Neurogastroenterology and Motility最新文献

Introduction: Fluid thickeners used in the management of oropharyngeal dysphagia exhibit non-Newtonian shear-thinning rheology, impacting their viscosity during deglutition. This study investigated how the rheological properties of thickened fluids affect pharyngeal swallowing parameters in patients with oropharyngeal motor disorders diagnosed by pharyngeal high-resolution manometry impedance (P-HRM-I).

Methods: Seventy-two patients (18-89 years) referred for P-HRM-I were diagnostically assessed with a 10 mL thin bolus. In 57 of the patients, 10 mL swallows of two moderately thick formulations-xanthan gum (XG) and sodium carboxymethylcellulose gum (CMC)-were also tested. The XG and CMC fluids had equivalent empirical thickness but different viscosity at pharyngeal phase shear rates: XG 87 mPa.s (83-91) versus CMC mean 157 mPa.s (148-164) at 300 s^-1. Standard metrics of pharyngeal and upper esophageal sphincter (UES) function were derived from P-HRM-I recordings and analyzed to characterize patients into one of four disorder subtypes: (i) No Disorder, (ii) UES Disorder, (iii) Pharyngeal Disorder, and (iv) Combination UES/Pharyngeal Disorder. Impedance recordings also assessed pharyngeal bolus transit.

Results: Patients with a Combination UES/Pharyngeal Disorder were most likely to have abnormal bolus transit (82%, p < 0.001). Increasing bolus viscosity significantly influenced UES residual pressure, UES opening area, and post-swallow residue. Patients with UES Disorder exhibited pronounced increases in UES residual pressure with CMC compared to XG. Pharyngeal contractility was unaffected by viscosity changes. Post-swallow residue increased with CMC, particularly in patients with a Combination Disorder. Case-by-case analysis revealed individual variability in response to the different viscosities.

Conclusion: The rheological properties of thickened fluids significantly affect swallowing function, with these effects dependent upon the disorder subtype.

Background: Gastric accommodation (GA) testing is gaining clinical recognition as novel and minimally invasive modalities emerge. We investigated the feasibility of hybrid nuclear imaging volumetry (SPECT/CT) and combined high-resolution manometry-nutrient drink test (HRM-NDT) to assess GA.

Methods: In this non-randomized pilot study, [^99mTc]NaTcO₄ gastric SPECT/CT (250 mL protocol) and proximal gastric HRM-NDT (~60 mL/min protocol) were performed separately within 30 days using Ensure Gold test meal (1.05 kcal/mL; Abbott). GA parameters were measured, and their preliminary associations were examined using Spearman's ρ and Hoeffding's D correlation tests. Data were presented as median ± normalized median absolute deviation.

Key results: Twenty healthy, asymptomatic individuals (11 females; 23.5 ± 2.2 years, 23.7 ± 2.2 kg/m²) completed both procedures without serious adverse events and interrupted sessions. The accommodation volume and postprandial-to-fasting volume ratio from SPECT/CT were 325.8 ± 28.5 mL and 5.31 ± 1.28, respectively. During HRM-NDT, the nadir-intragastric pressure (IGP) was -6.6 ± 3.6 mmHg at an ingested volume of 360.0 ± 177.9 mL, and the area-under-curve of IGP was -1566.0 ± 1596.8 mmHg·mL. The maximum tolerated volume for reaching satiety/maximum discomfort was 450.0 ± 177.9 mL, and the area-under-curve of satiation score was 900.0 ± 266.9 satiation-unit·mL. The area-under-curve of IGP showed significant associations with maximum tolerated volume (ρ: -0.702; D: 0.234) and the area-under-curve of satiation score (D: 0.119): all p < 0.01. No correlations were found between volumetric with manometric and subjective NDT GA parameters.

Conclusions & inferences: SPECT/CT and HRM-NDT are feasible and tolerable techniques for measuring GA in healthy individuals. Thus, determining their diagnostic utility among patient populations requires further optimization and standardization.

Background: Constipation is one of the most common non-motor symptoms in patients with Parkinson's disease (PD), which could manifest during the early stage of the disease. However, the etiology of constipation in PD remains largely unknown. Previous studies supported that gastrointestinal dysfunction may be associated with functional connectivity alterations in paraventricular hypothalamic nucleus (PVN). Therefore, this study aimed to investigate the potential contribution of the PVN to the pathogenesis of constipation in a cohort of early-stage patients with PD and to compare brain network organization between PD patients with and without constipation.

Methods: A total of 66 PD patients (PD with constipation and without constipation) and 30 healthy controls were prospectively enrolled. All participants acquired T1-weighted and resting-state fMRI scans. Then we employed voxel-based morphometry analysis and functional connectivity analysis.

Results: We observed a decreased functional connectivity in the PVN-pontine tegmentum pathway in PD patients with constipation compared to the patients without constipation (p = 0.006, t = 5.37), while we did not find any changes in basal ganglia circuitry between these two groups. In addition, we found that the functional connectivity between PVN and pontine tegmentum was negatively associated with the UPDRS I, II, III and NMSS scores (p < 0.05). Meanwhile, these two types of patients also showed substantial differences in functional connections linking the inferior frontal gyrus and cerebellum with multiple brain regions. We discovered no statistical difference in gray matter volume among these two groups.

Conclusions: Our study provides further insights into the dysfunctional mechanisms of constipation, suggesting that abnormal PVN functional connectivity may be related to the mechanism of constipation in PD. Meanwhile, the inferior frontal gyrus and cerebellum may be involved in the occurrence of constipation in PD patients.

Background: Refluxate volume and pH drop following gastroesophageal reflux are mostly cleared by peristalsis. We evaluated the roles of primary volume clearing peristaltic wave (VCPW), secondary VCPW, post-reflux swallow-induced peristaltic wave (PSPW), and late primary peristaltic wave (LPPW) in refluxate clearance.

Methods: We retrospectively analyzed pH-impedance studies performed off therapy in 40 patients with typical esophageal symptoms. Mechanism of refluxate clearance was evaluated for each reflux episode (primary VCPW vs. secondary VCPW vs. none), as well as presence of PSPW, LPPW when PSPW was absent, and pH recovery with each mechanism. Per-episode and per-patient analyses determined the dominant mechanism of refluxate clearance and pH recovery.

Results: Of 958 reflux episodes, 88% were acidic. A primary VCPW was the dominant mechanism for volume clearance (48.4% acid, 47.8% non-acid reflux episodes), and ≥ 50% pH recovery (58.7%). Of reflux episodes lacking pH recovery, PSPW resulted in ≥ 50% pH recovery in 40.2%, and LPPW in 60.9%. In logistic regression models, primary peristaltic wave (primary VCPW, PSPW, or LPPW) had the highest likelihood of pH recovery in per-episode analysis (OR 2.1, CI 1.3-3.0, p < 0.001), and in per-patient analysis (OR 11.0, CI 1.5-20.5, p = 0.025), among which primary VCPW was the most effective (OR 3.4, CI 1.5-7.7, p = 0.003).

Conclusions: A primary peristaltic wave from a swallow, either in the form of a VCPW, PSPW, or LPPW, is the dominant mechanism of pH recovery after gastroesophageal reflux. When a primary VCPW does not correct pH drop, PSPW, and LPPW are equivalent salvage mechanisms for pH recovery.

Investigations into mechanisms of cyclic(al) vomiting syndrome (CVS) began at the bedside more than a century ago. The modern era started with the formation of the Cyclic Vomiting Syndrome Association in 1993 that helped initiate robust efforts in education, advocacy, family physician conferences, scientific symposia, dedicated clinical programs, therapeutic guidelines, and research. Even today, bedside clues continue to emerge with the recent description of cannabinoid hyperemesis syndrome (CHS) and subsequent evidence of a perturbed endocannabinoid system. The clinical picture of CVS has evolved from that of a straightforward emetic disorder related to migraine requiring short-term antiemetics or prophylactic anti-migraine therapy, to a complicated, heterogenous one with multiple comorbid associations (anxiety, dysautonomia) and endophenotypes (migraine, Sato, CHS). This expanded view has important therapeutic implications which necessitate managing the comorbidities which can in turn impact the disease itself and proffered promising evidence that behavioral management (meditation) and vagal neuromodulation appear efficacious with few untoward effects, perhaps by reestablishing autonomic (parasympathetic) balance. The pathophysiologic picture now appears to be inscribed on an autonomic polyvagal design but multiple additional pathways interact, some confirmed (NK1, CB1, HPA axis, PPM1D gene, biological calendar, estrogen), and others, possible (TRPV-1, CGRP, GDF-15, mitochondrial dysfunction, impaired cation transport). CVS and its cousin CHS continue to challenge clinicians and perplex investigators and in the current era require not only a critical mass of specific pathway expertise but also syncretic biopsychosocial thinking to integrate these disparate threads. We may have reached such a tipping point at this Symposium.

Background: The human colon receives 2 L of fluid daily. Small changes in the efficacy of absorption can lead to altered stool consistency with diarrhea or constipation. Drugs and formulations can also alter colonic water, which can be assessed using the magnetic resonance imaging (MRI) longitudinal relaxation time constant, T1. We explore the use of regional T1 assessment in evaluating disorders of colonic function.

Methods: Individual participant data analysis of data from 12 studies from a single center of patients with constipation, irritable bowel syndrome with diarrhea (IBS-D), and healthy volunteers (HV). T1 was quantified by measuring the signal from the tissue at different times after a pulse which inverts the magnetization.

Key results: When diarrhea was induced by a macrogol laxative T1 in the ascending colon, T1AC was negatively correlated with stool bacterial content, r² = 0.78, p < 0.001. T1AC was increased by another laxative, rhubarb. Patients with IBS-D had elevated fasting T1AC (0.78 ± 0.28 s, N = 67) compared to HV (0.62 ± 0.21 s, N = 92) while those with constipation lay within the normal range (HV 10-90th centiles 0.33-0.91 s). Fasting T1AC in IBS-D was reduced by mesalazine treatment. T1 in the descending colon was consistently lower than T1AC, with a bigger reduction in patients with constipation than HV. Pre-feeding dietary fiber (bran, nopal, and psyllium) was associated with fasting T1AC at or above the normal 90th centile.

Conclusions and inferences: T1 is an MRI parameter which could be used to monitor effectiveness of novel agents designed to alter colonic water content and stool consistency.

Background: Disorders of gut-brain interactions (DGBI) affect more women, and marital quality may have been a factor that explains clinical manifestations of DGBI-however, the mechanism is unclear. This study aimed to elucidate supported relationships between DGBI with marital quality and clinical attributes in married Malay women.

Methods: This cross-sectional study involved married Malay women with functional dyspepsia (FD), irritable bowel syndrome (IBS), and FD-IBS overlap per Rome IV criteria. Multivariate analysis of variance (MANOVA) and Pearson correlation analysis were performed to determine the association between DGBI, marital quality, and clinical attributes of catastrophizing, psychological dysfunction, and quality of life. Path analysis models were developed, tested, and fitted to elucidate relationships that satisfied significance testing and fit indices (termed supported relationship).

Key results: Of 1130 screened participants, 513 were analyzed. The prevalence of FD, IBS, and FD-IBS overlap was 33.9% (n = 174), 29.5% (n = 151), and 36.6% (n = 188), respectively. Of 17 variables in MANOVA, significant differences in variables were observed for FD vs. FD-IBS overlap (10), IBS versus FD (10), and IBS versus FD-IBS overlap (5). Pearson correlation matrices found significant correlations for 15 of 17 variables. After testing and fitting, the third path model (Model 3) was deemed the final model. Model 3 suggested that relationships between DGBI and marital and clinical attributes were complex and bidirectional. The number of supported relationships were 50, 43, and 39 for FD-IBS overlap, FD, and IBS, respectively.

Conclusions and inferences: Relationships between DGBI, marital quality, and clinical attributes among married Malay women are complex and bidirectional.

Introduction: Colonic manometry (CM) is a diagnostic procedure used to evaluate pediatric patients with refractory constipation, fecal incontinence, Hirschsprung disease, and pediatric intestinal pseudo-obstruction. Pan-colonic high-amplitude propagated contractions (HAPCs), measured by CM, reflect an intact neuromuscular function of the colon. Current guidelines recommend starting CM with fasting recording for 1-2 h, but no prior evaluation has determined the diagnostic yield of the fasting phase. We aimed to determine the utility of the fasting phase during CM studies.

Methods: We evaluated CM studies conducted at a tertiary pediatric center (2018-2022). Fasting phases of normal CM studies were evaluated.

Key results: In 433 included studies 241 (55.7%) females, median age (9.7 years), the average fasting recording lasted 126 min. A total of 193 (44.6%) studies exhibited fasting HAPCs, with 123 (28.4%) being pan-colonic. The presence of pan-colonic HAPCs was based solely on the fasting phase in 11 (2.5%) studies. Patients with fasting pan-colonic HAPCs were younger (median age of 6.9 vs. 9.8 years, p = 0.0001) and had a higher rate of postprandial HAPCs (69.1% vs. 25.2%, p < 0.0001). Most fasting pan-colonic HAPCs presented during the first 60 min (94/123, 76.4%). All studies demonstrated HAPCs after stimulation with bisacodyl. In analyzing just the initial 30 min of fasting on CM, only 2 (0.5%) studies would have been misclassified as abnormal, with no bisacodyl administration in these studies.

Conclusions & inferences: Shortening the fasting phase minimally affects next-day CM results and could reduce patient inconvenience, hospital-related costs, and potential side effects.

Introduction: Postoperative ileus (POI) is an iatrogenic disorder marked by temporary impaired gastrointestinal (GI) motility post-abdominal surgery. Surgical handling of the intestine activates resident macrophages (Mfs), leading to inflammatory cytokine release and leukocyte recruitment into the muscularis, which compromises intestinal contractility. The mechanisms behind this activation are unclear. Recent studies suggest peritoneal Mfs, particularly large peritoneal macrophages (LPMs), might play a role in sterile intestinal inflammation by rapidly recruiting to the serosal layer of the gut and aiding in tissue damage resolution.

Methods: To identify immune cells involved in the early phase of POI, single-cell RNA sequencing (scRNA-seq) was conducted. The migration of LPMs post-surgery was studied using adoptive transfer techniques. LPMs were depleted via intraperitoneal injection of clodronate liposomes. Subsequently, flow cytometry, quantitative PCR (qPCR), and immunofluorescence were performed to assess the impact of LPM depletion and analyze cell populations and inflammatory effects.

Results: (1) Intestinal manipulation (IM) leads to the accumulation of monocytes, neutrophils, mature Mfs, CD8+ T cells, and LPMs within 2 h post-surgery. (2) Heparin treatment does not affect gut transit or reduce IL-6, IL-1a, and IL-1b expression in the early phase of POI. (3) Depletion of LPMs via clodronate liposome does not prevent monocyte, neutrophil, and Mfs infiltration in the muscularis externa, nor does it improve gut transit or reduce cytokine expression. (4) LPMs migrate to the serosa after IM but do not enter the muscularis externa.

Conclusion and inferences: LPMs adhere to the intestinal serosa following intestinal manipulation but do not migrate into the intestinal muscularis or participate in the inflammatory response and delayed transit. Consequently, LPMs are not involved in the pathogenesis of POI.

Background: The enteric nervous system plays a key role in the coordination of gastrointestinal motility together with sympathetic, parasympathetic, and extrinsic sensory pathways. In some cases, abnormalities in neural activity in these pathways contribute to disorders of gut motility. Where this is associated with damage or death of enteric neurons, usually detected by microscopy, this is considered a gut neuropathy.

Purpose: This review summarizes recent advances in the identification of neuropathies in a range of gastrointestinal motility disorders.