Gisela Chelimsky

Co-Morbidities Of Interstitial Cystitis

Introduction: This study aimed to estimate the proportion of patients with interstitial cystitis/painful bladder syndrome (IC/BPS) with systemic dysfunction associated co-morbidities such as irritable bowel syndrome (IBS) and fibromyalgia (FM). Materials and Methods: Two groups of subjects with IC/BPS were included: (1) physician diagnosed patients with IC/BPS and (2) subjects meeting NIDDK IC/PBS criteria based on a questionnaire (ODYSA). These groups were compared to healthy controls matched for age and socio-economic status. NIDDK criteria required: pain with bladder filling that improves with emptying, urinary urgency due to discomfort or pain, polyuria >11 times/24u2009h, and nocturia >2 times/night. The ODYSA instrument evaluates symptoms pertaining to a range of disorders including chronic fatigue, orthostatic intolerance, syncope, IBS, dyspepsia, cyclic vomiting syndrome, headaches and migraines, sleep, Raynaud’s syndrome, and chronic aches and pains. Results: IC/BPS was diagnosed in 26 subjects (mean age 47u2009±u200916u2009years, 92% females), 58 had symptoms of IC/BPS by NIDDK criteria (mean age 40u2009±u200917u2009years, 79% females) and 48 were healthy controls (mean age 31u2009±u200914u2009years, mean age 77%). Co-morbid complaints in the IC/BPS groups included gastrointestinal symptoms suggestive of IBS and dyspepsia, sleep abnormalities with delayed onset of sleep, feeling poorly refreshed in the morning, waking up before needed, snoring, severe chronic fatigue and chronic generalized pain, migraines, and syncope. Discussion: Patients with IC/BPS had co-morbid central and autonomic nervous system disorders. Our findings mirror those of others in regard to IBS, symptoms suggestive of FM, chronic pain, and migraine. High rates of syncope and functional dyspepsia found in the IC/BPS groups merit further study to determine if IC/BPS is part of a diffuse disorder of central, autonomic, and sensory processing affecting multiple organs outside the bladder.

Orthostatic Syndromes Differ in Syncope Frequency

BACKGROUNDnThere are conflicting opinions on whether postural tachycardia syndrome predisposes to syncope. We investigated this relationship by comparing the frequency of syncope in postural tachycardia syndrome and orthostatic hypotension.nnnMETHODSnWe queried our autonomic laboratory database of 3700 patients. Orthostatic hypotension and postural tachycardia syndrome were defined in standard fashion, except that postural tachycardia syndrome required the presence of orthostatic symptoms and a further increase in heart rate beyond 10 minutes. Syncope was defined as an abrupt decrease in blood pressure and often, heart rate, requiring termination of the tilt study. Statistical analysis utilized Fishers exact test and Students t test, as appropriate.nnnRESULTSnOf 810 patients referred for postural tachycardia syndrome, 185 met criteria while another 328 patients had orthostatic hypotension. Of the postural tachycardia syndrome patients, 38% had syncope on head-up tilt, compared with only 22% of those with orthostatic hypotension (P<.0001). In the postural tachycardia group, syncope on head-up tilt was associated with a clinical history of syncope in 90%, whereas absence of syncope on head-up tilt was associated with a clinical history of syncope in 30% (P<.0001). In contrast, syncope on head-up tilt did not bear any relationship to clinical history of syncope in the orthostatic hypotension group (41% vs 36%; P=.49).nnnCONCLUSIONnOur results demonstrate that syncope (both tilt table and clinical) occurs far more commonly in patients who have postural tachycardia syndrome than in patients with orthostatic hypotension. These findings suggest that one should be clinically aware of the high risk of syncope in patients with postural tachycardia syndrome, and the low-pressure baroreceptor system that is implicated in postural tachycardia syndrome might confer more sensitivity to syncope than the high pressure system implicated in orthostatic hypotension.

High Prevalence of Nausea in Children With Pain-associated Functional Gastrointestinal Disorders: Are Rome Criteria Applicable?

Objectives: The aim of the study was to determine the prevalence of nausea in pediatric patients with pain-associated functional gastrointestinal disorders (FGIDs), examine the effect on social and school functioning, and examine the applicability of pediatric Rome III criteria. Methods: A total of 221 pediatric patients (6–18 years of age) with chronic abdominal pain prospectively completed a demographic, history, and gastrointestinal symptom questionnaire adapted from the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS). The 6-item, revised Pediatric Migraine Disability Assessment Score tool was used to assess the effect of symptoms on school, home, and social disability. Rome III criteria were applied to all subjects. Results: A total of 183 patients with pain and nausea for a minimum of 2 months were identified. Ninety-six patients were studied after excluding those with vomiting and/or organic disease. Among these, 53% had nausea at least 2 times per week and 28% experienced daily nausea. Frequency of nausea was significantly correlated with poor school and social functioning, and uniquely predicted social disability beyond pain. Although 87% met adult Rome criteria for functional dyspepsia, only 29% met corresponding pediatric Rome criteria. Additionally, 22% met the criteria for irritable bowel syndrome (IBS)-diarrhea, 13% for IBS-constipation, 13% for abdominal migraine, and 31% were classified as having functional abdominal pain. Pediatric IBS-diarrhea and IBS-constipation overlapped in 5% of patients. Conclusions: Nausea is a prevalent symptom in patients with pain-associated FGIDs and correlates with poor school and social functioning. There is substantial overlap among FGIDs in children with nausea.

Joint Hypermobility: A Common Association with Complex Functional Gastrointestinal Disorders

OBJECTIVEnTo evaluate the prevalence of joint hypermobility (JH) and comorbid conditions in children and young adults referred to a tertiary care neurogastroenterology and autonomic disorders clinic for functional gastrointestinal complaints.nnnSTUDY DESIGNnThis was a retrospective chart review of 66 new patients aged 5-24 years who fulfilled at least 1 pediatric Rome III criteria for a functional gastrointestinal disorder (FGID) and had a recorded Beighton score (n = 45) or fibromyalgia tender point score (n = 45) based on physician examination. Comorbid symptoms were collected and autonomic testing was performed for evaluation of postural tachycardia syndrome (POTS).nnnRESULTSnThe median patient age was 15 years (range, 5-24 years), 48 (73%) were females, and 56% had JH, a significantly higher rate compared with population studies of healthy adolescents (P < .001; OR, 10.03; 95% CI, 5.26-19.13). POTS was diagnosed in 34% of patients and did not correlate significantly with hypermobility. Comorbid conditions were common, including sleep disturbances (77%), chronic fatigue (93%), dizziness (94%), migraines (94%), chronic nausea (93%), and fibromyalgia (24%).nnnCONCLUSIONnJH and other comorbid symptoms, including fibromyalgia, occur commonly in children and young adults with complex FGIDs. POTS is prevalent in FGIDs but is not associated with hypermobility. We recommend screening patients with complex FGIDs for JH, fibromyalgia, and comorbid symptoms such as sleep disturbances, migraines, and autonomic dysfunction.

Chronic Idiopathic Nausea of Childhood

OBJECTIVESnTo compare children with primary, chronic idiopathic nausea to those with secondary nausea associated with functional abdominal pain.nnnSTUDY DESIGNnRetrospective chart review of 45 children with a primary complaint of chronic nausea several times per week. Comparisons were made to prospectively collected data on 49 children with functional abdominal pain and comorbid nausea.nnnRESULTSnThe majority of those affected were adolescent Caucasian females. Subjects with chronic nausea had a more severe presentation with daily 88% (vs 26%) and constant 60% (vs 10%) nausea (P < .001), one-half with peak morning intensity. In the chronic nausea group, 62% had migraines, and 71% (vs 22%) had familial migraines (P < .001), 36% had postural tachycardia syndrome and 27% cyclic vomiting syndrome. Both groups suffered comorbid symptoms (anxiety, dizziness, fatigue, and sleep problems). The chronic nausea cohort underwent extensive, negative medical evaluations.nnnCONCLUSIONSnChronic idiopathic nausea of childhood is a poorly described symptom. Patients with primary (vs secondary) chronic nausea were more likely Caucasian, older adolescent females with severe, daily nausea and comorbid conditions such as anxiety, dizziness, and fatigue as well as significantly more migraine features. Chronic nausea is a major, disabling symptom that requires increased recognition as a separate functional entity. Future studies may need to focus on comorbid conditions including migraine and dysautonomia.

Effects of Chronic Pelvic Pain on Heart Rate Variability in Women

PURPOSEnInterstitial cystitis/bladder pain syndrome and myofascial pelvic pain are frequently comorbid chronic pelvic pain disorders. Differences in bladder function between interstitial cystitis/bladder pain syndrome and myofascial pelvic pain suggest that efferent autonomic function may differentiate these syndromes. Heart rate variability, defined as the difference in duration of successive heartbeats, serves as an index of autonomic function by measuring its ability to modify heart rate in response to neurophysiological changes. High frequency heart rate variability was used as a reflection of more rapid vagally mediated (parasympathetic) changes. Low frequency heart rate variability signified slower fluctuations related to the baroreflex and sympathetic outflow.nnnMATERIALS AND METHODSnHeart rate variability was derived by autoregressive frequency analysis of the continuous electrocardiogram recording of heart rate with the subject supine for 10 minutes, tilted 70 degrees with the head up for 30xa0minutes and supine again for 10 minutes. This institutional review board approved study included 105 female subjects, including 32 who were healthy, and 26 with interstitial cystitis/bladder pain syndrome, 12 with myofascial pelvic pain and 35 with interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain.nnnRESULTSnIn all positions healthy controls had higher high frequency heart rate variability than women with interstitial cystitis/bladder pain syndrome and interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain. Subjects with myofascial pelvic pain were similar to controls with greater high frequency heart rate variability at baseline (supine 1) and in upright positions than subjects with interstitial cystitis/bladder pain syndrome. Differences in low frequency heart rate variability were less evident while low-to-high frequency ratio differences appeared to be driven by the high frequency heart rate variability component.nnnCONCLUSIONSnSubjects with interstitial cystitis/bladder pain syndrome had diminished vagal activity and a shift toward sympathetic nervous system dominance. Overall these data support the hypothesis that changes in autonomic function occur in interstitial cystitis/bladder pain syndrome but not in myofascial pelvic pain. These changes may result from interstitial cystitis/bladder pain syndrome or contribute to its pathophysiology through abnormal self-regulatory function.

Comorbid Conditions Do Not Differ in Children and Young Adults with Functional Disorders with or without Postural Tachycardia Syndrome.

OBJECTIVEnTo determine if several multisystem comorbid conditions occur more frequently in subjects with tilt-table defined postural tachycardia syndrome (POTS) compared with those without.nnnSTUDY DESIGNnRetrospective chart review of 67 subjects aged 6-24 years, referred to a tertiary care neurogastroenterology and autonomic disorders clinic for a constellation of functional gastrointestinal, chronic pain, and autonomic complaints. All patients underwent formal autonomic testing, Beighton scores assessment for joint hypermobility (0-9), and fibromyalgia tender points (0-18) (43 subjects).nnnRESULTSnTwenty-five subjects (37%) met tilt table criteria for POTS. The median age of 16 years (range, 12-24 years) in the POTS group differed from 15 years (range, 6-21 years) in the no-POTS group (P = .03). Comorbidities including chronic fatigue, sleep disturbances, dizziness, syncope, migraines, functional gastrointestinal disorders, chronic nausea, fibromyalgia, and joint hypermobility did not differ between groups. All subjects with fibromyalgia by tender point-examination had a Beighton score ≥ 4 (P = .002).nnnCONCLUSIONSnComorbid conditions are equally prevalent in children and young adults with and without tilt-table defined POTS, suggesting that POTS itself is not a cause of the other comorbidities. Instead, POTS likely reflects another comorbid condition in children with functional disorders. Dizziness and syncope, classically associated with POTS, are not predictive of a diagnosis of POTS by tilt table, a test that is still required for formal diagnosis. These results suggest a paradigm shift in the concept of POTS as the physiological basis of many functional symptoms.

Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial

BACKGROUNDnDevelopment of safe and effective therapies for paediatric abdominal pain-related functional gastrointestinal disorders is needed. A non-invasive, US Food and Drug Administration-cleared device (Neuro-Stim, Innovative Health Solutions, IN, USA) delivers percutaneous electrical nerve field stimulation (PENFS) in the external ear to modulate central pain pathways. In this study, we evaluated the efficacy of PENFS in adolescents with abdominal pain-related functional gastrointestinal disorders.nnnMETHODSnIn this randomised, sham-controlled trial, we enrolled adolescents (aged 11-18 years) who met Rome III criteria for abdominal pain-related functional gastrointestinal disorders from a single US outpatient gastroenterology clinic. Patients were randomly assigned (1:1) with a computer-generated randomisation scheme to active treatment or sham (no electrical charge) for 4 weeks. Patients were stratified by sex and presence or absence of nausea. Allocation was concealed from participants, caregivers, and the research team. The primary efficacy endpoint was change in abdominal pain scores. We measured improvement in worst abdominal pain and composite pain score using the Pain Frequency-Severity-Duration (PFSD) scale. Participants with less than 1 week of data and those with organic disease identified after enrolment were excluded from the modified intention-to-treat population. This trial has been completed and is registered with ClinicalTrials.gov, number NCT02367729.nnnFINDINGSnBetween June 18, 2015, and Nov 17, 2016, 115 children with abdominal pain-related functional gastrointestinal disorders were enrolled and assigned to either PENFS (n=60) with an active device or sham (n=55). After exclusion of patients who discontinued treatment (n=1 in the PENFS group; n=7 in the sham group) and those who were excluded after randomisation because they had organic disease (n=2 in the PENFS group; n=1 in the sham group), 57 patients in the PENFS group and 47 patients in the sham group were included in the primary analysis. Patients in the PENFS group had greater reduction in worst pain compared with sham after 3 weeks of treatment (PENFS: median score 5·0 [IQR 4·0-7·0]; sham: 7·0 [5·0-9·0]; least square means estimate of change in worse pain 2·15 [95% CI 1·37-2·93], p<0·0001). Effects were sustained for an extended period (median follow-up 9·2 weeks [IQR 6·4-13·4]) in the PENFS group: median 8·0 (IQR 7·0-9·0) at baseline to 6·0 (5·0-8·0) at follow-up versus sham: 7·5 (6·0-9·0) at baseline to 7·0 (5·0-8·0) at follow-up (p<0·0001). Median PFSD composite scores also decreased significantly in the PENFS group (from 24·5 [IQR 16·8-33.3] to 8·4 [3·2-16·2]) compared with sham (from 22·8 [IQR 8·4-38·2] to 15·2 [4·4-36·8]) with a mean decrease of 11·48 (95% CI 6·63-16·32; p<0·0001) after 3 weeks. These effects were sustained at extended follow-up in the PENFS group: median 24·5 (IQR 16·8-33·3) at baseline to 12 (3·6-22·5) at follow-up, compared with sham: 22·8 (8·4-38·2) at baseline to 16·8 (4·8-33·6) at follow-up (p=0·018). Ten patients reported side-effects (three of whom discontinued the study): ear discomfort (n=6; three in the PENFS group, three in the sham group), adhesive allergy (n=3; one in the PENFS group, two in the sham group), and syncope due to needle phobia (n=1; in the sham group). There were no serious adverse events.nnnINTERPRETATIONnOur results show that PENFS with Neuro-Stim has sustained efficacy for abdominal pain-related functional gastrointestinal disorders in adolescents. This safe and effective approach expands treatment options and should be considered as a non-pharmacological alternative for these disorders.nnnFUNDINGnAmerican Neurogastroenterology and Motility Society.

Autonomic testing of women with interstitial cystitis/bladder pain syndrome

PurposeInterstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by urinary urgency, frequency, nocturia, pain worse as the bladder fills and improved after emptying. These features might suggest abnormal autonomic bladder control mechanisms. We compared the structural integrity of the autonomic nervous system (ANS) in IC/BPS and control subjects.MethodsIRB-approved study at University Hospitals Case Medical Center, Cleveland, OH to evaluate the structural integrity of the ANS in adult females. Testing included cardiovascular response to deep breathing, Valsalva maneuver, 30xa0min head up tilt, and sudomotor test.ResultsDifferences in ANS integrity for IC/BPS subjects and controls were determined by modified Composite Autonomic Severity Score (CASS) that includes sudomotor, adrenergic and cardiovascular indices. Baseline heart rate (HR) and HRs from each of three 10xa0min upright segments of a tilt test were compared and trend analyses performed using t tests. Healthy and IC/BPS subjects were demographically similar. The two groups did not differ in modified-CASS scores but elevated average peak heart rate was evident during baseline (supine; pxa0=xa00.057) for IC/BPS subjects prior to a tilt test. Difference at baseline was maintained at each interval during the tilt, with nearly identical slopes across intervals. The preliminary nature of this report denotes a small sample size and important differences may not be detected.ConclusionsThe findings show no structural ANS abnormalities in IC/BPS subjects. Higher baseline HR supports the concept of functional rather than structural change in the ANS, such as abnormality of sympathetic/parasympathetic balance that will require further evaluation.

Gastrointestinal involvement in the Ehlers–Danlos syndromes

Current evidence suggests that an association exists between non‐inflammatory hereditary disorders of connective tissue such as the Ehlers–Danlos syndromes (EDS) and gastrointestinal (GI) symptoms. Patients with EDS can present with both structural problems such as hiatus hernias, visceroptosis, rectoceles, and rectal prolapse as well as functional problems such as disordered gut motility. It has recently been demonstrated that patients with hypermobile EDS (hEDS) present with GI symptoms related to the fore and hind‐gut and these patients frequently meet the criteria for functional gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome. Presence of GI symptoms in EDS patients influences their quality of life. Specific evidence based management guidelines for the management of GI symptoms in EDS patients do not exist and these patients are often treated symptomatically. There is, however, recognition that certain precautions need to be taken for those patients undergoing surgical treatment. Future studies are required to identify the mechanisms that lead to GI symptoms in patients with EDS and more specific treatment guidelines are required.