Muscle sodium content in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

Background Muscle fatigue and pain are key symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Although the pathophysiology is not yet fully understood, there is ample evidence for hypoperfusion which may result in electrolyte imbalance and sodium overload in muscles. Therefore, the aim of this study was to assess levels of sodium content in muscles of patients with ME/CFS and to compare these to healthy controls. Methods Six female patients with ME/CFS and six age, BMI and sex matched controls underwent 23Na-MRI of the left lower leg using a clinical 3T MR scanner before and after 3 min of plantar flexion exercise. Sodium reference phantoms with solutions of 10, 20, 30 and 40 mmol/L NaCl were used for quantification. Muscle sodium content over 40 min was measured using a dedicated plugin in the open-source DICOM viewer Horos. Handgrip strength was measured and correlated with sodium content. Results Baseline tissue sodium content was higher in all 5 lower leg muscle compartments in ME/CFS compared to controls. Within the anterior extensor muscle compartment, the highest difference in baseline muscle sodium content between ME/CFS and controls was found (mean ± SD; 12.20 ± 1.66 mM in ME/CFS versus 9.38 ± 0.71 mM in controls, p = 0.0034). Directly after exercise, tissue sodium content increased in gastrocnemius and triceps surae muscles with + 30% in ME/CFS (p = 0.0005) and + 24% in controls (p = 0.0007) in the medial gastrocnemius muscle but not in the extensor muscles which were not exercised. Compared to baseline, the increase of sodium content in medial gastrocnemius muscle was stronger in ME/CFS than in controls with + 30% versus + 17% to baseline at 12 min (p = 0.0326) and + 29% versus + 16% to baseline at 15 min (p = 0.0265). Patients had reduced average handgrip strength which was associated with increased average muscle tissue sodium content (p = 0.0319, R2 = 0.3832). Conclusion Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.

ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

“…Positive studies: oxidative and nitrosative stress, mitochondrial and bioenergetic dysfunction, as reviewed in detail elsewhere (197). Decreased muscle mass action potential (M-wave amplitude and duration) (198) and impaired energy metabolism (201). Disturbed muscle membrane function in motor units, demonstrated by nerve conduction studies (199), and possibly secondary to autonomic dysfunction (200).…”

Repeated Hand Grip Strength is an Objective Marker for Disability and Severity of Key Symptoms in Post-COVID ME/CFS

“…In line with this, histological studies of muscles in PCS revealed capillary injury and rarefication, mitochondrial changes, and inflammation [25,26]. A MRI study revealed higher sodium content in muscles of ME/CFS patients compared to healthy controls and a correlation with HGS suggesting impaired function of ion transport presumably due to hypoperfusion [27].…”

Myalgic encephalomyelitis/chronic fatigue syndrome from current evidence to new diagnostic perspectives through skeletal muscle and metabolic disturbances

“…A number of studies have pointed out the dysfunction of skeletal muscles in ME/CFS, as well as changes in the ME/CSF muscle on the molecular, 34 organelle, 213,214 cellular, 34,215 and tissue 216,217 levels. These include the phenotype of skeletal muscle cells, excitation–contraction cycle, biogenesis of mitochondria, 34 redox status, 214 bioenergetic function, 218 oxidative and nitrosative stress management, metabolic activities, 33 gene expression, protein synthesis, electrolyte content, 219 ss2‐adrenergic receptor function, 32 acid handling, 220 membrane function, 221 etc. The specific skeletal muscle‐derived metabolomic plasmatic profile opens a window of opportunity for biomarker identification.…”