Petter et al. (2022)
- Authors: Elisabeth Petter, Carmen Scheibenbogen, Peter Linz, Christian Stehning, Klaus Wirth, Titus Kuehne, Marcus Kelm.
- Institutes: Institute of Medical Immunology, CharitĂ© UniversitĂ€tsmedizin Berlin, Germany; Institute of Computer-Assisted Cardiovascular Medicine, CharitĂ© UniversitĂ€tsmedizin Berlin, Germany; Department of Congenital Heart Disease, German Heart Center Berlin, Germany; Institute of Radiology, Friedrich-Alexander-UniversitĂ€t Erlangen-NĂŒrnberg (FAU), University Hospital Erlangen, Germany; Philips Healthcare, Hamburg, Germany; Institute of General Pharmacology and Toxicology, University Hospital Frankfurt am Main, Goethe-University, Frankfurt am Main, Germany; Berlin Institute of Health (BIH), Berlin, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site, Berlin, Germany.
- Publisher: Journal of Translational Medicine
- Link: DOI
Summary
This study provides the first direct, non-invasive evidence of a âsodium overloadâ in the muscles of ME/CFS patients. This finding supports the theory that impaired blood flow and cellular energy production lead to an inability of muscle cells to properly regulate electrolytes. This excess sodium, which worsens after even brief exertion, was directly linked to reduced muscle strength and offers a plausible biological explanation for key symptoms like muscle pain, weakness, and post-exertional malaise. Although this was a very small pilot study, it successfully demonstrates a new method for observing a key pathological process in ME/CFS and strengthens the case for targeting ion channel dysfunction in future treatment research.
What was researched?
This study aimed to assess and compare the sodium content in the lower leg muscles of patients with ME/CFS and healthy controls. The researchers measured sodium levels both at rest (baseline) and over a 40-minute period following a brief, standardized leg exercise, and correlated these findings with handgrip strength.
Why was it researched?
Muscle fatigue and pain are core symptoms of ME/CFS. Previous evidence points towards hypoperfusion (reduced blood flow) in ME/CFS, which is hypothesized to cause an electrolyte imbalance, specifically an overload of sodium in the muscles. This study was designed to directly test this hypothesis by non-invasively measuring muscle sodium content.
How was it researched?
This was a small pilot study involving six female ME/CFS patients and six age, BMI, and sex-matched healthy controls. The researchers used a specialized magnetic resonance imaging technique (-MRI) on a clinical 3T scanner to quantify sodium content in five different muscle compartments of the left lower leg. Measurements were taken before and repeatedly for 40 minutes after a 3-minute anaerobic plantar flexion exercise (heel raises), and handgrip strength was also assessed.
What has been found?
At baseline, ME/CFS patients had significantly higher tissue sodium content in all five lower leg muscle compartments compared to healthy controls. Following exercise, sodium content increased in both groups, but the increase was more pronounced and the recovery was slower in the ME/CFS group. Patients also exhibited reduced handgrip strength, and there was a significant inverse correlation: higher average muscle sodium content was associated with lower handgrip strength.
Discussion
The authors acknowledge that the primary limitation of this research is its very small sample size, as it was a preliminary pilot study. They also note that the results may have been influenced by the baseline immobility of the patients and potential variations in exercise intensity, which could be better controlled in future studies using an MRI-compatible exercise apparatus. The specific MRI protocol used was better at measuring extracellular sodium, and the authors recommend different techniques for future studies to more accurately differentiate between intracellular and extracellular sodium.
Conclusion & Future Work
The study concludes that -MRI confirms the hypothesis of increased sodium content in the muscles of ME/CFS patients, both at rest and after exercise. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and could open up new avenues for diagnostic and therapeutic strategies. The authors state that these encouraging results warrant further research with larger patient populations and refined methodologies.