Low prevalence of positive hydrogen breath tests in patients with functional gastrointestinal conditions and hypermobile Ehlers-Danlos syndrome.

BACKGROUND: Using hydrogen breath testing (HBT) to diagnose small intestinal bacterial overgrowth (SIBO) remains controversial in patients with functional gastrointestinal (GI) disorders, and unknown in those with hypermobility Ehlers-Danlos syndrome (hEDS). We assessed prevalence of positive HBTs in these groups, evaluated the predictive value of GI symptoms and the potential role of proton pump inhibitors (PPIs) on test results. METHODS: Sequential patients referred for HBT to a tertiary unit were classified into the following groups: GI maldigestion/malabsorption, GI sensorimotor disorders, hEDS, and functional GI disorders. All underwent standardized HBT, and the yield was assessed against symptoms and PPI use. KEY RESULTS: A total of 1062 HBTs were performed over 3 years (70% female, mean age 48 ± 16 years). Overall, 7.5% (80/1062) patients had a positive HBT. Prevalence of positive HBT was highest in patients with GI maldigestion/malabsorption (17.9%; DOR 16.16, p < 0.001), GI sensorimotor disorders (15.9%; DOR 8.84, p < 0.001), compared to functional GI disorders (1.6%; DOR 1.0) (p < 0.0001). None of the hEDS patients tested positive for HBT. A positive HBT was independently associated with increased age (DOR 1.03; p < 0.001) and symptoms of diarrhea (DOR 3.95; p < 0.0001). Patients on PPIs tended towards a positive HBT than patients off PPIs (16.1% vs 6.9%; DOR 2.47; p < 0.0001). CONCLUSIONS & INFERENCES: Less than 2% of patients with functional GI disorders, and none of the patients with hEDS had a positive HBT. Pre-test probability was higher in patients with: GI structural or neurological disorders; use of long-term PPIs and symptoms of diarrhea. These criteria may be helpful in making appropriate therapeutic decisions and avoiding unnecessary hydrogen breath testing.

The Clinical Relevance of Manometric Esophagogastric Junction Outflow Obstruction Can Be Determined Using Rapid Drink Challenge and Solid Swallows.

INTRODUCTION: Esophagogastric junction outflow obstruction (EGJOO) defined on high-resolution esophageal manometry (HRM) poses a management dilemma given marked variability in clinical manifestations. We hypothesized that findings from provocative testing (rapid drink challenge and solid swallows) could determine the clinical relevance of EGJOO. METHODS: In a retrospective cohort study, we included consecutive subjects between May 2016 and January 2020 with EGJOO. Standard HRM with 5-mL water swallows was followed by provocative testing. Barium esophagography findings were obtained. Cases with structural obstruction were separated from functional EGJOO, with the latter categorized as symptom-positive or symptom-negative. Only symptom-positive subjects were considered for achalasia-type therapies. Sensitivity and specificity for clinically relevant EGJOO during 5-mL water swallows, provocative testing, and barium were calculated. RESULTS: Of the 121 EGJOO cases, 76% had dysphagia and 25% had holdup on barium. Ninety-seven cases (84%) were defined as functional EGJOO. Symptom-positive EGJOO subjects were more likely to demonstrate abnormal motility and pressurization patterns and to reproduce symptoms during provocative testing, but not with 5-mL water swallows. Twenty-nine (30%) functional EGJOO subjects underwent achalasia-type therapy, with symptomatic response in 26 (90%). Forty-eight (49%) functional EGJOO cases were managed conservatively, with symptom remission in 78%. Although specificity was similar, provocative testing demonstrated superior sensitivity in identifying treatment responders from spontaneously remitting EGJOO (85%) compared with both 5-mL water swallows (54%; P < 0.01) and barium esophagography (54%; P = 0.02). DISCUSSION: Provocative testing during HRM is highly accurate in identifying clinically relevant EGJOO that benefits from therapy and should be routinely performed as part of the manometric protocol.

Achalasia diagnosed despite normal integrated relaxation pressure responds favorably to therapy.

BACKGROUND: Achalasia diagnosis requires elevated integrated relaxation pressure (IRP; manometric marker of lower esophageal sphincter [LES] relaxation). Yet, some patients exhibit clinical features of achalasia despite normal IRP and have LES dysfunction demonstrable by other means. We hypothesized these patients to exhibit equivalent therapeutic response compared to standard achalasia patients. METHODS: Symptomatic achalasia-like cases, despite normal IRP, displayed evidence of impaired LES relaxation using rapid drink challenge (RDC), solid swallows during high-resolution manometry, and/or barium esophagogram; were treated with achalasia therapies and compared to standard achalasia patients with raised IRP. Outcomes included equivalence for short- and long-term symptom response and stasis on barium esophagogram. KEY RESULTS: Twenty-nine normal IRP achalasia cases (14 males, median age 50 year, median Eckardt 6, barium stasis 12 ± 7 cm) and 29 consecutive standard achalasia controls underwent therapy. Among cases, LES dysfunction was most often identified by RDC and/or barium esophagogram. Short-term symptomatic success was equivalent in cases vs controls (90% vs 93%; 95% CI for difference: -19% to 13%). Median short-term (1 vs 1; 95% CI for difference: 0-1) and long-term Eckardt scores (2 vs 1; 95% CI for difference: 0-2) were similar in cases and controls, respectively. Adequate clearance was observed in 67% of cases vs 81% of controls on post-therapy esophagogram. CONCLUSIONS AND INFERENCES: We described a subset of achalasia patients with normal IRP, but impaired LES relaxation identifiable only on additional provocative tests. These patients benefited from treatment, suggesting that such tests should be performed to increase the number of clinically relevant diagnoses.

Efficacy of Percutaneous Posterior Tibial Nerve Stimulation for the Management of Fecal Incontinence in Multiple Sclerosis: A Pilot Study.

BACKGROUND: Fecal incontinence is a debilitating and highly prevalent problem among multiple sclerosis patients. Conservative therapies often fail to provide benefit. Posterior tibial nerve stimulation is a minimally invasive neuromodulatory therapy with proven efficacy for fecal incontinence in non-neurological settings. OBJECTIVE: To evaluate the efficacy of posterior tibial nerve stimulation in treating multiple sclerosis-related fecal incontinence. METHODS: Consecutive multiple sclerosis patients with fecal incontinence that had failed conservative therapy received posterior tibial nerve stimulation between 2012 and 2015. All patients had previously undergone anorectal physiology tests and endoanal ultrasound. Patients whose Wexner incontinence score reduced below 10 post-therapy or halved from baseline were deemed responders. RESULTS: Thirty-three patients (25 female, median age 43 years) were included. Twenty-three (70%) had urge, 4 (12%) passive, and 9 (27%) mixed fecal incontinence. Twenty-six (79%) were classified as responders. The majority of subjects had relapsing-remitting multiple sclerosis (67%); those had a significantly higher response rate (95% vs. 67% and 50% in primary and secondary progressive respectively, P < 0.05). Responders tended to be more symptomatic at baseline and had greater improvements in bowel symptom scores and quality of life scores with therapy. CONCLUSION: Posterior tibial nerve stimulation demonstrates potential as an effective therapy for fecal incontinence in multiple sclerosis. These findings provide the basis for future more definitive controlled studies.

Physiological study of the anorectal reflex in patients with functional anorectal and defecation disorders.

OBJECTIVE: Fecal incontinence (FI) and constipation can arise from a variety of alterations of anorectal function. This study aimed to investigate the components of the anorecal reflex in patients with these symptoms and to determine the functional significance of various physiological parameters. METHODS: Altogether 21 healthy volunteers (controls) and 78 FI-predominant and 74 constipation-predominant patients were recruited and administered Wexner incontinence and constipation questionnaires. All participants underwent standardized anorectal physiology assessments. RESULTS: Patients with passive FI had lower resting sphincter pressures than controls (38 cmH2 O vs 87 cmH2 O, P < 0.05), while those with urge FI had lower squeeze pressures than controls (37 cmH2 O vs 119 cmH2 O, P < 0.05). Patients with urge FI had lower maximal tolerable volumes (100 mL vs 166 mL, P < 0.05). Patients with slow-transit constipation had elevated rectal electrosensitivity thresholds compared with controls (31.4 mA vs 20.2 mA, P < 0.05), and rectal mucosal blood flow than patients with evacuation difficulty and controls (107 vs 162 flux units (FU) [evacuation difficulty] vs 169 FU [controls], P < 0.05). Only patients with passive FI were associated with reflex abnormalities (prolonged recovery phase (1.2 ms vs 0.5 ms, P < 0.05) and total duration of reflex (6.3 ms vs 4.3 ms, P < 0.05). CONCLUSIONS: Anorectal motor, sensory and reflex abnormalities are seen in distinct patterns in patients with FI and constipation. This would suggest distinct physiological differences that may predict the potential for different neuromodulation treatment and behavioral modalities in these conditions.

Autonomic rectal dysfunction in patients with multiple sclerosis and bowel symptoms is secondary to spinal cord disease.

BACKGROUND: Most patients with multiple sclerosis report bowel symptoms, but the underlying pathophysiology is unclear. OBJECTIVE: We hypothesize that rectal dysfunction in multiple sclerosis is secondary to involvement of the spinal cord by the disease and that this can be measured by assessing rectal compliance. DESIGN: This was a case-control study. SETTINGS: The study took place in a neurogastroenterology clinic and tertiary referral center. PATIENTS: Forty-five patients with multiple sclerosis, 19 with a spinal cord injury above T5, and 25 normal control subjects were included in this study. Patients with multiple sclerosis were subdivided into 2 groups according to the Expanded Disability Status Scale, below 5 (multiple sclerosis minor disability, n = 25) or above 5 (multiple sclerosis major disability, n = 20), as a reflection of spinal cord involvement. MAIN OUTCOME MEASURES: Rectal compliance, Wexner constipation, and Wexner incontinence scores were measured. RESULTS: Data are presented as mean and SD. Expanded Disability Status Scale correlated with rectal compliance but not with Wexner constipation or Wexner incontinence scores. Post hoc analysis showed no significant difference in Wexner constipation and Wexner incontinence between the 2 multiple sclerosis groups. LIMITATIONS: Limitations to this study include the lack of an asymptomatic group with multiple sclerosis and the small sample size to evaluate bowel symptoms. CONCLUSIONS: Rectal compliance correlates with disability, and observed alterations in the rectal properties are secondary to spinal cord involvement. Our findings suggest that, in patients with neurologic impairment, rectal compliance is a surrogate of reflex activity of the spinal cord regulating rectal function and both a potential predictor of outcome and target for treatment. Multiple sclerosis patient subgroups had similar symptom burden, arguing that bowel dysfunction is multifactorial.

Gut dysfunction in patients with multiple sclerosis and the role of spinal cord involvement in the disease.

OBJECTIVES: Bowel and bladder symptoms are highly prevalent in patients with multiple sclerosis (MS). Bladder dysfunction (affecting 75% of these patients) is caused by disease in the spinal cord, whilst the pathophysiology of bowel dysfunction is unknown. Pathways regulating both the organs lie in close proximity to the spinal cord, and coexistence of their dysfunction might be the result of a common pathophysiology. If so, the prevalence of bladder symptoms should be greater in patients with MS and bowel symptoms. This hypothesis is tested in the study. We also evaluated how patient-reported symptoms quantify bowel dysfunction. PATIENTS AND METHODS: The Neurogenic Bowel Dysfunction questionnaire and the presence of bladder symptoms were recorded in 71 patients with MS and bowel symptoms. Disability, a surrogate clinical measure of spinal cord disease, was assessed using the Expanded Disability Status Scale. Bowel and bladder symptoms were quantified by patient-reported frequency, expressed in time percentage (0, 25, 50, 75 or 100% of the time the symptom was perceived), and patient-reported severity on a visual analogue scale between 0 and 100. RESULTS: The prevalence of bladder symptoms was 85%, which is higher than that expected in an unselected population of patients with MS. Neurogenic Bowel Dysfunction score was significantly correlated with both patient-reported frequency (r=0.860, P<0.0001) and severity of bowel symptoms (r=0.659, P=<0.0001), as well as with the Expanded Disability Status Scale (r=0.526, P<0.0001). CONCLUSION: Our findings suggest that gut dysfunction in patients with MS is secondary to spinal cord disease. Patient-reported bowel symptoms quantify bowel dysfunction well.

Transanal irrigation for bowel symptoms in patients with multiple sclerosis.

BACKGROUND: Constipation and fecal incontinence affect 68% of patients with multiple sclerosis, but management is empirical. Transanal irrigation has been used successfully in patients with neurogenic bowel dysfunction. OBJECTIVE: The aim of this study was to evaluate the effect of transanal irrigation on the bowel symptoms and general health status in these patients and the characteristics of those that had successful treatment and to obtain data for power calculations necessary for future randomized controlled studies. DESIGN: This was a prospective observational study in which pre- and posttreatment questionnaires (bowel symptoms and health status) were compared. Patients for whom treatment resulted in at least 50% improvement in bowel symptoms were considered responders. Baseline variables including anorectal physiology tests and rectal compliance were compared between responders and nonresponders. SETTINGS: This study was conducted at a specialist neurogastroenterology clinic, tertiary referral center. PATIENTS: Included were 30 patients who had multiple sclerosis and constipation, fecal incontinence, or both. INTERVENTION: Transanal irrigation was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the Wexner Constipation and Wexner Incontinence scores. The secondary outcomes was the SF-36 health survey. All scores were recorded before and after 6 weeks of treatment. RESULTS: At 6 weeks posttreatment, the Wexner Constipation score significantly improved (12 (8.75/16) pretreatment vs 8 (4/12.5) posttreatment, p = 0.001), as well as the Wexner Incontinence score (12 (4.75/16) pretreatment vs 4 (2/8) posttreatment, p < 0.001). The SF-36 score did not improve significantly (51.3 ± 7.8 pretreatment vs 50.4 ± 7.8 posttreatment, p = 0.051). Sixteen patients were responders and had higher baseline Wexner Incontinence scores (14 (11/20) responders vs 9 (4/15) nonresponders, p = 0.038) and SF-36 (53.9 ± 6.3 responders vs 47.9 ± 7.8 nonresponders, p = 0.027), as well as greater maximum tolerated volume to rectal balloon distension (310 (220/320) mL responders vs 168 (108/305) mL nonresponders, p = 0.017) and rectal compliance (15.2 (14.5/17.2) mL/mmHg responders vs 9.2 (7.2/15.3) mL/mmHg nonresponders, p = 0.019). LIMITATIONS: This study was limited by its small sample size and the lack of control group with alternative treatment. CONCLUSIONS: Transanal irrigation is effective to treat bowel symptoms in patients with multiple sclerosis. Responders (53%) had higher baseline incontinence symptoms and better perception of their health, as well as a more capacious and compliant rectum.

Bowel biofeedback treatment in patients with multiple sclerosis and bowel symptoms.

BACKGROUND: Bowel symptoms are common in patients with multiple sclerosis, but current treatment is empirical. OBJECTIVE: This study aimed to identify effect of biofeedback on bowel symptoms, mood, and anorectal physiology in patients with multiple sclerosis. DESIGN: This was a prospective observational study: the amount of change between pre- and posttreatment values of outcome measures was compared and analyzed. Responders were considered to be patients who demonstrated an improvement greater than or equal to the 25th percentile of the change in bowel score. Comparison between responders and nonresponders was performed. SETTINGS: This investigation was conducted at a neurogastroenterology clinic, tertiary referrals center. PATIENTS: Thirty-nine patients with multiple sclerosis and constipation and/or fecal incontinence were included in the study. INTERVENTION: Patients were given bowel biofeedback therapy. MAIN OUTCOME MEASURES: The primary outcome measures were the Wexner Constipation and Wexner Incontinence scores. The secondary outcome measures were hospital anxiety and depression scores and anorectal physiology parameters. RESULTS: Data are reported as median and interquartile ranges. After biofeedback there was significant improvement in Wexner Constipation (12 (5-19) pretreatment vs 8 (4-14) posttreatment, P = .001), Wexner Incontinence (12 (3-15) pretreatment vs 4 (2-10) posttreatment, P < .001) and hospital depression scores (7 (3-11) pretreatment vs 5 (3-10) posttreatment, P = .015). The 5-second endurance squeeze pressure was also improved (21 (11-54) mmHg pretreatment vs 43 (26-59) mmHg posttreatment, P = .001). Posttreatment change of Wexner Constipation was -2(-5/0), and of Wexner Incontinence was -3(-9/0) ("-" indicates improvement). Therefore, those patients who had a reduction of at least 5 points in the Wexner Constipation score and/or of at least 9 points in the Wexner Incontinence score were considered responders (18 patients, 46%). They showed a greater improvement of only 5-second endurance squeeze pressure (23.5 (7.5/32.75) mmHg responders vs 4 (-6/20) mmHg nonresponders, P = .008); no difference was observed in the comparison of baseline variables with nonresponders. Significant negative relationship existed between the change in the Wexner Constipation score (-2 (-5/0)) and the pretreatment Wexner Constipation score (12 (5/19), ß = -0.463, P < .001), and the change in the Wexner Incontinence score (-3 (-9/0)) with the pretreatment Wexner Incontinence score (12 (3/15), ß = -0.590, P < .001). So, the higher the initial bowel symptom score, the greater the improvement. LIMITATIONS: This study was limited by the lack of a control group. CONCLUSIONS: Biofeedback improves bowel symptoms, depression, and 5-second endurance squeeze pressure in patients with multiple sclerosis.