Elsevier

The Lancet Neurology

Volume 14, Issue 6, June 2015, Pages 625-639
The Lancet Neurology

Review
Gastrointestinal dysfunction in Parkinson's disease

https://doi.org/10.1016/S1474-4422(15)00007-1Get rights and content

Summary

Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.

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

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”,

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