Moderate to severe but not mild RLS is associated with greater sleep-related sympathetic autonomic activation than healthy adults without RLS.

Abstract Introduction Restless legs syndrome (RLS) patients have been found to have high rates of transitory increases in the activity of the sympathetic autonomic nervous system with increases in heart rate and blood pressure. These were identified by evaluating heart rate or blood pressure changes independent of any leg movement analyses. There has been an implicit assumption this high rate of sympathetic activations is abnormal, but there has been no direct comparison for similar measures with a healthy population free of RLS. Thus, it is not known if during sleep the rates of sympathetic nervous system activation are greater for RLS than for a healthy population. The objectives of this study were to determine if: (1) RLS patients compared to healthy controls have a greater frequency of sympathetic nervous system activation (significant heart rate increases) with a higher percentage of leg movements associated with these activations; (2) the sympathetic activation frequency and its relation to leg movements correlate significantly with RLS severity in RLS patients; and (3) there is some minimum threshold for RLS severity defining an RLS population where most (eg 85%) have abnormally high rates of sympathetic activation. Methods Sleep data on 32 RLS patients and 21 matched healthy controls were obtained from a prior study. All leg movements during sleep (LMS) and periodic leg movements in sleep (PLMS) were identified following the new WASM criteria; LMS that were not PLMS were considered isolated leg movements in sleep (ILMS). All episodes with significant heart rate increases were identified following procedures established by Cassel et al., (2016, see further on for citation) ie a slope of linear regression ≥2.5 beats per minute over five consecutive heartbeats. Severity of RLS was evaluated using the International Restless Legs Study Group Scale (IRLS). Results RLS patients had significantly more heart rate increases than controls (67.88/hr vs. 9.87/hr). RLS patients had a significantly greater percentage of both LMS and PLMS occurring with heart rate increases than controls (44% vs. 30%; 48% vs. 18%, respectively). These measures correlated significantly with IRLS and also PLMS/hr. 85% of the RLS patients with IRLS scores >22 or PLMS >50/hr had rates of sympathetic activation that were >90th percentile for the healthy controls. Conclusion This is the first paper documenting that RLS patients showed clearly increased sympathetic activation when identified independent of PLMS. This, however, occurs for more severe RLS and not milder RLS. It has been proposed that the abnormally high rate of sympathetic activation for RLS patients relates to development of adverse cardiovascular health consequences observed in some studies. Thus, these data may provide a basic standard for possible use in epidemiological studies to identify the level of RLS severity more likely to have adverse health consequences (eg, cardiovascular disease). Since two-thirds of RLS patients have mild to even intermittent disease, including all RLS is likely to miss the potential health consequences of RLS.