Autoimmune Autonomic Ganglionopathy - Anyone Else Out There??

[dawson20]

Anyone else out there?

Just looking for experience!

[janelle]

Hi, I think i have it, but i think they call it differant things my label is pandysautonomia but it has many differant labels i've noticed in research articals.

I'm on my 5th month of treatment with ivig and have gotten a small benefit from it after my 4th session, but i notice fluctuating slight improvement between sessions.

I'm interested to know your journey,do you have your story posted, it's nice to know others are out there.

pandygirl

[dawson20]

Interesting - I'd never heard the term 'pandysautonomia' but when i googled it the symptoms are identical to AAG (as is the treatment)!

Clear like mud right?

my story is not posted - It's long and convoluted, and confused by several different diagnosis' along the way before everything lined up and I was dx'd with AAG.

Basically it started after I had my first child with severe OH and tachycardia issues. Dx'd initially with POTS, the NCS.

Mayo Clinic in '03 - major workup - dx'd with 'autoimmune endochrinopathy' though they couldnt define any specific antibodies, or endochrine abnormalities that weren't attributed to the meds I was on.

I pretty much 'gave up' on an answer/treatment for several years.

In '05 my son was diagnosed with a Mitochondrial Disorder (Complex 1 Deficiency) which threw everything off and for a few years I was believed to have Mito (what are the odds it was something else right?).

Things gradually worsened... pupil issues, dysmotility, UTI's constantly, Orthostatic Intolerance just got worse and worse in spite of increasingly high doses of meds. This past winter my 'sitting down' blood pressure was 70/40 on a good day.. standing up it was undetectable.

Anyways last summer I saw a mito specialist after having had a muscle biopsy to test for mito come back negative.

The specialist confirmed I do NOT have mito, but instead he said I seemed to fit the clinical profile for AAG perfectly - his colleague (a neuro at the autonomic clinic in the same hospital) consulted and agreed I fit the profile well and my pupils apparently impressed them.

They ordered the antibody titres at that point and suggested IVIG if the antibodies were positive.

They were negative.

that was earlier this year. My cardio still felt IVIG was worth a try as it has been reported to help in many seronegative cases of AAG.

While waiting to get into see the hemotologist that was going to consider trialling the IVIG, my motility hit an all time low and I wound up inpatient with severe malnutrition/hypoglycemia. They were discussing TPN and/or tube feeding at that point and everyone agreed it made sense to try the IVIG first in case it would work. basically we had nothing to lose.

I had my first round (a little over 2g/kg spread over 5 days) in April/May, then followed up with 450mg/kg every 3 weeks. 7 days after hte start of the first round my blood pressure and heart rate completely stabalized. My motility picked up and my pupils started doing what they were supposed to. It was phenomenal.

By my 2nd follow up dose (last week) it was clearly not working any longer - my heart rates and blood pressure readings were worsening fast, and my appetite was gone.

So they have just finished up another 3 day cylce of high dose IVIG (was supposed to be 4 but i got really sick (fever, headache, aches, etc) yesterday so they called off dose 4) and will resume at a more frequent and higher dose now.

The hope is that things will continue to improve over the next 6 months with the IVIG.

If things do not continue to improve at this point the next step is Plasma Exchange. We will know in the next week or two which route we will be going... I will be getting a port put in likely towards the end of the month once we know whether I'll be doing IVIG or Plasma Exchange long term (they use different types of ports depending on which treatment I'll be doing).

That is the short version... *sigh*

what is your story? Is it posted anywhere?

I'm very curious to hear more from someone in the same boat!!

[spaceorca]

Keely and Pandygirl, My son also has been diagnosed with pandysautonomia. He has been tested for AAG, twice I think, but the results were negative. His doctors say: "The pandysautonomia probably is caused by an autoimmune reaction. AAG is just one type of antibody that identifies an autoimmune reaction; there are at least dozens (probably hundreds) of others that we can't identify yet with clinical tests."

In other words, pandysautonomia, POTS, and other phrases identify the system that is broken in the body. For most patients, doctors don't know what is causing the damage. For ones who are positive for AAG, they reason that the damage might have been caused by those antibodies (although they still don't know for sure).

One of the points that has frustrated me is that my son's doctors have not been willing to pursue IVIg--although they clearly take his illness seriously and have prescribed numerous other treatments (including Remicade infusions, which he's currently doing). But IVIg seems to be a treatment that works for some patients and has relatively few side effects; so I've been frustrated that no one has been willing to try it.

Most recently, our neurologist said that he definitely would have ordered IVIg if he'd treated my son during the early months of his illness--but that he didn't think it would be effective so many years after the start of the illness. So I'm interested that your doctor was willing to start this so many years after the advent of your symptoms, and it's so great that you're responding somewhat.

What a frustrating disease--both the physical processes and the difficulties with physicians (even those who really want to help but don't seem to have a good knowledge base to draw upon for this disease).

[kitshalleen]

I just went to cleveland clinic and was diagnosed with aag. they didn't offer me ivig either. i would like to try it, because i have tried over 100 meds. i've been sick for almost 11 years now. i don't know who to go to that would give it to me though. so i hear you guys. it is very frustrating, and it sounds like docs really aren't sure who it will help or not.

[juliegee]

Hi Dawson20-

So glad the IVIG helped initially. I pray it will settle in & continue to do so. I have a question. Have your immunoglobulins ever been tested (prior to IVIG)? Are they normal or deficient? I ask because mine are quite low.

It is hard to find info about AAG. Do you have a site or link you can recommend?

Thanks for educating us-

Julie

[Babis]

I have had POTS for a year, and was recently diagnosed with AAG. I was positive for the alpha-3 ganglionic acetylcholine receptor autoantibody. There is a test called "Mayo Clinic Autoimmune Dysautonomia Evaluation"

http://www.mayomedicallaboratories.com/articles/hottopics/2011/02-auto-dys-eval/index.html

but most of my doctors refused to order it. I had to see 10 specialists before someone agreed to order the test, and when it was finally performed the result was positive. I then visited the Mayo Clinic neuroimmunology department, and they did a very good job, catching many things my previous doctors had missed. They also recommended immunotherapy, with IVIg or steroids, followed by azathiopine or CellCept. I am in a hospital in Germany right now and just finished my second day of IVIg (0.4 g / kg / day). I pray that it works; if not I will need plasma exchange or immunosupressants.

[lieze]

I hope this works for you.

Let us know how you're doing.

[Babis]

I hope this works for you.

Let us know how you're doing.

Thanks! I just finished my 5th and last day of IVIG. So far I do not feel any better, just nausea and horrible headache. Not sure if the headache is due to IVIG or the spinal tap they did just before that... I also had a tilt table test done today, and it still shows POTS (heart-rate 72 down, 118 up; almost identical to my tilt table test 6 months ago...)

I must say I am not overly optimistic. Early immunotherapy (ideally in the acute or subacute onset phase) is more likely to work... But my doctors wasted a year before testing for ganglionic autoantibodies, and starting immunotherapy...

[kmichaelson]

Hi Babis, I'm sorry you haven't had better results. I know how discouraging it is waiting for new treatments, tests, appointments and getting my hopes up that this time something will work. Thanks for sharing so much about what you've learned through this.

[Babis]

Btw, from what I hear, the brand of IVIg used makes a big difference in terms of side-effects. (I am not sure about effectiveness). The brand I was given was Privigen. Reading this comparison table, it does not seem such a big surprise that I got severe headache, fever and nausea. Let's see if the next round of IVIg goes better... My doctors said they plan to try 5 days of IVIg every 40 days.

They also recommended Mestinon (a parasympathomimetic and a reversible cholinesterase inhibitor) which increases the availability of acetylcholine. It is typically used in Myasthenia Gravis (which is caused by acetylcholine receptor autoantibodies in the neuromuscular junction) but sometimes it is recommended in AAG (caused by acetyclholine receptor antibodies in the neuiron-neuron junction). I have heard of POTS patients having good results from this. For me, unfortunately, Mestinon seems to triger GI problems, such as nausea, vomiting and abdominal pain, as if I did not have enough already from POTS.

However, there exist other cholinasterase inhibitors, such as Rivastigmine, that are available as a transdermal patch, and are much less likely to cause GI distress. These are mainly used for Alzheimer's but I will ask my doctors if I can try one of them...

[ramakentesh]

There are also a number of herbs that act in similar ways to mestonin and other acetylacholinasterase inhibators. Rhodiola rosea is an example although it has other functions as well.

AAG is an interesting thing. I think its under tested and most POTS doctors dont investigate this angle, even in the context of POTS patients with comorbid autoimmune diseases. The reported level of antibody titers was low in only 6% of patients tested, but there may potentially be other autoantibody-mediated targets and mestonin may help for other reasons (by increasing sympathetic as well as parasympathetic receptor activity).

Some doctors now seem to think the autoimmune vartiety of POTS is related to small fiber neuropathy and failed QSART tests rather than AAG.

[Babis]

I hope this works for you. Let us know how you're doing.

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

Then I received 5 more days of IVIg (Gamunex), and felt nothing for a week, but I had further 25% improvement after the 2nd week.

My symptoms of dysautonomia and encephalitis (severe very strange vision problems, confirmed in a PET scan as hypometabolism in the visual cortex) both improved, which proves that both problems were autoimmune.

I am very happy about this response, I hope I continue to improve.

I am scheduled for another round of IVIg in 6 weeks.

[Babis]

Just wanted to note that I had a further 25% imrpovement one week after my third round of IVIg. I am now 75% recovered :-)

I hope this continues after the next round of immunotherapy. It looks like I will be receiving 5 days of IVIg every 6 weeks, for at least a year....

From my experience, and my delayed diagnosis (which happened only after I insisted for the autoimmuned dysautonomia evaluation), I think AAG is massively underdiagnosed, and many people suffer unnecessarily....

Many autonomic labolatories, such as Froedert Hospital, are sometimes able to tell that someone has POTS, but do little to discover the underlying cause. So they give people symptomatic treatments, instead of the therapy that could actually cure them. I am lucky that I ended up in Mayo clinic neuroimmunology, and evel luckier to be in Europe now for treatment, where doctors are much more willing to offer IVIg, giving me my life back...

[issie]

There's also another supplement that works like mestinon and can cross the blood brain barrier also - it's huperzine A. It's thought that I have some sort of disorder in this area and I'm trialing it right now. The symptoms that Rama describes with the mestinon are the same ones I'm experienceing with the huperzine A. I can't say that it is helping a whole lot - yet. It has increased my exercise endurance and my give away muscle weakness. It really mellows you out and you do feel sort of out of it mentally - like Rama says stoned - but, not really in a good way. Sort of like . . .okay, I'm just sitting here - ladedaa! I'm not sure I like the feeling, but it seems to slow the tacky down and give you more muscle strength and endurance. I've read some reports of where people are having to take less mestinon when they take huperzine A. But, it too can give you the choloringenic storm - so you have to pay attention to your body and make sure you watch for symptoms of that. It's too soon for me to really form an opinion on it. But, thought I'd throw it into the mix.

Issie

[arizona girl]

Hi babis, I'm so happy you are improving with IVIG. Thank you for the update.

I also am on privigen for autoimmune sfn neuropathy / hypogammaglobulinemia. I also was just was diagnosed with hashimoto thyroid and autoimmune lichen planus. I had symptoms of both of those for years prior to any treatment and can't believe they went undiagnosed for so long. My docs are saying I have an undefined connective tissue disease UCTD.

I didn't have the mayo panel done, it would be interesting to see if I tested positive for it. Since I'm already getting treatment though not sure it is necessary.

I'm curious about your treatment dosing. I started with 70 grms a day for two days every four weeks. We are reducing me down and I am now at 45 grms a day for the two days every four weeks. I have had some improvements too, but I am now wondering if the reductions are flaring the other autoimmunity issues.

What specific kind of symptoms did you have that have improved and have your doctors told why they have you on the dosing plan they have you on? Do you know how much they are actually giving you?

I agree with you that many of us are only getting symptom treatment, which is helpful, but if you have something more serious going on symptom treatment isn't going to stop the progress of some disease states and you will continue to get worse though you may be managing some symptoms. When I saw dr. grubb in toledo, he said that they are continuing to find more of these kine of autoantibodies. He said they had found 5 already when I saw him two years ago.

If it makes you feel any better my cardio said I and patients like you are trail blazers and we are paving the way for those that come behind us. So, even though it has been difficult for us our struggles will help those that follow. It gives me some comfort to think that it is true.

[ramakentesh]

Interesting that remicade was mentioned.

[Babis]

Hi Arizona Girl,

My doctors give me a round of IVIg every 6-8 weeks.

In each round, I receive 30 gr / day for 5 days.

I was told that is reasonable, since the half life of IVIg is about 3-4 weeks.

This regimen was advised by European University doctors (Greece and Germany).

It is very similar to that used for Myasthenia Gravis.

I am now told that the dose will be reduced to 3 days (30 gr / day) every 8 weeks (probably to save money).

I am a little scared this might be insufficient, but we will see.

The protocol suggested by Mayo was a little different (5 days of IVIg initially, then once a week for 5 weeks, then stop IVIg and start immunosuppressants). The sides of immunosupressants are steep, so I have managed to avoid that so far, sticking to the (much more expensive) IVIg. The Mayo neuroimmunologist (Dr Andrew McKeon) said the European protocol is also reasonable.

The symptoms that I had and improved dramatically with immunotherapy were disabling & numerous.

They included sympomts of dysautonomia (dizziness, faintness, POTS, crashing fatigue, heat intolerance, GI dysmotility, irritable bowel, aerophagia etc etc).

They also included symptoms of encephalitis (sensory integration dysfunction; severe vision problems such as "frame-skipping" or jittery vision, inability to process moving or bright or complicated patterns, palinopsia; sensitivity to sound; brain 'numbness' or extremely uncomfortable "cotton brain" sensations, etc etc). My doctors did not take these symptoms seriously and for a year thought they were migrainous or psychological. I kept insisting it was not migraine nor psychological but nobody listened. Even Dr McKeon at Mayo thought these symptoms were migrainous initially. But then the Mayo radiologist did an excellent software analysis of my brain PET scan, which showed hypometabolism in the visual cortex and elsewhere. Then, given the AChR antobody positivity, Dr McKeon immediately suspected autoimmunity could cause the visual problems (in addition to dysautonomia), and suggested trying IVIg. This worked, which proves that his second hypothesis was right, finally...

Hi babis, I'm so happy you are improving with IVIG. Thank you for the update.

I also am on privigen for autoimmune sfn neuropathy / hypogammaglobulinemia. I also was just was diagnosed with hashimoto thyroid and autoimmune lichen planus. I had symptoms of both of those for years prior to any treatment and can't believe they went undiagnosed for so long. My docs are saying I have an undefined connective tissue disease UCTD.

I didn't have the mayo panel done, it would be interesting to see if I tested positive for it. Since I'm already getting treatment though not sure it is necessary.

I'm curious about your treatment dosing. I started with 70 grms a day for two days every four weeks. We are reducing me down and I am now at 45 grms a day for the two days every four weeks. I have had some improvements too, but I am now wondering if the reductions are flaring the other autoimmunity issues.

What specific kind of symptoms did you have that have improved and have your doctors told why they have you on the dosing plan they have you on? Do you know how much they are actually giving you?

I agree with you that many of us are only getting symptom treatment, which is helpful, but if you have something more serious going on symptom treatment isn't going to stop the progress of some disease states and you will continue to get worse though you may be managing some symptoms. When I saw dr. grubb in toledo, he said that they are continuing to find more of these kine of autoantibodies. He said they had found 5 already when I saw him two years ago.

If it makes you feel any better my cardio said I and patients like you are trail blazers and we are paving the way for those that come behind us. So, even though it has been difficult for us our struggles will help those that follow. It gives me some comfort to think that it is true.

[ramakentesh]

interesting post Babis thanks

[Clairefmartin]

The POTSgrrl blog has lots of info on IVIG - for Sjogren, which seems to have some major overlap with AAG.

Here is a blurb with some articles/links from my blog as well: Autoimmune Autonomic Ganglionopathy (AAG) and Autoimmune Autonomic Neuropathy (AAN): "The typical AAG case is a previously healthy young or middle-aged subject, more likely to be a female, presenting with a severe panautonomic failure that evolves within days to 1-2 weeks, similarly to the somatic counterpart Guillain-Barre' syndrome (GBS). The course is generally monophasic with slow, often incomplete recovery. The clinical picture is dominated by orthostatic hypotension, widespread anhidrosis, dry mouth, dry eyes, sexual dysfunction, urinary retention, impaired pupillary responses, reduced heart rate variability and gastrointestinal symptoms ranging from gastroparesis (manifesting as early satiety, postprandial abdominal pain, bloating and vomiting), diarrhea, constipation and in the most severe cases intestinal pseudoobstruction. the term autoimmune autonomic ganglionopathy (AAG) has replaced the more generic term autoimmune autonomic neuropathy (AAN). The autoimmune disorder was suspected in the original description when it was considered as an autonomic variant of Guillain-Barre' syndrome." (15) As in GBS, an antecedent event, such as a viral syndrome, recent immunizations or surgical procedures, is often reported. (15) Mayo Clinic findings report 15-25% of their patients with POTS have AAG. (16) "Milder forms of dysautonomia, such as postural tachycardia syndrome, are associated with ganglionic AChR in 10-15% of cases." (49)

Sources:

15.Other Autonomic Neuropathies Associated with Ganglionic Antibody. Paola Sandroni and Phillip A. Low, Auton Neurosci. 2009 March 12; 146(1-2): 13–17. Published online 2008 December 4.

16. The spectrum of autoimmune autonomic neuropathies. Klein C, et al. Ann Neurol. 2003;53:752–758. [PubMed]

49. Invited Article: Autonomic ganglia: target and novel therapeutic tool.Vernino S, Sandroni P, Singer W, Low PA. Neurology. 2008 May 13;70(20):1926-32.

[ramakentesh]

The percentage is claimed to by 25 % in POTS in unpublished data but this is not universally accepted.

[Clairefmartin]

It's very confusing, because the antibidy test actually doesn;t show a high percentage of AAG it seems, the symptoms overlap big time with Sjogrens - I guess the Sjogerns lip biopsy is the end all be all of that DX (they are puching for me to do this, but I'm waiting until everything else comes back first before jumping into having a numb lip for a year), and much of teh literature on it (whic isn't much) proposed to rename AAN as AAG. ???? No wonder there is so much disagreement and confusion going on in the reserach world.

[ramakentesh]

There is differing opinion on the target of autoimmune mediated autonomic disfunction in Sjorgens - some studies show compelling evidence that muscaranic receptors are involved (and these are vasodilatory in the vasculature).

There are also other targets for autoimmune etiology in POTS being investigated right now - beta 1 (grubb), beta 2, alpha 2, and perhaps other targets.

[jlmahon]

I have tested positive for the acetylcholine ganglionic antibody. Dr. Grubb told me it confirmed his suspicion that my dysautonomia has an autoimmune cause. When I was diagnosed with rheumatoid arthritis, I was put on methotrexate and felt better than I have felt in years as far as orthostatic symptoms/fatigue goes. I had to stop the methotrexate because I wanted to get pregnant. My symptoms got much worse. I'm currently taking a low dose of prednisone, and just started sulfasalazine, which is used as an immune suppressant. I'm hoping the sulfasalazine works magic too. I probably won't know for a while, as it takes time to build up in the body.

[ramakentesh]

Frequently reported. i wanted to try methotrexate but since I have ank Spond my rheumatologist said it is ineffectual in AS and would prescribe it.