Gastrointestinal Disturbances in Parkinson’s Disease Including the Management of Sialorrhea

doi:10.1017/9781009039291.014

Chapter 13 - Gastrointestinal Disturbances in Parkinson’s Disease Including the Management of Sialorrhea

Published online by Cambridge University Press: 05 March 2022

Wolfgang H. Jost and

Lisa Klingelhoefer

Edited by

Néstor Gálvez-Jiménez ,

Amos D. Korczyn and

Ramón Lugo-Sanchez

Show author details

Néstor Gálvez-Jiménez: Affiliation:
Florida International University
Amos D. Korczyn: Affiliation:
Tel-Aviv University
Ramón Lugo-Sanchez: Affiliation:
Cleveland Clinic

Book contents

Get access

Summary

Gastrointestinal complaints are the most frequent autonomic symptoms in Parkinson’s disease (PD) and affect almost all patients over the course of time [1, 2, 3]. The causes are not clear. It is likely to be a multifactorial event in which both central and peripheral degenerative processes play a role [4, 5]. In addition, influences from the medication have to be considered, which are certainly not predominant. The central degenerative process involving the dorsal vagal nucleus is certainly significant, but it does not explain the range of symptoms. Involvement of the enteric nervous system is likely to be more crucial, with PD typical changes involving the presence of Lewy bodies extending from the upper esophagus down to the rectum in the Plexus myentericus Auerbach and the Plexus submucosus Meissner [4, 6, 7, 8, 9, 10]. The functional disturbance can therefore affect the entire gastrointestinal tract [5]. Thus dysphagia can occur in addition to delayed gastric emptying and extended intestinal transit.

Type: Chapter
Information: Non-motor Parkinson's Disease , pp. 145 - 154

DOI: https://doi.org/10.1017/9781009039291.014 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2022

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Jost, WH. Autonome Regulationsstörungen beim Parkinson Syndrom. Fortschr Neurol Psychiatrie 1995; 63: 194–205.Google Scholar

Parkinson, J. An Essay on the Shaking Palsy. Sherwood, Neely, and Jones; 1817.Google Scholar

Barone, P, Antonini, A, Colosimo, C, et al. The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 2009; 24: 1641–1649.Google Scholar

Braak, H, Rüb, U, Gai, WP, Del Tredici, K. Idiopathic Parkinson’s disease. Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 2003; 110: 517–536.Google Scholar

Jost, WH. Gastrointestinal motility problems in patients with Parkinson’s disease: effects of antiparkinsonian treatment and guidelines for management. Drugs Aging 1997; 10: 249–258.Google Scholar

Braak, H, Del Tredici, K. Potential pathways of abnormal tau and α-synuclein dissemination in sporadic Alzheimer’s and Parkinson’s diseases. Cold Spring Harb Perspect Biol 2016; 8. DOI: 10.1101/cshperspect.a023630Google Scholar

Stokholm, MG, Danielsen, EH, Hamilton-Dutoit, SJ, Borghammer, P. Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann Neurol 2016; 79: 940–949.Google Scholar

Den Hartog Jager, WA, Bethlem, J. The distribution of Lewy bodies in the central and autonomic nervous system in idiopathic paralysis agitans. J Neurol Neurosurg Psychiatry 1960; 23: 283–290.Google Scholar

Fasano, A, Visanji, NP, Liu, LW, et al. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol 2015; 14: 625–639.Google Scholar

Wakabayashi, K, Takahashi, H, Ohama, E, Takeda, S, lkuta, F. Lewy bodies in the visceral autonomic nervous system in Parkinson’s disease. Adv Neurol 1993; 60: 609–612.Google Scholar

Adler, CH, Beach, TG. Neuropathological basis of nonmotor manifestations of Parkinson’s disease. Mov Disord 2016; 31: 1114–1119.Google Scholar

Braak, H, de Vos, RAI, Bohl, J, Del Tredici, K. Gastric a-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease related brain pathology. Neurosci Lett 2006; 396: 67–72.Google Scholar

Jost, WH, Bäumer, T, Laskawi, R, et al. Therapy of sialorrhea with botulinum neurotoxin. Neurol Ther 2019; 8: 554–563.Google Scholar

Arbouw, ME, Movig, KL, Koopmann, M, et al. Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology 2010; 74: 1203–1207.Google Scholar

Isaacson, SH, Ondo, W, Jackson, CE, et al. Safety and efficacy of rimabotulinumtoxinB for treatment of sialorrhea in adults: a randomized clinical trial. JAMA Neurol 2020. DOI: 10.1001/jamaneurol.2019.4565Google Scholar

Jost, WH, Friedman, A, Michel, O, et al. SIAXI: placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea. Neurology 2019; 92: e1982–e1991.CrossRef Google Scholar PubMed

Jost, WH, Friedman, A, Michel, O, et al. Long-term incobotulinumtoxinA treatment for chronic sialorrhea: eﬃcacy and safety over 64 weeks. Parkinsonism Rel Disord 2020; 70: 23–30.CrossRef Google Scholar PubMed

Pflug, C, Bihler, M, Emich, K, et al. Critical dysphagia is common in Parkinson disease and occurs even in early stages: a prospective cohort study. Dysphagia 2018; 33: 41–50.CrossRef Google Scholar PubMed

Suiter, DM, Leder, SB. Clinical utility of the 3-ounce water swallow test. Dysphagia 2008; 23: 244–250.Google Scholar

Leder, SB, Suiter, DM, Green, BG. Silent aspiration risk is volume-dependent. Dysphagia 2011; 26: 304–309.Google Scholar

Hughes, TA, Wiles, CM. Neurogenic dysphagia: the role of the neurologist. J Neurol Neurosurg Psychiatry 1998; 64: 569–572.CrossRef Google Scholar PubMed

Langmore, SE. Evaluation of oropharyngeal dysphagia: which diagnostic tool is superior? Curr Opin Otolaryngol Head Neck Surg 2003; 11: 485–489.Google Scholar

Suttrup, I, Warnecke, T. Dysphagia in Parkinson’s disease. Dysphagia 2016; 31: 24–32.Google Scholar

Olanow, CW, Kieburtz, K, Odin, P, et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind double-dummy study. Lancet Neurol 2014; 13: 141–149.CrossRef Google Scholar PubMed

Storch, A, Schneider, CB, Wolz, M, et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology 2013; 80: 800–809.Google Scholar

Thomaides, T, Karapanayiotides, T, Zoukos, Y, et al. Gastric emptying after semi-solid food in multiple system atrophy and Parkinson’s disease. J Neurol 2005; 252: 1055–1059.Google Scholar

Kurlan, R, Rubin, AJ, Miller, C, et al. Continuous intraduodenal infusion of levodopa for resistant on-off fluctuations in parkinsonism. Ann Neurol 1985; 18: 139.Google Scholar

Parkes, JD. Domperidone and Parkinson’s disease. Clin Neuropharmacol 1986; 9: 517–532.Google Scholar

Pierantozzi, M, Pietroiusti, A, Brusa, L, et al. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology 2006; 66: 1824–1829.Google Scholar

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: 2449–2464.Google Scholar

Tan, AH, Mahadeva, S, Thalha, AM, et al. Small intestinal bacterial overgrowth in Parkinson’s disease. Parkinsonism Rel Disord 2014; 20: 535–540.Google Scholar

Scheperjans, F, Aho, V, Pereira, PA, et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 2015; 30: 350–358.Google Scholar

Knudsen, K, Krogh, K, Østergaard, K, Borghammer, P. Constipation in Parkinson’s disease: subjective symptoms, objective markers, and new perspectives. Mov Disord 2017; 32: 94–105.Google Scholar

Parkinson Study Group. A randomized trial of relamorelin for constipation in Parkinson’s disease (MOVE-PD): trial results and lessons learned. Parkinsonism Relat Disord 2017; 37: 101–105.Google Scholar

Abbott, RD, Petrovitch, H, White, LR, et al. Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 2001; 57: 456–464.Google Scholar

Svensson, E, Henderson, VW, Borghammer, P, et al. Constipation and risk of Parkinson’s disease: a Danish population-based cohort study. Parkinsonism Relat Disord 2016; 28: 18–22.Google Scholar

Stirpe, P, Hoffman, M, Badiali, D, Colosimo, C. Constipation: an emerging risk factor for Parkinson’s disease? Eur J Neurol 2016; 23: 1606–1613.CrossRef Google Scholar PubMed

Savica, R, Carlin, JM, Grossardt, BR, et al. Medical records documentation of constipation preceding Parkinson disease: a case-control study. Neurology 2009; 73: 1752–1758.Google Scholar

Cersosimo, MG, Raina, GB, Pecci, C, et al. Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J Neurol 2013; 260: 1332–1338.Google Scholar

Gage, H, Kaye, J, Kimber, A, et al. Correlates of constipation in people with Parkinson’s. Parkinsonism Relat Disord 2011; 17: 106–111.Google Scholar

Lundin, E, Graf, W, Garske, U, et al. Segmental colonic transit studies: comparison of a radiological and a scintigraphic method. Colorectal Dis 2007; 9: 344–351.Google Scholar

Agachan, F, Pfeifer, J, Wexner, SD. Defecography and proctography. Results of 744 patients. Dis Colon Rectum 1996; 39: 899–905.Google Scholar

Jost, WH, Schrank, B, Herold, A, Leiß, O. Functional outlet obstruction: anismus, spastic pelvic floor syndrome, and dyscoordination of the voluntary sphincter muscles. Scand J Gastroenterol 1999; 34: 449–453.Google Scholar

Barichella, M, Pacchetti, C, Bolliri, C, et al. Probiotics and prebiotic fiber for constipation associated with PD. Neurology 2016; 87: 1274–1280.CrossRef Google Scholar

Zesiewicz, TA, Sullivan, KL, Arnulf, I, et al. Practice parameter: treatment of nonmotor symptoms of Parkinson disease: report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2010; 74: 924–931.CrossRef Google Scholar

Bushmann, M, Dobmeyer, SM, Leeker, L, et al. Swallowing abnormalities and their response to treatment in Parkinson’s disease. Neurology 1989; 39: 1309–1314.Google Scholar

Zangaglia, R, Martignoni, E, Glorioso, M, et al. Macrogol for the treatment of constipation in Parkinson’s disease. A randomized placebo-controlled study. Mov Disord 2007; 22: 1239–1244.Google Scholar

Liu, Z, Sakakibara, R, Odaka, T, et al. Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients. Mov Disord 2005; 20: 680–686.CrossRef Google Scholar

Freitas, ME, Alqaraawi, A, Lang, AE, Liu, LWC. Linaclotide and prucalopride for management of constipation in patients with parkinsonism. Mov Disord Clin Pract 2018; 5: 218–220.Google Scholar

Bassotti, G, Usai Satta, P, Bellini, M. Plecanatide for the treatment of chronic idiopathic constipation in adult patients. Expert Rev Clin Pharmacol 2019; 12: 1019–1026.Google Scholar

Ondo, WG1, Kenney, C, Sullivan, K, et al. Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease. Neurology 2012; 78: 1650–1654.Google Scholar

Klingelhoefer, L, Reichmann, H. Pathogenesis of Parkinson disease – the gut-brain axis and environmental factors. Nat Rev Neurol 2015; 11: 625–636.Google Scholar

Scheperjans, F, Derkinderen, P, Borghammer, P. The gut and Parkinson’s disease: hype or hope? J Park Dis 2018; 8: S31–S39.Google Scholar PubMed

Berg, D, Postuma, RB, Adler, CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord 2015; 30: 1600–1611.Google Scholar

Schrag, A, Horsfall, L, Walters, K, et al. Prediagnostic presentations of Parkinson’s disease in primary care: a case-control study. Lancet Neurol 2015; 14: 57–64.Google Scholar

Pan-Montojo, F, Anichtchik, O, Dening, Y, et al. Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One 2010; 5: e8762.Google Scholar

Inden, M, Kitamura, Y, Takeuchi, H, et al. Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone. J Neurochem 2007; 101: 1491–1504.Google Scholar

Tasselli, M, Chaumette, T, Paillusson, S, et al. Effects of oral administration of rotenone on gastrointestinal functions in mice. Neurogastroenterol Motil 2013; 25: e183–e193.Google Scholar

Yuan, YH, Yan, WF, Sun, JD, et al. The molecular mechanism of rotenone-induced α-synuclein aggregation: emphasizing the role of the calcium/GSK3β pathway. Toxicol Lett 2015; 233: 163–171.CrossRef Google Scholar PubMed

Ling, EA, Shieh, JY, Wen, CY, et al. The dorsal motor nucleus of the vagus nerve of the hamster: ultrastructure of vagal neurons and their responses to vagotomy. J Anat 1987; 152: 161–172.Google Scholar

Pan-Montojo, F, Schwarz, M, Winkler, C. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep 2012; 2: 898. DOI: 10.1038/srep00898Google Scholar

Holmqvist, S, Chutna, O, Bousset, L, et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol 2014; 128: 805–820.Google Scholar

Svensson, E, Horváth-Puhó, E, Thomsen, RW, et al. Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol 2015; 78: 522–529.Google Scholar

Liu, B, Fang, F, Pedersen, NL, et al. Vagotomy and Parkinson disease: a Swedish register-based matched-cohort study. Neurology 2017; 88: 1996–2002.Google Scholar

Tysnes, OB, Kenborg, L, Herlofson, K, et al. Does vagotomy reduce the risk of Parkinson’s disease? Ann Neurol 2015; 78: 1011–1012.Google Scholar

Qin, J, Li, R, Raes, J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010; 464: 59–65.CrossRef Google Scholar PubMed

Bedarf, JR, Hildebrand, F, Goeser, F, et al. Das Darm-Mikrobiom bei der Parkinson-Krankheit. Nervenarzt 2019; 90: 160–166.Google Scholar

Seguella, L, Sarnelli, G, Esposito, G. Leaky gut, dysbiosis, and enteric glia activation: the trilogy behind the intestinal origin of Parkinson’s disease. Neural Regen Res 2020; 15: 1037–1038.Google Scholar

Borghammer, P, Van den Berge N. Brain-first versus gut-first Parkinson’s disease: a hypothesis. J Park Dis 2019; 9: S281–S295.Google Scholar

Bedarf, JR, Hildebrand, F, Coelho, LPF, et al. Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients. Genome Med 2017; 9: 39.Google Scholar

Heintz-Buschart, A, Pandey, U, Wicke, T, et al. The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord 2018; 33: 88–98.Google Scholar

Iranzo, A, Fernández-Arcos, A, Tolosa, E, et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS One 2014; 9: e89741. DOI: 10.1371Google Scholar

Postuma, RB, Iranzo, A, Högl, B, et al. Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study. Ann Neurol 2015; 77: 830–839.Google Scholar

Schenck, CH, Boeve, BF, Mahowald, MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older males initially diagnosed with idiopathic REM sleep behavior disorder (RBD): 16 year update on a previously reported series. Sleep Med 2013; 14: 744–748.Google Scholar

Sampson, TR, Debelius, JW, Thron, T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 2016; 167: 1469–1480.Google Scholar

Hill-Burns, EM, Debelius, JW, Morton, JT, et al. Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome. Mov Disord 2017; 32: 739–749.Google Scholar

de Vos, WM, de Vos, EA. Role of the intestinal microbiome in health and disease: from correlation to causation. Nutr Rev 2012; 70(Suppl 1): S45–S56.Google Scholar

Visanji, NP, Brooks, PL, Hazrati, LN, Lang, AE. The prion hypothesis in Parkinson’s disease: Braak to the future. Acta Neuropathol Commun 2013; 1: 2. DOI: 10.1186/2051-5960-1-2CrossRef Google Scholar PubMed

Stolzenberg, E, Berry, D, Yang, D, et al. A role for neuronal alpha-synuclein in gastrointestinal immunity. J Innate Immun 2017; 9: 456–463.Google Scholar

Sulzer, D, Alcalay, RN, Garretti, F, et al. T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature 2017; 546: 656–661.Google Scholar

Jackson, A, Forsyth, CB, Shaikh, M, et al. Diet in Parkinson’s disease: critical role for the microbiome. Front Neurol 2019; 10: 1245.Google Scholar

Horsager, et al. Brain 2020 143; 3077–3088 Brain-first versus body-first PD: a multimodal imaging case-control study.Google Scholar