Motility Disorders in Childhood: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition

This is the authors' abstract. We don't add key points for this paper.

I. SUMMARY OF THE PROBLEM Gastrointestinal disorders result in a limited number of symptoms, including recurrent vomiting, abdominal pain and distension, constipation, and loose stools. A large body of evidence has accumulated in both adults and children to suggest that these functional symptoms may be largely caused by disordered gastrointestinal motility. The pathophysiology of the above symptoms is best understood by considering their production by disturbances of the control mechanisms of gut motor activity. Such disturbances may be produced by organic disease involving enteric nerves and muscle, alteration of the humoral environment of the nerves and muscle of the gut, and altered central nervous system input. The current body of information regarding the physiology of gastrointestinal motor activity started at the end of the last century with Bayliss and Starling's description of peristaltic movement. It soon became apparent that there were complex patterns of motor activity but it was not until the late 1960s and 70s that great impetus occurred in the understanding of the organization of gastrointestinal motor activity with the description of the migrating myoelectric complex by Szurszewski. In the late 1970s and early 1980s, systematic study of gastrointestinal motor activity started in children. Motility disorders occur across the ethnic spectrum and are commonest in infancy. Approximately 50% of mothers with healthy infants between the ages of 2 and 8 months report that their infants regurgitate two or more times daily, indicating that gastroesophageal reflux is an extremely common disturbance of foregut motility. If the United States alone is considered, then more than four million babies are born each year and at least half of them will have gastroesophageal reflux at some time during the first 2 years of life. Thus, what often seems to be a relatively minor problem has important economic and public health implications. Apart from constipation all the other motility disorders discussed in this report are much less common—even functional constipation, only accounting for perhaps 3% of pediatric outpatient visits and 25% of pediatric gastroenterology consultations. However, it is likely that every child at some time during their childhood may have an episode of constipation particularly associated with dehydration or an infection. The remaining disorders all account for less than 5% of children. In childhood, both congenital and acquired disease processes may produce the pathogenetic mechanisms resulting in symptoms that vary in severity from the chronic and recurrent obstruction of chronic intestinal pseudo-obstruction to the repeated passage of loose stools in chronic nonspecific diarrhea. In children, it is particularly important to consider that these disease processes operate on a background of the developmental processes that the child undergoes and also may be the result of the interaction of children with their parents and society. Increasing understanding of the above concepts and basic principles has resulted in the emergence of neurogastroenterology. Neurogastroenterology is a new and advancing subspecialty of clinical gastroenterology and digestive science. It embraces the innervation of the gut from brain and spinal cord through sympathetic parasympathetic divisions of the autonomic nervous system to the intrinsic enteric nervous system. Also included are smooth muscle, mucosal epithelium and the gut-associated lymphoid tissue of the immune system, which interact with the neural elements of the gut. Enteric innervation neural networks with control of gut function are positioned in the brain, spinal cord, prevertebral sympathetic ganglia, and in the walls of the organs that make up the gut. A hierarchy of four neural centers is involved in the control of gut motility (1). Level One is the enteric nervous system, which has local circuitry for integrated function and is independent of extrinsic nervous connections. Level Two includes the prevertebral sympathetic ganglia, which are influenced by preganglionic sympathetic fibers in the spinal cord. Levels Three and Four are within the central nervous system and consist of the sympathetic and parasympathetic outflow to the gut and the higher brain centers. Disease and malfunction of these systems are increasingly recognized as underlying motility disorders of the gut. The enteric nervous system coordinates the activity of primary effectors to produce meaningful patterns of behavior of the gut for the whole organ. It is a local mini-brain within which are stored a library of programs for different patterns of gut behavior. Such programs include emesis, swallow-induced peristalsis, and fasting small intestinal motor activity, amongst others. The enteric nervous system in many respects resembles the central nervous system, and indeed the neurones involved are essentially the same. The enteric nervous system works with three functional categories of neurones—sensory, inter, and motor neurones—and these are connected by synapses into networks that process sensory information and control the behavior of motor neurones. Multiple connections for logic circuits that decipher codes from sensory neurones and signals from elsewhere in the nervous system interact to produce an integrated motor output. Abnormalities in the inhibitory or excitatory input may lead to different disease states. A functional obstruction occurs in any condition in which inhibitory motor neurones are destroyed or the muscle coats have lost contractile activity. Without inhibitory controls, the self-excitable smooth muscle contracts continuously and behaves as an obstructing element. Loss or malfunction of inhibitory motor neurones is the pathophysiologic basis of this type of condition, and it underlies several forms of chronic intestinal pseudo-obstruction, Hirschsprung disease, and achalasia of the esophagus. In early life, this may be due to congenital maldevelopment of the enteric nervous system and in later life neuropathic degeneration. Neuropathic degeneration in its early stages may be manifest as symptoms that can be confused with the irritable bowel syndrome and other functional gastrointestinal disorders. An increasing body of evidence shows the interaction between mucosal-associated lymphoid tissue and the motor apparatus of the gut. The enteric immune system is colonised by populations of immune and inflammatory cells that are constantly changing according to luminal conditions and pathophysiological states. Due to the inability of the physical and chemical barrier of the luminal interface to entirely exclude antigens, the immune system is daily exposed to dietary antigens, bacteria, viruses, and toxins, causing the mucosal associated lymphoid tissue to be chronically challenged. The motor and secretory responses in the gut of animals sensitized to antigens such as food or bacterial toxins, together with the effects of infection in the human, show a direct link between the immune system and the motor apparatus. Immunoneural integration starts with either detection by epithelial cells of antigen or immunocytes in the lamina propria (2). The signal is transferred to the enteric nervous system, and the appropriate response occurs from the program library of the enteric nervous system. In general, detection by the enteric immune system and signal transmission to the enteric nervous system initiates a defensive behaviour analogous to the emetic response in the upper gastrointestinal tract, resulting in the forceful and rapid propulsion of ingested material over long distances (2). Several kinds of immune and inflammatory cells, including lymphocytes, macrophages, mast cells, and polymorphonuclear cells, are putative sources of paracrine signaling to the enteric nervous system. The use of signaling between mast cells and the enteric nervous system is best understood. Antigen-evoked degranulation of sensitized mast cells releases a wide variety of paracrine signals that include 5-hydroxytryptamine, histamine, platelet activating factor, tachykinins, prostaglandins, cytokines, and leukotrienes. Recurrent Vomiting Three functionally based syndromes resulting in recurrent vomiting occur. Infant regurgitation or gastroesophageal reflux, rumination, and cyclical vomiting. Regurgitation and rumination are both examples of gastroesophageal reflux. Cyclical vomiting is due to recurrent activation of the emetic reflex. Gastroesophageal Reflux Infant regurgitation or gastroesophageal reflux occurs commonly in infants during the first 18 months to 2 years of life. In 90%, symptoms resolve at this time (3). When gastroesophageal reflux causes or contributes to tissue damage or inflammation as in esophagitis, apnea, bronchospasm, pulmonary aspiration, failure to thrive, iron deficiency, anemia, or hematemesis and stricture of the esophagus, it is called gastroesophageal reflux disease. The episodes of reflux are most usually due to transient relaxation of the lower esophageal sphincter (4). However, several other mechanisms also may play a part, including low basal tone of the lower esophageal sphincter and prolonged opening of the lower esophageal sphincter during swallowing. Although dysfunction of the sphincter and loss of the barrier to a pressure gradient from abdomen to esophagus causes reflux whether gastroesophageal reflux disease occurs or not is mostly due to lack of acid clearance from the esophagus because of to impaired peristaltic activity of the body of the esophagus. Due to the improvement with age, it has generally been considered that the reflux is associated with the of control of the of the lower esophagus and However, evidence that in some children organic disease of enteric and muscle is and in that of the humoral environment of the esophageal and by food responses in regurgitation is particularly in infants or with minor Regurgitation also may occur in with such as and altered central nervous system input such as that which occurs in or The to the or child with on the with but symptoms of inflammation or not If there is a of esophagitis, either or and is disorders such as or may be by The to of of esophageal the that is causing symptoms, but a exclude as a of recurrent or symptoms such as such as for macrophages, to reflux or lack for The best for of to may more in the for gastroesophageal reflux is a transient for the most are to and often with of and small In the last year the of such as has been called into and as a not be for up or but may be there is gastroesophageal reflux disease. In such with secretory such as and also be In gastroesophageal reflux disease, may be and either by or is the of However, has a and a most for have esophagitis, symptoms, or failure to that not to The for all forms of rumination to be abdominal the lower esophageal sphincter is which is usually by swallowing. to be a behavior in and children evidence that it may be for these children to reflux because of a for lower esophageal sphincter relaxation during be as as the The of is to a environment and and to the or child to the of behavior. can often be by to and to the physical and However, in children, a may not be and such as and may be In children and or for behaviour may be A understanding of the underlying mechanisms this is can be It is that in some children with rumination, an interaction between the central nervous system and the enteric nervous system to the of pain or resulting from of Cyclical Vomiting Cyclical vomiting of repeated episodes of activation of the emetic reflex. of the emetic may occur a number of including of and organic and gastrointestinal mucosal In in there is not an underlying are to conditions that most of their and these include or physical of these have such as or The of the emetic to be a of understanding cyclical vomiting, and the causes of cyclical vomiting will all either central or input into the emetic The of and input into the emetic is as but from altered central The by in the input into the emetic in and extremely in a of children with cyclical vomiting. In with an of these the of may In of and during an episode may the A variety of other including and have all be to the or In to conditions that episodes be and as and of Motility is by failure of the to during of the esophageal body may be during the early of this disease. the esophagus and tone usually is in The from a lack of inhibitory innervation of the is in childhood, usually years of it may in the first or years and then is associated with an syndrome of and muscle or with the syndrome of and In disease be or other of the may as of achalasia is usually based on of that show esophageal and usually a esophageal by esophageal is with is and an for of the lower esophageal sphincter with transient but the for repeated this less for of childhood of the the muscle and may from If is to a with an esophageal is by prolonged in at least of the esophageal body have and prolonged peristaltic a esophagus. disorders are in children. A variety of nonspecific esophageal motility disorders by of and are the pathophysiologic of these for esophageal motility disorders are for have included into the esophageal muscle, and with A child with stools is is the commonest problem to to the pediatric A variety of mechanisms have been in chronic nonspecific including in intestinal and food and intestinal motor activity It is only in the last of these that there is evidence that may play a In a of children with chronic nonspecific of such have evidence of food and all were of the food commonly in of the intestinal motor activity to be an important for the production of the symptoms, with particularly lack of of fasting small intestinal motor activity by food resulting in a small bowel The of the response is not but be to be involved in the small bowel is information as as to whether this is caused by of or an immune response such as to a of the food or of a food resulting in an a variety of mechanisms may nonspecific and is that of the underlying condition in most In that have minor or are food and may be extremely In nonspecific with may control their and Recurrent to 25% of outpatient visits to a pediatric are for with In most children, the condition from a by the of months of the passage of children a A of children with constipation may have underlying with organic disease of the enteric with functional constipation due to a a number of important A of constipation is associated with loss of due to an infection with the of a of large that is to on from an due to at or due to developmental in some of these the relatively common of the of constipation in and infants that from the of into their In this the description of constipation in is of and this may be by an that in The use of an which may exclude and or in of in as many as of evidence also shows in up to 25% of that have the irritable bowel syndrome that may include of constipation, this occurs an enteric infection. have both the of an and in the of such It is of that the of cells that are involved are that produce and In a enteric disease may constipation or recurrent functional which may be both congenital and acquired The acquired disorders in childhood to be mostly disorders either or muscle of the these may also occur an apparent enteric infection. inflammatory enteric or are by inflammatory to either the or to the muscle coats of the the muscle there may also be mucosal inflammation perhaps associated with the enteric infection. to occur most in the disease and disease syndrome usually not a mucosal inflammatory In both conditions an process is often that as of a inflammatory and are in the inflammatory process and enteric neurones to in inflammatory with and or smooth muscle The of the inflammatory is different from that of the syndrome with In motility loss of enteric neurones is by and due to the loss of inhibitory motor neurones. In the disease, there are disorders are important for two the early with these conditions are either to functional gastrointestinal disease or are of an enteric these conditions are with which that the of Motility A variety of over the last of the esophagus and small have a process involving the of the muscle and the enteric Three of to an early of and an of many different and and a later of this is considered in this Although by the end of the the gut is the function of the enteric over the last with patterns of contractile activity in most of the gut by of esophageal motor activity have been to infants during the last and several have that motor patterns are common in infants but all have a pressure by of at the lower esophageal sphincter (4). and transient relaxation of the lower esophageal sphincter but the of pressure in the body of the esophagus of infants that have acid clearance reflux episodes occur and are more likely to gastroesophageal reflux disease. A number of of motor activity either or myoelectric activity have that that is relatively there is gastroesophageal reflux, often is and this to be by syndrome and the last a number of have been into the of small intestinal motor and all have four stages of fasting motor of activity, and cyclical migrating motor complex It seems that the of intestinal motor activity a more within increasing involved in are not entirely and both the of of paracrine from cells and the of the of the of to the is the time that infants will to A variety of have that this is by the of time on the of motor activity, and the of which to occur at of to be and in to the of is also associated with the of a cyclical activity in the fasting and a of activity in response to food food releases a variety of it is the of to these that is important in the to Thus, to be on the of the humoral response to food that the of the and the enteric neurones have to be to to the The of may play an important in The of these but increasing is the of more for OF The pathophysiological mechanisms for the motility disorders are to in disorders. In the some mechanisms may be more involved than by of the developmental that or is It is that the enteric through several stages of which occur and in early infancy. is at and the at which of occur are understood. is a or information regarding the of the central of gastrointestinal activity, but some information is to show that of the enteric may occur and that this be particularly associated with transient of childhood resulting in an altered humoral environment for the enteric are a number of at the basic and clinical The and of enteric and the of the causing congenital enteric disease. It is that the disordered motility of the and motility disturbances such as chronic intestinal pseudo-obstruction are due to either the of of the motor apparatus of the gut or to disease of the motor control have that the of motility is due to congenital of the of the enteric is best by Hirschsprung disease. Apart from Hirschsprung disease, the current of is to the clinical and of the underlying and is of and perhaps a understanding of the of the enteric at the and is and for enteric The of many enteric a understanding of the of and is also information to that occur during the first 2 years of life and later in life but the information is extremely between and disease, this is an that for motility disorders. the of the in Hirschsprung disease has resulted in understanding some of the for the of enteric of disease process by of material is a and the to underlying by result in much more rapid and is a to from have at least in the first enteric disease to to the of the tissue for the of enteric disease. Although enteric disease is over the last years have been but there is a lack of for the of tissue from is also a of information regarding many of the of the enteric which disease process to The involved in and tissue from the gut that only centers will have the to such is a to be to material to centers that have the to with the material and for of pediatric of children with enteric are relatively in children or perhaps are has on the of with centers in either their or of result in this together and result in the systematic of information regarding children and these The of and the brain involved in It is that the extrinsic innervation of the gastrointestinal is largely in of information to the brain to activity in the gut. of this information and its in many common motility disorders from vomiting to constipation and in are common that have a large and have a on the of life of many children. has been with understanding the circuits involved in this and there is some understanding of the central processes which are However, is at the gut end of this and this will the of both new for the and The of the between the immune system, the enteric and the central nervous system. Motility may occur not only because of or disease of the enteric but also of disturbance of the environment within which it is an increasing body of evidence to show that there is interaction between the immune system, enteric and It is likely that this of interaction with both the immune system and the central nervous system will to be for the of less motor disturbances and acquired It is these forms of motility disturbance that will be for it is to the of the is an to the involving and irritable bowel of responses and the in which the enteric and the of disease the gut both as of a and of the gut only are is a to as as to the of these disorders in the and to the of the for acquired It is that disease interaction with the enteric causing motility disorders is understanding their is resulting in the of food in constipation in in acquired disease. two are perhaps only the of of motility disorders from the of muscle to of the underlying disease. many motility are on developmental processes to occur or for to the of disease processes or causing disease to be and other as processes of gut of gastrointestinal is and the are often in their It is that the gut has a of muscle the gut has been a relatively of to for motility disorders. a body of information that may be influenced by of the and that constipation in with extrinsic neural dysfunction may be altered by these to be particularly in children, there is a to whether the neural codes are different from in adults and for appropriate to be for common motility disorders. are in an of rapid in health and the of or clinical is in many health that children with motility disorders that are complex and to appropriate it is for involved in such children to to that for which there is evidence of their are and that are not from children. in some such as gastroesophageal reflux and is a to for all the other motility disorders that have an understanding of and for which and is the effects of motility disorders on the of life of children and their It is every common that motility disorders have a great on the of life of children and their The symptoms may of as as of the is particularly in with enteric disease but it is also by the effects of constipation on children and their there have been of the of life of children and the to study it are and the above to be to and The of the above to be by the of have a to in this and there to be a for of and the of to and in this in be and and to what is for many of them a common However, in this and are perhaps only in the United States and United the of that are to is likely to be of the to make in the above of basic that most are to between clinical and basic is perhaps the only by which the basic information is to of with perhaps to that there is a for and are are that some are this Although it is that a great of is to in the much may also be by the that The of gastroenterology the particularly be to an for the of the of the for the of and the of of life The first be to motility in each of the and for them to their between the many of these to be and for at least to be the interface between and the motility and of the this is on the of and the may be to in the of for this to be in a more systematic