AccScience Publishing / AN / Volume 1 / Issue 1 / DOI: 10.36922/an.v1i1.9
REVIEW

Gastrointestinal symptoms of Parkinson’s disease: A systematic review from pathogenesis to management

Xiao-Yu Cheng1 Cheng-Jie Mao1 Ya-Li Wang2* Chun-Feng Liu1*
Show Less
1 Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China
2 Department of Neurology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
Advanced Neurology 2022, 1(1), 9 https://doi.org/10.36922/an.v1i1.9
Submitted: 13 December 2021 | Accepted: 23 February 2022 | Published: 18 March 2022
© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

The identification of Parkinson’s disease (PD) is mainly dependent on motor symptoms, while the non-motor symptoms exist even decades ahead of the PD diagnosis. According to Braak’s hypothesis, the enteric plexus is the first affected site during the pathological development of PD, and gastrointestinal (GI) symptoms appear during the onset of the disease. Although GI symptoms decrease the life quality of patients with PD, there is often less focus on GI symptoms compared with motor symptoms. In this review, we summarize the pathophysiological basis, clinical manifestation, diagnosis, and treatment of GI symptoms in patients with PD. We also discuss the treatment and research dilemmas, as well as the research direction in the near future.

Keywords
Parkinson’s disease
Non-motor symptoms
Gastrointestinal symptoms
Brain-gut axis
Management
Funding
Jiangsu Provincial Key R&D Program
Discipline Construction Program of the Second Affiliated Hospital Soochow University
Priority Academic Program Development of Jiangsu Higher Education Institutions
Seventh Batch of GuSu District Health Talent Training Project
Conflict of interest
The authors report no conflicts of interest.
References
[1]

Mukherjee A, Biswas A, Das SK, 2016, Gut dysfunction in Parkinson’s disease. World J Gastroenterol, 22(25): 5742–5752. https://doi.org/10.3748/wjg.v22.i25.5742

[2]

Scheperjans F, Aho V, Pereira PA, et al., 2015, Gut microbiota are related to Parkinson’s disease and clinical phenotype. Movement Disord, 30(3): 350–358. https://doi.org/10.1002/mds.26069

[3]

Korczyn AD, 1990, Autonomic nervous system disturbances in Parkinson’s disease. Adv Neurol, 53: 463–468.

[4]

Noyce AJ, Bestwick JP, Silveira–Moriyama L, et al., 2012, Meta–analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol, 72(6): 893–901. https://doi.org/10.1002/ana.23687

[5]

Fasano A, Visanji NP, Liu LW, et al., 2015, Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol, 14(6): 625–639. https://doi.org/10.1016/S1474–4422(15)00007–1

[6]

Sampson TR, Debelius JW, Thron T, et al., 2016, Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell, 167(6): 1469–1480.e12. https://doi.org/10.1016/j.cell.2016.11.018 

[7]

van Wamelen DJ, Leta V, Johnson J, et al., 2020, Drooling in Parkinson’s disease: Prevalence and progression from the non–motor international longitudinal study. Dysphagia, 35(6): 955–961. https://doi.org/10.1007/s00455–020–10102–5

[8]

Srivanitchapoom P, Pandey S, Hallett M, 2014, Drooling in Parkinson’s disease: A review. Parkinsonism Relat Disord, 20(11): 1109–1118. https://doi.org/10.1016/j.parkreldis.2014.08.013 

[9]

Kalf JG, de Swart BJ, Bloem BR, et al., 2012, Prevalence of oropharyngeal dysphagia in Parkinson’s disease: A meta-analysis. Parkinsonism Relat Disord, 18(4): 311–315. https://doi.org/10.1016/j.parkreldis.2011.11.006 

[10]

Suttrup I, Warnecke T, 2016, Dysphagia in Parkinson’s disease. Dysphagia, 31(1): 24–32. https://doi.org/10.1007/s00455-015-9671-9 

[11]

Leopold NA, Daniels SK, 2010, Supranuclear control of swallowing. Dysphagia, 25(3): 250–257. https://doi.org/10.1007/s00455-009-9249-5

[12]

Ortega O, Martin A, Clave P, 2017, Diagnosis and management of oropharyngeal dysphagia among older persons, state of the art. J Am Med Dir Assoc, 18(7): 576–582. https://doi.org/10.1016/j.jamda.2017.02.015

[13]

Lethbridge L, Johnston GM, Turnbull G, 2013, Co-morbidities of persons dying of Parkinson’s disease. Prog Palliat Care, 21(3): 140–145. https://doi.org/10.1179/1743291X12Y.0000000037

[14]

Soliman H, Coffin B, Gourcerol G, 2021, Gastroparesis in Parkinson disease: Pathophysiology, and clinical management. Brain Sci, 11(7): 831. https://doi.org/10.3390/brainsci11070831

[15]

Revicki DA, Rentz AM, Dubois D, et al., 2004, Gastroparesis cardinal symptom index (GCSI): Development and validation of a patient reported assessment of severity of gastroparesis symptoms. Qual Life Res, 13(4): 833–844. https://doi.org/10.1023/B: QURE.0000021689.86296.e4

[16]

Zheng S, Yao J, Chinese Geriatric Society EBoCJoG, 2018, Expert consensus on the assessment and treatment of chronic constipation in the elderly. Aging Med, 1(1): 8–17. https://doi.org/10.1002/agm2.12013

[17]

Chu H, Zhong L, Li H, et al., 2014, Epidemiology characteristics of constipation for general population, pediatric population, and elderly population in china. Gastroenterol Res Pract, 2014: 532734. https://doi.org/10.1155/2014/532734

[18]

Gallegos-Orozco JF, Foxx-Orenstein AE, Sterler SM, et al., 2012, Chronic constipation in the elderly. Am J Gastroenterol, 107(1): 18–25; quiz 26. https://doi.org/10.1038/ajg.2011.349

[19]

Pazo JH, Belforte JE, 2002, Basal ganglia and functions of the autonomic nervous system. Cell Mol Neurobiol, 22(5–6): 645–654. https://doi.org/10.1023/a:1021844605250

[20]

Del Tredici K, Hawkes CH, Ghebremedhin E, et al., 2010, Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease. Acta Neuropathol, 119(6): 703–713. https://doi.org/10.1007/s00401-010-0665-2

[21]

Suzuki M, Asada Y, Ito J, et al., 2003, Activation of cerebellum and basal ganglia on volitional swallowing detected by functional magnetic resonance imaging. Dysphagia, 18(2): 71–77. https://doi.org/10.1007/s00455-002-0088-x

[22]

Mu L, Sobotka S, Chen J, et al., 2013, Parkinson disease affects peripheral sensory nerves in the pharynx. J Neuropathol Exp Neurol, 72(7): 614–623. https://doi.org/10.1097/NEN.0b013e3182965886

[23]

Pellegrini C, Antonioli L, Colucci R, et al., 2015, Gastric motor dysfunctions in Parkinson’s disease: Current pre-clinical evidence. Parkinsonism Relat Disord, 21(12): 1407–1414. https://doi.org/10.1016/j.parkreldis.2015.10.011

[24]

Camilleri M, 2021, Gastrointestinal motility disorders in neurologic disease. J Clin Investig, 131(4): e143771. https://doi.org/10.1172/JCI143771

[25]

Braak H, Rub U, Gai WP, et al., 2003, Idiopathic Parkinson’s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna), 110(5): 517–536.

[26]

Braak H, de Vos RA, Bohl J, et al., 2006, Gastric alpha–- synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett, 396(1): 67–72. https://doi.org/10.1016/j.neulet.2005.11.012

[27]

Pan-Montojo F, Reichmann H, 2014, Considerations on the role of environmental toxins in idiopathic Parkinson’s disease pathophysiology. Transl Neurodegener, 3: 10. https://doi.org/10.1186/2047-9158-3-10

[28]

Benarroch EE, 2007, Enteric nervous system: Functional organization and neurologic implications. Neurology, 69(20): 1953–1957. https://doi.org/10.1212/01.wnl.0000281999.56102.b5

[29]

Nezami BG, Srinivasan S, 2010, Enteric nervous system in the small intestine: Pathophysiology and clinical implications. Curr Gastroenterol Rep, 12(5): 358–365. https://doi.org/10.1007/s11894-010-0129-9 

[30]

Lebouvier T, Chaumette T, Paillusson S, et al., 2009, The second brain and Parkinson’s disease. Eur J Neurosci, 30(5): 735–741. https://doi.org/10.1111/j.1460-9568.2009.06873.x

[31]

Tan AH, Mahadeva S, Thalha AM, et al., 2014, Small intestinal bacterial overgrowth in Parkinson’s disease. Parkinsonism Relat Disord, 20(5): 535–540. https://doi.org/10.1016/j.parkreldis.2014.02.019

[32]

Santos SF, de Oliveira HL, Yamada ES, et al., 2019, The gut and Parkinson’s disease-a bidirectional pathway. Front Neurol, 10: 574. https://doi.org/10.3389/fneur.2019.00574

[33]

Brudek T, 2019, Inflammatory bowel diseases and Parkinson’s disease. J Parkinsons Dis, 9(S2): S331–S344. https://doi.org/10.3233/JPD-191729

[34]

Kim S, Kwon SH, Kam TI, et al., 2019, Transneuronal propagation of pathologic alpha-synuclein from the gut to the brain models Parkinson’s disease. Neuron, 103(4): 627– 641.e627. https://doi.org/10.1016/j.neuron.2019.05.035

[35]

Nicaretta DH, de Rosso AL, Maliska C, et al., 2008, Scintigraphic analysis of the parotid glands in patients with sialorrhea and Parkinson’s disease. Parkinsonism Relat Disord, 14(4): 338–341. https://doi.org/10.1016/j.parkreldis.2007.07.008

[36]

Nobrega AC, Rodrigues B, Torres AC, et al., 2008, Is drooling secondary to a swallowing disorder in patients with Parkinson’s disease? Parkinsonism Relat Disord, 14(3): 243–245. https://doi.org/10.1016/j.parkreldis.2007.08.003

[37]

Ciucci MR, Russell JA, Schaser AJ, et al., 2011, Tongue force and timing deficits in a rat model of Parkinson disease. Behav Brain Res, 222(2): 315–320. https://doi.org/10.1016/j.bbr.2011.03.057

[38]

Umemoto G, Tsuboi Y, Kitashima A, et al., 2011, Impaired food transportation in Parkinson’s disease related to lingual bradykinesia. Dysphagia, 26(3): 250–255. https://doi.org/10.1007/s00455-010-9296-y

[39]

Seppi K, Weintraub D, Coelho M, et al., 2011, The movement disorder society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Movement Disord, 26(Suppl 3): S42–S80. https://doi.org/10.1002/mds.23884

[40]

Zhang ZX, Roman GC, Hong Z, et al., 2005, Parkinson’s disease in China: Prevalence in Beijing, Xian, and Shanghai. Lancet, 365(9459): 595–597. https://doi.org/10.1016/S0140-6736(05)17909-4

[41]

Marks L, Turner K, O’Sullivan J, et al., 2001. Drooling in Parkinson’s disease: A novel speech and language therapy intervention. Int J Lang Commun Disord, 36(Suppl): 282–287. https://doi.org/10.3109/13682820109177898

[42]

Postma AG, Heesters M, van Laar T, 2007, Radiotherapy to the salivary glands as treatment of sialorrhea in patients with parkinsonism. Movement Disord, 22(16): 2430–2435. https://doi.org/10.1002/mds.21752

[43]

Hunter PC, Crameri J, Austin S, et al., 1997, Response of parkinsonian swallowing dysfunction to dopaminergic stimulation. J Neurol Neurosurg Psychiatry, 63(5): 579–583. https://doi.org/10.1136/jnnp.63.5.579

[44]

Nagaya M, Kachi T, Yamada T, et al., 1998, Videofluorographic study of swallowing in Parkinson’s disease. Dysphagia, 13(2): 95–100. https://doi.org/10.1007/PL00009562

[45]

Simons JA, Fietzek UM, Waldmann A, et al., 2014. Development and validation of a new screening questionnaire for dysphagia in early stages of Parkinson’s disease. Parkinsonism Relat Disord, 20(9): 992–998. https://doi.org/10.1016/j.parkreldis.2014.06.008

[46]

Ali GN, Wallace KL, Schwartz R, et al., 1996, Mechanisms of oral-pharyngeal dysphagia in patients with Parkinson’s disease. Gastroenterology, 110(2): 383–392. https://doi.org/10.1053/gast.1996.v110.pm8566584

[47]

Taira K, Fujiwara K, Fukuhara T, et al., 2021, Evaluation of the pharynx and upper esophageal sphincter motility using high-resolution pharyngeal manometry for Parkinson’s disease. Clin Neurol Neurosurg, 2021: 106447. https://doi.org/10.1016/j.clineuro.2020.106447

[48]

Monteiro L, Souza-Machado A, Valderramas S, et al., 2012. The effect of levodopa on pulmonary function in Parkinson’s disease: A systematic review and meta-analysis. Clin Ther, 34(5): 1049–1055. https://doi.org/10.1016/j.clinthera.2012.03.001

[49]

Oh E, Jee S, Kim BK, et al., 2021. A new swallowing supplement for dysphagia in patients with Parkinson’s disease. Neurol Sci, 42(5): 1949–1958. https://doi.org/10.1007/s10072-020-04730-w

[50]

Park A, Jang SJ, Kim NE, et al., 2021, Swallowing outcomes following voice therapy in multiple system atrophy with dysphagia: Comparison of treatment efficacy with Parkinson’s disease. Dysphagia, 37(1): 198–206. https://doi.org/10.1007/s00455-021-10265-9

[51]

Born LJ, Harned RH, Rikkers LF, et al., 1996, Cricopharyngeal dysfunction in Parkinson’s disease: Role in dysphagia and response to myotomy. Movement Disord, 11(1): 53–58. https://doi.org/10.1002/mds.870110110

[52]

Restivo DA, Palmeri A, Marchese-Ragona R, 2002, Botulinum toxin for cricopharyngeal dysfunction in Parkinson’s disease. N Engl J Med, 346(15): 1174–1175. https://doi.org/10.1056/NEJM200204113461517

[53]

Quigley EM, 1996, Gastrointestinal dysfunction in Parkinson’s disease. Semin Neurol, 16(3): 245–250. https://doi.org/10.1055/s-2008-1040981

[54]

Larson JM, Tavakkoli A, Drane WE, et al., 2010, Advantages of azithromycin over erythromycin in improving the gastric emptying half-time in adult patients with gastroparesis. J Neurogastroenterol Motil, 16(4): 407–413. https://doi.org/10.5056/jnm.2010.16.4.407 

[55]

Doi H, Sakakibara R, Sato M, et al., 2014, Nizatidine ameliorates gastroparesis in Parkinson’s disease: A pilot study. Movement Disord, 29(4): 562–566. https://doi.org/10.1002/mds.25777

[56]

McCallum RW, Lembo A, Esfandyari T, et al., 2013, Phase 2b, randomized, double-blind 12-week studies of TZP– 102, a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil, 25(11): e705–e717. https://doi.org/10.1111/nmo.12184

[57]

Brinck CE, Mark EB, Klinge MW, et al., 2020, Magnetic tracking of gastrointestinal motility. Physiol Meas, 41(12): 12TR01. https://doi.org/10.1088/1361-6579/abcd1e

[58]

Arai E, Arai M, Uchiyama T, et al., 2012, Subthalamic deep brain stimulation can improve gastric emptying in Parkinson’s disease. Brain, 135(Pt 5): 1478–1485. https://doi.org/10.1093/brain/aws086

[59]

Jayanthi NV, Dexter SP, Sarela AI, et al., 2013, Gastric electrical stimulation for treatment of clinically severe gastroparesis. J Minim Access Surg, 9(4): 163–167. https://doi.org/10.4103/0972-9941.118833

[60]

Drossman DA, Dumitrascu DL, 2006, Rome III: New standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis, 15(3): 237–241.

[61]

Huang H, Xu H, Luo Q, et al., 2019, Fecal microbiota transplantation to treat Parkinson’s disease with constipation: A case report. Medicine, 98(26): e16163. https://doi.org/10.1097/MD.0000000000016163

[62]

Damian A, Adler CH, Hentz JG, et al., 2012, Autonomic function, as self-reported on the SCOPA-autonomic questionnaire, is normal in essential tremor but not in Parkinson’s disease. Parkinsonism Relat Disord, 18(10): 1089–1093. https://doi.org/10.1016/j.parkreldis.2012.06.008 

[63]

Forjaz MJ, Ayala A, Rodriguez-Blazquez C, et al., 2010, Assessing autonomic symptoms of Parkinson’s disease with the SCOPA-AUT: A new perspective from Rasch analysis. Eur J Neurol, 17(2): 273–279. https://doi.org/10.1111/j.1468-1331.2009.02835.x

[64]

Chaudhuri KR, Martinez-Martin P, Brown RG, et al., 2007, The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: Results from an international pilot study. Movement Disord, 22(13): 1901–1911. https://doi.org/10.1002/mds.21596

[65]

De Pablo-Fernandez E, Passananti V, Zarate-Lopez N, et al., 2019, Colonic transit, high-resolution anorectal manometry and MRI defecography study of constipation in Parkinson’s disease. Parkinsonism Relat Disord, 66: 195–201. https://doi.org/10.1016/j.parkreldis.2019.08.016

[66]

Edwards LL, Quigley EM, Harned RK, et al., 1994, Characterization of swallowing and defecation in Parkinson’s disease. Am J Gastroenterol, 89(1): 15–25.

[67]

Barichella M, Pacchetti C, Bolliri C, et al., 2016, Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT. Neurology, 87(12): 1274–1280. https://doi.org/10.1212/WNL.0000000000003127

[68]

Tan AH, Lim SY, Chong KK, et al., 2021, Probiotics for constipation in Parkinson disease: A randomized placebo-controlled study. Neurology, 96(5): e772–e782. https://doi.org/10.1212/WNL.0000000000010998

[69]

Cassani E, Privitera G, Pezzoli G, et al., 2011, Use of probiotics for the treatment of constipation in Parkinson’s disease patients. Min Gastroenterol Dietol., 57(2): 117–121.

[70]

Sakakibara R, Doi H, Sato M, et al., 2015, Nizatidine ameliorates slow transit constipation in Parkinson’s disease. J Am Geriatr Soc., 63(2): 399–401. https://doi.org/10.1111/jgs.13279

[71]

Sun WM, Hasler WL, Lien HC, et al., 2001, Nizatidine enhances the gastrocolonic response and the colonic peristaltic reflex in humans. J. Pharmacol. Exp. Ther, 299(1): 159–163.

[72]

Ondo WG, Kenney C, Sullivan K, et al., 2012, Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease. Neurology, 78(21): 1650–1654. https://doi.org/10.1212/WNL.0b013e3182574f28

[73]

Kuai XY, Yao XH, Xu LJ, et al., 2021, Evaluation of fecal microbiota transplantation in Parkinson’s disease patients with constipation. Microb Cell Fact, 20(1): 98. https://doi.org/10.1186/s12934-021-01589-0

[74]

Cadeddu F, Bentivoglio AR, Brandara F, et al., 2005, Outlet type constipation in Parkinson’s disease: Results of botulinum toxin treatment. Aliment Pharmacol Ther, 22(10): 997–1003. https://doi.org/10.1111/j.1365-2036.2005.02669.x

[75]

Morgan JC, Sethi KD, 2007, Tegaserod in constipation associated with Parkinson disease. Clin Neuropharmacol, 30(1): 52–54. https://doi.org/10.1097/01.WNF.0000240942.21499.97

[76]

Zangaglia R, Martignoni E, Glorioso M, et al., 2007, Macrogol for the treatment of constipation in Parkinson’s disease. A randomized placebo-controlled study. Movement Disord, 22(9): 1239–1244. https://doi.org/10.1002/mds.21243

[77]

Sullivan KL, Staffetti JF, Hauser RA, et al., 2006, Tegaserod (Zelnorm) for the treatment of constipation in Parkinson’s disease. Movement Disord, 21(1): 115–116. https://doi.org/10.1002/mds.20666

[78]

Chiu CM, Wang CP, Sung WH, et al., 2009, Functional magnetic stimulation in constipation associated with Parkinson’s disease. J Rehabil Med, 41(13): 1085–1089. https://doi.org/10.2340/16501977-0456

[79]

McClurg D, Hagen S, Jamieson K, et al., 2016, Abdominal massage for the alleviation of symptoms of constipation in people with Parkinson’s: A randomised controlled pilot study. Age Ageing, 45(2): 299–303. https://doi.org/10.1093/ageing/afw005

[80]

Tateno F, Sakakibara R, Yokoi Y, et al., 2011, Levodopa ameliorated anorectal constipation in de novo Parkinson’s disease: The QL-GAT study. Parkinsonism Relat Disord., 17(9): 662–666. https://doi.org/10.1016/j.parkreldis.2011.06.002

[81]

West CL, Mao YK, Delungahawatta T, et al., 2020, Squalamine restores the function of the enteric nervous system in mouse models of Parkinson’s disease. J Parkinsons Dis, 10(4): 1477–1491. https://doi.org/10.3233/JPD-202076

[82]

Albanese A, Brisinda G, Bentivoglio AR, et al., 2003, Treatment of outlet obstruction constipation in Parkinson’s disease with botulinum neurotoxin A. Am J Gastroenterol, 98(6): 1439–1440. https://doi.org/10.1111/j.1572-0241.2003.07514.x

[83]

Jost WH, Schimrigk K, 1993, Cisapride treatment of constipation in Parkinson’s disease. Movement Disord, 8(3): 339–343. 

[84]

Sakakibara R, Odaka T, Lui Z, et al., 2005, Dietary herb extract dai-kenchu-to ameliorates constipation in parkinsonian patients (Parkinson’s disease and multiple system atrophy). Movement Disord, 20(2): 261–262. https://doi.org/10.1002/mds.20352

[85]

Karasawa H, Pietra C, Giuliano C, et al., 2014, New ghrelin agonist, HM01 alleviates constipation and L-dopa-delayed gastric emptying in 6-hydroxydopamine rat model of Parkinson’s disease. Neurogastroenterol Motil, 26(12): 1771–1782. https://doi.org/10.1111/nmo.12459

[86]

Gourcerol G, Maltete D, Chastan N, et al., 2019, Does bilateral deep brain stimulation of the subthalamic nucleus modify ano-rectal motility in Parkinson’s disease? Results of a randomized cross-over study. Neuromodulation, 22(4): 478–483. https://doi.org/10.1111/ner.12947 

[87]

Liu Z, Sakakibara R, Odaka T, et al., 2005, Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in parkinsonian patients. Movement Disord, 20(6): 680–686. https://doi.org/10.1002/mds.20387

[88]

Kola S, Prichard DO, Bharucha AE, et al., 2021, A prospective pilot study of the effects of deep brain stimulation on olfaction and constipation in Parkinson’s disease. Clin Neurol Neurosurg, 207: 106774. https://doi.org/10.1016/j.clineuro.2021.106774

[89]

Chua KK, Wong A, Chan KW, et al., 2017, A randomized controlled trial of chinese medicine on nonmotor symptoms in Parkinson’s disease. Parkinsons Dis, 2017: 1902708. https://doi.org/10.1155/2017/1902708

[90]

McClurg D, Walker K, Aitchison P, et al., 2016, Abdominal massage for the relief of constipation in people with Parkinson’s: A qualitative study. Parkinsons Dis, 2016: 4842090. https://doi.org/10.1155/2016/4842090

[91]

Ashraf W, Pfeiffer RF, Park F, et al., 1997, Constipation in Parkinson’s disease: Objective assessment and response to psyllium. Movement Disord, 12(6): 946–951. https://doi.org/10.1002/mds.870120617

[92]

Pare P, Bridges R, Champion MC, et al., 2007, Recommendations on chronic constipation (including constipation associated with irritable bowel syndrome) treatment. Can J Gastroenterol, 21 Suppl B: 3B–22B.

[93]

Hauser RA, Sutherland D, Madrid JA, et al., 2019, Targeting neurons in the gastrointestinal tract to treat Parkinson’s disease. Clin Parkinsonism Relat Disord, 1: 2–7. https://doi.org/10.1016/j.prdoa.2019.06.001

[94]

Parthasarathy G, Chen J, Chen X, et al., 2016, Relationship between microbiota of the colonic mucosa vs feces and symptoms, colonic transit, and methane production in female patients with chronic constipation. Gastroenterology, 150(2): 367–379.e361. https://doi.org/10.1053/j.gastro.2015.10.005

[95]

Molsberry S, Bjornevik K, Hughes KC, et al., 2020, Diet pattern and prodromal features of Parkinson disease. Neurology, 95(15): e2095–e2108. https://doi.org/10.1212/WNL.0000000000010523

[96]

Rusch C, Beke M, Tucciarone L, et al., 2021, Effect of a mediterranean diet intervention on gastrointestinal function in Parkinson’s disease (the MEDI-PD study): Study protocol for a randomised controlled trial. BMJ Open, 11(9): e053336. https://doi.org/10.1136/bmjopen-2021-053336 

[97]

Li K, Wang Z, Chen Y, et al., 2019, Efficacy of electroacupuncture for the treatment of constipation in Parkinson’s disease: Study protocol for a multicentre randomised controlled trial. BMJ Open, 9(11): e029841. https://doi.org/10.1136/bmjopen-2019-029841 

[98]

Jin Z, Liu Z, Kang L, et al., 2020, A randomized double-blind placebo-controlled multicenter trial of Bushen Yisui and Ziyin Jiangzhuo formula for constipation in Parkinson disease. Medicine, 99(28): e21145. https://doi.org/10.1097/MD.0000000000021145

[99]

Stocchi F, Torti M, 107, Constipation in Parkinson’s disease. Int Rev Neurobiol, 134: 811–826. https://doi.org/10.1016/bs.irn.2017.06.003 

[100]

Braak H, Del Tredici K, Rub U, et al., 2003, Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging, 24(2): 197–211. https://doi.org/10.1016/s0197-4580(02)00065-9 

[101]

Cryan JF, O’Riordan KJ, Cowan CS, et al., 2019, The microbiota-gut-brain axis. Physiol Rev, 99(4): 1877–2013. https://doi.org/10.1152/physrev.00018.2018

[102]

Bohórquez DV, Shahid RA, Erdmann A, et al., 2015, Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells. J Clin Investig, 125(2): 782–786. https://doi.org/10.1172/JCI78361

[103]

Chandra R, Hiniker A, Kuo YM, et al., 2017, α-synuclein in gut endocrine cells and its implications for Parkinson’s disease. JCI Insight, 2(12): e92295. https://doi.org/10.1172/jci.insight.92295

[104]

Adams-Carr KL, Bestwick JP, Shribman S, et al., 2016, Constipation preceding Parkinson’s disease: A systematic review and meta-analysis. J Neurol Neurosurg Psychiatry, 87(7): 710–716. https://doi.org/10.1136/jnnp-2015-311680

[105]

Holmqvist S, Chutna O, Bousset L, et al., 2014, Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol, 128(6): 805–820. https://doi.org/10.1007/s00401-014-1343-6

[106]

Pan-Montojo F, Anichtchik O, Dening Y, et al., 2010, Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One, 5(1): e8762. https://doi.org/10.1371/journal.pone.0008762

[107]

Svensson E, Horvath-Puho E, Thomsen RW, et al., 2015, Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol, 78(4): 522–529. https://doi.org/10.1002/ana.24448

[108]

Liu B, Fang F, Pedersen NL, et al., 2017, Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology, 88(21): 1996–2002. https://doi.org/10.1212/WNL.0000000000003961 

[109]

Beach TG, Adler CH, Lue L, et al., 2009, Unified staging system for Lewy body disorders: Correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol, 117(6): 613–634. https://doi.org/10.1007/s00401-009-0538-8

[110]

Camacho M, Macleod AD, Maple-Grødem J, et al., 2021, Early constipation predicts faster dementia onset in Parkinson’s disease. NPJ Parkinsons Dis, 7(1): 45. https://doi.org/10.1038/s41531-021-00191-w

[111]

Rota L, Pellegrini C, Benvenuti L, et al., 2019, Constipation, deficit in colon contractions and alpha-synuclein inclusions within the colon precede motor abnormalities and neurodegeneration in the central nervous system in a mouse model of alpha-synucleinopathy. Translat Neurodegener., 8: 5. https://doi.org/10.1186/s40035-019-0146-z

[112]

Anselmi L, Toti L, Bove C, et al., 2017, A nigro-vagal pathway controls gastric motility and is affected in a rat model of parkinsonism. Gastroenterology, 153(6): 1581–1593. https://doi.org/10.1053/j.gastro.2017.08.069

[113]

Borghammer P, 2018, How does Parkinson’s disease begin? Perspectives on neuroanatomical pathways, prions, and histology. Mov Disord, 33(1): 48–57. https://doi.org/10.1002/mds.27138

[114]

Dai Y, Mao C, Ding M, et al., 2016, Correlations between constipation and the axial symptoms, related motor symptoms in Parkinson’s disease. Zhonghua Yi Xue Za Zhi, 96(5): 324–328. https://doi.org/10.3760/cma.j.issn.0376-2491.2016.05.002

Share
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing