Table Of ContentClinics in Developmental Medicine No. 191–192
CEREBELLAR DISORDERS IN CHILDREN
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Clinical in Developmental Medicine No. 191–192
Cerebellar Disorders
in Children
Edited by
EUGEN BOLTSHAUSER MD
Professor of Pediatric Neurology, Department of Pediatric Neurology,
University Children’s Hospital, Zurich, Switzerland
and
JEREMY D. SCHMAHMANN MD
Professor of Neurology, Harvard Medical School; Ataxia Unit, Cognitive
and Behavioral Neurology Unit, and Laboratory for Neuroanatomy and
Cerebellar Neurobiology, Department of Neurology, Massachusetts
General Hospital, Boston, MA, USA
2012
Mac Keith Press
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© 2012 Mac Keith Press
6 Market Road, London N7 9PW
Editor: Hilary M Hart
Managing Director: Caroline Black
Production Manager: Udoka Ohuonu
Project Manager: Mirjana Misuina
The views and opinions expressed herein are those of the authors and do not necessarily
refl ect those of the publisher
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system,
or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or
otherwise, without the prior written consent of the publisher
First published 2012
British Library Cataloguing-in-Publication data
A catalogue record for this book is available from the British Library
Cover Illustration: Drawing of a fl ower by an 8-year-old girl with progressive cerebellar atrophy of unknown cause.
The diagram is executed with inaccuracy, overshoot, and intention tremor, a consequence of the cerebellar motor syndrome.
The fi gure is overly simplifi ed, more in keeping with the drawing of a much younger child, and represents an excellent effort
by a child with defi cits in visual-spatial conceptualization and planning, as occurs in the cerebellar cognitive affective syndrome.
The panel of magnetic resonance images at bottom in four patients refl ects the characteristic features of, from left to right,
prenatal Dandy-Walker malformation, cerebellar atrophy, molar tooth sign in Joubert syndrome, and cerebellar agenesis.
ISBN: 978-1-907655-01-2
Printed by TJ International, Padstow, Cornwall, UK
Mac Keith Press is supported by Scope
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CONTENTS
Authors’ Appointments ix
Foreword xi
Preface xii
About the Editors xiv
Part 1: Cerebellar Development 1
1 Cerebellar Development 3
Kathryn E. Waimey, Samin A. Sajan, and Kathleen J. Millen
Part 2: Cerebellar Anatomy and Functions 21
2 Essential Anatomy of the Cerebellum and Related Structures 23
Patricia L. Musolino, Catherine J. Stoodley, and Jeremy D. Schmahmann
3 Approach to the Neurological Examination of Children with Cerebellar Disorders 45
Peter Tsai, Katherine B. Sims, and Jeremy D. Schmahmann
4 Impairments of Cognition and Emotion in Children with Cerebellar Disorders:
An Approach to Recognition, Evaluation, and Treatment 58
Jeremy D. Schmahmann, Annah N. Abrams, and Janet C. Sherman
Part 3: Imaging of the Cerebellum 77
5 Prenatal Cerebellar Imaging 79
Daniel A. Doherty and Deborah Levine
6 Neuroimaging of the Posterior Fossa 94
Thierry A.G.M. Huisman
Part 4: Malformations 113
Introductory comments and glossary 114
7 Cerebellar Agenesis 117
Andrea Poretti, Eugen Boltshauser, and Jeremy D. Schmahmann
8 Cerebellar Hypoplasia 122
Andrea Poretti and Eugen Boltshauser
9 Nonprogressive Congenital Ataxia 135
Eugen Boltshauser and Andrea Poretti
10 Dandy-Walker Malformation 140
Andrea Poretti, Kathleen J. Millen, and Eugen Boltshauser
11 Joubert Syndrome and Related Disorders 149
Enza Maria Valente, Francesco Brancati, and Bruno Dallapiccola
12 Chiari Type I Malformation 158
Michael S. Salman
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Contents
13 Chiari Type II Malformation 164
Michael S. Salman
14 Cerebellar Dysplasia 172
Andrea Poretti and Eugen Boltshauser
15 Cerebellar Cysts and Neuroimaging in Congenital Muscular Dystrophies 177
Andrea Poretti, Andrea Klein, and Eugen Boltshauser
16 Rhombencephalosynapsis and Gómez-López-Hernández Syndrome 184
Andrea Poretti and Eugen Boltshauser
17 Macrocerebellum 192
Andrea Poretti and Eugen Boltshauser
18 Hemicerebellar Megalencephaly 194
Andrea Poretti and Eugen Boltshauser
19 Brainstem Disconnection 198
Andrea Poretti and Eugen Boltshauser
20 Pontine Tegmental Cap Dysplasia 202
Andrea Poretti and Eugen Boltshauser
21 Brainstem Malformations Associated with Cerebellar Abnormalities 208
Andrea Poretti and Eugen Boltshauser
22 Posterior Fossa Cysts and Cyst-like Malformations (Blake’s Pouch Cyst,
Arachnoid Cysts, and Mega Cisterna Magna) 212
Andrea Poretti, Ianina Scheer, and Eugen Boltshauser
Part 5: Genetic and Metabolic Disorders 217
23 Pontocerebellar Hypoplasias 219
Peter G. Barth
24 Autosomal Dominant Spinocerebellar Ataxias 228
Andrea H. Nemeth
25 X-linked Cerebellar Disorders 241
Ginevra Zanni and Enrico Bertini
26 Recessive Ataxias 253
Alessandra Terracciano, Ginevra Zanni, and Enrico Bertini
27 Ataxia in Metabolic and White Matter Disorders 269
Nicole I. Wolf
28 The Episodic Ataxias 282
Tracey D. Graves and Michael G. Hanna
29 Neurocutaneous Syndromes with Cerebellar Involvement 291
Thierry A.G.M. Huisman
Part 6: Cerebellar Disruptions 303
30 Prenatal Cerebellar Disruptions 305
Andrea Poretti and Eugen Boltshauser
31 Cerebellar Injury in the Preterm Infant 314
Catherine Limperopoulos
Part 7: Vascular Disorders, Tumours, and Paraneoplastic Cerebellar Syndromes 323
32 Vascular Disorders of the Posterior Fossa 325
Maja Steinlin
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Contents
33 Posterior Fossa Tumours 336
Michael A. Grotzer
34 Paraneoplastic Cerebellar Syndromes: Neurodegeneration in Langerhans
Cell Histiocytosis 351
Andrea Poretti, Eugen Boltshauser, and Jeremy D. Schmahmann
35 Paraneoplastic Cerebellar Degeneration in Pediatric Hodgkin Disease 358
Eugen Boltshauser and Andrea Poretti
Part 8: Acute Ataxia 359
Introductory comments 360
36 Acute Ataxia: Epidemiology and Differential Diagnosis 361
Peter Baxter
37 Acute Inflammatory Diseases of the Cerebellum 364
Marc Tardieu
38 Opsoclonus-Myoclonus Syndrome 371
Michael Pike
39 Acute Ataxia: Other Causes 378
Peter Baxter
Part 9: Extrinsic Insults 385
40 Trauma to the Posterior Fossa 387
Daune L. MacGregor
41 Toxic Agents 392
Andrea Poretti and Eugen Boltshauser
42 Gluten Ataxia 394
Andrea Poretti and Eugen Boltshauser
Checklists 397
Andrea Poretti and Eugen Boltshauser
Table 1. Congenital ataxia 399
Table 2. Acute ataxia 401
Table 3. Intermittent ataxia 402
Table 4. Episodic ataxias 403
Table 5. Progressive ataxias 404
Table 6. Treatable causes of inherited ataxia 405
Table 7. Ataxia and ocular motor apraxia 406
Table 8. Ataxia and progressive external ophthalmoplegia 406
Table 9. Ataxia and retinopathy 406
Table 10. Ataxia and cataract 407
Table 11. Ataxia and polyneuropathy 408
Table 12. Ataxia and spasticity 408
Table 13. Ataxia ‘plus’ (additional suggestive signs or symptoms in selected ataxias) 409
Table 14. Cerebellar hypoplasia in childhood 410
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Contents
Table 15. Unilateral cerebellar hypoplasia 412
Table 16. Cerebellar atrophy in childhood: a pattern-recognition approach 412
Table 17. Acquired cerebellar atrophy in childhood 414
Table 18. Unilateral cerebellar atrophy in childhood 414
Table 19. Ataxia without cerebellar atrophy in childhood 414
Table 20. Cerebellar cortex hyperintensity 415
Table 21. Abnormalities of the dentate nuclei 415
Table 22. Cerebellar calcifications 416
Table 23. Abnormalities of the cerebellar white matter in metabolic and genetic diseases 416
Table 24. Small pons 417
Table 25. Macrocerebellum 418
Table 26. Hemicerebellar megalencephaly 418
Table 27. Molar tooth sign 419
Table 28. Abnormal tectum 419
Table 29. Brainstem clefts 420
Index 428
Colour plates appear after the index.
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AUTHORS’ APPOINTMENTS
Annah N. Abrams Assistant Professor of Psychiatry, Harvard Medical School; Associate
Director, Child Psychiatry Consultation Liason Service; Child Psychiatrist,
Division of Pediatric Hematology Oncology, Massachusetts General
Hospital, Boston MA, USA
Peter G. Barth Emeritus Professor in Pediatric Neurology, Emma Children’s Hospital; Academic
Medical Centre, University of Amsterdam, The Netherlands
Peter Baxter Consultant Paediatric Neurologist, Sheffield Childrens Hospital; Honorary
Senior Lecturer, University of Sheffield, Sheffield, UK
Enrico Bertini Head, Unit of Neuromuscular and Neurodegenerative Disorders,
Laboratory of Molecular Medicine, Department of Neurosciences,
Bambino Gesu’ Children’s Research Hospital, Rome, Italy
Eugen Boltshauser Professor of Pediatric Neurology Department of Pediatric Neurology,
University Children’s Hospital, Zurich, Switzerland
Francesco Brancati Research Associate, Medical Genetics Unit, University of Rome Tor Vergata,
and CSS Mendel Institute, Rome, Italy
Bruno Dallapiccola Scientific Director, IRCCS Bambino Gesù Pediatric Hospital, Rome, Italy
Daniel A. Doherty Associate Professor of Pediatrics, Divisions of Developmental Medicine;
Genetic Medicine, University of Washington, Seattle Children’s Hospital,
Seattle, WA, USA
Tracey D. Graves Specialist Registrar in Neurology, MRC Centre for Neuromuscular Disease,
National Hospital for Neurology and Neurosurgery, London, UK
Michael A. Grotzer Co-Head Oncology, Head Neuro-Oncology, University Children’s Hospital,
Zurich, Switzerland
Michael G. Hanna Professor of Clinicial Neurology, MRC Centre for Neuromuscular Disease,
National Hospital for Neurology and Neurosurgery, London, UK
Thierry A.G.M. Huisman Professor of Radiology and Radiological Science; Director of Pediatric
Radiology, Russell H. Morgan Department of Radiology and Radiological
Science, Johns Hopkins Hospital, Baltimore, MD, USA
Andrea Klein Consultant Paediatric Neurologist, Department of Pediatric Neurology,
University Children’s Hospital, Zurich, Switzerland
Deborah Levine Professor of Radiology, Department of Radiology, Beth Israel Deaconess
Medical Center; Harvard Medical School, Boston MA, USA
Catherine Limperopoulos Associate Professor of Pediatrics, George Washington University, Division of
Diagnostic Imaging and Radiology, Children’s National Medical Center,
Washington DC, USA
Daune L. Macgregor Professor of Paediatrics (Neurology), Interim Head, Clinical and Metabolic
Genetics, University of Toronto, The Hospital for Sick Children, Toronto,
Canada
Kathleen J. Millen Associate Professor, Seattle Children’s Research Institute Center for
Integrative Brain Research and The University of Washington Department of
Pediatrics, Seattle WA, USA
Patricia L. Musolino Clinical Fellow in Neurology, Partners Neurology Program; Harvard Medical
School, Boston, MA, USA
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Authors’ Appointments
Andrea H. Nemeth Consultant in Clinical Genetics, Department of Clinical Genetics,
Churchill Hospital; Senior Clinical Research Fellow, Nuffield Laboratory of
Ophthalmology, University of Oxford, Oxford, UK
Michael Pike Consultant Paediatric Neurologist, Children’s Hospital, Oxford, UK
Andrea Poretti Clinical and Research Fellow, Department of Pediatric Neurology,
University Children’s Hospital, Zurich, Switzerland
Samin A. Sajan Research Scientist, Seattle Children’s Research Institute Center for
Integrative Brain Research, Seattle, WA, USA
Michael S. Salman Paediatric Neurologist, Section of Paediatric Neurology, Children’s
Hospital; Associate Professor, Faculty of Medicine, University of Manitoba,
Winnipeg, Manitoba, Canada
Ianina Scheer Consultant Paediatric Neuroradiologist, Department of Diagnostic
Imaging, University Children’s Hospital, Zurich, Switzerland
Jeremy D. Schmahmann Professor of Neurology, Harvard Medical School; Ataxia Unit, Cognitive
and Behavioral Neurology Unit and Laboratory for Neuroanatomy and
Cerebellar Neurobiology, Department of Neurology, Massachusetts
General Hospital, Boston, MA, USA
Janet C. Sherman Assistant Professor of Psychology, Harvard Medical School; Director,
MGH Psychology Assessment Center; Chief of Neuropsychology,
Massachusetts General Hospital; Co-Director, Harvard Consortium
Fellowship in Neuropsychology, Massachusetts General Hospital
Psychology Assessment Center, Boston, MA, USA
Katherine B. Sims Associate Professor of Neurology, Harvard Medical School; Director,
Neurogenetics DNA Diagnostic Laboratory; Director, Developmental
Neurogenetics & Mitochondrial Clinics; Director, Pediatric Neurology
Residency Program, Department of Neurology, Massachusetts General
Hospital, Boston, MA, USA
Maja Steinlin Head of Paediatric Neurology, Development and Rehabilitation, Division
of Neuropaediatrics, Development and Rehabilitation, University Children’s
Hospital, Bern, Switzerland
Catherine J. Stoodley Assistant Professor, Department of Psychology, American University,
Washington DC, USA
Marc Tardieu Professor of Paediatrics (Neurology), University Paris-Sud, Hôpitaux
Universitaires Paris Sud, France
Alessandra Terracciano Post-doctoral Fellow, Unit of Molecular Medicine for Neuromuscular and
Neurodegenerative Disorders, Department of Neurosciences, Bambino
Gesu’ Children’s Research Hospital, Rome, Italy
Peter Tsai Fellow in Behavioural Neurology, Department of Neurology, Children’s
Hospital Boston; Harvard Medical School, Boston, MA, USA
Enza Maria Valente Associate Professor of Medical Genetics, University of Messina, Messina;
Head of Neurogenetics Unit, CSS-Mendel Institute, Rome, Italy
Kathryn E. Waimey Program Director, Oncofertility Consortium, Department of Obstetrics and
Gynecology, Northwestern University, Chicago, IL, USA
Nicole I. Wolf Assistant Professor, Department of Child Neurology, VU University Medical
Center, Amsterdam, The Netherlands
Gine vra Zanni Research Scientist in Medical and Molecular Genetics, Unit of Molecular
Medicine for Neuromuscular and Neurodegenerative Disorders,
Department of Neurosciences, Bambino Gesu’ Children’s Research
Hospital, Rome, Italy
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