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Pediatric Neuro-

Second Edition Michael C. Brodsky

Pediatric Neuro-Ophthalmology

Second Edition Michael C. Brodsky, M.D. Professor of Ophthalmology and Neurology Mayo Clinic Rochester, Minnesota USA

ISBN 978-0-387-69066-7 e-ISBN 978-0-387-69069-8 DOI 10.1007/978-0-387-69069-8 Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2010922363

© Springer Science+Business Media, LLC 2010 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connec-tion with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not ­identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with re-spect to the material contained herein.

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com) To the good angels in my life, past and present, who lifted me on their wings and carried me through the storms. Foreword

The first edition ofPediatric Neuro-Ophthalmology, published in 1995, filled an important gap in the disciplines of pediatric ophthalmology, neuro-ophthalmology, and pediatric neurology. It was written in a clear and concise style, which made the volume valuable to the general ophthalmologist seeing children and the pediatric specialists. The book’s large audience, com- bined with its readability and inclusive contents, combined to make Pediatric Neuro- Ophthalmology such a success in its genre. Almost 15 years have elapsed since the initial publication, and the growth of the body of knowledge of the developing , sensory and motor, as well as the diseases associ- ated with that sweeping cascade of events, is little short of astonishing. Hence, the need at this juncture for a revised second edition. This new edition is by no means a cursory glance back- ward at the published literature, as so many second editions of large, multi-authored books can be, but, rather, an in depth, concentrated and critical look at publications since. The author has fitted in the new pieces to update the text, photographs, and references where indicated. This new edition broadens our understanding not only on a phenomenological level but also by add- ing molecular and genetic mechanisms, insights from population genetics, epidemiology, and advances in other fields far from its domain it burnishes the insight and understanding of the reader. Pediatric Neuro-Ophthalmology very much bear the unique touch of its author. A glance at chapter one, “The Apparently Blind Infant,” will clarify what I mean. The chapter is nearly twice as long, with greatly expanded references. Most importantly, this growth is packed with important new insights without slighting the older but still valid and important observations from the past. For example, the discovery of melanopsin, a bistable visual protein found not in rods or cones but in ganglion cells of the , is now known to contribute to our normal pupillary reaction to light. Its probable role in the peculiar paradoxical constriction to darkness is both noted and the connection made to congenital stationary night blindness and achro- matopsia, along with other visual system conditions where anomalies are found. These are the types of insights that make this book a delight for the novice as well as for the clinician experienced in the field. In closing, I can but reprise my words from the first edition. “I see it as my responsibility to put this work in perspective for the reader- to-be”—be he novice or specialist, he or she will be rewarded with a truly unique text. “It is both a joy and privilege to write the Foreword again. I have learned immensely from the task.” John T. Flynn, MD Bolton Landing, Lake George, NY

vii Preface

Due to the generous representation of the afferent visual system within the brain, neurological disease may disrupt vision as a presenting symptom or as a secondary effect of the disease. Conversely, early developmental disturbances of vision often disrupt ocular motor control systems, giving rise to complex disorders such as , , and torticollis. The signs and symptoms of neurological disease are elusive by their very nature, presenting a con- founding diagnostic challenge. Neurological medications and neurosurgical treatments can produce neuro-ophthalmological dysfunction that can be difficult to distinguish from disease progression. Affected patients may experience substantial delays in diagnosis and are often subjected to extensive (and expensive) diagnostic testing. Scientific articles pertaining to spe- cific disorders are scattered throughout medical subspecialty journals. These children continue to “fall through the cracks” of our medical education system. The increasing recognition that pediatric neuro-ophthalmology comprises a distinct set of diseases from those seen in adults has led to its emergence as a dedicated field of study. Since the original publication of Pediatric Neuro-Ophthalmology nearly 14 years ago, interest in the field has burgeoned. Pediatric ophthalmology and pediatric neurology subspe- cialty conferences often include symposia dedicated to recent advances in pediatric neuro- ophthalmology. Technical advances in neuroimaging have given rise to a more integrated mechanistic classification of neuro-ophthalmological disease in children. Our understanding of neurodevelopmental disorders of the visual system has expanded, longstanding monoliths have been dissembled into component parts, basic molecular mechanisms have taken center stage, and genetic underpinnings have become definitional. Evolutionary alterations can now be observed at the level of the gene, adding a new dimension to our understanding of disease pathogenesis. New classifications now encompass clinically disparate conditions. Descriptive definitions have been supplanted by mechanistic ones, and clinical definitions superseded by genetic ones. Our concept of disease pathogenesis has been revised and in some cases over- turned. Bearing witness to these remarkable advancements has impelled me to enhance and expand the first edition of Pediatric Neuro-Ophthalmology into this new and revised one. In the first edition of this book, our goal was to present the clinical characteristics, diagnostic evaluation, and therapeutic options for the common neuro-ophthalmologic disorders of childhood. In so doing, we designed the book to provide a narrative journey through the thought processes involved in the clinical management of these disorders. In this edition, I have retained the basic narrative format of the original book, while expanding the exploration of these complex visual disorders in the context of the many new scientific advancements and discoveries that have come to light. These conditions are fun to diagnose, fascinating to understand, and gratifying to manage. Although my two excellent coauthors have graciously bowed out of rewriting this edition, their formidable contributions to the first edition provide the bedrock of this book, and my grati- tude to them is inestimable. Without them, this book would not exist. My hope is that the second edition will serve as a useful resource to ophthalmologists, neurologists, neurosurgeons, and pediatricians; and that it will spur more research into the basic mechanisms of these disorders. Michael C. Brodsky, MD Rochester, MN

ix Contents

1 The Apparently Blind Infant...... 1 Introduction...... 1 Hereditary Retinal Disorders...... 6 Leber Congenital Amaurosis...... 6 Joubert Syndrome...... 9 Congenital Stationary Night Blindness...... 10 ...... 10 Congenital Disorders...... 10 Cortical Visual Insufficiency...... 11 Causes of Cortical Visual Loss...... 12 Associated Neurologic and Systemic Disorders...... 19 Characteristics of Visual Function...... 21 Neuro-Ophthalmologic Findings...... 22 Diagnostic and Prognostic Considerations...... 25 Role of Visual Attention...... 27 Subcortical Visual Loss (or Periventricular Leukomalacia)...... 27 Neuroimaging Abnormalities and their Implications...... 27 Neuro-Ophthalmologic Findings...... 28 Perceptual Difficulties...... 30 Dorsal and Ventral Stream Dysfunction...... 31 Pathophysiology...... 33 Intraventricular Hemorrhage...... 34 Periventricular and Intraventricular Hemorrhage...... 34 Hemianopic Visual Field Defects in Children...... 35 Delayed Visual Maturation...... 38 Blindsight...... 41 The Effect of Total Blindness on Circadian Regulation...... 43 Horizons...... 45 References...... 46

2 Congenital Anomalies...... 59 Introduction...... 59 ...... 59 Excavated Optic Disc Anomalies...... 67 Morning Glory Disc Anomaly...... 67 Optic Disc Coloboma...... 71 Peripapillary Staphyloma...... 75 Megalopapilla...... 75 Optic Pit...... 76 Papillorenal Syndrome (The Vacant Optic Disc)...... 78

xi xii Contents

Congenital Tilted Disc Syndrome...... 79 Optic Disc Dysplasia...... 81 Congenital Optic Disc Pigmentation...... 81 Aicardi Syndrome...... 83 Doubling of the Optic Disc...... 85 Optic Nerve Aplasia...... 86 Myelinated (Medullated) Nerve Fibers...... 87 The Albinotic Optic Disc...... 88 References...... 89

3 The Swollen Optic Disc in Childhood...... 97 Introduction...... 97 ...... 98 Idiopathic Intracranial Hypertension (IIH) in Children...... 101 Optic Disc Swelling Secondary to Neurological Disease...... 110 Optic Disc Swelling Secondary to Systemic Disease...... 111 ...... 120 Posttraumatic Optic Disc Swelling...... 121 Intrinsic Optic Disc Tumors...... 122 Optic Disc Hemangioma...... 122 Tuberous Sclerosis...... 122 Optic Disc ...... 123 Combined Hamartoma of the Retina and RPE...... 123 Retrobulbar Tumors...... 123 in Children...... 124 History and Physical Examination...... 124 Postinfectious Optic Neuritis...... 124 Acute Disseminated ...... 124 MS and Pediatric Optic Neuritis...... 125 Devic Disease (Neuromyelitis Optica)...... 126 Prognosis and Treatment...... 127 Course of Visual Loss and Visual Recovery...... 127 Systemic Prognosis...... 128 Systemic Evaluation of Pediatric Optic Neuritis...... 128 Treatment...... 129 Leber Idiopathic Stellate Neuroretinitis...... 129 Ischemic ...... 132 Autoimmune Optic Neuropathy...... 133 Pseudopapilledema...... 133 ...... 133 Ocular Disorders Associated with Pseudopapilledema...... 140 Systemic Disorders Associated with Pseudopapilledema...... 140 References...... 142

4 Optic Atrophy in Children...... 155 Introduction...... 155 Epidemiology...... 156 Optic Atrophy Associated with Retinal Disease...... 159 Congenital Optic Atrophy Vs. Hypoplasia...... 160 Causes of Optic Atrophy in Children...... 161 Compressive/Infiltrative Intracranial Lesions...... 161 Noncompressive Causes of Optic Atrophy in Children with Brain Tumors...... 168 Hereditary Optic Atrophy...... 169 Contents xiii

Dominant Optic Atrophy (Kjer Type)...... 172 Leber Hereditary Optic Neuropathy...... 175 Recessive Optic Atrophhy...... 177 Behr Syndrome...... 177 (DIDMOAD)...... 178 Toxic/Nutritional Optic Neuropathy...... 179 Neurodegenerative Disorders with Optic Atrophy...... 180 Organic Acidurias...... 185 Optic Atrophy due to Hypoxia-Ischemia...... 187 Traumatic Optic Atrophy...... 188 Miscellaneous Causes ...... 188 Summary of the General Approach to the Child with Optic Atrophy...... 189 References...... 190

5 Transient, Unexplained, and Psychogenic Visual Loss in Children...... 213 Introduction...... 213 Transient Visual Loss...... 214 ...... 214 ...... 223 Posttraumatic Transient Cerebral Blindness...... 227 Cardiogenic Embolism...... 227 Nonmigrainous ...... 228 Miscellaneous Transient Visual Disturbances in Children...... 228 Toxic and Nontoxic Drug Effects...... 233 Summary of Clinical Approach to the Child with Transient Visual Disturbances..... 234 Laboratory Evaluation of Transient Visual Disturbances in Children...... 235 Unexplained Visual Loss in Children...... 235 Causes of Unexplained Visual Loss in Childhood...... 235 Psychogenic Visual Loss in Children...... 239 Clinical Profile...... 239 Neuro-Ophthalmologic Findings...... 240 Categories of Psychogenic Visual Loss in Children...... 241 Management of Psychogenic Visual Loss in Children...... 242 Horizons...... 244 References...... 244

6 Ocular Motor Nerve Palsies in Children...... 253 Introduction...... 253 ...... 256 Clinical Anatomy...... 256 Clinical Features...... 257 Partial Forms of Oculomotor Palsy...... 257 Oculomotor Synkinesis...... 260 Etiology...... 261 Vascular Third Nerve Palsy in Children...... 266 Differential Diagnosis...... 267 Management...... 268 Trochlear Nerve Palsy...... 270 Clinical Anatomy...... 270 Clinical Features...... 271 Bilateral Trochlear Nerve Palsy...... 273 Etiology...... 274 Differential Diagnosis...... 278 xiv Contents

Treatment...... 279 Abducens Nerve Palsy...... 281 Clinical Anatomy...... 281 Clinical Features...... 281 Causes of ...... 282 Differential Diagnosis...... 285 Duane Retraction Syndrome...... 285 Management of Sixth Nerve Palsy...... 293 Multiple Cranial Nerve Palsies in Children...... 294 Horizons...... 295 References...... 295

7 Complex Ocular Motor Disorders in Children...... 309 Introduction...... 309 Strabismus in Children with Neurological Dysfunction...... 309 Visuovestibular Disorders...... 311 Neurologic ...... 313 Neurologic ...... 315 Skew Deviation...... 316 Gaze Palsies, Gaze Deviations, and Ophthalmoplegia...... 318 Horizontal Gaze Palsy in Children...... 318 Congenital Ocular Motor Apraxia...... 319 Vertical Gaze Palsies in Children...... 323 Diffuse Ophthalmoplegia in Children...... 326 Chronic Progressive External Ophthalmoplegia...... 326 Myasthenia Gravis...... 328 Olivopontocerebellar Atrophy...... 335 Botulism...... 336 Fisher Syndrome: A Variant of Guillain–Barré Syndrome...... 337 Bickerstaff Brainstem ...... 338 Tick Paralysis...... 338 Wernicke ...... 338 Miscellaneous Causes of Ophthalmoplegia...... 338 Transient Ocular Motor Disturbances of Infancy...... 339 Transient Neonatal Strabismus...... 339 Transient Idiopathic Nystagmus...... 339 Tonic Downgaze...... 339 Tonic Upgaze...... 341 Neonatal Opsoclonus...... 342 Transient Vertical Strabismus in Infancy...... 342 Congenital Cranial Dysinnervation Syndromes...... 342 Congenital ...... 343 Marcus Gunn Jaw Winking (Trigemino-Oculomotor Synkinesis)...... 343 Congenital Fibrosis Syndrome...... 344 Congenital Horizontal Gaze Palsy with Scoliosis...... 346 Möbius Sequence...... 347 Monocular Elevation Deficiency, or “Double Elevator Palsy”...... 348 Brown Syndrome...... 350 Other Pathologic Synkineses...... 351 Internuclear Ophthalmoplegia...... 352 Cyclic, Periodic, or Aperiodic Disorders Affecting Ocular Structures...... 353 Ocular Neuromyotonia...... 356 Contents xv

Ocular Motor Adaptations and Disorders in Patients with Hemispheric Abnormalities...... 356 Eye Movement Tics...... 357 Abnormalities in Children...... 357 Congenital Ptosis...... 357 Excessive Blinking in Children...... 358 Hemifacial Spasm...... 360 Eyelid Retraction...... 360 Apraxia of Eyelid Opening...... 362 Pupillary Abnormalities ...... 362 Congenital Bilateral ...... 362 Accommodative Paresis...... 362 ...... 362 Horner Syndrome...... 364 References...... 366

8 Nystagmus in Children...... 383 Introduction...... 383 Infantile Nystagmus...... 384 Clinical Features...... 384 Onset of Infantile Nystagmus...... 385 Terminology...... 385 History and Physical Examination...... 386 ERG...... 388 Hemispheric Visual Evoked Potentials...... 388 Overlap of Infantile Nystagmus and Strabismus...... 389 Eye Movement Recordings in Infantile Nystagmus...... 389 Contrast Sensitivity and Pattern Detection Thresholds in Infantile Nystagmus...... 393 Theories of Causation...... 393 Visual Disorders Precipitating Infantile Nystagmus...... 394 When to Obtain Neuroimaging Studies in Children with Nystagmus...... 404 Treatment...... 405 Spasmus Nutans...... 410 Russell Diencephalic Syndrome of Infancy...... 412 Monocular Nystagmus...... 413 Nystagmus Associated with Infantile Esotropia...... 413 Torsional Nystagmus...... 413 Horizontal Nystagmus...... 414 Latent Nystagmus...... 414 Nystagmus Blockage Syndrome...... 417 Treatment of Nystagmus Blockage Syndrome...... 417 Vertical Nystagmus...... 417 Upbeating Nystagmus in Infancy...... 417 Congenital Downbeat Nystagmus...... 418 Hereditary Vertical Nystagmus...... 419 Periodic Alternating Nystagmus...... 419 Seesaw Nystagmus...... 420 Congenital versus Acquired Seesaw Nystagmus...... 420 Saccadic Oscillations that Simulate Nystagmus...... 421 Convergence-Retraction Nystagmus...... 421 Opsoclonus and Ocular Flutter...... 421 Voluntary Nystagmus...... 423 Ocular Bobbing...... 424 xvi Contents

Neurological Nystagmus...... 424 Leigh Subacute Necrotizing Encephalomyelopathy...... 425 Pelizaeus-Merzbacher Disease...... 425 Joubert Syndrome...... 425 Santavuori-Haltia Disease ...... 426 Infantile Neuroaxonal Dystrophy...... 426 Carbohydrate-Deficient Glycoprotein Syndromes...... 426 Down Syndrome...... 426 Hypothyroidism...... 426 Maple Syrup Urine Disease...... 426 Nutritional Nystagmus...... 427 Epileptic Nystagmus...... 427 Cobalamin C Methylmalonic Aciduria and ...... 427 Familial Vestibulocerebellar Disorder...... 427 Summary...... 427 References...... 429

9 Torticollis and Head Oscillations...... 443 Introduction...... 443 Torticollis...... 443 Ocular Torticollis...... 444 Head Tilts...... 445 Head Turns...... 450 Vertical Head Positions...... 452 Refractive Causes of Torticollis...... 453 Neuromuscular Causes of Torticollis...... 453 Systemic Causes of Torticollis...... 455 Head Oscillations...... 455 Head Nodding with Nystagmus...... 455 Head Nodding without Nystagmus...... 457 Visual Disorders...... 459 Otological Abnormalities...... 459 Systemic Disorders...... 459 References...... 460

10 Neuro-Ophthalmologic Manifestations of Neurodegenerative Disease in Childhood...... 465 Introduction...... 465 Neuronal Disease...... 467 Neuronal Ceroid Lipofuscinosis...... 467 Lysosomal Diseases...... 470 Gangliosidoses...... 470 Mucopolysaccharidoses...... 474 Subacute Sclerosing Panencephalitis...... 476 White Matter Disorders...... 477 Metachromatic Leukodystrophy...... 478 Canavan Disease (Spongy Degeneration of Cerebral White Matter)...... 478 ...... 479 Pelizaeus–Merzbacher Disease...... 479 Cockayne Syndrome...... 480 Alexander Disease...... 481 Sjögren–Larsson Syndrome...... 481 Cerebrotendinous Xanthomatosis...... 482 Peroxisomal Disorders...... 482 Contents xvii

Zellweger Syndrome...... 483 Adrenoleukodystrophy...... 483 ...... 485 Pantothenate Kinase-Associated ...... 485 Wilson Disease...... 486 Aminoacidopathies and Other Biochemical Defects...... 486 Maple Syrup Urine Disease...... 486 Homocystinuria...... 487 Abetalipoproteinemia...... 487 Mitochondrial Encephalomyelopathies...... 488 Chronic Progressive External Ophthalmoplegia (CPEO)...... 489 Leigh Subacute Necrotizing Encephalomyelopathy...... 490 Mitochondrial Encephalomyelopathy and -Like Episodes (MELAS)...... 492 and Ragged Red Fibers (MERRF)...... 492 Mitochondrial Depletion Syndrome...... 492 Congenital Disorders of Glycosylation...... 493 Horizons...... 493 References...... 494

11 Neuro-Ophthalmologic Manifestations of Systemic and Intracranial Disease ...... 503 Introduction...... 503 The Phakomatoses...... 503 Neurofibromatosis (NF1)...... 503 Neurofibromatosis 2 (NF2)...... 510 Tuberous Sclerosis...... 513 Sturge–Weber Syndrome...... 517 von Hippel–Lindau Disease...... 519 Ataxia Telangiectasia...... 521 Linear Nevus Sebaceous Syndrome...... 523 Klippel–Trenauney–Weber Syndrome...... 523 Brain Tumors...... 525 Suprasellar Tumors...... 527 Arachnoid Cysts...... 528 Cavernous Sinus Lesions...... 528 Hemispheric Tumors...... 529 Posterior Fossa Tumors...... 530 Brainstem Tumors...... 533 Tumors of the Pineal Region...... 536 Meningiomas...... 537 Epidermoids and Dermoids...... 537 Gliomatosis Cerebri...... 538 Metastasis...... 538 Complications of Treatment of Intracranial Tumors in Children...... 538 ...... 539 Hydrocephalus due to CSF Overproduction...... 540 Noncommunicating Hydrocephalus...... 540 Communicating Hydrocephalus...... 540 Common Causes of Hydrocephalus in Children...... 541 Clinical Features of Hydrocephalus...... 548 Effects and Complications of Treatment...... 551 Vascular Lesions...... 553 AVMs...... 553 xviii Contents

Cavernous Angiomas...... 556 Intracranial Aneurysms...... 556 Isolated Venous Ectasia...... 557 Craniocervical Arterial Dissection...... 557 in Children...... 557 Cerebral Venous Thrombosis...... 558 Cerebral Dysgenesis and Intracranial Malformations...... 559 Destructive Brain Lesions...... 560 Malformations Due to Abnormal Stem Cell Proliferation or Apoptosis...... 562 Malformations Due to Abnormal Neuronal Migration...... 564 Malformations Secondary to Abnormal Cortical Organization and Late Migration...... 565 Anomalies of the Hypothalamic–Pituitary Axis...... 568 Encephaloceles...... 568 Cerebellar Malformations...... 569 Miscellaneous...... 572 Congenital Corneal Anesthesia...... 572 Reversible Posterior Leukoencephalopathy...... 572 Cerebroretinal Vasculopathies...... 573 Syndromes with Neuro-Ophthalmologic Overlap...... 573 Proteus Syndrome...... 573 PHACE Syndrome...... 573 Goldenhar Syndrome (Oculoauriculovertebral Dysplasia)...... 573 Delleman (Oculocerebrocutaneous) Syndrome...... 574 Encephalocraniocutaneous Lipomatosis...... 574 Incontinentia Pigmenti (Bloch–Sulzberger Syndrome)...... 574 References...... 576

Index...... 597