Motor Fatigue Mechanisms in Multiple Sclerosis

Motor fatigue in multiple sclerosis arises from the interplay of central and peripheral processes that impede voluntary movement over time. Demyelination and axonal loss in the corticospinal tract slow neural conduction and reduce central motor drive, while compensatory synaptic changes in cortical networks may transiently preserve function. Concurrently, muscle perfusion deficits and mitochondrial dysfunction contribute to peripheral fatigability by altering energy metabolism in working fibres. Disruption of autonomic regulation further exacerbates exercise intolerance through impaired cardiovascular and thermoregulatory responses. Clinically, fatigue manifests both as a subjective sense of exhaustion and as performance fatigability, the measurable decline in motor output during sustained activity. Understanding these mechanisms has broad implications for the design of rehabilitative strategies, pharmacological interventions and assistive technologies aimed at improving daily function and quality of life for people with multiple sclerosis.

Research from Nature Portfolio

Recent studies have employed standardised walking tests to disentangle trait and state dimensions of fatigue in multiple sclerosis. Against able-bodied controls, participants with multiple sclerosis reported higher baseline (trait) fatigue yet exhibited comparable immediate declines (state fatigue) during six-minute and ten-metre walk tests. Crucially, patients experienced prolonged post-test fatigability, indicating a delayed recovery of motor performance. These findings support the use of simple gait assessments to capture both enduring fatigue and acute performance decline, highlighting the need for interventions that target sustained motor endurance rather than momentary exertion alone.

Motor Fatigue Mechanisms in Multiple Sclerosis publication trend

The graph below shows the total number of articles in motor fatigue mechanisms in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Fatigability: The measurable decline in motor performance during sustained activity.

Trait fatigue: A chronic, baseline perception of exhaustion reported by an individual.

State fatigue: The immediate sensation of tiredness experienced during or after exertion.

Transcranial magnetic stimulation (TMS): A non-invasive technique that uses magnetic fields to stimulate cortical motor areas.

Motor evoked potential (MEP): The electrical response recorded from muscles following TMS of the motor cortex.

Corticospinal tract: The white-matter pathway transmitting motor commands from the cortex to spinal motor neurons.

Diffusion tensor imaging (DTI): An MRI technique that measures the directional diffusion of water to infer white-matter integrity.

References

1. Fatigue insights from walking tests in spinal cord injury and multiple sclerosis individuals. Scientific Reports (2024).
2. Meaningful digital biomarkers derived from wearable sensors to predict daily fatigue in multiple sclerosis patients and healthy controls. iScience (2024).
3. The corticospinal tract in multiple sclerosis: correlation between cortical excitability and magnetic resonance imaging measures. Journal of Neural Transmission (2024).
4. Transcranial Magnetic Stimulation as a Potential Biomarker in Multiple Sclerosis: A Systematic Review with Recommendations for Future Research. Neural Plasticity (2019).