Neurology board review

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Neurology board review

  1. 1. Neurology Board Review An Illustrated Study Guide
  2. 2. Editors Nima Mowzoon, MD Kelly D. Flemming, MD MAYO CLINIC SCIENTIFIC PRESS AND INFORMA HEALTHCARE USA, INC. An Illustrated Study Guide Neurology Board Review i_xvi.qxd 3/8/07 10:33 AM Page iii
  3. 3. ISBN 0-8493-3791-7 / 978-0-8493-3791-8 The triple-shield Mayo logo and the words MAYO, MAYO CLINIC, and MAYO CLINIC SCIENTIFIC PRESS are marks of Mayo Foundation for Medical Education and Research. ©2007 by Mayo Foundation for Medical Education and Research. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means—electronic, mechanical, photocopying, recording, or otherwise—without the prior written consent of the copyright holder, except for brief quotations embodied in critical articles and reviews. Inquiries should be addressed to Scientific Publications, Plummer 10, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. For order inquiries, contact: Informa Healthcare, Kentucky Distribution Center, 7625 Empire Dr., Florence, KY 41041. E-mail: orders@taylorandfrancis.com www.informahealthcare.com Library of Congress Cataloging-in-Publication Data Neurology board review : an illustrated study guide / editors, Nima Mowzoon, Kelly D. Flemming. p. ; cm. Includes bibliographical references and index. ISBN-13: 978-0-8493-3791-8 (sb : alk. paper) ISBN-10: 0-8493-3791-7 (sb : alk. paper) 1. Neurology--Examinations, questions, etc. I. Mowzoon, Nima. II. Flemming, Kelly D. [DNLM: 1. Nervous System Diseases--Examination Questions. 2. Neurology--Examination Questions. WL 18.2 N494 2007] RC356.N4487 2007 616.8 0076--dc 22 2007005126 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from appli- cation of the information in this book and make no warranty, express or implied, with respect to the contents of the publi- cation. This book should not be relied on apart from the advice of a qualified health care provider. The authors, editors, and publisher have exerted efforts to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the read- er is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug. Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care providers to ascertain the FDA status of each drug or device planned for use in their clinical practice. Printed in Canada 10 9 8 7 6 5 4 3 2 1
  4. 4. To my wife, Bita, whose everlasting love and support have made everything possible. N. Mowzoon To Michael and Julia. K. Flemming and To the wonderful residents, fellows, and staff of Mayo Clinic Department of Neurology. v
  5. 5. vii PREFACE “To study the phenomenon of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.” Sir William Osler he elegance and complexity of the human nervous system continues to motivate many scholars and physicians in the fascinating field of neurology. The great many technological and research advances in this discipline have contributed to the ever-expanding volumes of textbooks often used as sources of reference by neurologists. Those studying for the American Board of Psychiatry and Neurology certification examination find it difficult to refer to many different sources for a complete review of the important topics and have been unable to be selective about the review material to be studied. We now introduce Neurology Board Review: An Illustrated Study Guide. This book provides a comprehensive review of neurology and includes principles of basic neuroscience, neuroanatomy, neurophysiology, neuropathology, neuroradiol- ogy, molecular biology and genetics of the neurologic systems and syndromes, and a detailed and thorough review of different neurologic disorders in a succinct outline format. The purpose of this book is to provide a comprehensive review guide for those who wish to read a substantial amount of information in an efficient and timely manner. With more than 500 figures of pathology, neuroimaging, EEG tracings, EMG waveforms and nerve conductions, and illustrations of neu- roanatomic pathways, this book is the first illustrated neurology board review book. This review book is intended primarily for candidates seeking certification and recertification in neurology. Although it best serves the written portion of the neurology board examination and the Resident In-Service Training Examination of the American Academy of Neurology, the book can also be used as an easy reference and study guide throughout residency and fellowship. Nima Mowzoon, M.D. Kelly D. Flemming, M.D. T
  6. 6. ix ACKNOWLEDGMENTS The editors would like to thank the following individuals for their assistance and contributions to this project: A. G. Engel, C. M. Harper, D. L. Renaud, G. A. Suarez, B. A. Crum, S. Kotagal, B. R. Younge, Y. E. Geda, K. A. Josephs, S. A. Cross, D. Selcen, C. J. Klein, W. N. Folger, S. Vernino, R. J. Spinner, P. J. Dyck, Jr., M. Tippmann- Peikert, O. H. Kantarci, G. R. Ghearing, M. L. Dodd, W. D. Freeman, M. L. Bell, J. A. Tracy, L. M. Lehwald, T. J. Young, D. H. Kilfoyle, L. K. Jones, S. C. Ahn, H. R.. Murali, G. A. Jicha, J. H. Uhm, and J. L. Corfits. Special thanks to the Mayo Clinic Section of Scientific Publications, including Dr. O. Eugene Millhouse, editor, Roberta Schwartz, production editor, Virginia A. Dunt, editorial assistant, and Kenna L. Atherton, proof- reader, to Media Support Services, including Karen E. Barrie, art director, James J. Tidwell, Paul W. Honermann, and Lynn Black, scientific illustrators, John V. Hagen and Carl G. Clingman, medical illustrators, JoLee J. Gruber, client service specialist, and James R. Hopfenspirger, medical photographer, and to Dr. Patrick H. Luetmer, Department of Radiology, and others who worked “behind the curtains,” without whom this seemingly endless project would not have been possible.
  7. 7. xi CONTRIBUTORS Sung C. Ahn, D.O. Fellow in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota Michael L. Bell, M.D. Fellow in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota Maryellen L. Dodd, M.D. Senior Associate Consultant, Division of Inpatient Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota Kelly D. Flemming, M.D. Consultant, Department of Neurology, Mayo Clinic; Assistant Professor of Neurology, Mayo Clinic College of Medicine; Rochester, Minnesota William D. Freeman, M.D. Senior Associate Consultant, Department of Neurology, Mayo Clinic, Jacksonville, Florida Yonas E. Geda, M.D. Consultant, Department of Psychiatry and Psychology, Mayo Clinic; Assistant Professor of Psychiatry, Mayo Clinic College of Medicine; Rochester, Minnesota Gena R. Ghearing, M.D. Fellow in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota Lyell K. Jones, M.D. Fellow in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota Orhun H. Kantarci, M.D. Senior Associate Consultant, Department of Neurology, Mayo Clinic; Assistant Professor of Neurology, Mayo Clinic College of Medicine; Rochester, Minnesota Dean H. Kilfoyle, M.B., Ch.B. Fellow in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota Lenora M. Lehwald, M.D. Fellow in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota Nima Mowzoon, M.D. Former Fellow in Neurology, Mayo Clinic, Rochester, Minnesota; presently in Private Practice, Albany, New York Hema R. Murali, M.B.B.S. Fellow in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota Deborah L. Renaud, M.D. Consultant, Division of Child and Adolescent Neurology, Mayo Clinic; Assistant Professor of Neurology and of Pediatrics, Mayo Clinic College of Medicine; Rochester, Minnesota Maja Tippmann-Peikert, M.D. Senior Associate Consultant, Department of Neurology, Mayo Clinic; Instructor in Neurology, Mayo Clinic College of Medicine; Rochester, Minnesota Jennifer A. Tracy, M.D. Resident in Neurology, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota Steven Vernino, M.D., Ph.D. Consultant, Department of Neurology, Mayo Clinic; Associate Professor of Neurology, Mayo Clinic College of Medicine; Rochester, Minnesota. Present address: Associate Professor of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas Timothy J. Young, M.D. Fellow in Sleep Medicine, Mayo School of Graduate Medical Education, Mayo Clinic College of Medicine, Rochester, Minnesota
  8. 8. xiii TABLE OF CONTENTS 1. Embryology and Developmental Disorders of the Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Nima Mowzoon, M.D. 2. Basic Principles of Neuroscience and Neurogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25 Orhun H. Kantarci, M.D., Gena R. Ghearing, M.D. 3. Neuro-ophthalmology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .83 William D. Freeman, M.D., Nima Mowzoon, M.D. 4. Disorders of the Cranial Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .127 Kelly D. Flemming, M.D. 5. Clinical Neurophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .163 Part A: Electroencephalogram (EEG) Gena R. Ghearing, M.D. Part B: Principles of Nerve Conduction Studies and Electromyography (EMG) Nima Mowzoon, M.D. 6. Basic Principles of Psychiatry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .225 Maryellen L. Dodd, M.D., Yonas E. Geda, M.D. 7. Behavioral Neurology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .279 Part A: Neurobiology of Cognitive Function Nima Mowzoon, M.D. Part B: Syndromes of Cognitive Dysfunction Nima Mowzoon, M.D. 8. Movement Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .333 Nima Mowzoon, M.D. 9. The Cerebellum and Cerebellar Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .377 Nima Mowzoon, M.D. 10. Principles of Critical Care Neurology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .401 Kelly D. Flemming, M.D. 11. Cerebrovascular Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .435 Kelly D. Flemming, M.D. 12. Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .485 Michael L. Bell, M.D. 13. Neurocutaneous Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .527 Lenora M. Lehwald, M.D., Kelly D. Flemming, M.D.
  9. 9. xiv 14. Inflammatory and Demyelinating Disorders of the Central Nervous System . . . . . . . . . . . . . . . . . .559 Orhun H. Kantarci, M.D. 15. Neurology of Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .589 Jennifer A. Tracy, M.D., Nima Mowzoon, M.D. 16. Neoplasms of the Nervous System and Related Topics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .627 Nima Mowzoon, M.D., Steven Vernino, M.D., Ph.D. 17. Toxic and Metabolic Disorders of the Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .679 Nima Mowzoon, M.D. 18. Headache . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .693 Kelly D. Flemming, M.D. 19. Neurology of Sleep Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .719 Timothy J. Young, M.D., Maja Tippmann-Peikert, M.D. 20. Disorders of the Spinal Cord and Anterior Horn Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .753 Nima Mowzoon, M.D. 21. Disorders of the Peripheral Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .777 Part A: Anatomy of the Peripheral Nervous System and Classification of Disorders by Localization Dean H. Kilfoyle, M.B., Ch.B., Lyell K. Jones, M.D., Nima Mowzoon, M.D. Part B: Specific Inherited and Acquired Disorders of the Peripheral Nervous System Dean H. Kilfoyle, M.B., Ch.B., Lyell K. Jones, M.D., Nima Mowzoon, M.D. 22. Disorders of the Autonomic Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .847 Nima Mowzoon, M.D. 23. Disorders of Neuromuscular Transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .867 Sung C. Ahn, D.O., Nima Mowzoon, M.D. 24. Disorders of Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .885 Nima Mowzoon, M.D. 25. Inborn Errors of Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .933 Hema R. Murali, M.B.B.S., Deborah L. Renaud, M.D. Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .981
  10. 10. xv HOW TO USE THIS BOOK his book is best suited for the written portion of the neurology board certification and recertification examinations administered by the American Board of Psychiatry and Neurology and the in-service examinations administered by the AmericanAcademyofNeurology. Thelonglistsoftopicscoveredintheseexaminationsseemendless. Readingvoluminous textbooks in an attempt to thoroughly review is often impossible, and many important topics are often missed by simply reviewing “high-yield” topics in undersized review texts. We now introduce a comprehensive source that provides detailed information in a succinct outline format. The guidelines sugggested below should be read before using the review text. Before the Preparation: 8 to 12 Months Before the Examination Our recommendation is to begin using this book as a reference guide at least 8 to 12 months in advance, making notes in the margins and referring to other sources. The text then becomes familiar and may be reviewed more easily in a short time before the examination. Tables, charts, anatomic drawings, index cards, and other such visual guides are often help- ful in remembering complex topics. Candidates are encouraged to review these pictorial guides in the text and to prepare their own during the year before the examination. This text should not replace references to other standard textbooks and journals. Initial Preparation: 4 Months Before the Examination Formal preparation needs to be initiated at this time. Each day, 1 to 3 hours should be allocated to formal study. This can be modified depending on many factors, including how quickly a candidate can study, the candidate’s schedule, the level of training and experience, and the examination itself. Part I of the neurology boards and the recertification exami- nations are designed for the general neurologist; however, there are often many questions on the written neurology board and in-service examinations that require detailed subspecialty knowledge. It is often the special attention to detail that separates those who excel in these examinations from those who simply “pass” the test. This text provides detailed infor- mation in each topic that can only be fully learned if the formal reviews are initiated several months in advance. Likewise, it is important for adult neurologists to allocate adequate time to cover pediatric neurology and psychiatry during this time because a thorough review of these topics is essential for part I of the neurology board examination. The topics important for pediatric neurology are found throughout the book, and psychiatry is discussed in a dedicated chapter. Core Preparation: 1 to 8 Weeks Before the Examination By this time, candidates should have studied most of the text and any other source that may be deemed useful. At this stage, candidates should review the chapters again, with emphasis on topics of weakness, answer questions at the end of each chapter, and refer to the text with each answer. In addition, question-and-answer books may be used, and reference should be made to the text. This facilitates “active learning,” which is more effective than passively reading the text. Readers may also find the outline format more helpful for “active learning” than passively reading long paragraphs in most standard text- books. Last-Minute Reviews Reviewing the “high-yield” boxes provided with each chapter, together with previously learned memory aids (tables, charts, index cards, etc.), will be helpful for “last-minute reviews.” The candidates should emphasize the topics of relative weakness throughout the core preparation and review these again during the week before the examination. Finally, it is important to realize that one cannot (and is not expected to) know all of neurology. N. Mowzoon K. Flemming T
  11. 11. I. NEURULATION: FORMATION OF THE NEURAL TUBE A. Gastrulation 1. Primitive streak (Fig. 1-1) a. Formed from ectoderm b. Gives rise to the mesoderm, which is formed between the endoderm and ectoderm c. Hensen’s node is at the end of the primitive streak 2. Notochord a. Mesodermal cells that induce the formation of the neural plate beginning at Hensen’s node b. Gives rise to part of the vertebral column B. Dorsal Induction 1. Transformation of neural ectoderm to neural tissue and formation of the neural plate and neural tube 2. Induction results from inactivation of bone morpho- genetic proteins (BMPs), which normally act to change ectoderm to epidermis. 3. Hensen’s node secretes factors, including chordin, nog- gin, and follisatin that inactivate BMPs and allow for- mation of the neural plate 4. Neural plate 1 EMBRYOLOGY AND DEVELOPMENTAL DISORDERS OF THE NERVOUS SYSTEM Nima Mowzoon, M.D. 1 a. First recognized in the middle of the third week after conception b. The first neural tissue formed from ectoderm under the influence of the underlying notochord 5. The ectoderm that transforms into the neural plate becomes columnar epithelium 6. The rest of the ectoderm becomes the skin and neural crest cells 7. Neural plate forms the neural tube (neurulation) (Fig. 1-1) a. Step 1: invagination along the midline axis b. Step 2: formation of the neural groove by the prolifera- tion and migration of the surface ectodermal neural plate (cells at lateral edges proliferate more rapidly than those at the center) c. Step 3: formation and elevation of the neural folds, which approach each other and fuse d. This process is driven partly by proliferation of the underlying mesodermal tissue and the accumulation of contractile cytoskeletal filaments in the apical poles of the neural folds e. Step 4: neural folds fuse by day 24 1) Fusion begins at the mid-cervical level and proceeds both caudally and cranially until the entire tube is closed 2) The initially unfused areas are termed “neuropores” 3) The anterior neuropore closes between days 24 and 26; the posterior neuropore between days 25 and 28 8. Folic acid is potentially important in neural tube closure 9. Primary neurulation: the formation of neural tube giv- ing rise to brain and spinal cord through the future S2 level 10. Secondary neurulation: the formation of lower sacral and coccygeal segments, giving rise to the future conus medullaris and filum terminale 11. Closure of the neural tube occurs by end of the fourth week of gestation Induction Transformation of ectoderm into neural tissue Formation of the neural plate Results from the inactivation of bone morphogenet- ic proteins, which normally act to change ectoderm into epidermis Results in formation of the neural tube
  12. 12. Hensen’s node Primitive streak Cloacal membrane Neural plate Oropharyngeal membrane Notochord Notochord Ectoderm Ectoderm Neural fold Neural Plate Neural groove Neural tube Endoderm Endoderm BMPs, Wnt SHH Mesoderm Paraxial mesoderm Somite Surface ectoderm Endoderm Notochord SomiteSomiteSomite Neural tube Surface ectoderm Endoderm Notochord Notochord Roof plate Floor plate 2 Chapter 1 Embryology and Developmental Disorders of the Nervous System Fig. 1-1. Development of the neural tube. Note the signals responsible for the anteroposterior patterning. BMPs and Wnt proteins are important for dorsal patterning and are expressed by dorsal neural tube. Shh is an impor- tant ventralizing signal produced by the floor plate and notochord. Shh, Sonic hedgehog; BMP, bone morpho- genetic protein. A B C D
  13. 13. Chapter 1 Embryology and Developmental Disorders of the Nervous System 3 2) Ventral patterning a) Primary ventralizing signal involved: Sonic hedge- hog (Shh) b) Important for determination of basal plate and development of ventral telencephalon and dien- cephalon, as well as ventral brainstem and spinal cord c) Signals are derived from notochord and floor plate D. Disorders of Neurulation (neural tube defects) and Related Conditions 1. Multifactorial disorders 2. Risk factors: family history, maternal risk factors (obe- sity, diabetes mellitus, hyperthermia, use of anticonvul- sants, folate deficiency) a. Risk of spina bifida cystica in mothers taking valproate is 1% to 2 % b. Risk of spina bifida cystica in mothers taking carba- mazepine is 0.5% to 1% 3. Detected by increased levels of α-fetoprotein (AFP) in maternal serum 4. If serum AFP is increased, ultrasonography is per- formed and amniotic fluid checked for AFP 5. Types of neural tube defects a. Craniorachischisis: congenital malformations of central nervous system due to defective neural tube closure C. Differentiation of the Neural Tube 1. Longitudinal differentiation: formation of forebrain, midbrain, and hindbrain and branchial arches and pla- codes (Fig. 1-2) a. With closure of neuropores, the neural tube is divided into three vesicles: forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon) (Fig. 1-2) b. Prosencephalon forms telencephalon (cerebral hemi- spheres) and diencephalon 1) Within the telencephalon, the dorsal zone gives rise to cerebral cortex and the ventral zone (ventral ganglion- ic eminence) produces basal ganglia 2) The diencephalon becomes thalamus, hypothalamus, optic nerves, and pineal gland c. The mesencephalon forms the midbrain d. The rhombencephalon forms the metencephalon (pons and granule cells of cerebellum) and myelencephalon (medulla) 1) Anteroposterior patterning of the hindbrain involves generation of segments of embryonic hindbrain called rhombomeres 2) Homeobox (Hox) genes are responsible for antero- posterior patterning of hindbrain 3) Arrangement of Hox gene on the chromosome corre- lates with and dictates the expression along the antero- posterior axis 4) Activation of correct Hox gene and segmental expres- sion require retinoic acid 2. Transverse differentiation of neural tube a. Proliferating neuroblasts accumulate in the lateral walls of neural tube, forming dorsolaterally situated alar plates and ventrolaterally situated basal plates, which are sepa- rated by sulcus limitans b. The middorsal and midventral portions of neural tube contain few proliferating neuroblasts and are termed roof plate and floor plate, respectively 1) Alar plates give rise to afferent sensory structures in the brainstem and spinal cord, including dorsal horns 2) Basal plates give rise to efferent motor structures in the brainstem and spinal cord, including anterior horns c. Signals involved in dorsoventral patterning 1) Dorsal patterning a) Primary dorsalizing signals involved: BMP and Wnt b) Important for determination of alar plate and development of dorsal telencephalon and cerebel- lum, as well as dorsal brainstem and spinal cord c) Signals are derived from dorsal ectoderm, paraxial mesoderm, and roof plate Segmentation and Patterning Rostrocaudal: dependent on TGF-β family proteins Homeotic genes necessary for hindbrain pat- terning, depend on retinoic acid Dorsoventral patterning Ventral patterning (secreted from floor plate and notochord): Sonic hedgehog protein Dorsal patterning (secreted from roof plate, dorsal ectoderm, and paraxial mesoderm): bone morphogenetic and Wnt proteins Disorders of Neurulation Detected by increased levels of α-fetoprotein in the maternal serum Risk factors include family history and maternal risk factors, especially folate deficiency and use of anti- convulsants during pregnancy, particularly valproate and carbamazepine
  14. 14. 4 Chapter 1 Embryology and Developmental Disorders of the Nervous System during first trimester of pregnancy (usually between days 18 and 29 of gestation), producing continguous expo- sure of brain and spinal column b. Anencephaly (absence of a major portion of the brain, skull, and scalp) 1) Due to failure of anterior neuropore closure 2) Defective notochord induction of the neuroectoderm 3) More common in females 4) Occasionally familial; certain populations may be at higher risk (France, Wales, Ireland) 5) Replacement of most of the intracranial contents by area cerebrovasculosa (vascular mass of small blood vessels admixed with variable amounts of mature and immature neuronal and glial cells) Fig. 1-2. Longitudinal differentiation of the neural tube. 11 22 33 Prosencephalon Cephalic flexure Isthmus Cervical flexure 1 2 3 Mesencephalon Rhombencephalon Telencephalon Lateral ventricle 3rd ventricle 4th ventricle Central canal Cerebral aqueduct Mesencephalon Metencephalon Myelencephalon Myelencephalon Pontine flexure 1a1a1a 1b1b1b 222 3a3a3a 3b3b3b Diencephalon 3a3a3a 3b3b3b 222 111 333 222 111 A A B B
  15. 15. Chapter 1 Embryology and Developmental Disorders of the Nervous System 5 c. Meningomyelocele (spina bifida cystica) 1) Herniation of spinal cord and meninges through a vertebral defect (Fig. 1-3 and 1-4) 2) Is often seen in Chiari type II malformation and is associated with hydrocephalus d. Spina bifida occulta 1) A defect in one or more vertebral arches 2) Spinal cord and meninges are normal e. Cranium bifidum 1) Defective fusion of cranial bones 2) Most common in the occipital portion of the cranium 3) Associated with herniated cerebral tissue and meninges (Fig. 1-5) f. Encephalocele 1) Extension of intracranial structures through the cra- nial vault from a defect in fusion of cranial bones a) Meningocele: herniated meninges through skull defect b) Meningoencephalocele: herniated brain tissue and meninges through skull defect c) Meningohydrocephalocele: herniated brain tissue, meninges, and ventricles through skull defect 2) Most common in the occipital (less common in the parietal) area a) Herniated tissue is usually arranged haphazardly and hamartomatous b) Both intracranial and herniated contents may show signs of migration abnormalities such as heterotopias (see below) c) Occipital encephalocele often contains vascular structures and is associated with Meckel-Gruber syndrome (autosomal recessive condition associated with occipital encephalocele, polycystic kidneys, liver fibrosis, cleft palate, and polydactyly; is usually fatal) 6. Chiari malformations (cerebellar deformities) a. Chiari type I malformation (Fig. 1-6) 1) Primary cerebellar ectopia: caudal displacement of cerebellar tonsils through the foramen magnum 2) May be congenital or acquired condition caused by downward herniation of the brain in patients with low intracranial pressure 3) Mean age at presentation: 41 years 4) Upper limits of normal for the position of the cerebel- lar tonsils below the foramen magnum depends on age: a) 6 mm for first decade b) 5 mm for second and third decades c) 4 mm for fourth to eighth decades d) 3 mm for ninth decade 5) Chiari type I malformation may be associated with a) Hydrocephalus b) Intermittent increase in intracranial pressure c) Syringomyelia, syringobulbia Fig. 1-3. Myelomeningocele (spina bifida cystica) is herniation of the spinal cord and meninges through a congenital defect in the vertebral arch. It is covered with skin. Chiari Malformations Chiari type I malformation: caudal displacement of cerebellar tonsils through the foramen magnum Chiari type II malformation: caudal displacement of cerebellar tonsils, cervicomedullary junction, pons, fourth ventricle, medulla Chairi type II malformation associated with Myelomeningocele Hydrocephalus Colpocephaly of the lateral ventricles Elongated fourth ventricle Interdigitating gyri (associated with hypoplastic falx cerebri) Skull abnormalities: lacunar skull, hypoplastic tentorium cerebelli, gaping foramen magnum Chiari type III malformation: low occipital/high cervical encephalocele with herniation of the cere- bellum, occipital lobes, pons, medulla Chiari type IV malformation Likely a variant of Dandy-Walker malformation Hypoplastic brainstem and cerebellum
  16. 16. 6 Chapter 1 Embryology and Developmental Disorders of the Nervous System d) Klippel-Feil syndrome, basilar impression, and occipitalization of the atlas e) Compression of brainstem structures and some rostral extension of the medulla 6) Presenting symptoms are due to any of the above asso- ciated abnormalities plus a) Headaches, especially brought on by neck exten- sion or the Valsalva maneuver (most common pre- senting symptom), sometimes associated with tinnitus, nausea, and vomiting b) Various cerebellar symptoms, lower cranial nerve dysfunction, diplopia and downbeat nystagmus, dissociated sensory loss (loss of pinprick and tem- perature sensation and relative preservation of large fiber modalities), and possibly pyramidal tract involvement c) May be asymptomatic 7) Surgical treatment: early surgery for symptomatic patients and observation for asympto