Has anyone here got Small Fiber Neuropathy? - Question

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In Israel in the CFS and especially in the Fibromyalgia groups, a significant amount of people have Small Fiber Neuropathy. That is why I am asking my question here.

I don't know if to bother to get tested for it because the biopsy test sounds painful.

I have extremely painful feet that get cold easily and my feet sometimes have odd sensations. But I don't have any burning feeling or burning pain, which is always listed in the list of symptoms of SFN.

Is it possible to have Small fiber Neuropathy without the burning pain?
 
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I got tested and found that I do not have small fiber neuropathy, but I have also heard that many people with ME/CFS have it.

I don't know if to bother to get tested for it because the biopsy test sounds painful.
It's actually not a painful test. The only part that hurts is when they inject a bit of lidocaine--that stings for a few seconds, but after that you won't feel a thing. Even once the lidocaine wore off the area was not painful.
 
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Is it possible to have Small fiber Neuropathy without the burning pain?
Yes it is possible.

I don't know if to bother to get tested for it because the biopsy test sounds painful.
The punch they use is very small and they use a local anesthetic so it is not painful. It's very quick. The difficult part is finding where to get the test done.
 

StarChild56

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I just had the biopsy done a bit over a week ago. Even the lidocaine injection was like a blip a teeny pinch for a second or two. She waited 5 minutes, did the punches on my leg that has the most pain, one on the lower leg one on the thigh (outer for both). No pain as PP mentioned even when the lidocaine wore off.

I do have lots of numbness and tingling, some pain. The soles of my feet burn but that is due to SS not SNF in my case.
 

Inara

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I didn't find anything. It seems to be treated symptomatically (e.g. pain killers).

I found this though, although I don't know what to make of it, and it's speculative:

A planned study for diabetic neuropathy: https://clinicaltrials.gov/ct2/show/NCT03685253
At the current time there is no effective disease modifying therapy for diabetic neuropathy (DN). The proposed study design employs a quantifiable early measure of DN, intraepidermal nerve fiber density (IENFD), allowing for accurate assessment of actual nerve fiber density. Preclinical data supports the use of Niagen® (3-(Aminocarbonyl)-1-β-D-ribofuranosyl-pyridinium chloride - NR) as a potential therapy for diabetic neuropathy. Phase I data indicates safety in humans. This study seeks to investigate the use of Niagen® (NR) as a potential treatment for diabetic neuropathy in subjects with type 2 diabetes mellitus or impaired glucose tolerance over a 6 month period. The endpoint measures in addition to the IENFD with determine changes in clinical and electrophysiological outcomes, quality of life and biochemical measures.
Dosage: 2 x 500mg per day for 6 months. Primary measure outcome: nerve density in a skin biopsy.

And from https://www.cell.com/neuron/fulltext/S0896-6273(17)30106-X, which might give the theoretical background for trying Niagen:
Summary
Axonal degeneration is an early and prominent feature of many neurological disorders. SARM1 is the central executioner of the axonal degeneration pathway that culminates in depletion of axonal NAD+, yet the identity of the underlying NAD+-depleting enzyme(s) is unknown. Here, in a series of experiments using purified proteins from mammalian cells, bacteria, and a cell-free protein translation system, we show that the SARM1-TIR domain itself has intrinsic NADase activity—cleaving NAD+ into ADP-ribose (ADPR), cyclic ADPR, and nicotinamide, with nicotinamide serving as a feedback inhibitor of the enzyme. Using traumatic and vincristine-induced injury models in neurons, we demonstrate that the NADase activity of full-length SARM1 is required in axons to promote axonal NAD+depletion and axonal degeneration after injury. Hence, the SARM1 enzyme represents a novel therapeutic target for axonopathies. Moreover, the widely utilized TIR domain is a protein motif that can possess enzymatic activity.
Edit: For me, the value also lies in the fact that it's an objective diagnosis.
 
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If one gets a diagnosis...is it anything to do about it?
Dr. Anne Oaklander has done quite a bit of research into small fiber neuropathy and treatment. Papers, podcasts, and videos are available on the interweb.

I found these articles by @Cort on Health Rising to be of help in understanding SFN
https://www.healthrising.org/blog/category/research/small-fiber-neuropathy/

For example in this article
Oaklander has been thinking about treating these small nerve fiber problems for quite some time. In her 2015 paper “Immunotherapy Prospects for Painful Small-fiber Sensory Neuropathies and Ganglionopathies” she proposed that the vast interplay between the small nerve fibers and the immune system suggest that immunotherapies will probably work better than opioid drugs.
Link : https://www.healthrising.org/blog/2...bromyalgia-chronic-fatigue-ivig-autoimmunity/
 
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If one gets a diagnosis...is it anything to do about it?
A number of people have told me not to try to get a diagnosis because the treatment is exactly the same as for fibromyalgia, the exact same pain killers. At least in Israel.

I read that in the USA, if you can prove an autoimmune basis for you SFN, you can get gamma globulin, which incidentally also helps some people with CFS.
 
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I was tested and was positive for SFPN. The biopsy is essentially painless.

I highly recommend watching Anne Oaklander’s Radcliffe lecture in 2018 on YouTube on this topic

She is a compelling speaker and explains how SFPN might be a source of a multi-systemic syndrome, causing general fatigue, muscle fatigue, cognitive dysfunction, and major GI issues, not just peripheral pain and tingling. It affects people of all ages, but left untreated tends to worsen with age.

David Systrom believes that there may be false negative skin biopsies, in that he thinks the cardiac preload failure he sees in the vast majority of MECFS patients is likely the result of small fiber dysfunction that reduces the ability of veins to properly squeeze blood back to the heart during exercise. But not every MECFS patient’s biopsy shows a reduction in small fiber nerve density in the skin.

Oaklander advocates the use of IVIG to try to reverse SFPN, since small fibers are not myelinated and can be regenerated if the autoimmune or immune issue is halted. However, more studies need to be funded to replicate her findings on the use of IVIG, since health insurers in the US only approve expensive treatments if multiple studies show its effectiveness. (I don’t know if the same is true in Israel.)

Since some cases of SFPN are linked to prediabetes (impaired glucose tolerance), a finding of SFPN might warrant a glucose tolerance test. If the test shows high glucose levels, it would make sense to adopt a low sugar, low starch diet. This would be an “easy win”, though probably not the cause of the problem for most MECFS patients.
 

Inara

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how SFPN might be a source of a multi-systemic syndrome, causing general fatigue, muscle fatigue, cognitive dysfunction, and major GI issues, not just peripheral pain and tingling. It affects people of all ages, but left untreated tends to worsen with age
Yes, I started to have such thoughts some days ago when I came across Inherited Peripheral Neuropathies, which seem to present with many symptoms, including muscle weakness in some.
SFN worsens, like any neuropathy, because it's a neurodegenerative process, i.e. cells are destroyed ("cell death").

I take s.c. Igg, and it doesn't seem it reversed or improved SFN in me. But I also heard Igg are suggested and, where possible, should be tried. But I think the actual cause is not the immune system in my case, but a disrupted calcium signaling pathway, therefore I will follow the Inherited Peripheral Neuropathy direction. From what I have read in others, it's possible that may be the cause in others, too, but it needs to be researched.

Neuropathies aren't rare in diabetics.
Relatively recent research looks at the link between endoplasmic reticulum stress (= accumulation of misfolded proteins) and diseases, like diabetes or neurodegenerative diseases and many more. It seems, at some point the system gets into a feedback loop where misfolded proteins can't be cleared enough (e.g. due to an increased number of misfolded proteins, plus problems with autophagy or other recycling processes which can lead to apoptosis/"cell death" for instance).
 

StarChild56

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I was tested and was positive for SFPN. The biopsy is essentially painless.

I highly recommend watching Anne Oaklander’s Radcliffe lecture in 2018 on YouTube on this topic

She is a compelling speaker and explains how SFPN might be a source of a multi-systemic syndrome, causing general fatigue, muscle fatigue, cognitive dysfunction, and major GI issues, not just peripheral pain and tingling. It affects people of all ages, but left untreated tends to worsen with age.

David Systrom believes that there may be false negative skin biopsies, in that he thinks the cardiac preload failure he sees in the vast majority of MECFS patients is likely the result of small fiber dysfunction that reduces the ability of veins to properly squeeze blood back to the heart during exercise. But not every MECFS patient’s biopsy shows a reduction in small fiber nerve density in the skin.

Oaklander advocates the use of IVIG to try to reverse SFPN, since small fibers are not myelinated and can be regenerated if the autoimmune or immune issue is halted. However, more studies need to be funded to replicate her findings on the use of IVIG, since health insurers in the US only approve expensive treatments if multiple studies show its effectiveness. (I don’t know if the same is true in Israel.)

Since some cases of SFPN are linked to prediabetes (impaired glucose tolerance), a finding of SFPN might warrant a glucose tolerance test. If the test shows high glucose levels, it would make sense to adopt a low sugar, low starch diet. This would be an “easy win”, though probably not the cause of the problem for most MECFS patients.

This is a great video, thanks for sharing.
 
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On the one hand, Anne Oaklander at Mass General Hospital and David Systrom at Brigham & Women's Hospital believe that small fiber polyneuropathy may contribute to a range of symptoms, including muscle fatigue and cognitive dysfunction, in ME/CFS and FMS.

For example, David Systrom posted a clinical trial in September that begins by stating: "The hypothesis of the investigators' study is that small fiber polyneuropathy is a cause of low biventricular filling pressures/preload failure of the heart and poor oxygen extraction in the muscle bed, leading to symptoms of exertional intolerance and post-exertional malaise [in CFS/ME]".

On the other hand, mainstream medicine does not seem to think SFPN could be a cause of multi-systemic illnesses like ME/CFS and FMS. For example, I was referred to a neurologist at Weill-Cornell by Susan Levine this week. I described my symptoms to him, including rapid muscle fatigue in my legs, muscle and joint aches after overextending, and poor appetite bordering on nausea a lot of the time. I also noted I have "typical" symptoms of SFPN, like tingling in my feet and cold extremities. (I tend not to go into issues like cognitive dysfunction and memory loss, as most doctors start to mentally check out when I list too many symptoms).

When I showed him the results of my skin biopsy for SFPN, his response was that small fiber neuropathy is not a cause of muscle fatigue, muscle aches, or any other symptoms except tingling and cold sensitivity in my feet. Rather than considering whether I might be a candidate for IVIG, he wants to evaluate me for some other neuromuscular cause of my symptoms. He also more or less dismissed the results of the iCPET I had done at Brigham & Women's Hospital recently.

I guess the implication is that a lot of neurologists and mainstream doctors are unlikely to order a skin biopsy to check for SFPN among patients with ME/CFS or FMS, regardless of what Oaklander and Systrom are finding in their research. That's another roadblock to getting IVIG, Oaklander's recommended treatment in many cases.
 

Inara

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minimus said:
On the one hand, Anne Oaklander at Mass General Hospital and David Systrom at Brigham & Women's Hospital believe that small fiber polyneuropathy may contribute to a range of symptoms, including muscle fatigue and cognitive dysfunction, in ME/CFS and FMS.
I start to think that, too. SFN plays a role in the autonomic nervus system (orthostatic dysregulation like POTS, NMH...) - that might be the reason why in a special clinic here orth. dysregulation and SFN are both tested. Furthermore, in another neurological clinic they made a special new test (for research) where the behavior of the small blood vessels in the finger are measured. I always wondered why neurologists do that because it's something from a cardiovascular area, but maybe it's because there is this connection:

minimus said:
: "The hypothesis of the investigators' study is that small fiber polyneuropathy is a cause of low biventricular filling pressures/preload failure of the heart and poor oxygen extraction in the muscle bed, leading to symptoms of exertional intolerance and post-exertional malaise [in CFS/ME]".
And last, in inherited polyneuropathies, muscle fatigue (in a paper the included fast muscle fatiguability and fast burning muscles which was new to me) is not untypical, and there seems to exist something like worsening of symptoms after physical activity (like climbing stairs, walking too long), but nothing like in ME, where "easy" things like too much reading or cooking can lead to PEM.
But I wonder...If in other neuropathies the brain gets "overtaxed" because it has to compensate for destroyed nerves, why doesn't it happen in case of lighter tasks, too? Like an overtrained muscle or inflamed/irritated nerve where every small movement like lifting an arm leads to pain?

minimus said:
On the other hand, mainstream medicine does not seem to think SFPN could be a cause of multi-systemic illnesses like ME/CFS and FMS.
Because, if it's true what neuropathy patients say (ok, I only asked one with HMSN), the PEM of ME doesn't resemble something they know; maybe in some very severe cases, but there everything started in the childhood.

minimus said:
I guess the implication is that a lot of neurologists and mainstream doctors are unlikely to order a skin biopsy to check for SFPN among patients with ME/CFS
That was my experience, too.
 

Peyt

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I was tested and was positive for SFPN. The biopsy is essentially painless.

I highly recommend watching Anne Oaklander’s Radcliffe lecture in 2018 on YouTube on this topic

She is a compelling speaker and explains how SFPN might be a source of a multi-systemic syndrome, causing general fatigue, muscle fatigue, cognitive dysfunction, and major GI issues, not just peripheral pain and tingling. It affects people of all ages, but left untreated tends to worsen with age.

David Systrom believes that there may be false negative skin biopsies, in that he thinks the cardiac preload failure he sees in the vast majority of MECFS patients is likely the result of small fiber dysfunction that reduces the ability of veins to properly squeeze blood back to the heart during exercise. But not every MECFS patient’s biopsy shows a reduction in small fiber nerve density in the skin.

Oaklander advocates the use of IVIG to try to reverse SFPN, since small fibers are not myelinated and can be regenerated if the autoimmune or immune issue is halted. However, more studies need to be funded to replicate her findings on the use of IVIG, since health insurers in the US only approve expensive treatments if multiple studies show its effectiveness. (I don’t know if the same is true in Israel.)

Since some cases of SFPN are linked to prediabetes (impaired glucose tolerance), a finding of SFPN might warrant a glucose tolerance test. If the test shows high glucose levels, it would make sense to adopt a low sugar, low starch diet. This would be an “easy win”, though probably not the cause of the problem for most MECFS patients.
Hi,
Thanks for posting the informative video.
On 1:03 of the video she mentions Eculizumab as an upcoming possible treatment , has anyone tried this for Small Fiber Neuropathy?
 
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Eculizumab (Soliris) is the fourth most expensive drug on the market in the US, costing $400,000 to $700,000 per year, it has only four FDA approved indications, all of them quite rare, and it is associated with some severe adverse events/risks. So I doubt it has been tried on anybody with ME/CFS and small fiber neuropathy.