The role of clinical neurophysiology in the definition and assessment of fatigue and fatigability.
Tankisi, Hatice, Versace, Viviana, Kuppuswamy, Annapoorna et al. · Clinical neurophysiology practice · 2024 · DOI
Quick Summary
This review article explains how doctors and researchers can better understand fatigue and 'fatigability'—the reduced ability to sustain physical or mental effort. The authors describe different types of tests that can measure these problems objectively by looking at how the brain, nerves, and muscles work, rather than relying only on what patients report. These specialized tests may help identify the actual cause of fatigue in different conditions, including long COVID and ME/CFS.
Why It Matters
For ME/CFS patients, this framework is crucial because fatigue and post-exertional malaise represent the core diagnostic features, yet objective biomarkers remain poorly defined. This review provides clinicians and researchers with practical guidance on which neurophysiological tests may help distinguish ME/CFS-specific mechanisms (potentially central or muscle-based) from other causes of fatigue, potentially enabling better diagnosis and targeted treatment.
Observed Findings
Central fatigability can be assessed using twitch interpolation, motor cortex stimulation (transcranial magnetic stimulation), EEG/MEG, and readiness potentials.
Peripheral fatigability can be measured via surface EMG, needle EMG, single-fiber EMG, and nerve conduction studies.
Fatigue occurs across diverse neurological and systemic disorders with differing pathological mechanisms.
Fatigue often includes a psychological component alongside physical causes.
Nearly all neurophysiological tests mentioned can be used to objectively measure fatigability in various disease states.
Inferred Conclusions
Neurophysiological testing can help identify whether fatigue originates from central nervous system dysfunction, peripheral nerve/muscle dysfunction, or psychological factors.
A structured clinical approach using appropriate neurophysiological biomarkers may enable clearer differentiation of fatigue types and their origins, leading to more targeted treatments.
Objective biomarkers are needed to complement subjective patient reports and improve diagnosis across long-term illnesses including long COVID.
Remaining Questions
Which specific neurophysiological tests are most sensitive and specific for ME/CFS fatigue and post-exertional malaise?
What This Study Does Not Prove
This review does not provide original evidence that specific neurophysiological tests definitively diagnose ME/CFS or demonstrate which tests are most sensitive/specific in ME/CFS populations specifically. It also does not prove that any single biomarker can fully explain ME/CFS fatigue; the condition likely involves multiple biological systems whose interactions remain unclear.