Dynamics of saccade parameters in multiple sclerosis patients with fatigue

Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis (MS). Its pathophysiology remains poorly understood and objective measures to quantify fatigue are unavailable to date. To investigate whether analysis of ocular motor movements can provide diagnostic information in MS patients with fatigue, 37 MS patients (21 female, age 44 +/- 9 years) and 20 age- and gender-matched healthy controls were prospectively recruited. Fatigue was assessed with the fatigue severity scale (FSS). Twenty-five MS patients were fatigued (defined as FSS >/= 4) and 12 MS patients were not. Subjects performed a saccadic fatigue task that required execution of uniform saccades over a period of 10 min. Saccadic amplitude, latency and peak velocities during the task were analysed and selected parameters were tested in a receiver operating characteristic (ROC) analysis. Fatigued patients showed a significantly larger decrease of saccadic peak velocity and amplitude when compared to patients without fatigue and healthy controls. Furthermore, fatigued patients showed significantly longer latencies compared to non-fatigued patients and healthy controls. Peak velocity change over time and latencies correlated with FSS scores. The best parameter to discriminate between fatigued and non-fatigued patients was peak velocity change over time (ROC; area under the curve = 0.857). Assessment of peak velocity, amplitude and latency in a saccade fatigue task is a promising approach for quantifying fatigue in MS patients

Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue

BACKGROUND: Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes. OBJECTIVE: We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density. METHODS: In 44 patients with relapsing-remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed. RESULTS: In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex. CONCLUSION: Fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis