Vertical saccadic slowing is associated with fatigue in multiple sclerosis

Area of Science:

• Neuroscience
• Ophthalmology
• Neurology

Background:

• Fatigue is a primary disabling symptom in multiple sclerosis (MS), often uncorrelated with physical disability.
• Central fatigue in MS is hypothesized to stem from dysfunction in brainstem arousal pathways, such as the Ascending Reticular Activating System (ARAS).
• Vertical saccades, originating in the mesencephalon, interact with arousal networks, suggesting their potential as an objective fatigue marker.

Purpose of the Study:

• To investigate the correlation between vertical saccadic parameters and fatigue severity in MS patients.
• To adjust for confounding factors including cognitive impairment and affective symptoms in the analysis.
• To explore the utility of vertical saccades as a biomarker for central fatigue in MS.

Main Methods:

• Included 44 MS patients (61.4% female, mean age 49.0 years, median EDSS 2.0).
• Analyzed the relationship between vertical saccadic peak velocity and fatigue severity.
• Employed multivariable regression models, adjusting for age, sex, cognition, lesion burden, depression, and anxiety.

Main Results:

• Fatigue severity showed a significant inverse association with vertical saccadic peak velocity, particularly for upward movements (r = -0.45, p < 0.01).
• Slower upward vertical peak velocity independently predicted greater fatigue severity, even after adjusting for multiple clinical and demographic factors (β = -0.0068, p = 0.028).
• This association remained significant across various sensitivity analyses, including adjustments for disease phenotype and infratentorial lesions.

Conclusions:

• Increased fatigue severity in MS is independently associated with slower upward vertical saccadic peak velocity.
• Vertical saccadic dynamics show promise as an objective correlate for central fatigue in MS.
• Findings support a pathophysiological link between central fatigue and mesencephalic arousal network dysfunction in MS.