MS and Fatigue: Possible Role of Autonomic Dysfunction

Abstract & Commentary

Source: Flachenecker P, et al. Fatigue in multiple sclerosis is related to sympathetic vasomotor dysfunction. Neurology. 2003;61:851-853.

Flachenecker and associates studied 60 patients with multiple sclerosis (MS) (mean age, 41.5; 72% female; 70% RRMS; mean disease duration, 12.8 years; median EDSS, 3.0) and 36 age- and sex-matched controls. Thirty-two of the MS patients were on immunomodulatory therapy, mainly with interferon-beta (n = 27; 45%). Patients taking beta-blockers, sympathomimetics, tricyclics, or alpha-sympatholytics were excluded.

Patients underwent standard autonomic function EKG and blood pressure tests to measure parasympathetic function (heart-rate responses to Valsalva maneuver, deep breathing, and active change in posture) and sympathetic vasomotor function (blood pressure responses to active change in posture and sustained handgrip). Fatigue was assessed by standardized questionnaires including the Fatigue Severity Scale and the Modified Fatigue Impact Scale with subscores for physical, cognitive, and emotional fatigue.

The median heart rate response to standing was significantly reduced, and blood pressure to handgrip tended to be lower in patients with MS compared to controls. The autonomic dysfunction was more pronounced in MS patients with higher fatigue scores.


To the clinician, fatigue in MS appears to be a universal complaint and often the most disabling symptom. The complex neurological substrate(s) underlying fatigue have been debated for years. This study corroborates a few earlier studies indicating that sympathetic vasomotor dysfunction may have a role in MS-related fatigue. Controlled clinical trials of sympathomimetics should be performed to test potential benefits for MS fatigue. The current clinical practice of treating fatigue with psychostimulants such as methylphenidate or modafinil is useful. — Brian R. Apatoff, Associate Professor of Neurology, New York Presbyterian Hospital-Cornell Campus, Assistant Editor, Neurology Alert.