Cardiac Autonomic Modulation Is Different in Terms of Clinical Variant of Multiple Sclerosis

Abstract

This study evaluates whether the cardiac autonomic response to head-up tilt test (HUTT) differs between patients with relapsing-remitting multiple sclerosis (RRMS) and those with progressive MS (PMS) as compared to healthy controls (HC). Baroreflex sensitivity, cardiac parameters, heart rate (HRV) and blood pressure variability (BPV) were compared between 28 RRMS, 21PMS and 25 HC during HUTT. At rest, PMS patients had higher values of the sympathovagal ratio, a low-frequency band HRV (LFnu-RRI) and lower values of parasympathetic parameters (HFnu-RRI, HF-RRI) compared to RRMS and HC. Resting values of cardiac parameters were significantly lower in RRMS compared to PMS patients. No intergroup differences were observed for post-tilt cardiac and autonomic parameters, except for delta HF-RRI with lower values in the PMS group. The MS variant corrected for age, sex and Expanded Disability Status Scale (EDSS) score was an independent predictor of changes in the sympathovagal ratio as measured by HRV. Furthermore, a higher overall EDDS score was related to a higher sympathovagal ratio, lower parasympathetic parameters at rest, and decrease post-tilt changes of the sympathovagal ratio of sBP BPV. Autonomic imbalance is markedly altered in the MS patient group compared to control changes were most pronounced in the progressive variant of MS disease. The MS variant appeared to have a potential influence on cardiac autonomic imbalance at rest.

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“…In the study by Studer et al [63], disease severity was associated with increased disruption of sympathetic reactivity during head-up tilt test in PPMS patients, while no difference was found between RRMS patients and HC. Likewise, in the study by Zawadka-Kunikowska et al [79], a higher overall EDSS score was linked to a higher sympathovagal ratio at rest and lower parasympathetic parameters at rest in variant-undefined MS patients. Other investigators did not find a similar significant difference [35,53,54,61].…”

“…Progression of the disease was reported to correlate with increased parasympathetic dysfunction [77]. Others, however, did not observe changes in HRV parameters in prolonged MS [54,56,[76][77][78][79]. A study including RRMS patients, determined that those with more than 5 years since formal diagnosis had a stronger decrease in PANS-related HRV than those with less than 5 years from diagnosis [52].…”

“…HRV impairment has also been connected to diseaserelated functional impairments. In MS, lower PANS activity [60,79], and SNS hyperactivity [63] are more apparent with increasing severity of functional impairments, as measured by the Expanded Disability Status Scale (EDSS). Accordingly, less affected MS patients are found to preserve higher levels of HRV [60].…”

“…It should be noted that in some of the studies described above [58,61,79], patients took an immunomodulating medication "Fingolimod" as a treatment for RRMS. Fingolimod and various other immunomodulating medications have been found to diminish cardiovagal responses to autonomic challenges as well as to reduce cardiac autonomic modulation at rest [8].…”

“…A difference in patterns of dysautonomia among MS variants has been established. Compared to HC and patients with RRMS, patients with PPMS have been particularly associated with higher sympathetic predominance at rest [61,63,79], and lower sympathetic reactivity during head up tilt-up [63,79,80] even when corrected for age, sex, and disease duration [80]. Specifically, a heightened basal sympathetic tone in PPMS, related to inadequate sympathetic reactivity during orthostatic stress [7].…”