Evaluation of upper endoscopic findings in patients with restless legs syndrome and gastric complaints

Abstract

Background: The effect of gastrointestinal system disorders on Restless Legs Syndrome/Willis-Ekbom disease (RLS/WED) has been previously demonstrated by using serological tests. However, this association has not been supported by histopathological studies so far. Objective: To investigate the relationship between RLS/WED, upper endoscopic imaging and histopathological results in patients diagnosed with RLS who underwent endoscopy because of gastrointestinal system (GIS) complaints. Methods: Case-control study, including 100 patients diagnosed with RLS who presented dyspeptic complaints and underwent upper GIS endoscopy and 106 age- and sex-matched controls. RLS diagnosis was evaluated according to the four main diagnostic criteria determined by the International RLS Study Group. All patients underwent upper GIS endoscopic intervention and at least one gastric and/or antral biopsy. Results: There was no significant difference between patients and controls in relation to endoscopically seen gastric ulcer, duodenal ulcer, gastroesophageal reflux disease (GERD) findings and Helicobacter pylori (HP) positivity (p>0.05). Intestinal metaplasia and mucosal atrophy were more common in RLS/WED patients compared to controls (p=0.026 and p=0.017, respectively). Additionally, ferritin levels were found to be lower than the reference value. Conclusions: The detection of increased severity of intestinal metaplasia, mucosal atrophy, and gastric inflammation in RLS/WED patients with dyspeptic complaints may entail the close gastrointestinal system evaluation of these patients. However, larger randomized and controlled trials are required on this subject where patients are evaluated by upper GIS endoscopic biopsy.

Resumo

Introdução: Os efeitos das doenças do sistema digestório sobre a Síndrome das Pernas Inquietas/doença de Willis-Ekbom (SPI/DWE) foram demonstrados previamente por testes sorológicos. No entanto, até o momento tal associação não foi corroborada por estudos histopatológicos. Objetivo: Investigar a relação entre a SPI/DWE, imagens de endoscopia digestiva alta e resultados histopatológicos em pacientes diagnosticados com SPI/DWE com queixas do sistema digestório. Métodos: Estudo caso-controle incluindo 100 pacientes com SPI/DWE e queixas dispépticas que foram submetidos à endoscopia digestiva alta, e 106 controles emparelhados para idade e sexo. O diagnóstico de SPI/DWE foi determinado com base nos quatro principais critérios do International RLS Study Group. Todos os pacientes foram submetidos à intervenção endoscópica do sistema digestório superior e a pelo menos uma biópsia gástrica e/ou antral. Resultados: Não houve diferença significativa entre os grupos em relação à úlcera gástrica endoscopicamente observada, úlcera duodenal, doença do refluxo gastroesofágico (DRGE) e positividade para Helicobacter pylori (HP) (p>0,05). Metaplasia intestinal e atrofia da mucosa foram mais comuns em pacientes com SPI/DWE em comparação aos controles (p=0,026 e p=0,017, respectivamente). Níveis de ferritina encontravam-se abaixo do valor de referência. Conclusão: A detecção de metaplasia intestinal grave, atrofia de mucosa e inflamação gástrica em pacientes com SPI/DWE com queixas dispépticas pode justificar a avaliação cuidadosa do sistema digestório nestes pacientes. Entretanto, são necessários estudos controlados e com amostras maiores com pacientes avaliados com biópsia por via endoscópica.

Keywords:

ferritin - Helicobacter pylori - RLS - sleep disorder - atrophic gastritis - intestinal metaplasia - endoscopy

Palavras-chave:

ferritina - Helicobacter pylori - distúrbio do sono - gastrite atrófica - metaplasia intestinal - endoscopia

• References

• 1 Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, et al. 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. 2014 Aug;15(8):860-73. https://doi.org/10.1016/j.sleep.2014.03.025
• 2 Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. 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. 2003 Mar;4(2):101-19. https://doi.org/10.1016/s1389-9457(03)00010-8
• 3 Rye DB, Trotti LM. Restless legs syndrome and periodic leg movements of sleep. Neurol Clin. 2012 Nov;30(4):1137-66. https://doi.org/10.1016/j.ncl.2012.08.004
• 4 Trenkwalder C, Winkelmann J, Inoue Y, Paulus W. Restless legs syndrome-current therapies and management of augmentation. Nat Rev Neurol. 2015 Jul;11(8):434-45. https://doi.org/10.1038/nrneurol.2015.122
• 5 Nagandla K, De S. Restless legs syndrome: pathophysiology and modern management. Postgrad Med J. 2013;89(1053):402-10. https://doi.org/10.1136/postgradmedj-2012-131634
• 6 Garcia-Borreguero D, Williams A-M. An update on restless legs syndrome (Willis-Ekbom disease): clinical features, pathogenesis and treatment. Curr Opin Neurol. 2014 Aug;27(4):493-501. https://doi.org/10.1097/WCO.20190192201901920117
• 7 Trenkwalder C, Högl B, Winkelmann J. Recent advances in the diagnosis, genetics and treatment of restless legs syndrome. J Neurol. 2009 Apr;256(4):539-53. https://doi.org/10.1007/s00415-009-0134-9
• 8 Hening WA, Allen RP, Washburn M, Lesage SR, Earley CJ. The four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions (“mimics”). Sleep Med. 2009 Oct;10(9):976-81. https://doi.org/10.1016/j.sleep.2008.09.015
• 9 Weinstock LB, Walters AS. Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth. Sleep Med. 2011 Jun;12(6):610-3. https://doi.org/10.1016/j.sleep.2011.03.007
• 10 Borji R, Fereshtehnejad SM, Taba Taba Vakili S, Daryani NE, Ajdarkosh H. Association between irritable bowel syndrome and restless legs syndrome: a comparative study with control group. J Neurogastroenterol Motil. 2012 Oct;18(4):426-33. https://doi.org/10.5056/jnm.2012.18.4.426
• 11 Weinstock LB, Walters AS, Mullin GE, Duntley SP. Celiac disease is associated with restless legs syndrome. Dig Dis Sci. 2010 Jun;55(6):1667-73. https://doi.org/10.1007/s10620-009-0943-9
• 12 Weinstock LB, Bosworth BP, Scherl EJ, Li E, Iroku U, Munsell MA, et al. Crohn’s disease is associated with restless legs syndrome. Inflamm Bowel Dis. 2010 Feb;16(2):275-9. https://doi.org/10.1002/ibd.20992
• 13 Franco RA, Ashwathnarayan R, Deshpandee A, Knox J, Daniel J, Eastwood D, et al. The high prevalence of restless legs syndrome symptoms in liver disease in an academic-based hepatology practice. J Clin Sleep Med. 2008;4(1):45-9.
• 14 Appak YÇ, Özyurt G, Karakoyun M, Baran M. Effects of chronic gastritis on sleep and quality of life in adolescents. J Pediatr Res. 2019;6(4):259-65. https://doi.org/10.4274/jpr.galenos.2019.60134
• 15 Weinstock LB, Walters AS, Paueksakon P. Restless legs syndrome - Theoretical roles of inflammatory and immune mechanisms. Sleep Med Rev. 2012 Aug;16(4):341-54. https://doi.org/10.1016/j.smrv.2011.09.003
• 16 Ford AC, Gurusamy KS, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people. Cochrane database Syst Rev. 2016 Apr;4:CD003840. https://doi.org/10.1002/14651858.CD003840.pub5
• 17 Chan SM, Wu JCY, Teoh AYB, et al. Comparison of early outcomes and quality of life after laparoscopic Heller’s cardiomyotomy to peroral endoscopic myotomy for treatment of achalasia. Dig Endosc. 2016 Jan;28(1):27-32. https://doi.org/10.1111/den.12507
• 18 Yamanishi S, Iizumi T, Watanabe E, Shimizu M, Kamiya S, Nagata K, et al. Implications for induction of autoimmunity via activation of B-1 cells by Helicobacter pylori urease. Infect Immun. 2006;74(1):248-56. https://doi.org/10.1128/IAI.74.1.248-256.2006
• 19 Rezvani F, Sayadnasiri M, Rezaei O. Restless legs syndrome in patients infected with Helicobacter pylori. Neurol Res. 2018 Apr;40(7):583-7. https://doi.org/10.1080/01616412.2018.1454704
• 20 Konno M, Muraoka S, Takahashi M, Imai T. Iron-deficiency anemia associated with Helicobacter pylori gastritis. J Pediatr Gastroenterol Nutr. 2000 Jul;31(1):52-6. https://doi.org/10.1097/00005176-200007000-00012
• 21 Ciacci C, Sabbatini F, Cavallaro R, et al. 17 P Helicobacter pylori impairs iron absorption in infected individuals. Dig Liver Dis. 2004 Jul;36:455-60. https://doi.org/10.1016/j.dld.2004.02.008
• 22 Annibale B, Capurso G, Lahner E, Castiglione F, Di Bella S, Iovino P, et al. Concomitant alterations in intragastric pH and ascorbic acid concentration in patients with Helicobacter pylori gastritis and associated iron deficiency anaemia. Gut. 2003 Apr;52(4):496-501. https://doi.org/10.1136/gut.52.4.496
• 23 Çamcı G, Oğuz S. Association between Parkinson’s Disease and Helicobacter Pylori. J Clin Neurol. 2016;12(2):147-50. https://doi.org/10.3988/jcn.2016.12.2.147
• 24 Olama SM, El-Arman M. Helicobacter pylori in Egyptian patients with fibromyalgia syndrome. Egypt Rheumatol. 2013 Jul;35(3):167-73. https://doi.org/10.1016/j.ejr.2013.01.004
• 25 Dukowicz AC, Lacy BE, Levine GM. Small intestinal bacterial overgrowth: a comprehensive review. Gastroenterol Hepatol (N Y). 2007 Feb;3(2):112-22.
• 26 Manchanda S, Davies CR, Picchietti D. Celiac disease as a possible cause for low serum ferritin in patients with restless legs syndrome. Sleep Med. 2009 Aug;10(7):763-65. https://doi.org/10.1016/j.sleep.2008.07.014