My Theory On What Is Causing Most Dysautonomia And Why There Are Wide Ranging Symptoms- Autonomic Neuropathy

[kitt]

Thank you Rich for sharing,

Here's a dysautonomia 'primer' about small fiber peripheral neuropathy published by The Dysautonomia Connection that might help people understand some basics.

Helped me to begin to understand small fiber peripheral neuropathy, and had it bookmarked. I reread my bookmarked articles and it helps me to continue to review the basics.

http://thedysautonomiaconnection.org/about-dysautonomia/small-fiber-peripheral-neuropathy/

[kitt]

And from another site on 'Group C nerve fiber'

http://en.wikipedia.org/wiki/Group_C_nerve_fiber

[RichGotsPots]

Fiber types Type Erlanger-Gasser

Classification Diameter Myelin[14] Conduction velocity

preganglionic fibers B 1-5 µm Yes 3–15 m/s

postganglionic fibers C 0.2-1.5 µm No 0.5-2.0 m/s

[RichGotsPots]

Opps my graph did not translate well here lol

[Lemons2lemonade]

Rich, have you ever heard of shingles? Random activation of herpes zoster, lives in the nerves.

[RichGotsPots]

Rich, have you ever heard of shingles? Random activation of herpes zoster, lives in the nerves.

Yes but again there are really over 40 known causes of small fiber neuropathy including infectious diseases. Would take me all day to list them and the relationship. What it comes down to is how to protect against damage or fix the damage..

It would be great if as a group we tried to zero in on all the researchers specifically focused on this. The typical Peripheral Neuropathy specialist hardly has anything to do with the autonomic part of it, they focus on the motor and sensory issues. I would like to get some more top notch college labs interested in this.

[Hope]

So thankful that you and others are taking the time and have the means to do this kind of research.

[Hope]

Rich, I didn't test positive for SFN - but, do have some neuropathy and it runs in my family. If they don't take the biopsy in the right place it won't be picked up. Yet, I couldn't feel needle sticks when tested that way. That being said ---I think we have to go deeper then just saying there are issues with nerve fibers and their dysfunction. That would be a side effect of what I think is the under lying problem.

Personally, I think it all comes down to the immune system. The body is attacking itself and CAUSING these issues. Work on the immune system and maybe we will get better. Since I've been doing this - I'm starting to get the feeling back in my feet and lower legs. I used to not be able to feel the bottoms of my shoes - and now I can. It used to be when I'd run my hand up my leg there would be a strange electrical - stinging type feeling (neuropathy) I seldom have this now. There are times when I have more numbness and pain and times where things are near normal. Why is it that the nerves will sometimes - not feel something and other times it will be there?

If we try to get to the core of the problem - correct that - then maybe we will start to get better. I think focusing on autoimmune issues, good healthy diet and maybe genetic mutations of known dysfunctions --- might help us all. This is my focus at the present time.

Rich, you've put an awful lot of thought and research into this. I think maybe you are finding some of your puzzle pieces. Thanks for posting your theories.

Issie

I certainly do not know what comes first here, the chicken or the egg, but working on my immune system has greatly improved my symptoms. Slacking for just a few days in my routine will throw me back into symptoms worsening, as they are today!

[tinkerbella]

I always wondered about childhood warts. The herpes virus for those of us that have had this forever. Later mono, EBV and then having very high titers. Just a thought. I had warts as a kid on my hands really bad , then the other two along with a terrible case of the chicken pox. I hope I never get shingles. I need to ask about the vaccine. I have been a bit afraid of it with POTS.

[RichGotsPots]

Here is an example of how nerves regenerated incorrectly:

Gustatory sweating, It is thought that ANS fibres to salivary glands have become connected in error with the sweat glands after nerve regeneration...

This is after an operation where they purposely try to cause small fiber neuropathy to reduce sweating in the chest, but it goes wrong..

[Kellysavedbygrace]

Rich, nice work on this theory. I do believe that it will be Dysautonomia patients that eventually unravel the mystery behind our complex and highly variable cases. I do hope, like Jangle, you are making your way to medical school. I'd like to come see you too once you begin accepting new patients. I have been thinking about your post for a couple of days now and have a few questions. As you answer, keep in mind that like you, I have no medical background and am a patient who has studied this for the past year and a half so I can help myself improve in my day to day functioning. I tend to know a lot about the ANS, mast cell hematology and cardiac, vascular, neurological and repiratory effects but am lacking in understanding of the whole picture.

1. You mention this is "theory #3,". What were theories # 1 and 2? Or were they infantile versions of this same theory?

2. So help me clarify your theory. This is my interpretation of what you've said. Please fill in any gaps or correct any wrongs:

-------

Dysautonomia may have many different causes (autoimmune, mast cell, viral, etc) but in a majority of the cases, where the real problem is an ANS issue and not simply mimicking autonomic dysfunction, the common mechanism behind Dysautonomia is a dysmyelination of the Group B fibers and/or a dysfunction of the group C fibers.

Furthermore this means that for most of us Dysautonomia is degenerative (unless we find a way to

regenerate the myelin sheath of our preganglionic fibers that have been damaged or a way to correct the non-myelinated post ganglionic fibers that are improperly functioning.)

3. I think I understand what you mean about dysmyelination of group B fibers but I am unclear on what you suspect is happening with the unmyelinated post ganglionic fibers.

4. In your theory do some of us have problems with group B fibers only, group C fibers only and/or a

combination of group B and C fibers? (you alluded to this but I was unclear)

5. Since there are exceptions to the mostly myelinated preganglionic fibers (in group such as the

preganglionic fibers that connect to the adrenal medulla where the preganglionic fibers are not

myelinated how does this theory apply? Or not apply?

6. What is the source of your stated percentages of efficacy of nerve conduction studies, QSART testing and SFN biopsies? And to clarify is 88% efficacy of SNF biopsies the higher level skin biopsy testing Group C or more traditional SFN biopsy testing group B? (interestingly while at Vanderbilt in January Dr.

Biaggioni said that approx 30% of the POTS patients they see test positive on QSART for SFN. Although anedotal in nature this is different than your stateed 50%.) At that time I was surprised it was so low. But furthermore, I was surprised during all three nerve tests I've had done (an EMG done locally, and two QSARTS - Cleveland Clinic and Vanderbilt) that they all came back normal. I've wondered, "How can that be when I have such difficulty with parasthesias, Allodynia, and frequent loss of feeling/ blood flow in my arms and legs?". This theory might begin to explain it.

7. Is the primary role of the CNS in this theory that of releasing various chemical mediators that effect

the PNS? Or do you suspect there significant dysmyelination and dysfunction occurring in the brain stem and spinal cord as well?

8. How do you suspect this dysmyelination affects something symptomatic like erratic hemodynamics? Or is that for studies on down the line?

Cheers! KSBG

[Kellysavedbygrace]

Don't know why I have an emotion icon there but it should say, "B."

[RichGotsPots]

1. You mention this is "theory #3,". What were theories # 1 and 2? Or were they infantile versions of this same theory?

2. So help me clarify your theory. This is my interpretation of what you've said. Please fill in any gaps or correct any wrongs:

-------

Dysautonomia may have many different causes (autoimmune, mast cell, viral, etc) but in a majority of the cases, where the real problem is an ANS issue and not simply mimicking autonomic dysfunction, the common mechanism behind Dysautonomia is a dysmyelination of the Group B fibers and/or a dysfunction of the group C fibers.

Furthermore this means that for most of us Dysautonomia is degenerative (unless we find a way to

regenerate the myelin sheath of our preganglionic fibers that have been damaged or a way to correct the non-myelinated post ganglionic fibers that are improperly functioning.)

3. I think I understand what you mean about dysmyelination of group B fibers but I am unclear on what you suspect is happening with the unmyelinated post ganglionic fibers.

4. In your theory do some of us have problems with group B fibers only, group C fibers only and/or a

combination of group B and C fibers? (you alluded to this but I was unclear)

5. Since there are exceptions to the mostly myelinated preganglionic fibers (in group such as the

preganglionic fibers that connect to the adrenal medulla where the preganglionic fibers are not

myelinated how does this theory apply? Or not apply?

6. What is the source of your stated percentages of efficacy of nerve conduction studies, QSART testing and SFN biopsies? And to clarify is 88% efficacy of SNF biopsies the higher level skin biopsy testing Group C or more traditional SFN biopsy testing group B? (interestingly while at Vanderbilt in January Dr.

Biaggioni said that approx 30% of the POTS patients they see test positive on QSART for SFN. Although anedotal in nature this is different than your stateed 50%.) At that time I was surprised it was so low. But furthermore, I was surprised during all three nerve tests I've had done (an EMG done locally, and two QSARTS - Cleveland Clinic and Vanderbilt) that they all came back normal. I've wondered, "How can that be when I have such difficulty with parasthesias, Allodynia, and frequent loss of feeling/ blood flow in my arms and legs?". This theory might begin to explain it.

7. Is the primary role of the CNS in this theory that of releasing various chemical mediators that effect

the PNS? Or do you suspect there significant dysmyelination and dysfunction occurring in the brain stem and spinal cord as well?

8. How do you suspect this dysmyelination affects something symptomatic like erratic hemodynamics? Or is that for studies on down the line?

Cheers! KSBG

1. I have previous posts with theory 1 and theory 2 on here somewhere. 1st was about regional BP, the second was about damaged Endothelial tissue affecting regional BP (Vandy is actually testing for endothelium dysfuction now as I understand)

2. Correct but I believe its Dysmyelination of group B (which I think messes up function that relate more to CNS but not directly and it causes disturbances they are more mental (for lack of a better term) like intolerance to noise or visual, feeling anxious, etc..) and the other part is that Group C fibers aren't just dysfunctional but they are totally damaged (neuropathy) which causes dysfunction.

Not exactly degenerative in both fibers only group C. The body constantly has a process to regenerate fibers its slightly different depending on whether myelin or unmyelinated fibers are involved. But I'm saying for dysmyelination group B they regenerated incorrectly so there isn't technically a neuropathy just malformed myelin sheath bouncing the messages around. In Group C there is degeneration and most likely the causes are preventing the regeneration, thats why when an autoimmune person get IVIG and the cause it cleared out temporarily the Group C fibers get a chance to regenerate themselves without disturbance.

3. I think answer 2 addresses this.

4. The only way we will really know is if we all get tested. i have polled on here and other forums and not even 1/10 have been tested. Also Mayo for example doesn't believe in the skin Biopsy, probably because they developed the QSART, which is the biopsy's competition. No one has looked into my Group B theory so don't know about that yet but even Mayo acknowledges that at least 50% have group C sfn. I figure its higher because the lack of sensitivity to both tests. So it remains to be seen yet..

5. group B fibers are very serious especially since they connect to the CNS. I think the only ones of us that would have this group of neuropathies are very very seriously degenerative illnesses like ALS or Parkinson's where the disturbances will be highly "mental" in nature. These illnesses have polyneuropathies and I think go a little deeper than a typical dysautonomia. Possibly a pure autonomic failure has some group b neuropathy. Again its hard to say unless we really start looking closer at this group b.

6. http://brain.oxfordjournals.org/content/131/7/1912.abstract?ijkey=57f7432bb3b0b7aa5145cd6f3e9d48a9c41cda1b&keytype2=tf_ipsecsha

7. Its not clear yet, but that will hopefully come in an update down the road. But my hunch is CNS has to do more with group B, but group C I feel definately plays a rold.

8. Its down the line it could be either group or both groups or just Group C neuropathy only. For example group C controls thermal regulations and sweat and maybe just that little dysfunction can throw off hymodynamics completely, an internal gloabal warming

[sue1234]

Your phrase "personal global warming" would exactly describe me. I have always thought that I could now actually almost believe in sponataneous combustion!

[issie]

The "mental" state that you speak of Rich - could be explained by an imbalance in the glutamate/GABA balance and that affects the function of the CNS and therefore, very possibly, the nervous system and it's function.

Even with the article you listed above ----the CORE issue probably is the immune system. I think what you are describing and saying is true about the neuropathies ----but, the underlying CORE reason for probably the majority could be addressed by working on the immune system. (My opinion for what it's worth.)

Most of what you read these days about MS, diabetes, etc. is the underlying problem is a faulty immune system. Correct this and possibly you will have the other correct itself. To correct this however, will be a complex thing. There is so much that has to be addressed to sort what is causing the malfunction in the first place and then to get it to start recognizing what it needs to so that it won't continue to attack the body in a negative way ---but, will recognize what it needs to for the body to start to heal.

Issie

[GypsySoulNicole]

The "mental" state that you speak of Rich - could be explained by an imbalance in the glutamate/GABA balance and that affects the function of the CNS and therefore, very possibly, the nervous system and it's function.

Even with the article you listed above ----the CORE issue is the immune system. I think what you are describing and saying is true about the neuropathies ----but, the underlying CORE reason for probably the majority could be addressed by working on the immune system. (My opinion for what it's worth.)

Most of what you read these days about MS, diabetes, etc. is the underlying problem is a faulty immune system. Correct this and possibly you will have the other correct itself. To correct this however, will be a complex thing. There is so much that has to be addressed to sort what is causing the malfunction in the first place and then to get it to start recognizing what it needs to so that it won't continue to attack the body in a negative way ---but, will recognize what it needs to for the body to start to heal.

Issie

Rich, I think your spot on. Issie, so are you! The below link is a MUST READ, it's long, but SO worth the read.

http://physrev.physiology.org/content/82/4/981.long

[issie]

Whew! That is a long read --but, well worth it. If we could figure out the best way to address the immune system and take care of the pain issues that go along with this ---our lives would be much happier. I've often said that I think getting out of pain helps with POTS. Interesting there was a connection to Glutamate/GABA - NMDA system. (Not a lot written - but some.) Also the connection with mast cells and their release of inflammatory cytokines. Maybe, that's why the GastroCrom is helping some of us --we are working on the mast cells and along with it our immune systems. The diet I'm doing is anti-inflammatory, lower protein, and eliminates foods known to cause inflammation, allergy and autoimmune issues. The treatment for the protozoa --focuses on the immune system, pathogens and virus. There is also massive amounts of enzymes (which also help to eliminate inflammation). So, like I said ---I think I'm on the right track --just have to hold the course and know it will take time. But, I really think what I'm doing, right at this minute, in my life - is the right way to go.

Nicole, that was a very good find. Thanks for posting it!

Issie

[RichGotsPots]

Issie

Rich, I think your spot on. Issie, so are you! The below link is a MUST READ, it's long, but SO worth the read.

http://physrev.physiology.org/content/82/4/981.long'>http://physrev.physiology.org/content/82/4/981.long

While I appreciated the link btwn both, I think the paper isn't anything new in that it's well known that autoimmune disease, diabetes (which is believed to be autoimmune in nature) and sarcoidosis (which is somewhat autoimmune) all can cause neuropathies. So no one would ever dispute that. I don't think the paper pointed to any insight as to why.

It was shocking that it stated,"Indeed, sympathectomy does not just relieve pathological pain in the body region ipsilateral to the CRPS-initiating event; rather, it also relieves pain arising from anatomically impossible mirror-image sites, that is, the identical body region contralateral to the initiating event." Sympathectomy is a rather unnerving procedure, excuse the pun hehe. Many people who have that surgery end up with autonomic neuropathy and dysfunction. I guess just bothered me that they focused only on sensory neuropathy rather than autonomic neuropathy..

[hholmes13]

So I was doing some reading and found an interesting study in patients with "idiopathic" sfn:

Gain of Function Na 1.7 Mutations in Idiopathic Small Fiber Neuropathy; Faber et al Ann Neurol. 2011 May 20;

Anyway the gist of this study was out of 28 patients, 8 (almost 30%) had cSNPs (coding mutations) in a sodium channel that is present in small fiber nerves. These mutations caused a hyper-excitability of neurons and they are hypothesizing that increased activity (i.e. more sodium coming through) may be causing some degeneration in the fibers. Apparently lots of sodium can be taxing on the neurons. 7 of 8 of the patients with these mutations had autonomic dysfunction and most had a younger than normal age of onset for the sfn and no other cause could be identified.

This is really interesting to me...I think I may do some experimenting on myself. A huge part of my job is analyzing human genomic DNA for mutations in the protein that our lab studies in relation to glaucoma. Well I have a ton of my own DNA in our lab's freezer because we all participated as "controls" in our current study. My boss has already told me he'd be fine with me sequencing proteins of interest to see if I can get to the bottom of some of my problems. I think I may check out to see if I could find anything out. We also do electrophysiological studies of proteins similar to those in this paper. I may even be able to do some functional testing of any potential mutations found to see if there are changes.

[issie]

hholmes13, I find the genetic component and mutations very interesting. I had 23&me genetic testing and have noted some mutations that could potentially be causing some of the issues that I have. Maybe trying to address some of those mutations and work around them may be of benefit. (It appears to be a very controversial subject. Some are on board with methylation pathways and genetic mutations and others don't think it will make a difference. Or, think that it is just theory and unproven. But, for the ones actively using the information available on the way this process works and what is thought to by-pass these mutations ---they feel that they are getting great benefit.) If we can sort out the links that are dysfunctional and tweak those - we may get some better gains with our health.

Let us know how it goes.

Issie

[looneymom]

So glad you posted this. I have really wondered about the vagus nerve. Before my son was ever diagnoised with POTS, he suffered from vocal cord disfunction and a vocal tic when he was in the first grade. My therory is his condition just kept progressing to POTS because of these conditions.

[voner]

rich And everyone,

Nice discussion. Has anyone had discussions with medical practitioners with a lot of experience With patients having autonomic dysfunction as to what they speculate is the core cause?

I've been watching the vagal nerve field for a few years. I personally think there has been a ignorance By researchers and medical practitioners of the electrical properties of the nervous system. Some interesting electrical procedures and gadgets are coming on board. The one I find most interesting is this one:

http://www.cerbomed.com/

Can't wait for it to come to the United States.

[davecom]

The genetic front is surely as important for our disease(s) as it is for any other chronic condition. Let us know how your research goes! In a not so long ago healthy life I studied computational biology as a large part of my graduate studies. I hardly have enough brain power left to string together these sentences, but I'm fairly sure focused researchers could find some interesting genes in our pool!

[hholmes13]

I'll definitely keep you all updated if I find anything. I just need to get the go ahead from my boss to order the necessary primers to run the tests. I'm interested to see what this brings. I've seen from firsthand experimental experience in the lab where I work how a simple amino acid change can wreak havoc on protein function. Especially if you are changing the charge of the amino acid. Simply going from a negatively charged amino acid to a positively charged one can change how the protein folds and impact transport function. I'm not saying that it's necessarily as simple as that, especially for everyone. However, knowing if a certain transporter in your body isn't functioning properly (and even better understanding what's wrong i.e. too much activity or too little) may help determine how you will react to certain medications/treatments.

[ramakentesh]

Has anyone had discussions with medical practitioners with a lot of experience With patients having autonomic dysfunction as to what they speculate is the core cause? I've been watching the vagal nerve field for a few years.

Yes I have them often. Each has their own theories.