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Parkinson’s Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects

  • Motility (H Parkman and R Schey, Section Editors)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose of Review

Gastrointestinal disturbances are seen in nearly all patients with Parkinson’s disease and lead to impaired quality of life, affect drug pharmacodynamics, and potentially worsen patient’s existing motor fluctuations, leading to further disability. Recent evidence links abnormal accumulations of α-synuclein aggregates in the periphery (gut) as seen in the cortex which causes dysfunctions impacting every level of the gastrointestinal tract from the esophagus, to the stomach, small bowel, colon, and rectum and can even predate the onset of the central neurologic disorder itself. Many treatments exist for the clinical phenotypes that result from the autonomic dysfunction and neuropathy involved in this neurodegenerative disorder.

Recent findings/summary

The treatments for the gut dysfunction seen in Parkinson’s disease (PD) depend on the specific area of the gastrointestinal tract affected. For dysphagia, behavioral therapies with speech pathology, neuromuscular electrical stimulation, or botulinum toxin injection may be helpful. For gastroparesis, domperidone may serve as an antiemetic while also blunting the hypotensive potential of Levodopa while new treatments such as ghrelin agonists may prove beneficial to help appetite, satiety, gastric emptying in those with constipation, and even improve constipation. Antibiotics such as rifaximin with poor systemic absorption may be used to treat small bacterial overgrowth also found in those with PD while the benefits of probiotics is yet to be determined. Finally, constipation in PD can be a reflection of pelvic floor dyssynergia, slow transit constipation, or both, thus treatments targeting the specific anorectal dysfunction is necessary for better outcomes.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. • Sharma A, Kurek J, Morgan JC, Wakade C, Rao SS. Constipation in Parkinson’s disease: a nuisance or nuanced answer to the pathophysiological puzzle? Curr Gastroenterol Rep. 2018;20(1):1–7 Great review done recently on the pathophysiology of constipation in Parkinson’s Disease.

    PubMed  Google Scholar 

  2. • Braak H, de Vos RA, Bohl J, Del Tredici K. Gastric α-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett. 2006;396(1):67–72 Highlighted for first suggesting Parkinson’s disease may start in the gastrointestinal tract rather than the central nervous system.

    CAS  PubMed  Google Scholar 

  3. Moshiree B, Ringel Y. Small bowel bacterial overgrowth syndrome. In: Handbook of gastrointestinal motility and functional disorders. Thorofare, NJ: SLACK Incorporated; 2015.

    Google Scholar 

  4. • Su A, Gandhy R, Barlow C, Triadafilopoulos G. Utility of high-resolution anorectal manometry and wireless motility capsule in the evaluation of patients with Parkinson’s disease and chronic constipation. BMJ Open Gastroenterol. 2016;3(1)1):e000118. eCollection 2016. This reference provides a comprehensive evaluation of the gastrointestinal dysfunction found in patient's with Parkinson’s disease by using validated diagnostic testing and finds a great degree of motility disturbances.

    PubMed  PubMed Central  Google Scholar 

  5. Bachmann CG, Trenkwalder C. Body weight in patients with Parkinson’s disease. Mov Disord. 2006;21(11):1824–30.

    PubMed  Google Scholar 

  6. Su A, Gandhy R, Barlow C, Triadafilopoulos G. Clinical and manometric characteristics of patients with Parkinson’s disease and esophageal symptoms. Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus. 2017;30(4):1–6.

    CAS  Google Scholar 

  7. Suttrup I, Suttrup J, Suntrup-Krueger S, Siemer ML, Bauer J, Hamacher C, et al. Esophageal dysfunction in different stages of Parkinson’s disease. Neurogastroenterol Motil. 2017;29(1). https://doi.org/10.1111/nmo.12915

    Google Scholar 

  8. Heetun ZS, Quigley EM. Gastroparesis and Parkinson’s disease: a systematic review. Parkinsonism Relat Disord. 2012;18(5):433–40.

    PubMed  Google Scholar 

  9. Barboza JL, Okun MS, Moshiree B. The treatment of gastroparesis, constipation and small intestinal bacterial overgrowth syndrome in patients with Parkinson’s disease. Expert Opin Pharmacother. 2015;16(16):2449–64.

    CAS  PubMed  Google Scholar 

  10. Fasano A, Bove F, Gabrielli M, Petracca M, Zocco MA, Ragazzoni E, et al. The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord. 2013;28(9):1241–9.

    CAS  PubMed  Google Scholar 

  11. Stewart WF, Liberman JN, Sandler RS, Woods MS, Stemhagen A, Chee E, et al. Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol. 1999;94(12):3530–40.

    CAS  PubMed  Google Scholar 

  12. Siddiqui M, Rast S, Lynn M, Auchus A, Pfeiffer R. Autonomic dysfunction in Parkinson’s disease: a comprehensive symptom survey. Parkinsonism Relat Disord. 2002;8(4):277–84.

    CAS  PubMed  Google Scholar 

  13. Postuma RB, Gagnon JF, Pelletier A, Montplaisir J. Prodromal autonomic symptoms and signs in Parkinson’s disease and dementia with Lewy bodies. Mov Disord. 2013;28(5):597–604.

    PubMed  Google Scholar 

  14. Lin C-H, Lin J-W, Liu Y-C, Chang C-H, Wu R-M. Risk of Parkinson’s disease following severe constipation: a nationwide population-based cohort study. Parkinsonism Relat Disord. 2014;20(12):1371–5.

    PubMed  Google Scholar 

  15. Sung H-Y, Park J-W, Kim J-S. The frequency and severity of gastrointestinal symptoms in patients with early Parkinson’s disease. J Mov Disord. 2014;7(1):7–12.

    PubMed  PubMed Central  Google Scholar 

  16. Jost WH. Gastrointestinal motility problems in patients with Parkinson’s disease. Drugs Aging. 1997;10(4):249–58.

    CAS  PubMed  Google Scholar 

  17. • Pflug C, Bihler M, Emich K, Niessen A, Nienstedt JC, Flügel T, et al. Critical dysphagia is common in Parkinson disease and occurs even in early stages: a prospective cohort study. Dysphagia. 2018;33(1):41–50 Interesting finding in this refernece is that dysphagia may predate findings in Parkinson’s disease.

    PubMed  Google Scholar 

  18. Miller RL, James-Kracke M, Sun GY, Sun AY. Oxidative and inflammatory pathways in Parkinson’s disease. Neurochem Res. 2009;34(1):55–65.

    CAS  PubMed  Google Scholar 

  19. Nagaya M, Kachi T, Yamada T, Igata A. Videofluorographic study of swallowing in Parkinson’s disease. Dysphagia. 1998;13(2):95–100.

    CAS  PubMed  Google Scholar 

  20. Potulska A, Friedman A, Królicki L, Spychala A. Swallowing disorders in Parkinson’s disease. Parkinsonism Relat Disord. 2003;9(6):349–53.

    PubMed  Google Scholar 

  21. Wakasugi Y, Yamamoto T, Oda C, Murata M, Tohara H, Minakuchi S. Effect of an impaired oral stage on swallowing in patients with Parkinson’s disease. J Oral Rehabil. 2017;44:756–62.

    CAS  PubMed  Google Scholar 

  22. Nienstedt J, Buhmann C, Bihler M, Niessen A, Plaetke R, Gerloff C, et al. Drooling is no early sign of dysphagia in Parkinson’ s disease. Neurogastroenterol Motil. 2018;30(4):e13259.

    CAS  PubMed  Google Scholar 

  23. Nóbrega AC, Rodrigues B, Torres AC, Scarpel RDA, Neves CA, Melo A. Is drooling secondary to a swallowing disorder in patients with Parkinson’s disease? Parkinsonism Relat Disord. 2008;14(3):243–5.

    PubMed  Google Scholar 

  24. Salat-Foix D, Suchowersky O. The management of gastrointestinal symptoms in Parkinson’s disease. Expert Rev Neurother. 2012;12(2):239–48.

    PubMed  Google Scholar 

  25. Videlock EJ, Mahurkar-Joshi S, Hoffman JM, Iliopoulos D, Pothoulakis C, Mayer EA, et al. Sigmoid colon mucosal gene expression supports alterations of neuronal signaling in irritable bowel syndrome with constipation. Am J Physiol Gastrointest Liver Physiol. 2018.

  26. Phillips RJ, Walter GC, Wilder SL, Baronowsky EA, Powley TL. Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: autonomic pathway implicated in Parkinson’s disease? Neuroscience. 2008;153(3):733–50.

    CAS  PubMed  Google Scholar 

  27. Higo R, Tayama N, Watanabe T, Niimi S. Abnormal elevation of resting pressure at the upper esophageal sphincter of Parkinson’s disease patients. Eur Arch Otorhinolaryngol. 2001;258(10):552–6.

    CAS  PubMed  Google Scholar 

  28. Jones C, Hoffman M, Lin L, Abdelhalim S, Jiang J, McCulloch T. Identification of swallowing disorders in early and mid-stage Parkinson’s disease using pattern recognition of pharyngeal high-resolution manometry data. Neurogastroenterol Motil. 2018;30(4):e13236.

    CAS  PubMed  Google Scholar 

  29. Vogel AP, Rommel N, Sauer C, Horger M, Krumm P, Himmelbach M, et al. Clinical assessment of dysphagia in neurodegeneration (CADN): development, validity and reliability of a bedside tool for dysphagia assessment. J Neurol. 2017;264(6):1107–17.

    PubMed  Google Scholar 

  30. Warnecke T, Suttrup I, Schroder JB, Osada N, Oelenberg S, Hamacher C, et al. Levodopa responsiveness of dysphagia in advanced Parkinson’s disease and reliability testing of the FEES-Levodopa-test. Parkinsonism Relat Disord. 2016;28:100–6. https://doi.org/10.1016/j.parkreldis.2016.04.034.

    Article  PubMed  Google Scholar 

  31. Tawadros PB, Cordato D, Cathers I, Burne JA. An electromyographic study of parkinsonian swallowing and its response to levodopa. Mov Disord. 2012;27(14):1811–5.

    PubMed  Google Scholar 

  32. Warnecke T, Suttrup I, Schröder JB, Osada N, Oelenberg S, Hamacher C, et al. Levodopa responsiveness of dysphagia in advanced Parkinson’s disease and reliability testing of the FEES-Levodopa-test. Parkinsonism Relat Disord. 2016;28:100–6.

    PubMed  Google Scholar 

  33. Restivo DA, Palmeri A, Marchese-Ragona R. Botulinum toxin for cricopharyngeal dysfunction in Parkinson’s disease. N Engl J Med. 2002;346(15):1174–5.

    PubMed  Google Scholar 

  34. Restivo DA, Ragona RM, Staffieri A, De Grandis D. Successful botulinum toxin treatment of dysphagia in oculopharyngeal muscular dystrophy. Gastroenterology. 2000;119(5):1416.

    CAS  PubMed  Google Scholar 

  35. Born LJ, Harned RH, Rikkers LF, Pfeiffer RF, Quigley EM. Cricopharyngeal dysfunction in Parkinson’s disease: role in dysphagia and response to myotomy. Mov Disord. 1996;11(1):53–8.

    CAS  PubMed  Google Scholar 

  36. Olchik MR, Ghisi M, Ayres A, Schuh AFS, Oppitz PP, de Mello Rieder CR. The impact of deep brain stimulation on the quality of life and swallowing in individuals with Parkinson’s disease. Intl Arch Otorhinolaryngol. 2018;22(2):125–9.

    Google Scholar 

  37. Derrey S, Chastan N, Maltete D, Verin E, Dechelotte P, Lefaucheur R, et al. Impact of deep brain stimulation on pharyngo-esophageal motility: a randomized cross-over study. Neurogastroenterol Motil. 2015;27(9):1214–22.

    CAS  PubMed  Google Scholar 

  38. Troche MS, Brandimore AE, Foote KD, Okun MS. Swallowing and deep brain stimulation in Parkinson’s disease: a systematic review. Parkinsonism Relat Disord. 2013;19(9):783–8.

    PubMed  PubMed Central  Google Scholar 

  39. Pitts T, Bolser D, Rosenbek J, Troche M, Okun MS, Sapienza C. Impact of expiratory muscle strength training on voluntary cough and swallow function in Parkinson disease. Chest. 2009;135(5):1301–8.

    PubMed  PubMed Central  Google Scholar 

  40. Manor Y, Mootanah R, Freud D, Giladi N, Cohen JT. Video-assisted swallowing therapy for patients with Parkinson’s disease. Parkinsonism Relat Disord. 2013;19(2):207–11.

    PubMed  Google Scholar 

  41. Stegemöller E, Hibbing P, Radig H, Wingate J. Therapeutic singing as an early intervention for swallowing in persons with Parkinson’s disease. Complement Ther Med. 2017;31:127–33.

    PubMed  Google Scholar 

  42. • Anselmi L, Bove C, Travagli RA. 741-Progression of alpha-synuclein transport in the gut-brain axis in a rodent model of parkinsonism. Gastroenterology. 2018;154(6):S–154 Novel insights into the pathophysiology of Parkinson’s disease and dysphagia.

    Google Scholar 

  43. Johnston BT, Colcher A, Li Q, Gideon MR, Castell JA, Castell DO. Repetitive proximal esophageal contractions: a new manometric finding and a possible further link between Parkinson’s disease and achalasia. Dysphagia. 2001;16(3):186–9.

    CAS  PubMed  Google Scholar 

  44. Natale G, Pasquali L, Ruggieri S, Paparelli A, Fornai F. Parkinson’s disease and the gut: a well known clinical association in need of an effective cure and explanation. Neurogastroenterol Motil. 2008;20(7):741–9.

    CAS  PubMed  Google Scholar 

  45. Qualman SJ, Haupt HM, Yang P, Hamilton SR. Esophageal Lewy bodies associated with ganglion cell loss in achalasia: similarity to Parkinson’s disease. Gastroenterology. 1984;87(4):848–56.

    CAS  PubMed  Google Scholar 

  46. Pandolfino JE, Zhang QG, Ghosh SK, Han A, Boniquit C, Kahrilas PJ. Transient lower esophageal sphincter relaxations and reflux: mechanistic analysis using concurrent fluoroscopy and high-resolution manometry. Gastroenterology. 2006;131(6):1725–33.

    PubMed  Google Scholar 

  47. Triadafilopoulos G, Gandhy R, Barlow C. Pilot cohort study of endoscopic botulinum neurotoxin injection in Parkinson’s disease. Parkinsonism Relat Disord. 2017;44:33–7.

    PubMed  Google Scholar 

  48. • Palma JA, Kaufmann H. Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies. Mov Disord. 2018;33(3):372–90 A detailed review of the autonomic dysfunction in Parkinson’s disease along with recommendations for the gastrointestinal effects.

    PubMed  PubMed Central  Google Scholar 

  49. Melamed E, Bitton V, Zelig O. Episodic unresponsiveness to single doses of l-Dopa in parkinsonian fluctuators. Neurology. 1986;36(1):100.

    CAS  PubMed  Google Scholar 

  50. Kurlan R, Rothfield K, Woodward W, Nutt J, Miller C, Lichter D, et al. Erratic gastric emptying of levodopa may cause “random” fluctuations of parkinsonian mobility. Neurology. 1988;38(3):419.

    CAS  PubMed  Google Scholar 

  51. Doi H, Sakakibara R, Sato M, Masaka T, Kishi M, Tateno A, et al. Plasma levodopa peak delay and impaired gastric emptying in Parkinson’s disease. J Neurol Sci. 2012;319(1):86–8.

    CAS  PubMed  Google Scholar 

  52. Lu P, Moore-Clingenpeel M, Yacob D, Di Lorenzo C, Mousa H. The rising cost of hospital care for children with gastroparesis: 2004–2013. Neurogastroenterol Motil. 2016;28(11):1698–704.

    CAS  PubMed  Google Scholar 

  53. Marrinan S, Emmanuel AV, Burn DJ. Delayed gastric emptying in Parkinson’s disease. Mov Disord. 2014;29(1):23–32.

    CAS  PubMed  Google Scholar 

  54. Tan A, Hew Y, Lim S, Ramli NM, Kamaruzzaman S, Ang B, et al. Body composition, sarcopenia and frailty in a multi-ethnic Asian cohort with Parkinson’s disease. Parkinsonism Relat Disord. 2018;46:e16–e7.

    Google Scholar 

  55. Moraveji S, Bashashati M, Elhanafi S, Sunny J, Sarosiek I, Davis B, et al. Depleted interstitial cells of Cajal and fibrosis in the pylorus: novel features of gastroparesis. Neurogastroenterol Motil. 2016;28(7):1048–54.

    CAS  PubMed  Google Scholar 

  56. • Anselmi L, Toti L, Bove C, Hampton J, Travagli RA. A nigro-vagal pathway controls gastric motility and is affected in a rat model of parkinsonism. Gastroenterology. 2017;153(6):1581–93 This study provides a pathophysiologic mechanism for gastroparesis found in Parkinson’s disease.

    PubMed  Google Scholar 

  57. Zhou L, Zheng L, Zhang X, Zhu J. Mo1541-activating alpha7 nicotinic acetylcholine receptor on macrophage attenuates gastric inflamation and gastroparesis in Parkinson’s disease rats. Gastroenterology. 2018;154(6):S–746.

    Google Scholar 

  58. Corbillé AG, Clairembault T, Coron E, Leclair-Visonneau L, Preterre C, Neunlist M, et al. What a gastrointestinal biopsy can tell us about Parkinson’s disease? Neurogastroenterol Motil. 2016;28(7):966–74.

    PubMed  Google Scholar 

  59. Annerino DM, Arshad S, Taylor GM, Adler CH, Beach TG, Greene JG. Parkinson’s disease is not associated with gastrointestinal myenteric ganglion neuron loss. Acta Neuropathol. 2012;124(5):665–80.

    PubMed  PubMed Central  Google Scholar 

  60. Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127(5):1592–622.

    PubMed  Google Scholar 

  61. Goetze O, Wieczorek J, Mueller T, Przuntek H, Schmidt WE, Woitalla D. Impaired gastric emptying of a solid test meal in patients with Parkinson’s disease using 13C-sodium octanoate breath test. Neurosci Lett. 2005;375(3):170–3.

    CAS  PubMed  Google Scholar 

  62. Kloetzer L, Chey W, McCallum R, Koch K, Wo J, Sitrin M, et al. Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule. Neurogastroenterol Motil. 2010;22(5):527–e117.

    CAS  PubMed  Google Scholar 

  63. Cassilly D, Kantor S, Knight L, Maurer A, Fisher R, Semler J, et al. Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy. Neurogastroenterol Motil. 2008;20(4):311–9.

    CAS  PubMed  Google Scholar 

  64. Ramprasad C, Moshiree B. Whole gut motility evaluation by wireless motility capsule in a patient with Parkinson’s disease. J Gastroenterol Pancreatol Liver Disord. 2016;3(6):1–3. https://doi.org/10.15226/2374-815X/3/6/00170.

    Article  Google Scholar 

  65. Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108(1):18–37.

    CAS  PubMed  Google Scholar 

  66. Moshiree B, Bollipo S, Horowitz M, Talley NJ. Epidemiology of gastroparesis. In: Parkman HP, RW MC, editors. Gastroparesis: Springer; 2012. p. 11–23.

  67. Sanaka M, Yamamoto T, Kuyama Y. Effects of proton pump inhibitors on gastric emptying: a systematic review. Dig Dis Sci. 2010;55(9):2431–40.

    CAS  PubMed  Google Scholar 

  68. Wod M, Hallas J, Andersen K, Rodríguez LAG, Christensen K, Gaist D. Lack of association between proton pump inhibitor use and cognitive decline. Clin Gastroenterol Hepatol. 2018;16(5):681–9.

    CAS  PubMed  Google Scholar 

  69. Avorn J, Gurwitz JH, Bohn RL, Mogun H, Monane M, Walker A. Increased incidence of levodopa therapy following metoclopramide use. JAMA. 1995;274(22):1780–2.

    CAS  PubMed  Google Scholar 

  70. Barone JA. Domperidone: a peripherally acting dopamine2-receptor antagonist. Ann Pharmacother. 1999;33(4):429–40.

    CAS  PubMed  Google Scholar 

  71. Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, et al. The movement disorder society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26 Suppl 3:S42-80. https://doi.org/10.1002/mds.23884.

    PubMed  PubMed Central  Google Scholar 

  72. Pasricha PJ, Yates KP, Sarosiek I, McCallum RW, Abell TL, Koch KL, et al. Aprepitant has mixed effects on nausea and reduces other symptoms in patients with gastroparesis and related disorders. Gastroenterology. 2018;154(1):65–76.e11.

    CAS  PubMed  Google Scholar 

  73. Parkman HP, Yates KP, Hasler WL, Nguyan L, Pasricha PJ, Snape WJ, et al. Dietary intake and nutritional deficiencies in patients with diabetic or idiopathic gastroparesis. Gastroenterology. 2011;141(2):486–98.e7.

    CAS  PubMed  Google Scholar 

  74. Homko C, Duffy F, Friedenberg F, Boden G, Parkman H. Effect of dietary fat and food consistency on gastroparesis symptoms in patients with gastroparesis. Neurogastroenterol Motil. 2015;27(4):501–8.

    CAS  PubMed  Google Scholar 

  75. Olausson EA, Störsrud S, Grundin H, Isaksson M, Attvall S, Simrén M. A small particle size diet reduces upper gastrointestinal symptoms in patients with diabetic gastroparesis: a randomized controlled trial. Am J Gastroenterol. 2014;109(3):375–85.

    CAS  PubMed  Google Scholar 

  76. Soykan I, Sarosiek I, Shifflett J, Wooten GF, McCallum RW. Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with Parkinson’s disease. Mov Disord. 1997;12(6):952–7.

    CAS  PubMed  Google Scholar 

  77. Lertxundi U, Domingo-Echaburu S, Soraluce A, García M, Ruiz-Osante B, Aguirre C. Domperidone in Parkinson’s disease: a perilous arrhythmogenic or the gold standard? Curr Drug Saf. 2013;8(1):63–8.

    CAS  PubMed  Google Scholar 

  78. Nishikawa N, Nagai M, Tsujii T, Iwaki H, Yabe H, Nomoto M. Coadministration of domperidone increases plasma levodopa concentration in patients with Parkinson disease. Clin Neuropharmacol. 2012;35(4):182–4.

    CAS  PubMed  Google Scholar 

  79. Shin CM, Kim J-M, Lee JY, Kim N, Lee DH, Choi YJ. Sa1563-therapeutic efficacy of Da-9701 on gastric motility in patients with Parkinson’s disease evaluated by magnetic resonance imaging: a randomized controlled trial. Gastroenterology. 2018;154(6):S–312.

    Google Scholar 

  80. Roy-Desruisseaux J, Landry J, Bocti C, Tessier D, Hottin P, Trudel J-F. Domperidone-induced tardive dyskinesia and withdrawal psychosis in an elderly woman with dementia. Ann Pharmacother. 2011;45(9):e51.

    PubMed  Google Scholar 

  81. Ejaz S, Slack R, Kim P, Shuttlesworth GA, Stroehlein JR, Shafi M. Sa1575-cardiac safety profile of patient treated with domperidone using an FDA approved ind protocol: a prospective 5-years study. Gastroenterology. 2018;154(6):S–316.

    Google Scholar 

  82. Waseem S, Moshiree B, Draganov PV. Gastroparesis: current diagnostic challenges and management considerations. World J Gastroenterol: WJG. 2009;15(1):25–37.

    PubMed  PubMed Central  Google Scholar 

  83. Broad J, Sanger GJ. The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin. Br J Pharmacol. 2013;168(8):1859–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Janssen P, Harris MS, Jones M, Masaoka T, Farré R, Törnblom H, et al. The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis. Am J Gastroenterol. 2013;108(9):1382–91.

    CAS  PubMed  Google Scholar 

  85. Chini P, Toskes PP, Waseem S, Hou W, McDonald R, Moshiree B. Effect of azithromycin on small bowel motility in patients with gastrointestinal dysmotility. Scand J Gastroenterol. 2012;47(4):422–7.

    CAS  PubMed  Google Scholar 

  86. Janssens J, Peeters T, Vantrappen G, Tack J, Urbain J, De Roo M, et al. Improvement of gastric emptying in diabetic gastroparesis by erythromycin: preliminary studies. N Engl J Med. 1990;322(15):1028–31.

    CAS  PubMed  Google Scholar 

  87. University VC. Erythromycin in Parkinson’s disease. Clinicaltrials.gov 2017. https://clinicaltrials.gov/ct2/show/NCT02005029?id=NCT02005029+OR+NCT02838797+OR+NCT01602549&rank=2&load=cart.

  88. Almalki ZS, Guo JJ. Cardiovascular events and safety outcomes associated with azithromycin therapy: a meta-analysis of randomized controlled trials. Am Health Drug Benefits. 2014;7(6):318–28.

    PubMed  PubMed Central  Google Scholar 

  89. Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med. 2004;351(11):1089–96.

    CAS  PubMed  Google Scholar 

  90. Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366(20):1881–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Nakatsuka A, Nagai M, Yabe H, Nishikawa N, Nomura T, Moritoyo H, et al. Effect of clarithromycin on the pharmacokinetics of cabergoline in healthy controls and in patients with Parkinson’s disease. J Pharmacol Sci. 2006;100(1):59–64.

    CAS  PubMed  Google Scholar 

  92. Marrinan SL, Otiker T, Vasist LS, Gibson RA, Sarai BK, Barton ME, et al. A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson’s disease. Mov Disord. 2018;33(2):329–32.

    CAS  PubMed  Google Scholar 

  93. GlaxoSmithKline. A study to assess the effect of repeat doses of GSK962040 on the pharmacokinetics of l-Dopa in subjects with Parkinson’s disease exhibiting delayed gastric emptying. 2018. https://clinicaltrials.gov/ct2/show/NCT01602549?term=camicinal&cond=Parkinson&rank=1.

  94. Doi H, Sakakibara R, Sato M, Hirai S, Masaka T, Kishi M, et al. Nizatidine ameliorates gastroparesis in Parkinson’s disease: a pilot study. Mov Disord. 2014;29(4):562–6.

    CAS  PubMed  Google Scholar 

  95. Futagami S, Shimpuku M, Song J, Kodaka Y, Yamawaki H, Nagoya H, et al. Nizatidine improves clinical symptoms and gastric emptying in patients with functional dyspepsia accompanied by impaired gastric emptying. Digestion. 2012;86(2):114–21.

    CAS  PubMed  Google Scholar 

  96. Tack J, Depoortere I, Bisschops R, Verbeke K, Janssens J, Peeters T. Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment Pharmacol Ther. 2005;22(9):847–53.

    CAS  PubMed  Google Scholar 

  97. Song N, Wang W, Jia F, Du X, Xie A, He Q, et al. Assessments of plasma ghrelin levels in the early stages of Parkinson’s disease. Mov Disord. 2017;32(10):1487–91.

    CAS  PubMed  Google Scholar 

  98. Camilleri M, McCallum RW, Tack J, Spence SC, Gottesdiener K, Fiedorek FT. Efficacy and safety of relamorelin in diabetics with symptoms of gastroparesis: a randomized, placebo-controlled study. Gastroenterology. 2017;153(5):1240–50.e2.

    CAS  PubMed  Google Scholar 

  99. Camilleri M, Acosta A. Emerging treatments in Neurogastroenterology: relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist. Neurogastroenterol Motil. 2015;27(3):324–32.

    CAS  PubMed  Google Scholar 

  100. Nelson AD, Camilleri M, Acosta A, Busciglio I, Linker Nord S, Boldingh A, et al. Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers. Neurogastroenterol Motil. 2016;28(11):1705–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Tack J, Camilleri M, Chang L, Chey W, Galligan J, Lacy B, et al. Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35(7):745–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Neira WD, Sanchez V, Mena MA, de Yebenes JG. The effects of cisapride on plasma l-Dopa levels and clinical response in Parkinson’s disease. Mov Disord. 1995;10(1):66–70.

    CAS  PubMed  Google Scholar 

  103. Moshiree B, Barboza J, Talley N. An update on current pharmacotherapy options for dyspepsia. Expert Opin Pharmacother. 2013;14(13):1737–53.

    CAS  PubMed  Google Scholar 

  104. Pinyopornpanish K, Soontornpun A, Kijdamrongthum P, Teeyasoontranon W, Angkurawaranon C, Thongsawat S. The effect of prucalopride on gastric emptying in Parkinson’s disease patients, a pilot randomized, open-label study. Thai J Gastroenterol. 2016;17:100–7.

    Google Scholar 

  105. Acosta A, Camilleri M. Prokinetics in gastroparesis. Gastroenterol Clin. 2015;44(1):97–111.

    Google Scholar 

  106. Asai H, Udaka F, Hirano M, Minami T, Oda M, Kubori T, et al. Increased gastric motility during 5-HT4 agonist therapy reduces response fluctuations in Parkinson’s disease. Parkinsonism Relat Disord. 2005;11(8):499–502.

    PubMed  Google Scholar 

  107. L Cloud. RQ-00000010 for gastroparesis and constipation in Parkinson’s disease (RQ-10). Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02838797?term=5HT+receptor+agonist&cond=Gastroparesis&rank=2. 2018.

  108. Malagelada J-R, Rees WD, Mazzotta LJ, Go VLW. Gastric motor abnormalities in diabetic and postvagotomy gastroparesis: effect of metoclopramide and bethanechol. Gastroenterology. 1980;78(2):286–93.

    CAS  PubMed  Google Scholar 

  109. Friedenberg FK, Palit A, Parkman HP, Hanlon A, Nelson DB. Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol. 2008;103(2):416–23.

    CAS  PubMed  Google Scholar 

  110. Rezaie A, Pimentel M, Rao SS. How to test and treat small intestinal bacterial overgrowth: an evidence-based approach. Curr Gastroenterol Rep. 2016;18(2):8.

    PubMed  Google Scholar 

  111. Schatz RA, Zhang Q, Lodhia N, Shuster J, Toskes PP, Moshiree B. Predisposing factors for positive D-xylose breath test for evaluation of small intestinal bacterial overgrowth: a retrospective study of 932 patients. World J Gastroenterol: WJG. 2015;21(15):4574–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Lewitan A, Nathanson L, Slade WR. Megacolon and dilatation of the small bowel in parkinsonism. Gastroenterology. 1951;17(3):367–74.

    CAS  PubMed  Google Scholar 

  113. Simrén M, Stotzer P. Use and abuse of hydrogen breath tests. Gut. 2006;55(3):297–303.

    PubMed  PubMed Central  Google Scholar 

  114. Khoshini R, Dai S-C, Lezcano S, Pimentel M. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci. 2008;53(6):1443–54.

    PubMed  Google Scholar 

  115. Quigley EM, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology. 2006;130(2):S78–90.

    CAS  PubMed  Google Scholar 

  116. Bouhnik Y, Alain S, Attar A, Flourié B, Raskine L, Sanson-Le Pors MJ, et al. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol. 1999;94(5):1327–31.

    CAS  PubMed  Google Scholar 

  117. Shah SC, Day LW, Somsouk M, Sewell JL. Meta-analysis: antibiotic therapy for small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2013;38(8):925–34.

    CAS  PubMed  Google Scholar 

  118. Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364(1):22–32.

    CAS  PubMed  Google Scholar 

  119. Koo HL, DuPont HL, Huang DB. The role of rifaximin in the treatment and chemoprophylaxis of travelers’ diarrhea. Ther Clin Risk Manag. 2009;5:841.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Gatta L, Scarpignato C, McCallum R, Lombardo L, Pimentel M, D’Incà R, et al. Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther. 2017;45(5):604–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Bohm M, Siwiec RM, Wo JM. Diagnosis and management of small intestinal bacterial overgrowth. Nutr Clin Pract. 2013;28(3):289–99.

    PubMed  Google Scholar 

  122. Lauritano EC, Gabrielli M, Scarpellini E, Lupascu A, Novi M, Sottili S, et al. Small intestinal bacterial overgrowth recurrence after antibiotic therapy. Am J Gastroenterol. 2008;103(8):2031–5.

    PubMed  Google Scholar 

  123. Saavedra JM. Clinical applications of probiotic agents. Am J Clin Nutr. 2001;73(6):1147S–51S.

    CAS  PubMed  Google Scholar 

  124. Parashar A, Udayabanu M. Gut microbiota: implications in Parkinson’s disease. Parkinsonism Relat Disord. 2017;38:1–7.

    PubMed  PubMed Central  Google Scholar 

  125. Hilton D, Stephens M, Kirk L, Edwards P, Potter R, Zajicek J, et al. Accumulation of α-synuclein in the bowel of patients in the pre-clinical phase of Parkinson’s disease. Acta Neuropathol. 2014;127(2):235–41.

    CAS  PubMed  Google Scholar 

  126. Whitehead WE, Wald A, Diamant N, Enck P, Pemberton J, Rao SSC. Functional disorders of the anus and rectum. Gut. 1999;45(suppl 2):II55–I9.

    PubMed  PubMed Central  Google Scholar 

  127. Kawimbe B, Papachrysostomou M, Binnie N, Clare N, Smith A. Outlet obstruction constipation (anismus) managed by biofeedback. Gut. 1991;32(10):1175–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Rao SS. Rectal exam: yes, it can and should be done in a busy practice! Am J Gastroenterol. 2018;1.

  129. Saad RJ, Hasler WL. A technical review and clinical assessment of the wireless motility capsule. Gastroenterol Hepatol. 2011;7(12):795–804.

    Google Scholar 

  130. Rao SS, Ozturk R, Laine L. Clinical utility of diagnostic tests for constipation in adults: a systematic review. Am J Gastroenterol. 2005;100(7):1605–15.

    PubMed  Google Scholar 

  131. Remes-Troche JM, Rao SS. Diagnostic testing in patients with chronic constipation. Curr Gastroenterol Rep. 2006;8(5):416–24.

    PubMed  Google Scholar 

  132. Daley A, Grimmett C, Roberts L, Wilson S, Fatek M, Roalfe A, et al. The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial. Int J Sports Med. 2008;29(9):778–82.

    CAS  PubMed  Google Scholar 

  133. Busby RW, Bryant AP, Bartolini WP, Cordero EA, Hannig G, Kessler MM, et al. Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol. 2010;649(1–3):328–35.

    CAS  PubMed  Google Scholar 

  134. Johanson J, Ueno R. Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety. Aliment Pharmacol Ther. 2007;25(11):1351–61.

    CAS  PubMed  Google Scholar 

  135. Freitas ME, Alqaraawi A, Lang AE, Liu LW. Linaclotide and prucalopride for management of constipation in patients with parkinsonism. Mov Disord Clin Pract. 2018;5(2):218–20.

    PubMed  PubMed Central  Google Scholar 

  136. Miner PB Jr, Koltun WD, Wiener GJ, De La Portilla M, Prieto B, Shailubhai K, et al. A randomized phase III clinical trial of plecanatide, a uroguanylin analog, in patients with chronic idiopathic constipation. Am J Gastroenterol. 2017;112(4):613–21.

    CAS  PubMed  Google Scholar 

  137. Zangaglia R, Martignoni E, Glorioso M, Ossola M, Riboldazzi G, Calandrella D, et al. Macrogol for the treatment of constipation in Parkinson’s disease. A randomized placebo-controlled study. Mov Disord. 2007;22(9):1239–44.

    PubMed  Google Scholar 

  138. Lembo A, Camilleri M. Chronic constipation. N Engl J Med. 2003;349(14):1360–8.

    CAS  PubMed  Google Scholar 

  139. Jost W, Schimrigk K. The effect of cisapride on delayed colonic transit time in patients with idiopathic Parkinson’s disease. Wien Klin Wochenschr. 1994;106(21):673–6.

    CAS  PubMed  Google Scholar 

  140. Jost WH, Schimrigk K. Long-term results with cisapride in Parkinson’s disease. Mov Disord. 1997;12(3):423–5.

    CAS  PubMed  Google Scholar 

  141. Morgan JC, Sethi KD. Tegaserod in constipation associated with Parkinson disease. Clin Neuropharmacol. 2007;30(1):52–4.

    CAS  PubMed  Google Scholar 

  142. Tack J, Müller-Lissner S, Stanghellini V, Boeckxstaens G, Kamm M, Simren M, et al. Diagnosis and treatment of chronic constipation—a European perspective. Neurogastroenterol Motil. 2011;23(8):697–710.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Liu Z, Sakakibara R, Odaka T, Uchiyama T, Uchiyama T, Yamamoto T, et al. Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients. Mov Disord. 2005;20(6):680–6.

    PubMed  Google Scholar 

  144. Nakajima A, Seki M, Taniguchi S. Determining an optimal clinical dose of elobixibat, a novel inhibitor of the ileal bile acid transporter, in Japanese patients with chronic constipation: a phase II, multicenter, double-blind, placebo-controlled randomized clinical trial. J Gastroenterol. 2018:1–10.

  145. Acosta A, Camilleri M. Elobixibat and its potential role in chronic idiopathic constipation. Ther Adv Gastroenterol. 2014;7(4):167–75.

    CAS  Google Scholar 

  146. Rao SS, Valestin J, Brown CK, Zimmerman B, Schulze K. Long-term efficacy of biofeedback therapy for dyssynergic defecation: randomized controlled trial. Am J Gastroenterol. 2010;105(4):890–6.

    PubMed  PubMed Central  Google Scholar 

  147. Rao SS. Dyssynergic defecation and biofeedback therapy. Gastroenterol Clin. 2008;37(3):569–86.

    Google Scholar 

  148. Tateno F, Sakakibara R, Yokoi Y, Kishi M, Ogawa E, Uchiyama T, et al. Levodopa ameliorated anorectal constipation in de novo Parkinson’s disease: the QL-GAT study. Parkinsonism Relat Disord. 2011;17(9):662–6.

    PubMed  Google Scholar 

  149. Albanese A, Brisinda G, Bentivoglio AR, Maria G. Treatment of outlet obstruction constipation in Parkinson’s disease with botulinum neurotoxin A. Am J Gastroenterol. 2003;98(6):1439–40.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Internal Medicine Residency, New York University School of Medicine, New York City, NY, USA

    Chethan Ramprasad MD

  2. Carolinas Healthcare-Charlotte, UNC School of Medicine, Charlotte Campus, 1025 Morehead Medical Dr. Suite 300, Charlotte, NC, 28204, USA

    Baharak Moshiree MD, MSc

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  1. Chethan Ramprasad MD
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  2. Jane Yellowlees Douglas PhD
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  3. Baharak Moshiree MD, MSc
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Chethan Ramprasad declares that he has no conflict of interest.

Jane Yellowlees Douglas declares that she has no conflict of interest.

Baharak Moshiree reports affiliations with Synergy Pharmaceuticals for research and on the speakers bureau, Allergan/Ironwood as an advisory board member and grant support, Medtronic for grant support and a speaker, and Cairn Diagnostics as a member of their advisory board and pending grant support.

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Ramprasad, C., Douglas, J.Y. & Moshiree, B. Parkinson’s Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects. Curr Treat Options Gastro 16, 489–510 (2018). https://doi.org/10.1007/s11938-018-0201-3

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