David Systrom, researcher, Brigham and Women's Hospital, USA

I also didn't think I had SFN since I don't have fibromyalgia but my skin biopsy showed a significant reduction in nerve fiber density (my sweat gland density was particularly poor at <20% of the minimum density needed to be in the normal range.) I also have sunburn-like sensations which have reduced some over time along with unexplained itching, which can be a symptom of SFN.

Dr Kaufman has told me and others that ~80% of the patients he has tested have been positive for SFN. I think some of our US experts have had luck getting IVIG approved for some people with SFN+POTS based on Oaklander's research, although only in people with private insurance since Medicare will only approve IVIG for people with a very specific set of diagnoses which doesn't include SFN.

 

I think this could be the same test? Dr Systrom mentioned briefly the test in that it involves a... blot? can't remember what term he used, and then a few weeks later nerve conductivity is tested.

I mentioned this because I caught that in the video. I seem to have misheard. I used the transcript from the video and Dr Systrom was talking about receptors on myelinated fibers. Unmyelinated, on myelinated.

 

He does not specifically mention burning sensations in the video. When he mentioned that small-fiber polyneuropathy was being found in skin biopsies of 40% of ME patients who also had "pre-load failure," and then mentioned that those fibers can produce "neuropathic pain" when they are misfiring, it occurred to me that such "pain" in the skin might include the prickly, sunburn-like sensations I've felt in my arms.

So, I looked at the Wikipedia entry for "small-fiber neuropathy" and found this:

 

One of the classic issues with small fiber polyneuropathy is burning feet syndrome, which is a misnomer in part because it happens in extremities. I used to get this. Now I can get it absolutely everywhere, including internal such as my lungs etc. Small fibers sense heat and cold. According to one theory the cold sensing fibers mostly die, leaving mostly the heat sensing fibers. So this means the brain gets fooled into thinking you have parts of you in a dangerously hot environment, like a fire.

 

Only skin biopsy. They take a small piece of skin, stain it with something (tagged antibody?) then after a while they count the number of stained small fibers. There is no other test that I know of. It has major limitations, not with false positives, but with false negatives. Nerve loss might be patchy, and this test does not apply to loss inside the body, such as deep blood vessels. If you find it in the skin its likely to be many places, but you can miss it too.

 

HealthRising has a number of blog posts on David Systrom (just search for Systrom). That's where I first stumbled across his idea that pyridostigmine could be potentially helpful so decided to experiment especially since I also have POTS and symptoms suggestive of small-fibre neuropathy (though I haven't been biopsied for this).

As I don't have access to this drug I tried various natural alternatives, some to simply boost acetylcholine and some that slow its breakdown. The latter provided a very brief buzz, all ended with me crashing. This was somewhat surprising because most supplements do precisely nothing for me, neither positive nor negative. So a consistent negative reaction on this particular system tells us something is going on, I'm just not sure what?!

Anecdotally other people report both positive and negative experiences when experimenting with the acetylcholine system. Typical!

 

N=1 experience here but just to temper expectations: I've dealt with a couple of myologists (Neurologist specialising in muscle disease) recently, one of which was the go-to guy for performing skin punch biopsy to investigate SFN. In the context of POTS, both felt it was an unnecessary investigation because confirming SFN leads to no further clinical treatment options. I pushed a bit further and queried Mestinon, to which I was told improvements were likely due to the 'stimulant effect' that it has and that patients get hooked on it.

I can't say if these docs were aware of the research discussed. They did hold an antiquated view of POTS, i.e. it is a non-issue, only deconditioning. So I imagine they are either ignorant to these developments or hold an opposing view for their own reasons.

I thought i'd mention it because it is probably reflective of the general medical community.

 

I tried mestinon for a month, working up to 60 or 90 mg every 6 hours I think. I can't remember exactly. I found it worse for my POTS than other drugs - florinef or midodrine - and I experienced no change in PEM or exercise intolerance. It is a mild stimulant but not like "I feel good" kind of stimulant. Noticeable though. No improvement in digestion, which I had hoped for. It did in fact make my headache/neuromuscular issues worse, but other ME/CFS symptoms were largely unchanged.

However, I have heard the occasional person has a much better response to it. It may be I'm in a different subgroup, or just not a responder. It does make sense as a drug to test for in ME/CFS.

But if they do test it for ME/CFS they must control first for POTS or else the results will be overstated and possibly for the stimulant aspect. I suspect a lot of pure POTS/autonomic patients get in to ME/CFS studies because it's almost impossible to say that don't have ME?CFS unless they make a full recovery from treatment.

I think they SFN are a good finding in that they add considerably and demonstrably to the 'this is a biologic' disease weight of evidence, along with all these metabolic studies. But I don't know that any of them reveal a pathology or treatment quite yet.

 

I've just recieved my referral to investigate for SFN, fully expected it to be a punch biopsy but was surprised to see it'll be an alternative method instead: Sympathetic Microneurography.

Looks to be a very specialised conduction technique. The referral has come from a neurocardiology autonomic dept with the promise that it discovers SFN in many of the POTS patients...so sounds like a promising alternative, especially if you don't particularly enjoy giving up body parts

 

No, not via nerve conduction test. That only tests the very large fibers. So if someone tells you "no neuropathy" after such a test, s/he is partly wrong.

To test for SFN, a skin biopsy is made, but I slightly remember this is only one part of the diagnostics.

Neuron specific enolase (ENS) could point to neuropathy; in type 2 diabetes this was discussed. I know a doctor who uses that marker to say something about neuropathy, but, well...
If I remember correctly, ENS is also a marker in MS and other neurodegenerative diseases.

A group in Würzburg also showed SFN in FM, but I can only remember a news article about that.

 

Hmmm...

Here's a small study from 15 years ago in 2003 in which they found mestinon helpful with chronic fatigue syndrome.



Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports.
Kawamura Y1, Kihara M, Nishimoto K, Taki M.

Abstract

Chronic fatigue syndrome (CFS) is characterized by persistent mental and physical fatigue for at least 6 months. Its pathophysiology is unknown and there is no proven effective treatment. We describe three cases who fulfill the criteria of CFS, in whom a defect of neuromuscular transmission and dysautonomia are present and who respond to acetylcholine-esterase inhibition.

Case 1: 18-year-old female with a 3-year history of CFS. Response of compound-muscle-action potential, recorded using surface recording electrode, over left abductor pollicis brevis muscle, to repetitive nerve stimulation (RNS) at a rate of 10 Hz showed a 42% incremental response. Composite autonomic scoring system (CASS) showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2). Serological tests for Epstein-Barr virus (EBV) revealed positive antiviral capsid antigens (anti-VCA) immunoglobulins G (IgG). Oral pyridostigmine therapy (30 mg) resulted in marked improvement in symptoms.

Case 2: 28-year-old female with 10-year history of CFS. RNS, using identical protocol, showed a 60% incremental response over the same muscle. CASS showed mild cholinergic impairment (cardiovagal score: 1; sudomotor score: 2) and this patient was also positive for EBV. This patient responded dramatically to 10-mg pyridostigmine.

Case 3: 29-year-old female with a history of CFS for longer than 15 years. Repetitive stimulation, using identical paradigm to left abductor pollicis brevis muscle, showed a 42% incremental response. CASS showed mildly cholinergic impairment (cardiovagal score: 2; sudomotor score: 1). EBV antibody titers were positive. Patient responded to 30-mg pyridostigmine with an improvement in her fatigue.

These three cases generate the hypothesis that the fatigue in some patients with clinical CFS might be due to a combination of mild neuromuscular transmission defect combined with cholinergic dysautonomia. Support for this thesis derives from the improvement with cholinesterase inhibition.

Abstract:
https://www.ncbi.nlm.nih.gov/pubmed/14567934

Full paper:
https://www.pathophysiologyjournal.com/article/S0928-4680(03)00007-5/fulltext

 

Does anyone know of any publications Dr Systrom has on his work on the prevalence of SFN in ME/CFS and/or POTS/OI?

In Dr Oaklander's talk (on another thread, also very interesting) she mentions an abstract that he published with her and others about this but I've been unable to turn it up on Google.

 

Given the vast array of Symptoms present in ME/CFS, i would say that the hypothesis discussed here is applicable to a small number of ME/CFS Patients and quite probably looks at a Symptom, not the cause.

 

Welcome @mariovitali !

 

Small Fibre Neuropathy in FM has been known for 5 years.
Now SFPN in ME.
Is it still all in the research phase or is any place, other than the people connected with MGH/Oaklander/Systrom, actually diagnosing and treating this yet?
If not, given that the treatment is IVIG, how likely is this to happen do you think?
If alternative medications are being sought, this could be a while couldn't it.

 

I got diagnosed with SFN some years back and later went to a neurologist specializing in dysautomia. In the video, Dr. Systrom recommended that ME/CFS could look for doctors listed with Dysautonomia International, wasn’t it? The autonomic specialist I went to tried me on Mestinon, in addition to the Midodrine and fludrocortison I already take, but I quickly stopped—I think at the 10 mg dose—due to some side effect. I think it was an increase in aching. Any drug which moves me in that direction, I don’t accept.

(If it had caused nausea, headache, depression or insomnia, I would not take it at all or take it above whatever low dose enabled me to avoid the side effects, but that level has sometimes been considered sub-therapeutic. This doctor commented on my current doses of medications as “homeopathic levels”. I thought that was funny, as he meant it to be, though he was also expressing his frustration.

Anyway, it could be that some level of trouble from a drug is worth the benefit of a therapeutic dose, but I do not always feel up to pursuing it to find out. I have been so fed up with my symptoms that I don’t want to accept any more, even with a medication that could potentially help. However, for those who are more hopeful, flexible or sporting than I, trying a new drug that might contribute to treatment is certainly worthwhile.)

 

Thanks for relaying your experience with it @Sing

Yes, it was Dysautonomia International mentioned in the video and I've checked their site for physicians in Ontario, Canada. They have an interactive map and I found 4 doctors within a 125 km or so. I haven't checked them all out fully yet but one of them refuses to see ME patients. Nothing is ever straightforward with this illness. Why should this be any different?

 

Isn’t that amazing—a doctor who outright refuses to see ME patients! Is that even legal?

 

That is discrimination and against the Code of conduct. Here:

Physicians must comply with the Code, and the expectations of the College, when making any decision relating to the provision of health services. This means that physicians cannot discriminate, either directly or indirectly, based on a protected ground under the Code when, for example:

• Accepting or refusing individuals as patients;
• Providing existing patients with health care or services;
• Providing information or referrals to existing patients or those seeking to become patients; and/or
• Ending the physician-patient relationship.