Baroreceptor sensitivity is related to treatment delay in ambulant multiple sclerosis subjects: a non-invasive autonomic function analysis

Background: Studies show that autonomic dysfunction relates to prognosis and extent of disease in multiple sclerosis (MS). Beat-to-beat baroreceptor sensitivity (BRS) measured by the sequence technique (ST) provides a near-instantaneous measure of intrinsic baroreceptor tone. The baroreflex mediates arterial blood pressure responses driven by sympathetic autonomic tone. Aims: To assess differences in short-term beat-to-beat non-invasive BRS, as well as heart rate variability (HRV), in MS subjects treated with immunomodulatory therapy early versus later in the course of their disease. Methods: Patients (n=39; age 49±13 SD years; 13 male) were studied using a finger cuff pressure device (Edwards Nextfin®). Recordings of 5 minutes were obtained and intrinsic BRS curves were derived by ST, then correlated with vasomotor, HRV and clinical characteristics, including disability. Subjects treated early (ET < 2 years) or later (NET > 2 years) were categorized into low BRS values (below the group median value of 9.96) or high BRS (those above the median). Electrocardiograms, time-based HRV and power spectral analysis (PSA) of HRV at very low frequencies (VLF < 0.04 Hz), low frequencies (LF 0.04–0.15 Hz) and high frequencies (HF 0.15–0.4 Hz) were also measured. The Mann-Whitney U test was used to compare inter-group differences, and χ2 was used for comparison of proportions, with significance set at P<0.05. Results: Average duration of diagnosis of MS was 14±12 years. ET vs. NET patients were younger (40±11 vs. 53±12 years; P<0.01) and had relatively higher BRS (9/11 in ET vs. 10/18 in NET; P<0.01). The mean BRS (mmHg/s) were 13.8±6.6 in ET vs. 10.3±5.2 in NET (P<0.07; not signifcant). In high BRS subjects PSA HF power (ms2 ) was 2621±2496 in ET vs. 3430±6325 in NET (P<0.01), with no differences at other frequencies. In low BRS subjects HF PDA was 592±73 in ET vs. 895±1361 in NET (P<0.01). Mean multiple sclerosis severity score (MSSS) values were 2.3±1.5 vs. 2.5±1.9 (P not significant) in ET vs. NET, respectively. Conclusions: Intrinsic BRS values measured by ST were higher in MS subjects treated early in the course of their disease. This was not explained by disability status scores accounting for time (MSSS) and raises the possibility that earlier treatment influences autonomic function in MS. Given that altered cardiac autonomic tone is an adverse prognostic factor in cardiovascular disease and cardiovascular mortality is overrepresented in MS, the impact of immunomodulatory medication on autonomic preservation warrants further study