Gastrointestinal dysfunction in Parkinson's Disease

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Abstract

Gastrointestinal (GI) motility is very frequently disturbed in Parkinson's disease (PD), manifesting chiefly as dysphagia, impaired gastric emptying and constipation. All these symptoms - constipation in particular – may precede the clinical diagnosis of PD for years. In the future, these symptoms might serve as useful early indicators in the premotor stage. Disturbed gastric emptying is an important factor in unpredictable fluctuations.

The most likely causes are degenerations of the dorsal vagal nucleus and the intramural plexus of the whole intestine. These degenerations are likely to develop prior to the degeneration of dopaminergic neurons of the substantia nigra. Diagnosis includes history, clinical examination, barium meal, breath test, scintiscan of stomach, and colonic transit time.

Therapeutic efforts are limited when it comes to disturbed motility of the upper GI-tract. Hypersalivation can be reduced by anticholinergics or botulinum toxin injections; motility of the upper gastrointestinal tract is only moderately impacted on by domperidone. In constipation, the conservative therapeutic option is administration of macrogol (polyethylene glycol), which leads to marked improvement.

Section snippets

Introduction and epidemiology

Parkinson's disease (PD) is a progressive neurodegenerative disease of midaged or older adults. The pathophysiology of its varied symptoms still remains hypothetic. We still don't know [1] whether the pathologic process originates in the brain or elsewhere in the nervous system. Apart from the cardinal signs - bradykinesia, rigidity, tremor at rest and postural instability - in the very beginning, patients complain of hyposmia, REM-sleep behaviour disorders, depression, and constipation.

Anatomy and pathology

The vagal nerve extrinsically innervates the gastrointestinal tract from the esophagus to the left colic flexure, and is mainly responsible for the motility of both esophagus and stomach. The remaining colon is innervated by the parasympathetic nucleus of the spinal cord (S2-4). Sympathetic innervation (via prevertebral ganglia) of the small and large bowel appears to be less important [4]. Colonic motility is predominantly governed by the intramural ganglia, the enteric nervous system (ENS) –

Upper gastroinestinal tract

Motility disorders of the upper GI-tract have to date not been met with greater interest. Sialorrhea alone was a reported symptom, but was seldom seen in connection with dysphagias.

Patients with Parkinson's disease present with delayed and/or disturbed motility of the upper gastrointestinal tract, which is primarily marked by swallowing problems and impaired gastric emptying. The esophageal sphincters, however, are disturbed as well involving above all the synergy between propulsion and

Diagnostic exploration of the upper gastrointestinal tract

Measurements by breath tests have become established routine in everyday clinical life since they are a feasible and usually well tolerated procedure [17]. Gastric motility can, in addition, be determined on gastric emptying scintiscan after ingestion of a radioactive meal.

Treatment

Anticholinergics have so far been recommended to treat sialorrhea in Parkinson patients. It would nevertheless make more sense to address the causatively involved dysphagias in the first place. Injections with botulinum toxin [18] may be considered a therapeutic option.

Dysphagias are quite refractory to treatment. You can advise patients to adopt an antidysphagic or pap diet to avoid ingestion of larger bits of food. Prokinetic medication may be helpful in addition - domperidone for instance -

Lower GI-tract

Constipation has been identified as a rather frequent symptom in patients with Parkinson's disease ever since the first description of the disease [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30]. Today, constipation is considered the most common manifestation of autonomic dysfunction in this disease occurring at a prevalence in the range of 70 to 80% [20], [21], [22], [23], [31], [32], [33], [34], [35]. Compared to age- and sex-matched controls, constipation is

Effect of antiparkinsonian therapy

Constipation in Parkinson's disease is often viewed as an adverse effect of medications. In 1958, Schwab and England [27] described constipating effects of almost all substances administered in Parkinson's disease. However, the most pronounced effect on gastrointestinal motility is ascribed to treatment with anticholinergics and levodopa [39]. Anticholinergics in particular have been accused of having a definitely constipative effect which may occasionally result in the development of megacolon

Slow transit constipation

Increasing evidence suggests that delayed colonic transit in Parkinson's disease is caused by disordered autonomic regulation due to central and peripheral degeneration of parasympathetic nuclei. Such degenerations are found in the vagal nucleus and intermediolateral nucleus as well as in the myenteric and submucous plexus of the gastrointestinal tract. Within the latter structures, the presence of Lewy bodies and a depletion of dopamine-producing neurons may be rated as characteristic

Outlet obstruction

Mathers et al. [53] were the first to describe a completely different mechanism of constipation in PD, namely a paradoxical contraction of the voluntary sphincters during defecation leading to marked difficulties in rectal evacuation. The authors assume that such anomalies in anorectal function represent a focal form of dystonia [53]. The latter hypothesis is supported by the findings reported by other groups [23], [54], [55], in which several patients with Parkinson's disease were found to

Diagnosis

The most important step in the diagnosis of constipation is thorough history-taking followed by physical examination. Occasionally, a structured interview using special questionnaires may be helpful, too [34]. Questions are aimed at differentiating abnormalities of colonic transit from those of defecation. Special emphasis is also put on the medication used, i.e. anticholinergics, calcium channel blockers, antidepressants, and diuretics.

Colonic transit abnormalities can easily be quantified by

Therapy

The simplest measures in the treatment of constipation focus on a high fiber diet [62], psyllium preparations [63], and perhaps - physiotherapy. In earlier years, treatment merely consisted in ordering increased fluid intake and the frequent administration of enteroclysis [27]. Unfortunately, these measures are efficient in mild cases of constipation only, but there is no appreciable effect in patients with transit times of more than five days [38]. Thus, most patients with constipation

Discussion

Gastrointestinal disorders are very common and involve the entire gastrointestinal tract. They are observed in the early stage already [14], [52], [58], [63], and increasingly so as the disease keeps progressing. Whether the neurodegenerative process might be set off in the enteric nervous system after all, is a current issue of discussion [8].

The pathophysiology of gastrointestinal dysfunction in PD seems to be multifactorial. Delayed intestinal transit is most likely caused by defective

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