Restless legs syndrome is a relevant comorbidity in patients with inflammatory bowel disease

  • Janek Becker
  • Felix Berger
  • Katharina A. Schindlbeck
  • Denis Poddubnyy
  • Peter M. Koch
  • Jan C. Preiß
  • Britta Siegmund
  • Frank Marzinzik
  • Jochen Maul
Original Article
First Online:
Accepted:
  • 50 Downloads

Abstract

Background and aims

In patients with inflammatory bowel disease (IBD), restless legs syndrome (RLS) may occur as an extraintestinal disease manifestation. Iron deficiency (ID) or folate deficiency/vitamin B12 deficiency (FD/VB12D) has previously been described to cause RLS. Here, we determined the prevalence and severity of RLS in IBD patients and evaluated the effect of iron and/or folic acid/vitamin B12 supplementation.

Methods

Patients were screened for ID and RLS by a gastroenterologist. If RLS was suspected, a neurologist was consulted for definitive diagnosis and severity. Patients with RLS and ID, FD, or VB12D received supplementation and were followed-up at weeks 4 and 11 after starting supplementation.

Results

A total of 353 IBD patients were included. Prevalence for RLS was 9.4% in Crohn’s disease (CD) and 8% in ulcerative colitis (UC). Prevalence for the subgroup of clinically relevant RLS (symptoms ≥ twice/week with at least moderate distress) was 7.1% (n = 16) for CD and 4.8% (n = 6) for UC. 38.7% of RLS patients presented with ID, FD, and/or VB12D. Most frequently ID was seen (25.8%; n = 8). Iron supplementation resulted in RLS improvement (p = 0.029) at week 4 in seven out of eight patients.

Conclusion

Although the overall prevalence of RLS in IBD did not differ to the general population, clinically relevant RLS was more frequent in IBD patients and, therefore, it is important for clinicians to be aware of RLS symptoms. Though for definite diagnosis and proper treatment of RLS, a neurologist must be consulted. Additionally, iron supplementation of IBD patients with ID can improve RLS symptoms.

Trial registration

ClinicalTrials.gov No. NCT03457571

Keywords

Restless legs syndrome Inflammatory bowel disease Iron deficiency Crohn’s disease Ulcerative colitis 
This is a preview of subscription content, log in to check access

Notes

Compliance with ethical standards

The study was approved (16 January 2014) by the ethics committee of the Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin (reference EA4/132/13).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

384_2018_3032_MOESM1_ESM.docx (42 kb)
ESM 1 (DOCX 41 kb)
384_2018_3032_MOESM2_ESM.docx (14 kb)
ESM 2 (DOCX 14 kb)

References

  1. 1.
    Repiso A, Alcántara M, Muñoz-Rosas C et al (2006) Extraintestinal manifestations of Crohn’s disease: prevalence and related factors. Rev Esp Enferm Dig 98:510–517CrossRefPubMedGoogle Scholar
  2. 2.
    Ferro JM, Oliveira SN, Correia L (2014) Chapter 40—Neurologic manifestations of inflammatory bowel diseases. In: Biller J, Ferro JM (eds) Handbook of clinical neurology, vol 120. Neurologic aspects of systemic disease part II. Elsevier, Amsterdam, pp 595–605. Available at: http://www.sciencedirect.com/science/article/pii/B9780702040870000401. Accessed 18 Feb 2016
  3. 3.
    Guagnozzi D, Lucendo AJ (2014) Anemia in inflammatory bowel disease: a neglected issue with relevant effects. World J Gastroenterol: WJG 20:3542–3551CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Allen RP, Earley CJ (2007) The role of iron in restless legs syndrome. Mov Disord 22(Suppl 1):S440–S448CrossRefPubMedGoogle Scholar
  5. 5.
    Weinstock LB, Bosworth BP, Scherl EJ, Li E, Iroku U, Munsell MA, Mullen GE, Walters AS (2010) Crohn’s disease is associated with restless legs syndrome. Inflamm Bowel Dis 16:275–279 Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864021/. Accessed 29 May 2015CrossRefPubMedGoogle Scholar
  6. 6.
    Takahara I, Takeshima F, Ichikawa T, Matsuzaki T, Shibata H, Miuma S, Akazawa Y, Miyaaki H, Taura N, Nakao K (2017) Prevalence of restless legs syndrome in patients with inflammatory bowel disease. Dig Dis Sci 62:761–767CrossRefPubMedGoogle Scholar
  7. 7.
    Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB, International Restless Legs Syndrome Study Group (2014) Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria—history, rationale, description, and significance. Sleep Med 15:860–873CrossRefPubMedGoogle Scholar
  8. 8.
    Whittom S, Dauvilliers Y, Pennestri M-H, Vercauteren F, Molinari N, Petit D, Montplaisir J (2007) Age-at-onset in restless legs syndrome: a clinical and polysomnographic study. Sleep Med 9:54–59CrossRefPubMedGoogle Scholar
  9. 9.
    Dauvilliers Y, Winkelmann J (2013) Restless legs syndrome: update on pathogenesis. Curr Opin Pulm Med 19:594–600CrossRefPubMedGoogle Scholar
  10. 10.
    Winkelmann J, Wetter TC, Collado-Seidel V, Gasser T, Dichgans M, Yassouridis A, Trenkwalder C (2000) Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients. Sleep 23:597–602CrossRefPubMedGoogle Scholar
  11. 11.
    Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Pütz B, Eckstein G, Hauk S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Peglau I, Eisensehr I, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Müller-Myhsok B, Meitinger T (2007) Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 39:1000–1006CrossRefPubMedGoogle Scholar
  12. 12.
    Trenkwalder C, Allen R, Högl B, Paulus W, Winkelmann J (2016) Restless legs syndrome associated with major diseases. Neurology 86:1336–1343CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Allen RP, Auerbach S, Bahrain H, Auerbach M, Earley CJ (2013) The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia. Am J Hematol 88:261–264CrossRefPubMedGoogle Scholar
  14. 14.
    Group TIRLSS (2003) Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4:121–132CrossRefGoogle Scholar
  15. 15.
    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 165:1286–1292CrossRefPubMedGoogle Scholar
  16. 16.
    Allen RP, Bharmal M, Calloway M (2011) Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord 26:114–120CrossRefPubMedGoogle Scholar
  17. 17.
    Ganzoni AM (1970) Intravenous iron-dextran: therapeutic and experimental possibilities. Schweiz Med Wochenschr 100:301–303PubMedGoogle Scholar
  18. 18.
    Silverberg MS, Satsangi J, Ahmad T, Arnott IDR, Bernstein CN, Brant SR, Caprilli R, Colombel JF, Gasche C, Geboes K, Jewell DP, Karban A, Loftus EV, Peña AS, Riddell RH, Sachar DB, Schreiber S, Steinhart AH, Targan SR, Vermeire S, Warren BF (2005) Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 19(Suppl A):5A–36ACrossRefPubMedGoogle Scholar
  19. 19.
    Allen RP, La Buda MC, Becker P et al (2002) Family history study of the restless legs syndrome. Sleep Med 3(Supplement):S3–S7CrossRefPubMedGoogle Scholar
  20. 20.
    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 164:196–202CrossRefPubMedGoogle Scholar
  21. 21.
    Ulfberg J, Nyström B, Carter N, Edling C (2001) Prevalence of restless legs syndrome among men aged 18 to 64 years: an association with somatic disease and neuropsychiatric symptoms. Mov Disord 16:1159–1163CrossRefPubMedGoogle Scholar
  22. 22.
    Winkelmann J, Ferini-Strambi L (2006) Genetics of restless legs syndrome. Sleep Med Rev 10:179–183CrossRefPubMedGoogle Scholar
  23. 23.
    Bjorvatn B, Leissner L, Ulfberg J et al (2005) Prevalence, severity and risk factors of restless legs syndrome in the general adult population in two Scandinavian countries. Sleep Med 6:307–312CrossRefPubMedGoogle Scholar
  24. 24.
    Hoek PD, Smits MG, de Roos NM et al (2015) Increased prevalence of restless legs syndrome in patients with Crohn’s disease. Eur J Gastroenterol Hepatol 27:951–955CrossRefPubMedGoogle Scholar
  25. 25.
    Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L (2007) Restless legs syndrome: prevalence and impact in children and adolescents—the Peds REST Study. Pediatrics 120:253–266CrossRefPubMedGoogle Scholar
  26. 26.
    Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L (2016) Iron deficiency anaemia. Lancet 387:907–916CrossRefPubMedGoogle Scholar
  27. 27.
    Walters AS, Hickey K, Maltzman J, Verrico T, Joseph D, Hening W, Wilson V, Chokroverty S (1996) A questionnaire study of 138 patients with restless legs syndrome: the “Night-Walkers” survey. Neurology 46:92–95CrossRefPubMedGoogle Scholar
  28. 28.
    Allen RP, Earley CJ (2000) Defining the phenotype of the restless legs syndrome (RLS) using age-of-symptom-onset. Sleep Med 1:11–19CrossRefPubMedGoogle Scholar
  29. 29.
    Trotti LM, Bhadriraju S, Becker LA (2012) Iron for restless legs syndrome. Cochrane Database Syst Rev 5:CD007834PubMedCentralGoogle Scholar
  30. 30.
    Sloand JA, Shelly MA, Feigin A, Bernstein P, Monk RD (2004) A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 43:663–670CrossRefPubMedGoogle Scholar
  31. 31.
    Grote L, Leissner L, Hedner J, Ulfberg J (2009) A randomized, double-blind, placebo controlled, multi-center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome. Mov Disord 24:1445–1452CrossRefPubMedGoogle Scholar
  32. 32.
    Wang J, O’Reilly B, Venkataraman R, Mysliwiec V, Mysliwiec A (2009) Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: a randomized, double-blind, placebo-controlled study. Sleep Med 10:973–975CrossRefPubMedGoogle Scholar
  33. 33.
    Schindlbeck KA, Becker J, Berger F et al (2016) Impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, and quality of life. Int J Color Dis:1–6Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medicine (Gastroenterology, Infectious Diseases, Rheumatology), Campus Benjamin FranklinCharité – Universitätsmedizin BerlinBerlinGermany
  2. 2.Department of Neurology, Campus Benjamin FranklinCharité – Universitätsmedizin BerlinBerlinGermany
  3. 3.Center for NeurosciencesFeinstein Institute for Medical ResearchManhassetUSA
  4. 4.Gastroenterologie, Hepatologie und DiabetologieVivantes Klinikum NeuköllnBerlinGermany
  5. 5.Gastroenterologie am Bayerischen PlatzBerlinGermany

Personalised recommendations