Digestive Diseases and Sciences

, Volume 53, Issue 5, pp 1252–1256 | Cite as

Restless Legs Syndrome in Patients with Irritable Bowel Syndrome: Response to Small Intestinal Bacterial Overgrowth Therapy

  • Leonard B. Weinstock
  • Steve E. Fern
  • Stephen P. Duntley
Original Paper

Abstract

Background Small intestinal bacterial overgrowth (SIBO) occurs in irritable bowel syndrome (IBS) and fibromyalgia. Since restless legs syndrome (RLS) occurs with fibromyalgia, a link between IBS, SIBO, and RLS was studied. Methods BS patients with abnormal lactulose breath tests received rifaximin 1,200 mg day−1 for 10 days, followed by tegaserod 3 mg, long-term, and 1 month of zinc 220 mg day−1 and once-daily probiotic (N = 11) or rifaximin monotherapy (N = 2). IBS symptom improvement was assessed after rifaximin. RLS symptoms, IBS symptoms, and overall IBS global improvement were assessed at last posttreatment visit: 8/10 patients were followed long-term (mean, 139 days; range, 54–450 days). Results Ten of 13 patients exhibited ≥80% improvement from baseline in RLS symptoms. Five maintained complete resolution of RLS symptoms. Global gastrointestinal symptom improvement was great (n = 6), moderate (n = 5), or mild (n = 2). Conclusion This study suggests that SIBO associated with IBS may be a factor in some RLS patients and SIBO therapy provides long-term RLS improvement.

Keywords

Antibiotic Irritable bowel syndrome Restless legs syndrome Rifaximin 

Notes

Acknowledgements

Financial disclosure: Partial funding provided by a grant from Salix Pharmaceuticals, Inc.

References

  1. 1.
    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 165:1286–1292PubMedCrossRefGoogle Scholar
  2. 2.
    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 164:196–202PubMedCrossRefGoogle Scholar
  3. 3.
    Lavigne GJ, Montplaisir JY (1994) Restless legs syndrome and sleep bruxism: prevalence and association among Canadians. Sleep 17:739–743PubMedGoogle Scholar
  4. 4.
    Allen R (2004) Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). Sleep Med 5:385–391PubMedCrossRefGoogle Scholar
  5. 5.
    Gigli GL, Adorati M, Dolso P, Piani A, Valente M, Brotini S, Budai R (2004) Restless legs syndrome in end-stage renal disease. Sleep Med 5:309–315PubMedCrossRefGoogle Scholar
  6. 6.
    Ondo W, Jankovic W (1996) Restless legs syndrome: clinicoetiologic correlates. Neurology 47:1435–1441PubMedGoogle Scholar
  7. 7.
    Iannaccone S, Quattrini A, Sferrazza B, Ferini-Strambi L (2000) Charcot–Marie–Tooth disease type 2 with restless legs syndrome. Neurology 54:1013–1014PubMedGoogle Scholar
  8. 8.
    Yunus MB, Aldag JC (1996) Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study. BMJ 312:1339PubMedGoogle Scholar
  9. 9.
    Prado GF, Allen RP, Trevisani VMF, Toscano VG, Earley CJ (2002) Sleep disruption in systemic sclerosis (scleroderma) patients: clinical and polysomnographic findings. Sleep Med 3:341–345PubMedCrossRefGoogle Scholar
  10. 10.
    Veale D, Kavanagh G, Fielding JF, Fitzgerald O (1991) Primary fibromyalgia and the irritable bowel syndrome: different expressions of a common pathogenetic process. Br J Rheumatol 30:220–222PubMedCrossRefGoogle Scholar
  11. 11.
    Lubrano E, Iovino P, Tremolaterra F, Parsons WJ, Ciacci C, Mazzacca G (2001) Fibromyalgia in patients with irritable bowel syndrome. An association with the severity of the intestinal disorder. Int J Colorectal Dis 16:211–215PubMedCrossRefGoogle Scholar
  12. 12.
    Sperber AD, Atzmon Y, Neumann L, Weisberg I, Shalit Y, Abu-Shakrah M, Fich A, Buskila D (1999) Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications. Am J Gastroenterol 94:3541–3546PubMedCrossRefGoogle Scholar
  13. 13.
    Chang L, Berman S, Mayer E, Suyenobu B, Derbyshire S, Naliboff B, Vogt B, FitzGerald L, Mandelkern MA (2003) Brain responses to visceral and somatic stimuli in patients with irritable bowel syndrome with and without fibromyalgia. Am J Gastroenterol 98:1354–1361PubMedCrossRefGoogle Scholar
  14. 14.
    Pimentel M, Wallace D, Hallegua D, Chow E, Kong Y, Park S, Lin HC (2004) A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. Ann Rheum Dis 63:450–452PubMedCrossRefGoogle Scholar
  15. 15.
    Lin HC (2004) Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome. JAMA 292:852–858PubMedCrossRefGoogle Scholar
  16. 16.
    van der Veek PPJ, van den Berg M, de Kroon YE, Verspaget HW, Masclee AA (2005) Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroenterol 100:2510–2516PubMedCrossRefGoogle Scholar
  17. 17.
    Riordan SM, McIver CJ, Wakefield D, Duncombe VM, Bolin TD, Thomas MC (1996) Mucosal cytokine production in small-intestinal bacterial overgrowth. Scand J Gastroenterol 31:977–984PubMedCrossRefGoogle Scholar
  18. 18.
    Barbara G, Stanghellini V, de Giorgia R, Cremon C, Cottrell GS, Santini D, Pasquinelli G, Morselli-Labate AM, Grady EF, Bunnett NW, Collins SM, Corinaldesi R (2004) Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 126:693–702PubMedCrossRefGoogle Scholar
  19. 19.
    Törnblom H, Lindberg G, Nyberg B, Veress B (2002) Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology 123:1972–1979PubMedCrossRefGoogle Scholar
  20. 20.
    Romagnuolo J, Schiller D, Bailey RJ (2002) Using breath tests wisely in a gastroenterology practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenterol 97:1113–1126PubMedCrossRefGoogle Scholar
  21. 21.
    Lupascu A, Gabrielli M, Lauritano EC, Scarpellini E, Santoliquido A, Cammarota G, Flore R, Tondi P, Pola P, Gasbarrini G, Gasbarrini A (2005) Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome. Aliment Pharmacol Ther 22:1157–1160PubMedCrossRefGoogle Scholar
  22. 22.
    Pimentel M, Chow EJ, Lin HC (2003) Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome: a double-blind, randomized, placebo-controlled study. Am J Gastroenterol 98:412–419PubMedGoogle Scholar
  23. 23.
    Pimentel M, Park S, Mirocha J, Kane JMSV, Kong Y (2006) The Effects of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of irritable bowel syndrome. Ann Intern Med 145:557–563PubMedGoogle Scholar
  24. 24.
    Weinstock LB, Todorczuk JR, Fern SE, Thyssen EP (2006) Comprehensive small intestinal bacterial (SIBO) therapy for irritable bowel syndrome (IBS). Am J Gastroenterol 101(Suppl 2):S470–S471Google Scholar
  25. 25.
    Pimentel M, Soffer EE, Chow EJ, Kong Y, Lin HC (2002) Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test, suggesting bacterial overgrowth. Dig Dis Sci 47:2639–2643PubMedCrossRefGoogle Scholar
  26. 26.
    Vantrappen G, Janssens J, Hellemans J, Ghoos Y (1977) The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest 59:1158–1166PubMedCrossRefGoogle Scholar
  27. 27.
    Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, Spiller RC (2006) Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol 101:1288–1294PubMedCrossRefGoogle Scholar
  28. 28.
    Plaza MA (2001) 5-Hydroxytryptamine and the gastrointestinal migrating motor complex. Curr Opin Investig Drugs 2:539–544PubMedGoogle Scholar
  29. 29.
    Sturniolo GC, Fries W, Mazzon E, Di Leo V, Barollo M, D’inca R (2002) Effect of zinc supplementation on intestinal permeability in experimental colitis. J Lab Clin Med 139:311–315PubMedCrossRefGoogle Scholar
  30. 30.
    Quigley EM, Quera R. (2006) Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology 130(Suppl 1):S78–S90PubMedCrossRefGoogle Scholar
  31. 31.
    Hening WA, Allen RP, Thanner S, Washburn T, Heckler D, Walters AS, Earley CJ (2003) The Johns Hopkins telephone diagnostic interview for the restless legs syndrome: preliminary investigation for validation in a multi-center patient and control population. Sleep Med 4:137–141PubMedCrossRefGoogle Scholar
  32. 32.
    Aaron LA, Buchwald D (2001) A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med 134:868–881PubMedGoogle Scholar
  33. 33.
    Blackburn-Munro G (2004) Hypothalamo–pituitary–adrenal axis dysfunction as a contributory factor to chronic pain and depression. Curr Pain Headache Rep 8:116–124PubMedCrossRefGoogle Scholar
  34. 34.
    Bomholt SF, Harbuz MS, Blackburn-Munro G (2004) Involvement and role of the hypothalamo–pituitary–adrenal (HPA) stress axis in animal models of chronic pain and inflammation. Stress 7:1–14PubMedCrossRefGoogle Scholar
  35. 35.
    Grinevich V, Ma X-M, Herman JP, Jezova D, Akmayev I, Aguilera G (2001) Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats. J Neuroendocrinol 13:711–723PubMedCrossRefGoogle Scholar
  36. 36.
    Pimentel M, Lin HC. Response to Dr. Parisi, et al. (2003) Am J Gastroenterol 98:2573–2574Google Scholar
  37. 37.
    Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (2006) Functional bowel disorders. Gastroenterology 130:1480–1491PubMedCrossRefGoogle Scholar
  38. 38.
    Raja KB, Latunde-Dada GO, Peters TJ, McKie AT, Simpson RJ (2005) Role of interleukin-6 in hypoxic regulation of intestinal iron absorption. Br J Haematol 131:656–662PubMedCrossRefGoogle Scholar
  39. 39.
    Liu X-B, Nguyen N-BH, Marquess KD, Yang F, Haile DJ (2005) Regulation of hepcidin and ferroportin expression by lipopolysaccharide in splenic macrophages. Blood Cells Mol Dis 35:47–56PubMedCrossRefGoogle Scholar
  40. 40.
    Alpers DH, Klein S (2003) Approach to the patient requiring nutritional supplementation. In: Yamada T, Alpers DH, Laine L, et al (eds) Textbook of gastroenterology, 2nd edn. Lippincott, Williams, & Wilkins, Philadelphia, pp 1056–1084Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Leonard B. Weinstock
    • 1
  • Steve E. Fern
    • 1
  • Stephen P. Duntley
    • 1
  1. 1.Washington University School of MedicineSt. LouisUSA

Personalised recommendations