CLINICAL GASTROENTEROLOGY

(1)

CLINICAL GASTROENTEROLOGY

Series Editor George Y. Wu

University of Connecticut Health Center, Farmington, CT, USA

For further volumes:

(2)

(3)

Christophe Faure • Carlo Di Lorenzo

Nikhil Thapar

Editors

Pediatric

Neurogastroenterology

Gastrointestinal Motility and

Functional Disorders in Children

(4)

Editors

Christophe Faure

Division of Pediatric Gastroenterology Sainte-Justine University Health Center Department of Pediatrics

Université de Montréal Montréal, QC, Canada Nikhil Thapar Gastroenterology Unit University College London Institute of Child Health Department of Paediatric

Gastroenterology,

Neurogastroenterology, and Motility Great Ormond Street Hospital

for Children London, UK

Carlo Di Lorenzo

Division of Pediatric Gastroenterology Nationwide Children’s Hospital The Ohio State University Columbus, OH, USA

ISBN 978-1-60761-708-2 ISBN 978-1-60761-709-9 (eBook) DOI 10.1007/978-1-60761-709-9

Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2012952724 © Springer Science+Business Media New York 2013

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speci fi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro fi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied speci fi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law.

The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speci fi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed on acid-free paper Humana Press is a brand of Springer

(5)

To my parents with love.

Christophe Faure

To my parents for their unconditioned

support and love.

Carlo Di Lorenzo

To my beloved father Baldev Sahai

Thapar—blessed by your and mum’s

unending love, forever my guiding light

and inspiration.

Nikhil Thapar

To our patients and all the children

af fl icted by motility and sensory digestive

disorders.

Christophe Faure

Carlo Di Lorenzo

(6)

(7)

vii

Foreword

Welcome to the fi rst comprehensive textbook of pediatric neurogastroenterol-ogy and motility. Thirty years have passed since the fi rst stirrings of interest in this fi eld. A number of factors coalesced to facilitate its evolution from oddity and anecdote to mainstream basic science, epidemiology, and clinical trials. First, there has been an increase in the number of pediatric gastroenter-ologists, providing a reservoir of intellectual curiosity. Second, medical tech-nology has advanced, so that we measure more, both in the basic science laboratory and in pediatric practice. Third, medical care has improved, so that infants who were dying before diagnosis now live, for example, on parenteral nutrition, so that their pseudo-obstruction can be characterized. Fourth, the 1999 publication of pediatric Rome criteria, symptom-based criteria for the diagnosis of functional gastrointestinal disorders, inspired new investigations into mind–body pediatric medicine. Motility themed advances dominated the fi rst 10 years. During the second 10 years the emphasis shifted to understand-ing visceral pain and other afferent sensory sensations and re fl exes. In the past 10 years the focus has been on brain–gut interactions and the functional gastrointestinal disorders. This text admirably covers all three areas of empha-sis. The publication of this volume marks the end of the beginning for pediat-ric neurogastroenterology and motility.

(8)

(9)

ix

Preface

In the past 20 years, major advances have been achieved in the care of chil-dren with pediatric gastrointestinal motility and sensitivity disorders. This is a re fl ection of the progress that has been made understanding such conditions at the developmental and molecular level as well as the development of novel tools to investigate and treat them. These progresses have led to the birth of a new “Science”, namely Neurogastroenterology , which is devoted to “study the interface of all aspects of the digestive system with the different branches of the nervous system” and which has now established itself as a major area of clinical practice and research. In the past two decades, there has been an almost exponential increase in publications of scienti fi c papers in the fi eld, a plethora of international fora for the discussion of such conditions and cre-ation of dedicated journals with respectable citcre-ation indices. Pediatric neuro-gastroenterology and motility has not lagged behind and arguably is fast becoming a major and popular subspecialty in its own right.

With this book we aimed to draw upon an extensive international expertise to provide a contemporary state-of-the-art reference textbook for pediatric neurogastroenterology and motility that both specialists and generalists alike will fi nd helpful.

Overview of the Book

The fi rst chapters are dedicated to some of the success stories of the fi eld. Utilizing a range of animal models and studies in the human itself we now have a remarkable understanding of the mechanisms involved in the forma-tion of a funcforma-tional enteric neuromusculature. It is clear that development is a complex spatiotemporal process involving the coordinated interplay of a number of genes regulating cellular properties and organogenesis. This com-plexity is re fl ected in one of the most commonly recognized gut motility disorders, Hirschsprung’s disease, a condition caused by a failure of devel-opment of the enteric nervous system. The ontogeny of motility patterns within the GI tract is now understood in great detail. Utilizing new technolo-gies, animal models, and some studies in humans, researchers have been able to show that GI motility is regulated by a number of mechanisms that vary in relation to stage of development, maturity, and region within the GI tract. It is very likely that the coming years will see an increasing recognition

(10)

x Preface

of the developmental and related functional pathogenic mechanisms under-lying a range of disorders involving enteric nerves, muscles and interstitial cells of Cajal. The rich sensory innervation that not only underlies the nor-mal functioning of the GI tract but has increasingly been implicated in a range of functional GI disorders is thoroughly described. This sensory inner-vation and its processing appear to be plastic and in fl uenced by a number of disease mechanisms and clinical states including infection, in fl ammation, and psychological stress. How visceral sensation is modulated by the inter-play among the CNS, neurogastrointestinal system, in fl ammation, and gut microbial ecosystem especially in relation to irritable bowel syndrome is addressed in a subsequent chapter. This theme is further developed with the discussion of the bio-psycho-social in fl uences on enteric neuromuscular function and how the social and cultural settings of patients act to modify physiologic responses.

The belly of the book summarizes the practical investigations that are available in the pediatric neurogastroenterologist’s armamentarium. In many respects this is where much of the recent strides of the fi eld have taken place, moving it into the realms of a high-tech futuristic specialty. Major highlights have been the advent of impedance and high-resolution manometry technolo-gies, which did not exist when the fi rst textbook on pediatric gastrointestinal motility was published, and are now well accepted and standardized diagnos-tic techniques. The role of sensitivity tests, namely barostat and satiety drink-ing tests, in recognizdrink-ing altered gut sensation as a key pathophysiologic component of functional gastrointestinal disorders, is discussed. The applica-tion to clinical investigaapplica-tion of radionucleotide scintigraphy tests which have seen in recent years a wider application given their improved tolerability, cost, and safety pro fi le is described in detail. Older and newer technologies ranging from electrogastrography and transit studies to 3D-ultrasonography and the wireless motility capsule are presented. Finally, there is a discussion of autonomic function testing as indirect measure of gastrointestinal function. The subsequent chapters deal with the practical approach to and description of the pathology of disorders of enteric neuromusculature and the genetic underpinning of motility disorders.

The next section of the book focuses on a journey through the GI tract detailing motility disorders that occur in each region. Feeding and swallow-ing disorders in a range of GI and systemic diseases are discussed. Pediatric esophageal and gastric motor disorders are summarized, and intestinal pseudo-obstruction syndrome and Hirschsprung’s diseases, the most severe forms of GI dysmotility, are discussed in great detail. The book then focuses on secondary (malformative) and postsurgical motor disorders.

The book then transitions from more classic motility disorders to func-tional GI disorders, arguably one of the most common and challenging group of conditions encountered by primary care providers and subspecialists. The role of the Rome criteria in developing the fi eld of pediatric functional disorders is highlighted. Infant regurgitation and gastroesophageal re fl ux disease, infantile colic, functional dyspepsia, irritable bowel syndrome, cyclic vomiting syndrome, aerophagia, adolescent rumination syndrome, and func-tional constipation are discussed.

(11)

xi Preface

The fi nal section of the book is dedicated to therapy, including pharmaco-therapy, cognitive behavioral pharmaco-therapy, gastric electrical stimulation, intestinal transplantation, and the potential use of stem cells.

Montreal , QC , Canada Christophe Faure

Columbus , OH , USA Carlo Di Lorenzo

(12)

(13)

xiii

Acknowledgments

To our wives (Sophie, Daniela, and Catherine) and children (Alexandre, Timothé, Clémentine, Gaspar, Mario, Cristina, Francesca, Valentina, Sachin, Nayan, and Kira) for all their love, support, and patience throughout the prep-aration of this book.

Montreal, QC, Canada Christophe Faure

Columbus, OH, USA Carlo Di Lorenzo

(14)

(15)

xv

Contributors

Anthony Alioto , PhD Department of Psychology , Nationwide Children’s Hospital , Columbus , OH , USA

Ann Aspirot , MD Department of Surgery, Pediatric Surgery Division , Sainte-Justine University Health Center, University of Montreal , Montreal , QC , Canada

Elizabeth A. Beckett , PhD Discipline of Physiology , School of Medical Sciences, University of Adelaide , Adelaide , SA , Australia

Marc A. Benninga , MD, PhD Department of Pediatric Gastroenterology , Emma Children’s Hospital/Academic Medical Centre , Amsterdam , The Netherlands

William Berquist , MD Pediatrics Department, Gastroenterology Division , Lucile Packard Children’s Hospital, Stanford University , Stanford , CA , USA

Lorenzo Biassoni , MSc, FRCP Nuclear Medicine, Department of Radiology , Great Ormond Street Hospital for Children , London , UK

Joel C. Bornstein , PhD Department of Physiology , University of Melbourne , Melbourne , VIC , Australia

Osvaldo Borrelli , MD, PhD Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology , Great Ormond Street Hospital for Children , London , UK

Roberta Buonavolontà , MD Department of Pediatrics , University of Naples , Naples , Italy

Rosa Burgers , MD Department of Pediatric Gastroenterology , Emma Children’s Hospital/Academic Medical Centre , Amsterdam , The Netherlands

Alan J. Burns , PhD Neural Development Unit , UCL Institute of Child Health , London , UK

Julie Castilloux , MD Pediatric Department, Gastroenterology Division , Centre Hospitalier Universitaire Laval , Quebec City , QC , Canada

(20)

xx Contributors

Gisela Chelimsky , MD Pediatric Gastroenterology Division, Pediatrics Department , Medical College of Wisconsin , Milwaukee , WI , USA

Thomas C. Chelimsky , MD Neurology Department , Medical College of Wisconsin , Milwaukee , WI , USA

Eric Chiou , MD Center for Motility and Functional Gastrointestinal Disorders, Children’s Hospital Boston , Boston , MA , USA

Denesh K. Chitkara , MD Pediatric Gastroenterology and Nutrition , Goryeb Children’s Hospital, Atlantic Health , Morristown , NJ , USA

Ashish Chogle , MD, MPH Pediatric Gastroenterology, Hepatology and Nutrition Division, Pediatrics Department , Children’s Memorial Hospital, Northwestern University , Chicago , IL , USA

Joseph M.B. Crof fi e , MD, MPH Division of Gastroenterology, Pediatrics Department , James Whitcomb Riley Hospital for Children , Indianapolis , IN , USA

Thierry Devreker , MD Pediatric Gastroenterology Department , Universitair Kinderziekenhuis Brussel , Brussels , Belgium

Carlo Di Lorenzo , MD Division of Pediatric Gastroenterology , Nationwide Children’s Hospital, The Ohio State University , Columbus , OH , USA

Christophe Faure , MD Division of Pediatric Gastroenterology , Department of Pediatrics, Sainte-Justine University Health Center, Université de Montréal , Montréal , QC , Canada

David R. Fleisher , MD Pediatric Gastroenterolgy Division, Department of Child Health , University of Missouri School of Medicine , Columbia , MO , USA

Alejandro Flores , MD Pediatric Gastroenterology , Tufts Medical Center , Boston , MA , USA

Sylvie Fortin , PhD Anthropology Department , Université de Montréal , Montréal , QC , Canada

John E. Fortunato , MD Department of Pediatrics, Gastroenterology Division , Wake Forest University , Winston-Salem , NC , USA

Cheryl E. Gariepy , MD Center for Molecular and Human Genetics , The Research Institute at Nationwide Children’s Hospital , Columbus , OH , USA Pediatric Gastroenterology, Hepatology and Nutrition Division, Pediatrics Department , The Ohio State University College of Medicine , Columbus , OH , USA

Jose M. Garza , MD, MS Gastroenterology, Heptaology and Nutrition Division, Pediatrics Department , Cincinnati Children’s Hospital Medical Center , Cincinnati , OH , USA

Annie Gauthier , PhD Research Center, Sainte-Justine University Health Center , Montreal , QC , Canada

(21)

xxi Contributors

Valentina Giorgio Division of Neurogastroenterology & Motility , Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Children , London , UK

Jonathan M. Gisser , MD MSc Center for Molecular and Human Genetics , The Research Institute at Nationwide Children’s Hospital , Columbus , OH , USA

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Pediatrics Department , The Ohio State University College of Medicine , Columbus , OH , USA

Liliana Gomez , MSc Research Center , Sainte-Justine University Hospital , Montreal , QC , Canada

Roberto Gomez , MD Pediatric Gastroenterology Department , Wake Forest University , Winston-Salem , NC , USA

Olivier Goulet , MD, PhD Pediatrics Department , Hôpital Necker-Enfants Malades at the University of Paris 5 René Descartes , Paris , France

Pediatric Gastroenterology-Hepatology and Nutrition and Reference Center for Rare Digestive Diseases , Intestinal Failure Rehabilitation Center , Paris , France

Ernesto Guiraldes , MD Ponti fi cia Universidad Católica de Chile and Universidad Mayor , Santiago , Chile

Aileen F. Har , MB, BCh Division of Gastroenterology, Pediatrics Department , James Whitcomb Riley Hospital for Children , Indianapolis , IN , USA

Bruno Hauser , MD Paediatric Gastroenterology Hepatology and Nutrition Division, Paediatrics Department , Universitair Kinderziekenhuis Brussel , Brussels , Belgium

Tiffany A. Heanue , PhD Division of Molecular Neurobiology , National Institute for Medical Research , Mill Hill , London , UK

Robert O. Heuckeroth , MD, PhD Pediatric Gastroenterology Division, Pediatrics Department , Washington University School of Medicine in St. Louis , St. Louis , MO , USA

Developmental Biology , St. Louis Children’s Hospital , St. Louis , MO , USA

Ryo Hotta , MD, PhD Department of Anatomy and Neuroscience , The University of Melbourne , Melbourne , Australia Department of Pediatric Surgery , Keio University School of Medicine , Tokyo , Japan

Jeffrey S. Hyams , MD Digestive Diseases , Connecticut Childrens Medical Center, University of Connecticut School of Medicine , Hartford , CT , USA

Paul E. Hyman , MD Gastroenterology Division , Children’s Hospital, Louisiana State University , New Orleans , LA , USA

Sabine Irtan , MD Pediatric Surgery , Hôpital Necker-Enfants Malades, University of Paris , Paris , France

(22)

xxii Contributors

Sudarshan R. Jadcherla , MD, FRCPI, DCH, AGAF Department of Pediatrics, Division of Neonatology, Pediatric Gastroenterology and Nutrition, The Ohio State University College of Medicine and Public Health

Section of Neonatology , Nationwide Children’s Hospital , Columbus , OH , USA

Ajay Kaul , MD Division of Gastroenterology, Pediatrics Department , Cincinnati Children’s Hospital Medical Center , Cincinnati , OH , USA

Oren Koslowe , MD Gastroenterology and Nutrition, Pediatrics Department , Goryeb Children’s Hospital/Atlantic Health System , Morristown , NJ , USA

Minou Le-Carlson , MD Pediatric Gastroenterology, Hepatology and Nutrition, Pediatrics Department , Stanford University Medical Center, Lucile Packard Children’s Hospital , Palo Alto , CA , USA

Alycia Leiby , MD Pediatric Gastroenterology and Nutrition , Goryeb Children’s Hospital, Atlantic Health , Morristown , NJ , USA

B . U.K. Li , MD Division of Gastroenterology, Hepatology and Nutrition, Pediatrics Department , Medical College of Wisconsin , Milwaukee , WI , USA

Keith J. Lindley , MD, PhD Division of Neurogastroenterology & Motility, Department of Paediatric Gastroenterology , Great Ormond Street Hospital for Children , London , UK

Vera Loening-Baucke , MD General Pediatric Division, Pediatrics Department , University of Iowa , Iowa City , IA , USA

Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie and Endokrinologie , Charité Universitätsmedizin , Berlin , Germany

H. Nicole Lopez , MD Pediatrics Department , Wake Forest University School of Medicine , Winston-Salem , NC , USA

Massimo Martinelli , MD Pediatric Gastroenterology Division, Pediatrics Department , University of Naples “Federico II” , Naples , Italy

Sonia Michail , MD The Children’s Medical Center, Gastroenterology, One Children’s Plaza, Dayton, OH , USA

Hayat Mousa , MD Pediatric Gastroenterology Hepatology and Nutrition, Department of Pediatrics , Nationwide Children Hospital, Ohio State University , Columbus , OH , USA

Dipa Natarajan , MSc, MPhil, PhD Neural Development Unit , UCL, Institute of Child Health , London , UK

Mun-Wah Ng , MD Pediatrics Department, Pediatrics Department, Gastroenterology & Nutrition Division, Children’s , Hospital Los Angeles , Los Angeles , CA , USA

Samuel Nurko , MD, MPH Center for Motility and Functional Gastrointestinal Disorders , Children’s Hospital , Boston , MA , USA

(23)

xxiii Contributors

Taher Omari , PhD Gastroenterology Unit , Child, Youth and Women’s Health Service, School of Paediatrics and Reproductive Health University of Adelaide , Adelaide , SA , Australia

Andrée Rasquin , MD Gastroenterology Division, Pediatrics Department , Hospital Ste Justine, University of Montreal , Montreal , QC , Canada

Brian P. Regan DO Pediatric Gastroenterology , Tufts Medical Center , Boston , MA , USA

Leonel Rodriguez , MD, MS Department of Medicine, Gastroenterology Division , Children’s Hospital Boston, Harvard Medical School , Boston , MA , USA

José Luis Roessler , MD Pediatric Gastroenterology Division, Pediatrics Department , Hospital Félix Bulnes , Santiago de , Chile

Nathalie Rommel , MSc, PhD Department Neurosciences, Faculty of Medicine, Experimental Otorhinolaryngology , University of Leuven , Leuven , Belgium

Rachel Rosen , MD, MPH Harvard Medical School, Center for Motility and Functional Gastrointestinal Disorders Children’s Hospital Boston, Boston , MA , USA

Marina Russo , MD Department of Pediatrics , University of Naples Federico II , Naples , Italy

Silvia Salvatore , MD Pediatric Department , University of Insubria, Ospedale “F. Del Ponte” , Varese , Italy

Miguel Saps , MD Pediatric Gastroenterology, Hepatology and Nutrition Division, Pediatrics Department , Children’s Memorial Hospital, Northwestern University , Chicago , IL , USA

Virpi Vanamo Smith , PhD, MRCPath Paediatric Surgery Unit , Institute of Child Head, University College London , London , UK

Manu R. Sood , MD(UK), FRCPCH Pediatric Gastroenterology Division, Medical College of Wisconsin, Children’s Hopsital of Wisconsin, Milwaukee, WI, USA

Annamaria Staiano , MD Pediatric Gastoenterology Division, Pediatrics Department , University of Naples “Federico II” , Naples , Italy

Bhanu Sunku , MD Mount Kisco Medical Group , Mount Kisco , NY , USA

Alexander Swidsinski , MD, PhD Gastroenterologie, Hepatologie and Endokrinologie , Medizinische Klinik und Poliklinik, Charité Universitätsmedizin , Berlin , Germany

Steven Teich , MD Pediatric Surgery , Nationwide Children’s Hospital , Columbus , OH , USA Clinical Surgery, Pediatric Surgery , The Ohio State University , Columbus , OH , USA

(24)

xxiv Contributors

Nikhil Thapar , BSc(Hon), BM(Hon), MRCP, MRCPCH, PhD

Gastroenterology Unit , University College London, Institute of Child Health, Division of Neurogastroenterology and Motility , London , UK

Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Children , London , UK

Rossella Turco , MD Department of Pediatrics , University of Naples Federico II , Naples , Italy

Miranda A.L. van Tilburg , PhD UNC Center for Functional GI and Motility Disorders, Chapel Hill, NC, USA

Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Yvan Vandenplas , MD, PhD Pediatrics , Universitair Ziekenhuis Brussel, Vrye Universiteit Brussel , Brussels , Belgium

Arine M. Vlieger , MD, PhD Department of Pediatrics , St. Antonius Hospital , Nieuwegein , The Netherlands

Heather M. Young , PhD Department of Anatomy & Neuroscience, University of Melbourne, Parkville, VIC , Australia

Nader N. Youssef , MD, FAAP, FACG Adolescent Gastroenterology , Digestive Health Care Center , Hillsborough , NJ , USA

Bella Zeisler , MD Division of Digestive Diseases, Hepatology, and Nutrition , Connecticut Children’s Medical Center , Hartford , CT , USA

CLINICAL GASTROENTEROLOGY