Chapters Transcript Evaluation/Management of Neurogastroenterology and Motility Disorders in the Pediatric Patient Awesome. Well, thank you guys for inviting me to speak today. It's really a privilege to talk to you guys about a series of uh disorders uh that are near and dear to me and um talk about evaluation and management of neurogastroenterology and motility disorders in the pediatric patient. Uh, these are my disclosures. Nothing relevant that's influencing today's talk. So here's our objectives for today. So, uh, first, we're going to start off by defining what neurogastroenterology and motility are, including some physiologic mechanisms of function and the disruption caused by dysfunction. We're going to describe normal motility by segment of the GI tract. Recognize the clinical presentation of neurogastro motility disorders based on the GI tract location. Outline a pragmatic approach for evaluation when these are suspected. Review the basic motility tests, uh, including options and interpretation of results, and examine the current management strategies based on diagnosis and location of the GI tract. So neurogastroentology includes the complex interaction between the nervous system and the digestive system, specifically, How the the enteric, the the central and the autonomic nervous systems regulate function of the GI tract. Motility is the coordinated movement within the digestive system, specifically how food and waste transit through the GI tract. So this interaction includes, as I mentioned, the central nervous system, so input from the cortex for awareness and anxiety, the limbic system, which can be related to emotional tone, stress reactivity. And then the hypothalamic pituitary adrenal axis to release of corticotropin releasing hormone. Uh, enteric input is, uh, from, uh, the my enteric plexus, which is also known as the A box plexus, uh, which is between the circular and longitudinal muscle layers. The submucosal plexus, also known as the Meisner's, and uh that's within the submucosa and then glial cells as well. And, uh, input from the autonomic nervous system, uh, specifically the parasympathetic, which promotes, uh, motility and secretion and digestion related, um, and mediated through the vagus nerve. Which uh innervates the esophagus through the mid-transverse colon, and also the pelvic splenic nerves, S2 through S4, which uh innervate the remainder of the colon and the rectosigmoid area. Uh, on the opposite side of the spectrum is the sympathetic nervous system, which inhibits motility and secretion. Um, and also important for neurogastro patients are these postganglionic fibers, which mediate pain and visceral hypersensitivity. So, uh, what's the importance of neurogastroenterology motility? So, um, it is critical for digestion, absorption, and removal of waste. Uh, there's several complex motor patterns, uh, involved in coordinating contractions and relaxations of these external muscle layers of the GI tract, and they each have distinct roles in, uh, gut motility. The coordinated movements also include mixing, propagating motor activity, and receptive relaxation. And we know that disruption can lead to, uh, several issues, including GI distression symptoms, uh, potential microbiome alterations, uh, such as overgrowth from stasis or dysmotility. And a negative impact on quality of life. So I thought I'd start by going over motility testing options, and then we'll kind of plug these in to um topics based on segment of the GI tract. So imaging options you'll see here include uh Scintigraphy, which most of us know about gastric scintigraphy, which is also known as gastric emptying scan, but there's also opportunities in the esophagus and the colon. Uh, there's also barium swallows, which may include video assisted swallow studies or modified barium swallow. Um, esophagram, and, um, Upper GI series. Uh, we know that barium swallow has poor sensitivity for, uh, detecting true motility disorders. It's around 30 to 40% in comparison to gold standard evaluation. So if you end up getting a barium swallow, and you see there's dysmotility on it, it doesn't necessarily predict uh manometric abnormalities. But also the opposite is true. Normal esophagram does not necessarily rule out motility disorders either. Talked about imaging, breath testing, manometry. Um, these include esophageal, antraduodenal, colonic, and anorectal. It's something called EOFLIB, which is uh endoluminal functional lumen imaging probe, and this can be used in various parts of the GI tract for motility assessment as well that we'll go over. You may hear or have heard of something called the wireless motility capsule. Uh, this has been taken off the market by the FDA. Um, there are some newer options that are being explored, but nothing currently available for motility evaluation. And then we do a reflux-based pH monitoring, which can uh be over a catheter or wireless. So, um, to talk about some of these more specifically, uh, gastric scantigraphy, also better known as gastric emptying scan. Some indications for this includes a patient uh with ongoing nausea, vomiting, bloating. Potentially regurgitation, early satiety, or, or dumping. Um, it can be used as a preoperative assessment as well. And the protocol is very specific. It includes the ingestion of eggs, 2 slices of toast with jam and a, and a small amount of water, and then uh abdominal images are obtained out to 4 hours post meal to assess the emptying. Um, and this image on the right is an example of a nuclear, uh, imaging photo series taken at all time points throughout the study. As the pictures go on, you'll notice that a majority of the radio tracer, uh, is excreted. So right here in the leftover quadrant, we're seeing a lot of this, uh, White show up on the screen here, and as we go through, it's less and less, and you can see it's kind of blurred by this uh text at the bottom here, but this is it entering into the small bowel. So, uh, cine MRI, uh, utilizes rapid repeated T2 weighted images where fluid appears bright to create a movie. Of a small bowel movement. Uh, one of the original protocols consisted of over 200 images within a 92nd period. Uh, and that was collected every 15 minutes for an hour to assess motility. Patients typically need to drink oral contrast to allow for distention and visualization of the small bowel. Um, it's a non-invasive assessment of the small bowel, which is very appealing, um, but it's mostly utilized in a research capacity at this time, and there's no widely adopted standardized protocols yet. Um, and also because of this, availability is limited. This is just a quick depiction of kind of what they're looking at. Um, in this circle bar in the middle, uh, is demonstrating the diameter of the small bowel through a series of images, which helps to get an understanding of contractility. There's also radio opaque markers, and uh these are available for patients over or at least 2 years of age. Indications include constipation or assessment of colonic motility. The protocol includes ingestion of a capsule filled with 24 markers on day one. And if a patient can't swallow this, they can be opened into a spoonful of applesauce, and then an abdominal X-ray on day 5. To, uh, that's used to assess the location and the retention of markers. And those who expel at least 80% of these, uh, or 19 or more, uh, are thought to have grossly normal colonic transit. Um, and if it's less, We consider things like colonic inertia or hyper hypomotility. Um, but certainly this may be investigated further with Manometry. And we also think about, you know, if there's accumulation in the rectosigmoid region, this may indicate outlet dysfunction. And here's an example of this, uh. You'll notice several of these markers are retained uh uh on the right side, in the right colon, the ascending colon. Uh, and then there's a few that are in the rectal sigmoid area, but this is an X-ray of day 5 with a toddler with abnormal testing. The breath testing has several indications. Uh, including, as we talked about, SIB or small intestinal bacteria overgrowth, and a newer, um, term called intestinal methanogen overgrowth. Uh, symptoms can be very non-specific but include nausea, vomiting, diarrhea, bloating, constipation. And we tend to see these in patients with underlying dysmotility or some pre predisposition that uh bacteria could climb up from the colon into the small bowel and start to ferment ferment uh nutritional products as they pass by. There's also a use for carbohydrate malabsorption such as lactose, fructose, and sucrose. Um, and then there are some options that are coming available for gastric emptying assessment too for, especially for those who um may not tolerate the scan. Um, and the protocol can vary. There's an in in-office or home collection option. Currently, we're doing the, uh, in-office collection, uh, at children's, but we are working on, uh, this at-home possibility as well. Um, and there's a standardized set of instructions, including stopping certain medications that may influence, uh, motility, uh, starting a low gas producing diet the day before testing. Uh, and then an NPO time that need to be followed. Uh, and then on the day of testing, initial baseline samples collected, and then the patient would ingest the sugar of choice, uh, for small bowel, uh, intestinal, and bacterial overgrowth. We're typically using lactulose. You can also use glucose. Um, and then a sample of exhaled air is collected every 15 minutes for 180 minutes. So these are just examples of, uh, on the left, what would be an at-home collection kit with a vial here. Uh, your mouth goes up to this, uh, right side, um, and you blow air into this bag, um, and at a certain time point, you lift the vial up to the bottom of this device and it collects a sample. Um, and on the right here is what we would use in office. So instead of collecting in these vials, we're collecting in a syringe that's immediately transferred to the, um, The actual uh system to interpret. And then this is just an example of uh the results that would come out uh from the breath testing. Which includes a baseline and then out to 180 minutes. And um this patient did test positive for both uh SIBO and for IMO based on the parameters. So for manometry, and this is a catheter-based testing, and this evaluates the pressure changes within the GI tract, uh, which is reflective of contractility, I'm sorry, contractility, sphincter tone, and coordination. So for oesophageal manometry, uh, interestingly, This was first developed by Doctor Ray Klaus in the early 2000s here at WashU. Um, and this was in, um, an advancement from conventional manometry that had been developed for, uh, probably 20 or 30 years at that time to make it more easily interpretable. And we'll, I'll show you, uh, how so in just a minute. Um, indications are listed here. Uh, dysphagia is a common one for us, um, globus, regurgitation, non-cardiac chest pain. We do get patients, uh, who need evaluation for refractory reflux, uh, something called a Belcher, which we'll talk about, um, in a preoperative assessment. Placement can be awake or uh with a sedated endoscopy. Um, and awake, uh, placement, there's some lidocaine jelly that briefly goes, uh, uh, in the nares, and probably about 5 minutes later, we attempt to place the catheter that way. The protocol lasts about 30 to 45 minutes. It's an outpatient study. It includes a series of different types of swallows, so wet, viscous, and solid, and these are in a few positions, supine and upright. And then there's a series of what are called provocative maneuvers where we try to, uh, stress the esophagus a little bit and understand if there is evidence of outflow obstruction. So this is showing what conventional manometry used to look like on the left, and basically what the conversion of it is on the right hand side. And you'll notice that, you know, this, this is a little bit harder to interpret compared to the, the right hand side here where um On the right hand side of this picture, we're noticing an increasing increasing spectrum of pressures from blue, green, yellow, orange, red, purple, that allows you to understand the the amplitude of contraction. Um, in real time without having to hover over each particular peak. And just to orient you, um, it's, it's on this, but, uh, This green bar up here is called the upper esophageal sphincter. This green bar down here is the lower esophageal sphincter, and this is the body of the esophagus with a peristaltic wave happening. You'll notice there's a slight change in color from green to blue right here. That's relaxation of the Upper sphincter as someone takes in a swallow. Um, and then we also nicely have a relaxation of the lower esophageal sphincter to allow passage of the contents into the stomach. And then these are just uh quick photos of what it may look like as we place these endoscopically, so in the hypopharynx and then in the esophagus. So, uh, next is a duodennomanometry indications, um. Symptoms that are concerning, nausea, vomiting, regurgitation, feeding intolerance is a big one, and bloating. And if there's any concern for pediatric intestinal pseudo obstruction, which we'll talk about later. Placement can be um either uh transnasal or through a gastrostomy stoma, and this is always with a sedated upper endoscopy because it has to go into the stomach and travel into the small bowel as well. Um, and the protocol, after the catheter is placed, these patients are recovering on our inpatient service with testing the fall the next morning because there's some suggestion that anesthesia influences the motility pattern in these cases. Um, and the study is much more involved than what we talked about for esophageal and what we'll talk about for anorectal manometry. But this is a, uh, at least a six-hour study, includes several Different phases, including a fasting phase, medication phase, and a meal phase. Um, and then just wanted you to, uh, see what this may look like, uh, after placement. Um, On the top here with the, the red star, this is the androduodenal catheter coming down the esophagus, making a little loop in the stomach here, uh, exiting through the pylorus into the small bowel and making its way in to the, the distal duodenum or proximal jejunum. Um, and then this patient also had a colonic catheter placed here with the Green Star, and you'll notice this is Traveling uh up here as well, probably at the level of the hepatic flexure. And I know this is a little hard to see, but I just wanted you to uh understand what what we're seeing on the screen as this is happening during the study. And this is uh one circumstance where conventional tracing is much more uh easy to interpret compared to high resolution. So, um, what you'll notice and to orient you. These bigger contractions here signify to me that we're at the level of the pylorus or in the stomach. So this would be the level of the, the stomach and above here. And then below, the smaller amplitude. Uh, squiggly lines that you see would be in the small bowel, and what we're looking for, uh, specifically in the fasting phase is something called the migratory motor complex. Which tells us that there are intact, uh, neuronal connections within the upper GI tract. Think of these as the street sweeper of the bowel, um, and they're typically occurring when you're not eating, where they're trying to push things down and out of the stomach and into the small bowel. And what you'll notice is this nice progression of contractions in these two locations. Which is normal. So, uh, for colonic manometry, indications are typically chronic refractory constipation. We use it in a preoperative or uh postoperative setting, and if there's concern for people as well. Placement occurs with a sedated endoscopy, and specifically a colonoscopy. Um, and similar, these patients are recovering on the inpatient side afterwards. They are typically bed and bowel rest, so that we don't dislodge the catheter before we start the study, and the study also takes about 6 hours and includes this similar phases. This is just a picture of what it would look like. And then these are um X-rays as we take that are part of the protocol where you'll notice uh the colon catheter going all the way to the cecum, um, and both of these. And then, um, this is just a depiction of what we would see on the actual, uh, screen as we're doing these studies. And we're looking for what are called high amplitude propagating contractions throughout the colon, and there's specific criteria we would look for that we won't get into. But, uh, you'll notice, I mean it's also hard to see on these, but these uh red bars coming down are contractions of the colon throughout the entire colon, um, which is normal. And then on the right side here, this is a patient that had some distal colonic dys motility related to uh dilation of the rectosigmoid area from chronic constipation. But you'll notice they do have uh these HAPCs, but they, they end right here when this, uh, these contraction blips down here is this is actually the anal sphincter right here. So this whole end area part right here is dismodal. And then anal rectum manometry. Indications are patients with constipation, fecal incontinence, concern for outlet dysfunction or dysynergia, which we'll talk about more. Um, We're using it a lot more frequently than a rectal suction biopsy now to uh look for something called the rectal anal inhibitory reflex, which is very helpful in ruling out Hirschsprung disease, which is where, uh, ganglion cells and neurons have not traveled to the end part of the bowel, so they're not functioning as they should, which tends tends to lead to chronic constipation and bloating. Uh, we also use it for preoperative or post-operative assessment. Um, these are placed awake. Um, the protocol lasts for 15 to 30 minutes. It's outpatient. Patients are in the left lateral position for this. Um, and then we've also incorporated what's called the balloon expulsion testing, which Nobody poops laying on their, down on their left side. So what we have them do is sit up on a commode. The end part of the catheter, uh, that you can see right here that's being uh calibrated has a small balloon on it that we use throughout the study, but this is slightly inflated to simulate. Uh, stool in the rectal vault, and the patient has a minute to try to pass that. And then endo flip, um. Uh, this, uh, Indications for this include concern for outflow obstruction, uh, inability to tolerate manometry, or it can be used for a stricture or narrowing assessment. Um, this is placed during a sedated endoscopy and removed prior to awakening. Um, and on the right hand side here, you'll see what the catheter looks like. Um, it's got a bunch of impedance electrodes. Along the distance here that are enclosed by uh a bag that fills with an electrolyte uh solution that allows us to utilize res impedance and resistance to uh create uh this display on the screen here which is looking at uh distensibility, diameter, and pressure of lumen. This is a close-up picture of what we may see on the screen. Uh, this is a patient, uh, with normal, uh, secondary peristalsis, uh, which we'll talk about, um, but what you're able to get with this is a contractile pattern. Which may have some correlation with high resolution manometry, uh, based on adult data. And then it gives us an assessment of right here, which would be the lower esophageal sphincter and the distensibility. How, uh, distendable is this area. And then the measurements are given here in real time. So then now transitioning to neurogastroenterology, specifically speaking about the Rome Foundation. Um, this was established in the 1990s to standardize diagnostic criteria for functional GI disorders. Uh, it's in its 4th iteration from 2016, where, uh, what were once termed functional GI disorders are, were renamed, uh, transition to disorders of gut-brain interaction or DGBIs. Um, and currently Ram 5 is being developed. There's several benefits from doing this, uh, including uniform diagnostic criteria to create consistency and identification, making these disorders, uh, researchable for, uh, clinical trials and drug and device development. It legitimizes the medical conditions these patients are experiencing as well. Uh, part of the old mantra used to be, you know, it, it's all in your head, or, uh, these aren't, these symptoms aren't real, uh, when they truly are a real pain or real nausea, real trouble swallowing that these patients are experiencing. But, uh, the pathophysiology is a little different from an organic etiology. Uh, and this, this, uh, certainly enables, uh, treatment precision. So I'm just gonna quickly show you the diagnoses, uh, and what you'll notice is there's a lot more diagnosis on the, the left-hand side, uh, for our adult colleagues, and that's kind of where, uh, this was first initiated, um. In comparison to uh the pediatric population, but a lot of these. There's a lot of overlap. Um, there may be some subtleties in the diagnostic criteria in regards to duration of symptoms, um, but a lot of these, including the esophageal disorders, um, You know, are, are definitely seen in the pediatric population, but the, the research is lacking to back some of these things. So now we'll talk about motility by segments, and I will talk through some of the most common things I see from each uh segment of the GI tract, um, and kind of the evaluation and management approach for these. So for the mouth and the pharynx, uh, this has two phases, uh, oral phase, which is a mastication, mixing with saliva, proportion of the bolus, uh, by anterior to posterior tongue movements against the palate. Um, and the pharyngeal phase, which, uh, is an involuntary reflux triggered when the bolus reaches the oropharynx. There's elevation of soft palate to prevent nasopharyngeal reflux, uh, the larynx, uh, elevation with epiglottis inversion, and sequential contractions of the pharyngeal constrictors, and there's superior, middle, and inferior constrictors. The inferior part, um, Which is the cricopharyngeal muscle, helps to form the upper esophageal sphincter. So for this section, I specifically wanted to talk about oropharyngeal dysphagia, uh, which occurs immediately when you're attempting to swallow, um, and it can be differentiated from oesophageal dysphagia, which occurs several seconds after swallowing based on clinical history of difficulty initiating a swallow, may include some nasopharyngeal regurgitation or aspiration, or residual food in the pharynx. These are some common signs and symptoms we'll see. There's several feeding-related symptoms. Um, there's some airway-related symptoms, and then sometimes, uh, this may be associated with a brief resolved, unexplained event, um, and there, there's some, uh, thought that, you know, a majority of the, these events in the past have been, uh, thought to be secondary to reflux, when in fact, A portion of these may be actually related to oropharyngeal dysphagia. So evaluation typically includes uh speech or feeding therapy and a video fluoroscopic swallow study or uh modified barium swallow. Um, and the management, uh, includes, uh, thickened feeds to slow the bolus flow. Um, this can be done in several different ways. There's anti-reflux formulas that come in 20 or 24 kcal options. Um, these require an acidic environment for activation, so avoid antacids, uh, like Pepcid or, uh, PPI therapy with these. Um, there's some food-based options like infant cereal, yogurt, bananas, apples, avocados, and, and some others. Um, these are, are useful for patients with a history of necrotizing enterocolitis, ischemic disease. Um, or herprung, and um, There has been, you know, some thought that the these Food-based options, specifically, uh, rice, uh, can be related to constipation. There's some prospective literature looking at this, um, and it, you know, it shows that 20% or 1/5 of these, uh, infants using rice cereal develop significant stooling difficulties that tends to improve with transition to oatmeal. Um, and then there's some, uh, commercially available products such as xanthan gum, caribo locust bean gum, pectin, cornstarch. You may consider cornstarch. There's a history of hypoglycemia. Uh, you may want to avoid these if there's blood in the stool, and, um, these can be utilized for patients on elemental or formula or breast milk. Uh, so now we're gonna talk about the esophagus, which is my favorite, uh, portion of the GI tract and where I devote most of my research endeavors. So this is comprised of striated, uh, the upper 1/3, uh, and smooth, uh, muscles, which is lower 2/3, includes an upper and lower esophageal sphincter. Uh, it's main job is the transfer of bolus between the pharynx and the stomach. Um, and coordinated contractions are required to do so. Um, and during the pharyngeal phase of swallowing, the UES, upper esophageal sphincter, relaxes, then there's sequential contractions, uh, of the LES to allow bolus to enter the stomach. Um, This is called primary peristalsis or initiated by a swallow. There's also secondary peristalsis, which is triggered by esophageal distention. Um, primary peristalsis is evaluated by esophageal manometry. Secondary peristalsis can be evaluated by endo flip. Um, and here's several disorders that we, we may see related to neurogastroenterology and motility, um. And first we're gonna talk about uh reflux disease. Uh, so, uh, gastroesophageal reflex is a normal physiologic process that happens throughout all age ranges, the retrograde movement of contents into the esophagus. But once there becomes bothersome symptoms or complications such as esophagitis, Barrett's esophagus, or peptic stricture, then we term it, uh, GERD. So typical symptoms are listed here. I think of heartburn, regurgitation, non-cardiac chest pain. Um, you can see increased salivation or water brush as well. And then there's also atypical symptoms. Most of these are under the umbrella term of laryngopharyngeal symptoms, such as hoarseness, cough, throat clearing, or sore throat. And I do see a fair number of patients who come in, uh, after being evaluated by their dentist and found to have dental erosions that are thought to be secondary to reflux. So empiric management include lifestyle modifications, avoid food consumption within several hours of bedtime, uh. Nighttime positioning with head elevation or left lateral, left lateral because the gastric fundus becomes the lowest point um and the contents pull away from the LES. Uh, weight management, uh, for overweight or obesity. For the uh older patients, cessation of vaping, or alcohol, and avoidance of dietary triggers. Um, and there's some of them listed here. Chocolate, peppermint can reduce LES pressures, uh, fatty or fried foods can delay gastric emptying. And then pharmacotherapy typically includes antacids, histamine type 2 receptor antagonists, or H2 blockers, um, PPIs, proton pump inhibitors, and then I'll briefly touch and tell you about something that's newer, uh, called potassium competitive acid blockers. So for milder infrequent symptoms, you can use as needed antacids or H2 blockers. Uh, Anacids work by neutralizing the acid directly. They give fast but short-term relief. Um, and the reason PPIs aren't in this group is because they typically take 10 to 14 days to reach their full therapeutic effect, uh, which is the time needed to inhibit the majority of the active proton pumps. Certainly, uh, symptoms become persistent or moderate or severe. Scheduled H2 blockers or PPIs uh are helpful. Um there's some dosing below of what we typically use for PPIs there. Um, And if you start with an H2 blocker and you're not seeing relief after 2 to 4 weeks, consider empiric PPI course for 4 weeks. If symptoms are improved at 4 weeks, you could consider continuing treatment for a total of 3 months before weaning off. Um, if symptoms are no better, this would be an indication for further evaluation. Um, and similarly, If you're unable to wean off a PPI, uh, this will be another indication for evaluation of GI. And then briefly, uh, PCABs or potassium competitive acid blockers. This is a novel class of anti-secretory therapy, uh, that competitively binds to the proton pump, but instead, uh, of PPIs that are in an irreversible manner, these are reversible, so it allows dissociation and inhibition of additional pumps. Um, the pharmakinetic and, uh, pharmacodynamic properties also offer several advantages over PPIs, um, that I'll, I'll briefly just show you here. Um, PPIs, as you may know, require, uh, Uh, 30 to 45 minutes before meal dosing. This is not required for PCAs. Um, The half-life is much shorter PPIs compared to PCABs. Um, and here, here's a big one as well, that it repeated doses are required for the onset of efficacy for PPIs, while PCAs have efficacy after the first dose. And then one other thing that I will briefly mention, uh, that we're thinking about more these days is metabolism through the cytochrome P450 system. So PPIs require uh Metabolism through uh the SIP 2C19 which um has several uh genetic polymorphisms associated with it, um, and this can be based on, you know, uh, genetics, um, and, uh, ethnicity as well, um, and these range from Poor metabolizers to intermediate to normal metabolizers to rapid metabolize to ultra rapid metabolizers. So there's quite a spectrum in there. Um, genetic testing is available, um, not widely though, and the cost may be prohibitive. So sometimes we will Consider switching to a PPI that's less absorbed uh through this, uh, or metabolized through this cytochrome 2C19 such as Nexium, um, if we're getting a little better but not totally um asymptomatic. Um, and just to bring up imaging, you could consider an ultrasound if there's, you know, regurgitation or vomiting, uh, that you're not quite sure if this is reflux or not, um, and then an esophagram or upper GI series. And what I will say is that quite frequently we do see reflux, uh, on these barium studies. And one thing to remember is that these are typically provoked where there's a water siphon test that the radiologist is performing. So, um, what we did is we recently looked at our own cohort and we were unable to identify, uh, any link between reflux on barium and pathologic reflux on PH impedance testing. It also be prudent to consider an upper endoscopy, then certainly pH monitoring, if it's not classic, if you're having refractory symptoms, uh, to understand more about the, the reflux burden. Uh, and briefly, this is, uh, on the left, this is what a pH impedance tracing would look like, and on the right here, um, you'll notice, um, this red is acid in the lower esophagus, and then this is the impedance tracing where it drops right here, and a drop indicates Uh, presence of water or, or liquid, um, and this can also show us, uh, by coloration, purple color is liquid, but you can see that there's a drop here, then a drop here, then a drop here, then a drop here. So a reflux episode going retrograde of the esophagus. Uh, briefly on tracheoesophageal fistula or esophageal resia, there's 5 types. Uh, you may be exposed to some of these patients. Uh, type C, uh, is the most common. And um that makes up about 85% of these patients. They're predisposed to dysmotility and reflux, and common symptoms for them include reading, uh, feeding difficulties, reflux, dysphagia, chronic food infections, or chronic cough. Chronic PPI therapy may be needed for them, um, and they're higher risk for complications of GERD and anastomotic strictures, and, uh, we utilize a multidisciplinary care team here including Aerodigestive, which is a general GI provider, pulmonary ENT, and then I'm typically involved from a motility aspect for these patients. Uh, now on to motor disorders of the esophagus. Symptoms are kind of like what we talked about before. There may be some overlap with reflux as well, uh, or reflux-like symptoms. Evaluation typically includes a barium study, an upper endoscopy, and then manometry, um, plus or minus endo flip. And I will say that uh calasia is very rare, 1 in 100,000 with a peak in adolescence, but we are seeing a lot of patients with what's called ineffective esophageal motility. This is about 1015 to 40% of studies. And management, uh, depends on the diagnosis. So if we're getting the normal manometry, we may shift, um, our management towards a DGBI overlap or reflux, um, if they have this IEM or ineffective esophageal motility, um. The thought is that uh symptomatic treatment should be provided and that this uh diagnosis should be thought of as more of a description rather than a reason for their symptoms, but there's typically is overlap with reflux. And then, um, if there is outflow obstruction or the lower esophageal sphincter is not relaxing as it should, uh, there's two varieties of this, either alagia, where, um, the esophageal body has poor or spastic spastic contractility, and EEGJ, esophageal gastric jun junction outflow obstruction, uh, where there's normal contractility, but the lower sphincter is not relaxing. We will proceed with confirmatory testing with Endoflip, but for alagia, uh, it's mostly about barrier disruption of the LES, which, um, in the short term could be Botox, could be intermittent pneumatic dilations, but, um, more recently, uh, patients, uh, have been undergoing what's called the perioral endoscopic myotomy. Uh, where the, uh, during an endoscopy, we're able to, uh, dig down, uh, basically underneath the mucosal layer, um, and create a channel down to the LES and make some, uh, make a myotomy incision there, uh, to kind of release or relax some of that tone. This is just a quick depiction of uh the Chicago classification version 4.0 diagnostic algorithm for the detection of esophageal motilia disorders, and just so you're aware that um, You, you know, there, there is a standardized, uh, algorithm, but it's solely based on adult derived metrics, uh, which creates some problems in pediatrics, which I'll briefly talk about, um. Uh, but here is a high resolution resolution image of a single wet swallow, um, similar to what we, we looked at before. But we also have the ability to look at bolus transit or assess that with the use of impedance during the study, and you'll see this purple uh color here is actually the bolus itself traveling down the esophagus and then below the lower esophageal sphincter into the stomach. So that's very helpful that we can assess the contractility, but also the transit of the bolus through the esophagus in relation to the symptoms the patient's experiencing. The current limitations, as we talked about, that these thresholds and protocols are derived from adult normative data. There's no validated reference metrics in pediatrics. Uh, patient cooperation may be limited, and there's likely over and under diagnosis of current guidelines. So we're doing a few things to address these problems. We did a multi-center study with 12 other centers, uh. And uh this was a cohort of 281 patients. The final cohort after some exclusions was 260. And, and what I'll briefly show is that a lot of these studies. They weren't necessarily adequate based on adult standards, so there's a lot of double swallowing in kids, or there is poor timing between swallows, which is not uncommon. Um, and, you know, a lot of patients, uh, a lot of centers were not able to follow the complete Chicago protocol, um. Or complete what we call these provocative maneuvers. Um, but, but most patients were able to, to do what's called the multiple rapid swallow, where we ask them to take 2 mL of liquid, uh, as quick as they can 5 times in a row. Um, and then I'll briefly share that when we looked at these other provocative maneuvers that could have been done, there was a whole variety that that were, um, identified as being able to be done, but we're not, uh, completed by the, the center, where they were indicated, but not completed. And, you know, all of this is just uh supportive evidence that, you know, we need pediatric specific metric protocols to ensure uniform diagnostic evaluation in children. Um, and then we're also developing, uh, Our normative data here at Children's, um, and, uh, creating a national and hopefully international registry. And then, uh, I'll briefly talk about retrograde cricopharyngeal dysfunction. Um, this, uh, patient may present with the inability to burp, some abdominal bloating, gurgling, and then, uh, chest or neck, or excessive flatulence. Here are things that can be done. Esophageal manometry, the carbonated beverage challenge, uh, is diagnostic, and you'll notice that, so the beverage challenge on the manometry started here, so taking several swallows in a row, and then what happens is, this is the lower esophageal sphincter relaxing, and you'll notice there's stuff coming up here, but the Upper sphincter actually stayed tight, and then what we classically see is this this wave of pressure that comes down here, which is called secondary peristalsis. Uh, which is in relation to that volume expansion. Um, so this is classical for, uh, retrograde cricopharyngeal dysfunction. And it's becoming more widely recognized, um, and there's varying degrees of, uh, you know, symptoms severity in these patients, but you can certainly, uh, Refer to us for further evaluation where we do manometry, and then they've confirmed uh ENT is uh A referral is indicated for a UES uh Botox injection. And then disorders of gut brain interaction in the esophagus. These require no significant findings on endoscopy, imaging or uh imaging and manometry, and the symptoms are ongoing for a defined period of time. Um, here's several disorders. These can be delineated by PH impedance testing, and management involves neuromodulation and gut-directed CBT. Uh, so, uh, for the stomach and the small bowel, the main disorder I wanted to mention was gastroparesis. There's several different, uh, causes. Symptoms include nausea, vomiting, early satiety, postprandial fullness, bloating, abdominal pain, and there's a whole series of evaluation including a gastric emptying scan that will help us to quantify, uh, the amount of delayed emptying. Management is typically multimodal as well, including uh dietary modifications, so small frequent meals, low fat, low fiber, more smoothies, soups, and shakes because liquids empty easier, um, and limit roughage like raw vegetables, high fiber, uh, skins or salads. Avoid carbonation, um, and we can always consider post pyloric feeds if needed. Uh, we have some promotility agents who may utilize. Uh, metoclopramide has limited long-term use because of dystonia or tardive dyskinesia. Um, erythromycin can cause tachyphylaxis over a series of 4 to 6 weeks of taking, and, uh, you have to keep an eye on the QT interval. Uh, Domperidone is not FDA approved, but there's an FDA IND for this, and Um, it also has some QT potential. Then procalippride is a newer agent, which is serotonin receptor agonist, which I think of as a whole body promotility agent that's very helpful in this circumstance. And then we have some anti-emetic options as well. Um, some newer things include neurostimulation, which we currently are not doing here. Um, it's available at a few centers nationwide, um, but gastricalelectrial stimulation where, uh, a device is planted within the abdomen and, uh, electrodes, uh, are within the wall of the, the stomach, and it helps mostly with symptoms more than, um, changing the motility pattern. And then we do have some endoscopic interventions for for refractory cases, including pyloric Botox to relax the outlet of the stomach to allow things to empty easier, um, and dilation. And then I'd mentioned a poem before in the esophagus, but there are some centers that do gastric poem as well, where the pylorus will be, uh, the muscle fibers will be cut a little bit to allow relaxation, better distension, and, uh, extendability and passage of contents. Similarly, uh, for the esophagus, uh, these in the stomach, DGBIs require no significant findings on endoscopy, uh, imaging, or labs. Um, and AD manometry and endo flip are not required for these diagnoses. Here's the disorders, uh, in the upper right, um, and treatment may vary, but lifestyle modifications, symptomatic therapy, neuromodulation, or gut-directed CBT. I'll mention cyclical vomiting syndrome because we, we do see this quite frequently. There's diagnostic criteria here on the left. Um, which is at least 2 episodes, uh, return to baseline between these episodes is key. We have some acute, uh, management for these patients, antiemetics, triptans, or prepotent, hydration, and then some maintenance options that we consider include cyproheptadine, uh, amitriptyline, or prepotent. Sometimes, uh, supplementation seems to be helpful, and then there's an emergent, uh, evidence for auricular neurostimulation. Uh, for these patients as a, a long term treatment. And I will mention uh a difference between CVS and uh abdominal migraine, uh, cause there is some overlap, but, uh, vomiting, uh, and nausea intensity are, are, are more prevalent in CVS. Well, abdominal migraine, it's these acute, uh, abdominal pain episodes. There may be some vomiting, um, but Uh, they also have a period of normality in between. And then rumination syndrome. I see this quite frequently, um, where patients come in, uh, say, you know, I've been vomiting for a long time, uh, or have reflux, and it's actually regurgitation of, of stomach contents, and so that's what rumination is, effortless effortless regurgitation of recently ingested foods, typically occurring with 30 minutes of eating and ongoing for 2 to 3 months. Um, it's an increase, uh, in the abdominal wall, uh, contractility. Uh, which causes increase in intragastric pressure, and then food comes up and out the esophagus and into the mouth. And we can confirm this on manometry, um, where we see we've been, we've given a a meal, we observed the patient for about 30 minutes, and, uh, sure enough, we see these episodes coming straight up from the abdomen, which are called R waves, uh, where food, uh, or drink comes straight up into the esophagus and sometimes out in the mouth. Sometimes you'll see these reflexive swallows as the patient tries to swallow the contents back down. Uh, the treatment for this, uh, is diaphragmatic breathing exercises done, uh, before, during, or after meals, and I, I tell the patient to place a hand on the chest, a hand on the abdomen, and when you're taking breaths, move the, the hand on the abdomen should move in and out, and your chest should not move much at all. And we want to do this 10 to 15 times before, during, or after meals, and kind of when you're feeling the sensation that you may regurgitate. Here's some dietary options for these patients that we try. Um, and then the big thing that it's hard to get by for this is, but re-swallowing the regurgitant is key to retraining the body for this behavioral disorder that, uh, up and out is not the correct, uh, pathway for stomach contents. And it's typically not acidic, it's, it's basically, you know, the food that they just ate, so, um, Patient, you know, it is a little gross, but um it, it really does help in them overcoming this disorder. And then we have some pharmacologic options that we may try to strengthen the LES barrier, improve esophageal contractility, or um help with gastric accommodation. And then we always have to think about overlapping disorders with rumination, uh, some mental health. Uh, gastroparesis or other GGBIs. Uh, small bowel disorders, uh, you may hear about something called pediatric intestinal pseudo obstruction, which was recurrent or chronic abdominal distension, vomiting, feeding intolerance, uh, nausea, vomiting, and it mimics mechanical obstruction, but there's no evidence of actual anatomic abnormalities. Um, and this needs, uh, diagnosis with, uh, manometries. And then as I've talked about, uh, for patients with dysmotility, we do see a small intestinal bacterial overgrowth a lot. Um, it comes with a variety of symptoms. A newer term is called intestinal mephanogen overgrowth, um, and this typically comes with, uh, similar symptoms. We use breath testing to diagnose this for the most part. Um, and then treatment includes 10 to 14 days of antibiotics. Uh, rifaximin, metronidazole Augmentin can be used, and then a combination of these two for, uh, intestine with antigenal growth. And lastly, to the, the colon and the rectum and the anal complex. Constipation accounts for 1/4 of outpatient GI visits nationwide, um, with a pretty high worldwide prevalence. The result impact on health care utilization and associated costs is immense, and it's associated with poor quality of life with worsening along the spectrum of simple constipation to those that are also experiencing fecal incontinence. And there, there's several associated conditions here, uh, that we tend to see with constipation. Uh, so for evaluation, you know, a clinical history is always, is always key. When did they pass meconium, onset of symptoms? What are their stools like? What are their symptoms do they have? Is there any sensation of incomplete evacuation or straining? Are they withholding? Do they have the sensation that they need to poop? Are they having any leakage and then other, uh, comorbidities in history? Exam, you may see distention, uh, palpable stool burden, and then always for younger kids, I would suggest looking at the anal opening to make sure that uh it's not one to anterior, especially in females, or that the uh the anus is positioned within the sphincter muscle for patients that are struggling. And certainly you consider labs, X-ray, um, for imaging to evaluate stool burden. You can get a contrast enema, which we use to look for, uh, look at anatomy and look for transition points, uh, which would be indicative of Hirschprung. But for the most part, what I'll see is rectosigmoid dilation redundancy, which are typical for someone with chronic constipation. Then certainly you could use depicography. We're, we're not really using that in clinical practice, uh, as much as our adult colleagues are. And then we will utilize anorectal and colonic manometry. Um, so I just wanted to show you on an interreal manometry study and orient you. This is a depiction of the bottom, uh, the catheter going in the bottom right here. So, uh, this is within the anal canal, this bar up here, this is external, and this is where the balloon is. So this is called a rectal anal inhibitory reflex, where you have a normal resting pressure. We inflate the balloon and then relaxation happens. So that tells us that the neurons and the ganglion cells within the, the bottom are intact. And then this is a patient we see quite frequently with uh evidence of pelvic floor dysynergia, where you'll notice this is at rest right here on the left hand side, and then right here we ask the patient to push like you're trying to pass stool or have a bowel movement. And what I want to see is that this green becomes more blue and relaxes during this time frame, but what I'm actually seeing is Increase sphincter tone, increased pressure, we're in, we're actually seeing this is the, uh, these are the glutes, and we're seeing these also tighten as well. So this is indicative of uh pelvic floor dysfunction, which may uh chronically lead to constipation if you're unable to evacuate everything efficiently from the rectum. Management is typically multifaceted, uh, non-pharmacologic measures, behavioral therapy, if there's withholding or other, um, anxiety around using the toilet. Uh, pelvic floor PT with biofeedback is super helpful. Biofeedback is where, um, these little electrodes, um, go on the stomach and then outside the bottom, um, on the skin, and Patient is actually playing like a video game where they're using their abdominal and um Uh, pelvic floor musculature to, you know, keep a spaceship within a certain area or collect stars, so it makes a game out of it and it helps them to understand the proper mechanics for, uh, stooling. We have several pharmacologic measures, but, you know, in my opinion, not, not enough. Um, we have osmotic laxatives that you guys can trial, MiraLax, lactulose, magnesium base. Consider a colonic stimulant, um, if things have been chronic because the bowel may be a little dilated and not able to contract or push things forward as, as usual. And then we have a lot of uh newer agents called secretagogues, which um are all related to activating a certain Ion channel, uh, or a certain process within the bowel wall that helps to, uh, excrete fluids into the, the bowel and help, uh, with motility. So, um, available for ages 6 to 17 is Linzess or leakottide for functional constipation, lubprostone or Amitiza for, uh, patients 6+ for chronic idiopathic constipation. And then a few other options for adults. And then percalapride um is also available, uh, currently only approved in adults for chronic idiopathic constipation. Then we'll also think about enemas and suppositories as needed, not a great option long term. Um, and then certainly for the most severe, uh, antigrade continence enemas or colonic resection, and we do think about Botox a lot. Let me just briefly tell you about Botox, um. This was a study we did, uh, within our, our group, uh, that was published recently looking at uh Botox in relation to quality of life, um. Um, and clinical outcomes as an adjunct to standard management. So we had 60, 60 consecutive children that underwent Botox. Um, we did surveys at baseline 2 weeks and 3 months. Uh, we assessed clinical symptoms, quality of life, and family functioning, and caregiver well-being. We had pretty good response rates for these. And what we concluded is that significant improvements in quality of life and caregiver well-being, uh, were noticed at 3 months after Botox injection, um, and there was a significant reduction in the odds for meeting Rome for criteria for functional constipation. So we do see, um, this, uh, being a helpful adjunct for patients, and what it does is, uh, helps to relax the internal anal sphincter that is controlled by our brain without our knowledge, um, to allow stool to more easily pass. And then I'll end with this, uh, talking about our motility program here at Children's. So this was established, uh, in October of 2024. We offer comprehensive motility testing, including manometry, end of flip breath testing, PH impedance, uh, and and wireless, uh, pH monitoring. They offer treatment along the uh neurogastroenterology and motility spectrum, um, and have non-pharmacologic, pharmacologic, and procedural interventions that can be utilized. Um, and if you, you would like to refer a patient, uh, there's no, uh, additional process to go through. It's just a standard, uh, pediatric GI referral, and, uh, it'll be funneled accordingly. So with that, I wanted to thank you guys for your attention and happy to answer any questions. Created by Presenters Trevor A. Davis, MD Pediatric Gastroenterology View full profile
