CME Lecture on Clinical Autonomic Disorders

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Dr. Glen A. Cook Jr., M.D. gives a CME lecture at Largo Medical Center on Clinical Autonomic Disorders. This CME was designed for the community-based practitioner in any area of medicine as an introduction to dysautonomia.

Dr. Glen Cook:  Hi, I am Dr. Glen Cook.  I am a clinical neurophysiologist and autonomic disorders specialist at Walter Reed National Military Medical Center.  We’re going to go through a brief overview of disorders of the autonomic nervous system.  I hope this is beneficial and that you enjoy this talk.

All right, a few disclaimers.  My own opinion is being expressed here not the opinions of the United States Government, I am presenting some research data here from human subjects’ research, and I have no relevant financial disclosures.  You can read the objectives.  You’re going to see a lot of illustrations here that were done by my mentor in autonomic medicine, David Goldstein.  I have a reference to his ebook at the end of this slide deck which is available online.  It is a very good reference.  So that’s where I adapted these from.  

So, in terms of how many patients with autonomic disorders we see, the answer is a lot.  I’m not going to read to you the numbers up there, but if we graph out different disorders of the autonomic nervous system in circles of diameter of relative prevalence compared to other diseases, it looks like this.  So, syncope – lots of people faint right?  Who in this room has fainted?  Who in this room has come close to fainting?  So very common, very common disease.  This is actually recurrent syncope, irritable bowel syndrome, COPD, common diseases, especially in the internal medicine world.  Postural tachycardia syndrome, not that small a circle, on the order of magnitude of breast cancer.  How many of you have had medical school or residency lectures on breast cancer?  How many of you had more than one lecture on breast cancer?  How many of you have had a lecture on postural tachycardia syndrome?  Okay, someone did, okay that’s great.  So, we are talking about something that is on the same order of magnitude so postural tachycardia syndrome more prevalent than Parkinson’s disease, way more prevalent than multiple sclerosis.  So, as we look at the burden of these diseases and think about, hey how much attention are we spending on these in terms of medical education, medical research?  We recognize, hey things may be a little bit out of balance. 

And that causes problems for our patients.  A not uncommon story that I hear is, Dr. Cook, I have been from doctor to doctor, I’ve seen cardiologists, you are the second, you’re the third neurologist I’ve seen.  Nobody knows what’s wrong with me.  Average time to diagnosis for people with postural tachycardia syndrome – old data, it was about six years.  More recent data, it’s actually come down, we’re doing better in terms of diagnosing people, down to about four years.  That’s a long time to have a disabling disease and not have a diagnosis.  So multiple system atrophy, an alpha synucleinopathy in the family of Parkinson’s disease.  Average time to diagnosis from the onset of motor symptoms is five to six years.  Again, newer data, it’s about five years.  A long time to not have a diagnosis especially when we are talking about a disease that average mortality is eight years after motor onset.  So, we’re talking five out of the eight years that a patient has left to live the patient is undiagnosed or misdiagnosed.  This average number of doctors being seen is from individuals with postural tachycardia syndrome – 7.3 doctors seen prior to diagnosis.  

All right so let’s talk about where these diseases and disorders are stemming from.  So, we throw around the term “autonomic nervous system” and that’s thanks to John Newport Langley who coined that term over a hundred years ago.  And what he was indicating there is that these functions are not independent but are self-regulating, they are automatic.  Now again, that does not mean independent so if I for example if I squeeze my hand my blood pressure goes up right?  So, these are highly integrated functions that happen largely without voluntary control.  So, you can think of the autonomic nervous system as the automatic nervous system.  And if we go back to Langley, he is the one who described the enteric nervous system, the parasympathetic nervous system and the sympathetic nervous system.  And it was a few years later that Walter Cannon came along and recognized that, hey, there’s this sympathetic nerve stuff going on, but these adrenal glands are doing something slightly different, so he described this sympathetic adrenergic system.  And it was just a few years later that Dale came along and described the sympathetic cholinergic system and demonstrated that sweating in humans is predominantly a cholinergic function mediated by the sympathetic nervous system. 

And it was stemming from the work of these three that we recognized the neurotransmitters that were responsible for these five components of the autonomic nervous system.  So sympathetic nervous system uses noradrenaline, or norepinephrine, at the effector site.  So, here’s kind of a neat key that I’m going to throw to you medical students.  You’ve learned this but no one often states it overtly – adrenaline and epinephrine are the same thing, right.  We know that, but we don’t think about it right.  And why do we have two names for it? Well it’s just Greek versus Latin.  So, adrenalin, adrenals – Latin.  Epinephrine, epinephros, upon the nephros kidney.  So, okay it means the same thing.  We don’t think about it that way often and when you’re when you’re talking with patients that is often helpful for them especially if you’re like me and you switch back and forth between epinephrine, adrenaline, norepinephrine, noradrenaline.  And I’m going to do that while talking today. I’m going to bounce back and forth.  So, noradrenaline equals norepinephrine, adrenaline equals epinephrine, just remember that and again when talking with patients, I try to make that clear up front so that I don’t confuse them more than I’m already confusing them.  

So, sympathetic nervous system uses noradrenaline at the effector site, parasympathetic nervous system uses acetylcholine at the effector site, just like the sympathetic cholinergic system does for sweating.  Now the sympathetic adrenergic system is kind of interesting because those adrenal medullary cells that make epinephrine really they’re just neurons that forgot that they were neurons so they come from the same embryonic origins as neurons.  They make a neurochemical but instead of releasing it right at an effector site they dump that neuro chemical into the bloodstream and so they get kind of called an endocrine gland instead of a nervous system tissue but they’re just neurons that forgot that they were neurons. So, remember that epinephrine is the daughter neurochemical of norepinephrine.  So, we talked about these four in the enteric nervous system.  Lots of neuro chemicals in the enteric nervous system, so a lot of serotonin in the gut, a lot of dopamine in the gut, a lot of acetylcholine in the gut, vasoactive intestinal peptide, nitric oxide, lots of stuff going on in the enteric nervous system. 

And just as a reminder, we can think about the central components of the autonomic nervous system housed in the brain in the spinal cord.  And then the peripheral components of the autonomic nervous system.  And those central components we refer to as this as the central autonomic network.  These different brain regions that are responsible for the regulation and coordination of these autonomic functions.  You don’t have to memorize this.  This one’s a little more important to understand and memorize because all of this central autonomic network feeds into the spinal cord or brain stem and then has to communicate with the rest of the body.  And let’s look at those components of the autonomic nervous system one by one.  So, let’s start with the sympathetic noradrenergic system.  So you remember there’s this little short preganglionic nerve that then synapses in a sympathetic ganglion and we’ve got this chain of sympathetic ganglia up and down our paravertebral region – those ganglia that the ancient Greeks recognized were responsible for the body working in harmony or sympathy with itself, hence the name sympathetic because this goes back two millennia to the Greeks saying, “hey these things are responsible for the body working in sympathy with itself”, hence the sympathetic nervous system.  So those preganglionic neurons are short and then those postganglionic neurons that release norepinephrine or noradrenaline are long.  And that’s different than our parasympathetic nervous system where those preganglionic neurons are long and then synapse in ganglia at or near their effector site with a short post ganglionic neuron so that our parasympathetic nervous system arising from the vagus nerve and from those sacral parasympathetic neurons.  And we talked about the sympathetic adrenergic system where preganglionic neuron actually goes all the way to the adrenal medulla and causes/stimulates release of adrenaline, dumping it into the bloodstream.  You’ll notice that all of these autonomic nervous systems synapses are acetylcholine releasing nerves.  And that becomes important in some of the diseases that we see. 

So, what happens when things go wrong with the autonomic nervous system?  Well it depends on which part of the autonomic nervous system is being disturbed.  For example, if I have a disturbance of my sympathetic noradrenergic function, I am going to have a problem keeping my blood pressure up.  Well that sympathetic innervation of my eyelid isn’t going to be there and so my eyelid’s going to droop. I am going to have ptosis.  I might have a problem mounting a heart rate response, though remember that at rest our heart rate is suppressed from its intrinsic chronometry by parasympathetic input so you can get your heart rate up just by removing that vagal tone to the heart.  But that beta-1 activation from norepinephrine is also important in getting heart rate up.  What happens if that sympathetic cholinergic function part goes wrong?  Well I’m not going to make sweat and that’s a problem if you live in Florida.  What happens if my sympathetic adrenergic system goes wrong?  Well, you have to think about what’s the other job of adrenaline in the body?  Well it’s the main job of adrenaline in the body and that really is glucose regulation, so gluconeogenesis, glycogenolysis.  It’s hard though because we don’t often see pure adrenal medullary failure, so hence the question marks.  What happens when the parasympathetic nervous system is disturbed?  Well that parasympathetic stuff that our body does gets messed up and this is what my mentor would say, the parasympathetic nervous system is responsible for stuff you do behind closed doors so peeing, pooping, sexual function and that’s bad when that goes wrong – people aren’t happy. I also get dry mouth, dry eyes, you’re not making spit appropriately.  What happens when the enteric nervous system goes wrong?  You can’t enjoy your Panera sandwich, well you might enjoy it, but you are going to feel full really early when you eat because your gut, your stomach is not emptying, might get profoundly constipated.  The fact that your gut’s not moving correctly might affect medication absorption.  That can really become a problem in our patients with Parkinson’s disease.  So, one of the things to think about in people with slowed gastric motility is hey, these meds that I’m giving them that in most people get absorbed normally from the gut, what happens when the gut doesn’t move?

All right.  So, from here we’re going to go on and talk about some of the specific things that we see in regard to autonomic nervous system dysfunction.  So, I already took my poll of who in the room is fainted, some of you missed that – we raised our hands if you have ever fainted in the room.  Lots of people have fainted or come close to fainting, happens a lot.  Why does it happen?  Well, why do people faint?  People faint because there’s not enough blood flow to the brain and it’s just, it’s temporary, it’s reversible.  So, syncope fainting is caused by transient global cerebral hypoperfusion – has to be transient otherwise it’s not fainting, it’s dead.  Do people die from fainting?  No, so people don’t die from fainting if they’re laid down, if they get their head down.  And this is important.  So. I see lots of people that faint and have to tell them like look, make sure people put you down.  We have had patients die from fainting.  One of our patients with autonomic failure fainted in an airplane bathroom and if you faint in an airplane lavatory there is no room to fall down and he passed away because of that.  I actually had a…I took care of a young sailor who had migraine-related syncope, as long she didn’t have a migraine, she was fine.  She got a migraine, she’d faint.  And her ship was actually in port in another country and she was out at a club and fainted and some of her buddies carried her out and propped her up against the wall outside the club and she sat there semi-unconscious in a half fainting state for a few minutes.  And then the neurologist in me went oh how many neurons did she lose? She was fine, eventually her blood pressure got back up she was okay.  And we got her headaches under control, she stopped fainting, and got back to her career.  So, people die from fainting, so if someone faints, head needs to get down to the level of the heart. 

Why does that happen?  Why does not enough blood flow get to the brain?  Well, let’s think about what gets blood flow to the brain?  Well there is a pump, the pump has to be pumping right.  If it doesn’t pump right, we call it cardiogenic syncope, either because there’s a structural problem with the heart or because there is an arrhythmia from the heart – that’s the dangerous one.  Any cardiologists in the room? Okay, then I can make up stuff as I go along.  Orthostatic hypotension – in this case the pump’s working just fine but there’s not enough pressure in the pipes, there’s not enough pressure in the pipes because maybe there’s not enough volume in the pipes or maybe it’s because the pipes don’t squeeze down appropriately.  Maybe that sympathetic input to the blood vessels that make them squeeze down to keep the blood pressure up is broken – we call that neurogenic orthostatic hypotension.  Another big one, this is one that we do with our prescription pads, medication-induce syncope.  So when I first took over the autonomic testing laboratory at Walter Reed Bethesda we actually had a big problem with people getting sent to the lab from, it was actually outside our department, for recurrent syncope and they’d come in and they’d have a diagnosis of hypertension and they would be on hydrochlorothiazide and some other agent and then they’d be on an alpha blocker because of prostatic hypertrophy and then they’d be on maybe another alpha blocker because they are not sleeping well or have PTSD.  And you just sent me someone to test for fainting who is on four medicines that make people faint.  Thanks for making my job easy.  So, so remember that.  We can do this.  So fainting can happen because the pump isn’t working, fainting can happen because there isn’t enough pressure in the pipes and then the big one, so all of you that raised your hands that have fainted or come close to fainting, for most of you, this is what it has been – vasovagal syncope.  All right, so that vasovagal syncope, super confusing because we called it all kinds of things over the past few decades.  This is the classic faint, this is the, I haven’t eaten since breakfast and I have been rounding with my attending since like 7:00 a.m. and now it’s 2 p.m. because he takes forever (I’m saying this to the residents by the way because I know you guys) because he takes forever with every with every patient and I am mildly hypoglycemic and it’s like 80 degrees up here on the 4th floor of the hospital and I’m in my white coat and I’m getting a little light-headed and I’m getting a little clammy, and I’m feeling a little nauseous – you guys know that feeling.  That’s the classic faint – that is vasovagal syncope.  Also called neurocardiogenic syncope, also called neurally mediated syncope.  At least one person’s thrown out the term autonomically mediated syncope.  So, we’ve got this grab bag of different terms, none of which are super great and sound like a lot of other things because neurocardiogenic – boy that sure sounds like neurogenic and it sounds like cardiogenic, so this is really confusing.  But remember vasovagal syncope, and this is most…vasovagal is mostly what’s being used in the literature now.  But just remember it’s the common faint.  Very much related to that is situational syncope, with some caveats, and then carotid sinus hypersensitivity is also lumped under that category of reflex syncope.  

Any mixed martial artists in the room?  So how can you choke someone out, with only getting pressure on a single carotid artery?  Because you can, and a lot of chokes rely on it where you’re not putting a lot of pressure on both sides of the neck, so you’re really not completely cutting off blood flow to the brain, you’re not, and it is hard to smash a carotid artery completely right?  You’re actually using the carotid sinus, that’s how you’re choking people out that way.  So, the autonomic nervous system is important in the clinic, it’s also important in the ring.  It’s my backup career.  And there are other miscellaneous causes of syncope that are, that are less common.  So, criteria, diagnosis of orthostatic hypotension, drop in systolic blood pressure of 20 mmHg or drop in diastolic pressure of 10 mmHg within three minutes of standing or upright tilt.  Those are, these are actually good. these are good numbers to chalk away in your memory bank.  Some would argue that if you stand up and you have any drop in diastolic blood pressure that’s probably abnormal.  Actually, when they actually came up with this consensus criteria that was actually specifically argued about.  But those are the numbers.  

All right.  So, we brought up neurogenic orthostatic hypotension.  Any neurologists in the room?  Okay so you and I have to remember this pathway, the rest of you don’t have to dedicate this to memory but it is pretty cool and pretty cool that we understand it, but you do have to remember what actually happens.  So first. stretch receptors in the carotid sinus and in the aortic arch sense blood pressure.  They send that signal to the brain stem.  The neurologist has to remember that it’s the nucleus of the tractus solitarius.  That message about blood pressure gets relayed to the vagal nerve nuclei and to the nuclei that control sympathetic tone.  So, if my blood pressure goes down, first thing that happens is my brain stem says hey, parasympathetic nervous system, you need to let the heart rate speed up a little bit.  Heart rate goes up.  And that says, hey sympathetic nervous system, you need to get some noradrenaline action going to make those blood vessels squeeze down to get the blood pressure up.  And so that signal comes out through the roster ventral lateral medulla down into the intermedia lateral cell column the spinal cord out through the sympathetic nerves, blood vessels squeeze down, blood pressure goes up, my brain is happy.  If that reflex loop is broken anywhere along that pathway, I’m going to have neurogenic orthostatic hypotension whether it’s because that message from those baroreceptors is not getting to the brain stem, or the brain stem doesn’t care about the blood pressure, or those sympathetic nerves that make the blood vessels squeeze down aren’t there or aren’t working appropriately, or we’ve given some medicine that blocks their function at the alpha-1 receptor.  Any of that’s going to cause neurogenic orthostatic hypotension. And that’s the baroreflex.  So that’s syncope.  

Tell me, questions about syncope, what questions do you have about syncope? Fainting?  Okay throw out one question.  Okay then I’ve got a question.  Why does that happen?  Why does vasovagal syncope happen?  There’s a question, it’s been around for a hundred and forty years, longer, longer, it’s been a long time that we’ve recognized that in the classic faint, we typically see a vasodepressor response followed by a cardioinhibitory response.  That’s where the word vasovagal came from actually, it was that cardioinhibitory response following that vasodepressor response.  So vaso- blood vessels, vagal – hey something is happening to the heart.  We actually know though that the vagus nerve is not necessary for people having the classic faint.  So, the common mediator as far as we have been able to measure actually the common mediator of the classic faint is an overwhelming adrenaline response where you get adrenalin released out of proportion to noradrenaline.  You get sympathoadrenal imbalance, you get increased skeletal muscle blood flow because of the overwhelming adrenaline response and blood pressure actually drops.  It’s actually kind of cool.  

All right let’s talk about, POTS, postural tachycardia syndrome.  How many of you have seen a patient with POTS?  How many of you diagnosed a patient with POTS?  So, what is it?  So postural orthostatic tachycardia syndrome.  Well the name tells you what it is.  A syndrome in which someone doesn’t tolerate standing up and they have an exaggerated orthostatic tachycardiac response.  Lots of stuff can do that.  And it does it actually to a lot of people.  We don’t have a super great idea of what the numbers are, um some estimates are probably a little bit on the low end, some are probably a little bit on the high end, because there are a little bit more than 300 million people in the United States and I don’t think 1 out of 100 has POTS, so probably somewhere in between there.  This is a common diagnosis, common enough that like, when we’re out in public my wife can be like, hey honey, she looks like one of your patients.  Like we talked about at the beginning, people with POTS often go a long time without being diagnosed or being misdiagnosed.  And we talked about the criteria:  orthostatic intolerance, that is not tolerating standing up, and an exaggerated orthostatic tachycardiac response.  How exaggerated?  Well our criteria says at least a 30 beats per minute increase on standing up or tilting up.  If someone’s in adolescence, we make them have a 40 beats per minute increase because younger people naturally have a higher heart rate increment with standing.  So, as we look back at our referral clinic, our military Autonomic Disorders Clinic, in a series of 215 patients, about a third of them had POTS.  As we look at those 215 patients, not directly related to POTS, about 40% of them had evidence of a small fiber neuropathy.  We take those numbers, put them together, of our patients with postural tachycardia syndrome, just over half of them had evidence of a small fiber neuropathy.  So, as we talk about things that can cause postural tachycardia syndrome, it appears that a small fiber neuropathy affecting those autonomic nerves plays a role in a significant number of patients.  Now you could argue that hey, how many of these are due to false positives in sweat testing or skin biopsies, probably there are some false positives mixed in there.  Nevertheless, it’s definitely a significant number of people with POTS have evidence of a small fiber autonomic, or small fiber autonomic and sensory, neuropathy.  And why is that important?  Well it’s important because you can test for it.  I mean without fancy equipment.  This is, this is bedside medicine here, looking for this stuff.  

So, as we talk about testing the autonomic nervous system, there’s stuff that we can do with fancy equipment, but this is 90% of it right here.  You’ve got to ask.  And so, I’ll talk specifically to the medical students here in the front row, how do you ask about the autonomic nervous system? Well it goes back to that chart that we that we showed at the beginning, what are the things that autonomic nervous system does?  Well just ask about it.  So, if you are thinking, this person has a lot of things that I think might be in the autonomic nervous system, let me delve in there a little bit more thoroughly.  Well do you have constipation?  Do you have problems with urination?  Let me ask you guys this, how do you ask patients about sexual dysfunction?  Awkwardly, that’s what a lot of people say.  So, I’ll give you a hint, a good way to ask someone if they have sexual dysfunction is to say do you have any sexual dysfunction? And it’s either yes or no.  And it’s actually really not awkward.  It’s actually even less awkward if you do it right after you asked about urinary problems, do you have any urinary problems, no; okay, do you have any sexual problems, no; okay moving on. Or yes, what kind of problems?  Well the patients tell you.  It’s actually pretty easy, so thanks for saying awkwardly, that was good. Doesn’t have to be.  History.  So, you’ve got to, got to ask. And you know what this takes time. 

So, I am going to take two minutes and tell a story about my first job, this is story I have never told being recorded before.  So, I grew up in Suburban Salt Lake City, so eastside of city, middle class neighborhood, pretty, pretty conservative place.  So, there is one guy in the neighborhood that all the neighborhood kids called Renegade.  Drove a jeep dude, long hair, often no shirt on.  Like no one really, none of the none of guys in the neighborhood know him, everyone called him Renegade.  So, I had a few lawns that I mowed with my best friends, we just mowed a few lawns in the neighborhood.  I was 14 years old, was out mowing someone’s lawn at the start of one summer and Renegade pulls up and he goes, you guys want a job?  Sure, I was 14, well I don’t know yeah, sure.  So that was my first job. I went to work for Renegade and his lawn care company.  Actually, a super good job, we got paid a pittance, but it was like a really good job as a 14-year-old kid.  And at the beginning of the summer we came in one morning and started loading up the truck and Renegade (that wasn’t his name by the way, we didn’t call him that, we got to know him) he goes, hey, I got a call yesterday and I had to go back and mow a lawn that you guys missed a section on.  I guess we missed a strip that he had to go back and he said, we hurry when we are loading the truck, we hurry when we dump the grass, but when we’re mowing, that’s where we take our time because that’s our job.  And I actually didn’t think about that as a teenager, actually wasn’t until I was like graduating residency and that came back to me and I was like, wow that was a really profound lesson there.  Like there’s a time where you need to hurry and be efficient, but you know what, in the clinic that is where we do our job.  That’s our lawn that we have to mow.  So, any surgeons in here?  Okay, so surgeons the operating room is your lawn, like you can’t cut corners there.  For those of us neurologists, I rarely go into the operating room unless I am with my neurosurgeons.  The clinic is my lawn, I can’t cut corners there.  So, so make sure that you’re taking the time that you need to do your job right to properly diagnose and take care of your patients. 

And after history comes the physical exam.  So, if you’ve got concerns about a small fiber neuropathy, well check those small fiber sensory modalities, check pinprick sensation, check temperature, it takes like 20 seconds each.  Listen to the heart, under the clothes, like you were taught to in medical school.  Ask about these things.  So, we can do these fancy things with our autonomic testing equipment, we can test the sympathetic cholinergic system, we can quantify the sweat response, but you can do this bedside as well.  You can actually look and see if someone’s palms are sweaty.  I stand up in front of a crowd, my palms of course they’re sweaty, but you can look at that in your clinic and sometimes, you can see it with the naked eye or you can take your otoscope and get a little magnification and you can see sweat droplets coming from the palm.  And just try it, try it on yourself, which is back here.  What is Dr. Cook talking about?  Like oh hey, I do. And then if you have a patient who says, you know what? I don’t make sweat anymore and you take a look, you’re like wait, oh my hands, I see it, your hand I don’t see it.  The other thing you can do – feel their socks.  That’s like the grossest thing I have to do as a neurologist.  It’s not that gross a job, but especially…it doesn’t work if they’re wearing sandals, which a lot of people in Florida are going to come in wearing sandals, but if they come in Florida wearing shoes and socks and they take their shoes off for you to do your exam, feel their socks, they should be damp and if they’re not you’re going to go,  your feet are not making sweat.  Huh, that’s a problem.  So that that’s the sock test.  If you drag a spoon or really any metal object across the skin there’s a certain amount of tension or drag, it’s pretty easy to appreciate.  Someone who is “anhidrotic” – that metal object will slide right away, so this is actually been published on using like a soup spoon. I don’t keep a soup spoon in my clinic, but I keep a tuning fork that has a flat metal surface, that’s what I use to check temperature sensation, I can drag that across the skin.  So, these are actually really easy things that are totally valid. 

All right, so we can test the cardio vagal reflexes.  We do that by testing a heart rate response to deep breathing, we have someone breathe in and out deeply and we measure that.  (That clock’s wrong correct?  Okay.)  And we compare that variation in heart rate to deep breathing to standardized norms.  But you don’t need a fancy machine to do that.  So, here’s one of our medics in Afghanistan actually doing a health check-up with some people.  I think it was this one who is actually a part of a first-aid class.  You can measure someone’s pulse.  You don’t need a fancy machine to do that, and you can have someone breathe in and out deeply.  And you can say hey, let me feel your pulse while you breathe in and out deeply, and if their heart rate stays at 61 beats per minute, wow, there was like no cardio vagal reactivity there.  If it goes up and down quite a bit, okay maybe it’s not broken.  No, it’s not quantitative right?  This is stuff you can do bedside.  

Orthostatic hypotension.  So, we got the blood pressure graphed in red down here so the top line is systolic, so this person went from about 150 mmHg systolic blood pressure lying down, tilted up to 70 degrees dropped down to around 100.  We got their blood pressure up a little bit, so criteria for orthostatic hypotension.  We do this in our lab with non-invasive beat-to-beat blood pressure measurements.  That’s pretty cool.  But you don’t need that. Manual blood pressure cuff, super easy, especially the automated ones. You can set those to cycle like every 30 seconds so you can actually get a lot of data on heart rate and blood pressure.  Do remember to have patients lying down for a few minutes before. We say 10 to 15 minutes, but make sure they’re at a good steady state before you have them stand up and check for it.  

All right, so we talked about the baroreflex and neurogenic orthostatic hypotension.  We talked about medications.  The other thing we do in the laboratory that’s, that’s harder to do bedside and get measurements is we have people perform a Valsalva maneuver and we look at the blood pressure and heart rate responses to the Valsalva maneuver and this is where you really do need beat-to-beat blood pressure measurement to get a good idea of what blood pressures doing with the Valsalva maneuver.  Unless it’s really, really broken. So those four things that I hit on are what we do in the autonomic testing lab, but there’s a lot done outside of an autonomics lab.  The gastric emptying studies, well that relies on enteric function, colonic motility studies likewise, our urologists and urogynecologists doing urodynamic studies. I don’t know who does the ambulatory blood pressure monitoring here.  Internal medicine?  My old hospital it’s the nephrology clinic that did it. These are things that that are often useful in my patients with autonomic disorders.  I’m just going to say a couple of things briefly about evaluating people with autonomic disorders.  So, in our look back at 215 consecutive patients in our clinic referred for evaluation of autonomic disorders, just over 2% of them actually had adrenal failure, so if someone’s fainting and not tolerating standing up check a morning cortisol.  Like adrenal failure is not that uncommon and again this is one that makes my job as the neurologist easy like oh, not your nervous system, you need to go see an endocrinologist.  Oh, those were our adrenal failure patients, so yeah check morning cortisol. Screening for small fiber neuropathies, remember that the most common cause is diabetes, second most common cause is alcohol use, if we look at the population as a whole.  Of our patients with POTS and small fiber neuropathy about 30% of them were classified as possible or probable autoimmune, as opposed to like six and a half percent of our POTS patients without small fiber neuropathy had evidence of an autoimmune disorder and there were a variety of diagnoses.  This is our small fiber neuropathy patients in general so if you’re seeing a small fiber neuropathy think about diabetes absolutely, think about alcohol absolutely, think about autoimmune conditions.  Okay so more autoimmune stuff.  These are the things that I want you to take away.  And I want to answer your questions. Questions?  Questions you have for me.  Residents or students are like I don’t know but at 1:00 p.m. I’m out the door.

Anonymous Man:  Thank you for the tremendous lecture.  You really brought some neuroanatomy and physiology back to baseline. Thank you.  Clinically in Parkinson’s patients with dysautonomia, how much of it is from the neurogenic effect, and how much is from the medication carbidopa/levodopa?

Dr. Glen Cook:  So, is there a concern that the levodopa that we give to patients with Parkinson’s disease lowers blood pressure and there probably is some of that effect.  In most patients it’s due to a neurogenic orthostatic hypotension.  By far and away that’s the much bigger burden and if you’re concerned about the levodopa in your carbidopa/levodopa causing further decrease in blood pressure, you just ask the patient like, hey does this get worse after you take your meds and they can usually tell you pretty clearly.  And that’s one if you have a question where a 24-hour ambulatory blood pressure monitor can also come in really helpful.  The other place where people with Parkinson’s disease tend to get in a lot of trouble with their blood pressure is after eating and getting postprandial hypotension, so that’s the other really big thing to ask Parkinson’s disease patients about and their blood pressure is, hey if you eat is it a lot worse?  And again, usually they’ll be able to tell you, then you can counsel them on ok, then you need to eat small frequent meals, avoid high carbohydrate loads, etc. Or just relax after you eat, like don’t plan on getting up to do something.  So, it really depends on where the patient is at in life.

Anonymous Man:  … tract surgery has been a focus of mine in my practice and it is not uncommon for me to get the consultation … gastroenteropathy or diabetic small fiber gastroparesis or even more the more vexing one – colonic psuedo motility disorder … or every week or two.  And if you have exhausted all of the conventional treatments that are available –  prokinetics, SSRIs, and any other things that can make their symptoms more palliable, they get asked to see a surgeon about getting a gastric drainage procedure, and it’s very frustrating for me to tell them physiologically your stomach does not work even if I fix the pipes to make it drain by dependent position we’re not going to look at predictable outcome, so for these patients who come to my office, how do I tell them there might be autonomic disarrangement that cannot be fixed by a surgeon and taking out your colon or draining your stomach is not going to help.  What test you do offer them?

Dr. Glen Cook:  Yeah so, I am going to restate the question, you guys probably heard it but also for the video.  So the question was, in patients with refractory gastrointestinal dysmotility who have failed conventional even non-conventional pharmacologic interventions, sometimes they get referred for surgical procedures to say hey, guts not moving, can we do something mechanically to make things work a little bit better?  That’s a hard one and we’ve got basically this much data on that.  And like you pointed out, if the gut’s not moving, taking out part of it, diverting part of it – that’s not going to make the gut move.  So, I think I you really have to have that conversation with the patient.  You can get more information that may help you make an anatomical decision when you have the data from gastric emptying studies, colonic motility studies.  So for example, if you were to see it, if you were to say hey look, we got a guy, and I’ll actually take one of my patients for example, 56-year-old guy with normal or near-normal gastric emptying but with severely slowed colonic motility who has debilitating constipation, would it be reasonable for him to undergo a hemicolectomy?  Because that’s where all the all of the stool is getting stuck.  Well based on what we know, if the upper gut is moving okay, taking the part out where everything is getting locked up, maybe that could be considered.  We don’t know.   And that, you still have to have that “we don’t know” conversation with the patient.  If the whole gut’s dead, I don’t have a good answer for surgery.

Anonymous Man:  You talked about cranial …for the parasympathetic system even if the vagal cortex is working there is no guarantee that removing the functional obstruction downstream is going to help.

Dr. Glen Cook:  Say that again.

Anonymous Man: Cranial … If we know that a vagal intervention is working that constitutes a…motility and we don’t have the…parasympathize testing to know whether these interventions will help, then we really say ok, anatomic position point is here and by adjusting this we can make you better.  I don’t think I can…

Dr. Glen Cook:  Yeah I think that is very good to say like look, we don’t know but I think if you’re sure that the foregut is normal and sure that the colon is not moving, then you could say hey let’s do a partial colectomy, try it, to get around the place where things are getting obstructed.  The one other thing that could be considered that I would consider on an investigational basis would be sacral nerve stimulators.  So that’s the other thing to do.  If there are physiotherapists who do pelvic floor therapy and they can actually work, they can actually get some pretty good results with, just external mechanical interventions as well, so that that is a very tough one but I am glad to hear that you are slow to move to surgery.

Anonymous Man:  You cannot fix non-anatomic problems with surgery.


Dr. Glen Cook:  Yes, I’m going to restate.  You can’t fix non-anatomic problems with surgery.  It’s not mechanical, you can’t fix it by operating on it.  Yeah.  What other questions?  Okay, so I’ll be around afterward as well.  So where do you go to learn more?  So, you’ve been gifted this copy of The Dysautonomia Project book that has a lot of information that includes a lot of lifestyle type things, a lot of good tips and tricks for dealing with the lifestyle factors of autonomic disorders.  The American Autonomic Society website has a lot of information, Dysautonomia International has a lot of information, The Dysautonomia Project’s website. I mentioned Dr. Goldstein’s eBook – that’s available online if you go to Dr. Goldstein’s lab page under “selected publications” you can actually download that, it’s in the public domain so you get it as official duty as a government employee so this is actually a super good resource, wonderful illustrations, it’s a long book, but it is actually fun to read.  So, okay any other questions before we wrap up?  There is the book.  Well thank you, thank you for being here.

Glen Cook, MD

Department of Neurology, Walter Reed National Military Medical Center 
Uniformed Services University F. Edward Hebert School of Medicine, Bethesda

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