Fatigue in Multiple Sclerosis: General and Perceived Fatigue Does Not Depend on Corticospinal Tract Dysfunction.

Area of Science:

• Neuroscience
• Immunology
• Neurology

Background:

• Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disorder characterized by inflammation, demyelination, and axonal damage.
• Fatigue is a primary disabling symptom in MS, with poorly understood neurophysiological underpinnings.

Purpose of the Study:

• To investigate the neurophysiological mechanisms of fatigue in MS patients compared to healthy controls.
• To explore correlations between fatigue levels and neurophysiological changes induced by a fatiguing task.

Main Methods:

• A cohort of 17 MS patients and 16 healthy controls underwent neurophysiological assessments.
• Transcranial magnetic stimulation and peripheral electrical stimulation were used to evaluate corticospinal and peripheral functions before and after a handgrip fatiguing task.
• Fatigue levels were measured using the Fatigue Severity Scale, Fatigue Rating, dynamometry, and the Borg Rating of Perceived Exertion Scale.

Main Results:

• MS patients exhibited greater fatigue and central motor conduction time, alongside reduced motor cortex excitability and handgrip strength.
• In controls, fatigue state correlated with perceived fatigue and led to reduced motor evoked potentials, indicating central fatigue.
• MS patients did not show this correlation or reduction in motor evoked potentials, despite similar fatigue states.

Conclusions:

• Fatigue in MS appears to stem from neurophysiological mechanisms distinct from those observed in healthy individuals.
• The pathogenesis of MS fatigue may involve central abnormalities upstream of the primary motor cortex, rather than direct corticospinal dysfunction.
• These findings highlight unique neurophysiological pathways contributing to fatigue in multiple sclerosis.