Surgical Neuroangiography: Vol. 3: Clinical and Interventional Aspects in Children (Surgical Neuroangiography)

Surgical Neuroangiography 3

The complete three-volume set consists of Volume 1

Clinical Vascular Anatomy and Variations Volume 2

Clinical and Endovascular Treatment Aspects in Adults Volume 3

Clinical and Interventional Aspects in Children

Surgical Neuroangiography

P. Lasjaunias K. G. ter Brugge A. Berenstein

3

Clinical and Interventional Aspects in Children

Second Edition With 865 Figures in 2277 Separate Illustrations and 102 Tables

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Pierre Lasjaunias, M.D., Ph.D. Professeur des Universités en Anatomie Chef de Service de Neuroradiologie Diagnostique et Thérapeutique Centre Hospitalier Universitaire de Bicêtre 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France Karel G. ter Brugge, M.D., FRCPC The David Braley and Nancy Gordon Chair in Interventional Neuroradiology University of Toronto Head, Division of Neuroradiology Toronto Western Hospital, UHN 399 Bathurst St., 3MCL – 434,Toronto, ON M5T 2S8, Canada Alejandro Berenstein, M.D. Professor of Radiology and Neurosurgery Albert Einstein School of Medicine, NY Director of the Hyman-Newman Institute of Neurology and Neurosurgery, and of The Center for Endovascular Surgery Roosevelt Hospital Medical Center 1000 10th Ave. 10 G, New York, NY 10019, USA

ISBN 10 3-540-41681-1 Springer Berlin Heidelberg New York ISBN 13 978-3-540-41681-4 Springer Berlin Heidelberg New York Library of Congress Control Number: 00049688 This work is subject to copyright. All rights reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in databanks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September, 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag.Violations are liable for prosecution under the German Copyright Law. Springer is a part of Springer Science+Business Media springer.com © Springer-Verlag Berlin Heidelberg 1997, 2006 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and there forefree for general use. Productliability: The publisher cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Editor: Dr. Ute Heilmann, Heidelberg Desk Editor: Dörthe Mennecke-Bühler, Heidelberg Production: LE-TeX Jelonek, Schmidt & Vöckler GbR, Leipzig Reproduction and Typesetting: AM-productions GmbH, Wiesloch Cover design: E. Kirchner, Heidelberg Printed on acid-free paper 21/3100/YL – 5 4 3 2 1 0

Preface to the Second Edition

This volume completes the 3-volume series of the second edition of “Surgical Neuroangiography”. In the first volume, functional vascular anatomy, collateral circulation and vascular variations affecting the brain and spinal cord were described in detail. The second volume dealt with neurovascular diseases in adults and their management by surgical neuroangiography. This third volume focuses on the management of vascular diseases affecting the brain, spinal cord, and head and neck areas in the pediatric age group. Twenty-seven years have elapsed since the original publication of the first part of volume 1,“The Craniofacial and Upper Cervical Arteries”, in 1979. Eighteen years later the first edition of the volume on “Vascular Diseases in Neonates, Infants and Children” was published, which documented our improved understanding and growing experience with the endovascular management of pediatric patients. Similar to our experience in adults, we were able to make significant discoveries in the pediatric population, allowing us to break down previously established obstacles, widen the scope of our specialty, and create new reference points. This in turn is likely to facilitate the evolution of new management strategies as it will stimulate the participation of experts with different clinical backgrounds. It took us 10 years to create the second edition of the 6 previously published books and convert them into 3 large volumes. These books are based on shared practices, thoughts, and doubts, rather than on a compromise between 3 different individuals. They demonstrate a common vision generated by 30 years of practice and commitment. Our different personal skills and knowledge were enhanced by the others’ visions and thoughts. These books are therefore not multi-author books but the reflection of 3 experiences integrated into a common larger one. Recognition of the specificities of pediatric diseases is particularly challenging. It reflects the degree of sophistication and maturation of a given society. The development of pediatric hospitals and pediatric neurosurgery in the second half of the twentieth century already signified this evolution. These 3 volumes are meant to constitute the theoretical background of modern management of neurovascular diseases in adults and children. Our desire to share and teach this experience started in the early 1980s with the New York University/Paris XI University joint courses, the ABC Courses that were started in Paris 15 years ago, and more recently the

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Perface

Toronto Course. Finally, this text corresponds to the Syllabus of the present Masters Degree in Neurovascular Diseases, jointly created by the Paris XI and Mahidol Universities, taught in Asia and open to students from all over the world. However, our task has not been finished yet. As new frontiers keep appearing, they allow new fields to be explored and new teaching challenges to be resolved. We believe that these 3 volumes will contribute to an improved understanding of neurovascular disorders and that they represent a solid foundation upon which the development of new approaches of treatment can be based. October 2006

Pierre Lasjaunias, Karel ter Brugge, Alex Berenstein

We wish to thank our colleagues from the pediatric ICUs, Pediatric Neurology, Neurosurgery and Maxillofacial Surgery, and their teams without whom we could not have accomplished this work. Our particular thanks go to: Prof. Denis De Victor Dr. Philippe Durand Dr. Laurent Chevret Prof. Marc Tardieu Prof. Pierre Landrieu Prof. Michel Zerah Prof. Marc Tadié Prof. Marie Paule Vazquez Prof. Dan Benhamou Prof. Jacques Duranteau Prof. Fred Epstein* (*deceased) Prof. Mark Persky Prof. Milton Waner Prof. Mark Kupersmith Dr. Peter Dirks Dr. Derek Armstrong Dr. Gabrielle deVeber

Preface to the First Edition

This volume on vascular diseases in neonates, infants and children represents the fruit of our labour and experience in interventional neuroradiology in children that started in 1975, and now accounting for 30% of the activity in our unit at Bicêtre in Paris. The competence and support of the anaesthesia, paediatric intensive care, and paediatric neurology departments in Bicêtre have been key factors in our development, and their specific contributions are included in these pages. Through collaboration, I have learned that “multidisciplinary approach” is not just a turn of phrase, but rather the way adults who respect one another share information, and I have also learned that children are not small adults. I am especially indebted to Karel ter Brugge, to whom I owe the development, in 1984, of my paediatric interventional practice. Over the past 15 years, beyond our friendship, our practical and academic collaboration has never ceased. It is reflected in this book: not only did Karel edit the whole of this work, he also wrote the core of the chapter on aneurysms (with Jehad Al-Watban) as well as the chapter on cerebral arterial ischaemia (with Guillaume Sebire). Throughout the years, encouragement from the neurosurgeons has been precious. I also particularly appreciate the continuous support of A. Raimondi, who in Child’s Nervous System provided us with a forum to publish our material. Because vascular diseases are rare in neonates, infants and children and geographically dispersed, the international neuroradiology network that we have created has been very beneficial. The greater part of the information used in this volume was contributed via this network. This is not, then, a multi-author book, but rather the result of observations converging at various intervention sites: Toronto (Karel ter Brugge), Lisbon (Augusto Goulao), London (Wendy Taylor), Berlin (Jörg Meisel and Christian Koch), Singapore (Robert Kwok), Riyadh (Jehad Al-Watban), Bangkok (Sirintara Pongpech and Suthisak Suthipongchai), Stockholm (Michael Soderman), Cape Town (Steve Beningfield), and Bicêtre, Paris (Georges Rodesch and Hortensia Alvarez). Is a book the best means of communicating or sharing experience? Textbooks are only seldom quoted and often hardly read. Until recently, a written work was a synonym for book, but nowadays it may also appear on the computer screen. Although it may seem archaic - technically speaking - when compared to electronic publications, a book appeals to more of the senses and its content is more likely to be remembered. It must, however, choose between having its own style, and thus being controversial, or becoming sterile, politically correct, and consensual. No

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doubt books of the latter kind will become an endangered species, for they lose the elements of human imperfection and coherence. Most of those we have trained at Bicêtre or elsewhere have contributed to our analysis of paediatric vascular pathologies, and their work has usually been published. All or part of this material has been grouped within the corresponding chapters: – Aneurysmal malformations of the vein of Galen: Ricardo GarciaMonaco (Buenos Aires), Hortensia Alvarez, Michel Zerah (Paris), Nadine Girard (Marseille), Soichi Inagawa (Hamamatsu), Jehad Al-Watban, Maria Moersdorf (Trier), and Dominique Fournier (Angers) – Pial arteriovenous malformations: Hortensia Alvarez, Yuo Iizuka (Tokyo), and Robert Willinsky (Toronto) – Dural arteriovenous shunts: Ronie Piske (Sao Paulo), Augusto Goulao, Jean de Villiers, Francis Hui (Singapore), Georges Magufis (Athens), Wendy Taylor, and Robert Kwok – Venous ischaemia: Michael Soderman – Venous malformations and abnormalities: R. Piske, Karel ter Brugge, Jörg Meisel, and Philippe Pruvost (Bicêtre) – Traumatisms and epistaxis: Suthisak Suthipongchai (Bangkok) and Hortensia Alvarez – Para-notochordal fistulas: Georges Rodesch and Marco Trosselo Pastore (Bologna) – Spinal cord: Georges Rodesch As for the chapters on maxillofacial malformations and facial haemangiomas, Patricia Burrows (currently in Boston) contributed an essential part of the content. In the last chapter, finally, we are privileged to be able to reproduce work of very high quality: a part of Jeanne-Claudie Larroche’s (Paris) foetal pathology atlas, meningeal spaces anatomy studied by Roy O. Weller (Southampton), meningeal vascularisation in the foetus by Claude Maillot and Pierre Kherli (Strasbourg), and a perinatal cerebral myelinisation MRI atlas by Nadine Girard. In agreement with Alex Berenstein, with whom all five volumes of Surgical Neuroangiography were published from 1986 to 1992, certain of the cases presented in volumes 2,3 and 5 have been used again here, completed by follow-up X-rays taken nearly 10 years after embolisation in some cases. Accent has been put on the clinical experience acquired. Whenever the benefit of therapeutic hindsight was pertinent and the number of patients sufficient, the resulting figures were given. As it was impossible for this work to be exhaustive, we do not make any such claims. More often than not, we present our cases in terms of global care, whether lesions were embolised or not. Arterial and venous ischaemia are thus discussed in this volume, too, to reflect their clinical significance in a practice such as ours.Technique has thus been relegated to a position of secondary importance, which justifies the title of this work. In Vascular Diseases in Neonates, Infants and Children, rarely is the disease itself presented but rather its consequences. The morphological approach in vascular pathology is actually blatantly inadequate. Our knowledge of vascular diseases today is about equivalent to that of infectious

Preface

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diseases at the end of the eighteenth century: an abscess or a pleural effusion could be drained, just as we can obstruct a vascular malformation or an aneurysm; however, the causes and remedies remain to be found for affected vessels just as infectious agents and antibiotics did for an abscess or pleurisy then. Notions far removed from the usual preoccupations of a diagnostic and therapeutic neuroradiologist have been introduced: for example, the postnatal nature (as opposed to the congenital nature) of cerebral arteriovenous malformations, angiogenesis, vascular disease genetics, apoptosis, and vascular remodelling. The complete excision of a vascular lesion in a child often proves to be very mutilating and the long-term burden of handicap and dependence too heavy to bear. Hence, our intuition that partial treatment is valid has been confirmed.Whereas initially it resulted from failure to do better, it is now a therapeutic goal in itself - and sometimes the only acceptable one. These disorders are not necessarily treated to obliterate the image of the vascular lesion, but rather to correct the underlying causes of failure of the natural repairing systems. Vascular remodelling and the restoration of normal maturation processes complement endovascular treatments. Many interpretations of the facts have been offered. They illustrate the logical decision-making pathway we had to construct so as to make sound and reproducible decisions. It is this logic that has cemented our experience and grounded our teaching. The logic we use, though it appears to many to be a working hypothesis, is necessary when communicating with parents and children. Trusting relationships with children differ from those which can be established with adults. Trust is not won with eloquence, false seduction or pontificating certitudes. It is not difficult to gain, but it is the result of a simple relationship, free of deception or worries. Children are not usually afraid and are actually extraordinarily brave, in the adult sense of the term. They do not love the doctor; they simply trust him. January 1997

Pierre Lasjaunias

To Dr. Yvette Viallard Physician in Yemen

Pour le sillon qu’elle a tracé.

Contents

1

Embryological and Anatomical Introduction . . . .

1

1.1

Preliminary Remarks . . . . . . . . . . . . . . . . . . . .

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1.2

Leptomeninges

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1.3 1.3.1 1.3.2 1.3.3 1.3.3.1 1.3.3.2

Subpial Space . . . . . . . . . . . Anatomy . . . . . . . . . . . . . . Relationships of the Subpial Space Pathology . . . . . . . . . . . . . Inflammation . . . . . . . . . . . Tumors . . . . . . . . . . . . . . .

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22 22 23 23 23 24

2

Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts . . . .

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2.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . .

28

2.2

From Adults to Children . . . . . . . . . . . . . . . . . .

28

Vascular Lesion Types and Disease Groups . . . . . . . . Nonproliferative Lesions . . . . . . . . . . . . . . . . . . Arteriovenous Lesions . . . . . . . . . . . . . . . . . . . Isolated Brain AVMs . . . . . . . . . . . . . . . . . . . . Cerebral Arteriovenous Fistulas . . . . . . . . . . . . . . Vein of Galen Aneurysmal Malformations . . . . . . . . Cerebrofacial Arteriovenous Metameric Syndromes . . . Dural Lesions . . . . . . . . . . . . . . . . . . . . . . . . Telangiectasias . . . . . . . . . . . . . . . . . . . . . . . The Blue Rubber-Bleb Nevus or Bean Syndrome . . . . . Venous Malformations (Cavernomas) . . . . . . . . . . Venous Angiomas or Developmental Venous Anomalies Cerebrofacial Venous Metameric Syndrome (Sturge-Weber Syndrome) . . . . . . . . . . . . . . . . . 2.3.1.12 Induced Pial Shunts . . . . . . . . . . . . . . . . . . . . . 2.3.1.13 Spinal Cord AVM . . . . . . . . . . . . . . . . . . . . . . 2.3.1.14 General Conclusions on Vascular Lesions . . . . . . . . . 2.3.2 Proliferative Lesions . . . . . . . . . . . . . . . . . . . . 2.3.2.1 PHACE or PHACES . . . . . . . . . . . . . . . . . . . . . 2.3.2.2 Diffuse Angiodysplasia . . . . . . . . . . . . . . . . . . .

31 34 34 35 39 39 39 41 41 41 44 45

2.3 2.3.1 2.3.1.1 2.3.1.2 2.3.1.3 2.3.1.4 2.3.1.5 2.3.1.6 2.3.1.7 2.3.1.8 2.3.1.9 2.3.1.10 2.3.1.11

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47 47 48 48 49 51 51

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2.4 2.4.1 2.4.2 2.4.3 2.4.4

Classification of CAVMs by Age Group Fetal Age . . . . . . . . . . . . . . . . Neonatal Age . . . . . . . . . . . . . Infancy . . . . . . . . . . . . . . . . . After 2 Years . . . . . . . . . . . . . .

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2.5 2.5.1 2.5.2 2.5.3

Classification by Symptom Group . Congestive Cardiac Manifestations Hydrodynamic Disorders . . . . . Melting-Brain Syndrome . . . . . .

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63 63 64 73

2.6

Clinical Evaluation Scores . . . . . . . . . . . . . . . . .

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2.7

Revised Concept of the Congenital Nature of Vascular Malformations . . . . . . . . . . . . . . . 2.7.1 Genetics . . . . . . . . . . . . . . . . . . . . . . . . . 2.7.1.1 Familial Hemiplegic Migraine . . . . . . . . . . . . . 2.7.1.2 Familial Cerebral Aneurysms . . . . . . . . . . . . . 2.7.1.3 PKD1 and Bourneville PDK1-PDK2 . . . . . . . . . . 2.7.1.4 Ehlers-Danlos Type IV . . . . . . . . . . . . . . . . . 2.7.1.5 Multiple Cutaneous Mucous Venous Malformations, Blue Rubber Bleb Nevus Syndrome . . . . . . . . . . 2.7.1.6 CADASIL . . . . . . . . . . . . . . . . . . . . . . . . . 2.7.1.7 Familial Paragangliomas . . . . . . . . . . . . . . . . 2.7.1.8 Familial Cavernomas . . . . . . . . . . . . . . . . . . 2.7.1.9 Neurofibromatosis-1 and Other Collagen Diseases . 2.7.1.10 Hemorrhagic Hereditary Telangiectasia or Rendu-Osler-Weber Disease . . . . . . . . . . . . 2.8

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2.8.4 2.8.5

Vascular Remodeling and the Congenital Nature of Arteriovenous Shunts . . . . . . . . . . . . . . . . . . Endothelium as a Sensor and Transducer of Signals . . . Endothelium-Specific Receptor-Coupled Event . . . . . Endothelium and Mediator-Effector Molecules Involved with Remodeling . . . . . . . . . . . . . . . . . . . . . . Role of Matrix Modulators in Vascular Remodeling . . . Clinical Implications of Vascular Remodeling . . . . . .

3

Vein of Galen Aneurysmal Malformation . . . . . . 105

3.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 106

3.2 3.2.1 3.2.2

Historical Landmarks . . . . . . . . . . . . . . . . . . . 107 Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 Clinical Aspects . . . . . . . . . . . . . . . . . . . . . . . 107

3.3

Modern Concept of Vein of Galen Aneurysmal Malformation

2.8.1 2.8.2 2.8.3

93 94 95 95 95 95

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3.4

Vein of Galen Aneurysmal Dilatation . . . . . . . . . . . 112

3.5

Dural Arteriovenous Shunts with Aneurysmal Dilatation of the Vein of Galen

3.6

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Vein of Galen Varix . . . . . . . . . . . . . . . . . . . . . 117

Contents

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3.7

Vein of Galen Aneurysmal Malformation . . . . . . . . . 117

3.8

Natural History of Vein of Galen Aneurysmal Malformation

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3.9

Cardiac Manifestations . . . . . . . . . . . . . . . . . . . 143

3.10

Macrocrania and Hydrocephalus . . . . . . . . . . . . . 152

3.11

Late Natural History of Vein of Galen Aneurysmal Malformation with Patent Sinuses

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3.12

Dural Sinus Occlusion and Supratentorial Pial Congestion and Reflux . . . . . 167

3.13 3.13.1

Dural Sinus Thrombosis and Infratentorial Pial Reflux . 180 Spontaneous Thrombosis . . . . . . . . . . . . . . . . . 184

3.14 3.14.1 3.14.2 3.14.2.1 3.14.2.2 3.14.3

Objectives and Methods of Treatment General Remarks . . . . . . . . . . . Neonates . . . . . . . . . . . . . . . . Reducing Oxygen Consumption . . . Improving Oxygen Delivery . . . . . Infants and Children . . . . . . . . .

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191 191 191 197 197 200

3.15 3.15.1 3.15.2 3.15.3 3.15.4 3.15.5

Technical Management . . . . . . . . General Remarks . . . . . . . . . . . Follow-Up . . . . . . . . . . . . . . . Complications: Morbidity . . . . . . Overall Mortality . . . . . . . . . . . Neurological Outcome by Age Group

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203 203 205 210 220 221

3.16 3.16.1 3.16.2 3.16.3

Other Techniques . . . Surgery . . . . . . . . . Transvenous Treatment Radiosurgery . . . . .

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221 221 223 224

4

Cerebral Arteriovenous Fistulas . . . . . . . . . . . . 227

4.1

Definitions and Anatomic Spaces . . . . . . . . . . . . . 227

4.2 4.2.1 4.2.2

Angioarchitecture . . . . . . . . . . . . . . . . . . . . . . 228 Single CAVFs . . . . . . . . . . . . . . . . . . . . . . . . 228 Multiple CAVFs . . . . . . . . . . . . . . . . . . . . . . . 231

4.3 4.3.1 4.3.2

Associated Conditions . . . . . . . . . . . . . . . . . . . 236 Hereditary Hemorrhagic Telangiectasia . . . . . . . . . 236 Encephalocraniocutaneous Lipomatosis . . . . . . . . . 246

4.4 4.4.1

Presentation . . . . . . . . . . . . . . . . . . . . . . . . . 249 Natural History . . . . . . . . . . . . . . . . . . . . . . . 265

4.5

Management

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5

Cerebral Arteriovenous Malformations . . . . . . . 291

5.1

General Remarks . . . . . . . . . . . . . . . . . . . . . . 292

5.2 5.2.1

Angioarchitecture of Cerebral Arteriovenous Malformations . . . . . . . . . . . . . . . 298 Single Nidus Versus Multifocal Niduses . . . . . . . . . . 298

5.3

Conditions Associated with CAVMs . . . . . . . . . . . . 302

5.4 5.4.1 5.4.2 5.4.3 5.4.4 5.4.5

Conditions Mimicking CAVMs . . . . . False Pial Arteriovenous Malformations Perinidal Angiogenesis . . . . . . . . . Postischemic Luxury Perfusion . . . . Proliferative Angiopathy . . . . . . . . Induced Pial AV Shunts Secondary to Dural Sinus High-Flow Lesions . . .

5.5 5.5.1 5.5.2 5.5.3 5.5.4 5.5.5 5.5.6 5.5.7

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306 306 306 306 306

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Angioarchitectural Progression of CAVMs in Children Venous Angiopathy . . . . . . . . . . . . . . . . . . . Dural Sinus High Flow . . . . . . . . . . . . . . . . . Venous Ischemia and Thrombosis . . . . . . . . . . Venous Hemorrhage . . . . . . . . . . . . . . . . . . Venous Enlargement . . . . . . . . . . . . . . . . . . Arterial Angiopathy . . . . . . . . . . . . . . . . . . . Spontaneous Thrombosis of Arteriovenous Malformations . . . . . . . . . . .

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311 311 312 315 316 321 324

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5.6 5.6.1 5.6.2 5.6.3 5.6.3.1 5.6.3.2 5.6.4 5.6.5

Objectives of Treatment . . . . . . . . Complete Exclusion . . . . . . . . . . . Partial Treatment . . . . . . . . . . . . Neonates and Infants . . . . . . . . . . Hydrodynamic Disorders . . . . . . . Multiple Arteriovenous Malformations Children . . . . . . . . . . . . . . . . . Rebleeding . . . . . . . . . . . . . . . .

5.7 5.7.1 5.7.2 5.7.2.1 5.7.2.2

Technical Management General Remarks . . . Other Techniques . . . Surgery . . . . . . . . . Radiation Therapy . .

6

Cerebrofacial Arteriovenous Metameric Syndrome

6.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 359

6.2 6.2.1

Clinical Manifestations . . . . . . . . . . . . . . Retinal AVMs and AVMs Along the Optic Nerve and Chiasm . . . . . . . . . . . . . . . . . . . . Retinal AVMs . . . . . . . . . . . . . . . . . . . Optic Nerve and Chiasmatic AVMs . . . . . . .

6.2.1.1 6.2.1.2

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Contents

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6.2.2 6.2.3 6.2.4

Cerebral AVMs . . . . . . . . . . . . . . . . . . . . . . . 376 Facial AVMs, Nasal AVMs, and Mandibular AVMs . . . . 382 Investigation for CAMS Patients . . . . . . . . . . . . . . 384

6.3

CAMS and Angiogenic Activity

7

Dural Arteriovenous Shunts . . . . . . . . . . . . . . 389

7.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 389

7.2 7.2.1 7.2.2

Classification . . . . . . . . . . . . . . . . . . . . . . . . 390 Age Groups . . . . . . . . . . . . . . . . . . . . . . . . . 392 Disease Groups . . . . . . . . . . . . . . . . . . . . . . . 392

7.3 7.3.1 7.3.1.1 7.3.2

Dural Sinus Malformations . . . . . . DSM with Giant Pouches . . . . . . . . Fetal and Postnatal Changes of Sinuses DSM of the Jugular Bulb . . . . . . . .

7.4

Infantile Dural Arteriovenous Shunts (AVS) . . . . . . . 436

7.5

Adult Type of Dural Arteriovenous Shunts in Children

7.6 7.6.1 7.6.2

Other Dural Shunts . . . . . . . . . . . . . . Vein of Galen Aneurysmal Malformation . . Dural Supply to Pial Cerebral Arteriovenous Malformations . . . . . . . . . . . . . . . . Proliferative Angiopathic Disease . . . . . . Systemic Disorders . . . . . . . . . . . . . . Recurrence in Intradural AVS and Secondary Transdural Supply . . . . . .

7.6.3 7.6.4 7.6.5

. . . . . . . . . . . . . . 384

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

396 398 398 434

. 444

. . . . . . . 447 . . . . . . . 447 . . . . . . . 447 . . . . . . . 448 . . . . . . . 448 . . . . . . . 449

7.7

General Remarks on Treatment . . . . . . . . . . . . . . 451

8

Venous Anomalies and Malformations . . . . . . . . 455

8.1 8.1.1 8.1.2 8.1.3

Developmental Venous Anomalies Single Abnormalities . . . . . . . Associated Features . . . . . . . . Associated Cavernomas . . . . .

8.2

Segmental and Nonsegmental Cerebro-orbito-facial Venous Lesions Sturge-Weber Syndrome . . . . . . . From SWS to Cerebrofacial Venous Metameric Syndrome . . . . Orbitofacial Venous Lesions . . . . .

8.2.1 8.2.2 8.2.3

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

455 455 459 473

. . . . . . . . . . . 478 . . . . . . . . . . . 478 . . . . . . . . . . . 485 . . . . . . . . . . . 496

8.3

Complex Pseudo-metameric Cerebrofacial Venous Syndrome . . . . . . . . . . . . . . . . . . . . . . 499

8.4 8.4.1 8.4.2 8.4.3

Blue Rubber Bleb Nevus (Bean Syndrome) The Association of BRBN with DVA . . . . Cerebral Venous Malformations in BRBN BRBN and HHT1 . . . . . . . . . . . . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

. . . .

503 504 507 507

XVI

Contents

9

Craniopagus and Cranial Midline Epidural Venous Anomalies . . . . . . . . . . . . . . . 509

9.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 509

9.2

Postulated Relationships Between the Superior Sagittal Sinus and Adjacent Structures . . . 511

9.3

Ladan and Laleh’s Angiographic Anatomy . . . . . . . . 521

9.4

Technical Remarks and Functional Testing . . . . . . . . 531

9.5

Discussion on Surgical Management . . . . . . . . . . . 534

10

Cerebral Venous Thrombosis . . . . . . . . . . . . . . 537

10.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 537

10.2

Pathophysiology and Risk Factors . . . . . . . . . . . . . 539

10.3

Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . 545

10.4

Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . 547

10.5

Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . 556

10.6

Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . 557

11

Hemangiomas . . . . . . . . . . . . . . . . . . . . . . . 559

11.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 560

11.2

Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . 562

11.3

Histological Findings . . . . . . . . . . . . . . . . . . . . 563

11.4

Clinical Presentation of Hemangiomas . . . . . . . . . . 564

11.5

Diagnosis

11.6

Complications in Hemangiomas

11.7

Management of Hemangiomas

11.8 11.8.1 11.8.2 11.8.3 11.8.4 11.8.5

Pharmacological Therapy of Hemangiomas Corticosteroids . . . . . . . . . . . . . . . . Interferon-Alpha 2a . . . . . . . . . . . . . . Vincristine . . . . . . . . . . . . . . . . . . . Aminocaproic Acid . . . . . . . . . . . . . . Other Treatments . . . . . . . . . . . . . . .

11.9

Laser Treatment of Hemangiomas

11.10 11.10.1 11.10.2

Endovascular Treatment of Hemangiomas . . . . . . . . 580 Arterial Embolization . . . . . . . . . . . . . . . . . . . 580 Intralesional Embolization . . . . . . . . . . . . . . . . . 582

11.11

Noninvoluting Capillary Hemangiomas

11.12

Subglottic Hemangiomas . . . . . . . . . . . . . . . . . . 588

11.13

Periorbital Hemangiomas . . . . . . . . . . . . . . . . . 590

. . . . . . . . . . . . . . . . . . . . . . . . . . 570 . . . . . . . . . . . . . 574 . . . . . . . . . . . . . . 577 . . . . . .

. . . . . .

. . . . . .

. . . . . .

. . . . . .

. . . . . .

. . . . . .

578 578 579 579 579 579

. . . . . . . . . . . . 580

. . . . . . . . . 585

Contents XVII

11.14

Oral Hemangiomas . . . . . . . . . . . . . . . . . . . . . 592

11.15

Salivary Gland Hemangioma

11.16

Bone Hemangiomas

11.17

Associated Anomalies . . . . . . . . . . . . . . . . . . . . 598

11.18

Psychological Impact . . . . . . . . . . . . . . . . . . . . 598

11.19

Kaposiform Hemangioendothelioma and Consumption Coagulopathy, the Kasabach-Merritt Syndrome Phenomena

. . . . . . . . . . . . . . . 592

. . . . . . . . . . . . . . . . . . . . 595

. . . . . . 602

12

PHACES . . . . . . . . . . . . . . . . . . . . . . . . . . . 607

12.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 607

12.2 12.2.1 12.2.2 12.2.3 12.2.4 12.2.5 12.2.6 12.2.7

Clinical Aspects . . . . . . . . . . . . . . . Posterior Fossa Abnormalities . . . . . . . Hemangiomas . . . . . . . . . . . . . . . . Arterial Anomalies . . . . . . . . . . . . . Coarctation and Congenital Heart Disease Eye Abnormalities . . . . . . . . . . . . . Sternal Cleft . . . . . . . . . . . . . . . . . Stenotic Arterial Disease . . . . . . . . . .

12.3

PHACES, a Congenital Malformation and a Proliferative Disease . . . . . . . . . . . . . . . . . 631

13

Cervicofacial Vascular Malformations . . . . . . . . 633

13.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 634

13.2

Traditionally Postulated Embryogenesis . . . . . . . . . 638

13.3

Diagnostic and Pretherapeutic Evaluation . . . . . . . . 640

13.4

Clinical Diagnosis of a Vascular Malformation

13.5 13.5.1 13.5.1.1 13.5.1.2 13.5.2 13.5.2.1 13.5.2.2 13.5.3

Arteriovenous Shunts . . . . . . . Soft Tissue AVMs . . . . . . . . . Intramuscular AVMs . . . . . . . Cutaneous AVMs . . . . . . . . . Intra-osseous AVMs . . . . . . . Mandibular and Maxillary AVMs Signs and Symptoms . . . . . . . Metameric Cerebrofacial AVMs .

13.6

Intra-osseous Slow-Flow Malformations . . . . . . . . . 659

13.7

Arteriolar-Capillary Malformations

13.8

Capillary Venous Malformations

13.9

Venous Vascular Malformations . . . . . . . . . . . . . . 660

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

609 611 618 622 623 627 627 627

. . . . . 640 . . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . . . . . .

641 643 643 644 646 646 651 657

. . . . . . . . . . . 659

. . . . . . . . . . . . . 659

XVIII Contents

13.10

Complex Cerebrofacial Venous Syndromes (CVMS or Sturge-Weber Syndrome) . . . . . . . . . . . . 670

13.11

Lymphatic Malformations . . . . . . . . . . . . . . . . . 670

13.12

Mixed Vascular Malformations . . . . . . . . . . . . . . 681

13.13

Multifocal AVMs . . . . . . . . . . . . . . . . . . . . . . . 681

13.14 13.14.1 13.14.2

False Maxillofacial Vascular Malformations . . . . . . . 681 Idiopathic Facial Vascular (Venous) Dilatations . . . . . 681 Facial Venous Dilatation Associated with Intracranial Vascular Lesions . . . . . . . . . . . . . 685

14

Parachordal Arteriovenous Fistulas (Extracranial and Extraspinal Arteriovenous Fistulas) . . . . . . . 687

14.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 687

14.2

Specific Clinical Features . . . . . . . . . . . . . . . . . . 689

14.3

Topographic Approach . . . . . . . . . . . . . . . . . . . 696

14.4 14.4.1 14.4.2

Branchial Arteriovenous Shunts . . . . . . . . . . . . . . 696 Maxillary Artery/Vein Arteriovenous Fistulas . . . . . . 697 Ascending Pharyngeal-Internal Jugular Arteriovenous Fistulas . . . . . . . . . . . . . . . . . . . 699

14.5

Vertebro-vertebral Arteriovenous Fistulas . . . . . . . . 700

14.6

Paraspinal Arteriovenous Fistulas

14.7

Technical Management of High-Flow Fistulas . . . . . . 719

15

Spinal Cord Arteriovenous Malformations . . . . . 721

15.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 721

15.2

Classification

15.3

Natural History and Clinical Aspects . . . . . . . . . . . 737

15.4

Neonatal and Infants . . . . . . . . . . . . . . . . . . . . 737

15.5

Children Over 2 Years of Age . . . . . . . . . . . . . . . . 743

15.6

Diagnosis

15.7

Angioarchitecture . . . . . . . . . . . . . . . . . . . . . . 750

15.8 15.8.1 15.8.2 15.8.3

Treatment . . . . . . . . . . . Therapeutic Abstention . . . Embolization . . . . . . . . . Results . . . . . . . . . . . . .

. . . . . . . . . . . . 714

. . . . . . . . . . . . . . . . . . . . . . . . 722

. . . . . . . . . . . . . . . . . . . . . . . . . . 750 . . . .

. . . .

. . . .

. . . .

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. . . .

. . . .

. . . .

758 758 759 761

Contents

XIX

16

Vascular Trauma and Epistaxis . . . . . . . . . . . . . 767

16.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 767

16.2

Traumatic Carotid-Cavernous Fistulas . . . . . . . . . . 768

16.3

Post-traumatic Sinus Thrombosis . . . . . . . . . . . . . 776

16.4

Traumatic Dissections

16.5

Intracranial Arterial Aneurysms

16.6

Iatrogenic Injury . . . . . . . . . . . . . . . . . . . . . . 780

16.7

Traumatic Insult of Vascular Malformation

16.8

Epistaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . 785

16.9

Technical Remarks

17

Intracranial Aneurysms in Children . . . . . . . . . 789

17.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 789

17.2

Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . 793

17.3

Presentation . . . . . . . . . . . . . . . . . . . . . . . . . 795

17.4

Etiology

17.5

Traumatic Aneurysms

17.6

Infectious Aneurysms . . . . . . . . . . . . . . . . . . . . 803

17.7

Saccular Aneurysms

17.8

Dissecting Aneurysms

17.9

Location . . . . . . . . . . . . . . . . . . . . . . . . . . . 835

17.10

Therapeutic Strategies . . . . . . . . . . . . . . . . . . . 836

18

Arterial Ischemic Stroke . . . . . . . . . . . . . . . . . 851

18.1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 851

18.2

Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . 852

18.3

Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . 852

18.4

Clinical Presentation . . . . . . . . . . . . . . . . . . . . 853

18.5

Imaging of Arterial Stroke in Children . . . . . . . . . . 856

18.6

Outcome and Prognosis

18.7

Etiology

18.8

Cardiac Disorders . . . . . . . . . . . . . . . . . . . . . . 867

18.9

Acute Regressive Cerebral Arteriopathy

18.10

Dissections . . . . . . . . . . . . . . . . . . . . . . . . . . 878

18.11

Moyamoya Disease . . . . . . . . . . . . . . . . . . . . . 885

. . . . . . . . . . . . . . . . . . . 777 . . . . . . . . . . . . . 779 . . . . . . . 783

. . . . . . . . . . . . . . . . . . . . . 787

. . . . . . . . . . . . . . . . . . . . . . . . . . . 797 . . . . . . . . . . . . . . . . . . . 798 . . . . . . . . . . . . . . . . . . . . 813 . . . . . . . . . . . . . . . . . . . 823

. . . . . . . . . . . . . . . . . . 860

. . . . . . . . . . . . . . . . . . . . . . . . . . . 866 . . . . . . . . . 870

XX

Contents

18.12

Hematological Disorders and Coagulopathies . . . . . . 892

18.13

Metabolic Disorders

18.14

Proliferative Angiopathy . . . . . . . . . . . . . . . . . . 893

18.15

PHACE . . . . . . . . . . . . . . . . . . . . . . . . . . . . 899

18.16

Hereditary Hemorrhagic Telangiectasia, or Rendu-Osler-Weber Disease . . . . . . . . . . . . . . . 899

18.17

Spinal Cord Strokes . . . . . . . . . . . . . . . . . . . . . 899

18.18

Treatment and Management . . . . . . . . . . . . . . . . 905

19

References . . . . . . . . . . . . . . . . . . . . . . . . . 909 Subject Index

. . . . . . . . . . . . . . . . . . . . 893

. . . . . . . . . . . . . . . . . . . . . . . 967

1 Embryological and Anatomical Introduction

1.1

Preliminary Remarks 1

1.2

Leptomeninges 21

1.3 1.3.1 1.3.2 1.3.3 1.3.3.1 1.3.3.2

Subpial Space 22 Anatomy 22 Relationships of the Subpial Space 23 Pathology 23 Inflammation 23 Tumor 24

1.1 Preliminary Remarks In this section we have collected illustrations that are relevant to the basic principles described in the various chapters of this book. Vascularization of dural covers in the fetus, particularly the venouslike channels, points to the role that they may play before granulation maturation. This rich vascularization contrasts with the rarity of true dural arteriovenous malformation in clinical practice. On the other hand, it may also constitute a reservoir for the sometimes dramatic response of the dural covers to angiogenic stimulation (Figs. 1.1, 1.2). C. Larroche and N. Girard have allowed us to reproduce some of their work; we have used fetal brain sections published by Larroche in an atlas that is no longer in print (Figs. 1.3–1.8) and magnetic resonance imaging (MRI) evaluation by Girard of myelinization in the perinatal period (Figs. 1.9–1.18). These pictures are not intended to formally establish what constitutes a normal appearance, but rather to help visualize the path that the myelinization process follows in neonates and infants. The subpial space has been extensively studied by various authors. Weller (1992; Nicholas and Weller 1988) has contributed to the better understanding of both the anatomy and the role of the subpial space. The following text and images illustrate this particular meningeal space (Figs. 1.19–1.25). An understanding of meningeal relationships in terms of the biology of the barrier that they constitute should explain why hemorrhage in one space gives rise to a spasm, but a few millimeters after a transpial passage the same vessel does not show a spastic reaction to the same abluminal stimuli. On the venous side, in neonates subpial congestion gives rise to multiple trophic changes, which are very mild if the congestion occurs only in the subarachnoid space. The responses to inflammatory diseases certainly account for the transdural contributions and indicate that several cellular proliferative reactions can cross this barrier very easily.

2

1 Embryological and Anatomical Introduction

Fig. 1.1A–F. Anatomic preparation of neonatal dural coverings. A Axial section showing the occipital lobe, the falx cerebri and the striate sinus. Note the multiple vascular spaces contained in the torcular region. B Higher horizontal section above the torcular showing the parietal suture and the superior sagittal sinus. Note the bilobed appearance of the superior sagittal sinus (see the sinus malformations illustrated in Chap. 4). Many vascular channels can be seen within the dura. C Horizontal section showing the straight sinus and the tentorium at the torcular level. Highly vascularized dural spaces can still be seen. D Vertical section demonstrating the straight sinus and two additional venous channels in the falx. The arachnoid covers can be clearly seen. E Parasagittal section showing the lateral sinus and the marginal sinus at the lower edge of the occipital bone. The cerebellum and the tentorium are easily recognizable. F Vertical section demonstrating a superior sagittal sinus in its mid-third portion. Multiple venous channels are seen surrounding the sinus itself. The arachnoid and pia mater can be clearly seen. v, Vascular spaces. (Courtesy of P. Kherli and C. Maillot, unpublished data). E–F see p. 3

Preliminary Remarks

3

Fig. 1.1 (continued). E Parasagittal section showing the lateral sinus and the marginal sinus at the lower edge of the occipital bone. The cerebellum and the tentorium are easily recognizable. F Vertical section demonstrating a superior sagittal sinus in its mid-third portion. Multiple venous channels are seen surrounding the sinus itself. The arachnoid and pia mater can be clearly seen. v, Vascular spaces. (Courtesy of P. Kherli and C. Maillot, unpublished data)

4

1 Embryological and Anatomical Introduction

Fig. 1.2A, B. Injected newborn specimen. A Medial face of the dural tentorium, demonstrating the arterial capillary network and a converging drainage in a perforating vein, joining the external surface of the dura mater (arrows). B Arterial capillary network on the tentorium cerebelli. The arrow points to the free margin of the tentorium. (Courtesy of C. Maillot, unpublished data)

Preliminary Remarks

5

Fig. 1.3. Fronto-oblique section passing through the frontal lobe and the olfactory nerve, the optic and infundibula recesses, the pons and trigeminal nerve, and the large fourth ventricle in a 13-week-old fetus. (Reprinted from Fess-Higgins and Larroche 1987, with permission)

Fig. 1.4A–F. A 40-g fetus. A Horizontal section for a gestational age of 12–13 weeks. The germinal matrix is well demonstrated. The choroid plexus fills the lateral ventricle entirely. B On the frontal section, the choroid plexus of the third ventricle can be clearly seen. A corpus callosum has not developed yet. C Mid-sagittal view. 1, Corpus callosum; 2, fornix; 3, lamina comissuralis; 4, olfactory bulb; 5, infundibulum; 6, mesencephalic aqueduct; 7, quadrigeminal plate; 8, fourth ventricle; 9, cerebellum. D Superior view. 1, Longitudinal fissure of the cerebrum; 2, cerebellum; 3, fourth ventricle; 4, medulla oblongata; 5, medulla spinalis. E Basal view. 1, Olfactory bulb; 2, optic chiasm; 3, infundibulum; 4, lateral fossa; 5, transverse fissure of the cerebrum; 6, pons; 7, cerebellum; 8, medulla oblongata; 9, medulla spinalis. F Lateral view. 1, Lateral fossa; 2, cerebellum; 3, medulla oblongata; 4, medulla spinalis. (Reprinted from Fess-Higgins and Larroche 1987, with permission) C–F see p. 6

6

1 Embryological and Anatomical Introduction

Fig. 1.4 C–F (continued). C Mid-sagittal view. 1, Corpus callosum; 2, fornix; 3, lamina comissuralis; 4, olfactory bulb; 5, infundibulum; 6, mesencephalic aqueduct; 7, quadrigeminal plate; 8, fourth ventricle; 9, cerebellum. D Superior view. 1, Longitudinal fissure of the cerebrum; 2, cerebellum; 3, fourth ventricle; 4, medulla oblongata; 5, medulla spinalis. E Basal view. 1, Olfactory bulb; 2, optic chiasm; 3, infundibulum; 4, lateral fossa; 5, transverse fissure of the cerebrum; 6, pons; 7, cerebellum; 8, medulla oblongata; 9, medulla spinalis. F Lateral view. 1, Lateral fossa; 2, cerebellum; 3, medulla oblongata; 4, medulla spinalis. (Reprinted from Fess-Higgins and Larroche 1987, with permission)

Fig. 1.5. A Frontal section of a 280-g fetus, 19–20 weeks of gestation. The deep nuclei are clearly demonstrated, in particular the thalamic and amygdaloid complex. B The trigeminal matrix and cells that have migrated toward the cortical surface can be clearly seen. (Reprinted from Fess-Higgins and Larroche 1987, with permission)

Preliminary Remarks

7

Fig. 1.6. A Axial and B frontal section of a 1,140-g embryo, 28 weeks of gestation, showing the development of the corpus callosum and the cortical layers. The matrix cannot be seen very well. The choroid plexus is reduced in size. Note the subarachnoid and pial spaces filled with small vessels. (Reprinted from Fess-Higgins and Larroche 1987, with permission)

Fig. 1.7. Mid-sagittal section of a 2,600-g embryo, 36 weeks of gestation, showing the choroid fissure. The same aspect is demonstrated Fig. 1.8. (Reprinted from Fess-Higgins and Larroche 1987, with permission)

8

1 Embryological and Anatomical Introduction

Fig. 1.8. Frontal view of 2,510-g embryo, 37 weeks of gestation. (Reprinted from Fess-Higgins and Larroche 1987, with permission)

Fig. 1.9A–C. Axial T1-weighted images (T1WI) in a 23-week-old fetus. C Axial T2-weighted image (T2WI) in a 21-week-old fetus. A The brain is agyric and the sylvian fissures are wide open, as they should be at this stage. The lateral ventricles are large; this feature corresponds to the relative hydrocephalus of the fetus. The cortical ribbon has a high signal, as do the germinal matrix and the migrant cells, which results in a multilayered pattern. High signal intensity is observed in the basal ganglia, corresponding to the high cellularity. B This is also the case in the posterior part of the brain stem as a result of myelination. C The cortical ribbon has low signal intensity on T2WI. (Courtesy of N. Girard)

Preliminary Remarks

9

Fig. 1.10A–H. Coronal T1-weighted images (T1WI) in a 29-week-old fetus. T2-weighted images (T2WI) in a 28-week-old fetus in C axial and D sagittal planes. E, G Axial T1WI and F, H axial T2WI of a 28-week-old premature newborn. A, B The cortical ribbon can still be seen as high signal intensity, while the migrant cells are no longer as visible. A, C The ventricles are now thinner than in Fig. 1.9. C The cortical ribbon can be seen as low signal intensity that is well delineated from the white matter and the subarachnoid spaces, which appear as high signal intensity. Moreover, early gyration can be seen and is better depicted on T2WI. The brain stem appears as B high signal intensity on T1WI and D low signal intensity on T2WI secondary to the completion of myelination. In the 28-week-old premature newborn, the cortical ribbon shows G high signal intensity on T1WI and H low signal intensity on T2WI E–H see p. 10

10

1 Embryological and Anatomical Introduction

Fig. 1.10E–H (continued). The posterior part of the pons looks mature, displaying E a high signal intensity on TlWI and F low signal intensity on T2WI. The internal capsules do not yet show any process of myelination, since they demonstrate G low signal intensity on T1WI and H high signal intensity on T2WI. The white matter appears as lower signal intensity on T2WI than on prenatal study (probably because the sequence used is different). (Courtesy of N. Girard)

Preliminary Remarks

11

Fig. 1.11. A Axial T1-weighted image (T1WI) in a 31-week-old fetus. B Axial T2weighted image (T2WI) in a 32-week-old fetus. High signal intensity can be seen on T1WI in the posterior limb of the right internal capsule, corresponding to the myelination process. A The hemispheric parenchyma appears homogeneous on T1WI. B It is easily recognizable on T2WI as high signal intensity. Note that the pons demonstrates low signal intensity on T2WI secondary to maturation. (Courtesy of N. Girard)

Fig. 1.12A, B. Axial T1-weighted images (T1WI) in a 35-week-old fetus. The ventricles are almost invisible, as are the subarachnoid spaces. The cortical ribbon is not well delineated from the subarachnoid spaces and the white matter on T1WI. B The optic radiations display a high signal intensity (clearly seen on the left side). A The central area also has high signal intensity. These features correspond to the developing process of myelination, since the so-called myelination gliosis has high signal intensity on T1WI. (Courtesy of N. Girard)

12

1 Embryological and Anatomical Introduction

Fig. 1.13. A–C Legend see p. 13

Preliminary Remarks

13

▲

Fig. 1.14. A Coronal T1-weighted image (T1WI) and B axial T2-weighted image (T2WI) in a 1-month-old child. A The optic radiations are not yet myelinated, since they show myelination gliosis only on T1WI as high signal intensity. B They appear as high signal intensity on T2WI. (Courtesy of N. Girard)

Fig. 1.13. A–C Axial T1-weighted images (T1WI), D–F axial T2-weighted images (T2WI) and G–I axial proton density-weighted images (PDWI) in a 3-week-old newborn. The posterior part of the pons shows high signal intensity on C T1WI and low signal intensity on F T2WI and (I) PDWI, corresponding to the complete maturation of the sensory pathways of the pons. The central area appears as high signal intensity on A T1WI and as low signal intensity on D T2WI and G PDWI; this results from the complete maturation of the central area. B, E, H This feature is also observed in the occipital area. On the other hand, at this stage the internal capsules only show myelination gliosis on B T1WI as high signal intensity, since it appears as high signal intensity on E T2WI and H PDWI. The internal capsules are difficult to delineate on T1WI only, since the basal ganglia also display high signal intensity on T1WI. The immature white matter shows low signal intensity on A–C T1WI and high signal intensity on D–F T2WI and G–I PDWI. Note also that the basal ganglia demonstrate high signal intensity on B T1WI and low signal intensity on D T2WI and H PDWI. (Courtesy of N. Girard)

14

1 Embryological and Anatomical Introduction

Fig. 1.15. A Axial T2-weighted image (T2WI), B proton density-weighted image (PDWI), and c axial T1-weighted image (T1WI) in a 2.5-month-old child. (The child in C is a different one from the one in A, B.) Myelination begins in the posterior limb of the internal capsules as low signal intensity on A T2WI and B PDWI. The optic radiations are not myelinated, since they show high signal intensity on both A T2WI and C T1WI. The immature white matter still appears as low signal intensity on T1WI and as high signal intensity on T2WI. (Courtesy of N. Girard)

Fig. 1.16. A–C Axial T2-weighted images (T2WI), D lateral T1-weighted image (T1WI), and E sagittal T1WI in a 4-month-old child. High signal intensity is observed on T1WI in the semioval center, the central area, the internal capsule, and the optic radiations. The deep white matter displays a similar signal as the cortex on T1WI and no longer has the low signal intensity seen in neonates. A On T2WI, myelination begins in the semioval center. B, C The internal capsules are entirely myelinated, as are the optic radiations, since they show low signal intensity on T2WI. On the other hand, the deep white matter is still unmyelinated on T2WI. D, E see p. 15

Preliminary Remarks

15

Fig. 1.16 (continued). E The corpus callosum shows high signal intensity on TlWl. C However, myelination is not complete on T2WI. (Courtesy of N. Girard)

Fig. 1.17A–C. Axial T2-weighted images (T2WI) in an 8-month-old child. A Myelination is complete in the semioval center. B It is also complete in the corpus callosum. C The optic radiations show complete myelination in their lower portion. The upper part is not fully myelinated. Note at this stage that the hemispheric parenchyma appears homogeneous, but the subcortical white matter fibers are not yet myelinated. (Courtesy of N. Girard)

16

1 Embryological and Anatomical Introduction

Fig. 1.18. A–C Axial T1-weighted images (T1WI) and D–F axial T2-weighted images (T2WI) in a 19-month-old child. The pattern is similar to that found in adults. The deep white matter, including the subcortical fiber tracts, appears as high signal intensity on T1WI and as low signal intensity on T2WI. (Courtesy of N. Girard)

Preliminary Remarks

Fig. 1.19. Relationships of the subpial space. (From Weller 1994)

17

18

1 Embryological and Anatomical Introduction

Fig. 1.20. The subpial space (sps) of the human cerebral cortex. The pia mater is at the top, and an artery surrounded by two or three layers of smooth muscle cells is seen in the center. A thin layer of pial cells (PC) surrounds the artery, enclosing its perivascular space. The subpial space separates the artery from the glia limitans (gl). Transmission electron micrograph (TEM), ¥5,000. (Reproduced from Zhang et al. 1990, with permission)

Fig. 1.21. The subpial space (higher magnification than Fig. 1.20). The pia mater is at the top, and the glia limitans at the bottom. Within the subpial space is a thin-walled vein filled with erythrocytes. Collagen bundles (coll) are distributed through the subpial space and dissociated leptomeningeal cells are also seen. A thin basement membrane coats the astrocyte processes of the glia limitans. Transmission electron micrograph (TEM), ¥6,700. (Reproduced from Alcolado et al. 1988, with permission)

Preliminary Remarks

19

FFig. 1.22. Collagen bundles within the spinal subpial space. Scanning electron micrograph (SEM), ¥1,000

Fig. 1.23A, B. The subpial space (sps) in inflammation. A The subarachnoid space (top) is filled with macrophages and dead polymorphonuclear leukocytes. Three vessels in the subarachnoid space have expanded perivascular spaces surrounded by black-stained reticulin fibers. In the center, the subpial space is expanded by inflammatory cells. Surface of the cerebral cortex (bottom). B Inflammatory cells fill the subpial space, separating the pia mater (p) from the glia limitans (gl). An artery is seen entering the cerebral cortex. Light microscopy, reticulin stain, ¥470. (Reproduced with permission from Hutchings and Weller 1986)

20

1 Embryological and Anatomical Introduction

Fig. 1.24. Subpial space: inflammation. Inflammatory cells (P, polymorphonuclear leukocyte; L, lymphocyte; M, monocyte/macrophage) enter the subarachnoid space or the subpial space from the veins (right) and are then distributed into the perivascular spaces of meningeal vessels. There is little penetration into the perivascular spaces of the brain

Fig. 1.25. Subpial space: tumors. Leukemic or primary cerebral lymphoma cells (L) enter the subarachnoid and subpial spaces from the vessels and form a dense reticulin network. Cells penetrate the brain either by direct invasion or along perivascular spaces. Carcinoma (Ca) and malignant melanoma cells may remain in the subarachnoid space or they may penetrate the subpial spaces and pass along perivascular spaces into the central nervous system. Carcinoma cells may also penetrate directly through the glia limitans into the brain

Leptomeninges

21

1.2 Leptomeninges MRI with gadolinium enhancement (Bradley and Bydder 1990) has proved to be of great value in detecting the two major pathologies of the leptomeninges, i.e., inflammation and invasion by neoplastic cells (Weller 1990). Meningeal enhancement has been reported in a number of different conditions, including tuberculous meningitis (Kioumehr et al. 1994), Lyme disease (Demaerel 1994), and primary meningeal lymphoma (Berciano et al. 1996); MRI appears to be more suitable than computed tomography (CT) for the identification of leptomeningeal metastases, particularly in the spinal cord (Chamberlain et al. 1990). Leptomeninges cover the surface of the brain and spinal cord as well as the nerve roots and blood vessels within the subarachnoid space (Weller 1995). The outer, arachnoid mater, is composed of multiple layers of leptomeningeal cells, which form an impermeable barrier to cerebrospinal fluid (Alcolado et al. 1988). Separating the arachnoid and pia mater is the subarachnoid space containing cerebrospinal fluid and major arteries and veins supplying the central nervous system. Delicate ligaments and perforated sheets of leptomeninges traverse the subarachnoid space, forming compartments filled with cerebrospinal fluid. Sheet-like and filiform trabeculae traversing the subarachnoid space are composed of bundles of collagen fibers and a thin outer coating of leptomeningeal cells (Weller 1995; Alcolado et al. 1988; Hutchings and Weller 1986). Blood vessels within the subarachnoid space are suspended by such trabeculae, which have a structure similar to the major dorsal and ventral ligaments of the spinal cord and the dentate ligaments (Nicholas and Weller 1988). The pia mater (Alcolado et al. 1988) is a delicate sheet, often only one cell thick; it is in contact with the surface of the brain, spinal cord, and nerve roots. Pia follows the gyri and sulci of the cerebral hemispheres and the folia of the cerebellum and closely invests the surface of the spinal cord. It is separated from the surface of the brain by the subpial pace and, as it is reflected onto the surface of blood vessels in the subarachnoid space, pia mater separates the subpial space from the subarachnoid space. Individual cells of the pia mater are joined by desmosomes and gap junctions (Alcolaclo et al. 1988; Spray et al. 1991), and they form a designated interface between the cerebrospinal fluid of the subarachnoid space and the surface of the brain (Feuer 1991). The pia mater appears to act as an active barrier, and its cells actively pinocytose particulate matter and contain enzymes such as catechol-O-methyl transferase (Kaplan 1981) and glutamine synthetase (Feuer 1991), which degrade neurotransmitters. Growth factors such as transforming growth factor b (TGFb) have also been identified in leptomeningeal cells (Johnson et al. 1992).

22

1 Embryological and Anatomical Introduction

1.3 Subpial Space 1.3.1 Anatomy

The anatomy of the subpial space is summarized in Fig. 1.19. The subpial space is normally difficult to discern with light microscopy and was not well recognized as a separate compartment until ultrastructural studies (Huntchings 1986) confirmed that it was bound on one side by a complete sheet of pia mater and on the other by the glia limitans (Alcolado et al. 1988; Huntchings and Weller 1986; Zhang et al. 1990). As shown in Fig. 1.19, the pia mater is reflected onto the surface of arteries and veins in the subarachnoid space and coats collagenous trabeculae extending from the arachnoid to the pia mater. A sheath of pia mater cells extends from the deep aspect of the pia mater proper to accompany arteries into the brain, but this sheath is either incomplete or absent around veins (Zhang et al. 1990). The perivascular space formed by this tube-like insertion of pia mater appears to be a major pathway for the drainage of interstitial fluid from the brain into the perivascular spaces of the leptomeningeal arteries and thence into the subarachnoid space (Weller et al. 1992). With the barrier and enzymatic properties of the pia mater mentioned above, the sheath of pia mater may also form a regulatory interface separating blood vessels and their nerve supplies from the surrounding brain tissue. The glia limitans is composed of compacted astrocyte processes, often joined by gap junctions (Peters and Feldman 1976). A basement membrane coats the astrocytic component of the glia limitans and separates it from the small collagen fibers that form a web-like matrix on the surface of the brain. Over the surface of the cerebral hemispheres, the subpial space largely contains arterioles (Fig. 1.20), small veins (Fig. 1.21) and bundles of collagen of varying size, dissociated pia mater cells, and occasional inflammatory cells. Bundles of collagen fibers extend from the trabeculae that cross the subarachnoid space and expand in a fan-like manner into the subpial space (Fig. 1.19), apparently forming an anchor for the trabecula (Alcolado et al. 1988). Similar anchorage is seen in the arachnoid mater (Weller 1995; Alcolado et al. 1988). Arterioles within the subpial space are fine branches of the major arteries in the subarachnoid space. They have smooth muscle coats of varying thickness and an outer coating of leptomeningeal (pia mater) cells. Small veins in the subpial space, on the other hand, are larger in diameter and have thin walls with few smooth muscle cells and no outer coating of pia mater cells. The subpial space of the spinal cord contains a thicker layer of collagen bundles (Nicholas and Weller 1988), as seen in the scanning electron micrograph in Fig. 1.22. This thick layer of collagen is continuous with the dentate ligaments laterally and may play a role in stabilizing the cord (Nicholas and Weller 1988). The nerve supply of the leptomeninges and the vessels in the subpial space has been mainly investigated at the level of the spinal cord in experimental animals. Innervation of the pia and leptomeningeal ligaments by

Inflammation

23

small sensory fibers appears to be derived from ventral roots (Risling et al. 1994; Parke and Whalen 1993), although this origin is disputed (Karlsson and Hildebrand 1993). Over the surface of the cerebral cortex, some blood vessels may be supplied by branches from cortical neurons (McKenzie 1990). Small nerve branches consisting of myelinated and nonmyelinated fibers can be identified within the spinal leptomeninges of the spinal cord in humans (Nicholas and Weller, unpublished observations).

1.3.2 Relationships of the Subpial Space

Although the subpial space is separated from the subarachnoid space by the pia mater, it is continuous with the perivascular spaces of the central nervous system. A sheath of pia mater surrounds the arteries as they enter the brain and divides the periarterial space into two compartments (Fig. 1.19). It is probably the inner space between the pia mater sheath and the vessel that is the conduit for fluid drainage (Weller 1992), but which of these spaces should be called the Virchow Robin space is unclear. The relationships of the subpial space are particularly important when considering pathological reactions within the space.

1.3.3 Pathology 1.3.3.1 Inflammation

Inflammatory leptomeningitis may be due to a number of different types of organisms or may even be due to the escape into the cerebrospinal fluid of sterile inflammatory agents, such as cholesterol or keratin, from epidermoid cysts or craniopharyngiomas. A variety of blood-borne cells may be associated with inflammation of the leptomeninges, and the time course and nature of the inflammation depend upon the stimulating agent (Weller 1990). Pyogenic bacterial infections, such as streptococcal or staphylococcal leptomeningitis, result in exudation of large numbers of polymorphonuclear leukocytes into the subarachnoid and subpial spaces. In the later stages of infection, when the polymorphonuclear leukocytes have ingested bacteria and died, macrophages derived from blood monocytes (Fig. 1.23) replace and ingest the dead polymorphs, dead bacteria, fibrin, and tissue debris. Macrophages generally arrive 2–3 days after the initial infection. The pattern of inflammation in viral meningitis is mainly that of lymphocyte exudation into the subarachnoid and subpial spaces; in fungal and tuberculous infections, there is granulomatous inflammation in addition to lymphocyte infiltration, often with multinucleate macrophagederived giant cells and areas of caseation (Weller 1990). The time course and intensity of breakdown of the blood–brain barrier is different in each of these cases. In purulent leptomeningitis, significant alteration in the blood-brain barrier may only last for a few days to

24

1 Embryological and Anatomical Introduction

1 week before the barrier is restored. In more chronic infections, such as tuberculosis, disruption of the blood-brain barrier may last much longer. Inflammatory cells, polymorphonuclear leukocytes, monocytes, or lymphocytes pass from the blood into either the subarachnoid space or the subpial space through the walls of veins (Fig. 1.24). Although in the rest of the body most of the traffic of inflammatory cells is through the walls of postcapillary venules, they escape from large veins into the subarachnoid space. Traffic of inflammatory cells through the walls of smaller veins in the subpial space may be an important route for cells to enter both the subpial and the subarachnoid spaces. Figure 1.24 shows how inflammatory cells entering the subpial space may be distributed along perivascular spaces of arteries and veins in the subarachnoid space and penetrate the pia mater (Krahn 1981) to enter the subpial space. By expanding the subpial space, the relationships between the pia mater and the glia limitans become clearer by light microscopy, and the presence of a leptomeningeal sheath around blood vessels in the subarachnoid space is clearly demonstrated (Fig. 1.23). Although there is a connection between the subpial space and perivascular spaces within the brain, inflammatory cells rarely extend far into the perivascular spaces of the central nervous system. It appears that the pia mater is an effective barrier to the spread of bacteria into the subpial space. The pia mater also forms a barrier to the spread of red blood cells from the subarachnoid space, and blood does not usually penetrate the perivascular spaces of the brain following subarachnoid hemorrhage (Hutchings and Weller 1986). Hemorrhage does occur in the subpial space, particularly in infants (Friede 1972). Subpial hemorrhage can be distinguished from subarachnoid hemorrhage, since subpial hemorrhage usually remains closely confined and spreads in the subpial space into sulci rather than filling the sulci, as occurs in subarachnoid hemorrhage.

1.3.3.2 Tumor

Breakdown of the blood-brain barrier and gadolinium enhancement is well recognized in association with poorly differentiated glial tumors, such as glioblastoma multiforme and anaplastic astrocytoma, as is the absence of a blood-brain barrier in association with solid metastatic carcinomas and primary lymphomas in the nervous system (Bradley and Bydder 1990). Enhancement due to breakdown of the blood-brain barrier also occurs in carcinomatous, lymphomatous, and leukemic meningitis and is well demonstrated by MRI (Berciano et al. 1996; Chamberlain et al. 1990). Neoplastic cells enter the subarachnoid and subpial spaces by penetrating blood vessel walls. However, leukemic and lymphoma cells show a different pattern of invasion from carcinomas. Although leukemic involvement of the central nervous system is common, it is usually only primary lymphomas of the central nervous system that invade the parenchyma of the brain and spinal cord (Weller 1990; Berciano et al. 1996).

Tumor

25

Leukemic and lymphoma cells in the subarachnoid and subpial spaces induce the formation of a delicate network of reticulin (small collagen; Fig. 1.25). From the subpial space, cells penetrate the glia limitans and invade the surface of the brain or penetrate deeply into the parenchyma along perivascular spaces (Fig. 1.25). Carcinomas and malignant melanoma, on the other hand, invade the subarachnoid space but may be prevented either by the pia or the glia limitans from directly invading the brain. Some carcinomas remain almost totally confined to the subarachnoid space with minimal invasion of the brain, whereas other carcinomas and malignant melanomas enter the subpial space and penetrate deep into the brain along perivascular spaces (Fig. 1.25). Direct invasion through the glia limitans is also seen in some carcinomas. Such invasion may increase the thickness of the zone of blood–brain barrier breakdown and thus enhancement on MRI. The mechanisms of blood–brain barrier breakdown in carcinomatous meningitis are not entirely clear. Once the carcinoma has entered the subpial and arachnoid spaces, it appears that the tumor cells continue to influence the characteristics of blood vessels in the region, as with solid metastases. Carcinoma cells are known to produce growth factors (Wiestler 1994), which may modify the permeability characteristics of the brain vessels in the region of leptomeningeal metastases. The significance of the subpial space lies mainly in the blood vessels that traverse it, in its proximity to the surface of the brain and in its connections with the perivascular spaces of the central nervous system. For the most part, inflammatory cells entering the subpial space pass into the subarachnoid space rather than into the brain. In many cases of leptomeningitis, there is only a microglial reaction in the surface regions of the brain rather than direct invasion by inflammatory cells. The picture is rather different in carcinomatous or lymphomatous meningitis, in which invasion of the surface of the brain is as common as invasion of the perivascular spaces.

2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

2.1

Introduction 28

2.2

From Adults to Children 28

2.3 2.3.1 2.3.1.1 2.3.1.2 2.3.1.3 2.3.1.4 2.3.1.5 2.3.1.6 2.3.1.7 2.3.1.8 2.3.1.9 2.3.1.10 2.3.1.11 2.3.1.12 2.3.1.13 2.3.1.14 2.3.2 2.3.2.1 2.3.2.2

Vascular Lesion Types and Disease Groups 31 Nonproliferative Lesions 34 Arteriovenous Lesions 34 Isolated Brain AVMs 35 CAVFs 39 VGAMs 39 Cerebrofacial Arteriovenous Metameric Syndromes 39 Dural Lesions 41 Telangiectasias 41 The Blue Rubber-Bleb Nevus or Bean Syndrome 41 Venous Malformations (Cavernomas) 44 Venous Angiomas or Developmental Venous Anomalies 45 Cerebrofacial Venous Metameric Syndrome (Formerly Sturge-Weber Syndrome) 47 Induced Pial Shunts 47 Spinal Cord AVM 48 General Conclusions on Vascular Lesions 48 Proliferative Lesions 49 PHACE or PHACES 51 Diffuse Angiodysplasia 51

2.4 2.4.1 2.4.2 2.4.3 2.4.4

Classification of CAVMs by Age Group 56 Fetal Age 56 Neonatal Age 59 Infancy 59 After 2 Years 62

2.5 2.5.1 2.5.2 2.5.3

Classification by Symptom Group 63 Congestive Cardiac Manifestations 63 Hydrodynamic Disorders 64 Melting-Brain Syndrome 73

2.6

Clinical Evaluation Scores 77

2.7

Revised Concept of the Congenital Nature of Vascular Malformations 85 Genetics 85 Familial Hemiplegic Migraine 85 Familial Cerebral Aneurysms 86 PKD1 and Bourneville PDK1-PDK2 86 Ehlers-Danlos Type IV 87 Multiple Cutaneous Mucous Venous Malformations, Blue Rubber Bleb Nevus Syndrome 87 CADASIL 87 Familial Paragangliomas 87 Familial Cavernomas 87 Neurofibromatosis-1 and Other Collagen Diseases 88 Hemorrhagic Hereditary Telangiectasia or Rendu-Osler-Weber Disease 88

2.7.1 2.7.1.1 2.7.1.2 2.7.1.3 2.7.1.4 2.7.1.5 2.7.1.6 2.7.1.7 2.7.1.8 2.7.1.9 2.7.1.10

28 2.8 2.8.1 2.8.2 2.8.3 2.8.4 2.8.5

2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts Vascular Remodeling and the Congenital Nature of Arteriovenous Shunts 93 Endothelium as a Sensor and Transducer of Signals 94 Endothelium-Specific Receptor-Coupled Event 95 Endothelium and Mediator-Effector Molecules Involved with Remodeling 95 Role of Matrix Modulators in Vascular Remodeling 95 Clinical Implications of Vascular Remodeling 95

2.1 Introduction Since 1982, more than 3,000 patients with cerebral arteriovenous malformations (CAVMs) have been referred to the three authors, including 800 children under the age of 16 years. Our active involvement in the management of vein of Galen aneurysmal malformations (VGAMs) started in 1984; since then, 350 children with VGAMs have been seen by the group in Bicêtre Hospital alone, where it accounts for 50% of total pediatric intradural intracranial AVS patients. More than 25 new VGAM patients are now referred to us each year. Over the past 20 years, these centers combined have collected about 500 VGAMs. In comparison, the two historically important series describing the surgical management of this disease show referral patterns of roughly one new patient with VGAM per year: the Hospital for Sick Children in Toronto (29 patients over 30 years) and the Royal Alexandra Hospital in Sydney (13 patients in 10 years). It is also of interest to note that in these surgical series, VGAM represented 34% of all the CAVM managed in children. A survey on the European continent (Raimondi 1992) showed that in the year 1989 in a population of 530 million people, 189 surgical procedures were performed for vascular disease in children, i.e., about one procedure a year per 3 million people. Most active neurosurgical centers in Europe perform between 10 and 15 procedures for this disease in children, which in most cases consists of cavernoma removal. In our interventional centers, 100–170 pediatric neurovascular procedures are performed each year, mostly AVMs. The large number of patients seen does not reflect a true population profile with any epidemiological significance, but rather our status as a quaternary referral center for Europe and North America. In view of the distances involved, only the more complex cases tend to be referred while the simpler ones are more likely managed locally. Our current practice and management reflects both the improvement in fetal and neonatal diagnosis and care of children with neurovascular disease as well as the progressive shift toward endovascular management in the treatment of children with brain AVSs.

2.2 From Adults to Children Cerebral arteriovenous (AV) shunts have different characteristics in children than in adults. Children can have multifocal lesions, induced remote AV shunts (Garcia Monaco 1991c; Iizuka 1992), large venous ectasias, highflow lesions, and single hole arteriovenous fistulas (Weon et al. 2005; Yoshi-

From Adults to Children

29

da et al. 2004), venous thrombosis, brain atrophy, and systemic phenomena (Cronqvist 1972; Cumming 1980; Willinsky et al. 1990a). Conversely, highflow angiopathic changes are rare in children, as are flow-related arterial aneurysms (Lasjaunias 1988a), while proximal occlusive arteriopathy is more frequent. For this reason, management protocols derived from experience in adults should not be applied to the pediatric population. In particular, adult-based classifications and AVM grading according to the expected surgical outcome is particularly inappropriate in children, in whom (a) cerebral eloquence is difficult to assess, particularly in the first few years of life, (b) most lesions are fistulas or multifocal, (c) drainage usually affects the entire venous system, and (d) the potential for recovery is different. It is often believed that the adult type of classification and grading of AVMs indicates or in some way corresponds to the natural evolution of the lesion, and, although unintentionally, this has created a significant amount of misunderstanding and confusion.A difficult to operate AVM (i.e., a high-grade AVM) is not necessarily a dangerous one for the patient if not operated upon or more dangerous for the patient than a low-grade AVM. In addition to the conventional objectives, the decision-making process in children must take into consideration additional specific details pertaining to the veins and the myelinization process. Thereafter, staged partial treatment of progressive deficits associated with congested cerebral veins, poorly controlled seizures, hemorrhagic episodes with or without specific changes upstream or downstream from the AVM, or headaches in children without ventricular enlargement or macrocrania may all represent good indications for treatment. Neurocognitive evaluation is the key follow-up criterion in children even without deficits, hemorrhage, or seizures, as it helps in the assessment of treatment quality and success. Failure to obtain a normal maturation process may constitute a therapeutic failure if the optimum moment for intervention has been missed (therapeutic window). When discussing CAVMs or vascular diseases in children, one might wonder whether it represents an artificially created grouping. AVMs in children are primarily characterized by diagnostic and therapeutic difficulties specific to the population in which they occur. CAVM corresponds more to a clinical group than a nosological one. However, some rare lesions (see Chaps. 4, 7, 12, this volume) are exclusively encountered in children, mainly in neonates and infants. In addition, the anatomic and physiologic characteristics of the neonatal and infant brain and the immaturity of its systemic flexibility (hydrovenous) create a specific group of nonhemorrhagic symptoms and therapeutic challenges. This vulnerability means that the lesion rapidly becomes lethal or creates a disabling state, whereas a similar lesion in an adult might produce only few symptoms. The clinical characteristics of CAVMs in children are therefore related to the children themselves and their specific anatomy and physiology. Children are not small adults and the therapeutic challenges cannot be measured in terms of size of the target, but is related to our capability to understand the other structures and processes involving the brain and its vasculature and anticipate the potential interferences between the CAVM and the maturing brain. For a long time, vascular lesions in children were divided into nonproliferative and proliferative lesions. The former group comprises vascular

30

2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Scheme 2.1. Role of structural weaknesses in disease development

Scheme 2.2. Vascular diseases according to the arterio-veno-lymphatic tree

Vascular Lesion Types and Disease Groups

31

malformations, the latter hemangiomatous lesions. In fact, such a distinction, which was helpful during the past 20 years, has also greatly benefited from recent biological contributions as well as the recognition of shear stress mechanisms in vascular modeling and remodeling.Actually angiogenesis is involved in both so-called malformations and hemangiomas, but they are different in terms of trigger factor (agent), target, and timing (Schemes 2.1, 2.2).They will be discussed in the various chapters dealing with brain and maxillofacial AVMs and hemangiomas.

2.3 Vascular Lesion Types and Disease Groups Many and often confusing classifications have been proposed in the past. The role of coagulation disorders, systemic manifestations, topography, size, eloquence of the involved brain, and extrapolation from experience with adult lesions has led to emphasis being placed on many different aspects, which, in combination with technical advances, tended to focus on certain particular details rather than on an understanding of the problem as a whole. The assumption that AVMs are congenital, the rarity of the disease, the small number of patients in the clinical series reported, and the aggregation of various pathologies described in literature reviews further added to this confusion (Govaert 1993; Raimondi 1980; Edwards and Hoffman 1989). Basic classifications of vascular diseases use pathological, biological, and clinical data. For instance, one should now be able to distinguish AV shunts from venous lesions or malformations. Furthermore one should be able to recognize and differentiate venous variations from malformations. Similarly, one should not label an associated arterial variation or embryonic persistence a malformation when associated with a CAVM or a giant aneurysm. This distinction is not only of academic interest, but may also have clinical consequences. A true malformation is not an anatomic variant, and the isolated persistence of an embryonic disposition does not give a congenital character to a lesion even if in some cases it is a time marker of an embryonic event, which may not necessarily be related. When considering vascular lesions in children, one should keep in mind several keys to approaching the questions raised and understanding the clinical expression (phenotypes) of the various diseases involved. Even in an apparently single-disease category such as CAVMs, several entities must be distinguished as their predictable presentation or progression requires different management at different times. The generic name artificially regrouping different situations expresses the use of a single key (the arteriovenous shunt for example) where two or three would reveal the differences: single hole AVF (Yoshida 2004; Weon et al. 2005), familial disorder for HHT (Mahadevan 2004), metameric disease for CAMS (Bhattacharya et al. 2001), proliferative activity for proliferative angiopathy, PHACE (Bhattacharya et al. 2004), etc.

32

2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Table 2.1a. Vascular diseases, genetics: karyotypes Diseasea HHTb Cavernomas

MCMVM: BRBN (Bean syndrome) ED IV NF1 NF2 VHL Moyamoya Bourneville TSC1 TSC2 CADASIL FHM Paragangliomas Polycystic kidney disease a

b

Chromosome location Ch 9q33–34 endoglin Ch 12q Alk 1 Ch 7q21–22 CCM1 (KRIT1 is the mutated protein CCM1) Ch 7p13–15 (CCM2) Ch 3q25,2–27 (CCM3) Ch 9p Tie 2/Ch1 cutaneous Chromosome 2 Ch 17q22 Chromosome 22 Ch 3p25–26 Ch 17q25 Ch 3p24.2-p26 Ch 9q34 Ch 16p13 Ch 19q Ch 19 11q23 Ch 16p13.3 (PDK1) Ch 4 (PDK2)

The same effects are expected to follow functional blockade of a gene rather than single type of structural alteration in each patient: when the gene involves interactions (ligand), the mutations are multiple; when the gene makes a protein active, the mutations are often identical: lack of stage (protein or mRNA is missing), poor emission of signal or wrong destination (pigmentation), no reception of signal (ligand), insufficient message (too short, too few), hyperactive protein. Each family has its own mutation >100.

Table 2.1b. Vascular diseases, genetics: angiogenic activity Arterial angiogenesis VHL NF1 Moyamoya PHACE Proliferative angiopathy CAMS Primary arterial angiectasiaa Aneurysms

a

Not flow-induced.

Venous angiogenesis HHT BRBN Cavernomas CVMS

Primary venous angiectasiaa DSM DVAs Venous angiogenesis Lymphatic angiogenesis LM

Vascular Lesion Types and Disease Groups

Scheme 2.3. Timing of triggering events and phenotypic expressions

Scheme 2.4A. „Age“ of vascular lesions

33

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Scheme 2.4B. So-called congenital or malformative vs acquired neurovascular lesions

The following keys can be put forward:
Proliferative or nonproliferative lesion
Type of disorder (Table 2.1): – Monogenetic (surface protein dysfunction, improper collagen structure, extracellular matrix deficiency), progressive dysfunction (triggered structural defect or failed repair or inadequate maintenance systems), extrinsic and acquired damage (infectious, traumatic) (Scheme 2.1)
Location on the vessel tree: – From the arterial tree to the arterial capillary, venous junction venules, veins, sinuses, and lymphatics (Scheme 2.2)
Time of occurrence: – Germinal mutation transmitted, early somatic mutation, early stage metamerically arranged defect, fetal failed signaling, postnatal mutation, failed remodeling during vascular renewal (Scheme 2.3)
Time of revelation: – In utero, fetal period, neonatal, infancy prior to 2 years of age, 2–6 years, and after 6 years (Scheme 2.4)
Clinical evolution and natural history: – Permanent increase in flow, arterial occlusion, spontaneous thrombosis (see Chap. 7, this volume).
Secondary effects on the maturing or remaining vasculature:
High-flow angiopathy, jugular bulb maturation, cerebral vein opening into the cavernous sinus, pacchionian granulations development (see Chaps. 3, 5, this volume).

2.3.1 Nonproliferative Lesions 2.3.1.1 Arteriovenous Lesions

The AV lesions that can be encountered depend on the meningeal space from which they primarily develop: dural, pial, subarachnoid, or choroidal (Scheme 2.5). These locations give rise to several subtypes and may be unifocal, multifocal, hereditary, etc. (Scheme 2.6).

Isolated Brain AVMs

35

Scheme 2.5. Spaces hosting intracranial ateriovenous (AV) shunts. VGAM, vein of Galen aneurysmal malformation; AVM, arteriovenous malformation

Scheme 2.6. Subtypes of vascular lesions in children. AVM, arteriovenous malformation

2.3.1.2 Isolated Brain AVMs

Pial AV Shunt in Children Micro/Macro AVM Micro/Macro AVF Multifocal CAMS Familial Proliferative angiopathy Hemorrhagic angiopathy False and induced AV shunts

These can be small (micro-AVM; see Fig. 2.1) or large (macro-AVM; Fig. 2.2), and this distinction is of nosological interest, as the passage from one type to the other cannot be demonstrated. Of interest is the distinction between the nidus type (with an arteriolar network; Fig. 2.1) and the fistulous type (single or multiple large, direct AV communication; see Fig. 2.3). The former consists of a group of small AV shunts within a vascular meshwork within the nidus, while the latter is a direct opening of an artery or arteries into an unusually enlarged or giant draining vein, with or without outflow restriction. This distinction is a significant one, and in our opinion similar to what was said for micro- and macro-AVMs, there

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.1A, B. Typical aspect of a cortical micro-AVM revealed by an intralobar hematoma in a young boy

Fig. 2.2A, B. Medium-sized deep-seated AVM discovered incidentally in a young boy. Both lesions were treated successfully by embolization

is no transition from AVMs to AVFs or vice-versa. CAVMs can occur in the subpial space, where they can be superficial or deep, corticoventricular, or buried in the white matter; in this latter location they should be distinguished from hemorrhagic angiopathy (see below and Chap. 18, this volume) (Fig. 2.4). From their origin onwards, they contain no neurons or nerve fibers within their nidus, which had led some authors to describe pial AVM (PAVM) as extracerebral. This justifies the distinction of proliferative angiopathy as a distinct group of diseases (see below and Chap. 18, this volume). Fistulas are also subpial; they drain either immediately into subarachnoid vein(s) or within the subpial venous network. They are superficial at the cerebral cortex or the surface of the cord. They are not supplied by ventral longitudinal neural perforators.

Isolated Brain AVMs

37

Fig. 2.3. A, B A 7-day-old child presented with cardiac failure, for which a cerebral arteriovenous fistula (AVF) was diagnosed. There was a family history suggestive of HHT. The AVF was embolized at the age of 3 years. There was no focal melt in relation to the direct subarachnoid vein opening of this cortical fistula. C The child is neurologically normal at 12 years of age, the lesion is partially excluded, and there is no evidence of melting-brain syndrome

Fig. 2.4. A 5-year-old boy presenting with hemianopia in relation to a subcortical hemorrhage. B, C Angiography demonstrates a hemorrhagic angiopathy. D, E One year after radiation therapy, the lesion is no longer visible

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.5. A A male infant presented with macrocrania with vein of Galen aneurysmal malformation (VGAM) of the mural type. Untreated cardiac overload was also noted at that time. He was referred to us at the age of 3 years following an episode of generalized seizure. B Almost complete occlusion was obtained in one session. C, D A small remaining shunt was seen 2 years later (arrow, remaining venous drainage) and final spontaneous disappearance was verified. At the age of 8 years, the child’s score was 4 and he was not taking any antiepileptic medication

Cerebrofacial Arteriovenous Metameric Syndromes

39

2.3.1.3 CAVFs

We have treated cerebral arteriovenous fistulas in children in a separate chapter since they raise specific nosological clinical and therapeutic challenges (Yoshida et al. 2004; Weon et al. 2005). Their linkage with hereditary hemorrhagic telangiectasia is remarkable (see Chap. 4, this volume) (Mahadevan 2004). Drainage into subpial or subarachnoid veins is of paramount importance in this topography, particularly in neonates and infants (Fig. 2.3; see Sects. 2.4.2 and 2.4.3). Finally, there is no gender dominance in CAVM in children (see Chap. 5, this volume)

2.3.1.4 VGAMs

Galenic Vascular Lesions in Children Choroidal VGAM Mural VGAM VGAD Dural VGAV shunt Venous dilatation

VGAM is a unique, well-defined group of malformations that occur at the end of the embryonic period (Fig. 2.5). They constitute a separate group from other lesions such as CAVMs, and they are often called non-Galenvein AV malformations, particularly in neonates and infants. In the VGAM group, there is a 2–3:1 male predominance (see Chap. 3, this volume).

2.3.1.5 Cerebrofacial Arteriovenous Metameric Syndromes

The diagnosis of cerebrofacial arteriovenous metameric syndromes (CAMS) (Chap. 6, this volume) encompasses a spectrum of phenotypic expressions. Features of the syndrome as originally described and common to all cases include arteriovenous malformations of the brain and orbit (with retinal and/or retrobulbar lesions) (Bonnet-Dechaume-Blanc or Wyburn-Mason syndrome) and maxillofacial lesions. A portion of these patients will manifest the complete expression of the disease with additional high-flow arteriovenous malformations of the maxilla or

Fig. 2.6. Cerebrofacial vascular metameric syndromes. Three territories linking the brain to the face can be recognized. Depending upon the type of cell involved, arteriovenous (CAMS 1–3) or venolymphatic (CVMS 1–3) metameric syndromes are involved. At the first cervical segment, SAMS 1 (green arrow) (SAMS 1–31) is represented. (From Bhattacharya 2001)

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.7A–C. CAMS 2. A 4-yearold boy presented with a retinal AVM. A At that time, MR was normal. B, C Six years later, a diencephalic lesion associated with the previous lesion can be seen

mandibular regions. These represent distinct and additional life-threatening risks because of epistaxis or oral hemorrhage. We have suggested segmental patterns of involvement in what is likely to be a disease of the neural crest and/or adjacent cephalic mesoderm.A newly proposed rational classification reflects the putative, underlying disorder and calls for a new label: cerebrofacial arteriovenous metameric syndrome (CAMS) (Bhattacharya et al. 2001) (see Chap. 6) (Fig. 2.6). The various lesions associated with CAMS may reveal themselves over time in a consecutive fashion suggesting pseudo de novo lesions (Fig. 2.7).

The Blue Rubber-Bleb Nevus or Bean Syndrome

41

Fig. 2.8. In utero MR diagnosis of dural sinus malformation (DSM)

2.3.1.6 Dural Lesions

Dural AV Shunt in Children Sinus malformation High-flow lesions Multifocal „Adult“ types Post-traumatic

Dural lesions can be encountered at any age in children, but represent different disease entities. We will describe them in detail (see Chap. 7, this volume), since they can represent true malformations in very young children and secondary AV shunts in older patients. The former are encountered in neonates and infants and can be diagnosed in utero (Barbosa 2003) (Fig. 2.8). The latter are usually multifocal and contain large sinuses and high-velocity flow phenomena, but are originally associated with low pressure in the dural sinuses (Fig. 2.9). They become symptomatic during childhood and create remote manifestations on the dural sinuses as well as the cerebral cortex caused by the venous sump effect. Their treatment is particularly difficult. Different types of dural lesions are encountered with different frequency in various age groups (Scheme 1.3).

2.3.1.7 Telangiectasias

Telangiectasias are usually included in the malformation group and they are occasionally described in children at autopsy. They are likely to represent improper capillary remodeling (see Sect. 2.7.1). They can be secondary to local ischemia or hemorrhage, but are seldom the cause of it (Fig. 2.10).

2.3.1.8 The Blue Rubber-Bleb Nevus or Bean Syndrome

The blue rubber-bled nevus or bean syndrome (BRBN) can produce multiple types of central nervous system (CNS) involvement. These features consist of multiple VMs (venous malformations similar to large telangiectasias), DVAs (developmental venous anomalies) in supratentorial

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.9A–F. Legend see p. 43.

▲

The Blue Rubber-Bleb Nevus or Bean Syndrome

Fig. 2.9A–G. A 1-month-old boy presenting with progressive macrocrania and referred at the age of 2 years. A, B Computed tomography (CT), C magnetic resonance imaging (MRI), and D–F angiography demonstrate a typical multifocal dural arteriovenous lesion with venous restriction (jugular dysmaturation) at the base and tonsillar prolapse. G Note the flowrelated aneurysm on the AICA contribution (subarcuata artery)

Fig. 2.10A–C. MRI and angiographic aspect of an hemorrhagic micro-AVM or telangiectasia in a child presenting with a family history of HHT

43

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.11A, B. BRBN, blue rubber bled nevus.Association of intracerebral telangiectasia (A, B) and large cerebellar DVA, with capillarectasia (see Chap. 8, this volume). (From Chung 2003)

brain, cerebellum, and tectum mesencephali (Fig. 2.11). Since its first description by Bean there have been many cases of BRBN manifesting with gastrointestinal bleeding with or without associated hemorrhage. Cases with CNS involvement are rare; many of the reported descriptions are confusing with various terms used to describe them such as capillary venous malformation, hemangiomas, and vascular malformations. The association with DVAs was recognized in some cases but is likely underestimated because of the use of different nomenclature in the published cases. Although as in Chung’s case (2003) BRBN can be sporadic, its familial transmission is frequent and the link with HHT1 unlikely despite the involvement of the same chromosome (chromosome 9p) (Boon et al. 1994; Gallione et al. 1995; see Chap. 8, this volume).

2.3.1.9 Venous Malformations (Cavernomas)

Venous malformations are located outside the nervous tissue and therefore do not contain nervous or glial elements. They are referred to as being cavernous and can be isolated or multiple. In the latter case, they are often familial with autosomal dominant transmission. These lesions are malformations (Fig. 2.12) and can be found in autopsy series in any location within the intradural space (subarachnoid, subpial). They increase in size following intralesional hemorrhage. They occasionally have the appearance of a tumor (in particular in children) or a cyst, through confluence of recurrent hematomas. Patients most often present with a hemorrhagic episodes leading to acute symptoms (epilepsy, sudden headache, deficit, and very occasionally subarachnoid hemorrhage in the case of subpial location or intraventricular hemorrhage in subependymal le-

Venous Angiomas or Developmental Venous Anomalies

45

Fig. 2.12A, B. Multiple intradural intraneural and subarachnoid cavernomas in a young adult (familial case)

sions). Different from AVMs in HHT, new cavernomas may become apparent, as the disease is potentially multifocal with other microsatellite lesions still too small to be detected with imaging. Subsequent growth is secondary to intralesional hemorrhage, although these episodes may be subclinical (see Chap. 8, this volume). They can be associated with venous anomalies or other malformations such as dural sinus AV malformations (DSMs) (Fig. 2.13) and be induced by radiation therapy.

2.3.1.10 Venous Angiomas or Developmental Venous Anomalies

Venous angiomas or developmental venous anomalies (DVAs) are anatomic variations that can involve one or both hemispheres and be located infratentorially. They do not exist at the spinal cord level or where no secondary germinal matrix migration has occurred. Their symptomatic character is primarily dependent upon associated malformations (AV or cavernomatous). The lack of flexibility due to the extreme anatomic disposition of the venous drainage to the brain in the region may also produce ischemic episodes manifesting various levels of clinical severity. The venous channels are morphologically normal and drain normally functioning brain, although transit time through their venules is sometimes rapid and almost similar to that in a slow-flow AVM. Careful analysis of the venous anatomy always provides the necessary information to make the proper diagnosis. DVAs should therefore never be a target for treatment (see Chap. 8, this volume).

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.13. A, B A 6-month-old infant with right frontal cutaneous venous malformation, torcular DSM and posterior fossa DVA. C, D Eight months later, multiple cavernomas with intracerebral hemorrhagic changes are noted. Dramatic enlargement of the DSM and extension to the right transverse sinus can be seen. (From Mohamed et al. 2002)

Induced Pial Shunts

47

2.3.1.11 Cerebrofacial Venous Metameric Syndrome (Formerly Sturge-Weber Syndrome)

Cerebrofacial venous metameric syndrome (CVMS, formerly SturgeWeber Syndrome) consists of cutaneous, facial, port-wine stain (venular malformation), subcutaneous lymphatic malformations (with secondary maxillofacial bone and soft tissue hypertrophy), and cerebral, cortical vein thrombosis with cortical atrophy, secondary angiogenesis, and transhemispheric venous drainage, with or without choroid plexus hypertrophy (Fig. 2.14). The disease is not hereditary. In line with CAMS, Ramli (2003) suggested the name of cerebrofacial venous metameric syndrome (CVMS; see Chap. 8, this volume). In CVMS, a linkage between various craniofacial vascular disorders can be identified as related to the neural crest/mesodermic segmentation. Involvement of the maxillofacial and skull base bone, skin, subcutaneous tissue, and vessels are in the same metameric distribution. The facial involvement represents the distal destination of the migrating neural crest cells, contributing to the vascular network rather than the trigeminal dermatome. The cerebral abnormalities when present are also in the same metameric distribution.

2.3.1.12 Induced Pial Shunts

Induced pial shunts are unique in juvenile dural arteriovenous lesions and occur only in children. They develop with the sump effect from the abnormal dural sinus, retrograde to the cerebral vein, with subsequent pial AV shunt formation (Figs. 2.9, 2.15). This observation has been confirmed by sequential angiographs and spontaneous post-therapeutic regression of the induced AV shunts (see Chap. 7, this volume).

Fig. 2.14A, B. Cerebrofacial venous metameric syndrome CVMS Sturge-Weber (see Chap. 8, this volume). A CVMS 1, 2; B CVMS 2, 3. (From Ramli et al. 2003)

48

2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts Fig. 2.15. An 11-year-old girl, who had presented at the age of 2 with right proptosis related to an orbital hematoma. Angiography performed at that time failed to demonstrate any intracranial anomaly. Over a period of 10 years, she developed progressive right-sided hemiparesis, dysphasia, and ataxia. Although angiography had been normal at the age of 2 at the intracranial cavity, note the juvenile type of dural arteriovenous shunt and the remote cortical and basal pial arteriovenous communications (single and double arrows) induced by the lesion. (From Garcia-Monaco et al. 1991c)

2.3.1.13 Spinal Cord AVM

Spinal cord AVMs and spinal cord cavernous malformations present the same characteristics as those mentioned in the brain. Similar to the cranial region, spinal arteriovenous metameric syndromes (SAMS) are recognized, enriching the historical description of Cobb’s syndrome (see Chap. 15, this volume). Thirty-one segments to the spinal division allow for single or multimetameric syndromes (Matsumaru et al. 1999).

2.3.1.14 General Conclusions on Vascular Lesions

Vascular malformations are multifocal twice as often in children as in adults. This multifocal character has been underestimated in children due to poor-quality angiographic studies and lesions not being recognized on magnetic resonance imaging (MRI). Some can be truly multifocal with interposed normal tissue between two AV shunt niduses (Fig. 2.16) and separate or distinct draining veins. Others can be contiguous, simulating compartments within a single lesion. Proof of the presence of these compartments is sometimes hard to establish; however, they may represent individual therapeutic goals at the time of endovascular treatment. The most typical is probably CAMS syndrome, which encompasses vascular malformations in adjacent locations such as the optic nerve, diencephalon, and occipital cortex. These lesions may reveal sequentially over several years (as much as 20 years in the cases of Jiarakongmun et al. 2002), illustrating the effect of the surrounding relationships along the migration pathway on the impaired cells, each region compensating differently (and revealing differently) for the quiescent defect that originated from the early stages of metameric organization. Some associated lesions cannot be integrated into the CAMS scheme even though obviously linked (Fig. 2.17).

Proliferative Lesions

49

Fig. 2.16A, B. A 7-year-old boy presented with generalized seizures in relation to a brain AVM. Note the multifocality demonstrated at angiography

Within these multifocal lesions, some may be false AV shunts. Following hemorrhage or ischemia, the true lesion may induce angiogenesis (neoangiogenesis or capillarectasia) and early venous return. The final appearance is sometimes difficult to understand unless prior angiography had been performed. Interestingly, the number of thrombosed lesions also seems to be more frequent on follow-up of CAVMs in children.

2.3.2 Proliferative Lesions

Proliferative vascular lesions in children form a distinct group of disorders; the name „angioma“ is often given indiscriminately to all apparently congenital, nonischemic vascular lesions. The failure to differentiate between nonproliferative and proliferative lesions has been the source of misinterpretations and erroneous prediction of the course of the disease. The name „angioma“ (vascular growth) should be abandoned or reserved for hemangiomas, which are benign tumors of blood vessel origin in infants (see Chap. 11, this volume). Some hemangiomas can be seen intracranially but such localization is rare and usually associated with superficial hemangiomas (see Chap. 12, this volume). Infant hemangiomas appear to be rare in Asian populations. The older the child, the more likely the angioarchitecture of these vascular tumors will be of the cavernous type. Yet some of them keep a capillary angioarchitecture and are called NICH (noninvoluting capillary hemangiomas).

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.17A–D. A 6-year-old child presented with an external ear capillary lesion on the left side (A, B), associated with an ipsilateral intracranial cerebellar arteriovenous malformation (AVM) discovered incidentally (C, D). These findings suggest a CAMS 3 syndrome

Diffuse Angiodysplasia

51

2.3.2.1 PHACE or PHACES

These are acronyms for a syndrome of variable phenotypic expression comprising posterior fossa malformations, facial hemangiomas, arterial anomalies, coarctation and other cardiac disorders, eye abnormalities, and stenotic arterial disease; many of the elements of this disorder could reflect an underlying abnormality of cell proliferation and apoptosis (see Chap. 12, this volume) (Bhattacharya et al. 2001).

2.3.2.2 Diffuse Angiodysplasia

Diffuse angiodysplasia was reported in neonates by Hasper (1983) and Flower (1972): it is characterized by glomeruloid hypertrophy of perithelial and endothelial cells and can be associated with hydranencephaly and hydrocephalus. Schmitt (1984) reported possible cytomegalovirus transplacental transmission in one infant, while Flament-Durand (1981) identified an associated adenovirus type 4 infection. In children and young adults, proliferative and angioectatic diseases are frequently triggered by spontaneous or traumatic dissections, viral infections, immune phenomena, and other causes. Moyamoya disease, moyamoya-like syndromes, and proliferative angiopathy in children are the most typical disorders in this group (Figs. 2.18, 2.19). They combine neoangiogenesis (production of lumen) and angiectasia (production of vessel wall), which may be difficult to differentiate; however, in such instances there is a discrepancy between the apparent size of the nidus-like network of vessels and the draining veins that are often normal or slightly enlarged. In angiectasia, the architecture of the nidus is homogeneous and appears normal, while it is unpredictable in angiogenesis. The rapid venous filling is usually due to a faster capillary transit time and seldom caused by true AV shunts in capillarectasia (in some DVAs for example). The evolution of these proliferative diseases is unpredictable (see Chap. 18, this volume). Hemorrhagic angiopathy is another entity that we encounter in some rare cases of intracerebral hematomas in children. Most often after the age of 5 they correspond to a network of intracerebral subcortical arterioles with normal morphological and sequential venous drainage. They may rehemorrhage and can therefore be partially embolized when the area of weakness in the angioarchitecture can be identified; if it is not possible to identify such a target, one may consider radiosurgery. The response to radiation therapy is amazingly rapid and effective (Fig. 2.4). Even this approach to vascular lesions is too static, since not all malformations are seen at the same age and are invariably not seen at the beginning of their development. The age of a given lesion is therefore unknown (Scheme 2.4). They often represent significant anatomic differences and yet are usually discussed as a group, thereby creating confusing statistical population projections. They are thought to be congenital, which has never been proven, and are believed to be essentially stable in size. Our experience contradicts both statements. Over time, certain CAVMs may appear to increase in size, while others spontaneously thrombose without

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.18A–D. Legend see p. 53

▲

Diffuse Angiodysplasia

53

Fig. 2.18A–F. A 12-year-old boy presented at the age of 1 month with a generalized seizure. A–C MRI was performed. D–F A few months after additional seizures and transient right-sided deficit, angiography shows a stenotic disease of the ICA anterior division involving the A1 and M1 segments. There is intracerebral lenticulostriate angiectasia and angiogenesis corresponding to the first stage of moyamoya disease. The vertebral artery injection demonstrates the sparing of the posterior fossa arteries

symptoms. However, one never sees a micro-AVM becoming a large one or a nidus arranged AVM becoming a fistulous lesion. Whenever it is possible to compare high-quality angiographic studies 10 years apart, amazing changes in the vasculature can be observed. These changes are less spectacular in adults, where the vascular plasticity does not cover the same range of possibilities as in children and therefore does not show the same degree of variability. This introduces two new approaches to the problem of CAVMs in children: the aspect of age and symptoms vs the impact of vascular remodeling in the congenital concept of CAVM. The fact that the remodeling is the same during the perinatal period as in infants and children is probably only a gross approximation and not completely correct.

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Fig. 2.19A–D. Legend see pp. 56

Diffuse Angiodysplasia

Fig. 2.19E, F. Legend see p. 56

55

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2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.19A–G. A 15-year-old girl presenting with generalized seizures was diagnosed a proliferative angiopathy. A, B Note on the MRI section the amount of dilated vessel running at the surface of the cortex. C–F Angiographically, there are several cortical artery interruptions with local „explosive“ angiectasia. Diffuse supra- and infratentorial transdural supply at the base and the convexity testify to the active angiogenic activity of this disorder. G Despite medical treatment, the patient died 4 years after the diagnosis from major ischemic stroke

2.4 Classification of CAVMs by Age Group In caring for children over time, one must consider the different phases of their development. Depending on individual interests and experience, one may wish to emphasize age, symptoms, or various diseases. However, clinical practice forces us to constantly switch from one to the other to establish the most accurate prognosis. To illustrate these various methods and their contributions to decision making, we will consider them sequentially based on age group.

2.4.1 Fetal Age

Intrauterine antenatal ultrasound or MRI diagnosis of a large fetal intracranial mass as a pseudocystic, nonechogenic or poorly echogenic spherical image, depending on its topography, illustrates either a VGAM or a dural sinus malformation (DSM) (Fig. 2.20). In a few cases we made a prenatal diagnosis of CAVM (Scheme 2.7). Despite all the possible features associated with each type of lesion involved (see the corresponding chapters), we will concentrate on two abnormalities: macrocrania with or without encephalomalacia and cardiac tolerance (Scheme 2.8). With regard to the mother, there has not been any effect observed during pregnancy of a prenatal diagnosed intracranial AV shunt. We have not found any trigger responsible for the occurrence of such a shunt at that time. With regard to the fetal brain, macrocrania can be seen in both VGAM and DSM, but it has opposing prognostic values. In VGAM, macrocrania (in the absence of ventricular enlargement) is usually a benign obser-

Intracranial AV Shunt in Children Age Groups Fetuses Neonates (30 days) Infants (200/mn, ventricular extrasystoles, tricuspid insufficiency) Macrocrania Ventriculomegaly Brain loss

High-output cardiac manifestations are the most frequent systemic manifestation encountered. Liver and renal insufficiency occurs secondary to congestive cardiac failure (CCF). Their extent should be carefully assessed in neonates before the therapeutic decision is made (see neonatal score in Sect. 2.6). Cerebral AV shunts are infrequent causes of CCF.When CCF is suspected following clinical examination including cranial auscultation, then confirmation can easily be obtained by transfontanel ultrasound (Pellegrino et al. 1987). Unfortunately, many of these infants are initially considered to have congenital heart disease (Cumming 1980; Long et al. 1974; Massey et al; 1982) and are sometimes subjected to cardiac catheterization (Long et al; 1974; Massey et al. 1982; Pellegrino et al. 1987). Cardiac manifestations secondary to intracranial cerebral AV shunts are extremely variable in extent and vary from severe heart failure with multiorgan failure resistant to medical treatment, to well-tolerated mild cardiac overload or incidental discovery of an enlarged cardiac silhouette. In the past, the prognosis of a newborn presenting with severe heart failure from a CAV shunt was poor, with a mortality rate of 100% (Hoffman et al. 1982; Johnston et al. 1987). However, in recent years, the use of endovascular therapy in newborns and infants has significantly changed this traditionally poor outcome in these patients (Garcia Monaco 1991a). Arterial embolization, although technically challenging in babies weighing only a

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few kilograms, can result in dramatic improvement of cardiac function (see Chaps. 3, 4). Among 600 referred cases (adults and children) with cerebrocranial vascular lesions, only 30 (5%) presented with cardiac symptoms (Garcia Monaco 1991a). However, when only the pediatric population was considered, this figure rose to 19%. Some types of isolated high-flow fistulas in children are surprisingly infrequently associated with cardiac manifestations (see Chap. 4). VGAMs, in contrast, are frequently associated with cardiac manifestations. They account for 73% of the population with CCF or cardiomegaly of cranial cause (Garcia Monaco 1991a). Cardiac angiography is not indicated and may result in transient or permanent impairment of the femoral vasculature. The cardiac manifestations are not specific in suggesting a cranial cause, but occur in the presence of right-to-left shunt, an atrial communication or patent ductus arteriosus (Cumming 1980; Maheut et al. 1987; Pellegrino et al. 1987), or ventricular septal defects. This persistence of a fetal type of circulation should not be regarded as a true cardiac anomaly, since it reflects right atrium volume and pressure overload. In Garcia Monaco’s series, severe heart failure in newborns was always secondary to an intracranial vascular lesion. However, in some instances management of a patent ductus arteriosus may have to be considered (Chevret 2002) prior to active treatment of the intracranial shunt itself. Besides VGAM, cerebral or dural AV shunts can also result in severe CCF (Chan and Weeks 1988; Albright et al. 1983). In addition, CAV shunts produce cardiac failure only at a very young age (1–19 days in Garcia Monaco’s series). The older the child, the lower the chances are of cardiac manifestations and the milder they will be. Mild heart failure or simple cardiomegaly is observed in infants whose chief complaints are macrocrania or other neurological manifestations. In these cases, the etiologic diagnosis occurs later, usually after 6 months of age. The prognosis of severe CCF of cranial origin in newborns or infants has traditionally been considered to be very poor, but this has improved significantly with modern endovascular techniques. Treatment of CCF with giant capillary hemangiomas of the face is different. Symptoms start with the proliferation phase of the lesion at 4–12 months of age. The objective here is to exclude the lesion from the general circulation and to gain time to allow spontaneous regression to occur (see Chap. 11, this volume).

Intracranial AV Shunt in Children Systemic Manifestations Cardiac failure Pulmonary hypertension Renal dysfunction Hepatic insufficiency Coagulation disorders

2.5.2 Hydrodynamic Disorders

A special relation between cerebral veins and water absorption has been suspected for a long time: The hypothesis that cerebrospinal fluid is absorbed by the Pacchionian granulations is instantly shattered by the fact that these structures only develop in time. They do not exist in infants and young children, nor do they exist in many animals. (Dandy 1929)

According to Le Gros Clark (1920) and Gomez et al. (1981), changes leading to the development of arachnoid villi and granulations are confined to the posterior half of the superior sagittal sinus; lacunas are present

Intracranial AV Shunt in Children Hydrodynamic Manifestations Macrocrania Ventriculomegaly Hydrocephaly Tonsillar prolapse Melting brain syndrome Hydromyelia

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during the 26th week, and by the 35th week typical arachnoid villi are seen. These increase in size and complexity during childhood. The first appearance of complex proliferations has been reported by the 18th month. However, both contributions do not provide information on the function of the developing arachnoid villi and granulations. More recently, Welch and Friedman described the flow patterns through the labyrinth of small tubes in monkey villi: the tubes are closed by high pressure in the venous sinus and opened by high CSF pressure. However, the CSF flow through human arachnoid granulations may not be as responsive to venous sinus pressure as in the animal villi (Upton and Weller 1985) The various steps and the schedule of this maturation are poorly understood. Only a few facts seem established or accepted, e.g., the development of the villi is not mechanically related to the formation of the subarachnoid space. Villi have been described in the lungs of South American Indians living at a high altitude; the presence of the villi was related to the permanent edema present in the interstitial tissue. The growth of the villi is linked to the superior sagittal sinus (SSS) development. For a long time, evidence of villi could only be found along the posterior half of the SSS. Although visible at neonatal and infant ages, villi and granulations do not show full complex development until infancy or early childhood. Although factors of functional maturation are unknown, relationships can be postulated between villi function and venous hemodynamics. The venous system continues developing during the first few months of life, and this venous hemodynamic maturation may play a significant role in villi development. In normal situations, specific features of cranial venosinus flow include pulsatility, negative pressure (sump effect), and absence of valves. In babies, Valsalva episodes are more frequent, which primarily increases venous pressure, but also suppresses the diastolic flow in the arteries to the brain. These observations led to the belief that most of the cerebral blood flow is, to a significant extent, sumped by the venous system rather than pushed as in any other part of the body (with the possible exception of the lungs). In abnormal conditions such as high-flow AV shunts, the sinusal negative pressure is diminished. The arterial steal phenomenon, noted in some rare cases, is associated with the disappearance of the arterial diastolic flow. If these changes are sufficient to create the link between villi and sinuses and their progressive postnatal maturation, then the question remains of where the water is reabsorbed in the meantime (Scheme 2.9). Again, certain facts should be recalled: (a) the lack of ependymal resistance to free exchange between the fluid in the extracellular space (ECS) and the CSF, and (b) the similar composition of ECS and CSF may have a direct bearing on the possibility that the parenchyma is the main source of nonchoroidal CSF formation responsible for up to 10%–20% of CSF production (McComb 1983). Since the venular endothelium is comparable to that of the capillary bed, the venular endothelial cells possess a comparable polarity and perhaps participate in the active regulation of the ECS and CSF environment. It has been suggested that the intraparenchymal vasculature is directly linked to the sequestration and removal of substances moving in and between the CSF and the ECS. Such a vascular uptake of CSF sub-

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Scheme 2.9. Cranial hydrodynamic circuits. CSF, cerebrospinal fluid

stances may have a significant role in the absorption of CSF and the maintenance of a homeostatic environment (Povlishock and Levine 1984). From our experience in vascular disorders in neonates and infants, we believe that, both normally and in the presence of an intracranial AV shunt, the intrinsic and CSF fluids are mainly reabsorbed into medullary veins of the brain and cerebellum. As soon as the conditions are met to recruit villi functions, a progressive shift will take place, separating the intrinsic system and the extrinsic types of resorption. Since all cerebral veins open into the torcula at birth, the system is obviously convergent and therefore poorly compliant in the case of early intracranial AV shunt; normal secondary capture of the middle cerebral veins by the cavernous sinus is the earliest diverging opportunity for venous drainage of the brain. Ophthalmic and facial veins as well as the pterygoid plexuses may become important associated venous (and water) pathways, despite their different hemodynamic regimen in the facial and external jugular veins. In high-flow AV shunts draining into the torcula, the facial veins have a comparatively lower pressure than the SSS; pulmonary hypertension, maturation of fetal circulation, and progressive skull base growth will all further increase the positive pressure changes in the sinuses. We therefore accept the observations that hydrodynamic disorders are usually absent in neonates and develop after a free interval in infants. Later on, the fusion of the sutures will contribute further to the advent of a poorly

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Fig. 2.23. A 12-year-old boy presented with a vein of Galen dilation due to a choroid plexus arteriovenous lesion. Following chronic venous sinus congestion, note the significant enlargement of the cranial bones

Scheme 2.10. Events likely to interfere with the hydrovenous maturation process

compliant hydrovenous system, in particular when the villi have not become functional. Diploic engorgement and bone thickening (Figs. 2.23) are associated with this search for collateral circulation into the subgaleal veins and cranial lymphatics (Scheme 2.10). The sequence of hydrodynamic impairment events may occur as follows in intracranial AV shunts: a stabilized shift in hydrovenous function with abnormal parameters creates macrocrania.A ventriculocortical gradient allows reabsorption of the secreted water as well as some transmeningeal passage in the dural venous network present at that age. Progressive failure in the medullary venous system, worsened by jugular stenosis that progressively accompanies the macrocrania, produces a loss in the ventriculocortical gradient and causes ventricular enlargement, hydrocephalus with raised intracranial pressure (ICP). Subependymal atrophy (with normal ICP) resulting in slowly progressive ventriculomegaly represents a different effect of the same constraints and failure.

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Fig. 2.24A–C. A female neonate presented with cardiac failure. A MRI performed at that time shows the small vein of Galen aneurysmal malformation. At 5 months, following progressive macrocrania, the child was shunted. She rapidly developed neurological problems in relation to a slit ventricle syndrome. B, C MRI performed at that time demonstrated the rapid tonsillar prolapse with the enlargement of all the perimesencephalic and pontine veins. D see p. 69

It points to the trophic role of the hydrovenous equilibrium in the interstitial space. At the hydrocephalic stage, ventricular shunting will reverse the necessary ventriculocortical gradient without treating the cause and often leaves residual ventriculomegaly through subependymal atrophy. Rapid disequilibrium provoked by the ventricular shunting may sometimes lead to slit ventricles (Fig. 2.24). These facts and speculative remarks derived from our experience require special comments for the posterior fossa. In intracranial AV shunts in neonates and infants, the usual posterior fossa drainage takes place through the petrosal vein and superior petrosal sinus toward the cavernous sinus or caudally to the jugular bulb or

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Fig. 2.24 (continued) D Emergency embolization resulted in an almost complete occlusion of the malformation, improvement of the tonsillar prolapse, and a decrease in the basal vein network. Clinically, the child improved significantly, but a mild deficit remained following the slit ventricle episode, as well as some degree of mental retardation. She is now 13 years old and has a score of 1

spinal cord veins (Scheme 2.11). Stenosis or thrombosis of the transverse, sigmoid sinus, jugular bulb, or jugular vein will lead to venous reflux into the cerebellar veins from the lateral sinuses or petrosal veins (Scheme 2.12). If at this time the cavernous sinus is not sufficiently developed, then there is insufficient venous outflow pathways for the posterior fossa, resulting in interference with the absorption of the cerebellar water. Hence there is accumulation of intrinsic fluids, leading to an increase in posterior fossa water contents with resultant tonsillar prolapse (Figs. 2.24–2.26).A normal or small fourth ventricle is noted.As the accumulation of brain water supratentorially results in macrocrania, the infratentorial venocongestive status depends on the available outlets and it manifests itself as tonsillar prolapse. Tonsillar prolapse expresses the combined impact of all the posterior fossa hydrodynamic disorders. It is primarily due to the particular physiology of CSF circulation in neonates and infants, but also the congestion of the cerebellar veins into the sinuses (initially patent) and the stiffness of the bony sutures. Secondarily, it is caused by the progressive occlusion of the jugular foramen, which increases the congestion and further delays granulation maturation. It is reversible through a decrease in the sinus venous hyperpressure if the available outlets are sufficient (Fig. 2.27). The fourth ventricle has a slit-like appearance rather than being small in relation to a presumed aqueduct compression by an ectatic venous pouch. Finally, caudal engorgement may involve the spinal ECS, leading to longitudinal cavitation or atrophy (Fig. 2.28). Such a situation is encountered in all types of intracranial AV shunts, VGAM, pial AV shunts, and DAV, provided that the appropriate sequence and timing of events are given.

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Scheme 2.11. (left) Neonatal cerebral venous drainage. At this age, venous drainage converges into superior and posterior sinuses. Posterior fossa drainage is via the mesencephalic vein and the superior petrosal sinus to the cavernous sinus and caudally to the jugular bulb. There is no cortical venous drainage to the cavernous sinus yet (hatched). Arrows indicate pathway flow Scheme 2.12. (right) Infant venous drainage and distal sigmoid venous occlusion (asterisk). With high pressure caused by the arteriovenous shunt in the sinus, flow of the cortical vein is forward into the cavernous sinus. Flow is reversed in the temporal vein as well as in the petrosal and cerebellar veins (hatched). Cavernous high flow via the inferior petrosal sinus to the jugular bulb occurs, as well as via the ophthalmic vein or the vein of the oval foramen. Posterior fossa drainage depends critically on the adequacy of the venous channel supratentorially, the cavernous sinus drainage, and the presence of the patent jugular vein distal to the occluded bulb (double arrow). If there is inadequate drainage, venous flow in the posterior fossa vein becomes stagnant and enlarges the cervical spine veins caudally

Fig. 2.25A, B. A male neonate presented with mild cardiac failure. He was referred at the age of 5 months, at which time he was found to have slight acquisition delay (score of 2). MRI demonstrated single-hole high-flow fistula in the prefrontal branch of the left middle cerebral artery. Note the moderate atrophy around the lesion and the tonsillar prolapse

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Fig. 2.26A–D. A male infant presented at the age of 6 months with epistaxis. Macrocrania was noted. He was referred at the age of 2 years with left-sided exophthalmos, intense facial collateral circulation and no neurocognitive delay. On MRI there is evidence of a small vein of Galen aneurysmal malformation with rerouting of the venous blood flow through the left superior petrosal sinus, cavernous sinus, and orbital vein. The tonsillar prolapse points to the posterior fossa hydrovenous disorders

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Fig. 2.27A, B. A young girl was referred to us at the age of 5 years with significant macrocrania already shunted. A MRI demonstrated tonsillar prolapse. B Following embolization, there is almost complete occlusion of the vein of Galen aneurysmal malformation with shrinkage of the ectatic pouch. Also note the hypersignal and the thickening of the cranial vault bones

Fig. 2.28A–C. A young adult male had had a torcular dural sinus malformation with macrocrania since infancy. After 10 years, the lesion is partially thrombosed; note a tonsillar prolapse, upper cervical spinal cord cavitation, and bone hypertrophy. Solid arrows, arterial supply (A), venous drainage (open arrows) (B), and partially thrombosed torcular herophili (arrows) (C). (From Apsimon et al. 1993)

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2.5.3 Melting-Brain Syndrome

Melting-brain syndrome consists in the rapid destruction of the brain, usually the white matter, with secondary ventricular enlargement. This phenomena is associated with severe neurological manifestations and no signs of increased intracranial pressure, although they are usually present before the morphological damage is seen. When brain suffering leads to trophic changes, these are usually bilateral and symmetrical; they correspond to a regional decrease in the cerebral blood flow caused by retrograde venous hyperpressure,leading to hydrovenous dysfunction.Arterial steal is not present or accessory in this syndrome.The local atrophy around a PAVM can be a focal expression of this phenomenon (Fig. 2.29). These findings are never encountered in adults. It illustrates the role played by the subpial and medullary veins in the maintenance and development of the white matter. It may not be seen in lesions that open without restriction into a subarachnoid venous outlet. We have observed it in neonates and young infants (up to 3 months of age) in all types of AV shunts: VGA, DSM, and PAVM. However, while the mechanism is the same, each lesion creates the condition (regional hydrovenous dysfunction) in a different fashion (Table 2.3).

Fig. 2.29A, B. A 10-year-old girl presented a cerebellar arteriovenous malformation revealed by a generalized seizure. Note the cerebellar atrophy detected at MRI examination. Clinically, she has mild cerebellar ataxia

Table 2.3. Melting-brain syndrome Etiology

Prenatal

Neonatal

Early infancy

Late infancy

VGAM DAVS PAVM

++a + –

+++ ++b 0

– +++ ++c

+ – +++

Cumulative negative factors include the following: no cavernous sinus opening of cerebral venous drainage; pial vein congestion, or decreased venous flow with hydrodynamic disorders; progressive sinus stenosis and secondary thrombosis; venodural sinus junction incompetence with or without raised intrasinusal pressure and pial vein reflux. VGAM, vein of Galen aneurysmal malformation; DAVS, dural arteriovenous shunt; PAVM, pial arteriovenous malformation; +++, very frequent; ++, frequent; +, possible; –, not seen. a Systemic mechanism. b Dural malformative mechanism. c Hydrovenous congestive mechanism.

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Fig. 2.30A–C. Legend see p. 75

▲

Melting-Brain Syndrome

Fig. 2.30A–H. A young boy presented at the age of 4 months with macrocrania. A–C At the age of 6 months, initial MRI (not shown) and angiogram confirmed the diagnosis of a small vermian arteriovenous malformation; retrograde congestion of the torcular in relation to bilateral stenosis of jugular bulbs had already occurred. The venous drainage of the carotid injection demonstrates the difficulty of drainage associated with restriction of the outlets. One month later, the child became comatose. D, E Angiography demonstrated a complete occlusion of the jugular bulbs. F–H Major melting-brain syndrome is seen in the frontal region. Note in this particular patient the small size of the lesion and the absence of arterial steal phenomenon. The child died soon after these examinations. (Courtesy of R. Piske)

75

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In VGAM, the damage starts during fetal development in relation to the systemic failure; the combination of venous and arterial disorders may accelerate the melting phenomena. In DSM, the malformation of the sinus and the early occlusion of the few venous outlets available rapidly precipitate the central venous drainage. In CAVM, the phenomenon occurs late (at 7–8 months of age) and progressive spontaneous thrombosis of the venous drainage has to occur to provoke the syndrome in the absence of patent alternate pathways (Fig. 2.30). This mechanism is progressive and once it starts, it develops fairly rapidly, although it is slow enough to result in a loss of substance rather than a hemorrhagic infarct, which supports the role played by water in the maintenance of brain tissue. In some cases, following limited hemorrhagic infarct, progressive melting is noted despite treatment (Fig. 2.21). In this situation, the venous congestion has been partially or totally relieved, but the insult has remained irreversible. If the insult is even slower, calcifications will take place with a moderate tissue loss until a new equilibrium is found between the remaining brain substance, the available nutrition, and venous outflow. The different outcome in diffuse melting-brain syndrome and the regional type and local atrophy encountered in young children depends on the role played by subpial and subarachnoid venous drainage (Table 2.4). Subpial veins actually communicate with subependymal veins via the medullary veins located in the Virchow Robin spaces and are therefore capable of interfering with the water (intrinsic) equilibrium. In contrast, the subarachnoid veins directly travel in the pericerebral spaces with little impact on the intrinsic water physiology as long as the dural sinuses are sufficiently patent. Thus two high-flow lesions both apparently located on the surface of the brain may have different effects on the underlying cerebral tissue, depending on whether they open directly into subpial or subarachnoid outlets almost independently of the flow they carry. In neonates and infants, this equilibrium represents a highly sensitive system. Any shift in the hydrodynamics will have a regional effect, and any decrease in the ventriculocortical gradient will alter the growth of the corticosubcortical substance. Water retention is often noted before the obvious destructive phase of the brain: most melting-brain syndromes provoke macrocrania before the head circumference curve falls below normal values. The fear of being confronted with such a syndrome should prompt therapeutic attempts, provided that one is able to identify irreversible damage and predict the degree of residual disability if treatment succeeds in limiting damage (Fig. 2.22). Appropriate knowledge and understanding of the natural history and pathophysiology of VGAM, DSM, and CAVM disorders in neonates and infants is mandatory. The so-called melting of brain tissue may be an apoptotic phenomenon triggered by the hydrovenous disorders described above.

Intracranial AV Shunt in Children Cerebral Manifestations Venous congestion Venous ischemia Haemorrhagic infarct Melting brain syndrome Arterial steal

Intracranial AV Shunt in Children Neurological Symptoms Mental retardation Epilepsy Deficit Hypertony and abnormal movements Headaches

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Table 2.4. Systemic hydrovenous manifestations in arteriovenous shunts and their specific main venous drainage Manifestation

Drainage

Cardiac failure

Melting-brain syndrome

VGAM AVF pial AVM subpial Nidus or fistula Subpial AVF Epidural AVF

Choroidal vein Subarachnoid vein Subpial vein

+ + ±

+ – ++

Subarachnoid vein Epidural venous system

± ±

– ±

VGAM, vein of Galen aneurysmal malformation; AV, ateriovenous; AVF AV, fistula; AVM, AV malformation.

2.6 Clinical Evaluation Scores With the tendency to use sophisticated tools to approach brain function in children, combined with our lack of knowledge on the physiology and plasticity of the brain at this age, clinical evaluation represents one of the most important and difficult aspects of management in children. Perinatal and early childhood examinations are challenging for neurologists and even more so for neuroradiologists. With the quality of images obtained, a strict morphological result, elegantly photographed, is often felt to be eloquent enough. However, this satisfaction cannot be complete without appropriate clinical assessment and follow-up. This is the primary therapeutic goal and challenge for us: a child growing normally is more important than one that is morphologically cured but disabled. With the increasing role of neurological interventions in children and the full-time involvement of pediatric neurosurgeons, attention has been directed toward the peritherapeutic clinical follow-up, with an attempt to use reliable scores and evaluation scales. More recently, we have been contributing to pretherapeutic evaluation in neonates and follow-up in these children in order to anticipate early delays and identify reversible situations. This subsequently led us to the therapeutic window concept, in which early management is a complex technical challenge with few chances of a good clinical outcome (see Chap. 3, this volume), and late management, although easier, will not be able to correct irreversible functional damage (see Chap. 4, this volume). Three aspects of the classical clinical references available illustrate the difficulties we face in trying to compare our individual results: 1. The adult scores do not apply: Glasgow (initial and outcome) and Karnowski (Tables 2.5–2.7). 2. Pediatric scores are usually simple but do not take into consideration the vascular nature of the lesion, but rather the static analysis of a traumatic insult to an otherwise normal brain (Tables 2.8, 2.9; Seshia 1988;Yager 1990; Reilly-Simpson 1982, 1988; Raimondi 1984).

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Table 2.5. Adult Glasgow Coma Scale Score

Eye opening

Verbal response

Motor response

6 5 4 3 2 1

– – Spontaneous To speech To pain None

– Oriented Confused conversation Inappropriate words Incomprehensible words None

Carrying out commands Localization of pain Withdrawal from pain Abnormal flexion Extensor response None

World Federation of Neurological Societies grading is as follows: grade I, for a total Glasgow score of 15; grade II, for a total Glasgow score of 13/14 without deficit; grade III, for a total Glasgow score of 13/14 with deficit; grade IV, a Glasgow score of 7–12; grade V, a total Glasgow score of 3–6.

Table 2.6. Adult Glasgow Outcome Score Score

Outcome

5 4

Good recovery; full independent life with minimal neurological deficit Moderately disabled; neurological or intellectual impairment, but independent Severely disabled; conscious, but totally dependent on others Vegetative Death

3 2 1

Table 2.7. Karnovsky Scale Score

Patient’s condition

100 90 80 70 60 50 40 30 20 10 0

Normal, no complaints Normal activity, minor signs Normal activity with effort Can care for self, but unable to carry out normal activities or do active work Requires occasional assistance Requires considerable assistance and frequent medical care Disabled; requires special care and assistance Severely disabled; hospitalization necessary Very sick; hospitalization necessary Moribund Dead

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Table 2.8. Modified Adelaide Pediatric Glasgow Coma Scale (Simpson et al. 1991) Score

Eye opening

Verbal response

Motor response

6 5 4

– – Spontaneous

Carrying out of commands Localization of pain Withdrawal from pain

3

To speech

2

To pain

1

None

– Oriented (smiles) Words (can be consoled when crying) Vocal sounds (inconsistent, consolable) Cries (not consolable, irritable, restless) None

Abnormal flexion to pain (decortication) Extension to pain (decerebration) None

Modified from the Children’s Coma Scale (CCS), derived from the Glasgow Comas Scale by Hahn (1988).

Table 2.9. Pediatric milestones (Adelaide Pediatric Coma Scale; Simpson et al. 1991)

Motor responsesa

Verbal responsesb

a b

Age

Response

Birth 12 weeks 20 weeks 26 weeks 32 weeks 48 weeks 52 weeks 18 months 2 years Birth 8 weeks 16 weeks 28 weeks 48 weeks 52 weeks 18 months 24 months 3 years 4 years 5 years

Spontaneous and reflex flexion and extension Selective movement of limb when pricked Voluntary grasp Voluntary transfer Gazes directly at limb when pricked Gives toy to examiner Localizes prick exactly Obeys simple orders Points to parts of the body Cries Vocalizes (chiefly vowels) Laughs, uses consonants Syllables (ba, da, ka, mu) One-word utterances with meaning Two- and three-word utterances with meaning Jargon, many intelligible words Spontaneous two- or three-word sentences Asks questions, uses pronouns Talks fluently, often fabricates or fantasizes Answers age questions correctly, knows name, draws man

Motor coma norms: flexion, 0–26 weeks; localization or pain, 6 months to 2 years; obeys orders after 2 years. Verbal coma norms: cries, 0–26 weeks; vocal sounds, 26–52 weeks; words, 1–5 years; oriented verbal response, after 5 years.

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3. Neonatal neurological assessment is a particularly difficult issue, with little attention paid to possible systemic manifestations (Duncan et al. 1981; Table 2.10). We therefore have had to develop several scores and have combined these in accordance with our personal experience since 1982: – A neonatal score, particularly oriented to choose the timing for embolization and predict the neurological outcome in severe systemic disorders. Most of these neonates have a limited neurological examination (Table 2.11). – An initial and outcome score for infants and older children, introducing developmental delays with focal neurological deficits and systemic cardiac manifestations. This gross categorization attempts to introduce the quality of a cognitive result, despite the neurologically normal examinations often reported (Table 2.12). – The Denver and Brunet Leisine test for neurocognitive evaluation was chosen by our pediatric neurology group, despite its imperfection, for its ease of use and acceptable quantification regardless of cultural differences (Schemes 2.13, 2.14). We have found these tools useful, not to give universal rules but rather to compare and rationalize our decisions over time. We have been able to assess the stability and accuracy of the criteria chosen to establish the therapeutic objectives.(Scheme 2.15; Fig. 2.30) Our experience has shown that these scores do not seem to apply only to Caucasians, but can be applied in many different cultures, and they appear to confirm that cultural differences in terms of life, death, and handicap are smaller among children than adults.

Table 2.10. Neonatal Coma Scale (Duncan 1981) Score

Response to bell

Response to light

Motor response

6

–

–

5 4 3 2 1

Facial and extremity movements Grimace, blink Increase in righting reaction Seizures/extensor posturing No response

– Blink, facial/extremity Blink Seizures/extensor posturing No response

Spontaneous periods of activity alternating with sleep Occasional spontaneous movements Extremity movementsa Grimace/facial movementsa Seizures/extensor posturinga No responsea

a

Response to sternal rub.

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Table 2.11. Bicêtre Neonatal Evaluation Score Pointsa

Cardiac function

Cerebral function

Respiratory function

Hepatic function

Renal function

5 4

Normal Overload, no medical treatment Failure: stable with medical treatment Failure: not stable with medical treatment Ventilation necessary

Normal Subclinical isolated EEG Abn’s Nonconvulsive intermittent neurologic signs Isolated convulsion

Normal Tachypnea, finishes bottle

– –

– –

No hepatomegaly, normal function

Normal

Hepatomegaly, normal function

Transient anuria

Permanent neurological signs

Moderate or transient hepatic insufficiency Abn coagulation, elevated enzymes

Unstable diuresis with treatment

Resistant to medical treatment

Tachypnea, does not finish bottle Assisted ventilation, normal saturation FIO2 25% Assisted ventilation, desaturation

3

2

1

0

Seizures

Anuria

a

Maximal score: 5 (cardiac) + 5 (cerebral) + 5 (respiratory) + 3 (hepatic) + 3 (renal) = 21. Abn, abnormal; FIO2, inspirated fraction of oxygen.

Table 2.12. Bicêtre Admission and Outcome Scoresa (BAS and BOS) Score

Condition

5 4

Normal (N) Minimal non-neurological symptoms (MS), not treated and/or asymptomatic enlargement of the cardiac silhouette Transient neurological symptoms (TNS), not treated and/or asymptomatic cardiac overload with treatment Permanent minor neurological symptoms, mental retardation of up to 20%; nonpermanent neurological symptoms (MNS) with treatment; normal school with support and/or cardiac failure stabilized with treatment Severe neurological symptoms (SNS), mental retardation of more than 20%; specialized school and/ or cardiac failure unstable despite treatment Death (D)

3 2

1

0 a

Does not apply to neonates.

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Scheme 2.13. The Denver and Brunet Leisine test for neurocognitive evaluation

Clinical Evaluation Scores

Scheme 2.14. Percentage of children who passed the test in Scheme 2.13

Scheme 2.15. A Typical curve in a macrocranic female and response following transarterial embolization (E). Normal curves in (B) boys and (C) girls (see p. 71)

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Scheme 2.15. B,C

Familial Hemiplegic Migraine

85

2.7 Revised Concept of the Congenital Nature of Vascular Malformations With increasing knowledge on neural crest derivatives, it is clear that the homeobox-containing genes and endothelial cell physiology genetics in vascular diseases will provide the key to future understanding and management of vascular disorders. Clinical, surgical, and autopsy data have provided a great deal of information and probably have not reached their limits. However, they appear to be advancing too slowly for the questions raised today. Biology, genetics, and morphology are introducing time as a new dimension (the fourth dimension: time and duration) in our practice. Unfortunately, our culture and capacity of imagination are limited, since they do not evolve at the same speed as the advances currently underway.

2.7.1 Genetics Familial Diseases (seldom symptomatic at pediatric age) Arterial aneurysm (PKD, Chr16, Chr4, ... ) Pial arteriovenous shunts (HHT, Chr12, Chr9) Usually high-flow (multifocal AVFs) ED chr.2, NF1chr.17: „spontaneous“ AVFs, para chordal AVFs Cavernomas Chr7: often multiple in the brain and the cord BRBN Chr 1, Chr 9

Several diseases are known to be hereditary. Some have been related to a chromosome disorder, and others have been localized to a single gene (Table 2.1). In clinical practice, the quest for familial disease is imperative and yet seldom fruitful. Although little use can be made of such findings today, future gene therapy and genetic counseling will transform the prognosis of many of these diseases. Some genealogical trees are difficult to establish, and patient interviews may be misleading if precise inquiries are not undertaken in order to establish the reality of a hereditary disease. The possibility of including information pertaining to relatives or even requiring their presence for possible interview purposes should be strongly considered. We had such an opportunity with a family in which three male members of the same generation presented with neonatal or infantile hemiplegia (Scheme 2.16). The decoding process of the events described by the family members was particularly fruitful, and the exceptional character of the initial findings was not as unique as we initially thought. The following diseases were recently identified or are entering direct research programs (obviously many more are being considered for genetic research, but the following are often discussed in our daily practice).

2.7.1.1 Familial Hemiplegic Migraine

Familial hemiplegic migraine (chromosome 19; Joutel et al. 1993) is similar to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and consists of migraine attacks marked by the occurrence of a transient hemiplegia during the aura. The age of onset varies from 5 to 30 years, but it is predominant during youth.

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Scheme 2.16. Genealogical tree of a HHT family affected by neonatal/pediatric hemiplegia. Asterisks indicate patients seen as out-patients. PAVF, pulmonary arteriovenous fistula. The numbers are the ages of the family members(y, years; m, months) (see Fig. 18.1)

2.7.1.2 Familial Cerebral Aneurysms

In Finland, 10% of patients with ruptured aneurysms have a family history of aneurysmal subarachnoid hemorrhage (91 families with 203 arterial aneurysms). Of these, 54% are female and aged around 49 years. Middle cerebral arterial aneurysm was found in 47% of these patients (Ronkainen et al. 1993). A prospective study in healthy family members showed incidental arterial aneurysms in 12%. The chromosomes involved are not yet known (see Chap. 17, this volume).

2.7.1.3 PKD1 and Bourneville PDK1-PDK2

These are the two recognized genes of Polycystic kidney disease (PKD). They are located, respectively, on chromosome 16 (translocation that represents 85% of PKD cases, in the vicinity of the Bourneville disease), and on chromosome 4. PDK1 codes a polycystin membrane protein. With the advancement of molecular genetics, the deletion of the TSC2/PKD1 gene at chromosome 16p13.3 has been discovered to be responsible for the tuberous sclerosis complex sharing some of the clinical manifestations of autosomal dominant adult polycystic kidney disease such as multiple renal cysts and intracranial aneurysms (see Chap. 17, this volume).

Familial Cavernomas

87

2.7.1.4 Ehlers-Danlos Type IV

This belongs to the collagen diseases. Diagnosis is established on cultured fibroblasts that synthesize abnormal type III collagen. A mutation in the gene for the type III procollagen (COL 3A1) is the cause of the disease, which is transmitted as an autosomal dominant trait on chromosome 2. It is associated with arterial ruptures and aneurysms (see Chap. 17, this volume).

2.7.1.5 Multiple Cutaneous Mucous Venous Malformations, Blue Rubber Bleb Nevus Syndrome

The dominantly inherited gene lies within a 24-cM interval on chromosome 9p. The alpha and beta interferon gene cluster and the putative tumor suppressor genes MTS1 and MTS2 are also incorporated into this locus, chromosome 9p. A few cases of autosomal dominant inheritance have been reported, but most cases published are sporadic. BRBN is characterized by multiple cutaneous venous malformations in association with visceral lesions, most commonly affecting the gastrointestinal tract. Some case reports have demonstrated involvement of the central nervous system (see Chap. 8, this volume).

2.7.1.6 CADASIL

This disease (Tournier Lasserve 1993; chromosome 19q12) leads to dementia, but starts in early or mid-adulthood. There is no arterial hypertension, no atherosclerosis, and no amyloid angiopathy (see Chap. 18, this volume).

2.7.1.7 Familial Paragangliomas

This disease (Hentink 1992; chromosome 11q23ter) shows that clinical manifestations are determined by the sex of the transmitting parent. All affected individuals have inherited the mutated gene from their father. Expression of the phenotype is not observed in the offspring of an affected female until subsequent transmittance of the gene through a male carrier (see Chap. 4, Vol. 2).

2.7.1.8 Familial Cavernomas

Familial cavernomas are autosomal dominant, and the genetic localizations are on chromosome 7q21–22 CCM1 (KRIT1 is the mutated protein CCM1), 7p13–15 (CCM2), 3q25,2–27 (CCM3) (Günel 1995) (see Chap. 8, this volume).

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2.7.1.9 Neurofibromatosis-1 and Other Collagen Diseases

Only neurofibromatosis-1 (NF1) leads to vascular anomalies; known as peripheral neurofibromatosis, it is carried by chromosome 17 (17qll.2), and the gene was recently cloned. Vascular lesions will result from infiltration of the vessel wall, and are characterized by stenosis, occlusions, aneurysms, and fistulas by rupture of a weakened arterial wall. Meningoceles and dural ectasias are also noted. Renal stenosis is the most frequent vascular lesion, but is only associated with significant renovascular hypertension in less than 1% of cases (Pope et al. 1991; Schievink and Piepgras 1991) (see Vol. 2, Chap. 7). Neurofibromatosis-2 (NF2) is carried by chromosome 22 does not lead to vascular manifestations. In fact, familial diseases and genetic discussions tend to simplify to a mechanical sort of relationship a demonstrated gene alteration and a function or a disease. The phenotypic expression of HHT is very illustrative of this type of challenge.

2.7.1.10 Hemorrhagic Hereditary Telangiectasia or Rendu-Osler-Weber Disease

The clinical aspects of the disease (chromosome 9q33–34; Shovlin et al. 1994) will be discussed in Chaps. 4 and 5, this volume. However, the authors concluded that HHT is a heterogeneous disorder, which certainly fits with our observations. According to Shovlin, based on its map location (9q33–34) and expression in vascular tissues, type V collagen is a possible candidate gene for HHT. If a single genotype is considered, several mutations involving endoglin can be seen, one per family. Certain manifestations (head and neck vs digestive tract) are frequently seen within one family. Yet in the head and neck group of families, certain characteristics are not transmitted, in particular CAVM or CAVF. It seems, however, that AVFs are typical if not specific of AVSs in young children (Fig. 2.31). The AVSs in adults tend to be expressed through nidus arranged lesions (AVMs). Since there are several foci in both types, why would this occur?

▲

Fig. 2.31A–E. A 1-year-old boy with familial history of ROW disease was first admitted with disturbances of consciousness and intraventricular hemorrhage on CT (A). Angiography (B–D) revealed three AVMs, two in the right cerebellar lobe and one SCAVM at C2 and C3. The main cerebellar arteriovenous shunt (AVS), supplied by the right AICA, appeared with an ectatic venous drainage of the posterior fossa and venous pseudoaneurysm. The cord lesion seemed more nidus arranged. In HHT, the cerebral AV shunts (with the same apparent genotype) diagnosed in children vs those in adults are very different. They are likely to represent two morphological expressions of the same venous malformation triggered at different maturation stages or phases of the endothelial cell (re)generation cycle. For comparison (C, E), see experimental lesion in mice end +/- Toronto group

Hemorrhagic Hereditary Telangiectasia or Rendu-Osler-Weber Disease

Fig. 2.31A–E. Legend see p. 88

89

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Is there a different genotype? It is unlikely that the two genotypes presently known and the AVF trait are linked to one group of other phenotypic expressions.
Is there a different mutation? If one mutation is specific for a given family this trait would be more frequently expressed in that family in comparison with others with the same genotype.
Do all cells share the same defect because its expression is related to environmental conditions? These will either compensate or on the contrary betray the quiescent damage or dysfunction. The fact that the AVF is seen in babies points to the early timing of disclosure (or failure to compensate). The same genotype and mutation better compensated or triggered later will show itself later in older children. The fact that the architecture of the lesions (nidus) is different does not point to a specific genotype but rather to a difference in timing of the window of exposure (perinatal vs childhood). The power of interference of the endoglin deficiency varies with age, or an unknown associated failure of a compensatory system does not allow the vascular tree to pass this window of vulnerability (Mahadevan et al. 2004).
One can only be puzzled by the peculiarities of HHT: no new intradural shunts have been seen during patient follow-up; all lesions in a given place, whether AVFs or AVMs, appear at the same time. This is specific of the brain and spinal cord, as pulmonary AVFs do appear during follow-up. This favors a rather systemic type of secondary event in relation to the multifocality of the disease expression to support the simultaneous appearance of the AVFs and AVMs. It is unlikely that a focal event would impact simultaneously remote sites on different cerebral hemispheres, supra- and infratentorially or in the brain and spinal cord.
In contrast, the impact of the mutation on the vessel wall remodeling in other areas with different environments and life spans (maxillofacial) leads to progressive appearance of telangiectasias with age (they are absent in children when the disease may have already expressed with highflow multifocal CAVFs). This points to the potential role of the surroundings (brain or maxillofacial) with respect to vessel wall (vein) construction, renewal, and thus vulnerability. This compensatory role can protect, repair, or reveal an impaired structure (or cascade) and directly interfere with the disease expression according to place (Scheme 2.17) and age (Scheme 2.18). This links certain disease geotropism and age of onset.
The fact that an AVF reveals at perinatal age does not prove the overall systemic weakness of the fetus; it remains as a focal problem with good systemic compensatory resources; properly treated at the right time, such a situation will lead to normal neurocognitive development. Improperly treated or at the wrong time, the permanence of the induced hemodynamic conditions will rapidly compromise the maturing system and engender new disorders.
In other situations, the weakness that led to the AVF revelation impacted the rest of the maturing cascades, reducing the compensatory resources to inefficiency; at that stage, regardless of what will be done on the AVF, the entire body enters an irreversible disequilibrium. Between these extreme situations each neonate and infant reacts with its own systemic resources that is best appreciated with the neonatal score.

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Scheme 2.17. Underlying steps from genotypic to phenotypic expression in neural crest migration. ML, medial lateral; CC, craniocaudal; VD, ventrodorsal

The younger the child, the more dynamic and interrelated the developing organs and functions, and the more compliant and adaptable the child is as well. Looking at diseases as fixed targets requiring mechanical correction ignores the dynamic nature of the morphological growth of the perinatal phase. The risk is to overcorrect a situation. Interdependence between systems should be corrected to relieve the bulk of abnormal signals, allowing for spontaneous repair. Partial targeted embolization, staged procedures and proper timing are key issues in the management of such diseases at that age. In other situations, we tend to ignore the identity changes that tissues have undergone following maturation and integration to a given environment. In this later misconception all arteries or veins are postulated to be the same throughout the body and therefore have equal capacity to express a genetic disorder. Experience shows that although shared by all cells, genetic defects will express in some areas and will spare others. This segmental vulnerability is well illustrated in diseases that affect the arterial wall. For example, describing a distal, subpial MCA aneurysm as a „berry aneurysm of the distal branches of the MCA“ (Peters et al. 2001) is a misnomer since this denomination is traditionally used for subarachnoid aneurysms. The former ruptures and gives intracerebral hematoma and the latter a subarachnoid hemorrhage. Stressing the role played by the extravascular space certainly points to the fact that the subpial environment is significantly different from the subarachnoid environment in the generation of the aneurysm, its rupture, and the response to that rupture. The age of the lesion (how long has aneurysm been present unruptured) and the exact time(s) of rupture are both unknown. Using the STA or another, easy-to-access artery for structural comparison and extrapolation is probably incorrect. It mistakenly postulates that the arterial system is homogeneous and that vessels such as the middle

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Scheme 2.18A. Vascular vulnerability phenotypic expression: continuous variability

Scheme 2.18B. Vascular vulnerability phenotypic expression: uncertain variability

Vascular Remodeling and the Congenital Nature of Arteriovenous Shunts

93

cerebral artery (MCA) and superficial temporal artery (STA) can be compared. The segmental vulnerability will show that these vessels have significant phylogenetic, embryologic, and hemodynamic differences. The hemodynamics and shear stresses in both systems are different, with no diastolic flow occurring in the STA. In addition, the STA does not develop aneurysms, which is a characteristic of the external carotid biological evolution in comparison to the internal carotid branches. The few aneurysms described in the superficial temporal arterial system are seen following trauma or MCA–STA anastomoses, which introduces a diastolic flow in the external carotid artery (ECA) and subsequently in the STA. This certainly emphasizes the role played by the environment and that of the signals coming from a distal territory, the surrounding tissue in the regulation and expression of the various genes. One can also question the maturation over time of some genetic programs of modeling and remodeling of the brain vessels. The cell turnover and the repair capacities are unlikely to be continuous but rather spread over equal periods throughout life. Postnatal maturation presents additional challenges that one should foresee in interpreting gene expression disorders (Lasjaunias 2000).

2.8 Vascular Remodeling and the Congenital Nature of Arteriovenous Shunts The provocative statement made by Professor G. Yasargil in the 1980 s regarding the possible noncongenital origin of cerebral AVM was not fully accepted at that time, although some felt it might be correct. The role of the endothelial cell is becoming better understood, and experience gained in prenatal diagnosis and progressive treatment of these lesions gives further credibility to Yasargyl’s observation and allows a general hypothesis to be elaborated. In what is considered the normal vascular tree, continuous remodeling will take place. The emerging concept of vascular remodeling is as follows (Gibbons and Dzau 1994). The vessel wall is an active, integrated organ composed of endothelial, smooth-muscle, and fibroblast cells combined with each other in a complex autocrine–paracrine set of interactions. The vasculature is capable of sensing changes within its milieu, integrating these signals by intercellular communication, and changing itself through the local production of mediators that influence structure as well as function. Vascular remodeling is an active process of structural alteration that involves changes in at least four cellular processes – cell growth, cell death, cell migration, and production or degradation of extracellular matrix – and is dependent on a dynamic interaction between locally generated growth factors, vasoactive substances, and hemodynamic stimuli. Remodeling is usually an adaptive process that occurs in response to long-term changes in hemodynamic condition, but it may subsequently contribute to the pathophysiology of vascular diseases and circulatory disorders. The biological process of vascular remodeling may be divided into the following components: (a) the detection of signals due to changes in hemodynamic conditions and humoral factors (sensors);

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(b) the relay of signals within the cell and to adjacent cells (transducers); (c) the synthesis and release of activation of substances that influence cell growth, death, or migration or the composition of the extracellular matrix (mediators); and (d) the resulting structural changes in the vessel wall (both cellular and noncellular components). The endothelial surface is constantly exposed to humoral factors, inflammatory mediators, and physical forces. The endothelium is strategically located to serve as a sensory cell assessing hemodynamic and humoral signals, as well as an effector cell eliciting biological responses that may eventually affect the structure of the vessel.

2.8.1 Endothelium as a Sensor and Transducer of Signals

Hemodynamic stimuli involve, in essence, the vessel remodeling itself in response to long-term changes in flow such that the luminal diameter is reshaped to maintain a constant predetermined level of shear stress. The capacity of the endothelium to sense shear stress is therefore an important determinant of luminal diameter and overall vessel structure (Fig. 2.32). In vitro, increases in shear stress alter the balance of endothelial cellderived mediators involved in the regulation of vascular tone, hemostasis, vascular-cell growth, and matrix production. New evidence suggests that shear stress activates a genetic program that alters the balance of the mediators of remodeling by activating the transcription of genes for factors such as nitric oxide synthase, platelet-derived growth factor (PDGF), and transforming growth factor b1 (TGF-b1).

Fig. 2.32. Arterial adaptations to increased pressure and increased blood flow. (Berdeaux 1994, adapted from Langille 1993)

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2.8.2 Endothelium-Specific Receptor-Coupled Event

Endothelial cells regulate vascular tone, hemostasis, inflammation, lipid metabolism, cell growth, cell migration, and interactions with the extracellular matrix through many receptor-mediated mechanisms. Similarly, the delicate balance between thrombosis and fibrinolysis involves specific endothelial-cell receptors for proteins involved in both enzymatic cascades.

2.8.3 Endothelium and Mediator-Effector Molecules Involved with Remodeling

Endothelial cells can participate directly in vascular remodeling by releasing or activating substances that influence the growth, death, and migration of cellular elements or the composition of the extracellular matrix. The contents of vessel walls may be determined by a balance between cell growth and programmed cell death, or apoptosis. In contrast to cell necrosis, apoptosis is a selective process of cell loss that occurs without evoking an inflammatory response.

2.8.4 Role of Matrix Modulators in Vascular Remodeling

The extracellular matrix is composed of the scaffolding elements of collagens (type I, III, IV, and IV) and elastin embedded in a mixture of glycoproteins (e.g., fibronectin) and proteoglycans (e.g., heparin sulphate).Vascular remodeling entails the reconstruction of the matrix scaffolding and therefore a process of active proteolysis and resynthesis of these proteins. The theme of homeostatic balance is again evident in that the proteolytic factors produced within the vasculature are counterbalanced by endogenous protease inhibitors. Alterations in the balance of factors modulating matrix composition appear to be important determinants of vessel architecture.

2.8.5 Clinical Implications of Vascular Remodeling

Vascular injury is induced by tissue ischemia resulting from occlusion of the vase vasorum and mechanical injury. Studies suggest that PDGF and TGF-b1 are involved in the neointimal proliferative response to surgical injury. The increased intraluminal pressure appears to result in thickening of the vessel wall. An imbalance between endogenous growth promotors and inhibitors may allow occlusion of vein grafts. Patients with saphenous vein grafts have impaired generation of nitric oxide by endothelial cells and increased angiotensin-converting enzyme activity. Thus, the adaptive response of vein grafts to surgical implantation into the arterial circulation involves a dynamic interplay among vasoactive substances, local growth factors, and hemodynamic stimuli.

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The possible closure of the ductus arteriosus can be induced either by the increased generation of local vasoconstrictors (e.g., endothelin) in response to increased oxygenation at the time of birth or by pharmacological blockade of endogenous vasodilators (e.g., prostacyclins by indomethacin). Hypertensive vessels in animals and in humans are characterized by a thickened media, a reduced lumen, and an increased extracellular matrix. Structural changes in hypertensive vessels are associated with increased expression of growth factors such as TGF-b1, local vasoactive substances such as angiotensin II, matrix proteins such as collagen and elastin, and matrix proteinaceous such as collagenase and elastase. These alterations predispose patients with hypertension to the sequelae of this disorder. Vascular remodeling also influences the natural history of atherosclerotic lesions. The endothelium appears to have a central role in this initiation of atherogenesis by regulating the infiltration of mononuclear cell and endothelial malfunction. We postulate that vascular stenosis increases shear stress and thereby induces an increase in the vessel radius to normalize shear stress, as described above in normal vessels. If this compensatory mechanism fails to keep pace with the growth of the plaque, the stenosis may lead to flow disturbances that further enhance the progression of the lesion and favor platelet aggregation and plaque rupture. Why does balloon angioplasty increase the luminal diameter in the vast majority of cases? Four factors determine the characteristics of flow after angioplasty: capacity of the regenerated endothelial surface to act as a transducer, the relative balance between cell growth and cell death, and the capacity of the remodeled matrix to contract and maintain the geometry of the vessel affected by the endovascular procedure. The resultant luminal diameter will depend on the net balance between factors promoting shear stress-induced expansion of the area of the lumen and the reparative response to injury that promotes restenosis due to the formation of neointima and matrix modulation. With time, the remodeling results in a gradual decrease in compliance, although it usually remains compatible with function. This results in a progressive morphological shift in the angioarchitectural features of the vascular anatomy. The normal endothelial cells adjacent to an AVM play a central role in the remodeling process, and their plasticity is a key factor in understanding the natural history of an AV shunt. It has been demonstrated that in the arterial wall proximal to an AV shunt, changes in pressure within the vessel result in a change in wall thickness (with release of local growth factors), while velocity changes result in lumen enlargement (preserving the wall thickness). The concept of secondary angiopathy related to chronic high flow (or flow changes beyond normal equilibrium) applies to a normally reacting vasculature that has been abnormally triggered by an AVM. This intraluminal trigger is a stress trigger, which can be related to flow, pressure, or other factors (Schemes 2.19a–c, 2.20).

Clinical Implications of Vascular Remodeling

Scheme 2.19A. Constitution of a quiescent AVM

Scheme 2.19B. Revelation of the dormant defect into an AVM

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Scheme 2.19C. Induced high-flow angiopathy

It may be postulated that, if triggering events were eradicated, highflow angiopathy would no longer develop or persist. This can be achieved by controlling the AV shunt and is well demonstrated by the disappearance of flow-related arterial aneurysms following successful treatment of a CAVM. This has served as a rationale to offer partial, targeted treatment for certain types of AVMs. Over time, the increased rigidity and fragility of this stressed vascular system becomes evident, when even partial and limited attempts to remediate the abnormal shunting zone lead to failure of the remaining normal vasculature, with early rupture and hemorrhage or ischemia as a result of intervention. These remarks point to the difference that should be made between primary lesion and secondary induced changes that are not part of the CAVM diseases, even if they represent its clinically eloquent part. Still, CAVM, even with variable high-flow angiopathic changes, is a heterogeneous group of abnormalities. With this apparent heterogeneity, some specific features are recognized in young children, including systemic manifestations, hydrodynamic disorders, and severe cerebral trophic changes. The specific morphological alterations encountered during the course of the disease in this age group are striking, as most of them are not observed in otherwise similar AVMs discovered in adults. If the lesions were present during the first few years of life– the time of specific vulnerability of the maturing brain– one would expect to find some degree of brain damage. It has become apparent that AVMs diagnosed in

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Scheme 2.20. Different phases necessary for the development of cerebral arteriovenous malformation (AVM). 1, Quiescent cellular dysfunction; 2, triggered susceptible cell; 3, active AV shunt developing stress trigger (ST) on the proximal and distal vasculature; 4, high-flow angiopathy with proximal arterial aneurysm, distal venous ectasia, and stenosis. RT, revealing trigger

adults are not present at birth, and if their initial course is clinically silent, the lesion was probably morphologically occult (Fig. 2.33). The term „malformation“ means failure to comply to a molded morphology or visible shape. Adding congenital to this denomination needs further explanation. The term „congenital“ means the period of the development that resides in the matrix. This does not mean embryology or genetics. Congenital in short means before birth. If we postulate that AVMs are the result of a congenital event, although occult, its expression will later become morphologically detectable. Its impact is primarily structural, cellular, linked somehow to vascular modeling and remodeling. The quiescent dysfunction that results (and persists over time) must involve the endothelial cells or any cell that interacts directly with its function (e.g., astrocytes, pial, ependymal). For this dysfunction to be eventually revealed as a morphological abnormality, a trigger factor is necessary. We call such postulated triggers revealing triggers (Schemes 2.21, 2.22).

100 2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

Fig. 2.33A–F. Legend see pp. 102

Clinical Implications of Vascular Remodeling

Fig. 2.33G–K. Legend see p. 102

101

102 2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts Fig. 2.33A–K. A 10-week-old boy admitted to the hospital was suspected of having meningitis. On admission he was noted to have on the lower right arm a 3¥4-cm capillary. On CT (not shown) of the skull, a dural arteriovenous fistula of the superior sagittal sinus (SSS) was noted. Electroencephalogram (EEG) showed a left parieto-occipital focal disorder detected in otherwise normal background activity. Antibiotics were given. A At 3 months, magnetic resonance angiography (MRA) confirmed the parieto-occipital, dural arteriovenous venous malformation of the superior sagittal sinus. B Cerebral angiography showed a dural arteriovenous shunt on the superior sagittal sinus. A small associated pial AVM was diagnosed draining into the SSS. C–E MRI shows the focal cerebral atrophy. F–G At the time of embolization of the dural arteriovenous shunt, an increase in the size of the pial parieto-occipital shunt vascular malformation was noted without parallel modification of the dural lesion. At 10 months, there was a slight statomotor developmental delay, possibly due to his environment. Physical examination showed facial venous circulation, especially under the right eyelid. At 15 months, the child had age-appropriate reactions and was in good general and nutritional condition; left-frontal and left-periorbital venous circulation had increased. H–K Follow-up MRI shows two de novo cavernomas, one in the brain stem and the other in the white matter below the enlarged pial shunt. Cerebral MRI of the mother revealed no AVM and no cavernoma

Scheme 2.21. Vascular malformation: target, timing, trigger

Scheme 2.22. Vascular malformation: target, timing, trigger (causative and revealing)

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These triggers may not be identifiable, but are likely to include mechanical, hormonal, pharmaceutical, hemodynamic, thermal, radiation, viral, infectious and metabolic triggers. The nature and timing of the revealing trigger (or triggers) and the nature and timing of the abnormally functioning endothelial cell (or cells) may result in the variety of AVMS that are now recognized (Table 2.1, Scheme 2.6). The developing central nervous system (CNS) is clearly more vulnerable than the mature one; if revealing triggers act during cell migration, myelinization or CSF physiology maturation, while the embryonic brain matures to a fetal one and then to a fully myelinated brain, or until the skull base has largely grown and sutures are fixed, the revealing trigger may affect the vascular target more severely (e.g.? widespread, multifocal). An AVM morphologically and clinically present early in life must have had a more severe initial abnormality to have been effectively triggered over such a short period of time. This suggests that most adult AV shunts are either not present in the child or, if a cellular dysfunction is present, it has not been triggered yet. Therefore, classifications of brain AVMs in fact describe different types of abnormalities that may reveal the underlying timing and/or nature of an initial event (Schemes 2.4, 2.20). For example, there are genetic „dysfunctions“ which lead to multiorgan, multifocal, polymorphic and inherited types of AV shunts: HHT disease, collagen disorders, NF1. An early dysfunction, when hox genes are operating and para-axial neural crest or mesodermic cell groups are still migrating and differentiating (see Chap. 6, this volume), may result later in CAMS, SAMS, or CVMS (Cobb-, Sturge-Weber- or Wyburn-Mason -type abnormalities). Macro-AVM, proliferative angiopathy, and micro-AVM are likely to result from an acquired nonreversible abnormal remodeling process. However, many multifocal AVMs encountered in children do not fall into any of the proposed categories, but rather express the overall cerebrovascular vulnerability to revealing triggers. The vulnerability of the vasculature actually changes throughout life from structural weakness to damaged function. The vessel wall considered then as an organ and not as a semi-passive wall can express a wide range of dysfunctions, many of which are repaired (Scheme 2.18). In our experience, two lesions mainly result from a prenatal revealing trigger. The first occurs at the end of the embryonic period and results in VGAM. The second occurs during the 4th–6th month and corresponds to DSM with AV shunts. Both revealing triggers are certainly different, although they still remain unknown.Although we recently discovered the presence of CAVFs in utero, this remains an exceptional occurrence and represents less then 1% of our total clinical CAVF/CAVM experience (see Chaps. 3, 5, 7, this volume). Some AV shunts may be the result of a remote abnormality (usually downstream and venous), and not the expression of an in situ abnormal cell function; such AV shunts are an upstream normal response to abnormal stress triggers. If the primary cause can be identified and corrected, this AV shunting will spontaneously regress. Unfortunately, in most cases the primary cause of such conditions is difficult to detect. The remote alteration of the vascular remodeling process can produce tertiary abnor-

104 2 Introduction and General Comments Regarding Pediatric Intracranial Arteriovenous Shunts

malities (nonmorphological, such as venous thrombosis and subsequent venous hypertension), which are often considered primary causes; thus the effect is mistaken for the cause and the disease history is read in reverse. Dural AV shunts probably belong to this type of process in which a remote anomaly engenders a proximal AV shunt. This response is potentially multifocal and (as yet) its actual location is unpredictable. It is possible that it develops in a region in which there is a locally increased sensitivity. The aim should be to treat the remote causal anomaly, if detectable, as well as the secondary irreversible undesirable effects. Some iatrogenic interference may actually exacerbate the situation rather than ameliorate it and may behave as a new trigger (therapeutic venous sinus occlusion). Venous approaches to dural AV shunts that achieve sinus occlusion can create new shunting zones away from the primary site. Some lesions result from both postulated processes, for example, the perinatally diagnosed CAVM and even VGAMs, which are triggered by the hemodynamic changes at birth. In this situation, these normal hemodynamic perinatal changes create natural stress triggers that reveal an underlying endothelial cell dysfunction. The neonatal AV shunt in turn engenders specific abnormal stress triggers on the rest of the vasculature; it then becomes a morphologically and eventually clinically detectable AVM. Some rare DSMs revealed at birth and triggered by the normal perinatal changes will continue growing and expressing additional associated lesions in an irrepressible fashion, rapidly leading to fatal outcome regardless of treatment (Fig. 2.13) (Mohamed et al. 2002). An acquired event (revealing trigger) might have the same consequences as the postulated congenital one described above, provided that it affects a target related to vascular remodeling for a certain length of time (extracellular matrix and cells). In these instances, the revealing triggers produce a lesion that mimics a congenital AVM. Vascular malformation is thus a very unsatisfactory term for the cerebral and even more so for the dural AV shunts found in the adult or pediatric populations. Unless we accept the concept of embryonic, fetal, postnatal, and acquired AV malformations, we should rather speak of pial or dural AV shunts. Finally, the AV lesions that most often develop during the embryonic period are VGAMs; some DSMs with secondary AV shunts develop during the fetal period. Nearly all the other intracranial AV lesions develop at the earliest during the perinatal period and most likely after infancy. Such remarks suggest that AVMs are in fact manifestations of various types of vascular failure of normal wall remodeling.

3 Vein of Galen Aneurysmal Malformation

3.1

Introduction 106

3.2 3.2.1 3.2.2

Historical Landmarks 107 Lesions 107 Clinical Aspects 107

3.3

Modern Concept of Vein of Galen Aneurysmal Malformation 109

3.4

Vein of Galen Aneurysmal Dilatation 112

3.5

Dural Arteriovenous Shunts with Aneurysmal Dilatation of the Vein of Galen 117

3.6

Vein of Galen Varix 117

3.7

Vein of Galen Aneurysmal Malformation 117

3.8

Natural History of Vein of Galen Aneurysmal Malformations 141

3.9

Cardiac Manifestations 143

3.10

Macrocrania and Hydrocephalus 152

3.11

Late Natural History of Vein of Galen Aneurysmal Malformation with Patent Sinuses 162

3.12

Dural Sinus Occlusion and Supratentorial Pial Congestion and Reflux 167

3.13 3.13.1

Dural Sinus Thrombosis and Infratentorial Pial Reflux 180 Spontaneous Thrombosis 184

3.14 3.14.1 3.14.2 3.14.2.1 3.14.2.2 3.14.3

Objectives and Methods of Treatment 191 General Remarks 191 Neonates 191 Reducing Oxygen Consumption 197 Improving Oxygen Delivery 197 Infants and Children 200

3.15 3.15.1 3.15.2 3.15.3 3.15.4 3.15.5

Technical Management 203 General Remarks 203 Follow-Up 205 Complications: Morbidity 210 Overall Mortality 220 Neurological Outcome by Age Group 221

3.16 3.16.1 3.16.2 3.16.3

Other Techniques 221 Surgery 221 Transvenous Treatment 223 Radiosurgery 224

106 3 Vein of Galen Aneurysmal Malformation

3.1 Introduction Over the past 10 years, written contributions on cerebral arteriovenous malformations (CAVMs) in children have evolved from anecdotal case reports to short series, offering a better understanding of the disease, the therapeutic strategies, and the results of various management strategies (Ventureyra and Herder 1987; Gerosa et al. 1981; Fong and Chan 1988; Hoffman et al. 1982; Johnston et al. 1987; Lasjaunias et al. 1995, 1996a; Maheut 1987; Mori et al. 1980; So 1978; Raimondi 1987; Seidenwurm et al. 1991). Historical contributions from the neurosurgical point of view have demonstrated limitations in the management of these difficult lesions and relinquished them to interventional neuroradiology. Generally speaking, a review of the literature pertaining to CAVM in the pediatric age group is difficult. The upper limit of the pediatric age group has varied between 15 and 20 years. Few reports have documented the management of AVMs that were not vein of Galen malformations in neonates and infants, or in antenatal series. To differentiate between cortical, deep, and infratentorial AVMs is technically of interest, but the topography is known to be the least important factor in the anticipated natural history (Berenstein 1983; Brown et al. 1988; Crawford et al. 1986; Ondra et al. 1990). Choroidal AVMs, which are rarely analyzed separately, are probably a distinct entity within the CAVMs (see Chap. 5, this volume). Most series are small and difficult to analyze since, for example, a distinction between vein of Galen aneurysmal malformation (VGAM) and CAVM is not always clearly made. Most recent reports no longer confuse VGAM and CAVM, but within the VGAM group, the vein of Galen aneurysmal dilatations (VGAD) (Lasjaunias et al. 1987b) and the true VGAMs are often not distinguished, particularly by those who still use Yasargil’s classification (Yasargil 1988). In large groups of nonoperated patients, information regarding outcome is often lacking. Partial surgical treatment with feeder ligation, while not promoted as such, is often performed. This type of intervention differs from partial embolization with bucrylate, and therefore comparing the two treatment strategies and their results is of little interest. Many of the cases included in the surgical series as children are in fact operated on in adulthood. Evidence of anatomic obliteration and clinical status is often difficult to assess, since few follow-up angiograms have been done and neurocognitive testing has rarely been carried out or reported. Patient selection has been insufficiently documented, and the associated management mortality varies from 0% to 35%, depending upon the aggressiveness of a given team in desperate situations. Technical morbidity/mortality is not distinguished from expected morbidity/mortality despite attempted treatment. This lack of precision tends to promote unnecessary hazardous procedures in potentially nonfatal situations. The same comments apply to reports of series of endovascular VGAM treatment that have appeared in the literature. While emphasizing mainly technical solutions, they often have failed to provide satisfactory mid-term results (Ciricillo et al. 1990; Dowd et al. 1990; King et al. 1989; Mickle and Quisling 1986). Mental retardation in these young children,

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107

while often present, is seldom mentioned or tested. Unnecessary premature interventions have also interfered with the quality of the results. To degrade the therapeutic challenge to a strictly morphological goal ignores fundamental aspects of neonatal and infant anatomy and fluid physiology (Andeweg 1989; Girard et al. 1994; Zerah et al. 1992). In fact, in certain reports anatomic exclusion of lesions is counted as technical success even if the child died shortly after treatment.

3.2 Historical Landmarks 3.2.1 Lesions

The first description of a possible VGM occurred in 1895 (Steinhel, cited by Dandy 1928); it was actually a CAVM of the diencephalon draining into a dilated vein of Galen. Today it would be described as a false vein of Galen malformation (Berenstein 1992a; Lasjaunias et al. 1987b). The first therapeutic attempts were recorded at the beginning of this century describing an infant who presented with intracranial hypertension and subsequently underwent bilateral internal carotid ligation. In 1946, Jeager reported bilateral arteriovenous (AV) communications draining into an aneurysmally dilated vein of Galen, and in 1949 Boldrey and Miller treated two similar patients with arterial ligation. Only the last case seems to correspond to a VGAM. Most authors have subsequently used the same generic name, VGAM, for very different entities. Failure to recognize the true nature of the lesion resulted in imprecise anatomic and natural history descriptions (Agee et al. 1969; Amacher et al. 1979; Gold 1946; Gold et al. 1964; Grossman et al. 1984; Horowitz et al. 1994; Martelli et al. 1980; Merland et al. 1987; Norman and Becker 1974; Stehbens et al. 1973; Watson et al. 1976; Yasargil et al. 1976). In fact, Litvak et al. in 1960, Raimondi in 1972, Clarisse et al. in 1978, and Diebler et al. in 1981 already suggested the possible existence of true and false vein of Galen malformations. Subsequent surgical series (Agee et al. 1969; Amacher and Shillito 1973; French and Peyton 1954; Gibson et al. 1959; Hoffman et al. 1982; Johnston et al. 1987; Massey et al. 1982; Menezes et al. 1981; Mickle and Quisling 1986, Mickle and Peters 1993; Raimondi 1987; Smith and Donat 1973) and endovascular series (Casasco et al. 1991; Ciricillo et al. 1990; Dowd et al. 1990; Mickle and Quisling 1986; Reichman et al. 1993) attempted to deal with this rare, and still poorly understood disease entity, often emphasizing the technical challenge related to the treatment, but failed to grasp the real nature of the disease.

3.2.2 Clinical Aspects

The link between the lesion and cardiac failure in neonates was noted by Pollock and Laslett in 1958, Claireaux and Newman in 1960, and Glatt and Rowe in 1960. Since that time, the relationship between intracranial AV lesions and, for instance, hydrodynamic disorders with ventricular enlargement, facial venous collateral circulation in infants, and epistaxis has been accepted. In 1964 in a review of 34 patients, Gold described three

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consecutive clinical stages: neonates with cardiac insufficiency, infants and young children with hydrocephaly and convulsions, and older children or adults with headaches and subarachnoid hemorrhage. In 1978, Amacher (1973) added a fourth group, which included neonates and infants with macrocephaly and minimal cardiac symptoms. Knudson and Alden (1979) reviewed all cases of cardiac failure secondary to AV shunt and noted that 64% were caused by VGAM. In fact, these contributions were inadvertently combining clinical sequelae created by both the natural evolution of the disease and their post-therapeutic modifications. In his excellent review, Johnston et al. (1987) exhaustively analyzed the clinical presentations of VGAM. In 82 infants, he found the following symptoms: CSF disorders, 70%; neurological deficits, 31%; and neurocognitive delay, 12%. In children 1–5 years of age, these symptoms occurred in 61%, 33%, and 5%, respectively. For comparison, in our series of neonates and infants in the same age group, more than 50% had neurocognitive delay and almost none had neurological manifestations unless they had been previously shunted. This apparent discrepancy in the clinical profile of our material emphasizes the variability in the way symptoms have been documented and interpreted by various specialists.We will, therefore, not use this type of approach in the analysis of the natural history. We favor the understanding of the various disease processes rather than the knowledge of the anticipated frequency of their occurrence.

Table 3.1. VGAM patients referred to Bicêtre per age group each year (1981–2002)

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The potential for prenatal diagnosis of VGAM has already been documented using noninvasive tools such as ultrasound, including color flow Doppler and magnetic resonance imaging (MRI) (Abbitt et al. 1990; Cubberlay et al. 1982; Heibel et al. 1993; Martinez-Lage et al. 1993; Saliba et al. 1987a; Sivakoff and Nouri 1982; Stockberger et al. 1993). From October 1984 to October 2002, 317 children with VGAM were studied in Bicêtre Hospital (Table 3.1). We consider this group of patients to be homogeneous, since the neuroradiological assessment, the technical principles involved, and the perioperative clinical management have been similar over the past 20 years and were carried out by the same group of physicians. The following observations were derived from this experience.

3.3 Modern Concept of Vein of Galen Aneurysmal Malformation Raybaud et al. (1989) was the first to recognize that the ectatic vein in VGAM was actually the median vein of the prosencephalon, the embryonic precursor of the vein of Galen itself. This was based on the choroidal nature of the arterial vascularization of this malformation (Figs. 3.1–3.3). A complete pathology specimen of a neonatal case of VGAM was carefully analyzed and illustrated by Landrieu in the late 1980 s (Fig. 3.4). We assessed the dural sinus abnormalities (Lasjaunias et al. 1987b) and persistent alternative embryonic routes of the deep venous drainage associated with this condition (Lasjaunias 1991). From then on, the vein of Galen malformation was recognized as an embryonic vascular malformation (as the timing for the causative trigger). It is a choroidal AV malformation (as a target for that causative trigger) (Fig. 3.4).

Fig. 3.1. Arterial supply to vein of Galen aneurysmal malformation (VGAM). All the various choroidal and subependymal arteries are represented. 1, Posterior callosal artery; 2, anterior choroidal artery; 3, posterolateral choroidal artery; 4, posteromedial choroidal artery; 5, circumferential artery (tectal) 6, subependymal artery; 7, hypothalamo-subependymal artery; 8, thalamostriate and subependymal artery

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Fig. 3.2A–D. Embryology of vein of Galen aneurysmal malformation (VGAM). View from above. A The vein primarily drains the choroidal afferents and secondarily collects the lenticulostriate afferents. B The final disposition of the normal vein of Galen is that of the deep venous confluent opening into the straight sinus. C In some instances, the median vein of the prosencephalon persists and bulges because of an arteriovenous shunt. The choroidal vein (single arrow) and thalamostriate vein (double arrow) then drain separately. D Very occasionally, the median vein of the prosencephalon retains its choroidal vein drainage, while the lenticulostriate venous system still opens in a separate fashion; in this instance, anastomoses may open with time with the inferior striate veins

Fig. 3.3. View from above of the choroidal fissure showing the triangular shape of the nidus in choroidal type of vein of Galen aneurysmal malformation (VGAM) (single arrow). The dilated median vein of the prosencephalon is seen posterior to the base of triangular shaped nidus (double arrow)

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Fig. 3.4A–D. Legend see p. 112

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Fig. 3.4A–D. Neonatal specimen showing the choroidal type of VGAM opening into the median vein of the prosencephalon and secondarily into a falcine sinus. Postmortem study was obtained (courtesy of Prof. Landrieu). The general pathology showed no extracranial malformation. Neuropathological examination at autopsy showed that the cranium was unusually thick and the fontanelles appeared ossified. The brain weight was 220 g after fixation. There was a diffuse, symmetric atrophy of the cerebral mantle, and the ventricles were markedly dilated. The ependyma was thickened with the formation of numerous ependymal rosettes and astrocytic proliferation. The destruction of the cerebral mantle was either complete or characterized by a multicystic degeneration of the cortical zone invaded by macrophages. In the residual cortex, white matter, central grey nuclei, and subependymal zones, there were multiple malacic lesions from various ages and types: recent hemorrhagic infarcts; calcium deposits and incrustation of cellular process; nets of glial spumous cells; and pseudo-crystalline lipidic deposits. The periphery of these malacic lesions was frequently underlined by a slight astrocytic reaction. Diffuse subpial hemorrhagic necrosis and congestion of the subarachnoid vessels were prominent in the occipitotemporal areas, but vascular dilatation was also present, to a lesser extent, in all subarachnoid and parenchymal areas. The brain stem appeared malacic and edematous, without cavitation or glial reaction. The cerebellum was largely preserved, but focal depopulation of Purkinje cells and neurons of dentate nuclei is noticeable. The mesencephalic aqueduct appeared permeable, but could not be precisely measured. The vascular malformation was situated in the tectal area, in close connection with the posterior part of the circle of Willis. This malformation consisted of a large, entirely extracerebral cluster of intermingled vessels, closely associated with formations of mature choroid plexus. The small vessels displayed very irregular walls forming valvule-like folds, the media and the intima showing considerable variations in thickness. There was an internal elastic membrane showing sharp interruptions in those areas in which the dysplastic vessels shunt together or make shunts with venous-like branchs ending in the dilated Galen vein. The vascular cluster was nourished, through large shunts, by many arterial branches coming from the circle of Willis, especially from choroidal arteries. These nourishing arteries also appeared dysplasic with irregular walls. The dilated vein of Galen, 30 mm at its maximum diameter, was situated posterior to the bulk of the vascular malformation. Its wall, 500 mm thick, was made of a thin intima and of thick fibrous adventice. Many vascular fistulas appeared at the opening of the ampulla, in the lateral and anterior walls, measuring 200–500 mm. The dilated vein opened posteriorly into a patent falcorial sinus of normal histological structure. Comments: (A) the vascular malformation is entirely extracerebral, appears as a dysplastic process affecting the arteriovenous differentiation of the small choroidal vessels, resulting in the formation of numerous shunts, each of variable importance; (B) the hemodynamic and/or hydrodynamic consequences are largely prenatal, as shown by the pathology of the cerebral lesions

3.4 Vein of Galen Aneurysmal Dilatation Vein of Galen aneurysmal dilatations (VGADs) (Figs. 3.5–3.7) belong to the group of cerebral AVMs (CAVMs) draining into the deep venous system with an acquired ectatic dilatation of the vein of Galen confluence due to either stenosis at the venodural junction or thrombosis of the straight sinus. The dilated vein in this instance is the vein of Galen (great cerebral vein): it drains the AVM as well as normal brain tissue. The presence of reflux into the normal cerebral venous tributaries that open into the venous pouch indicates and confirms the presence of a matured Galenic confluent, the diagnosis of VGAD, and definitively excludes the

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Fig. 3.5. A Typical appearance of vein of VGAM with the choroidal supply to the dilated median vein of the prosencephalon. B Typical appearance of the choroidal supply to a choroidal arteriovenous malformation (AVM) associated with a dilated vein of Galen and reflux in the deep vein of the brain following straight sinus thrombosis

diagnosis of VGAM (Fig. 3.8). The evidence of primary opening of the shunt in a nonchoroidal vein, even without reflux, confirms the diagnosis of VAGD. In neonates and infants, the occurrence of VGAD is infrequent. However, 10 years ago 20% of children referred with the diagnosis of VGAM were actually VGAD patients. Today this confusion is much less frequent. VGADs are encountered in older children, corresponding in most cases to a deep-seated CAVM; they may show all the symptoms associated with this location and type of lesion. Tectal CAVM locations are those most closely resembling VGAMs; however, the transmesencephalic arteries will be seen at the time of angiography to be projecting below the P2 segment of the posterior cerebral artery, on the lateral projection of the vertebral injection and easily seen on axial MRI sections.

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Fig. 3.6A, B. False VGAM diagnosed at the age of 6 months in a young boy presenting with a macrocrania. C Note the cingulate gyrus AVM draining into a posterior callosal vein and into a large vein of Galen

Subependymal arteries can be seen in VGAD in certain choroid plexus AVMs. Thalamoperforating arteries are also seen in VGADs of thalamic AVM origin. Proper analysis of the venous anatomy and clinical correlations will always enable one to differentiate the type of malformation involved. Characteristic symptoms are progressive neurological deficits associated with the mass effect and/or retrograde venous congestion, and hemorrhage of venous origin, either thalamic or subependymal. Epilepsy and other cortical manifestations are rare. Although theoreti-

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Fig. 3.7A–D. Typical aspect of a vein of Galen dilatation in a 2-year-old boy; note the opening of the left basal vein into the matured and dilated vein of Galen

cally possible, cardiac and hydrodynamic disorders are also rare. It is interesting to note that VGADs develop postnatally (no melting-brain syndrome despite pial veins reflux, no mental retardation, no jugular bulb dysmaturation), and lesions have usually already been present for a long time by the time they are diagnosed (acquired venous thrombosis, venous ectasia). Analysis of high-flow angiopathy changes in such patients will help in deciding on the best treatment strategy and its timing.

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Fig. 3.8A–D. Typical aspect of a vein of Galen dilatation in a 10-year-old boy; note in addition to the opening of the right basal vein into the matured and dilated vein of Galen, the cerebral venous congestion of both supra- and infratentorial spaces

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3.5 Dural Arteriovenous Shunts with Aneurysmal Dilatation of the Vein of Galen Dural AV shunts (DAVSs) with aneurysmal dilatation of the vein of Galen were described in children by Fournier et al. in 1991; vein of Galen aneurysmal dilatation (VGAD) was secondary to a vermian AVM with dilatation of the Galen vein (thrombosis of the straight sinus). In a 2-year-old boy presenting with intraventricular hemorrhage, computed tomography (CT) and angiography demonstrated a small vermian cerebellar AVM with reflux in the Galen vein afferents. A mild macrocrania had been noted at 3 months but was not further investigated, and the child was shunted (ventricular-peritoneal). Following embolization of the AVM and subsequent surgical removal of the remainder of the lesion, a 6-month follow-up angiogram demonstrated a dural shunt remote from the surgical field. The AV shunts were located within the wall of the previously dilated Galen vein. Feeders corresponded to vasa vasorum of the normal Galen vein, thus contributing to a nidus type of network extending from the venous wall into the intraluminal clot partially filling the ectatic lumen. These lesions are usually seen in adults and probably reflect the longstanding presence of triggering factors and secondary changes before they become clinically evident (see Vol. 2).

3.6 Vein of Galen Varix Vein of Galen varices constitute a group of dilatations of the vein without the presence of an AV shunt. Two types have been encountered in children. The first are transient dilatations of the Galen vein in neonates presenting with cardiac failure of another origin. This dilatation persists for a few days after birth and then disappears on follow-up ultrasound studies. The dilatation does not lead to any symptoms and the disappearance parallels the cardiovascular improvement. The second type of vein of Galen varix occurs when hemispheric venous drainage of the brain converges toward the deep venous system. This condition does not always correspond to a postthrombotic collateral circulation, but sometimes to an obvious anomalous disposition of the overall venous system (complex DVA). It will not give any specific symptoms, but the lack of compliance of this type of venous drainage system over time may create venous insufficiency manifestations.

3.7 Vein of Galen Aneurysmal Malformation It is possible to distinguish the angioarchitectural differences between an AVM involving the vein of Galen forerunner, which we call VGAM, and an AVM with venous drainage into a dilated, but already formed vein of Galen, which will be called VGAD (Lasjaunias 1987b). The VGAM involves the choroidal fissure and extends from the interventricular foramen rostrally to the atrium laterally (Fig. 3.3).

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Fig. 3.9. Schematic representation of VGAM illustrating in particular the choroidal supply as well as the limbic arterial arch. The subependymal and lamina terminalis supplies are not represented. (Courtesy of J. Bhattacharya)

The arterial supply usually involves all the choroidal arteries (Figs. 3.9, 3.10,), including subfornical and anterior choroidal contributions (Figs. 3.11, 3.12); it may also receive a significant contribution from the subependymal network originating from the posterior circle of Willis. These arteries should be differentiated from transmesencephalic arteries (their involvement, in fact, would exclude the diagnosis of VGAM and indicate a tectal location of the AVM). The subependymal arteries pierce the floor of the third ventricle and run subependymal to join the choroid fissure, where they contribute to the opacification of the lesion. Very rarely are thalamoperforating arteries recruited, and this occurrence is grossly overestimated in the literature (Fig. 3.11). Subependymal and transcerebral contributions appear accessory in the supply to the shunt, possibly created by the sump effect of the venous drainage. Their contribution can sometimes be used for an endovascular approach (Fig. 3.13), but they usually disappear following the proper occlusion of the most prominent shunts (see Fig. 3.14). The persistent limbic arterial arch (see Vol. 1, Chap. 6), which bridges the cortical branch of the anterior choroidal artery initially (Fig. 3.15) and the posterior cerebral artery (Fig. 3.16) secondarily with the pericallosal artery, is seen in nearly half of neonatal cases. It should be distinguished from subcallosal and subfornical supply to the choroidal shunts (Fig. 3.17). Its presence should be anticipated at the time of embolization into a lateral choroidal artery when it arises far distally along the posterior cerebral main stem. The limbic arterial arch on each side can anastomose and may even fuse on the midline in the supracallosal region (Figs. 3.18, 3.19). The circle(s) regress (mature) after obliteration of the VGAM by means of embolization (Fig. 3.17), leaving behind various anatomical dispositions where the posterior cerebral artery (PCA) supplies the ipsilateral or contralateral para central gyrus (Figs. 3.18, 3.19). Cerebellar arteries do not contribute to the supply of the VGAM, except

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Fig. 3.10A–C. Legend see p. 120

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Fig. 3.10A–E. Female neonates presenting with moderate cardiac overload. A, B Because of the MRI appearance with enlarged arteries within the capsular region, the diagnosis of vein of Galen was questioned. Angiography was performed (C), showing a significant intraparenchymal angiectasia joining the choroid fissure on the right side. Note supply to an arteriovenous fistula at the interventricular foramen. D, E angiographie and MRI demonstration of the subependymal artery in a retromammilar position

indirectly through their dural branches, which can be enlarged, as they may participate in the supply to the vasa vasorum at the venodural junction. Other dural contributions can be seen in true VGAM and may be located at a distance from the choroid fissure shunting zone. They often represent secondary dural AV shunts after sinus thrombosis (usually sigmoid; Fig. 3.53) or AV dural communications caused by the sump effect from an otherwise patent sinus [usually the superior sagittal sinus (SSS)]. In three premature babies who presented with severe cardiac failure, we encountered a rare arterial aspect resembling a moyamoya network (Fig. 3.20). In all three patients, the damage to the cerebral tissue appeared irreversible and the babies died during the next 48 h. This condition was the only one to resemble an early high-flow angiopathy type of response of the remaining vasculature to the shunt. Some rare stenoses are seen along the course of large choroidal feeders to mural types of VGAM (see below; see Fig. 3.56). Since they are located at the edge of the tentorium cerebelli, they are likely to express the mechanical effects of the ectasia by the stiff dural margin on the enlarged feeders. We suspect that a further slight increase in this pressure phenomenon (by ventricle enlargement) might lead to occlusion of the artery involved. Subsequent spontaneous thrombosis of the VGAM will occur if the number of compressed feeders to the lesion is limited, as in a mural type of VGAM.

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Fig. 3.11A–D. A 2-month-old girl presenting with cardiac overload equilibrated with medical treatment as well as macrocrania and already moderate ventricular dilatation. She presented with a generalized seizure and a mild motor deficit. When we saw her at 6 months of age, there was already a delay in neurological acquisitions. A, B Angiography and C, D MRI demonstrates an explosive transhemispheric network of vessels reaching the choroid fissure and opening into the vein of Galen malformation

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Fig. 3.12A, B. Two different VGAMs with an interventricular foramen arteriovenous fistula, associated with a more posteriorly located usual VGAM in a choroidal form

The nidus of the lesion is usually located in the midline and therefore receives a bilateral and symmetrical supply (Fig. 3.17). In certain instances, one side may be more prominent, and this will cause the dilated pouch to be shifted by the force of the jet of the fistula away from the prominent supply toward the opposite side (see Fig. 3.42). In general terms, two types of angioarchitecture are encountered: choroidal and mural. The former corresponds to a very primitive condition, with the contribution of all the choroidal arteries and an interposed network before opening into the large venous pouch (see Figs. 3.12, 3.16). This condition is encountered in most neonates with low clinical scores (see Sect. 3.8). The latter corresponds to direct AV fistulas within the wall of the median vein of the prosencephalon (see Figs. 3.17, 3.39). These fistulas can be single or (more often) multiple and either converge into a single venous chamber or into multiple venous lobulations located along the anterior aspect of the pouch or along the afferent choroidal veins of the fissure (Fig. 3.11). This mural form is often better tolerated and encountered in infants who do not develop cardiac symptoms and who have a better disease tolerance and feature higher clinical scores. Intermediate forms can occur, but their identification does not assist in the understanding of the disease, and they are only interesting from a technical and management point of view. So far, we have not seen a true VGAM associated with another type of AVM.

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Fig. 3.13A–F. Legend see p. 124

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Fig. 3.13A–G. A 3-year-old boy presented macrocrania at the age of 4 months. MRI (A, B), 3D angiography in superior (C) and lateral (D, E) views, demonstrating the recurrent artery from the ACA-A1 segment supply an interventricular foramen AV shunt associated with a choroidal VGAM (E). F, G MR follow-up following embolization of the Heubner as well as choroidal contributors to the lesions

Since the choroidal veins are the embryonic tributaries of the median vein, potentially fistulous communications can be located at some distance from the pouch (Figs. 3.10, 3.13). They usually occur at the level of the interventricular foramen, where they can recruit a specific perforating branch (Fig. 3.13) from the anterior communicating artery or the Heubner artery. Some multifocal AVSs can associate mural communications with an additional shunting zone at the rostral end of the choroid fissure (Fig. 3.10). In this case, a choroidal venous segment is seen prior to its opening into the ectatic vein. The venous drainage of the VGAM is, by definition, toward the dilated median vein of the prosencephalon, forerunner of the Galen vein, and no communication exists with the deep venous system of the brain nuclei. In VGAM patients, thalamostriate veins open into the posterior and inferior thalamic (diencephalic) veins, as occurs normally during the 3rd month in utero (Figs. 3.21, 3.22). They secondarily join the anterior confluence, a subtemporal vein, or (more often) the lateral mesencephalic vein to open into the superior petrosal sinus, demonstrating a typical epsilon shape on the lateral angiogram (see Figs. 3.23, 3.24). In older children, the choroidal veins opening into the VGAM may become visible; if restriction in the skull base outlet has occurred (see Fig. 3.25) subependymal-striate anastomoses may open and become visible on the venous phase of vertebral angiograms. These can be the cause of intraventricular hemorrhages following transvenous approaches. The remainder of the venous drainage is variable, with the straight sinus being absent in almost all cases. Falcine dural channel(s) drain the pouch toward the posterior third of the superior sagittal sinus, which also happens to be where granulations are expected to appear first (see Chap. 2, this volume). In most cases, restrictions at the venodural

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Fig. 3.14. A A 26-year-old woman with more than 20% mental retardation and right-sided hemiparesis showing VGAM revealed at the age of 5 months. Note the subependymal contribution to the anteriorly located shunting zone to the ectatic vein. B Immediately following embolization, there was still flow inside the lesion. C After spontaneous secondary thrombosis, the subependymal supply, although not embolized, regressed spontaneously

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Fig. 3.15. Typical limbic circle of the archaic type: anterior choroidal to anterior cerebral artery in a young girl presenting with a VGAM diagnosed in infancy with mild macrocrania

Fig. 3.16A, B. Three-dimensional aspect of a persistent limbic arch. A Lateral and slightly anterior oblique view. B Medial and slightly anterior oblique view. Note the choroidal and subependymal feeders

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Fig. 3.17. A,B Legend see p. 128

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Fig. 3.17. A An infant girl presented with macrocrania at the age of 6 months leading to the diagnosis of a large VGAM. She was referred at the age of 8 months. There is a posterior cerebral to anterior cerebral limbic system with a midline fusion phenomenon of the anterior cerebral artery. B Following embolization of the main feeders and despite persistence of minimal shunt at the end of the second embolization, spontaneous thrombosis occurred concomitantly with (C) the maturation of the limbic circle and shrinkage of the mass

junction or in the falx create upstream and downstream turbulence and significant dilatations (Fig. 3.25). Other embryonic sinuses persist, such as the occipital and marginal sinuses (Fig. 3.26), particularly in neonates. The appearance of the remainder of the venous system is difficult to predict, even though all cerebral veins converge at birth toward the posterior sinuses. A few months after birth, the cavernous sinus matures and is able to „capture“ the sylvian veins, offering the brain a potential drainage through the orbit, pterygoid plexus, or inferior petrosal sinus (Fig. 3.27). Drainage of the cerebral veins into unusual transcranial channels may take place, apparently without significant functional implications (Figs. 3.28, 3.29). The plasticity of the venous system in these instances is remarkable. Although the anatomic framework is exact and predictable, it is crucial to remember that it changes with spontaneous modification of the hemodynamics, the influence on growth and maturation induced by the disease and, eventually, the treatment undertaken. The timing of interference with this anatomic maturation continuum is as important as the extent of the corrections proposed. At this age, it is more important to restore normal growth conditions than a normal appearance, which is often the therapeutic goal in adults. Other midline malformations (clefts, sinus pericranii, coarctation) have been noted in some rare cases, although they rarely correspond to existing or potential syndromes (Fig. 3.30).

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Fig. 3.18. A, B Persisting limbic arch immediately after embolization. C–F Unilateral remodeling of the supply to the paracentral gyrus after completion of the VGAM occlusion

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Fig. 3.19A–F. A 13-year-old boy presented at the age of 5 years with macrocrania. Subcallosal anastomosis between right and left posterior cerebral arteries (PCAs) (A, B) is likely to correspond to an asymmetrical maturation of the limbic circle. Note the right A1 agenesis (C), and P2 on the left (D). Bilateral distribution of the left anterior cerebral artery (ACA) (E, F). These features point to the capacity of midline fusion in the limbic system as well as ACA remnants

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Fig. 3.20A–C. Premature girl presented with cardiac failure immediately after birth. Stabilization was obtained with medical treatment. At the age of 2 months, A MRI and B, C angiography were performed because of the failure to thrive and abnormal neurological findings. A focal infarct was noted on MRI corresponding to arterial occlusive disease associated with VGAM. This neonatal moyamoya-like condition is a contraindication for treatment when noted, as it adds arterial depravation to venous ischemic congestion

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Fig. 3.21A–D. Schematic representation of different types of deep venous drainage. A Usual disposition, B epsilon aspect noted in VGAM, C medial parietal opening of the internal cerebral vein, D associated transosseous drainage in the orbital region (see Fig. 3.29). (Courtesy of J. Bhattacharya)

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Fig. 3.22A, B. Typical venous pattern of the cerebral drainage in a previously embolized VGAM. Note the cortical anastomosis between the frontal and sylvian veins and the epsilon-shaped deep venous system bilaterally. B Incomplete capture of the sylvian vein on the left side and A its almost complete opening on the right side. Note also the superior and inferior petrosal sinuses that are clearly demonstrated on both sides

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Fig. 3.23A–C. Late venous phase of the carotid (A) and vertebral angiogram (B), 3D angiographic aspect (C). Epsilon-shaped deep venous drainage into the superior petrosal sinus via the lateral mesencephalic vein

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Fig. 3.24A–C. Typical aspect of the epsilon-shaped venous return in a 13-year-old patient with a completely excluded VGAM. Note the bilateral drainage of the supratentorial collectors into the lateral mesencephalic vein and petrous vein infratentorially. Occlusion of the right sigmoid sinus promoted the transcortical drainage into the deep venous system

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Fig. 3.25. A VGAM with bilateral sigmoid sinus occlusion secondary to jugular bulb dysmaturation. All possible supra- and infratentorial anastomotic channels are recruited to provide drainage. Subependymal anastomoses create a nidus-like network in the vicinity of the VGAM itself. B, C Oblique posterior and superior 3D views of the venous drainage

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Fig. 3.26A–E. A 12-month-old child presenting a VGAM with already existing venous outlet restrictions and reflux in sinuses and subependymal veins (A, B). C One year after partial embolization, although the child was normal, there was an increase in the pial reflux. D At short-term follow-up, there was spontaneous occlusion of the falcine outlets requiring rapid completion of the exclusion of the remaining shunts (E)

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Fig. 3.27. A A 6-year-old boy with choroidal VGAM diagnosed 1 year before with prominent facial veins and moderate macrocrania without neurological symptoms or retardation. B On the MRI, note the stigmata and the chronic venous sinus congestion, which over time created subependymal anastomoses. C, D The angiographic study demonstrates the subependymal inferior striate vein opening and its secondary opening into the cavernous sinus

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Fig. 3.28A, B. VGAM with restricted outlet and transcranial opening in the subgaleal veins

Fig. 3.29A–F. A 20-month-old boy presenting a supraorbital varix and a choroidal VGAM (A, B). C Bone X-rays suggested sinus pericranii confirmed on the venous phase of carotid angiography with basal and lateral views on venous 3D angiography (D–F). C–F see p. 140

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Fig. 3.29C–F. Legend see p. 139

Natural History of Vein of Galen Aneurysmal Malformations

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Fig. 3.30. Infant boys presenting with VGAM and maxillofacial midline disorders: A cleft palate; B tip-of-the-nose hemangioma

3.8 Natural History of Vein of Galen Aneurysmal Malformations Similar to other types of vein of Galen AV lesions, VGAMs are not hereditary. In our series, two cousins presented with vein of Galen-type AV shunts diagnosed at neonatal and infant age, but upon analysis they did not seem to represent true VGAMs. Neither in our series of children with hereditary hemorrhagic telangiectasia (HHT) disorder, nor in the group of adult patients with cerebral localizations of HHT was there a VGAM present. Boynton and Morgan (1973) reported a case of a neonate with a rapidly lethal vein of Galen AVM fed by posterior, anterior, and middle cerebral arteries and a family history of HHT. In 1987, Salazar reported a similar case, but from the description in both cases we doubt that the AVM was a true VGAM. Despite the male dominance in this type of AVM (it is the only arteriovenous malformation with a sex dominance), there is presently no convincing evidence to suggest a hereditary genetic influence on the development of VGAM (Scheme 3.1A). The natural history of VGAM is unclear from what is documented in the literature. In particular, since many classic descriptions were not actually VGAMs but were descriptions of VGADs, much of the so-called natural history of the surviving children was learned from babies who had undergone shunting procedures. The need for emergency treatment in many patients certainly represented an acceptable explanation for the delay in appreciating the associated negative effects of ventricular drainage on the neurological progression in these children. In particular, the onset of seizures traditionally described in the late phase of VGAMs reflects this progressions in babies who had been shunted. Most neurological symptoms and hemorrhages reported in the literature are in mistakenly diagnosed VGAMs or are the result of changes in angioarchitecture, which in turn alter the consequences of the initial lesion. All these

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3 Vein of Galen Aneurysmal Malformation

Scheme 3.1A. Natural history of vein of Galen aneurysmal malformations

phases are predictable, and most prodromes are recognizable; early management does not necessarily mean emergency interventions. Finally, endovascular management of this population has given us a chance to observe the anatomic and clinical progression in nonsurgical circumstances. Several papers (Andeweg 1989; Del Bigio et al. 1985; Girard et al. 1992; Larroche 1977a; Le Gros Clark 1920; Quisling and Mickle 1989; Saliba et al. 1987b; Schroth and Klose 1992a; Seidenwurm et al. 1991; Weed 1923) provide crucial insights into the physiology and vasculature of the prenatal brain. They serve as a basis for us to better understand the original material that we were able to collect (Garcia-Monaco et al. 1991b; Girard et al. 1994; Lasjaunias et al. 1991b, 1995; Rodesch et al. 1994; Zerah et al. 1992) and to improve our interpretation of the literature. We have chosen a diagrammatic presentation of the natural history of VGAM to highlight the path followed by each individual case. Thus, once previous stages have been identified, the subsequent ones can be more easily anticipated. The therapeutic window outlines the optimal moment for the endovascular approach. this has become the objective of our decision as to therapeutic timing and points to the treatment and clinical goals to be targeted. We will concentrate only on the clinical aspect in this section and will consider the technical management and global results later. The reader is referred to Chap. 2 to gain a broader prospective with regard to the diagnostic challenge in the different age groups.

Cardiac Manifestations

143

3.9 Cardiac Manifestations Cardiac manifestations were reviewed for neonates (Garcia Monaco 1991b) and have been prenatally diagnosed in VGAMs (Rodesch et al. 1994). In contrast to the cardiac failure observed in large hemangiomas, where they occur in infancy at the proliferative stage of the disease, the congestive cardiac failure (CCF) in VGAMs can be present during the neonatal period (see Chap. 11, this volume) (Scheme 3.1B). In his series of 18 antenatally diagnosed VGAM patients, Rodesch noted that 17 were born with cardiac failure and only one without. During prenatal ultrasound examination, some cardiac enlargement was noted in four out of 17 patients. In all four of the patients in which this finding was demonstrated, the neonatal score was low (95th percentiles) VGAM diagnosis (days of life) CCF diagnosis (days of life) MV onset (days of life) Bicêtre PICU admission (days of life) Inotropic drugs use Endovascular treatment Yes First session (days) Neurological outcome Developmental delay Epilepsy

All 24

Death 12

Survival 12

P

37.5 40 (36–42.7) 75th 50% 2.5 (0–15) 1.5 (0–14) 3 (0–19) 12 (0–25) 54%

42 40 (36.7–41) 75th 50% 1.5 (0–15) 2 (0–14) 2.5 (1–19) 12 (2–22) 100%

33.3 39 (36–42.7) 75th 50% 3 (0–8) 1 (0–5) 3 (0–17) 11.5 (0–25) 8.3%

1 0.58 1 1 0.1 0.2 0.47 0.56