Treatment suggestions for Orthostatic Intolerance (POTS or NMH)

[MErmaid]

Changes in levels of sodium or potassium may be relevant to feeling ill but we are discussing orthostatic intolerance and I do not see their relevance to that. I think some people think that a low serum sodium goes with a low blood volume or in simple terms 'not enough salty fluid' but that is not the case. In most cases low sodium is associated with too much fluid.

As indicated above the general assumption behind the term OI is that the heart is unable to pump enough blood to the brain. The commonest reason for that is a low blood volume relative to the context. That gets complicated to explain so there is no single definition of low blood volume relevant here. In haemorrhagic shock you cannot stand up because there is literally an abnormally low amount of blood. But in most faints the problem is that there is not enough blood to fill a dilated vascular tree with the result that not enough blood is being returned to the heart for it to pump out enough to keep the brain full.

As I indicated, I am sceptical that OI in ME has anything to do with either situation, but I am pretty sure that all the physicians who deal with OI think it does - which is why they think heart rate matters. I suspect heart rate may be irrelevant.

I have labwork dating back to when I was healthy, and can see the sharp contrast of healthy vs ME for calcium, sodium, and potassium.

So I was curious if @ahimsa had low values in her labs too.

 

[Jonathan Edwards]

I would not describe my symptoms as faintness, but mental confusion and a feeling of weakness/heaviness all over ( e.g. in arms, legs, trunk, etc). Also a bit sweaty sometimes which I assume was adrenaline.

As a keen hiker and excerciser before ME I can confirm that a 30 BPM increase in heart rate was fine before i got sick and felt absolutely nothing like the POTS feeling.

As far as, “what symptoms does it cause that are problematic?” I personally can't say. some of the symtoms could be driven by POTS, but might not be. i’ve never been able to sort it out and I’ve never run across a medical provider who had a clue, even ones very experienced ones with POTS treatment.

Interesting comments.

It makes me think that maybe the shift in posture produces an adrenergic response that affects thinking and also affects the heart. Which would suggest that the tachycardia is not itself of any importance, just a sign of the adrenergic drive. The question then is what sparks the adrenergic drive - it seems tome it must be some central neural mechanism maybe from the hypothalamus. In which case things like drinking water and eating salt would seem to be irrelevant.

 

[Jonathan Edwards]

for a education on Dysautonomia, I suggest going to the website for, “dysautonomia international”.

It says:

dysautonomia is an umbrella term used to describe different medical conditions that cause a malfunction of a person's autonomic nervous system. Even though most people have never heard this term, dysautonomia is actually very common.

To me this is unhelpful. Umbrella terms are no use to us in science. We want to trace out mechanisms. If we are not interested in mechanisms there isn't even any point in talking about autonomic systems. So for me dysautonomia is not a scientific term. It may sound very erudite but I am afraid it is a smoke screen.

And autonomic nervous system problems are not common. They cannot be common if I never came across cases while seeing thousands of people for a range of medical disorders over the years. Moreover, I attended hundreds of Grand Rounds where interesting cases were presented and I cannot recall any. One or two colleagues claimed to see cases but they were the sort of doctors I tended to think did not have a very clear idea of physiology.

It seems for sure that there is some sort of autonomic problem for some PWME (which I do not regard as very common) if they feel terrible when they stand but it looks from the sources cited that the 'experts' are muddling issues of blood volume control with something quite different. Maybe one could devise a real time test for adrenergic drive (like skin conductance) that would be better than heart rate, because heart rate could reflect deconditioning.

 

[MErmaid]

Interesting comments.

It makes me think that maybe the shift in posture produces an adrenergic response that affects thinking and also affects the heart. Which would suggest that the tachycardia is not itself of any importance, just a sign of the adrenergic drive. The question then is what sparks the adrenergic drive - it seems tome it must be some central neural mechanism maybe from the hypothalamus. In which case things like drinking water and eating salt would seem to be irrelevant.

Agree, that tachycardia is a downstream effect, not the cause of OI.

 

[Marco]

And autonomic nervous system problems are not common. They cannot be common if I never came across cases while seeing thousands of people for a range of medical disorders over the years. Moreover, I attended hundreds of Grand Rounds where interesting cases were presented and I cannot recall any. One or two colleagues claimed to see cases but they were the sort of doctors I tended to think did not have a very clear idea of physiology.

That's surprising given how common diabetes is and that autonomic neuropathy is a common 'complication'.

http://wrmedical.foxia.com/Files/wrmedical/files/readings/Autonomic/A_014.pdf

 

[Jonathan Edwards]

That's surprising given how common diabetes is and that autonomic neuropathy is a common 'complication'.

http://wrmedical.foxia.com/Files/wrmedical/files/readings/Autonomic/A_014.pdf

I agree that peripheral neuropathy is common enough in diabetes but this is not a specifically autonomic problem and itself is merely an aspect of a more general microvascular damage problem. By and large the clinically relevant complications arise from the microvascular failure (foot gangrene etc.). I am sure that if someone researching the autonomic system in diabetes looks hard enough they will find various abnormal test results but I am doubtful that they have much to do with the patients' lives.

The problem with reviews like this is that they are written by people with highly selected referral patterns. The only figure I can see in the abstract mentions 20% of asymptomatic diabetics. So presumably the findings are not that important to the patient?

I guess I am referring to specifically autonomic nervous system problems that are not part of some barn door pathology affecting all cells like diabetes.

 

[Marco]

I agree that peripheral neuropathy is common enough in diabetes but this is not a specifically autonomic problem and itself is merely an aspect of a more general microvascular damage problem. By and large the clinically relevant complications arise from the microvascular failure (foot gangrene etc.). I am sure that if someone researching the autonomic system in diabetes looks hard enough they will find various abnormal test results but I am doubtful that they have much to do with the patients' lives.

Peripheral neuropathies may well be due to microvascular failure but I suspect there's a tendency to associate peripheral neuropathies with the usual numb/tingling extremities rather than innervation of the major organs including the heart which is presumably where the autonomic related symptoms such as OI and exercise intolerance arise. As diabetes related cardiac autonomic neuropathy can result in sudden death I'd say that's pretty clinically relevant and why I somewhat wryly referred to 'complications'.

The problem with reviews like this is that they are written by people with highly selected referral patterns. The only figure I can see in the abstract mentions 20% of asymptomatic diabetics. So presumably the findings are not that important to the patient?

What I picked up from the paper is that autonomic neuropathy can develop insidiously with the appearance of clinical symptoms often delayed so it may not be surprising to find objective evidence of autonomic neuropathy without reported symptoms especially early in the disease process. Table 1 in the linked paper gives prevalence rates of autonomic dysfunction from various cohorts and the tests used. Unfortunately it doesn't mention the symptoms reported or any indication of which symptoms should be attributed to autonomic dysfunction and which are 'just diabetes'.

I guess I am referring to specifically autonomic nervous system problems that are not part of some barn door pathology affecting all cells like diabetes.

Point taken. Perhaps autonomic dysfunction following mild traumatic brain injury (following mTBI but not directly due to gross damage to relevant brain areas) would be closer?

 

[voner]

It says:

dysautonomia is an umbrella term used to describe different medical conditions that cause a malfunction of a person's autonomic nervous system. Even though most people have never heard this term, dysautonomia is actually very common.

To me this is unhelpful. Umbrella terms are no use to us in science. We want to trace out mechanisms. If we are not interested in mechanisms there isn't even any point in talking about autonomic systems. So for me dysautonomia is not a scientific term. It may sound very erudite but I am afraid it is a smoke screen.

And autonomic nervous system problems are not common. They cannot be common if I never came across cases while seeing thousands of people for a range of medical disorders over the years. Moreover, I attended hundreds of Grand Rounds where interesting cases were presented and I cannot recall any. One or two colleagues claimed to see cases but they were the sort of doctors I tended to think did not have a very clear idea of physiology.

It seems for sure that there is some sort of autonomic problem for some PWME (which I do not regard as very common) if they feel terrible when they stand but it looks from the sources cited that the 'experts' are muddling issues of blood volume control with something quite different. Maybe one could devise a real time test for adrenergic drive (like skin conductance) that would be better than heart rate, because heart rate could reflect deconditioning.

I am fine with using the term "autonomic problems” instead of dysautonomia. my observations have been that ME/CFS Patients have a range of autonomic symptoms. I think there are commonly used (in the uncommon world of autonomic system dysfunction) sweat tests as I have heard some patients complain about them.

here is one reference on sweat testing...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046462/

I think for me personally, and this might be quite possibly true for others, that one reason I pursued for a while investigating my autonomic dysfunction is that it was one area where I could actually provide the medical providers with some verifiable/Testable data. look doctor! my heart rate goes up 40 bpm when I stand or stay upright and it stays there for as long as I’m standing!

 

[Trish]

look doctor my heart rate goes up 40 bpm when I stand or stay upright and it stays there for as long as I’m standing!. i

My problem is, I have no idea what my pulse rate did when I was healthy, so I don't know to what extent this sort of result is a signal of disorder. Maybe I should test a few healthy friends of my age and gender to see what their pulse rates do in parallel circumstances!

 

[Valentijn]

In reviewing my older medical files, I did see that I had low pulse pressure during one visit when I was sick, a couple years before ME onset. But usually my blood pressure was normal then.

 

[Jonathan Edwards]

I think for me personally, and this might be quite possibly true for others, that one reason I pursued for a while investigating my autonomic dysfunction is that it was one area where I could actually provide the medical providers with some verifiable/Testable data. look doctor! my heart rate goes up 40 bpm when I stand or stay upright and it stays there for as long as I’m standing!

I can understand that line of thinking. What puzzles me is that looking at the reviews ahimsa quoted it seems that a rising heart rate is not a sign of autonomic dysfunction. It said that if the autonomic system is failing you would not expect to get any change in heart rate - which makes sense. If the heart rate rises the autonomic system must be responding briskly. The problem would seem to be that something else is triggering an autonomic response when it is not needed.

It also said that a rise in heart rate of 30bpm can occur in normal people so is not in itself diagnostic. It is only diagnostic if associated with the relevant symptoms but it does not say what those are.

My understanding is that one would expect an autonomic problem to lead to postural hypotension, not POTS, with a fall in blood pressure due to a failure of the autonomic system to increase vascular tone in response to a shift in blood distribution with gravitational forces.

 

[voner]

Jonathan, here is a description from dysautonomia international of POTS symptoms.

Signs and Symptoms
While the diagnostic criteria focus on the abnormal heart rate increase upon standing, POTS usually presents with symptoms much more complex than a simple increase in heart rate. It is fairly common for POTS patients to have a drop in blood pressure upon standing, but some POTS patients have no change or even an increase in blood pressure upon standing. POTS patients often have hypovolemia (low blood volume) and high levels of plasma norepinephrine while standing, reflecting increased sympathetic nervous system activation. approximately 50% of POTS patients have a small fiber neuropathy that impacts their sudomotor nerves. Many POTS patients also experience fatigue, headaches, lightheadedness, heart palpitations, exercise intolerance, nausea, diminished concentration, tremulousness (shaking), syncope (fainting), coldness or pain in the extremities, chest pain and shortness of breath. Patients can develop a reddish purple color in the legs upon standing, believed to be caused by blood pooling or poor circulation. The color change subsides upon returning to a reclined position.

A lot of those symptoms reflect the symptoms of many ME/CFS Patients. how does a clinician separate the POTS patients from the ME/CFS patients? That I’d like to know. I suspect it comes down to postexertional malaise.


you said,

My understanding is that one would expect an autonomic problem to lead to postural hypotension, not POTS, with a fall in blood pressure due to a failure of the autonomic system to increase vascular tone in response to a shift in blood distribution with gravitational forces.

I would agree, but my study of the physiology of blood flow in the human body has lead me to the understanding of my profound levels of ignorance of physiology, especially blood flow dynamics.

in the case of somebody like me, who has my heart rate rise 40 bpm upon standing and it stays at that level while standing and it is accompanied by apparently extreme vascular construction in my lower extremities - my calves, shins and feet are colder than hell ( The skin temperature is 20° colder than my skin temperature in other parts my body), and there is no accompanying blood pressure drop whatsoever (upon and remaining standing), would not Low blood volume be a reasonable guess as to a causative factor? if not, what would explain this? a nerve signaling problem?

 

[Jonathan Edwards]

Jonathan, here is a description from dysautonomia international of POTS symptoms.

As you say, the trouble with this list is that it overlaps with ME/CFS features. Also it is very unclear which of these symptoms go with standing and which are simply symptoms that people with POTS have at other times (not related to the physiological stress of standing). It also includes symptoms due to low blood pressure (syncope, lightheadedness) and the puzzle is why people whose BP does not drop have symptoms. I am sceptical that this list is more than just a list of things the reviewer can think of in people with OI.

 

[Jonathan Edwards]

in the case of somebody like me, who has my heart rate rise 40 bpm upon standing and it stays at that level while standing and it is accompanied by apparently extreme vascular construction in my lower extremities - my calves, shins and feet are colder than hell ( The skin temperature is 20° colder than my skin temperature in other parts my body), and there is no accompanying blood pressure drop whatsoever (upon and remaining standing), would not Low blood volume be a reasonable guess as to a causative factor? if not, what would explain this? a nerve signaling problem?

Vasoconstriction in the lower limbs on standing does not seem to fit with low blood volume. The vasoconstriction ought to be there all the time - as in shock. It sounds more like autonomic/adrenergic overdrive. That in turn would suggest an operating autonomic system being pushed by some central nervous mechanism.

It is just possible that venous pooling on standing reduces venous return to the heart enough to be critical because of a low blood volume and that this triggers an adrenergic vasoconstriction, as in a compensated or pre-shock situation. However, I would still expect a tachycardia even recumbent I think.

Maybe the finding of high brain natriuretic peptide is relevant to this - in the new thread.

 

[Marco]

It sounds more like autonomic/adrenergic overdrive. That in turn would suggest an operating autonomic system being pushed by some central nervous mechanism.

At the risk of sounding like a stuck record, I mentioned autonomic dysfunction in traumatic brain injury. Two theories predominate (and damned if I can find the sources today) (a) a 'decoupling' between the cerebral cortex and other brain centres - presumably the pre-frontal conrtex can modulate ANS activity (b) - which I like - is that following TBI, afferent sensory signals are 'misinterpreted' and evoke an exaggerated ANS response as in the extreme case of 'sympathetic storming'.

Interesting that on day 2 of the repeat CPET test the ventilatory threshold is reduced which is the point at which respiration control switches from parasympathetic to sympathetic which may suggest that day 1 triggers an increase in sympathetic activity in PWME.

 

[voner]

Vasoconstriction in the lower limbs on standing does not seem to fit with low blood volume. The vasoconstriction ought to be there all the time - as in shock. It sounds more like autonomic/adrenergic overdrive. That in turn would suggest an operating autonomic system being pushed by some central nervous mechanism.

It is just possible that venous pooling on standing reduces venous return to the heart enough to be critical because of a low blood volume and that this triggers an adrenergic vasoconstriction, as in a compensated or pre-shock situation. However, I would still expect a tachycardia even recumbent I think.

in my case (of n=1),The vasoconstriction (which I’m assuming is there because of The cold feet Symptom) occurs intermittently at all times. this means it is not dependent upon me being upright or lying down. It is also intermittent. This means that that certain times of the day I can be almost assured of cold feet, and at other times of the day, or other days, my feet can have a normal temperature. i’ve noticed that walking can push my feet from being icy cold to normal temperature. it’s seems pretty darn variable...

i wish more people would chime in on this discussion.....it might help Jonathan ferrret out his thinking on these autonomic problems...

 

[ahimsa]

i wish more people would chime in on this discussion.....it might help Jonathan ferrret out his thinking on these autonomic problems...

Hi @voner

I'm still not feeling up to joining this discussion, sorry.

But for those who do feel up to it, the Feb. 2015 IOM report is another source of data. Go to this website to download a PDF of the full report - http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx (can also be read online, I think)

On page 107 there's a section titled "Orthostatic Intolerance and Autonomic Dysfunction"

Starting on page 119 there's a list of references (includes references for several sections, not just the one I mentioned).

For those who just want a reminder of what this IOM report is, there's a summary on MEpedia: http://me-pedia.org/wiki/Institute_of_Medicine_report

 

[Sing]

I have had a very difficult problem with OI for 8 years now. It involves a slow heart rate which does not try to compensate, as with POTS, for the hypotensive state which makes it an increasing struggle to stay standing until I have to get my head way down to begin a temporary recovery. If I do not, I will go from strain, dizziness, visual greying, incoordination, inability to think, to blackout. I go through about 14 of these episodes between getting up in the morning and having the cup of coffee I am seeking as quickly as possible.

To be more scientific, what interests me most now is the research into peripheral neuropathy, actually polyneuropathy, that Dr. Anne Oaklander at MGH in Boston (Harvard teaching hospital) is doing. Here is a talk she gave in the fall of 2015.

More recently she is studying the value of IVIG for a certain type of patient with polyneuropathy. www.neuropathycommons.org is her public website.

I was diagnosed with Small Fiber Neuropathy a number of years ago but, with unusual pain, sensitivity all over, it looks like I am one of those whose neuropathy goes beyond the small fiber endings in my extremities.

It is increasingly difficult to manage! I agree that increased salt, water (balanced with potassium) have only a temporary good effect followed by the body having to work to get rid of all it regards as unnecessary. I think I have mostly given my kidneys a lot of extra work. The recommended drugs don’t help much and have side effects, in my experience, but if they help someone else, don’t let me discourage you.

 

[Sing]

It seems as though the smaller fiber nerves are being damaged. After the nonmyelinated small fibers, the next smallest fibers belong to the sympathetic nervous system—that very useful capacity for fight or flight, adrenergic action. Considerably larger fibers, I have been told, are the parasympathetic ones, rest and digest. A doctor explained this to me, but I don’t technically know what is going on.

So it seems to me that whatever is damaging the nervous system first affects the very smallest fibers, then on to the small sympathetic fibers? How important those are to heart rate and blood pressure, maybe bladder control....I am having trouble in these areas, as well as pain, burning and sometimes itching or numbness. And cognitive and memory issues for even longer.

 

[Trish]

Hi, @ Sing, I'm sorry to hear you are having such horrible problems. All I can offer is sympathy and a virtual hug.