Aag (Autoimmune Autonomic Ganglionopathy) Vs Pots

[Guest Alex]

I've read a lot of recent posts on AAG as a cause for POTS and I'm slightly confused, so I'm asking those of you who can help me figure things out to pitch in:

To my knowledge, one of the criteria for diagnosing AAG is a positive blood test for the AChR antibody, BUT there are people who have AAG that are AChR negative, just like there are people who test positive for the antibody yet are NOT dx-ed with AAG.

My understanding is that the test is considered positive if the blood level is over 0.05 nmol/L but it's only the higher level titers (over 0.5 nmol/L) that are further evaluated for AAG.

Trademark symptoms of AAG according to dr Steve Vernino - the dr who (as part of a team of drs at Mayo TX) patented the blood test:

- orthostatic HYPOTENSION

- gastroinetstinal dysmotility

- dry mouth, dry eyes, (dry mucous membranes in general)

- impaired pupilary constriction

- BLUNTED HEART RATE RESPONSES

So, here is where my confusion lies:

* orthostatic hypotension is incongruent with hyper POTS (in most cases - I've learned recently of people with hyper POTS and hypotension)

* the blunted heart rate response is not what we're dealing with in POTS, on the contrary, our heart rate responses are anything BUT blunted

One of the articles on these antibodies:

http://www.nejm.org/doi/full/10.1056/NEJM200009213431204#t=articleTop

In table # 2 note patient 20 - the patient had postural tachycardia.

Also, the same article associates the said antibodies with various forms of dysautonomia, definitely with different types of autoimmune neuropathies, but it does not list AAG as a cause for POTS.

Am I misinterpreting this?

Several other articles:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779006/pdf/7074.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739271/pdf/nihms123352.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963144/pdf/nihms-237579.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677210/pdf/nihms102466.pdf

notice here table 1 on page 13:

AAG and POTS are listed as SEPARATE entities, each described by a certain level of antibodies - lower levels for POTS and higher levels for AAG; and again, different antibodies levels are associated with different disorders (POTS and dysautonomia are only some of the disorders listed in that table!)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536520/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637993/pdf/nihms86030.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190728/pdf/nihms35145.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615674/pdf/nihms-35218.pdf

http://archneur.jamanetwork.com/article.aspx?articleid=785281

http://jn.physiology.org/content/90/3/2053.full.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671239/pdf/nihms102467.pdf

Another little piece of 'trivia' - thank you rama for stating it so well, so I'll take the liberty of quoting you here:

"All sorts of people have all sorts of low titered autoantibodies in their bodies without any demonstrable pathology."

This is again an open invitation for those of you who know more about this than I do, who have a different understanding than I have on these issues, to please chime in and post your understanding of things.

Happy reading and thank you,

Alex

[diabeticgonewild]

I have more reading to do from your above post. Thank you for all of the information.

A lot of people have opposite symptoms of the characteristic features of AAG.

For example, I have urge incontinence, chronic diarrhea and tachycardia.

The tachycardia is present because my body is able to compensate for the low blood pressure by the higher heart rate. Basically, my baroreflexes have not been lost from the AAG (yet).

So, technically you can have AAG with tachycardia, and probably even orthostatic HYPERtension, as long as you have not lost baroreflexes due to the AAG.

Wikipedia article about Baroreflex

[Guest Alex]

So if my understanding is correct, you've been dx-ed with AAG SOLELY based on the antibody levels?

Again, according to the articles I posted above (all of which are full text - I saw no point in posting those we could access abstracts only) a positive antibody can mean a variety of disorders. So, what I'm trying to say is that a positive AChR does not always equal AAG. At least not according to dr Vernino.

Alex

[diabeticgonewild]

Ok, the article that you posted, on page 13, on Table 1:

Basically, that is the percentage of people with AAG in the different diagnosis categories. It is entirely posible to have both "POTS" and "Chronic AAG".

He is just explicitly listing various diagnostic categories (that patients have been diagnosed with), with percentages for the positive antibodies, so that doctors can spot potential individuals with AAG, AKA a treatable form of dysautonomia.

[diabeticgonewild]

So if my understanding is correct, you've been dx-ed with AAG SOLELY based on the antibody levels?

Again, according to the articles I posted above (all of which are full text - I saw no point in posting those we could access abstracts only) a positive antibody can mean a variety of disorders. So, what I'm trying to say is that a positive AChR does not always equal AAG. At least not according to dr Vernino.

Alex

I essentially have all of the symptoms, too, in addition to positive antibodies.

AAG will never be a cause of POTS. POTS is considered to be a limited form of dysautonomia.

Also AAG is a disease; POTS is not. POTS is a syndrome. AAG supersedes a diagnosis of POTS, due to the fact that it caused dysautonomia and explains the POTS-like symptoms. In fact, a prior diagnosis of POTS is a misdiagnosis, for somebody with AAG, even if it was the most fitting diagnosis at the time.

AAG is usually systematic, or at least it is when it's full blown.

The AAG started with my bladder after I was diagnosed with diabetes, almost 20 years ago. It slowly progressed.

[Guest Alex]

OK, so let me ask you this then:

what does your heart rate to when going from supine to standing?

Is it blunted (like the AAG dx criteria states) or does it increase by at least 30 bpm, thus leaning towards POTS?

AAG indeed seems to be systemic - it should impact all those areas: GI system, cardiovascular (HR and BP), pupils etc.

Alex

[diabeticgonewild]

OK, so let me ask you this then:

what does your heart rate to when going from supine to standing?

Is it blunted (like the AAG dx criteria states) or does it increase by at least 30 bpm, thus leaning towards POTS?

AAG indeed seems to be systemic - it should impact all those areas: GI system, cardiovascular (HR and BP), pupils etc.

Alex

It depends. It is not consistent.

I guess it would go to about 120. It's not uncommon for it to go above 180. I am not going to call it POTS, but it is POTS-like.

It does increase significantly while standing. Heart rate is not blunted for me and this symptom is not universally considered a symptom of AAG.

[looneymom]

Diabeticgonewild

Thanks for posting the information about the testing. My son was seen by MAYO in December of 2011 but this panel was not run. My son will be seeing his cardiologist in June and I am forwarding this information on to him. He suspects an autoimmune problem and this panel sounds like a good place to start.

Hope you are able to get the wheelchair you need. Insurance companies want the proof that you really need one. My son has not been able to maintain much mobility since he was diagnosed with POTS. He has been working with a physical therapist since his POTS diagnosis.

[ramakentesh]

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.

[diabeticgonewild]

I was initially diagnosed with POTS, before I ever had orthostatic hypotension. My autonomic neuropathy progressed gradually.

Citing the journal article that alex74alex used where he mentioned table 1 on page 13 , it is entirely possible to fit both "POTS" and "Chronic AAG" criteria, based on the criteria for values listed in that particular table. They are not mutually exclusive.

My antibody levels were greater than the "POTS" titer at testing, and fit both the "Chronic AAG" and the "subacute AAG" category (I converted units).

Considering that the half-life of an antibody is roughly three weeks, the level of the antibodies is pretty irrelevant once the disease criteria is met.

[diabeticgonewild]

Well, I found the ultimate test for determining whether it is AAG or not. I can't embed the image on this forum.

http://img209.imageshack.us/img209/1277/screenshot20130514at346.png

I obtained this off of a google books document via screenshot when I suspected I had the disease about a year and a half ago. I have the whole book chapter and it has all you need to know about AAG.

Keep in mind that "high" antibody titers are not clearly defined. Anything greater than or equal to 0.05 nmol/L is not normal. That is something that is universally agreed upon.

[ramakentesh]

Universally agreed upon by whom?

[ramakentesh]

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.

[ramakentesh]

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.

[diabeticgonewild]

Universally agreed upon by whom?

Well, first of all, the Mayo Clinic Laboratories. That is the cutoff value.

Even articles that Vernino participated in have this value cited.

http://www.google.com/search?q=%22%3C+0.05+nmol%2FL%22&sugexp=chrome,mod=11&sourceid=chrome&ie=UTF-8#q=%22%3C+0.05+nmol/L%22+AND+%22Autoimmune+autonomic+ganglionopathy%22&psj=1&ei=pnmSUc2_K-iD0QHL5YFI&start=0&sa=N&bav=on.2,or.r_qf.&fp=3a4dc8ae193cbe98&biw=1669&bih=952

[Guest Alex]

Thanks for the replies.

I've been re-reading some of the articles I've posted, and things are quite clear for me now.

An AChR level over 0.05 nmol/L is NOT equivalent to AAG, and definitely POTS and AAG have different clinical presentations. Also, this antibody has been reported in a variety of other conditions, ableit infrequent and with low titer. Yes there seems to be consensus that in high titers this antibody is highly specific for AAG, but in POTS patients the titers (if found) are consistently low.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671239/

diabeticgonewild, you made an excellent point: the level of the antibodies is pretty irrelevant once the disease criteria is met and that's what I've been trying to say. The blood test (be it positive for the AChR antibody) cannot and should not be used as the UNIQUE criteria for dx-ing AAG. In fact, it's the clinical findings that should be considered and that - in my non-medical opinion - should be the primary dx tool, even more so since there are many AAG patients who test negative for the AChR antibody.

As far as the cutoff value - I've seen sources that go as low as 0.03 nmol/L, but none of those sources list this value as borderline positive for AAG, they just list it as possibly abnormal. I've even read statements about the possibility of some meds to interfere with the antibody values, but I couldn't find any specific details - what meds?!

I would also be extremely curious to learn about that simple test your neuro performs to dx AAG without blood work. The one you mentioned here:

“My neurologist was showing a neurology resident a way to tell if somebody had AAG without a blood test. I was in a hospital bed in an upright position when they did it, but I don't think that bodily position matters.

1. Basically, she had a wooden cotton swab. She snapped it in half.

2. Then she scratched the middle of my shin, vertically. She did it once, making one line (scratch mark) down my leg.

3. She watched the response (I guess the redness), and she and the resident could tell I had AAG.

I don't know how or why it works. I will ask my neurologist the next time I see her, at the end of June.”

rama, the reflex tachy in postural hypotension is an 'exclusion' (so to say) criteria for POTS according to some drs (I agree with you on this), but there is still controversy in the medical community about that. If drs like Grub or Stewart or Raj won't flinch when asked such a question, and would actually confirm what you're saying, other POTS drs might pause and think and may not be able to come up with a straightforward answer, but hey, everyone is entitled to an opinion. At the end of the day, I don't think it's the dx/label that should count for the patient but finding a treatment that helps and restores their quality of life.

back to the google book, here is a larger excerpt from it:

http://books.google.ca/books?id=NIn8iwzvARIC&pg=PA490&lpg=PA490&dq=parients+with+AAG+and+rabits+with+EAAG+have+a+unique+laboratory+profile&source=bl&ots=zP9NwJ6uZg&sig=A_Pz2BOt2jfz_LfZcvSJdPPY0LA&hl=en&sa=X&ei=5GySUcGiKci9ywGXpYDQCA&redir_esc=y#v=onepage&q&f=false

" Autoimmune Autonomic Ganglionopathy

Description:

The typical presentation of AAG (formerly known as acute pandysautonomia or idiopathic subacute autonomic neuropathy) is highly characteristic. The typical syndrome occurs in a previously healthy individual in whom autonomic failure develops over the course of a few days or weeks. The onset of symptoms may follow a viral prodrome, minor surgical procedure, or routine immunization. There is a slightly female predominance. The average age at onset in reported cases is around 55 years, but there is a wide age range.

The most common syndrome is SEVERE GENERALIZED sympathetic and parasympathetic autonomic failure as dry mouth, dry eyes, sexual dysfunction, constipation, impaired pupillary light response, and fixed heart rate. Gastrointestinal dysmotility is common (70% patients) and presents with symptoms of anorexia, early satiety, postprandial abdominal pain and vomiting, constipation or diarrhea. In severe cases, objective autonomic abnormalities are obvious and include orthostatic hypotension, tonic pupils and a fixed heart rate. The spectrum and severity of dysautonomia, however, varies from patient to patient. Less common presentations are selective cholinergic failure, selective adrenergic neuropathy, or isolated gastrointestinal dysmotility.

About 25% of patients report neuropathic symptoms, such as tingling in the distal extremities, but sensory examination and nerve conduction studies are normal. Patients with objective evidence of sensory neuropathy may be better classified as subacute sensory and autonomic neuropathy.

Pathogenesis

The most convincing evidence of an autoimmune pathogenesis for AAG is the demonstration of high titers of gangllionic nicotinic acetylcholine receptor (AChR) antibodies in the serum of about 50% of patients. A number of studies have shown that serum levels of this antibody correlates with the severity of the symptoms. For orthostatic hypotension, there is a sygmoidal relationship. Orthostatic hypotension becomes prominent when antibody levels are greater than 1 nmol/L, worsens as antibody levels rise and then reaches a maximal severity. Similar antibody thresholds likely exist for other autonomic symptoms in AAG, such as sicca symptoms and bladder sysfunction. In some series, only patients with antibody levels higher than 3 nmol/L had clinically evident impairment in pupilary light reflex.

As further proof that AAG is an antibody mediated disorder, experimental AAG can be produced in animal models. Rabbits immunized against the ganglionic AChR or mice develop autonomic dysfunction similar to patients with AAG. Antibodies from AAG patients specifically inhibit membrane currents through alpha-3-type ganglilonic AChR. In addition, ganglionic AChR antibodies rapidly inhibit ganglionic synaptic transmission in isolated sympathetic ganglia. After passive transfer of antibodies to mice, quantal size (the responsiveness of the postural synaptic neuron) is reduced for up to 2 weeks. These antibody effects do not require complement and appear to result from antibody crosslinking and internalization of synaptic ganglionic AChR.

Patients with AAG and rabbits with EAAG have a unique laboratory profile consistent with impaired ganglionic synaptic transmission. Levels of plasma catecholamines are low while imaging of cardiac sympathetic innovation is normal. This pattern of normal cardiac sympathetic innervation with reduced sympathetic activity is unique and best explained by impairment of neurotransmission at the level of the autonomic ganglia.

Diagnosis

The diagnosis of idiopathic AAG is suspected in cases of acquired autonomic failure without somatic neuropathy when toxic or paraneoplastic causes have been excluded. Patients with paraneoplastic autonomic neuropathy may be clinically indistinguishable from idiopathic AAG until a cancer, usually small cell carcinoma of the lung, is detected. History of an antecedent event (viral syndrome or surgical procedure) or a personal or family history of other autoimmune disorders (such as autoimmune thyroiditis, pernicious anemia, type I diabetes, or myasthenia gravis) support the diagnosis of AAG.

A high serum level of ganglionic AChR antibody confirms the diagnosis of AAG. Based on a review of autonomic findings in seropositive patients, a particular combination of cholinergic autonomic symptoms (neurogenic bladder, impaired pupillary function, gastroparesis and dry eyes and dry mouth) are most suggestive of AAG. Lower antibody values show more diverse clinical associations, including limited or chronic forms of autonomic failure. Slowly progressive AAG may resemble pure autonomic failure (PAF) an insidious presumed degenerative autonomic disorder with predominant sympathetic adrenergic and sudomotor failure. Gastrointestinal dysmotility and impaired pupillary responses common in AAG are not seen in PAF. A comparison of the clinical features of AAG, PAF and multiple system atrophy is presented in Table 100.2 (the same table I referenced in one of Dr Vernino’s articles)

Although antibody testing is diagnostically important, many patients with clinical features of AAG do not have ganglionic AChR antibodies and assessment of these seronegative causes remains difficult. Nevertheless, it is reasonable to consider an autoimmune etiology for cases of subacute autonomic failure. Several case reports describe patients with seronegative AAG that improved after treatment with immunotherapy.. Further investigations of seronegative AAG looking for novel diagnostic markers that can predict response to immunotherapy are still needed."

Alex

[diabeticgonewild]

Thanks for the replies.

I've been re-reading some of the articles I've posted, and things are quite clear for me now.

An AChR level over 0.05 nmol/L is NOT equivalent to AAG, and definitely POTS and AAG have different clinical presentations. Also, this antibody has been reported in a variety of other conditions, ableit infrequent and with low titer. Yes there seems to be consensus that in high titers this antibody is highly specific for AAG, but in POTS patients the titers (if found) are consistently low.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671239/

diabeticgonewild, you made an excellent point: the level of the antibodies is pretty irrelevant once the disease criteria is met and that's what I've been trying to say. The blood test (be it positive for the AChR antibody) cannot and should not be used as the UNIQUE criteria for dx-ing AAG. In fact, it's the clinical findings that should be considered and that - in my non-medical opinion - should be the primary dx tool, even more so since there are many AAG patients who test negative for the AChR antibody.

As far as the cutoff value - I've seen sources that go as low as 0.03 nmol/L, but none of those sources list this value as borderline positive for AAG, they just list it as possibly abnormal. I've even read statements about the possibility of some meds to interfere with the antibody values, but I couldn't find any specific details - what meds?!

I would also be extremely curious to learn about that simple test your neuro performs to dx AAG without blood work. The one you mentioned here:

“My neurologist was showing a neurology resident a way to tell if somebody had AAG without a blood test. I was in a hospital bed in an upright position when they did it, but I don't think that bodily position matters.

1. Basically, she had a wooden cotton swab. She snapped it in half.

2. Then she scratched the middle of my shin, vertically. She did it once, making one line (scratch mark) down my leg.

3. She watched the response (I guess the redness), and she and the resident could tell I had AAG.

I don't know how or why it works. I will ask my neurologist the next time I see her, at the end of June.”

rama, the reflex tachy in postural hypotension is an 'exclusion' (so to say) criteria for POTS according to some drs (I agree with you on this), but there is still controversy in the medical community about that. If drs like Grub or Stewart or Raj won't flinch when asked such a question, and would actually confirm what you're saying, other POTS drs might pause and think and may not be able to come up with a straightforward answer, but hey, everyone is entitled to an opinion. At the end of the day, I don't think it's the dx/label that should count for the patient but finding a treatment that helps and restores their quality of life.

back to the google book, here is a larger excerpt from it:

http://books.google.ca/books?id=NIn8iwzvARIC&pg=PA490&lpg=PA490&dq=parients+with+AAG+and+rabits+with+EAAG+have+a+unique+laboratory+profile&source=bl&ots=zP9NwJ6uZg&sig=A_Pz2BOt2jfz_LfZcvSJdPPY0LA&hl=en&sa=X&ei=5GySUcGiKci9ywGXpYDQCA&redir_esc=y#v=onepage&q&f=false

" Autoimmune Autonomic Ganglionopathy

Description:

The typical presentation of AAG (formerly known as acute pandysautonomia or idiopathic subacute autonomic neuropathy) is highly characteristic. The typical syndrome occurs in a previously healthy individual in whom autonomic failure develops over the course of a few days or weeks. The onset of symptoms may follow a viral prodrome, minor surgical procedure, or routine immunization. There is a slightly female predominance. The average age at onset in reported cases is around 55 years, but there is a wide age range.

The most common syndrome is SEVERE GENERALIZED sympathetic and parasympathetic autonomic failure as dry mouth, dry eyes, sexual dysfunction, constipation, impaired pupillary light response, and fixed heart rate. Gastrointestinal dysmotility is common (70% patients) and presents with symptoms of anorexia, early satiety, postprandial abdominal pain and vomiting, constipation or diarrhea. In severe cases, objective autonomic abnormalities are obvious and include orthostatic hypotension, tonic pupils and a fixed heart rate. The spectrum and severity of dysautonomia, however, varies from patient to patient. Less common presentations are selective cholinergic failure, selective adrenergic neuropathy, or isolated gastrointestinal dysmotility.

About 25% of patients report neuropathic symptoms, such as tingling in the distal extremities, but sensory examination and nerve conduction studies are normal. Patients with objective evidence of sensory neuropathy may be better classified as subacute sensory and autonomic neuropathy.

Pathogenesis

The most convincing evidence of an autoimmune pathogenesis for AAG is the demonstration of high titers of gangllionic nicotinic acetylcholine receptor (AChR) antibodies in the serum of about 50% of patients. A number of studies have shown that serum levels of this antibody correlates with the severity of the symptoms. For orthostatic hypotension, there is a sygmoidal relationship. Orthostatic hypotension becomes prominent when antibody levels are greater than 1 nmol/L, worsens as antibody levels rise and then reaches a maximal severity. Similar antibody thresholds likely exist for other autonomic symptoms in AAG, such as sicca symptoms and bladder sysfunction. In some series, only patients with antibody levels higher than 3 nmol/L had clinically evident impairment in pupilary light reflex.

As further proof that AAG is an antibody mediated disorder, experimental AAG can be produced in animal models. Rabbits immunized against the ganglionic AChR or mice develop autonomic dysfunction similar to patients with AAG. Antibodies from AAG patients specifically inhibit membrane currents through alpha-3-type ganglilonic AChR. In addition, ganglionic AChR antibodies rapidly inhibit ganglionic synaptic transmission in isolated sympathetic ganglia. After passive transfer of antibodies to mice, quantal size (the responsiveness of the postural synaptic neuron) is reduced for up to 2 weeks. These antibody effects do not require complement and appear to result from antibody crosslinking and internalization of synaptic ganglionic AChR.

Patients with AAG and rabbits with EAAG have a unique laboratory profile consistent with impaired ganglionic synaptic transmission. Levels of plasma catecholamines are low while imaging of cardiac sympathetic innovation is normal. This pattern of normal cardiac sympathetic innervation with reduced sympathetic activity is unique and best explained by impairment of neurotransmission at the level of the autonomic ganglia.

Diagnosis

The diagnosis of idiopathic AAG is suspected in cases of acquired autonomic failure without somatic neuropathy when toxic or paraneoplastic causes have been excluded. Patients with paraneoplastic autonomic neuropathy may be clinically indistinguishable from idiopathic AAG until a cancer, usually small cell carcinoma of the lung, is detected. History of an antecedent event (viral syndrome or surgical procedure) or a personal or family history of other autoimmune disorders (such as autoimmune thyroiditis, pernicious anemia, type I diabetes, or myasthenia gravis) support the diagnosis of AAG.

A high serum level of ganglionic AChR antibody confirms the diagnosis of AAG. Based on a review of autonomic findings in seropositive patients, a particular combination of cholinergic autonomic symptoms (neurogenic bladder, impaired pupillary function, gastroparesis and dry eyes and dry mouth) are most suggestive of AAG. Lower antibody values show more diverse clinical associations, including limited or chronic forms of autonomic failure. Slowly progressive AAG may resemble pure autonomic failure (PAF) an insidious presumed degenerative autonomic disorder with predominant sympathetic adrenergic and sudomotor failure. Gastrointestinal dysmotility and impaired pupillary responses common in AAG are not seen in PAF. A comparison of the clinical features of AAG, PAF and multiple system atrophy is presented in Table 100.2 (the same table I referenced in one of Dr Vernino’s articles)

Although antibody testing is diagnostically important, many patients with clinical features of AAG do not have ganglionic AChR antibodies and assessment of these seronegative causes remains difficult. Nevertheless, it is reasonable to consider an autoimmune etiology for cases of subacute autonomic failure. Several case reports describe patients with seronegative AAG that improved after treatment with immunotherapy.. Further investigations of seronegative AAG looking for novel diagnostic markers that can predict response to immunotherapy are still needed."

Alex

Thank you, Alex. I still have to read your whole post.

I don't mean to nit-pick over details. However, in the article you cited in the post, there is a POTS patient with an antibody level of 0.44 nmol/L, which is greater than the < 0.25 nmol/L "cutoff" for "POTS" and fits the "Chronic AAG" titer.

Technically, I am contradicting myself by referring to antibody levels, after saying it is irrelevant after the disease is diagnosed.

I guess my point is, that there is autoimmunity involved, and it shouldn't be discarded. I think autoimmunity needs to be treated seriously.

There are a lot of articles, basically with opinions of professionals. There is a lot of contradictory information, even in these articles.

I will ask my neurologist about the quick test. She knows I am an engineering student who is curious and she will explain it to me.

[diabeticgonewild]

Alex, it is true that the presence of symptoms in combination with the antibodies, is diagnostic criteria for AAG.

In this November 2011 article, with a cohort of Mayo people, including Vernino, they specifically cite AAG as diagnostic from limited type of autonomic dysfunction such as cardiovagal dysfunction.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469317/

"Patients with abnormalities in either adrenergic, cardiovagal, or sudomotor function on standard clinical autonomic testing and a positive antibody levels (>0.05 nmol/L) were deemed to have antibody-positive AAG."

I'm just saying, once you make the cutoff, you have AAG. (At least according to this article!)

[Guest Alex]

Got your point.

Thanks for the book fragment upload - the whole book would be nice .

Alex

[kitt]

Diabeticgonewild,

You've done a great job on this topic.

Not only do you have AAG, but you've cleared up several misconceptions. Notably, that the primary symptoms listed are not always present. You listed your symptoms which in some cases are opposite of those listed, and made a technical topic 'real'

The links you provided are excellent, but it's your personal experience that I appreciate most.

Interesting that it 'started in your bladder'...How in the world did you go from experiencing 'urge incontinence' to getting AAG dx? You're fortunate to have a diagnose with this rare disease. Can you talk about that experience?

Thank you for sharing your personal journey with AAG.

Wishing you the best,

K

[diabeticgonewild]

Diabeticgonewild,

You've done a great job on this topic.

Not only do you have AAG, but you've cleared up several misconceptions. Notably, that the primary symptoms listed are not always present. You listed your symptoms which in some cases are opposite of those listed, and made a technical topic 'real'

The links you provided are excellent, but it's your personal experience that I appreciate most.

Interesting that it 'started in your bladder'...How in the world did you go from experiencing 'urge incontinence' to getting AAG dx? You're fortunate to have a diagnose with this rare disease. Can you talk about that experience?

Thank you for sharing your personal journey with AAG.

Wishing you the best,

K

K,

Thank you.

I was diagnosed with diabetes when I was five years old. My bladder problems started when I was five, and the problem manifests itself the same way as when I was five, except I have responded to treatment. I have improved. For about ten years, this was the prominent symptom of AAG; the other issues were more transient. All of the other autonomic problems, especially the severe gastroparesis, started with a more insidious onset.

My endocrine (diabetes) nurse practitioner came across the disease on the Internet and tested me for it. I had ran across this disease via the Internet on my phone in the ER about a month before she came across it, but I did not directly pass on the name of the potential disease (that I have now been formally diagnosed with). I already knew that I had serious problems, and that autoimmunity was absolutely a possibility in my case. However, AAG is a rare and a relatively obscure diagnosis. None of my current doctors at the time had ever heard of this disease.

I just told her that I did not think the autonomic neuropathy was due to my diabetes. I basically told her about my bladder problem (autonomic neuropathy is essentially never present at diagnosis with TYPE 1 diabetes, especially prior to puberty). I also asked her "are you sure this isn't autoimmune?".

We both did googling, but my endocrine nurse practitioner deserves credit for figuring this out.

[diabeticgonewild]

I would also like to point out that my doctors refer to my disease, AAG as:

"Autoimmune autonomic ganglionopathy"

"Autoimmune dysautonomia"

"Immune-mediated dysautonomia"

This may help individuals seeking treatment if there is autoimmunity present, because an individual can refer to those names, especially the last two, to their doctors.

[kitt]

Very, very fortunate that you had a nurse practitioner who was determined and went the extra mile to help find your dx.

I find most doctors don't take the time to Google on the internet looking for answers.

My experience with endocrinologists, (I have Hashimoto's Disease) is that they order tons of lab work, and use that data as their basis for all diagnostic and treatment plans.

Many patients with CFS have an HPA axis disorder. HPA = Hypothalalamic-Pituitary-Adrenal

It's almost impossible to find a endo who's willing and able to think outside the box, and figure out how to test for this.

You're lucky indeed to have encountered the nurse practitioner that you did.

Thank you again for sharing your story.

K