Neural control of bowel function

Neural control of the colon is complex. Intrinsic to the wall of the gastrointestinal tract is an extensive network known as the enteric nervous system. This, in turn, is influenced by the central nervous system via peripheral autonomic and somatic connections.

The enteric nervous system comprises more neurons than the entire spinal cord. It is the basis of the primary reflex circuit that mediates both the filling and emptying of the distal colon and coordinates peristalsis, secretion, and absorption of luminal contents in the gut. The enteric nervous system neurons are organized into two groups: the myenteric plexus, which controls the smooth muscles of the gut, and the submucosal plexus, which regulates the secretomotor and sensory components of gut function (28).

Many neurotransmitters are present in the enteric nervous system, including acetylcholine, norepinephrine, serotonin and other monoamines, GABA, glutamate, ATP, nitric oxide, substance P, enkephalins, somatostatin, neuropeptide Y, and vasoactive intestinal polypeptide (28; 34). The enteric nervous system can function autonomously, albeit less efficiently, if disconnected from the central nervous system. Intrinsic reflexes can sense bowel contents, propel material forward, and coordinate secretion and absorption.

The central nervous system modulates gastrointestinal activity via several pathways. Parasympathetic connections are critical. The vagus nerve innervates the gastrointestinal tract from the esophagus to the colon’s splenic flexure. The descending colon, rectum, and internal anal sphincter are innervated by the parasympathetic pelvic nerve, which originates in the S2-4 intermediolateral cell column. Visceral sensory afferents also run in these nerves, allowing for the perception of gut distension, pain, and irritation. In general, parasympathetic stimulation facilitates peristalsis (particularly intermittent mass movements within the colon), intraluminal secretion, and relaxation of the internal anal sphincter. Sympathetic innervation of the colon is via the mesenteric nerve (T5-T12) and hypogastric nerve (L1-3). Sympathetic activation reduces colonic motility, reduces intraluminal secretion, and increases internal anal sphincter tone.

Somatic innervation is essential in anorectal function. The pudendal nerve, whose motor neurons lie in Onuf nucleus (S2-4), innervates the striated external anal sphincter and puborectalis muscles. These muscles act as a functional unit, tonically contracting to maintain continence while relaxing during defecation. When contracted, the puborectalis muscle “kinks” the angle between the rectum and anal canal, resisting the extrusion of contents. The pudendal nerve also innervates other pelvic floor muscles, including the levator ani group. These muscles help support the rectum and anus, maintain continence, and facilitate defecation. Sensory receptors in the anal canal and mechanoreceptors in the pelvic floor and anal sphincter also project via the pudendal nerve. Together with visceral sensation from the rectum, this sensory input is required for reflexive adjustment of muscle tone to maintain continence and conscious perception of anorectal contents. Finally, more distant muscle groups, such as those of the abdominal wall and diaphragm, help generate the pressure gradients to propel contents from the rectum (22).

The brain’s control of defecation is not fully understood. Animal studies suggest that the pelvic organ control center (also known as the Barrington nucleus and pontine micturition center) directs the functions of all pelvic organs, including the rectum (51). Fecal incontinence following brain lesions has been long described; however, the specific neuroanatomical mechanisms are not known. Still, the gut-brain axis, consisting of a series of integrated physiological functions (neural, endocrine) based on the bidirectional interaction of the intestine and CNS, is well established. The brain can influence commensal organisms (enteric microbiota) indirectly via changes in gastrointestinal motility, secretions, and intestinal permeability or directly via signaling molecules released into the gut lumen from enterochromaffin cells, neurons, and immune cells in the lamina propria (60). Enterochromaffin cells are important bidirectional transducers that regulate communication between the gut lumen and the nervous system. Vagal afferent innervation provides a direct pathway for enterochromaffin-cell signaling to neuronal circuits, which may have an essential role in pain and immune-response modulation, control of background emotions, and other homeostatic functions (60).

Neurogenic bowel dysfunction

Neurogenic bowel dysfunction can be defined as the loss of normal bowel function due to nerve injury, neurologic disease, or congenital nervous system defects (39). Symptoms include fecal incontinence, constipation, and gastroparesis, causing abdominal pain and bloating. Neurogenic bowel dysfunction is seen in neurologic disorders, including spinal cord injury, multiple sclerosis, stroke, and Parkinson disease. The symptoms vary between individuals and depend on factors including the underlying neurologic defect, immobility, medications, and chronicity. The symptoms of bowel dysfunction have a severe impact on quality of life, and they are often considered a more significant problem than loss of mobility by many patients (24).

Constipation. Constipation is often subject to individual perception and generally refers to infrequent bowel action and difficulty releasing stool. Other symptoms may be present, including bloating, fatigue, and abdominal pain (55). A more inclusive construct is the Rome III criteria, designed to identify chronic functional constipation in the absence of diarrhea, irritable bowel syndrome, and structural or biochemical causes. These criteria should have been fulfilled for the last 3 months, with symptom onset at least 6 months prior to the diagnosis of functional constipation (20).

Neurologic diseases can directly result in constipation via several mechanisms. First, impaired gut mobility or gastroparesis prolong colon transit time. This is known as “slow transit constipation.” There is excessive water absorption from the feces and a reduction in stool frequency. Second, there may be difficulty evacuating stool due to impaired relaxation of the sphincter function, sometimes compounded by weakness of the levator ani or abdominal muscles (15). The terms “outlet constipation” or “dyssynergic defecation” are sometimes used to describe this type of constipation. It is difficult to separate slow transit constipation from outlet constipation based on history alone. Additional factors may contribute to constipation, such as diet, medications, metabolic disorders, and gastrointestinal malignancy. Notable causes include opioids, anticholinergics (including some antidepressants and antipsychotics), dopaminergic agents, iron, calcium and aluminum antacids, calcium channel blockers, calcitonin gene-related peptide (CGRP) antagonists used for migraine headache prophylaxis, and diuretics. Metabolic disorders, including hypothyroidism and hypercalcemia, can cause constipation. An abrupt or otherwise unusual history of bowel dysfunction may be suspicious for colorectal neoplasm, prolapse, rectocele, or other nonneurologic structural causes (13; 15).

Fecal incontinence. Fecal incontinence, the involuntary loss of solid or liquid stool, is less common than urinary incontinence. This is because the rectum is filled less often than the bladder, and stool is usually solid. Fecal incontinence significantly affects quality of life, and many patients report that these symptoms affect aspects of physical, mental, and sexual health as well as socialization and travel. Even infrequent fecal incontinence may curtail important life activities and cause avoidance of social occasions. This may explain, in part, why patient-reported outcomes for bladder and bowel interventions are limited to select heterogeneous studies (52).

Fecal incontinence has many known associations: residence in a nursing home, urinary incontinence, older age, physical disability, poor general health, female gender (especially with prior childbirth), and previous anorectal surgery. Diarrhea of any cause is strongly associated with fecal incontinence. Chronic constipation or fecal impaction can result in fecal incontinence and paradoxical or overflow diarrhea as liquid stool passes around the obstruction. This may occur primarily in the elderly or severely disabled. Comorbid conditions include diabetes, multiple sclerosis, spinal cord injury, stroke, and dementia (49). Anal sphincter dysfunction of any cause, impaired anorectal sensation, or abnormal cognition can all cause incontinence.

Anal continence requires appropriate rectal musculosensory function and proper tone in the internal and external anal sphincters. The internal anal sphincter is comprised of smooth muscle and is controlled by the autonomic nervous system (excitatory sympathetic and inhibitory parasympathetic input).

The striated external anal sphincter is under voluntary control via the pudendal nerve, extending from the Onuf nucleus in the sacral vernal horn. Thus, in complete spinal cord injury, the voluntary control of the external anal sphincter is lost (54).

Anal rectal sensation is also essential for continence. Loss of sensation may predispose patients to incontinence and fecal impaction (especially in those with caudal equine lesions and flaccid rectum) (16).

Bowel dysfunction in selected neurologic diseases

The following discussion focuses on a few neurologic disorders whose association with bowel dysfunction has been most studied.

Spinal cord injury. Bowel dysfunction affects almost all patients with a chronic spinal cord injury, with up to 95% reporting constipation and 75% reporting fecal incontinence at least once per year (54). These symptoms have a significant impact on quality of life. As mentioned, gut motility involves a complex interplay of the enteric nervous system and autonomic nervous system. Given that parasympathetic innervation accelerates motility via the lower sacral roots (S2-S4) more distally in patients with spinal cord injury, the dysfunctional gut segment is usually the distal colon. Sympathetic innervation (T9-L2) slows intestinal transit. These neuroanatomical mechanisms help provide a framework for the different clinical patterns of bowel dysfunction observed in patients with spinal cord injury (15).

Supraconal injury above the conus medullaris causes loss of inhibitory input. This results in slowed whole gut transit and induces hypertonia and hyperreflexia of the hindgut distal to the splenic flexure. Rectal hypertonia results in reduced rectal compliance and predisposes to reflex defecation and fecal incontinence.

Cord injury within the conus or at cauda equina results in the loss of excitatory sacral parasympathetic supply. In this case, the efferent limb of the reflex arc to the hindgut is interrupted, resulting in hypotonia and hyporeflexia (15).

Bowel symptoms also change with time after spinal cord injury. Over a 10-year period, patients were more likely to experience constipation-related symptoms and less likely to experience fecal incontinence (27). Aging or altered treatment strategy could not explain this.

Injury to the spinal cord due to spinal vascular malformations also results in bowel incontinence. In arteriovenous malformations of the spinal cord, the early stages are characterized by slowly progressive, nonspecific symptoms such as gait disturbances, paresthesia, diffuse sensory symptoms, and radicular pain. In the late stages, bowel and bladder incontinence, erectile dysfunction, and urinary retention may arise, especially for malformations due to congestive myelopathy (04).

Pathophysiology is explained by an increase in venous pressure due to a congenital or acquired shunted blood flow reducing arteriovenous pressure gradient, which causes congestion in medullary veins and reduced intramedullary blood flow resulting in ischemic hypoxia. Both endovascular and surgical treatment of spinal vascular malformations improve long-term recovery from myelopathic symptoms and quality of life for most patients (04).

Multiple sclerosis. Neurogenic bowel dysfunction is common in multiple sclerosis and affects 39% to 73% of patients, depending on the population studied (55). Constipation affects over half of people with multiple sclerosis, and 50% of patients may experience fecal incontinence at some point (17; 55). These rates are considerably higher than in the general population.

Bowel dysfunction may occur even before diagnosis or early in the disease course. In a cohort of 56 patients diagnosed in the previous 2 to 5 years, 31% of patients reported constipation, 16% reported diarrhea, and 12% reported fecal incontinence (50). These symptoms correlated with lower quality-of-life ratings.

Bowel dysfunction in multiple sclerosis is likely multifactorial and includes direct neurologic injury intrinsic to multiple sclerosis and external factors, such as medication use, diet, immobility, and cognitive and behavioral difficulties (74; 55). Patients may have a combination of slowed colonic transit, overactive external anal sphincter, decreased voluntary sphincter control, or reduced anorectal sensation.

As with other neurologic diseases, neuroanatomic and pathophysiologic correlations of bowel dysfunction in multiple sclerosis are not well defined due to difficulty with study design and small sample size. A greater degree of disability, as measured by the Expanded Disability Status Scale (EDSS), has been shown to correlate with rectal compliance but not with constipation or incontinence score measures. This suggests that these observed alterations in rectal compliance may be secondary to spinal cord involvement, though it does not directly translate to the severity of constipation or incontinence (56).

Finally, the gut microbiota in multiple sclerosis is an area of increased interest. Studies have provided evidence of alterations at the levels of phyla and genera in multiple sclerosis patients, such as an increase in Methanobrevibacter and Akkermansia and a decrease in Butyricimonas (32; 30).

Constipation affects 30% to 60% of patients post-stroke, and chronic fecal incontinence affects 15% of patients (19; 29).

Fecal incontinence commonly follows stroke, especially acutely. In the Copenhagen Stroke Study, which assessed 935 acute stroke patients, fecal incontinence occurred in up to 40% of patients 2 weeks post-stroke and in up to 9% of patients 6 months later. Fecal incontinence immediately poststroke was more likely with older age, more extensive infarct, presence of diabetes, presence of another disabling disease, and clinical severity. Forty-five patients with initial fecal incontinence were deceased at discharge (48). Patients with fecal incontinence after stroke almost always have urinary incontinence as well. (48; 10). The findings in the Copenhagen Stroke Study are consistent with multiple studies showing that urinary incontinence is a strong marker of poor outcomes because there is considerable overlap between the two forms of incontinence (45).

Another study examined factors associated with de novo fecal incontinence after stroke in a large community-based registry (29). Researchers found that 15% of stroke survivors reported fecal incontinence 3 years after their stroke, and incontinence increased the risk of long-term care placement and death. They also found that fecal incontinence at 3 months was independently associated with the need for toileting assistance and the use of anticholinergic medications. Acute stroke factors such as infarct size and location, Glasgow Coma Score, and initial visual impairment or neglect were not independently associated with fecal incontinence 3 months later.

Constipation is also common poststroke and is estimated to affect almost 50% of patients (41). Constipation and fecal incontinence after stroke may be due, in part, to direct interruption of brain circuits critical in bowel control, although these have not yet been precisely delineated. Several potential mechanisms for microbiota imbalance after stroke have been proposed based on experimental studies, including suppression of systemic immunity, release of proinflammatory mediators from brain infarct lesions, activation of the sympathetic nervous system, stress induction, and impaired intestinal motility (43).

Stroke patients often have significant changes in microbial diversity and bacterial counts in fecal samples, independent of age, hypertension, and type 2 diabetes. However, the underlying mechanisms for microbiota changes are still poorly understood. Challenges include heterogeneous clinical pathology, diets, and lifestyle, which significantly influence the gut microbiome composition (72).

Ischemic stroke may also lead to significant damage to intestinal epithelium and activated intestinal immunity (43). Studies have shown significant intestinal epithelial necrosis and shedding after stroke, which worsened over time. This is thought to be due to the release of proinflammatory mediators.

Stroke patients are also at an increased risk of gastrointestinal bowel obstruction. Bowel obstruction in the setting of an acute stroke is associated with a higher incidence of intubation, venous thromboembolism, sepsis, acute kidney injury, gastrointestinal hemorrhage, transfusions, and hemorrhagic strokes. One study found that administration of thrombolytic therapy was associated with a 30% increased likelihood of gastrointestinal bowel obstruction. Secondary intracerebral hemorrhage was associated with a 49% increased likelihood of gastrointestinal bowel obstruction (61).

Other associated factors such as immobility, insufficient fluids, medications, or cognitive decline often play a significant role in constipation. However, when comparing patients with hemiplegic stroke to a group of patients with major orthopedic injuries who were similarly immobile at least 3 months post-event, de novo constipation was significantly greater in the stroke group (30%) versus the orthopedic group (7%) (08). Even after correction for age, sex, mobility, and medications, the difference persisted. This supports the notion that brain infarct is an independent risk factor for constipation.

Parkinson disease. Constipation is common in Parkinson disease and gastrointestinal symptoms may predate the clinical onset of the central neurologic disorder (58). In a retrospective chart review, patients with Parkinson disease were more likely to have constipation documented over 20 years prior to motor onset, versus age-matched controls (64).

One study showed that 37% of patients reported daily unsuccessful attempts at defecation (38). A sense of incomplete rectal emptying at evacuation was reported at least once per week by 23%, and 27% had bowel movements less than once every second day. The frequency of fecal incontinence is not increased in Parkinson disease.

The pathophysiology of bowel dysfunction in Parkinson disease is related to both dystonia of the striated pelvic floor muscles and prolonged colonic transit time (31).

Extrapyramidal dysfunction. Patients with Parkinson disease frequently experience emptying difficulties, straining, and stool outlet obstruction. This may be due to dystonia of several striated muscles important in coordinating defecation. Voluntary squeeze of the external anal sphincter may be reduced in the off state, paralleling motor fluctuations (06). The puborectalis muscle fails to relax in many patients during defecation (23). The external anal sphincter has also shown inappropriate activity in Parkinson disease. Dystonia of the striated muscles of the pelvic floor and external anal sphincter explains the defecation dysfunction; this etiological factor is supported by the observation that pelvic floor dysfunction is alleviated with L‐dopa (15).

Slow colonic transit. Two crucial factors likely contribute to prolonged colonic transit: (1) the reduced number of dopaminergic neurons in the colonic wall, and (2) the accumulation of Lewy bodies in the enteric ganglia (71; 65; 54).

Disordered intrinsic and extrinsic innervation of the colon results in slowed motility and transit, producing constipation. Mean colon transit time was twice as long in patients with Parkinson disease as in spousal controls (23).

Observational studies have found that men with less than one bowel movement a day were 2.7 times more likely to develop Parkinson disease in later life than men with one bowel movement per day and were 4.5 times more likely to develop Parkinson disease than men with greater than two bowel movements a day (01). This suggests that Parkinson disease may not just be a degenerative disorder of the CNS but also of the enteric nervous system.

Evidence links abnormal accumulations of α-synuclein aggregates in the periphery (gut), similar to those seen in the cortex, to dysfunction at every level of the gastrointestinal tract, including esophagus, stomach, small bowel, colon, and rectum. At autopsy, non-parkinsonian older men with low bowel movement frequency were more likely to have incidental Lewy bodies in the substantia nigra and locus coeruleus (02).

Alterations in the gut microbiota have also been reported in Parkinson disease. The abundance of Prevotellaceae in feces of Parkinson disease patients was shown to be reduced by 77.6% compared with unaffected individuals, and the relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty (30).

Constipation in Parkinson disease is thought to be due to several factors (35; 53). First, there is degeneration of the vagal dorsal motor nucleus, which provides parasympathetic innervation to most of the gut, including the colon proximal to splenic flexure. Second, there is degeneration within the enteric nervous system itself, with loss of dopaminergic neurons and the appearance of Lewy bodies (71; 65). Disordered intrinsic and extrinsic innervation of the colon results in slowed motility and transit, producing constipation.

In addition, medications used to treat Parkinson disease, including dopamine agonists and anticholinergics, may contribute to constipation. However, delayed colonic transit occurs in both naive patients with Parkinson disease and those on drug treatment (31).

Prominent autonomic dysfunction is a major feature of multiple system atrophy, another neurodegenerative condition associated with parkinsonism. Bowel dysfunction may occur early and be particularly severe. In many cases, multiple system atrophy can closely resemble idiopathic Parkinson disease. External anal sphincter electromyography has been proposed as a means of differentiating the two. Denervation-reinnervation changes in external anal sphincter electromyography are thought to be common in multiple system atrophy (due to degeneration of Onuf nucleus) and unexpected in early Parkinson disease. If present within 5 years of onset, such findings may suggest multiple system atrophy over Parkinson disease. However, the absence of early denervation is still consistent with multiple system atrophy (77). Conversely, sphincter denervation can be noted in longstanding Parkinson disease (42). Neurologists should, therefore, not rely on sphincter EMG for a diagnosis.

Alzheimer dementia. Neuropathological hallmarks of Alzheimer disease brain are neurofibrillary tangles of Tau protein aggregates and plaques of amyloid beta peptide. In transgenic murine models with a high accumulation of amyloid beta peptides, significant alterations were observed in muscarinic acetylcholine receptors, excretion parameters, histopathological structure, capability of mucin secretion, and endoplasmic reticulum stress response (36). This study suggests that Alzheimer disease–induced constipation may be due to dysregulation of muscarinic acetylcholine receptor signaling pathways and alteration in cellular stress responses. In addition, it has been shown that diet and specific nutrients can modify the composition of the gut microbiota, influencing the production and aggregation of amyloid proteins through mechanisms of molecular mimicry, resulting in alteration of the gut-brain axis (30). Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding and induce microglial priming (37).

Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately, neurodegeneration. A growing body of experimental and clinical data confirms a crucial role of gut dysbiosis and gut microbiota-host interactions in neurodegeneration. Vice versa, the convergence of gut-derived inflammatory response, aging, and poor diet in the elderly may contribute to the pathogenesis of Alzheimer disease (37).

Computational studies also associated cognitive decline in Alzheimer disease with metabolites such as succinic acid, mannitol, 4‐hydroxybenzoic acid (DOPAC), and trimethylamine N-oxide (TMAO, a small molecule produced by the metaorganismal metabolism of dietary choline from meat and fat) (70). Clinical studies performed on cerebrospinal fluid samples have demonstrated that TMAO may be relevant to the neurodegenerative changes in Alzheimer disease‐related tau pathology, thus confirming the role of the gut-brain axis in the pathophysiology of Alzheimer disease (70).

Peripheral nervous system disorders. Many disorders of the peripheral nervous system can lead to bowel dysfunction.

Autonomic neuropathies may alter gastrointestinal motility, producing constipation and sometimes diarrhea. Causes of autonomic neuropathy include diabetes, amyloidosis, HIV, porphyria, toxins, and acute inflammatory demyelinating polyradiculoneuropathy. The pathogenesis of bowel dysfunction in these disorders is not yet elucidated. Some diseases, such as amyloidosis and diabetes, may also alter gut function via nonneural means.

Diabetes mellitus is considered a risk factor for gastrointestinal symptoms, including constipation, gastroparesis, diarrhea, and fecal incontinence. Most agree that these symptoms are more common in people with diabetes compared to the general population, but the reported prevalence varies substantially by study (21).

Autonomic neuropathy has been proposed to explain bowel dysfunction in diabetes. However, many studies have noted a weak correlation between diabetic bowel dysfunction and autonomic and peripheral neuropathy. Other mechanisms have been postulated, such as metabolic derangements, intestinal bacterial overgrowth, and hyperglycemia. For instance, acute hyperglycemia alone may increase proximal gastric compliance, slow gastric emptying, and increase perceptions of fullness, nausea, and bloating (62; 21).

Bowel dysfunction arises in other disorders of the peripheral nervous system. Focal injury to pelvic or pudendal nerves from surgery, childbirth, or tumor infiltration may cause symptoms, especially when occurring bilaterally. Sacral polyradiculopathy of any cause can cause constipation or incontinence. Examples are cauda equina syndrome from a herniated lumbar disk, which typically requires immediate surgery, and polyradiculitis from cytomegalovirus in AIDS. Myotonic dystrophy is associated with diarrhea, constipation, and fecal incontinence. Other disorders, such as myasthenia gravis and amyotrophic lateral sclerosis, are notable for sparing the neurologic mechanisms involved in bowel function and continence; however, dysphasia, gastroparesis, and chronic intestinal pseudo-obstruction may occur.

Management of neurologic bowel dysfunction

Assessment

A complete bowel history should be obtained from the patient and any caregivers. Bowel habits before injury or disease onset should be explored, especially in patients with Parkinson disease, where bowel dysfunction may precede neurologic symptoms (54).

Current symptoms should be assessed, including frequency of bowel movements, stool consistency, episodes of fecal incontinence or urgency, maneuvers required for bowel management (eg, digital anorectal stimulation), and laxative or antidiarrheal usage (25). Score systems, such as the Cleveland constipation score (03) and St Mark’s incontinence score (68), may help quantify symptoms. Past medical history, including any coexisting gastrointestinal disorders such as irritable bowel syndrome, histories of pelvic organ prolapse, and surgical procedures involving the gastrointestinal tract, should be assessed. All of these factors are relevant and may affect treatment outcomes (25). A drug history can also reveal constipating agents, such as antimuscarinics or drugs used for spasticity, eg, baclofen (55). Finally, a detailed history regarding limitations in quality of life is critically important as symptoms of neurogenic bowel dysfunction have a substantial negative impact on quality of life, social integration, and personal independence (24).

A 2-week bowel diary, with a log of patient-recorded liquid intake, stool frequency, consistency, urge sensations, and leakage can be helpful to characterize daily habits, accurately quantify symptoms, and evaluate a bowel management routine (66).

A digital rectal examination allows a crude assessment of anal sensation, tone, and squeeze. Specialized anorectal physiology tests are indicated for patients with severe or persistent symptoms. Specific tests can measure somatovisceral anorectal sensation, anal sphincter pressures, colonic transit time, and the integrity of the anal sphincters (55).

Treatment

The goal of neurogenic bowel management is to accomplish complete evacuation of the rectum regularly, thus, reducing the risk of fecal impaction, urgency, and incontinence (76). Still, there is sparse research identifying optimal treatment strategies for patients with neurogenic bowel dysfunction. A 2014 Cochrane review found little published research on neurogenic bowel dysfunction management, identifying only 20 randomized trials with limited evidence and stating that, in general, it is not possible to make recommendations based on this level of evidence (13).

Treatment of neurogenic bowel dysfunction should be tailored to the individual’s situation and symptom profile. The goal is to establish a bowel regimen and develop a routine that works for the patient. Some patients may opt for a more interventional approach, whereas others may choose to try conservative measures first. Management of neurogenic bowel is often described in a stepwise approach from more conservative measures to more invasive, but, in reality, patients often require a combination of interventions.

Constipation. Neurologists should be familiar with basic management options for constipation. In severe cases, management may be best guided by specialists. The approach to constipation has been summarized in previously published reviews (05). There is a lack of evidence guiding the management of constipation, specifically in patients with nervous system disease (14). Presently, the management of bowel dysfunction in patients with multiple sclerosis remains inadequate, but some evidence is available from studies in patients with spinal cord injury, who may share similarities (55).

Fecal incontinence. Management of fecal incontinence can be complex, especially because constipation is often present as well, and treatment for one bowel symptom can worsen the other. There are no reliable evidence-based guidelines for the management of fecal incontinence, especially in patients with neurologic disease (14).

The following are various treatment options aimed at maximizing bowel emptying to prevent fecal impaction and incontinence, minimizing time spent toileting, and improving quality of life.

Lifestyle and behavioral modifications
	Dietary modifications
		• Stool consistency can be manipulated by modulating fiber and water intake. The goal is to balance having enough fiber to add bulk and soften stools but also to avoid bloating. Fiber supplements, such as psyllium, may help increase stool frequency but may be intolerable for some due to gas and bloating. In patients with slow-transit constipation, fiber may not relieve symptoms. Increased bulk may lead to fecal impaction in patients prone to intestinal obstruction related to severe colonic delay or immobility without adequate water intake.
		• Caffeine, alcohol, and food containing the sweetener sorbitol may loosen stool and should be used with caution in those with fecal incontinence.
		• In a randomized controlled trial, biofeedback therapy showed benefit in more than 70% of patients with functional outlet obstruction, but patients with neurologic disease were excluded (59). In a case-control study, patients with incomplete spinal cord injury had a similar significant response to biofeedback compared to functional anorectal disorder-matched controls (46). Biofeedback and pelvic floor retraining are free of morbidity and are shown to improve rectoanal coordination during defecation.
		• Other nonpharmacologic measures include abdominal massage and Valsalva, perhaps by promoting bowel movements. In a small study, patients with multiple sclerosis and constipation reported alleviation in constipation symptoms after abdominal massage for 4 weeks (47).
Pharmacological interventions
	Oral medications
		• Oral osmotic laxatives, such as milk of magnesia, lactulose, and polyethylene glycol, are commonly used. They increase stool softness and frequency by preferentially retaining water in the intestinal lumen. Polyethylene glycol appears to be safe and effective, even with daily treatment for 6 months (18). In an 8-week randomized controlled trial, polyethylene glycol improved stool frequency and consistency in Parkinson disease but did not improve straining. The benefit was maintained in the second month, and patients tolerated it well (78). However, overuse can cause dehydration and electrolyte abnormalities in vulnerable patients. Based on data from the general population, osmotic laxatives are generally first-line therapy, and many start with an every-other-day or 3 times a week regimen and then reassess (33). The stool softener docusate is also widely used; however, its efficacy has not been shown to be greater than placebo in multiple studies (45). Milk of magnesia is another commonly used osmotic laxative, but there is a lack of evidence on its efficacy in chronic constipation.
		• Stimulant laxatives, such as bisacodyl or sennosides, activate contractions of the intestinal wall, thereby promoting transit. There are limited data on the use of these medications in neurogenic bowel patients. Still, systematic reviews and meta-analyses have shown that these agents are helpful in those with chronic constipation or idiopathic constipation (44; 33).
		• Lubiprostone is a prostaglandin derivative that increases intestinal secretion by activating chloride channels and was approved in the United States in 2008 for irritable bowel syndrome and idiopathic chronic constipation. It has not been tested in neurologic disease, specifically.
		• Linaclotide is a minimally absorbed 14-amino acid peptide. It acts as a selective agonist of the guanylate cyclase-C receptor on the luminal surface of intestinal enterocytes. It plays a critical role in the regulation and secretion of intestinal fluid (67). Linaclotide was approved in 2012 for the treatment of irritable bowel syndrome and chronic constipation after two phase 3 trials (40; 12).
		• Prucalopride (Prudac, Motegrity), a selective, high-affinity 5-HT4 agonist, was approved by the FDA for chronic idiopathic constipation. It was efficacious over placebo in severe chronic constipation in three large, randomized controlled trials. An integrated analysis of six main clinical trials showed significantly more patients treated with prucalopride (27.8%) versus placebo (13.2%) who achieved an average of three or more spontaneous, complete bowel movements each week over the 12-week treatment period (11; 57); neurologic disease was excluded in the trial. Two previous nonselective 5-HT4 agonists, cisapride and tegaserod, were withdrawn from the U.S. market in 2007 due to adverse cardiac events.
		• Pyridostigmine, a cholinesterase inhibitor, has also been shown to accelerate colonic transit time, but it is not currently approved for this purpose. Historical studies have shown that pyridostigmine reduces constipation in patients with Parkinson disease, autoimmune neuropathy (63), and diabetes with chronic constipation (07).
	Suppositories
		• Rectal medications, including suppositories and enemas, are also key components of neurogenic bowel management. These medications help control the timing and predictability of a bowel movement and, thus, manage both constipation and fecal incontinence. Stimulant suppositories contain medication, such as bisacodyl, and stimulate bowel reflex. These suppositories are usually inserted 15 to 30 minutes before planned bowel emptying. In general, rectal bisacodyl will produce a bowel movement much faster (within an hour) compared to oral bisacodyl (6 to 12 hours). Lubricating suppositories that contain nonmedicated substances, such as glycerin, may also be helpful to hold water in the bowel, soften stool, and make it easier to pass. There is relatively little research on the use and effectiveness of suppositories and enemas in neurogenic bowel patients. Still, a small number of prospective controlled trials support their use and have noted that these agents decrease total bowel care time (33).
Transanal irrigation methods
		• Transanal irrigation allows for the evacuation of stool by introducing water into the colon and rectum through the anus and induces reflex colorectal voiding. A single-use cone or catheter is used to insert the water, and after the device is removed, the proximal colon and rectal contents are emptied. Regular usage helps to reestablish control over bowel function and allows the patient to better time their evacuation. A study that assessed the long-term use of transanal irrigation found that a majority of patients continued treatment at long-term follow-up, and regular use was associated with lower rates of urinary tract infections, episodes of fecal incontinence, and stoma surgery as well as improved quality-adjusted life years compared to conservative management (26).
Neuromodulation / electrical stimulation
		• Sacral nerve stimulation can be achieved via an implantable stimulator or peripherally via the tibial nerve. Nerve stimulation can reestablish neurogenic control and alleviate bowel dysfunction symptoms (75). Interventions may include sacral anterior root stimulator, sacral nerve stimulation, nerve rerouting, tibial nerve stimulation, dorsal genital nerve stimulation, and magnetic stimulation. Intradural sacral anterior root stimulation, which has the greatest efficacy for neurogenic bladder in select patients with spinal cord injury, may help with bowel symptoms in some patients (69). Sacral nerve stimulation with an implantable device was safe and effective in a prospective study of 120 subjects with chronic fecal incontinence (73), leading to the 2011 FDA approval of the InterStim® device (Medtronic; Minneapolis, MN) for chronic fecal incontinence in patients who failed or are not candidates for more conservative therapies. A small trial in spinal cord injury showed statistically significant improvement in total bowel care time using electrical stimulation of abdominal muscles compared with no electrical stimulation (MD 29.3 minutes, 95% CI 7.35 to 51.25) (13).
Surgical intervention
		• Surgical formation of a stoma is generally considered a last option given that it is more invasive and irreversible. Even in a tertiary center with a strong presence of surgical referrals, only 5% of cases in this highly selected cohort justified surgical treatment (05). However, such surgical interventions are associated with improved quality of life and reduced bowel management time (09). Still, there is a significant risk of complications, such as rectal mucus discharge, postsurgical adhesions, and diversion colitis (25).
		• Other surgical procedures include anal sphincteroplasty or artificial anal sphincter implantation. The evidence supporting these techniques is limited.

Summary

Neurogenic bowel dysfunction is highly prevalent in patients with neurologic conditions. Patients may experience constipation, fecal incontinence, or some combination of both. These symptoms can have a tremendous impact on quality of life. Assessment involves obtaining a comprehensive history of bowel habits and symptoms and may include more invasive physiological investigations. Treatment should be tailored to each patient and may involve a multidisciplinary approach.