Pre-print Small Fiber Neuropathy after COVID-19: A Key to Long COVID Abstract Objectives: Report a case series of new onset small fiber neuropathy (SFN) after COVID-19 treated with intravenous immunoglobulin (IVIG). SFN is a critical objective finding in long COVID and amenable to treatment. Methods: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We documented demographics, symptoms, treatments, diagnostics, and clinical response to treatment. Results: Sixteen patients were diagnosed with length dependent or independent SFN on skin biopsy (median age 47, 75% female, 75% Caucasian). Among the nine patients tested for autoantibodies, six were positive for either trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor 3 (FGFR3). Eight patients underwent treatment with IVIG and experience significant clinical improvement in their neuropathic symptoms. 92% of patients reported post-exertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and six patients underwent invasive cardiopulmonary exercise testing (iCPET), which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Discussion: Here we present preliminary evidence that SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating post-infectious small fiber neuropathy. https://www.medrxiv.org/content/10.1101/2023.11.07.23297764v1 Link to published version: Small Fiber Neuropathy after COVID-19: A Key to Long COVID, 2023, McAlpine et al
Since almost everyone has had Covid now I do not see how cases of small fibre neuropathy can be attributed to the Covid. They may just be cases of neuropathy. The report on use of IvIg is uncontrolled so useless. CPET has been shown to be different statistically in ME patients in some studies but I not sure how it is used to indicate neuromuscular dysregulation and dysautonomia. Not a very helpful report.
Ignoring the unblinded treatment, the CPET results and the small sample size, which all don't seem too meaningful, from what I've understood, your more general point of criticism is mainly in regards to SFN and how it is diagnosed based on counting some lines under a microscope via a tissue sample. Do you think a more general focus on neuropathy (not that I'd know when fibers are considered to be "Small Fibers" within the diagnostic process of SFN) would be more fruitful? Especially given that I'd also imagine (or at least hope) most people with LC/ME/CFS that are part of studies, would have undergone a standard nerve conduction study and electromyogram with negative results (which is the case in this study as well). In a chronic condition (not that that is apparent in this study, especially as I can't see an illness duration) with an infectious onset I'd assume it should be very possibly to determine patients that have developed permanent symptoms that appear to be of neuropathic nature. At least I don't see why this would be less reliable than any other symptom reporting. There would probably have to be some longitudinal data as I'd assume neuropathy could also be quite self-resolvent in LC, especially for patients of a short illness duration (at least I'm assuming short lived neuropathy exists and could even possibly be induced, for example by prescribing Thiamazole to a large group of people, without that being useful in any manner). This is more of a general question rather than specific to this study, especially since a large chunk of the patients in this study were also hospitalized and there's also a large chunk of diabetic and pre-diabetic patients.
I am not questioning the diagnosis of neuropathy here, just the labelling of it as post-Covid. We are all post-Covid these days so these may just be people who got their neuropathy around that time - nothing to do with the Covid.
This doesn’t seem particularly specific to neuropathy though or if so why would that be the case? Any ideas how to do things differently?
No it isn't specific to neuropathy. It is a problem for any unexplained symptoms that might be attributed to Covid. It is a bit like calling them 'Long 2019 disease'. We all had 2019 so all symptoms could be blamed on 2019.
Now published as — Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19 Lindsay McAlpine , Adeel S Zubair, Phillip Joseph, Serena Spudich OBJECTIVES To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment. METHODS A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention. RESULTS Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; p = 0.02). DISCUSSION Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN. CLASSIFICATION OF EVIDENCE This study provides Class III evidence. It is a retrospective cohort study. Link | PDF (Neurology Neuroimmunology & Neuroinflammation)
It is not used to indicate that via the mechanism of the dysfunction of the autonomic nerves that control the constriction of veins (constricting insufficiently), leading to reduced return to the heart and another dysautonomic feature causing reduced blood flow to muscles (via something called arterio-venous shunts), with both resulting in exercise intolerance? Isn’t that the proposed mechanism?
This study is one that addresses the above point: Insights From Invasive Cardiopulmonary Exercise Testing of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome https://journal.chestnet.org/article/S0012-3692(21)00256-7/fulltext This study is discussed with some excerpts and media in a thread over at the Phoenix Rising forum; if I’m allowed to link to that I will.
Thread here: Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS, 2021, Joseph et al You can link public posts from other social media including PR.
