Can small fiber neuropathy present like ME/CFS?

I was diagnosed with small fiber neuropathy via skin biopsy. I'm trying to understand my health issues and I'm wondering if it's possible to have a painless form of SFN that presents with fatigue, poor sleep, exertion intolerance, mild intolerance of upright position.

I later developed more typical symptoms of SFN that include pain, but could it be that it was SFN all along?

I visited a forum for SFN patients and read patient descriptions of symptom aggravation that occurs with a delay after exertion.

 

Do SFN patients feel really unwell. Like, really unwell ME-unwell? Physical *and cognitive* exhaustion? Immune (flu-like) symptoms, sore throat, tender lymph nodes, worse in PEM/crashes..? From what I've read that's not the case, although there is of course significant symptom overlap.

I guess what I'm saying is: is there a severe 'malaise' in SFN, of the type that characterises PEM (rather than just symptom exacerbation)? I've not read anything to suggest there is.

One study found 1/3 of ME/CFS patients have SFN, so you could have both.

 

I think there may be a problem with using skin biopsies for diagnosing SFN. As I understand it the number of small nerve fibres is counted. Whether it is really possible together a reliable number out or not I don't know. I would expect the method to be very open to subjective bias.

I would not expect SFN in itself to produce fatigue, poor sleep or malaise as in PEM. Whatever caused the SFN might do but I am not sure we have much idea what the causes are, other than maybe standard things like diabetes.

 

@Hoopoe,

I have been diagnosed with SFN and have PEM like symptoms also and have wondered about this. As Jonathan says, there doesn’t seem to be any good understanding of causitive factors.

You might find this of interest. Dr. Todd Levine in the USA has a classification system he’s developed:

https://www.youtube.com/watch?v=WbvhPa-l4W4

 

I apparently have both as I get significant pem/malaise/flu like symptoms along with widespread pain and pots. I started off with mild pain and autonomic symptoms post virally which are now severe. The neuropathic pain has spread post covid from just my arms and legs to my entire face and scalp which is really unpleasant along with chronic migraines.

I’ve had a specialised neurophysiology test called microneurography which looked at the function of the varying small fibre nerves, C-fibre nerves which generate pain, along with autonomic and sudomotor nerves. All have spontaneous depolarisation meaning they were essentially over active or dysfunctional apparently not seen in healthy controls. They think the remaining “nerve sprouts” after the nerves have been damaged and regenerated cause the spontaneous activity. But it’s a specialised test so not widely in use and not been replicated much to my knowledge.

Anecdotally some of my friends who’ve had microneurography too have had over-activity of their autonomic nerves but not the c-fibre pain nerves but both were affected in my case. This seemed to correlate with whether or not they had significant pain.

This was in addition to a skin biopsy showing reduced nerve fibre density too. Genetic tests have ruled out a genetic neuropathy and other bloods for metabolic causes like diabetes and so it has been deemed idiopathic.

As I’m sure you know David Systrom/Fluge and Mella and co have speculated that SFN of the autonomic nerves can impair blood flow to the muscle and return of blood flow back to the heart so question whether hypoxia in exercising muscle is the cause of some of the symptoms like exertion intolerance.

I haven’t seen anything that has hypothesised the cause of flu like symptoms/malaise although some researchers assume that the nerves release things like CGRP/histamine/cytokines in excess. Although there’s no data to support this yet from what I know.

As my SFN has worsened I’ve developed flushing and red ear syndrome too which some class as erythromelalgia possibly due to dysfunctional small fibre nerves not controlling blood flow as they should. This has been classified as a “neurogenic flare response” of small fibre nerves by researchers such as Dr Anne Oaklander at Harvard. I have also developed what is thought of as neuropathic itch so something isn’t right with my nerves to cause all of the above.

But the question is, is the SFN a cause or consequence and what role does it play in ME especially as not all have it. Most of this is unanswered frustratingly and it’s even harder when you see yourself declining over many years.

 

Surly there is, though? It's not uncommon in diabetes, and another causal factor is long term vitamin B12 deficiency (that's why I have it). It's linked with some medications, and post-chemotherapy it can be quite severe. There are probably other known causes too.

 

Certain causes of neuropathy are quite well understood, yes. Although generally not small fibre specific. B12 goes for dorsal columns. Diabetes hits all nerve types I think. Vincristine neuropathy has a specific pattern etc.

The small fibre neuropathy said to be associated with fibromyalgia or with pain syndromes or even ME/CFS is, as far as I know, of completely unknown origin. About 50% of neuropathies have no discoverable cause - maybe the majority.

 

I was thinking of doing a members survey on neuropathy but have no idea on how to phrase it or if it would be worthwhile.

I know I have some sensory neuropathy, early in my illness a doc did a test where he moved my big toes and I could’t feel him doing so. And I do have odd loss of sensation, but can move them fine. I’ve even wondered if the level changes depending upon how bad I am, but don’t know if that is even possible.

I’ve heard of autonomic neuropathy which could help explain some symptoms I have. Others talk of pain, tingling, etc.

Maybe this is linked to ME/CFS or maybe I’m like Kitty and it was B12 (my B12 was low, along with other things, when tested early on, I had been ill in the previous year with a significant infection so…)

So what do others think? Worth a wider members survey, any thoughts on structure? There seems to be a lot of different types of neuropathy and not a lot of clear tests.

 

I think the trouble is that we have very little reliable information about this. I don't think symptoms of ME/CFS are consistent with neuropathy as a rule. Tests for small fibre neuropathy look to me unreliable. I have looked after many people with neuropathies and the picture is not present in ME/CFS.

There is a lot of confusion between 'dysautonomia' and autonomic neuropathy. Postural tachycardia is not a sign of a neuropathy. People with autonomic neuropathy tend to have oedema from changes in vascular permeability. Position sense is large fibre dorsal column neurons, which are affected in B12 deficiency but not autonomic.

 

Thanks @Jonathan Edwards that’s useful. They definitely confuse me! And I suspect many others, so we may just get a lot more confusion rather than much useful information.

 

I think a survey might be a good idea. Because SFN is not at all understood, bad things can happen.
Last week I had an EMG for possible polyneuropathy, although I asked my GP and the neurologist to test for SFN.
I didn't have enough knowlegde to object to an EMG. I was glad to get a test.

Before the EMG my legs and arms were put in a really hot water. When is SFN on its worst; in hot weather, or going from warm to cold or cold to warm.
The hospital I was sent to can't even test for SFN, the neurologist said after the EMG and my GP isn't allowed to send me to the right hospital.
The only hospital that can really test SFN is a 2 x 5 hours travel away.

To me 2 times can't from docs meant I was tortured in a hospital. Heating up and then sending currents right through.

 

My understanding is that a big part of the problem may be that the people who specialise in diagnosing SFN do not understand it and one of the bad things that happens is that it is diagnosed without reliable evidence.

An EMG (or strictly neuroelectrophysiological study) is worth doing if there is any suggestion of any sort of neuropathy. SFN is a polyneuropathy, just a restricted type one. You would want to know if others fibres are affected. But it isn't very pleasant and as you say it does not exclude a pure SFN.

 

There was a member in my group who was diagnosed with SFN by a specialist who teaches at a university. Then he went to another doctor as part of his quest to understand what is going on with him and he mentioned the SFN diagnosis. This other doctor shook his head in disbelief and said something like "it is very odd that everyone comes back with an SFN diagnosis from there".

So he clearly had seen enough such patients and had his doubts and it made me remember how Jonathan Edwards also always says that this diagnosis is not so reliable and quite subjective. I think I agree that we probably need more and better evidence of this.

 

Yes. SFN was one of my first ME/CFS symptoms. I went to various doctors complaining about it, but none of them were much interested to do anything beyond an EMG, which cannot diagnose SFN type of neuropathy. Oh well, not different to ME/CFS in that regard. Just another symptom that lots of people seem to report also recently in association with long COVID, but nobody is much interested.

 

I understand that there can be doubt when a skin biopsy shows you are in the 4th percentile of the population. There must be variation sample to sample even in the same person, and I'm not sure how they calculated the 5% line and if the 5% cutoff accounts for age distribution.

I had a 14 fold lower density than the 5% cutoff and at the time I was one year with severe ME and the pain was just some discomfort in my foot. Similar to @JES so well described it has progressed over 8 years to terrible pain in arms and legs, migraines that amplify the pain, and the dysautonomia just gets worse or worse.

I agree that nobody is much interested.

I think @Hoopoe asks a valid question "Can small fiber neuropathy present like ME/CFS?". A big part of ME/CFS is orthostatic intolerance...... could neuropathy be one path among many that leads to that outcome, and if so what else could be similar.

 

This is something I’ve thought about. The thing is it varies so much for me. There are times I cannot even sit and being upright is torture, while others I can sit comfortably and even stand for a couple of minutes. To me that variation and the lack of oedema as Jonathan mentioned mean perhaps not traditional neuropathy? But then what?

 

Autonomic neuropathy? I have a difficult time understanding my OI symptoms as well. All that is obvious to me is that it is related to the same crappy immune response that causes my ME/CFS symptoms and that temporarily almost goes away when I get stuck with an acute cold.

When my POTS was bad, I experienced a largely increased pulse when standing, shortness of breath, cold hands and worsened "pins and needles" or whatever neuropathy you attribute this to. I also noticed my feet and hands would turn more red than normal when standing, but not anything like oedema either.

I also experienced day to day variations, but I'm not sure how relevant they are. For example I once many years ago was supposed to keep a presentation and was barely able to stand due to bad OI/POTS and started to think I would not get through this. However, when the adrenaline kicked in it somehow got manageable and got through it.

 

Thank you for your answer.

When I'm really heated up before an EMG, does that mean in my simple words, that the nerves are wide open, to let the current run through easier? That must be vasodilation, right?
I suspect vasoconstriction, OI, probably low bood volume, are causing SFN, made worse by diabetes.(Joseph..Systrom, 2021)
The clinical picture was polyneuropathy, the neurologist said. The EMG just showed that I have nerves and they work.
Compare it to this.
A specialist ordered a new car, a nice grey BMW, but the salesman only has a yellow VW beetle and says you have to take this, they are both german, for the same price as the other one? Ridiculous, isn't it. Not in the medical world. Or compare it with diagnosing ME/CFS. Just a bit of testing to rule out some things, concluding it must be ME/CFS.

SFN to me feels as problems with the the nerves just under the skin. I've had over 40 years of restless legs, that felt as inside my body, Diabetes/Metformin stopped that. To be replaced by SFN soon after.

I once had to undergo a knee-arthroscopy while the sedation didn't work, I made a (concious) decision not to ask for more sedation, I could handle it, I just wanted to go home early.
The surgeon tapped my upper leg and told me to relax my muscles. With an epidural should I not have been incapable to contract my muscles? Or feel the tapping?
So normally I was not overreacting to pain. I'm still the same person.
With SFN there must be plenty(poly) of nerves reacting, because they are all screaming at me, at it's worst when I lie down. It can take up to two hours before the pain eases and I can finally sleep.

 

Yes, it only diagnoses one very specific type of SFN. There are other types of small fibre nerves but they are almost never tested.

We can't generalise on the results of skin biopsies to other forms of SFN and vice versa.

 

SNF features in sarcoid and Ehler Danlos which can be marked by fatigue and non specifics overlapping with ME/CFS and fibro. Speaking for sarcoid the symptoms often do not match lab tests (e.g. PFT) nor imaging and some specialists suspect SNF may be a culprit in some of this phenomenon, but it's uncertain. One input into a complex scenario probably, which may be more or less important in any individual.