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Atlas of Clinical Neurology Third Edition Editor Roger N. Rosenberg, MD The Abe (Brunky), Morris, and William Zale Distinguished Chair in Neurology Professor of Neurology Department of Neurology University of Texas Southwestern Medical Center Dallas, Texas With 55 contributors CURRENT MEDICINE GROUP LLC, PART OF SPRINGERR SCIENCE+BUSINESS MEDIA LLC 400 Market Street, Suite 700 • Philadelphia, PA 19106 Senior Developmental Editors...................................... ElizabethOrthmann, Diana Winters Editorial Assistant................................................ Juleen Deaner Design and Layout ............................................... Dan Britt, Julia Cappiello, William Whitman Jr. Illustrators ...................................................... Wieslawa Langenfeld and Maureen Looney Production Coordinator........................................... Carolyn Naylor Indexer ......................................................... Holly Lukens Library of Congress Cataloging-in-Publication Data Atlas of clinical neurology / editor, Roger N. Rosenberg. -- 3rd ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-57340-283-5 (alk. paper) 1. Nervous system--Diseases--Atlases. 2. Neurology--Atlases. I. Rosenberg, Roger N.II. Title. [DNLM: 1. Nervous System Diseases--Atlases. WL 17 A8814 2008] RC358.8.A85 2008 616.80022’2--dc22 2008009864 Additional material to this book can be downloaded from http://extras.springer.com. ISBN 978-1-57340-283-5 Although every effort has been made to ensure that drug doses and other information are presented accurately in this publication, the ultimate responsibility rests with the prescribing physician. Neither the publishers nor the authors can be held responsible for errors or for any consequences arising from the use of information contained herein. Products mentioned in this publication should be used in accordance with the prescribing information prepared by the manufacturers. No claims or endorsements are made for any drug or compound at present under clinical investigation. © 2009 Current Medicine Group LLC, part of Springer Science+Business Media LLC. All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC., 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. www.springer.com For more information, please call 1 (800) 777-4643 or email us at [email protected] www.currentmedicinegroup.com 10 9 8 7 6 5 4 3 2 1 Printed in China by Hong Kong Graphics and Printing LTD This book was printed on acid-free paper P REFACE The third edition of theAtlas of Clinical Neurologyy highlights and risk factor for AD is the presence of the E4 allele of apoliopopro- underscores the enormous strides being made in the biologic teinE(chromosome 19). Additional detailed images related to understanding of neurologic disease. Neurology is a highly visual the dementias are included in the third edition of the atlas. These specialty. The neurologic examination, MRI, electroencephalog- clinical–molecular correlations are all very recent and attest to raphy, PET, functional MRI, and light and electron microscopy the scientific vigor of current neruoscientific research.It is my are examples of visual images that define neurologic disease and view that in the near future these data will lead to effective new normal brain functions. This atlas has been designed to provide therapies for AD that will slow its rate of progress and significantly a comprehensive visual exposition and integration of all aspects reduce the incidence of this major, debilitating disease. PET and of neurologic disease, including clinical syndromes and related functional MRI have effectively defined regional brain areas for neuropathology, neuroradiology, neurophysiology, neurophar- behaviors. The clarity of insights into heterogeneous brain function macology, neurochemistry, and molecular biology. The goal is to by PET and MRI is literally revolutionizing our concept of how our provide a holistic visual concept of neurologic disease to provide brains think. the clinician with an overall image of a specific neurologic dis- The topics covered in this atlas represent the most common and order. Quality patient management requires the good judgment important neurologic diseases authored by experts in their field. and factual knowledge of an experienced physician. The Atlas of The descriptive text for each disease sets the stage for use of the Clinical Neurologyyis intended to provide essential information detailed images for self-instruction and also for lecture presenta- about neurologic disease in an immediate and integrated manner tions. Several hundred images, algorithms, tables, and schematic to facilitate the neurologist in the primary function of providing drawings have been selected carefully for their clarity in conveying excellence in patient care. the essence of a particular disorder. The collection of figures for There has been great progress in the past decade in our under- a specific disease is intended to provide a thorough and compre- standing of the cellular and molecular basis of many neurologic hensive description that enables the clinician to generate a clear diseases. As a result, each chapter has been revised and updated concept of current thinking about pathogenesis of that disorder to reflect these advances. New therapies have been developed and finally a framework for rational therapy. as a result of this recent knowledge. Thrombolytic therapy for I am grateful to my colleagues for conceptualizing the atlas stroke, deep brain stimulation for Parkinson’s disease, new classes with me initially and for updating the third edition.Our overall of anti-convulsants, and effective immune therapy for multiple educational objectives of integrating illustrated text with well- sclerosis represent examples of recent significant therapeutic focused images to provide the final detailed visual imprint of each advances in neurology. Of great importance to the understand- neurologic disorder have been achieved. We believe our efforts ing of gene structure and function in the nervous system has been provide highly useful educational material for the student and the discovery of DNA triplet repeat expansions in autosomal teacher alike. dominant neurogenetic diseases, including Huntington’s disease, It is important to recognize those who have assisted in the olivopontocerebellar atrophy (SCA1), Machado-Joseph disease, entire process of formulating and producing this atlas.Elizabeth dentatorubropallidoluysian atrophy, fragile-X disease, myotonic Orthmann and Diana Winters, Senior DevelopmentalEditors at muscular dystrophy, and Friedreich’s ataxia. The leading cause of Current Medicine Group, have been most efficient and effective in dementia in our society, Alzheimer’s disease (AD), affecting over 4 developing the third edition with the our authors and we are most million Americans and countless millions more around the world, grateful to them. has been shown to be a clinical syndrome due to specific genetic It is our hope that theAtlas of Clinical Neurology will be of value mutations in selected families with dominantly inherited disease. to neurologists and physicians of all specialties caring for patients Mutations in the amyloid precursor protein gene (chromosome with neurologic disorders, as well as neurologic investigators and 21), the presenilin 1 gene (chromosome 14), and the presenilin 2 teachers of neurology, and in the final analysis that it will benefit gene (chromosome 1) result in dominantly inherited AD. A major our patients. Roger N. Rosenberg, MD Editor iii C ONTRIBUTORS Alma R. Bicknese, MD Stanley Fahn, MD Steven M. Greenberg, MD, PhD Associate Professor H. Houston Merritt Professor of Neurology Associate Professor Department of Neurology and Psychiatry Department of Neurology Department of Neurology Department of Pediatrics Columbia University Medical Center Harvard Medical School University Health Sciences Center New York, New York Director, Hemorrhagic Stroke Research Saint Louis University School of Medicine Massachusetts General Hospital Glen A.Fenton, MD Saint Louis, Missouri Boston, Massachusetts Professor Shawn J. Bird, MD Department of Neurology and Psychiatry PaulE. Greene, MD Associate Professor of Neurology Saint Louis University Associate Professor of Clinical Neurology Department of Neurology Saint Louis, Missouri Department of Neurology University of Pennsylvania Director Columbia University Karen L. Fink, MD, PhD Electromyography Laboratory Associate Attending in Neurology Department of Neurology Director of Neuro-Oncology Department of Neurology Hospital of the University of Pennsylvania Neuro-Oncology Associates Columbia University Medical Center Philadelphia, Pennsylvania Baylor University Medical Center New York, New York Dallas, Texas Thomas D. Bird, MD David M. Greer, MD BlairFord, MD Professor Assistant Professor of Neurology Departments of Neurology and Medicine Associate Professor Harvard Medical School (Medical Genetics) Department of Neurology Department of Neurology University of Washington Columbia University Medical Center Massachusetts General Hospital Research Neurologist New York, New York Boston, Massachusetts Geriatrics Research Center Steven J. Frucht, MD DanielFFF. Hanley, MD VA Medical Center Seattle, Washington Associate Professor of Clinical Neurology Jeffrey and Harriet Legum Professor of Columbia University Medical Center Acute Neurological Medicine Susan B. Bressman, MD New York, New York Director Professor Acute Care Neurology Division Karen L. Furie, MD, MPH Department of Neurology Division of BrainInjury Associate Professor, Department of Neurology AlbertEinstein College of Medicine Baltimore, Maryland Harvard Medical School Chairman Director, Stroke Service Suman Jayadev, MD Department of Neurology Massachusetts General Hospital Assistant Professor Beth Israel Medical Center New York, New York Boston, Massachusetts Department of Neurology University of Washington Thomas J. Geller, MD Charles Brock, MD Seattle, Washington Associate Professor Program Director Department of Neurology and Psychiatry Burk Jubelt, MD Neurology Residency Program Saint Louis University Departments of Neurology, Pain Management Fellowship Saint Louis, Missouri Chief, Neurology Service Microbiology/Immunology and Neuroscience James A. Haley Veterans Hospital Romergryko G. Geocadin, MD SUNY Upstate Medical University Associate Professor Associate Director, Neurosciences Syracuse, New York Department of Neurology Critical Care Division Shahmir Kamalian, MD University of SouthFlorida College of Medicine Johns Hopkins Medical Institutions Division of Neuroradiology Tampa, Florida Director, Neurosciences Critical Care Unit Massachusetts General Hospital Dennis K. Burns, MD Johns Hopkins Bayview Medical Center Boston, Massachusetts Assistant Professor Professor Departments of Neurology, Neurologic Surgery, Cathrine E. Kinnecom, MS Department of Pathology and Anesthesiology/Critical Care Medicine Genzyme Corporation Division of Neuropathology Baltimore, Maryland Cambridge, Massachusetts University of Texas Southwestern Medical Center Dallas, Texas Thomas J. Grabowski, Jr., MD J. Philip Kistler Professor of Neurology and Radiology Director, Stroke Unit Juan-Ricardo Carhuapoma, MD Director Professor of Neurology Departments of Neurology, Neurologic Surgery, Laboratory of Computational Neuroimaging Harvard Medical School and Anesthesiology/Critical Care Medicine Department of Neurology Massachusetts General Hospital Johns Hopkins University School of Medicine University of Iowa Carver College of Medicine Boston, Massachusetts Baltimore, Maryland Iowa City,Iowa Matthew Koenig, MD MarthandEswara, MD Dorothy K. Grange, MD Assistant Professor Director, Regional Genetics Program Professor Departments of Neurology, Neurologic Surgery, Sutter Medical Center Department of Pediatrics and Anesthesiology/Critical Care Medicine Sacramento, California Washington University School of Medicine Baltimore, Maryland Saint Louis Children’s Hospital Saint Louis, Missouri iv Suresh Kotagal, MD Christopher S. Ogilvy, MD John T. Sladky, MD Consultant Professor of Surgery Professor Departments of Neurology and Pediatrics Department of Neurosurgery Department of Pediatrics and Neurology Mayo Clinic Director of Neurovascular Surgery Emory University School of Medicine Rochester, Minnesota Massachusetts General Hospital Atlanta, Georgia Harvard Medical School Marc E. Lenaerts, MD Peter S. Spencer, PhD Boston, Massachusetts Associate Professor of Neurology Professor of Neurology Department of Neurology Thomas Pittman, MD School of Medicine Headache Section Professor, Pediatric Neurological Surgery Senior Scientist and Director, Center for Research Oklahoma University Health Sciences Center Department of Neurosurgery onOccupational andEnvironmental Toxicology Oklahoma City, Oklahoma University of Kentucky Interim Director, Global Health Center Lexington, Kentucky Oregon Health and Sciences Center Michael H. Lev, MD Portland, Oregon Director David E. Pleasure, MD Emergency Neuroradiology and Neurovascular Lab Professor, Neurology and Pediatrics Robert D. Stevens, MD Massachusetts General Hospital Director,Institute for Pediatric Assistant Professor Associate Professor of Radiology Regenerative Medicine Johns Hopkins University School of Medicine Harvard Medical School UC Davis School of Medicine Departments of Neurology, Neurological Surgery, Boston, Massachusetts Sacramento, California and Anesthesiology/Critical Care Medicine Baltimore, Maryland David S. Martin, MD Leon D. Prockop, MD Williamson Medical Center Founding Chairman, Emeritus Michael R. Swenson, MD, MSc Franklin, Tennessee Professor of Department of Neurology Fellow, American Academy of Neurology University of SouthFlorida Lander, Wyoming Marek A. Mirski, MD Chair Associate Professor of Anesthesia and Daniel Tranel, PhD Environmental Neurology Research Group Critical Care Medicine (ENRG)/World Federation of Neurology (WFN) Professor Johns Hopkins Medical Institutions Tampa,Florida Department of Neurology Baltimore, Maryland University of Iowa Elisabeth J. Rushing, MD Iowa City,Iowa Alim P. Mitha, MD, SM Chair ResearchFellow Paul C. Van Ness, MD Neuropathology and Ophthalmic Pathology Division of Neurosurgery Associate Professor ArmedForcesInstitute of Pathology Harvard Medical School Adjunct Professor Department of Neurology Boston, Massachusetts Department of Pathology University of Texas Neurosurgery Resident Georgetown University School of Medicine Southwestern Medical Center Department of Neurosurgery Washington, District of Columbia Dallas, Texas University of Calgary Calgary, Alberta, Canada Erica Cristina Sa de Camargo, Gil I. Wolfe, MD MD, MMSc, PhD Dr. Bob and Jean SmithFoundation Neeraj S. Naval, MD Distinguished Chair in Neuromuscular ResearchFellow Assistant Professor Disease Research Department of Neurology, Stroke Service Neurocritical Care Division Professor Massachusetts General Hospital and Departments of Neurology, Neurologic Surgery, Department of Neurology Harvard Medical School and Anesthesiology/Critical Care Medicine University of Texas Southwestern Medical Center Boston, Massachusetts Johns Hopkins Medical Institutions Dallas, Texas Baltimore, Maryland Danita Y. Sanborn, MD Wendy C. Ziai, MD, MPH Cardiac Ultrasound Laboratory Michael A. Nigro, DO, FFFACN Assistant Professor of Neurology, Harvard Medical School Michigan Institute for Neurological Disorders Neurological Surgery, Anesthesiology and Massachusetts General Hospital Farmington Hills, Michigan Critical Care Medicine Boston, Massachusetts Johns Hopkins Medical Institutions Paul A. Nyquist, MD, MPH Steven S. Scherer, MD, PhD Departments of Neurology, Neurologic Surgery, Neurosciences Critical Care Unit William N. Kelley Professor and Anesthesiology/Critical Care Medicine Cerebrovascular Division Department of Neurology Baltimore, Maryland Assistant Professor University of Pennsylvania Departments of Neurology, and Neurologic Surgery Earl A. Zimmerman, MD Philadelphia, Pennsylvania Johns Hopkins School of Medicine Professor and Bender Endowed Chair of Neurology Baltimore, Maryland Scott B. Silverman, MD Director, Clinical Research Massachusetts General Hospital The Neurosciences Institute Boston, Massachusetts Albany Medical College Albany, New York v C ONTENTS Chapter 1 Developmental Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Suresh Kotagal, Alma R. Bicknese, MarthandEswara, Glen A. Fenton, Thomas J. Geller, Dorothy K. Grange, David S. Martin, Michael A. Nigro, and Thomas Pittman Chapter 2 Genetic Diseases of the Nervous System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Thomas D. Bird and Suman Jayadev Chapter 3 Neuroendocrine Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 Earl A. Zimmerman Chapter 4 Critical Care Neurology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Marek A. Mirski, Robert D. Stevens, Romergryko G. Geocadin, Juan-Ricardo Carhuapoma, Wendy C. Ziai, DanielFFF. Hanley, Paul A. Nyquist, Neeraj S. Naval, and Matthew Koenig Chapter 5 Cerebrovascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 David M. Greer, Shahmir Kamalian, Scott B. Silverman, Alim P. Mitha, CathrineE. Kinnecom, Danita Y. Sanborn, Steven M. Greenberg, Christopher S. Ogilvy, Michael H. Lev, J. Philip Kistler, Karen L. Furie, andErica Cristina Sa de Camargo Chapter 6 Dementias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 Thomas J. Grabowski, Jr. Chapter 7 Behavioral Neurologyy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 Daniel Tranel and Thomas J. Grabowski, Jr. Chapter 8 Neuro-oncology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289 Karen L. Fink andElisabeth J. Rushing Chapter 9 Movement Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 Stanley Fahn, Paul E. Greene, BlairFord, Susan B. Bressman, and Steven J. Frucht Chapter 10 The Epilepsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395 Paul C. Van Ness Chapter 11 Neuromuscular Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423 Gil I. Wolfe, David E. Pleasure, Shawn J. Bird, Steven S. Scherer, John T. Sladky, and Dennis K. Burns Chapter 12 Infectious Diseases of the Nervous System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441 Burk Jubelt Chapter 13 Neuroimmunology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517 Michael R. Swenson Chapter 14 Neurotoxic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543 Leon D. Prockop, Charles Brock, and Peter S. Spencer Chapter 15 Headache . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565 MarcE. Lenaerts Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 599 vi Developmental Disorders Suresh Kotagal, Alma R. Bicknese, Marthand Eswara, Glen A. Fenton, Thomas J. Geller, Dorothy K. Grange, David S. Martin, Michael A. Nigro, and Thomas Pittman This chapter covers a varied group of disorders that develop as a consequence of genetic abnormalities, infections, ischemia, or uncertain etiology. All lead to abnormal development of the nervous system. Some disorders have been selected because of the challenge they pose in diagnosis and management, and others because they illustrate important concepts in neurodevelopment or pathophysiology. Advances in molecular genetics and neuroimaging play an ever-increasing role in furthering our understanding of congenital central nervous system malformations [1,2]. A thorough general physical examination provides valuable diagnostic information in infants and children who present with seizures and developmental delay. Nowhere is this principle more important than in connection with the phakomatoses, clues to the specifi c diagnosis of which become apparent during a careful general physical examination. We now also have a better understanding of the mechanisms underlying abnormal cell proliferation, angiogenesis, and synaptogenesis in neurocutaneous syndromes such as tuberous sclerosis and neurofi bromatosis [3]. As a general rule, the more severe the disturbance of brain development, the earlier the onset of clinical symptoms. Thus, seizures, microcephaly, macrocephaly, hemiparesis, external defects, and developmental delay regularly accompany developmental disorders presenting in infancy or early childhood. 1 CHAPTER 2 Atlas of Clinical Neurology M YELOMENINGOCELE Figure 1-1. A myelomeningocele. About 1 child in 1000 is born with a myelomeningocele. Symptoms vary depending on the level of the lesion. Bowel and bladder dysfunc- tion are nearly universal, but motor disability is specific to the functional level; that is, children with thoracic lesions have flaccid paraplegia, whereas those with lumbar lesions have various degrees of lower extremity weakness. Almost all affected children have hydrocephalus; many have macrocephaly apparent at birth, but others do not develop signs of intracranial hypertension until the back has been surgically closed. Over 90% of patients with myelomeningocele have asymptomatic type II Chiari malformations that require no treatment. The treatment of children with myelomeningoceles that require intervention involves back closure, usually performed within the first 24 hours of life; delay beyond that time increases the likelihood of infection. A ventriculoperitoneal shunt can be placed at the same time, but many neurosurgeons prefer to perform the two proce- dures separately. Many children will have problems with bony deformity and contrac- tures, and almost all with higher lesions ultimately develop scoliosis. Recurrent urinary tract infections, vesicoureteral reflux associated with a spastic bladder, and problems with continence and sexual function are also common. Sleep-disordered breathing, Research on the effect of maternal folic consisting of a combination of hypoventilation and central and obstructive sleep apnea, acid supplementation offers some hope may lead to daytime fatigue and pulmonary hypertension. Finally, as they grow, some for prevention [4], but presently the dis- patients with myelomeningoceles become symptomatic from tethering of the spinal order is continuing to occur in the United cord that is manifested by back pain, progressive weakness, and changes in bowel and States at an incidence of 0.5 to 1 per 1000 bladder habits. Symptomatic tethering usually requires operative intervention. pregnancies [5]. A NENCEPHALY Figure 1-2. Lateral view of an infant with anencephaly showing lack of normal development of the brain, skull, and scalp. Anencephaly and other neural tube defects can be diagnosed prenatally through maternal serum alpha-fetoprotein screening and fetal ultrasonography. The defect results from failed closure of the anterior neuropore of the neural tube. All cases of anencephaly should be detectable by ultrasonography by 14 weeks of gestation with state-of-the-art equipment [6]. After the first affected offspring, the recurrence risk for any neural tube defect in a subsequent pregnancy is approximately 4%. Neural tube defects are multifactorial in etiology, with a group of genes inherited from each parent acting in association with environmental factors to cause the defect [7]. Maternal folic acid deficiency can contribute to the incidence of neural tube defects. For women who have had a previous pregnancy with a neural tube defect, the consumption of folic acid, 4 mg/d, can reduce the recurrence risk to 0.5% to 1% [4]. To reduce the overall incidence of neural tube defects, it is now recommended that all women of childbear- ing age ingest folic acid, 0.4 mg/d [5]. Since the average intake of dietary folic acid is about involve actin regulation, supporting the 0.2 mg/d, government agencies are recommending periconceptional maternal folic acid postulation that actin plays a key role in supplementation [8]. The genes mutated in several mouse models of neural tube defects neurulation [9]. E NCEPHALOCELE Figure 1-3. Newborn infant with a massive occipital encephalocele. An encephalocele is a neural tube defect in which there is extrusion of cranial contents through a bony defect in the skull [10]. The pathogenesis is poorly understood but most likely involves defective development of the skull base [11]. Encepha- loceles can be located anywhere over the cranium, although most appear in the occipital (70%–80%) or frontal locations [7,10]. Parietal, nasal, and nasopharyngeal lesions may occur as well. Temporal lesions are the least common. Most defects are skin covered, although some have only a thin membranous cov- ering that can rupture during delivery or with manipulation. The clinical consequences and prognosis are related directly to the contents of the encephalocele sac rather than the size of the Continued on the next page 3 Developmental Disorders Figure 1-3. (Continued)defect. The infant shown had severe er neural tube defects. All infants with encephaloceles should microcephaly with a bony defect in the occipital region of be examined carefully for additional anomalies, because a the skull; most of the brain tissue was contained within the significant number of recognizable genetic syndromes include encephalocele sac. Approximately 20% of affected children encephaloceles. The presence of a specific syndrome would are mentally retarded or have neurologic abnormalities [7]. alter the recurrence risk figures for future pregnancies. There is a high frequency of associated anomalies of the brain, Encephaloceles occur in 1 in 5000 to 1 in 10,000 births [7]. The such as neuronal migrational defects, absent corpus callosum, recurrence risk for future pregnancies after the first affected and hydrocephalus, and posterior fossa anomalies, including child is about 6%. As with other neural tube defects, maternal Dandy-Walker and Arnold-Chiari malformations [7]. Extracranial use of folic acid before and during pregnancy may reduce the anomalies occur more often with encephalocele than with oth- risk of recurrence [12]. C R S AUDAL EGRESSION EQUENCE Figure 1-4. Frontal view of an infant with caudal regression Figure 1-5. Posterior view of the same infant as in Figure 1-4, sequence showing a “frog leg” appearance of the lower extremi- showing flat buttocks and sacral dimples, as well as a spinal ties. There are abduction and flexion deformities of the hips as projection of the lower back. Radiographic examination showed well as popliteal webs, a talipes equinovarus deformity of the absence of the sacrum and lumbar vertebrae, fused iliac bones, left foot, and a calcaneovalgus deformity of the right foot. The and hypoplastic femurs. Hydronephrosis was present. upper body appears normal, but there is marked hypoplasia of Caudal regression sequence is a developmental field defect the lower body. Primary neurulation occurs during embryonic with absence or defects of structures derived from the embry- days 18 to 27 and involves the formation of the neural plate, onic caudal axis [14,16]. Sacral agenesis and variable abnormali- neural tube, and spinal cord. Secondary neurulation occurs ties of the lumbar vertebrae are commonly seen. Hypoplasia of during embryonic days 28 to 48 and results in formation of the the sacrum leads to flattening of the buttocks, shortening of the spinal cord below the lumbosacral junction [13]. The paired intergluteal cleft, or dimpling of the buttocks. There is frequent- somites, derived from mesoderm, develop along the spinal ly severe lack of growth in the caudal region. Sensory sparing cord. The vertebral segments form from a portion of each is characteristic and suggests a relative preservation of neural somite. The caudal eminence, or tailbud, gives rise to the ter- crest cells. There may be abnormalities of the distal spinal cord minal spinal cord, the caudal notochord, vertebral segment S-2 with neurologic impairment [13]. Other anomalies include through the last coccygeal segment, and parts of the hindgut imperforate anus or rectal agenesis, hypoplasia of the external and urogenital system. Thus, an insult to the caudal eminence genitalia, and renal anomalies or agenesis [17]. may cause malformations in any of the structures normally Caudal regression has been previously grouped with sireno- derived from it, and might result in agenesis of sacral and coc- melia, or sympodia, in which the lower extremities are fused, cygeal vertebrae and in lower gastrointestinal and urogenital with posterior alignment of the knees and feet; these defects anomalies [13,14]. (From Gellis et al. [15]; with permission.) are now thought by some investigators to be pathogenetically different, with sirenomelia being caused by vitelline artery steal [17]. Caudal regression sequence should also be distinguished from isolated sacral agenesis with or without spina bifida, which is probably a separate autosomal dominant condition [18]. (From Gellis et al. [15]; with permission.)