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Postural orthostatic tachycardia syndrome (POTS) is a disabling condition characterized by orthostatic intolerance with tachycardia in the absence of drop-in blood pressure. A custom-built near-infrared spectroscopy device (NIRS) is applied to monitor the muscle oxygenation, noninvasively in patients undergoing incremental head-up tilt table (HUT). Subjects (6 POTS patients and 6 healthy controls) underwent 30mins of 70∘ on a HUT. The results showed a significant difference in deoxyhemoglobin (Hb), change-in-oxygenation (ΔOxy) and blood volume (ΔBV) between patients and healthy controls. However, oxyhemoglobin (HbO2) showed a significantly faster rate of change in the healthy controls during the first 10mins of the tilt and during the recovery. This NIRS muscle oximetry tool provides quantitative measurements of blood oxygenation monitoring in diseases such as POTS.

Purpose: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning., Methods: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains., Results: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI., Conclusion: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Whether evaluating patients clinically, documenting care in the electronic health record, performing research, or communicating with administrative agencies, the use of a common set of terms and definitions is vital to ensure appropriate use of language. At a 2017 meeting of the Pediatric Section of the American Autonomic Society, it was determined that an autonomic data dictionary comprising aspects of evaluation and management of pediatric patients with autonomic disorders would be an important resource for multiple stakeholders., Methods: Our group created the list of terms for the dictionary. Definitions were prioritized to be obtained from established sources with which to harmonize. Some definitions needed mild modification from original sources. The next tier of sources included published consensus statements, followed by Internet sources. In the absence of appropriate sources, we created a definition., Results: A total of 589 terms were listed and defined in the dictionary. Terms were organized by Signs/Symptoms, Triggers, Co-morbid Disorders, Family History, Medications, Medical Devices, Physical Examination Findings, Testing, and Diagnoses., Conclusion: Creation of this data dictionary becomes the foundation of future clinical care and investigative research in pediatric autonomic disorders, and can be used as a building block for a subsequent adult autonomic data dictionary., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aims: To develop an innovative community-academic partnership to advance, test and promote intimate partner violence screening and referral protocols by comparing the effect of integrating intimate partner violence advocates versus enhancing medical training in medical clinic settings serving women from vulnerable populations. Detecting intimate partner violence in healthcare settings allows for survivors to connect to safety and referral resources prior to violence escalating. Screening for intimate partner violence and connecting patients to referral resources requires creating a safe and trusting relationship between healthcare providers and patients. Developing screening and referral protocols responsive to survivors' needs requires involvement of clinic staff, survivors and community agencies that support survivors., Design: Three phases of the project include Discovery, Implementation and Dissemination. Mixed-methodology will help in understanding current practices and effects of interventions., Methods: Actions included in each phase: Discovery: 1) nurse-led focus groups of clinic staff, providers and survivors to understand current clinic practices; 2) retrospective chart review of the number of screens performed, positive screens detected and interventions performed., Implementation: 1) randomization of patients to be interviewed by a trained advocate or by healthcare provider with enhanced training; and 2) assess the number of screenings and referrals performed in each arm and 3) evaluate outcomes of intervention. Dissemination through: presentations, manuscripts and policy recommendations at the institutional and regional level. This IRB-approved proposal was funded in July 2021 by an Advancing a Healthier Wisconsin grant., Discussion: The partnership has improved channels of communication and understanding between diverse clinical care providers, survivors and community agency staff as they navigate the complex challenges to the development and integration of screening and referral protocols., Impact: This project will provide evidence of the most effective intimate partner violence screening and referral methodology that can be utilized in a wide variety of medical settings., (© 2022 John Wiley & Sons Ltd.)

Background: Both implicit bias-referred to as unconscious bias-and explicit bias affect how clinicians manage patients. The Implicit Association Test (IAT) has incremental predictive validity relative to self-reports of unconscious bias. Few studies have uniquely specified the impact of unconscious bias in pediatric practices., Objective: We aimed to assess the influence of unconscious bias on decision-making in the faculty in a pediatric academic center using the IAT, in addition to and separately applying clinical vignettes with racial and socioeconomic class associations in both tools as it relates to clinicians' race, gender, years in practice, education achieved by the clinician's parents, and language spoken., Methods: We conducted a prospective quality control evaluation of faculty in an academic center's pediatrics department. An anonymous online tool was used to gather IAT responses, clinical vignette responses, demographics, and explicit bias questions., Results: Of 295 faculty members (73% females), 230 completed the questionnaire, at least in part. Faculty reported on the explicit bias questions, neutral feelings when comparing the demands of educated vs noneducated patients, African American vs European American patients, and patients in the upper vs lower socioeconomic class. Of the approximately two-thirds who answered the IAT, faculty showed preference for European American and upper socioeconomic class. However, the clinical vignettes revealed no differences in how faculty responded to patients based on race or socioeconomic status when stratified by factors listed above, except physicians who favor upper socioeconomic class over lower socioeconomic class were more likely to give a detailed explanation of options if the patient's parent was upper socioeconomic class ( P  = 0.022)., Conclusions: Pediatricians exhibit racial and socioeconomic unconscious bias that minimally affects decision-making, at least based on vignette responses., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

High dietary salt (NaCl) increases blood pressure (BP) and can adversely impact multiple target organs including the vasculature, heart, kidneys, brain, autonomic nervous system, skin, eyes, and bone. However, patients with orthostatic disorders are told to increase their NaCl intake to help alleviate symptoms. While there is evidence to support the short-term benefits of increasing NaCl intake in these patients, there are few studies assessing the benefits and side effects of long-term high dietary NaCl. The evidence reviewed suggests that high NaCl can adversely impact multiple target organs, often independent of BP. However, few of these studies have been performed in patients with orthostatic disorders. We conclude that the recommendation to increase dietary NaCl in patients with orthostatic disorders should be done with care, keeping in mind the adverse impact on dietary NaCl in people without orthostatic disorders. Modest, rather than robust, increases in NaCl intake may be sufficient to alleviate symptoms but also minimize any long-term negative effects., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Fatigue is often the primary complaint of children with functional gastrointestinal disorders (FGDI) and other chronic overlapping pain disorders (COPC). The basis for this symptom remains unknown. We evaluated mitochondrial function in the white blood cells of these patients., Methods: This prospective Children's Wisconsin IRB approved study recruited subjects aging 10-18 years from pediatric neurogastroenterology clinics and healthy comparison subjects (HC). Environmental and oxidative stressors can damage the mitochondrial respiratory chain. The known low-grade inflammation in COPC could, therefore, impact the respiratory chain and theoretically account for the disabling fatigue so often voiced by patients. Mitochondrial energy generation can be easily measured in peripheral mononuclear cells (PMC) as a general marker by the Seahorse XF96 Extracellular Flux Analyzer. We measured 5 parameters of oxygen consumption using this methodology: basal respiration (BR), ATP linked oxygen consumption (ATP-LC), maximal oxygen consumption rate (max R), spare respiratory capacity (SRC), and extracellular acidification rate (ECAR), which reflect non-electron chain energy generation through glycolysis. In health, we expect high ATP linked respiration, high reserve capacity, low proton leak, and low non-mitochondrial respiration. In disease, the proton leak typically increases, ATP demand increases, and there is decreased reserve capacity with increased non-mitochondrial respiration. Findings and clinical data were compared to healthy control subjects using a Mann-Whitney test for skewed variables, Fisher's exact test for dichotomous variables, and regression tree for association with functional outcome (functional disability inventory, FDI)., Results: 19 HC and 31 COPC showed no statistically significant difference in age. FGID, orthostatic intolerance, migraine, sleep disturbance, and chronic fatigue were present in the majority of COPC subjects. BR, ECAR, and ATP-LC rates were lower in the COPC group. The low BR and ATP-LC suggest that mitochondria are stressed with decreased ability to produce ATP. Tree analysis selected SRC as the best predictor of functional disability: patients with SRC >150 had a greater FDI (more disability) compared to patients with SRC <=150, p -value = 0.021., Conclusion: Subjects with COPC have reduced mitochondrial capacity to produce ATP. Predisposing genetic factors or reversible acquired changes may be responsible. A higher SRC best predicts disability. Since a higher SRC is typically associated with more mitochondrial reserve, the SRC may indicate an underutilized available energy supply related to inactivity, or a "brake" on mitochondrial function. Prospective longitudinal studies can likely discern whether these findings represent deconditioning, true mitochondrial dysfunction, or both., Competing Interests: Thomas and Gisela Chelimsky are co-owners of PainSTakers LLC (no income yet)., (Copyright © 2021 Gisela Chelimsky et al.)

Background: Women with chronic pelvic pain (CPP) have poor cardiovagal modulation. It is unclear whether this finding reflects a broader abnormality across many systems such as gastro-vagal modulation., Aim: To determine if maladaptive cardiovagal activity in females with CPP is accompanied by maladaptive gastric myoelectric activity., Methods: A total of 36 health controls (HC) and 75 CPP underwent supine (10 min), then upright (tilted 70° head up; 30 min), and back to supine (10 min) positions. High-frequency heart rate variability (HF-HRV; 0.15-0.4 Hz) was measured as an index of cardiovagal activity. Cutaneous electrogastrography (EGG) assessed gastric myoelectric activity pre- and during-upright tilt. EGG measures from 16 HC and 31 CPP patients were available for analysis and included relative percentage of gastric activity within the normal (2-4 cpm) and tachygastria (4-10 cpm) ranges, plus ratio of normal/tachygastria., Results: HF-HRV was lower in CPP individuals at all time points (each p < .05). CPP individuals showed lesser decrease in HF-HRV from supine to upright, and poorer HF-HRV recovery from upright back to supine (F[1, 106] = 4.62, p = .034). HC showed increase in tachygastria activity (t[15] = -2.09, p = .054) while the CPP group showed no change in tachygastria activity from pre-upright to upright (t[30] = -0.62, p = .537)., Conclusions: Individuals with CPP going from supine to upright demonstrate an impairment in both tachygastria and the parallel decrement in HRV. These results support the hypothesis of a generalized blunting in the physiological modulation in CPP individuals affecting both cardiovascular and gastric systems., (© 2020 Wiley Periodicals LLC.)

Orthostatic hypotension (OH), a debilitating disorder characterized by a drop in blood pressure when in the upright position, may be treated through several pharmacologic and lifestyle modifications. The treatment is aimed at decreasing the symptoms, mainly the falls, increase the standing time, and improve the activities of daily life. A recent expert consensus outlined the management of orthostatic hypotension and included 4 sequential steps: 1) review medications and modify or remove those that may aggravate or cause OH; 2) non-pharmacologic measures; 3) pharmacologic measures and 4) treatment combinations. The aim of this manuscript is to review the non-pharmacological approach. In milder cases, this approach may suffice, but with more severe symptoms, such as falls, syncope or near-syncope, a pharmacological strategy is simultaneously employed. Furthermore, most non-pharmacological measures are combined. The non-pharmacological approach is aimed at optimizing blood volume, decreasing postural venous pooling, reducing heat and post-prandial induced vasodilation, emphasizing physical conditioning, and minimizing nocturnal diuresis., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Human papillomavirus (HPV) vaccination has been anecdotally connected to the development of dysautonomia, chronic fatigue, complex regional pain syndrome and postural tachycardia syndrome., Objectives: To critically evaluate a potential connection between HPV vaccination and the above-noted conditions., Methods: We reviewed the literature containing the biology of the virus, pathophysiology of infection, epidemiology of associated cancers, indications of HPV vaccination, safety surveillance data and published reports linking HPV vaccination to autonomic disorders., Results: At this time, the American Autonomic Society finds that there are no data to support a causal relationship between HPV vaccination and CRPS, chronic fatigue, and postural tachycardia syndrome to other forms of dysautonomia., Conclusion: Certain conditions are prevalent in the same populations that are vaccinated with the HPV vaccine (peri-pubertal males and females). This association, however, is an insufficient proof of causality.

Previous studies examining the resting-state functional connectivity of the periaqueductal gray (PAG) in chronic visceral pain have localized PAG coordinates derived from BOLD responses to provoked acute pain. These coordinates appear to be several millimeters anterior of the anatomical location of the PAG. Therefore, we aimed to determine whether measures of PAG functional connectivity are sensitive to the localization technique, and if the localization approach has an impact on detecting disease-related differences in chronic visceral pain patients. We examined structural and resting-state functional MRI (rs-fMRI) images from 209 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We applied three different localization techniques to define a region-of-interest (ROI) for the PAG: 1) a ROI previously-published as a Montreal Neurological Institute (MNI) coordinate surrounded by a 3 mm radius sphere (MNI-sphere), 2) a ROI that was hand-traced over the PAG in a MNI template brain (MNI-trace), and 3) a ROI that was hand-drawn over the PAG in structural images from 30 individual participants (participant-trace). We compared the correlation among the rs-fMRI signals from these PAG ROIs, as well as the functional connectivity of these ROIs with the whole brain. First, we found important non-uniformities in brainstem rs-fMRI signals, as rs-fMRI signals from the MNI-trace ROI were significantly more similar to the participant-trace ROI than to the MNI-sphere ROI. We then found that choice of ROI also impacts whole-brain functional connectivity, as measures of PAG functional connectivity throughout the brain were more similar between MNI-trace and participant-trace compared to MNI-sphere and participant-trace. Finally, we found that ROI choice impacts detection of disease-related differences, as functional connectivity differences between pelvic pain patients and healthy controls were much more apparent using the MNI-trace ROI compared to the MNI-sphere ROI. These results indicate that the ROI used to localize the PAG is critical, especially when examining brain functional connectivity changes in chronic visceral pain patients., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To describe the frequency, intensity and duration of urological chronic pelvic pain syndrome symptom exacerbations ('flares'), as well as risk factors for these features, in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Epidemiology and Phenotyping longitudinal study., Participants and Methods: Current flare status ('urological or pelvic pain symptoms that are much worse than usual') was ascertained at each bi-weekly assessment. Flare characteristics, including start date, and current intensity of pelvic pain, urgency and frequency (scales of 0-10), were assessed for participants' first three flares and at three randomly selected times when they did not report a flare. Generalized linear and mixed effects models were used to investigate flare risk factors., Results: Of the 385 eligible participants, 24.2% reported no flares, 22.9% reported one flare, 28.3% reported 2-3 flares, and 24.6% reported ≥4 flares, up to a maximum of 18 during the 11-month follow-up (median incidence rate = 0.13/bi-weekly assessment, range = 0.00-1.00). Pelvic pain (mean = 2.63-point increase) and urological symptoms (mean = 1.72) were both significantly worse during most flares (60.6%), with considerable within-participant variability (26.2-37.8%). Flare duration varied from 1 to 150 days (94.3% within-participant variability). In adjusted analyses, flares were more common, symptomatic, and/or longer-lasting in women and in those with worse non-flare symptoms, bladder hypersensitivity, and chronic overlapping pain conditions., Conclusion: In this foundational flare study, we found that pelvic pain and urological symptom flares were common, but variable in frequency and manifestation. We also identified subgroups of participants with more frequent, symptomatic, and/or longer-lasting flares for targeted flare management/prevention and further study., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Background and Objectives: Though reduced cardiovagal modulation accompanies adult IBS, adolescents with functional gastrointestinal disorders (FGID) have not been studied. We aim to investigate whether adolescents with FGID have reduced cardiovagal modulation., Methods: After 10-minute supine rest, we recorded ECG for 5-minute supine and 5-minute standing without support in healthy and FGID-affected adolescents. After analysis with Kubios 2.2 for high-frequency (hf) and low-frequency (lf) heart rate variability (HRV), Wilcoxon signed-ranks test compared individual paired supine and standing HRV data, while Kruskal-Wallis and Mann-Whitney U tests compared HRV across groups., Results: A total of 50 FGID subjects (90% females; median age 17 years [range 11-21]) and 22 healthy comparison group (HC) (59% females; median age 14 years [range 10-18]) participated. Both absolute and relative supine hfHRV exceeded standing in both groups. Absolute supine lfHRV was higher than standing in FGID patients and not in HCs, while relative supine lfHRV power was actually lower in both groups. Compared to HC, FGID group showed significantly lower absolute HRV, while relative HRV did not differ between groups., Conclusions: Cardiovagal modulation is lower in adolescents with FGID. This difference impacts these subjects significantly. Whether this finding reflects a cause or a consequence of FGID is unknown., (© 2019 John Wiley & Sons Ltd.)

Orthostatic intolerance, including postural tachycardia syndrome, is often associated with gastrointestinal symptoms. In the vast majority of the cases, the gastrointestinal symptoms are not secondary to the orthostatic disorder, but rather just a comorbid condition. This concept is critical, since treatment aimed at the orthostatic condition will not improve the gastrointestinal symptoms. Only when the gastrointestinal symptoms develop in the upright position and improve or resolve in the supine position, they may be related to the orthostatic stress. The most common symptoms associated with orthostatic intolerance include nausea, dyspepsia, bloating and constipation. The majority of subjects do not have gastroparesis. The chapter discusses available treatments of these conditions., (Copyright © 2018. Published by Elsevier B.V.)

Orthostatic intolerance (OI), having difficulty tolerating an upright posture because of symptoms or signs that abate when returned to supine, is common in pediatrics. For example, ∼40% of people faint during their lives, half of whom faint during adolescence, and the peak age for first faint is 15 years. Because of this, we describe the most common forms of OI in pediatrics and distinguish between chronic and acute OI. These common forms of OI include initial orthostatic hypotension (which is a frequently seen benign condition in youngsters), true orthostatic hypotension (both neurogenic and nonneurogenic), vasovagal syncope, and postural tachycardia syndrome. We also describe the influences of chronic bed rest and rapid weight loss as aggravating factors and causes of OI. Presenting signs and symptoms are discussed as well as patient evaluation and testing modalities. Putative causes of OI, such as gravitational and exercise deconditioning, immune-mediated disease, mast cell activation, and central hypovolemia, are described as well as frequent comorbidities, such as joint hypermobility, anxiety, and gastrointestinal issues. The medical management of OI is considered, which includes both nonpharmacologic and pharmacologic approaches. Finally, we discuss the prognosis and long-term implications of OI and indicate future directions for research and patient management., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Boris has served as a paid expert witness on the subject of postural orthostatic tachycardia syndrome. H. Lundbeck A/S (which underwrote a meeting of the Pediatric Subgroup of the American Autonomic Society) produces Northera (droxidopa) to treat orthostatic intolerance as well as citalopram and escitalopram; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Aim: To describe a sensory map of pelvic dermatomes in women with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). We hypothesized that if IC/BPS involves changes in central processing, then women with IC/BPS will exhibit sensory abnormalities in neurologic pelvic dermatomes., Methods: Women with IC/BPS and healthy controls underwent neurologic examination that included evaluation of sharp pain sensitivity and vibration in dermatomes T12, L1, L2, S1-5. Peripheral nervous system sensitivity to pressure, vibration, and pinprick were scored using numeric rating scales (NRS). Bilateral comparisons were made with Wilcoxon signed-rank test and comparisons between groups were made by the Mann-Whitney U-test., Results: Total of 74 women with IC/BPS and 36 healthy counterparts were included. IC/BPS and control groups had similar age (43.0 ± 14.1 and 38.6 ± 15.3 years, P = 0.14) and BMI (28.9 ± 8.0 kg/m 2 and 26.9 ± 8.4 kg/m 2 , P = 0.24), respectively. Women with IC/BPS reported hyperalgesia (elevated bilateral NRS pain intensity) in all pelvic dermatomes compared to healthy controls. S4-S5 region had the highest pain intensity in all participants. All IC/BPS participants exhibited vibration sensation hypoesthesia, at least unilaterally, in all of the pelvic dermatomes except L1 compared to healthy controls., Conclusion: This detailed map of neurologic pelvic dermatomes in women with IC/BPS found hyperalgesia in all pelvic dermatomes, and some evidence of vibration sensation hypoesthesia, compared to healthy controls. These findings support the hypothesis that IC/BPS may involve changes in central signal processing biased towards nociception., (© 2017 Wiley Periodicals, Inc.)

Objectives: Little is known about the relationship between autonomic dysfunction and sleep disturbances. This study aimed to identify patterns of sleep disturbances and autonomic dysfunction in children., Methods: A retrospective chart review of 14 children who underwent sleep and autonomic testing was performed. Subjects were divided into three groups based on sudomotor Composite Autonomic Severity Score Scale score and postural tachycardia syndrome criteria. Sleep quality, sleep architecture, and number of comorbidities were analyzed., Results: There were no statistically significant differences between groups in measures of sleep quality, sleep architecture, and number of comorbidities., Conclusion: Patients with postural tachycardia syndrome and autonomic dysfunction experience multiple sleep-related complaints. The low power of our study did not allow firm conclusions, but there is no pattern to these abnormalities., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The hypothalamus plays a critical role in maintaining visceral homeostasis. Altered hypothalamus activation has been implicated in functional gastrointestinal disorders, including irritable bowel syndrome (IBS). One important aspect of homeostatic regulation is the cortical modulation of limbic and paralimbic subsystems, including the hypothalamus, which in turn affects the descending regulatory processes mediating visceral homeostasis. Using neuroimaging, we evaluated hypothalamus functional connectivity in adolescent patients with IBS and age-matched healthy controls who received rectal distension stimulations. More extensive hypothalamus connectivity was observed in liminal than subliminal condition in controls, but not in patients with IBS. Compared with controls, patients with IBS showed significantly reduced hypothalamus connectivity in the bilateral prefrontal cortices, supplementary motor and premotor areas, bilateral sensorimotor cortex, and limbic subareas, which are specifically involved in homeostatic regulation. The findings support the generalized homeostatic regulation model that reduced cortical and limbic modulations of hypothalamus functioning underlies disrupted visceral homeostasis in patients with IBS.

Background: Development 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., Methods: In 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., Findings: Between 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., Interpretation: Our 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., Funding: American Neurogastroenterology and Motility Society., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Structural autonomic disorders (producing structural damage to the autonomic nervous system or autonomic centers) are far less common than functional autonomic disorders (reflected in abnormal function of a fundamentally normal autonomic nervous system) in children and teenagers. This article focuses on this uncommon first group in the pediatric clinic. These disorders are grouped into 2 main categories: those characterized by hypoventilation and those that feature an autonomic neuropathy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To determine if children with benign joint hypermobility (BJH) syndrome and chronic functional pain disorders have more autonomic dysfunction., Study Design: Retrospective chart review study of pediatric patients seen in the pediatric neurogastroenterology and autonomic clinic who underwent autonomic testing and had either a Beighton score of ≥6 and met Brighton criteria for BJH (with BJH) or a score of ≤2 (no BJH)., Results: Twenty-one female subjects (10 without BJH) met inclusion criteria; 64% of BJH had diagnosis confirmed by genetics consultation. We evaluated for postural tachycardia syndrome, syncope, orthostatic intolerance, and orthostatic hypotension. None of these diagnoses, as well as baseline heart rate, peak heart rate in first 10 minutes of head up tilt (P = .35 and P = .61, respectively), and sudomotor index (suggestive of autonomic neuropathy) (P = .58), showed differences between the groups. Age of onset of symptoms was also similar (P = .61) (BJH vs without BJH: median [range]:15.6 years [12.9-17.5] vs 15.4 years [11.1-18.2]). There was no difference between groups in complaints of migraine, chronic nausea, chronic fatigue, lightheadedness, dizziness, fainting >3 times/lifetime, delayed onset of sleep, irritable bowel syndrome, dyspepsia, abdominal migraine, functional abdominal pain, constipation, or fibromyalgia., Conclusions: Children with chronic functional pain disorders and BJH have autonomic testing findings and comorbid features compared with a similar cohort of subjects without BJH, suggesting that BJH is not the driver of the autonomic and comorbid disorders., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To determine the feasibility of a detailed pain sensitivity assessment using body-wide musculoskeletal tender points (TPs) in women with different types of chronic pelvic pain (CPP) and compare phenotypic differences., Materials and Methods: Seventy women with CPP and 35 pain-free women underwent musculoskeletal evaluation of TPs in the pelvic floor, abdomen, groin, inner thigh, and all 18 fibromyalgia TPs. Patients scored elicited pain on a numeric rating scale. TP pain scores were used for intergroup comparison and intragroup correlation., Results: Women with CPP were grouped as having either bladder pain syndrome (BPS, n=24) or myofascial pelvic pain (MPP, n=11) singularly or both concomitantly (BPS+MPP, n=35). TP pain scores for all evaluations were higher in women with CPP compared with healthy women (P<0.001). Women with BPS+MPP had elevated TP pain for each evaluation compared with women with BPS alone. Pelvic floor and fibromyalgia TP scores correlated strongly in the MPP group, moderately in the BPS+MPP group, and weakly in the BPS alone group. Although some moderate and strong correlations between different body locations were present in all 3 groups, only the BPS+MPP group showed moderate to strong correlations between all body TPs., Conclusions: Detailed musculoskeletal evaluation of women with CPP is feasible and well tolerated. Careful phenotyping differentiated BPS, MPP, and BPS+MPP groups. Attending to the differences between these groups clinically may lead to more effective treatment strategies and improved outcomes for patients with CPP.

Purpose: We determined whether abnormal autonomic nervous system innervation of the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome) differently than other chronic pelvic pain., Materials and Methods: In this institutional review board approved protocol 39 healthy controls and 134 subjects were enrolled, including 36 with IC/BPS, 14 with myofascial pelvic pain and 42 with IC/BPS plus myofascial pelvic pain. Three subjects were excluded from study. Autonomic nervous system evaluations included deep breathing, the Valsalva maneuver, and the tilt table and sudomotor tests. The latter evaluates autonomic neuropathy. A modified validated composite autonomic laboratory score was applied., Results: Median age in the IC/BPS group was 47.5 years (range 21 to 78), greater than in healthy controls (34 years, range 20 to 75, p = 0.006), the myofascial pelvic pain group (33 years, range 22 to 56, p = 0.004) and the IC/BPS plus myofascial pelvic pain group (38 years, range 18 to 64, p = 0.03). Body mass index did not significantly differ but the myofascial pelvic pain and IC/BPS plus myofascial pelvic pain groups had a higher body mass index than healthy controls (p = 0.05 and 0.03, respectively). Cardiovascular and adrenergic indexes did not differ. The tilt table test showed more orthostatic intolerance in all chronic pelvic pain groups. Tilt table test diagnoses (orthostatic hypotension, postural tachycardia syndrome and reflex syncope) were rare. Baseline heart rate was higher in all chronic pelvic pain groups (p = 0.004). Compared to healthy controls all myofascial pelvic pain groups showed significantly more clear-cut autonomic neuropathy, defined as a sweat score of 3 or greater (vs IC/BPS plus myofascial pelvic pain p = 0.007 and vs myofascial pelvic pain p = 0.03)., Conclusions: Some chronic pelvic pain types show autonomic neuropathy and some show vagal withdrawal. In all types orthostatic intolerance likely reflects central sensitization and perhaps catastrophizing. Some of these findings suggest novel therapeutic targets., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the prevalence of nausea and its association with functional gastrointestinal disorders (FGIDs) in a large-scale, population-based study of Latin American school children., Study Design: This cross-sectional study collected data from children in 3 Latin American countries. A Spanish version of the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version (QPGS-III) was administered to school children in Central and South America. Subjects were classified into FGIDs based on Rome criteria (QPGS-III). Students from 4 public and 4 private schools in the countries of El Salvador, Panama, and Ecuador participated in this epidemiologic study., Results: A total of 1137 school children with mean age 11.5 (SD 1.9, range 8-15) years completed the QPGS-III (El Salvador n = 399; Panama n = 321; Ecuador n = 417). Nausea was present in 15.9% of all school children. Two hundred sixty-eight (24%) children met criteria for at least 1 FGID. Nausea was significantly more common in children with FGIDs compared with those without: El Salvador 38% vs 15% (P < .001); Panama 22% vs 7% (P < .001); Ecuador 25% vs 13% (P = .004). Among children with FGIDs, those with functional constipation had a high prevalence of nausea. Nausea was significantly more common in girls and children attending private schools., Conclusions: Nausea is commonly present in Latin American school children. FGIDs are frequently associated with nausea., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Interstitial 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., Materials and Methods: Heart 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 30 minutes 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., Results: In 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., Conclusions: Subjects 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., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To determine if several multisystem comorbid conditions occur more frequently in subjects with tilt-table defined postural tachycardia syndrome (POTS) compared with those without., Study Design: Retrospective 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)., Results: Twenty-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)., Conclusions: Comorbid 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Functional gastrointestinal disorders (FGIDs) are a common problem in pediatric patients and can affect quality of life. However, the extent of these disorders may vary in different subpopulations of children. This study investigated the prevalence of FGIDs in an inner-city primary care practice. Healthy patients between the ages of 9 and 17 were administered a validated questionnaire that assessed for FGIDs and other somatic complaints. Eleven of 145 patients (7.5%) met criteria for FGIDs based on Rome III Diagnostic Criteria. Raynaud-like symptoms tended to occur more often in patients meeting criteria for FGIDs, although this association was not statistically significant (P = .07). The lower prevalence of FGIDs in this population compared with earlier studies may suggest a link between socioeconomic status and the prevalence of FGIDs. Larger population-based studies consisting of a heterogeneous cohort from a variety of socioeconomic backgrounds are necessary to further elucidate the true connection between FGIDs and socioeconomic status.

Objective: To 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., Study Design: This 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)., Results: The 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%)., Conclusion: JH 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Interstitial 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., Methods: IRB-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, 30 min head up tilt, and sudomotor test., Results: Differences 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 10 min 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; p = 0.057) 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., Conclusions: The 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.

Background and Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is relatively common and associated with severe pain, yet effective treatment remains elusive. Research typically emphasized the bladder's role, but given the high presence of systemic comorbidities, the authors hypothesized a pathophysiologic nervous system role. This paper reports the methodology and approach to study the nervous system in women with IC/BPS. The study compares neurologic, urologic, gynecologic, autonomic, gastrointestinal, and psychological features of women with IC/BPS, their female relatives, women with myofascial pelvic pain (MPP), and healthy controls to elucidate the role of central and peripheral processing., Methods and Results: In total, 228 women (76 IC/BPS, 76 MPP, 38 family members, and 38 healthy controls) will be recruited. Subjects undergo detailed screening, structured neurologic examination of limbs and pelvis, tender point examination, autonomic testing, electrogastrography, and assessment of comorbid functional dysautonomias. Interpreters are blinded to subject classification. Psychological and stress response characteristics are examined with assessments of stress, trauma history, general psychological function, and stress response quantification. As of December 2012, data collection is completed for 25 healthy controls, 33 IC/BPS ± MPP, eight MPP, and three family members. Recruitment rate is accelerating and strategies emphasize maintaining and encouraging investigator participation in study science, internet advertising, and presentations to pelvic pain support groups., Conclusion: The study represents a comprehensive, interdisciplinary approach to sampling autonomic and psychophysiologic characteristics of women with IC/BPS. Despite divergent opinions on study methodologies based on specialty experiences, the study has proven feasible to date and different perspectives have proved to be one of the greatest study strengths.

Objectives: To compare children with primary, chronic idiopathic nausea to those with secondary nausea associated with functional abdominal pain., Study Design: Retrospective 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., Results: The 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., Conclusions: Chronic 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Many teenagers who struggle with chronic fatigue have symptoms suggestive of autonomic dysfunction that may include lightheadedness, headaches, palpitations, nausea, and abdominal pain. Inadequate sleep habits and psychological conditions can contribute to fatigue, as can concurrent medical conditions. One type of autonomic dysfunction, postural orthostatic tachycardia syndrome, is increasingly being identified in adolescents with its constellation of fatigue, orthostatic intolerance, and excessive postural tachycardia (more than 40 beats/min). A family-based approach to care with support from a multidisciplinary team can diagnose, treat, educate, and encourage patients. Full recovery is possible with multi-faceted treatment. The daily treatment plan should consist of increased fluid and salt intake, aerobic exercise, and regular sleep and meal schedules; some medications can be helpful. Psychological support is critical and often includes biobehavioral strategies and cognitive-behavioral therapy to help with symptom management. More intensive recovery plans can be implemented when necessary., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Chronic nausea is a prevalent but poorly described symptom in adolescents. It often co-occurs with other functional gastrointestinal disorders (FGIDs) but may also present in isolation. A multitude of triggers and complex neural pathways underlie the sensation of nausea. These include gastrointestinal and blood-borne insults, dysmotility, vestibular or central nervous system pathways, an aberrant autonomic nervous system, and psychosocial factors. Although clinical algorithms are lacking, diagnosis is typically made on the basis of a thorough clinical history and without extensive testing. Treatment is mainly empiric and may be directed at comorbid symptoms such as migraine, delayed gastric emptying, orthostatic intolerance, and visceral hypersensitivity. Chronic idiopathic nausea is an increasingly prevalent symptom that needs careful clinical assessment and individualized treatment plans., (Copyright 2014, SLACK Incorporated.)

Abdominal migraines present with debilitating symptoms in adolescence. At our institution, the gastroenterology, neurology, and autonomic departments collaborated in treating patients with such presentations. This case series describes 6 patients who were given intravenous dihydroergotamine (DHE) for presumed abdominal migraines. DHE was only used when other agents like amitriptyline, verapamil, topiramate, or depakote had proved ineffective. DHE was started at 0.5 mg dose and on average 7 to 9 mg were given on each hospitalization. Patient ages ranged from 13 to 19 years with the majority being female. One patient did not respond to treatment. One patient was admitted 4 times for symptoms of abdominal migraines resolving with DHE. The average time between symptom relapse was about 5 to 12 months. Five of our 6 patients responded to the infusion without significant side effects. Based on these case series, DHE may be a treatment option in children with intractable abdominal migraine.

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.

Introduction: Autonomic testing is used clinically. Yet, the prevalence of "abnormal" variants in the healthy population has not been reported., Results: We report the results of autonomic testing in healthy females >18 years, in whom we found decrease or absent sudomotor function in 1-2 locations., Conclusions: These findings should caution physicians in the interpretation of autonomic testing. This report underscores the need of larger studies to determine the prevalence of these findings.

Functional gastrointestinal disorders (FGIDs) are currently classified under the Rome criteria based on symptoms and absence of organic disease. Preliminary studies have shown that FGIDs are probably not restricted to the GI tract, but may represent a systemic disorder with comorbidities affecting other parts of the body, including migraine, fatigue, aches and pains, etc. The autonomic nervous system (ANS) provides the extrinsic control of GI motility, secretions, and even immune response. The role of the ANS in the development of FGIDs and comorbidities is still unclear. Limited data demonstrate orthostatic intolerance such as reflex syncope and postural tachycardia syndrome in a large subset of subjects with FGIDs. Some studies have found improvement in the GI symptoms with treatment of the orthostatic intolerance it produces. Prospective studies are needed to determine the chronology of the development of the comorbidities, the triggers that induce these syndromes, and effective treatments. This chapter aims to review current understanding of the role of the ANS in FGIDs., (Copyright © 2013. Published by Elsevier Inc.)

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/24 h, 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 47 ± 16 years, 92% females), 58 had symptoms of IC/BPS by NIDDK criteria (mean age 40 ± 17 years, 79% females) and 48 were healthy controls (mean age 31 ± 14 years, 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.

Functional gastrointestinal disorders (FGIDs) are common. The poor health-related quality of life in FGIDs is a combination of gastrointestinal symptoms and comorbid conditions. We determined by using the Ohio Dysautonomia questionnaire the medical comorbidities in 38 children with FGID. Almost all of the subjects had a comorbid disorder, with orthostatic symptoms in 89%, fainted >3×/lifetime in 17%, headaches with migrainous features in 40%, other types of chronic pain in 50%, and fatigue lasting >6 months in approximately 33%. These findings constitute a critical first step in changing the paradigm of our approach to FGID as a broader systemic disorder, not one limited to the gastrointestinal tract.

Objective: A subgroup of syncope patients report migraine headaches immediately preceding or following syncope, and some respond to anti-migrainous prophylactic agents. This study aimed to describe the frequency of migrainous features concurrent with episodes of syncope and to propose clinical criteria for assessing whether a migrainous mechanism might underlie syncope., Methods: This retrospective, questionnaire-based study developed criteria for syncopal migraine based on the International Classification of Headache Disorders II (ICHD-II) migraine criteria. Two hundred and forty-eight recurrent syncope subjects (>3 episodes) were stratified based on the presence (N = 127) or absence (N = 121) of a headache concurrent with syncopal episodes. Syncopal headaches were classified as either syncopal migraine (meeting ICHD-II criteria for migraine or probable migraine, without aura) or nonspecific (not meeting the criteria for syncopal migraine). The syncope groups were then compared to 199 subjects with migraine headaches using chi-square and Cochran-Armitage test for trend., Results: Nearly one-third of recurrent syncope subjects met criteria for syncopal migraine. This group resembled the migraine headache population more than the syncope population in age, gender, autonomic testing, and comorbid conditions. The syncopal migraine group also reported a longer duration of syncope and a longer recovery time to normal. Finally, anti-migrainous medications reduced syncope in half of the syncopal migraine subjects., Interpretation: Syncope may have a migrainous basis more commonly than previously suspected, and we suggested criteria to identify these patients. Syncopal migraine appears epidemiologically more closely related to migraine than to reflex syncope.

OBJECTIVE. To describe the reasons for referral, autonomic diagnoses, test results, and patient management in a large pediatric population referred for testing for an autonomic disorder. DESIGN. The authors reviewed autonomic testing data and medical records for patients aged 18 years and younger who underwent testing between 1993 and 2007 and who had adequate clinical data. Relevance of test results to clinical symptoms was ranked on a 3-point scale. Treatments were noted and their benefit ranked on a 5-point scale. RESULTS. Among 142 pediatric patients identified, postural tachycardia syndrome was most common (71%) while orthostatic hypotension was rare (5%). Testing provided relevant information regarding the patient's symptoms in 88% of the cases. Beta-blockers were the most commonly prescribed medication (59%); 73% improved. CONCLUSIONS. Postural tachycardia syndrome was common in this large pediatric population, whereas orthostatic hypotension was infrequent. The symptomatic improvement in the majority bears an unclear relationship to treatment. Prospective studies are needed.

Objective: The aim of this study was to determine whether patients who faint earlier in the course of a tilt table study represent a separate population with a poorer prognosis or different pathophysiology. We analyzed differences across patients with different syncopal times on the tilt-table study to answer this question., Methods: This was a retrospective, approved, chart review. From our database of over 6000 patients, we identified 1222 patients with syncope. After excluding patients with orthostatic hypotension, postural tachycardia syndrome and diabetes, we were left with 131 patients with pure reflex syncope. We divided fainters into an early (<20 minutes) and late (>20 minutes) faint times. Along with the tilt table test all patients underwent heart rate response for deep breathing, Valsalva maneuver and quantitative sudomotor axon reflex tests., Results: By 10 minutes in the tilt study, only 18% of subjects had fainted, 65% by 20 minutes, 92% by 30 minutes and 96% by 35 minutes. Age was evenly distributed across all syncopal times. Neither the 14 abnormal cardiac responses to deep breathing nor the 20 abnormal Valsalva maneuvers, nor the 28 abnormal axon reflex responses clustered with an early or late faint time., Conclusion: A 10-minute tilt will miss 82% of syncopal episodes, while a 30- minute tilt increases the yield 10-fold, missing only 8%. Patients with early faint times did not differ from patients with late fainting times with regard to age or autonomic test abnormalities. Timing of syncope during the tilt table test does not associated with more severe dysautonomia. A prospective study is needed to confirm these observations.

Objective: To investigate the frequency of various nonorthostatic complaints in children with postural orthostatic tachycardia syndrome (POTS)., Study Design: We used our autonomic laboratory database to identify all pediatric patients with traditionally defined POTS who had completed the Ohio Dysautonomia Survey (ODYSA). The responses of the patients to questions targeting various autonomic complaints, including syncope, gastrointestinal symptoms, sleep disturbances, headaches, urinary symptoms, chronic pain, and Raynaud-like symptoms, were collected and analyzed., Results: A total of 53 pediatric patients completed the ODYSA questionnaire. The participants reported high frequencies of sleep abnormalities, chronic pain, Raynaud-like symptoms, and gastrointestinal abnormalities, with lower rates of headaches, syncope, and urinary complaints., Conclusions: Our findings demonstrate the occurrence of various nonorthostatic symptoms in pediatric patients with POTS. These findings suggest the need for an interdisciplinary approach to the treatment and management of POTS, as well as for further investigation into the mechanisms that lead to the concurrent presentation of both orthostatic and nonorthostatic symptoms in these patients., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objectives: Some patients with functional abdominal pain report worsening of symptoms in the upright position. Many of these have a postural tachycardia syndrome (POTS). We investigated whether the electrical activity of the stomach changes during the upright portion of a tilt table test in patients with and without POTS., Patients and Methods: All of the children undergoing autonomic testing were offered enrollment in this institutional review board-approved prospective study between October 2007 and January 2009. Electrogastrography was recorded 10 minutes in the supine position and during the entire upright portion of tilt. Children were divided into 2 groups: POTS and No-POTS. Findings were correlated with this grouping using Fisher exact test and either Student t test or Wilcoxon rank sum test as appropriate., Results: Forty-nine patients participated (35 girls), with a mean age of 14.7 + 3.5 years, 25 with POTS and 24 without. The POTS and No-POTS groups did not differ in baseline normal gastric activity. The change from supine to standing showed a significant difference in the electrogastrographic tracing between the POTS and No-POTS groups (P < 0.04-0.09), best seen in channels 1 and 4. In particular, gastric activity became more abnormal in the upright position in the POTS group, whereas the opposite occurred in the No-POTS group., Conclusions: The electrical activity of the stomach changes during the upright position in children with POTS, but not in children without this diagnosis. These changes could relate to their report of worsening pain in the upright position.