Understanding neuromuscular disorders in chronic fatigue syndrome

Abstract

Muscle failure has been demonstrated in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Neurophysiological tools demonstrate the existence of both central and peripheral fatigue in these patients. Central fatigue is deduced from the reduced amplitude of myopotentials evoked by transcranial magnetic stimulation of the motor cortex as well as by the muscle response to interpolated twitches during sustained fatiguing efforts. An impaired muscle membrane conduction velocity assessed by the reduced amplitude and lengthened duration of myopotentials evoked by direct muscle stimulation is the defining feature of peripheral fatigue. Some patients with ME/CFS show an increased oxidative stress response to exercise. The formation of lipid hydroperoxides in the sarcolemma, which alters ionic fluxes, could explain the reduction of muscle membrane excitability and potassium outflow often measured in these patients. In patients with ME/CFS, the formation of heat shock proteins (HSPs) is also reduced. Because HSPs protect muscle cells against the deleterious effects of reactive oxygen species, the lack of their production could explain the augmented oxidative stress and the consecutive alterations of myopotentials which could open a way for future treatment of ME/CFS.

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome

“…The present observations confirm the existence of redox disorders in many ME/CFS patients [3][4][5][6][7][8][9][10][11][14][15][16]. These data also show that abnormal redox status is generally present in ME/CFS patients with abnormal muscle membrane excitability, in contrast to patients with no muscle abnormalities.…”

“…Several body systems including the muscular and nervous systems are affected in ME/CFS [3][4][5]. Potential causes of muscle dysfunction in ME/CFS patients may include oxidative stress with reduced heat-shock protein production.…”

“…Potential causes of muscle dysfunction in ME/CFS patients may include oxidative stress with reduced heat-shock protein production. Experimental evidence indicates that exercising skeletal muscles are often affected in ME/CFS Page 2 of 8 Jammes et al J Transl Med (2020) 18:173 because marked alterations in myopotential occur in response to direct muscle stimulation (M-wave) [5][6][7][8][9][10][11]. M-wave alterations show impaired muscle membrane excitability and begin early in the exercising muscles before culminating during the 10-min recovery period [6][7][8].…”

Recursive ensemble feature selection provides a robust mRNA expression signature for myalgic encephalomyelitis/chronic fatigue syndrome

“…Finally, evidence has emerged that oxidative stress levels are raised in ME/CFS, for example in response to exercise, perhaps causing some of the symptoms seen in ME/CFS 47 , 48 . DNA damage caused by exposure to ROS leads to mutagenesis or cell death, OGG1 specifically repairs this DNA damage.…”

Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

“…Finally, akin to critical illness, it has been suggested (but not yet trialed) to incorporate the upregulation of HSP into future treatments for ME/CFS (262). Studies have shown that ME/CFS is also characterized by impaired HSP production (263) whichcombined with O&NS and low-grade inflammation-could explain muscle dysfunction and exercise intolerance (264,265).…”