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Evaluation of contributing factors to restless legs syndrome in migraine patients

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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.

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References

  1. Ekbom KA (1960) Restless legs syndrome. Neurology 10:868–873

    PubMed  CAS  Google Scholar 

  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):1286–1292

    Article  PubMed  Google Scholar 

  3. Winkelmann J (2008) Genetics of restless legs syndrome. Curr Neurol Neurosci Rep 8(3):211–216

    Article  PubMed  CAS  Google Scholar 

  4. Clemens S, Rye D, Hochman S (2006) Restless legs syndrome: revisiting the dopamine hypothesis from the spinal cord perspective. Neurology 67(1):125–130

    Article  PubMed  Google Scholar 

  5. Ekbom K, Ulfberg J (2009) Restless legs syndrome. J Intern Med 266(5):419–431

    Article  PubMed  CAS  Google Scholar 

  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):1307–1309

    PubMed  CAS  Google Scholar 

  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):164–170

    Article  PubMed  Google Scholar 

  8. Bartell S, Zallek S (2006) Intravenous magnesium sulfate may relieve restless legs syndrome in pregnancy. J Clin Sleep Med 2(2):187–188

    PubMed  Google Scholar 

  9. Bachmann CG, Guth N, Helmschmied K, Armstrong VW, Paulus W, Happe S (2008) Homocysteine in restless legs syndrome. Sleep Med 9(4):388–392

    Article  PubMed  Google Scholar 

  10. Patrick LR (2007) Restless legs syndrome: pathophysiology and the role of iron and folate. Altern Med Rev 12(2):101–112

    PubMed  Google Scholar 

  11. Rijsman RM, de Weerd AW (1999) Secondary periodic limb movement disorder and restless legs syndrome. Sleep Med Rev 3(2):147–158

    Article  PubMed  CAS  Google Scholar 

  12. Ferini-Strambi L (2007) RLS-like symptoms: differential diagnosis by history and clinical assessment. Sleep Med 8(Suppl 2):S3–S6

    Article  PubMed  Google Scholar 

  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):2076–2080

    Article  PubMed  Google Scholar 

  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):196–202

    Article  PubMed  Google Scholar 

  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):239–246

    Article  PubMed  CAS  Google Scholar 

  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 6:139–145

    Article  Google Scholar 

  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):2363–2369

    Article  PubMed  Google Scholar 

  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):598–601

    Article  PubMed  Google Scholar 

  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):1576–1586

    Google Scholar 

  20. Charbit AR, Akerman S, Goadsby PJ (2010) Dopamine: what’s new in migraine? Curr Opin Neurol 23(3):275–281

    Article  PubMed  CAS  Google Scholar 

  21. Chen PK, Fuh JL, Chen SP, Wang SJ (2010) Association between restless legs syndrome and migraine. J Neurol Neurosurg Psychiatry 81(5):524–528

    Article  PubMed  Google Scholar 

  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–S172

    Article  PubMed  Google Scholar 

  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):1255–1260

    Article  PubMed  CAS  Google Scholar 

  24. Headache Classification Subcommittee of the International Headache Society (2004). The International Classification of Headache Disorders: 2nd edn. Cephalalgia 24 Suppl 1:9–160

  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):101–119

    Article  PubMed  Google Scholar 

  26. American Academy of Sleep Medicine (2005) International classification of sleep disorders: diagnostic and coding manual, 2nd edn. Westchester, IL, pp 178–181

    Google Scholar 

  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):976–981

    Article  PubMed  Google Scholar 

  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):121–132

    Article  PubMed  Google Scholar 

  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):988–994

    PubMed  CAS  Google Scholar 

  30. Beck AT, Stear RA, Brown GK (1996) The Beck Depression Inventory, 2nd edn. Houghton Mifflin, Boston

    Google Scholar 

  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):193–213

    Article  PubMed  CAS  Google Scholar 

  32. Fukuhara S, Takegami M, Suzukamo Y, et al (2006) The Japanese version of the Epworth Sleepiness Scale (JESS) J Jap Respir Soc 44:896–898

    Google Scholar 

  33. Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14(6):540–545

    PubMed  CAS  Google Scholar 

  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):982–992

    Article  PubMed  CAS  Google Scholar 

  35. Hosmer DW, Lemeshow S (2000) In: Applied logistic regression, 2nd edn. Wiley, New York, p 375

  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):589–597

    PubMed  Google Scholar 

  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):1155–1157

    Article  PubMed  Google Scholar 

  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):226–230

    PubMed  CAS  Google Scholar 

  39. Russell MB (2007) Genetics in primary headaches. J Headache Pain 8(3):190–195

    Article  PubMed  Google Scholar 

  40. Winkelmann J, Ferini-Strambi L (2006) Genetics of restless legs syndrome. Sleep Med Rev 10(3):179–183

    Article  PubMed  Google Scholar 

  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):161–167

    Article  PubMed  CAS  Google Scholar 

  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):1485–1492

    Article  PubMed  Google Scholar 

  43. Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther 113(2):296–320

    Article  PubMed  CAS  Google Scholar 

  44. Ferrari MD, Saxena PR (1993) On serotonin and migraine: a clinical and pharmacological review. Cephalalgia 13(3):151–165

    Article  PubMed  CAS  Google Scholar 

  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):197–206

    Article  PubMed  Google Scholar 

  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):833–839

    Article  PubMed  Google Scholar 

  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):1832–1842

    Article  PubMed  Google Scholar 

  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):2403–2412

    Article  PubMed  Google Scholar 

  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):35–42

    Article  PubMed  Google Scholar 

  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):43–47

    Article  PubMed  Google Scholar 

  51. Hornyak M (2010) Depressive disorders in restless legs syndrome: epidemiology, pathophysiology and management. CNS Drugs 24(2):89–98

    Article  PubMed  Google Scholar 

  52. MacGregor EA (2008) Menstrual migraine. Curr Opin Neurol 21(3):309–315

    Article  PubMed  CAS  Google Scholar 

  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):799–802

    Article  PubMed  Google Scholar 

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Acknowledgments

We are very grateful to Dr. Masatomo Watanabe and the medical staff from the outpatient clinic for assistance with this study.

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Authors and Affiliations

  1. Department of Neurology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan

    Shiho Suzuki, Keisuke Suzuki, Masayuki Miyamoto, Tomoyuki Miyamoto, Yuka Watanabe, Ryotaro Takashima & Koichi Hirata

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  1. Shiho Suzuki
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  2. Keisuke Suzuki
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Correspondence to Keisuke Suzuki.

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Suzuki, S., Suzuki, K., Miyamoto, M. et al. Evaluation of contributing factors to restless legs syndrome in migraine patients. J Neurol 258, 2026–2035 (2011). https://doi.org/10.1007/s00415-011-6064-3

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  • DOI: https://doi.org/10.1007/s00415-011-6064-3

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