As populations age, the prevalence of neurologic disease in the community continues to increase, and consultations relating to gastrointestinal motility problems in the patient afflicted with a neurologic disorder become ever more common.
Although in theory several gastrointestinal functions could be disturbed in neurologic disorders in relation either to a given disease process or to its therapy, this article focuses on the gastrointestinal function that has received the greatest attention in this context, namely, gastrointestinal motility.
Gut Motor Function and its Relevance to Neurologic Disease
Given its essential role in digestion, absorption, secretion, and excretion, the gastrointestinal tract and its associated organs play an essential role in homeostasis. The various physiologic processes of the gastrointestinal tract serve these functions; thus, motility propels food, chyme, and stool and promotes mixing to increase contact time and thereby digestion. Gut muscle and nerve are integrated into a “mini-brain” and are adapted to subserve these homeostatic functions. Throughout most of the gastrointestinal tract, gut smooth muscle is arranged in two layers, an outer longitudinal layer and an inner circular layer. However, at the beginning and end of the gut, striated muscle is found in the oropharynx, upper esophageal sphincter (UES), proximal part of the esophagus, external anal sphincter, and pelvic floor muscles. In these locations, somatic innervation plays a crucial role in the regulation of swallowing and defecation; these functions are, not surprisingly, particularly prone to disruption, and in neurologic disease and dysphagia, constipation and fecal incontinence are prominent issues.
Throughout the remainder of the gut, several levels of control are evident. Myogenic regulation of motility refers to intrinsic properties of gut muscle cells and their interactions with one another. The biochemistry and molecular biology of enteric smooth muscle has much in common with its striated counterpart, thus explaining the high frequency of gut involvement in muscular dystrophies.
The next layer of control is provided by the enteric nervous system (ENS), which is now recognized as a distinct and independent division of the autonomic nervous system. The ENS may represent the most important level of neuronal control of motility. It is capable of generating and modulating many functions within the gastrointestinal tract without input from the more traditional divisions of the autonomic system and central nervous system (CNS). Through variations in neuronal morphology and in the electrophysiologic properties of individual neurons, as well as through the presence of a wide variety of neurotransmitters and neuromodulatory peptides, the ENS demonstrates striking plasticity. Of relevance to any discussion of the gut in CNS disorders, it is now recognized that the ENS and CNS share many similarities, both morphologic and functional. Thus the basic organization of the ENS (neurons, ganglia, glia, an ENS-blood barrier), as well as the ultrastructure of its components, are similar to that of the CNS, and almost all neurotransmitters identified within the CNS are also found in enteric neurons. The concept of ENS involvement in neurologic disease should not, therefore, come as a great surprise.
Although the ENS is primarily responsible for the generation and modulation of most motor activities within the gut, input from autonomic nerves and the CNS also modulates motor activity. Autonomic input is now recognized to be exerted primarily though the modulation of ENS activity rather than through a direct input to effector cells in the gut, be they smooth muscle or epithelial secretory cells. Given the prevalence of autonomic dysfunction in a number of neurologic syndromes, as well as the existence of a number of primary and secondary disorders of autonomic function, disturbed autonomic modulation of gut motor function may be an important contributory factor to symptomatology in some scenarios.
It is now evident that the gut has important sensory functions. Although usually subconscious, gut sensation may be relayed to and perceived within the CNS. Sensory input is also fundamental to several reflex events in the gut, such as the viscerovisceral reflexes that coordinate function along the gut. The role of sensory dysfunction in the mediation of common symptoms, such as abdominal pain and nausea, in the patient with CNS disease with gastrointestinal manifestations has not been extensively investigated, however.
The Pathogenesis of Gastrointestinal Dysfunction in Neurologic Disease
Whereas a whole range of disease processes affecting central, peripheral, and autonomic nervous systems may affect gut motor function, the two predominant neurologic disorders encountered in gastrointestinal practice are cerebrovascular disease and parkinsonism.
Cerebrovascular Disease
Because of the aforementioned location of the swallowing center in the brain stem, it should come as no surprise that severe dysphagia can occur as a result of brainstem infarcts, especially if bilateral. Dysphagia following cortical strokes is a well-recognized and common complication, occurring in up to 50% of ischemic strokes, and its occurrence is associated with increased mortality and impaired functional outcome. Poststroke dysphagia is multifactorial and is largely attributable to oropharyngeal dysfunction. Abnormalities include incomplete lip closure, poor tongue movement, increased pooling, weak laryngeal elevation, and an increased frequency of airway penetration. Elegant imaging studies have provided considerable insights into the pathophysiology of dysphagia and its recovery in hemispheric strokes. These studies have emphasized the importance of cortical as well as brain stem control in the regulation of the swallowing mechanism. In humans, one hemisphere usually demonstrates dominance in the control of swallowing. At the cortical level, ischemic events that involve projections from the precentral gyrus to the internal capsule are most likely to be complicated by dysphagia. Brain stem strokes are especially likely to result in dysphagia, which may be slower to recover from and is more likely to result in aspiration. Given the role of the dorsal motor nucleus of the vagus in the medulla in the control of the smooth muscle esophagus and lower esophageal function, peristaltic dysfunction and gastroesophageal reflux would be expected in the stroke patient; however, there have been few studies of these aspects of esophageal function in the aftermath of acute stroke.
The good news is that, thanks to neuronal plasticity within the CNS, dysphagia resolves spontaneously in most cortical stroke patients within 2 weeks of the ischemic insult. Recovery seems to represent assumption by the unaffected hemisphere of the cortical control of swallowing rather than recovery of function in the damaged area; swallowing improvement may therefore occur independent of any recovery of limb function. This aspect of recovery is important and suggests that one should not be rushed into interventions in the interim but rather maintain close observation for risks for and the occurrence of aspiration.
Although little studied, there is indirect evidence to suggest that gastric emptying may be delayed following an acute stroke, which may have implications for feeding and drug administration. Stroke is also associated with constipation and anorectal dysfunction including incontinence, and instances of intestinal pseudo-obstruction have been reported. In contrast to swallowing function, gastric, small intestinal, colonic, and anorectal motor or sensory function have been little studied in the context of stroke, and therefore the pathophysiology of complications involving these parts of the gastrointestinal tract is less clearly understood. Whereas immobility may play some role, it is likely that cortical regulation of colonic and anorectal physiology is more important.
Parkinson Disease
Idiopathic Parkinson disease (PD) causes widespread and sometimes severe derangement of gastrointestinal motility. There are two basic contributors to gastrointestinal dysfunction in PD. First, striatal muscle dysfunction in the oropharynx, proximal esophagus, and anal canal is based on the same neurologic abnormalities that cause the cardinal manifestations of this disorder. The second component, dysfunction in the smooth muscle parts of the gastrointestinal tract, is less well understood but may reflect pathology in the autonomic and/or ENS systems. Indeed, neuropathologic changes reminiscent of CNS Parkinson features, such as dopamine depletion and the presence of Lewy neuritis, have been demonstrated in the myenteric and submucosal plexuses.
The pathogenesis of dysphagia in PD was studied in detail by Ali and colleagues in a detailed videofluoromanometric study of the swallowing process. The most prominent abnormalities, disturbed tongue movement and reduced amplitude of pharyngeal peristalsis, conspired to impair upper sphincter opening and thereby retard bolus passage into the esophagus. Cricopharyngeal bars and hypopharyngeal diverticula have also been described in PD. Involvement of the dorsal motor nucleus of the vagus and of central noradrenergic neurons, as well as the ENS of the esophagus, may contribute to the occurrence of esophageal dysphagia in PD.
With regard to the stomach, small intestine, and colon, similar hypotheses have been advanced to explain the high prevalence of symptoms related to these organs in PD, but in these regions the role of autonomic and ENS pathologic abnormalities looms large. The contribution of autonomic dysfunction is illustrated by the higher prevalence of gastrointestinal symptoms as well as postural instability among patients with a PD variant, multiple system atrophy, in which autonomic dysfunction is especially common. For some of these symptoms, such as nausea, the contribution of antiparkinsonian medications and dopaminergics in particular must be remembered.
Delayed gastric emptying has been well-documented in PD, and delayed emptying of solids has been linked in some studies to the severity of motor impairment. Here again, the impact of levodopa must be accounted for. The association between gastric emptying delay and the presence of levodopa response fluctuations, coupled with irregular patterns of drug absorption and the documentation of improved symptom control with intrajejunal or transdermal administration of antiparkinsonian drugs, underlines the potential clinical relevance of gastric emptying delay: by retarding drug delivery and absorption, gastroparesis could induce or further exacerbate response fluctuations. Several factors, however, limit the interpretation of reports of delayed gastric emptying and its association with upper gastrointestinal symptoms in PD. These factors include variations in patient population studied (eg, age, gender, disease severity, study location), the definition of gastroparesis, and the methodology used to assess gastric emptying rate (meal, test technique, study protocol, and manner of interpretation). Variations between studies in these parameters make it difficult to attempt real comparisons or draw firm conclusions. Nevertheless, delayed gastric emptying may occur in as many as 70% to 100% of PD patients attending specialist neurology clinics; the prevalence of symptomatic gastroparesis in PD, however, remains unknown. Indeed, there has been a lack of a consistent correlation between gastric emptying rate and upper gastrointestinal symptoms in PD. Although it is reasonable to assume that gastroparesis contributes to the weight loss that has been well-documented in PD, it is unclear whether nutrient delivery is affected by delayed gastric emptying, and a relationship between delayed gastric emptying and weight loss is yet to be demonstrated. Electrogastrography has also been used to study gastric motor activity in PD, but correlations with symptoms have been poor. Parenthetically, Helicobacter pylori and Helicobacter heilmannii infection have been implicated not only in contributing to gastrointestinal symptoms and weight loss in PD, but also in systemic proinflammatory cytokine activation and even in the pathogenesis of PD itself.
Orocecal and colonic transit times are significantly prolonged in patients with PD, and small intestinal bacterial overgrowth, presumed to be consequent to impaired small intestinal motility, has been documented.
Constipation, a common and at times dominant symptom in PD, is probably multifactorial, with delayed colonic transit, anorectal dysfunction, drug therapy, and reduced physical activity all contributing to the problem. Difficulty with the act of defecation may be an especially distressing symptom for affected patients; this symptom seems to be associated with PD severity, and its pathophysiology is based on the involvement of the anal sphincter and pelvic floor musculature by the PD process ( Fig. 1 ). Accordingly, responses have been documented for apomorphine injection. Megacolon, at times requiring surgical intervention and even resulting in perforation and fatal outcome, has been well-documented in PD ( Fig. 2 ).
Related posts:
A 21st Century Look at the Spectrum of Gastrointestinal Motility Disorders. What is Dysmotility; What is Functional?
Enteric Neuromuscular Pathology Update
Postoperative Problems 2011: Fundoplication and Obesity Surgery
Enteric Neuromuscular Pathology Update
Postoperative Problems 2011: Fundoplication and Obesity Surgery
Challenges in the Swallowing Mechanism: Nonobstructive Dysphagia in the Era of High-Resolution Manometry and Impedance
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
