Heart rate variability is differentially altered in multiple sclerosis: implications for acute, worsening and progressive disability

Valeria Studer, Camilla Rocchi, Caterina Motta, Benedetta Lauretti, Jacopo Perugini, Laura Brambilla, Lorena Pareja-Gutierrez, Giorgia Camera, Francesca Romana Barbieri, Girolama A Marfia, Diego Centonze, Silvia Rossi, Valeria Studer, Camilla Rocchi, Caterina Motta, Benedetta Lauretti, Jacopo Perugini, Laura Brambilla, Lorena Pareja-Gutierrez, Giorgia Camera, Francesca Romana Barbieri, Girolama A Marfia, Diego Centonze, Silvia Rossi

Abstract

Background: Sympathovagal imbalance has been associated with poor prognosis in chronic diseases, but there is conflicting evidence in multiple sclerosis.

Objectives: The objective of this study was to investigate the autonomic nervous system dysfunction correlation with inflammation and progression in multiple sclerosis.

Methods: Heart rate variability was analysed in 120 multiple sclerosis patients and 60 healthy controls during supine rest and head-up tilt test; the normalised units of low frequency and high frequency power were considered to assess sympathetic and vagal components, respectively. Correlation analyses with clinical and radiological markers of disease activity and progression were performed.

Results: Sympathetic dysfunction was closely related to the progression of disability in multiple sclerosis: progressive patients showed altered heart rate variability with respect to healthy controls and relapsing-remitting patients, with higher rest low frequency power and lacking the expected low frequency power increase during the head-up tilt test. In relapsing-remitting patients, disease activity, even subclinical, was associated with lower rest low frequency power, whereas stable relapsing-remitting patients did not differ from healthy controls. Less sympathetic reactivity and higher low frequency power at rest were associated with incomplete recovery from relapse.

Conclusions: Autonomic balance appears to be intimately linked with both the inflammatory activity of multiple sclerosis, which is featured by an overall hypoactivity of the sympathetic nervous system, and its compensatory plastic processes, which appear inefficient in case of worsening and progressive multiple sclerosis.

Keywords: Sympathetic nervous system; autonomic nervous system; autonomic nervous system disorder; neuronal plasticity; primary progressive multiple sclerosis; relapsing remitting multiple sclerosis.

Figures

Figure 1.
Figure 1.
Basal heart rate variability (HRV) parameters of the study subjects. The graphs show that there was no difference in basal HRV parameters between multiple sclerosis (MS) patients and healthy controls (HC), in terms of LF component (a), HF component (b) and LF/HF ratio (c). The same HRV parameters showed similar variations after tilting in both patients with MS and HC (d-f).
Figure 2.
Figure 2.
Progressive disease affects heart rate variability (HRV). Patients with progressive disease showed higher sympathetic tone at rest and lower sympathetic reactivity (a, b). Higher disease severity was associated with greater HRV alteration in progressive multiple sclerosis (PMS) subjects (c). *P < 0.05 with respect to healthy controls (HCs) and relapsing–remitting multiple sclerosis (RRMS) patients.
Figure 3.
Figure 3.
Sympathetic system is defective in active multiple sclerosis (MS). An altered low frequency (LF)/high frequency (HF) ratio with significantly lower LF power and higher HF power was found in the gadolinium (Gd)+ group compared to the Gd– group and healthy controls (HCs). Active MS was also associated with greater sympathetic reactivity. *P < 0.05 with respect to HCs.
Figure 4.
Figure 4.
Sympathetic system is ineffective in worsening multiple sclerosis (MS). Active not relapsing patients showed a higher increase of low frequency power (LFnu) after head-up tilt test (HUTT) with respect to relapsing subjects (a), despite comparable heart rate variability parameters at rest (b). Incomplete recovery from relapse was associated with lower LFnu increase after HUTT (c). LF/HF: low frequency/high frequency ratio. *P < 0.05 with respect to healthy controls; #P < 0.05 with respect to active not relapsing MS.

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