Small Fiber Polyneuropathy (SFPN) Proposed as Cause of Exercise Intolerance In ME/CFS

[Cort]

Just did a blog on this - it was prompted by two media articles - which described the many different symptoms that SFPN can cause. I was a bit surprised. Oaklander, though, clearly thinks that much of FM is SFPN.

https://www.healthrising.org/blog/2...me-small-fiber-polyneuropathy/#comment-980379

As I was writing the blog, two SFPN more papers popped up - one talked about a new concept of "in a new concept of autoimmune neurosensory dysautonomia". The other which argues that SFPN is behind the exercise problems in ME/CFS (!).

These papers are taking SFPN far beyond what most neurologists think it can do. Time will tell. For me, I like the hypothesis...


Complex Syndromes of Chronic Pain, Fatigue and Cognitive Impairment Linked to Autoimmune Dysautonomia and Small Fiber Neuropathy

Yehuda Shoenfeld 1, Varvara A Ryabkova 2, Carmen Scheibenbogen 3, Louise Brinth 4, Manuel Martinez-Lavin 5, Shuichi Ikeda 6, Harald Heidecke 7, Abdulla Watad 8, Nicola L Bragazzi 9, Joab Chapman 10, Leonid P Churilov 2, Howard Amital 10
Affiliations expand

• PMID: 32171889
• DOI: 10.1016/j.clim.2020.108384

Abstract

Chronic fatigue syndrome, postural orthostatic tachycardia syndrome, complex regional pain syndrome and silicone implant incompatibility syndrome are a subject of debate among clinicians and researchers. Both the pathogenesis and treatment of these disorders require further study. In this paper we summarize the evidence regarding the role of autoimmunity in these four syndromes with respect to immunogenetics, autoimmune co-morbidities, alteration in immune cell subsets, production of autoantibodies and presentation in animal models.

These syndromes could be incorporated in a new concept of autoimmune neurosensory dysautonomia with the common denominators of autoantibodies against G-protein coupled receptors and small fiber neuropathy. Sjogren's syndrome, which is a classical autoimmune disease, could serve as a disease model, illustrating the concept. Development of this concept aims to identify an apparently autoimmune subgroup of the disputable disorders, addressed in the review, which may most benefit from the immunotherapy.

 

[wigglethemouse]

Complex Syndromes of Chronic Pain, Fatigue and Cognitive Impairment Linked to Autoimmune Dysautonomia and Small Fiber Neuropathy

We have a thread for that paper here
https://forums.phoenixrising.me/thr...ysautonomia-and-small-fiber-neuropathy.79792/

 

[pattismith]

hello @Cort

I'm glad you got interested in Dr Oaklander work, and if you dig a bit, you will find that her hypothesis is not an isolated one, it fit with many other neurologists findings.

I'm myself convinced "from the inside" that autonomic and sensory SFN is the main part of my disease from the start 35 years ago.

Many CFS/ME have red hand palm/foot plant which is probably a step to erythromelagia (also caused by SFN, see Dr Todd Levine's work, I posted some articles he wrote on PR).

And also you have to consider that SFN diagnosis is not yet standardized and that the skin biopsy that we thought once to be the gold standard is not! I posted a new french study showing that.

I also posted about the ASIC3 probably involved in the small nerve fibers hyperexcitability in some ME/CFS patients with muscle pain/exercise intolerance.

(ASICs apart from activation by lactic acid, are sensitive to cold and some lipides and mechanical stimuli)

 

[Badpack]

The answer from oaklander to sfn is ivig. She claims to have helped 75% of her patient with it. But no one ever could replicate it. Also the studies about cfs and ivig are pretty mediocre. I got a skin Biopsie and had a normal Count. My friend who got cfs on the same day as me after the same viral infection we caught has extreme sfn. So 2 cases of Cfs from the same origin, one with sfn, one without. Seams pretty clear to me that sfn is a consequence of Cfs. No the other way around. Or, as the article claims, skin Biopsie isn’t good enough to give insight about small fibers around the inner organs and the vascular system.
Also, my friend got 3! Years ivig for small fieber and Cfs. It did absolutely nothing for him. So I’m very skeptical about this whole field tbh.

 

[Wishful]

Seams pretty clear to me that sfn is a consequence of Cfs. No the other way around.

ME seems to trigger or influence a lot of further complications. If ME is affecting immune system function, then it's logical that some people would develop additional immune system related problems. I wouldn't want ME resources to go towards finding a treatment for SFN or other downstream problems, since those resources should go towards figuring out the root cause, and a treatment for ME should also treat all those additional problems.

 

[Badpack]

One doctor in Berlin Charite tried to replicate Oaklanders findings and gave around 10 ppl high doses of ivig for a long time. Because Oaklander stated that it could take years till a ivig treatment would help. The consequence was that not even close to 75% showed signs of improvement. It got so bad that the department for SFN got closed because of the high expanses and bad results.

 

[Wishful]

The consequence was that not even close to 75% showed signs of improvement.

Putting it that way actually sounds promising. I'm guessing that if a significant percentage of patients did report improvement, it was only a very minor (hard to be sure of ) improvement. If a treatment provided a dramatic improvement in even 10% of the patients, it would be worth trying to figure out what they had in common, so that maybe the subset could be identified.

 

[Cort]

hello @Cort

I'm glad you got interested in Dr Oaklander work, and if you dig a bit, you will find that her hypothesis is not an isolated one, it fit with many other neurologists findings.

I'm myself convinced "from the inside" that autonomic and sensory SFN is the main part of my disease from the start 35 years ago.

Many CFS/ME have red hand palm/foot plant which is probably a step to erythromelagia (also caused by SFN, see Dr Todd Levine's work, I posted some articles he wrote on PR).

And also you have to consider that SFN diagnosis is not yet standardized and that the skin biopsy that we thought once to be the gold standard is not! I posted a new french study showing that.

I also posted about the ASIC3 probably involved in the small nerve fibers hyperexcitability in some ME/CFS patients with muscle pain/exercise intolerance.

(ASICs apart from activation by lactic acid, are sensitive to cold and some lipides and mechanical stimuli)

It makes sense to me. Oaklander agrees with the problems regarding test standardization or rather that the reference norms labs use are not effective with false negatives being the main problem. If you have a URL to that study or the post that would be great to have.

ASIC3 makes me think of Alan Light's work if I remember correctly (lol)

 

[Cort]

The answer from oaklander to sfn is ivig. She claims to have helped 75% of her patient with it. But no one ever could replicate it. Also the studies about cfs and ivig are pretty mediocre. I got a skin Biopsie and had a normal Count. My friend who got cfs on the same day as me after the same viral infection we caught has extreme sfn. So 2 cases of Cfs from the same origin, one with sfn, one without. Seams pretty clear to me that sfn is a consequence of Cfs. No the other way around. Or, as the article claims, skin Biopsie isn’t good enough to give insight about small fibers around the inner organs and the vascular system.
Also, my friend got 3! Years ivig for small fieber and Cfs. It did absolutely nothing for him. So I’m very skeptical about this whole field tbh.

Time will tell. IVIG works really well for some and not all that well for others. Certainly not a miracle drug - and so expensive. If it wasn't so expensive it wouldn't be a miracle drug.

She does like steroids....but apparently very little study on that.

 

[wigglethemouse]

If you have a URL to that study or the post that would be great to have.

This is the thread created by @pattismith on the paper comparing different diagnostic techniques.
https://forums.phoenixrising.me/thr...thy-diagnosis-a-french-team-study-2020.80576/

 

[Cort]

ME seems to trigger or influence a lot of further complications. If ME is affecting immune system function, then it's logical that some people would develop additional immune system related problems. I wouldn't want ME resources to go towards finding a treatment for SFN or other downstream problems, since those resources should go towards figuring out the root cause, and a treatment for ME should also treat all those additional problems.

With regards to root cause Systrom thinks it may be SFPN -

Small fiber (autonomic) polyneuropathy may be an underlying mechanism behind
the exertional intolerance of preload failure and ME/CFS. SFPN is associated with a lack of
peripheral sympathetic tone, impaired venoconstriction during exercise, low cardiac filling
pressures, decreased cardiac output, and exertional intolerance.

Time will tell!

 

[Cort]

This is the thread created by @pattismith on the paper comparing different diagnostic techniques.
https://forums.phoenixrising.me/thr...thy-diagnosis-a-french-team-study-2020.80576/

Thanks!

 

[Badpack]

Systrom also thinks that mestinon will cure Cfs and makes another study with it paid by OMF. The drug that has been used for over 40 years in Cfs history without any success.

 

[Wishful]

With regards to root cause Systrom thinks it may be SFPN -

SFPN seems to be limited to peripheral nerves. My ME seems to be cerebral-only. My body seems basically unaffected by ME. I don't see how peripheral nerves would cause major cerebral effects without showing peripheral signs. It sounds more like an explanation for some (admittedly common) downstream symptoms of ME.

 

[Wishful]

The drug that has been used for over 40 years in Cfs history without any success.

One would think that any drug used for many decades would have been used on some patient that had ME, and that its effect would be noticed. If I was given a drug, for whatever disease, and it cured me of ME, I'd be dancing around and telling everyone about it. Actually, I pretty much did that for both cumin and T2 (not ME cures, but wonderful anyway), but neither worked for anyone else.

 

[Badpack]

@Wishful thats exact my thinking to. Thats why my interest is in newer unused drugs. Like SS31. Or things that also showed some help in the nano needle like Copaxone, Suramin. All underresearched. Yet, another Mestinon trail which will def. work in the 41 year or the 100th trail.

 

[pattismith]

@Cort @wigglethemouse
this is just released:

Long-term efficacy of immunoglobulins in small fiber neuropathy related to Sjögren’s syndrome

Do you have an access to the full paper?

 

[Badpack]

@pattismith https://sci-hub.st/https://link.springer.com/article/10.1007/s00415-020-10033-z#citeas

 

[Rebeccare]

Thank you so much for sharing! This is an interesting topic, and it certainly seems like there is a lot of possibility in this field of research.

It is important to note, however, that SFN affected about 40-50% of the ME/CFS or FM patients these doctors described. This is not insignificant, especially if this subset of patients could potentially be treated. But at the same time this is still fewer than half of the patients, meaning that this is only one piece of the puzzle. What about the rest of us?

I would be curious to know what the rate of SFN is in the general population: if you were to grab 100 people at random off the street, how many would have SFN? That might give us a better idea of the significance of the numbers.

 

[Badpack]

@RebeccaRe depends on the population you chose. Nearly every diabetic develops a form of neuropathy after some time. But the normal average person should not have any signs of it.

50% is a big number, so high that it definitely isnt a random occurrence. But just like diabetes, it seems more like a problem which develops over time because of the bad circulation and energy state of the body. And not the other way around. Just like the missing insulin / insensitive insulin receptor is the cause for diabetes so something else must be the cause in Cfs.