What is Sjogrens related Ganglionopathy and is it so rare?

[MAT51]

Since this is what my neurologist tells me I have, in mild form, along with my very difuse SFN, I googled it. I found an extremely rare form called AAG (Autoimmune Autonomic Ganglionopathy) - so did she mean this I wonder? Or did she mean some other form of dysautonomia perhaps? Is it very rare or do a lot of people with Sjogrens have it? How does it differ to autonomic neuropathy or sensory neuropathy? Does it usually keep on progressing or does it sometimes stop or go away?

I really just want to know that I'm not alone with this ganglionopathy business - I think I'll manage it better if I have others who have it to speak to. The only new thing I'm trying is a supplement called Taurine - recommended by a person on the NeuroTalk PN forum. I'm a bit concerned that it might make my immune system even more hyperactive. But I want to get shot of my tinnitus so badly that I'll try almost anything.

[Jasper]

Mat51 .....

Here is a link to an article by Dr. Julius Birnbaum of Johns Hopkins Sjogren's Center.

Scroll down a little until you get to the part on THE DISTINCT PNS MANIFESTATIONS ASSOCIATED WITH SJ?GREN SYNDROME. Most of the rest of the article is about Sjogren's neuropathies.

Perhaps after reading Dr. Birnbaum's article things will be a little clearer to you, or maybe not, since he really covers a lot.

I cannot remember all of your symptoms, so I don't know where you might fit (in terms of symptoms).

There are other types of ganglionopathies ..... not just the rare Autoimmune Autonomic Ganglionopathy.


For the record, I have both small fiber neuropathy and sensory polyneuropathy/ganglionopathy. Rituximab infusions have helped my neuropathy. Hopwever, I think IVIG is usually the drug of choice for neuropathies. There are some on the forum who are on IVIG for their neuropathies.

[MAT51]

Sorry Jasper. I wrote a proper reply but my broadband is playing up and it wouldn't send. My symptoms relate to proprioception problems apparently caused by the SFN which affects all of me now. I'm not always in much pain but there are triggers such as hot and cold - especially hot water - and vigorous exercise such as jogging or aerobics (gentle) that seem to preticipate a couple of days of extreme flare. Other than this my main problems are disequillibrium with occasional vertigo, stiffness, weak arms, fatigue, awful taste, breathlessness, strange kind of painless constipation (not like constipation really but improperly digested food and lack of usual impulse to go), inability to sweat appropriately, itching with no itch, dry itchy finger tips and pins and needles everywhere, no libido at all and tinnitus.

On testing she got mild reflex responses from my legs but none from my arms. She is very anti me trying more drugs as she knows I'm highly allergic (tried four anti rheumatic drugs -immuran hospitalised me last year twice!). She calls drugs like Rituximab "sinister" and will be telling my rheumatologist that, in her opinion, non of my neuro symptoms warrant these kind of drugs. She said she would change her mind if new nerve conduction tests show it has spread to my large nerve fibres now but these are not until months away so I'm worrying that I've been left high and dry. I'm in Scotland and not convinced that Birnbaum's ideas have fully been recognised in my hospital.although it's a large teaching hospital with a good reputation so I maybe wrong. Meanwhile I seem to still be a watch and wait patient.

[MAT51]

Mat51 .....

Here is a link to an article by Dr. Julius Birnbaum of Johns Hopkins Sjogren's Center.

Scroll down a little until you get to the part on THE DISTINCT PNS MANIFESTATIONS ASSOCIATED WITH SJ?GREN SYNDROME. Most of the rest of the article is about Sjogren's neuropathies.

Perhaps after reading Dr. Birnbaum's article things will be a little clearer to you, or maybe not, since he really covers a lot.

Ps I have already read this Birnbaum piece many times but I'm not sure on the ganglionopathy -which type is this as there seem to be many types. The type that's most common with SFN Sjogrens I'm guessing? Maybe same as yours
I cannot remember all of your symptoms, so I don't know where you might fit (in terms of symptoms).

There are other types of ganglionopathies ..... not just the rare Autoimmune Autonomic Ganglionopathy.


For the record, I have both small fiber neuropathy and sensory polyneuropathy/ganglionopathy. Rituximab infusions have helped my neuropathy. Hopwever, I think IVIG is usually the drug of choice for neuropathies. There are some on the forum who are on IVIG for their neuropathies.

Ps thanks for the link which I've read already many times but not sure where mine fits still.

[anita]

Hi MAT,

I don't think you have the rare AAG form.  There are body tests to confirm this type, but your symptoms are the same...and this type really focuses on the autonomic aspects, which you have very little.

I do not have the positive lab for this, but it is believed that I have it due to my severe BP issues along with my gastroparesis, and almost every aspect of autonomic dysfunction (heart rate, BP, GI, double vision, urine retention and difficulty starting, sexual dysfunction, livedo reticularis, cardiac arterial vasospasms) and APS.  I have even had plasmapheresis when I was having TIA's every day, all day.

Keep in mind there is still so much to be learned about autonomic dysfunction.  There are so many conditions that are similar in presentation...and many overlap each other.

I do have confirmed ganglionopathy.  I had a special MRI/MRN to look specifically at the dorsal root ganglia and it did, in fact, have bilateral increased signal and significant enlargement...both consistent with ganglionopathy.  The severity of my neuropathies is why I get the IVIG.

[MAT51]

Hi MAT,

I don't think you have the rare AAG form.  There are body tests to confirm this type, but your symptoms are the same...and this type really focuses on the autonomic aspects, which you have very little.

I do not have the positive lab for this, but it is believed that I have it due to my severe BP issues along with my gastroparesis, and almost every aspect of autonomic dysfunction (heart rate, BP, GI, double vision, urine retention and difficulty starting, sexual dysfunction, livedo reticularis, cardiac arterial vasospasms) and APS.  I have even had plasmapheresis when I was having TIA's every day, all day.

Keep in mind there is still so much to be learned about autonomic dysfunction.  There are so many conditions that are similar in presentation...and many overlap each other.

I do have confirmed ganglionopathy.  I had a special MRI/MRN to look specifically at the dorsal root ganglia and it did, in fact, have bilateral increased signal and significant enlargement...both consistent with ganglionopathy.  The severity of my neuropathies is why I get the IVIG.

Thanks Anita - after posting this I was regretfully thinking you might still be away so glad you were able to respond and explain.

I never think that what I have is in your league and of course I don't think I have AAG - I just couldn't find anything else when I looked online,  although she did say my gangliopathy is still mild. However the list of autonomic features is growing to include several of those you mention, including Livedo Reticularis, sexual dysfunction, breathlessness, vasovagal attacks etc and, without going into grizzly detail, my constipation isn't normal constipation, it is dysmotity - plus increasingly I find my oesophagus locks down with all remotely hard foods. This and my hoarseness with breathlessness could just be dryness/ lack of saliva. But I don't think it is as my mouth doesn't feel particularly dry.

However last night I found a copy of the British Sjogrens Syndrome Association mag from earlier this year, which is dedicated to SFN and Ganglionopathy. And I read it for the first time since the diagnoais and understood more about what you are explaining.

So I suppose the thing that has been concerning me the most is the increase in arm weakness I'm experiencing,  along with increase in nights of pain in elbows and the rest plus all the usual pins and needles etc. I'm finding it harder to lift my arms or hold things up for long. My arms feel increasingly exhausted and need resting on soft pillows when still.

When the neuro did reflex tests on my knees and elbows she got a small response from my knees but nothing at all from my elbows/arms. And from what I read last night this corresponds with Sjogrens Sensory Ganglionopathy and is presumably why she has referred me for repeat nerve conduction tests now.

I don't think they will test me in the way that you've been tested - but I spoke to my former GP when I was visiting him about the tinnitus,  which is now plaguing me. He said he felt I should be allowed to try IViG and thought the neuro should be putting me forward for this,especially if anything shows up in nerve conduction tests to indicate large fibre involvement. Awful as it sounds I hope it does.

And even though it's not rare in the way that AAG is, the magazine says that SFN affects around 5-20% of SS sufferers but Sensory Ganglionopathy affects around 5% -which makes it pretty rare still and could be why it isn't included in the guidelines/criteria for IViG in Scotland yet as this is quite a small population?

By the way do you suffer from tinnitus as well? I'm worried because both my sisters are profoundly deaf and my dad (who died from cardiac arrest from vasovagal attack) had hearing problems all his life. So I'm going to push for hearing tests but I was just wondering if it could alternatively be a neuropathic tinnitus as part of my other issues? Just wondered if you happened to know about this at all?

[anita]

Yes I'm still on vacation (heading home today), but had some time to catch up on emails and such.  I saw your post a couple days ago, but didn't have time to reply until last night.

And yes, I do have tinnitis...pretty severe as well.  I'm having my hearing checked later this week with the ENT, while at the same time having an infected salivary gland under my jaw assessed. 

It will be interesting to see if there is any change in the NCS/EMG on your arms.

Sensory ganglionopathy is rare.  I personally think that some with sensory ganglionopathy really have AAG (early stages).  As they learn more about these conditions, I think you'll find that more people are found to have the same condition (although better defined) vs having so many different sub-groups of conditions.

[MAT51]

Thanks Anita. I agree that most probably these are all subheadings under the same broad condition. Interesting about the tinnitus being another shared symptom. I know it's common and has many causes but, having grown up with deafness to such an extent as I have and having never seen an ENT despite the balance issues,and bearing in mind autoimmunity etc I feel this should be checked out now for me too. However, bring dependent on the NHS, I'll probably get stuck on a six month backlog as I am for NCS and gynaecology

Good luck with the infected salivary gland and the ENT tests - post about this afterwards if you can. Mat x

[POTSgrrl]

Hello,

I haven't been on here in a long time, but I have Sjogren's with dorsal root ganglionopathy, trigeminal ganglionopathy (which is essentially the cranial nerve equivalent of the spinal dorsal root ganglia) and possibly some autoimmune based damage to my autonomic ganglia, but not official "autoimmune autonomic ganglionopathy"  (AAG).

AAG is a specific form of dysautonomia that requires certain clinical criteria to be met.  AAG is extremely rare, with the world's leading expert (Dr. Steven Vernino at UT Southwestern) having only heard of about 150 cases in his career.  About half of AAG patients have high titers of the ganglionic acetlycholine receptor (g-AchR) antibody (different from the muscle acetylcholine receptor antibody commonly found in myasthenia gravis).  This antibody is not believed to contribute to dorsal root ganglionopathy, as it binds to the receptors in the autonomic ganglia and the dorsal root ganglia are sensory ganglia. You can be tested for the g-AChR antibody through Mayo Clinic's autoimmune dysautonomia panel or paraneoplastic panel. Quest now offers this test too, but I would not bother having them do it because they don't report a titer value, and the test result is useless without the titer value.

It's important to remember that not all forms of autonomic neuropathy caused by an autoimmune disease are "AAG." A lot of patients and doctors get this confused because the older name for AAG was autoimmune autonomic neuropathy. They changed the name when it became apparent that the damage was occurring to the autonomic ganglia (although a minority of AAG patients do develop a neuropathy impacting their small fiber autonomic nerves).

However, there is another antibody that has been found in Sjogren's that attacks the lining of the ganglia, anti-ganglia antibody.  This is likely involved in dorsal root ganglionopathy, and possibly some cases of autonomic ganglionopathy - not enough research to know for sure.  Unfortunately, it's a research based test, so you can't go to the local blood lab to have it tested.

Separate from autonomic ganglionopathy, 100% of Sjogren's patients have some aspect of dysautonomia.  The dryness itself is caused by a problem with the parasympathetic nervous system failing to stimulate the glands, which then leads to local immune system changes, and eventually structural changes to the glands. The antibody most implicated in this is the muscarinic 3 receptor antibody (a different kind of acetylcholine receptor), which has been found in 90% of early Sjogren's patients and is suspected to be pathogenic early in the course of the disease. This is also a research based test, for now.

As to how common/rare dorsal root ganglionopathy is in Sjogren's - it's probably not as rare as we think, and is likely underdiagnosed.  Most neurologists don't even know how to properly diagnose a common distal small fiber neuropathy, no less a ganglionpathy, which typically comes with worse small fiber neuropathy proximally (closed to head/trunk) and less severe small fiber neuropathy distally (at the feet/hands).

I was super nerd excited when Birnbaum & colleagues published their Sjogren's DRG imaging study with pre and post IVIG imaging, showing inflammed DRG that correlated to the location of neuropathic pain in Sjogren's patients.  I think this was a very important paper, not just for Sjogren's patients, but for anyone with unexplained neuropathic pain. You can read the full article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632907/.

Here's a long term outcome paper on Sjogren's dorsal root ganglionopathy.  IVIG did not have good long term results, but steroids and mycophenelate mofetil (Cellcept). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902517/

Here's the transcript of a web chat I hosted with Dr. Vernino on AAG: http://www.dysautonomiainternational.org/pdf/AAG_Webchat.pdf


Hope some of that helps...

[MAT51]

Thanks so much for sharing your research/ knowledge and experience here POTSgrrl. As a relative newcomer to PoTS and Dysautonomia (not symptomatically, but diagnostically) I've actually indulged in enough nerdishness myself to have already read all your links bar the last one which I look forward to looking at. They are all very useful.

I'm based in Scotland,  but I do think my young German neurologist is pretty well informed about this - although she explained that she takes a very conservative line on drugs - especially for me because of severe reactions to four immunosuppressants. Her husband is an internationally reknowned neurology professor and lecturer.

So my question here was really - what kind of Ganglionopathy is she diagnosing me with and how do they differ? As I have a clear cut diagnosis of Sjogrens now I imagine it is the same as yours - especially as the SFN is more severe nowadays in my arms and face. The tests she did were asking me to walk toe to toe - I was very wobbly at this. She shone a torch into my eyes and asked me to move them. She asked me to hold my arms up in front of me - this was hard because of the weakness so they shook and wavered. She did a reflex knock on each knee and these responded okay, then she did the same with both arms but no response. Six months ago she performed a Romberg's test on me and commented that I leaned instantly to the right. Also she and previous neuro both did pin prick tests on feet etc at earlier appointments and found loss of sensation.

So at the end of the day it's not rocket science to follow her train of thought from what you and Annita are telling me here. She's very logical and much more switched on about autoimmune neuropathies than my previous neuro - who was put off diagnosing me clinically once a badly executed skin biopsy showed up negative last year. This neuro disagreed that any of this is "functional" as her predecessor had decided. She waited until rheumatology had done their investigations and diagnosed Sjogrens by lip biopsy. Now she says my symptoms and signs (high inflammatory markers, +ANA and IgG plus paired oligloclonal bands) all make sense to her.

I guess it's all down to whether my new rheumatologist will agree to let me try Cellcept now. I'm feeling sufficiently alarmed by the ramping up of my autonomic symptoms now, that I've decided to give it a try. The neuro won't be happy with this if I do because she told me it will make it harder for her to gauge whether the SFN and Ganglionopathy are progressing, so she warned me to think very hard about this. But for me it's a no brainer now because things are progressing and I don't want to wait for this to become any worse than it is already.

Good to have you back about and thanks again for clarifying things for me.

[anita]

Thanks for your informative reply.

Dr. Birnbaum has been my physician for the last 8+ years and I was part of a DRG study involving the new MRN imaging.  It is how I was Dx with dorsal root ganglionopathy.  Yes, AAG is very rare, but Dr. Birnbaum suspects that it may also be under-diagnosed in those with some severe forms of dysautonomia...same as he feels that autonomic neuropathy is under-diagnosed (we have had several discussion on this).  He thought that with the findings of my DRG using this new imaging, that my autonomic ganglia might likewise have the same enlargement/inflammation.  POTS patients have no drop in BP when they stand...just their heart rate increases.  I have a very significant drop in BP when I stand (even with medication)...along with profound gastropareis (only 4% emptying)...which of course includes significant constipation (from dismotility, not lack of fluids from Sjogren's).

I was seen at Mayo, but not tested for this antibody....it may not have been offered back in '97 when I was seen.

Dr. Birnbaum also feels that IF damage to the DRG is aggressively treated (with IVIG and/or Cellcept) within the first year of onset, the results are much better.  After that, the results drop.  However, I can personally report that I have some minimal improvement with my IVIG in regards to the neuropathy.  It clearly has slowed progression in my opinion (based upon how I was progressing for the last 20 years), and I do get some decreased pain (which is obviously the IVIG benefit, as it returns after the 3rd week---and IVIG only has a 21 days half-life).

You are correct that most neuros don't know how to properly Dx SFN or dorsal root ganglionopathy.  This word seems to get spit out frequently now...with only a clinical sign of SFN (not even a skin biopsy done).

I have talked to many people with profound autonomic problems over the last 20 years, and I honestly believe that many have possible AAG.  I think in the coming years, more research and studies will show other forms of autonomic neuropathy falling under AAG...just my opinion.

Hello,

I haven't been on here in a long time, but I have Sjogren's with dorsal root ganglionopathy, trigeminal ganglionopathy (which is essentially the cranial nerve equivalent of the spinal dorsal root ganglia) and possibly some autoimmune based damage to my autonomic ganglia, but not official "autoimmune autonomic ganglionopathy"  (AAG).

AAG is a specific form of dysautonomia that requires certain clinical criteria to be met.  AAG is extremely rare, with the world's leading expert (Dr. Steven Vernino at UT Southwestern) having only heard of about 150 cases in his career.  About half of AAG patients have high titers of the ganglionic acetlycholine receptor (g-AchR) antibody (different from the muscle acetylcholine receptor antibody commonly found in myasthenia gravis).  This antibody is not believed to contribute to dorsal root ganglionopathy, as it binds to the receptors in the autonomic ganglia and the dorsal root ganglia are sensory ganglia. You can be tested for the g-AChR antibody through Mayo Clinic's autoimmune dysautonomia panel or paraneoplastic panel. Quest now offers this test too, but I would not bother having them do it because they don't report a titer value, and the test result is useless without the titer value.

It's important to remember that not all forms of autonomic neuropathy caused by an autoimmune disease are "AAG." A lot of patients and doctors get this confused because the older name for AAG was autoimmune autonomic neuropathy. They changed the name when it became apparent that the damage was occurring to the autonomic ganglia (although a minority of AAG patients do develop a neuropathy impacting their small fiber autonomic nerves).


Hope some of that helps...

[MAT51]

I will just feel lucky to be allowed Cellcept the way things are going my end Anita. But actually I'm relieved in some ways that my neurologist is prepared to accept that my confirmed diagnosis of Sjogrens at least means she feels my SFN and Ganglionopathy are both givens - after doing Romberg, pin prick, looking into my eyes etc. If my skin biopsies came back negative again then I'd be royally stuffed - and she is a top neurology consultant here so her word carries weight re drug funding and antirheumatic drugs in Scotland.

And if it's not SFN and Ganglionopathy then what else could it be that has turned my life upside down over the past six years so massively?! Not Fibro or ME as these don't cause paired o bands or very high sed rate and +ANA, IgG, IgA etc?!

[anita]

Thanks Anita. I agree that most probably these are all subheadings under the same broad condition. Interesting about the tinnitus being another shared symptom. I know it's common and has many causes but, having grown up with deafness to such an extent as I have and having never seen an ENT despite the balance issues,and bearing in mind autoimmunity etc I feel this should be checked out now for me too. However, bring dependent on the NHS, I'll probably get stuck on a six month backlog as I am for NCS and gynaecology

Good luck with the infected salivary gland and the ENT tests - post about this afterwards if you can. Mat x

I had ENT appt this morning.  Thankfully, the blocked/infected salivary gland has resolved.  He said, if a stone is in there, that it will return after antibiotics stopped (which was yesterday)...so we'll see.  I'm optimistic that it won't return (so is doctor).

The hearing exam wasn't good news.  My hearing isn't actually bad (only abnormal with background noise)...but she said the problem is my inability to 'process' sound properly due to damage in brain from both Sjogren's (documented on EEG) and 3 strokes in 2002 (documented on MRI).  She said location of damage on EEG is right within auditory system region, also to a lesser extent in the area of stroke damage.  But she feels confident that it's the damage affecting my hearing...which is not fixable, since the brain damage is permanent.  However, she thinks it's worth trying a low level amplifier hearing aid to see if increasing volume will help.  She said research shows that doing so makes it easier for brain to 'process' the sound info.  So I have appt for demonstration Nov 14th.  If I purchase a hearing aid, I have 45 day trial and if it doesn't work, or I don't like, I can return (they are very expensive and insurance doesn't cover them---even when medical (brain damage) cause is determined).

Honestly, it can be hard for some to make this type of decision ( I see posts all the time about these decisions).  kind of like the decision to stop driving, getting a walker/cane, etc.  Just 'acceptance' decisions.  I'm not one to make big deal of these types of decisions and never balked when I had to stop driving for time periods (still do have periods I can't drive) or that I use a cane (after years of using a walker).  I don't care what people think of me with a hearing aid, etc.  I just don't know if it's 'time' (as in bad enough) to make this decision.  But then again, if it improves my hearing even a little, then the time doesn't matter, I guess.

I make actually start a thread asking if others have hearing aids from brain damage...or on the Neurotalk forum.

[MAT51]

Sorry that the damage is the brain rather than anywhere else Anita. I guess not many forms of tinnitus or deafness are fixable. My brother in law (both my deaf sisters married deaf men) has had a cochlea implant for a few years.he struggles with it because it's so invasive if you've never heard anything before and he tells me it gives him tinnitus. Ear related suffering is much more stressful than we realise until it happens to us. Mind you someone I met yesterday was saying that tinnitus is so awful because it's invisible. I found myself saying - my whole body has tinnitus! 

Good idea to ask on the main NT forum about this - I bet lots of those affected by strokes encounter similar stuff. And no I really wouldn't worry about waiting until the time is right. Just get them ASAP and hope they work! You never know it might be like the first time I finally got glasses and everything swam into place. Here's hoping!