Archana Kedar

Gastric stasis in migraineurs: Etiology, characteristics, and clinical and therapeutic implications

Background Migraine is a disabling neurological disorder often complicated by gastrointestinal conditions such as gastric stasis. The association between migraine and gastric stasis has received very little attention in the literature, but the existing evidence suggests that they may share a common etiology. Results Patients with migraine and those with gastric stasis exhibit abnormal autonomic nervous system function. Furthermore, empirical studies demonstrate that migraineurs experience significant delays in gastric emptying, both during and outside of attacks, when compared to non-migrainous controls. Conclusion More research is needed to establish the relationship between gastric stasis and migraine burden and to determine the impact of gastric stasis on migraine treatment.

Long-term outcomes of gastric electrical stimulation in children with gastroparesis

BACKGROUND Gastric electrical stimulation (GES) has been used in adults with gastroparesis. However its use has been limited in children. We describe the largest experience with GES in children with long-term outcomes. METHODS Data were collected on children who underwent GES over a 10-year period. Data regarding demographics, medical history, hospital course, and outcomes were collected and analyzed. Symptom scores (validated Likert scores) were compared using a paired Students t test. RESULTS Overall, 97 patients underwent GES, and a majority were teenage Caucasian girls. Ninety-six had temporary GES (tGES), and 66 had improvement in their symptoms. A total of 67 underwent permanent implantation (pGES), and there was significant reduction in all individual symptoms (p<0.001) as well as the total symptom score (TSS) (p<0.0001) at 1, 6, 12, and >12 months. Recurrence of symptoms leading to device removal occurred in 7 cases. Forty-one patients had continued improvement in symptoms for over 12 months, with a mean follow-up of 3.5 years (range 1-9 years). CONCLUSIONS This study represents the largest experience of systematic application of GES in children. GES is a safe and effective therapy for selected children with intractable GP with continued symptomatic improvement at 1 year and beyond.

Serum Catecholamines and Dysautonomia in Diabetic Gastroparesis and Liver Cirrhosis

Background:Plasma catecholamine influences autonomic function and control, but there are few reports correlating them. In this study, 47 individuals (mean age, 38 years) were studied: 19 diabetes mellitus (DM) patients with gastroparesis, 16 with liver disease and 12 control subjects. Methods:Noninvasive autonomic function was assessed for sympathetic adrenergic functions as peripheral vasoconstriction in response to cold stress test and postural adjustment ratio (PAR) and cholinergic function as Valsalva ratio, represented by change in R-R intervals. Measurements were compared by analysis of variance and Spearmans correlation, and results were reported as mean ± standard error. Results:Plasma norepinephrine (1902.7 ± 263.3; P = 0.001) and epinephrine (224.5 ± 66.5; P = 0.008) levels, as well as plasma dopamine levels (861.3 ± 381.7), and total plasma catecholamine levels were highest for patients with liver disease, who also had significant negative correlation between norepinephrine level and vasoconstriction (P = 0.01; r = −0.5), PAR1 (P = 0.01; r = −0.5), sympathetic adrenergic functions (P = 0.005; r = −0.6), total autonomic index (P = 0.01–0.5) and total autonomic function (P = 0.01; r = −0.2) and also negative correlation between epinephrine plasma level and total autonomic function (P = 0.04; r = 0.4). DM patients were next highest in norepinephrine level (133.26 ± 7.43), but lowest for plasma catecholamine; a positive correlation between dopamine level and PAR1 (P = 0.008; r = 0.6) was also seen in this group. Plasma dopamine levels and spider score correlated negatively (P = 0.04; r = −0.5) and total plasma catecholamine positively with encephalopathy (P = 0.04; r = 0.5) in patients with liver disease. Conclusions:Plasma catecholamine levels correlated with adrenergic functions in control subjects and patients with DM and liver disease, with no significant correlation seen for cholinergic function.

Temporary Endoscopic Stimulation in Gastroparesis-like Syndrome.

Background/Aims Gastroparesis-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. Methods Five 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. Results After 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. Conclusions Gastric 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.

Immunomodulation for treatment of drug and device refractory gastroparesis.

Objective Patients with generalized autoimmune dysautonomia may also present with gastroparesis. Immune dysfunction in such patients can be evaluated using antibodies to glutamic acid decarboxylase (GAD) and full thickness biopsy of stomach. In this study, we utilize immunotherapy for treatment of drug and Gastric Electrical Stimulation (GES) resistant gastroparetic patients with evidence of neuroinflammation on full thickness gastric biopsy and had positive GAD65 autoantibodies. Material and methods We conducted a retrospective chart review of 11 female patients with drug and device resistant gastroparesis. Patients were treated for a total of 8–12 weeks with either intravenous immunoglobulin (IVIg), or combined mycophenolate mofetil (MM) and methylprednisolone, or only MM. Patients were excluded if they had previous side effects from steroid therapy, low scores on dual-energy X-ray absorptiometry (DEXA) scan results, immune-compromised conditions with infections like tuberculosis and zoster. Symptoms of nausea, vomiting, abdominal pain, early satiety/anorexia, bloating and total symptom score (TSS) as reported by the patients were recorded before and after the treatment at a follow up visit 2 to 16 weeks after initiation of therapy. Results Maximum symptom improvement was seen in patients treated with IVIg (67%). 6 patients (55%) had improvement in vomiting, whereas 5 patients (45%) had improvements in nausea, abdominal pain and bloating. Conclusions Immunomodulatory therapy shows positive outcomes in improving vomiting symptom in some gastroparetic patients who have coexisting positive autoimmune profiles. This preliminary data suggests the need for further investigations in immunotherapy targeted to patients with gastroparetic symptoms refractory to approved drug and device therapies.

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

Background/Aims Cyclic 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. Methods A 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. Results Total 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. Conclusions In 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.

Autonomic Evaluation of Patients With Gastroparesis and Neurostimulation: Comparisons of Direct/Systemic and Indirect/Cardiac Measures.

Background Disorders of nausea, vomiting, abdominal pain, and related problems often are manifestations of gastrointestinal, neuromuscular, and/or autonomic dysfunction. Many of these patients respond to neurostimulation, either gastric electrical stimulation or electroacupuncture. Both of these therapeutic techniques appear to influence the autonomic nervous system which can be evaluated directly by traditional testing and indirectly by heart rate variability. Methods We studied patients undergoing gastric neuromodulation by both systemic autonomic testing (39 patients, six males and 33 females, mean age 38 years) and systemic autonomic testing and heart rate variability (35 patients, seven males and 28 females, mean age 37 years) testing before and after gastric neuromodulation. We also performed a pilot study using both systemic autonomic testing and heart rate variability in a small number of patients (five patients, all females, mean age 48.6 years) with diabetic gastroparesis at baseline to compare the two techniques at baseline. Systemic autonomic testing and heart rate variability were performed with standardized techniques and gastric electrical stimulation was performed as previously described with electrodes implanted serosally in the myenteric plexus. Results Both systemic autonomic testing and heart rate variability measures were often abnormal at baseline and showed changes after gastric neuromodulation therapy in two groups of symptomatic patients. Pilot data on a small group of similar patients with systemic automatic nervous measures and heart rate variability showed good concordance between the two techniques. Conclusions Both traditional direct autonomic measures and indirect measures such as heart rate variability were evaluated, including a pilot study of both methods in the same patient group. Both appear to be useful in evaluation of patients at baseline and after stimulation therapies; however, a future full head-to-head comparison is warranted.

Gastric Dysmotility and Low Serum Vitamin D Levels in Patients with Gastroparesis

Nutritional abnormalities are common in patients with gastroparesis (Gp), a disorder that may affect gastric motility and may delay emptying. The aim of this work was to identify relationships between serum nutrition markers including 25-OH vitamin D and gastric motility measures in Gp patients. We enrolled 59 consecutive gastric motility clinic patients (48 females, 11 males; mean age 44 years; 42 idiopathic; 17 diabetes mellitus) with Gp symptoms. The 25-OH vitamin D levels, for most patients slightly above the lower limit of normal (96.98 nmol/l ± 60.99), were lowest in diabetic range (DM) (75.68 nmol/l ± 34.22) vs. idiopathic (ID) (105.03 nmol/l ± 67.08) gastroparesis patients. First hour GET: one unit increase in 25-OH vitamin D level was associated 0.11% improvement (95% CI -0.22, 0.01 p=0.056) in gastric motility in all patients; this association, although marked in ID Gp patients, (-0.13, CI -0.25, -0.01 p=0.034), was not seen in DM Gp, (0.2, CI -0.45, 0.87, p=0.525). Fourth hour GET: Every unit increase of 25-OH vitamin D was associated with significant improvement in all patients, ( 0.11% CI -0.23, 0.01, p=0.053), and some weak improvement in ID group, (0.11% -0.24, 0.01, p=0.076) and absent in patients with DM (0.03, CI -0.66, 0.72, p=0.932). It is concluded that 25-OH vitamin D levels may influence gastric emptying. Underlying mechanisms for this observation might include the impact of 25-OH vitamin D on the health of the enteric nervous system. 25-OH vitamin D contributions to enteric nerve functions should be explored, particularly where autonomic nervous system comorbidities exist.

Intravenous immunoglobulin in drug and device refractory patients with the symptoms of gastroparesis—an open-label study

Gastroparesis is a complex clinical entity; many aspects of which remain unknown. Although most patients have idiopathic, diabetic, or postsurgical gastroparesis, many are thought to have measurable neuromuscular abnormalities. Immunotherapy has recently been utilized to treat suspected autoimmune gastrointestinal dysmotility.

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.