Abnormalities on Electrogastrography in Nausea and Vomiting Syndromes: A Systematic Review, Meta-Analysis, and Comparison to Other Gastric Disorders.

BACKGROUND: Functional nausea and vomiting syndromes and gastroparesis, collectively grouped as nausea and vomiting syndromes (NVS), are overlapping conditions with incompletely understood pathophysiology. Gastric slow wave abnormalities are thought to contribute. AIMS: This study aimed to systematically review and meta-analyze the prevalence of slow wave abnormalities measured by electrogastrography (EGG) in patients with NVS. METHODS: MEDLINE, EMBASE, EMBASE classic, and CENTRAL databases were systematically searched for articles using EGG in adults (≥ 18 years) with NVS. EGG metrics of interest were percentage time in bradygastria, normogastria, and tachygastria as well as dominant frequency and dominant power. Outcomes were also compared with functional dyspepsia (FD), gastroesophageal reflux disease (GORD), and control cohorts. RESULTS: Seven hundred and sixty NVS patients and 308 controls were included from 24 studies. Overall, 64% of patients had EGG abnormalities. Average percent time in normogastria was low during fasting (50%; 95% CI 40-63%) and fed (53%; 95% CI 41-68%) states in patients, with substantial periods in fasting bradygastria (34.1%; 95% CI 25-47%) and postprandial tachygastria (21%; 95% CI 17-26%). Across gastric disorders, pooling of 84 studies showed a comparably high prevalence of EGG abnormalities in NVS (24 studies; n = 760) and GORD (13 studies; n = 427), compared to FD (47 studies; n = 1751) and controls (45 studies; n = 1027). CONCLUSIONS: Frequency-based gastric slow wave abnormalities are prominent in NVS. The strength and consistency of these associations across many studies suggests that gastric dysrhythmia may be an important factor in NVS, motivating the development of more reliable methods for their clinical assessment.

The gastric conduction system in health and disease: a translational review.

Gastric peristalsis is critically dependent on an underlying electrical conduction system. Recent years have witnessed substantial progress in clarifying the operations of this system, including its pacemaking units, its cellular architecture, and slow-wave propagation patterns. Advanced techniques have been developed for assessing its functions at high spatiotemporal resolutions. This review synthesizes and evaluates this progress, with a focus on human and translational physiology. A current conception of the initiation and conduction of slow-wave activity in the human stomach is provided first, followed by a detailed discussion of its organization at the cellular and tissue level. Particular emphasis is then given to how gastric electrical disorders may contribute to disease states. Gastric dysfunction continues to grow in their prevalence and impact, and while gastric dysrhythmia is established as a clear and pervasive feature in several major gastric disorders, its role in explaining pathophysiology and informing therapy is still emerging. New insights from high-resolution gastric mapping are evaluated, together with historical data from electrogastrography, and the physiological relevance of emerging biomarkers from body surface mapping such as retrograde propagating slow waves. Knowledge gaps requiring further physiological research are highlighted.

Clinical associations of functional dyspepsia with gastric dysrhythmia on electrogastrography: A comprehensive systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a common gastroduodenal disorder, yet its pathophysiology remains poorly understood. Bioelectrical gastric slow-wave abnormalities are thought to contribute to its multifactorial pathophysiology. Electrogastrography (EGG) has been used to record gastric electrical activity; however, the clinical associations require further evaluation. AIMS: This study aimed to systematically assess the clinical associations of EGG in FD. METHODS: MEDLINE, EMBASE, and CENTRAL databases were systematically searched for articles using EGG in adults with FD. Primary outcomes were percentage normal versus abnormal rhythm (bradygastria, normogastria, and tachygastria). Secondary outcomes were dominant power, dominant frequency, percentage coupling, and the meal responses. RESULTS: 1751 FD patients and 555 controls from 47 studies were included. FD patients spent less time in normogastria while fasted (SMD -0.74; 95%CI -1.22 to -0.25) and postprandially (-0.86; 95%CI -1.35 to -0.37) compared with controls. FD patients also spent more fasted time in bradygastria (0.63; 95%CI 0.33-0.93) and tachygastria (0.45; 95%CI 0.12-0.78%). The power ratio (-0.17; 95%CI -0.83-0.48) and dominant frequency meal-response ratio (0.06; 95%CI -0.08-0.21) were not significantly different to controls. Correlations between EGG metrics and the presence and timing of FD symptoms were inconsistent. EGG methodologies were diverse and variably applied. CONCLUSION: Abnormal gastric slow-wave rhythms are a consistent abnormality present in FD, as defined by EGG and, therefore, likely play a role in pathophysiology. The aberrant electrophysiology identified in FD warrants further investigation, including into underlying mechanisms, associated spatial patterns, and symptom correlations.

Gastric dysrhythmia in gastroesophageal reflux disease: a systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a commonly diagnosed gastrointestinal disorder, with a substantial impact on the quality of life. The underlying pathophysiology of GERD is multifactorial and incompletely understood. Abnormal gastric electrical activity, measured using electrogastrography (EGG), may contribute. This study aimed to systematically review and meta-analyse the existing literature in which EGG was used in patients with GERD. METHODS: Databases were systematically searched for studies using EGG in adults with GERD. The primary outcome was the percentage of recording time in the normogastric frequency range. Secondary outcomes were dominant frequency, dominant power, power ratio and prevalence of any EGG abnormality. RESULTS: In total, 591 participants (427 patients with GERD; 164 healthy controls) from 13 studies were included. GERD patients spent 17.3% (SMD - 1.18, 95%CI: - 1.84, - 0.52) and 18.7% (SMD - 1.11, 95%CI: - 1.55, - 0.68) less of the preprandial and postprandial recording time in normogastric frequency ranges, respectively, compared to healthy controls. The dominant frequency, dominant power and power ratio were not significantly different to healthy controls in the preprandial and postprandial periods. The pooled prevalence of any EGG abnormality was significantly greater in patients with GERD than in healthy controls [46% (95%CI: 39-64%) vs. 10% (95%CI: 4-23%); p < 0.0001]. Correlations between GERD symptoms and EGG recordings were inconsistently studied. EGG techniques were heterogeneous. CONCLUSIONS: Consistent abnormalities in gastric slow-wave activity, as measured by EGG, were identified in adults with GERD. Further investigation into these abnormalities using novel emerging electrophysiology techniques is desirable, to better define their contribution toward GERD pathophysiology.

Body surface mapping of the stomach: New directions for clinically evaluating gastric electrical activity.

BACKGROUND: Gastric motility disorders, which include both functional and organic etiologies, are highly prevalent. However, there remains a critical lack of objective biomarkers to guide efficient diagnostics and personalized therapies. Bioelectrical activity plays a fundamental role in coordinating gastric function and has been investigated as a contributing mechanism to gastric dysmotility and sensory dysfunction for a century. However, conventional electrogastrography (EGG) has not achieved common clinical adoption due to its perceived limited diagnostic capability and inability to impact clinical care. The last decade has seen the emergence of novel high-resolution methods for invasively mapping human gastric electrical activity in health and disease, providing important new insights into gastric physiology. The limitations of EGG have also now become clearer, including the finding that slow-wave frequency alone is not a reliable discriminator of gastric dysrhythmia, shifting focus instead toward altered spatial patterns. Recently, advances in bioinstrumentation, signal processing, and computational modeling have aligned to allow non-invasive body surface mapping of the stomach to detect spatiotemporal gastric dysrhythmias. The clinical relevance of this emerging strategy to improve diagnostics now awaits determination. PURPOSE: This review evaluates these recent advances in clinical gastric electrophysiology, together with promising emerging data suggesting that novel gastric electrical signatures recorded at the body surface (termed "body surface mapping") may correlate with symptoms. Further technological progress and validation data are now awaited to determine whether these advances will deliver on the promise of clinical gastric electrophysiology diagnostics.

Detection of gastric slow oscillatory contraction using parasagittal cine MR images: Comparison with simultaneously measured electrogastrogram.

PURPOSE: To determine if parasagittal gastric cine magnetic resonance imaging (MRI) is able to measure gastric oscillatory contractions around 0.05 Hz and to determine its relationship with electrical activity as measured by electrogastrography (EGG). METHODS: Assessment of the gastric motility is important for the research of the enteric nervous system and for the diagnosis of functional gastric disorders. Electrogastrography is a non-invasive method that can measure gastric oscillatory electrical activity around 0.05 Hz (slow wave) using electrodes on the abdominal skin, but its sensitivity and specificity of the slow wave detection is limited. We used parasagittal gastric cine MRI around the angular incisure to measure gastric oscillatory contraction around 0.05 Hz in 24 healthy volunteers. Cine MRI was acquired with time resolution of 1 s for 10 min while freely breathing participants were lying on the bed. The gastric area of the cross section was measured for each MR image and assessed its change over time. The results were compared with those for simultaneously recorded EGG. RESULTS: The main frequency of the gastric area change for each participant ranged from 0.041 to 0.059 Hz (mean ± S.D. = 0.049 ± 0.004), which corresponds to the gastric slow wave frequency (mean ± S.D. = 0.049 ± 0.004) as measured by EGG (p = 7.9585 × 10 -8, Kendall 's tau test). Cross correlation analysis showed that 22 of 24 participants' gastric area changes were significantly (p < 0.05) related to the EGG waveforms. Displacement of the stomach due to respiration did not affect gastric area measurements. CONCLUSIONS: Parasagittal cine MRI is correlated with EGG recordings and able to detect and quantifying gastric motility abnormalities.

A Miniature Configurable Wireless System for Recording Gastric Electrophysiological Activity and Delivering High-Energy Electrical Stimulation.

The purpose of this paper is to develop and validate a miniature system that can wirelessly acquire gastric electrical activity called slow waves, and deliver high energy electrical pulses to modulate its activity. The system is composed of a front-end unit, and an external stationary back-end unit that is connected to a computer. The front-end unit contains a recording module with three channels, and a single-channel stimulation module. Commercial off-the-shelf components were used to develop front- and back-end units. A graphical user interface was designed in LabVIEW to process and display the recorded data in real-time, and store the data for off-line analysis. The system was successfully validated on bench top and in vivo in porcine models. The bench-top studies showed an appropriate frequency response for analog conditioning and digitization resolution to acquire gastric slow waves. The system was able to deliver electrical pulses at amplitudes up to 10 mA to a load smaller than 880 Ω. Simultaneous acquisition of the slow waves from all three channels was demonstrated in vivo. The system was able to modulate -by either suppressing or entraining- the slow wave activity. This study reports the first high-energy stimulator that can be controlled wirelessly and integrated into a gastric bioelectrical activity monitoring system. The system can be used for treating functional gastrointestinal disorders.

A novel retractable laparoscopic device for mapping gastrointestinal slow wave propagation patterns.

BACKGROUND: Gastric slow waves regulate peristalsis, and gastric dysrhythmias have been implicated in functional motility disorders. To accurately define slow wave patterns, it is currently necessary to collect high-resolution serosal recordings during open surgery. We therefore developed a novel gastric slow wave mapping device for use during laparoscopic procedures. METHODS: The device consists of a retractable catheter constructed of a flexible nitinol core coated with Pebax. Once deployed through a 5-mm laparoscopic port, the spiral head is revealed with 32 electrodes at 5 mm intervals. Recordings were validated against a reference electrode array in pigs and tested in a human patient. RESULTS: Recordings from the device and a reference array in pigs were identical in frequency (2.6 cycles per minute; p = 0.91), and activation patterns and velocities were consistent (8.9 ± 0.2 vs 8.7 ± 0.1 mm s-1; p = 0.2). Device and reference amplitudes were comparable (1.3 ± 0.1 vs 1.4 ± 0.1 mV; p = 0.4), though the device signal-to-noise ratio was higher (17.5 ± 0.6 vs 12.8 ± 0.6 dB; P < 0.0001). In the human patient, corpus slow waves were recorded and mapped (frequency 2.7 ± 0.03 cycles per minute, amplitude 0.8 ± 0.4 mV, velocity 2.3 ± 0.9 mm s-1). CONCLUSION: In conclusion, the novel laparoscopic device achieves high-quality serosal slow wave recordings. It can be used for laparoscopic diagnostic studies to document slow wave patterns in patients with gastric motility disorders.

Preliminary study on high resolution mapping in human gastric electrical activities / 中华消化杂志

Objective To investigate the spatio-temporal characteristics of normal gastric electrical activity.Methods From January 1st to February 29th,2016,fasting gastric electric slow wave signal was collected by high resolution mapping (HRM) under anesthesia before operation in patients without gastric lesions but needed laparoscopic surgery.Parameters of slow wave signal activity was calculated,gastric activity map and velocities was drawn and then spatio-temporal characteristics of gastric electrical activity of different part of the stomach were obtained.Independent sample t test was performed for comparison of two groups and one-way analysis of variance was used for multiple group comparisons.Results The normal gastric pacing zone located in the upper middle part of gastric body near greater curvature.Electrical activity of gastric body spread to gastric antrum along the long axis of the stomach.No slow signal was recorded in the gastric fundus and the gastric cardia.The frequencies of slow waves of different parts of gastric was same and the mean value was 2.61 ±0.11 cycle per minute.Compared with that of gastric body,the slow wave amplitude of gastric pacing zone was higher ((4.19±0.73) mV vs (1.67± 0.89) mV) and the speed was faster (7.24± 1.37) mm/s vs (4.94± 0.20) mm/s);the differences were statistically significant (t=18.89 and 4.95,both P＜0.01).The slow wave amplitude of gastric antrum was higher than that of gastric body ((3.21±0.49) mV vs (1.67±0.89) mV) and the speed was also faster ((6.44±0.82) mm/s vs (4.94±0.20) mm/s);the differences were statistically significant (t=4.85 and 4.95,both P＜0.05).The slow wave amplitude of gastric antrum was lower than that of pacemaker area ((3.21±0.49) mV vs (4.19±0.73) mV),and the difference was statistically significant (t =-3.67,P＜0.05);however,there was no significant difference in wave velocity ((6.44±0.82) mm/s vs (7.24±1.37) mm/s,P＞0.05).Conclusions The normal human gastric pacemaker is located in mid and upper corpus near the greater curvature,which produces slow wave and control whole gastric electrical activity.The amplitude and velocity of slow waves are in gradient changes in different gastric regions.HRM is a mature and reliable research method to study the spatio-temporal characteristics of gastric electrical activity,which provides the possibility for the study of abnormal gastric electrical activity.

Preliminary study on high resolution mapping in human gastric electrical activities / 中华消化杂志

Objective To investigate the spatio-temporal characteristics of normal gastric electrical activity.Methods From January 1st to February 29th,2016,fasting gastric electric slow wave signal was collected by high resolution mapping (HRM) under anesthesia before operation in patients without gastric lesions but needed laparoscopic surgery.Parameters of slow wave signal activity was calculated,gastric activity map and velocities was drawn and then spatio-temporal characteristics of gastric electrical activity of different part of the stomach were obtained.Independent sample t test was performed for comparison of two groups and one-way analysis of variance was used for multiple group comparisons.Results The normal gastric pacing zone located in the upper middle part of gastric body near greater curvature.Electrical activity of gastric body spread to gastric antrum along the long axis of the stomach.No slow signal was recorded in the gastric fundus and the gastric cardia.The frequencies of slow waves of different parts of gastric was same and the mean value was 2.61 ±0.11 cycle per minute.Compared with that of gastric body,the slow wave amplitude of gastric pacing zone was higher ((4.19±0.73) mV vs (1.67± 0.89) mV) and the speed was faster (7.24± 1.37) mm/s vs (4.94± 0.20) mm/s);the differences were statistically significant (t=18.89 and 4.95,both P＜0.01).The slow wave amplitude of gastric antrum was higher than that of gastric body ((3.21±0.49) mV vs (1.67±0.89) mV) and the speed was also faster ((6.44±0.82) mm/s vs (4.94±0.20) mm/s);the differences were statistically significant (t=4.85 and 4.95,both P＜0.05).The slow wave amplitude of gastric antrum was lower than that of pacemaker area ((3.21±0.49) mV vs (4.19±0.73) mV),and the difference was statistically significant (t =-3.67,P＜0.05);however,there was no significant difference in wave velocity ((6.44±0.82) mm/s vs (7.24±1.37) mm/s,P＞0.05).Conclusions The normal human gastric pacemaker is located in mid and upper corpus near the greater curvature,which produces slow wave and control whole gastric electrical activity.The amplitude and velocity of slow waves are in gradient changes in different gastric regions.HRM is a mature and reliable research method to study the spatio-temporal characteristics of gastric electrical activity,which provides the possibility for the study of abnormal gastric electrical activity.

Simultaneous anterior and posterior serosal mapping of gastric slow-wave dysrhythmias induced by vasopressin.

NEW FINDINGS: What is the central question of this study? This study aimed to provide the first comparison of simultaneous high-resolution mapping of anterior and posterior gastric serosa over sustained periods. What is the main finding and its importance? Episodes of spontaneous gastric slow-wave dysrhythmias increased significantly following intravenous infusion of vasopressin compared with the baseline state. A number of persistent dysrhythmias were defined, including ectopic activation, conduction block, rotor, retrograde and collision/merger of wavefronts. Slow-wave dysrhythmias could occur either simultaneously or independently on the anterior and posterior gastric serosa, and interacted depending on activation-repolarization and frequency dynamics. High-resolution mapping enables mechanistic insights into gastric slow-wave dysrhythmias and is now achieving clinical translation. However, previous studies have focused mainly on dysrhythmias occurring on the anterior gastric wall. The present study simultaneously mapped the anterior and posterior gastric serosa during episodes of dysrhythmias induced by vasopressin to aid understanding of dysrhythmia initiation, maintenance and termination. High-resolution mapping (8 × 16 electrodes on each serosa; 20-74 cm2 ) was performed in anaesthetized dogs. Baseline recordings (21 ± 8 min) were followed by intravenous infusion of vasopressin (0.1-0.5 IU ml-1 at 60-190 ml h-1 ) and further recordings (22 ± 13 min). Slow-wave activation maps, amplitudes, velocity, interval and frequency were calculated, and differences compared between baseline and postinfusion. All dogs demonstrated an increased prevalence of dysrhythmic events following infusion of vasopressin (17 versus 51%). Both amplitude and velocity demonstrated significant differences (baseline versus postinfusion: 3.6 versus 2.2 mV; 7.7 versus 6.5 mm s-1 ; P < 0.05 for both). Dysrhythmias occurred simultaneously or independently on the anterior and posterior serosa, and then interacted according to frequency dynamics. A number of persistent dysrhythmias were compared, including the following: ectopic activation (n = 2 animals), conduction block (n = 1), rotor (n = 2), retrograde (n = 3) and collision/merger of wavefronts (n = 2). We conclude that infusion of vasopressin induces gastric dysrhythmias, which occur across a heterogeneous range of frequencies and patterns. The results demonstrate that different classes of gastric dysrhythmias may arise simultaneously or independently in one or both surfaces of the serosa, then interact according to their relative frequencies. These results will help to inform interpretation of clinical dysrhythmia.

Multi-channel wireless mapping of gastrointestinal serosal slow wave propagation.

BACKGROUND: High-resolution (HR) extracellular mapping allows accurate profiling of normal and dysrhythmic slow wave patterns. A current limitation is that cables traverse the abdominal wall or a natural orifice, risking discomfort, dislodgement or infection. Wireless approaches offer advantages, but a multi-channel system is required, capable of recording slow waves and mapping propagation with high fidelity. METHODS: A novel multi-channel (n = 7) wireless mapping system was developed and compared to a wired commercial system. Slow wave signals were recorded from the porcine gastric and intestinal serosa in vivo. Signals were simultaneously acquired using both systems, and were filtered and processed to map activation wavefronts. For validation, the frequency and amplitude of detected events were compared, together with the speed and direction of mapped wavefronts. KEY RESULTS: The wireless device achieved comparable signal quality to the reference device, and slow wave frequencies were identical. Amplitudes of the acquired gastric and intestinal slow wave signals were consistent between the devices. During normal propagation, spatiotemporal mapping remained accurate in the wireless system, however, during ectopic dysrhythmic pacemaking, the lower sampling resolution of the wireless device led to reduced accuracy in spatiotemporal mapping. CONCLUSIONS & INFERENCES: A novel multichannel wireless device is presented for mapping slow wave activity. The device achieved high quality signals, and has the potential to facilitate chronic monitoring studies and clinical translation of spatiotemporal mapping. The current implementation may be applied to detect normal patterns and dysrhythmia onset, but HR mapping with finely spaced arrays currently remains necessary to accurately define dysrhythmic patterns.

Recent progress in gastric arrhythmia: pathophysiology, clinical significance and future horizons.

Gastric arrhythmia continues to be of uncertain diagnostic and therapeutic significance. However, recent progress has been substantial, with technical advances, theoretical insights and experimental discoveries offering new translational opportunities. The discoveries that interstitial cells of Cajal (ICC) generate slow waves and that ICC defects are associated with dysmotility have reinvigorated gastric arrhythmia research. Increasing evidence now suggests that ICC depletion and damage, network disruption and channelopathies may lead to aberrant slow wave initiation and conduction. Histological and high-resolution (HR) electrical mapping studies have now redefined the human 'gastric conduction system', providing an improved baseline for arrhythmia research. The application of HR mapping to arrhythmia has also generated important new insights into the spatiotemporal dynamics of arrhythmia onset and maintenance, resulting in the emergence of new provisional classification schemes. Meanwhile, the strong associations between gastric functional disorders and electrogastrography (EGG) abnormalities (e.g. in gastroparesis, unexplained nausea and vomiting and functional dyspepsia) continue to motivate deeper inquiries into the nature and causes of gastrointestinal arrhythmias. In future, technical progress in EGG methods, new HR mapping devices and software, wireless slow wave acquisition systems and improved gastric pacing devices may achieve validated applications in clinical practice. Neurohormonal factors in arrhythmogenesis also continue to be elucidated and a deepening understanding of these mechanisms may open opportunities for drug design for treating arrhythmias. However, for all translational goals, it remains to be seen whether arrhythmia can be corrected in a way that meaningfully improves organ function and symptoms in patients.