Neurological Sciences

, Volume 39, Issue 11, pp 1927–1934 | Cite as

Prevalence of restless legs syndrome in individuals with migraine: a systematic review and meta-analysis of observational studies

  • Xinglong Yang
  • Bin Liu
  • Baiyuan Yang
  • Shimei Li
  • Fang Wang
  • Kelu Li
  • Fayun Hu
  • Hui RenEmail author
  • Zhong XuEmail author
Original Article



Recent studies have shown an association between migraine and restless legs syndrome (RLS), but RLS prevalence among individuals with migraine differs substantially across studies. The present work aimed to comprehensively assess available evidence to estimate RLS prevalence among individuals with migraine and non-migraine controls.


Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were searched for observational and case-control studies of RLS prevalence among individuals with migraine. Eligible studies were meta-analyzed using Stata 12.0 software.


Pooled RLS prevalence in migraine was 19%, and the prevalence was lower in Asia (16%) than outside Asia (21%). Pooled RLS prevalence was 18.8% among individuals with migraine with aura, and 18.5% among individuals with migraine without aura; the RLS prevalence in migraine with aura (MA) was higher than that of migraine without aura (MO) (OR 1.17, 95%CI 1.01–1.34; p = 0.037). Pooled RLS prevalence in a case-control study was significantly higher among individuals with migraine (17.9%) than among non-migraine controls (7.1%) (OR 2.65, 95%CI 2.26–3.10; p < 0.001).


Our meta-analysis provides the first reliable pooled estimate of RLS prevalence among individuals with migraine, and it provides strong evidence that RLS risk is higher among individuals with migraine than among controls.


Migraine Restless legs syndrome Prevalence Meta-analysis 


Fund resource

This research was supported by the Yunnan Province Medical Health Research Institute Project (2018NS0102), the First Affiliated Hospital of Kunming Medical University Doctoral Research Fund Project (2017BS005), and the National Natural Science Foundation of China (81371281).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

10072_2018_3527_Fig5_ESM.png (305 kb)
Supplemental Fig. 1

Sensitivity analysis of all included studies. (PNG 305 kb)

10072_2018_3527_MOESM1_ESM.tif (9 kb)
High resolution image (TIF 8 kb)
10072_2018_3527_Fig6_ESM.png (12 kb)
Supplemental Fig. 2

Funnel plot to assess bias in RLS prevalence among migraine patients. (PNG 12 kb)

10072_2018_3527_MOESM2_ESM.tif (1.5 mb)
High resolution image (TIF 1561 kb)
10072_2018_3527_Fig7_ESM.png (24 kb)
Supplemental Fig. 3

Forest plot of RLS prevalence among MA individuals. (PNG 24 kb)

10072_2018_3527_MOESM3_ESM.tif (1.5 mb)
High resolution image (TIF 1535 kb)
10072_2018_3527_Fig8_ESM.png (22 kb)
Supplemental Fig. 4

Forest plot of RLS prevalence among MO individuals. (PNG 22 kb)

10072_2018_3527_MOESM4_ESM.tif (1.5 mb)
High resolution image (TIF 1579 kb)
10072_2018_3527_Fig9_ESM.png (36 kb)
Supplemental Fig. 5

Funnel plot to assess bias in the comparison of RLS prevalence between MA and MO. (PNG 36 kb)

10072_2018_3527_MOESM5_ESM.tif (148 kb)
High resolution image (TIF 147 kb)
10072_2018_3527_Fig10_ESM.png (36 kb)
Supplemental Fig. 6

Funnel plot to assess bias in the comparison of RLS prevalence between migraine patients and healthy controls. (PNG 35 kb)

10072_2018_3527_MOESM6_ESM.tif (150 kb)
High resolution image (TIF 150 kb)


  1. 1.
    Headache Classification Subcommittee of the International Headache S. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24 Suppl 1:9–160Google Scholar
  2. 2.
    Drake ME Jr, Pakalnis A, Andrews JM, Bogner JE (1990) Nocturnal sleep recording with cassette EEG in chronic headaches. Headache 30(9):600–603CrossRefGoogle Scholar
  3. 3.
    Della Marca G, Vollono C, Rubino M, Di Trapani G, Mariotti P, Tonali PA (2006) Dysfunction of arousal systems in sleep-related migraine without aura. Cephalalgia 26(7):857–864PubMedGoogle Scholar
  4. 4.
    Young WB, Piovesan EJ, Biglan KM (2003) Restless legs syndrome and drug-induced akathisia in headache patients. CNS Spectr 8(6):450–456CrossRefGoogle Scholar
  5. 5.
    Bigal ME, Lipton RB (2009) The epidemiology, burden, and comorbidities of migraine. Neurol Clin 27(2):321–334CrossRefGoogle Scholar
  6. 6.
    Leonardi M, Steiner TJ, Scher AT, Lipton RB (2005) The global burden of migraine: measuring disability in headache disorders with WHO’s Classification of Functioning, Disability and Health (ICF). J Headache Pain 6(6):429–440CrossRefGoogle Scholar
  7. 7.
    Abstracts of the 15th Congress of the International Headache Society. June 23–26, 2011. Berlin, Germany. Cephalalgia. 2011;31(1 Suppl):1–242Google Scholar
  8. 8.
    Chen PK, Fuh JL, Chen SP, Wang SJ (2010) Association between restless legs syndrome and migraine. J Neurol Neurosurg Psychiatry 81(5):524–528CrossRefGoogle Scholar
  9. 9.
    Cho SJ, Chung YK, Kim JM, Chu MK (2015) Migraine and restless legs syndrome are associated in adults under age fifty but not in adults over fifty: a population-based study. J Headache Pain 16:554CrossRefGoogle Scholar
  10. 10.
    Chung PW, Cho SJ, Kim WJ, Yang KI, Yun CH, Chu MK (2017) Restless legs syndrome and tension-type headache: a population-based study. J Headache Pain 18(1):47CrossRefGoogle Scholar
  11. 11.
    Cologno D, Cicarelli G, Petretta V, d’Onofrio F, Bussone G (2008) High prevalence of dopaminergic premonitory symptoms in migraine patients with restless legs syndrome: a pathogenetic link? Neurol Sci 29(Suppl 1):S166–S168CrossRefGoogle Scholar
  12. 12.
    d’Onofrio F, Bussone G, Cologno D, Petretta V, Buzzi MG, Tedeschi G et al (2008) Restless legs syndrome and primary headaches: a clinical study. Neurol Sci 29(Suppl 1):S169–S172CrossRefGoogle Scholar
  13. 13.
    d’Onofrio F, Cologno D, Petretta V, Finocchi C, Autunno M, Marsala G et al (2011) Restless legs syndrome is not associated with migraine with aura: a clinical study. Neurol Sci 32(Suppl 1):S153–S156CrossRefGoogle Scholar
  14. 14.
    Ferreira KS, Eckeli A, Dach F, Speciali JG (2013) Comorbidities, medications and depressive symptoms in patients with restless legs syndrome and migraine. Arq Neuropsiquiatr 71(2):87–91CrossRefGoogle Scholar
  15. 15.
    Karthik N, Kulkarni GB, Taly AB, Rao S, Sinha S (2012) Sleep disturbances in ‘migraine without aura’--a questionnaire based study. J Neurol Sci 321(1–2):73–76CrossRefGoogle Scholar
  16. 16.
    Lin GY, Lin YK, Lee JT, Lee MS, Lin CC, Tsai CK, Ting CH, Yang FC (2016) Prevalence of restless legs syndrome in migraine patients with and without aura: a cross-sectional, case-controlled study. J Headache Pain 17(1):97CrossRefGoogle Scholar
  17. 17.
    Lucchesi C, Bonanni E, Maestri M, Siciliano G, Murri L, Gori S (2012) Evidence of increased restless legs syndrome occurrence in chronic and highly disabling migraine. Funct Neurol 27(2):91–94PubMedPubMedCentralGoogle Scholar
  18. 18.
    Rhode AM, Hosing VG, Happe S, Biehl K, Young P, Evers S (2007) Comorbidity of migraine and restless legs syndrome--a case-control study. Cephalalgia 27(11):1255–1260CrossRefGoogle Scholar
  19. 19.
    Seidel S, Bock A, Schlegel W, Kilic A, Wagner G, Gelbmann G et al (2012) Increased RLS prevalence in children and adolescents with migraine: a case-control study. Cephalalgia 32(9):693–699CrossRefGoogle Scholar
  20. 20.
    Sevindik MS, Demirci S, Goksan B, Ozge A, Savrun FK, Onur H et al (2017) Accompanying migrainous features in pediatric migraine patients with restless legs syndrome. Neurol Sci 38(9):1677–1681CrossRefGoogle Scholar
  21. 21.
    Suzuki S, Suzuki K, Miyamoto M, Miyamoto T, Watanabe Y, Takashima R, Hirata K (2011) Evaluation of contributing factors to restless legs syndrome in migraine patients. J Neurol 258(11):2026–2035CrossRefGoogle Scholar
  22. 22.
    Valente M, Janes F, Russo V, Fontana A, Travanut A, Sommaro M, Canal G, Gentile C, Luigi Gigli G (2017) Prevalence of restless legs syndrome in migraine patients: a case-control study. Analysis of risk factors for restless legs syndrome in migraine patients. Headache 57(7):1088–1095CrossRefGoogle Scholar
  23. 23.
    van Oosterhout WP, van Someren EJ, Louter MA, Schoonman GG, Lammers GJ, Rijsman RM et al (2016) Restless legs syndrome in migraine patients: prevalence and severity. Eur J Neurol 23(6):1110–1116CrossRefGoogle Scholar
  24. 24.
    Pratt DP (2016) Restless legs syndrome/Willis-Ekbom disease and periodic limb movements: a comprehensive review of epidemiology, pathophysiology, diagnosis and treatment considerations. Curr Rheumatol Rev 12(2):91–112CrossRefGoogle Scholar
  25. 25.
    Fernandez-Matarrubia M, Cuadrado ML, Sanchez-Barros CM, Martinez-Orozco FJ, Fernandez-Perez C, Villalibre I et al (2014) Prevalence of migraine in patients with restless legs syndrome: a case-control study. Headache 54(8):1337–1346CrossRefGoogle Scholar
  26. 26.
    Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J, Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health, International Restless Legs Syndrome Study Group (2003) Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 4(2):101–119CrossRefGoogle Scholar
  27. 27.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560CrossRefGoogle Scholar
  28. 28.
    Zhang TS, Zhong WZ (2012) Applied methodology for evidence-based medicine. University Press, Changsha, pp 166–75Google Scholar
  29. 29.
    Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):1533–1537CrossRefGoogle Scholar
  30. 30.
    De Martino P, Peila E, Rainero I et al (2012) Migraine and restless legs syndrome: further investigating the link. Neurology 78(Suppl):04249Google Scholar
  31. 31.
    Muayqil T, Al-Jafen BN, Al-Saaran Z, Al-Shammari M, Alkthiry A, Muhammad WS et al (2018) Migraine and headache prevalence and associated comorbidities in a large Saudi sample. Eur Neurol 79(3–4):126–134CrossRefGoogle Scholar
  32. 32.
    Schurks M, Winter A, Berger K, Kurth T (2014) Migraine and restless legs syndrome: a systematic review. Cephalalgia 34(10):777–794CrossRefGoogle Scholar
  33. 33.
    Yang FC, Lin TY, Chen HJ, Lee JT, Lin CC, Huang WY, Chen HH, Kao CH (2016) Increased risk of restless legs syndrome in patients with migraine: a nationwide population-based cohort study. Medicine 95(5):e2646CrossRefGoogle Scholar
  34. 34.
    Clemens S, Rye D, Hochman S (2006) Restless legs syndrome: revisiting the dopamine hypothesis from the spinal cord perspective. Neurology 67(1):125–130CrossRefGoogle Scholar
  35. 35.
    Kagan R, Kainz V, Burstein R, Noseda R (2013) Hypothalamic and basal ganglia projections to the posterior thalamus: possible role in modulation of migraine headache and photophobia. Neuroscience 248:359–368CrossRefGoogle Scholar
  36. 36.
    Yucel M, Akgun H, Oz O, Demirkaya S (2013) Migraine and restless leg syndrome co-morbidity may be due to iron deficiency. Ann Indian Acad Neurol 16(3):461CrossRefGoogle Scholar
  37. 37.
    Cologno D, Cicarelli G, Petretta V, d’Onofrio F, Bussone G (2008) Highprevalence of dopaminergic premonitory symptoms in migraine patients with restless legs syndrome: apathogenetic link? Neurol Sci 29 Suppl 1:S166–S168CrossRefGoogle Scholar
  38. 38.
    Suzuki K, Suzuki S, Miyamoto M, Miyamoto T, Numao A, Watanabe Y, et al. Does pramipexole treatment improve headache in patients with concomitant migraine and restless legs syndrome? Tremor and other hyperkinetic movements. 2013;3.Google Scholar
  39. 39.
    Yeh P, Walters AS, Tsuang JW (2012) Restless legs syndrome: a comprehensive overview on its epidemiology, risk factors, and treatment. Sleep Breath 16(4):987–1007CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Geriatric NeurologyFirst Affiliated Hospital of Kunming Medical UniversityKunmingPeople’s Republic of China
  2. 2.Department of NeurologyThe Seventh People’s Hospital of ChengduChengduPeople’s Republic of China
  3. 3.Department of AnesthesiaKunming Xishan District People’s HospitalKunmingPeople’s Republic of China
  4. 4.Department of NeurologyWest China Hospital, SCUChengduPeople’s Republic of China

Personalised recommendations