Impact of Sleep Disturbance on Fatigue, Nausea, and Pain: Mediating Role of Depressive Symptoms Among Youth With Disorders of Gut-Brain Interaction.

OBJECTIVES: A high degree of sleep disturbance is reported among youth with disorders of gut-brain interaction (DGBIs). Given that sleep quality impacts a range of pediatric health outcomes including somatic sensations (eg, pain) and depressive mood occurs relatively frequently among youth with DGBIs, there is a dire need to disentangle the unique contributions of sleep and depressive mood on the somatic sensations experienced by youth with DGBIs. We aimed to examine whether depressive mood mediates the relations among sleep disturbance and pain intensity, nausea, and fatigue among youth with DGBIs. METHODS: One hundred eighteen patients aged 8-17 years ( Mage = 14.05, SD = 2.88; 70.34% female), 83.05% White/non-Hispanic recruited at a pediatric neurogastroenterology clinic completed measures of sleep disturbance, nausea, fatigue, pain intensity, and depressive mood. Three mediation models examined the effect of sleep disturbance on nausea, fatigue, and pain, with depressive mood as a mediator. RESULTS: Participants reported moderate sleep disturbance. Depressive mood partially mediated the significant, respective relations between greater sleep disturbance and more severe nausea and fatigue. Sleep disturbance was significantly associated with higher pain intensity; however, depressive mood was not a significant mediator of this relation. CONCLUSIONS: Sleep quality is a major concern among youth with DGBIs. Low sleep quality may worsen nausea and fatigue via co-occurring increases in depressive mood symptoms. In contrast, sleep disturbance may directly increase pain, regardless of youths' depressive mood symptoms. Future research should explore these relations through prospective studies leveraging a combination of subjective and objective assessment approaches.

Intrapyloric Botulinum Toxin Injection for Refractory Nausea and Vomiting in Pediatric Patients.

OBJECTIVES: Chronic nausea and vomiting may be associated with gastroparesis or other conditions. Poor mechanistic understanding of symptoms often precludes targeted therapy. Numerous case series suggest that intrapyloric botulinum toxin injection (IPBI) may be beneficial in treating gastroparesis and dyspepsia in children. We hypothesized that nausea, vomiting, and other symptoms, independent of gastroparesis, may improve with IPBI. We sought to identify gastric emptying (GE) and manometric patterns in IPBI responders versus nonresponders. METHODS: Electronic records of 25 pediatric patients who received IPBI for refractory nausea, vomiting, or both were retrospectively reviewed. We assessed symptom improvement post-IPBI and compared symptoms, GE, and antroduodenal manometry (ADM) findings between IPBI responders and nonresponders. RESULTS: At least one major symptom improved in 19 patients (76%) after IPBI. Of 22 patients completing a GE study, 14 had delayed GE with no significant difference between IPBI responders and nonresponders. Of 22 patients who underwent ADM, 18 had normal fasting peristalsis, 5 had postprandial antral hypomotility, 4 had neuropathic findings, and 19 had pylorospasm. IPBI responders, compared to nonresponders, demonstrated higher antral pressures with feeding ( P < 0.0001) and shorter duration of pylorospasm ( P = 0.0036). Antral pressures did not differ significantly with fasting or following motilin agonists. CONCLUSIONS: Our findings suggest that IPBI may have therapeutic benefit in pediatric patients with chronic nausea and/or vomiting, independent of gastroparesis. ADM findings of intact antral peristalsis and elevated antral pressures, in conjunction with efficacy of IPBI, support pyloric non-relaxation as a potential contributor to nausea and/or vomiting in pediatric patients.

Creating a data dictionary for pediatric autonomic disorders.

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.

Assessment of comorbid symptoms in pediatric autonomic dysfunction.

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.

Use of Cluster Analysis to Identify Subtypes of Pediatric Functional Nausea.

OBJECTIVE: The aim of the study was to evaluate whether there are clinical subtypes in children with functional nausea based on comorbidities and responses to the Nausea Profile questionnaire. METHODS: Patients from the Neurointestinal and Motility Program clinical registry at Lurie Children's Hospital were included if they met Rome IV criteria for functional nausea. Patients completed the Nausea Profile, a multidimensional measure of nausea with gastrointestinal, emotional, and somatic subscales. Comorbidities were assessed by chart review and self-report measures. Latent class analysis was used to identify patient groups based on comorbidities. To assess if model-identified groups were predictive of differences in nausea quality, Nausea Profile subscale means were compared between groups and used to predict group membership. Conversely, k-means analysis was used to divide the sample into groups based upon Nausea Profile subscale scores, to determine if identified groups had different comorbidities. RESULTS: Seventy-two patients (n = 53 girls) with a mean age (±SD) 14.5 ±â€Š2.9 were included. Two clinical subtypes were identified based on comorbidities, with responses on the emotional subscale of the Nausea Profile predicting group membership (P < 0.04). When patients were grouped by nausea quality, the resulting clusters differed on psychiatric comorbidities (P < 0.001). CONCLUSIONS: Our findings support the existence of nausea subtypes within the broad diagnosis of functional nausea. One such subtype is an emotional predominant nausea supporting the notion that anxiety and depression constitute a subset of patients with nausea. Thus, patients may benefit from a treatment approach that integrates both GI assessment and psychiatric support in their care.

Food protein-induced enterocolitis syndrome: Dynamic relationship among gastrointestinal symptoms, immune response, and the autonomic nervous system.

OBJECTIVE: To explore the relationship among gastrointestinal (GI) symptoms, immune response, and autonomic nervous system (ANS) in food protein-induced enterocolitis syndrome (FPIES) in relation to the current understanding of disease phenotype and pathogenesis. DATA SOURCES: Relevant studies related to FPIES, GI symptomatology, and ANS were reviewed. Literature search was performed using PubMed, with keyword combinations including but not limited to FPIES, allergic GI disorders, ANS, autonomic dysfunction, dysautonomia, GI, diarrhea, vomiting, neuroimmune, and clinical phenotyping tools. STUDY SELECTIONS: Peer-reviewed case-control studies, observational studies, reviews and guidelines, and systematic reviews related to FPIES and ANS were selected for review. RESULTS: There is limited research directly relating GI symptoms and FPIES to the ANS and immunologic response. To support the proposed mechanisms of action related to patient symptoms, studies relevant to coexisting GI-autonomic processes and FPIES immunologic triggers were examined. These related disease processes were extrapolated to FPIES based on the current knowledge of FPIES phenotype and pathogenesis. CONCLUSION: The etiology of FPIES and the underlying mechanisms triggering symptoms are not well understood. On the basis of the exaggerated GI symptoms and hemodynamic response observed, the ANS likely plays an important role in FPIES, possibly as a compensatory response. The trigger for this cascade of symptoms may be related to the disruption of immunologic homeostasis that typically contributes to immune tolerance. To more accurately evaluate FPIES pathophysiology necessitates understanding the diverse spectrum of presenting symptoms. A consistent and comprehensive symptom assessment tool may improve our understanding of this dynamic relationship.

Children with Functional Nausea-Comorbidities outside the Gastrointestinal Tract.

OBJECTIVE: To detail common comorbidities and procedures performed to evaluate functional nausea in children. STUDY DESIGN: In total, 63 children age 7-18 years seen in a tertiary care pediatric clinic who met Rome IV criteria for functional nausea prospectively completed an Intake Questionnaire, the Pediatric and Parent-Proxy PROMIS-25 Profile v 2.0, the Pediatric and Parent-Proxy Pediatric Sleep Disturbance-Short Form 4a, and the COMPASS 31 orthostatic intolerance scale to assess comorbidities. Medical records were reviewed for diagnostic tests performed to evaluate nausea and for additional comorbidities. Summary statistics were used to determine the most common comorbidities and diagnostic yield of the procedures. Intraclass correlation coefficients assessed agreement between parent and child reports on the PROMIS scales. RESULTS: Patients with functional nausea experienced multisystem comorbidities. A majority reported abdominal pain, headache, orthostatic intolerance, fatigue, disturbed sleep, anxiety, constipation, allergies, and vomiting. Agreement between parent-proxy and child report of symptoms on PROMIS scales was good to excellent (intraclass correlation coefficients = .78-.83; all P < .001). Patients underwent extensive diagnostic testing: 96 endoscopic procedures, 199 radiologic tests, and 4 cholecystectomies. Most of the procedures were not diagnostically informative. CONCLUSIONS: Children with functional nausea have comorbidities outside the gastrointestinal tract that warrant evaluation. Gastrointestinal diagnostic tests were of low-yield in identifying a cause. Understanding the relationship with comorbidities may provide insight into etiologies for the nausea and define clinical phenotypes to better tailor care.

Proceedings of the 2018 Advances In Motility and In NeuroGastroenterology: AIMING for the Future Single Topic Symposium.

OBJECTIVES: Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. METHODS: The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. CONCLUSIONS: The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.

Children with orthostatic intolerance exhibit elevated markers of inflammation in the dorsal medulla.

Children with orthostatic intolerance (OI) have exaggerated decreases in heart rate variability (HRV) and suppression of baroreflex sensitivity (BRS) with standing. Accompanying brain transmitter and metabolite profiles are unknown. In this study, we used proton (1H) magnetic resonance spectroscopy (1H-MRS) to quantify markers of neuronal and glial integrity in a pilot study of children with OI compared with asymptomatic controls. Eighteen participants ages 10-18 yr were evaluated for blood pressure, heart rate (HR), and calculated indexes of autonomic function in supine and upright positions and, within an average of 2 wk, underwent 1H-MRS scans of dorsal medulla on a clinical 3T magnet while supine. As a result, of the 18 participants, 11 tested positive for OI and 7 did not. OI subjects exhibited higher HR and lower HRV and high-frequency α-index (HFα), an index of parasympathetic vagal tone, during standing compared with non-OI. HRV, sequence all (Seq All), high- and low-frequency (HFα and LFα) estimates of the spontaneous BRS decreased significantly, while BP variabilty increased significantly during standing only in subjects with OI. OI subjects had higher myoinositol (mIns) and total choline (tCho), markers of glial inflammation. Upright HFα and Seq All inversely correlated to supine tCho and mIns, respectively, independent of age and sex. In conclusions, in this pilot study, children with OI exhibit higher mIns and tCho in the dorsal medulla while supine that may reflect the well-established impairment in regulation of the autonomic nervous system upon standing. Neuroinflammation as an underlying cause or consequence of autonomic dysfunction is an intriguing possibility requiring further study.NEW & NOTEWORTHY (1H) magnetic resonance spectroscopy detected elevated markers of neuroinflammation in the dorsal medulla in children with impaired autonomic responses to head upright tilt. This first report of altered brain metabolites in this population provides a basis for future clinical studies using this methodology to aide in understanding complex autonomic disease states.

Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options.

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI.

Use of an allostatic neurotechnology by adolescents with postural orthostatic tachycardia syndrome (POTS) is associated with improvements in heart rate variability and changes in temporal lobe electrical activity.

Autonomic dysregulation and heterogeneous symptoms characterize postural orthostatic tachycardia syndrome (POTS). This study evaluated the effect of high-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM(®)), a noninvasive, allostatic neurotechnology for relaxation and auto-calibration of neural oscillations, on heart rate variability, brain asymmetry, and autonomic symptoms, in adolescents with POTS. Seven subjects with POTS (three males, ages 15-18) underwent a median of 14 (10-16) HIRREM sessions over 13 (8-17) days. Autonomic function was assessed from 10-min continuous heart rate and blood pressure recordings, pre- and post-HIRREM. One-minute epochs of temporal high-frequency (23-36 Hz) brain electrical activity data (T3 and T4, eyes closed) were analyzed from baseline HIRREM assessment and subsequent sessions. Subjects rated autonomic symptoms before and after HIRREM. Four of seven were on fludrocortisone, which was stopped before or during their sessions. Heart rate variability in the time domain (standard deviation of the beat-to-beat interval) increased post-HIRREM (mean increase 51%, range 10-143, p = 0.03), as did baroreflex sensitivity (mean increase in high-frequency alpha 65%, range -6 to 180, p = 0.05). Baseline temporal electrical asymmetry negatively correlated with change in asymmetry from assessment to the final HIRREM session (p = 0.01). Summed high-frequency amplitudes at left and right temporal lobes decreased a median of 3.8 µV (p = 0.02). There was a trend for improvements in self-reported symptoms related to the autonomic nervous system. Use of HIRREM was associated with reduced sympathetic bias in autonomic cardiovascular regulation, greater symmetry and reduced amplitudes in temporal lobe high-frequency electrical activity, and a trend for reduced autonomic symptoms. Data suggest the potential for allostatic neurotechnology to facilitate increased flexibility in autonomic cardiovascular regulation, possibly through more balanced activity at regions of the neocortex responsible for autonomic management. Clinical trial registry "Tilt Table with Suspected postural orthostatic tachycardia syndrome (POTS) Subjects," Protocol Record: WFUBAHA01.

Associated Factors for Antegrade Continence Enemas for Refractory Constipation and Fecal Incontinence.

OBJECTIVE: Determine clinical and manometric parameters associated with success of antegrade continence enemas (ACEs) administered via cecostomy in the treatment of constipation and fecal overflow incontinence. METHODS: We performed a retrospective review of clinical symptoms and manometry (colonic and anorectal) before cecostomy in 40 pediatric patients (20 males, 20 females). The mean age at time of follow-up was 9.5 ±â€Š4.4 years with a mean follow-up time of 12.2 ±â€Š10.9 months. Clinical outcomes were defined as good, if subjects had >3 bowel movements per week, <2 episodes of soiling per week, and absence of pain at the time of follow-up after cecostomy. RESULTS: Before cecostomy, the mean duration of constipation and/or fecal incontinence was 7.7 ±â€Š4.4 years, mean number of BMs was 1.5 ±â€Š0.9 per week, and soiling episodes 4.12 ±â€Š3.5 per week; 24 (60%) patients had abdominal pain. At follow-up 30 out of 40 patients had a good outcome, and 10 had a poor outcome; with a difference in the number of weekly BM of 5.7 ±â€Š2.2 versus 1.5 ±â€Š0.9, P < 0.001, and soiling episodes (0.4 ±â€Š1.5 vs 4 ±â€Š3.1, P < 0.001). There was no difference in the duration of symptoms between groups. Obesity was more common in the poor-outcome group, 60% versus 21% (P = 0.01). Abdominal pain was more common in the poor-outcome group, 100% versus 47% (P = 0.003). Normal colonic manometry was associated with good outcome, whereas absence of high-amplitude propagating contraction (HAPC) in any part of the colon was associated with poor outcome. No other differences in colonic manometry were observed between the good- and poor-outcome groups with the exception of a trend toward decreased number of sigmoid HAPCs in the poor-outcome group (P = 0.07). No differences were observed in anorectal manometry measurements between good- and poor-outcome groups with the exception of an observable increased baseline resting pressure in the poor outcome (P = 0.05). CONCLUSIONS: Obesity and abdominal pain tend to be associated with poor outcomes after cecostomy for refractory constipation. Normal colonic and anorectal manometry were associated with good outcome. Absence of HAPC in any part of the colon, and increased baseline resting pressure of the anal canal were more associated with poor outcome. No other specific differences in either colonic or anorectal manometric parameters were observed in patients with good versus poor outcomes with cecostomy. Large prospective studies potentially combining other diagnostic modalities such as colonic transit studies are needed to determine the optimal tests to predict successful outcomes from cecostomy.

EUS and EUS-Guided Interventions Alter Clinical Management in Children With Digestive Diseases.

OBJECTIVES: Endoscopic ultrasound (EUS) ± fine needle aspiration (FNA) is a useful tool to evaluate gastrointestinal tract disorders in adults because of its established feasibility and safety. Its role in children has not been well established and continues to evolve. Our objective was to evaluate the utility and impact on clinical management of EUS and EUS-guided interventions in the pediatric population at our institution. METHODS: Retrospective, single-center study including 43 patients undergoing EUS and EUS-FNA between August 2005 and January 2012. RESULTS: Fifty-one EUS procedures were performed in 43 patients, 30 girls, median age 14.5 (range 4-18). The most common indications were suspected biliary obstruction in 11 of 51 (22%), pancreatic cysts in 10 of 51 (20%), acute or recurrent pancreatitis in 9 of 51 (18%), and abdominal pain in 8 of 51 (16%). The most common findings of EUS included normal 11 of 51 (22%), pancreas cyst 6 of 51 (12%), pancreatic pseudocyst 5 of 51 (10%), biliary system sludge or stones 9 of 51 (18%), and acute and chronic pancreatitis 5 of 51 (10%). EUS-FNA was performed in 13 cases: 7 solid masses or nodes, 4 pancreatic pseudocyst, 1 pancreatic cyst, and 1 celiac plexus block. FNA cyst drainage was successful in resolving all 4 pancreatic pseudocysts. EUS prompted a surgical procedure in 13 cases (25%), ERCP in 5 cases (10%), and repeat EUS in 5 cases (10%). EUS led to a new diagnosis in 34 of 43 (79%) patients and prompted further intervention in 24 of 51 (47%) procedures. CONCLUSIONS: In this large cohort study, we found that EUS and EUS-guided interventions assist in diagnosing and altering clinical management in pediatric patients and should be considered in cases with vexing pancreaticobiliary disorders.

Relationship among nausea, anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea.

This study evaluated the relationship among nausea, anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea. We enrolled 48 patients (36 females) aged 15 ± 2 years. Patients completed the Nausea Profile, State-Trait Anxiety Inventory for Children and underwent 70° head upright tilt testing (HUT) to assess for orthostatic intolerance (OI) and measure heart rate variability (HRV). We found nausea to be significantly associated with trait anxiety, including total nausea score (r = 0.71, p < 0.01) and 3 subscales: somatic (r = 0.64, p < 0.01), gastrointestinal (r = 0.48, p = 0.01), and emotional (r = 0.74, p < 0.01). Nausea was positively associated with state anxiety, total nausea (r = 0.55, p < 0.01), somatic (r = 0.48, p < .01), gastrointestinal (r = .30, p < .05), and emotional (r = .64, p < .01) subscales. Within 10 min of HUT, 27 patients tested normal and 21 demonstrated OI. After 45 min of HUT, only 13 patients (27%) remained normal. Nausea reported on the Nausea Profile before HUT was associated with OI measured at 10 min of tilt (nausea total r = 0.35, p < 0.05; nausea emotional subscale r = 0.40, p < 0.01) and lower HRV at 10 min of HUT (F = 6.39, p = 0.01). We conclude that nausea is associated with both anxiety symptoms and OI. The finding of decreased HRV suggests an underlying problem in autonomic nervous system function in children and adolescents with chronic unexplained nausea.

Impact of eating restriction on gastrointestinal motility in adolescents with IBS.

OBJECTIVE: Gastrointestinal disturbances as a result of changes in eating patterns have been described in eating disorders. Many patients who experience irritable bowel syndrome report changes in eating patterns as a way to cope with their symptoms. Little is known about the consequences of these practices. The aim of this study was to explore whether repeated eating restriction (defined as not eating ≥ 4 hours while hungry) is associated with motility disturbances. METHODS: Of 17 patients with irritable bowel syndrome, subjects were divided into those who habitually restrict their eating (n = 8) and those without eating restriction (n = 9) (age range 15-21, mean 19.2; 64.7% girls). Whole-gut transit time was measured by radiopaque markers, gastric sensitivity was measured by water load test (drinking max of 800 mL of water in 5 minutes or until full), and gastric dysrhythmias by an electrogastrogram. RESULTS: Restrictors drank less water (mean 464.4 mL) than nonrestrictors (mean 613 mL; P = 0.02). No difference was found in gastric dysrhythmias (62.5% vs 77.8%; P = 0.5). Whole-gut transit tended to be slower in the restrictors (mean 51.0 hours) than in nonrestrictors (mean 37.5 hours), but this was not significant. CONCLUSIONS: Eating restriction appears to be associated with increased gastric sensation. More data are needed from larger studies to determine whether eating behaviors are associated with other motility disturbances.

Effect of fludrocortisone acetate on chronic unexplained nausea and abdominal pain in children with orthostatic intolerance.

BACKGROUND: We hypothesized that orthostatic intolerance (OI) is associated with gastric dysrhythmias, nausea, and abdominal pain, which improves using fludrocortisone to treat OI. METHODS: Patients (n=16, girls) with OI completed questionnaires before and after fludrocortisone treatment (age 14.8 ± 2.8 years). Ten patients underwent electrogastrograms (EGGs) before fludrocortisone. RESULTS: All EGGs showed gastric dysrhythmias. Fludrocortisone reduced mean scores as follows: nausea, 3.1 ± 0.8 to 2.1 ± 1.1 (P=0.016); dizziness, 3.0 ± 1.0 to 2.2 ± 1.1 (P=0.0371); abdominal pain, 2.8 ± 1.3 to 1.9 ± 1.4 (P=0.0063); flushing, 2.3 ± 1.2 to 1.5 ± 1.4 (P=0.0476); and missing school, 2.2 ± 1.5 to 1.2 ± 1.5 (P=0.0078). CONCLUSIONS: Chronic nausea and abdominal pain accompany OI and improve with OI treatment.

Somatic, emotional, and gastrointestinal symptom severity are increased among children and adolescents with COVID-19.

BACKGROUND: Post-infectious disorders of gut-brain interaction (PI-DGBI) have significant impact on children and adolescents. The effect of COVID-19 on PI-DGBI-associated symptoms in this population, however, is unknown. METHODS: We performed electronic medical record searches to identify patients 8-17 years old with a SARS-CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April-October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms-Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID-19 test or the test result. RESULTS: One hundred and ninety-six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self-reported their child's COVID-19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID-19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID-19 testing that was highest among patients with a positive COVID-19 test. Abdominal pain and diarrhea prior to COVID-19 testing predicted higher NP scores. CONCLUSIONS: Among symptomatic COVID-19 tested children, we found increased severity of nausea-associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID-19 test.

Children with chronic nausea and orthostatic intolerance have unique brain network organization: A case-control trial.

BACKGROUND: Determine whether subjects with chronic nausea and orthostatic intolerance share common alterations in key brain networks associated with central autonomic control: default mode, salience, and central executive networks, and the insula, a key component of the salience network. METHODS: Ten subjects (ages 12-18 years; 8 females, 2 males) with nausea predominant dyspepsia, orthostatic intolerance, and abnormal head-upright tilt test were consecutively recruited from pediatric gastroenterology clinic. These subjects were compared with healthy controls (n = 8) without GI symptoms or orthostatic intolerance. Resting-state fMRI and brain network modularity analyses were performed. Differences in the default mode, salience, and central executive networks, and insular connectivity were measured. KEY RESULTS: The community structure of the default mode network and salience network was significantly different between tilt-abnormal children and controls (p = 0.034 and 0.012, respectively), whereas, no group difference was observed in the central executive network (p = 0.48). The default mode network was more consistently "intact," and the consistency of the community structure in the salience network was reduced in tilt-abnormal children, especially in the insula. CONCLUSIONS AND INFERENCES: Children with chronic nausea and orthostatic intolerance have altered connectivity in the default mode network and salience network/insula, which supports over-monitoring of their body and altered processing of bodily states resulting in interoceptive hyper self-awareness. The connectivity of the salience network would not support optimal regulation of appropriate attention to internal and external stimuli, and the hyper-connected default mode network may result in a persistent self-referential state with feelings of emotion, pain, and anxiety.