Heart rate variability and fatigue in MS: two parallel pathways representing disseminated inflammatory processes?

Background Fatigue is a disabling symptom of multiple sclerosis. Its biological causes are still poorly understood. Several years ago, we proposed that fatigue might be the subjective representation of inflammatory processes. An important step for a straight-forward evaluation of our model would be to show that the level of fatigue is associated with vagal activation. The heart rate is under partial control of the vagus nerve. Using power spectrum analysis allows to separate, at least partly, sympathetic and parasympathetic impact on heart rate variability. Methods This narrative review summarizes the evidence for heart rate variability changes in MS patients, their relationship with fatigue and disease course. To do this, we conducted a literature search, including 45 articles relevant to the topic treated in this review. Results We illustrate that (1) inflammation leads to a change in cardiac behavior during acute and chronic phases, both in animals and in humans; (2) MS patients show changes of heart rate variability (HRV) that resemble those during acute and chronic inflammation due to multiple causes; (3) existing evidence favors a set of specific predictions about fatigue and parallel HRV changes; and (4) that MS-related brainstem lesions or neurological impairments do not completely explain HRV changes, leaving enough place for an explanatory relation between HRV and fatigue. Discussion We discuss the results of this review in relation to our model of fatigue and propose several observational and experimental studies that could be conducted to gain a better insight into whether fatigue and HRV can be interpreted as a common pathway, both reflecting activated autoimmune processes in MS patients.