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  • 1. DIAGNOSTIC IMAGING BRAIN
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  • 3. DIAGNOSTIC IMAGING BRAIN Anne G. Osborn, MD, FACR Gary L. Hedlund, DO Distinguished Professor of Radiology William H. and Patricia W. Child Presidential Endowed chair in radiology University of Utah School of Medicine Clinical Associate Professor of Radiology University of Utah Pediatric Neuroradiologist Department of Medical Imaging Primary Children's Medical Center Amersham Visiting Professor in Diagnostic Imaging Armed Forces Institute of Pathology Anna Illner, MD Susan I. Blaser, MD, FRCPC Assistant Professor of Radiology Division of Pediatric Neuroradiology Riley Children's Hospital Indiana University School of Medicine Staff Neuroradiologist Hospital for Sick Children Associate Professor of Diagnostic Imaging University of Toronto, Canada H. Ric Harnsberger, MD Karen L. Salzman, MD Professor of Radiology R.C. Willey Chair in Neuroradiology University of Utah School of Medicine Assistant Professor of Radiology Division of Neuroradiology University of Utah School of Medicine james A. Cooper, MD Gregory L. Katzman, MD Diagnostic Radiology and Neuroradiolgy Radiology Medical Group, Inc Associate Professor, Radiology and Medical Informatics Chief, Radiology Clinical Research University of Utah School of Medicine james Provenzale, MD Professor of Radiology Chief, Neuroradiology Department of Radiology Duke University Medical Center Blaise V. jones, MD Associate Professor, Radiology & Pediatrics Director, Division of Neuroradiology Department of Radiology Cincinnati Children's Hospital Medical Center Bronwyn E. Hamilton, MD Mauricio Castillo, MD, FACR Assistant Professor of Radiology Oregon Health & Science University Professor of Radiology Chief of Neuroradiology University of North Carolina School of Medicine AMI RSYS® A medical reference publishing company 111
  • 4. AMIRSYS® A medical reference publishing company First Edition Text - Copyright Anne G Osborn MD 2004 Drawings - Copyright Amirsys Inc 2004 Compilation - Copyright Amirsys Inc 2004 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or media or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from Amirsys Ine. Composition by Amirsys Inc, Salt Lake City, Utah Printed by Friesens, Altona, Manitoba, Canada ISBN: 0-7216-2905-9 Notice and Disclaimer The information In this product C'Product is provided as a reference for use by licensed medical professionals and no others. It does not and should not be construed as any form of medical diagnosis or professional medical advice on any matter. Receipt Of use of this Product, in whole or in part, does not constitute or create a doctor-patient, therapist-patient, or other healthcare professional relationship between Amirsys Ioe. C'Amirsysll) and any recipient. This Product may not reflect the most current medical developments, and Amirsys makes no claims, promises, or guarantees about accuracy, completeness, or adequacy of the information contained in or linked to the Product. The Product is not a substitute for or replacement of professional medical judgment. Amirsys and its affiliates, authors, contributors! partners, and sponsors disclaim all liability or responsibility for any injury and/or damage to persons or property in respect to actions taken or not taken based on any and all Product information. ll ) In the cases where drugs or other chemicals arc prescribed! readers are advised to check the Product information currently provided by the manufacturer of each drug to be administered to verify the recommended dose! the method and duration of administration, and contraindications. It is the responsibility of the treating physician relying on experience and knowledge of the patient to determine dosages and the best treatment for the patient. To the maximum extent permitted by applicable law, Amirsys provides the Product AS is AND WITH ALL FAULTS,AND HEREBY DISCLAiMS ALL WARRANTIES AND CONDITIONS, WHETHER EXPRESS. IMPLIED OR STATUTORY,INCLUDING BUT NOT LIMITED TO, ANY (IF ANY) IMPLIED WARRANTIES OR CONDITIONS OF MERCHANTABILITY. OF FiTNESS FOR A PARTICULAR PURPOSE, OF LACK OF VIRUSES, OR ACCURACY OR COMPLETENESS OF RESPONSES, OR RESULTS,AND OF LACK OF NEGLIGENCE OR LACK OF WORKMANLIKE EFFORT. ALSO, THERE IS NO WARRANTY OR CONDITION OF TITLE, QUIET ENJOYMENT~QUIET POSSESSION. CORRESPONDENCE TO DESCRIPTION OR NON-INFRINGEMENT, WITH REGARD TO THE PRODUCT. THE ENTIRE RISK AS TO THE QUALITY OF OR ARISING OUT OF USE OR PERFORMANCE OF THE PRODUCT REMAINS WITH THE READER. Arnirsys disclaims all warranties of any kind if the Product was customized, repackaged or altered in any way by any third party. Library of Congress Cataloging-in-Publication Data Diagnostic imaging. Brain / Anne 0. Osborn ... let al.]. p. ;cm. Includes bibliographical references and index. ISBN 0-7216-2905-9 l. Brain--Imaging--Handbooks, manuals, etc. r. Title: Brain. II. Osborn, Anne G., 1943[DNLM: l. Brainnradiography. 2. Central Nervous System Diseases--diagnosis. 3. Diagnosis, Differential. 4. Neuroradiography--methods. WL 141 053472004] RC386.6.D52D53 2004 616.8'04757ndc22 2004047735 tv
  • 5. To my beloved husband and eternal sweetheart Ron Now and forever together. Thanks for your unfailing patience, support and humor. You make me laugh every day. v
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  • 7. DIAGNOSTIC IMAGING: BRAIN The neuroimaging, neurology, neurosurgery, neuropathology communities have been waiting a long time for a new "Osborn". We at Amirsys and Elsevier are proud to present a precedent-setting, image- and graphics-packed series that debuts with a brand-new work by Anne G. Osborn and colleagues. This splendid work represents the textbook of the twenty-first century: Not your old-fashioned, dense prose exposition with comparatively few images. The unique bulleted format of the Diagnostic Imaging books allows our authors to present approximately twice the information and four times the images per diagnosis, compared to the old-fashioned traditional prose textbook. These richly illustrated books will cover all major body areas and follow a similar format. The same information is in the same place: Every time! A welcome innovation is the new visual differential diagnosis "thumbnail" that provides at-a-glance looks at entities that can mimic the diagnosis in question. "Key Pacts" boxes provide a succinct summary for quick, easy review. In short, this is a product designed with you, the reader, in mind. Today's typical practice settings demand efficiency in both image interpretation and learning. We think you'll find the Diagnostic Imaging format a highly efficient and wonderfully rich resource. Enjoy! H. Ric Harnsberger, MD Chairman and CEO, Amirsys Inc Vll
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  • 9. ~.: IL-- F_O_R_E_W_O_R_D _ It looks like Anne Osborn has done it again! After several years of taking the pulse of the medical community, lecturing far and wide, and hearing the "pros" and "cons" of her earlier books (mostly "pros") she has decided to abandon the usual conventions of medical textbooks. In this volume, she and her co-authors (a cadre of neuroradiological household names), and Dr. James Cooper, a medical illustrator in the tradition of Frank Netter, deliver diagnostic neuroradiology in its most concise and user-friendly format to date. Building on the experience and success of the series of "Top 100 Diagnoses", this is now the one volume that makes the radiologist conversant with his or her clinical constituency, not only in arriving at a diagnosis, but in discussing the pathology, anatomy, clinical manifestations, and treatment rationales. As radiology has become the cornerstone of medical diagnosis, the radiologist is often the first physician with whom a patient interacts. This book assumes that there are many instances in which the radiologist is thrust into the role of primary physician, and it provides a concise package of facts about a given disease or radiological sign that can be quickly and easily accessed and included in a written report or a discussion, adding value for the patient and referring physician. It would be difficult to find a wasted word in this book. The authors have studied the economics of verbiage and concluded that 50% of the words in a standard medical textbook could be eliminated and it would still deliver the same bolus of information to today's physicians, most of whom have been weaned on reading e-mail. As a result, hordes of words have been reduced to a small arsenal of bullets and bulleted statements. This conservation of linguistic space allows profuse inclusion of illustrations. The quality of photographs is superb and there is ample use of color for the pathologic and anatomic photos, many of which are positioned adjacent to Dr. Cooper's near in-vivo drawings. Illustrations of major anatomy, pathology, and radiological findings are uniformly 6x6 cm (a size which most readers are accustomed to seeing on a PACSstation) and the illustrations of differential diagnoses, being of less importance, are 3x3 cm. Figures are well spaced and are not cluttered with overuse of arrows and other notation. Diagnostic Imaging: Brain, in a single volume, is the "internet" of neuroradiology and diseases of the central nervous system: complete, accessible, concise, and up to date. The only thing that seems to be missing is a chain and lock to keep it from being stolen from the table next to the PACSstation. Perhaps that will be an option with the next edition. Michael S. Huckman, MD Professor of Radiology Rush Medical College Director of Neuroradiology Rush University Medical Center IX
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  • 11. PREFACE Just about every place I go, I'm asked, "Are you writing a second edition of The Red Book (Diagnostic Neuroradiology)?" The answer has been-and remains-an emphatic "No!" Now you know why. The proverbial cat is out of the bag, and you literally see it in front of your eyes: An exciting, brand-new approach to teaching textbooks in diagnostic radiology. Ric Harnsberger and I had a vision when we started Amirsys. We wanted to found an author-centric company that would be both market-facing and database-driven, specializing in highly innovative yet simple ways of presenting complex content. The changes we've all experienced in our practice patterns over the last decade necessitate-even dictate-new approaches. We've become victims of our own success: We are getting better and better at imaging more and more stuff. This translates into an ever-increasing case load. Time is a luxury most of us don't have. We need our information in easily accessible format. The closer to the "point-of-care" the better! We began with the highly successful PocketRadiologist® concept. The available PRs-iS in all-now cover all parts of the body and are available in both print and PDA. The Diagnostic Imaging series has just started with David Stoller's spectacular book on Orthopaedics (he likes the British-style spelling!). We love the graphics and high information density that is the result of using bulleted text (rather than traditional prose). You don't have time to read extra words that don't carry essential information-so we don't write them! We added Key Facts boxes to each diagnosis for quick review and have chosen selected references for your further delectation and delight. You will note that there are many 2004 references included-the references were updated to include key articles published within a month of the book going to press. For example when the March 2004 issue of A]NR appeared with an important new (to neuroradiologists) entity-Susac syndrome-on the cover, we were able to include it both in the text and the references. Diagnostic Imaging: Brain is divided into two parts: The first part organizes diagnoses according to general pathology category (congenital malformations, trauma, neoplasms, etc). The second, shorter part is organized according to anatomy. Here we present diagnoses for which location is key to the diagnosis. Where appropriate, we have included some special introductory overviews of general anatomy or embryology and pathology to assist the reader in thinking about the diagnoses that follow. Finally, we couldn't have produced such a monumental book in less than a year without the stellar author team listed on the book cover. As Michael Huckman noted in his Forward, many are literally household names in neuroradiology-and the others are all promising new young academics. The templated approach we took and the use of bulleted information eliminates nearly all the stylistic differences that have plagued multi-author textbooks in the past. Without looking at the Table of Contents, you probably can't tell who wrote what. We feel the sacrifice of individual creativity for the sake of uniformity is a plus. So sit down, fasten your seat belt, and dig in. Have fun reading-and know that we had fun putting this project together. Enjoy! Anne G. Osborn, MD, FACR Distinguished Professor of Radiology William H. and Patricia W. Child Presidential Endowed Chair in Radiology University of Utah School of Medicine Amersham Visiting Professor in Diagnostic Imaging Armed Forces Institute of Pathology Washington, D.C. Xl
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  • 13. ACKNOWLEDGMENTS Illustrations James A. Cooper, MD Art Direction and Design Lane R. Bennion, MS Richard Coombs, MS Image/Text Editing Angie D. Mascarenaz Cassie L. Dearth Kaerli Main Medical Text Editing Gregory L. Katzman, MD Karen L. Salzman, MD Richard H. Wiggins III, MD Andre Macdonald, MD Mingqian Huang, MD A. Roxana Gafton, MD Case Management David Harnsberger Roth LaFleur Production Lead Melissa A. Morris Xlll
  • 14. XIV
  • 15. SECTIONS PART I Pathology-Based Diagnoses Congenital Malformations [I] Trauma ~ Subarachnoid Hemorrhage and Aneurysms Stroke [!J ffiJ Vascular Malformations ffiJ Neoplasms and Tumorlike lesions Primary Non-Neoplastic [ZJ Cysts Infection and Demyelinating Disease Metabolic/Degenerative Toxic/Metabolic/Degenerative ru [ID Disorders, Inherited Disorders, Acquired [2] [ill PART II Anatomy-Based Diagnoses rn rn Ventricles and Cisterns Sella and Pituitary CPA-lAC [l] Skull, Scalp, and Meninges @] xv
  • 16. TABLE OF CONTENTS Malformations of Cortical Development PART I Pathology-Based Diagnoses 1-1-50 Microcephaly Gary 1. Hedlund, DO Congenital Muscular Dystrophy SECTION 1 Congenital Malformations Introduction Congenital Heterotopic 1-1-62 Pachygyria -Polymicrogyria 1-1-4 Anne G. Osborn, MD, FACR Hindbrain 1-1-58 Gray Matter Susan I. Blaser, MD, FRCP(C) and Overview Malformations 1-1-54 Susan I. Blaser, MD, FRCP(C) Gary 1. Hedlund, DO 1-1-66 Lissencephaly Type 1 Susan I. Blaser, MD, FRCP(C) Herniations, Miscellaneous Malformations 1-1-8 Chiari 1 1-1-70 Schizencephaly Susan I. Blaser, MD, FRCP(C) 1-1-74 Hemimegalencephaly Susan I. Blaser, MD, FRCP(C) Susan I. Blaser, MD, FRCP(C) 1-1-12 Chiari 2 Susan I. Blaser, MD, FRCP(C) 1-1-16 Chiari 3 Mauricio Castillo, MD, FACR Susan I. Blaser, MD, FRCP(C) 1-1-22 Lipoma Anne G. Osborn, MD Neurofibromatosis Type 2 1-1-82 Blaise V. Jones, MD 1-1-86 von Hippel Lindau 1-1-26 1-1-94 Sturge- Weber Syndrome Susan I. Blaser, MD, FRCP(C) 1-1-30 Susan I. Blaser, MD, FRCP(C) Vermian Hypoplasia 1-1-90 Susan I. Blaser, MD, FRCP(C) FRCP(C) Rhombencephalosynapsis 1-1-98 Meningioangiomatosis Mauricio Castillo, MD, FACR 1-1-34 Susan I. Blaser, MD, FRCP(C) 1-1-100 Basal Cell Nevus Syndrome Mauricio Castillo, MD, FACR 1-1-104 Disorders of Diverticulation/Cleavage HHT Holoprosencephaly Encephalocraniocutaneous 1-1-38 Susan I. Blaser, MD, FRCP(C) Holoprosencephaly Variants Septooptic Dysplasia Mauricio Castillo, MD, FACR Anne G. Osborn, MD, FACR Lipomatosis 1-1-108 Anna Illner, MD 1-1-42 Anna Illner, MD XVI 1-1-78 Tuberous Sclerosis Complex Malformations Dandy Walker Spectrum Congenital Type 1 Anne G. Osborn, MD, FACR Hindbrain Susan I. Blaser, MD, Neurofibromatosis Susan I. Blaser, MD, FRCP(C) 1-1-18 Callosal Dysgenesis Familial Tumor/Neurocutaneous Syndromes Cowden Syndrome 1-1-112 Mauricio Castillo, MD, FACR 1-1-46 Neurocutaneous Anna Illner, MD Melanosis 1-1-116
  • 17. Superficial Siderosis 1-3-8 H. Ric Harnsberger, MD Aneurysms Primary Effects of CNS Trauma Saccular Aneurysm 1-3-12 Anne G. Osborn, MD, FACR Missile and Penetrating 1-2-4 Injury 1-2-6 Epidural Hematoma Gregory L. Katzman, Bronwyn E. Hamilton, 1-2-10 Bronwyn E. Hamilton, 1-2-14 Bronwyn E. Hamilton, Blood Blister-like Aneurysm 1-2-20 1-2-22 Hemorrhage Introduction and Overview MD 1-2-26 Cerebral Contusion MD Stroke Anatomy and Imaging Issues 1-2-30 Nontraumatic Intracranial Hemorrhage MD 1-2-34 Subcortical Injury MD 1-2-38 Trauma Susan 1. Blaser, MD, FRCP(C) Intracerebral Hematoma Gregory L. Katzman, Spontaneous Herniation Hypertensive MD MD Castillo, 1-2-54 MD 1-2-56 Dissection MD, FACR Atherosclerosis, 1-4-20 MD Intracranial Atherosclerosis, 1-4-24 MD Extracranial Arteriolosclerosis Bronwyn E. Hamilton, 1-4-28 1-4-32 MD 1-2-58 James Provenza Ie, MD Nonatheromatous Vasculopathy Traumatic Carotid-Cavernous Castillo, 1-4-16 James A. Cooper, MD Traumatic Extracranial Dissection Mauricio Hemorrhage Remote Cerebellar Hemorrhage Bronwyn E. Hamilton, Brain Death Mauricio 1-4-12 Atherosclerosis and Carotid Stenosis 1-2-50 Traumatic Cerebral Ischemia Traumatic Intracranial Hemorrhage 1-2-46 Susan I. Blaser, MD, FRCP(C) Bronwyn E. Hamilton, Intracranial Bronwyn E. Hamilton, Traumatic Cerebral Edema Gregory L. Katzman, Intracranial James A. Cooper, MD 1-2-42 Syndromes 1-4-8 MD James A. Cooper, MD Secondary/Vascular Effects of CNS Trauma Bronwyn E. Hamilton, 1-4-4 Anne G. Osborn, MD, FACR Diffuse Axonal Injury (DAI) Intracranial 1-3-22 MD Traumatic Subarachnoid Gregory L. Katzman, 1-3-20 MD Mixed Subdural Hematoma Nonaccidental Fusiform Aneurysm, Non-ASVD 1-2-16 Chronic Subdural Hematoma Gregory L. Katzman, 1-3-18 Anne G. Osborn, MD, FACR MD Bronwyn E. Hamilton, Fusiform Aneurysm, ASVD Anne G. Osborn, MD, FACR MD Subacute Subdural Hematoma Gregory L. Katzman, 1-3-16 Anne G. Osborn, MD, FACR MD Acute Subdural Hematoma Gregory L. Katzman, Pseudoaneurysm Anne G. Osborn, MD, FACR James A. Cooper, MD 1-2-62 Fistula MD, FACR Persistent Trigeminal Artery Mauricio 1-4-38 Sickle Cell Disease SECTION 3 Subarachnoid Hemorrhage Aneurysms Mauricio and 1-4-36 Castillo, MD, FACR Castillo, MD, FACR 1-4-42 Moyamoya Susan 1. Blaser, MD, FRCP(C) Primary Arteritis of the CNS 1-4-46 James A. Cooper, MD Subarachnoid Aneurysmal Subarachnoid Hemorrhage Hemorrhage Anne G. Osborn, MD, FACR Nonaneurysmal Perimesencephalic Anne G. Osborn, MD, FACR 1-4-50 Vasculitis 1-3-4 James A. Cooper, MD Systemic Lupus Erythematosus SAH 1-3-6 1-4-54 James Provenza Ie, MD Cerebral Amyloid Disease Bronwyn E. Hamilton, 1-4-58 MD XVll
  • 18. 1-4-62 CADASIL James Provenza Ie, MD Astrocytic Tumors-Infiltrating Diffuse Astrocytoma, Low Grade Cerebral Ischemia and Infarction 1-4-66 Hydranencephaly Anna Illner, MD 1-4-68 HIE, Preterm Gary L. Hedlund, DO 1-4-72 HIE, Term Susan I. Blaser, MD, FRCP(C) 1-4-76 Acute Cerebral Ischemia-Infarction MD Bronwyn E. Hamilton, 1-4-80 Subacute Cerebral Infarction 1-6-8 Karen L. Salzman, MD Pediatric Brainstem Glioma 1-6-12 Susan 1. Blaser, MD, FRCP(C) Anaplastic Astrocytoma 1-6-16 Karen L. Salzman, MD Glioblastoma Multiforme 1-6-20 Karen L. Salzman, MD 1-6-24 Gliosarcoma Karen L. Salzman, MD Gliomatosis Cerebri 1-6-26 Karen L. Salzman, MD James A. Cooper, MD 1-4-84 Chronic Cerebral Infarction Astrocytic Tumors-localized James A. Cooper, MD 1-4-88 Lacunar Infarction James A. Cooper, MD 1-4-92 Hypotensive Cerebral Infarction Bronwyn E. Hamilton, MD 1-4-96 Dural Sinus Thrombosis Bronwyn E. Hamilton, MD 1-4-100 Cortical Venous Thrombosis Bronwyn E. Hamilton, MD 1-4-104 Deep Cerebral Venous Thrombosis Bronwyn E. Hamilton, MD Pilocytic Astrocytoma 1-6-30 Blaise V. Jones, MD Pleomorphic Xanthoastrocytoma 1-6-34 Karen L. Salzman, MD Subependymal Giant Cell Astrocytoma 1-6-38 Gary L. Hedlund, DO Oligodendroglial and Miscellaneous Tumors Oligodendroglioma 1-6-42 Karen L. Salzman, MD Anaplastic Oligodendroglioma SECTION 5 Vascular Malformations > i'."··.·"·.··"·"·.'··' ..'.'·.·..·"."·"·'" 1-6-46 Karen L. Salzman, MD . 1-6-50 Astroblastoma Karen L. Salzman, MD CVMs With A-V Shunting Arteriovenous Malformation Ependymal Tumors 1-5-4 Ependymoma Anne G. Osborn, MD, FACR Dural A-V Fistula 1-5-8 Subependymoma Anne G. Osborn, MD, FACR Vein of Galen Malformation 1-5-12 1-6-52 Blaise V. Jones, MD 1-6-56 Karen L. Salzman, MD Anna Illner, MD Choroid Plexus Tumors CVMs Without A-V Shunting Developmental Venous Anomaly Choroid Plexus Papilloma 1-5-16 Choroid Plexus Carcinoma Anne G. Osborn, MD, FACR Sinus Pericranii 1-5-20 1-6-60 Gary L. Hedlund, DO 1-6-64 Gary L. Hedlund, DO Anna Illner, MD Cavernous Malformation 1-5-24 Anne G. Osborn, MD, FACR Capillary Telangiectasia 1-5-28 Anne G. Osborn, MD, FACR Neuronal, Mixed Neuronal-Glial Tumors Ganglioglioma 1-6-66 Karen L. Salzman, MD Dysplastic Cerebellar Gangliocytoma 1-6-70 Blaise V. Jones, MD Desmoplastic Infantile Ganglioglioma Mauricio DNET Introduction and Overview Neoplasms Pathology and Imaging Issues Anne G. Osborn, MD, FACR XV111 1-6-74 Castillo, MD, FACR 1-6-76 Susan 1. Blaser, MD, FRCP(C) 1-6-4 Central Neurocytoma Karen L. Salzman, MD 1-6-80
  • 19. Anne G. Osborn, MD, FACR Pineoblastoma 1-6-84 Anna I/lner, MD 1-7-12 Dermoid Cyst Gregory L. Katzman, MD Pineocytoma 1-6-88 Karen L. Salzman, MD Embryonal and Medulloblastoma Neuroblastic Tumors (PNET-MB) 1-6-92 1-6-96 PNET Atypical Teratoid-Rhabdoid 1-7-20 Neuroglial Cyst Anne G. Osborn, MD, FACR 1-7-22 Enlarged Perivascular Spaces Anne G. Osborn, MD, FACR Gary L. Hedlund, DO 1-7-26 Pineal Cyst Anne G. Osborn, MD, FACR Tumor 1-6-100 Blaise V. Jones, MD Neuroblastoma, 1-7-16 Epidermoid Cyst Gregory L. Katzman, MD Blaise V. Jones, MD Supratentorial 1-7-8 Colloid Cyst Pineal Parenchymal Tumors Metastatic Anne G. Osborn, MD, FACR 1-6-104 Blaise V. Jones, MD Tumors of Cranial/Peripheral Schwannoma 1-7-34 Ependymal Cyst Karen L. Salzman, MD Nerves 1-6-108 Anne G. Osborn, MD, FACR Neurofibroma 1-7-30 Choroid Plexus Cyst Porencephalic 1-7-36 Cyst Anne G. Osborn, MD, FACR Neurenteric 1-7-40 Cyst Anne G. Osborn, MD, FACR 1-6-112 Anne G. Osborn, MD, FACR Blood Vessel and Hemopoietic Tumors Hemangioblastoma 1-6-114 Congenital/Neonatal Anne G. Osborn, MD, FACR Hemangiopericytoma 1-6-118 Karen L. Salzman, MD Primary CNS Lymphoma (Angiocentric) Lymphoma 1-6-122 1-8-4 Congenital HIV 1-8-8 Mauricio Castillo, MD, FACR 1-6-126 Karen L. Salzman, MD Congenital Herpes 1-8-10 Mauricio Castillo, MD, FACR 1-6-128 Leukemia Acquired Infections Blaise V. Jones, MD Group B Streptococcal Meningitis Germ Cell Tumors Gary L. Hedlund, DO Gary L. Hedlund, DO Carcinoma 1-6-138 Syndromes 1-8-20 Meningitis 1-8-24 Abscess 1-8-28 Ventriculitis Karen L. Salzman, MD 1-8-30 Empyema 1-6-140 Karen L. Salzman, MD Herpes Encephalitis Anne G. Osborn, MD, FACR Paraneoplastic 1-8-16 Karen L. Salzman, MD Metastatic Tumors and Remote Effects of Cancer Metastases Meningitis Karen L. Salzman, MD Gary L. Hedlund, DO Parenchymal Citrobacter Gary L. Hedlund, DO 1-6-136 Teratoma 1-8-12 Anna I/lner, MD 1-6-132 Germinoma Embryonal Infections CMV Gary L. Hedlund, DO Karen L. Salzman, MD Intravascular Congenital 1-6-144 Encephalitis Karen L. Salzman, MD 1-8-34 Karen L. Salzman, MD (Miscellaneous) 1-8-38 Karen L. Salzman, MD Rasmussen Encephalitis 1-8-42 Mauricio Castillo, MD, FACR Tuberculosis 1-8-46 Karen L. Salzman, MD Neurocysticercosis Arachnoid Cyst 1-7-4 1-8-50 Karen L. Salzman, MD Anne G. Osborn, MD, FACR XIX
  • 20. 1-8-54 Parasites, Miscellaneous 1-9-46 Urea Cycle Disorders Mauricio Castillo, MD, FACR Karen L. Salzman, MD 1-8-58 Fungal Diseases 1-9-48 Glutaric Aciduria Type 1 Mauricio Castillo, MD, FACR Mauricio Castillo, MD, FACR 1-8-62 Rickettsial Diseases 1-9-52 Canavan Disease Gary L. Hedlund, DO Mauricio Castillo, MD, FACR 1-8-64 Lyme Disease 1-9-54 Alexander Disease Anna Illner, MD Mauricio Castillo, MD, FACR 1-8-66 HIV Encephalitis Miscellaneous James Provenza Ie, MD 1-8-70 Opportunistic Infection, AIDS James Provenza Ie, MD 1-9-58 van der Knaap Leukoencephalopathies Susan I. Blaser, MD, FRCP(C) Demyelinating Anna Illner, MD 1-8-74 Multiple Sclerosis 1-9-62 Hallervorden-Spatz Syndrome Disease 1-9-66 Huntington Disease James Provenza Ie, MD Gregory L. Katzman, MD ADEM 1-8-78 1-9-70 Wilson Disease James Provenzale, MD Gregory L. Katzman, MD Subacute Sclerosing Panencephalitis 1-8-82 Mauricio Castillo, MD, FACR SECTION.10 Toxi.c/MetaboUc/Degenerative SECTION 9 Disorders, Acquired Metabolic/Degenerative Disorders, Inherited Normal/Variant Normal Myelination 1-9-4 Toxic, Metabolic, Nutritional, Systemic Diseases with eNS Manifestations 1-10-4 Hypoglycemia Blaise V. Jones, MD Hypomyelination 1-9-8 Mauricio Castillo, MD, FACR 1-10-6 Kernicterus Blaise V. Jones, MD Mauricio Castillo, MD, FACR Mitochondrial Leigh Syndrome James Provenza Ie, MD 1-9-12 Anna Illner, MD MELAS 1-9-16 Anne G. Osborn, MD, FACR 1-9-20 1-9-24 1-9-28 1-10-28 1-10-32 Idiopathic Intracranial Hypertension 1-10-36 1-10-38 James Provenza Ie, MD 1-9-36 Osmotic Demyelination Syndrome 1-10-42 Anne G. Osborn, MD, FACR 1-9-38 Susan I. Blaser, MD, FRCP(C) Radiation and Chemotherapy 1-10-46 Karen L. Salzman, MD Organic and Aminoacidopathies xx Chronic Hypertensive Encephalopathy CO Poisoning Gary L. Hedlund, DO Susan I. Blaser, MD, FRCP(C) PRES Mauricio Castillo, MD, FACR Peroxisomal Disorders Maple Syrup Urine Disease Acute Hypertensive Encephalopathy, James Provenza Ie, MD 1-9-32 X-Linked Adrenoleukodystrophy 1-10-24 Hepatic Encephalopathy Anne G. Osborn, MD, FACR Gregory L. Katzman, MD Zellweger 1-10-20 James Provenza Ie, MD Gary L. Hedlund, DO Krabbe 1-10-16 Fahr Disease Anne G. Osborn, MD, FACR Anna Illner, MD Metachromatic Leukodystrophy (MLD) James Provenza Ie, MD Alcoholic Encephalopathy Susan I. Blaser, MD, FRCP(C) Gangliosidosis (GM2) 1-10-12 Hypothyroidism James Provenza Ie, MD Lysosomal Disorders Mucopol ysaccharidoses 1-10-8 Drug Abuse Disorders 1-9-42 Mesial Temporal Sclerosis 1-10-50 Karen L. Salzman, MD Status Epilepticus Karen L. Salzman, MD 1-10-54
  • 21. Dementias and Degenerative Disorders 1-10-58 Aging Brain, Normal James Provenza Ie, MD Introduction 1-10-62 Alzheimer Dementia James Provenza Ie, MD Sella, Para sellar Anatomy-Imaging Congenital 1-10-70 Dementia 1-10-74 Disease (C1D) James Provenza Ie, MD 1-10-78 Parkinson Disease Susan I. Blaser, MD, FRCP(C) 11-2-12 Tuber Cinereum Hamartoma Mauricio Castillo, MD, FACR 11-2-16 Rathke Cleft Cyst James Provenza Ie, MD 1-10-82 Multiple System Atrophy Anne G. Osborn, MD, FACR James Provenza Ie, MD Neoplasms 1-10-86 Lateral Sclerosis (ALS) 11-2-20 Pituitary Microadenoma James Provenza Ie, MD 1-10-90 Wallerian Degeneration Anne G. Osborn, MD, FACR 11-2-24 Pituitary Macroadenoma James Provenzale, MD Hypertrophic 11-2-8 Pituitary Stalk Anomalies James Provenza Ie, MD Amyotrophic 11-2-4 1-10-66 James Provenza Ie, MD Creutzfeldt-lakob Issues Anne G. Osborn, MD, FACR Multi-infarct Dementia Frontotemporal and Overview 1-10-94 Olivary Degeneration Anne G. Osborn, MD, FACR 11-2-28 Pituitary Apoplexy James Provenza Ie, MD Anne G. Osborn, MD, FACR 11-2-32 Craniopharyngioma Gary L. Hedlund, DO PART II Anatomy-Based 11-2-36 Pituicytoma Karen L. Salzman, MD Diagnoses Miscellaneous 11-2-38 Pituitary Hyperplasia SECTION 1 Ventricles and Cisterns Karen L. Salzman, Lymphocytic MD 11-2-40 Hypophysitis Anne G. Osborn, MD, FACR Introduction and Overview Ventricles, Cisterns Anatomy-Imaging Issues 11-1-4 SECTION 3 CPA-lAC Anne G. Osborn, MD, FACR Normal Variants 11-1-8 Cavum Septi Pellucidi (CSP) Anne G. Osborn, MD, FACR Cavum Velum Interpositum Introduction and Overview CPA-lAC Anatomy and Imaging Issues (CVI) 11-1-10 11-3-4 H. Ric Harnsberger, MD Anne G. Osborn, MD, FACR Enlarged Subarachnoid Spaces Congenital 11-1-12 Susan I. Blaser, MD, FRCP(C) Lipoma, CPA-lAC 11-3-8 H. Ric Harnsberger, MD Hydrocephalus Obstructive Hydrocephalus Epidermoid Cyst, CPA-lAC 11-1-16 James A. Cooper, MD Aqueductal Stenosis 11-3-12 H. Ric Harnsberger, MD Arachnoid Cyst, CPA-lAC 11-1-20 11-3-16 H. Ric Harnsberger, MD James A. Cooper,MD Normal Pressure Hydrocephalus 11-1-24 James Provenza Ie, MD CSF Shunts and Complications Inflammatory Ramsay Hunt Syndrome 11-1-28 11-3-20 H. Ric Harnsberger, MD Susan I. Blaser, MD, FRCP(C) Vascular Vascular Loop Compression, CPA-lAC 11-3-24 H. Ric Harnsberger, MD XXI
  • 22. Malignant Nonmeningothelial Neoplasms Acoustic Schwannoma 11-3-28 H. Ric Harnsberger, MD Meningioma, CPA-lAC 11-3-32 11-3-36 H. Ric Harnsberger, MD Introduction and Overview Issues 11-4-4 Anne G. Osborn, MD, FACR Congenital Craniostenoses 11-4-8 Susan 1. Blaser, MD, FRCP(C) Atretic Cephalocele 11-4-12 Gary 1. Hedlund, DO Trauma Calvarium Fracture 11-4-14 Gregory 1. Katzman, MD Pneumocephalus 11-4-18 Gregory 1. Katzman, MD Hypotension 11-4-22 Anne G. Osborn, MD, FACR Nonneoplastic and Tumorlike Disorders Pseudotumors 11-4-26 H. Ric Harnsberger, MD Pachymeningitis 11-4-30 Anne G. Osborn, MD, FACR Fibrous Dysplasia 11-4-34 Susan 1. Blaser, MD, FRCP(C) Paget Disease 11-4-38 Gregory 1. Katzman, MD Extramedullary Hematopoiesis 11-4-42 Gregory 1. Katzman, MD Thick Skull 11-4-44 Gregory 1. Katzman, MD Histiocytosis 11-4-48 Gary 1. Hedlund, DO Neurosarcoid 11-4-52 Gregory 1. Katzman, MD Neoplasms Meningioma 11-4-56 Gregory 1. Katzman, MD Atypical and Malignant Meningioma 11-4-60 Gregory 1. Katzman, MD Benign Nonmeningothelial Gregory 1. Katzman, MD XXll Myeloma Skull and Meningeal Metastases Gregory 1. Katzman, MD Skull, Scalp, Meninges Anatomy-Imaging Hypertrophic Hemangioma 11-4-72 11-4-76 Gregory 1. Katzman, MD Metastases, CPA-lAC Intracranial 11-4-68 Gregory 1. Katzman, MD H. Ric Harnsberger, MD Intracranial Tumors Gregory 1. Katzman, MD Tumors 11-4-64 11-4-80
  • 23. XXlll
  • 24. XXiV
  • 25. ABBREVIATIONS IH: Proton 3T (imaging): CST: Cavernous sinus thrombosis 3 Tesla CVD: Collagen vascular disease AC: Arnold Chiari CVT: Cerebral venous thrombosis ACA: Anterior cerebral artery DSA: Digital subtraction angiography AcoA: Anterior communicating ACTH: Adrenocorticotrophic artery hormone ECA: External carotid artery EMA: External maxillary artery ADC: Apparent diffusion coefficient EpC: Epidermoid cyst ADHP: Autosomal dominant FlU: Follow-up holoprosencephaly AICA: Anterior inferior cerebellar artery FDG: Fluordeoxygluose ApoE: Apolipoprotein E GAl: Glutaric academia type 1 ASVD: Atherosclerotic vascular disease GFAP: Glial fibrillary acidic protein BIT: Between GM1/2: BA: Basilar artery BCKD: Branched-chain Gangliosidosis 1/2 GSW: Gunshot wound Alpha-keto dehydrogenase HA:. Headache BFGF: Basic fibroblast growth factor HGBL(s): Hemangioblastoma(s) BaS fx: Base of skull fracture HHT: Hereditary hemorrhagic CBLL: Cerebellar HMPAO: Hexamethylopropyleneamine Cele: Encephalocele HU: Hounsfield unit Cf: Compare HUS: Hemolytic-uremic CHARGE: Coloboma; Heart defects; Atresia of choanae; Retardation of growth; Genitourinary abnormalities; Ear abnormalities ICA: Internal carotid artery Cho: Choline CN(s): Cranial nerve(s) CNS: Central nervous system COHb: Carboxyhemoglobin COP: Carbon monoxide poisoning COW: Circle of Willis CPA-lAC: Cerebellopontine angle-internal auditory canal ICH: Intracranial telangiectasia oxime syndrome hemorrhage IC-PCoA: Internal carotid-posterior artery junction communicating IEL: Internal elastic lamina INO: Internuclear Ino: ophthalmopligia Inositol ION: Inferior olivary nucleus ISF: Interstitial fluid Cr: Creatine ISUIA: International Aneurysms CSF: Cerebrospinal fluid IVH: Intraventricular Study on Unruptured Intracranial hemorrhage LHX3: 11M homeobox 3 gene xxv
  • 26. LHX4: LIM homeobox 4 gene TOF: Time of flight LV: Lateral ventricle TPIT: Treponema pallidum immobilization MCA: Middle cerebral artery TS: Transverse sinus MEN1: Multiple endocrine neoplasia 1 TIP: Thrombotic thromocytopenic MIB-1: Histiologic marker of cell proliferation VA: Vertebral artery MIH: Melanotropin VACTERL: Vertebral Anal Cardiac Tracheal Esophageal Renal Limb release-inhibiting hormone purpura MIP: Maximum intensity projection VEGF: Vascular endothelial growth factor MSH: Melanotropin stimulating hormone VHL: von Hippel Lindau NAT: Nonaccidental trauma WaD: Wallerian degeneration NF: Neurofibromatosis WM: White matter NIH: National Institutes of Health (USA) WWS: Walker- Warburg syndrome NSE: Neural-specific enolase NTD(s): Neural tube defect(s) OMIM: Online Mendelian Inheritance in Man PAS: Periodic acid schiff PCA: Posterior cerebral artery PCoA: Posterior communicating PcomA: artery Posterior communicating artery PnSAH: Perimesencephalic non aneurysmal subarachnoid hemorrhage PICA: Posterior inferior cerebellar artery PPm: Mean ocular perfusion pressure PRL: Prolactin PVSs: Perivascular space(s) rCBF: Relative cerebral blood flow rCBV: Relative cerebral blood volume SIP: Following (status post) SAH: Subarachnoid hemorrhage SOY: Superior ophthalmic vein SPECT: Single photon emission computed tomography SPGR: Spoiled gradient refocused SPS: Superior petrosal sinus SS: Straight sinus SSAC(s): Suprasellar arachnoid cyst(s) SSS: Superior sagittal sinus SVC: Superior vena cava TBI: Traumatic brain injury TCE: T-cell TIAs: Transient ischemic attack(s) XXVI test
  • 27. XXVll
  • 28. XXVlll
  • 29. DIAGNOSTIC IMAGING BRAIN XXIX
  • 30. xxx
  • 31. PART I PathololY-Based Dlaposes Congenital Malformations Trauma [I] rn Subarachnoid Hemorrhage and Aneurysms rn Stroke @] Vascular Malformations rn Neoplasms and Tumorlike Lesions lliJ Primary Non-Neoplastic Cysts [l] Infection and Demyelinating Disease Metabolic/Degenerative [ID Disorders, Inherited ~ Toxic/Metabolic/Degenerative Disorders, Acquired [1Q] 10
  • 32. PART I SECTION 1 Consenltal Malformations The human brain is subject to a variety of developmental anomalies that vary from mild to so evere that they are incompatible with life. Formation of the S is a tunningly complex proce with many cycles of development, mod ling and remod ling that b gins in early fetal life and continues into th third postnatal decade. Mor than 2000 different malformations have been described in the clinical and imaging literature. n exhau tive (even comprehensive) discus i n of S anomalies is far beyond the cope of this text. We have att mpted to select for discussi n those malformations that are either stati tically among the most c mmon ncountered in g n ral imaging practice or tho e that are e pecially important to rec gnize. It should be empha ized that our understanding of the genetic and in uter environmental influences on brain devel pment and malformati n continu t evolve. Imaging is only a part of the larger puzzl . Knowledge of th basic principl underlying S development is the foundation for approaching c ngenital malformations f the brain. While an ind pth discu sion of neuroembryology i al 0 beyond th scope of thi book, we present a bri f review of "embr ology in a nutshell" that is helpful as a starting point in und rstanding the specific diagnoses in thi s ction. We begin the discussion of ongenital malformations f the brain with hindbrain herniati n and malformations. Included in this group are the hiari malf rmations, a 'r up of mostly embryolo 'i ally unrelated hindbrain anomalies in which cereb liar tissue i di placed into the cervi al canal. Also included in hindbrain malformations are the posterior fo a cystic malf rmations (DandyWalk r "com pi XU including the Dandy-Walker malformation and variant ). Oth r cerebellar malformations such as rhombencephalo ynapsis are discus ed here. Di erticulation and cleavage disorder of the developing brain include the sp ctrum of h I prosen ephalies and their variants. Malf rmations of cortical development are a large and diverse group. The major ones are discu sed in this s ction. The ection concludes with a group of disorders that no one knows quite what to call: eurocutaneous syndromes? ot all have cutaneous manifestation. Phakomat ses? ot all have spots. Inherited tumor yndromes? ot all hav associated neoplasms. Inherited genetic syndrom ? ot all are kn wn, and some (such as Sturge-Weber malformation) are not inherited. Whatever you want to call them, here they ar !
  • 33. SECTION 1: Congenital Malformations Introduction and Overview Congenital Malformations 1-1-4 Hindbrain Herniations, Miscellaneous Malformations Chiari 1 Chiari 2 Chiari 3 Callosal Dysgenesis Lipoma 1-1-8 1-1-12 1-1-16 1-1-18 1-1-22 Hindbrain Malformations Dandy Walker Spectrum Rhombencephalosynapsis Congenital Vermian Hypoplasia 1-1-26 1-1-30 1-1-34 Disorders of Diverticulation/Cleavage Holoprosencephaly Holoprosencephaly Variants Septooptic Dysplasia 1-1-38 1-1-42 1-1-46 Malformations of Cortical Development Microcephaly Congenital Muscular Dystrophy Heterotopic Gray Matter Pachygyria -Polymicrogyria Lissencephaly Type 1 Schizencephaly Hemimegalencephaly 1-1-50 1-1-54 1-1-58 1-1-62 1-1-66 1-1-70 1-1-74 Familial Tumor/Neurocutaneous Syndromes Neurofibromatosis Type 1 Neurofibromatosis Type 2 von Hippel Lindau Tuberous Sclerosis Complex Sturge- Weber Syndrome Meningioangiomatosis Basal Cell Nevus Syndrome HHT Encephalocraniocutaneous Lipomatosis Cowden Syndrome Neurocutaneous Melanosis 1-1-78 1-1-82 1-1-86 1-1-90 1-1-94 1-1-98 1-1-100 1-1-104 1-1-108 1-1-112 1-1-116
  • 34. CONGENITAL MALFORMATIONS 1 4 Graphic shows neural plate (red, upper left). Upper right: NT folds. Lower left: NT closes. Lower right: Cutaneous, neuroectoderm separate; neural crest (blue) migrates laterally Clinical photograph shows NTDS with MMC. The protruding raw red mass is the dorsal surface of the unclosed neural tube that remains open, everted (Courtesy C. Hedlund, MO). ITERMINOLOGY Abbreviations • and Synonyms • Neural tube defects (NTDs) • Malformations of cortical development (MCD) Definitions • Congenital malformations are primary disorders resulting from disturbed embryonic/fetal development • Encephaloclastic defects are secondary disorders that result from in utero insults to otherwise normally-developed brain (e.g., vascular, infectious, toxic, etc) and are considered acquired disorders I PATHOLOGY ISSUES • Classification • Many classifications proposed; none universally accepted • Neural tube defects/dysraphic disorders o Exencephaly, anencephaly o Myelomeningocele with Chiari II malformation o Herniations through cranial defects (covered in Part II) • Cephalocele (named for bone through which they pass) • Meningocele • Disorders of forebrain induction o Holoprosencephaly (HPE) (no absolute distinction between categories; overlap common) • Alobar • Semilobar • Lobar • Kallman syndrome and HPE variants (e.g., central incisor syndrome) o Septo-optic dysplasia (+/- hypothalamic-pituitary dysfunction) o Arrhinencephaly o Callosal dysgenesis • Partial • • • Agenesis • With or without lipoma Malformations of cortical development (proliferation, migration, organization) o Lissencephalies (classic, cobblestone types) o Pachygyria (incomplete lissencephaly) o Polymicrogyria o Schizencephaly ("open" or "closed" lip) o Hemimegalencephaly o Gray matter heterotopias • Subependymal heterotopia • Focal subcortical ("masslike") heterotopia • Band heterotopia ("double cortex") o Focal cortical dysplasias Cerebellar malformations o Cerebellar agenesis (sometimes termed "Chiari IV") o Joubert syndrome (congenital vermian aplasia/hypoplasia) o Tectocerebellar dysraphia o Rhombencephalosynapsis o Dandy-Walker malformation Miscellaneous malformations o Lipoma (maldifferentiation of primitive developing meninges) Familial tumor/neurocutaneous syndromes o With CNS neoplasm (major CNS listed) • Nfl (plexiform neurofibroma, MPNST, optic glioma, astrocytoma) .' NF2 (schwan noma, meningioma, ependymoma) • von Hippel-Lindau (hemangioblastoma) • Tuberous sclerosis (subependymal giant cell astrocytoma) • Li-Fraumeni (astrocytoma, PNET) • Cowden (dysplastic cerebellar gangliocytoma) • Turcot (medulloblastoma, GBM) • Nevoid basal cell carcinoma (Gorlin) syndrome (medulloblastoma) o Without CNS neoplasm • Sturge- Weber syndrome • Wyburn-Mason syndrome
  • 35. CONGENITAL MALFORMATIONS 1 DIFFERENTIALDIAGNOSIS Chromosomal anomalies with CNS manifestations • Trisomies (21, 18, 13) Neural tube defects (NTDs) • Anencephaly • Cephaloceles • Myelomeningocele (with Chiari II) Abnormalities of brain cleavage, diverticulation • Holoprosencephaly • Septooptic dysplasia • Kallman syndrome • Hereditary hemorrhagic telangectasia (HHT or Rendu-Osler- Weber syndrome) • Ataxia-telangiectasia • Neurocutaneous melanosis (can have intracranial malignant melanoma) • Meningioangiomatosis (can be locally invasive) • Encephalo-craniocutaneous lipomatosis IClINICAllMPlICATIONS Clinical Importance • Approximately 3% of newborns have major malformations o Approximately 60% of congenital malformations remain of unknown etiology o Approximately 20% are multifactorial (combination of hereditary tendencies, nongenetic influences) o 7.5% are monogenic o 6% have major chromosomal anomalies o 12-15% acquired encephaloclastic disorders (e.g., toxins, drugs, infection, nutrition) • > 75% of fetal deaths have cerebral malformations o More than 2,000 different congenital cerebral malformations have been described o One-third of all major malformations involve the CNS IEMBRYOLOGY Embryologic Events • Primary neurulation o Notochordal process, prechordal plate induce development of neural plate o Lateral portions of neural plate thicken, fold o Neural folds bend medially towards each other o Neural folds fuse, neural crest cells detach from lateral lips of neural folds and migrate laterally o Neural tube closes bidirectionally in "zipper-like" fashion o Surface ectoderm fuses, neural tube separates and sinks into mesenchyme of posterior body wall 5 Hindbrain malformations • • • • • • Chiari I Chiari II Chiari III Dandy-Walker spectrum Cerebellar, vermian hypoplasias Rhombencephalosynapsis Malformations • • • • • • • of cortical development Microcephaly Congenital muscular dystrophy Heterotopic gray matter Pachygyria-polymicrogyria Lissencephaly type 1 Hemimegalencephaly Schizencephaly o Neural tube bends, forms primary, then secondary vesicles • Prosencephalon (forebrain) gives rise to telencephalon, diencephalon • Mesencephalon gives rise to midbrain • Rhombencephalon (hindbrain) gives rise to developing pons, cerebellum, medulla o Cerebral hemispheres, ventricles develop as diverticulae from lateral walls of forebrain, expand rapidly to cover diencephalon • "H"-shaped central monoventricle formed with developing lateral ventricles communicating with central3rd V through an interventricular foramen (of Monro) • Choroid fissure runs length of lateral ventricles, contains choroid plexus that elaborates CSF • Proliferating cells around ventricles form germinal zones of neuroblasts • Neuroblasts migrate peripherally in waves, creating cortex in an "inside-out" sequence (Le., from deep to superficial layer • Commissural tracts (anterior, hippocampal, corpus callosum) form at cranial end of telencephalon • Corpus callosum undergoes bidirectional thickening; anterior portion of genu, posterior callosal body form"'! same time; rostrum forms last (after splenium) o Diencephalic alar plate forms thalamus, hypothalamus; roof plate and ependyma form choroid plexus, circumventricular organs o Primitive mesenchymal tissue ("leptomeninx") differentiates into arachnoid, pia; arachnoid space is created as mesenchumal tissue between arachnoid, pia is resorbed leaving scattered arachnoidal trabeculae or struts • Secondary neurulation o Mesodermal cells in caudal eminence (tail mass) fuse o Vacuoles in tail mass form, fuse ~ hollow tube o Lumen of caudal eminence fuses/becomes continuous with neural tube o Caudalmost part of neural tube eventually regresses, forming filum terminale
  • 36. CONGENITAL MALFORMATIONS 1 6 NTOS with Chiari II. Elongated 4th V (open arrow), tissue "cascade" (vermian nodulus, choroid plexus) (curved arrow), medullary spur (white arrow) and kink (black arrow) (Courtesy S. VandenBerg and Rubinstein collection). • Failure of part of neural neural tube closure ~ neural tube defects (NTDS) that range from mild, simple spina bifida to myelomeningocele • Defective development of ventromedial forebrain ~ defects ranging from mild anomalies of olfactory bulbs to alobar holoprosencephaly • Faulty neuronal migration ~ lissencephaly, subcordical band heterotopia, etc • Failure of normal commissural development ~ corpus callosum anomalies • Maldifferentiation of primitive leptomeninix ~ lipoma DIFFERENTIAL DIAGNOSIS Small head (2 S D below mean for age) • Primary microcephaly o Familial and autosomal dominant microcephaly o Trisomy 21, 13 o Rubinstein-Taybi syndrome • Secondary microcephaly o Severe intrauterine hypoxic-ischemic injury o Fetal alcohol syndrome o Congenital infection ("TORCH" syndromes) Large head (> 2 S D above mean or percentile by at least 0.5 cm) Small posterior fossa • • • • Chiari II malformation Occipital cephalocele Achondroplasia Chiari I malformation (variable) Large posterior fossa • Dandy-Walker syndrome • Large bulky congenital infratentorial neoplasm (rare; e.g., atypical teratoid/rhabdoid tumor) I Prominent sutures • "Pseudosplit" sutures o Normally seen in infants up to 2-4 mos (due to underossification) ! • Increased intracranial pressure • NFl with sutural defects • Metastases (leukemia, neuroblastoma) • Hypothyroidism, hypophosphatasia • Osteogenesis imperfecta I SELECTED 1. > 97th • Hydrocephalus o Aqueductal stenosis o Dandy-Walker, other malformations • Chronic subdural fluid collections • Enlarged subarachnoid spaces (benign macrocrania infancy) • Neurocutaneous syndrome (Nfl, TSC) • Metabolic storage diseases (e.g., mucopolysaccharidoses) • Dysmyelinating disorders (Alexander, Canavan) • Achondroplasia MO). • Megalencephaly, cerebral gigantism (Sotos syndrome), etc • Neoplasm (large, bulky mass; prior to sutural closure) Practical Implications ICUSTOM Sagittal gross pathology shows Chiari II malformation with callosal dysgenesis. Note high-riding 3rd V, small posterior fossa contents (arrows) (Courtesy R. Hewlett, 2. 3. of 4. 5. 6. REFERENCES Glass RB] et al: The infant skull: A vault of information. RadioGraphies 24: 507-22, 2004 Kurul S et al: Agyria-pachygyria complex: MR findings and correlation with clinical features. Pediatr Neurol. 30(1):16-23,2004 Garcia-Cazorla A et al: White matter alterations associated with chromosomal disorders. Dev Med Child Neural. 46(3):148-53,2004 Sisodiya SM: Malformations of cortical development: burdens and insights fram important causes of human epilepsy. Lancet Neural. 3(1):29-38, 2004 Larsen W]: Human Embryology (3rd ed), Churchill Livingstone, 2001 Barkovich A]: Pediatric Neuraimaging (3rd ed), Lippincott Williams and Wilkins, 2000
  • 37. CONGENITAL MALFORMATIONS 1 I IMAGE GAllERY 7 Normal vs. Pathology (Left) Lateralgross pathology shows normal early fetal brain development. Note shallow, open sylvian fissure (arrow) and virtually complete lack of sulcation/gyration (Courtesy S. Stensaas, PhO). (Right) Lateralgross pathology shows brain of infant born with near-complete agyria (lissencephaly). Minimal sulcation/gyration is seen. Compare with normal fetal brain on left (Courtesy R. Hewlett, MO). Normal vs. Pathology (Left) Axial gross pathology of a normally developing fetal brain (same case as above) shows completely smooth hemispheres. (Right) Coronal gross pathology, section through posterior ventricles (same case as above) shows essentially agyric brain with smooth, thin cortex. Note subependymal gray matter (arrows) in germinal matrix. Normal vs. Pathology (Left) Submentovertex gross pathology of normal fetal brain shows lobulation but little evidence for significant sulcation or gyration. Note shallow, open Sylvian fissures (arrows). (Right) Coronal gross pathology, section through thalami again shows agyric brain. Compare to normal fetal brain on left. Periventricular germinal hemorrhage is present (arrows).
  • 38. CHIARI1 1 8 Sagittal T7WI M R shows sliver of tonsils (curved arrow) protruding through the foramen magnum posteriorly compressing the upper cervical cord. There is mild ventriculomegaly (arrow). Sagittal graphic shows caudal descent of nucleus gracilis (curved arrow) marking obex. The tonsils (arrow) protrude through foramen magnum and the cisterna magna is obliterated. • Morphology o Tonsils can normally lie below FM (:::;5 mm in adults, slightly more in children < 4 y) o Unless tonsils ~ 5 mm and/or pointed, probably not Ch 1 o Tonsillar impaction in FM without caudal herniation can also be symptomatic • Look for absent cisterna magna, posteriorly angled odontoid with compressed brainstem, short posterior arch C1, short supra occiput, syrinx ITERMINOlOGY Abbreviations and Synonyms • Chiari type I malformation tonsil ectopia (Ch 1); cerebellar (CBLL) Definitions • Caudal protrusion foramen magnum of "peg-shaped" CBLL tonsils below (FM) Radiographic Findings !IMAGING FINDINGS • Radiography o 4th occipital sclerotome syndromes> 50% • Short clivus, craniovertebral segmentation/fusion anomalies, pro-atlas remnants, atlas assimilation, odontoid retroflexion • Small occipital enchondral skull: Basiocciput, exocciput, supra occiput • 1 Angulation of posteriorly tilted odontoid process (more common in females) => 1 symptoms o Suspect Ch 1 if • Cervical lordoses > 0 degrees • Thoracic kyphosis> 40 degrees o Suspect syrinx if enlarged cervical spinal canal on lateral film General Features • Best diagnostic clue o Low-lying, pointed (not rounded) "peg-like" CBLL tonsils o Tonsillar sulci have vertical (not horizontal) orientation o Compressed/absent cisterna magna • Size o Age-related tonsil descent below "opisthion-basion line" • 1st decade (6 mm) (most pronounced at"" 4 y, then tonsils "retreat") • 2nd/3rd decades (5 mm) • 4th to 8th decades (4 mm) • 9th decade (3 mm) CT Findings • NECT DDx: Protrusion of Cerebellar Tonsils Ch I at .f Yrs Resolution by (, Yrs Congenital Shunt /cquirpcl Malformations Ch I Epcnclym( )fna
  • 39. CHIARI1 1 Key Facts Terminology • Chiari type I malformation (Ch 1); cerebellar (CBLL) tonsil ectopia • Caudal protrusion of "peg-shaped" CBLL tonsils below foramen magnum (FM) • I::=asymptomatic: 14-50%, treatment • II::=brainstem compression • III::=hydrosyringomyelia Clinical Issues • Treatment aim ::= restore normal CSF flow at FM Imaging Findings • Tonsils can normally lie below FM (::; 5 mm in adults, slightly more in children < 4 y) • Unless tonsils 2: 5 mm and/or pointed, probably not Ch 1 • Small bony PF ::>low torcular, effaced PF cisterns • "Crowded" FM controversial Diagnostic Checklist • Low tonsils with normal rounded shape are usually asymptomatic • Tonsils with peg/triangular shape + obliteration of surrounding CSP are abnormal at any level below opisthion-basion line Pathology • "Mismatch" between posterior fossa size (small), CBLL (normal) ::>tonsillar "ectopia" o Small bony PF ::>low torcular, effaced PF cisterns o "Crowded" FM o Lateral/3rd ventricles usually normal (89%) MR Findings • TlWI o Sagittal: Pointed, triangular-shaped ("peg-like") tonsils 2: 5 mm below FM o Surrounding CSF in PM effaced o Short clivus::> apparent descent 4th ventricle, medulla • T2WI: Look for upper cervical cord edema, syrinx (15-75%) • Phase-contrast cine MR shows pulsatile systolic tonsillar descent, obstructed CSF flow through FM Ultrasonographic Findings • Color Doppler: Loss of bidirectional CSF flow, peak velocity of 3-5 cm/s, and waveform that exhibits vascular and respiratory variations Nuclear Medicine Findings • Radionuclide cisternography: Patients with demonstrable FM block have more predictable relief of symptoms following posterior fossa decompression and duraplasty than those with syrinx and free tracer flow across foramen magnum Imaging Recommendations • Best imaging tool: MR brain with thin sagittal views of the craniocervical junction • Protocol advice o MR brain +/- CSF flow studies o Spine MRI to detect syrinx, low/tethered cord, +/fatty filum I DIFFERENTIAL DIAGNOSIS Acquired tonsillar ectopia/herniation • Basilar invagination • "Pull from below" o Lumbar puncture hypotension or (LP) shunt::> intracranial • "Sagging" brain stem, acquired tonsillar herniation o Spontaneous intracranial hypotension • "Push from above" o Chronic ventriculo-peritoneal shunt (thick skull, premature sutural fusion, lumbar arachnoidal adhesions) o Tonsillar herniation 2° 1 ICP, mass effect or tumor I PATHOLOGY General Features • General path comments o Embryology • Underdeveloped occipital enchondrium ::>small posterior fossa (PF) vault ::>crowded PF ::> downward herniated hindbrain::> obstructed FM ::>lack of communication between cranial/spinal CSF compartments • Genetics o Syndromic/familial • Craniosynostoses; midline anomalies • Mutated LHX4 gene (Chr 1q25): Posterior pituitary ectopia, Ch 1 • Etiology o "Mismatch" between posterior fossa size (small), CBLL (normal) ::>tonsillar "ectopia" o Hydrodynamic theory of symptomatic Chiari 1 • Systolic piston-like descent of impacted tonsils/medulla::> abnormal intraspinal CSF pressure-wave • Hydrosyringomyelia develops as secondary phenomenon • Epidemiology: 0.01 % of population • Associated abnormalities o Craniocervical junction bony anomalies frequent • 4th occipital sclerotome anomalies, underdeveloped basichondrocranium, Klippel-Feil, Sprengel deformity, platybasia o NFl patients comprise approximately 5% of symptomatic Chiari 1 o FG syndrome Congenital Malformations 9
  • 40. Gross Pathologic & Surgical Features 10 • • • • Herniated, sclerotic tonsillar pegs Tonsils grooved by impaction against opisthion Arachnoid adhesions between CBLLtonsils, medulla Thickened leptomeninges and/or thickened dura mater at CVJ Microscopic Features • Purkinje/granular cell loss Staging, Grading or Classification Criteria • I = asymptomatic: 14-50%, treatment controversial • II = brainstem compression • III = hydrosyringomyelia Syrinx shunted only if syrinx persists or progresses post suboccipital decompression • Treatment aim = restore normal CSF flow at FM o Suboccipital decompression/resect posterior arch Cl; +/- duraplasty, CBLLtonsil resection • > 90% ~ !brainstem signs • > 80% ~ ! syringohydromyelia • Scoliosis arrests (improves in youngest) • Progression of spinal deformity post suboccipital decompression 1 with older age, severity of initial symptoms, double scoliosis curve, thoracic kyphosis, rotation, large curve o 1·.[)IA{jN4QSl"I(iCEHECEl{~.ISI Consider I.C~lNICA.l-ISSl,lES Presentation • Most common signs/symptoms o Up to 50% asymptomatic • Prevalence of symptoms 1 if canal diam < 19 mm o "Chiari 1 spells": Cough or sneezing ~ acute 1 intrathecal pressure due to obstructed CSF flow ~ headache or syncope o Symptomatic brainstem compression • Hypersomnolence/central apnea/sudden death (infant) • Bulbar signs (e,g" lower CN palsies) • Neck or back pain, torticollis, ataxia o Symptomatic syringohydromyelia • Paroxysmal dystonia, unsteady gait, incontinence • Atypical scoliosis (progressive, painful, atypical curve) • Dissociated sensory loss/neuropathy (hand muscle wasting) o Other: Hiccoughs, trigeminal facial pain, may mimic multiple sclerosis • Clinical profile o Infant/very young child: Impaired oropharyngeal function common o Child: Headache, neck pain, syrinx and scoliosis o Adult: Neck pain, and drop attacks • Etiologies other than Ch 1 when tonsillar descent seen on spine MRI first (hydrocephalus and brain tumors "push" tonsils down) Image Interpretation 1, 2, 3, 4. S, 6, Demographics • Age o Very young child: Mean 3.3 years o Pediatric: Mean 11 years (range in one series 2 months to 20 years) o Adult: Mean age 34 years • Gender: M:F = 1:1.3 Natural History & Prognosis • Increasing ectopia + 1 time ~ 1 likelihood symptoms • Children respond better than adults; treat early • Postoperative complications o Cerebellar ptosis o Regrowth/ossification of resected bone Pearls • Low tonsils with normal rounded shape are usually asymptomatic • Tonsils with peg/triangular shape + obliteration of surrounding CSF are abnormal at any level below opisthion-basion line 7. 8, 9, Flynn JM et al: Predictors of progression of scoliosis after decompression of an Arnold Chiari 1 malformation, Spine 29(3):286-92, 2004 Arora P et al: Chiari 1 malformation related syringomyelia: Radionuclide cisternography as a predictor of outcome, Acta Neurochir 146(2)119-30, 2004 Schijman E, Steinbok P: International survey on the management of Chiari 1 malformation and syringomyelia, Childs Nerv Syst, 2004 Tubbs RSet al: Inclination of the odontoid process in the pediatric Chiari 1 malformation. J Neurosurg 98(lSuppl):43-9, 2003 Venureyra EC et al: The role of cine flow MRI in children with Chiari 1 malformation, Childs Nerv Syst 19(2):109-13, 2003 Tubbs RSet al: Surgical experience in 130 pediatric patients with Chiari 1 malformations, J Neurosurg 99(2):291-6, 2003 Loder RT et al: Sagittal profiles of the spine in scoliosis associated with an Arnold-Chiari malformation [type 11 with or without syringomyelia, J Pediatr Orthop 22(4):483-91,2002 Kyoshima K et al: Syringomyelia without hindbrain herniation: Tight cisterna magna, J Neurosurg 96(2Suppl):239-49,2002 Greenlee JD et al: Chiari 1 malformation in the very young child: The spectrum of presentations and experience in 31 children under age 6 years, Pediatrics 110(6):1212-9, 2002 Treatment • Controversial: International consensus states "no intervention for asymptomatic Chiari 1 unless syrinx" o Most will also intervene if scoliosis, even in absence of syringohydromyelia Congenital Malformations
  • 41. 1 11 (Left) Sagittal T2WI MR shows posteriorly tilted odontoid (curved arrow) indenting the junction of the medulla and upper cervical cord. There is abnormal cervical cord signal (arrow) and Ch 7 (open arrow). (Right) Sagittal NECT 30 reconstruction shows a short, flat clivus and a posteriorly angled, bulbous odontoid tip (curved arrow). (Left) Sagittal T7WI MR shows an "impacted" foramen magnum in Proteus syndrome and megalencephaly. The cisterna magna is effaced and the pointed tonsils (arrow) protrude slightly through foramen magnum. (Right) Sagittal T2WI MR shows marked protrusion of cerebellar tonsils through foramen magnum. The odontoid is posteriorly angled; medulla is indented (arrow). The tonsils are round and surrounded by CSF. (Left) Axial T2WI MR shows cerebellar tonsils (open arrow) protrude through the foramen magnum to surround and compress the cervical cord. Posterior fossa cisterns are obliterated. (Right) Coronal T2WI MR shows moderate unilateral protrusion of the right cerebellar tonsil (arrow). The left cerebellar tonsil remains in normal position. Congenital Malformations
  • 42. 12 Sagittal graphic shows small PF, large massa intermedia, beaked tectum, callosal dysgenesis, elongated 4th Vand (in order) herniating nodulus, choroid plexus, and medullary spur (arrows). Sagittal TlWI MR shows beaked tectum (arrow), large massa intermedia (curved arrow), dysgenetic corpus callosum, small 4th ventricle, and protrusion of tissue through foramen magnum. Radiographic Findings Abbreviations • Arnold-Chiari and Synonyms malformation (AC2), Chiari type II Definitions • Complex malformation of hindbrain virtually 100% associated with neural tube closure defect (NTD), usually lumbar myelomeningocele (MMC) r·IMAGINYFINOlNG$ General Features • Best diagnostic clue o Presence of MMC o Small posterior fossa o Elongated, "straw-like" 4th ventricle • Location: Hindbrain • Size: Small posterior fossa • Morphology o "Cascade" of tissue herniates through foramen magnum behind upper cervical cord • Vermis (nodulus) • Choroid plexus of 4th V • Medullary "spur" • Radiography o "Lacunar" (Lucken shadel) skull • Universal at birth, largely resolves by 6 months • Craniolacunia involves inner, outer tables (squamous bones) • Caused by mesenchymal defect (not i ICP!) o Incorporation of accessory frontal bone ~ transient "bifrontal foramina" o Widened upper cervical canal (Chiari malformation +/- syrinx) • Myelography o Tethered cord o Nerve roots pass horizontal or even upwards CT Findings • NECT o Small posterior fossa (PF) • Low lying tentorium/torcular inserts near foramen magnum • Large, funnel-shaped foramen magnum • "Scalloped" petrous pyramid, "notched" clivus o Dural abnormalities • Fenestrated/hypoplastic falx ~ interdigitated gyri • "Heart-shaped" incisura • Absent falx cerebelli DDx: The Chiari Malformations Chiari 7 Chiari 2 Chiari 3 Congenital Malformations Chiari 4
  • 43. CHIARI2 1 Key Facts • Other Chiari malformations Terminology • Arnold-Chiari malformation (AC2), Chiari type II • Complex malformation of hindbrain virtually 100% associated with neural tube closure defect (NTD), usually lumbar myelomeningocele (MMC) Imaging Findings • Presence of MMC • Small posterior fossa • "Cascade" of tissue herniates through foramen magnum behind upper cervical cord • "Lacunar" (Lucken shadel) skull • Universal at birth, largely resolves by 6 months • Caused by mesenchymal defect (not 1 ICPl) Top Differential Diagnoses • Severe, chronic shunted congenital Diagnostic Checklist • Imaging features due to long term effects of mechanical distortion • "Too small" PF • Cerebellar contents herniate!, 1 hydrocephalus • Reported"" MR Findings • T1WI o Small PF ~ contents shift! into cervical canal, herniate upward through incisura • Cerebellar (CBLL) hemispheres/tonsils "wrap" anteriorly around medulla • Pons, cranial nerve roots often elongated • Compressed, elongated, low-lying 4th V often lacks fastigium, may pouch into cervical canal • "Towering" cerebellum protrudes up through incisura, compresses tectum o Associated abnormalities: Dysgenetic corpus callosum (CC) 90% • T2WI o Ventricles • Lateral: Pointed anterior horns, colpocephaly • 3rd: Large massa intermedia, high-riding (if CC agenesis present) • 4th: Elongated, "straw-like" without posterior point (fastigium) o Small PF • Concave clivus, temporal bones • Low-lying torcular, TSs • Obliterated basal cisterns • "Cascade" or "waterfall" of tissue down, behind medulla • MRV: Torcular, transverse sinuses extremely low • MR spine o Open dysraphism, MMC almost 100% (lumbar> > cervical) o Hydrosyringomyelia 20-90% o Posterior arch Cl anomalies 66% o Diastematomyelia 5% Ultrasonographic Pathology • MTHFR mutations + folate deficiency ~ 1 risk NTD • Decreases in serum folate are seen with anti-epileptic drugs, oral contraceptives, and smoking • Abnormal neurulation ~ CSF escapes through NTD ~ failure to maintain 4th ventricular distention ~ hypoplastic PF chondrocranium ~ displaced/distorted PF contents Findings • Real Time o Fetal ultrasound (US) • MMC defined as early as 10 weeks on on US • AC2 ("lemon," "banana" signs) recognized as early as 12 weeks gestation • Lacunar skull identified by irregular echogenicity of skull to fetal MRI for assessing spinal level Imaging Recommendations • Best imaging tool: MRI brain + spine • Protocol advice o Initial screening MR (brain, spine) o Follow-up for • Symptoms of brainstem compression • Increasing ventricular size • Increasing spinal symptoms I DIFFERENTI~[DI~GN0$1$ Severe, chronic shunted congenital hydrocephalus • May cause collapsed brain, upward herniated cerebellum, but no spina bifida Other Chiari malformations • Chiari 1: Herniated CBLL tonsils • Chiari 2: Vermis may be impacted, rather than herniated or may "disappear" due to compressive injury • Chiari 3: Chiari 2 PLUS encephalocele • Chiari 4: Controversial, not just hypoplastic cerebellum o Some reserve term for severe hypoplasia of cerebellum in association with Chiari 2 I P~TI-I0[0G¥ General Features • General path comments: Neurogenic, renal, & orthopedic complications are the norm • Genetics o 4-8% risk recurrence if have one affected child o Menthylene-Tetra-Hydrofolate-Reductase (MTHFR) mutations (esp C677T) associated with abnormal folate metabolism o MTHFR mutations + folate deficiency ~ 1 risk NTD Congenital Malformations 13
  • 44. 14 o Decreases in serum folate are seen with anti-epileptic drugs, oral contraceptives, and smoking • Etiology o Embryology • Origins during 4th fetal week • Abnormal neurulation =} CSF escapes through NTD =} failure to maintain 4th ventricular distention =} hypoplastic PF chondrocranium =} displaced/distorted PF contents o New studies demonstrate that vimentin is focally upregulated in the ependyma in dysgenetic regi0foLs • Theory that genetic defect may also playa role III etiology of Ch 2 brain malformation • Epidemiology: 0.44:1000 births, decreasing with folate replacement and elective termination of affected fetus • Associated abnormalities o 4th ventricular glial or arachnoidal cysts, choroidal nodules and subependymoma • Situated in the roof of 4th ventricle, closely associated with choroid plexus • Rarely identified on imaging Gross Pathologic & Surgical Features • Basic abnormality = small PF with herniated hindbrain, hydrocephalus • Associated abnormalities o "Polygyria" (too many small crowded gyri) with normal 6 layer lamination o +/- Absent septum pellucidum/fused forniceal columns o Heterotopias o Aqueduct stenosis Microscopic Features • Purkinje cell loss • Variable sclerosis of herniated tissues Staging, Grading or Classification Criteria • Hydrocephalus, brain malformation o Size of PF o Degree of hindbrain descent relate to Presentation • Most common signs/symptoms: Neonate: MMC • Clinical profile oMMC o Enlarging head o Lower extremity paralysis, sphincter dysfunction o Bulbar signs Demographics • Age o Identified in utero or at birth • Fetal screening: i lX-feto protein • Gender: Slight female predominance • Ethnicity o I Incidence in Mexico o Probably associated with high prevalence of MTHFR mutation Natural History & Prognosis • AC2 most common cause of death in MMC o Brainstem compression/hydrocephalus o Intrinsic brain stem "wiring" defects Treatment • Folate supplements given to mothers o From pre-conception to 6 weeks post conception !! (but doesn't eradicate) risk of MMC • Chiari decompression • CSF diversion/shunting • Fetal repair MMC in selected patients may ameliorate severity AC2 Consider • Brainstem compression anesthesia risks Image Interpretation may cause sedation and Pearls • Imaging features due to long term effects of mechanical distortion o "Too small" PF o Cerebellar contents herniate!, i 1. Sarnat HB: Regional Ependymal Upregulation of Vimentin in Chiari II Malformation, Aqueductal Stenosis, and Hydromyelia.Pediatr Dev Pathol. 7(1), 2004 . 2. Reimao R et al: Frontal foramina, Chiari II malformatIOn, and hydrocephalus in a female. Pediatr Neurol 29(4):341-4, 2003 3. Tulipan N et al: Intrauterine myelomeningocele repair. Clin Perinatol. 30(3):521-30, 2003 4. McLone DG et al: The Chiari II malformation: cause and impact. Childs Nerv Syst. 19(7-8):540-50, 2003 5. Aaronson OS et al: Myelomeningocele: prenatal evaluationncomparison between transabdominal US and MR imaging. Radiology 227(3):839-43, 2003 6. Tubbs RSet al: Absence of the falx cerebelli in a Chiari II malformation. Clin Anat 15(3):193-5, 2002 7. Northrup H et al: Spina bifida & other neural tube defects. CUff Probl Pediatr 30:313-32, 2000 8. Coley BD: Ultrasound diagnosis of luckenschadel (lacunar skull). Pediatr Radiol. 30(2):82-4, 2000 9. Mutchinick OM et al: High prevalence of the thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects. Mol Genet Metab 68(4):461-7, 1999 10. Rollins N et al: Coexistent holoprosencephaly and Chiari II malformation. AJNRAm J Neuroradio120(9):1678-81, 1999 11. Lewis DP et al: Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate. Ann Pharmacother 32(7-8):802-17, 1998 Congenital Malformations
  • 45. 1 15 Typical (Left) Axial T2WI MR shows heart-shaped tectum. Shape is due to fusion of collicular bodies (arrow). There is abnormal orientation of the folia of the hypoplastic cerebellum (open arrow). (Right) Axial T2WI MR shows colpocephaly (open arrows), enlarged massa intermedia (arrow), typical pointed anterior horns. Typical (Left) Axial T2WI MR shows interdigitating gyri along the posterior interhemispheric fissure (open arrow), polygyria (arrow). (Right) Axial T2WI MR shows interdigitation (arrow) of gyri due to dehiscent falx (open arrow). Multiple subcortical heterotopias (curved arrow) are seen. Note too many small, short gyri (" stenogyria"). Typical (Left) Sagittal T7 WI MR shows "cascade" (open arrow) of vermis and medullary kink and spur. Pons and 4th ventricle (arrow) are caudally displaced and elongated. Clivus (curved arrow) is scalloped. (Right) Coronal T2WI MR shows "towering" cerebellum due to upward herniation (open arrows) through dehiscent incisural leaves. Deficiency of medial occipital tissue in region of calcar avis (arrow). Congenital Malformations
  • 46. 1 16 Sagittal T7WI MR shows occipital encephalocele, beaked tectum (arrow) and large massa intermedia. Abbreviations • Cisterns, 4th ventricle, dural sinuses (50%) o Hydrocephalus; occasionally absent ventricles o Chiari 2 features • T2WI: Tissues in sac may be bright (gliosis) • MRV: ± Veins in cephalocele and Synonyms • Chiari III, Ch 3 Definitions • High cervical/occipital meningoencephalocele intracranial Chiari 2 malformation + General Features • Best diagnostic clue: Low occipital, high cervical meningoencephalocele • Size: Variable CT Findings • NECT o Occipital squama defect ~ may involve high cervical vertebrae o Bony features of Chiari 2 • Small posterior cranial fossa, scalloped clivus, lacunar skull MR Findings • TIWI o Sac contents • Meninges, cerebellum, Axial T7WI MR shows dysplastic cerebellum and occipital encephalocele. Note that the venous sinuses (arrows) lie intracranially Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Sag Tl WI and MR venogram Isolated occipital encephalocele • Lack intracranial findings of Chiari 2 Other occipital encephaloceles • Iniencephaly: Occipital defect, ectatic foramen magnum +/- encephalocele, dorsal medullary cleft, cervical dysraphism/Klippel-Feil, severe cervicothoracic lordosis, fixed retroflexion of head • Syndromic occipital encephalocele o Meckel-Gruber: Occipital encephalocele, multicystic kidney, polydactyly o Dandy-Walker malformation, Goldenhar-Gorlin, MURCS (Mullerian, renal, cervical-spine), Walker-Warburg, amniotic band ± brain stem DDx: Occipital Encephaloceles Occ Cephalocele C-O-Parietal Cele o Walker + Cele Congenital Malformations Parietal Cele
  • 47. CHIARI3 1 Key Facts Terminology Top Differential • Chiari III, Ch 3 • High cervical/occipital meningoencephalocele intracranial Chiari 2 malformation • Isolated occipital encephalocele + Imaging Findings • • • • Sac contents Cisterns, 4th ventricle, dural sinuses (50%) Hydrocephalus; occasionally absent ventricles Chiari 2 features Diagnoses Pathology • Rare form of Chiari malformations Clinical Issues • Cerebrospinal fluid diversion • Resect or repair sac (most structures in sac are non-functioning) • Mechanical traction brainstem, respiratory deterioration, lower cranial nerve dysfunction IPATHOI..O~¥ General Features • General path comments o High cervical-occipital meningoencephalocele with herniated cerebellar tissue and caudal displacement of brainstem o Embryology-anatomy • Failure of enchondral bone induction by incomplete closure neural tube • Failure of fusion of ossification centers • Parietal extension: Faulty induction or pressure erosion by sac • Genetics o Nearly half NTD cases have 677C ~ T mutation on methylene-tetra-hydrofolate reductase (MTHFR) gene • Especially occipital encephalocele or extensive spina bifida • Leads to t amniotic homocysteine levels • Etiology o Etiologies NTD • Maternal dietary folate deficiency; folate antagonists (anti epileptics) • Toxins: Tripterygium wilfordii (Chinese herbs), arsenic • Maternal hyperthermia • Epidemiology o Rare form of Chiari malformations o 1.5-1/150 of all Chiari cases Demographics • Age: Newborns • Gender: Girls over represented (as in all NTDs) Natural History & Prognosis • Proportional to amount and type of herniated tissue Treatment • Cerebrospinal fluid diversion o Diversion pre-resection sac may allow decreased tension on brain stem • Resect or repair sac (most structures in sac are non-functioning) o Beware venous structures and brainstem! I DIA~NOSTIC CHIECKI..IST Consider • Chiari 3 in newborn with occipital encephalocele I SIEI..IECTIEDRIEFIERIENCIES 1. 2. 3. Caldarelli M et al: Chiari type III malformation. Childs Nerv Syst 18(5):207-10, 2002 Castillo M et al: Chiari III malformation: Imaging features. A]NR 13:107-13, 1992 Cohen MM et al: Syndromes with cephaloceles. Teratology 25(2):161-72, 1982 Gross Pathologic & Surgical Features • Sac contents: Disorganized cerebellum, occasionally occipital/parietal brain tissues Microscopic IIMA~IE ~AI..I..IERY Features • Tissues in sac o Disorganized (neuronal migration anomalies, cortical dysplasias) • Lining of sac may show gray matter heterotopias I CI..INIGAI.. ISSI.JIES Presentation • Most common signs/symptoms: Occipital encephaloceles, microcephaly • Discovered by fetal sonography/MRI or at birth • Developmental delay, spasticity, hypotonia, seizures (Left) 3D CT of midline occipital squama and upper cervical defect (arrows). (Right) Axial T1WI MR shows brainstem!cerebellum protruding through defect (white arrow) (Courtesy S. Blaser, MO). Congenital Malformations 17
  • 48. CALLOSAL DYSGENESIS 18 Coronal graphic shows corpus callosal agenesis with widely spaced lateral ventricles (arrows), high riding 3rd ventricle and "Probst bundles" (open arrows) along the lateral ventricles. Abbreviations • Genu • Body, isthmus • Splenium and Synonyms • Agenesis/dysgenesis ACC corpus callosum (CC), agen CC, Definitions • One or all segments of CC absent (if partial, body remains) General Features • Best diagnostic clue o Axial: Parallel lateral ventricles o Coronal: "Trident" anterior horns resemble "viking helmet" or "moose head" • Location: Midline anomaly • Size o CC remnants vary in size, shape • Remnant may be paper thin or bulbous • Prior to myelin maturation, may be difficult to define • Morphology o CC segments front to back • Lamina rostralis (unmyelinated) • Rostrum (myelinated) DDx: Incomplete Partial Absence Coronal T2WI MR in fetus shows trident shaped lateral ventricles, agenesis of Cc, age appropriate smooth cortex, "Probst bundle" (curved arrow) and vertical hippocampus (arrow). Radiographic Findings • Radiography o Orbital hypertelorism o Rim calcified lipoma (if present) CT Findings • NECT o Lateral ventricles are key to diagnosis • Parallel (non-converging) • Widely separated o Persistent fetal shape • Occipital horns often dilated (colpocephaly) • Pointed frontal horns o Variable findings • Midline cyst, calcified lipoma, high-riding 3rd ventricle • CTA o "Meandering" anterior cerebral arteries (ACAs) o ACAs course directly upwards in interhemispheric fissure MR Findings • TlWI o Sagittal • Radially arrayed gyri "point to" 3rd ventricle Visualization of the Corpus Callosum Callosotomy Callosotomy Congenital Malformations Stretched
  • 49. CALLOSAL DYSGENESIS 1 Key Facts Terminology Top Differential • Agenesis/dysgenesis corpus callosum (CC), agen CC, ACC • One or all segments of CC absent (if partial, body remains) • Destruction of CC • Stretched CC (e.g., hydrocephalus) Imaging Findings • • • Pathology • Most common anomaly seen with other central nervous system (CNS) malformations • Axial: Parallel lateral ventricles • Coronal: "Trident" anterior horns resemble "viking helmet" or "moose head" • Occipital horns often dilated (colpocephaly) • Radially arrayed gyri "point to" 3rd ventricle • Probst bundles: Compact longitudinally oriented white matter tracts, brighter than other myelin on TlWI • Diagnoses • Absent cingulate gyrus • Exquisite demonstration of lipoma if present o Coronal • "Trident-shaped" anterior horns • Elongated foramina of Monro • "Keyhole" temporal horns & vertical hippocampi • Probst bundles: Compact longitudinally oriented white matter tracts, brighter than other myelin on TlWI T2WI o Probst bundles • Represent non-crossing commissural fibers that would have formed CC • Darker than other myelin on T2WI • Indent medial ventricular walls • Course front to back, not side to side (across midline) o Heterotopias and cortical dysplasias not uncommon T2* GRE: Calcified rim of lipoma DWI: DTI: Fiber tracts from all brain regions converge on remnant of CC if partial, form Probst bundles if complete agen MRA o ACAs "meander", no CC genu to curve around o +/- Azygous ACA Clinical Issues • Gender: If isolated finding M > F • Sporadic/isolated ACC: 75% normal or near normal at 3 years • Subtle cognitive defects become apparent with increasing complexity of school tasks Imaging Recommendations • Best imaging tool: MR • Protocol advice o Multiplanar MR (look for additional malformations) o If MR unavailable, multiplanar US or CT will diagnose ACC I DIFFERENTIAL DIAGNOSIS Destruction of CC • Surgery (callosotomy), trauma o Acquired =} interhemispheric disconnection syndrome • Hypoxic ischemic encephalopathy (HIE), infarcts • Metabolic (Machiafavi-Bignami with necrosis, longitudinal splitting of cc Stretched CC (e.g., hydrocephalus) • Thinned CC but all parts present • Severe hydrocephalus often present Immature CC • Pre-myelinated CC may be difficult to confirm, look for cingulate gyrus • MRV o Occasional midline venous anomalies • Persistent falcine sinus common Ultrasonographic I PrTHOlOG¥ Findings General Features • Real Time o Coronal • Absent CC • Trident lateral ventricles • Widely spaced lateral ventricles, colpocephaly o Sagittal • Radially arranged gyri "point to" 3rd ventricle • Color Doppler: ACAs wander between frontal lobes Angiographic Findings • Conventional o ACAs don't conform to normal CC shape o +/- Azygous ACA • General path comments o Associated syndromes/malformations common (50-80%) • Midline anomalies: Lipoma, dorsal/interhemispheric cysts, inferior vermian hypoplasia • Ocular/spinal/facial anomalies • Cortical maldevelopment: Heterotopias, schizencephaly, lissencephaly o Embryology • CC forms in midline lamina between 8-20 fetal weeks Congenital Malformations 19
  • 50. CALLOSAL DYSGENESIS 1 20 • Genetics o Genetics of associated/syndromic CC anomalies • Mendelian syndromes, chromosomal anomalies (trisomy 13) • Midline anomalies (Dandy Walker, Arnold-Chiari) • Malformations of embryonic forebrain occurring prior to CC formation (holoprosencephaly, frontal encephaloceles) • Syndromes/anomalies with mutations in neural adhesion molecules (11CAM) guiding axonal outgrowth and pathfinding • Etiology o Axons fail to form (rare, seen only in severe cortical malformations like cobblestone lissencephaly) o Axons not guided to midline (mutations in adhesion molecules) o Axons reach midline but fail to cross (absence or malfunction of midsagittal guiding "substrate") o Axons turn back, form large aberrant, longitudinal fiber bundles (Probst bundles) o Miscellaneous • Toxic: Fetal alcohol exposure may affect 11 neuronal cell adhesion molecules • Infection: In-utero cytomegalovirus (CMV) • Inborn errors of metabolism: Non-ketotic hyperglycinemia, PDH deficiency, maternal phenylketonuria (PKU), Zellwegers • Epidemiology o 0.5-70 per 10,000 live births o 4% of CNS malformations o Can be isolated (often males), or associated with other CNS malformations • Associated abnormalities o Most common anomaly seen with other central nervous system (CNS) malformations • Too many syndromes to count! Gross Pathologic & Surgical Features • Leaves of septum pellucidum laterally displaced to form membranous roof of lateral ventricles o Project between fornices, Probst bundles • Probst bundles formed by longitudinal callosal bundle o Only form if callosal neurons present o Variable sized bundles smaller than normal CC o Covered with leptomeninges Microscopic Features • Variability of signal ( !T1WI over time) and size (i over time) due to maturation of axonal cytoskeleton Staging, Grading or Classification Criteria • Complete (agenesis) vs partial/variable (dysgenesis) I CI.IN ICA.I.ISSl..JES • Gender: If isolated finding M > F Natural History & Prognosis • Sporadic/isolated ACC: 75% normal or near normal at 3 years o Subtle cognitive defects become apparent with increasing complexity of school tasks • ACC + associated/syndromic anomalies = worst Treatment • Treat associated endocrine deficiencies, seizures Consider • Syndromic associations common • Presence of congenital malformation inherited disorder of metabolism Image Interpretation does not exclude Pearls • Don't stop with the obvious • Look for additional lesions (they are commonly present) I SELECTED REFERENCES Lee SK et al: Diffusion tensor MR imaging visualizes the altered hemispheric fiber connection in callosal dysgenesis. AJNR Am J Neuroradiol. 25(1): 25-28, 2004 2. Moutard M-L et al: Agenesis of corpus callosum: Prenatal diagnosis and prognosis. Childs Nerv Syst 19:471-476, 2003 3. Kuker W et al: Malformations of the midline commissures: MRI findings in different forms of callosal dysgenesis. Eur Radiol. 2003 13(3): 598-604. Epub, 2002 Sato N et al: MR evaluation of the hippocampus in patients 4. with congenital malformations of the brain. AJNR Am J Neuroradiol. 22(2): 389-93, 2001 5. Giedd IN et al: Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study. Prog Neuropsychopharmacol BioI Psychiatry. 23(4): 571-88, 1999 6. Pirola B et al: Agenesis of the corpus callosum with Probst bundles owing to haploinsufficiency for a gene in an 8 cM region of 6q25. J Med Genet. 35(12): 1031-3, 1998 7. Kier EL et al: The lamina rostralis: modification of concepts concerning the anatomy, embryology, and MR appearance of the rostrum of the corpus callosum. AJNR Am J Neuroradiol. 18(4): 715-22, 1997 8. Dobyns WB: Absence makes the search grow longer. (Editorial) AmJ Hum Genet 58:7-16,1996 9. Kier EL et al: The normal and abnormal genu of the corpus callosum: An evolutionary, embryologic, anatomic, and MR analysis. AJNR 17:1631-41,1996 10. Pujol J et al: When does human brain development end? Evidence of corpus callosum growth up to adulthood. Ann Neurol. 34(1): 71-5, 1993 1. Presentation • Most common signs/symptoms o Seizures, developmental delay, microcephaly o Hypopituitarism hypothalamic malfunction • Clinical profile: Hypertelorism Demographics • Age: Any age, usually identified early childhood Congenital Malformations
  • 51. 1 21 Typical (Left) Sagittal T2WI MR shows complete agenesis of the corpus callosum and a radial array (arrow) of gyri "pointing" to the 3rd ventricle. (Right) Sagittal sonography shows radially arranged gyri "pointing" (arrow) to the third ventricle. Typical (Left) Coronal T2WI MR shows agenesis of the corpus callosum, trident shaped lateral ventricles, vertical hippocampi (open arrow), enlarged, "keyhole" shaped temporal horns and Probst bundles (curved arrow). (Right) Axial T2WI MR shows parallel, widely spaced lateral ventricles. Note adjacent Probst bundle (open arrow). Typical (Left) Axial NECT with widened "windows" shows colpocephaly, calcified (arrow) midline lipoma that extends through choroid fissures into lateral ventricles (open arrows). (Right) Axial TlWI MR shows parallel ventricles, colpocephaly, and a midline lipoma. Note lipoma (arrow) protruding into the lateral ventricles. Congenital Malformations
  • 52. 22 Coronal graphic shows CC agenesis with a bulky tubonodular-type interhemispheric lipoma (open arrow) that extends into lateral ventricles (arrows), encasing ACAs (curved arrow). Abbreviations • Intracranial and Synonyms lipoma (lCL); lipomatous hamartoma Definitions • Mass of mature non-neoplastic adipose tissue o CNS lipomas are congenital malformations, not true neoplasm o Lipoma variants in the CNS include: Angiolipoma, hibernoma, osteolipoma General Features • Best diagnostic clue: Well-delineated lobulated extra-axial mass with fat attenuation/intensity • Location o Midline location common o 80% supratentorial • 40-50% interhemispheric fissure (over corpus callosum; may extend into lateral ventricles, choroid plexus) • 15-20% suprasellar (attached to infundibulum, hypothalamus) • 10-15% pineal region (usually attached to tectum) DDx: lipoma Ossified Falx Sagittal TlWI MR shows a classic curvilinear interhemispheric lipoma (arrows). Other than mild hypoplasia of the splenium, the CC appears normal. • Uncommon: Meckel cave, lateral cerebral fissures, middle cranial fossa o 20% infratentorial • Cerebellopontine angle (may extend into lAC, vestibule) • Uncommon: Jugular foramen, foramen magnum • Size: Varies from tiny to very large • Morphology o Lobulated pial-based fatty mass that may encase vessels & cranial nerves o Two kinds of interhemispheric lipoma • Curvilinear type (thin ICL curves around CC body, splenium) • Tubulonodular type (bulky mass; frequent CaH, usually associated with CC agenesis) Radiographic Findings • Radiography o Usually normal o Very large interhemispheric lipomas may show low density o Tubulonodular lipomas may show rim Ca++ CT Findings • NECT o -50 to -100 H (fat density) o Ca++ varies from none to extensive • Present in 65% of bulky tubulonodular lipomas (T1 Shortening) Pineal Teratoma Ruptured Dermoid Congenital Malformations Thrombosed Aneurysm CC
  • 53. LIPOMA 1 Key Facts Terminology Top Differential • Mass of mature non-neoplastic adipose tissue • CNS lipomas are congenital malformations, not true neoplasm • • • • Imaging Findings • Best diagnostic clue: Well-delineated lobulated extra-axial mass with fat attenuation/intensity • 40-50% interhemispheric fissure (over corpus callosum; may extend into lateral ventricles, choroid plexus) • -50 to -100 H (fat density) • Ca++ varies from none to extensive • Standard SE: Hyperintense on TlWI • Becomes hypointense with fat suppression • Standard SE: Hypointense with striking chemical shift artifact (CSA) on T2WI • Rare in posterior fossa, para sellar lesions • CECT: Doesn't enhance • CTA: May demonstrate aberrant ACA course in interhemispheric CC lipoma associated with callosal dysgenesis Diagnoses Dural dysplasia Dermoid Teratoma Lipomatous differentiation/transformation neoplasm • Subacute hemorrhage 23 of Pathology • Cranial, spinal intradural fat is a congenital anomaly (not a true neoplasm) • Persistence, maldevelopment of embryonic meninx primitiva I DIFFERENTIAl.. DIAGN0818 Dural dysplasia • Fat not normally found inside dura • Metaplastic ossified dura may contain fat MR Findings Dermoid • TlWI o Standard SE: Hyperintense on Tl WI o Becomes hypo intense with fat suppression • T2WI o Standard SE: Hypointense with striking chemical shift artifact (CSA) on T2WI • Round/linear "filling defects" present where vessels, cranial nerves pass through lipoma • May show low signal intensity foci (Ca++) o FSE: Iso- to hyperintense (j-coupling) • PD/lntermediate o Standard SE: Iso- to hyperintense (depending on TR/TE) • Striking CSA • STIR: Hypointense • FLAIR: Hyperintense • DWI: Diffusion tensor imaging visualizes altered fiber connections if associated callosal dysgenesis present • Tl C+: Doesn't enhance • MRA: May show aberrant ACA in callosal agenesis • Density usually 20 to 40 H • Signal intensity usually more heterogeneous than lipoma • Rupture with cisternal fat droplets common • Usually no associated malformations (common with lipoma) • Dermoids often calcify, lipomas in locations other than interhemispheric don't Ultrasonographic Findings • Real Time o Generally hyperechoic o May show other fetal anomalies (CC agenesis, etc) Angiographic Findings • Conventional o ACA courses directly superiorly if CC agenesis present o Arteries & veins often embedded within lipoma Imaging Recommendations • Best imaging tool: MR • Protocol advice: Add fat suppression confirmation sequence for Teratoma • Locations similar to lipoma • Tissue from all 3 embryonic germ layers o May have prominent adipose component o Other: Mucous cysts, chondroid nodules, bony spicules o Teeth, well-formed hairs rarely present • Imaging appearance usually more heterogeneous o May show foci of contrast-enhancement Lipomatous differentiation/transformation neoplasm • May occur occasionally in neuroectodermal tumors (PNETs, ependymoma, gliomas) • Cerebellar liponeurocytoma o Newly-recognized mixed mesenchymal/neuroectodermal posterior fossa neoplasm o Primarily hypointense on Tl WI, mixed with hyperintense foci o Patchy, irregular enhancement • Other neoplasms with prominent lipomatous elements o Meningioma (lipomatous transformation uncommon) o Metastases tumor (rare) Congen ital Malformations of
  • 54. 1 24 Subacute hemorrhage Demographics • Tl shortening can be confused with lipoma • Use T2* (hemorrhage blooms), fat-saturation (hemorrhage doesn't suppress) • Age: Any age • Gender: M = F • Ethnicity: None known Natural History & Prognosis General Features • General path comments o Fat not normally present in CNS o Cranial, spinal intradural fat is a congenital anomaly (not a true neoplasm) • Genetics o No known defects in sporadic ICL o Occurs in encephalocraniocutaneous lipomatosis, a congenital neurocutaneous syndrome • Etiology o Persistence, maldevelopment of embryonic meninx primitiva • Normally differentiates into leptomeninges, cisterns • Maldifferentiates into fat instead o Developing pia-arachnoid invaginates through embryonic choroid fissure • Explains frequent intraventricular extension of interhemispheric lipomas • Epidemiology: < 0.5% of all intracranial tumors (not true neoplasm) • Associated abnormalities o Most common: Interhemispheric lipoma + corpus callosum anomalies o Other congenital malformations • Cephaloceles • Closed spinal dysraphism o Encephalocraniocutaneous lipomatosis => Fishman syndrome o Pai syndrome => facial clefts, skin lipomas; occasional ICLs, usually interhemispheric Gross Pathologic & Surgical Features • Yellow lobulated fatty mass attached to leptomeninges, sometimes adherent to brain • Cranial nerves, arteries/veins pass through lipoma Microscopic Features • Identical to adipose tissue elsewhere • Cells vary slightly in shape/size, measure up to 200 microns • Occasional nuclear hyperchromasia • Mitoses rare/absent • Liposarcoma = extremely rare malignant intracranial adipose tumor Presentation • Most common signs/symptoms o Usually found incidentally at imaging, autopsy o Rare: Cranial neuropathy (vestibulocochlear dysfunction, facial pain), seizures (associated with other congenital anomalies) • Benign, usually stable • May expand with corticosteroids o High-dose, long-term administration neural compressive symptoms may result in Treatment • Generally not a surgical lesion; high morbidity/mortality • Reduce/eliminate steroids I DIAGNOSTIC CHECKLIST Consider • Could high signal on T1WI be due to other substances with short T1 (e.g., subacute hemorrhage)? Image Interpretation Pearls • When in doubt, use fat-saturation I SELECTED sequence REFERENCES 1. Lee SKet al: Diffusion tensor MR imaging visualizes the altered hemispheric fiber connection in callosal dysgenesis. AJNR25: 25-8, 2004 2. Gaskin CM et al: Lipomas, lipoma variants, and well-differentiated liposarcomas (atypical lipomas). AJR 182: 733-9, 2004 3. Tankere F et al: Cerebellopontine angle lipomas: report of four cases and review of the literature. Neurosurg 50: 626-31, 2002 4. Fitoz S et al: Intracranial lipoma with extracranial extension through foramen ovale in a patient with encephalocraniocutaneous lipomatosis syndrome. Neuroradiol44: 175-8, 2002 5. Kiymaz N et al: Central nervous system lipomas. Tohoku J Exp Med. 198: 203-6, 2002 6. Kurt G et al: Hypothalamic lipoma adjacent to mammillary bodies. Childs Nerv Syst 18: 732-4, 2002 Ickowitz V et al: Prenatal diagnosis and postnatal follow-up 7. of peri callosal lipoma: Report of seven new cases. AJNR 22: 767-72,2001 8. Feldman RP et al: Intracranial lipoma of the sylvian fissure. Case report and review of the literature. J Neurosurg. 94(3):515-9,2001 9. Alafaci C et al: Trigeminal pain caused by a cerebellopontine-angle lipoma. Case report and review of the literature. J Neurosurg Sci. 45(2):110-3, 2001 10. Kieslich M et al: Midline developmental anomalies with lipomas in the corpus callosum region. J Child Neurol. 15(2):85-9, 2000 11. Ichikawa T et al: Intracranial lipomas: demonstration by computed tomography and magnetic resonance imaging. J Nippon Med Sch. 67(5):388-91, 2000 12. Amor DJ et al: Encephalocraniocutaneous lipomatosis (Fishman syndrome): a rare neurocutaneous syndrome. J Paediatr Child Health. 36(6):603-5, 2000 Congenital Malformations
  • 55. 1 25 Typical (Left) Sagittal Tl WI MR shows a small interhemispheric lipoma (arrows) above the corpus callosum, found incidentally at MR imaging in this patient with headache. (Right) Sagittal Tl WI MR with fat-saturation shows complete signal suppression (open arrows), confirming the diagnosis of intracranial lipoma. (Left) Sagittal TlWI MR shows a well-circumscribed high signal lesion in the pineal region (arrow). The patient was asymptomatic. (Right) Axial gross pathology shows a quadrigeminal lipoma (arrow) with classic yellowish, slightly lobulated appearance. The lesion was found incidentally at autopsy (Courtesy E.T. Hedley-Whyte, MO). Variant (Left) Sagittal Tl WI MR shows a small hypothalamic lipoma (arrow), found incidentally in this patient with headache and normal neurologic examination. Also note the "empty sella". (Right) Sagittal TlWI MR shows an enormous lipoma occupying most of the posterior fossa and cervical spine (open arrows). Note large cutaneous lipoma (arrow). Encephalocraniocutaneous lipomatosis. Congenital Malformations
  • 56. DANDY WALKER SPECTRUM 26 Sagittal graphic shows enlarged posterior fossa, elevated torcular Herophili (arrow), superior rotation of small vermian remnant (open arrow) over large cyst with thin wall (curved arrow). Abbreviations General Features and Synonyms • Dandy Walker (DW) spectrum (DWS); DW complex (DWC); "classic" DW malformation (DWM); DW variant (DWV) • Persistent Blake pouch cyst (BPC), mega cisterna magna (MCM) Definitions • DWS represents a broad spectrum of cystic posterior fossa (PF) malformations o 4th ventriculocele variant of DWM • DWM in which large cyst erodes occipital bone =} "encephalocele" OR encysted 4th ventricle (4th V) herniates into occipital encephalocele o "Classic" DWM • Cystic dilatation of 4th V =} enlarged PF, superiorly rotated vermian remnant o DW "variant" • Vermian hypoplasia + partial obstruction 4th V o BPC • Failure of regression of BPC + compression/obliteration of basal cisterns may explain appearance of "open 4th ventricle" oMCM • Enlarged cisterna magna communicates freely with 4th V, basal subarachnoid spaces Classic OWS Sagittal T2WI MR shows large rotated vermian remnant. There is a hypoplasdc fastigial crease (curved arrow). The cyst wall is visible (arrow) and the posterior fossa is expanded. OW Variant • Best diagnostic clue o DWM: Large PF + big cerebrospinal fluid (CSF) cyst, normal 4th ventricle (V) absent o DWV, BPC: Failure of "closure" of 4th V • Location: Posterior fossa • Size: Varies from slightly enlarged cisterna magna to huge PF cyst • Morphology o DWS (from most to least severe) • 4th ventriculocele (10-15% of cases): DWM plus posterior outpouching • "Classic" DWM: Small hypoplastic vermis superiorly rotated by cyst, torcular arrested in fetal position (cyst mechanically hinders caudal migration) • DWV (mild form of DW complex): Variable vermian hypoplasia, no or small cyst, normal sized PF/brainstem, "keyhole" vallecula • BPC: "Open" 4th ventricle communicates with cyst, basal cisterns +/- completely effaced • MCM: Large PF, normal vermis/4th ventricle, cistern crossed by falx cerebelli, tiny veins Radiographic Findings • Radiography Open 4th Ventricle Congenital Malformations Retro CBLL Cyst
  • 57. DANDY WALKER SPECTRUM ,-----------------------------------------------, 1 Key Facts Terminology Top Differential • Dandy Walker (DW) spectrum (DWS); DW complex (DWC); "classic" DW malformation (DWM); DW variant (DWV) • Persistent Blake pouch cyst (BPC), mega cisterna magna (MCM) • DWS represents a broad spectrum of cystic posterior fossa (PF) malformations • 4th ventriculoceIe variant of DWM • PF arachnoid cyst (retrocerebellar, supravermian or in cerebellopontine angle) • Congenital vermian hypoplasia (prototype = Joubert anomaly) • Isolated 4th ventricle • 2/3 have associated CNS/extracranial Imaging Findings Clinical Issues • DWM: Large PF + big cerebrospinal fluid (CSF) cyst, normal 4th ventricle (V) absent • DWV, BPC: Failure of "closure" of 4th V • DWM: Macrocephaly, bulging fontanel, etc • Classic DWM: Early death common (up to 44%) o Enlarged calvarium, particularly posterior fossa o DWM: Lambdoid-torcular inversion (transverse sinus grooves elevated above lambda) • Sinuses are originally above lambda in fetus, cyst mechanically hinders descent Diagnoses 27 Pathology anomalies • FLAIR: Very slight differentiation between cyst, compressed basal cisterns may be present • DWI: Very slight diffusion restriction in cyst may be seen • MRV: Elevated torcular Herophili (DWM) CT Findings Ultrasonographic • NECT o DWM: Large posterior fossa • Variable-sized cyst communicates with 4th V • Torcular-lambdoid inversion (torcular above lambdoid suture) o Occipital bone may appear scalloped, remodeled with all DWS types, including MCM • Real Time: Fetal diagnosis of DWM and DWV possible Findings Imaging Recommendations • Best imaging tool: MR best characterizes severity, associated anomalies • Protocol advice: Routine MR imaging (thin sagittal views crucial) MR Findings • TIWI o Sagittal DWM • Floor 4th V present • 4th v opens dorsally to variable-sized CSF cyst • Cyst wall difficult to discern • Vermian remnant (variable presence of fastigium, fissures) rotated up, over cyst • +/- Remnant fused to tentorium • Elevated torcular with high/steeply sloping tentorium (classic) o Sagittal DWV • Smaller PF +/- cyst • 4th V "open" with partial rotation vermis, presence of fastigium and fissures variable o Sagittal BPC • Rotated but normal-appearing vermis • Free communication of 4th V with prominent inferior CSF space • Basal cisterns compressed posteriorly or effaced o Sagittal MCM • Normal vermis (not rotated/hypoplastic) • 4th V is "closed" • T2WI o Associated anomalies • Cortical dysplasia, heterotopias, myelination delays (syndromic DWS) I DIFFERENTIAL DIAGNOSIS DW spectrum • "In-between" cases common PF arachnoid cyst (retrocerebellar, supravermian or in cerebellopontine • • • • angle) Included in DW spectrum by some authors Normal 4th V compressed or displaced AC not traversed by falx cerebelli, tiny veins ACs lined by arachnoid cells/collagen Congenital vermian hypoplasia (prototype Joubert anomaly) = • Episodic hyperpnea, oculomotor apraxia, retinal dystrophy; +/- renal cysts, hepatic fibrosis • Split vermis, "bat-wing" 4th V, mesencephalon shaped like "molar-tooth" Isolated 4th ventricle • Inferior 4th ventricle "closed" versus "open" in DWM/DWV on sagittal view • May be normal or 1 size Congenital Malformations
  • 58. DANDY WALKER SPECTRUM 1 28 Demographics • Age: DWM: 80% diagnosed by 1 Y • Gender: M ::0; F General Features • General path comments o Embryology • Common association DWM/DWV with facial, cardiovascular anomalies suggests onset between formation, migration of neural crest cells (3rd-4th post-ovulatory week) • Genetics o Majority sporadic, X-linked DWM reported o Many, many syndromes with DWS • Chromosomal or midline anomalies; PHACE (facial hemangiomas, coarctation, DW in 81 %) • Etiology o Rhombencephalic roof divides into cephalic (anterior membranous area AMA) and caudal (posterior membranous area PMA) • AMA invaded by neural cells =}becomes CBLL • PMA expands then disappears to form outlet foramina of 4th V o Hindbrain development arrest • Defective formation AMA and PMA =} DWM and DWV • Defective PMA only =} BPC and MCM • Epidemiology o 1:25,000-100,000 births o Accounts for 1-4% of all hydrocephalus cases • Associated abnormalities o 2/3 have associated CNS/extracranial anomalies • Craniofacial, cardiac/urinary tract anomalies, polydactyly, orthopedic and respiratory problems Gross Pathologic & Surgical Features • DWM: Large posterior fossa with big CSF-containing cyst o Inferior margin vermian remnant continuous with cyst wall o 4th V choroid plexus absent or displaced into lateral recesses Microscopic Natural History & Prognosis • Classic DWM: Early death common (up to 44%) • Cognitive outcome dependent upon associated syndromes or supratentorial anomalies/hydrocephalus and completeness of residual vermis o Intelligence normal in 35 to 50% of classic DWM • If small remnant without fissures or fastigium: Seizures, developmental delay, poor motor skills/balance • If large remnant with normal lobulation and fastigium and normal supratentorial brain: Good outcome even if classic DWM Treatment • CSF diversion IF hydrocephalus: shunt/marsupialization I.D1AGNt)SIl(J(Jt-(E()ls:lIS-r Consider • Many associated syndromes, Image Interpretation • DWM: Outer cyst wall layer continuous with leptomeninges o Intermediate stretched neuroglial layer is continuous with vermis o Inner layer of glial tissue lined with ependyma/ependymal nests o Anomalies of inferior olivary nuclei/corticospinal tract crossings Staging, Grading or Classification Criteria 1. 2. 4. 5. 6. 7. 8. 9. • Most common signs/symptoms o DWM: Macrocephaly, bulging fontanel, etc o MCM: Incidental finding • Clinical profile: Marked heterogeneity in genetic, clinical findings Pearls I SELECTED REFERENCES • Spectrum: DWM with 4th ventriculocele (most severe) =} classic DWM=} DWV =} BPC =} MCM (mildest) Presentation "look-alikes" • Presence of fastigium/vermian lobulation predicts good outcome • Thin sagittal views in Tl-, T2WI crucial for delineation, diagnosis 3. Features VP shunt (+/-) cyst ten Donkelaar HJ et al: Development and developmental disorders of the human cerebellum. J Neurol 250(9):1025-36, 2003 Klein 0 et al: Dandy-Walker malformation: Prenatal diagnosis and prognosis. Childs Nerv Syst 19(7-8):484-9, 2003 Boddaert N et al: Intellectual prognosis of the Dandy-Walker malformation in children: The importance of vermian lobulation. Neuroradiology 45(5):320-4, 2003 Patel S et al: Analysis and classification of cerebellar malformations. AJNR 23(7):1074-87,2002 Calabro F et al: Blake's pouch cyst: An entity within the Dandy-Walker continuum. Neuroradiology 42(4):290-5, 2000 Kalidasan V et al: The Dandy-Walker syndrome--a lO-year experience of its management and outcome. Eur J Pediatr Surg 5 Suppll:16-8, 1998 Tortori-Donati P et al: Cystic malformations of the posterior cranial fossa originating from a defect of the posterior membranous area. Mega cisterna magna and persisting Blake's pouch: Two separate entities. Childs Nerv Syst 12:303-8, 1996 Pascual-Castroviejo I et al: Dandy-Walker malformation: analysis of 38 cases. Childs Nerv Syst 7(2):88-97, 1991 Barkovich AJ et al: Revised classification of posterior fossa cysts and cyst-like malformations based on the results of multiplanar MR imaging. AJR 153:1289-300, 1989 Congenital Malformations
  • 59. 1 29 Typical (Left) Coronal oblique 3D MR SPCR reconstruction with removal of the cyst wall shows tentorial elevation and hypoplastic cerebellar hemispheres. The small vermian remnant (arrow) is superiorly rotated. (Right) Axial T2WI MR shows enlarged posterior fossa and hypoplastic cerebellar hemispheres. The vermis is absent. (Left) Coronal T2WI MR shows "keyhole" configuration formed by large 4th ventricle communicating with large vallecula (arrows). There are hypoplastic cerebellar hemispheres. (Right) Coronal T2WI MR in another child shows Inverted "Y" of elevated tentorium (arrows) and torcular (open arrow). (Left) Sagittal T2WI MR shows elevation of the torcular Herophili (arrow). There is expansion of the posterior fossa and formation of a 4th ventriculocele (curved arrow). The vermian remnant is small. (Right) Lateral MR venogram demonstrates angled "transverse" sinuses (curved arrows) rising to the elevated torcular Herophili (arrow) in the same child. Congenital Malformations
  • 60. RHOMBENCEPHALOSYNAPSIS 30 Axial graphic shows absence of vermis. There is fusion of folia, interfoliate sulci, dentate nuclei (arrow) and cerebellar white matter (open arrow) across the midline. Axial T2WI MR in a neonate shows similar features. There is fusion of the dentate nuclei (arrow) and of the folia across the midline (open arrows). o Narrow diamond or "keyhole" shaped 4th ventricle o Narrowed transverse diameter of cerebellum Abbreviations and Synonyms • Rhombencephalosynapsis MR Findings (RES) Definitions • Congenital fusion of cerebellar hemispheres, dentate nuclei, and superior cerebellar peduncles; vermian agenesis I.INf;(jlN(jfINDtNG;~ General Features • Best diagnostic clue: Hypoplastic, single lobed cerebellum • Location: Midline posterior fossa • Size: Narrowed transverse diameter of cerebellum • Morphology: One hemisphere, not two Radiographic Findings • Radiography o Bilateral lambdoid synostosis => "flattened" occiput o Occasionally associated with holoprosencephaly => hypotelorism or midline facial anomalies/clefts CT Findings • NECT o Cerebellar hemispheric • TlWI o Coronal • Fused cerebellar hemispheres: Total or partial • Absent or severely hypoplastic vermis • +/- Septo-optie-dysplasia or holoprosencephaly o Sagittal • Absent primary fissure (usually easy to find in normal cerebellum) • +/- Fastigial recess of 4th ventricle appears upwardly rounded • +/- Aqueductal stenosis => hydrocephalus • +/- Corpus callosum dysgenesis (especially posterior) o Axial • Narrow diamond or "keyhole" shaped 4th ventricle • +/- Holoprosencephaly • T2WI o Transverse folia o Absent posterior cerebellar notch and vallecula o Fused horseshoe-shaped dentate nuclei • May be "apposed, not fused" in mild cases o +/- Cortical dysplasias • FLAIR: No gliosis fusion DDx: Transverse Folia Deformed Post-shunt Post-shunt Partial RES Congenital Malformations Partial RES
  • 61. RHOMBENCEPHALOSYNAPSIS Key Facts Terminology Pathology • Rhombencephalosynapsis (RES) • Congenital fusion of cerebellar hemispheres, dentate nuclei, and superior cerebellar peduncles; vermian agenesis • Likely genetic defect "isthmic organizer" ::} abnormal dorsal patterning • Extremely rare but increasingly recognized on MR • Prosencephalic and midline facial anomalies common Imaging Findings Clinical Issues • Best diagnostic clue: Hypoplastic, single lobed cerebellum • Size: Narrowed transverse diameter of cerebellum • Morphology: One hemisphere, not two • Narrow diamond or "keyhole" shaped 4th ventricle Top Differential • Short lifespan usual Diagnostic Checklist • Remember to define associated supratentorial anomalies Diagnoses • Chronic shunting • Congenital vermian hypoplasia (prototype == Joubert) • T2* GRE: Occasional TORCH-related or dystrophic Ca++ of supratentorial white matter • MRA o Azygous anterior cerebral artery (if holoprosencephaly present) o No posterior circulation arterial anomalies described Ultrasonographic • Findings • Real Time: Has been reported in fetal sonography (rare) Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Multiplanar MRI • I DIFFERENTIAL DIAGNOSIS Chronic shunting • Distortions especially in Chiari 2 malformation rotation or unilateral herniation with Congenital vermian hypoplasia (prototype Joubert) • Vermian agenesis or hypogenesis, hemispheres not fused = but cerebellar Syndromic vs non-syndromic rhombencephalosynapsis • Complicated midline anomaly syndromes • Gomez-Lopez-Hernandez (cerebellotrigeminal dysplasia) o Rhombencephalosynapsis o Trigeminal anesthesia o Midface hypoplasia o Scalp: Bilateral bands of alopecia I PATHOLOGY General Features • General path comments o Embryology-Anatomy dermal • • • Failure of induction/differentiation of normal midline structures • Lateral structures relatively preserved Genetics o Likely genetic defect "isthmic organizer" ::} abnormal dorsal patterning • FGF8 and Lmxla genes being considered o Gomez-Lopez-Hernandez syndrome • Likely under-recognized • Inheritance unknown o Anecdotal reports • Interstitial deletion chromosome 2q • Parental consanguinity Etiology o Disturbed early cerebellar development (genetic or acquired): 33-34 days gestation o Maternal environment • Hyperpyrexia • Diabetes • Phencyclidine or alcohol Epidemiology o Extremely rare but increasingly recognized on MR o Approximately SO cases reported Associated abnormalities o Prosencephalic and midline facial anomalies common o Occasional associated extracranial anomalies • Segmentation and fusion anomalies in spine • Cardiovascular (conotruncal) anomalies reported • Variable respiratory, GU anomalies reported • Musculoskeletal anomalies common: Phalangeal and radial-ray Gross Pathologic & Surgical Features • Usual o Fused cerebellar hemispheres o Fused cerebellar white matter::} large corpus medullare o Absent posterior cerebellar incisura, vallecula o Horseshoe-shaped dentate nuclei o Agenesis or hypogenesis anterior vermis, velum medullare anterior and nuclei fastigii o Hypoplastic posterior vermis: Nodulus may form Congen ital Malformations 1 31
  • 62. RHOMBENCEPHALOSYNAPSIS 32 • Often o Supratentorial midline anomalies • Commissural (corpus callosum, anterior commissure) dysgenesis/hypoplasia • Holoprosencephaly or septo-optic dysplasia • Fused inferior colliculij absent dorsal olivary nuclei o Aqueductal stenosis-related hydrocephalus o Craniosynostosis (especially lambdoid) • Rare o Aventriculy (also called synencephaly or telencephalosynapsis)j encysted 4th ventricle Staging, Grading or Classification Criteria • Isolated or involves supratentorial • Fusion can be partial or total midline structures ICtINIC)l.IS$lJES Presentation • Most common signs/symptoms o Variable neurological signs • Ataxia, gait abnormalities • Involuntary head movement • Developmental delay • Seizures • Cerebral palsy • Compulsive self-injurious behavior common • Rare: Near normal patients have been discovered at autopsy • Clinical profile o Ataxia o Developmental delay o Variable growth hormone deficiency (depends on supratentorial midline anomalies) • Remember to define associated supratentorial anomalies Image Interpretation Pearls • Can be simulated by mechanically induced cerebellar deformation in chronically shunted patients 1. Demaerel P et al: Partial rhombencephalosynapsis. AJNR 25(1):29-31,2004 2. Toelle SP et al: Rhombencephalosynapsis: Clinical findings and neuroimaging in 9 children. Neuropediatrics 33:209-14,2002 3. Patel S et al: Analysis and classification of cerebellar malformations. AJNR23:1074-87,2002 4. Yachnis AT:Rhombencephalosynapsis with massive hydrocephalus: Case report and pathogenetic considerations. Acta Neuropathol103(3):305-6, 2002 5. Brocks D et al: Gomez-Lopez-Hernandez syndrome: Expansion of the phenotype. Am J Med Genet 94(5):405-8, 2000 6. Takanashi J et al: Partial midline fusion of the cerebellar hemispheres with vertical folia: A new cerebellar malformation. AJNR20(6):1151-3, 1999 7. Utsonomiya H et al: Rhombencephalosynapsis: Cerebellar embryogenesis. AJNR 19(3):547-9, 1998 8. Romanengo M et al: Rhombencephalosynapsis with facial anomalies and probable autosomal recessive inheritance: A case report. Clin Genet 52(3):184-6, 1997 9. Isaac M et al: Two cases of agenesis of the vermis of cerebellum, with fusion of the dentate nuclei and cerebellar hemnipheres. Acta Neuropathol 74(3):278-80, 1987 10. Lopez-Hernandez A. craniosynostosis, ataxia, trigeminal anaesthesia and parietal alopecia with pons-vermis fusion anomaly (atresia of the fourth ventricle). Report of two cases. Neuropediatrics 13(2):99-102, 1982 Demographics • Age o Usually found during early infancy or childhood o Rare incidental finding • Gender: No gender or ethnic predilection Natural History & Prognosis • Short lifespan usual • Occasional survival to early adult life o Developmental delay o Psychiatric disorders (self-injurious, bipolar, hyperactive) • Additional midline supratentorial anomalies and hydrocephalus ~ worse prognosis Treatment • Treat related hydrocephalus, monitor hypothalamic-pituitary axis IOIAGNgSTIGGI--iECKEIST Consider • Isolated rhombencephalosynapsis is less common than rhombencephalosynapsis with supratentorial anomalies Congenital Malformations
  • 63. RHOMBENCEPHALOSYNAPSIS 1 33 Typical (Left) Axial T2WI MR shows fusion of the interfoliate sulci and of the gray and white matter (arrow) of the folia across the midline. (Right) Coronal T2WI MR shows typical transverse folia (arrow) and sulci. (Left) Axial NECT shows a "keyhole" shaped 4th ventricle. There is a narrow transverse cerebellar diameter, midline fusion of the cerebellar white matter (arrow) and faint frontal Ca++ (curved arrow). (Right) Axial T2WI MR shows "keyhole" shaped 4th ventricle (arrow) and midline fusion of cerebellar white matter. Note lack of normal vermian tissue and lack of hemispheric separation. (Left) Sagittal T2WI MR shows slight rounding of the fastigial recess (arrow) and absence of the primary fissure in a child with isolated rhombencephalosynapsis. (Right) Sagittal TlWI MR in a patient with atrophy of an otherwise normal cerebellum shows a sharp fastigial recess (arrow) and a well defined primary fissure (open arrow). Congenital Malformations
  • 64. CONGENITAL VERMIAN HYPOPLASIA 34 Sagittal T1WI MR shows vermian remnant (arrows). 4th ventricle and cisterna magna are large. Fastigial point and primary fissure are lacking. The brainstem and pituitary axis are small. Axial T2WI MR shows the typical "molar tooth" (arrow) appearance of the brainstem. There is clefting of the vermis (curved arrow). o +/- Pre and postaxial polydactyly o Syndactyly Abbreviations and Synonyms CT Findings • Congenital vermian hypoplasia (CVH) o Prototype = Joubert syndrome, Joubert-Boltshauser syndrome • Cerebelloparenchymal disorder IV (CPD IV) Definitions • Inherited hypoplasia or aplasia of vermis characterized by transient episodic hyperpnea, oculomotor abnormalities, ataxia, variable mental retardation • NECT o Enlarged, "bat-wing" or "open umbrella" 4th ventricle o "Molar-tooth" pons/midbrain • Deficient anterior vermis • Thin or thick superior cerebellar (CBLL) peduncles o "Buttocks sign" • Only narrow cleft separates CBLL hemispheres MR Findings General Features • Best diagnostic clue o "Molar tooth" brainstem o "Bat-wing" or " umbrella" shaped 4th ventricle o Cleft vermis • Location: Vermis of cerebellum • Size: Vermian remnant variable size • Morphology: Complex brainstem malformation ~ "molar-tooth" brainstem appearance Radiographic Findings • Radiography • TlWI o Above PLUS • +/- Small vermian remnant (if residual, often cleft) • +/- Variable brainstem hypoplasia • Abnormally deep interpeduncular fossa • Midline anomalies common (holoprosencephaly, frontonasal dysplasia, facial clefting) • Pituitary hypoplasia • Enlarged superior ampulla of aqueduct • T2WI o +/- t Signal periventricular white matter o +/- t Signal in decussation of superior CBLL peduncles . o +/- Persistent embryonic vessels along CBLL folIa o +/- Hamartomas or heterotopias Congenital Malformations
  • 65. CONGENITAL VERMIAN HYPOPLASIA Key Facts Terminology • Rhombencephalosynapsis • Congenital vermian hypoplasia (CVH) • Prototype = Joubert syndrome, Joubert-Boltshauser syndrome • Inherited hypoplasia or aplasia of vermis characterized by transient episodic hyperpnea, oculomotor abnormalities, ataxia, variable mental retardation Imaging Findings • • • • "Molar tooth" brainstem "Bat-wing" or " umbrella" shaped 4th ventricle Cleft vermis Size: Vermian remnant variable size Top Differential • Dandy-Walker Ultrasonographic Diagnoses I PATHOLOGY Findings Imaging Recommendations • Best imaging tool: MRI brain • Protocol advice o MRI brain o Abdominal sonogram I DIFFERENTIAL DIAGNOSIS Dandy-Walker spectrum (DWS) Anterior vermian remnant present in DWS Posterior vermian remnant usually remains in CVH Cyst in classic DWS Widely separated CBLL hemispheres in DWV and classic DWS "CVH-plus" (numerous) Diagnostic Checklist • Special care in sedation or anesthesia for neuroimaging examinations • Look for fastigial point of 4th ventricle, primary fissure on sagittal views as first clues to diagnosis spectrum (DWS) • Real Time o Posterior anomalies difficult to confirm on head ultrasound o Non-cranial ultrasound • Renal anomalies (often cysts) • +/- Hepatic fibrosis • +/- Cardiac anomalies • • • • Pathology • Many syndromes with congenital vermian hypoplasia • Joubert syndrome is prototype: Only brain findings on imaging • If more than brain findings = one of many "CVH plus" syndromes: (+ Renal cysts/hepatic fibrosis/ocular abnormalities) eponymous syndromes • Mohr; Rischer-Schinzel; Varadi (soft tissue tumors in tongue) • Meckel-Gruber; Dekaban; ectodermal dysplasia/brain cysts; Arima • Senior-Loken: Leber congenital amaurosis plus juvenile nephronophthisis • Coach (includes hepatic fibrosis); cerebello-oculo-hepa to- renal • Look for extra cranial features in all of above Rhombencephalosynapsis • No vermis, but cerebellar hemispheres are fused General Features • General path comments o If Joubert: CVH only o If cerebello-oculo-renal = CVH + some of the following • Renal: Congenital renal cysts; cystic dysplastic kidney, juvenile nephronophthisis NH1; renal cystic disease unlikely in patients without retinal dystrophy • Oculo: Retinal dystrophy similar to Leber congenital amaurosis, chorioretinal colobomata • Other: Congenital hepatic fibrosis; poly- or syn-dactyly; nail hypoplasia; cardiac; cleft palate/bifid uvula; short neck o Embryology-anatomy • Abnormal patterning of midbrain-hindbrain by homeotic genes • Genetics o Autosomal recessive, clinically and genetically heterogeneous o Loci mapping to Chr 9q34.3 OBTS1) and 17p11.2 do not explain all cases in Joubert syndrome o llp12-q13.3 (CORS2) mutation: Cerebello-oculo-renal syndrome • Etiology o Anomaly of mesencephalic/rhombomere 1 development o Possible malposition of isthmic organizer • Epidemiology: 1 in 30,000 - 100,000 (likely under reported) • Associated abnormalities o Many syndromes with congenital vermian hypoplasia • Joubert syndrome is prototype: Only brain findings on imaging • If more than brain findings = one of many "CVH plus" syndromes: (+ Renal cysts/hepatic fibrosis/ocular abnormalities) Congen ital Malformations 1 35
  • 66. CONGENITAL VERMIAN HYPOPLASIA 1 36 Gross Pathologic & Surgical Features I DIAGNOSTIC CHECKLIST • CBLL vermian deficiency • +/- Other midline CNS anomalies o Callosal dysgenesis o Posterior pituitary ectopia o Occasional encephalocele Consider Microscopic • Look for fastigial point of 4th ventricle, primary fissure on sagittal views as first clues to diagnosis • Special care in sedation or anesthesia for neuroimaging examinations Image Interpretation Features • • • • • Elongated locus coeruleus Lack of decussation of superior CBLL peduncles Dysplastic dentate nuclei Hypoplasia or fragmentation of brainstem nuclei Absent posterior sulcus of medulla with fused fasciculi gracilis and cuneatus • Hypoplasia of middle CBLL peduncles • CBLL heterotopias • Occasional cortical dysplasias Staging, Grading or Classification Criteria • CVH or "CVH plus" I SELECTED REFERENCES 1. 2. 3. 4. I ClINliCAL ••S5l.JE·S I 5. Presentation • Most common signs/symptoms o Classic: Episodic hyperpnea plus abnormal eye movements (70%+) o Rhythmic tongue protrusion o Triangular shaped mouth stays open o "Cerebellar speech": Hoarse voice/dysarthria o Early hypotonia, ataxia o Maxillary recession, mandibular protuberance with age • Clinical profile o Mental retardation may be severe (majority), autistic-like, or near normal • If near normal, have typical poor judgment o Variable phenotype even within sibships 6. 7. 8. Gleeson JG et al: Molar tooth sign of the midbrain-hindbrain junction: Occurrence in multiple distinct syndromes. Am J Med Genet. 125A(2):125-34, 2004 Padgett KR et al: Ex vivo high-resolution magnetic resonance imaging of the brain in Joubert syndrome. J Child NeuroI17(12):911-3, 2002 Yachnis AT et al: Neuropathology of Joubert syndrome. J Child NeuroI14(10):655-9, 1999 Quisling RG et al: MRI features and classification of CNS malformations in Joubert syndrome. J Child Neurol 14:628-36, 1999 Satran D et al: Cerebello-oculo-renal syndromes including Arima, Senior-Loken and Coach syndromes: More than just variants of Joubert syndrome. Am J Med Genet 86(5):459-69, 1999 Maria BL et al: Clinical features and revised diagnostic criteria in Joubert syndrome. J Child NeuroI14(9):583-90, 1999 Yachnis AT et al: Cerebellar and brainstem development: An overview in relation to Joubert syndrome. J Child NeuroI14(9):570-3, 1999 Maria BL et al: Molar tooth sign in Joubert syndrome: Clinical, radiologic, and pathologic significance. J Child NeuroI14(6):368-76, 1999 Demographics • Age: Presentation in infancy • Gender: M:F = 2:1 • Ethnicity: Increased in population Pearls isolates Natural History & Prognosis • Neonatal hyperpnea usually (not always) intermitten t/transien t • Hypotonia improves over time o 75% learn to sit o 50% learn to walk • CVH alone Goubert): Poor, significant mental retardation is usual o Likely under-reporting of milder cases • "CVH plus" syndromes: Renal disease may progress to renal failure • Both: Prone to apnea in early life Treatment • Care in sedation/anesthesia o t Sensitivity to respiratory depressant effects of anesthesia/opioids Congenital Malformations
  • 67. CONGENITAL VERMIAN HYPOPLASIA 1 37 Typical (Left) Axial T2WI MR shows small vermian remnant (arrow). The superior cerebellar peduncles (curved arrow) are well seen due to hypoplasia of the usually intervening anterior vermian lobules. (Right) Axial Tl WI MR shows prominent vermian clefting (arrow). Typical (Left) Axial T2WI MR shows hypertelorism and frontonasal dysplasia. Note large aqueduct of Sylvius with disturbed flow (curved arrow). Superior CBLL peduncles (arrow) are well seen. CBLL is dysplastic. (Right) Axial TlWI MR shows typical cleft (arrow) leading into the deformed 4th ventricle. The combination gives the appearance of an open "umbrella". Typical (Left) Coronal T2WI MR shows apposed cerebellar hemispheres and heterotopic nodule (arrow) embedded within the white matter. (Right) Coronal T2WI MR shows small remnant (open arrow) of the vermis. Abnormal axis due to central up-tilting of the hemispheres. Prominent cisterna magna (curved arrow). Congenital Malformations
  • 68. HOLOPROSENCEPHALY 38 Coronal oblique 30 SPCR surface reconstruction shows absence of interhemispheric fissure and fusion of the gyri across the midline. • Lines drawn tangentially through Sylvian fissures = Sylvian angle (SA) • Anteriorly displaced Sylvian fissures ~ 1 SA • 1 SA ~ 1 severity frontal lobe hypoplasia ITERMINOl.OGY Abbreviations and Synonyms • Holoprosencephaly (HPE) • Formerly called arrhinencephaly Radiographic Findings Definitions • Spectrum of congenital structural forebrain anomalies defined by degree of frontal lobe fusion • Most common "brain plus face" malformation o "Face predicts brain": Severe midline anomaly ~ severe HPE o Function predicted by degree of non-separation of brain structures I IMAGING .FlN.[J1NGS General Features • Best diagnostic clue o Monoventricle + fused (uncleaved) frontal lobes ~ absent anterior midline falx/fissures o Fusion (non-cleavage) diencephalon> basal ganglia (BG) > thalami (THAL) • Location: Predominantly anterior brain process • Morphology o Anomaly defined by degree of frontal lobe fusion DDx: Holoprosencephaly MIH Variant Axial T2WI MR shows fusion of basal ganglia (arrow). The frontal lobe is hypoplastic and cortex and white matter are fused across the midline (open arrow). • Radiography: Hypotelorism, fused metopic suture or single frontal "plate" of bone, variable degree of microcephaly CT Findings • NECT o Uncleaved basal nuclei/ventricles; variable absence interhemispheric fissure (IHF) o Ventricles • Lobar: Absent septum pellucidum; formed lateral ventricles including temporal and occipital horns (anterior may be deficient) • Semilobar: Absent septum pellucidum; anterior horns absent, partial occipital and temporal horns • Alobar: Monoventricle, often incompletely covered posteriorly by brain ~ dorsal "cyst" o Skull base/vault • Cleft palate; variable optic canal hypoplasia • Absent or hypoplastic ethmoid sinus, anterior falx (and superior sagittal sinus), crista galli Variants MIH, CC-GM Fusion Lobar HPE, Note Genu Congenital Malformations SOD, Note Chiasm
  • 69. HOLOPROSENCEPHALY 1 Key Facts Terminology • Marked hydrocephalus • Holoprosencephaly (HPE) • Spectrum of congenital structural forebrain anomalies defined by degree of frontal lobe fusion • Most common "brain plus face" malformation • "Face predicts brain": Severe midline anomaly => severe HPE + ruptured septum pellucidum Clinical Issues Imaging Findings • Monoventricle + fused (uncleaved) frontal lobes => absent anterior midline falx/fissures • Fusion (non-cleavage) diencephalon> basal ganglia (BG) > thalami (THAL) • Location: Predominantly anterior brain process Top Differential Diagnostic Checklist • HPE variants (lobar, septooptic dysplasia, single central midline incisor) may still present with hypothalamic/pituitary crisis • Sylvian angle (of Barkovich) key to understanding neuroanatomic anomalies variant (MIH): ZIC2 MR Findings • Tl WI: Corpus callosum (CC) "replaced" by fused anterior brain • T2WI o Delayed myelin maturation in classical HPE, but normal in middle hemispheric variant (MIH) o Following are variable • Degree of frontal lobe hypoplasia, basal nuclei fusion • Presence of dorsal cyst (suprapineal recess) • Degree of hypoplasia or absence olfactory nerves (best seen on coronal views) • Subcortical heterotopia anterior to IHF and subjacent to shallow frontal sulci • DWI: DTI (alobar) demonstrates absence of corticospinal tracts • MRA o Azygous or absent anterior cerebral artery (ACA) o Single midline anterior arterial trunk with fan-like array of arteries over surface of frontal lobe • MRV o Absent superior sagittal, inferior sagittal and straight sinuses o Cortical veins and deep veins drain directly to torcular Findings • Real Time: Diagnosable on fetal ultrasound (and fetal MRI) • Color Doppler: Absent superior sagittal sinus, variable absence deep and midline venous structures Angiographic = Diagnoses • Middle interhemispheric Ultrasonographic • Clinical profile: Mentally retarded microcephalic infant with midline facial anomalies, disturbed endocrine function • Clinical severity relates to degree of hemispheric and deep gray nuclei non-separation (alobar HPE worst) Findings • Conventional o (+1-) Azygous (unpaired) or absent ACA o Fan-like array of arteries over surface of "pancake" hemisphere o If ACA absent, middle cerebral arteries have more medial course Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Multiplanar MR imaging with special attention to midline structures I DIFFER.ENTIAI. DIAGNOSIS Middle interhemispheric variant (MIH): ZIC2 • Sylvian fissures connected across midline over vertex (86%) • Non-cleavage THAL > BG • Heterotopias and dysplastic cortex common (86%) • Thought to reflect abnormal induction of embryonic roof plate (classic HPE = abnormal induction of embryonic floor plate) Other holoprosencephaly disorders spectrum • Septo-optic dysplasia • Central incisor syndrome • Non-specific midline dysplasias & frontonasal dysplasia, agnathia-otocephaly, anencephaly Marked hydrocephalus + ruptured septum pellucidum • Macrocephalic (HPE usually microcephalic) I PATHOI.OGY General Features • General path comments o Embryology-anatomy • Normal prosencephalic cleavage occurs 4-6 wks • Genetics o Cytogenetic abnormality in 50%: Especially trisomy 13; also 18q-, 18p-, 3p, 7-, trisomy 9, lq15q, llq12-q13 (DHCR7 gene mutation = Smith-Lemli-Opitz) o Classic HPE: Sonic hedgehog (SSH: Chr 7q36), SIX3 (2p21), TGIF (18pl1.3) all => ventrodorsal gradient => non-cleavage midline, disorganized neocortex (anterior), formation dorsal cyst Congenital Malformations 39
  • 70. HOLOPROSENCEPHALY 1 40 o Middle interhemispheric (MIH) variant: ZIC2 (13q32) =>dorsoventral gradient • Etiology o Mutations affecting signaling genes (e.g., Sonic hedgehog) which regulate neural tube patterning o Disruption in dorsoventral axis patterning of secondary prosencephalon • Epidemiology: 1 to 1.4 per 10,000 live births (more common in early embryogenesis with high spontaneous miscarriage rates) • Associated abnormalities o Non-facial/non-CNS anomalies 65% • Developmental field defects: Extensive midline, schisis anomalies o Maternal factors • ETOH, diabetes, retinoic acid o 80% Correlation severity facial anomalies with severity HPE • +/- Midline facial clefting; premaxillary agenesis if severe; absent superior lingual frenulum • +/- Central incisor; proboscis; single nare; single nasal bone/absent internasal suture and caudal metopic suture • Infants of diabetic mothers: Alobar HPE with normal facies Gross Pathologic & Surgical Features • Extreme hypoplasia of neocortex • Variable degree of fusion of diencephalon and THAL/BG with incorporation into upper brain stem • Dorsal cyst (especially in association of noncleaved thalamus) felt to represent expansion of partially blocked posterodorsal 3rd ventricle • Variable attenuation of anterior recess 3rd ventricle Microscopic Features • Fused diencephalon structures and variable fusion of deep gray Staging, Grading or Classification Criteria • 1 SA => 1 frontal lobe deficiency and clinical severity • Lobar: Formed lateral ventricles; j or no dorsal cyst; fused diencephalon or fornices, (+/-) partial fusion BG > THAL; near normal IHF; small or normal olfactory nerves • Semilobar: Partial occipital/temporal horns; 1 moderate dorsal cyst; fused diencephalon, partial fusion BG > THAL; posterior IHF; (-) or small olfactory nerves • Alobar: "pancake brain" or "horseshoe" brain; monoventricle; 11 dorsal cyst; fused diencephalon, BG and THAL=> may form gray matter fusion mass, no IHF; (-) olfactory nerves o Severity of pituitary/hypothalamic malfunction (75%, esp diabetes insipidus) and disturbed body temperature regulation correlates with degree of hypothalamic non-separation o Seizures (50%) and mental retardation: Most severe with cortical malformations o Dystonia and hypotonia: Severity correlates with degree of BG non-separation • Clinical profile: Mentally retarded microcephalic infant with midline facial anomalies, disturbed endocrine function Demographics • Age: Presentation in infancy (can be diagnosed with fetal US or MRI) • Gender: M:F = 1.4:1 Natural History & Prognosis • Over-represented in fetal demise, stillbirths • Clinical severity relates to degree of hemispheric and deep gray nuclei non-separation (alobar HPE = worst) Treatment • Treat seizures and endocrine dysfunction IDItGN()s-rtci(SI-I~<Sf(1..1ST Consider • HPE variants (lobar, septooptic dysplasia, single central midline incisor) may still present with hypothalamic/pituitary crisis Image Interpretation Pearls • Sylvian angle (of Barkovich) key to understanding neuroanatomic anomalies ISELECTED 1. 2. 3. 4. 5. REFERENCES Hayashi M et al: Neuropatholigcal evaluation of the diencephalon, basal ganglia and upper brainstem in alobar holoprosencephaly. Acta Neuropathol107(3):190-6, 2004 Blaas HG et al: Brains and faces in holoprosencephaly: Preand postnatal description of 30 cases. Ultrasound Obstet GynecoI19(1):24-38, 2002 Simon EM et al: The middle interhemispheric variant of holoprosencephaly. AJNR23(1):151-6,2002 Barkovich AJ et al: Analysis of the cerebral cortex in HPE with attention to the Sylvian fissures. AJNR23:143-50, 2002 Simon EM et al: The dorsal cyst in holoprosencephaly and the role of the thalamus in its formation. Neuroradiology 43(9):787-91,2002 I CUN1CAL1SSUES Presentation • Most common signs/symptoms o Worst (classic alobar HPE) = cyclopia, proboscis, midline facial clefting, microcephaly Congenital Malformations
  • 71. 1 41 Tvpical (Left) Axial T2WI MR shows arteries wandering over brain surface (open arrow), fused anterior lobes and basal ganglia (arrow), and dorsal cyst. Note the partially fused thalami (curved arrow). (Right) Axial TlWI MR in the same child shows a "pancake" hemisphere and monoventricle. Small posterior tissue band (arrows) represents hippocampal formation. Typical (Left) Sagittal T2WI MR shows "shield"-like hemisphere, hippocampal band (open arrow) and monoventricle/dorsal cyst. Cyst wall (arrows) is comprised of telencephalic roof plate and tela choroidea remnants. (Right) Sagittal oblique NECT (30) shows "pancake brain" "wrapped" around space occupied by dorsal cyst. (Left) Axial T2WI MR shows venous structure draining to midline venous trunk (arrow). Be and thalami form midline fusion mass (open arrow). (Right) Axial MRA shows azygous (unpaired) anterior cerebral artery (arrow). Congenital Malformations
  • 72. HOLOPROSENCEPHALY VARIANTS 42 SMMCI. Coronal NECT shows a single median maxillary central incisor (SMMCI) (arrow). Note the precise midline location. Abbreviations and Synonyms • Solitary median maxillary central incisor (SMMCI); solitary central maxillary incisor • Middle interhemispheric variant of holoprosencephaly (MIH); syntelencephaly Definitions • SMMCI: One of several "microforms" of autosomal dominant holoprosencephaly (HPE) • MIH: Variant of HPE characterized by mid-interhemispheric fusion I IMAGING I FIN DING $ General Features • Best diagnostic clue o SMMCI: Single, midline central maxillary incisor o MIH: Interhemispheric fusion of posterior frontal/parietal lobes + normal separation of frontal/occipital poles • Location o SMMCI: Midline, superior alveolar ridge o MIH: Posterior frontal and parietal lobes • Size: SMMCI: Equivalent to normal central incisor • Morphology: SMMCI: Normal central incisor DDx: Holoprosencephaly MIH. Axial 3D SPCR shows interhemispheric fusion of the sylvian fissure (SF), posterior frontal and parietal lobes. Note branches of the middle cerebral artery in the SF (arrows). ·MIH o Distinguishing features compared with classic HPE • Fusion sylvian fissures (SF)/posterior frontal and parietal lobes across midline • Normal separation frontal poles with present anterior interhemispheric fissure (IHF)/falx • Callosal (CC) dysgenesis characterized by presence of genu and splenium with absent body • Normal separation hypothalamus & basal ganglia o Frequent features MIH • Incomplete thalamic separation 33% • Cortical dysplasia/heterotopia o Occasional features MIH • Cerebellar abnormalities 20%: Cerebellar hypoplasia, Chiari 1 & 2, cephalocele o Features in common with classic HPE • Absent septum pellucidum • Azygous anterior cerebral artery CT Findings • NECT o SMMCI • Single, midline central maxillary incisor • Midpalatal vomerine ridge • V-shaped palate oMIH • Interhemispheric isodense band of brain + sylvian fissure (SF) Variants .- It f . Mesiodens Lobar HPE Congen ital Malformations Semi/obar HPE
  • 73. HOLOPROSENCEPHALY VARIANTS 1 Key Facts Terminology Top Differential • Solitary median maxillary central incisor (SMMCI); solitary central maxillary incisor • Middle interhemispheric variant of holoprosencephaly (MIH); syntelencephaly • SMMCI: One of several"microforms" of autosomal dominant holoprosencephaly (HPE) • MIH: Variant of HPE characterized by mid-interhemispheric fusion • SMMCI vs hypodontia • SMMCI vs mesiodens • MIH vs classic holoprosencephaly Imaging Findings Clinical Issues • SMMCI: Single, midline central maxillary incisor • MIH: Interhemispheric fusion of posterior frontal/parietal lobes + normal separation of frontal/occipital poles • Isolated SMMCI: Eruption deciduous SMMCI; absent upper labial frenulum • MIH: Spasticity, hypotonia, seizures, developmental delay (DD) Pathology • Several genetic mutations linked to SMMCI; sonic hedgehog (SHH) mutation, 7q36, most common • MIH: Linked to ZIC2 mutation at 13q32 o MIH: MR with 3D SPGR sequence • Protocol advice: SMMCI: Thin section axial/coronals • CTA oMIH • Azygous ACA • MCA branches in abnormal SF I DIFFERENTIAL DIAGNOSIS MR Findings • TIWI o SMMCI: Dental abnormality more difficult to identify compared with CT • Occasional pituitary/stalk hypoplasia oMIH • Abnormal SF spans both hemispheres • Fused posterior frontal, parietal lobes isointense on all pulse sequences • Normal myelin maturation (in contrast to classic HPE) • Dysgenetic CC (genu present more often than splenium) • T2WI o MIH: 25% hyperintense dorsal cyst • Occurs with thalamic non-cleavage ~ obstructs third ventricle • MRA oMIH • Azygous ACA • MCA branches identified in abnormal SF Ultrasonographic Diagnoses Findings SMMCI vs hypodontia • Congenital absence of teeth • Permanent dentition> deciduous • Second premolars, third molars, and maxillary lateral incisors most commonly affected SMMCI vs mesiodens • Supernumary permanent tooth between central maxillary incisors • Conical, slightly off midline MIH vs classic holoprosencephaly • Failure of cleavage of basal forebrain structures • Severity of malformation related to degree of anterior development of brain o Alobar (least differentiated): Lack of IHF, falx and CC with pancake-like mass of brain o Semilobar (moderate differentiation): Partially formed IHF/falx posteriorly; splenium CC present o Lobar (most differentiated): IHF/falx extend into frontal region; genu CC aplastic/hypoplastic; frequent minimal frontal lobe fusion • Prenatal US o MIH identified on 2nd trimester US o Often initially identified as lobar HPE I PATH0 LOG¥ Angiographic General Features Findings • Conventional oMIH • Azygous ACA • MCA branches identified in abnormal SF Imaging Recommendations • Best imaging tool o SMMCI: CT (brain), include bone alga (face/jaw) • Supplemental MR for neurological, endocrine abnormalities • General path comments o SMMCI: Deciduous & permanent teeth affected o Embryology-anatomy • SMMCI: Odontogenic maxillary epithelium forms along inferolateral frontalnasal prominence day 35 gestation • SMMCI: Central incisors formed by division midline 'epithelial dental lamina and lateral growth day 37-38 gestation Congenital Malformations 43
  • 74. HOLOPROSENCEPHALY VARIANTS 1 44 • • • • • MIH: Mitosis/apoptosis of embryonic roof plate form IHF after neural tube closure (fetal weeks 3-4) Genetics o SMMCI: Microform of autosomal dominant HPE (ADHPE); fewer sporadic cases • Variable expression ADHPE accounts for wide range of craniofacial and CNS phenotypes (cyclopia/alobar HPE to microforms/normal intelligence) • 70% penetrance ADHPE =} risk SMMCI, or other microform in offspring of obligate carrier = 13-14% • Risk of severe (semilobar/alobar) HPE in offspring obligate carrier ADHPE = 16-21% o Several genetic mutations linked to SMMCI; sonic hedgehog (SHH) mutation, 7q36, most common • SHH expressed in large number fetal tissues; responsible for induction ventral patterning in neuraxis • Less common mutations: SIX3 at 2p21, TGIF at 18pl1.3, 22qll deletion and ring chromosome 18 o MIH: Linked to ZIC2 mutation at 13q32 • In mice, ZIC2 plays role in differentiation of embryonic roof plate; mutations cause neural tube defects, HPE • In contrast to genes linked to classic HPE (SHH, for eg), ZIC2 not involved in ventral patterning of neuraxis =} accounts for lack of severe midline facial dysmorphisms in MIH Etiology o SMMCI: Theory: Lack of midline cell division and lateral growth of dental lamina creates single, midline "fused" central incisor o MIH: Impaired expression of roof plate properties alters mitosis and apoptosis leading to faulty IHF formation and fusion of the cerebral hemispheres Epidemiology o SMMCI: 1:50,000 o MIH: Rare Associated abnormalities o SMMCI: Rare reports VACTERL, CHARGE, velocardiofacial syndrome, vertebral anomalies o MIH: Report of 5 patients with ZIC2 mutations with limb, renal, genital anomalies Gross Pathologic & Surgical Features • MIH: IHF present frontal, occipital poles; hemispheric fusion posterior frontal and parietal lobes; fused SF • MIH: Foci of undifferentiated cortex, subependymal gray matter heterotopia Microscopic Features • +/- Other microforms ADHPE: Cleft lip, mid-face hypoplasia, microcephaly, coloboma, choanal atresia, midnasal stenosis, pyriform aperture stenosis, developmental delay, learning difficulties • Presence of SMMCI with severe manifestations ADHPE (cyclopia/alobar HPE) uncommon o MIH: Spasticity, hypotonia, seizures, developmental delay (DD) • Dx frequently known at birth (prenatal US) • Mild facial dysmorphisms frequent: Hypertelorism, cleft lip/palate, SMMCI • Severe facial dysmorphisms (as seen with classic HPE) do not occur • Clinical profile o SMMCI • Infant with SMMCI, short stature, hypotelorism • Isolated SMMCI in mother with offspring with classic HPE o MIH: Infant/young child with spasticity, DD Demographics • Age: SMMCI: 1-2 yrs of age (eruption deciduous teeth) • Gender: Isolated SMMCI more common in females Natural History & Prognosis • Prognosis o SMMCI: Determined by CNS involvement; isolated SMMCI or other microforms, good to excellent o MIH: Mild/moderate psychomotor delay, seizures • Clinical profile MIH most similar to lobar HPE Treatment • SMMCI: No treatment for isolated dental abnormality o Hormone replacement, corrective surgery for other microforms ADHPE • MIH: Anti-epileptics I DIAGNOSTIC Image Interpretation Pearls • SMMCI: Careful scrutinization additional anomalies of brain and face for I SELECTED REFERENCES 1. 2. 3. • MIH: Callosal fibers identified anteriorly, posteriorly 4. Presentation • Most common signs/symptoms o Isolated SMMCI: Eruption deciduous SMMCI; absent upper labial frenulum • Short stature (50%) and hypotelorism frequent (33% short stature 2° to growth hormone deficiency) CHECKLIST 5. Simon EM et al: The middle interhemispheric variant of holoprosencephaly. AJNR Am J Neuroradiol. 23(1): 151-6, 2002 Heussler HS et al: Extreme variability of expression of a Sonic Hedgehog mutation: attention difficulties and holoprosencephaly. Arch Dis Child. 86(4): 293-6, 2002 Lewis AJ et al: Middle interhemispheric variant of holoprosencephaly: a distinct cliniconeuroradiologic subtype. Neurology. 59(12): 1860-5, 2002 Nanni L et al: SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature. Am J Med Genet. 102(1): 1-10, 2001 Hall RK et al: Solitary median maxillary central incisor, short stature, choanal atresia/midnasal stenosis (SMMCI) syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 84(6): 651-62, 1997 Congenital Malformations
  • 75. HOLOPROSENCEPHALY VARIANTS 1 45 Typical (Left) SMMCI. Axial NECT shows an unerupted single median maxillary central incisor (SMMCI). Note normal incisor morphology. The prominent vomerine ridge is seen in the mid palate (arrow). (Right) SMMCI. Axial NECT in a patient with SMMCI shows overgrowth of the nasal process of maxilla (arrows) consistent with nasal pyriform aperture stenosis (NPAS). SMMCI is seen in 60% NPAS. Typical (Left) MIH. Sagittal T1WI MR shows a dysgenetic corpus callosum (CC) with only a normal genu (arrow) identified. In classic forms HPE, the genu is the least well formed portion of the cc. Note Chiari 7. (Right) MIH. Axial T2WI MR shows fusion of posterior ventricles, absent septum pellucidum, findings also seen in classic HPE. However, note normal cleavage of the basal ganglia, findings typical of MIH. Typical /~ , , , i . . ~~ ~ Congenital Malformations (Left) MIH. Axial T1WI MR shows clear separation of the frontal and occipital poles with the interhemispheric fissure (lHF) identified anteriorly and posteriorly (arrows). (Right) MIH. Axial 30 SPCR through the rostral brain shows interhemispheric fusion of posterior frontal and parietal lobes with focal absence of IH F (arrow). Note right frontal lobe pachygyria (open arrow).
  • 76. SEPTOOPTIC DYSPLASIA 1 46 Coronal graphic depicts flat-roofed anterior horns & absence of midline septum pellucidum. Anterior horns are draped inferiorly around fornices (open arrow). Optic chiasm (arrow) small. Abbreviations • • • • • • Coronal T1WI MR shows absent septum pellucidum, flat roof of lateral ventricles, frontal horns "pointing" down and hypoplastic pituitary stalk (arrow). • Location: Optic nerves, pituitary gland, septum pellucidum • Size o Small optic nerves o Small pituitary gland with ectopic posterior lobe o Absent septum pellucidum • Morphology o Coronal imaging shows • Flat-roofed ventricles • Downward pointing anterior horns and Synonyms Septooptic dysplasia (SOD) De Morsier syndrome Kaplan-Grumbach-Hoyt syndrome Suprasellar dysgenesis Septo-optic-pituitary dysgenesis SOD plus: Abnormal optic nerves/chiasm, septum pellucidum, pituitary gland, + cortical dysplasias Definitions CT Findings • SOD = heterogeneous disorder characterized by hypoplasia of optic nerves/tract, absent septum pellucidum, hypothalamic-pituitary dysfunction • De Morsier (1956): Described 7 patients with SOD • Hoyt (1978): Described the association of SOD with hypopituitarism • Some authors consider SOD, lobar holoprosencephaly same disorder • NECT o Absent septum pellucidum o Large lateral ventricles o Small bony optic foramina on axial and coronal imaging MR Findings I·IMAClN(j··.·.· •• FlN[)lNG~ General Features • Best diagnostic clue: Absent septum pellucidum, optic chiasm small DDx: Small Optic Nerves/Posterior DID DID • TlWI o Three planes crucial to identify all findings • Absent septum pellucidum (remnants may be present) • Flat roof of frontal horns, inferior aspect of frontal horns "point down" • Small optic chiasm/nerves (fat-sat aides visualization of optic nerves) • +/- Thin pituitary stalk • Posterior pituitary ectopia Ectopic Pituitary lobe Ectopic Lobe Congen ital Malformations Ectopic Lobe
  • 77. SEPTOOPTIC DYSPLASIA Key Facts Terminology • De Morsier syndrome • SOD = heterogeneous disorder characterized by hypoplasia of optic nerves/tract, absent septu~ pellucidum, hypothalamic-pituitary dysfunctIOn Imaging Findings • Absent septum pellucidum (remnants may be present) • Flat roof of frontal horns, inferior aspect of frontal horns "point down" • Small optic chiasm/nerves (fat-sat aides visualization of optic nerves) • +/- Thin pituitary stalk Top Differential • Lobar holoprosencephaly • Isolated ectopic posterior pituitary lobe Pathology • Optic nerve hypoplasia (ONH) • 60% have brain abnormalities (not just schizencephaly) • 62-88% have pituitary insufficiency • Frequently associated with other cerebral anomalies • Most common = schizencephaly • Midline malformations (callosal dysgenesis, etc) • Ocular anomalies (coloboma, anophthalmia, microphthalmia) • Olfactory tract/bulb hypoplasia Diagnoses • Kallman syndrome • Callosal-forniceal continuation or fused midline fornices • Thin corpus callosum • Vertical hippocampi • +/- Hypoplastic/absent olfactory nerves • +/- Schizencephaly • +/- Heterotopias, cortical dysplasias • T2WI: Deficient falx (esp anteriorly); +/hypomyelination • Tl C+ o Enhancement of infundibulum, ectopic posterior pituitary lobe o Delayed enhancement of anterior pituitary lobe on dynamic MRI Imaging Recommendations • Best imaging tool: MRI • Protocol advice o Coronal, sagittal thin sections through sella/orbits o Use fat-sat to better visualize optic nerves I DIFFERENTIAL DIAGNOSIS Syndromes overlapping with septooptic dysplasia • Optic-infundibular dysplasia (OlD), normal septum • Schizencephaly: EMX 2 gene mutations reported in some severe cases Kallman syndrome • Absent olfactory nerves • +/- Visual, septal, pituitary abnormalities Lobar holoprosencephaly • Similar to SOD • Many consider it same disorder Isolated ectopic posterior pituitary lobe • Normal chiasm/nerves, septum pellucidum IPATHOlOG¥ General Features • General path comments o Sudden death reported from hypothalamic-pituitary axis malfunction o Embryology-Anatomy • Disorder of midline prosencephalic development (6th wk gestation): Pituitary gland, forebrain, eyes, olfactory bulbs • HESXl (homeobox gene): Needed for pituitary/forebrain development • Genetics o Most are sporadic o Some are autosomal dominant or recessive o Some cases have mutations in Hesxl/HESXl genes • Homozygous mutations = full syndrome • Heterozygous mutations = milder pituitary phenotypes o Inactivation of Hesxl (3p21.2-3p21.2) by an Arg53Cys substitution leads to deficient anterior pituitary lobe (doesn't occur in sporadic SOD) • Etiology o Theories • Midline heritable defect (mild holoprosencephaly variant) • Or secondary degeneration of optic nerve fibers due to cerebral lesion • Or vascular disruption (field defect) during brain development • Epidemiology olin 50,000 o Optic nerve hypoplasia (ONH) • 60% have brain abnormalities (not just schizencephaly) • 62-88% have pituitary insufficiency • 30% have both of the above • 25-50% have absent septum pellucidum o Septooptic dysplasia (SOD) • 75-90% have brain abnormalities; 45% have pituitary insufficiency • Bilateral optic nerve hypoplasia 70% Congenital Malformations 1 47
  • 78. 1 48 • Associated abnormalities o Frequently associated with other cerebral anomalies • Most common ::= schizencephaly • Peri-Sylvian cortical dysplasias • Midline malformations (callosal dysgenesis, etc) • Ocular anomalies (coloboma, anophthalmia, microphthalmia) • Olfactory tract/bulb hypoplasia o Overlapping syndromes with optic, septal, frontal lobe, midline, olfactory deficiencies Natural History & Prognosis • Hypothalamic and pituitary crises; sudden death (hypocortisolism) • Depends upon severity of associated brain and pituitary malformations Treatment • Hormonal replacement therapy Gross Pathologic & Surgical Features • • • • Small optic chiasm/nerves Small or absent geniculate nucleus Deficient/absent septum pellucidum Forniceal columns (+/- fused) =:> run along roof of 3rd ventricle • Common: Hypoplasia pituitary, olfactory lobes Microscopic Features • Optic nerves, chiasm have sparse or absent myelinated fibers • Geniculate nucleus (if found): Disorganized layering of small neurons Staging, Grading or Classification Criteria • Isolated ONH: Visual defect only; intelligence and growth normal • ONH and septal deficiency: Same as isolated • ONH and septal and pituitary deficiency: May have developmental delay • Above plus hemispheric migrational anomaly: Plus seizures • Intrauterine or perinatal insult (especially meningitis) as cause of optic nerve, chiasmatic, and hypothalamic deficiency I.Gll .• NJ.GAliISSUES Presentation • Most common signs/symptoms o Newborns: Hypoglycemic seizures, apnea, cyanosis, hypotonia, prolonged conjugated jaundice, (and microphallus in boys) o Abnormal endocrine function (60%): Look for multiple pituitary deficiencies o Normal endocrine function (40%): Usually have schizencephaly, seizures • Clinical profile o Child with short stature, endocrine dysfunction o Normal or color blindness, visual loss, nystagmus, strabismus o +/- Mental retardation, spasticity, microcephaly, anosmia Consider • SOD in small stature pediatric patient with absent septum pellucidum Image Interpretation I SELECTED REFERENCES Gasparetto EL et al: Septo-optic dysplasia plus: case report. Arq Neuropsiquiatr. 61(3A):671-6, 2003 2. Campbell CL: Septo-optic dysplasia: a literature review. Optometry. 74(7):417-26,2003 3. Wakeling EL et al: Septo-optic dysplasia, subglottic stenosis and skeletal abnormalities: a case report. Clin Dysmorphol. 12(2):105-7,2003 4. Camino R et al: Septo-optic dysplasia plus. Lancet Neurol. 2(7):436, 2003 5. Tajima T et al: Sporadic heterozygous frameshift mutation of HESXl causing pituitary and optic nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient. J Clin Endocrinol Metab. 88(1):45-50, 2003 6. Dattani M: Structural hypothalamic defects. J Pediatr Endocrinol Metab. 15 SuppI5:1423-4, 2002 7. Antonini SR et al: Cerebral midline developmental anomalies: endocrine, neuroradiographic and ophthalmological features. J Pediatr Endocrinol Metab. 15(9):1525-30, 2002 8. Orrico A et al: Septo-optic dysplasia with digital anomalies associated with maternal multi drug abuse during pregnancy. Eur J Neurol. 9(6):679-82, 2002 9. Miller SP et al: Septo-optic dysplasia Plus: A spectrum of malformations of cortical development. Neurology 54:1701-3,2000 10. Dattani MT et al: Molecular genetics of septo-optic dysplasia. Horm Res 53(S): 26-33, 2000 11. Barkovich AJ et al: Septo-optic dysplasia: MR imaging. Radiology 171:189-92, 1989 1. Demographics • Age o Generally detected in infants o More common among younger mothers & first-born • Gender: M ::= F Congenital Pearls • Small optic nerves, + ectopic posterior pituitary lobe, + absent septum pellucidum ::= SOD Malformations
  • 79. 1 49 Typical (Left) Sagittal Tl WI M R shows calloso-forniceal continuation and large lateral ventricles in SOD. (Right) Coronal Tl WI M R shows tiny optic nerves (arrows). Typical (Left) Coronal TlWI MR shows absent septum pellucidum (arrow) and a right open lip schizencephaly. (Right) Coronal TlWI MR in same patient shows absent septum pellucidum, frontal horns "pointing down ", thin pituitary stalk and small pituitary gland (arrow). Typical (Left) Axial FLAIRMR shows large lateral ventricles and absent septum pellucidum (arrow). (Right) Coronal T2WI MR in same patient confirms absent septum pellucidum, typical shape of frontal horns (arrows) and small stalk and pituitary gland. Congenital Malformations
  • 80. 50 Sagittal T2WI MR shows profound microcephaly (microlissencephaly), thinning of the corpus callosum and dysplasia of the cerebellum (arrow). Abbreviations and Synonyms • Primary (genetic) microcephaly, secondary (nongenetic) microcephaly, micrencephaly, microencephaly Definitions • Microcephaly: Small head size o Primary (genetic): Mendelian inheritance OR associated with a specific genetic syndrome o Secondary (nongenetic): Results from noxious agent that affects fetal/infant brain growth • Micrencephaly: Brain reduced in size as a result of genetic or noxious insult IIMAOINO •• ·FINOINCS General Features • Best diagnostic clue o !Craniofacial proportions o Sutural apposition or overlap o Simplified cortical gyral pattern • Imaging findings: Dictated by the cause of microcephaly o Primary (genetic) microcephaly Coronal T2WI MR of microlissencephaly shows: Simplified gyral pattern, reduced white matter volume, and indistinct gray-white differentiation (impaired neuronal migration) (arrows). • Small, but grossly normal brain ~ gyral simplification • OR ± pachygyric, lissencephalic, holoprosencephalic • OR ± hypoplastic cerebellum, hypomyelination o Secondary (nongenetic) microcephaly • Hypoxic ischemic encephalopathy: ± Cortical, white matter, or basal ganglia volume loss • (S)TORCH infection: Ca++, abnormal WM , neuronal migration anomalies • Fetal alcohol syndrome (FAS): Callosal abnormalities, ventriculomegaly • Nonaccidental head injury (NAHI); Encephalomalacia, chronic subdurals, ± parenchymal lacerations • Lateral radiograph, CT topogram, or sagittal MRI o ! Craniofacial proportions (skull: Face ratio) • Normal craniofacial ratios: Premature (5:1), term (4:1),2 yrs (3:1), 3 yrs (2.5:1), 12 yrs (2:1), adult (1.5:1) • Fetal Sonography or FMRI Findings o Difficult to confirm microcephaly until late 2nd or early 3rd trimester Radiographic Findings • Radiography: !Craniofacial ratio, slanted forehead, closely apposed or overlapping calvarial sutures DDx: Microcephaly Congenital CMV HIE NAHI Chronic Congen ital Malformations Fetal Alcohol
  • 81. MICROCEPHALY 1 Key Facts Terminology • Microcephaly: Small head size • Primary (genetic): Mendelian inheritance OR associated with a specific genetic syndrome • Secondary (nongenetic): Results from noxious agent that affects fetal/infant brain growth Imaging Findings • 1 Craniofacial proportions • Imaging findings: Dictated by the cause of microcephaly • Normal craniofacial ratios: Premature (5:1), term (4:1),2 yrs (3:1), 3 yrs (2.5:1), 12 yrs (2:1), adult (1.5:1) • Small yet normal brain ~ simplified gyral pattern (oligogyria) ~ microlissencephaly CT Findings • NECT o Small cranial vault: Sutures closely apposed, overlapping or with secondary craniosynostosis o Ca++ in (S)TORCH and heredito-genetic (S)TORCH look-alikes (pseudo-TORCH syndromes) o Cortical surface: Normal ~ simplified ~ migrational abnormalities ~ micro lissencephaly o White matter attenuation: Normal ~ diminished (secondary to hypomyelination or demyelination) • ± Various telencephalic anomalies: Callosal absence or dysgenesis, holoprosencephaly Pathology • Primary (genetic) microcephaly is typically autosomal recessive (example: Familial form - 1/40,000 births) • Primary microcephaly is associated with many syndromes Clinical Issues • Criteria for the diagnosis of microcephaly: Head circumference> 3 SD below the mean for age and sex Diagnostic Checklist • Presence of cerebellar hypoplasia more common primary (genetic) microcephaly • If midline anomalies accompany microcephaly, consider fetal alcohol syndrome (FAS) • FLAIR: Periventricular: Cavitation (1 signal), gliosis (1 signal), ± hyperintense chronic subdural collections • T2* GRE: Sequelae to non accidental trauma: Hypointensities from hemorrhagic parenchymal shear injury • DWI: T2 shine-through in states associated with gliosis or demyelination • MRS: 1 NAA, myoinositol and choline may be 1 in states of ongoing demyelination and neurodegeneration Ultrasonographic MR Findings • TlWI o Primary (genetic) microcephaly • Small yet normal brain ~ simplified gyral pattern (oligogyria) ~ microlissencephaly • Normal myelination ~ hypomyelination ~ demyelination • ± Various telencephalic anomalies: Callosal absence or dysgenesis, holoprosencephaly • ± Cerebellar hypoplasia (more common in genetic causes of microcephaly) o Secondary (nongenetic) microcephaly • Destructive changes: Encephalomalacia, ± Ca++ (S)TORCH infections, ± subdural collections • T2WI o Primary (genetic) microcephaly • Sulci (%-Vz normal depth), cortex simplified ~ pachygyric~ heterotopic ~ microlissencephalic • 1 Commisural fiber tracts, normal basal ganglia volume, ± cerebellar hypoplasia • White matter maturation: Normal ~ hypomyelinated ~ demyelinated o Secondary (nongenetic) microcephaly • White matter: Gliosis, cavitation, demyelination, diminished volume, ± hypointensity (Ca++) • Cortex: Normal ~ simplified ~ polymicrogyria (TORCH) • Possible midline anomalies: Absent corpus callosum, holoprosencephaly • PD/Intermediate: Gliosis (1 signal) and Ca++ (! signal) more common in secondary microcephaly (infection) in Findings • Real Time o Small fontanel due to sutural overlap, sulcal and ventricular expansion o ± Basal ganglia or thalamic Ca++ (TORCH or HIE), ± periventricular volume loss (TORCH or HIE) Imaging Recommendations • Best imaging tool o NECT detects: Ca++ (TORCH, pseudo-TORCH, HIE), encephalomalacia, and subdural collections o MR depicts: Gyral pattern, cortical organization/migration, myelination, midline anomalies, gliosis, hemorrhage • Protocol advice o Consider liberal us of NECT to detect Ca++ o MR brain: GRE T2* (blood and Ca++), 3D SPGR to evaluate brain convolutions, FLAIR for detecting subdurals I DIFFERENTIAl.. DIAGNOSIS Secondary (nongenetic) microcephaly • Antenatal causes: Pre-eclampsia, maternal infection (TORCH), maternal diabetes, FAS, hyperphenylalaninemia • Perinatal causes: Hypoxic ischemic encephalopathy (HIE), infection • Postnatal: Prolonged status epilepticus, HIE, hypoglycemia, meningo-encephalitis, neurodegenerative, NAT Congenital Malformations 51
  • 82. MICROCEPHALY 1 52 • Noxious insult: Prenatal irradiation, maternal ingestion of anticonvulsants, ETOH, cocaine, excessive vitamin A [PATHOL()GY Demographics General Features • General path comments o Skull changes: Sloping forehead, flattened vault, prominent ears, up-slanting palpebral fissures o Embryology-anatomy • Pathways in which genes affect neuronal progenitor cells & brain size • Genetics o Primary (genetic) microcephaly is typically autosomal recessive (example: Familial form ~ 1/40,000 births) • MCPH genetic heterogeneity: Mutations MCPHS (1q31) most prevalent • Primary microcephaly is associated with many syndromes • Etiology: Heterogeneous: Inherited or acquired • Epidemiology o Incidence of microcephaly in the general population: 0.6-1.6% o Incidence of genetically determined microcephaly: Familiall/40,OOO, Down synd 1/800 • Associated abnormalities: Frequently seen as a component of other severe malformations Gross Pathologic & Surgical Features • Skull capacity < 1300 ml, brain weight < 900 grams • Extreme microcephaly (as low as 300 gms, HC = S-10 SD below mean) • General reduction in cerebral hemisphere size • Simple gyral pattern (oligogyria) • Short central sulcus, sulci (shallow, narrow or wide) • Sulcus parieto-occipitalis may be enlarged - simian fissure • Island of Reil remains uncovered (incomplete operculization) • ± Lissencephaly, oligogyria, heterotopias, holoprosencephaly, cerebellar hypoplasia • Acquired microcephaly: ± Cystic degeneration of white matter, infarcts, Ca++, hemorrhagic products Microscopic • Clinical profile: Slanted forehead, prominent nose and ears, up-slanting palpebral fissures, conical head, ± overlapping sutures • Criteria for the diagnosis of microcephaly: Head circumference> 3 SD below the mean for age and sex • Age o Primary (genetic) microcephaly often reveals itself either in utero or shortly after birth o Secondary (nongenetic) microcephaly usually results from insults within the first two years of life • Gender: Variable based upon type: Primary (autosomal recessive inheritance) vs secondary (nongenetic) • Ethnicity: The common genetic forms;::; pan-ethnic, certain syndromic causes of microcephaly may show ethnicity Natural History & Prognosis • Dictated by the cause of microcephaly Treatment • Supportive, genetic testing available for some microcephalic disorders • Variable degree of mental retardation and motor handicap I DIAGNOSIICctI-lE<:I<.LIST Consider • Presence of cerebellar hypoplasia more common in primary (genetic) microcephaly • If midline anomalies accompany microcephaly, consider fetal alcohol syndrome (FAS) Image Interpretation I SELECTED REFERENCES 1. 2. 3. Features • MCPHS: No evidence of abnormal neuronal migration or architecture • Other forms may occur with 4 layer cortex (lissencephalic) Staging, Grading or Classification Criteria • Grouped by: Myelination, neuronal organization migration, and associated congenital anomalies and Pearls • MR provides the most sensitive tool for investigating the simplified cortex in microcephaly 4. 5. Bond J et al: ASPM is a major determinant of cerebral cortical size. Nat Genet 32:316-20,2002 Jackson AP: Identification of microcephalin, a protein implicated in determining the size of the human brain. Am J Hum Genet 71(1):136-42, 2002 Custer DA et al: Neurodevelopmental and neuroimaging correlates in nonsyndromal microcephalic children. J Dev Behav Pediatr 21(1): 12-18,2000 Barkovich AJ et al: Microlissencephaly: A heterogeneous malformation of cortical development. Neuropediatrics 29(3):113-19, 1998 Swayze VW et al: Magnetic resonance imaging of brain anomalies in fetal alcohol syndrome. Pediatrics 99(2):232-40, 1997 I CLiN ICALlSSLJES Presentation • Most common signs/symptoms: Severe mental retardation, ± seizures, developmental delay Congenital Malformations
  • 83. 1 53 Typical (Left) Sagittal T7WI MR in a patient with familial microcephaly (autosomal recessive), shows a diminished craniofacial ratio. (Right) Axial T2WI MR in a patient with familial microcephaly shows simplified gyral pattern, mild ventriculomegaly, and subarachnoid space enlargement. Variant (Left) Axial T2WI MR in a child with periventricular leukomalacia (PVL), shows profound 1055 of white matter volume. Note the gyral indentation against the ventricular margins (arrows). (Right) Axial NECT in a microcephalic infant who experienced chronic profound hypoxia, shows diffuse cerebral hemispheric atrophy, calcification of the thalami, and marked sutural overlap (arrows). Variant (Left) Axial FLAIR MR in a microcephalic infant with PEHO syndrome (progressive encephalopathy, hypsarrhythmia, and optic atrophy) shows periventricular bright signal (gliosis) mimicking PVL (arrows). (Right) Axial NECT in a child with Aicardi-Coutieres syndrome (Pseudo-TORCH), shows extensive periventricular calcification (arrows), and moderate ventriculomegaly secondary to white matter volume 1055. Congenital Malformations
  • 84. CONGENITAL MUSCULAR DYSTROPHY 54 Axial T2WI MR in Walker-Warburg; the most severe of the CMOs. Showing cobblestone lissencephaly (arrows), hypomyelination, absence of septum pellucidum and ventriculomegaly. Sagittal T2WI MR shows a flexed or "Z-shaped", hypoplastic brainstem. The belly of the pons is notched (arrow). The cerebellum is severely hypoplastic and rotated. There is hydrocephalus. o Example: Merosin (-) CMD with brain malformations Abbreviations and Synonyms • Congenital muscular dystrophy (CMD 1): Merosin positive (+) or merosin negative (-) CMD • CMD 2-4: Cobblestone lissencephaly (LIS); type 2 LIS; CMD with severe CNS malformations General Features • Best diagnostic clue: "Z-shaped" brainstem in a hypotonic infant • Morphology o CMDs with major brain malformations (WWS most severe) • Cortical dysplasia, cobblestone LIS or pachygyria • Varying degrees agenesis or hypogenesis of corpus callosum, septum pellucidum, vermis • Flat or "Z-shaped" brain stem or "notched" pons • +/- Hydrocephalus or encephalocele Definitions • CMDs = heterogeneous group of autosomal recessive myopathies presenting at birth with hypotonia • CMDs without major brain malformations are either me rosin positive or merosin negative o CMD 1 Merosin (-): Significant dys-/hypomyelination of white matter (WM) o CMD 1 Merosin (+): Normal/very mild imaging findings (cerebellar CBLL hypoplasia, non-specific WM changes, focal polymicrogyria PMG) • "" 50% of children with CMD (CMD 2-4) have major brain abnormalities with a spectrum of overlapping findings including abnormal signal of WM & ocular, cortical (cobblestone LIS), and CBLL anomalies o CMD 2: Fukuyama (FCMD) = least severe o CMD 3: Santavuori muscle-eye-brain or Finnish type (MEB) o CMD 4: Walker-Warburg syndrome (WWS) = most severe • Mixed patterns occur CT Findings • NECT o All imaging findings most severe in WWS • I Attenuation WM, vermian dysgenesis (looks like Dandy Walker spectrum) • +/- Occipital cephalocele, +/- hydrocephalus, shallow or absent sulci MR Findings • TlWI DDx: Cerebellar Cysts and Brainstem Hypoplasia Cystic CBLL Mets Non CMD CBLL Cysts Congenital DWM Normal Pons Malformations HGPS
  • 85. CONGENITAL MUSCULAR DYSTROPHY Key Facts • All imaging findings most severe in WWS Terminology • CMDs:::: heterogeneous group of autosomal recessive myopathies presenting at birth with hypotonia • CMD 1 Merosin (-): Significant dys-/hypomyelination of white matter (WM) • CMD 1 Merosin (+): Normal/very mild imaging findings (cerebellar CBLL hypoplasia, non-specific WM changes, focal polymicrogyria PMG) • '" 50% of children with CMD (CMD 2-4) have major brain abnormalities with a spectrum of overlapping findings including abnormal signal of WM & ocular, cortical (cobblestone LIS), and CBLL anomalies • Mixed patterns occur Pathology • Marked phenotypic overlap amongst FCMD, Walker- Warburg, and MEB • Muscle biopsy: Mild to moderate dystrophic changes, +1- inflammatory infiltrate, +1- absent staining laminin-lX2 Clinical Issues • Clinical profile: Floppy newborn • No treatment other than supportive: Major respiratory and cardiovascular concerns Imaging Findings • Best diagnostic clue: "Z-shaped" brainstem hypotonic infant in a o Thin, dysplastic, polymicrogyria (PMG) or "pebbled" supratentorial cortex, +1- hydrocephalus o +1- Callosal, vermian, or septal hypogenesis o Flat, deeply clef ted, notched or "Z-shaped" brain stem • T2WI o Polymicrogyria of cerebellar cortex, +1- cysts o CMD merosin (-): Dysmyelination of centrum semiovale, +1- subcortical U-fibers o FCMD, MEB: WM abnormalities in half o WWS: Severe WM hypomyelination Ultrasonographic • Findings • Real Time: Fetal US or fetal MRI may be diagnostic Imaging Recommendations • Best imaging tool: MRI • Protocol advice: Multiplanar T2/FLAIR of posterior fossa to define CBLL cysts and brain stem malformation I DIFFERENTIAl.. DIAGNOSIS Dandy Walker malformation • Small vermian remnant rotated superiorly by cyst; pons usually normal in size and not clefted or notched Multiple disorders with brainstem c1efting • Joubert (mesencephalon and vermian hypoplasia); midline clefting syndromes • Horizontal gaze palsy associated with progressive scoliosis (HGPS): Chr 11q23 • Horizontal gaze palsy, progressive scoliosis, brainstem hypoplasia/clefting, mild CBLL volume loss • IPATHOI..OGY • General Features • General path comments o Marked phenotypic overlap amongst FCMD, Walker-Warburg, and MEB o Muscle biopsy: Mild to moderate dystrophic changes, +1- inflammatory infiltrate, +1- absent staining laminin-lX2 Genetics o CMD 1 Merosin (+): Genetic defect(s) unknown o CMD 1 Merosin (-): Mutation in gene for laminin-lX2 on Chr 6 o CMDs with brain anomalies have hypoglycosylation of lX-dystroglycan allowing neuronal overmigration through gaps in external lamina ~ "pebbled" surface of brain • FCMD: Mutation in gene encoding fukutin (FCMD at 9q31) • MEB: O-Mannoside N-acetyl-glucosaminyl-transversae (POMGnT1 at 1p32-p34) • WWS: O-Mannosyltransferase gene (POMT1) o Mutations in FKRP (fukutin-related protein gene) may cause congenital or late onset phenotypes o Other CMD variants with known defects • CMD with mutation integrin-lX7 gene on Chr 12 • CMD with familial junctional epidermolysis bullosa (plectin gene on Chr 8) • CMD with spine rigidity (linked to Chr 1 in some) o Mixed patterns and intermediate forms occur • CMD Merosin (-) with brain anomalies, cerebellar cysts, vermis hypoplasia, mental retardation Etiology o Mutations in molecules with roles in cell migration and connection • Merosin (laminin-lX2) utilized in migration of oligodendrocyte precursors • Merosin is a skeletal muscle extracellular matrix protein that binds dystrophin associated glycoprotein complex Epidemiology: 7-12 per 100,000 children in Japan; incidence elsewhere uncertain Associated abnormalities: Some associated features in CMD variants with "not yet found" mutations are occipito-temporal polymicrogyria, occipital agyria, calf-hypertrophy, arthrogryposis, ptosis, adducted thumbs Congenital Malformations 1 55
  • 86. CONGENITAL MUSCULAR DYSTROPHY 1 56 Gross Pathologic & Surgical Features Natural History & Prognosis • CMDs with brain malformations o Supratentorial: Disorganized cortex: Coarse gyri, agyric regions, +/- hydrocephalus and focal interhemispheric fusion o Brainstem: Variable degrees of pontine hypoplasia and fused colliculi ~ flat, cleft or "Z-shaped" brainstem o Infratentorial: CBLL hypoplasia, PMG and cysts related to PMG, +/- encephalocele o Ocular anomalies: Retinal/optic nerve dysplasias, microphthalmia, buphthalmos, glaucoma, anterior chamber dysplasias, cataracts • CMD 1 with normallaminin-oc.2 expression (merosoin +): Decreased fetal movement, hypotonia, proximal weakness, contractures, mild or nonprogressive course, most can sit, some can walk, intellect usually normal • CMD 1 with deficient laminin-<x2 expression (merosoin -): More severe than above, intellect usually normal, but some have Sz • FCMD: Severely hypotonia, Sz, MR, contractures early, rarely learn to walk, death before 20 yrs • MEB: Severe hypotonia, Sz, MR, may survive to 20 yrs, but develop spasticity and contractures • WWS: Most severely affected, lethal in infancy, little spontaneous movement, no motor/cognitive skills, usually die in first year of life Microscopic Features • Cerebral and CBLL PMG • Fibroglial proliferation of leptomeninges (leads to pebbled surface and trapped CSF "cysts") • Hypoplasia of corticospinal tracts Treatment • No treatment other than supportive: Major respiratory and cardiovascular concerns Staging, Grading or Classification Criteria • CMD IA: Congenital merosin-deficient muscular dystrophy (abnormal WM) • CMD 2: FCMD (moderate dysplasia of neocortex, CBLL cortex and abnormal WM) o Frontal polymicrogyria, occipital cobblestone cortex, delayed myelin with "peripheral first" myelination pattern • CMD 3: Finnish type MEB (less severe than CDM 4) o Hydrocephalus, vermian hypogenesis, dysplastic cortex, patchy abnormal WM, +/- callosal dysgenesis • CMD 4: Walker-Warburg (most severe) o Hydrocephalus, vermian hypogenesis, kinked pons-midbrain, cobblestone cortex, no myelin, +/cephalocele, +/- callosal dysgenesis Consider • Typical brainstem and cerebellar findings should prompt the diagnosis of CMD, even if eyes and supratentorial cortex radiographically normal Image Interpretation 1. Presentation 2. • Most common signs/symptoms: Hypotonia, mentally retarded, delayed motor, poor vision, elevated serum creatine kinase • Clinical profile: Floppy newborn 3. 4. Demographics • Age o CMD with brain malformations can be diagnosed in utero via US and MRI, otherwise in early infancy o FCMD: High percentage spontaneous abortions • Gender: Autosomal recessive: M = F usual (some M > F or F > M variants) • Ethnicity o FCMD most common in Japan (carrier state 1:88) o MEB more prevalent in Finland o WWS has worldwide distribution o Other country and population-isolate specific variants are known Congenital Pearls • Not all "Z-shaped" brainstems are CMD, clinical and laboratory features are crucial for the diagnosis • Not all CMD have "Z-shaped" brainstems, remember merosin (-) CMD 5. 6. 7. 8. Zolkipli Z et al: Occipito-temporal polymicrogyria and subclinical muscular dystrophy. Neuropediatrics 34(20):92-5, 2003 Lopate G et al: Congenital muscular dystrophy. eMedicine (topic 549), 2003 Triki C et al: Merosin-deficient CMD with mental retardation and cerebellar cysts. Neuromuscul Disord 13(1):4-12,2003 Olson EC et al: Smooth, rough and upside-down neocortical development. Curr Opin Genet Dev 12(3):320-7, 2002 Mercuri E et al: Early white matter changes on brain magnetic resonance imaging in a newborn affected by merosin-deficient congenital muscular dystrophy. Neuromuscul Disord 11(3):297-9, 2001 Philpot] et al: Brain magnetic resonance imaging abnormalities in merosin-positive congenital muscular dystrophy. Eur] Paediatr NeuroI4(3):109-14, 2000 Barkovich A]: Neuroimaging manifestations and classification of congenital muscular dystrophies. A]NR 19:1389-96, 1998 Santavuori P et al: Muscle-eye-brain disease: Clinical features, visual evoked potentials and brain imaging in 20 patients. Eur] Paediatr Neurol 2(1):41-7, 1998 Malformations
  • 87. CONGENITAL MUSCULAR DYSTROPHY 1 57 Typical (Left) Sagittal T2WI MR shows flexed brainstem, unusual tectum (open arrow), hypoplastic pons, vermian dysgenesis, tiny cerebellar cysts (arrow) and hydrocephalus. (Right) Coronal T2WI MR shows occipital cobblestone lissencephaly (arrow), dysplastic cerebellum with cysts (curved arrow) and ventriculomegaly. Typical (Left) Axial T2WI MR shows disorganized cerebellar folia with cysts (arrow) and a hypoplastic pons. (Right) Axial FLAIRMR in another child shows notched pons (arrow) and multiple cerebellar cysts (curved arrow). Typical (Left) Axial T2WI MR in a child with CMD and brain malformations shows abnormal frontal white matter and pachygyria/polygyria of the frontal lobes (open arrow). (Right) Axial T2WI MR in a child with merosin negative CMD shows diffusely abnormal periventricular, lobar, and subcortical WM (arrows). Congenital Malformations
  • 88. 58 Axial graphic shows extensive bilateral subependymal heterotopia (arrow) lining the lateral ventricles. Gray matter cortical ribbon is thin and the sulci are shallow. Abbreviations • Heterotopic and Synonyms gray matter (HGM) Definitions • Arrested/disrupted neurons along migrat