To systematically evaluate the relationship between fatigue severity, autonomic symptom burden, and autonomic physiological markers in patients with multiple sclerosis (MS).

Autonomic dysfunction (AD) is common in patients with MS and is correlated with disability, disease duration, and progression. Previous investigations have shown up to 80% of patients with MS exhibit dysautonomia. However, few studies have examined the influence of these abnormalities on disabling patient-centered outcomes, such as fatigue.

We recruited patients with MS (EDSS<6) from the Salt Lake City region (via University Clinics and National MS Society) and administered the Fatigue Severity Scale (FSS) to identify patients with and without significant fatigue. Participants with FSS score <4 were considered to have mild to no fatigue (n=7), compared to FSS score > 4 (significant fatigue, n=8). Autonomic assessment, using the Composite Autonomic Symptom Score 31 (COMPASS 31) and standardized cardiovascular autonomic reflex testing was performed on all patients.  Autonomic measures were compared between fatigue and non-fatigue groups, as well as correlation analysis between FSS scores.

Clinical characteristics of sample: Mean age 47.4 years (range 76-31); 66% female; mean disease duration 12.7 years (range 1.4-30 years); mean EDSS 3.1 (range 1.5-6). There were no statistically significant differences in the above parameters between groups. COMPASS-31 scores were significantly greater in the significant fatigue group, compared to the low fatigue group (36.5 vs 10.0, p<0.01). High FSS scores significantly correlated with high COMPASS-31 scores (r= 0.74, p<0.05).  Similarly, the significant fatigue group exhibited greater BP variability at rest, as well as greater HR on tilt table testing compared to the low fatigue group.

While the pathophysiology of MS-related fatigue remains unclear, our data suggests that AD may represent potential physiological mechanisms for at least a portion of patient-reported fatigue and importantly could serve as a potential treatment target.