Overview of Autonomic Failure with David Goldstein, MD, PhD

[Music] hi everybody i'm al rochelle and welcome as we continue our conversations about dis on anomia right now we're talking to dr. David Goldstein dr. thank you so much for joining us we're gonna be talking about the history of autonomic failure among other things so give me a little of your background and how long you've been involved with all of this well I've been doing research clinical research on how the brain regulates the cardiovascular system dating back to college to college days okay and so that's basically most of my life more than 50 years doing some sort of research related to the brain and the heart and the the intervening system that mediates effects of the brain on the heart is the autonomic nervous system so 1997 that's a significant year what's significant about that year 1997 there were three major discoveries that I think changed the field of autonomic research first in 1997 the the it was discovered that a rare Greek Italian American kindred where Parkinson disease was transmitted as an autosomal dominant trait that means half the family had Parkinson's the the genetic specific genetic cause was identified and this was mutation a mutation is like a typo and the genetic encyclopedia oh gosh and the the mutation was for a protein called alpha synuclein nobody knows what alpha synuclein does to this day but somehow a mutation of alpha synuclein was found to be the first identified cause of familial Parkinson disease now you could say this is a very rare situation Parkinson's is most of the time sporadic there isn't any identified genetic cause yeah but in 1997 another key discovery was that alpha-synuclein deposits occur inside nerve cells and these deposits are called Lewy bodies le WY although the guy was actually a German researchers name was levy it's a whole story yeah but Lewy bodies are a path a pathologic hallmark of Parkinson's just sporadic Parkinson's so what it was found that there was alpha synuclein deposition in Lewy bodies this meant that alpha synuclein had something to do with Parkinson disease overall yeah so far I haven't said anything about the autonomic nervous there but a third discovery in 1997 was by art by our group we we found that in Parkinson disease as well as another classic form of autonomic failure Carl called pure autonomic failure that there's a substantial loss of nerves autonomic nerves in the heart in in in the movement disorder Parkinson disease okay this was a complete surprise huh until then it was thought that Parkinson's basically a movement problem it's a brain disease but this discovery meant that Parkinson's is a more generalized disease it's not just the brain disease and it involves a loss of particular nerves called sympathetic nerves in the heart that meant that Parkinson's and is a disorder no Meah okay so those are the three discoveries that I think changed views about what causes Parkinson's and whether and and and and the fact that the the the lesion the problem involves more than the brain but also involves the heart now when you talked about pure autonomic failure does that have anything to do with any kind of a chemical deficiencies within the body yes pure autonomic failure had other names yeah for then but it's characterized by orthostatic hypotension or the static hypotension is a fall and blood pressure every time every time the patient stands up and the orthostatic hypotension is due to a biochemical problem the biochemical problem is that for whatever reason the chemical messenger of the sympathetic nervous system which is called norepinephrine or noradrenaline is not reaching its receptors where the receptors are blocked in the case of pure autonomic failure it's not reaching its receptors because it's not being released it's not being released because the nerves that contain norepinephrine aren't there anymore or they don't store or they don't store the norepinephrine and package it in a way that it can be released so pure autonomic failure in people the definitional issues here right but in my book PAF by definition involves a loss of stores of the chemical norepinephrine mm-hmm and all of this is tied up in the autonomic nervous system as well I mean now so from what you learned about Parkinson's then how does that translate into what you know about the autonomic nervous system in terms of what may cause it or what may trigger it good question I mentioned the Lewy bodies and it's a like a pathologic hallmark of Parkinson's they're also biochemical hallmarks what causes the movement disorder in Parkinson's is known it's been known for a half century sure and that is loss of a particular chemical called dopamine in a particular brain pathway that's what causes the movement disorder well dopamine and norepinephrine are like father and son in a small chemical family called catecholamines right there are only three catecholamines in the body dopamine norepinephrine and adrenaline which is the most famous catecholamine yeah that's it so the the concept is that there's something something relates catecholamine neurons which are rare in the nervous system and Lewy bodies what is why is that why is there that association and our theory which we've been pursuing for several years is that alpha synuclein that protein that's deposited in the catecholamine neurons interacts with products of oxidation of dopamine or norepinephrine and it's that interaction that destroys the nerves that's the idea does does the the PAF we talked about that does it ever evolve into what we call multiple system atrophy are they related that's a controversial question okay this controversial Europe in the I don't think there's much doubt that PAF can evolve into Parkinson disease with orthostatic hypotension about 40% of people with with Parkinson's have orthostatic hypotension and and one way Parkinson's with orthostatic hypotension can occur is as an evolution from from PAF a multiple system atrophy also involves alpha-synuclein deposits but the characteristic is not alpha-synuclein deposits and nerves instead its alpha-synuclein deposits in glial cells these are like helper cells in the in their brain they're not neurons but they're very important and the alpha-synuclein deposits are in the glial cells outside the brain most patients with multiple system atrophy have nothing wrong yeah and so when you look for norepinephrine deficiency by scanning techniques for instance that that I developed there's nothing wrong so there's a drastic difference between PAF or Parkinson's with orthostatic hypotension or dementia with Lewy bodies which is another thing that PAF can evolve into and msai if you don't take into account the loss of the loss of norepinephrine especially in the heart if you don't if you don't consider that yeah then it's possible that PAF what you think is PAF right can evolve into msai we've been having a bit of a debate about all the terms used to describe the same condition and abnormal drop in blood pressure upon standing with symptoms of syncope or pre syncope of all the terms that are out there what term would you use to describe that a new one a new one because what's out there pretty much always includes a presumption about mechanism so when you say vasovagal syncope vaso means blood vessels vagal means a particular part of the nerve of the autonomic nervous system and vasovagal syncope implies there's something wrong with the vagus nerve or or blood vessels or something like that neuro cardiogenic syncope is another term that also implies there's something in the nervous system that's the nervous supply to the heart that's causing the loss of consciousness so ordering an early mediated hypotension is another one new early mediator implies that the nerves are responsible for the fall in blood pressure there are the terms as well they all contain an a an inherent presumption about mechanism so I wanted to come up with something that doesn't it's just simply a description of the phenomenon and when people are worked up for for syncope or frequent fainting orthostatic intolerance meaning they just can't tolerate standing up for a long time they often undergo a tilt table test and and it was and the one of the purposes of the tilt table test that's a see if you could provoke the same phenomenon that the the patients are complaining about and so we look for a at some point during the tilting a sudden fall in blood pressure and we know when that happens yeah that's that's going to cause a loss of consciousness pretty quick yeah well that's tilt evoked hypotension nobody's gonna argue about that so I've started to refer to this this phenomenon during tilt table testing as tilt evoke evoked hypotension okay is it possible that the the things we've been talking about could actually be secondary causes of autonomic failure if such as we're talking about diabetes alcohol game based learning them all of those kind of things is that possible well by definition a secondary cause means you know the the person has a disease that's already been established to be associated with chronic autonomic failure a classic example is diabetes there's very substantial literature that at least a subgroup of of diabetes diabetic patients have something called diabetic autonomic neuropathy which can include orthostatic hypotension usually includes other stuff so when you when you're trying to work up a patient who has orthostatic hypotension you don't come up with a diagnosis like pure autonomic failure right before your before you exclude other secondary causes of orthostatic hypotension I think that's what it's about okay and and just very quickly one line that you would say for physicians that are watching us right now what's your word advice to them just very quickly read my book I wrote a book called as part of my official job duties I went for the government so it's free you just go to my website and download it's called principles of autonomic medicine and lastly for patients what would you want them to know same book say no that's what's special and I may be unique about this book I put it together to be a shared resource for for clinicians for students and for patients you could say well how can you do that they're totally different competencies totally different education czar totally different expectations I did it by kind of clumping together two other books one a handbook for patients with disorder no meais okay great and another a textbook academic textbook on the autonomic nervous system this website as well thank you for all your information or it's nice to know that somebody is delving in with their entire life a topic this excessive in this doctor thank you so much sir [Music] [Music]

Channel: The Dysautonomia Project

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Id: IEaT0Kb22ao

Length: 16min 3sec (963 seconds)

Published: Sun Jun 14 2020