Acetylcholine Nicotonic Receptor

[erikainorlando]

Hi all,

I am so hurting the last couple of days...so tired of feeling horrible. I have been researching any connection between the Guillain Barre I had in 2001 and this onset of POTS in 2008. It looks like there is a nicotnic acetylchonline receptor antibody that may be present in some POTS cases and also in Guillain Barre. Has anyone been tested for this antibody? It looks like there may be treatment options like IVIG (had it with Guillain Barre...didn't really help tho).

Does anyone have any more information on this antibody. No one, including my neurologist that has seen me since Guillain Barre has even hinted at this possible antibody being evident and perhaps the cause of my POTS. Furthermore, would the antibody still be evident in my blood work even tho I have had POTs for 1 1/2 years now?

For those of you who are not familiar with Guillain Barre, it is an autoimmune neurological disorder in which the peripherial nervous system is attacked rendering the patient paralyzed. Its onset for me followed a virus...much like preceding POTS. I am not saying that Guillain Barre caused POTS...I am saying my body seem to attack the nervous system in some sort of abnormal manner in an autoimmune response.

I just see links that are ont being followed here by either of my main doctors. I see an EP for my POTS diagnosis...and my neurologist seems to think POTS is a cardiac disorder.

I know there are many out there with lots of knowledge...any help would be great.

Thanks!!

Erika

[firewatcher]

Erika, here are some PubMed abstracts regarding AchR-antibodies. They appear to be measurable in many autonomic disorders and auto-immune conditions that effect the nervous system. Mayo Rochester seems to be the hub of research for it. A little light reading:

Neurology. 2009 Nov 3;73(18):1501-6.

Sudomotor dysfunction in autoimmune autonomic ganglionopathy.

Kimpinski K, Iodice V, Sandroni P, Fealey RD, Vernino S, Low PA.

Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. low@mayo.edu

BACKGROUND: Autoimmune autonomic ganglionopathy is characterized by impairment of multiple autonomic domains of which sudomotor function is among the most common. Many patients with this disorder have difficulties with thermoregulation and anhidrosis. Our objective was to characterize the distribution and severity of sudomotor dysfunction in this disorder. METHODS: Sudomotor function was analyzed in a cohort of 21 patients with ganglionic alpha3 nicotinic acetylcholine receptor (nAChR) antibody positive autoimmune autonomic ganglionopathy. Standard measurements of sudomotor function were used including the Thermoregulatory Sweat Test and Quantitative Sudomotor Axon Reflex Test. RESULTS: The clinical presentation in all patients was characterized by widespread sudomotor dysfunction. Sudomotor impairment was predominantly postganglionic in 17 of the 21 patients studied. Higher ganglionic alpha3 nAChR antibody levels resulted in progressive postganglionic predominant dysfunction (postganglionic, r = 0.637, p = 0.002; mixed ganglionic, r = 0.709, p < 0.001). The pattern of anhidrosis on Thermoregulatory Sweat Testing was consistent with a ganglionopathy in the majority of patients (14 of 21) and a distal pattern in a minority of patients (8 of 21). These patterns of anhidrosis coupled with increasing postganglionic dysfunction in a proximal to distal pattern (foot > distal leg > proximal leg > forearm) indicate lesions at both the ganglia and distal axon of the postganglionic sudomotor sympathetic neuron. CONCLUSIONS: Our data characterize the unique sudomotor dysfunction in autoimmune autonomic ganglionopathy as widespread, predominantly postganglionic, and a result of lesions at both the ganglia and distal axon. This study provides important support to the hypothesis that this disorder represents a ganglionic neuropathy.

PMID: 19884578

Auton Neurosci. 2009 Mar 12;146(1-2):13-7. Epub 2008 Dec 4.

Other autonomic neuropathies associated with ganglionic antibody.

Sandroni P, Low PA.

Mayo Clinic, Department of Neurology, 200 First Street SW, Rochester, MN 55905, USA.

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer. This review describes the autonomic neuropathies most frequently encountered in clinical practice in which an autoimmune etiology is suspected. They include a chronic form (pure autonomic failure) and limited autonomic neuropathies with predominant involvement of one neurotransmitter type (i.e., cholinergic vs. adrenergic) or one system (such as the gastrointestinal system) or a distal small fiber dysfunction. In each of these conditions, occasional positivity to the G-AchR antibody has been found, but the pathogenetic significance of such finding is still uncertain. Other antigens and antibodies yet to be identified are more likely to be responsible in these disorders.

PMID: 19058765

Arch Neurol. 2009 Jun;66(6):735-41.

Ganglionic acetylcholine receptor autoantibody: oncological, neurological, and serological accompaniments.

McKeon A, Lennon VA, Lachance DH, Fealey RD, Pittock SJ.

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.

OBJECTIVE: To describe the clinical utility of the nicotinic ganglionic acetylcholine receptor (alpha3-AChR) autoantibody as a marker of neurological autoimmunity and cancer. DESIGN: Case-control study. SETTING: Mayo Clinic, Rochester, Minnesota. PATIENTS: A total of 15,000 patients seen at Mayo Clinic (2005-2007) and evaluated on a service basis for paraneoplastic neurological autoimmunity for whom clinical information was obtained retrospectively by medical record review as well as 457 neurologically asymptomatic patients or control subjects of whom 173 were healthy, 245 had lung cancer, and 39 had systemic lupus erythematosus or Sj?gren syndrome. OUTCOME MEASURES: Neurological, oncological, and serological associations of alpha3-AChR autoantibody seropositivity. RESULTS: Of 15,000 patients tested on a service basis, 1% were seropositive (median, 0.12 nmol/L; range, 0.03-18.8 nmol/L; normal, < or =0.02 nmol/L), 55% were male, and the median age was 65 years. Cancer was found (new or by history) in 24 of 78 patients evaluated for cancer while at Mayo Clinic (30%); 43% had adenocarcinoma (more patients had breast cancer than prostate, lung, and gastrointestinal cancers; each of the latter groups had about the same number of patients). Of 12 patients with high antibody values (> or =1.00 nmol/L), 83% had pandysautonomia. Of 85 patients with medium antibody values (0.10-0.99 nmol/L), neurological presentations were more diverse and included peripheral neuropathies (36%), dysautonomia (20%, usually limited), and encephalopathy (13%). Of 58 patients with low antibody values (0.03-0.09 nmol/L), 54% had a nonautoimmune neurological disorder or no neurological disorder. Of 245 control patients with lung cancer, 7.8% were seropositive. Only 1 of 212 control patients without cancer (0.5%) was seropositive (P < .001). CONCLUSION: The detection of alpha3-AChR autoantibody aids the diagnosis of neurological autoimmunity and cancer.

PMID: 19506133

J Neurol. 2007 May;254 Suppl 2:II96-101.

Autonomic dysfunction in Guillain-Barr? syndrome and multiple sclerosis.

Flachenecker P.

Neurological Rehabilitation Center "Quellenhof", Kuranlagenallee 2, 75323, Bad Wildbad, Germany. peter.flachenecker@quellenhof.de

Erratum in: J Neurol. 2008 Feb;255(2):309-10.

This review gives an overview of autonomic dysfunction encountered in Guillain-Barr? syndrome (GBS) and multiple sclerosis (MS). In GBS, cardiovascular dysregulation is common and may lead to serious bradyarrhythmias that need to be recognised for the early initiation of appropriate therapy. Although standardised autonomic tests were useful for the diagnosis of autonomic failure, they were not able to indicate vagal over-reactivity. In this regard, eyeball pressure testing may correctly identify patients at risk for impending and potentially life-threatening bradyarrhythmias which may easily be administered at the bedside. In MS, cardiovascular autonomic dysfunction is usually of minor clinical importance. However, orthostatic intolerance may be present in approximately 50% of patients and could easily be detected by routine measurements of heart rate and blood pressure during rest and during standing. More subtle alterations may require more sophisticated methods such as autonomic reflex testing or baroreflex stimulation. Several in vitro, animal and clinical studies provide evidence that there are many interactions between the sympathetic nervous system and the immune system giving rise to the hypothesis that autonomic dysfunction in MS may not only be a consequence of the disease, but may in itself affect the course of MS.

PMID: 17503142

[sue1234]

My brain is not working this week, but I hope more thinkers work on this. I know since I quit sweating, I have continually run into acetylcholine(and it's nicotinic and muscarinic receptors) in looking up causes. I would like to know how it might relate to POTS. My pulmonologist is testing me for myathenia gravis, which is related to acetylcholine. Although I don't believe I have MG, I think some relative of it could be a possibility.

[erikainorlando]

I was tested for MG and was negative. But I just know there is something to this.

I have a friend who has MG and CIDP (both neurological autoimmune responses)...this is what has put me on this path. CIDP is a form of Guillain Barre in which it is chronic. "I had the Guillain Barre now POTS...But you can see where I am going with this...if there is a potential antibody for those of us who got this as an autoimmune thing..especially those with 2 neurologic autoimmune problems..I am just not smart enough to decipher the informaiton I pull up on the web...I don't understand the implications..

I dont' know where to get all this information and my doctors are not much help....I don't want to come off as a know it all but obviously when your life has been turned upside down one is very very motoviated to figure out why!!

Is there a doctor one can talk to from the Neurological Disorders Organization..anyone who might be thinking. My doctors are just used to the nomral case...even with Guillain Barre...most had never even seen a case of it..it was horrible!

Thanks!! And keep any thoughts coming!

Erika

[futurehope]

I'm chiming in here, but pleading ignorance. My Achr antibody titer has been elevated for years, yet I do not display Myasthenia Gravis. I do not know if my test involved muscarinic and/or nicotinic receptors or both?

I'm staying tuned to this thread.

[firewatcher]

All I can recommend is to look at the authors of the abstracts you are finding...you'll begin to see several names more often than others. Those doctors are whom you go to, with letters from your doctors requesting help. Mayo Rochester seems to be the hub for the most research. Myasthenia Gravis comes up the most frequently with anti-body titers, but even there, there is no definitive treatment.

[Babis]

Hi guys. This is what Dr Andrew McKeon at Mayo Clinic neuroimmunology told me:

The antibodies of myasthenia gravis (muscular acetylcholine receptor autoantibodies) target the neuromuscular junction.

The antibodies of autoimmune autonomic ganglionopathy (alpha-3 ganglionic acetylcholine receptor autoantibodies) target the membrane of autonomic ganglia. That is, they target the neuron to neuron junction.

I have the alpha-3 ganglionic acetylcholine receptor autoantibody, and it can be detected with a blood test called the Mayo Clinic Autoimmune Dysautonomia Evaluation. It is nicely explained here:

http://www.mayomedic...eval/index.html

Treatment for AAG is similar to that of Myasthenia. It includes immunomodulation (IVIG, immunosupressants) and acetylcholinesterase inhibitors (Mestinon).

[Babis]

Hi all,

I am so hurting the last couple of days...so tired of feeling horrible. I have been researching any connection between the Guillain Barre I had in 2001 and this onset of POTS in 2008. It looks like there is a nicotnic acetylchonline receptor antibody that may be present in some POTS cases and also in Guillain Barre. Has anyone been tested for this antibody? It looks like there may be treatment options like IVIG (had it with Guillain Barre...didn't really help tho).

Does anyone have any more information on this antibody. No one, including my neurologist that has seen me since Guillain Barre has even hinted at this possible antibody being evident and perhaps the cause of my POTS. Furthermore, would the antibody still be evident in my blood work even tho I have had POTs for 1 1/2 years now?

For those of you who are not familiar with Guillain Barre, it is an autoimmune neurological disorder in which the peripherial nervous system is attacked rendering the patient paralyzed. Its onset for me followed a virus...much like preceding POTS. I am not saying that Guillain Barre caused POTS...I am saying my body seem to attack the nervous system in some sort of abnormal manner in an autoimmune response.

I just see links that are ont being followed here by either of my main doctors. I see an EP for my POTS diagnosis...and my neurologist seems to think POTS is a cardiac disorder.

I know there are many out there with lots of knowledge...any help would be great.

Thanks!!

Erika

Hey, Erika: How many rounds of IVIg did you receive? How many days was each round?

And how long after the symptom onset was your IVIg treatment?

I ask because many rounds of IVIg may be needed to see a result, and because shorter delay for immunotherapy leads to better results.

I also have the neuronal ganglionic alpha-3 AChR autoantibody.

I received 5 days of IVIg (Privigen), and had no improvement for the first 3 weeks, but I saw a mild (25%-50%) improvement the 4th week.

Then I received 5 more days of IVIg (Gamunex), and felt nothing for a week, but I had significant improvement (50-75%) the 2nd week.

If I add physical therapy for POTS and further rounds of IVIg that are scheduled, I think I may fully recover...

The literature suggests that if a single round of IVIg has no result, then many rounds of IVIg, or combined immunotherapy (IVIg, Plasma Exchange, Immunosupressants) plus physical therapy can lead to a response.

[sue1234]

Babis, Ericka hasn't been on this forum for over a year. Her story is that she ultimately was diagnosed with Stiffman Syndrome and had IVIG treatment for it(if I remember correctly). She improved tremendously, and in her last post, said she was doing great and "living life". I assume she still is, and that's why she is no longer posting.

She is the only person I've seen on this forum that has actually gotten a "diagnosis" that had a "curative" treatment. I've been on this forum for a few years, and she's the only person I recall that said "I'm fixed!". Last time I mentioned Ericka in a post, that she was "cured", I got a little flack about calling it a cure. But, as I stated back, when someone was so disabled that her daughter had to carry her in her arms, and after treatment she was playing at the beach, that's a "cure" to me.

[sue1234]

I was just reading up on Medscape about autoimmune autonomic ganglionopathy. I find I actually seem to have alot of the issues, such as dry eyes and mouth(awful dry mouth), eye coordination issues, stomach bloating and heat intolerance/lack of sweating. It does mention that autoimmune might be a cause when it had a sudden onset. I acutally had it just happen one day. I've had POTS for almost 6 years now since that day it suddenly appeared.

I was reading around on some of the medical literature published on AAG, and there's actually a neurologist just 6 hours away from me that has an article on AAG--"Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies" and states an interest in "serologic evaluation of patients with dysautonomia". I think I might make an appointment--it can't hurt. The loss of sweating always makes me think of acetylcholine in my case. No doctor has ever offered Mestinon to see if it would help any of my symptoms.

I forgot to mention, this doctor got his Neurology fellowship at Mayo! Since I can't fly, this might be the next best thing. The one neuro I went to see at a large medical center over a year ago just told me "POTS is fairly new, and there's just not much we can do for it". And that was that. No trying any meds, nothing.

[ramakentesh]

A fascinating thread. And some great links. yes Mayo are the team that are following up the possible autoimmune leads the most frequently,

[ramakentesh]

It may be interesting to note that potentially some POTS patients have neuropathy of the stomach vasculature rather than the arms and legs.

[sue1234]

Oh, Rama, I could totally fit that picture! I have lost 30 lbs. two years ago, and my stomach is still the same size. I still look pregnant.

[ramakentesh]

I think I read somewhere that there are as many stomach poolers as there are hand and feet poolers.

[L4UR3N]

I was recently tested for this antibody and am still awaiting the results. They had to send it to the Mayo clinic, so it can take 3 or more weeks for results. My neurologist came from the Mayo Clinic, so he is up on the current research. After reading the articles and seeing the small % of POTS patients who are actually positive for this antibody, I do not have my hopes up. I do however believe that it is definitely worth studying the mechanisms behind myasthenia gravis and POTS, though I dont claim to fully understand it.

[Babis]

Hey Sue,

If the neurologist you refer to is Steven Vernino, he seems an excellent choice. He has published many articles on AAG and is among the leaders in the field. He was in the team that discovered the ganglionic acetylcholine receptor autoantibodies, and designed the essay used to detect and measure them at Mayo.

And yes, most doctors I saw shrug their shoulders or offered my salt and water or symptomatic treatments; nobody was willing to test for antibodies; I had to see tens of doctors and beg them for testing me for a whole year, before somebody agreed to order the test. Even after it came back positive, they thought little of it and were unwilling to offer immunotherapy. Extremely frustrating. They said many things that contradicted the literature and common sense, just to avoid the responsibility of immunotherapy. I explained to them I had severe visual symptoms and many things that my brain could no longer do, and they told me I was stressed and depressed, even though they knew I had dysautonomia and ganglionic antibodies. Luckily, I trusted myself and the literature more than these doctors. With the positive result in my hands, I thought I had wasted enough time trying to educate them, and decided to go to someone who is educated already.

So I e-mailed one of the neuroimmunologists at Mayo involved in publications on these antibodies. He was kind enough to offer me an appointment in 2 days (as opposed to 3 months I had to wait to see the incompetent doctors at Froedert Hospital). Once I got to Mayo, I asked if immunotherapy could help, and he said yes, and offered to do a month of IVIg right there and then. Since I was scheduled to move to Europe, it could not be done, so I asked him to write his regimen in detail in his summary letter, which he happily did. He also sent me a revised interpretation of my brain PET scan (which had been misinterpreted as normal at Froedert Hospital) and was strongly suggestive of autoimmune encephalitis, mainly in the visual cortex. This is seen in a small percentage of people with AAG. After moving to Europe, I showed my Mayo records to the neuros at the hospital, and luckily they agreed to follow the Mayo suggestions for immunotherapy and even improve them further. My dramatic response after 2 months of IVIg shows that both the encephalitis and the dysautonomia were indeed autoimmune. I now have my life back, thanks to Mayo neuroimmunology, and thanks to trusting myself and the literature, instead of some illiterate "doctors".

My advice: do not settle for salt & water or symptomatic therapies. These are useful but not enough. Seek an accurate diagnosis of the underlying causes, and therapies that treat those causes, not the symptoms. From my experience (saw over 50 doctors) 90% of doctors do not really know what dysautonomia is, 95% of them cannot properly diagnose it, and 99% of them cannot properly treat it. So your best bet is to go to pubmed, seek doctors with extensive publications on the subject, and pay them a visit. This has worked remarkably well for me, both in terms of diagnosis and treatment.

I was just reading up on Medscape about autoimmune autonomic ganglionopathy. I find I actually seem to have alot of the issues, such as dry eyes and mouth(awful dry mouth), eye coordination issues, stomach bloating and heat intolerance/lack of sweating. It does mention that autoimmune might be a cause when it had a sudden onset. I acutally had it just happen one day. I've had POTS for almost 6 years now since that day it suddenly appeared.

I was reading around on some of the medical literature published on AAG, and there's actually a neurologist just 6 hours away from me that has an article on AAG--"Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies" and states an interest in "serologic evaluation of patients with dysautonomia". I think I might make an appointment--it can't hurt. The loss of sweating always makes me think of acetylcholine in my case. No doctor has ever offered Mestinon to see if it would help any of my symptoms.

I forgot to mention, this doctor got his Neurology fellowship at Mayo! Since I can't fly, this might be the next best thing. The one neuro I went to see at a large medical center over a year ago just told me "POTS is fairly new, and there's just not much we can do for it". And that was that. No trying any meds, nothing.

[sue1234]

Babis, yes, that is the doctor. I will make an appt., as, if for some reason this IS autoimmune and I don't do any treatments, then that means I won't ever get better. I'd rather know one way or the other if I have the antibodies. If I don't have the antibodies, then I am right back where I'm at now. If I do have the antibodies and try the treatment, I have a shot at getting better!

[Babis]

Sue, the autoimmune dysautonomia evaluation detects roughly 50% of cases of autoimmune dysautonomia. Than means there is another 50% of cases in which the antibodies are not known, and yet may still respond to immunotherapy. So, if you had subacute onset and there is suspicion of autoimmunity, a couple of months of IVIg may be worthwhile to try, even if you are antibody negative...

Since this conclusion comes from articles written by Steven Vernino himself, you could ask him if it might be worth trying IVIg even if you are antibodies come back negative negative.

You can also have a look at this

. Autoimmune dementia shares many similarities with autoimmune dysautonomia and autoimmune encephalitis (they all have subacute onset, they are commonly missed treatable conditions, they are immunotherapy responsive, etc).

Babis, yes, that is the doctor. I will make an appt., as, if for some reason this IS autoimmune and I don't do any treatments, then that means I won't ever get better. I'd rather know one way or the other if I have the antibodies. If I don't have the antibodies, then I am right back where I'm at now. If I do have the antibodies and try the treatment, I have a shot at getting better!

[issie]

Thought some might enjoy this thread - since many of us have autoimmune issues and are finding that this could be one of our connections to our dysautonimia.

I know some are on mestinon and have found it beneficial and that's connected to the AChR antibodies.

I also have sensitivites to glutamates and that's connected to the GAD65 antibodies.

Interesting that there are so many different issues with antibodies that can/could affect dysautonomia.

Here's a link to the test that Mayo does for this : http://www.mayomedicallaboratories.com/articles/hottopics/transcripts/2011/02-auto-dys-eval/13.html

Issie