Faecal incontinence is associated with an impaired rectosigmoid brake and improved by sacral neuromodulation

Background and aims: The rectosigmoid brake, characterized by retrograde cyclic motor patterns on high-resolution colonic manometry has been postulated as a contributor to the maintenance of bowel continence. Sacral neuromodulation (SNM) is an effective therapy for faecal incontinence, but its mechanism of action is unclear. This study aims to investigate the colonic motility patterns in the distal colon of patients with faecal incontinence, and how these are modulated by SNM. Methods: A high-resolution fibre-optic colonic manometry catheter, containing 36 sensors spaced at 1-cm intervals, was positioned in patients with faecal incontinence undergoing Stage 1 SNM. One hour of pre-meal and post-meal recordings were obtained followed by pre- and post-meal recordings with suprasensory SNM. A 700-kcal meal was given. Data were analysed to identify propagating contractions. Results: Fifteen patients with faecal incontinence were analysed. Patients had an abnormal meal response (fewer retrograde propagating contractions compared to controls; p=0.027) and failed to show a postmeal increase in propagating contractions (mean 17 +/- 6/h pre-meal vs 22 +/- 9/h post-meal, p = 0.438). Compared to baseline, SNM significantly increased the number of retrograde propagating contractions in the distal colon (8 +/- 3/h pre-meal vs 14 +/- 3/h pre-meal with SNM, p = 0.028). Consuming a meal did not further increase the number of propagating contractions beyond the baseline upregulating effect of SNM. Conclusion: The rectosigmoid brake was suppressed in this cohort of patients with faecal incontinence. SNM may exert a therapeutic effect by modulating this rectosigmoid brake.

Duodenal and proximal jejunal motility inhibition associated with bisacodyl induced colonic high amplitude propagating contractions

Bisacodyl is a stimulant laxative often used in manometric studies of pediatric constipation to determine if it can initiate propulsive high amplitude propagating contractions. While the effects of bisacodyl infusion on colonic motility are well described, the effects of the drug on other regions of the gut after colonic infusion are not known. The aim of the present study was to characterize the effects of bisacodyl on both colonic and small bowel motility. Methods. Twenty seven children (9.3 + 1.2 years) undergoing simultaneous high resolution antroduodenal and colonic manometry were included. Small bowel and colonic motor patterns were assessed prior to and after colonic infusion of bisacodyl. Patients were divided into 2 groups; responders and non-responders based on the presence of high amplitude propagating contractions (HAPC) after bisacodyl infusion. Results. Nineteen patients were responders. 188 post-bisacodyl HAPCs were identified with a mean count of 10.4 ± 5.5 (range, 3 -22), at a frequency of 0.6 ± 0.2/min and mean amplitude of 119.8 ± 23.6 mmHg.No motor patterns were induced in the small bowel. However, in the 19 responders the onset of HAPCs was associated with a significant decrease in small bowel contractile activity. In the non-responders there was no detectable change in small bowel motility after bisacodyl infusion. Conclusion. Bisacodyl induced HAPCs are associated with a significant reduction in small bowel motility probably mediated by extrinsic sympathetic reflex pathways. This inhibition is potentially related to rectal distension, caused by the HAPC anal propulsion of colonic content.

Bowel transit studies in children: evidence base, role and practicalities

Constipation is common in children and adults with varied worldwide prevalence. The majority of children have functional constipation as defined by Rome clinical criteria and respond favourably to standard medical therapy; up to one-third can develop difficult-to-treat constipation requiring investigation and specialist treatment. Colon function tests aim to assess the neuromuscular integrity, the movement of faeces across the colon and evaluate/predict response to the therapy. The ‘ideal’ test should be practical, non-invasive, widely available and cost-effective. None of the available diagnostic tools is designed to provide a comprehensive assessment of colon function and clinicians often have to combine more than one test to answer different questions. In this review, we aim to assess the strengths and limitations of the commonly available diagnostic investigations (radiopaque marker studies, scintigraphy, wireless motility capsule and colonic manometry) used to assess colon transit in children and to provide guidance on the most appropriate test for particular clinical settings.

Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives

The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson’s disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.

A35 ASSOCIATIONS BETWEEN AUTONOMIC DYSFUNCTION, COLONIC DYSMOTILITY AND ABSENT DEFECATION REFLEXES IN PATIENTS WITH CHRONIC REFRACTORY CONSTIPATION

Background A defecation reflex involves sensory information from the colon sent to the central nervous system which results in propulsive motor patterns in the colon through programmed neural activity from the autonomic nervous system. Neurological causes of constipation are recognized but specific neurological pathways that contribute to pathophysiology of the disease is underexplored. Diagnosis and treatment usually do not involve the autonomic nervous system. Aims Our objective was to assess autonomic dysfunction and abnormal defecation reflexes as a possible cause of chronic constipation. Methods Defecation reflexes were assessed by high-resolution colonic manometry through balloon distention, meal intake, and rectal bisacodyl. Specific heart rate variability (HRV) parameters were used to assess general orthostatic autonomic reactivity, and autonomic functioning during high resolution colonic manometry, in 14 patients with chronic refractory constipation considered for surgery. Results All patients had a unique combination of motility, reflex ability and HRV profiles. Patients overall did not generate HAPWs or had lower HAPW amplitude and lower propulsive activity compared to healthy individuals. Half of the 14 patients were tested to have high sympathetic tone based on Baevsky’s stress index prior to HRCM, and 11 of the patients had sympathetic hyper-reactivity and/or low parasympathetic reactivity to at least one type of colonic stimulation during HRCM. Abnormal autonomic tone or autonomic reactivity to colonic stimulation was present in all four patients with absence of the vagosacral defecation reflex. Five of the seven patients with absence of the sacral defecation reflex showed high sympathetic tone or high sympathetic reactivity to stimulation. Only two patients had abnormality in coloanal coordination and this was associated with low parasympathetic reactivity to stimulation in both patients. Conclusions The assumption that colonic resection was needed to remove an inert colon was wrong in most patients, but most patients had some form of reflex abnormality. Sympathetic dominance far outweighed parasympathetic dysfunction. Incorporation of assessments of defecation reflexes and autonomic nervous system activity into diagnosis of chronic refractory constipation provides a comprehensive pathophysiological understanding of specific defective neurological pathways contributing to dysmotility. This forms the basis for our individualized treatment efforts through sacral neuromodulation. Funding Agencies CIHR

Automated Analysis Using a Bayesian Functional Mixed-Effects Model With Gaussian Process Responses for Wavelet Spectra of Spatiotemporal Colonic Manometry Signals

Manual analysis of human high-resolution colonic manometry data is time consuming, non-standardized and subject to laboratory bias. In this article we present a technique for spectral analysis and statistical inference of quasiperiodic spatiotemporal signals recorded during colonic manometry procedures. Spectral analysis is achieved by computing the continuous wavelet transform and cross-wavelet transform of these signals. Statistical inference is achieved by modeling the resulting time-averaged amplitudes in the frequency and frequency-phase domains as Gaussian processes over a regular grid, under the influence of categorical and numerical predictors specified by the experimental design as a functional mixed-effects model. Parameters of the model are inferred with Hamiltonian Monte Carlo. Using this method, we re-analyzed our previously published colonic manometry data, comparing healthy controls and patients with slow transit constipation. The output from our automated method, supports and adds to our previous manual analysis. To obtain these results took less than two days. In comparison the manual analysis took 5 weeks. The proposed mixed-effects model approach described here can also be used to gain an appreciation of cyclical activity in individual subjects during control periods and in response to any form of intervention.

Simultaneous assessment of colon motility in children with functional constipation by cine-MRI and colonic manometry: a feasibility study

Background Colonic manometry is the current reference standard for assessing colonic neuromuscular function in children with intractable functional constipation (FC). Recently, cine magnetic resonance imaging (cine-MRI) has been proposed as a non-invasive alternative. We compared colonic motility patterns on cine-MRI with those obtained by manometry in children, by stimulating high-amplitude propagating contractions (HAPCs) with bisacodyl under manometric control while simultaneously acquiring cine-MRI. Methods After Institutional Review Board approval, adolescents with FC scheduled to undergo colonic manometry were included. A water-perfused 8-lumen catheter was used for colonic manometry recordings. After an intraluminal bisacodyl infusion, cine-MRI sequences of the descending colon were acquired for about 30 min simultaneously with colonic manometry. Manometry recordings were analysed for HAPCs. MRI images were processed with spatiotemporal motility MRI techniques. The anonymised motility results of both techniques were visually compared for the identification of HAPCs in the descending colon. Results Data regarding six patients (three males) were analysed (median age 14 years, range 12–17). After bisacodyl infusion, three patients showed a total of eleven HAPCs with colonic manometry. Corresponding cine-MRI recorded high colonic activity during two of these HAPCs, minimal activity during seven HAPCs, while two HAPCs were not recorded. In two of three patients with absent HAPCs on manometry, colonic activity was recorded with cine-MRI. Conclusions Simultaneous acquisition of colonic cine-MRI and manometry in children with FC is feasible. Their motility results did not completely overlap in the identification of HAPCs. Research is needed to unravel the role of cine-MRI in this setting.