Chronic Intestinal Dysmotility Research Articles

Current insights on chronic intestinal dysmotility: pseudo-obstruction and enteric dysmotility.

Chronic intestinal dysmotility is a rare and debilitating digestive disorder characterized by symptoms of mechanical obstruction without an organic lesion. It has diverse causes and involves various pathological mechanisms. Small bowel manometry is the preferred diagnostic method, particularly for patients with severe and progressive symptoms. The condition can be categorized as intestinal pseudo-obstruction and enteric dysmotility, both entities share abnormal small bowel motility, but with important differences in prognosis and management.

Systemic Sclerosis Sine Scleroderma as a Rare Etiology of Chronic Intestinal Pseudo-Obstruction

Chronic intestinal pseudo-obstruction (CIPO) is a disruption of the enteric nervous system characterized by chronic intestinal dysmotility and dilation. It has many underlying causes. We present a 52-year-old woman with 53 kg unintentional weight loss, abdominal pain, and vomiting. She had dilated small bowel loops with air fluid levels and no transition point on CT. Esophagogastroduodenoscopy (EGD) revealed aperistalsis and undigested duodenal food. The secondary cause was found to be Undifferentiated Connective Tissue Disorder (UCTD), a rheumatologic disorder that does not meet criteria for any single disease. This is the first reported case of UCTD being presented by CIPO.

Nutritional considerations in severe primary chronic small intestinal dysmotility.

To provide an update on the recent evidence underpinning the approach to nutritional care in patients with severe primary chronic small bowel dysmotility. Patients with severe chronic small intestinal dysmotility suffer nutritional and nonnutritional morbidity, both as a result of their underlying polysymptomatic, poorly understood condition and the interventions required. A proportion require artificial nutrition support; however, this is associated with impaired quality of life and associated complications. The approach to nutritional support must therefore engage a multidisciplinary team (MDT) to ensure that decisions to escalate beyond oral nutrition reflect individualised risk-benefit discussions while adopting a holistic approach to symptom management. Since nutritional outcomes are worse in those with the chronic intestinal pseudo-obstruction (CIPO) phenotype, differentiation into CIPO and non-CIPO subgroups, using a pragmatic diagnostic approach rather than invasive/poorly tolerated investigations, can be an important step in achieving nutritional care tailored to the individual. Malnutrition in patients with severe chronic small intestinal dysmotility is multifactorial. Early engagement of a broad team that includes dietitians, psychologists and pain management experts is crucial to achieving the most beneficial and least harmful patient-centred nutritional care outcomes.

The management of adult patients with severe chronic small intestinal dysmotility

Adult patients with severe chronic small intestinal dysmotility are not uncommon and can be difficult to manage. This guideline gives an outline of how to make the diagnosis. It discusses...

Su1989 - Severe Gastrointestinal Dysmotility Related Intestinal Failure: Chronic Intestinal Pseudo-Obstruction, Enteric Dysmotility or a ‘Pragmatic’ Approach? Experience from a UK National Referral Centre

Introduction Gastrointestinal dysmotility (GID) is a recognised cause of Type 3 Intestinal Failure (IF). Diagnosis is challenging, with uncertain merits of subclassifying into chronic intestinal pseudo-obstruction (CIPO) and Enteric Dysmotility (ED) 1 . A ‘pragmatic’ algorithm for GID has been proposed to address these difficulties 2 . Retrospectively, we evaluated the performance of ED/CIPO diagnostic criteria and pragmatic GID criteria in predicting outcomes of patients with ‘dysmotility’ requiring home parenteral nutrition (HPN). Method Patients with primary dysmotility referred for HPN to a national IF Unit (1999–2015) were identified. 2 investigators reviewed casenotes for clinical histories, motility tests, imaging, full-thickness biopsies (FTB), breath tests, HPN and survival outcomes. Cases were excluded if they did not meet pragmatic GID criteria (morbidity + either >1 region abnormal motility test or positive FTB + small bowel (SB) involvement). Patients satisfying GID criteria were then sub-categorised into; ED (objective SB dysmotility), CIPO (ED criteria + non-mechanical SB dilatation) and ‘non-CIPO/ED’ if neither criteria were met. Outcomes were compared between subgroups. Results 44 patients met GID criteria (median age 40, 30 females, 18/44 with abnormal FTBs (myopathy n=12, neuropathy n=6) and median follow-up 5 years)), whereas 7 patients not meeting pragmatic criteria were excluded. HPN improved BMI (median pre 18.3 vs. post 21.2 kg/m 2 , p=0.01). HPN outcomes: survival at 1, 5 and 10 years was 95%, 77% and 47%, median catheter-related blood stream infection rate (CRBSI) 0.5/1000 days, and 18% achieved HPN independence. 25/44 (57%) met criteria for CIPO, 12/44 (27%) ED and 7/44 (16%) were ‘non-CIPO/ED’ patients that met GID criteria. CIPO was associated with bacterial overgrowth (13/25 vs. 3/19, p=0.03), and HPN dependency (1/25 weaned off HPN vs. 7/19, p=0.01) when compared to the ED and ‘non-CIPO/ED’ groups. Other factors including the yield of FTBs, opiate-dependence and HPN complications (CRBSI, IF associated liver disease and catheter related venous thromboses) did not significantly differ between the three groups. Conclusion Our data emphasise important prognostic implications of CIPO diagnosis in the IF/GID population as a predictor of HPN dependency. Combining pragmatic evidence-based criteria with imaging to exclude CIPO is likely to give the maximum diagnostic and prognostic yield across the spectrum of GID. References . Wingate, et al. Journal of Gastroenterology and Hepatology200217:S1–S14 . Paine, et al. Alimentary pharmacology & therapeutics201338(10):1209–1229. Disclosure of Interest None Declared

Heterotrimeric G Stimulatory Protein α Subunit Is Required for Intestinal Smooth Muscle Contraction in Mice

The α subunit of the heterotrimeric Gstimulatory protein (Gsa), encoded by the guanine nucleotide binding protein, α-stimulating gene (Gnas, in mice), is expressed ubiquitously and mediates receptor-stimulated production of cyclic adenosine monophosphate and activation of the protein kinase A signaling pathway. We investigated the roles of Gsa invivo in smooth muscle cells of mice. We performed studies of mice with Cre recombinase-mediated disruption of Gnas in smooth muscle cells (GsaSMKO and SM22-CreERT2, induced in adult mice by tamoxifen). Intestinal tissues were collected for histologic, biochemical, molecular, cell biology, and physiology analyses. Intestinal function was assessed in mice using the whole-gut transit time test. We compared gene expression patterns of intestinal smooth muscle from mice with vs without disruption of Gnas. Biopsy specimens from ileum of patients with chronic intestinal pseudo-obstruction and age-matched control biopsies were analyzed by immunohistochemistry. Disruption of Gnas in smooth muscle of mice reduced intestinal motility and led to death within 4 weeks. Tamoxifen-induced disruption of Gnas in adult mice impaired contraction of intestinal smooth muscle and peristalsis. More than 80% of these died within 3 months of tamoxifen exposure, with features of intestinal pseudo-obstruction characterized by chronic intestinal dilation and dysmotility. Gsa deficiency reduced intestinal levels of cyclic adenosine monophosphate and transcriptional activity of the cyclic adenosine monophosphate response element binding protein 1 (CREB1); this resulted in decreased expression of theforkhead box F1 gene (Foxf1) and protein, and contractile proteins, such as myosin heavy chain 11; actin, α2, smoothmuscle, aorta; calponin 1; and myosin light chain kinase. We found decreased levels of Gsa, FOXF1, CREB1, and phosphorylated CREB1 proteins in intestinal muscle layers ofpatients with chronic intestinal pseudo-obstruction, compared with tissues from controls. Gsa is required for intestinal smooth muscle contraction in mice, and its levels are reduced in ileum biopsies of patients with chronicintestinal pseudo-obstruction. Mice with disruption of Gnasmight be used to study human chronic intestinal pseudo-obstruction.

Primary Gastrointestinal Amyloidosis With Multiple Myeloma

Primary systemic amyloidosis (AL) is characterized by the deposition of fibrils composed of monoclonal light chains in the extracellular matrix of various organs including the gastrointestinal (GI) tract. A 53 year old African American female with history of hypertension presented with complaints of progressively worsening dysphagia and weight loss for the past 5 months. Recently, her dysphagia progressed from solids to liquids, leading to a 50 pound weight loss, associated with abdominal fullness, early satiety, and postprandial vomiting. Review of systems revealed dyspnea on minimal exertion and easy fatigability. She had no prior personal or family history of malignancy, renal failure or inflammatory conditions. She was found to have new anemia with a hemoglobin of 7.8 gm/dl, concerning for a GI malignancy. Esophagogastroduodenoscopy did not reveal any evidence of bleeding or esophageal or gastric masses, but showed generalized mucosal wall thickening in the stomach. The gastric biopsy showed vascular and stromal amyloid deposition, confirmed with Congo red stain (Figure 1) showing bright apple green birefringence under polarized light. Colonoscopy confirmed similar evidence of amyloid deposition. A bone marrow biopsy was obtained which showed evidence of advanced multiple myeloma (MM) (Figure 2), confirmed by electrophoresis showing elevated Kappa free light chains. An echocardiogram showed infiltrative cardiomyopathy with reduced ejection fraction. She was started on borteozomib and dexamethasone but ultimately developed intestinal obstruction requiring TPN, and palliative treatment was offered.Figure 1Figure 2AL due to any cause is a common disorder; however, primary GI amyloidosis (GAL) is found in approximately 8% of biopsy proven, and only 1% of clinically symptomatic patients with AL. Hepatic amyloidosis is more common than intestinal amyloidosis. 50% of GAL are seen in patients with chronic degenerative arthropathies (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis), chronic renal failure, and multiple myeloma. GAL can present with symptoms of either GI bleeding, chronic intestinal dysmotility causing intestinal obstruction, malabsorption and/or protein-losing enteropathy. Diagnosis is obtained by biopsy of the GI mucosa deep enough to include lamina propria since apple green birefringence is best identified in the wall of blood vessels. Treatment is largely dependent on reducing the production of amyloid precursor and controlling the primary cause. A few case reports have shown improvement with experimental humanized anti-IL6 receptor antibody. GAL causes significant morbidity, but death is usually due to underlying cardiomyopathy, renal failure or advanced malignancy.

Chronic Intestinal Dysmotility (CID) Secondary to Consumption of Sushi: A Case Series and Literature Review

Chronic intestinal dysmotility (CID) applies to abnormal contractions caused by uncoordinated muscular activity in the intestines. Various associations and hypotheses have been postulated, but the etiology of CID is not clear. We present a case series of four young patients aged 16 - 30 years who presented with non specific gastrointestinal symptoms of abdominal pains, nausea, vomiting and constipation. There was no radiological evidence of intestinal dilatation. Laboratory and endoscopic evaluation failed to reveal any clear etiology. Dietary history revealed frequent consumption of sushi by all four patients. Chronic mercury toxicity via frequent sushi consumption was postulated to be the possible etiology of CID in these patients. Patients were advised to stop further sushi consumption. They were treated symptomatically with acid suppressing medications, anti-emetics, analgesics, antispasmodics and laxatives as needed. A remarkable improvement in symptoms was seen within 2 - 3 months. The present article systematically reviews the underlying etiology and presentation of CID secondary to sushi consumption with a focus on its public health importance. J Med Cases. 2014;5(2):98-104 doi: http://dx.doi.org/10.14740/jmc1688e

Voltage‐gated potassium channel (Kv1) autoantibodies in patients with chagasic gut dysmotility and distribution of Kv1 channels in human enteric neuromusculature (autoantibodies in GI dysmotility)

Autoantibodies directed against specific neuronal antigens are found in a significant number of patients with gastrointestinal neuromuscular diseases (GINMDs) secondary to neoplasia. This study examined the presence of antineuronal antibodies in idiopathic GINMD and GINMD secondary to South American Trypanosomiasis. The GI distribution of voltage-gated potassium channels (VGKCs) was also investigated. Seventy-three patients were included in the study with diagnoses of primary achalasia, enteric dysmotility, chronic intestinal pseudo-obstruction, esophageal or colonic dysmotility secondary to Chagas' disease. Sera were screened for specific antibodies to glutamic acid decarboxylase, voltage-gated calcium channels (VGCCs; P/Q subtype), nicotinic acetylcholine receptors (nAChRs; α3 subtype), and voltage-gated potassium channels (VGKCs, K(V) 1 subtype) using validated immunoprecipitation assays. The distribution of six VGKC subunits (K(V) 1.1-1.6), including those known to be antigenic targets of anti-VGKC antibodies was immunohistochemically investigated in all main human GI tract regions. Three patients (14%) with chagasic GI dysmotility were found to have positive anti-VGKC antibody titers. No antibodies were detected in patients with idiopathic GINMD. The VGKCs were found in enteric neurons at every level of the gut in unique yet overlapping distributions. The VGKC expression in GI smooth muscle was found to be limited to the esophagus. A small proportion of patients with GI dysfunction secondary to Chagas' disease have antibodies against VGKCs. The presence of these channels in the human enteric nervous system may have pathological relevance to the growing number of GINMDs with which anti-VGKC antibodies have been associated.

Full-thickness biopsy findings in chronic intestinal pseudo-obstruction and enteric dysmotility

Full-thickness biopsy findings in chronic intestinal pseudo-obstruction and enteric dysmotility

Health Care Use in Patients With Chronic Intestinal Dysmotility Before and After Introducing a Specialized Day-Care Unit

Patients with chronic intestinal dysmotility (CID) have a lifelong disease, and no curative treatment is available. Interventions are needed to improve the care and support of the patients. The aim of this study was to measure health-care consumption in adult patients with CID before and after the introduction of a specialized day-care unit. Retrospective analysis was made of medical and nursing records from 3 different health-care delivery systems: period I, traditional care (1987-1996); period II, outpatient clinic (1997-1999); and period III, specialized day-care unit (2000-2002). There were 54 patients (44 women) with a median age of 47 years (range, 22-80 years). The need for admissions to hospital care decreased from 80% to 35% of the patients after the introduction of the specialized day-care unit (P < .002). Also, the mean number of days in hospital care per patient and year was reduced from 39.4 to 3.3 days. The number of outpatient visits remained unaltered. The average cost per patient-year decreased from $32,698 during traditional health-care services to $9,681 after introducing the specialized day-care unit (P < .002). Irrespective of the form of care delivery, the majority of patients (67%-77%) needed daily treatment with analgesics, and 81%-84% needed nutritional support on a regular basis. Individually tailored care at a specialized day-care unit leads to substantially decreased needs for hospital stays and lower costs in patients with CID.

Findings in patients with chronic intestinal dysmotility investigated by capsule endoscopy

BackgroundCapsule endoscopy (CE) is a unique tool to visualize the mucosa of the small intestine. Chronic intestinal dysmotility (CID) is a group of rare disorders of gastrointestinal motility that often are complicated by bacterial overgrowth. The aim of this study was to determine the prevalence of small bowel mucosal abnormalities in patients with CID. We also studied the usefulness of CE in the diagnosis of intestinal dysmotility.MethodsWe conducted a prospective study using CE in 18 patients; six with myopathic, 11 with neuropathic and one with indeterminate CID. A control group was used for comparison of small bowel transit.ResultsMucosal breaks (erosions and ulcerations) were found in 16/18 (89%) patients. The capsule reached the caecum in 11/18 (61%) patients with a median transit time of 346 minutes. In the control group the capsule reached the caecum in 29/36 (81%) cases with a median transit time of 241 minutes. The difference in transit time was not significant (p = 0.061) in this material. The capsule was retained in the stomach in 3/18 patients. None of the patients developed symptoms or signs of mechanical obstruction.ConclusionA high frequency of mucosal breaks and signs of motility disturbances were seen in CID patients. CE is feasible for the examination of small bowel mucosa in patients with CID. The relevance of observed mucosal abnormalities in CID remains uncertain.

Small intestinal motility

The aim of this article is to review recently published studies presenting novel and relevant information on small intestinal motility. The reviewed studies covered a variety of topics with several themes emerging. The presentation and causes of chronic intestinal dysmotility continue to expand. Evidence continues to accrue that at least a subset of patients with severe colonic inertia may have a more diffuse motility disorder highlighting the need for careful assessment prior to embarking on surgery for refractory constipation. While interest in bacterial overgrowth in irritable bowel syndrome continues, the utility and specificity of lactulose hydrogen breath testing is yet again being called into question. Methane appears to slow intestinal transit and constipation appears more common among methane-positive patients. The association is presently only correlative and further study is needed. Small intestinal motility remains an understudied area. Recent publications provide additional new information related to physiology and pathophysiology of small bowel motility. These findings should be of interest to clinician and investigator alike.

Clinical, Radiologic, and Manometric Characteristics of Chronic Intestinal Dysmotility: The Stanford Experience

The clinical spectrum of chronic intestinal dysmotility (CID) is not well known. We determined the spectrum of motor abnormalities, underlying pathology, clinical course, and response to treatment of adults with CID at a tertiary referral center. This was a descriptive retrospective analysis of a CID cohort conducted at a tertiary referral gastrointestinal (GI) motility center. A total of 113 referred patients underwent gastroduodenal manometry, other motility studies as appropriate, and radiologic and/or endoscopic assessment to exclude mechanical intestinal obstruction. Common symptoms included abdominal distention, abdominal pain, nausea, and constipation. The course was chronic with intermittent symptoms. Gastroduodenal manometry was abnormal in all patients; a pattern suggestive of a neuropathic process was the most common. Other GI motility studies showed delayed gastric, gallbladder, and colonic transit, nonspecific esophageal dysmotility, sphincter of Oddi hypertonicity, and poor rectal balloon sensation/expulsion. Treatment involved nutritional support, prokinetics, analgesics, antinausea agents, and laxatives, with variable response and high morbidity, multiple emergency admissions, need for nutritional support, and poor response to surgery. Nearly 40% of the patients underwent abdominal surgery. Patients with CID have a chronic course and high morbidity. Because any segment of the GI tract may be involved in CID, functional assessment of the entire GI tract is recommended. CID presents several unmet clinical needs even in tertiary centers with expertise.

Gastrointestinal dysfunction in neurologic disease.

Gastrointestinal motor dysfunctions result when extrinsic autonomic nerves are diseased and are unable to modulate the motor functions of the digestive tract, which depend on the enteric nervous system and the automaticity of the smooth muscles. Gut motor dysfunction may result from disorders at all anatomic levels of the extrinsic neural control and degenerations of gut smooth muscle. It illustrates the important modulation of gut motor function by the nervous system. Although much emphasis has been placed on dysphagia and constipation in neurologic disorders, more recent studies have highlighted incontinence, vomiting, and abdominal distention in the symptomatology of such patients. Strategies that evaluate the motor functions of the digestive tract and the extrinsic neural control are available; they aid in selection of rational therapies for these patients, which include physical therapy and biofeedback training (for dysphagia or incontinence), prokinetic agents (for neuropathic forms of gastroparesis, chronic intestinal dysmotility, or slow transit colonic disorders), and nutritional support using the enteral or parenteral route. Electrical or magnetic stimulation of lumbosacral roots provides a novel method to alleviate constipation in paraplegics.

Exclusion of linkage between RET and neuronal intestinal dysplasia type B

Neuronal Intestinal Dysplasia type B (NID B) is a complex alteration of the enteric nervous system belonging to the group of intestinal dysganglionoses which may involve rectum, colon, and small intestine. Second only to Hirschsprung disease (HSCR), NID B is one of the most frequent causes of chronic constipation and pseudo-obstructive intestinal dysmotility. Since NID B is often associated with HSCR and point mutations in the RET proto-oncogene have been identified in HSCR patients, we analyzed two NID B pedigrees to investigate if RET mutations might cause also the NID B phenotype. Linkage analysis demonstrated that the NID B locus is not linked to RET in the pedigrees analyzed. Further genetic analyses will possibly improve the understanding of the cause and facilitate diagnostic procedures in NID B.

Continued symptomatic improvement during one-year treatment of neuropathic chronic intestinal dysmotility with cisapride: [formula omitted], R.K. Balm, A.R. Zinsmeister. Mayo Clinic, Rochester, MN

Continued symptomatic improvement during one-year treatment of neuropathic chronic intestinal dysmotility with cisapride: [formula omitted], R.K. Balm, A.R. Zinsmeister. Mayo Clinic, Rochester, MN

Appraisal of medium- and long-term treatment of gastroparesis and chronic intestinal dysmotility.

To evaluate the medium- and long-term treatment of patients with gastroparesis and chronic intestinal dysmotility (CID). This assessment is timely, inasmuch as several treatment trials have been published within the past 2 yr, necessitating an appraisal of the outcome of treatments. Literature review based on Medline Search using key words: gastroparesis, chronic intestinal pseudo-obstruction, enteral nutrition, feeding jejunostomy, prokinetics, gastric atony, gastrectomy, Roux-Y gastrectomy. Restoration of nutrition can be achieved orally, enterally, or parenterally, depending on the severity of the clinical syndrome. Combinations of antiemetics and prokinetics are useful for symptomatic and objective benefits. Intravenous erythromycin is chiefly beneficial in the acute presentation. The weight of current evidence favors cisapride as the prokinetic of choice in the medium and long term. Surgical approaches are restricted to providing a means for decompression, access to the small bowel for nutrition, and resection for localized disease or completion of gastrectomies for atony after gastric surgery. More rational choices of access for nutritional supplementation, selection of prokinetic agents, and indications for surgical treatment can be made on the basis of clinical experience and published studies; however, several unanswered questions remain and call for further outcome-based studies in patients with gastroparesis and CID.