Preprint Beyond pain: Using Unsupervised Machine Learning to Identify Phenotypic Clusters of Small Fiber Neuropathy 2024 Murin et al

Hoopoe said:
I found this interesting because it claims that in small fiber neuropathy, most patients had intense fatigue, myalgia, and subjective weakness and lower intensity of neuropathic pain.
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Not sure what is meant by lower intensity of neuropathic pain. Cluster 1 looks to have intense pain and cluster 3 less pain with intense fatigue. Cluster 1 and cluster 3 seem to have similar levels of fatigue.
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Also:
While previous studies showed higher intensity pain in large fiber- as compared to small fiber neuropathy patients, comparisons between the MFN and SFN cohorts yielded no differences in symptoms frequency or severity.
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Cluster 1 and cluster 3 look very similar for fatigue based on the data. If anything Fig A vs FigC shows a higher intensity of fatigue on average for cluster 1, with what look like similar levels of prevalence of fatigue in Clusters 1 & 3 - Fig D & Fig F.

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Patients in cluster 1 suffered from many symptoms at high intensities (Fig. 4A) with an average of 7.5/10 for “numbness” and 7.2/10 for “burning pain” (Fig. 4A). Fatigue (average 7.2/10) and muscle cramps (average 7.1/10).
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The third cluster (n = 60) was characterized by patients who exhibited mostly symptoms of moderate severity with one or two symptoms of higher intensity (Fig. 3). Upon further inspection, patients in cluster 3 had especially severe fatigue (average 5.6; Figs. 3, 4C),
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So their wording seems off. Why highlight that cluster 3 had especially severe fatigue (5.6) when cluster 1 had a higher average value of fatigue (7.2)?

I don't understand their method of "Unsupervised machine learning" but it sure looks like it's based on the surveys. If that is the case, then all this paper is telling us is that MFN vs SFN is indistinguishable from each other by looking at symptoms, and SFN causes widespread pain and fatigue and other symptoms, which many people may not be aware off.

The clusters seem meaningless to me for interpreting anything.

This seemed interesting as lipids has been highlighted quite a bit in ME.
The most common comorbidity was hyperlipidemia (33%). In line with hyperlipidemia being frequently observed, the most frequent abnormal laboratory value was elevated lipids in 62.3% of patients.
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The biggest cluster in our cohort was characterized by fatigue, which was more severe and prevalent than the other symptoms in the cluster. This is in accord with a previous study that also revealed fatigue as one of five most prevalent symptoms in SFN19. Fatigue is a well described symptom in several neurological disorders, including multiple sclerosis32, stroke33, Parkinson’s Disease and other movement disorders34, but is rarely assessed in standard neuropathic pain screening questionnaires35. Recent work identified associations between chronic fatigue syndrome and SFN in post-acute COVID-19 patients36 and between reduced IENFD and fatigue in complex regional pain syndrome37.

Here, we extend this finding by suggesting that fatigue is a common, high intensity symptom of SFN for which treatments should be developed. The pathophysiology of fatigue has been hypothesized to be secondary to an overactive or dysregulated immune response38 resulting in both higher and lower levels of pro- inflammatory cytokines39. Given the more generalized localization of symptoms and the high intensity of fatigue in most patients in cluster 3, it is tempting to speculate that an immune dysfunction contributes to the symptom presentation in that cluster.
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wigglethemouse said:
Cluster 1 and cluster 3 look very similar for fatigue based on the data.
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A cluster 3 patient would be a patient for whom fatigue is the worst symptom. They would have other symptoms but usually of low to moderate intensity. I always thought of sensory nerve abnormalities (pain, abnormal sensations, lack of sensation) as being the main symptoms of SFN but this study shows something different.
 
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It's certainly interesting and raises many questions for me. Was there some biased selection of the participants? How common is a finding of SFN in people who would rate themselves as healthy? How many of the people in the Type 3 group would meet ME/CFS diagnostic criteria?

SFN has been raised as a comorbidity of ME/CFS for a while now. I'm not sure that we have any really good data on its prevalence though. It's too easy for the selection of participants to be biased.

Possibly, people who have some pins and needles, the occasional burning pains in their feet but are otherwise healthy might just ignore those symptoms, thinking 'everyone probably gets that'. I think that would have been the case for me. Whereas if someone is debilitated by fatigue/PEM/fatiguability, they might start assessing and reporting every symptom they have, in order to find a clue?
 
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The most common comorbidity was hyperlipidemia (33%). In line with hyperlipidemia being frequently observed, the most frequent abnormal laboratory value was elevated lipids in 62.3% of patients.
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According to standard annual bloods my lipids have always been within normal, apart from a couple of borderline results over the years.

Plus a couple of times my fasting sugar levels have been borderline, but the follow up test for diabetes has been negative.

Only consistently abnormal standard lab result for me is alkaline phosphatase, which is always high (typically around 140-160, IIRC), and has been since at least my mid-20s.
 
Sean said:
According to standard annual bloods my lipids have always been within normal, apart from a couple of borderline results over the years.

Plus a couple of times my fasting sugar levels have been borderline, but the follow up test for diabetes has been negative.

Only consistently abnormal standard lab result for me is alkaline phosphatase, which is always high (typically around 140-160, IIRC), and has been since at least my mid-20s.
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If ALP is high how is your GGT ?
If it's not high as well then it can be indicative of bone issues / vit D deficiency
( Took a look at LFTs when daughter had low vitD)

GGT being high has been mooted as being potentially indicative of early NAFLD , and perhaps insulin resistance .
 
Don't know if I have been tested for GGT levels. But I don't think there have been any liver function tests.

The high ALP was originally noted by the professor of immunology who diagnosed me with ME/CFS. Neither he nor any other clinician since has thought it something worth following up on, and I have asked about it a number of times. Main responses have been that it was too unspecific a finding to tell us much, particularly in the absence of other findings or symptoms, and that is was not so high as be a significant concern. The normal range is not well defined and can very quite a bit, and depending on which authority you read it can overlap with my range, and my understanding is that it is not considered worth following up on until it is above about 200, particularly in the absence of other signs or indicators. All complicated by having osteoarthritis, and also getting old (early 60s), both of which can be associated with raised ALP.

Will ask my doctor about GGT next visit.
 
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