We identified references for this Review from searches of our personal files and textbooks. We also searched PubMed for papers published in English from Jan 1, 1965, to Jan 26, 2015, with the search terms “gastrointestinal dysfunction”, “weight loss”, “dysphagia”, “gastroparesis”, “gastric emptying”, “small intestine”, “colon”, “anorectal”, “dental”, “drooling”, “taste”, “burning mouth”, “dry mouth”, “nutrition”, “helicobactor pylori”, “small intestinal bacterial overgrowth”, “constipation”,
ReviewGastrointestinal dysfunction in Parkinson's disease
Introduction
Progress in the understanding of the extent and role of gastrointestinal dysfunction in Parkinson's disease has increased substantially in the past decade.1 Not only is the gastrointestinal system impaired from both a motor and dysautonomic standpoint, but it also plays an active part in the pathophysiological changes that underlie motor fluctuations through its effects on absorption of antiparkinsonian drugs. A wealth of evidence2, 3, 4 strongly implicates pathophysiological changes in the gastrointestinal tract in the pathogenesis of Parkinson's disease, and many studies5 indicate that the enteric nervous system might serve as a conduit for the propagation of α-synuclein, initiating the characteristic spread of degeneration through the CNS.
Here, we review current knowledge of gastrointestinal involvement in Parkinson's disease. First, we assess the growing body of experimental evidence supporting the hypothesis that the gastrointestinal tract might be the site of initiation of Parkinson's disease, along with evidence for the potential use of gastrointestinal α-synuclein deposition (from the submandibular gland to the appendix and the colon) as a diagnostic biomarker. Second, we discuss the effect of gastrointestinal dysfunction on clinical symptoms, including oral difficulties, swallowing problems, and constipation. As a result of their frequency, these salient gastrointestinal symptoms are important in disease progression and constitute a major source of disability. We also review evidence describing the deleterious effect of small intestinal bacterial overgrowth (SIBO) and Helicobacter pylori infection on the absorption of antiparkinsonian drugs and the potential effects on the pathophysiological changes in patients with Parkinson's disease and motor fluctuations.
Owing to the substantial role of the gastrointestinal system in Parkinson's disease, we believe that thorough assessment and treatment of gastrointestinal dysfunction in patients with the disease is essential. To this end, we have designed a practical algorithm for the assessment of the gastrointestinal system in patients with Parkinson's disease and provide an evidence-based approach to treatment. We conclude by discussing the next crucial steps that are needed in research, treatment, and understanding of gastrointestinal involvement in Parkinson's disease.
Section snippets
Synucleinopathy in the gastrointestinal tract
The pathological changes of Parkinson's disease are defined by abnormal α-synuclein accumulation in the brain in characteristic Lewy bodies or Lewy neurites. However, evidence for abnormal α-synuclein accumulation outside the brain, including throughout the enteric nervous system, is growing (figure 1). α-Synuclein deposition occurs in the myenteric and submucosal plexuses and mucosal nerve fibres, with a clear rostrocaudal gradient in deposition throughout the enteric nervous system.13 A study
Dental problems
Patients with Parkinson's disease brush their teeth and seek dental care less frequently than healthy individuals.19 The ability of patients to brush their teeth effectively is hampered by decreased manual dexterity and difficulty opening the jaw,20 leading to increased periodontal disease, an increased frequency of caries, and fewer remaining teeth.21 Excessive saliva (sialorrhoea) might change salivary pH and composition in some patients, and xerostomia might impair the mouth's self-cleaning
Swallowing disorders
Oropharyngeal and oesophageal dysphagia are frequently reported in patients with Parkinson's disease, with a prevalence ranging from 9% to 77% (table 1). In a meta-analysis,60 the pooled prevalence was estimated to be 35% for subjective oropharyngeal dysphagia; however, because many patients are unaware of symptoms, objective testing resulted in a higher prevalence of 82%.60 Pharyngeal dysfunction and oropharyngeal transit abnormalities increase the risk of aspiration, thus contributing to risk
Malnutrition
The prevalence of malnutrition in Parkinson's disease ranges from 0% to 24% and risk of malnutrition from 3% to 60%.66 Malnutrition is an established determinant of health in elderly people and is linked to reduced functional ability, quality of life, and survival in patients with Parkinson's disease.67 Motor impairment (dysphagia), fear of increased off-time, fasting associated with drug administration, drug-induced nausea, and anorexia can all affect food intake. Female sex, ageing, loss of
Motility disorders
Recognition of impaired gastric emptying in Parkinson's disease is growing; prevalence ranges from 70% to 100%, although not all affected individuals have symptoms.74 Gastroparesis can be present in both early and advanced Parkinson's disease, with delays in gastric emptying more likely to be associated with solid meals.75 Nausea, vomiting, early satiety, excessive fullness, bloating, and abdominal distension characterise gastroparesis.76 Because levodopa is absorbed in the small intestine,
Small intestinal bacterial overgrowth
In healthy people, intrinsic mechanisms control the number and composition of small intestine microbiota: gastric acid destroys many bacteria entering the stomach; biliary and pancreatic secretions limit bacterial growth; the migrating motor complex (which has the housekeeping function of gastrointestinal motility) reduces luminal growth potential; the intestinal mucus traps and fights bacteria; and the ileocaecal valve inhibits retrograde migration of bacteria from the colon into the ileum.90
Constipation
Constipation is the most common gastrointestinal symptom in Parkinson's disease, reported in 80–90% of patients (table 1), and in view of its emergence long before the onset of motor symptoms, is an especially noteworthy gastrointestinal feature of the disease. A population-based study reported that risk of development of Parkinson's disease increases with constipation severity (hazard ratios ranged from 3·3 to 4·2).96 Not only is the risk increased in individuals with constipation, but
A practical algorithm for management
All patients with Parkinson's disease with gastrointestinal symptoms or with a suboptimum response to dopaminergic drugs (possibly related to poor absorption) should be assessed and treated (figure 4). Identification of modifiable factors is a crucial first step in the management of these patients. In some cases, Parkinson's disease treatment should be optimised—eg, because drooling is common during off-times, treatment of fluctuations should first be addressed, although this must be weighed
Conclusions
Understanding of the pivotal role of the gastrointestinal system in the pathophysiology and possibly also the cause of Parkinson's disease has grown substantially during the past decade. Although some progress has been made in the development of effective treatments for gastrointestinal dysfunction in these patients, much remains to be accomplished. More effective treatment modalities for dysphagia are sorely needed. Problems with potential cardiotoxic effects have impeded the introduction of
Search strategy and selection criteria
References (173)
Gastrointestinal dysfunction in Parkinson's disease
Lancet Neurol
(2003)- et al.
Expression pattern and localization of alpha-synuclein in the human enteric nervous system
Neurobiol Dis
(2012) - et al.
Pathological correlates of gastrointestinal dysfunction in Parkinson's disease
Neurobiol Dis
(2012) - et al.
Alpha-synuclein transgenic mice display age-related slowing of gastrointestinal motility associated with transgene expression in the vagal system
Neurobiol Dis
(2012) - et al.
Increased frequencies of caries, periodontal disease and tooth loss in patients with Parkinson's disease
J Clin Neurosci
(2009) - et al.
Drooling in Parkinson's disease: a review
Parkinsonism Relat Disord
(2014) - et al.
Is silent aspiration a risk factor for respiratory infection in Parkinson's disease patients?
Parkinsonism Relat Disord
(2008) - et al.
Autonomic dysfunction in Parkinson's disease: a comprehensive symptom survey
Parkinsonism Relat Disord
(2002) - et al.
Scintigraphic analysis of the parotid glands in patients with sialorrhea and Parkinson's disease
Parkinsonism Relat Disord
(2008) - et al.
Nonmotor symptoms in de novo Parkinson disease before and after dopaminergic treatment
J Neurol Sci
(2009)
The impact of and the factors associated with drooling in Parkinson's disease
Parkinsonism Relat Disord
Autonomic function, as self-reported on the SCOPA-autonomic questionnaire, is normal in essential tremor but not in Parkinson's disease
Parkinsonism Relat Disord
Abnormality of taste and smell in Parkinson's disease
Parkinsonism Relat Disord
The influence of age and gender on motor and non-motor features of early Parkinson's disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort
Parkinsonism Relat Disord
Prediagnostic presentations of Parkinson's disease in primary care: a case-control study
Lancet Neurol
Prevalence of oropharyngeal dysphagia in Parkinson's disease: a meta-analysis
Parkinsonism Relat Disord
Prolonged swallowing time in dysphagic Parkinsonism patients with aspiration pneumonia
Archs Phys Med Rehabil
Gastrointestinal dysfunction in Parkinson's disease
Parkinsonism Relat Disord
Gastroparesis and Parkinson's disease: a systematic review
Parkinsonism Relat Disord
American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis
Gastroenterology
Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology
Neurosci Lett
Small intestinal bacterial overgrowth in Parkinson's disease
Parkinsonism Relat Disord
Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics
Gastroenterology
Colonic inflammation in Parkinson's disease
Neurobiol Dis
Effects of gastrointestinal inflammation on enteroendocrine cells and enteric neural reflex circuits
Auton Neurosci
Risk of Parkinson's disease following severe constipation: a nationwide population-based cohort study
Parkinsonism Relat Disord
Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon
Gastroenterology
Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders
Acta Neuropathol
Enteric alpha-synuclein expression is increased in Parkinson's disease but not Alzheimer's disease
Movement Disord
Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen
J Neural Transm
Parkinson's disease: the presence of Lewy bodies in Auerbach's and Meissner's plexuses
Acta Neuropathol
Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects
Mov Disord
Submandibular gland biopsy for the diagnosis of Parkinson disease
J Neuropathol Exp Neurol
Submandibular gland needle biopsy for the diagnosis of Parkinson disease
Neurology
Colonic biopsies to assess the neuropathology of Parkinson's disease and its relationship with symptoms
PloS One
Colonic mucosal alpha-synuclein lacks specificity as a biomarker for Parkinson disease
Neurology
Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease
Movement Disord
Alimentary, my dear Watson? The challenges of enteric α-synuclein as a Parkinson's disease biomarker
Mov Disord
The prion hypothesis in Parkinson's disease: Braak to the future
Acta Neuropathol Commun
α-synuclein in the appendiceal mucosa of neurologically intact subjects
Mov Disord
Parkinson's disease and the gut: ‘the wheel is come full circle’
J Parkinsons Dis
Caries and periodontal disease in patients with Parkinson's disease
Spec Care Dentist
Orofacial function and oral health in patients with Parkinson's disease
Eur J Oral Sci
Alimentary disorder in Parkinsonism
Austral Ann Med
Gastrointestinal symptoms in Parkinson's disease
Mov Disord
Characterization of swallowing and defecation in Parkinson's disease
Am J Gastroenterol
Patient-reported autonomic symptoms in Parkinson disease
Neurology
Study of an integrated non-motor symptoms questionnaire for Parkinson's disease
Chin Med J
Autonomic and sensory symptoms and signs in incident, untreated Parkinson's disease: frequent but mild
Mov Disord
Gender differences in non-motor symptoms in early, drug naive Parkinson's disease
J Neurol
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