Autonomic nervous system (ANS) dysfunction is frequently present in people with MS and more pronounced with disease duration and increase in neurologic disability (1). Siponimod is a S1P receptor1,5 modulator registered for treatment of secondary progressive MS (SPMS). Like other S1P receptor modulators, siponimod has been associated with decrease in heart rate (HR) at treatment initiation and development of hypertension during treatment. It has been shown that MS related ANS dysfunction may be implicated in fingolimod (S1P receptor1,3,5 modulator) related decrease in HR at treatment initiation (2).
In the January 2021 issue of Clinical Neurophysiology, a study was published that investigated whether ANS dysfunction identified prior to treatment initiation can predict siponimod related decrease in HR after treatment initiation (3). In 26 people with SPMS the following ANS testing protocol was applied: 10-min supine resting position, Valsalva maneuver, deep breathing test, 10 min tilt-up table test, 5-min supine resting period, ingestion of siponimod, followed by 180-min supine resting period recordings. Heart rate variability (HRV) parameters were investigated as possible predictors of decrease in HR (ΔHR) after treatment initiation.
After treatment initiation, there was a statistically significant drop in HR (71.1 ± 9.2 to 66.3 ± 8.1, p < 0.001) and elevation of systolic blood pressure (113.2 ± 12.4 to 117.1 ± 10.8, p = 0.04). In a multivariable regression model, disease duration and standard deviation of NN intervals (SDNN) were identified as independent predictors for ΔHR, where increase in SDNN and longer disease duration predict smaller ΔHR.
1. Adamec I, Crnošija L, Junaković A, Krbot Skorić M, Habek M. Progressive multiple sclerosis patients have a higher burden of autonomic dysfunction compared to relapsing remitting phenotype. Clin Neurophysiol. 2018 Aug;129(8):1588-1594.
2. Hilz MJ, Intravooth T, Moeller S, Wang R, Lee DH, Koehn J, Linker RA. Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing. PLoS One. 2015 Jul 6;10(7):e0132139.
3. Habek M, Crnošija L, Junaković A, Adamec I, Barun B, Gabelić T, Krbot Skorić M. Autonomic nervous system abnormalities predict cardiovascular changes after initiation of siponimod in secondary progressive multiple sclerosis. Clin Neurophysiol. 2021 Jan 15;132(2):581-585.