disease more than any other disease 56:34 i think it is the best time because of uh three things one is 56:41 that we saw in patients that the symptoms go precede 56:48 the development of the non-motor symptoms such as depression the brain 56:53 behavior disorder uh constipation etc and all those 56:59 develop ears lack of smell uh years before the motor symptoms 57:07 so that shows what are the areas affected 57:13 uh and that they are affected uh very early and there is 57:21 a phenomenal study that show using different pet scans for the 57:27 different uh chemicals that are in the different areas of the brain how patients that had only rem behavior 57:35 disorder compared to those that had parkinson's disease 57:42 they had all these same areas affected except those that had to do with the 57:49 motor system so it is clear how the 57:55 the disease is progressing uh and then when we look at pathology the 58:02 same happens so i think that this is kind of the 58:08 and if we do experiments uh as the one that i mentioned for for uh psp 58:15 and cortical basal degeneration if we do experiments with a brain of somebody that had parkinson's 58:22 and we put it into uh into a mice and the disease has the same lesion and spreads so 58:30 we have evidence from pathology we have evidence from the clinical symptoms and we have 58:38 evidence from the physiology that all that is going in the same direction 58:45 this is the first time that we can see how all the research is showing us a 58:53 path so now it comes our time to try to search for the what is the medication that 59:01 would be the best one and there are several opportunities multiple 59:06 in fact uh one of them is the antibodies another one is to act 59:13 over the proteins that are that are abnormal um 59:19 so there so there's genetic uh ways nowadays that are being 59:26 experimented uh in animal models so i think 59:31 that this is extremely exciting to see that finally 59:37 it's not just that we do this little treatment but we don't know much about it it's just that we saw that there was 59:44 oxidation and so we use an antioxidant we saw this and we use that here there is a whole um 59:53 amount of data that are going in the same direction so it seems like we're on the right path 1:00:01 and that is something that is for me at least i never thought i would see all this so 1:00:06 i'm very very excited um as well so how can 1:00:12 you help or there are multiple ways in which you can help you can help participate in research uh 1:00:19 you can help by spreading the voice about uh the disease and 1:00:25 making people aware that exist many people i would say incredible amount of people 1:00:31 have no idea that this is exist or even that 1:00:36 parkinson's can be treated or even that parkinson's are not 1:00:42 people that the first year of the disease are going to be wheelchair bound so when we 1:00:48 give the diagnosis to someone that they have parkinson's disease it's 1:00:54 almost like giving the diagnosis of having cancer that you have just a 1:00:59 very short period of time to live and your life came apart and i think 1:01:05 uh fortunately there are several ways of improving that so educating is extremely important 1:01:14 and then uh lobbying you can lobby in with your congressman and just 1:01:21 say we want funding for our disease more funding is needed as there is need 1:01:28 you know funding that goes to research with alzheimer's we want also funding go to go 1:01:36 to research such as parkinson's disease so there's a myriad of ways and of course donating the brain 1:01:46 when the time comes is another way so i can't um stress so much 1:01:53 more how you and us uh can go together and 1:01:59 being really uh trying to search for ways in which in which we can improve 1:02:08 uh the care of these diseases and hopefully diagnose them early and hopefully 1:02:14 finding a treatment that's slow stop them or diagnosing them so early so 1:02:20 early that perhaps we have brain behavior disorder and that's about it you know that would be lovely 1:02:27 absolutely well that's very inspirational um irene there's been a lot of positive comments they want you back they want to 1:02:34 do two hours with you next time or something i don't know it's like we could spend all day on here but um such an interesting area and so much 1:02:40 hope and research going on and you're leading so much of it so i'm so proud of you and 1:02:46 continue to and be inspired by you so thank you so much for spending the time i know you're very busy 1:02:51 and um i'll hand it back to you andrea for our goodbye wave yes thank you so much for inviting me it 1:02:58 was lovely to be with all of you and to receive all these very intelligent questions 1:03:07 very good well we always show our gratitude with a wave so if you put your camera 1:03:13 on and if you switch it to gallery view you can scroll through and if everyone can show their 1:03:20 appreciation for dr lipbin and as always dr subramanian thank you everyone for joining great questions 1:03:28 this was excellent to spend this hour learning with all of you bye lovely 1:03:35 bye 54:47 NOW PLAYING