Skip to main content

Advertisement

SpringerLink
Log in

Analysis of the clinical features of early Parkinson’s disease with comparatively integrated intestinal function

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Objective

Constipation is among the most frequently delineated nonmotor symptoms (NMS) with a high occurrence in Parkinson’s disease (PD). The purpose of our study was to investigate whether PD with comparatively integrated intestinal function (without constipation) in the early stage had different clinical features compared to constipated PD.

Method

We conducted a study of 105 consecutive de novo as well as early treated (treated for shorter than 3 months), aged 50 years or older outpatients. Subjects were administered motor and nonmotor questionnaires as well as constipation associated examinations. Then, we explored the distinctive features of nonconstipated contrasted to constipated PD by using univariate, multiple regression analysis and correlation analysis.

Results

Nonconstipated PD tended to have fewer motor deficits, as well as lower Hoehn and Yahr (H&Y) stage and they mainly presented as tremor-dominant (TD), while constipated group had a higher occurrence of posture instability and gait difficulty (PIGD); nonconstipated patients were inclined to live in urban area, the NMSloads and prevalence of NMS were lower compared to constipated ones. Correlation analysis found a discord between NMSloads and disease severity based on H&Y stage and motor scores in nonconstipated PD.

Conclusions

These results suggest that PD without constipation in early stage may represent a unique clinical phenotype, which may be more benign than PD with constipation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. 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(7):916–923

    Article  Google Scholar 

  2. Savica R, Carlin JM, Grossardt BR, Bower JH, Ahlskog JE, Maraganore DM et al (2009) Medical records documentation of constipation preceding Parkinson disease: a case-control study. Neurology 73(21):1752–1758

    Article  CAS  Google Scholar 

  3. Adams-Carr KL, Bestwick JP, Shribman S, Lees A, Schrag A, Noyce AJ (2016) Constipation preceding Parkinson’s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 87(7):710–716

    Article  Google Scholar 

  4. Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF (2015) Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol 14(6):625–639

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Pellegrini C, Antonioli L, Colucci R, Ballabeni V, Barocelli E, Bernardini N et al (2015) Gastric motor dysfunctions in Parkinson’s disease: current pre-clinical evidence. Parkinsonism Relat Disord 21(12):1407–1414

    Article  Google Scholar 

  7. Kim JS, Park IS, Park HE, Kim SY, Yun JA, Jung CK et al (2017) α-Synuclein in the colon and premotor markers of Parkinson disease in neurologically normal subjects. Neurol Sci 38(1):171–179

    Article  Google Scholar 

  8. Hawkes CH, Del Tredici K, Braak H (2007) Parkinson’s disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol 33(6):599–614

    Article  CAS  Google Scholar 

  9. 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 (Vienna) 110(5):517–536

    Article  CAS  Google Scholar 

  10. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211

    Article  Google Scholar 

  11. Derkinderen P, Rouaud T, Lebouvier T, Bruley d, Varannes S, Neunlist M, De Giorgio R (2011) Parkinson disease: the enteric nervous system spills its guts. Neurology 77(19):1761–1767

    Article  CAS  Google Scholar 

  12. Benarroch EE (2007) Enteric nervous system: functional organization and neurologic implications. Neurology 69(20):1953–1957

    Article  Google Scholar 

  13. Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci 18(7):435–450

    Article  CAS  Google Scholar 

  14. Kalaitzakis ME, Graeber MB, Gentleman SM, Pearce RK (2008) The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson’s disease: a critical analysis of alpha-synuclein staging. Neuropathol Appl Neurobiol 34(3):284–295

    Article  CAS  Google Scholar 

  15. Attems J, Jellinger KA (2008) The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson’s disease. Neuropathol Appl Neurobiol 34(4):466–467

    Article  CAS  Google Scholar 

  16. Annerino DM, Arshad S, Taylor GM, Adler CH, Beach TG, Greene JG (2012) Parkinson’s disease is not associated with gastrointestinal myenteric ganglion neuron loss. Acta Neuropathol 124(5):665–680

    Article  Google Scholar 

  17. Pfeiffer RF (2014) Parkinson’s disease and the gut: ‘the wheel is come full circle’. J Parkinson Dis 4(4):577–578

    Google Scholar 

  18. Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ (2009) A clinico-pathological study of subtypes in Parkinson’s disease. Brain 132(Pt 11):2947–2957

    Article  CAS  Google Scholar 

  19. Halliday G, Lees A, Stern M (2011) Milestones in Parkinson’s disease--clinical and pathologic features. Mov Disord 26(6):1015–1021

    Article  Google Scholar 

  20. Sauerbier A, Jenner P, Todorova A, Chaudhuri KR (2016) Non motor subtypes and Parkinson’s disease. Parkinsonism Relat Disord 22(Suppl 1):S41–S46

    Article  Google Scholar 

  21. Erro R, Vitale C, Amboni M, Picillo M, Moccia M, Longo K et al (2013) The heterogeneity of early Parkinson’s disease: a cluster analysis on newly diagnosed untreated patients. PLoS One 8(8):e70244

    Article  CAS  Google Scholar 

  22. Zhu L, Liu W, Alkhouri R, Baker RD, Bard JE, Quigley EM et al (2014) Structural changes in the gut microbiome of constipated patients. Physiol Genomics 46(18):679–686

    Article  CAS  Google Scholar 

  23. Jankovic J, McDermott M, Carter J, Gauthier S, Goetz C, Golbe L et al (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson study group. Neurology 40(10):1529–1534

    Article  CAS  Google Scholar 

  24. Burn DJ, Landau S, Hindle JV, Samuel M, Wilson KC, Hurt CS et al (2012) Parkinson’s disease motor subtypes and mood. Mov Disord 27(3):379–386

    Article  Google Scholar 

  25. Thenganatt MA, Jankovic J (2014) Parkinson disease subtypes. JAMA Neurol 71(4):499–504

    Article  Google Scholar 

  26. Atac Ucar C, Gokce Cokal B, Unal Artik HA, Inan LE, Yoldas TK (2017) Comparison of neutrophil-lymphocyte ratio (NLR) in Parkinson’s disease subtypes. Neurol Sci 38(2):287–293

    Article  Google Scholar 

  27. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184

    Article  CAS  Google Scholar 

  28. Pont-Sunyer C, Hotter A, Gaig C, Seppi K, Compta Y, Katzenschlager R et al (2015) The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Mov Disord 30(2):229–237

    Article  Google Scholar 

  29. Reijnders JS, Ehrt U, Lousberg R, Aarsland D, Leentjens AF (2009) The association between motor subtypes and psychopathology in Parkinson’s disease. Parkinsonism Relat Disord 15(5):379–382

    Article  CAS  Google Scholar 

  30. Rajput AH, Voll A, Rajput ML, Robinson CA, Rajput A (2009) Course in Parkinson disease subtypes: a 39-year clinicopathologic study. Neurology 73(3):206–212

    Article  CAS  Google Scholar 

  31. 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(11):1623–1629

    Article  Google Scholar 

  32. Chaudhuri KR, Healy DG, Schapira AH (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5(3):235–245

    Article  Google Scholar 

  33. Rodriguez-Violante M, de Sarachaga AJ, Cervantes-Arriaga A, Millan-Cepeda R, Leal-Ortega R, Estrada-Bellmann I et al (2016) Self-perceived pre-motor symptoms load in patients with Parkinson’s disease: a retrospective study. J Parkinson Dis 6(1):183–190

    Article  Google Scholar 

  34. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA (1999) Functional bowel disorders and functional abdominal pain. Gut 45(Suppl 2):Ii43–Ii47

    PubMed  PubMed Central  Google Scholar 

  35. Stirpe P, Hoffman M, Badiali D, Colosimo C (2016) Constipation: an emerging risk factor for Parkinson’s disease? Eur J Neurol 23:1606–1613

    Article  CAS  Google Scholar 

  36. Marras C, Chaudhuri KR (2016) Nonmotor features of Parkinson’s disease subtypes. Mov Disord 31(8):1095–1102

    Article  CAS  Google Scholar 

  37. Eggers C, Pedrosa DJ, Kahraman D, Maier F, Lewis CJ, Fink GR et al (2012) Parkinson subtypes progress differently in clinical course and imaging pattern. PLoS One 7(10):e46813

    Article  CAS  Google Scholar 

  38. van der Heeden JF, Marinus J, Martinez-Martin P, Rodriguez-Blazquez C, Geraedts VJ, van Hilten JJ (2016) Postural instability and gait are associated with severity and prognosis of Parkinson disease. Neurology 86(24):2243–2250

    Article  Google Scholar 

  39. de Lau LM, Verbaan D, Marinus J, van Hilten JJ (2014) Survival in Parkinson’s disease. Relation with motor and non-motor features. Parkinsonism Relat Disord 20(6):613–616

    Article  Google Scholar 

  40. Hariz GM, Forsgren L (2011) Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease, and in comparison to healthy controls. Acta Neurol Scand 123(1):20–27

    Article  Google Scholar 

  41. Muslimovic D, Post B, Speelman JD, Schmand B, de Haan RJ (2008) Determinants of disability and quality of life in mild to moderate Parkinson disease. Neurology 70(23):2241–2247

    Article  CAS  Google Scholar 

  42. Kadastik-Eerme L, Rosenthal M, Paju T, Muldmaa M, Taba P (2015) Health-related quality of life in Parkinson’s disease: a cross-sectional study focusing on non-motor symptoms. Health Qual Life Outcomes 13:83

    Article  Google Scholar 

  43. Zhang LM, Zhang XP (2015) Investigation of urination disorder in Parkinson’s disease. Chin Med J 128(21):2906–2912

    Article  Google Scholar 

  44. Visanji N, Marras C (2015) The relevance of pre-motor symptoms in Parkinson’s disease. Expert Rev Neurother 15(10):1205–1217

    Article  CAS  Google Scholar 

  45. Erro R, Picillo M, Amboni M, Moccia M, Vitale C, Longo K et al (2015) Nonmotor predictors for levodopa requirement in de novo patients with Parkinson’s disease. Mov Disord 30(3):373–378

    Article  CAS  Google Scholar 

  46. Sakakibara R, Shinotoh H, Uchiyama T, Yoshiyama M, Hattori T, Yamanishi T (2001) SPECT imaging of the dopamine transporter with [(123)I]-beta-CIT reveals marked decline of nigrostriatal dopaminergic function in Parkinson’s disease with urinary dysfunction. J Neurol Sci 187(1–2):55–59

    Article  CAS  Google Scholar 

  47. Winge K, Friberg L, Werdelin L, Nielsen KK, Stimpel H (2005) Relationship between nigrostriatal dopaminergic degeneration, urinary symptoms, and bladder control in Parkinson’s disease. Eur J Neurol 12(11):842–850

    Article  CAS  Google Scholar 

  48. Hattori T, Yasuda K, Kita K, Hirayama K (1992) Voiding dysfunction in Parkinson’s disease. Jpn J Psychiatry Neurol 46(1):181–186

    CAS  PubMed  Google Scholar 

  49. Lim SY, Fox SH, Lang AE (2009) Overview of the extranigral aspects of Parkinson disease. Arch Neurol 66(2):167–172

    Article  Google Scholar 

  50. Djaldetti R, Lev N, Melamed E (2009) Lesions outside the CNS in Parkinson’s disease. Mov Disord 24(6):793–800

    Article  Google Scholar 

  51. Khoo TK, Yarnall AJ, Duncan GW, Coleman S, O'Brien JT, Brooks DJ et al (2013) The spectrum of nonmotor symptoms in early Parkinson disease. Neurology 80(3):276–281

    Article  Google Scholar 

  52. Pezzoli G, Cereda E (2013) Exposure to pesticides or solvents and risk of Parkinson disease. Neurology 80(22):2035–2041

    Article  CAS  Google Scholar 

  53. Pan-Montojo F, Schwarz M, Winkler C, Arnhold M, O'Sullivan GA, Pal A et al (2012) Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep 2:898

    Article  Google Scholar 

  54. Gokce Cokal B, Yurtdas M, Keskin Guler S, Gunes HN, Atac Ucar C, Aytac B et al (2017) Serum glutathione peroxidase, xanthine oxidase, and superoxide dismutase activities and malondialdehyde levels in patients with Parkinson’s disease. Neurol Sci 38(3):425–431

    Article  Google Scholar 

  55. Ghaisas S, Maher J, Kanthasamy A (2016) Gut microbiome in health and disease: linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacol Ther 158:52–62

    Article  CAS  Google Scholar 

  56. Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E et al (2015) Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 30(3):350–358

    Article  Google Scholar 

  57. Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA et al (2011) Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS One 6(12):e28032

    Article  CAS  Google Scholar 

  58. Mayer EA, Tillisch K, Gupta A (2015) Gut/brain axis and the microbiota. J Clin Invest 125(3):926–938

    Article  Google Scholar 

  59. Lema Tome CM, Tyson T, Rey NL, Grathwohl S, Britschgi M, Brundin P (2013) Inflammation and alpha-synuclein's prion-like behavior in Parkinson’s disease--is there a link? Mol Neurobiol 47(2):561–574

    Article  CAS  Google Scholar 

  60. Felice VD, Quigley EM, Sullivan AM, O'Keeffe GW, O'Mahony SM (2016) Microbiota-gut-brain signalling in Parkinson’s disease: implications for non-motor symptoms. Parkinsonism Relat Disord 27:1–8

    Article  Google Scholar 

  61. Grenham S, Clarke G, Cryan JF, Dinan TG (2011) Brain-gut-microbe communication in health and disease. Front Physiol 2:94

    Article  Google Scholar 

  62. Li-Na Z, Deng C, Da X, Si-Han C, Hai-Jiao W, Ling L (2017) Mesencephalic astrocyte-derived neurotrophic factor and its role in nervous system disease. Neurol Sci 38(10):1741–1746

    Article  Google Scholar 

  63. Neunlist M, Rolli-Derkinderen M, Latorre R, Van Landeghem L, Coron E, Derkinderen P et al (2014) Enteric glial cells: recent developments and future directions. Gastroenterology 147(6):1230–1237

    Article  CAS  Google Scholar 

  64. Clairembault T, Leclair-Visonneau L, Neunlist M, Derkinderen P (2015) Enteric glial cells: new players in Parkinson’s disease? Mov Disord 30(4):494–498

    Article  Google Scholar 

  65. McGeer PL, McGeer EG (2004) Inflammation and neurodegeneration in Parkinson’s disease. Parkinsonism Relat Disord 10(Suppl 1):S3–S7

    Article  Google Scholar 

  66. Gao HM, Hong JS, Zhang W, Liu B (2003) Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson’s disease. J Neurosci 23(4):1228–1236

    Article  CAS  Google Scholar 

  67. Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl 3):S26–S36 discussion S-8

    Article  CAS  Google Scholar 

  68. Leung L, Riutta T, Kotecha J, Rosser W (2011) Chronic constipation: an evidence-based review. J Am Board Fam Med 24(4):436–451

    Article  Google Scholar 

  69. Doty RL (2009) The olfactory system and its disorders. Semin Neurol 29(1):74–81

    Article  Google Scholar 

Download references

Funding

This research was supported by the National Natural Science Foundation of China (No. 81471334, 81100981) and the National Key Clinical Specialties Construction Program of China.

Author information

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China

    Xiaoxue Guan, Yuchan Wang, Qun Li, Ming Wei, Lili Chen & Oumei Cheng

  2. Department of Neurology, The First People’s Hospital of the City of Xiangyang, Xiangyang, China

    Xiaoxue Guan

Authors
  1. Xiaoxue Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuchan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lili Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Oumei Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oumei Cheng.

Ethics declarations

All subjects provided written informed consent and the study was approved by the Ethics Committee of the First Affiliated Hospital, Chongqing Medical University in China.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Yuchan Wang is the co-first author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guan, X., Wang, Y., Li, Q. et al. Analysis of the clinical features of early Parkinson’s disease with comparatively integrated intestinal function. Neurol Sci 39, 1847–1856 (2018). https://doi.org/10.1007/s10072-018-3502-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-018-3502-3

Keywords

Search

Navigation