Sleep and Breathing

, Volume 22, Issue 4, pp 1005–1012 | Cite as

Basal sympathetic predominance in periodic limb movements in sleep after continuous positive airway pressure

  • Meng-Ni Wu
  • Chiou-Lian Lai
  • Ching-Kuan Liu
  • Chen-Wen Yen
  • Li-Min Liou
  • Cheng-Fang Hsieh
  • Ming-Ju Tsai
  • Sharon Chia-Ju Chen
  • Chung-Yao HsuEmail author
Sleep Breathing Physiology and Disorders • Original Article



This study investigated the basal autonomic regulation in patients with obstructive sleep apnea (OSA) showing periodic limb movements in sleep (PLMS) emerging after therapy with continuous positive airway pressure (CPAP).


Data of patients with OSA undergoing a first polysomnography for diagnosis and a second polysomnography for therapy with CPAP were reviewed. Patients with OSA showing PLMS on the first polysomnography were excluded. By using heart rate variability analysis, epochs without any sleep events and continuous effects from the second polysomnography were retrospectively analyzed.


Of 125 eligible patients, 30 with PLMS after therapy with CPAP (PLMS group) and 30 not showing PLMS on both polysomnography (non-PLMS group) were randomly selected for the analysis. No significant differences in the demographic characteristics and variables of polysomnographies were identified between the groups. Although one trend of low root mean square of successive differences (RMSSD) between intervals of adjacent normal heart beats (NN intervals) in the PLMS group was observed, patients in the PLMS group had significantly low normalized high-frequency (n-HF) and high-frequency (HF) values, but high normalized low frequency (n-LF) and high ratio of LF to HF (LF/HF ratio). After adjustment for confounding variables, PLMS on the second polysomnography was significantly associated with RMSSD (β = − 6.7587, p = 0.0338), n-LF (β = 0.0907, p = 0.0148), n-HF (β = − 0.0895, p = 0.0163), log LF/HF ratio (β = 0.4923, p = 0.0090), and log HF (β = − 0.6134, p = 0.0199).


Patients with OSA showing PLMS emerging after therapy with CPAP may have a basal sympathetic predominance with potential negative cardiovascular effects.


Obstructive sleep apnea Sleep-disordered breathing Autonomic nervous system Heart rate variability Parasomnia Continuous positive airway pressure 



The authors are grateful to Miss Yen-Ju Chuang, Miss Fu-Huei Tsai, Miss Huei-En Cheng, and Mr. Ming-Hung Sun in the Sleep Center of Kaohsiung Medical University Hospital for their assistance in data collection.

Funding information

This study was supported by a grant from the Kaohsiung Medical University Hospital (grant number: KMUH-101-1M49), but this funding source had no involvement of the study design or interpretation of results.

Compliance with ethical standards

Ethical statement

This study was approved by the Institutional Review Board (KMUH-IRB-20110421) and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study, formal consent is not required because of the retrospective design of this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11325_2018_1620_MOESM1_ESM.pdf (685 kb)
ESM 1 (PDF 684 kb)


  1. 1.
    Hornyak M, Feige B, Riemann D, Voderholzer U (2006) Periodic leg movements in sleep and periodic limb movement disorder: prevalence, clinical significance and treatment. Sleep Med Rev 10(3):169–177. CrossRefPubMedGoogle Scholar
  2. 2.
    Warnes H, Dinner DS, Kotagal P, Burgess RC (1993) Periodic limb movements and sleep apnoea. J Sleep Res 2(1):38–44. CrossRefPubMedGoogle Scholar
  3. 3.
    Baran AS, Richert AC, Douglass AB, May W, Ansarin K (2003) Change in periodic limb movement index during treatment of obstructive sleep apnea with continuous positive airway pressure. Sleep 26(6):717–720CrossRefGoogle Scholar
  4. 4.
    Aritake-Okada S, Namba K, Hidano N, Asaoka S, Komada Y, Usui A, Matsuura M, Inoue Y (2012) Change in frequency of periodic limb movements during sleep with usage of continuous positive airway pressure in obstructive sleep apnea syndrome. J Neurol Sci 317(1-2):13–16. CrossRefPubMedGoogle Scholar
  5. 5.
    Shamsuzzaman AS, Gersh BJ, Somers VK (2003) Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 290(14):1906–1914. CrossRefPubMedGoogle Scholar
  6. 6.
    Koo BB, Blackwell T, Ancoli-Israel S, Stone KL, Stefanick ML, Redline S, Osteoporotic Fractures in Men Study G (2011) Association of incident cardiovascular disease with periodic limb movements during sleep in older men: outcomes of sleep disorders in older men (MrOS) study. Circulation 124(11):1223–1231. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Walters AS, Rye DB (2009) Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke. Sleep 32(5):589–597. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Boulos MI, Murray BJ, Muir RT, Gao F, Szilagyi GM, Huroy M, Kiss A, Walters AS, Black SE, Lim AS, Swartz RH (2017) Periodic limb movements and white matter hyperintensities in first-ever minor stroke or high-risk transient ischemic attack. Sleep 40(3).
  9. 9.
    Aurora RN, Kristo DA, Bista SR, Rowley JA, Zak RS, Casey KR, Lamm CI, Tracy SL, Rosenberg RS, American Academy of Sleep M (2012) The treatment of restless legs syndrome and periodic limb movement disorder in adults—an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine clinical practice guideline. Sleep 35:1039–1062. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Murase K, Hitomi T, Hamada S, Azuma M, Toyama Y, Harada Y, Tanizawa K, Handa T, Yoshimura C, Oga T, Mishima M, Chin K (2014) The additive impact of periodic limb movements during sleep on inflammation in patients with obstructive sleep apnea. Ann Am Thorac Soc 11(3):375–382. CrossRefPubMedGoogle Scholar
  11. 11.
    MN W, Lai CL, Liu CK, Yen CW, Liou LM, Hsieh CF, Tsai MJ, Chen SC, Hsu CY (2015) Basal sympathetic predominance in periodic limb movements in sleep with obstructive sleep apnea. J Sleep Res 24(6):722–729. CrossRefGoogle Scholar
  12. 12.
    Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996). Circulation 93:1043–1065Google Scholar
  13. 13.
    Dekker JM, Crow RS, Folsom AR, Hannan PJ, Liao D, Swenne CA, Schouten EG (2000) Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC study. Atherosclerosis Risk In Communities. Circulation 102(11):1239–1244. CrossRefPubMedGoogle Scholar
  14. 14.
    Liao D, Cai J, Rosamond WD, Barnes RW, Hutchinson RG, Whitsel EA, Rautaharju P, Heiss G (1997) Cardiac autonomic function and incident coronary heart disease: a population-based case-cohort study. The ARIC study. Atherosclerosis Risk in Communities Study. Am J Epidemiol 145(8):696–706. CrossRefPubMedGoogle Scholar
  15. 15.
    Tsuji H, Larson MG, Venditti FJ Jr, Manders ES, Evans JC, Feldman CL, Levy D (1996) Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation 94(11):2850–2855. CrossRefPubMedGoogle Scholar
  16. 16.
    Aydin M, Altin R, Ozeren A, Kart L, Bilge M, Unalacak M (2004) Cardiac autonomic activity in obstructive sleep apnea: time-dependent and spectral analysis of heart rate variability using 24-hour Holter electrocardiograms. Tex Heart Inst J 31(2):132–136PubMedPubMedCentralGoogle Scholar
  17. 17.
    Gula LJ, Krahn AD, Skanes A, Ferguson KA, George C, Yee R, Klein GJ (2003) Heart rate variability in obstructive sleep apnea: a prospective study and frequency domain analysis. Ann Noninvasive Electrocardiol 8(2):144–149. CrossRefPubMedGoogle Scholar
  18. 18.
    Ferrillo F, Beelke M, Canovaro P, Watanabe T, Arico D, Rizzo P, Garbarino S, Nobili L, De Carli F (2004) Changes in cerebral and autonomic activity heralding periodic limb movements in sleep. Sleep Med 5(4):407–412. CrossRefPubMedGoogle Scholar
  19. 19.
    Guggisberg AG, Hess CW, Mathis J (2007) The significance of the sympathetic nervous system in the pathophysiology of periodic leg movements in sleep. Sleep 30(6):755–766. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Manconi M, Ferri R, Zucconi M, Clemens S, Rundo F, Oldani A, Ferini-Strambi L (2011) Effects of acute dopamine-agonist treatment in restless legs syndrome on heart rate variability during sleep. Sleep Med 12(1):47–55. CrossRefPubMedGoogle Scholar
  21. 21.
    Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force (1999). Sleep 22:667–689Google Scholar
  22. 22.
    Manconi M, Zavalko I, Fanfulla F, Winkelman JW, Fulda S (2015) An evidence-based recommendation for a new definition of respiratory-related leg movements. Sleep 38:295–304. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    McCall WV, Haponik E (1993) Relationship of nasal continuous positive airway pressure to periodic limb movement disorder in a patient without sleep apnea. Chest 103(5):1609–1611. CrossRefPubMedGoogle Scholar
  24. 24.
    Guerrero ML, Kim D, Rupp TL, Balkin TJ (2010) Oral appliance titration in patients with obstructive sleep apnea induces the appearance of periodic limb movements. Sleep Breath 14(4):359–363. CrossRefPubMedGoogle Scholar
  25. 25.
    Fry JM, DiPhillipo MA, Pressman MR (1989) Periodic leg movements in sleep following treatment of obstructive sleep apnea with nasal continuous positive airway pressure. Chest 96(1):89–91. CrossRefPubMedGoogle Scholar
  26. 26.
    Exar EN, Collop NA (2001) The association of upper airway resistance with periodic limb movements. Sleep 24(2):188–192. CrossRefPubMedGoogle Scholar
  27. 27.
    Siddiqui F, Strus J, Ming X, Lee IA, Chokroverty S, Walters AS (2007) Rise of blood pressure with periodic limb movements in sleep and wakefulness. Clin Neurophysiol 118(9):1923–1930. CrossRefPubMedGoogle Scholar
  28. 28.
    Ross AJ, Yang H, Larson RA, Carter JR (2014) Sleep efficiency and nocturnal hemodynamic dipping in young, normotensive adults. Am J Physiol Regul Integr Comp Physiol 307(7):R888–R892. CrossRefPubMedGoogle Scholar
  29. 29.
    Hornyak M, Kopasz M, Feige B, Riemann D, Voderholzer U (2005) Variability of periodic leg movements in various sleep disorders: implications for clinical and pathophysiologic studies. Sleep 28(3):331–335PubMedGoogle Scholar
  30. 30.
    Ferri R, Fulda S, Manconi M, Hogl B, Ehrmann L, Ferini-Strambi L, Zucconi M (2013) Night-to-night variability of periodic leg movements during sleep in restless legs syndrome and periodic limb movement disorder: comparison between the periodicity index and the PLMS index. Sleep Med 14(3):293–296. CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyKaohsiung Medical University HospitalKaohsiung CityTaiwan
  2. 2.Department of Master’s Program in NeurologyKaohsiung Medical UniversityKaohsiung CityTaiwan
  3. 3.Department of Mechanical and Electro-mechanical EngineeringNational Sun Yat-Sen UniversityKaohsiungTaiwan
  4. 4.Division of Geriatrics and Gerontology, Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung CityTaiwan
  5. 5.Faculty of Medicine and Graduate Institute of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiung CityTaiwan
  6. 6.Division of Pulmonary and Critical Care Medicine, Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung CityTaiwan
  7. 7.Department of Medical Imaging and Radiation SciencesKaohsiung Medical UniversityKaohsiung CityTaiwan

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