Central Fatigue in Multiple Sclerosis (MS)

Abstract

In MS patients fatigue is manifested as a decrease in motor function, often associated with exercise. This decrease in muscle function is caused by inadequate central activation rather than peripheral abnormalities. Transcranial magnetic stimulation (TMS) studies have been used to detect central conduction abnormalities in subjects with definite MS. Previous work in our laboratory has demonstrated that these conduction changes are accentuated after fatiguing exercise. PURPOSE: To determine if cortical excitability is altered following fatiguing exercise in MS patients vs healthy controls. METHODS: Cortical excitability was assessed during motor tasks (finger flexion and extension) before and after fatiguing exercise (3-min maximal hand grip) using functional magnetic resonance imaging (fMRI). MS patients (n=5, mean age = 39.5 yr, Expanded Disability Status Score ranging from 1 to 6) were compared to controls (n=6, mean age 35.7). RESULTS: Activated cortical volume in the motor strip was significantly greater in MS patients compared to controls before (3947 ± 1073 vs 1624 ±227) and after (3150 ± 1042 vs 1774 ± 617) the fatigue paradigm. Cortical activation in MS patients was 143% and 77% higher for pre- and post-exercise, respectively, (p <0.05). Increased activated volume observed in MS patients is consistent with magnetic resonance spectroscopic imaging studies that demonstrate adaptive changes in the cerebral cortex consistent with axonal injury. Although pre- to post-exercise changes were not statistically significant, controls remained fairly stable while MS patients demonstrated a decrease in activated volume following exercise. The largest decreases were observed in the MS patients with greater disability. These results support previous TMS studies that indicate a reduction in cortical excitability with fatigue in individuals with MS. CONCLUSION: A similar study should be completed with a larger sample to verify these results. It may be possible to assess the effects of therapies (drug and rehabilitation) on development and recovery of central fatigue using this method.