Treatment of Pediatric Neurologic Disorders doc

Avellino Division of Pediatric Neurosurgery, Children’s Hospital andRegional Medical Center, University of Washington School of Medicine, Seattle,Washington, U.S.A.. Cohn Johns Hopkins H

of Pediatric Neurologic DisordersDK2943_FM_Series 3/4/05 5:05 PM Page 1

NEUROLOGICAL DISEASE AND THERAPY

Advisory Board

Louis R Caplan, M.D.

Professor of NeurologyHarvard University School of MedicineBeth Israel Deaconess Medical CenterBoston, Massachusetts

St Louis, Missouri

Bruce Ransom, M.D., Ph.D.

Warren Magnuson ProfessorChair, Department of NeurologyUniversity of Washington School of Medicine

Seattle, Washington

Kapil Sethi, M.D.

Professor of NeurologyDirector, Movement Disorders ProgramMedical College of GeorgiaAugusta, Georgia

Mark Tuszynski, M.D., Ph.D.

Associate Professor of NeurosciencesDirector, Center for Neural RepairUniversity of California–San Diego

La Jolla, CaliforniaDK2943_FM_Series 3/4/05 5:05 PM Page 2

1 Handbook of Parkinson’s Disease, edited by William C Koller

2 Medical Therapy of Acute Stroke, edited by Mark Fisher

3 Familial Alzheimer’s Disease: Molecular Genetics and Clinical Perspectives, edited by Gary D Miner, Ralph W Richter, John P Blass, Jimmie L Valentine, and Linda A Winters-Miner

4 Alzheimer’s Disease: Treatment and Long-TermManagement, edited by Jeffrey L Cummings and Bruce L Miller

5 Therapy of Parkinson’s Disease, edited by William C Koller and George Paulson

6 Handbook of Sleep Disorders, edited by Michael J Thorpy

7 Epilepsy and Sudden Death, edited by Claire M Lathersand Paul L Schraeder

8 Handbook of Multiple Sclerosis, edited by Stuart D Cook

9 Memory Disorders: Research and Clinical Practice, edited by Takehiko Yanagihara and Ronald C Petersen

10 The Medical Treatment of Epilepsy, edited by Stanley R Resor, Jr., and Henn Kutt

11 Cognitive Disorders: Pathophysiology and Treatment, edited by Leon J Thal, Walter H Moos,

and Elkan R Gamzu

12 Handbook of Amyotrophic Lateral Sclerosis, edited byRichard Alan Smith

13 Handbook of Parkinson’s Disease: Second Edition, Revisedand Expanded, edited by William C Koller

14 Handbook of Pediatric Epilepsy, edited by Jerome V Murphy and Fereydoun Dehkharghani

15 Handbook of Tourette’s Syndrome and Related Tic and Behavioral Disorders, edited by Roger Kurlan

16 Handbook of Cerebellar Diseases, edited by Richard Lechtenberg

17 Handbook of Cerebrovascular Diseases, edited by Harold P Adams, Jr

18 Parkinsonian Syndromes, edited by Matthew B Stern and William C Koller

19 Handbook of Head and Spine Trauma, edited by Jonathan Greenberg

20 Brain Tumors: A Comprehensive Text, edited by Robert A Morantz and John W Walsh

21 Monoamine Oxidase Inhibitors in Neurological Diseases,edited by Abraham Lieberman, C Warren Olanow,Moussa B H Youdim, and Keith Tipton

DK2943_FM_Series 3/4/05 5:05 PM Page 3

22 Handbook of Dementing Illnesses, edited by John C Morris

23 Handbook of Myasthenia Gravis and MyasthenicSyndromes, edited by Robert P Lisak

24 Handbook of Neurorehabilitation, edited by David C Good and James R Couch, Jr

25 Therapy with Botulinum Toxin, edited by Joseph Jankovicand Mark Hallett

26 Principles of Neurotoxicology, edited by Louis W Chang

27 Handbook of Neurovirology, edited by Robert R McKendall and William G Stroop

28 Handbook of Neuro-Urology, edited by David N Rushton

29 Handbook of Neuroepidemiology, edited by Philip B Gorelick and Milton Alter

30 Handbook of Tremor Disorders, edited by Leslie J Findleyand William C Koller

31 Neuro-Ophthalmological Disorders: Diagnostic Work-Upand Management, edited by Ronald J Tusa

and Steven A Newman

32 Handbook of Olfaction and Gustation, edited by Richard L Doty

33 Handbook of Neurological Speech and LanguageDisorders, edited by Howard S Kirshner

34 Therapy of Parkinson’s Disease: Second Edition, Revised and Expanded, edited by William C Koller and George Paulson

35 Evaluation and Management of Gait Disorders, edited by Barney S Spivack

36 Handbook of Neurotoxicology, edited by Louis W Changand Robert S Dyer

37 Neurological Complications of Cancer, edited by Ronald G Wiley

38 Handbook of Autonomic Nervous System Dysfunction,edited by Amos D Korczyn

39 Handbook of Dystonia, edited by Joseph King Ching Tsuiand Donald B Calne

40 Etiology of Parkinson’s Disease, edited by Jonas H Ellenberg, William C Koller, and J William Langston

41 Practical Neurology of the Elderly, edited by Jacob I Sageand Margery H Mark

42 Handbook of Muscle Disease, edited by Russell J M Lane

43 Handbook of Multiple Sclerosis: Second Edition, Revised and Expanded, edited by Stuart D Cook

DK2943_FM_Series 3/4/05 5:05 PM Page 4

44 Central Nervous System Infectious Diseases and Therapy,edited by Karen L Roos

45 Subarachnoid Hemorrhage: Clinical Management, edited by Takehiko Yanagihara, David G Piepgras, and John L D Atkinson

46 Neurology Practice Guidelines, edited by Richard Lechtenberg and Henry S Schutta

47 Spinal Cord Diseases: Diagnosis and Treatment, edited byGordon L Engler, Jonathan Cole, and W Louis Merton

48 Management of Acute Stroke, edited by Ashfaq Shuaiband Larry B Goldstein

49 Sleep Disorders and Neurological Disease, edited byAntonio Culebras

50 Handbook of Ataxia Disorders, edited by Thomas Klockgether

51 The Autonomic Nervous System in Health and Disease,David S Goldstein

52 Axonal Regeneration in the Central Nervous System, edited by Nicholas A Ingoglia and Marion Murray

53 Handbook of Multiple Sclerosis: Third Edition,edited by Stuart D Cook

54 Long-Term Effects of Stroke, edited by Julien Bogousslavsky

55 Handbook of the Autonomic Nervous System in Healthand Disease, edited by C Liana Bolis, Julio Licinio, and Stefano Govoni

56 Dopamine Receptors and Transporters: Function, Imaging, and Clinical Implication, Second Edition, edited by Anita Sidhu, Marc Laruelle, and Philippe Vernier

57 Handbook of Olfaction and Gustation: Second Edition,Revised and Expanded, edited by Richard L Doty

58 Handbook of Stereotactic and Functional Neurosurgery,edited by Michael Schulder

59 Handbook of Parkinson’s Disease: Third Edition, edited byRajesh Pahwa, Kelly E Lyons, and William C Koller

60 Clinical Neurovirology, edited by Avindra Nath and Joseph R Berger

61 Neuromuscular Junction Disorders: Diagnosis andTreatment, Matthew N Meriggioli, James F Howard, Jr.,and C Michel Harper

62 Drug-Induced Movement Disorders, edited by Kapil D Sethi

DK2943_FM_Series 3/4/05 5:05 PM Page 5

63 Therapy of Parkinson’s Disease: Third Edition, Revised andExpanded, edited by Rajesh Pahwa, Kelly E Lyons, andWilliam C Koller

64 Epilepsy: Scientific Foundations of Clinical Practice, edited by Jong M Rho, Raman Sankar,

and José E Cavazos

65 Handbook of Tourette’s Syndrome and Related Tic and Behavioral Disorders: Second Edition, edited by Roger Kurlan

66 Handbook of Cerebrovascular Diseases: Second Edition,Revised and Expanded, edited by Harold P Adams, Jr

67 Emerging Neurological Infections, edited by Christopher Power and Richard T Johnson

68 Treatment of Pediatric Neurologic Disorders,Harvey S Singer, Eric H Kossoff, Adam L Hartman,and Thomas O Crawford

DK2943_FM_Series 3/4/05 5:05 PM Page 6

of Pediatric Neurologic Disorders

Harvey S Singer Eric H Kossoff Adam L Hartman Thomas O CrawfordDK2943_FM_Series 3/4/05 5:05 PM Page 7

Cover Illustration: Steven Moskowitz

Published in 2005 by Taylor & Francis Group

6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742

© 2005 by Taylor & Francis Group, LLC

No claim to original U.S Government works Printed in the United States of America on acid-free paper

10 9 8 7 6 5 4 3 2 1 International Standard Book Number-10: 0-8247-2693-6 (Hardcover) International Standard Book Number-13: 978-0-8247-2693-5 (Hardcover) This book contains information obtained from authentic and highly regarded sources Reprinted material is quoted with permission, and sources are indicated A wide variety of references are listed Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials

or for the consequences of their use.

No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers

For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc (CCC) 222 Rosewood Drive, Danvers, MA

01923, 978-750-8400 CCC is a not-for-profit organization that provides licenses and registration for a variety of users For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.

Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe.

Library of Congress Cataloging-in-Publication Data

Catalog record is available from the Library of Congress

Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com

Taylor & Francis Group

is the Academic Division of T&F Informa plc.

DK2943_Discl Page 1 Tuesday, March 8, 2005 3:58 PM

Published in 2005 by

Taylor & Francis Group

6000 Broken Sound Parkway NW

Boca Raton, FL 33487–2742

#2005 by Taylor & Francis Group, LLC

No claim to original U.S Government works

Printed in the United States of America on acid-free paper

10 9 8 7 6 5 4 3 2 1

International Standard Book Number-10: 0–8247–2693–6 (Hardcover)

Cover Illustration: Steven Moskowitz

This book contains information obtained from authentic and highly regarded sources Reprinted material

is quoted with permission, and sources are indicated A wide variety of references are listed Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use.

No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers.

For permission to photocopy or use material electronically from this work, please access www.copyright.com (http:==www.copyright.com=) or contact the Copyright Clearance Center, Inc (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978–750–8400 CCC is a not-for-profit organization that provides licenses and registration for a variety of users For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.

Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe.

Library of Congress Cataloging-in-Publication Data Catalog record is available from the Library of Congress

Visit the Taylor & Francis Web site at http :==www.taylorandfrancis.com

Preface xvii

Contributors xxi

1 Craniosynostosis 1 Benjamin S Carson, Sr.

Introduction 7

Myelomeningocele 7

Holoprosencephaly 10

3 Spasticity=Cerebral Palsy 15 April Puscavage and Alec Hoon

5 Scoliosis 37 Leslie A Morrison

Introduction 79

Diagnosis 79

Evaluation—Etiology 80

Treatment 81

Prognosis 83

Summary 83

13 Landau–Kleffner Syndrome (LKS) and Epilepsy with Continuous

Spike-Waves During Slow-Wave Sleep (CSWS) 85 William H Trescher

Diagnosis and Treatment of Subacute Language Regression,

With or Without Seizures 88

14 Juvenile Myoclonic Epilepsy 91 Traci D Swink

Mitochondrial Epilepsy With Ragged Red Fibers (MERRF) 98

Lafora Body Disease 98

Neuronal Ceroid Lipofuscinosis (NCL) 99

Sialidosis (Cherry-Red Spot Myoclonus Syndrome) 99

Uncommon Causes of PME 99

Diagnosis 100

Treatment 101

Summary 101

16 Intractable Epilepsy 103 Eric H Kossoff

Introduction 103

Diagnostic Options 103

Treatment 106

17 Infantile Spasms 111 Eric H Kossoff

18 Benign Epilepsy with Centrotemporal Spikes 117 James E Rubenstein

Diagnosis and Evaluation 139

Specific Disorders and Treatment 139

Prognosis 143

Summary 144

23 Tremor in Childhood 145 Leon S Dure, IV

25 Combined Muscle and Brain Diseases 161 Ronald D Cohn

Disorders of Protein Glycosylation, ‘‘Dystroglycanopathies’’ 161

Congenital Muscular Dystrophy Due To Laminin a2 Deficiency 163

Myotonic Dystrophy, Steinert’s Disease, DM1 163

Congenital Fiber Type Disproportion 165

26 Inflammatory Neuropathies: Guillan-Barre´ Syndrome (GBS)

and Chronic Inflammatory Demyelinating

Polyradiculoneuropathy (CIDP) 167 Charlotte J Sumner

Other Spinal Muscular Atrophy Syndromes 199

30 Therapy for Neuromuscular

Junction Disorders 201 Thomas O Crawford

Limb–Girdle Muscular Dystrophies 215

Other Muscular Dystrophies 216

32 Dysphagia 217 Maureen A Lefton-Greif

First Line Therapies 227

38 Supratentorial Tumors of Childhood 265 Kaleb Yohay

Brief Description of Disease and Treatment 294

Public Health Measures and Prevention 296

Prognosis 300

Summary 300

43 Neurocysticercosis 303 Constance Smith-Hicks and Eric H Kossoff

Diagnosis and Evaluation by Clinical Presentation 309

Incidence and Epidemiology 329

Clincial Presentation and Evaluation 329

Early Assessment and Intervention 335

Long-Term Management and Prognosis 340

Brain Death 340

Summary 341

Appendix 342

48 Postconcussion Syndrome 345 William R Leahy

50 Pantothenate Kinase-Associated Neurodegeneration (PKAN) 355 Susan J Hayflick

Introduction 361

Menkes Disease 361

Wilson Disease 363

52 Metachromatic Leukodystrophy 367 Gerald V Raymond

56 Plumbism: Elevated Lead Levels in Children 393 Cecilia T Davoli

69 Behavioral Interventions 475 Dana D Cummings

Introduction 475

Behavior Modification 476

Relaxation Training and Biofeedback 477

70 Interpretation of Neuropsychological Testing 481

E Mark Mahone

Introduction 481

Overview of Pediatric Neuropsychological Assessment 482

Challenges for the Conceptualization and Description of

Diagnosis and Clinical Features 501

Treatment for Anxiety Disorders 504

Introduction 513

Co-Morbidities and Differential Diagnosis 514

Introduction 519

Diagnosis and Evaluation 520

Treatment 521

Chronic Treatment of Established Dependence=Addiction 523

77 Neuroleptic Malignant Syndrome, Serotonin Syndrome, and Malignant Hyperthermia 525 Ian Butler and Pedro Mancias

Introduction 525

Neuroleptic Malignant Syndrome (NMS) 525

Diagnosis and Evaluation 526

Normal Sleep Development 533

Specific Disorders and Treatment 534

79 Sturge–Weber Syndrome 539 Anne M Comi and Bernard L Maria

Introduction 545

Neurofibromatosis 1: Clinical Features and Treatment 546

Neurofibromatosis 2: Clinical Manifestations and Treatment 551

Diagnosis and Evaluation 553

Treatment 557

Prognosis 558

82 Hypomelanosis of Ito 561 Lori L Olson and Bernard L Maria

The decision to pursue the challenge of producing a high quality text on treating orders in child neurology was undertaken after much deliberation In part, our ulti-mate motivation was based on both the need for such a book and a desire to includethe expertise of individuals who have had a role in the child neurology program atthe Johns Hopkins Hospital It is, therefore, with great pleasure that we note thatmultiple chapters have been written by individuals, both faculty members and resi-dents, with current or past ties to the program The four editors, two senior faculty,one junior faculty, and a senior child neurology resident, have produced a text that

dis-we hope will be broadly acceptable to readers at all levels of experience Lastly, dis-weare proud to include a brief description of the history of the child neurology program

at the Johns Hopkins University We dedicate this book to the past leaders of theprogram, with special recognition to the first Director of the training program,

Dr John M Freeman

Harvey S SingerEric H KossoffAdam L HartmanThomas O CrawfordDivision of Child NeurologyJohns Hopkins University School of Medicine,

Baltimore, Maryland

xvii

HISTORY OF CHILD NEUROLOGY AT JOHNS HOPKINS HOSPITAL

The Department of Neurology and its accompanying division of Child Neurologywere formally established at Johns Hopkins in 1969 Before this time, there alreadyexisted a distinguished history of individuals with expertise in pediatric neurology,including such luminaries as William Osler, Frank Ford, and David Clark

William Osler was Chief of Medicine at the Johns Hopkins Hospital from 1889

to 1905 His contributions to internal medicine and neurology are legendary, but hisresearch and case presentations on pediatric topics are often overlooked His biblio-graphy contains publications on cerebral palsy, chorea, tics, muscular dystrophy,epilepsy, meningitis, and childhood migraine

Frank Ford was one of the earliest child neurologists in the United States.Ford was born and schooled in Baltimore and ultimately rose to be head of neurol-ogy at Johns Hopkins, a position he held from 1932 to 1958 Based in part on hisobservations at the Harriet Lane Home Outpatient Clinic and interest in neuroanat-omy and pathology, he was coauthor of a book entitled Birth Injuries of the NervousSystem Included in the section written by Ford was a description of developmentalneurobiology, with an emphasis on perinatal birth injury His second text on pedia-tric neurology, first published in 1937, was an encyclopedic 950 pages entitledDiseases of the Nervous System in Infancy, Childhood and Adolescence

David Clark received his medical degree from the University of Chicago andtrained in medicine and neurology at Johns Hopkins As one of Frank Ford’s stu-dents, he became an energetic, outstanding clinician and teacher, well known forhis case analyses and virtuoso performances in case conferences Clark left Hopkins

in 1965 to become the chairman of the Department of Neurology at the University ofKentucky

In the 1950s there were seven neurology faculty members within the neurologydivision of the Department of Medicine, three in pediatric neurology (Frank Ford,David Clark, and John Menkes) John Menkes left in 1966 to head child neurology

in Los Angeles

Although the concept of establishing a separate Department of Neurology hadbeen frequently discussed, the decision to create the department was not finalizeduntil Vernon Mouncastle, who held a strong belief in the "science of the brain andbehavior," convinced the then Director of Medicine A McGee Harvey of the bene-fits Based, in part, on a recommendation by Robert Cooke, Chair of the Depart-ment of Pediatrics, Guy McKhann was selected as the first Neurology DepartmentChairman

McKhann attended the Yale Medical School, trained in pediatrics at Yale andHopkins, received neurology training at Boston Children’s Hospital under the men-torship of Phillip Dodge, and spent several years studying cerebral metabolism at theNIH In January 1969, he was the first chair of the newly created department and itssole child neurologist It is said that he impressed the Hopkins pediatricians duringhis first month when he was asked to consult on a child with the acute onset of ataxiaand opsoclonus For reasons unclear to them, he requested a chest x-ray looking for

a neuroblastoma Although they were mystified at first, when the neuroblastoma wasremoved and the child improved, the future of child neurology was ensured.One of Guy McKhann’s earliest faculty appointments was a chief of pediatricneurology; he wisely chose John Freeman Freeman completed his pediatric training

at Hopkins where David Clark had served as his mentor and role model This wasfollowed by a child neurology fellowship at the Columbia Neurological Institute,

under the mentorship of Dr Sidney Carter Freeman was initially recruited byMcKhann to join him at Stanford, but after enjoying sunny California for only 3years, he repacked and returned to the East coast It is notable that three of the fourinitial neurology residents, Gary Goldstein, William Logan, and Mark Molliver,were all pediatric neurology trainees Apparently, the Osler medical residents werenot informed that they were being supervised by mere pediatricians The goal fromthe outset was to train academic neurologists who would advance the field, as well astrain others.

In starting the child neurology program, Freeman’s initial goal was to reversethe segregation policy that had been in place during his residency He established anintegrated clinic that wall open to all—black, white, rich or poor—and staffed it withresidents and medical students under his supervision Freeman also organized a com-bined service for pediatric neurology and neurosurgery patients Clearly, the patientsreceived better and more consistent care than if they had been on only a surgical ser-vice Unfortunately, in later years because of house staff shortages, billing, and otherissues, this unique concept had to be abandoned The goal of the pediatric neurologytraining program was identical to that of adult neurology, i.e., to train the futureacademic leaders of the field In this regard, Freeman achieved success During histenure as Director of Child Neurology from 1969 to 1990, he trained 44 individuals

in child neurology Thirty-one of the 44 entered academic neurology and most went

on to run their own training programs—wonderful legacy! His philosophy was to

attract the best and the brightest and instill in than the joys of academia As one

of his pupils, I can personally attest to his strong character, teaching and tional skills, academic achievements, but most importantly to his ability to be afriend and long-term counselor

motiva-This book is a testimony to the quality and quantity of an impressive group ofresidents trained over the years at Johns Hopkins

Harvey S Singer, M.D.Haller Professor of Pediatric Neurology

Director, Child NeurologyJohns Hopkins University School of Medicine

Anthony M Avellino Division of Pediatric Neurosurgery, Children’s Hospital andRegional Medical Center, University of Washington School of Medicine, Seattle,Washington, U.S.A

James F Bale Division of Neurology, Department of Pediatrics, The University ofUtah School of Medicine, Salt Lake City, U.S.A

Baltimore, Maryland, U.S.A

Anita L Belman Department of Neurology, School of Medicine, State University

of New York (SUNY) at Stony Brook, Stony Brook, New York, U.S.A

Medical Institutions, Baltimore, Maryland, U.S.A

Ronald D Cohn Johns Hopkins Hospital, Children’s Center, McKusick-NathansInstitute of Genetic Medicine, Baltimore, Maryland, U.S.A

Anne M Comi Johns Hopkins Hospital, Baltimore, Maryland, U.S.A

National Medical Center, Washington, D.C., U.S.A

Helen E Courvoisie Division of Child and Adolescent Psychiatry, Department ofPsychiatry and Behavioral Sciences, The Johns Hopkins Medical Institutions,Baltimore, Maryland, U.S.A

xxi

Thomas O Crawford Johns Hopkins Hospital, Baltimore, Maryland, U.S.A.Dana D Cummings Kennedy Krieger Institute, Baltimore, Maryland, U.S.A.Nancy P Dalos All Children’s Hospital, Clearwater, Florida, U.S.A.

Cecilia T Davoli Kennedy Krieger Institute, Baltimore, Maryland, U.S.A.Martha Bridge Denckla Johns Hopkins University School of Medicine, KennedyKrieger Institute, Baltimore, Maryland, U.S.A

Leon S Dure, IV Division of Pediatric Neurology, Department of Pediatrics, TheUniversity of Alabama at Birmingham, Birmingham, Alabama, U.S.A

Linda M Famiglio Geisinger Health System, Danville, Pennsylvania, U.S.A.Paul Grahan Fisher The Beirne Family Director of Neuro-Oncology at PackardChildren’s Hospital, Stanford University, Stanford, California, U.S.A

John M Freeman Pediatrics and Neurology, Johns Hopkins Hospital, Baltimore,Maryland, U.S.A

Disorders Clinics, Cincinnati, Ohio, U.S.A

Fiona Goodwin Department of Pediatric Neurology, Child Health, University ofSouthampton and Southampton University Hospitals, Southampton, U.K

Division of Child and Adolescent Psychiatry, Baltimore, Maryland, U.S.A

Baltimore, Maryland, U.S.A

Carolyn Elizabeth Hart Mecklenburg Neurological Associates, Charlotte, NorthCarolina, U.S.A

Adam L Hartman Johns Hopkins Hospital, Baltimore, Maryland, U.S.A.Susan J Hayflick Molecular and Medical Genetics, Pediatrics and Neurology,Oregon Health & Science University, Portland, Oregon, U.S.A

J Michael Hemphill Department of Neurology, Medical College of Georgia,Savannah Neurology, Savannah, Georgia, U.S.A.

Institute, Baltimore, Maryland, U.S.A

Medicine, Baltimore, Maryland, U.S.A

Rebecca N Ichord Department of Neurology, Children’s Hospital of Philadelphia,Philadelphia, Pennsylvania, U.S.A

Maryland, U.S.A

Kennedy Krieger Institute, Johns Hopkins University School of Medicine,Baltimore, Maryland, U.S.A

Huntington, West Virginia, U.S.A

Lori C Jordan Department of Neurology, Johns Hopkins University School ofMedicine, Baltimore, Maryland, U.S.A

Medicine, Baltimore, Maryland, U.S.A

Hopkins University School of Medicine, Baltimore, Maryland, U.S.A

Stephen L Kinsman Departement of Pediatrics, University of Maryland School ofMedicine, Baltimore, Maryland, U.S.A

Eric H Kossoff The Johns Hopkins Hospital, Baltimore, Maryland, U.S.A.Chitra Krishnan Department of Neurology, Johns Hopkins University School ofMedicine, Baltimore, Maryland, U.S.A

William R Leahy Neurological Medicine, Greenbelt, Maryland, U.S.A

Benjamin H Lee Departments of Anesthesiology, Critical Care Medicine, andPediatrics, The John Hopkins Hospital, Baltimore, Maryland, U.S.A.

Baltimore, Maryland, U.S.A

David Lieberman Johns Hopkins Hospital, Departments of Pediatric Neurologyand Pediatric Infectious Disease, Baltimore, Maryland, U.S.A

Baltimore, Maryland, U.S.A

Lonnie J Miner Division of Neurology, Department of Pediatrics, The University

of Utah School of Medicine, Salt Lake City, U.S.A

Neurobiology & Anatomy, and Pediatrics, Rochester, New York, U.S.A

Leslie A Morrison Department of Neurology, University of New Mexico,Albuquerque, New Mexico, U.S.A

Hugo W Moser Kennedy Krieger Institute, Johns Hopkins University, Baltimore,Maryland, U.S.A

Stewart Mostofsky Kennedy Krieger Institute, Baltimore, Maryland, U.S.A

Medical Center, Rochester, New York, U.S.A

Robert Ouvrier TY Nelson Department of Neurology and Neurosurgery,Children’s Hospital at Westmead, Sydney, Australia

Neurology, Children’s National Medical Center, The George WashingtonUniversity, Washington, D.C., U.S.A

U.S.A

Frank S Pidcock Department of Pediatric Physical Medicine and Rehabilitation,Johns Hopkins University School of Medicine, Kennedy Krieger Institute,Baltimore, Maryland, U.S.A

Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A

Neurology and Pediatrics, Southern Illinois University School of Medicine,Springfield, Illinois, U.S.A

April Puscavage Johns Hopkins University School of Medicine, Kennedy KriegerInstitute, Baltimore, Maryland, U.S.A

Gerald V Raymond Kennedy Krieger Institute, Johns Hopkins University School

of Medicine, Baltimore, Maryland, U.S.A

Leeds, Leeds, U.K

Hopkins Hospital, Baltimore, Maryland, U.S.A

Michael X Repka Johns Hopkins Hospital, Baltimore, Maryland, U.S.A

Mark Riddle Department of Psychiatry, The Johns Hopkins Hospital, Baltimore,Maryland, U.S.A

James E Rubenstein Johns Hopkins Medical Institutions, Baltimore, Maryland,U.S.A

Paediatrics and Child Health, Children’s Hospital at Westmead, Sydney, Australia

Epilepsy Management Center, Montefiore Medical Center, Albert Einstein College

of Medicine, Bronx, New York, U.S.A

Baltimore, Maryland, U.S.A

Harvey S Singer Departments of Neurology and Pediatrics, Johns HopkinsUniversity School of Medicine, Baltimore, Maryland, U.S.A.

U.S.A

Donna J Stephenson Wilmington, Delaware, U.S.A

Charlotte J Sumner National Institute of Neurological Disorders and Stroke,National Institutes of Health, Bethesda, Maryland, U.S.A

Traci D Swink Marshfield Clinic, Marshfield, Wisconsin, U.S.A

School of Medicine, Baltimore, Maryland, U.S.A

Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.Elizabeth A Thiele Harvard Medical School, Massachusetts General Hospital,Boston, Massachusetts, U.S.A

William H Trescher Kennedy Krieger Institute, Baltimore, Maryland, U.S.A.Adeline Vanderver Department of Neurology, Children’s National Medical Center,Washington, D.C., U.S.A

Hopkins Hospital, Baltimore, Maryland, U.S.A

University School of Medicine, Baltimore, Maryland, U.S.A

Baltimore, Maryland, U.S.A

Pediatrics, The Johns Hopkins Hospital, Baltimore, Maryland, U.S.A

Kaleb Yohay Departments of Neurology and Pediatrics, Johns Hopkins Hospital,Baltimore, Maryland, U.S.A

Medical Center, Rochester, New York, U.S.A

Andrew W Zimmerman Kennedy Krieger Institute, Baltimore, Maryland, U.S.A

Craniosynostosis

Benjamin S Carson, Sr

Department of Neurological Surgery, Johns Hopkins Medical Institutions,

Baltimore, Maryland, U.S.A

INTRODUCTION

Craniosynostosis, premature fusion of the coronal, sagittal, metopic, and=or doidal sutures, may be primary or secondary to a wide range of poorly characterizedgenetic, nutritional, toxicological, and mechanical influences Craniosynostosis alsocan be found when intracranial contents are markedly reduced, such as whenpatients are overshunted and sutures subsequently override and fuse or in cases ofsevere cerebral atrophy The condition may be ‘‘isolated,’’ involving a single suture,

lamb-or ‘‘complex,’’ involving multiple sutures Approximately 100 different flamb-orms havebeen described The manifestations have been classified as ‘‘nonsyndromic’’ and

‘‘syndromic.’’ The latter have been linked to several chromosomes Defects in blast growth factor receptor (FGFR) genes have been identified by several groups.Apert, Pfeiffer, Jackson-Weiss, and Crouzon syndrome associate with mutations

fibro-in FGFR genes However, pathophysiology may be heterogenous because clfibro-inicalfeatures are not always associated with specific mutations (1)

Statistics regarding the incidence of craniosynostoses are difficult to assemblebecause cranial deformities often are not lethal, and are not always recognized atbirth or recorded in adults Studies have suggested a baseline of 0.2–0.5 cases per

1000 births With lambdoidal craniosynostosis, anomalies in skull morphologyusually precede complications such as visual impairment and increased intracranialpressure (ICP) Hydrocephalus frequently occurs with syndromic synostosis, and israrely found in simple, nonsyndromic craniosynostosis, but increased ICP is notunusual Elevated ICP appears to be the driving force behind the neurologicaldeficits The pressure may not be readily apparent on imaging studies or fromclinical signs or symptoms

A subset of the craniosynostoses, unilambdoidal synostosis, attracted lar interest in the early 1990s because several reports indicated a significant increase

particu-in the particu-incidence, which was generally considered to be about 0.05 per 1000 births, orabout 1% of the craniosynostosis cases Pediatric neurosurgeons noted that lambdoi-dal craniosynostosis and positional plagiocephaly (sometimes referred to as ‘‘occipi-tal plagiocephaly’’ and ‘‘functional plagiocephaly’’) had similar morphologicalcharacteristics The suspected increase in lambdoidal synostosis was, in fact, an

1

increase in positional plagiocephaly, an increase related to the American Academy ofPediatrics recommendations (in 1992) that healthy infants avoid the prone sleepingposition Asymmetric skull flattening tends to be perpetuated or accentuated bysupine positioning of the infant; the head will turn to the flatter side by forces ofgravity, or because of varying degrees of torticollis (2).

DIFFERENTIAL DIAGNOSIS

Pediatricians and family practitioners often request neurosurgical consultation forinfants with abnormal head circumference in relation to standard growth curves,yet who are otherwise normal in growth and development, typically at about 6months of age An assessment model is shown in Fig 1 Anomalies frequentlyare noted at birth; parents report a progressive worsening of the deformity androutinely express a concern about potential developmental problems Differentialdiagnoses include torticollis, positional molding, and craniosynostosis Other intra-cranial causes including tumors are less common Positional molding may haveclinical manifestations similar to that of an actual craniosynostosis, but the suturesappear open on plain x-rays and CT scans in such cases Torticollis involves ashortened sternocleidomastoid muscle, which can result in flattening of the tem-poral and occipital region The anterior deformity can be greater than the posteriordeformity, and is on the side of the abnormality The usually mild deformityimproves with neck exercises and physical therapy The muscle rarely needs

to be divided or lengthened Torticollis can cause or potentiate positionalplagiocephaly

The large majority of misshapen heads seen in primary care relate to tional plagiocephaly These anomalies usually are mild and noticed at birth or soonthereafter Anatomically, the occipital region in positional plagiocephaly is flat-tened with anterior compensatory changes and asymmetry in the ear position Con-tralateral anterior flattening and unilateral anterior bossing generally are mild.Unilateral cases have compensatory growth in the contralateral parieto-occipitalregion, manifested by bossing and vertex elongation This elongation is more pro-minent in bilateral deformities, which also have lateral parietal widening, and occi-pital flattening with anterior narrowing and increased frontal projection Infantsmay sleep on their back and have slight flattening of the occipital region Theseproblems generally correct themselves as the infant grows and begins to roll over,although assistive devices are sometimes useful Similar shaping can be seen innewborns with substantial developmental delays or torticollis, and in hypotonicinfants who do not move their heads Table 1 outlines the differential diagnosisbetween patients with lambdoidal synostosis and those with posterior plagioce-phaly (3)

posi-Figure 2 illustrates the effects of synostoses on the shape of the skull A long,narrow, ‘‘keel’’-shaped head, scaphocephaly, indicates sagittal synostosis Unilateraland bilateral coronal synostoses are recognized by their anterior craniofacial defor-mities A trigonocephaly-shaped forehead characterizes metopic synostosis

Standard skull radiography historically has been used for preoperative mation More recently, advances in computer tomography (CT) imaging andthree-dimensional (3D) reconstruction have been adopted as standard diagnostictools Reconstruction provides detailed information about the cranial anatomyand sutures that are not possible with routine radiographs

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Indications for procedures need to be considered by the craniomaxillofacial team foreach case based on clinical signs, syndromic and genetic information, radiographicindicators, and whether the child is stable or developing symptoms Positional plagi-ocephaly can be corrected by changing the child’s position slightly during napsand sleeping Frequently, neck exercises prescribed by an occupational therapist

Table 1 Clinical Differences Between (Common) Positional Plagiocephaly and (Rare)Lambdoidal Craniosynostosis

Occipital bone Flattening with little or

Anterior subarachnoid

spaces

Figure 2 Illustrations of skull shapes and synostoses Panel 2 (left to right): Typical elongatedpicture seen in sagittal synostosis Panel 3: Anterior plagiocephaly characteristic of unilateralright coronal synostosis Panel 4: Towering, bilateral widening, and forehead flattening withforeshortening characteristic of bilateral coronal synostosis Panel 5: Keeled shape and bipar-ietal widening characteristically seen with metopic synostosis (Adapted from Vannier MW.Radiographic Evaluation of Craniosynostosis In: Cohen, MacLean, eds Craniosynostosis,Diagnosis, Evaluation, and Management New York: Oxford University Press; 2000.)

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are helpful Many therapists know how to carve a pillow out of foam rubber thatredistributes the weight of the head and is comfortable for the child The costs areminor and the results appear to be excellent Craniosynostosis is thought by some

to be an aesthetic problem with infrequent consequences for brain function and opment Although clinical impressions have associated appearance with the adoles-cent’s ability to socialize, school performance, and adult behavioral problems,studies have suggested that abnormal skull shapes do not directly affect intelligencetest scores Mental development, measured by intelligence quotient tests, in infantswith nonsyndromic, single-suture craniosynostosis appears to be normal in theabsence of increased ICP and other pathologies In this regard, it is of interest to notethe anthropological studies of the many civilizations that practised cranial deforma-tion for cosmetic and political gains Such practices imply that an abnormal skullshape does not interfere with normal intelligence, although one cannot conclude thatthe physiological results of congenital and cosmetic deformations are the same (4).Apparently well-tolerated craniosynostosis, however, can abruptly worseneither spontaneously or following head injury Skull base deformities can worsen

devel-to the point of affecting vision, hearing, and breathing, and oral occlusion lies in skull morphology usually precede complications such as visual impairmentand increased ICP Multiple-suture synostoses and syndromic synostoses frequentlyassociate with increased ICP, hydrocephalus, and progressive mental impairment

Anoma-SURGICAL INTERVENTION

The cranium, cranial base, and facial region must be evaluated as growing structures.Brain development, vision, sinuses, and airway must also be considered The cranio-maxillofacial team also must evaluate midfacial growth in childhood and adoles-cence, as well as occlusion and mastication in the primary mixed and permanentdentition phase A typical evaluation includes pediatric neurology, radiology, neuro-surgery, anesthesiology, ophthalmology, and orthodontics Major issues to be con-sidered are: 1) frontal–orbital retrusion, usually manifest secondary to coronalsynostosis affecting the frontal–orbital region; 2) posterior constraint occurring withgrowth anomalies in the parietal, occipital, and squamosal sutures; 3) posterior andanterior growth anomalies; and 4) midfacial anomalies In addition, the evaluationfrequently encounters Chiari malformations, hydrocephalus, hypertelorism, cleftpalate, extraocular muscle movement, and ocular anomalies Shunts further compli-cate reconstruction and increase opportunities for infection Because abnormality at

a single suture strongly influences the development of other areas in the craniofacialcomplex, there is a clinical impression that surgical correction during the neonatalperiod yields superior results, although in the absence of clinical or radiological signs

of raised ICP, surgery may be delayed to 12–15 months (5)

Numerous approaches have been described, and many are being refined withadvances in adsorbable plating materials, hardware, and microsurgical technology.Craniofacial surgeons have become more aggressive in trying to correct the sutureand the associated deformities Cranial vault remodeling involves excision of thefrontal, parietal, and occipital bones, which are trimmed, shaped, relocated, andaffixed with biomaterials Specialized texts should be cited for details Two new stra-tegies, which currently are being evaluated, are outlined here

In single-suture cases, the traditional aim has been to excise, or ‘‘strip,’’ the fusedsuture in the hope that mechanical forces would automatically correct the