Abstract
To assess the prevalence of gastrointestinal symptoms (GIS) in Parkinson’s disease (PD) compared to control subjects and their timing of appearance in relationship to the onset of motor symptoms. There is a rostrocaudal gradient of alpha-synuclein (α-SYN) neuropathology in the enteric nervous system at early stages of PD with higher burden in the upper than the lower gut. However, only constipation has been recognized as a premotor gastrointestinal manifestation of PD. 129 PD patients and 120 controls underwent a structured questionnaire to assess the presence of GIS and, in PD patients, the time of their appearance respect to the onset of motor manifestations. GIS significantly more prevalent in PD patients were dry mouth, drooling, dysphagia, constipation and defecatory dysfunction. Constipation and defecatory dysfunction preceded motor manifestations. Whereas gastroparesis symptoms preceded motor manifestations, their prevalence was not significantly different from controls. Despite evidence of a higher α-SYN burden in the upper gut, only constipation and defecatory dysfunction were prominent premotor GIS of PD.
Similar content being viewed by others
References
Braak H, Rub U, Gai WP, Del Tredici K (2003) Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110:517–536
Braak H, Del Tredici K, Rub U, de Vos RAI, Jansen Steur ENH, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211
Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Grastric alpha-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 396:67–72
Wakabayashi K, Takahashi H, Takeda S, Ohama E, Ikuta F (1988) Parkinson’s disease: the presence of Lewy bodies in Auerbach’s and Meissner’s plexuses. Acta Neuropathol 76:217–221
Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL et al (2010) Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 119:689–702
Del Tredici K, Hawkes CH, Ghebremedhin E, Braak H (2010) Lewy body pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson´s disease. Acta Neuropathol 119:703–713
Lebouvier T, Chaumette T, Damier P, Coron E, Touchefeu Y, Vrignaud S, Naveilhan P, Galmiche JP, Bruley des Varannes S, Derkinderen P, Neunlist M (2008) Pathological lesions in colonic biopsies during Parkinson’s disease. Gut 57:1741–1743
Lebouvier T, Neunlist M, Bruley des Varannes S, Coron E, Drouard A, N’Guyen JM, Chaumette T, Tasselli M, Paillusson S, Flamand M, Galmiche JP, Damier P, Derkinderen P (2010) Colonic biopsies to assess the neuropathology of Parkinson’s disease and its relationship with symptoms. PLoS One 5(9):e12728
Shannon KM, Keshavarzian A, Mutlu E, Dodiya HB, Daian D, Jaglin JA, Kordower JH (2012) Alpha-synuclein in colonic submucosa in early untreated Parkinson’s disease. Mov Disord 27:709–715
Cersósimo MG, Perandones C, Micheli FE, Raina GB, Beron AM, Nasswetter G, Radrizzani M, Benarroch EE (2011) Alpha-synuclein immunoreactivity in minor salivary gland biopsies of Parkinson’s disease patients. Mov Disord 26:188–190
Pouclet H, Lebouvier T, Coron E, Neunlist M, Derkinderen P (2012) Lewy pathology in gastric and duodenal biopsies in Parkinson’s disease. Mov Disord 27:708
Edwards LL, Quigley EMM, Hofman R, Pfeiffer RF (1992) Gastrointestinal dysfunction in Parkinson’s disease: frequency and pathophysiology. Neurology 42:726–732
Pfeiffer RF (1998) Gastrointestinal dysfunction in Parkinson’s disease. Clin Neurosci 5:136–146
Pfeiffer RF (2003) Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol 2:107–116
Pfeiffer RF (2011) Gastrointestinal dysfunction in Parkinson’s disease. Parkinsonism Relat Disord 17:10–15
Cloud LJ, Greene JG (2011) Gastrointestinal features of Parkinson’s disease. Curr Neurol Neurosci Rep 11:379–384
Edwards LL, Pfeiffer RJ, Quigley EMM, Hofman R, Baluff M (1991) Gastrointestinal symptoms in Parkinson’s disease. Mov Disord 6:151–156
Byrne KG, Pfeiffer R, Quigley EM (1994) Gastrointestinal dysfunction in Parkinson’s disease. A report of clinical experience at a single center. J Clin Gastroenterol 19:11–16
Chaudhuri KR, Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P et al (2006) International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 21:916–923
Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, MacPhee G et al (2007) Prevalence of nonmotor symptoms in Parkinson’s disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients. Mov Disord 22:1623–1629
Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP et al (2009) The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 24:1641–1649
Chaudhuri KR, Prieto-Jurcynska C, Naidu Y, Mitra T, Frades-Payo B et al (2010) The nondeclaration of nonmotor symptoms of Parkinson’s disease to health care professionals: an international study using the nonmotor symptoms questionnaire. Mov Disord 25:704–709
Abbott RD, Petrovitch H, White LR et al (2001) Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 57:456–462
Abbott RD, Ross GW, Petrovitch H et al (2007) Bowel movement frequency in late-life and incidental Lewy bodies. Mov Disord 22:1581–1586
Savica R, Carlin JM, Grossardt BR, Bower JH, Ahlskog JE, Maraganore DM, Bharucha AE, Rocca WA (2009) Medical records documentation of constipation preceding Parkinson disease: a case-control study. Neurology 24(73):1752–1758
Gao X, Chen H, Schwarzschild MA, Ascherio A (2011) A prospective study of bowel movement frequency and risk of Parkinson’s disease. Am J Epidemiol 1(174):546–551
Ross GW, Abbott RD, Petrovitch H, Tanner CM, White LR (2012) Pre-motor features of Parkinson’s disease: the Honolulu-Asia Aging Study experience. Parkinsonism Relat Disord 18(Suppl 1):S199–S202
Fahn S, Elton RL, UPDRS development committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne D, Goldstein M (eds) Recent developments in Parkinson’s disease. Florham Park, Macmillam, pp 153–164
Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progresión and mortality. Neurology 17:427–442
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy if clinical diagnosis of idiopathic Parkinson´s disease: a clinic-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184
Cersosimo MG, Raina GB, Calandra CR, Pellene A, Gutierrez C, Micheli FE, Benarroch EE (2011) Dry mouth: an overlooked autonomic symptom in Parkinson’s disease. J Parkinson Dis 1:169–173
Heetun ZS, Quigley EM (2012) Gastroparesis and Parkinson’s disease: a systematic review. Parkinsonism Relat Disord 18:433–440
Proulx M, de Courval FP, Wiseman MA, Panisset M (2005) Salivary production in Parkinson’s disease. Mov Disord 20:204–207
Cersósimo MG, Benarroch EE (2008) Neural control of the gastrointestinal tract: implications for Parkinson Disease. Mov Disord 23:1065–1075
Kuo YM, Li Z, Jiao Y et al (2010) Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated alpha-synuclein gene mutations precede central nervous system changes. Hum Mol Genet 19:1633–1650
Sakakibara R, Odaka T, Uchiyama T, Asahina M, Yamaguchi K, Yamaguchi T et al (2003) Colonic transit time and rectoanal videomanometry in Parkinson’s disease. J Neurol Neurosurg Psychiatry 74:268–272
Acknowledgments
We thank Dr. Valeria Hirschler for helping with the statistics.
Conflicts of interest
The authors have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cersosimo, M.G., Raina, G.B., Pecci, C. et al. Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J Neurol 260, 1332–1338 (2013). https://doi.org/10.1007/s00415-012-6801-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-012-6801-2