Neurogastroenterology and Motility最新文献

Background: Chronic gastroduodenal symptoms arise from heterogeneous gastric motor dysfunctions. This study applied multimodal physiological testing using gastric emptying scintigraphy (GES) with intragastric meal distribution (IMD) and Gastric Alimetry body surface gastric mapping (BSGM) to define motility and symptom associations.

Methods: Patients with chronic gastroduodenal symptoms underwent simultaneous supine GES and BSGM with a 30 m baseline, 99mTC-labeled egg meal, and 4 h postprandial recording. IMD (ratio of counts in the proximal half of the stomach to the total gastric counts) was calculated immediately after the meal (IMD0), with < 0.568 defining abnormal IMD. BSGM phenotyping followed a consensus approach, based on normative spectral reference intervals.

Results: Among 67 patients (84% female, median age 40 years, median BMI 24 kg/m²), median IMD0 was 0.76 (IQR: 0.69-0.86) with 5 (7.5%) meeting abnormal IMD criteria. Delayed gastric emptying (n = 18) was associated with higher IMD0 (median 0.9 vs. 0.7, p = 0.004). On BSGM, 15 patients had abnormal spectrograms (5 [7.5%] high frequency and 10 [14.9%] low rhythm stability and/or amplitude); and in these patients, higher IMD0 (proximal retention) strongly correlated to delayed BSGM meal responses (R = -0.71, p = 0.003). Lower IMD, indicating antral distribution, correlated with higher gastric frequencies (R = -0.27, p = 0.03). BSGM abnormalities paired with abnormal IMD were associated with worse dyspeptic symptoms.

Conclusion: Proximal retention of food as assessed by IMD correlated with delayed emptying, and in the presence of neuromuscular spectral abnormalities (abnormal frequencies or rhythms), delayed motility responses on BSGM. Patients with multiple motor abnormalities experience worse dyspeptic symptoms.

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are associated with gastrointestinal (GI) immune-related adverse events (IrAEs). GI dysautonomia is a rare IrAE due to enteric nervous system dysfunction with/without generalized autonomic failure. Here, we present a case series of GI dysautonomia following ICI therapy and conduct a systematic review of the literature.

Methods: We present three patients with ICI-induced GI dysautonomia referred to our tertiary ICI-neurotoxicity service. A systematic review was conducted in OVID, Cochrane, and Scopus until December 2024 for studies evaluating ICI-induced GI dysautonomia, including clinical presentation, treatment choice, and mortality.

Key results: Three male patients were treated with ICIs for melanoma (n = 2) and chondrosarcoma. Severe GI symptoms developed at seven years, two months, and three weeks from treatment initiation at ages 77, 60, and 57 years old, respectively. All three had panenteric involvement with additional autonomic dysfunction. Two patients had poor outcomes with enteral and parenteral nutrition dependence, respectively, and died from GI complications. The third case responded well to prolonged high-dose corticosteroids and mycophenolate maintenance. On systematic review, 18 individual cases were reported in 15 publications, with the onset of GI dysautonomia at a mean time of 13.6 weeks (SD 14.3) from ICI exposure. Corticosteroids were the primary treatment in 72% (n = 13), with a limited duration and low (< 1 mg/kg/day prednisolone equivalent) dose used in 46.2% (n = 6/13). There was GI recovery in 38.5% (n = 5) and mortality in 47.0% (n = 8; 1 missing).

Conclusion: ICI-induced GI dysautonomia is a potentially life-threatening IrAE requiring early recognition and effective immunosuppression to optimize outcome.

Background: Colon displays structural and functional diversity. However, the region-specific motility effects of spinal nerves on the colon are unclear. We mapped the regional colonic motor response to thoracolumbar (T12-L1) (TLNS) and sacral (S1-S4) (SNS) roots nerve electrical stimulation (ES) in an anesthetized porcine model, with or without concomitant afferent (AB) or efferent (EB) transmission block.

Methods: Adult male Yucatan pigs (n = 16) underwent a laminectomy followed by unilateral (left root) SNS (S1-S4, 30 Hz, 0.3 ms, 0.5 mA, PT, 30 s ON/90 s OFF) or with concomitant AB or EB (40 kHz, 0.1 ms, 2 mA). In a separate group (n = 7), TLNS (T12-L1, 10 Hz, 0.3 ms, 0.5 mA, continuous or 30 Hz, 0.3 ms, 0.5 mA, PT, 30 s ON/90 s OFF) of the left root concomitant with or without EB was applied. Proximal (pC), transverse (tC), distal (dC) colon and anal canal (AC) luminal manometry were monitored before, during and after stimulation. Area under the curve of contraction (AUC), luminal pressure heat maps, and contraction spectral analysis were analyzed.

Key results: S2 ES increased the power of the contraction frequency spectrum in both dC and AC during stimulation and increased the AUC of contraction in dC and AC during and post-stimulation. AB and EB partially reduced dC, while EB abolished the increase in AC. In contrast, S1, S3, or S4 ES as well as TLNS had little effect on motility.

Conclusions: In anesthetized male pigs, S2 ES induces a robust motility response in the distal colon via the central network while in the anal canal via efferent pathways.

Introduction: A significant, yet often overlooked, complication of subarachnoid hemorrhage (SAH) is the development of acidosis. Denervation atrophy is a recognized cause of neural ganglion damage following primary motor neuron damage, but the effect of tissue pH changes has not been thoroughly investigated.

Aim: This study investigates whether acidosis causes Auerbach ganglia damage following SAH.

Methods: Twenty-four hybrid rabbits were selected, and five (GI; n = 5) were used for the analysis of the Auerbach ganglia. Six animals (GII; n = 6) were allocated to the SHAM group, receiving 1 cc of saline. The remaining 13 animals (GIII; n = 13) were allocated to the study group, receiving 1 cc of autologous arterial blood injected into the cisterna magna to induce subarachnoid hemorrhage under general anesthesia. Blood pH values were recorded before the experiment, on the seventh day, and immediately before sacrifice. Animals were sacrificed after 1 week, and the degenerated neuron density of the Auerbach ganglia in 1 cm segments of the ascending colon was estimated. The pH values and degenerated Auerbach ganglia neuron densities (n/mm³) were compared using the Mann-Whitney U test.

Results: The presurgical blood pH values of all animals were 7.431 ± 0.032. On the seventh day, pH values were 7.403 ± 0.052 in GI; 7.395 ± 0.024 in GII; and 7.264 ± 0.045 in GIII. At the end of the experiment, pH values were 7.431 ± 0.037 in GI; 7.395 ± 0.062 in GII; and 7.330 ± 0.035 in GIII. Degenerated neuron densities of Auerbach ganglia neurons were 13 ± 4 in GI, 34 ± 6 in the SHAM group, and 87 ± 15 in GIII. The p values were: p < 0.005 for GII/GI; p < 0.0001 for GII/GIII; and p < 0.00005 for GI/GIII.

Conclusion: Acidosis is a potential causative factor of Auerbach ganglia degeneration following SAH, a phenomenon not previously described.

Objective: Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to ameliorate symptoms of both functional dyspepsia (FD) and depression/anxiety, while the central mechanism underlying taVNS effects on depression and anxiety in FD remains unclear. The aim of this study was to investigate taVNS-induced depression-like behavioral changes and cerebral activity alterations in a rodent model of FD.

Methods: Neonatal Sprague-Dawley (SD) rats were gavaged with iodoacetamide (IA) to induce a FD model. taVNS was performed for 30 min once daily for 14 days consecutively. The open field test (OFT) and forced swimming test (FST) were conducted to assess depression-like behaviors. The amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo) were derived from resting-state functional magnetic resonance imaging. Correlations between differential ALFF and ReHo values and depression-like behaviors were analyzed to identify taVNS-related central changes.

Results: taVNS increased both horizontal and vertical scores in the OFT and reduced the immobility time of the FST. After taVNS intervention, the ALFF and ReHo values of the right brainstem were decreased. Conversely, the ALFF values of the left molecular layer of the cerebellum and the ReHo values of the right entorhinal cortex were increased. The horizontal score of the OFT was negatively correlated with the ALFF of the right brainstem. Both the vertical score of the OFT and the immobility time of the FST were negatively correlated with the ReHo values of the entorhinal cortex.

Conclusion: taVNS alleviates depressive state in FD rats, possibly mediated by enhancing local neural coordination in the right entorhinal cortex and suppressing spontaneous neural activity in the right brainstem. These findings support further exploration of taVNS as a candidate approach for FD-related depression.

Background and aim: Achalasia's insidious onset and nonspecific presentation contribute to diagnostic delays, often exceeding 20 months from symptom onset to confirmation. The four-domain CARS endoscopic score (Content, Anatomy, Resistance, Stasis) may expedite risk stratification. We performed a meta-analysis to assess diagnostic accuracy, interobserver reliability, and treatment-monitoring potential.

Methods: We searched PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov through June 2025. Study-level 2 × 2 contingency data were then synthesized using bivariate random-effects models to derive pooled sensitivity, specificity, positive predictive value, and negative predictive value, generate HSROC curves, and construct Fagan nomograms at 5% and 25% pre-test probabilities.

Results: We screened 49 studies and ultimately included five studies encompassing 1112 patients with a mean age of 54.5 years and overall achalasia prevalence of 31.7%. For a CARS threshold ≥ 4, pooled sensitivity was 0.73 (95% CI 0.69-0.78), specificity 1.00 (0.99-1.00), positive predictive value 0.99, and negative predictive value 0.88; employing a dual-threshold strategy (CARS = 0 to rule out; ≥ 4 to rule in) further improved sensitivity to 0.95 (0.92-0.98), specificity to 0.99 (0.97-1.00), positive predictive value to 0.99, and negative predictive value to 0.96. The HSROC AUC approached 0.99, and moreover interobserver agreement was almost perfect with a pooled Cohen's κ = 0.84 (95% CI 0.76-0.91).

Conclusions: CARS reliably stratifies patients into low-risk (CARS = 0), moderate-risk (1-3), and high-risk (≥ 4) groups facilitating deferred testing, targeted manometry, or prompt invasive evaluation while demonstrating excellent interobserver agreement, underscoring its clinical utility.

Trial registration: PROSPERO number: CRD420251007005.

Background: The reference standard for the assessment of esophageal motility and sphincter function is high-resolution esophageal manometry (HRM). Diagnostic values for HRM are determined by the Chicago Classification (CC v4.0), which is based almost entirely on distal esophageal function without measures to address the proximal esophageal segment. Therefore, we sought to determine normal HRM values for proximal esophageal function when obtained in the standard HRM positions (supine and upright).

Methods: Healthy, asymptomatic adults (≥ 18 years) were recruited. All participants completed a standard protocol. CC v4.0 measurements, along with a proximal contractile integral (PCI) (millimeters mercury-seconds-centimeters[mmHg-s-cm]), temporal measures of proximal and distal contractility (seconds), and lengths of proximal and distal esophagus (centimeters), were performed. Summary statistics, tests of normality, and paired two-sided t-tests were performed.

Results: HRM data from 30 participants were included. Mean supine PCI was 423.9 mmHg-s-cm with a mean contraction time of 3.2 s and a mean length of 5.5 cm. The mean upright PCI was 183.9 mmHg-s-cm with a mean contraction time of 2.2 s, and a mean length of 4.5 cm. All proximal values were significantly different comparing the two positions (PCI p < 0.0001; time p < 0.0001; length p < 0.0001). All distal measurements fell within the ranges of normal, and all measures for contractile integral, contraction time, and contraction length were statistically significantly different (p < 0.0001 for all) comparing proximal versus distal measurements.

Conclusions: These preliminary data represent our first attempt to quantify normal proximal esophageal function using HRM measurements of contractile vigor, contraction length, and time.

Background: The UCon neurostimulator is a novel device providing dorsal genital nerve (DGN) stimulation for treating fecal incontinence (FI)/fecal urgency (FU). The primary aim was to explore its safety and secondarily its performance, hypothesizing that DGN stimulation would be feasible and safe, while reducing FI/FU.

Method: This was a prospective two-center feasibility study conducted in Denmark. Adults ≥ 18 years, with FI ≥ 1/week, and/or strong FU ≥ 3/week, and a St. Mark's Incontinence Score ≥ 9 were eligible. DGN stimulation was self-administered at home daily for 4 weeks in either a time-limited (30 min/day) or urge/on-demand (60 s upon urgency) modality. Safety was assessed through patient-reported adverse and device-related events. Efficacy was evaluated by comparing baseline data with the last 14 days of the intervention using symptom diaries, the St. Mark's Incontinence Score, and bowel-related quality-of-life measures.

Results: Forty patients consented (39 women), median age 62 years (Q1-Q3: 54-69), and 26 patients completed the study. An adverse and device-related median of 1.5 events per patient was reported, but these were mild and transient. Among patients completing the 4-week intervention, 74% (n = 19) with FI and 43% (n = 14) with strong FU achieved ≥ 50% symptom reduction (p = 0.005 and p ≤ 0.001, respectively). St. Mark's Incontinence Score (n = 26) reduced significantly from 16.0 (13-18) to 11.5 (9-15) (p ≤ 0.001).

Conclusion: Using the UCon neurostimulator in a home setting is safe and feasible. A 4-week stimulation period demonstrated significant positive results in treating FI and FU.

Clinical trials registration: The conducted research was preregistered at ClinicalTrials.gov with the following link: (https://ClinicalTrials.gov/study/NCT05368246?cond=UCon&rank=5).

Background: Irritable bowel syndrome (IBS) is characterized by recurrent visceral pain associated with low-grade gut inflammation. Electroacupuncture (EA) at acupoint ST36 (Zusanli) is reputed to alleviate gastrointestinal disorders, but its effects on IBS-related visceral hypersensitivity and inflammation remain to be fully elucidated. This study evaluated whether EA at ST36 attenuates visceral pain and modulates key inflammatory mediators in the IBS rat model.

Methods: Forty male rats were randomly assigned to Control, IBS model, IBS + EA, and IBS + Sham groups (n = 10 each). IBS was induced by intracolonic acetic acid enema combined with daily restraint stress for 1 week, validating the IBS-D model. EA was applied at bilateral ST36 (2/100 Hz alternating frequency, ~0.5 mA, 20 min) every other day for 2 weeks; sham treatment used superficial needling with no electrical current. Visceral pain was assessed by abdominal withdrawal reflex (AWR) scores and electromyographic responses to graded colorectal distension. Colonic tissues were analyzed for pro-inflammatory cytokines (interleukin-1β, IL-6, tumor necrosis factor-α) by ELISA and for the expression of pain or inflammation-related proteins (TRPV1 and nuclear factor kappa B, NF-κB) by Western blot analyses.

Results: IBS model rats exhibited pronounced visceral hypersensitivity, with AWR scores significantly elevated (e.g., score 3 threshold volume reduced by ~40% vs. controls, p < 0.01). EA at ST36 markedly alleviated visceral pain, increasing pain threshold and reducing AWR scores by ~30%-50% compared to untreated IBS (p < 0.05). EA also significantly downregulated colonic IL-1β, IL-6, and TNF-α levels (by 45%-60% vs. IBS, p < 0.01) and reduced TRPV1 and NF-κB expression toward normal levels.

Conclusion: EA at ST36 produced significant analgesic and anti-inflammatory effects in IBS model rats. Visceral hypersensitivity was blunted and colonic inflammatory biomarkers (cytokines, TRPV1, NF-κB) were suppressed by EA, suggesting that EA at ST36 modulates neuro-immune pathways to relieve IBS-related pain. These findings support the therapeutic potential of ST36-targeted electroacupuncture for managing IBS visceral pain via inflammatory mechanism attenuation.

Background: Polyethilenglicole (PEG), bisacodyl, prucalopride, and linaclotide were demonstrated to be superior to placebo for the treatment of chronic constipation. In a recent study, we reported the actions of PEG, bisacodyl, and prucalopride on colonic motor patterns. The aim of the present study was to evaluate the effect of linaclotide as compared to placebo on colonic motility assessed with high-resolution manometry (HRM).

Methods: In 10 volunteers (30.3 ± 10.6 years), two colonic HRM studies (40 solid-state sensors, 2.5 cm spaced) were performed at least 10 days apart. After 90 min of basal recording, linaclotide 290 μg or placebo was administered orally in double-blind, randomized, cross-over fashion, and the recording continued for 180 min before and after a standardized meal. Colonic motility index (MI) of the right, left colon, and rectum, expressed as a ratio of the baseline value, was compared between treatments by means of a mixed model analysis. The number of high-amplitude propagated sequences, of long-distance propagating sequences, and of pan-colonic pressurizations was compared between treatments.

Results: Linaclotide induced more long-distance propagating sequences than placebo (34.9 ± 41.2 vs. 3.0 ± 5.2, p = 0.026), especially during the meal and post-meal phases of the recording. The total number of pancolonic pressurizations did not differ between treatments. However, a significant increase in the mean number of pre-prandial pancolonic pressurizations was observed following linaclotide administration (p = 0.043). No treatment effect was found on the change in colonic MI from the baseline in any region of the colon.

Conclusions: In healthy controls, acute administration of linaclotide increases the total number of long-distance propagating sequences and the pre-prandial pancolonic pressurizations.