Temporary Gastric Electrical Stimulation Research Articles

The role of gastric electrical stimulation in postsurgical gastroparesis: a retrospective analysis from 2 centers

BackgroundPostsurgical gastroparesis, resulting from surgical interventions on the stomach or vagal nerve injury, poses significant clinical challenges with patients presenting symptoms such as nausea, vomiting, and abdominal pain. Although gastric electrical stimulation (GES) offers potential relief, its efficacy in refractory postsurgical gastroparesis requires further examination. This study evaluated the clinical response to GES in patients with refractory postsurgical gastroparesis. MethodsA retrospective study was conducted across 2 study sites, involving 185 patients with drug-refractory postsurgical gastroparesis who underwent both temporary and permanent GES placements. Patients were categorized based on their surgical history: bariatric surgery, Nissen fundoplication, and others. The impact of GES was evaluated using Food and Drug Administration–compliant patient-reported outcomes scores and other relevant clinical metrics at baseline, after temporary GES placement, and 6 months after permanent GES placement. All 3 groups were also analyzed by the symptom improved group vs the unimproved group at baseline and 6 months after GES placement. ResultsAfter GES implantation, all patient groups significantly improved upper gastrointestinal symptoms. The bariatric surgery group and Nissen fundoplication group specifically identified anorexia as the most severe symptom after GES after temporary GES placement among 3 groups (2.5 [0.4–3.5] and 1.5 [0.0–2.5], respectively). Nissen fundoplication patients had the highest score of anorexia among the 3 groups 6 months after GES (3.0 [2.0–3.5], P = .018). Despite these improvements, GES did not enhance gastric emptying test results. Symptomatic improvements were notably significant in patients who initially reported higher symptom severity than those who did not. ConclusionGES shows promise in alleviating symptoms of refractory postsurgical gastroparesis, particularly in those with severe initial symptoms. However, its impact on gastric emptying remains inconclusive. Further research is needed to establish GES as a standard treatment for postsurgical gastroparesis.

Low-Resolution Electrogastrogram at Baseline and Response to Temporary Gastric Electrical Stimulation—A Comparison of Cutaneous With Mucosal Recordings

IntroductionGastric electrical stimulation (GES) is a widely accepted therapy for gastroparesis symptoms, but how a brief cutaneous electrogastrogram (EGG) can be used in conjunction with GES has not been well defined. We evaluated the clinical importance of EGG, its correlation with mucosal electrograms (mEGs), gastric emptying tests (GETs), and gastrointestinal symptoms before and after temporary GES (tGES). Materials and MethodsWe studied 1345 patients; 991 had complete data. EGG measurements like frequency and amplitude were recorded at baseline and five days post-tGES using short recording periods. A total of 266 participants having additional cutaneous propagation values were separately analyzed. Patients underwent solid GET before and after tGES and self-reported symptoms using standardized traditional patient-reported outcomes (TradPRO) scores. Pearson correlations were assessed at baseline, post-stimulation, and their changes over the follow-up period. ResultsEGG measures correlated with symptoms and GET results. Patients with abnormal baseline cutaneous frequency had higher baseline total symptom scores (p < 0.003). Post-tGES, one-hour gastric emptying was significantly changed (p < 0.0001) and was mainly observed with abnormal baseline cutaneous frequencies (p < 0.0001). Cutaneous frequency significantly increased after tGES (p < 0.0001), correlating positively with TradPRO scores and one-hour gastric emptying. Mucosal and cutaneous measures correlated pre- and post-treatment. Of the 266 patients, 153 changed propagation states between baseline and temporary; changing states from lower at baseline to higher at temporary was more likely than vice versa. Short EGG recording times can demonstrate changes after the bioelectric therapy of GES. ConclusionEGG is valuable in the diagnosis of delayed gastric emptying and comparable with mEG. It is less invasive and can identify patients who may require GES. Frequency, amplitude, their ratio (frequency-amplitude ratio), and propagation appear to be reliable measures of EGG. EGG provides cost-effective measurement of electrophysiological properties and significantly correlates with important clinical measures. Shorter EGG recording times may be adequate to see changes from bioelectric therapies. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT03876288.

Baseline predictive factors for foregut and hindgut response to long-term gastric electrical stimulation using augmented energy.

Gastric electrical stimulation (GES) has been recommended for drug refractory patients with gastroparesis, but no clear baseline predictors of symptom response exist. We hypothesized that long-term predictors to GES for foregut and hindgut symptoms exist, particularly when using augmented energies. We evaluated 307 patients at baseline, 1week post temporary GES, and one year after permanent GES. Baseline measures included upper and lower symptoms by patient-reported outcomes (PRO), solid and liquid gastric emptying (GET), cutaneous, mucosal, and serosal electrophysiology (EGG, m/s EG), BMI, and response to temporary stimulation. Foregut and hindgut PRO symptoms were analyzed for 12-month patient outcomes. All patients utilized a standardized energy algorithm with the majority of patients receiving medium energy at 12months. Patients were categorized based on change in average GI symptom scores at the time of permanent GES compared to baseline using a 10% decrease over time as the cutoff between improvers versus non-improvers. By permanent GES implant, average foregut and hindgut GI symptom scores reduced 42% in improved patients (n=199) and increased 27% in non-improved patients (n=108). Low BMI, baseline infrequent urination score, mucosal EG ratio, and proximal mucosal EG low-resolution amplitude remained significant factors for improvement status. GES, for patients responding positively, improved both upper/foregut and lower/hindgut symptoms with most patients utilizing higher than nominal energies. Low baseline BMI and the presence of infrequent urination along with baseline gastric electrophysiology may help identify those patients with the best response to GES/bio-electric neuromodulation.

Gastric electrical stimulation improves symptoms and need for supplemental nutrition in children with severe nausea and vomiting: A ten-year experience.

Gastric electrical stimulation (GES) is a promising therapy for children with severe nausea and vomiting, but information on long-term outcomes is limited. We sought to evaluate the long-term efficacy and safety of GES and to describe patient benefit and satisfaction. Using a prospective registry, we identified patients aged <21years treated with GES at our institution between 2009 and 2019. Encounters were selected at baseline prior to GES and at follow-up at 1month, 12months, and the most recent visit. We compared symptoms, route of nutrition, and medication usage at baseline to follow-up timepoints. Factors associated with improvement were evaluated. We recorded complications and need for battery replacement. We contacted families to administer the Glasgow Children's Benefit Inventory (GCBI) and a parent satisfaction questionnaire. Eighty-five patients (68.2% female, median age 15.8years) completed a trial of temporary GES due to severe nausea and vomiting. Seventy-seven (90.6%) had a positive response and underwent permanent stimulator placement. Use of tube feeding or parenteral nutrition (PN) decreased from 72.7% at baseline to 29.9% at the most recent follow-up (p<0.001). Higher baseline vomiting severity was associated with the ability to stop supplemental nutrition by 1month (p<0.05). Fourteen patients (18.2%) had complications, primarily due to stimulator-associated discomfort, and 29 (37.7%) required battery replacement. Median GCBI was +52.1, indicating health-related benefit. Children with severe nausea and vomiting treated with GES experienced significant and durable improvement in symptom severity and their ability to tolerate oral nutrition.

116 – Electrogastography At Baseline and Response to Temporary Gastric Electrical Stimulation – a Comparison of Cutaneous with Mucosal Recordings

116 – Electrogastography At Baseline and Response to Temporary Gastric Electrical Stimulation – a Comparison of Cutaneous with Mucosal Recordings

Gastroparesis syndromes: Response to electrical stimulation

Factors underlying gastroparesis are not well defined, nor is the mechanism of action of gastric electrical stimulation (GES). We hypothesized that GES acts via several mechanisms related to underlying disordered pathophysiology. We studied 43 consecutive eligible patients with gastroparetic symptoms, previously evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal; and also categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. We then studied 41 patients who underwent temporary GES for 5-7days. Thirty-six of those patients were implanted and 30 were followed up at 6months after permanent GES. In previous but separately reported work, patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status and all patients demonstrated abnormalities in each of the five areas studied. After GES, patients showed early and late effects of electrical stimulation with changes noted in multiple areas, categorized by improvement status. Patients with symptoms of gastroparesis have multiple abnormalities, including systemic inflammation and disordered hormonal status. GES affects many of these abnormalities. We conclude electrical stimulation improves symptoms and physiology with (a) an early and sustained anti-emetic effect; (b) an early and durable gastric prokinetic effect in delayed emptying patients; (c) an early anti-arrhythmic effect that continues over time; (d) a late autonomic effect; (e) a late hormonal effect; (f) an early anti-inflammatory effect that persists; and (g) an early and sustained improvement in health-related quality of life. This study is registered with Clinicaltrials.gov under study # NCT03178370 (https://clinicaltrials.gov/ct2/show/NCT03178370).

Ambulatory gastric mucosal slow wave recording for chronic experimental studies.

Dysrhythmic bioelectric slow wave activity have been implicated in major functional motility disorders such as gastroparesis and chronic unexplained nausea and vomiting, but its correlation to symptoms is still unclear. For patients with severe gastroparesis, high-frequency gastric stimulation is offered as a therapy in some centers. Temporary gastric electrical stimulation has also been proposed an approach to screen patients who would benefit from the implantation of a permanent stimulator. In this study we introduced novel methods for recording slow wave activity from the gastric mucosa during the entire temporary stimulation phase of 5 days, in 3 patients. An ambulatory recording system was applied to record 3 channels of mucosal slow wave activity, as well as three axis accelerometer data to monitor when the patient was mobile. Techniques were developed to detect large movements and these time periods were excluded from analyses of mucosal slow waves. The frequency and amplitude of the slow waves was calculated in a 5 min segment, with 75% overlap, for the entire duration. In feasibility studies, the slow wave frequency and amplitude for the patients were 3.0±0.96 cpm and 1.43±1.75 mV. Large variations in slow wave amplitude were seen in comparsion to slow wave frequency, which were concordant with previous studies. The use of the ambulatory system will allow for investigation of pathophysiology, correlation of electrophysiology data to patient symptoms and to determine the effects of post-prandial and noctural slow wave patterns. We anticipate that future use of slow wave information alongside patient symptoms may allow improved selection of patients for stimulaton techniques.

Gastric Electrical Stimulation Is an Option for Patients with Refractory Cyclic Vomiting Syndrome.

Background/AimsCyclic vomiting syndrome (CVS) is a disabling migraine variant manifesting as severe episodes of nausea and vomiting and often refractory to many therapies. Gastric electrical stimulation (GES), which can reduce nausea and vomiting in gastroparesis, may provide symptomatic relief for drug-refractory CVS. This study assessed the utility GES in reducing the symptoms of CVS and improving the quality of life.MethodsA one-year, non-randomized, clinical study was conducted. Eleven consecutive patients with drug refractory, cyclic vomiting syndrome based on Rome III criteria and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), underwent treatment with temporary GES (Temp GES) and permanent GES (Perm GES). Post-treatment follow up was done up to one year after permanent gastric electrical stimulation therapy.ResultsTotal symptom score decreased by 68% and 40% after temporary and permanent GES therapies, respectively. Hospital admission events significantly decreased to 1.50 (± 1.00) events from 9.14 (± 7.21) annual admissions prior to treatment with permanent GES. Vomiting episodes fell by 83% post Temp GES and 69% after Perm GES treatments. Mucosal electrogram values also changed after temporary stimulation.ConclusionsIn a small group of drug-refractory CVS patients, treatments with temporary and permanent GES significantly reduced the severity of gastrointestinal symptoms and frequency of hospital admissions.

Treating an oft-unrecognized and troublesome entity: using gastric electrical stimulation to reduce symptoms of malignancy-associated gastroparesis.

Malignancy-associated gastroparesis (MAG) is a cause of morbidity in cancer patients but therapies are lacking. Gastric electrical stimulation (GES) is a novel treatment for MAG. Here, we describe 19 patients with MAG who underwent temporary GES placement. Nineteen patients (6 males, 13 females) with various malignancies were reviewed for symptom scores and physiologic measures at baseline and after temporary GES placement. Symptoms were scored by three variables: nausea (N), vomiting (V), and GI total symptom score (TSS). Physiologic profiles were measured by solid and liquid phase gastric emptying scans (GET) at 1, 2, and 4h and cutaneous electrogastrogram (EGG) and mucosal electrogram (EG) frequencies. Symptoms were measured for 5days after temporary endoscopic GES placement, and measures were repeated post GES placement. Baseline GET results displayed delayed gastric emptying in 16 of 19 patients (mean solid retention 21.7% at 4h, normal <10%; mean liquid retention 10.4% at 4h, normal <5%). Cutaneous EGG (mean frequency 5.5cpm) and EG (mean proximal frequency 5.1cpm; mean distal frequency 5.1cpm) showed evidence of neuromuscular dysfunction (normal 2.5-3.3cpm). Symptom scores in N, V, and TSS showed statistically significant reduction after GES placement. A small sample of patients with MAG and receiving temporary GES experienced symptom improvement, with less change on gastric emptying time or gastric electrical amplitude or frequency. GES may provide a potential therapeutic option for symptomatic management of MAG and evaluation of these MAG patients after permanent GES placement is ongoing. Prospective studies of MAG using temporary and permanent GES may be warranted.

Sa1690 Comparison of Neurohormonal Changes With Gastroparesis in Response to Temporary Gastric Electrical Stimulation

Sa1690 Comparison of Neurohormonal Changes With Gastroparesis in Response to Temporary Gastric Electrical Stimulation

Expanding Indications of Gastric Electrical Stimulation

Gastroparesis is a chronic motility disorder that delays, in the absence of mechanical obstruction, the occurrence of gastric emptying. The most common forms come with idiopathic, diabetic, and post-surgical complications. Delayed gastric emptying has been focused on as the main pathophysiologic abnormality manifested by gastroparesis. Other mechanisms, including loss of neuronal nitric oxide synthase and loss of the interstitial cells of Cajal, are coming to be widely recognized.1 The operative mechanisms of gastric motility are heterogeneous and only incompletely understood. Current medical treatment options are classified as either prokinetics or symptom modulators such as antiemetics.2 Unfortunately, these have failed to effect any remarkable progress in the last 30 years. A promising alternative treatment option for medically refractory gastroparesis is gastric electrical stimulation (GES). In the late 1990s, GES-manipulated gastric pacing improved symptoms in patients with gastroparesis and accelerated gastric emptying.3 Later, in 2003, surgical insertion of a pair of electrodes with subcutaneous positioning of a neurostimulator in the abdominal wall reduced vomiting frequency in gastroparetic patients.4 Then, in 2005, placement of temporary GES electrodes via both endoscopic and percutaneous endoscopic gastrostomy showed rapid, significant, and sustained symptom improvement in patients with refractory gasroparesis.5 Apart from gastroparesis, GES will be clinically significant therapy in the treatment for morbid obesity. GES for 6 months improved glucose control, and induced weight loss in obese type 2 diabetes patients.6 Fecal incontinence, and constipation can be possible clinical applications using electrical stimulation of the gastrointestinal tract.7 In this issue of the Journal of Neurogastroenterology and Motility, Singh et al8 report on the effects of temporary GES in gastroparesis-like syndrome (GLS). The aim of their prospective study was to explore the effects of endoscopy-based temporary GES in patients showing symptoms of gastroparesis with non-delayed gastric emptying. First, the authors tried temporary GES as a therapeutic option for patients with GLS. GLS patients can show symptoms of gastroparesis but without delays in gastric emptying.9 In fact, it is generally known that symptom severity in gastroparesis correlates poorly with the grade of gastric emptying delay. In a study on diabetes and upper-gastrointestinal symptoms, the scintigraphy results showed that 42% of the patients had normal, 36% delayed, and 22% rapid gastric emptying.10 The benefits of temporary GES relative to permanent GES are fewer side effects such as infection, lead dislodgement, and migration of the device, as well as the ability to predict the treatment effect before committing to permanent GES. Diabetic patients with refractory nausea and vomiting as their predominant symptoms seem to be the best candidates for temporary GES. Unfortunately, an individual’s response to temporary GES remains unpredictable.11 The authors indicated that temporary GES improved nausea, vomiting, and total symptom scores without accelerating gastric emptying. However, they did not consider abdominal pain, another common symptom of gastroparesis, as a parameter after insertion of the temporary GES electrode pair and neurostimulator. Another factor to consider is the temporary placebo effects of GES in this study. Patients’ psychiatric history and medication history for anti-psychotic drugs should be considered. In addition, most of the patients (80%) in the study were females, and females typically have a higher probability of having a functional gastrointestinal disorder than males. Second, the authors found that temporary GES improved the symptoms in the patients with rapid gastric emptying by normalizing their gastric emptying, though they could not identify the exact mechanism. For those patients, transient GES is another possible treatment option. Third, the authors demonstrated the prevalence of GLS among their patients. As many as 40% of their patients with refractory nausea and vomiting had GLS. Indeed, gastroparesis appears to be just the tip of a large hidden iceberg.12 Gastrointestinal symptoms, for example, are common in patients with diabetes.13 It has been reported that among symptomatic diabetic patients for over 10 years, gastroparesis developed in 5.2% (Type 1 diabetes), 1.0% (Type 2 diabetes), and 0.2% (controls).14 Meanwhile, in a Korean population-based study, 13% of type 2 diabetic patients showed dyspeptic symptoms.15 Furthermore, as the incidence rate of diabetes rises, so too with that of gastroparesis. In summary, the symptoms of gastroparesis and the grade of gastric emptying are not as yet clearly correlated. The study by Singh et al showed that endoscopy-based temporary GES improved the total symptom scores in both non-delayed gastric emptying and delayed gastric emptying patients. With the help of the authors’ work, GES is expanding its indications. Temporary GES might be useful in patients with nausea and vomiting who are intolerant to medical treatment despite having non-delayed gastric emptying. It also can provide pivotal information regarding the decision to adopt permanent GES for patients with refractory gastroparesis.

Temporary Endoscopic Stimulation in Gastroparesis-like Syndrome.

Background/AimsGastroparesis-like syndrome (GLS) is defined as gastroparesis-like symptoms with normal gastric scintigraphy. While the efficacy of gastric electrical stimulation (GES) in gastroparesis is well known, the utility of GES in GLS is largely unknown. Our aim was to clarify the role of GES in GLS. We implanted consecutive patients with symptoms of gastroparesis with temporary gastric electrical stimulation and observed changes in gastric scintigraphy and total symptom score.MethodsFive hundred and fifty-one patients suffering from symptoms of gastroparesis (nausea, vomiting, bloating/distension, anorexia/early satiety, and abdominal pain) with negative endoscopy underwent gastric scintigraphy with analysis of 1) solid radio-nuclide gastric emptying at 1, 2, and 4 hours (% remaining); 2) area under the gastric emptying curve (AUC) at 1, 2, and 4 hours; and 3) total gastric emptying test (GET) (the sum of 1, 2, and 4 hour values). Patients were stratified into: delayed gastric emptying, normal gastric emptying, and rapid gastric emptying (Appendix). Of the 551 patients in the larger cohort, 379 had implantation of temporary gastric electrical stimulation (tGES). Gastrointestinal symptoms and gastric emptying were com -pared pre and post tGES implantation.ResultsAfter tGES, 2 hour gastric retention decreased (P < 0.01) for the delayed patients, and increased (P < 0.001) for normal and rapid patients. These changes were accompanied by improvements (P < 0.001) in vomiting, nausea, and total symptom scores in all 3 subgroups.ConclusionsGastric electrical stimulation may be an effective therapy for treating the symptoms of gastroparesis with normal gastric emptying. Further exploration of endoscopic electrical stimulation as a treatment for gastroparesis-like symptoms with non-delayed gastric emptying is needed.

Tu1210 Long Term Symptom Outcome After an Evidence Based Medicine Trial of Gastric Electrical Stimulation

Background: We previously published (GIE 2011; 74: 496-503) an evidence based medicine study (CTRN 00432835) designed to evaluate the capacity of a 72 hour course of temporary mucosal gastric electrical stimulation (GES) to reduce nausea and vomiting, as well as other symptoms associated with the syndrome of gastroparesis. Following this study, we examined the outcomes data available from our long term clinical care of patients enrolled in the original trial subsequently implanted with permanent GES devices. Methods: Of the 58 patients in the original cross-over trial, 38 were approved by insurers and returned for permanent GES. The mean patient age was 46 years, 78% were female, 68% white, with 30% diabetic and 70% non-diabetic status. Average follow-up time in our clinical records was 4.1 years, with a maximum follow-up of 5.5 years (61% returned for 6-month followup, 71% for 12-month follow-up, and 63% for follow-up between 2.2 and 5.5 years after permanent stimulator placement). We employed a linear mixed model (random intercept), empirical Bayes approach to use the full longitudinal outcome trajectories in estimating patient-specific average long-term symptom levels after permanent placement. We then examined relationships between patient-specific final results with temporary stimulation (ON phase) during the trial and patient-specific, average long-term symptom levels. Results: Positive relationships between short-term and long-term outcomes existed, with significant associations for the Nausea and Total Symptom Score measures. We noted that 76% of the patients had no vomiting (Final Temp GES vomiting score=0) after 72 hours of temp GES, which, though a positive result from the original trial, interferes with our ability to determine associations with long-term outcomes due to minimal variation in the predictor of Vomiting (x-axis). For each unit increase in final temporary GES symptom Nausea, long-term Nausea outcomes showed associated increases of 0.3 units, 95% CI (0.02, 0.32) p=0.030. TSS showed similar significant associations between short and long-term outcomes, with a positive association of 2.1 units, (0.1, 4.1) p=0.045 (Figure 1). Gastric emptying tests (GET) for the whole group of patients changed little with temporary stimulation but did improve with long term GES, although the results were not statistically significant (Table 1). Conclusion: Long term follow up of a temporary double masked trial of endoscopic GES shows good correlation with the original symptoms improvements. We conclude that a trial of temporary GES can predict long term permanent GES outcome in patients with the symptoms of gastroparesis. Gastric motility measures pre and post treatment with GES: (N=37)

Su1421 The Electrogastrogram Analysed by Quantitative Signal Averaging Can Detect Changes Induced by Temporary Gastric Electrical Stimulation

Su1421 The Electrogastrogram Analysed by Quantitative Signal Averaging Can Detect Changes Induced by Temporary Gastric Electrical Stimulation

Su1422 Autonomic and Enteric Responses to Temporary Gastric Electrical Stimulation

Su1422 Autonomic and Enteric Responses to Temporary Gastric Electrical Stimulation

Mo1298 One-Year Response Rate to Gastric Electrical Stimulation in Patients Selected for Treatment by Temporary Percutaneous Gastric Electrical Stimulation

Mo1298 One-Year Response Rate to Gastric Electrical Stimulation in Patients Selected for Treatment by Temporary Percutaneous Gastric Electrical Stimulation

Sa1340 Proximal Gastric Measurements May Predict Clinical Response in Patients With Nausea and Vomiting Undergoing Temporary Endoscopic Gastric Electrical Stimulation

Sa1340 Proximal Gastric Measurements May Predict Clinical Response in Patients With Nausea and Vomiting Undergoing Temporary Endoscopic Gastric Electrical Stimulation

Mo1303 Low Resolution Gastric Mucosal Mapping Correlates With ICC Values in Patients Undergoing Temporary Gastric Electrical Stimulation

Mo1303 Low Resolution Gastric Mucosal Mapping Correlates With ICC Values in Patients Undergoing Temporary Gastric Electrical Stimulation

To audit the use of temporary gastric electrical stimulation in selecting patients with intractable gastroparesis for treatment with permanent gastric electrical stimulation

To audit the use of temporary gastric electrical stimulation in selecting patients with intractable gastroparesis for treatment with permanent gastric electrical stimulation

Gastric Electrical Stimulation for Abdominal Pain in Patients with Symptoms of Gastroparesis

Abdominal pain physiology may be better understood studying electrophysiology, histology, and symptom scores in patients with the symptoms of gastroparesis (Gp) treated with gastric electrical stimulation (GES). Ninety-five Gp patients' symptoms were recorded at baseline and during temporary and permanent GES. Gastric-emptying times and cutaneous, mucosal, and serosal electrogastrograms were obtained. S100-stained, full-thickness gastric biopsies were compared with autopsy controls. Sixty-eight patients reported severe pain at baseline. Severe pain patients' mean pain scores decreased with temporary GES from 3.62 to 1.29 (P < 0.001) and nonsevere pain from 1.26 to 0.67 (P = 0.01). With permanent GES, severe mean pain scores fell to 2.30 (P < 0.001); nonsevere pain changed to 1.60 (P = 0.221). Mean follow-up was 275 days. Mean cutaneous, mucosal, and serosal frequencies and frequency-to-amplitude ratios were markedly higher than literature controls. For patients with Gp overall and subdivided by etiology and severity of pain, S-100 neuronal fibers were significantly reduced in both muscularis propria layers. GES improved severe pain associated with symptoms of Gp. This severe pain is associated with abnormal electrogastrographic activity and loss of S100 neuronal fibers in the stomach's inner and outer muscularis propria and, therefore, could be the result of gastric neuropathy.