Dysautonomia, also called autonomic dysfunction, is a term used to describe a variety of conditions, including POTS (postural orthostatic tachycardia syndrome), diabetic autonomic neuropathy, and autoimmune autonomic ganglionopathy, in which the autonomic nervous system is not operating correctly.
Dysautonomias are generally considered rare, although like hEDS and HSD, they are probably more undiagnosed than rare. They do, rare or not, share many of burdens of rare diseases.
The condition most commonly associated with Ehlers-Danlos Syndrome is POTS.
This page is a collection of resources to help you understand more about dysautonomia, including POTS, and its relationship to EDS. I am trying to include a variety of media, since we all learn differently. Some of the resources are links to foundations dedicated to dysautonomia research, some are articles, some are videos.
My goal is to put access to all of the resources that I’ve found most helpful in trying to get a handle on dysautonomia as it affects me. I’ve scoured the internet looking for information; I have pages saved in many different bookmarks folders; I’ve lost and rediscovered information over and over again. So I figured, if I’m going to tackle organizing it all for me, I may as well share it with everyone else.
As always, please bear in mind that none of the information on this website should be considered medical advice. This website is for informational purposes only, to provide patients with knowledge that they can share and discuss with their physicians.
Organizations
The Ehlers-Danlos Society
The Ehlers-Danlos Society hosts articles on their website from the 2017 International Symposium on EDS. The article “Cardiovascular Autonomic Dysfunction in Ehlers–Danlos Syndrome – Hypermobile Type” from the symposium discusses dysautonomia in hEDS.
Dysautonomia Project
This organization in particular has a TON of information and resources for dysautonomia patients. They are a great advocacy group pushing really hard to reach and educate physicians as well as patients.
Dysautonomia Information Network
Dysautonomia International
POTS UK
Publications
Dr. David Goldstein works for the NIH National Institute of Neurological Disorders and Stroke – Clinical Neurocardiology Section. He’s pretty much *the* guy when it comes to the autonomic nervous system. You can say he wrote the book on autonomic medicine, because in the course of his work at the NIH, he wrote Principles of Autonomic Medicine, a free PDF book available online. [Per pages 1 and 2 of the book, it is in the public domain, however not all images included in the document are copyright free].
The book at first seems like a bit of a beast – it’s a 756 page PDF document! Yikes! But for all that, I’ve found it fairly approachable. It goes very in depth into the history of the discovery of the autonomic nervous system (ANS), as well as how the ANS operates, physically and chemically. VERY in depth. Soooo… for now I skipped quite a bit of the background and went into the dysautonomia section (p. 248). To be quite honest, I think the biggest drawback of the book isn’t the length, but rather the formatting. Sometimes pictures get cut off, captions are misplaced, or pictures are oddly far from the associated text.
Despite its shortcoming’s however, it’s still worth a dedicated look! I wouldn’t try to tackle the whole thing at once, but if there is a particular autonomic condition that you want to know more about or a particular treatment you would like to understand or just to learn about how the ANS works, it’s certainly a gold mine of information. I do think it should include a small graphic warning, however. There are pictures of real life body parts that might be too gory for some, and he also quite casually mentions animal testing (including death) that some may find distressing.
Dr. Goldstein also co-authored the Dysautonomia Project book, “Understanding Autonomic Nervous System Disorders for Physicians and Patients.” I haven’t read this book. At the time of this post, it’s about $22 and you can purchase it through their website.
Videos
Some of these videos provide background on the nervous system, others cover dysautonomia in particular, and some deal with POTS/dysautonomia within the setting of EDS or hypermobility.
I’ve embedded my favorite videos here, but for the most up to date list you can check out my Understanding Dysautonomia Playlist on YouTube! As new videos come out or I come across others, I will add them to the playlist but most likely won’t update this post.
Crash Course
This series of videos is a fun, informative look at the basics of how the nervous system *should* work. It’s a tiny portion of the larger Anatomy and Physiology “Crash Course” theme they ran.
Dysautonomia International
A short overview of POTS (postural orthostatic tachycardia syndrome), which is considered to be commonly comorbid with EDS.
Dysautonomia Project
This might be my favorite video of the bunch! If you’re going to watch one long video, watch this one. Dr. Cook covers a lot about how the ANS works and provides a lot of useful information about what doctors understand right now about different dysautonomias. If the Dr. Goldstein book was a bit too much to tackle, try this video instead.
I also came across a copy of the slides he uses in the presentation.
Chiari & Syringomyelia Foundation
This video features Dr. James Glenn. As many of you know, Chiari malformation is another common comorbidity of EDS, so it makes sense for the Chiari & Syringomyelia Foundation to have hosted a lecture on this topic. There’s a bit of a long introduction, so I’ve skipped ahead a little in the video below.
The Ehlers-Danlos Society
The Ehlers-Danlos Society has done an excellent job of posting videos of talks given at a variety of the conferences they host. I highly recommend checking out the webinars they host! I’ve embedded a couple of their autonomic dysfunction focused videos here. I like these two because they talk more about how to deal with dysautonomia, whereas many of the other videos discussed more of the physiological aspects of dysautonomia.
Medical Research & Articles
Alright, so here’s where things get a little dicier and a bit less fleshed out. But I think it’s important to include links to the medical literature. These are the primary sources. And when there can be a lot of confusion in “pop culture” so to speak, or the myths and misconceptions that go along with so many of these conditions, I think it’s incredibly important to be able to look back at the research and say, “no, this was the actual finding.” Unfortunately, I was not able to find freely available full-text copies of all the articles that looked interesting or important. I try to note when this is the case; however usually even just the abstracts give some useful information.
I have some articles about autonomic dysfunction in general, like the COMPASS study that lots of speakers reference, but I also fell down a bit of a rabbit hole trying to understand my own atypical symptoms, so there are many articles relating to blood pressure variability and the so called “hyperadrenergic” variation of POTS. I’ve tried to distill some sense of order, make comments, and pull quotes where I can, but it’s quite a bit of literature to sift through! Maybe I will edit for more clarity at a later time, but for the moment I’m more interested in getting the information “out there.”
Autonomic Dysfunction
The effect of different body positions on blood pressure by Eşer I, Khorshid L, Güneş UY, Demir Y. (2007)
Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome, first author Roy Freeman (2011)
COMPASS 31: A Refined and Abbreviated Composite Autonomic Symptom Score by David M. Sletten, Guillermo A. Suarez, Phillip A. Low, Jay Mandrekar, and Wolfgang Singera (2012)
Validation of the Composite Autonomic Symptom Scale-31 (COMPASS-31) in patients with and without Small-fiber Polyneuropathy by Roi Treister, Kate O’Neil, Heather M. Downs, and Anne Louise Oaklander
A composite autonomic index as unitary metric for heart rate variability: a proof of concept, first author Roberto Sala (2017) full text not available
How to interpret the results of a sleep study by Deepak Shrivastava, Syung Jung, Mohsen Saadat, Roopa Sirohi, Keri Crewson (2014)
POTS (Postural Orthostatic Tachycardia Syndrome)
Increasing Functional Abilities of People with Postural Orthostatic Tachycardia Syndrome through Occupational Therapy by Jennifer R. Dochod and Cynthia Grapczynski (2019)
Postural Orthostatic Tachycardia Syndrome (POTS): Association with Ehlers-Danlos Syndrome and Orthopaedic Considerations by Emmanouil Grigoriou MD, Jeffrey R. Boris MD, John P. Dormans MD (2011)
Hyperadrenergic POTS
Clinical presentation and management of patients with hyperadrenergic postural orthostatic tachycardia syndrome. A single center experience by Khalil Kanjwal, Bilal Saeed, Beverly Karabin, Yousuf Kanjwal, Blair P. Grubb (2011)
“This form [hyperadrenergic] of postural tachycardia syndrome is called hyperadrenergic POTS, and comprises about 10% of all POTS patients. Patients suffering from hyperadrenergic POTS have been observed to have an orthostatic plasma norepinephrine level ≥ 600 pg/mL and a rise of systolic blood pressure (SBP) of ≥ 10 mm Hg upon standing [1, 2, 6–8].”
Khalil Kanjwal et al
Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders by Cyndya Shibao, Carmen Arzubiaga, L. Jackson Roberts II, Satish Raj, Bonnie Black, Paul Harris, Italo Biaggioni (2005)
“patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79+/-4 to 114+/-6 bpm), increased systolic blood pressure on standing (from 117+/-5 to 126+/-7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157+/-12 versus 117+/-9 in normal controls and 1197 mm Hg in POTS; P0.048), and an exaggerated phase IV blood pressure overshoot (50+/-10 versus 17+/-3 mm Hg in normal controls; P0.05).”
Cyndya Shibao et al
“Diagnosis requires biochemical documentation of MCA because other causes of flushing can be associated with POTS. A correct diagnosis is important because the presence of MCA mandates a different approach in the treatment of these patients. β-Blockers, a commonly used therapeutic option in POTS patients, should be used with caution, if at all, because of the risk of triggering MCA. These patients can be treated with H1/H2histamine antagonist and central sympatholytics.”
Cyndya Shibao et al
Orthostatic Hypertension
Orthostatic Hypertension: When Pressor Reflexes Overcompensate by Joshua Fessel and David Robertson (2006)
“It has long been recognized that minor minute-to-minute fluctuations in blood pressure occur in healthy individuals, and that many factors influence these fluctuations. Perhaps the easiest to observe is the influence of posture. Assumption of upright posture from a recumbent position results in a small but measurable decrease in systolic blood pressure (SBP) due primarily to a redistribution of blood volume into the lower abdomen, buttocks and legs under the influence of gravity. In most people, this decrease in blood pressure is very slight and evanescent, as a whole host of response mechanisms are immediately engaged to maintain blood pressure.”
“Unlike pure autonomic failure or multiple system atrophy, however,
episodic tachycardia and labile hypertension are prominent features in baroreflex failure. (11–13) The postural tachycardia syndrome (POTS) also presents clinically with symptoms of cerebral
hypoperfusion. (14,15) Interestingly, however, this disorder more often involves either no change in blood pressure or orthostatic hypertension of mild severity.”“Orthostatic hypertension is an under appreciated but potentially clinically important entity. As alluded to above, orthostatic hypertension is defined simply as an increase in blood pressure upon assumption of upright posture… The magnitude of increase in sphygmomanometric pressure required for a diagnosis of orthostatic hypertension has often been operationally defined in individual studies, with an increase in SBP of 20 mmHg or more being a common recent diagnostic criterion (Box 1). Recognition of the presence and degree of orthostatic hypertension might be clinically important for a number of reasons. First, orthostatic hypertension might be a symptom of another treatable condition, such as pheochromocytoma (17,18) or mast-cell activation disorder in the context of POTS. (19) Second, orthostatic hypertension resulting from any number of causes might be an important risk factor for silent cerebrovascular ischemia and infarct.”
“Orthostatic hypertension has also been associated with a number of conditions involving some form of autonomic dysfunction. In a
Fessel & Robertson
recent study of patients with POTS in the context of disordered mast-cell activation, 38% (3/8) were shown to have orthostatic hyper tension. (19) Interestingly, in this group of patients, the orthostatic hypertension manifested as either a persistent hypertensive
response to assumption of an upright posture or as a hypertensive crisis, with BP as high as 240/140, with upright posture. This has not been observed in patients who have POTS but do not have mast-cell activation disorder. Patients with baroreflex failure may also occasionally experience episodes of orthostatic hypertension. (26–29)”
Orthostatic hypertension: Recognizing an underappreciated clinical condition by Lovely Chhabra and David H. Spodick (2013)
“Orthostatic hypertension refers to an increase in the blood pressure upon assuming an upright posture. This clinical condition has been understudied and is often underappreciated in clinical practice probably because of its unfamiliarity to many clinicians including subspecialists.”
“Orthostatic hypertension is an underappreciated and understudied clinical phenomenon and has no standard definition yet, but an operational definition based upon previous studies refers to it as an increase in systolic blood pressure of 20 mmHg when changing position from supine to standing.”
Chhabra and Spodick
Orthostatic Hypertension – The Last Hemodynamic Frontier by David Robertson (2011)
Orthostatic Hypertension Due to Vascular Adrenergic Hypersensitivity by Neal L. Benowitz et al (1996)
Blood Pressure Variability
Fluctuation in systolic blood pressure is a major systemic risk factor for development of primary open-angle glaucoma by Na Young Lee, Younhea Jung, Kyungdo Han & Chan Kee Park (2016)
Effect of Antihypertensive Agents on Blood Pressure Variability by Yi Zhang , Davide Agnoletti , Michel E. Safar , and Jacques Blacher (2011)
“From a physiological point of view, autonomic nervous system (ANS) regulates BP and HR synchronously and, therefore, contributes to stabilizing their fluctuation. The close association of BPV with HRV in different time frames is probably a universal phenomenon, which could be a consequence of the ANS regulation. Furthermore, the significant relationship between the reduction in BPV and in HRV, consistently observed in the present study, indicates a proportional decrease in the fluctuation of both BP and HR, which is probably attributable to amelioration of the ANS regulation. However, the pharmaceutical mechanism is still unknown.”
Yi Zhang et al
“However, the mechanism underlying the reduction in BPV has yet to be clarified, especially its potential interaction with arterial stiffness and/or reflection waves. Given the increasing importance of BPV in the prevention of stroke, as well as other target-organ damage, further studies are undoubtedly warranted.”
Yi Zhang et al
Aortic stiffness and blood pressure variability in young people: a multimodality investigation of central and peripheral vasculature, first author Henry Boardman (2017)
Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage: a LIFE substudy. first author Vishram JK (2015) full text not available
Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension by Rothwell PM (2010) full text not available
Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke, first author Rothwell PM (2010) full text not available
Prognostic Significance of Blood Pressure and Heart Rate Variabilities – The Ohasama Study, lead author Masahiro Kikuya (2000)
Blood Pressure Variability and Organ Damage in a General Population – Results from the PAMELA Study, lead author Roberto Sega (2002)
Blood pressure variability and cardiovascular disease: systematic review and meta-analysis, first author Sarah L Stevens (2016)
“Long term variability in blood pressure is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease. Limited data for mid-term and short term variability showed similar associations.”
Stevens et al