Byungjoo Jin1, Allan Wang2, Christopher Earley3, Richard Allen4. 1. School of Arts and Sciences, Johns Hopkins University, USA. 2. Bloomberg School of Public Health, Johns Hopkins University, USA. 3. Dept of Neurology, Hopkins Bayview Medical Center, Johns Hopkins University, USA. 4. Dept of Neurology, Hopkins Bayview Medical Center, Johns Hopkins University, USA. Electronic address: richardjhu@mac.com.
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.
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) RLSpatients 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 RLSpatients; 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 RLSpatients 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:RLSpatients had significantly more heart rate increases than controls (67.88/hr vs. 9.87/hr). RLSpatients 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 RLSpatients 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 RLSpatients 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 RLSpatients 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 RLSpatients have mild to even intermittent disease, including all RLS is likely to miss the potential health consequences of RLS.
Keywords:
Arousal in sleep; Cardiovascular disease; Leg movements in sleep; Periodic leg movements in sleep; Restless legs syndrome; Sympathetic autonomic activity
Authors: Christoforos D Giannaki; Paris Zigoulis; Christina Karatzaferi; Georgios M Hadjigeorgiou; Keith P George; Konstantinos Gourgoulianis; Yiannis Koutedakis; Ioannis Stefanidis; Giorgos K Sakkas Journal: J Clin Sleep Med Date: 2013-02-01 Impact factor: 4.062
Authors: Brian B Koo; Reena Mehra; Terri Blackwell; Sonia Ancoli-Israel; Katie L Stone; Susan Redline Journal: J Clin Sleep Med Date: 2014-01-15 Impact factor: 4.062
Authors: José Haba-Rubio; Helena Marti-Soler; Pedro Marques-Vidal; Nadia Tobback; Daniela Andries; Martin Preisig; Gérard Waeber; Peter Vollenweider; Zoltán Kutalik; Mehdi Tafti; Raphaël Heinzer Journal: Ann Neurol Date: 2016-02-12 Impact factor: 10.422
Authors: Werner Cassel; Karl Kesper; Axel Bauer; Frank Grieger; Erwin Schollmayer; Lars Joeres; Claudia Trenkwalder Journal: Sleep Med Date: 2015-02-23 Impact factor: 3.492
Authors: Axel Bauer; Werner Cassel; Heike Benes; Karl Kesper; David Rye; Domenic Sica; John W Winkelman; Lars Bauer; Frank Grieger; Lars Joeres; Kimberly Moran; Erwin Schollmayer; John Whitesides; Hannah C Carney; Arthur S Walters; Wolfgang Oertel; Claudia Trenkwalder Journal: Neurology Date: 2016-04-13 Impact factor: 9.910
Authors: Cameron S McAlpine; Máté G Kiss; Sara Rattik; Shun He; Anne Vassalli; Colin Valet; Atsushi Anzai; Christopher T Chan; John E Mindur; Florian Kahles; Wolfram C Poller; Vanessa Frodermann; Ashley M Fenn; Annemijn F Gregory; Lennard Halle; Yoshiko Iwamoto; Friedrich F Hoyer; Christoph J Binder; Peter Libby; Mehdi Tafti; Thomas E Scammell; Matthias Nahrendorf; Filip K Swirski Journal: Nature Date: 2019-02-13 Impact factor: 49.962