Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology

Highlights:

• Myopathic changes in qEMG and/or increased jitter in sfEMG were seen in 63% of 84 patients with Long COVID neuromuscular symptoms.

• Low quality of life score correlated with higher mean jitter values in sfEMG but not with qEMG measures.

• Electron microscopy showed damage of terminal nerves and motor endplate.Abstract:

Objective: To describe neurophysiological abnormalities in Long COVID and correlate quantitative electromyography (qEMG) and single fiber EMG (sfEMG) results to clinical scores and histopathology.

Methods: 84 patients with non-improving musculoskeletal Long COVID symptoms were examined with qEMG and sfEMG. Muscle biopsies were taken in a subgroup.

Results: Mean motor unit potential (MUP) duration was decreased in ≥1 muscles in 52% of the patients. Mean jitter was increased in 17% of the patients in tibialis anterior and 25% in extensor digitorum communis. Increased jitter was seen with or without myopathic qEMG. Low quality of life score correlated with higher jitter values but not with qEMG measures. In addition to our previously published mitochondrial changes, inflammation, and capillary injury, we show now in muscle biopsies damage of terminal nerves and motor endplate with abundant basal lamina material. At the endplate, axons were present but no vesicle containing terminals. The post-synaptic cleft in areas appeared atrophic with short clefts and coarse crests.

Conclusions: Myopathic changes are common in Long COVID. sfEMG abnormality is less common but may correlate with clinical scores. sfEMG changes may be due to motor endplate pathology.

Significance: These findings may indicate a muscle pathophysiology behind fatigue in Long COVID.

Source: Jane Agergaard, Benjamin Yamin Ali Khan, Thomas Engell-Sørensen, Berit Schiøttz-Christensen, Lars Østergaard, Eva K. Hejbøl, Henrik D. Schrøder, Henning Andersen, Jakob Blicher, Thomas Holm Pedersen, Thomas Harbo, Hatice Tankisi,
Myopathy as a cause of Long COVID fatigue: Evidence from quantitative and single fiber EMG and muscle histopathology,
Clinical Neurophysiology, 2023, ISSN 1388-2457, https://doi.org/10.1016/j.clinph.2023.01.010.
https://www.sciencedirect.com/science/article/pii/S1388245723000196 (Full text)

Single fibre EMG studies in chronic fatigue syndrome: a reappraisal

Comment on: Single fibre EMG studies in chronic fatigue syndrome: a reappraisal. [J Neurol Neurosurg Psychiatry. 1994]

 

We were interested in the short report from Roberts and Byrne concerning single fibre EMG studies in chronic fatigue syndrome. They concluded that there was no evidence of abnormality at the terminal axon, neuromuscular junction, or muscle membrane in patients with chronic fatigue syndrome-a finding that concurs with our own of essentially normal jitter in 34 of 35 patients with chronic unexplained fatigue. We did detect some evidence of raised fibre density in a small subgroup of patients with pronounced myalgia who also had mild abnormalities on muscle biopsy.

Raised fibre density is usually a result of collateral sprouting after reinnervation, but can also be due to fibre splitting as can occur in some myopathic states. Therefore we believe that fibre density estimation performed in addition to jitter measurement adds considerably to the information obtained from single fibre EMG studies.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073160/pdf/jnnpsyc00039-0137a.pdf

 

Source: Connolly S, Fowler CJ. Single fibre EMG studies in chronic fatigue syndrome: a reappraisal. J Neurol Neurosurg Psychiatry. 1994 Sep;57(9):1157. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1073160/

 

Single fibre EMG studies in chronic fatigue syndrome: a reappraisal

Abstract:

Single fibre EMG studies were carried out on the right extensor digitorum communis muscle in 30 subjects with chronic fatigue syndrome and in 30 age and sex matched controls. Abnormal jitter was seen in five patients with chronic fatigue syndrome. Slight but significant differences between the mean consecutive differences in the remainder of the chronic fatigue subjects and the control subjects were recorded. Overall the differences were so minor that it seems unlikely that a disturbance of neuromuscular function as reflected by jitter measurement has a pathogenetic role. It is suggested that the increased jitter seen may be explained by the effects of the variability of motor unit firing rates on the myogenic component of the jitter.

Comment in: Single fibre EMG studies in chronic fatigue syndrome: a reappraisal. [J Neurol Neurosurg Psychiatry. 1994]

 

Source: Roberts L, Byrne E. Single fibre EMG studies in chronic fatigue syndrome: a reappraisal. J Neurol Neurosurg Psychiatry. 1994 Mar;57(3):375-6. http://www.ncbi.nlm.nih.gov/pubmed/8158191

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1072834/pdf/jnnpsyc00033-0119.pdf

 

Chronic fatigue: electromyographic and neuropathological evaluation

Abstract:

Single fibre electromyography of extensor digitorum communis muscle (EDC) was performed on 35 patients with chronic fatigue, the majority of whom also had creatine kinase estimation and biopsy of EDC.

The subjects were categorised as having an acute-onset post-viral fatigue syndrome, a non-specific chronic fatigue or possible muscle disease in view of pronounced myalgia.

Of 11 subjects who had myalgia as a significant symptom, abnormalities in fibre density were found in 6, and 5 of these had some non-specific abnormalities on muscle biopsy, with creatine kinase levels being normal in all cases. Fibre density estimation may be a useful way of identifying a subgroup of chronic fatigue sufferers with a possible primary muscle disorder.

 

Source: Connolly S, Smith DG, Doyle D, Fowler CJ. Chronic fatigue: electromyographic and neuropathological evaluation. J Neurol. 1993 Jul;240(7):435-8. http://www.ncbi.nlm.nih.gov/pubmed/8410086