Gastrointestinal manifestations seen in pediatric patients diagnosed with small fiber neuropathy.

OBJECTIVES: Small fiber neuropathy (SFN) affects the fibers involved in cutaneous and visceral pain and temperature sensation and are a crucial part of the autonomic nervous system. Autonomic dysfunction secondary to SFN and autoimmune receptor antibodies is being increasingly recognized, and gastrointestinal (GI) manifestations include constipation, early satiety, nausea, vomiting, and diarrhea. Enteric nervous system involvement may be a possible explanation of abnormal GI motility patterns seen in these patients. METHODS: Children suspected to have SFN based on symptoms underwent skin biopsy at the Child Neurology clinic at Arnold Palmer Hospital for Children, which was processed at Therapath™ Neuropathology. SFN was diagnosed using epidermal nerve fiber density values that were below 5th percentile from the left distal leg (calf) as reported per Therapath™ laboratory. RESULTS: Twenty-six patients were diagnosed with SFN. Retrospective chart review was performed, including demographic data, clinical characteristics, and evaluation. A majority of patients were white adolescent females. Autonomic dysfunction, including orthostasis and temperature dysregulation were seen in 61.5% of patients (p = 0.124). Somatosensory symptoms, including pain or numbness were seen in 85% of patients (p < 0.001). GI symptoms were present in 85% of patients (p < 0.001) with constipation being the most common symptom seen in 50% of patients. This correlated with the motility testing results. CONCLUSIONS: Pediatric patients with SFN commonly have GI symptoms, which may be the main presenting symptom. It is important to recognize and look for symptoms of small fiber neuropathy in children with refractory GI symptoms that may explain multisystemic complaints often seen in these patients.

Prevalence of Exocrine Pancreatic Dysfunction Based on Direct Function Testing in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) frequently have extraintestinal manifestations. The goal of this pilot study was to assess exocrine pancreatic function in cases with suspicion for or an established diagnosis of IBD. METHODS: Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD, in both newly diagnosed and established cases. Demographic, clinical, and laboratory parameters were entered into a database and analyzed. RESULTS: Among the 74 children, 49 were newly diagnosed and 25 had an established diagnosis of IBD. A majority had the diagnosis of Crohn disease (CD) (n = 48; 32 new and 16 established cases) with male predominance (64.6%). Altogether, 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). Twenty-four of the 48 CD children (50%) had abnormal ePFT. In those with ulcerative colitis (UC), 18 of the 26 (62.9%) had abnormal ePFT. The highest abnormality rate was in lipase enzyme activity. Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). Peak protein concentration in collected pancreatic fluid was significantly lower in children with CD who had abnormal ePFT ( P = 0.013). CONCLUSIONS: This pilot study revealed a relatively high prevalence of EPI in children with IBD through use of ePFT. EPI can result in maldigestion, with decreased capacity to digest fat. Further prospective studies are needed to assess need and efficacy of pancreatic enzyme replacement therapy in children with IBD and abnormal ePFT.

Effect of Caffeine on Colonic Manometry in Children.

OBJECTIVES: Coffee and caffeinated products have been widely consumed for many centuries. Previous adult studies have suggested that both coffee and decaffeinated beverages induce colonic motility. However, no study has been conducted in pediatrics, and the role of caffeine alone in pediatric colonic motility needs to be explored. METHODS: A prospective study of pediatric patients undergoing standard colonic motility testing that were able to consume caffeinated coffee, decaffeinated coffee, and caffeine tablet during colonic manometry. Patients who had a gastrocolonic reflex and high amplitude propagated contractions (HAPCs) in response to intraluminal administration of bisacodyl in the colon were included in the final analyses. RESULTS: Thirty-eight patients were recruited, 22 of which were excluded, 11 due to abnormal studies (no HAPC seen in response to intraluminal response to bisacodyl), and 11 due to inability to consume all study agents or complete the study. Sixteen patients met criteria for final analyses. Intracolonic bisacodyl produced a larger area under the curve (AUC) compared to all other agents. Caffeinated coffee resulted in a higher AUC, motility index (MI), and time to HAPC compared with decaffeinated coffee ( P < 0.05). There was no significant difference between caffeinated coffee and caffeine tablet, or caffeine tablet and decaffeinated coffee. CONCLUSIONS: Caffeine is indeed a colonic stimulant; however, other components of caffeinated and non-caffeinated beverages likely induce colonic response and require further evaluation for possible use as a colonic stimulant.

Prospective Evaluation of Transanal Irrigation With a Validated Pediatric Neurogenic Bowel Dysfunction Scoring System.

OBJECTIVES: To evaluate the efficacy of transanal irrigation (TAI) in pediatric patients with neurogenic bowel dysfunction (NBD) who were treatment naïve to catheter-based TAI using Peristeen device (Coloplast). METHODS: Prospective recruitment of patients with NBD who were unsatisfied with their bowel regimen or had no bowel regimen in place, were assessed using the neurogenic bowel dysfunction score (NBDS) before initiating treatment (Time 0) with Peristeen. NBDS scores were reassessed twice: within the first 6 months (Time 1) of initiation of Peristeen and again after greater than 6 months of usage with Peristeen (Time 2). RESULTS: Over a 26-month period, 104 patients with NBD were enrolled. Mean age was 10.6 years ± 4.7 (range 3-18 years). The NBDS at Time 1 had an average reduction of 14 points from the original score. A similar trajectory was seen at Time 2, with an average reduction of 13 points from original score. There was a statistically significant decrease of 14 points, P < 0.001 at Time 1 and this response was sustained at Time 2 with a statistically significant decrease in scores from initiation by 13 points, P < 0.001. Improved patient satisfaction and quality of life with Peristeen was seen at Time 1 and Time 2. CONCLUSION: Our results suggest that Peristeen can improve quality of life in pediatric patients with NBD. Significant improvement in NBDS occurred in our pediatric patients with NBD when initiated on Peristeen. Lower scores were seen at both Time 1 and Time 2, which indicated an improvement in their overall NBD.

Respiration and substrate transport rates as well as reactive oxygen species production distinguish mitochondria from brain and liver.

BACKGROUND: Aberrant mitochondrial function, including excessive reactive oxygen species (ROS) production, has been implicated in the pathogenesis of human diseases. The use of mitochondrial inhibitors to ascertain the sites in the electron transport chain (ETC) resulting in altered ROS production can be an important tool. However, the response of mouse mitochondria to ETC inhibitors has not been thoroughly assessed. Here we set out to characterize the differences in phenotypic response to ETC inhibitors between the more energetically demanding brain mitochondria and less energetically demanding liver mitochondria in commonly utilized C57BL/6J mice. RESULTS: We show that in contrast to brain mitochondria, inhibiting distally within complex I or within complex III does not increase liver mitochondrial ROS production supported by complex I substrates, and liver mitochondrial ROS production supported by complex II substrates occurred primarily independent of membrane potential. Complex I, II, and III enzymatic activities and membrane potential were equivalent between liver and brain and responded to ETC. inhibitors similarly. Brain mitochondria exhibited an approximately two-fold increase in complex I and II supported respiration compared with liver mitochondria while exhibiting similar responses to inhibitors. Elevated NADH transport and heightened complex II-III coupled activity accounted for increased complex I and II supported respiration, respectively in brain mitochondria. CONCLUSIONS: We conclude that important mechanistic differences exist between mouse liver and brain mitochondria and that mouse mitochondria exhibit phenotypic differences compared with mitochondria from other species.

Utilization of Single-Incision Laparoscopy in the Management of Ingested Magnets.

Background: A ban on neodymium magnets was lifted by the U.S. Consumer Product Safety Commission in 2016. Pediatric gastroenterologists and surgeons were increasingly tasked with removing these problematic objects. The purpose of this study was to assess the utility of single-incision laparoscopic surgery (SILS) in the management of ingested magnets. Patients and Methods: This is a single-center, retrospective assessment of surgical interventions for ingested magnets. International Classification of Disease, 10th revision codes were used to identify 349 patients ≤21 years of age evaluated for foreign body ingestion over a 4.5-year period. A medical record review helped isolate 29 (8.3%) magnet ingestions, 9 requiring surgical intervention. RedCap was used for analysis. Results: Of 9 surgical patients, 7 underwent SILS intervention by 1 surgeon. Another surgeon performed an open operation, whereas a third performed a multiport operation. Of the 7 SILS cases, 3 were completed without conversion to open. In one of these cases, bowel resection with primary anastomosis was performed. For SILS cases, average operating room time was 109 minutes (38-170 minutes), time to enteral feeds was 23 hours (0.28-79.2 hours), and hospital length of stay (LOS) was 3.8 days (1.96-6.68 days). Thirty-day readmission for SILS was 14.3%. No other complications were observed. Conclusions: SILS has been safely utilized for magnet retrieval. It offers an ability to identify the affected intestinal segment and an opportunity to intervene extracorporeally through an uncapped port. In addition, knowing where matted bowel is located can direct a limited incision during conversion to laparotomy. This may confer benefits of decreased pain, shortened time to enteral feeds, and decreased hospital LOS.