A magnetic resonance imaging study of gastric motor function in patients with dyspepsia associated with Ehlers-Danlos Syndrome-Hypermobility Type: A feasibility study.

BACKGROUND: The clinical use of Magnetic Resonance Imaging (MRI) for investigating gastric motor function in dyspepsia is limited, largely due to protocol complexity, cost and limited availability. In this study, we explore the feasibility of a sub 60-minute protocol using a water challenge to assess gastric emptying, motility and accommodation in a cohort of Ehlers-Danlos Syndrome-Hypermobility type (EDS-HT) patients presenting with dyspepsia. METHODS: Nine EDS-HT patients (mean age 33, range: 26-50 all female) with a history of dyspepsia were recruited together with nine-matched controls. Subjects fasted for 6 hours prior to MRI. A baseline anatomical and motility scan was performed after which the subjects ingested 300 mL water. The anatomical and motility scans were then repeated every 10 minutes to a total of 60 minutes. Gastric emptying time, motility, and accommodation were calculated based on the observations of two observers for each EDS-HT subject and compared to their matched control using paired statistics. KEY RESULTS: Median motility increase following the water challenge was lower in EDS-HT subjects (11%, range: 0%-22%) compared to controls (22%, range: 13%-56%), P=.03. Median gastric emptying time was non-significantly decreased in EDS-HT subjects (12.5 minutes, range: 6-27) compared to controls (20 minutes, range: 7-30), P=.15. Accommodation was non-significantly reduced in EDS-HT subjects (56% increase, range: 32%-78%) compared to healthy controls (67% increase, range: 52%-78%), P=.19. CONCLUSIONS & INFERENCES: This study demonstrates the feasibility of a water challenge MRI protocol to evaluate gastric physiology in the clinical setting. Motility differences between EDS-HT and controls are worthy of further investigation.

Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome.

BACKGROUND: The joint hypermobility syndrome (JHS) is a common non-inflammatory connective tissue disorder which frequently co-exists with postural tachycardia syndrome (PoTS), a form of orthostatic intolerance. Gastrointestinal symptoms and dysmotility have been reported in PoTS. Dysphagia and reflux are common symptoms in JHS, yet no studies have examined the physiological mechanism for these, subdivided by PoTS status. METHODS: Thirty patients (28 female, ages: 18-62) with JHS and symptoms of reflux (n=28) ± dysphagia (n=25), underwent high-resolution manometry and 24 hour pH-impedance monitoring after questionnaire-based symptom assessment. Esophageal physiology parameters were examined in JHS, subdivided by PoTS status. RESULTS: Fifty-three percent of JHS patients with reflux symptoms had pathological acid reflux, 21% had reflux hypersensitivity, and 25% had functional heartburn. Acid exposure was more likely to be increased in the recumbent than upright position (64% vs 43%). The prevalence of hypotensive lower esophageal sphincter (33%) and hiatus hernia (33%) was low. Forty percent of patients with dysphagia had minor disorders of motility, 60% had functional dysphagia. Eighteen (60%) patients had coexistent PoTS-they had significantly higher dysphagia (21 vs 11.5, P=.04) and reflux scores (24.5 vs 16.5, P=.05), and double the prevalence of pathological acid reflux (64% vs 36%, P=.1) and esophageal dysmotility (50% vs 25%, P=.2) though this was not significant. CONCLUSIONS AND INFERENCES: A large proportion of JHS patients with esophageal symptoms have true reflux-related symptoms or mild esophageal hypomotility, and this is more likely if they have PoTS.

Gastrointestinal disorders in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: A review for the gastroenterologist.

BACKGROUND: Joint hypermobility syndrome (JHS)/Ehlers-Danlos syndrome hypermobility type (EDS-HT) is the most common hereditary non-inflammatory disorder of connective tissue, characterized by a wide range of symptoms, mainly joint hyperextensibility and musculoskeletal symptoms. A majority of patients also experiences gastrointestinal (GI) symptoms. Furthermore, JHS/EDS-HT has specifically been shown to be highly prevalent in patients with functional GI disorders, such as functional dyspepsia and irritable bowel syndrome. PURPOSE: The aim of this review was to examine the nature of GI symptoms and their underlying pathophysiology in JHS/EDS-HT. In addition, we consider the clinical implications of the diagnosis and treatment of JHS/EDS-HT for practicing clinicians in gastroenterology. Observations summarized in this review may furthermore represent the first step toward the identification of a new pathophysiological basis for a substantial subgroup of patients with functional GI disorders.

The association between Ehlers-Danlos syndrome-hypermobility type and gastrointestinal symptoms in university students: a cross-sectional study.

BACKGROUND: Patients with Ehlers-Danlos syndrome-hypermobility type (EDS-HT) have increased prevalence of gastrointestinal (GI) symptoms, particularly reflux and dyspepsia. EDS-HT is associated with dysautonomia, psychopathology, and chronic pain which can be associated with GI symptoms. The association between GI symptoms and EDS-HT in a 'non-patient' population and the effect of the above-mentioned factors has never been studied. METHODS: In a cross sectional study, a hypermobility questionnaire was used to screen university students; further clinical examination established the diagnosis of EDS-HT. Validated questionnaires assessed for GI, somatic, pain and autonomic symptoms, psychopathology and quality of life (QOL). These were compared in students with and without EDS-HT; logistic regression analysis examined associations between EDS-HT, GI symptoms and other variables. KEY RESULTS: Of 1998 students screened, 162 were included: 74 EDS-HT (21.0 years, 53% female) vs 88 Non-EDS-HT (21.5 years, 65% female). Compared to non-EDS-HT students, EDS-HT students were more likely to have multiple GI symptoms (41.9% vs 27.3% P=.05), particularly postprandial fullness (34.4% vs 15.9%, P=.01) and early satiety (32% vs 17%, P=.03), greater autonomic (P<.001) and somatic symptoms (P=.04) but not psychopathology (P>.8). The association between EDS-HT and postprandial symptoms was dependent on autonomic factors but independent of pain and psychopathology. Pain-related QOL scores were reduced in the EDS-HT group (80 vs 90, P=.03). CONCLUSIONS AND INFERENCES: The previously described association between EDS-HT, dyspepsia, pain and autonomic symptoms in patients is also present in non-patient groups. Future studies are necessary to explore the etiological role of connective tissue in GI and extra intestinal symptoms.

Comparative quantitative assessment of global small bowel motility using magnetic resonance imaging in chronic intestinal pseudo-obstruction and healthy controls.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is characterized by dilatation of the bowel lumen and abnormal motility. In this study, we aimed to quantify small bowel dysmotility in CIPO using a validated pan-intestinal motility assessment technique based on motion capture magnetic resonance imaging (MRI) compared to normal controls. In addition, we explored if motility responses of CIPO patients to neostigmine challenge differed from healthy volunteers. METHODS: Twenty healthy volunteers (mean age 28, range 22-48) and 11 CIPO patients (mean age 47, range 19-90) underwent MRI enterography to capture global small bowel motility. Eleven controls and seven CIPO patients further underwent a randomized placebo-controlled crossover study of either intravenous neostigmine (0.5 mg) or saline with motility MRI repeated at a mean of 3 weeks. Motility was quantified in regions of interest placed to encompass the whole small bowel volume using a validated, postprocessing technique to give a global motility index in arbitrary units (AU). Baseline and stimulated motility was compared using Wilcoxon rank-sum paired T-tests. KEY RESULTS: Baseline global small bowel motility was significantly lower in CIPO patients compared to controls (mean 0.25 AU vs 0.35 AU, p < 0.001). Motility in both groups increased significantly after neostigmine (0.06 AU increase, p = 0.016 in CIPO and 0.06 AU increase, p = 0.002 in controls). Three patients with scleroderma had a reduced response to neostigmine. CONCLUSIONS & INFERENCES: Global small bowel motility in CIPO patients is significantly lower than controls and response to the pro-kinetic agent neostigmine may differ according to disease phenotype. Software-quantified bowel motility using cine MRI has potential as a future tool to investigate enteric dysmotility.

Functional gastrointestinal disorders are associated with the joint hypermobility syndrome in secondary care: a case-control study.

BACKGROUND: The overlap of unexplained gastrointestinal (GI) and somatic symptoms is well established in patients with functional gastrointestinal disorders (FGID). Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder associated with GI and somatic symptoms. We aimed to determine whether there is an association between diagnosis of JHS and FGID and the impact of this association on comorbidities and quality of life (QOL). METHODS: Prospective case-control study in secondary care GI clinics over 2 years. JHS was assessed by the first author prior to consultation in 641 consecutive new patients. Diagnosis of FGID (cases, n = 336) or organic disorders (controls, n = 305) was established blind to JHS status. JHS prevalence was compared in cases (FGID patients) and controls (organic disorders patients). Extra-intestinal comorbidity and QOL were compared in FGID patients with and without JHS. KEY RESULTS: JHS prevalence was higher in FGID compared to organic GI disorders (39.0% vs 27.5%, ORadj: 1.51, CI: 1.07-2.12, p = 0.02), and particularly associated with functional gastroduodenal disorders (44.1%, ORadj: 2.08, CI: 1.25-3.46, p = 0.005), specifically postprandial distress syndrome (51%, ORadj: 1.99, CI: 1.06-3.76, p = 0.03). FGID patients with JHS had increased chronic pain (23.2% vs 11.9%, p = 0.01), fibromyalgia (10.5% vs 3.1%, p = 0.01), somatization scores (13 vs 10, p < 0.001), urinary autonomic scores (30.5 vs 20.7, p = 0.03), and worse pain-related QOL scores (45.0 vs 63.5, p = 0.004). CONCLUSIONS & INFERENCES: JHS is significantly associated with FGID, and this subgroup of patients have increased comorbidity and decreased QOL. Further research is required to understand the pathophysiological basis of this association.