ramakentesh

http://www.ncbi.nlm.nih.gov/m/pubmed/22723437/

And more pots patients may have epigenetic suppression if this gene rather than functional mutations.

The funniest thing about this whole discussion is that in recent years mayo have adopted the position that chronic cases of pots are sustained by somatic hypervigilance and symptom catastrophising. All while a student from there publishes works identifying new autoantibodies in pots against cardiac remodeling proteins and then cardiac raft cells. there pediatric program where they tell the parents of children with pots that if they buy in to the physical nature of their child's illness then the child will be more disabled and that the child nerds to ignore their symptoms to improve (ie force them to go to school, etc) is certainly a new and interesting direction. you can read all about in the notes for the talks from the 2012 autonomic symposium. And people found the grinch syndrome controversial.. At least it had SOME evidentiary basis.

But in relation to whether the reflex tachycardia in postural hypotension constitutes pots I invite you to contact any of the leading authorities in pots and pose them that question - since they all agreed to the recent consensus statement.

Its pretty simple - it might present with orthostatic tachycardia because even profound orthostatic hypotension (reduced orthostatic msna, impaired notepinephrine release or sympathetic innervation) but nearly all pots patients have normal or increased msna and are normotensive or hypertensive orthostatically. the causes of pots are multiple but all I'm telling you is that the doctor that suggested some pots have underlying aag did not replicate those results. Ben Levine now tells people that pots and aag are different entities and since he works with the doc that identified aag in the first place I'm inclined to accept that - particularly when other groups also now view the aag and pots as distinct entities (with etiologies including net deficiency, low aldosterone and underlying sight specific autonomic neuropathies that are poorly characterized) pots remains a syndrome. every research group have their own view - some suggest preliminary research constitutes fact, others are more conservative.

Universally agreed upon by whom?

I posted in the other thread. Vernino while working at Mayo found these specific autoantibodies in cases of orthostatic hypotension and wider dysautonomia. They thought that perhaps POTS was a milder form of this disease and found very low titers in a small percentage of POTS patients. Subsequently another major research group looked for these autoantibodies in POTS patients and didnt find them in any. Mayo still suspect that many POTS is however autoimmune. Subsequently Vernino left Mayo and was hired by Dr Levine in Texas - and was unable to find these autoantibodies in any of their POTS patients. This doesnt provide a compelling argument that these autoantibodies are involved in the pathophysiology of POTS most or even any cases. This doesnt mean that POTS isnt possibly an autoimmune process in some cases (abnormal QSART might suggest an underlying small fiber and perhaps autonomic sympathetic neuropathy specific to certain regions (low limbs or splanchnic vasculature) and autoantibodies are always being looked for in POTS. But at the last two symposiums on autonomic disorders POTS and AAG were spoken about on different days and where classified as different entities.

Firewatcher posted this recently.

I wonder how they go with AIDS. its a syndrome

Hi Rama, As I said, I'm very familiar with the fact that pots and AAG are separate identities. Am going to stand behind the links I've already posted, and let them speak for themselves. Mayo has a panel of over ten different antibodies that they check for in pots patients looking for an autoimmune cause to pots. To your point that, (Quoting you) "All sorts of people have all sorts of low titered autoantibodies in their bodies without any demonstratable pathology" Absolutely true! Thank you for making that point. Many, many times people have low titers of antibodies, and Mayo will be to the first to tell you this is 'an incidental finding', and not meaningful. Mayo is very quick to find all sorts of anomalies in their exhaustive, and I mean exhaustive! testing, and I know firsthand they consider many of those anomalies, (including low levels of various antibodies to all sorts of things) to be 'incidental findings', and not meaningful. Rama, I've been to Mayo more times than I can count, and have had several major surgeries there. To suggest that a pots-related Facebook page has a doctor claiming (quoting you) that Mayo now send may of their POTS patients to him because they 'cant treat them' seems absurd to me. Am curious to see the Facebook page please? Mayo is far from perfect, but it's one of the finest diagnostic facilities in the world, and many of us have not only been treated there, but been helped tremendously by Mayo. I know you're not in the US, but Mayo is in a class unlike any other. Also regarding hypotension...You're saying hypotension rules out pots? Not in my case. I have hypotension and I have hyper pots. Not unique. Unusual but not unique. Am guessing you agree that many pots patients have an autoimmune etiology? Some of us with other autoimmune illnesses have good reason to suspect we may well have an autoimmune basis for our pots. When I was dx with Hashimoto's years ago by Mayo they told me that it put me at greater risk for developing Addison's 'later on'. When a person is dx with one autoimmune disease, it increases their risk of developing others. Thanks for sharing Rama. Let's try and move forward and share data that may help others looking for information on autoimmune pots data. Best, K Mayo do have a panel "dysautonomia panel' that they often use on POTS patients - however only a few of them have been demonstrated to be pathological and none have been proven and there is minimal evidence that they are pathological in POTS. that doesnt mean that POTS isnt autoimmune or that most POTS patients who exhibit many characteristics of autoimmunity (such as abrupt onset, 80% female, relapsing remitting, comorbid autoimmune diseases) - evidence is strong that in many it may be an autoimmune process, but there is no compelling published evidence that demonstrates that the specific autoantibodies on the MAYO panel are involved in the etiology of POTS in any cases. Yeah i just posted that Dr Alo's comments for a laugh. Doctors commonly diagnose all orthostatic intolerance syndromes with tachycardia as POTS but compensatory tachycardia can occur in postural hypotension and according to the recent consensus statement significant postural hypotension excludes from the diagnosis of POTS - you can email Blair Grubb or Julian Stewart and ask them. But patient forums are full of people with postural hypotension who have been diagnosed with POTS by other doctors and since the understanding of the undlerying etiology of either is unclear who knows whether its correct or not. Personally i dont think its that relevant. Similar to the break up of hyper v non hyper - its basically a useless delineation in terms of working out the underlying cause - although it might help with treatment. What I think is the most compelling work connecting autoimmunity with POTS is related to the neuropathic POTS variant. If you have a systemic autoimmune disease and you have POTS then according to some doctors you DONT actually have POTS - you have autonomic neuropathy. But its the same illness I hear you say? Exactly... What I tend to find and what docs tend to tell me is that most with POTS and comorbid autoimmune conditions seem to also exhibit abnormal QSART results or signs of patchy small fiber neuropathy. In diabetes and sarcoidosis it has been proven that patients ewith these conditions who have OI symptoms and small fiber neuropathy have neuropathy of the autonomic sympathetic nerves of the smooth muscle (IE wider autonomic involvement). But no one has yet proven this to be the case in POTS with SFN or POTS that appears with other autoimmune diseases. But its probable. Anyone who has an autoimmune disease and POTS should get a QSART test or skin biospy because it may open doors to treatments like IVIG which many do very well on. Hope that makes sense as im on a train...

In relation to Mayo there is some interesting information being offered by a doctor on one of the major POTS-related facebook pages. A doctor claims that Mayo now send may of their POTS patients to him because they 'cant treat them'

First time it just went away on its own with me doing nothing other than eating bacon for breakfast and I used to believe one beer a night helped as well until I was diagnoised and told that it just couldnt help LOL. then it came back a little and I exercised it away I think. For me the only thing that settles it is time.

Anthony Ocon is a student associated with Dr Stewart's research group.

Goldstein did a paper recently that Rich posted that listed about 20 different pharmocological therapies even including once Id never heard of like using tyramine with MAO inhibitors - cool.

Come on issie - i think ive posted it about ten times now: http://edrv.endojournals.org/cgi/content/meeting_abstract/33/03_MeetingAbstracts/OR48-1 Would be interesting - pity they didnt look at alpha 2 postganglionic receptors. Those guys would explain a lot

Exactly.

Rama, Perhaps Vernino was unable to find a3 acetylcholine nicorinic receptors in pots patients, but Mayo has. Pasting: The pathophysiology has been well characterized owing to the discovery of nicotinic ganglionic acetylcholine receptor antibodies in patients with AAG, though at least half of cases presents without detectable autoantibodies. Here's the link. http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P03.024 Hi Kitt Dr Vernino was THE doctor at Mayo that identified (among others) the acetylcholine a3 nicotinic autoantibodies firstly in obvious cases of orthostatic hypotension and then it was suggested in some POTS patients. The work was published but critics of the paper suggested that the number of POTS patients that exhibited these autoantibodies were low (10-13%) and more importantly the titer levels in the POTs patients tested were TINY. All sorts of people have all sorts of low titered autoantibodies in their bodies without any demonstratable pathology. As an example Ankylosing Spondylitis patients have over 150 weird autoantibodies floating around, most inactive. Subsequent to publishing the early study on the a3 autoantibodies in POTS, Dr Theiben published anotehr paper suggesting that because of the presentation of POTS it is likely autoimmune. But then another major research group were unable to find the a3 nicotinic autoantibodies in any POTS patients. And when Dr Vernino left Mayo and was hired by Ben Levine's group in Texas they were unable to replicate the previous results - that is the same doctor from Mayo who identified the a3 nicotinic receptor autoantibodies and implicated them in POTS was unable to replicate those results. So AAG and POTS remain seperate entities. And of even more interest was the fact that a Mayo related student published to more recent papers on new autoantibodies in POTS but all the patients in the cohort had profound orthostatic hypotension, excluding them from a diagnosis of POTS according to the recent consensus statement.

Dr David kem did a more recent one including pots patients but again small cohorts but interesting

Vernino now works with Ben Levine and the two of them were unable to find the a3 acetylcholine nicotinic receptors in any pots patients.

My relapses can last up to 14 months unmedicated but are much easier to manage with medication.

Lol

I think most forms of pots will eventually be treated with ivig.

The presence of autoantibodies even at high tigers does not prove they are pathological. Do you know if they were interfering with calcium ion channel activity? if calcium channel input at the sympathetic synapse was being reduced it would mean that normal levels of notepinephrine would have reduced effect on post ganglionic alpha 1 and alpha 2 adrenoreceptors causing reduced vasoconstriction. the opposite would cause enhanced orthostatic vasocobstriction and cerebral vasospasm.

The question is which ion channels? Diosmin extends calcium ion channel activity which can prolong norepibephrines effects in the synaptic cleft and enhance vasoconstriction but it may also worsen cerebral vasospasm potentially (although its unclear if this is a cause it effect scenario.) sodium channels are probably irrelevant other than perhaps in promoting neuropathy.

Mestinon is ok. While it boosts parasympathetic activity it also enhances vasoconstriction and I had no side effects