Measures of Autonomic Dysfunction in Diabetic and Idiopathic Gastroparesis.

BACKGROUND: Gastroparesis is a condition classically characterized by delayed gastric emptying and is associated with considerable morbidity. While the etiology of gastroparesis remains elusive, autonomic dysfunction may play an important role, especially as many patients with gastroparesis also have diabetes. The aim of this study was to determine whether measures of autonomic function differ between adults with diabetic gastroparesis (DG) and adults with idiopathic gastroparesis (IG). METHODS: Tests of systemic autonomic function were performed among 20 adults with GD (six men and 14 women, mean age: 42 years) and 21 adults with IG (seven men and 14 women, mean age: 37 years). Measures included vagal cholinergics by R-R interval percentage variation (RRI-PV) and sympathetic adrenergics by vasoconstriction to cold (VC) and postural adjustment ratio (PAR). The two groups were compared using Wilcoxon rank sum tests and linear regression analysis (STATA 10.0). RESULTS: In univariate analysis, the following autonomic measures differed significantly between DG and IG: VC (P = 0.004), PAR (P = 0.045), VC + PAR (P = 0.002) and RRI-PV (P < 0.001). In multivariate analysis (P = 0.002, R2 = 0.55), only RRI-PV (adjusted odds ratio (aOR): 1.02, 95% confidence interval (CI): 1.01 - 1.03) differed significantly between DG and IG patients. CONCLUSIONS: Vagal cholinergics are affected to a greater degree in DG compared to IG, suggesting that impaired vagal tone is not a universal mechanism for gastroparesis.

Sweat pore reactivity as a surrogate measure of sympathetic nervous system activity in trauma-exposed individuals with and without posttraumatic stress disorder.

Stress analysis by FLIR (forward-looking infrared) evaluation (SAFE) has been demonstrated to monitor sweat pore activation (SPA) as a novel surrogate measure of sympathetic nervous system (SNS) activity in a normal population. SNS responses to a series of 15 1-s, 82 dB, white noise bursts were measured by skin conductance (SC) and SAFE monitoring of SPA on the fingers (FiP) and face (FaP) in 10 participants with posttraumatic stress disorder (PTSD) and 16 trauma-exposed participants without PTSD (Mage = 48.92 ± 12.00 years; 26.9% female). Within participants, SC and FiP responses across trials were strongly correlated (r = .92, p < .001). Correlations between SC and FaP (r = .76, p = .001) and between FiP and FaP (r = .47, p = .005) were smaller. The habituation of SNS responses across the 15 trials was substantial (SC: d = -2.97; FiP: d = -2.34; FaP: d = -1.02). There was a strong correlation between habituation effects for SC and FiP (r = .76, p < .001), but not for SC and FaP (r = .15, p = .45) or FiP and FaP (r = .29, p = .16). Participants with PTSD showed larger SNS responses to the first loud noise than those without PTSD. PTSD reexperiencing symptoms assessed by the PTSD Checklist on the day of testing were associated with the SNS responses to the first loud noise measured by SC (d = 1.19) and FiP (d = .99), but not FaP (d = .10). This study confirms convergence of SAFE and SC as valid measures of SNS activity. SAFE FiP and SC responses were highly predictive of self-rated PTSD reexperiencing symptoms. SAFE may offer an attractive alternative for applications in PTSD and similar populations.

Autonomic and Enteric Nervous System Dysfunction May Play a Role in Hyperemesis Gravidarum.

BACKGROUND: Nausea and vomiting, seen in 70-85% of all pregnancies, becomes intractable in hyperemesis gravidarum (HG). We aimed to investigate the relationship between HG and autonomic nervous system functioning and gastric electrical activity. METHODS: Twenty-seven pregnant patients, 21 with HG and six normal, were studied with sympathetic adrenergic; percent vasoconstriction (%VC) and postural adjustment ratio (PAR); parasympathetic vagal cholinergic functions by R-to-R intervals (RRIs), a total autonomic score; and enteric nervous system measured by electrogastrography (EGG). RESULTS: Significant differences were found in parasympathetic measures (RRI for HG 29.98 ± 2.95 vs. control 40.91 ± 2.38, P < 0.05); sympathetic PAR was significantly lower in patients (PAR for HG 24.5 ± 5.0 vs. 67.6 ± 11.4 for controls, P < 0.01); mean total autonomic score was significantly lower in HG (131.75 ± 9.61 vs. 196.87 ± 12.8, P < 0.05). EGG results were borderline different (normal < 3.3, HG 3.4 vs. controls 3.0, P = 0.07). CONCLUSION: Autonomic and enteric nervous system dysfunction may play a role in the pathophysiology of HG.

Electrophysiologic, morphologic, and serologic features of chronic unexplained nausea and vomiting: lessons learned from 121 consecutive patients.

BACKGROUND: Despite substantive morbidity, unexplained nausea and vomiting has not been evaluated in a systematic manner via surgically obtained biopsies and direct electrophysiology of the gut, and this information has not been correlated with serologic information. We investigated consecutive patients with unexplained and refractory chronic nausea and vomiting to define the presence of morphologic, physiologic, and/or serologic abnormalities. METHODS: In all, 101 of 121 consecutive patients who experienced chronic nausea and vomiting of unknown etiology evaluated in 1 tertiary referral center over a 10-year period were profiled qualitatively by full-thickness small bowel biopsies with hematoxylin and eosin (H&E) and Smith's Silver stains, quantitatively by intraoperative gastric electrophysiology, and semiquantitatively, when it became available, by serum autoimmune Western blot analysis. RESULTS: Overall, 79 of 101 patients had abnormal full-thickness biopsy (70 neuropathies and 9 myopathies) and frequent serum autoimmune abnormalities (mean score = 13.2, normal < 3.0). In addition, 96 of 101 patients had abnormal frequency and/or uncoupling on gastric electrophysiology. Patients with small-intestinal myopathy showed a diversity of diagnoses; some patients with neuropathy had abdominal pain that correlated with autoimmune scores on Western blot. CONCLUSION: Patients with refractory and unexplained nausea and vomiting have a high incidence of both small bowel morphologic abnormalities (primarily neuropathies) and gastric electrophysiologic abnormalities, which are associated commonly with serologic autoimmune activation. Similar histomorphologic, physiologic, and serologic measures should be considered in the diagnostic evaluation of any patient with refractory or unexplained nausea and vomiting.

Gastric electrical stimulation is safe and effective: a long-term study in patients with drug-refractory gastroparesis in three regional centers.

BACKGROUND: Drug-refractory gastroparesis has previously been without acceptable alternative therapies. Although gastric electrical stimulation has been used for over a decade, no long-term multicenter data exist. METHODS: We studied 214 consecutive drug-refractory patients with the symptoms of gastroparesis (146 idiopathic, 45 diabetic, 23 after surgery) who consented to participate in a variety of clinical research and clinical protocols at three centers from January 1992 through January 2005, resulting in 156 patients implanted with a gastric electrical stimulation device and the other 58 patients serving as controls. The patients were stratified into three groups: (1) consented but never permanently implanted; (2) implanted with permanent device, and (3) consented while awaiting a permanent device. The patients were followed over time for gastrointestinal symptoms, solid gastric emptying, health-related quality of life, survival, device retention, and complications. Demographics, descriptive statistics, and t tests were used for comparison between baseline and latest follow-up. RESULTS: At latest follow-up, median 4 years for 5,568 patient months, most patients implanted (135 of 156) were alive with intact devices, significantly reduced gastrointestinal symptoms, and improved health-related quality of life, with evidence of improved gastric emptying, and 90% of the patients had a response in at least 1 of 3 main symptoms. Most patients explanted, usually for pocket infections, were later reimplanted successfully. There were no deaths directly related to the device. CONCLUSION: Based on this sample of patients, implanted with gastric electrical stimulation devices at three centers and followed for up toward a decade, gastric electrical stimulation for drug-refractory gastroparesis is both safe and effective.

Gastric electrical stimulation has an immediate antiemetic effect in patients with gastroparesis.

BACKGROUND: Electrical stimulation has been successfully employed to treat diseases involving electro-pathology in the heart, skeletal muscles, and the brain, but not in the GI tract. AIM: This study examined the clinical feasibility and efficacy of GES in treating patients with severe gastroparesis. METHODS: Nausea, vomiting, GEA, and liquid and solid gastric emptying were monitored in eleven patients with refractory gastroparesis at baseline and after one week of continuous electrical stimulation administered at 12 cycles/min. Eight patients were subsequently implanted with permanent stimulation devices. Follow-up studies were conducted after 1, 3, 6, and 12 mo. of stimulation. RESULTS: After one week of stimulation, patients' quantified symptoms of nausea and vomiting decreased significantly, and liquid emptying and GEA improved. This improvement was maintained over time in the patients who continued to receive stimulation. Emptying of solids showed progressive improvement that became significant after 3 mo. The three patients who did not receive stimulation after the trial period showed significantly higher symptoms at 12 mo. CONCLUSION: This paper demonstrates that GES at a frequency of 12 cycles/min has an immediate antiemetic effect, followed by an improvement in disordered gastric emptying.

Pilot study on gastric electrical stimulation on surgery-associated gastroparesis: long-term outcome.

OBJECTIVES: Patients with postgastric surgery gastroparesis are often unresponsive to conventional medical therapy. Gastric electrical stimulation (GES) with the use of high-frequency and low-energy neural stimulation is an approved technique for patients with idiopathic and diabetic gastroparesis. METHODS: We hypothesized that GES would improve symptoms, health resource utilization, and gastric emptying in six patients with postsurgical gastroparesis from a variety of surgical procedures. Patients were evaluated by means of the following criteria: symptoms, health-related quality of life, and gastric emptying tests at baseline over time. RESULTS: All patients noted improvements after device implantation for up to 46 months: the frequency score for weekly vomiting went from a baseline of 3.2 down to 0.4 immediately after treatment before settling at 1.4 by the long-term follow up. Total gastrointestinal symptom score went from 36.5 at baseline down to 12.3 before settling at 20.5 at long-term follow up. Improvements were also seen in health-related quality of life and solid and liquid gastric emptying. CONCLUSIONS: We conclude that GES is associated with clinical improvements in this group of patients with either postsurgical or surgery-associated gastroparesis. This pilot study with long-term outcomes offers evidence for a new therapy for otherwise refractory patients with gastroparesis associated with previous surgery.

Driving gastric electrical activity with electrical stimulation.

Gastric electrical stimulation (GES) therapy is generating a lot of interest, but it is still investigational. Its efficacy in driving gastric electrical activity and improving motility, and the ideal frequency for bringing this about are still controversial. In this study, a rule-based computer model of tissue electrical response to stimulation was developed to examine the interaction between tissue electrical refractoriness and the onset of tissue activation. The results were compared to response to GES in 8 dogs implanted with electrodes and strain gauges and stimulated at frequencies ranging from 3 to 30 cycles/min. Simulated electrical control activity at an intrinsic frequency of 5/min was entrained from 2.0 cycles/min to 7.92 cycles/min. The regularity of the ECA elicited by stimulation depended on the number of pulses injected. Electrical stimulation in canine stomach entrained the native electrical control activity from a baseline average of 5.14 +/- 0.32 cycles/min up to 9.2 cycles/min. Contractile response to stimulation at 20-30 cycles/min were significantly higher (p < 0.05). Computer simulation of GES may be a useful tool to complement and reduce some of the costs associated with empirical studies of gastric electrical stimulation in establishing its possible use in treating drug refractory gastroparesis.

Temporary gastric electrical stimulation with orally or PEG-placed electrodes in patients with drug refractory gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) has been shown to be efficacious for drug refractory gastroparesis, but GES requires surgery. Placement of temporary GES electrodes endoscopically (ENDOstim) or via a PEG (PEGstim) is feasible, thereby allowing rapid assessment and comparison of temporary use (TEMP) with permanent (PERM) implantation. METHODS: Twenty consecutive patients with gastroparesis had TEMP electrodes placed (6 ENDOstim, 14 PEGstim). TEMP alone and TEMP vs. PERM placement of GES devices in 13 of 20 patients were compared via the following: average vomiting frequency score (VFS), total symptom score, days to symptom improvement, electrode impedance, and gastric emptying test. RESULTS: For patients receiving TEMP, GES demonstrated a rapid, significant, and sustained improvement in VFS, results similar to those for PERM. CONCLUSIONS: Both ENDO and PEG placement of GES electrodes are safe and effective in patients with gastroparesis, with outcomes that correspond to those achieved with permanent GES implantation.

Gastric electrical stimulation in intractable symptomatic gastroparesis.

BACKGROUND: The treatment of gastroparesis remains unsatisfactory despite prokinetic and anti-emetic drugs. Gastric electrical stimulation has been proposed as a therapeutic option. We have assessed the effect of gastric electrical stimulation on symptoms, medical treatment, body weight and gastric emptying in patients with intractable symptomatic gastroparesis in a non-placebo-controlled study. METHODS: In this multicenter study, 38 highly symptomatic patients with drug-refractory gastroparesis were enrolled. Patients first received temporary electrical stimulation using percutaneous electrodes. The 33 responders to temporary stimulation then underwent surgical implantation of a permanent stimulator. Severity of vomiting and nausea was assessed before and after stimulation. Patients were reassessed 3, 6, and 12 months after permanent implantation. RESULTS: With stimulation, 35/38 patients (97%) experienced >80% reduction in vomiting and nausea. This effect persisted throughout the observation period (2.9-15.6 months, 341 patient-months). Gastric emptying did not initially change, but improved in most patients at 12 months. At 1 year, the average weight gain was 5.5% and 9/14 patients initially receiving enteral or parenteral nutrition were able to discontinue it. CONCLUSION: Electrical stimulation of the stomach has an immediate and potent anti-emetic effect. It offers a safe and effective alternative for patients with intractable symptomatic gastroparesis.