News: 2023 August 05
Muscle issue research; DDN - biomarkers in ME/CFS; US ICD code for PEM update
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News:
Research into Muscle Dysfunction
Consequences of Sarcolemma Fatigue on Maximal Muscle Strength Production in Patients with ME/CFS was published Aug 3, 2023 and discusses muscle fatigability issues in patients who have ME. This study used 58 participants who fulfilled the International Consensus Criteria (ICC). It discussed possible causes for the muscle fatigability issue including:
“Muscle failure called “peripheral fatigue” may result from a failure of different metabolic processes such as the imbalance between oxygen demand and supply, the reduced excitation–contraction coupling, and the impaired muscle membrane excitability due to the altered flux of potassium through the sarcolemma… may have also a central origin resulting from a reduced central motor command to muscles…”
This research points to how this muscle issue could be used as a biomarker:
“In conclusion, this study suggest[s] that post-exercise sarcolemma fatigue often measured in ME/CFS patients could be the cause of muscle failure and MHGS [Maximal handgrip strength] measurement constitutes a good index of global muscle performance and fatigability in ME/CFS patients. This simple and unexpansive method could represent a potential screening tool.”
If I understood this correctly, there were two different patterns within this patient group. They compared 30 patients with and 28 without electromyography (EMG) abnormalities. EMG is a technique for evaluating and recording the electrical activity produced by skeletal muscles.
This difference between the two groups may be a result of issues with placement of the electrodes. The paper states this as a limitation: “we cannot give absolute normal or abnormal values of M wave configuration due to the variability of skin electrodes position and skin conductivity between patients.”
FYI - Sarcolemma is the plasma membrane of the muscle cell.
Note: The original description of ME included “muscle fatigability”. And the IC Primer states that patients have a
“pathological low threshold of physical and mental fatigability in response to exertion.”
This lack of stamina in the muscles has also been suggested as a biomarker in the 2021 Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS paper.
“Repeat HGS [hand grip strength] assessment is a sensitive diagnostic test to assess muscular fatigue and fatigability and an objective measure to assess disease severity in ME/CFS.”
This is a promising area of research which I think could be moved into the clinical area if doctors were aware to look. I do a grip strength test as part of my yearly physical (my doctor offers more in depth screening than most practices). I can see (and feel) the decline in muscle function as I repeat the hand grip test during the physical.
Article about "ME/CFS" in Drug Discovery News
I was interested to see Drug Discovery News (DDN) publish an article this week entitled Blood tests for CFS that included some fairly useful information. A search using "myalgic" shows they did a couple other articles about ME/CFS in 2017.
This article gives a fairly good overview about looking for biomarkers in "ME/CFS" as well as the importance of having biomarkers to test efficacy of drugs. It includes information about the nanoneedle from Ron Davis's team and the work of Maureen Hanson.
"Hanson and her team analyzed proteins in plasma and extracellular vesicles from 49 patients and 49 healthy controls. Using machine learning, they identified a set of 20 proteins that distinguished the two groups with 86 percent accuracy. Many of these proteins are related to immune function..."
It also includes the important point that we don't need a biomarker to test drugs. The article quoted Maureen Hanson:
“I have heard people say that we can't have clinical trials for ME/CFS because we don't have a molecular marker. In my mind, that is ridiculous. You can still have clinical trials using health surveys that have been vetted and tested that are used in other diseases to find out whether a drug is doing any good…"
The article also gives information about Alain Moreau, head of the Interdisciplinary Canadian Collaborative ME Research Network (ICanCME), developing a diagnostic tool based on circulating microRNA. His work includes finding a gentler way to induce post-exertional malaise.
"The team used an arm cuff that inflated and deflated to deliver a massage-like stimulation for 90 minutes. Even this gentler method triggered post-exertional malaise in patients with ME/CFS. "
Who is DDN?
Their website states: "DDN provides engaging stories about scientific breakthroughs that will help life science researchers develop diagnostic and therapeutic approaches for improving human health."
I was very disappointed that the article’s picture focused on "fatigue" and the title of the article used "chronic fatigue syndrome". Another indication that the systemic bias against ME runs deep in our society!
In regard to any research for biomarkers, I think it is important to make sure that researchers use stratified patient groups; starting with patient selection based on the ICC. We also have evidence that there are biological differences within ME subgroups so stratification is key to knowing what treatments apply to which patients. Stratifications should include: type of onset (sudden or gradual), length of time sick, gender, pre or post menopausal, etc.
To understand the importance of stratification, see some of the research listed under the stratification section in this ICC research list and in this Canadian Consensus Criteria (CCC) research list. Both lists are from the ME-ICC Info group on Facebook.
Those lists also notate whether a research finding may be useful as a biomarker.
Let's use what we have learned!
ICD Code for PEM Update
I was contacted on August 3, 2023 by Lisa McCorkill of the Patient-led Research Collaborative (PLRC) about the proposal to add post-exertional malaise (PEM) to the US ICD coding she is spearheading. Her message stated:
"Update: the PEM/PESE ICD-10-CM code proposed in March was not approved. It will be revisited at the upcoming September meeting with minor changes in response to feedback. We do not yet have final details on what the changes will be but will share when we do."
I have serious concerns about what this proposal could mean for people with myalgic encephalomyelitis. I submitted my concerns to the CDC last April in response to the original submission. I have no idea if the next proposal will take those concerns into account. I wrote about that in my article “Burying Myalgic Encephalomyelitis (M.E.) using ICD-codes” in the ME Global Chronicle.
To understand how this could impact patients outside of the ME community (who may not be aware this is happening), the ME-ICC Info group on Facebook created the following information sheet: Post-exertional Malaise (PEM) in Various Conditions.
There isn't much to be done until we know what the new proposal looks like and we may not know that until September.
I welcome feedback about news items people would like to see me cover.
Information provided here or in comments is not to be considered medical advice
Sources:
F. Retornaz, C. Stavris and Y. Jammes, Consequences of sarcolemma fatigue on maximal muscle strength production in patients with myalgic encephalomyelitis/chronic fatigue syndrome, Clinical Biomechanics (2023), https://doi.org/10.1016/j.clinbiomech.2023.106055
äkel, B., Kedor, C., Grabowski, P. et al. Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS. J Transl Med 19, 159 (2021). https://doi.org/10.1186/s12967-021-02774-w
Hannah Thomasy, PHD, Blood tests for chronic fatigue syndrome, Drug Discovery News, Aug 01, 2023, (July 2023, Internal Medicine) https://www.drugdiscoverynews.com/blood-tests-for-chronic-fatigue-syndrome-15723