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The pathophysiology is complex and not fully understood, with inhibitory dysfunction of dopaminergic neurons or increased sympathetic activity being discussed. Aim of this study was to shed light on the association between dysfunction of the autonomic nervous system and RLS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>6 RLS patients diagnosed according to consensus criteria were compared with 9 gender- and age-matched healthy controls. Patients were clinically characterized using the International RLS Severity Scale (IRLS), the Epworth Sleepiness Scale (ESS) and the RLS Quality of Life Questionnaire (RLSQoL). Multi-unit sympathetic microneurography was performed in the peroneal nerve. Cardiovascular parameters (systolic and diastolic blood pressure, heart rate) and muscle sympathetic nerve activity (MSNA) were assessed at rest and during baroreflex stimulation using lower body negative pressure (LBNP).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>MSNA at rest was higher in RLS patients (burst frequency [BF]: 42.4\u2009\u00b1\u20091.7 bursts\/min; burst incidence [BI]: 64.0\u2009\u00b1\u20092.7 bursts\/100 heartbeats) compared to controls (BF: 29.5\u2009\u00b1\u20091.4 bursts\/min, F\u2009=\u200915.332, p\u2009=\u20090.002; BI: 42.9\u2009\u00b1\u20093.2 bursts\/100 heartbeats, F\u2009=\u200921.156, p\u2009=\u20090.001). After baroreflex stimulation, RLS patients had increased absolute values of MSNA (BF: F\u2009=\u200915.096; p\u2009=\u20090.002; BI: F\u2009=\u200921.115; p\u2009&lt;\u20090.001) compared to controls. In RLS patients, BF and BI dropped below baseline values, while in healthy controls BF and BI remained above baseline. After normalization of BF and BI data, the MSNA outflow during baroreflex stimulation was lower in RLS patients than those of healthy controls (BF: F\u2009=\u20094.574; p\u2009=\u20090.002, BI: F\u2009=\u20096.259; p\u2009&lt;\u20090.001).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The current study is the first to directly demonstrate increased sympathetic neuronal activity in RLS. Possible explanations include a dysfunction in inhibitory projections to sympathetic neurons in the intermediate lateral column of the spinal cord or a disease-unspecific effect of sleep deprivation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-13285-9","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:21:43Z","timestamp":1753867303000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["RLS shows increased resting state sympathetic activity and decreased sympathetic response capability"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7195-4272","authenticated-orcid":false,"given":"Christoph","family":"Best","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Luiza C.","family":"Sayegh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Janzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang H.","family":"Oertel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidrun H.","family":"Kr\u00e4mer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"13285_CR1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/j.1524-4733.2005.03010.x","volume":"8","author":"L Abetz","year":"2005","unstructured":"Abetz L, Vallow SM, Kirsch J, Allen RP, Washburn T, Earley CJ (2005) Validation of the restless legs syndrome quality of life questionnaire. 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A.L.S.: there are no conflicts of interest. A.J.: received grants from Parkinson Fonds Deutschland, unrelated to this publication. W.H.O.: received lecturing honoraria from Abbvie, Stada Pharma and the International Movement Disordert Society and consulting fees from Intrabio, Lario Therapeutics and MODAG\u2014all unrelated to this publication. H.H.K.: received travel grants from Alexion and Grifols, lecturing honoraria and consulting fees from Sanofi, Alexion, Roche Pharma, Argenx, UCB and Amgen and research support from Roche and Argenx, unrelated to this publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Before inclusion into the study all participants had given their written informed consent. The study was approved by the local ethics committee of the Medical Faculty of the Justus-Liebig-University, Giessen, Germany (161\/11) and performed in accordance with the standards of the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"545"}}