Journal of Neurology

, Volume 258, Issue 11, pp 2026–2035 | Cite as

Evaluation of contributing factors to restless legs syndrome in migraine patients

  • Shiho Suzuki
  • Keisuke Suzuki
  • Masayuki Miyamoto
  • Tomoyuki Miyamoto
  • Yuka Watanabe
  • Ryotaro Takashima
  • Koichi Hirata
Original Communication

Abstract

Recent studies have provided evidence for a positive association between migraine and restless legs syndrome (RLS), although the exact mechanisms and contributing factors remain unclear. A cross-sectional, case–control study was conducted, including patients with migraine (n = 262) and headache-free control subjects (n = 163). Migraine was diagnosed according to International Classification of Headache Disorders II criteria. RLS diagnosis was made based on four essential criteria as described by the International Restless Legs Syndrome Study Group. All patients completed the Migraine Disability Assessment (MIDAS) questionnaire, Beck Depression Inventory (BDI)-II scores, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). A total of 210 blood samples were collected to correlate various parameters with RLS. RLS frequency was significantly greater in patients with migraine than in controls (13.7 vs. 1.8%). Migraine patients with RLS had high scores for MIDAS, BDI-II, PSQI, and ESS compared with those without RLS. In addition, migraine patients with RLS had a high rate of smoking and RLS family history, as well as increased levels of serum phosphorus and urea nitrogen compared with those without RLS. However, there was no difference in serum iron and ferritin levels between the groups. In migraine patients, logistic regression analysis revealed that positive RLS family history, BDI-II, ESS, and serum phosphorus levels were significant RLS predictors. Our study confirmed a positive association between RLS and migraine. RLS comorbidity in migraine patients was associated with insomnia, daytime sleepiness, depressive symptoms, headache-related disability, and increased serum phosphorus levels. These findings may provide a better understanding of RLS pathogenesis in migraine.

Keywords

Migraine Restless legs syndrome Sleep disorders Depression Phosphorus levels 

References

  1. 1.
    Ekbom KA (1960) Restless legs syndrome. Neurology 10:868–873PubMedGoogle Scholar
  2. 2.
    Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, Ferini-Strambi L (2005) Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 165(11):1286–1292PubMedCrossRefGoogle Scholar
  3. 3.
    Winkelmann J (2008) Genetics of restless legs syndrome. Curr Neurol Neurosci Rep 8(3):211–216PubMedCrossRefGoogle Scholar
  4. 4.
    Clemens S, Rye D, Hochman S (2006) Restless legs syndrome: revisiting the dopamine hypothesis from the spinal cord perspective. Neurology 67(1):125–130PubMedCrossRefGoogle Scholar
  5. 5.
    Ekbom K, Ulfberg J (2009) Restless legs syndrome. J Intern Med 266(5):419–431PubMedCrossRefGoogle Scholar
  6. 6.
    Eisensehr I, Wetter TC, Linke R, Noachtar S, von Lindeiner H, Gildehaus FJ, Trenkwalder C, Tatsch K (2001) Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome. Neurology 57(7):1307–1309PubMedGoogle Scholar
  7. 7.
    Michaud M, Soucy JP, Chabli A, Lavigne G, Montplaisir J (2002) SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep. J Neurol 249(2):164–170PubMedCrossRefGoogle Scholar
  8. 8.
    Bartell S, Zallek S (2006) Intravenous magnesium sulfate may relieve restless legs syndrome in pregnancy. J Clin Sleep Med 2(2):187–188PubMedGoogle Scholar
  9. 9.
    Bachmann CG, Guth N, Helmschmied K, Armstrong VW, Paulus W, Happe S (2008) Homocysteine in restless legs syndrome. Sleep Med 9(4):388–392PubMedCrossRefGoogle Scholar
  10. 10.
    Patrick LR (2007) Restless legs syndrome: pathophysiology and the role of iron and folate. Altern Med Rev 12(2):101–112PubMedGoogle Scholar
  11. 11.
    Rijsman RM, de Weerd AW (1999) Secondary periodic limb movement disorder and restless legs syndrome. Sleep Med Rev 3(2):147–158PubMedCrossRefGoogle Scholar
  12. 12.
    Ferini-Strambi L (2007) RLS-like symptoms: differential diagnosis by history and clinical assessment. Sleep Med 8(Suppl 2):S3–S6PubMedCrossRefGoogle Scholar
  13. 13.
    Peralta CM, Frauscher B, Seppi K, Wolf E, Wenning GK, Hogl B, Poewe W (2009) Restless legs syndrome in Parkinson’s disease. Mov Disord 24(14):2076–2080PubMedCrossRefGoogle Scholar
  14. 14.
    Berger K, Luedemann J, Trenkwalder C, John U, Kessler C (2004) Sex and the risk of restless legs syndrome in the general population. Arch Intern Med 164(2):196–202PubMedCrossRefGoogle Scholar
  15. 15.
    Tison F, Crochard A, Leger D, Bouee S, Lainey E, El Hasnaoui A (2005) Epidemiology of restless legs syndrome in French adults: a nationwide survey: the INSTANT Study. Neurology 65(2):239–246PubMedCrossRefGoogle Scholar
  16. 16.
    Nomura T, Inoue Y, Kusumi M, Oka Y, Nakashima K (2008) Email-based epidemiological surveys on restless legs syndrome in Japan. Sleep Biol Rhythms 6:139–145CrossRefGoogle Scholar
  17. 17.
    Nomura T, Inoue Y, Kusumi M, Uemura Y, Nakashima K (2008) Prevalence of restless legs syndrome in a rural community in Japan. Mov Disord 23(16):2363–2369PubMedCrossRefGoogle Scholar
  18. 18.
    Tsuboi Y, Imamura A, Sugimura M, Nakano S, Shirakawa S, Yamada T (2009) Prevalence of restless legs syndrome in a Japanese elderly population. Parkinsonism Relat Disord 15(8):598–601PubMedCrossRefGoogle Scholar
  19. 19.
    Leonardi M, Raggi A, Bussone G, D’Amico D (2010) Health-related quality of life, disability and severity of disease in patients with migraine attending to a specialty headache center. Headache 50(10):1576–1586Google Scholar
  20. 20.
    Charbit AR, Akerman S, Goadsby PJ (2010) Dopamine: what’s new in migraine? Curr Opin Neurol 23(3):275–281PubMedCrossRefGoogle Scholar
  21. 21.
    Chen PK, Fuh JL, Chen SP, Wang SJ (2010) Association between restless legs syndrome and migraine. J Neurol Neurosurg Psychiatry 81(5):524–528PubMedCrossRefGoogle Scholar
  22. 22.
    d’Onofrio F, Bussone G, Cologno D, Petretta V, Buzzi MG, Tedeschi G, Bonavita V, Cicarelli G (2008) Restless legs syndrome and primary headaches: a clinical study. Neurol Sci 29(Suppl 1):S169–S172PubMedCrossRefGoogle Scholar
  23. 23.
    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):1255–1260PubMedCrossRefGoogle Scholar
  24. 24.
    Headache Classification Subcommittee of the International Headache Society (2004). The International Classification of Headache Disorders: 2nd edn. Cephalalgia 24 Suppl 1:9–160Google Scholar
  25. 25.
    Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J (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):101–119PubMedCrossRefGoogle Scholar
  26. 26.
    American Academy of Sleep Medicine (2005) International classification of sleep disorders: diagnostic and coding manual, 2nd edn. Westchester, IL, pp 178–181Google Scholar
  27. 27.
    Hening WA, Allen RP, Washburn M, Lesage SR, Earley CJ (2009) The four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions (“mimics”). Sleep Med 10(9):976–981PubMedCrossRefGoogle Scholar
  28. 28.
    Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C (2003) Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4(2):121–132PubMedCrossRefGoogle Scholar
  29. 29.
    Stewart WF, Lipton RB, Whyte J, Dowson A, Kolodner K, Liberman JN, Sawyer J (1999) An international study to assess reliability of the Migraine Disability Assessment (MIDAS) score. Neurology 53(5):988–994PubMedGoogle Scholar
  30. 30.
    Beck AT, Stear RA, Brown GK (1996) The Beck Depression Inventory, 2nd edn. Houghton Mifflin, BostonGoogle Scholar
  31. 31.
    Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28(2):193–213PubMedCrossRefGoogle Scholar
  32. 32.
    Fukuhara S, Takegami M, Suzukamo Y, et al (2006) The Japanese version of the Epworth Sleepiness Scale (JESS) J Jap Respir Soc 44:896–898Google Scholar
  33. 33.
    Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14(6):540–545PubMedGoogle Scholar
  34. 34.
    Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53(6):982–992PubMedCrossRefGoogle Scholar
  35. 35.
    Hosmer DW, Lemeshow S (2000) In: Applied logistic regression, 2nd edn. Wiley, New York, p 375Google Scholar
  36. 36.
    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):589–597PubMedGoogle Scholar
  37. 37.
    Earley CJ, Allen RP, Connor JR, Ferrucci L, Troncoso J (2009) The dopaminergic neurons of the A11 system in RLS autopsy brains appear normal. Sleep Med 10(10):1155–1157PubMedCrossRefGoogle Scholar
  38. 38.
    Sevim S, Dogu O, Kaleagasi H, Aral M, Metin O, Camdeviren H (2004) Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey. J Neurol Neurosurg Psychiatry 75(2):226–230PubMedGoogle Scholar
  39. 39.
    Russell MB (2007) Genetics in primary headaches. J Headache Pain 8(3):190–195PubMedCrossRefGoogle Scholar
  40. 40.
    Winkelmann J, Ferini-Strambi L (2006) Genetics of restless legs syndrome. Sleep Med Rev 10(3):179–183PubMedCrossRefGoogle Scholar
  41. 41.
    Soragna D, Vettori A, Carraro G, Marchioni E, Vazza G, Bellini S, Tupler R, Savoldi F, Mostacciuolo ML (2003) A locus for migraine without aura maps on chromosome 14q21.2–q22.3. Am J Hum Genet 72(1):161–167PubMedCrossRefGoogle Scholar
  42. 42.
    Bonati MT, Ferini-Strambi L, Aridon P, Oldani A, Zucconi M, Casari G (2003) Autosomal dominant restless legs syndrome maps on chromosome 14q. Brain 126(Pt 6):1485–1492PubMedCrossRefGoogle Scholar
  43. 43.
    Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther 113(2):296–320PubMedCrossRefGoogle Scholar
  44. 44.
    Ferrari MD, Saxena PR (1993) On serotonin and migraine: a clinical and pharmacological review. Cephalalgia 13(3):151–165PubMedCrossRefGoogle Scholar
  45. 45.
    Odegard SS, Engstrom M, Sand T, Stovner LJ, Zwart JA, Hagen K (2010) Associations between sleep disturbance and primary headaches: the third Nord-Trondelag Health Study. J Headache Pain 11(3):197–206PubMedCrossRefGoogle Scholar
  46. 46.
    Takaki J, Nishi T, Nangaku M, Shimoyama H, Inada T, Matsuyama N, Kumano H, Kuboki T (2003) Clinical and psychological aspects of restless legs syndrome in uremic patients on hemodialysis. Am J Kidney Dis 41(4):833–839PubMedCrossRefGoogle Scholar
  47. 47.
    de Toledo FG, Thompson MA, Bolliger C, Tyce GM, Dousa TP (1999) Gamma-l-glutamyl-l-DOPA inhibits Na(+)-phosphate cotransport across renal brush border membranes and increases renal excretion of phosphate. Kidney Int 55(5):1832–1842PubMedCrossRefGoogle Scholar
  48. 48.
    Connor JR, Wang XS, Allen RP, Beard JL, Wiesinger JA, Felt BT, Earley CJ (2009) Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome. Brain 132(Pt 9):2403–2412PubMedCrossRefGoogle Scholar
  49. 49.
    Winkelman JW, Shahar E, Sharief I, Gottlieb DJ (2008) Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study. Neurology 70(1):35–42PubMedCrossRefGoogle Scholar
  50. 50.
    Mizuno S, Mihara T, Miyaoka T, Inagaki T, Horiguchi J (2005) CSF iron, ferritin and transferrin levels in restless legs syndrome. J Sleep Res 14(1):43–47PubMedCrossRefGoogle Scholar
  51. 51.
    Hornyak M (2010) Depressive disorders in restless legs syndrome: epidemiology, pathophysiology and management. CNS Drugs 24(2):89–98PubMedCrossRefGoogle Scholar
  52. 52.
    MacGregor EA (2008) Menstrual migraine. Curr Opin Neurol 21(3):309–315PubMedCrossRefGoogle Scholar
  53. 53.
    Ghorayeb I, Bioulac B, Scribans C, Tison F (2008) Perceived severity of restless legs syndrome across the female life cycle. Sleep Med 9(7):799–802PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shiho Suzuki
    • 1
  • Keisuke Suzuki
    • 1
  • Masayuki Miyamoto
    • 1
  • Tomoyuki Miyamoto
    • 1
  • Yuka Watanabe
    • 1
  • Ryotaro Takashima
    • 1
  • Koichi Hirata
    • 1
  1. 1.Department of NeurologyDokkyo Medical UniversityMibuJapan

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