Fatigue is a common and disabling symptom in patients with MS and has been associated with decrease in quality of life and employment, yet the cause of MS-related fatigue remains unknown. Numerous potential mechanisms have been proposed, including contributions from demyelination, central conduction block, axonal injury, inflammatory mediators, neuroendocrine dysfunction and autonomic regulatory systems. Given that few studies have directly examined the influence of autonomic dysfunction (AD) on MS-related fatigue, our aim was to compare cardiovascular autonomic measures in MS patients with and without significant fatigue.

Patients with an MS diagnosis and EDSS≤ 6 were recruited from the Salt Lake City; the Fatigue Severity Scale (FSS) was used to identify patients with and without significant fatigue. FSS score <4 was considered to indicate minimal fatigue (n=8), whereas FSS score >4 indicative of significant fatigue (n=11). Autonomic assessment, using the Composite Autonomic Symptom Score 31 (COMPASS-31) and standardized cardiovascular autonomic testing, including quantitative analysis of heart rate and blood pressure variability were performed on all patients. Autonomic measures were compared between fatigue and non-fatigue groups.

Clinical characteristics: mean age 49.3 years (31-76); 68% female; mean disease duration 14.8 years (1.4-42 years); mean EDSS 3.0 (1.5-6). There were no statistically significant differences in the above parameters between groups. Autonomic symptoms (COMPASS-31) scores were significantly greater in the fatigue group, compared to the minimal fatigue group (25.1 vs 9.8, p<.01). The fatigue group exhibited greater BP variability at rest, as well as greater HR increment on head-up tilt testing compared to the minimal fatigue group.

This pilot study supports the possibility that cardiovascular AD is associated with patient-reported fatigue in MS patients, and could serve as a potential treatment target.