Swaiman's pediatric neurology : principles and practice

✍ Scribed by Kenneth F. Swaiman (editor)

• Publisher: Elsevier
• Year: 2018
• Tongue: English
• Leaves: 1412
• Edition: 6
• Category: Library

✦ Table of Contents

Front Matter
Copyright Page
Dedication
Preface to the First Edition
Preface to the Sixth Edition
Acknowledgments
Contributors
Part I: Clinical Evaluation
1 General Aspects of the Patient’s Neurologic History
References
Selected References
2 Neurologic Examination of the Older Child
Observation/Mental Status
Screening Gross Motor Function
Physical Examination
Cranial Nerve Examination
Olfactory Nerve: Cranial Nerve I
Optic Nerve: Cranial Nerve II
Oculomotor, Trochlear, and Abducens Nerves: Cranial Nerves III, IV, and VI
Trigeminal Nerve: Cranial Nerve V
Facial Nerve: Cranial Nerve VII
Auditory Nerve: Cranial Nerve VIII
Glossopharyngeal and Vagus Nerves: Cranial Nerves IX and X
Spinal Accessory Nerve: Cranial Nerve XI
Hypoglossal Nerve: Cranial Nerve XII
Skeletal Muscles
Muscle Testing
Deep Tendon Reflexes
Other Reflexes
Sensory System
Cerebellar Function
Gait Evaluation
References
Selected References
3 Neurologic Examination after the Newborn Period Until 2 Years of Age
Evaluation of the Patient
Stage 1
Head
Cranial Nerves
Motor Evaluation
Sensory Testing and Cutaneous Examination
Stage 2
Motor Performance Instruments
Developmental Reflexes
Stage 3
Stage 4
General Considerations
References
Selected References
4 Neurologic Examination of the Term and Preterm Infant
The Term Infant
Observation
Cranial Vault Evaluation
Developmental Reflexes
Motor Function
Cranial Nerve Examination
The Preterm Infant
General Examination
Neurologic Examination
Environmental Interaction
Formal Scale of Gestational Assessment
Deep Tendon Reflex Assessment
Body Attitude
Muscle Tone
Cranial Nerves
Developmental Reflexes
Assessment of Head Growth Patterns
References
Selected References
5 Muscular Tone and Gait Disturbances
Tone
Pathology
Evaluation of the Patient
History
Examination
Diagnosis
Clinical Laboratory Studies
Gait Impairment
Physiologic Considerations
Evaluation of the Patient
Differential Diagnosis
Spastic Hemiplegic Gait
Spastic Diplegic Gait
Cerebellar Gait
Extrapyramidal Gait
Other Dyskinetic Gaits
Steppage Gait
Hip Weakness Gait
Gait Apraxia
Antalgic Gait (Painful Gait)
Conversion Disorder
References
Selected References
6 Vision Loss
Visual Development
Assessment and Quantification of Visual Acuity
Vision Assessment in Infancy
Vision Assessment in Children
Assessment of Color Vision
Assessment of Visual Fields
Assessment of Ocular Motility
Assessment of Optic Nerve and Retinal Nerve Fiber Layer Integrity
Clinical Features Associated with Vision Loss
Examination of Children with Vision Loss
Vision Loss in Infants
Clinical Manifestations
Differential Diagnosis of Vision Loss in Infants
Structural Anomalies
Retinopathy of Prematurity.
Congenital Cataracts.
Corneal Opacity.
Ocular Coloboma.
Retinal Dysplasia.
Optic Nerve Hypoplasia.
Ocular or Oculocutaneous Albinism.
Leber Congenital Amaurosis.
Vision Loss Caused by Cortical Visual Impairment
Structural Cerebral Anomalies Causing Cortical Visual Impairment
Hydrocephalus.
Structural Brain Anomalies.
Vision Loss Caused by Epilepsy.
Delayed Visual Maturation.
Diagnostic Evaluation of Infants with Poor Vision
Vision Loss in Children
Symptoms and Signs of Vision Loss
Differential Diagnosis of Vision Loss in Children
Amblyopia
Ocular Anomalies Causing Vision Loss
Eyelid Abnormalities: Ptosis.
Corneal Anomalies.
Anomalies of the Retina.
Retinitis Pigmentosa.
Neurometabolic Retinal Dysfunction.
Optic Nerve Disorders
Papilledema.
Pseudopapilledema.
Optic Neuritis.
Optic Atrophy.
Cerebral Vision Impairment
Nystagmus in Infancy
Transient Episodic Vision Loss in Children
References
Selected References
7 Hearing Impairment
Introduction
Anatomy and Physiology of the Ear and Auditory System
Hearing Loss
HL Classification
Classification by Definition of Impairment Site
1. Conductive HL.
2. Sensorineural HL.
3. Auditory Neuropathy Spectrum Disorder.
4. Central HL.
Classification by Severity and Profile of Thresholds Elevation
Evaluation of Auditory Function
The Cross-Check Principle
Behavioral Methods
Objective Methods
Tympanometry
Objective Audiometry
Imaging
Hearing Problems in the Pediatric Population
Conductive HL and External Ear Malformations
Sensorineural HL
Ototoxicity
Auditory Neuropathy Spectrum Disorder
Genetic Hearing Loss
Nonsyndromic Hearing Loss
Autosomal Recessive Inheritance
Autosomal Dominant Inheritance
X-Linked and Mitochondrial Inheritance
Genetic Diagnostics for Nonsyndromic Hearing Loss
Syndromic Hearing Loss
Consequences of Hearing Impairment
Clinical Evaluation and Specialized Testing of Suspected Hl
Patient and Family Histories
Clinical Evaluation and Specialized Testing
Audiological Evaluation
Management of Hearing Loss
Reconstructive Surgery for External and Middle Ears Malformation
Choice of Communication Mode for Severe to Profound HL
Assistive Devices
Cochlear Implants
Brainstem Implants
Future Developments
References
Selected References
8 Vertigo
Introduction
Physiologic Basis of Balance
Evaluation of Patients with Dizziness
History
Chief Complaint
Physical Examination
Videonystagmography
Caloric Testing
Rotational Testing
Computerized Dynamic Platform Posturography
Posturography and Vestibular Disorders— Results from the Medical Literature
Vestibular-Evoked Myogenic Potentials
Disorders Producing Vertigo
Acute Nonrecurring Spontaneous Vertigo
Head Trauma
Vestibular Neuritis
Recurrent Vertigo
Migraine-Related Dizziness
Ménière’s Disease
Seizure Disorders
Familial Episodic Ataxia
Nonvertiginous Disequilibrium
Bilateral Peripheral Vestibular Loss
Central Nervous System Disorders
Drug-Induced Dizziness
Nonneurotologic Disorders
Treatments
References
Selected References
9 Taste and Smell
Chemical Senses
Taste, Smell, and Flavor
The Taste System
The Olfactory System
Flavor
Clinical Disorders of Taste and Smell
The Ontogeny of Taste Perception and Preferences
Clinical Significance of Taste in Infants and Children
The Ontogeny of Olfactory and Flavor Perception
Clinical Significance of Olfaction in Infants and Children
Summary
References
Selected References
10 Neuropsychological Assessment
Introduction
Neuropsychological Assessment
What is a Neuropsychological Assessment?
Multicultural Factors
Neuropsychological Testing
When to Refer for Neuropsychological Evaluation
The Neuropsychological Report
Conclusion
References
Selected References
Part II: Neurodiagnostic Testing
11 Spinal Fluid Examination
Introduction
Cerebrospinal Fluid Formation, Flow, and Absorption
Cerebrospinal Fluid Function
Diagnostic Sampling of Cerebrospinal Fluid
Indications
Contraindications and Cautions
Procedure
Complications
Cerebrospinal Fluid Analysis
Appearance
Cells
Microorganisms
Glucose
Protein
Immunologic Analysis
Neurometabolic Studies
References
Selected References
12 Pediatric Neuroimaging
Cranial Ultrasound
Computed Tomography
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Spectral Metabolites Using Proton Magnetic Resonance Spectroscopy
Diseases Studied with Proton Magnetic Resonance Spectroscopy
Diffusion-Weighted Imaging
Diffusion Tensor Imaging
Perfusion Magnetic Resonance Imaging
Susceptibility-Weighted Imaging
Functional Magnetic Resonance Imaging
Magnetic Source Imaging
Spinal Imaging
Angiography
Single-Photon Emission Computed Tomography and Positron Emission Tomography
Acknowledgments
References
Selected References
13 Pediatric Neurophysiologic Evaluation
Utility of Pediatric Neurophysiological Studies
Guidelines for Interpretation
Newborn Electroencephalographic Patterns
Normal Electroencephalographic Patterns in Infancy Through Adolescence
Waking Patterns
Mu Rhythm
Beta Activity
Theta and Delta Slowing
Lambda Waves
Hyperventilatory Response
Photic Stimulation
Drowsy Patterns
Sleep Activation Procedures
Sleep Patterns
Electroencephalographic Neonatal Sleep as an Ultradian Rhythm
Infant and Childhood Sleep
Vertex Waves and Sleep Spindles
Occipital Sharp Transients
Frequency Distribution During Sleep
Arousal Patterns
Patterns of Uncertain Significance
Abnormal Electroencephalographic Patterns
Abnormal Neonatal Electroencephalographic Patterns
Assessment of Prognosis
Focal Abnormalities
Neonatal Seizures
Focal Periodic Patterns
Spikes and Sharp Waves
Epileptiform Abnormalities
Spike-and-Wave Patterns.
Sharp-Wave and Slow-Wave Complexes.
Hypsarrhythmia.
Generalized Periodic Discharges.
Focal Epileptiform Patterns
Rolandic Spikes.
Occipital Spikes.
Temporal Spikes and Sharp Waves
Multiple Independent Spike Foci
Periodic Discharges
References
Selected References
Part III: Emerging Neuroscience Concepts
14 Microstructural and Functional Connectivity in the Developing Brain
Abbreviations
Introduction
Assessment Strategies for Connectivity
Anatomic Covariance
Tools of Network Science
Intrinsic Connectivity Networks
Categorization of Disorders of Connectivity
Fetal Development
Microstructural Studies
Fetal Functional Imaging
Environmental Perturbations
Connectivity in Typically Developing Children
Maturation of Microstructural Networks: Increases in Anisotropy, Decreases in Diffusivity
Functional Maturation: Increases in Integration and Segregation
Influence of Genes and the Environment
Preterm Birth Results in Long-Term Alterations in Connectivity
dMRI Studies Provide Evidence of Widespread Microstructural Abnormalities
Functional Studies: Alterations in Neural Networks in the Prematurely Born
Graph-Theory Analyses Support These Data
Environmental Factors Alter Connectivity in the Prematurely Born
Autism Spectrum Disorder
Tourette Syndrome
Attention-Deficit/Hyperactivity Disorder
Sports-Related Concussion
Epilepsy
Perinatal Stroke
Imaging Genetics
Undiagnosed Developmental Disorders: The Role of Connectivity
Current Clinical Applications
Conclusions
Acknowledgments
References
Selected References
15 Stem Cell Transplantation for Childhood Neurologic Disorders
Neural Stem Cell Biology
Definition of Neural Stem Cells
Stem Cell Niche and Function of Neural Stem Cells in the Developing Central Nervous System
Isolation and Propagation of Neural Stem Cells in Vitro
Generation of Human and Murine Neural Stem Cells from Embryonic Stem Cells
Generation of Neural Stem Cells from Induced Pluriporent Stem Cells
Transplantation of Neural Stem Cells
Detection of Donor Neural Stem Cells in the Host Mouse Brain
Homing of Neural Stem Cells
Bystander Effects of Engrafted Neural Stem Cells
Therapeutic Potential of NSCs
Lysosomal Storage Disorders
Bystander Effects of Neural Stem Cells in Lysosomal Storage Disorders
Cell Replacement of NSCs in LSDs
Hypoxic Ischemic Brain Injury and Stroke
Summary
Future Applications
References
Suggested References
16 Cellular and Animal Models of Neurologic Disease
Introduction
Spontaneously Occurring Mutant Animals
Genetically Engineered Mouse Models
Transgenic Mice
Knock-out and Knock-in Mice
Genome Engineering Using CRISPR-Cas9 Technology
Cellular Model Systems: Cell Lines and Primary Neuronal Cultures
Induced Pluripotent Stem Cells: A Novel Human Cell Model for Neurologic Diseases
Insights from Induced Pluripotent Stem Cells to Model Neurodevelopmental Disorders
References
Selected References
Part IV: Perinatal Acquired and Congenital Neurologic Disorders
17 Neonatal Neurointensive Care
Introduction
Establishing a Multidisciplinary Neurointensive Care Nursery
Resuscitation and Supportive Care to Prevent Brain Injury
Current Treatment Options for Neonates with Hypoxic-Ischemic Encephalopathy
Brain Monitoring and Seizure Management
Brain Imaging
Palliative Care
References
Selected References
18 Neonatal Seizures
Introduction
Pathophysiology
Mechanisms of Excitability in the Developing Brain
The Effect of Seizures on Early Brain Development
Epidemiology
Incidence of Neonatal Seizures
Risk Factors for Neonatal Seizures
Etiology
Acute Symptomatic Seizures
Developmental Brain Abnormalities
Epilepsy Syndromes
Diagnosis
Neonatal Electroencephalogram Monitoring
Conventional Video Electroencephalogram
Indications for Electroencephalogram Monitoring
Duration of EEG Recording
Diagnostic Considerations for Neonates with Seizures
Treatment
Acute Treatment
Treatment of Acute Symptomatic Seizures
Discontinuation of Medication for Acute Symptomatic Seizures
Treatment of Early Onset Epilepsy Syndromes
Outcomes After Neonatal Seizures
Mortality After Neonatal Seizures
Cognitive Outcomes After Neonatal Seizures
Cerebral Palsy After Neonatal Seizures
Postneonatal Epilepsy
Conclusions
References
Selected References
19 Hypoxic-Ischemic Brain Injury in the Term Newborn
Scope of the Problem
Etiology of Brain Injury in the Term Newborn
Clinical Syndrome and Natural History
Clinical Syndrome
Management of Neonatal Encephalopathy
Brain Imaging of Newborns With Encephalopathy
Advanced Magnetic Resonance Techniques.
Magnetic Resonance Spectroscopy.
Diffusion Imaging.
Brain Perfusion.
Patterns of Brain Injury
Progression of Neonatal Brain Injury
Outcomes
Motor Function
Vision and Hearing
Cognition
Outcome and Therapeutic Hypothermia
Outcome Prediction
Pathophysiology of Neonatal Hypoxic-Ischemic Brain Injury and Neuroprotection
Cerebral Blood Flow and Energy Metabolism
Excitotoxicity
Oxidative Stress
Inflammation
Cell Death
Other Neuroprotection Strategies
Neurotrophic Factors
Stem Cells
Hypoxic-Ischemic Brain Injury in the Preterm Infant
Future Directions
References
Selected References
20 Cerebrovascular Disorders in the Newborn
Introduction
Definitions
Acute Symptomatic Perinatal Arterial Ischemic Stroke (PAIS)
Epidemiology
Pathophysiology and Potential Risk Factors
Clinical Presentation
Diagnosis: Neuroimaging
Acute Management
Outcomes and Rehabilitation
Motor: Cerebral Palsy
Nonmotor Disabilities
Outcome Prediction
Recurrence
Psychology and Mental Health
Presumed Perinatal Ischemic Stroke (PPS)
Arterial Presumed Perinatal Stroke
Periventricular Venous Infarction (PVI)
Neonatal Cerebral Sinovenous Thrombosis (CSVT)
Epidemiology
Pathophysiology and Risk Factors
Clinical Presentation and Diagnosis
Management
Outcomes
Perinatal Intracerebral Hemorrhage
Definitions and Epidemiology
Pathophysiology and Risk Factors
Clinical Presentation and Diagnosis
Management
Outcomes
References
Selected References
21 Neonatal Nervous System Trauma
Introduction
Intrauterine Trauma
Perinatal Trauma by Location
Extracranial Injury
Intracranial Hemorrhage
Peripheral Nerve Injuries
Trauma Associated with Specific Obstetric Maneuvers
Perinatal Counseling for Avoidance of Birth-Associated Trauma
Iatrogenic Neurotrauma during the Newborn Period
Trauma Mimics
References
Selected References
22 Injury to the Developing Preterm Brain
Introduction
Intraventricular Hemorrhage
Pathophysiology
Intraventricular Hemorrhage Is a Complex Disorder
Clinical Risk Factors
Anatomic Factors Are Permissive for Hemorrhage
Alterations in Cerebral Blood Flow Contribute to IVH
Candidate Genes for IVH
Neuropathology
Neuroimaging
Clinical Findings
Neonatal Outcome
Long-Term Outcome
Prevention of Intraventricular Hemorrhage
Cerebellar Hemorrhage
White Matter Injury of the Premature Newborn
Neuropathology
Pathogenesis
Hypoxia-Ischemia
Inflammation/Infection
Vulnerability of Immature White Matter
Additional Risk Factors
Intraventricular Hemorrhage.
Postnatal Corticosteroid Use.
Nutrition.
Clinical Presentation
EEG
Neuroimaging
Ultrasound
Magnetic Resonance Imaging
Recommendations for Imaging the Preterm Neonate and Child Born Preterm
Outcome
Cognitive
Social/Behavioral
Motor
Visual
Epilepsy
Prevention and Management
NICU Management
Management After NICU Discharge
Acknowledgments
References
Selected References
23 Perinatal Metabolic Encephalopathies
Introduction
General Approach
Correctable Disturbances of Glucose and Salt Balance
Hypoglycemia
Disturbances of Sodium Balance
Hyponatremia
Hypernatremia
Inborn Errors of Metabolism
Acute Fulminant Metabolic Diseases
Maple Syrup Urine Disease
Other Organic Acidopathies
Primary Lactic Acidosis Resulting From Defects in Oxidative Phosphorylation
Glutamine Synthetase Deficiency
Fructose-1,6-Biphosphatase Deficiency
Fatty Acid Oxidation Defects
Urea Cycle Disorders
Subacute Epileptic Encephalopathies
Glycine Cleavage Defects
Pyridoxine-Dependent and Pyridoxal Phosphate-Dependent Epileptic Encephalopathies
Sulfite Oxidase and Molybdenum Cofactor Deficiency
Serine Biosynthesis Defects
Purine Biosynthesis Defects
l-Amino Acid Decarboxylase Deficiency
Asparagine Synthetase Deficiency
Chronic Encephalopathies Without Multiorgan Involvement
Hyperphenylalaninemia
Succinic Semialdehyde Dehydrogenase Deficiency
Glutaric Aciduria
Chronic Encephalopathies With Multiorgan Involvement
Congenital Disorders of Glycosylation
Peroxisomal Disorders
Cholesterol Biosynthesis Defects (Smith–Lemli–Opitz Syndrome)
References
Selected References
Part V: Congenital Structural Defects
24 Overview of Human Brain Malformations
Introduction
Epidemiology
Classification
Brain Imaging Recognition
Relationships to Other Neurologic Disorders
Relationship to Environmental Factors
Genetic Counseling
References
Selected References
25 Disorders of Neural Tube Development
Introduction
Anatomy and Embryology
Formation of the Neural Tube
Molecular Patterning of the Neural Tube
Epidemiology and Pathogenesis
Incidence
Complex Genetic Contributions
Gene-Environment Interactions in Neural Tube Defects
Teratogens
Classification of Neural Tube Defects
Nomenclature
Embryologic Classification of Neural Tube Defects
Myelomeningocele
Antenatal Diagnosis
Clinical Features
Secondary Abnormalities
Central Nervous System Complications
Bladder and Bowel Dysfunction
Orthopedic Problems
Chiari II Malformation
Classification.
Clinical Features.
Management
Fetal Repair of Myelomeningocele
Management in the Newborn Period
Treatment of Chiari II Malformation
Outcome
Anencephaly
Pathogenesis
Differential Diagnosis
Pathology
Encephalocele
Etiology
Clinical Characteristics
Management
Occult Forms of Spinal Dysraphism
Spinal Cord Lipoma
Dermal Sinus Tract
Spina Bifida Occulta
Meningocele
Split Cord Malformations
Embryology
Clinical Characteristics
Disorders of Secondary Neurulation
Fibrofatty Filum Terminale
Sacral Agenesis
References
Selected References
26 Disorders of Forebrain Development
Introduction
Prosencephalon Patterning
Prosencephalic Cleavage
Holoprosencephaly
Epidemiology
Definition and Subtypes of Holoprosencephaly
Etiology
Clinical Manifestations and Outcomes
Management
Prenatal Diagnosis and Imaging
Genetic Counseling and Testing
Agenesis of the Corpus Callosum
Epidemiology
Prenatal Diagnosis and Prediction of Outcomes
Development of the Corpus Callosum
Imaging and the Corpus Callosum
Etiology
Genetic
Nongenetic
Clinical Manifestations
Association of Agenesis of the Corpus Callosum With Autism and Related Neurodevelopmental Disorders
Management
Septooptic Dysplasia
Definition and Subtypes
Etiology
Clinical Manifestations
Management
References
Selected References
27 Disorders of Cerebellar and Brainstem Development
Introduction
Clinical Features
Approach to Neuroimaging
Approach to Genetic Testing
Disorders Primarily Affecting Cerebellum
Cerebellar Hypoplasias Primarily Affecting Vermis
Dandy-Walker Malformation
Joubert Syndrome
Global CH with Involvement of Both Vermis and Hemispheres
Unilateral Cerebellar Hypoplasia
Cerebellar Atrophy
Cerebellar Dysplasias
Cerebellar Hyperplasia and Chiari Type I Malformation
Cerebellar Hyperplasia
Chiari I Malformation
Rhombencephalosynapsis
Disorders Affecting Cerebellum and Brainstem
Pontocerebellar Hypoplasias
Congenital Muscular Dystrophies Due to Defective α-Dystroglycan Glycosylation
Tubulinopathies
Pontine Tegmental Cap Dysplasia
Cerebellar Agenesis
Disorders Primarily Affecting Brainstem
Horizontal Gaze Palsy and Progressive Scoliosis
Brainstem Disconnection
Other Disorders with Predominantly Brainstem Involvement
References
Selected References
28 Disorders of Brain Size
Introduction
Microcephaly
Pathology
Neuroimaging
Clinical Features
Etiology
Genetics
Antenatal Diagnosis
Genetic Counseling
Summary
Megalencephaly (and Macrocephaly)
Definition and Classification
Pathology and Pathogenesis
Etiology
References
Selected References
29 Malformations of Cortical Development
Introduction
Embryology
Biologic Pathways
Lissencephaly and Subcortical Band Heterotopia
Brain Imaging
Clinical Features
Epilepsy
Survival
Tubulinopathies
Brain Imaging
Clinical Features
Cobblestone Malformations
Brain Imaging
Clinical Features
Prognosis and Management
Neuronal Heterotopia
Periventricular Nodular Heterotopia.
Brain Imaging
Clinical Features
Polymicrogyria and Schizencephaly
Brain Imaging
Clinical Features
Perisylvian Polymicrogyria.
Other Patterns.
Epilepsy.
Schizencephaly.
Focal Cortical Dysplasia and Hemimegalencephaly
Brain Imaging
Clinical Features
Etiology, Genetic, and Molecular Basis
Treatment
Summary
References
Selected References
30 Hydrocephalus and Arachnoid Cysts
Hydrocephalus
Definition
Classification
Epidemiology
Cerebrospinal Fluid Production, Circulation, and Absorption
Etiology and Pathophysiology
Congenital Causes in Infants and Children
Acquired Causes in Infants and Children
Clinical Characteristics
Symptoms and Signs in Infants
Symptoms and Signs in Older Children
Genetics
Neuroimaging
Cranial Ultrasound
Computed Tomography
Magnetic Resonance Imaging
Diagnosis
Differential Diagnosis
Pathology
Management
Prognosis
Intracranial Arachnoid Cysts
Definition
Clinical Characteristics
Sylvian Fissure/Middle Cranial Fossa
Sellar Region
Posterior Fossa
Complications
Epilepsy
Subdural Hematoma and Hygroma
Neuropsychiatric Disorders
Management
Conclusions
References
Selected References
31 Congenital Anomalies of the Skull
Introduction
Craniosynostosis Versus Deformational Plagiocephaly
Sutural Anatomy and Head Shape
Epidemiology of Craniosynostosis
Kleeblattschädel (Cloverleaf Skull)
Treatment and Outcomes of Craniosynostosis
Nonsyndromic Craniosynostosis Neurocognitive Development
Wide Cranial Sutures
Anomalies of Fontanels
Cranial Dermal Sinus
Parietal Foramina (Including Cranium Bifidum)
Wormian Bones
Scalp Vertex Aplasia
Thin Cranial Bones
Undermineralization of the Skull
Craniotabes
Thick Cranial Bones
Sclerosis and Hyperostosis of the Skull
Anomalies of the Sella Turcica
Anomalies of Temporal Bone
Anomalies of Foramen Magnum
Anomalies of the Other Basal Foramina and Canals
Basilar Impression
Bathrocephaly
Occipital Horns
References
Selected References
32 Developmental Encephalopathies
Definition of Developmental Encephalopathies
Relationship to Epileptic Encephalopathies
Relationship to Disorders With Prominent Brain Malformations
Relationship to Autism Spectrum Disorders
Biological Pathways Involved
Specific Developmental Encephalopathies
Rett Syndrome
CDKL5 Disorder
FOXG1 Disorders
MEF2C Disorder
Pitt-Hopkins Syndrome
Mowat-Wilson Syndrome
Chromosome 15q Disorders
Angelman Syndrome
Prader-Willi Syndrome
Duplication of Maternal 15q11q13
CNTNAP2 and NRXN1 Disorders
DYRK1A Disorder
PURA Disorder
Conclusions
References
References
33 Prenatal Diagnosis of Structural Brain Anomalies
Introduction
Prenatal Assessment of Normal Brain Development in the First Trimester
Prenatal Assessment of Normal Development of the Cortex
Prenatal Assessment of Normal Development of the Corpus Callosum
Prenatal Assessment of Normal Development of the Posterior Fossa
Prenatal Diagnosis of Ventriculomegaly
Prenatal Diagnosis of Abnormalities of the Corpus Callosum
Prenatal Diagnosis of Malformations of Cortical Development
Prenatal Diagnosis of Lissencephaly Type I
Prenatal Diagnosis of Cobblestone Complex
Prenatal Diagnosis of Complex Cortical Malformations
Prenatal Diagnosis of Periventricular Nodular Heterotopia
Prenatal Diagnosis of Polymicrogyria
Prenatal Diagnosis of Schizencephaly
Prenatal Diagnosis of Posterior Fossa Anomalies
Prenatal Diagnosis of Chiari Type II Malformation
Prenatal Diagnosis of Dandy–Walker Malformation
Prenatal Diagnosis of Mega Cisterna Magna, Posterior Fossa Arachnoid Cyst, and Blake’s Pouch Cyst
Prenatal Diagnosis of Vermis Hypoplasia/Agenesis
Prenatal Diagnosis of Cerebellar Hypoplasia
Prenatal Diagnosis of Rhombencephalosynapsis
Prenatal Diagnosis of Molar Tooth-Related Syndromes
Prenatal Diagnosis of Brainstem Anomalies
References
Selected References
Part VI: Genetic, Metabolic and Neurocutaneous Disorders
34 Neurogenetics in the Genome Era
Introduction to the Human Genome
Genomic Variation
Chromosomal Structural Rearrangements
History of Cytogenetics
Fluorescence in Situ Hybridization
Copy Number Variations
Indels
Short Tandem Repeats
Mutations, Single Nucleotide Variants, and Single Nucleotide Polymorphisms
Methods of General Mutation Detection
DNA Sequence Analysis
Sanger Sequencing.
Deletion/Duplication Analysis.
Methylation Studies.
Chromosomal Microarray.
Southern Blot.
Next-Generation Sequencing.
Resources for Interpreting Genomic Testing
Somatic Mosaicism and Challenges of Tissue of Origin for DNA
Standards of Genomic Care
Looking Toward the Future
Example of Principles in Practice
References
Selected References
35 Chromosomes and Chromosomal Abnormalities
Methods of Chromosome Analysis
Chromosome Preparation
Chromosome Banding
Molecular Cytogenetics
Chromosomal Abnormalities
Numerical Abnormalities
Structural Abnormalities
Deletions and Duplications
Translocations
Inversions
Insertions
Marker and Ring Chromosomes
Isochromosomes
Cytogenetic Nomenclature
Incidence of Chromosomal Abnormalities
Clinical Indications for Cytogenetic Analysis
Specific Cytogenetic Syndromes
Polyploidy
Aneuploidy
Trisomy 13 (Patau Syndrome)
Trisomy 18 (Edwards’ Syndrome)
Trisomy 21 (Down Syndrome)
Turner Syndrome
Klinefelter Syndrome
Other Sex Chromosome Aneuploidies
Structural Abnormalities
22q11.2 Deletion Syndrome
Prader–Willi and Angelman Syndromes
William–Beuren Syndrome
1p36 Deletion Syndrome
Wolf–Hirschhorn Syndrome
Cri du Chat Syndrome
Chromosome 9q Subtelomeric Deletion
Jacobsen Syndrome
Charcot–Marie–Tooth Neuropathy Type 1A and Hereditary Neuropathy With Liability to Pressure Palsies
Smith–Magenis Syndrome and Potocki–Lupski Syndrome
Miller–Dieker Syndrome
Neurofibromatosis Type 1
X-Linked Ichthyosis Resulting From Steroid Sulphatase Enzyme Deficiency
Loss of Function of the MECP2 Gene/Duplication of the MECP2 Region (Xq28)
The Future of Clinical Cytogenetics
References
Selected References
36 Approach to the Patient with a Metabolic Disorder
Introduction
Inheritance
Laboratory Evaluation
Classification
Part 1: Clinical Presentation of IEMs in the Neonate or Infant Less Than 2 Years of Age
Acute Encephalopathy
Epilepsy
Abnormal Development Associated With Congenital Anomalies and/or Dysmorphic Physical Features
Abnormal Development in the Absence of Congenital Anomalies or Dysmorphic Physical Features
Associated Neurologic Symptoms
Associated Nonneurologic Symptoms (Table 36-4)
Neuroimaging
Neuromuscular Weakness
Clinical Presentation of IEMs in Childhood (Greater Than 2 Years of Age) and Adolescence
Ataxia
Dystonia
Recurrent Rhabdomyolysis
Vascular Stroke
Cognitive and Motor Regression
Psychiatric Symptoms
Conclusions
References
Selected References
37 Aminoacidemias and Organic Acidemias
Signs and Symptoms: General Concepts
Physical Findings: General Concepts
Laboratory Approaches to Diagnosis: General Concepts
Treatment: General Concepts
Inheritance and Genetic Counseling: General Concepts
Aminoacidemias
Phenylketonuria
Biopterin Disorders
Hepatorenal Tyrosinemia
Other Categories of Tyrosinemia
Maple Syrup Urine Disease
Clinical Manifestations
Classic Maple Syrup Urine Disease.
Intermediate Maple Syrup Urine Disease.
Intermittent Maple Syrup Urine Disease.
Thiamine-Responsive Maple Syrup Urine Disease.
Dihydrolipoyl Dehydrogenase–Deficient Maple Syrup Urine Disease.
Laboratory Tests
Genetics
Treatment
Glycine Encephalopathy
Sulfur Amino Acid Metabolism and the Homocystinurias
Hartnup’s Disease
Histidinemia
Organic Acidemias
Propionic Acidemia
Methylmalonic Acidemias
Pathophysiology
Clinical Manifestations
Laboratory Tests
Treatment
Isovaleric Acidemia
3-Methylcrotonyl-CoA Carboxylase Deficiency
Biotinidase Deficiency
Holocarboxylase Synthetase Deficiency
3-Methylglutaconic Aciduria
Beta-Ketothiolase Deficiency
Canavan’s Disease
Glutaric Aciduria Type I
5-Oxoprolinuria
Isobutyryl-CoA Dehydrogenase Deficiency
3-Hydroxyisobutyric Aciduria
2-Methylbutyryl-CoA Dehydrogenase Deficiency
Mevalonate Kinase Deficiency
References
References
38 Inborn Errors of Urea Synthesis
The Urea Cycle
Clinical Description of Urea Cycle Disorders
N-Acetylglutamate Synthase Deficiency
Carbamoyl-Phosphate Synthase 1 Deficiency
Ornithine Transcarbamylase Deficiency
Citrullinemia
Citrullinemia Type II or Citrin Deficiency
Argininosuccinic Aciduria
Argininemia
Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome
Common Clinical Presentations of Urea Cycle Disorders
Histopathologic Features of Urea Cycle Disorders
Mechanism of Neuropathology
Downregulation of Astrocytic Glutamate Transporters
Elevated Glutamine Levels
Altered Water Transport
Altered Glucose Metabolism/Disturbed Energy Metabolism
Interference With the Normal Flux of Potassium Ions
Oxidative and Nitrosative Stress
Differential Diagnosis
Treatment
Dietary Therapy
Alternative-Pathway Therapy
N-Carbamyl-L-Glutamate
Liver Transplantation
Management of Hyperammonemic Crises
Therapies Under Investigation
Hepatocyte Transfer
Gene Therapy
Neuroprotection
Nitric Oxide Supplementation Therapy
Outcome
Summary
Acknowledgment
References
Selected References
39 Diseases Associated with Primary Abnormalities in Carbohydrate Metabolism
Introduction
Abnormalities of Galactose Metabolism
Galactosemia
Galactose-1-Phosphate Uridyltransferase Deficiency
Pathology.
Biochemistry.
Clinical Characteristics.
Clinical Laboratory Tests.
Management.
Uridine Diphosphogalactose Epimerase Deficiency
Galactokinase Deficiency
Biochemistry.
Clinical Characteristics.
Management.
Abnormalities of Fructose Metabolism
Hereditary Fructose Intolerance
Biochemistry
Clinical Characteristics and Differential Diagnosis
Clinical Laboratory Tests and Diagnosis
Management
Fructose-1,6-Diphosphatase Deficiency
Glycogen Storage Diseases
Glucose-6-Phosphatase Deficiency (Von Gierke Disease, Glycogen Storage Disease Type I, Hepatorenal Glycogenosis)
Pathology
Biochemistry
Clinical Characteristics
Clinical Laboratory Tests
Management
Acid α-Glucosidase (GAA, Acid maltase) Deficiency, Infantile Type (Pompe Disease, Idiopathic Generalized Glycogenosis, Glycogen Storage Disease Type II)
Pathology
Biochemistry
Clinical Characteristics
Clinical Laboratory Tests
Genetics
Management
Late Infantile GAA Deficiency
Clinical Laboratory Tests
Biochemistry
Management
Juvenile and Adult GAA Deficiency
Amylo-1,6-Glucosidase Deficiency (Debrancher Deficiency, Cori Disease, Forbes Disease, Limit Dextrinosis, Glycogen Storage Disease Type III)
Pathology
Biochemistry
Clinical Characteristics
Infantile Type.
Childhood Type.
Adult Type.
Clinical Laboratory Tests
Genetics
Management
Amylo-1, 4 →1,6 Transglucosidase Deficiency (Brancher Enzyme Deficiency, Glycogen Storage Disease Type IV)
Pathology
Biochemistry
Clinical Characteristics
Clinical Laboratory Tests
Genetics
Management
McArdle Disease (Myophosphorylase Deficiency, Glycogen Storage Disease Type V)
Pathology
Biochemistry
Clinical Characteristics
Clinical Laboratory Tests
Genetics
Management
Hepatophosphorylase Deficiency (Hers Disease, Glycogen Storage Disease Type VI)
Biochemistry
Clinical Characteristics
Genetics
Management
Muscle Phosphofructokinase Deficiency (Tarui Disease, Glycogen Storage Disease Type VII)
Biochemistry
Clinical Characteristics
Clinical Laboratory Tests
Genetics
Hepatic Phosphorylase Kinase Deficiency (Glycogen Storage Disease, type IX) and Activation Abnormalities
Phosphohexose Isomerase Deficiency (Satoyoshi Disease)
Phosphoglucomutase Deficiency (Thomson Disease)
Other Defects of Glycolysis Causing Glycogen Storage
Defects Impairing Glycogen Formation
Conclusions
References
Selected References
40 Disorders of Glycosylation
Defining Types of Glycosylation
N-Linked Glycosylation
Overview
Biosynthesis
N-Linked Glycan Biosynthesis
Congenital Disorders of Glycosylation
Diagnosis
General Clinical Features
Specific Disorders
Defects in Protein N-Glycosylation
PMM2-CDG (Ia)
MPI-CDG (Ib)
ALG6-CDG (Ic)
DPAGT1-CDG (Ij)
ALG1-CDG (Ik)
TUSC3-CDG
SRD5A3-CDG (Iq)
NGLY1-CDG
Defects in Protein O-Glycosylation
Defects in Glycosphingolipids (GSL)
Glycosylphosphatidylinositol Glycosylation
Defects in Multiple Glycosylation and Other Pathways
SLC35C1-CDG (IIc)
COG Complex
When to Suspect and Test for Congenital Disorders of Glycosylation
Summary
References
Selected References
41 Lysosomal Storage Diseases
Overview and General Concepts
Sphingolipidoses
GM1 Gangliosidosis
GM2 Gangliosidoses
α-Galactosidase a deficiency (Fabry Disease)
β-D-Glucosidase Deficiency (Gaucher Disease)
Sphingomyelinase Deficiency (Niemann–Pick Disease Types a and B)
Niemann–Pick Disease Types C and D
Acid Ceramidase Deficiency (Farber Disease)
Galactosylceramidase Deficiency (Krabbe Disease)
Arylsulfatase a Deficiency (Metachromatic Leukodystrophy)
Mucopolysaccharidoses
Neurologic Manifestations
Ophthalmologic Manifestations
Otolaryngologic Manifestations
Cardiovascular Manifestations
Gastroenterologic Manifestations
Orthopedic Manifestations
Treatment
Oligosaccharidoses and Mucolipidoses
Mannosidoses
Fucosidosis
Aspartylglycosaminuria
Sialidosis (Mucolipidosis I)
Galactosialidosis
Schindler–Kanzaki Disease
Other Lysosomal Storage Disorders
Mucolipidosis II/III
Mucolipidosis IV (ML IV)
Cystinosis
Neuronal Ceroid Lipofuscinoses
Ophthalmologic Manifestations
Neurologic Manifestations
Diagnostic Testing
Treatment
References
Selected References
42 Mitochondrial Diseases
History and Mitochondrial Genetics
Classification of Mitochondrial Diseases
Metabolic Disturbances
Histopathologic Disturbances
Defects of the Krebs Cycle
Mendelian Defects of the Respiratory Chain
1. Respiratory Chain “Direct Hits”
Complex I.
Complex II.
Complex III.
Complex IV.
Complex V.
2. Respiratory Chain “Indirect Hits”
Complex I.
Complex III.
Coenzyme Q10 Defects.
Complex IV.
Complex V.
Defects of Protein Importation
3. Defects of mtDNA Translation
Abnormal tRNA Modifications.
Mutations of Aminoacyl-tRNA Synthetases.
Defects of Mitoribosomes
4. Defects of the IMM Lipid Milieu
5. Defects of Mitochondrial Dynamics
6. Defects of mtDNA Maintenance
mtDNA Depletion Syndromes (MDS)
Myopathic MDS.
Encephalomyopathic MDS.
Hepatocerebral MDS.
Syndromes Due to Multiple mtDNA Deletions
Mutations in ANT1.
Mutations in PEO1.
Mutations in POLG.
Mutations in OPA1.
Coexistence of mtDNA Depletion and mtDNA Multiple Deletions
Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE).
Defects of Oxidation-Phosphorylation Coupling
Diseases Due to Primary mtDNA Mutations (Fig. 42-4)
KSS
Therapy
Mitochondrial Replacement Therapy (MRT)
Shifting Heteroplasmy
Enhancement of Respiratory Chain Function
Elimination of Noxious Compounds
Alteration of Mitochondrial Dynamics
References
Selected References
43 Peroxisomal Disorders
Structure and Function of Peroxisomes
Metabolic Function of Peroxisomes
Classification of Peroxisomal Disorders
Conditions Resulting From Defective Peroxisome Biogenesis
Molecular Etiology of Disorders of Peroxisome Assembly
Zellweger Spectrum Disorders
Clinical and Pathologic Features
Zellweger Syndrome
Neonatal Adrenoleukodystrophy and Infantile Refsum Disease
Laboratory Diagnosis
Prenatal Diagnosis
Therapy
Defects of Single Peroxisomal Enzymes
Defects of Single Peroxisomal β-Oxidation Enzymes
Adrenoleukodystrophy
Biochemical and Molecular Basis
Clinical and Pathologic Features of X-Linked Adrenoleukodystrophy and Adrenomyeloneuropathy
Childhood Cerebral Form of Adrenoleukodystrophy
Adolescent Cerebral Form of Adrenoleukodystrophy
Adult Cerebral Form of Adrenoleukodystrophy
Adrenomyeloneuropathy
Addison Disease Only
Asymptomatic Patients With the Biochemical Defect of Adrenoleukodystrophy
Symptomatic Heterozygotes
Pathogenesis of Adrenoleukodystrophy
Therapy for Adrenoleukodystrophy
Newborn Screening for XALD
Current and Future Outlook
References
Selected References
44 Neurotransmitter-Related Disorders
Monoaminergic Neurotransmitter Deficiency States With Hyperphenylalaninemia
Overview
Role of BH4 in the Central Nervous System
6-Pyruvoyltetrahydropterin Synthase Deficiency
Dihydropteridine Reductase Deficiency
Autosomal-Recessive Guanosine Triphosphate Cyclohydrolase Deficiency
Pterin-4a-Carbinolamine Dehydratase Deficiency (Primapterinuria)
Monoaminergic Neurotransmitter Deficiency States Without Hyperphenylalaninemia
Overview
Segawa Disease or Autosomal-Dominant Dopa-Responsive Dystonia
Aromatic L-Amino Acid Decarboxylase or Dopa-Decarboxylase Deficiency
Sepiapterin Reductase Deficiency
Tyrosine Hydroxylase Deficiency or Autosomal-Recessive Dopa-Responsive Dystonia
Tryptophan Hydroxylase Deficiency
Dopamine B-Hydroxylase Deficiency
Monoamine Oxidase Deficiency
Monoamine Oxidase A Deficiency
Monoamine Oxidase B Deficiency
Monoamine Oxidase A and B Deficiency
Dopamine Transporter Deficiency
Vesicular Monoamine Transporter 2 Deficiency
Disorders of Amino Acid Neurotransmitters
Overview
Gamma-Aminobutyric Acid Transaminase Deficiency
Succinic Semialdehyde Dehydrogenase Deficiency
Secondary Neurotransmitter Deficiency States
Undefined Neurotransmitter Deficiency States
Approach to Treatment in Patients With Neurotransmitter Deficiency States
Neurologic Disorders Characterized by Excess Neurotransmitter Levels
Glycine Encephalopathy
References
Selected References
45 Phakomatoses and Allied Conditions
The Neurofibromatoses
Neurofibromatosis Type 1
Clinical Characteristics
Pathology
Genetics
Management
Neurofibromatosis Type 2
Clinical Characteristics and Pathology
Genetics
Management
Schwannomatosis
Tuberous Sclerosis Complex (TSC)
Clinical Characteristics
Clinical Laboratory Testing
Pathology
Genetics
Management
Von Hippel-Lindau Disease (VHL)
Clinical Characteristics
Pathology
Genetics
Management
Sturge-Weber Syndrome (Encephalofacial Angiomatosis) (SWS)
Clinical Characteristics
Pathology
Management
Maffucci Syndrome
Epidermal Nevus Syndrome
Parry-Romberg Syndrome (Facial Hemiatrophy)
Neurocutaneous Melanosis
Klippel-Trénaunay-Weber Syndrome (KTW)
Incontinentia Pigmenti (Bloch-Sulzberger Syndrome)
Incontinentia Pigmenti Achromians (Hypomelanosis of Ito)
Wyburn-Mason Syndrome (Retinocephalic Angiomatosis)
References
Selected References
46 Disorders of Vitamin Metabolism
Thiamine (Vitamin B1)
Rogers Syndrome
Biotin- or Thiamine Responsive Basal Ganglia Disease
Thiamine Pyrophosphokinase Deficiency
Amish Lethal Microcephaly and Bilateral Striatal Necrosis Resulting From SLC25A19 Mutations
Riboflavin (Vitamin B2)
Riboflavin Deficiency
Riboflavin-Dependent Enzymatic Reactions
Disorders of Riboflavin Transport
Riboflavin Deficiency
Riboflavin Transporter Deficiency Neuronopathy
Niacin (Vitamin B3)
Niacin Dependency
Vitamin B6
Vitamin B6 Deficiency, Dependency, and Responsiveness
Pyridoxine-Dependent Epilepsy
Pyridox(am)ine 5′-Phosphate Oxidase Deficiency
Hyperprolinemia Type II
Congenital Hypophosphatasia
Pyridoxine Versus PLP to Test for Vitamin B6 Responsiveness
Vitamin B12 (Cobalamine)
Cobalamin Deficiency
Cobalamin Dependency
CblC, CbD-MMA/HC, CbF, and CblJ Deficiency (Combined Defects of Ado- and MetCbl)
CblE, CblG, and CblD-HC Deficiency (Defects of MetCbl; Remethylation Defects)
CblA-MMA, CblB-MMA, and CblD-MMA Deficiency (Defects of AdoCbl)
Tocopherol (Vitamin E)
Disorders of Vitamin E Metabolism
Ataxia With Vitamin E Deficiency (= Familial Isolated Vitamin E Deficiency)
Biotin (Vitamin H)
Biotinidase Deficiency
Biotin-Dependent Holocarboxylase Synthetase Deficiency (Multiple Carboxylase Deficiency)
Biotin-Responsive Basal Ganglia Disease
Folate
Nutritional Folate Deficiency
Disorders of Folate Metabolism
Dihydrofolate Reductase Deficiency
Methylenetetrahydrofolate Reductase Deficiency
MTHFD1-Encoded Enzyme Deficiency (Methylenetetrahydrofolate Dehydrogenase Deficiency)
Formiminotransferase Deficiency
Disorders of Folate Transport
Hereditary Folate Malabsorption
Cerebral Folate Transport Deficiency
References
Selected References
47 Nutrition and the Developing Brain
Protein-Calorie Malnutrition
Micronutrients
Minerals
Iron
Zinc
Iodine
Vitamins
Folate
Cobalamin (Vitamin B12)
Vitamin D
Other Vitamins
Long-Chain Polyunsaturated Fatty Acids
References
Selected References
48 The Neuronal Ceroid Lipofuscinosis Disorders
Introduction
Historical Clinical Characterization
Nomenclature
Clinical Description and Characterization
Molecular Genetics
Pathology
Pathobiology
NCL Models and Clinical Trials
Diagnosis
CLN1 (PPT1; OMIM #256730)
Clinical Description
Other Presentations
Genetics and Pathology
CLN2 (TPP1; OMIM #204500)
Clinical Description
Other Presentations
Genetics and Pathology
CLN3 (CLN3; OMIM #204200)
Clinical Description
Other Presentations
Genetics and Pathology
CLN4 (DNAJC5; Autosomal Dominant Kufs; OMIM #162350)
Clinical Description
Genetics and Pathology
CLN5 (CLN5; OMIM #256731)
Clinical Description
Other Presentations
Genetics and Pathology
CLN6 (CLN6; OMIM #601780)
Clinical Description
Other Presentations
Genetics and Pathology
CLN7 (MFSD8; OMIM #610951)
Clinical Description
Other Presentations:
Genetics and Pathology
CLN8 (CLN8; OMIM #600143)
Clinical Description
Genetics and Pathology
CLN10 (CTSD; OMIM #610127)
Clinical Description
Other Presentations:
Genetics and Pathology
CLN11 (GRN; OMIM #614706)
Clinical Description
Genetics and Pathology
FTLD Biology/Pathology
NCL-FTLD Overlap
CLN 12 (ATP13A2; Autosomal Recessive Kufs Disease; OMIM#610513)
Clinical Description
Genetics and Pathology
CLN13 (CTSF, OMIM#615362)
Clinical Description
Genetics and Pathology
CLN14 (KCTD7; OMIM #611725)
Clinical Description
Other Presentation
Genetics and Pathology
Management and Treatment of NCL Disorders
References
Selected References
49 Channelopathies
Introduction
Epilepsy Syndromes
Dravet Syndrome
Clinical Features
Genetics/Pathophysiology
Clinical Laboratory Tests
Treatment
Generalized Epilepsy with Febrile Seizures Plus
Clinical Features
Genetics/Pathophysiology
Treatment
Benign Familial Neonatal Seizures
Clinical Features
Genetics/Pathophysiology
Clinical Laboratory Tests
KCNQ2 Encephalopathy
Clinical Features
Genetic/Pathophysiology
Treatment
Developmental Delay, Epilepsy, and Neonatal Diabetes
Other Genetic Generalized Epilepsies
Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy
Benign Familial Infantile–Neonatal Seizures
Childhood Absence Epilepsy
Juvenile Myoclonic Epilepsy
Familial Pain Syndromes
Clinical Features
Inherited Erythromelalgia, Primary Erythermalgia.
Paroxysmal Extreme Pain Disorder.
Congenital Indifference to Pain.
Genetics/Pathophysiology
Treatment
Migraine and Ataxia Syndromes
Familial Hemiplegic Migraines
Clinical Features
Genetics/Pathophysiology
Clinical Laboratory Tests
Treatment
Episodic Ataxia
Clinical Features
Genetics/Pathophysiology
Clinical Laboratory Tests
Treatment
Spinocerebellar Ataxia
Clinical Features
Genetics/Pathophysiology
Clinical Laboratory Tests
Treatment
References
Selected References
Part VII: Neurodevelopmental Disorders
50 Neurodevelopmental Disabilities: Conceptual Framework
General Conceptions and Considerations When Approaching a Child with Suspected Developmental Disabilities
Spectrum of Neurodevelopmental Disabilities
Overview and Scope of the Problem
Determinants and Risk Factors
Commonalities
Overlap in Neurodevelopment Disorders
Approach to the Evaluation of a Child with Suspected Neurodevelopmental or Intellectual Disability
The Developmental History
Birth History
Social History
Family History
Physical Examination
Testing
Multidisciplinary Approach to the Care of the Child with a Neurodevelopmental Disorder
References
Selected References
51 Global Developmental Delay and Intellectual Disability
Definitions
Epidemiology
Diagnosis
Definitions and Testing
Advances in Diagnostic Testing
Genomic Microarray
Advances in Imaging
Etiology
General Considerations
Genetic Causes
Fragile X Syndrome
Other X-Linked ID Conditions
De Novo Dominant GDD and ID
Other Etiologic Considerations
Evaluation of the Patient
History
Physical Examination
Laboratory and Other Diagnostic Testing
Consultation
Medical Management of Coexisting Conditions
Outcome and Prognosis
Acknowledgments
References
Selected References
52 Cognitive and Motor Regression
Introduction
Definition
Epidemiology
Etiology
Diagnostic Evaluation
History
Developmental History
Family History
Maternal History
Neonatal History
Environmental History
General Medical History
Examination
Laboratory Testing
Brain Biopsy
Diagnostic Approach
Management
Future Directions
References
Selected References
53 Developmental Language Disorders
Introduction
Neural Substrates of Language
Neuroanatomy of Specific Language Impairment
Factors Associated With Developmental Language Disorders
Genetics
Diagnosis
Nosology of Developmental Language Disorders
Articulation and Expressive Fluency Disorders
Pure Articulation Disorders
Stuttering and Cluttering
Phonological Programming Disorder
Verbal Dyspraxia
Disorders of Receptive and Expressive Language
Phonological Syntactic Syndrome
Verbal Auditory Agnosia
Higher-Order Language Disorders
Semantic Pragmatic Syndrome
Lexical Syntactic Syndrome
Outcome of Developmental Language Disorders
Evaluation of the Child With a Suspected Developmental Language Disorder
Treatment
References
Selected References
54 Nonverbal Learning Disabilities and Associated Disorders
Introduction
What Are Nonverbal Learning Disabilities?
Coexistent Issues
Neuropsychological Findings
Verbal-Performance IQ Split
Language
Achievement
Visual–Spatial and Motor Skills
Executive Functioning
Social Perception and Psychopathology
Neuroimaging Findings in NLD and AS/ASD
fMRI
Neurologic Aspects of Nonverbal Learning Disabilities
References
Selected References
55 Dyslexia
Dyslexia Is Specific—Learning Disabilities Are Not
Definition of Dyslexia
Epidemiology and Etiology
Phonologic Model of Dyslexia
Neurobiological Evidence Supporting Dyslexia
Making a Hidden Disability Visible
Implications of Brain Imaging Studies
Diagnosis
Tests Helpful in the Evaluation of Children for Dyslexia
Phonological Processing
Letter Knowledge
Academic Achievement
Physical and Neurologic Examination and Laboratory Tests
Outcome: Phonologic Deficit in Adolescence and Adult Life
Essential Components of Diagnosis in Adolescents and Young Adults
Lack of Automaticity
Measure of Intelligence
Treatment
Accommodations
Acknowledgments
References
Selected References
56 Attention Deficit–Hyperactivity Disorder
Diagnosis and Controversies in the Diagnosis of Attention Deficit–Hyperactivity Disorder
Coexisting Conditions
Neurobiology of Attention Deficit–Hyperactivity Disorder
Structural Imaging
Functional Imaging
Genetic Studies
Other Potential Causes of Attention Deficit–Hyperactivity Disorder
Coexisting Conditions
Diagnostic Evaluation
Laboratory Studies
Electroencephalography
Sleep Studies
Imaging Studies
Treatment
Nonpharmacologic Therapies
Sleep
Biofeedback Programs
Pharmacologic Therapy
Stimulant Medications
Methylphenidate
Dexmethylphenidate
Dextroamphetamine
Noradrenergic Potentiation
Atomoxetine
Nonstimulant Medications
Tricyclic Antidepressants
Alpha-Adrenergic Agonists
Complementary and Alternative Medications
Outcome
Conclusions
References
Selected References
57 Autistic Spectrum Disorders
Clinical Features of ASD
Persistent Deficits in Social Communication and Social Interaction
Restricted, Repetitive Patterns of Behavior, Interests, or Activities
Onset Patterns in ASD
Epidemiology
Sibling Studies
Neonatal Intensive Care and Prematurity
Parental Age and Other Factors
Autoimmune Factors
Vaccines
Animal Models
Neuropathology
Neurotransmitters
Neuroimaging
Genetics of ASD
Screening and Diagnostic Evaluation for ASD
Screening Instruments for ASD
Diagnostic Instruments for ASD
Speaking with Parents about a New Diagnosis of ASD
Recommendations for a Child with Newly Diagnosed ASD
The Neurologic Evaluation in Autism
Large Head Size and Somatic Overgrowth
Motor Disturbances in Tone, Gait, Praxis, and Stereotypies
Clinical Testing
Definitive Evaluation of Hearing
Lead Level
Electroencephalography
Neuroimaging Studies
Metabolic Testing
Tests of Unproven Value
Coexistent Medical Conditions
Gastrointestinal Problems
Sleep Disturbances
Epilepsy
Pharmacologic Therapy
Neuroleptic Agents
Opiate Antagonists
Serotonin Reuptake Inhibitors (SRIs)
Medications to Treat Hyperactivity
Antiseizure Drugs
Cholinesterase Inhibitors
Glutaminergic and Gamma-Aminobutyric Acidergic Agents
Complementary and Alternative Medicine
Educational and Behavioral Interventions
Resources for Families and Practitioners
Disclaimer
References
Selected References
58 Management of Common Comorbidities Associated with Neurodevelopmental Disorders
Hypertonia
Assessment
Interventions
Spasticity Interventions
1. Nonpharmacologic Rehabilitation Strategies
2. Oral Medications for Spasticity
3. Neurosurgical Procedures
4. Botulinum Toxin Injections
Treatment of Dystonia
Musculoskeletal Deformities
Feeding and Gastrointestinal Issues
Assessment of Feeding and Nutrition
Investigations
Management of Common Feeding and Nutritional Issues
Gastroesophageal Reflux
Constipation
Need for Gastrostomy Feeding Tubes
Seizures in Neurodevelopmental Disorders
Diagnosis
Treatment
Antiepileptic Drug Adverse Effects
Polypharmacy
Withdrawal of Antiepileptic Drugs
Drug-Resistant Epilepsy
Treating Seizures in Children with Attention-Deficit/Hyperactivity Disorder
Treating Seizures in Children with Cerebral Palsy
Fragility Fractures (Osteoporosis)
Sleep Disorders
Behavior
Assessment of Behavior
General Principles of Management of Behavior Problems
Psychopharmacology
References
Selected References
59 Treatment of Neurodevelopmental Disorders
Introduction
Rett Syndrome, Down Syndrome, Tuberous Sclerosis, and Fragile X Syndrome
General Concepts Surrounding Treatment for Neurodevelopmental Disorders
Rett Syndrome
Down Syndrome
Tuberous Sclerosis
Fragile X Syndrome
Generalization of Treatment From Single-Gene Disorders to NDDs and ASD
Inborn Errors of Metabolism
Intellectual Developmental Disabilities
Diagnostic Approach to Treatable Inborn Errors of Metabolism
Treatments, Outcomes, and Evidence
Treatable Inborn Errors of Metabolism Presenting With Other Neurodevelopmental Disorder Phenotypes
Epilepsy
Atypical Cerebral Palsy
Psychiatric Disease
Congenital Hypothyroidism
Conclusions and Future Directions
References
Selected References
60 Neuropsychopharmacology
Introduction
Stimulants for ADHD
Nonstimulant Medications for ADHD
Antidepressants
Tricyclic Antidepressants
Selective Serotonin Reuptake Inhibitors
Other Antidepressants
Anxiolytics
Mood Stabilizers
Lithium
Valproic Acid
Carbamazepine
Other Mood Stabilizers
Dopamine Receptor Antagonists: Typical Antipsychotics
Atypical Antipsychotics
Risperidone
Olanzapine
Quetiapine
Ziprasidone
Aripiprazole
Clozapine
Conclusion
References
Selected References
Part VIII: Epilepsy
61 Overview of Seizures and Epilepsy in Children
Introduction
An Ancient Disease in Modern Times
New Conceptual and Practical Definitions
Conceptual Evolution and a New Lexicon for the Epilepsies
Epidemiology
Diagnosis
Overview and Summary
Acknowledgment
References
Selected References
62 Principles of Management and Outcome
Starting Antiseizure Treatment
Which Medicine to Start With?
Routines of Care
Predication of Seizure Outcome
Intractability
When to Stop Antiseizure Medicines
Social Outcome
References
Selected References
63 Neurophysiology of Seizures and Epilepsy
Classification of Seizures
Cellular Electrophysiology
Excitation–Inhibition Balance
Overview of Ion Channels
Voltage-Dependent Membrane Conductances
Depolarizing Conductances
Hyperpolarizing Conductances
Synaptic Physiology
Inhibitory Synaptic Transmission
Excitatory Synaptic Transmission
Abnormal Neuronal Firing
Synchronizing Mechanisms
Glial Mechanisms for Modulating Epileptogenicity
Physiology of Absence Epilepsy
Increased Seizure Susceptibility of the Developing Brain
Development of Ionic Channels and Membrane Properties
Development of Neurotransmitters, Receptors, and Transporters
Structural Maturation of the Brain and Seizure Susceptibility
Regulation of the Ionic Environment
Epileptogenesis in the Developing Brain
Antiseizure Drug Mechanisms
Summary
References
Selected References
64 Epilepsy Genetics
Introduction
Epilepsies With Onset in Neonatal Period
Benign Familial Neonatal Epilepsy
KCNQ2 Encephalopathy
Ohtahara Syndrome (Early Infantile Epileptic Encephalopathy)
Benign Familial Neonatal-Infantile Epilepsy
Epileptic Encephalopathy Associated With SCN2A
Epilepsies With Onset in Infancy
Benign Familial Infantile Epilepsy
Epileptic Encephalopathy Associated With Cyclin-Dependent Kinase-Like 5 (CDKL5)
Epilepsy of Infancy With Migrating Focal Seizures
West Syndrome
Dravet Syndrome and Genetic Epilepsy With Febrile Seizures Plus
Epileptic Encephalopathy Associated With SCN8A
Epilepsy Associated With Protocadherin 19 (PCDH19)
Other Early-Onset Epilepsies
Syndromes With Onset in Childhood and Adolescence
Epilepsy-Aphasia Syndromes
Idiopathic Generalized Epilepsies
Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy
Autosomal-Dominant Focal Epilepsy With Auditory Features
Familial Focal Epilepsy With Variable Foci and DEPDC5-Related Epilepsies
References
Selected References
65 Febrile Seizures
Definitions
Epidemiology
Initial Evaluation
Pathophysiology
Related Morbidity and Mortality
Recurrent Febrile Seizures
Febrile Seizures and Subsequent Epilepsy
Febrile Seizures, Mesial Temporal Sclerosis, and Temporal Lobe Epilepsy
Genetics
Treatment
Counseling and Education
Acknowledgments
References
Selected References
66 Generalized Seizures
Generalized Tonic-Clonic Seizures
Electroencephalographic Findings
Initial Evaluation
Comorbidities Associated with Generalized Seizures
Medical Treatment
Absence Seizures
Initial Evaluation
Electroencephalographic Findings
Treatment
Prognosis
Myoclonic Seizures
Clinical Features
Electroencephalographic Findings
Tonic Seizures
Electroencephalographic Findings
Atonic Seizures
Electroencephalographic Findings
References
Selected References
67 Focal and Multifocal Seizures
Introduction
Types of Focal Seizures in Children
Alteration of Consciousness
Semiologic Classification Schemes
Auras
Autonomic
Automotor
Behavioral Arrest or Hypomotor
Clonus or Myoclonus—Focal
Dialeptic or Dyscognitive
Epileptic Spasms With Asymmetric Features
Gelastic
Hypermotor
Tonic
Versive
Ontogeny of Focal Seizures
Evaluation and Management
References
Selected References
68 Epileptic Spasms and Myoclonic Seizures
Introduction
Epilepsy Syndromes With Prominent Myoclonic Seizures
Benign Myoclonic Epilepsy of Infancy (BMEI)
EEG
Treatment and Outcome
Dravet Syndrome
Myoclonic-Astatic Epilepsy of Doose (MAE)
Etiology
Seizure Semiology
EEG
Treatment
Outcome
Juvenile Myoclonic Epilepsy (JME)
Seizure Semiology.
EEG.
Treatment.
Outcomes.
Infantile Spasms
Electroclinical Features
Spasms
Hypsarrhythmia and the Ictal EEG
Classification
Etiologic Factors
Diagnostic Evaluation
Course and Prognosis
Treatment
Hormonal Therapy
Acth
Corticosteroids
Vigabatrin
Surgical Therapy
Other Treatments
Late Onset Epileptic Spasms
References
Selected References
69 Status Epilepticus
Epidemiology
Definitions
Etiology
Clinical Presentation and Initial Management
Time to Treatment
Rationale Behind the Need for Rapid Treatment
Changes in Neurotransmitter Receptors in the Seizing Brain
Time Elapsed From Seizure Onset to Treatment Administration in SE
Treatment Options
Treatment Guidelines for SE
Benzodiazepines as First-Line Treatment
Lorazepam as the Preferred First-Line Drug for SE
Alternatives to the Intravenous Route of Administration
Nonbenzodiazepine Antiseizure Drugs
Refractory SE
Super-Refractory SE
Autoimmune SE and Immune Therapies
Outcome
Neonatal Status Epilepticus
Nonconvulsive Status Epilepticus
Summary
References
Selected References
70 Electroclinical Syndromes: Neonatal Onset
1.0 Introduction
2.0 Benign Neonatal Seizures
2.1 Clinical Features
2.2 Etiology
2.3 Diagnosis
2.4 Differential Diagnosis
2.5 Prognosis
2.6 Management
3.0 Benign Familial Neonatal Epilepsy (BFNE)
3.1 Clinical Features
3.2 Etiology
3.3 Diagnosis
3.4 Differential Diagnosis
3.5 Prognosis
3.6 Management
4.0 Ohtahara Syndrome
4.1 Clinical Features
4.2 Etiology
4.3 Diagnosis
4.4 Differential Diagnosis
4.5 Prognosis
4.6 Treatment
5.0 Early Myoclonic Encephalopathy (EME)
5.1 Clinical Features
5.2 Etiology
5.3 Diagnosis
5.4 Differential Diagnosis
5.5 Prognosis
5.6 Management
6.0 Conclusion
References
Selected References
71 Electroclinical Syndromes: Infantile Onset
Introduction
Generalized Syndromes
Myoclonic Epilepsy in Infancy
Seizures
Other Neurologic Findings
Etiology
EEG Findings
Neuroimaging
Other Laboratory Studies
Differential Diagnosis
Treatment
Outcome
Myoclonic Encephalopathies in Nonprogressive Disorders
Etiology
Seizures and EEG
Neuroimaging
Other Neurologic Findings
Other Laboratory Studies
Differential Diagnosis
Treatment
Outcome
Focal Syndromes
Epilepsy of Infancy With Migrating Focal Seizures
Seizures
Other Neurologic Findings
Etiology
EEG Findings
Neuroimaging
Other Laboratory Studies
Differential Diagnosis
Treatment
Outcome
Benign Epilepsy of Infancy/Benign Familial Infantile Epilepsy
Seizures
Other Neurologic Findings
Etiology
EEG Findings
Neuroimaging
Differential Diagnosis
Treatment
Outcome
Hemiconvulsions, Hemiplegia, and Epilepsy Syndrome (HHE)
Seizures
Other Neurologic Findings
Etiology
EEG Findings
Neuroimaging
Other Laboratory Studies
Differential Diagnosis
Treatment
Outcome
Undifferentiated Syndromes
West Syndrome
Seizures
Other Neurologic Findings
Etiology
EEG Findings
Neuroimaging
Other Laboratory Studies
Treatment
Outcome
Dravet Syndrome
Seizures
Other Neurologic Findings
Etiology
EEG Findings
Neuroimaging
Treatment
Outcome
Genetic Epilepsy With Febrile Seizures Plus (GEFS +)
Seizures
Other Neurologic Findings
Etiology
EEG Findings
Neuroimaging
Treatment
Outcome
Conclusions
References
Selected References
72 Electroclinical Syndromes: Childhood Onset
Introduction
Childhood Generalized Epilepsy Syndromes
Childhood Absence Epilepsy (CAE)
Clinical Characteristics
EEG Findings
Etiology
Treatment
Prognosis
Generalized Epilepsy With Eyelid Myoclonia (Jeavons Syndrome)
Epilepsy With Myoclonic Absences (Tassinari Syndrome)
Epilepsy With Myoclonic-Atonic (Formerly Astatic) Seizures (EMAS)
Lennox-Gastaut Syndrome
Clinical Characteristics
EEG Findings
Etiology
Treatment
Prognosis
Childhood Focal Epilepsy Syndromes
Benign Epilepsy With Centrotemporal Spikes (BECTS, or Benign Rolandic Epilepsy)
Clinical Characteristics
EEG Findings
Etiology
Treatment
Prognosis
Early Onset Childhood Occipital Epilepsy (Panayiotopoulos Syndrome)
Late-Onset Childhood Occipital Epilepsy (Gastaut Syndrome)
Childhood Epilepsies Undetermined Whether Focal or Generalized
Epileptic Encephalopathy With Continuous Spike and Wave During Sleep (CSWS)
Acquired Epileptic Aphasia (Landau-Kleffner Syndrome)
Conclusion
References
Selected References
73 Electroclinical Syndromes: Childhood Onset
Introduction
Ontogenesis and Classification
Epidemiology and Psychosocial Implications of Adolescent Epilepsy
Cognitive, Behavioral, and Compliance Issues
Adolescent Generalized Epilepsies
Juvenile Myoclonic Epilepsy
Juvenile Absence Epilepsy
Genetic Generalized Epilepsies With Convulsions
Genetics of Nonmendelian-Inherited Adolescent Epilepsy
Rare Mendelian-Inherited Progressive Generalized Adolescent Epilepsies
Adolescent Focal Epilepsies
Mesial Temporal Lobe Epilepsy Resulting From Hippocampal Sclerosis
Autosomal-Dominant Partial Epilepsy With Auditory Features
Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy
Treatment
Treatment of Genetic Generalized Epilepsies
Treatment of Focal Epilepsies
Additional Diagnostic Considerations
Chronobiology
Biomarkers
Pharmacogenetics—The Horizon of Epilepsy Treatment
Conclusion
References
Selected References
74 Focal Structural Epilepsy
Introduction
Focal Structural Epilepsy With Focal Malformations of Cortical Development
Focal Cortical Dysplasia
Pathology
Imaging Features
Clinical Features
Etiology
Management
Hemimegalencephaly
Neurologic Features
Neuroimaging
Nonneurologic Features
Etiology
Focal Structural Epilepsy With Neurocutaneous Syndromes
Tuberous Sclerosis Complex
Sturge–Weber Syndrome
Neurologic Features
Neuroimaging
Etiology
Clinical Management
Megalencephaly Capillary Malformation Syndrome
Neurologic Features
Etiology
STRADA (LYK5)–Related Megalencephaly
Focal Structural Epilepsy With Other Lesions
Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis
Neurologic Features
Neuroimaging
Etiology
Medical Treatment
Surgical Treatment
Gelastic Seizures With Hypothalamic Hamartoma
Neurologic Features
Nonneurologic Features
Neuroimaging
Etiology
Clinical Management
Rasmussen Encephalitis
Neurologic Features
Neuroimaging
Etiology
Clinical Management
References
References
75 Other Acquired Epilepsies
Posttraumatic Epilepsy
Early Versus Late Posttraumatic Seizures
Epidemiology
Risk Factors
Natural History and Treatment
Poststroke Epilepsy
Early Versus Late Poststroke Seizures
Epidemiology
Risk Factors
Natural History and Treatment
Epilepsy Associated With Brain Tumors
Epidemiology
Risk Factors
Natural History and Treatment
References
Selected References
76 Inherited Metabolic Epilepsies
Introduction
General Principles
Small Molecule Disorders
Amino and Organic Acid Disorders
Fatty Acid Oxidation Disorders
Mitochondrial Diseases
Urea Cycle Disorders
Disorders of Glucose Homeostasis
Vitamin Dependency States
Neurotransmitter Disorders
Purine and Pyrimidine Defects
Large Molecule Disorders
Disorders of Glycosylation
Lysosomal Storage Disorders
Peroxisomal Diseases
Leukodystrophies
Conclusion
References
Selected References
77 Antiseizure Drug Therapy in Children
Pharmacokinetic Principles
Pharmacodynamics
Dose–Response or Concentration–Response Concept
Tolerance
Physiologic Factors Affecting Drug Disposition in Children
General Considerations
Neonates
Infants and Children
Drug Interactions
Absorption
Protein Binding
Metabolism
Dosage Formulations and Routes of Administration
Monitoring Antiseizure Drug Therapy
Clinical Monitoring of Efficacy
Clinical Monitoring of Adverse Effects
Monitoring of Drug Concentrations
Interpretation of “Optimal Therapeutic Ranges”
When to Obtain Drug Concentrations
What to Measure
Laboratory Tests for Idiosyncratic Reactions
Adverse Drug Reactions to Antiseizure Drugs
Central Nervous System Adverse Reactions
Gastrointestinal Effects
Weight Gain
Weight Loss
Gastric Irritation
Gingival Hyperplasia
Increased Seizures
Osteomalacia
Tremor and Movement Disorders
Other Effects
Anticonvulsant Hypersensitivity Syndrome in Children
Clinical Features
Pathogenesis
Prevention
Managing Adverse Effects
Discontinuation of Antiseizure Drug Therapy
Benefits of Drug Discontinuation
Risks of Drug Discontinuation
References
Selected References
78 Epilepsy Surgery in the Pediatric Population
Historical Background
Indications for Epilepsy Surgery
Preoperative Evaluation
Techniques and Technologies
Seizure Semiology
Physical Examination
Electroencephalography
Magnetic Resonance Imaging
Single-Photon Emission Computed Tomography
Positron Emission Tomography
Magnetic Resonance Spectroscopy
Magnetoencephalography
Functional Mapping
Concept of Congruence
Invasive Intracranial Electroencephalography Monitoring
Types of Surgery
Goals of Surgery
Research Issues: Trends for the Future
References
Selected References
79 Neuromodulation in Epilepsy
Introduction
Vagus Nerve Stimulation
Anterior Nucleus of the Thalamus Deep-Brain Stimulation
Responsive Neurostimulation
Trigeminal Nerve Stimulation
Repetitive Transcranial Magnetic Stimulation for Seizure Suppression
Diagnostic Transcranial Magnetic Stimulation
Transcranial Direct Current Stimulation
Conclusion
References
Selected References
80 Ketogenic Diets
History
Efficacy
Efficacy of the Classic Ketogenic Diet
Efficacy of the Ketogenic Diet for Adults
Efficacy of Alternative Ketogenic Diets
Mechanisms of Action
Oxidation of Fatty Acids: Ketogenesis
Clinical Studies of Ketosis
Experimental Studies of Diets in Animal Models
Selection of Candidates for the Diet
Value of the EEG in Ketogenic Diet Prediction
Initiation and Maintenance
Prehospital Evaluation
Hospitalization
Side Effects
Advantages (and Disadvantages) Compared With Other Treatments for Epilepsy
Advantages
Disadvantages
The Ketogenic Diet in the 21st Century
References
Selected References
Resources
Websites
81 Pediatric Psychogenic Nonepileptic Seizures and Psychiatric Disorders
1. Overview
2. Evaluation of the Patient
Risk Factors
History
Differential Diagnosis Between Epilepsy and PNES
Multidisciplinary Assessment Including Psychiatric Evaluation
3. Psychopathology in Children With PNES
4. Multidisciplinary Treatment Model
The Role of the Neurologist
Basic Principles of Psychiatric PNES Treatment
5. Outcome
Summary
References
Selected References
82 Behavioral, Cognitive, and Social Aspects of Childhood Epilepsy
Cognitive and Behavioral Disorders
Cognitive Disabilities in Children With Epilepsy
Learning Disabilities and Academic Underachievement
Attention Deficit, Impulsivity, and Overactivity
Autism and Autistic Spectrum Disorders
Psychiatric Disorders in Childhood Epilepsy
Behavioral Problems, Conduct Disorders, and Delinquency
Cognitive and Behavioral Outcome of Specific Epilepsy Syndromes
Epileptic Encephalopathy, a Model of System Epilepsy
Infantile Spasms
Epileptic Encephalopathies of Infancy
Lennox–Gastaut Syndrome
Electrical Status Epilepticus in Sleep and Landau–Kleffner Syndrome
Self-Limited Focal Epilepsies of Childhood
Childhood Absence Epilepsy
Effects of Antiseizure Medications on Behavior, Attention, and Mood
General Effects
Psychotropic Effects and Adverse Psychiatric Effects
Forced Normalization
Mood Disorders
Psychosis
Fear of Side Effects and Effective Medication Use
Behavioral and Cognitive Effects of the Older Versus Newer Antiseizure Medications
Phenobarbital
Phenytoin
Valproic Acid
Carbamazepine
Oxcarbazepine
Lamotrigine
Felbamate
Topiramate
Zonisamide
Levetiracetam
Clobazam
Gabapentin
Vigabatrin
Lacosamide
Perampanel
Management of Cognitive, Social, Academic, and Behavioral Problems Associated With Epilepsy
School Inclusion and Academic Planning
Behavior Problems and Discipline
Peer Relationships, Teasing, and Social Isolation
Social and Occupational Adjustment of Adults With Childhood-Onset Epilepsy
References
Selected References
83 Mortality in Children with Epilepsy
Introduction
Epidemiology
Sudden Unexpected Death in Epilepsy
Clinical Risk Factors for Sudden Unexpected Death in Epilepsy
Discussions About Sudden Unexpected Death in Epilepsy With Families and Patients
Prevention of Mortality Related to Seizures
Prevention of Mortality Not Related to Seizures
Conclusions
References
Selected References
Part IX: Nonepileptiform Paroxysmal Disorders and Disorders of Sleep
84 Headache in Children and Adolescents
Introduction
Classification
Migraine Without Aura
Migraine with Aura
Chronic Migraine
Migraine Variants
Tension-Type Headache
Trigeminal Autonomic Cephalalgia
Epidemiology
Migraine Pathophysiology
Evaluation of the Child with Headaches
Neuroimaging
Lumbar Puncture
Clinical Laboratory Testing
Electroencephalogram
Management of Pediatric Migraine
Pharmacologic Therapies for Migraine Headache
Acute Therapy/Outpatient Abortive Therapy
Emergency Room Management of Migraine Exacerbation
Antidopaminergic Drugs.
Nonsteroidal Anti-Inflammatory Drugs.
Antiepileptic Drugs.
Triptan Compounds.
Dihydroergotamine Use in the Emergency Department.
Inpatient Therapy for Severe Debilitating Acute Exacerbation of Primary Headache
Dihydroergotamine Use in the Inpatient Setting.
Sodium Valproate.
Preventive Treatment
Antidepressants.
Antiepileptic Drugs.
Antihistamines.
Beta Blockers.
Botulinum Toxin.
Nutraceuticals for Headache Prevention.
Nonpharmacologic Treatment
Specific Secondary Headache Syndromes
Posttraumatic Headache
Idiopathic Intracranial Hypertension
Intracranial Hypotension
Headache Secondary to a Brain Tumor
Chiari Malformation
Metabolic Causes of Headache in Children
MELAS
CADASIL
References
Selected References
85 Breath-Holding Spells and Reflex Anoxic Seizures
Breath-Holding Spells
Clinical Features
Clinical Laboratory Tests
Pathophysiology
Cyanotic Spells
Pallid Spells
Genetics
Treatment
Reflex Anoxic Seizures
Clinical Features
Pathophysiology
Clinical Laboratory Tests
Treatment
References
Selected References
86 Syncope and Postural Orthostatic Tachycardia Syndrome
Syncope
Epidemiology
Etiology
Cardiovascular-Mediated Syncope
Neurocardiogenic Syncope
Clinical Features
Pathophysiology
Diagnostic Evaluation
Tilt-Table Testing
Treatment
Prognosis
Convulsive Syncope
Reflex Syncope
Situational Syncope
Hyperventilation Syncope
Suffocation or Strangulation Syncope
Metabolic and Drug-Induced Syncope
Psychogenic Syncope
Postural Orthostatic Tachycardia Syndrome
Introduction
Clinical Features
Pathophysiology
I. Hypovolemic and Deconditioned POTS
II. Hyperadrenergic POTS
III. Neuropathic POTS
Comorbidities in POTS
I. Visceral Pain and Dysmotility
II. Chronicfatigue, Neurocognitive Disorders, Insomnia, and Fibromyalgia
III. Nutritional Deficiencies
IV. Headache
V. Ehlers-Danlos Syndrome (EDS)
Clinical and Laboratory Evaluation
Treatment
Conclusions
References
Selected References
87 Nocturnal Paroxysmal Disorders
A. Parasomnias
I. Disorders of Arousal from NREM Sleep
Sleepwalking
Confusional Arousals
Sleep Terrors
Sleep-Related Eating Disorder
Diagnosis
II. Parasomnias Associated with REM Sleep
Nightmares
REM Sleep Behavior Disorder
Recurrent Isolated Sleep Paralysis
III. Other Parasomnias
Nocturnal Enuresis
Exploding Head Syndrome
Sleep-Related Hallucinations
IV. Normal Variants
Sleep Talking
Sleep Starts
V. Other Disorders
Catathrenia
Hypnic Headaches
Head Banging
B. Nocturnal Panic Attacks
C. Sandifer Syndrome
References
Selected References
88 Disorders of Excessive Sleepiness
Assessment of Sleepiness
Clinical Assessment
History
Physical Examination
Subjective Evaluation Tools
Objective Evaluation Tools
Actigraphy
Nocturnal Polysomnography
Multiple Sleep Latency Test (MSLT)
The Maintenance of Wakefulness Test (MWT)
Cerebrospinal Fluid Hypocretin-1 Levels
Histocompatibility Antigen (HLA) Subtypes
Narcolepsy Type 1 (Narcolepsy with Cataplexy)
Pathophysiology
Diagnosis
Treatment
Treatment of Daytime Sleepiness
Wake-Promoting Agents
Stimulants
Treatment of Cataplexy
Treatment of Nocturnal Sleep Fragmentation
Sodium Oxybate
Future Treatments
Narcolepsy Type 2
Kleine-Levin Syndrome (KLS)
Insufficient Sleep Syndrome (ISS)
References
Selected References
89 Restless Legs Syndrome and Periodic Limb Movement Disorder in Children and Adolescents
Introduction
Prevalence
Symptoms
Presentation
Diagnosis
Iron Deficiency
Iron and Neuroimaging
Family History and Genetics
Coexistent Conditions
Treatment
Conclusions
References
Selected References
90 Apparent Life-Threatening Event and Sudden Infant Death Syndrome
Apparent Life-Threatening Events
Introduction
Definition
Epidemiology
Risk Factors
Etiology/Differential Diagnosis
Evaluation
History
Physical Examination
Diagnostic Testing
Inpatient Versus Outpatient Management
Home Monitoring
Risk of SIDS
Risk of Death
Sudden Infant Death Syndrome
Introduction
Definition
Pathogenesis
The Triple-Risk Model
The 5-Hydroxytryptamine System
Epidemiology
Risk Factors
Prone and Side Sleep Position
Bed-Sharing
Soft Bedding and Bedding Accessories
Overheating
Maternal Smoking
Prematurity
Infection
Genetics
Prevention
References
Selected References
Part X: Disorders of Balance and Movement
91 The Cerebellum and the Hereditary Ataxias
The Language and Logic of Cerebellar Dysfunction
Nonhereditary Causes of Ataxia
The Hereditary Ataxias
Autosomal Recessive Inherited Syndromes
Friedreich Ataxia (Spinocerebellar Ataxia— MIM 229300)
Ataxia-Telangiectasia (Louis-Bar Syndrome— MIM 208900)
Early Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia (Ataxia-Oculomotor Apraxia 1, AOA1—MIM 208920)
Mitocondrial DNA Depletion Syndrome 7 (Hepatocerebral Type) (MTDPS7—MIM 271245); Infantile Onset Spinocerebellar Ataxia
Autosomal Dominant Inherited Ataxias (Spinocerebellar Ataxias)
Episodic Ataxias
Hereditary Spastic Ataxias
X-Linked Spinocerebellar Ataxias
Management of Cerebellar Dysfunction and Ataxia
References
Selected References
92 Acute Cerebellar Ataxia
Clinical Evaluation of Acute Ataxia
Causes of Acute Cerebellar Ataxia
Inflammatory Cerebellitis
Infectious/Postinfectious
Demyelinating
Paraneoplastic
Intoxication
Mass Lesions
Trauma
Vascular
Metabolic/Genetic
Other Neurologic Disorders
Psychogenic
Investigations in Acute Ataxia
Computed Tomography and Magnetic Resonance Imaging
Cerebrospinal Fluid
Electromyography and Electroencephalography
Toxicology
Urinary Catecholamines/Metaiodobenzylguanidine Scintigraphy
Other Tests
Treatment and Prognosis
References
Selected References
93 Movement Disorders
Introduction
Characteristic Features of Pediatric Movement Disorders
Diagnosis of Movement Disorders
Etiology of Movement Disorders in Children
Approach to Treatment
Classification of Childhood Movement Disorders
Chorea
Sydenham Chorea
Medication-Induced Chorea
Genetic Chorea
Chorea Associated With Systemic Illness and Autoimmune Disorders
Ballism
Treatment of Chorea
Dystonia
Genetic Dystonias
DYT-1 Dystonia
DYT-5 Dystonia (Dopa-Responsive Dystonia)
DYT11 Dystonia (Myoclonus Dystonia Syndrome)
Dystonias Associated With Neurodegenerative Disorders
Pantothenate Kinase-Associated Neurodegeneration (PKAN)
Lesch-Nyhan Disease
Dystonia Associated With Other Metabolic Disorders
Organic Acidemias
Non-Dopa-Responsive Disorders of Dopamine Synthesis and Metabolism
Dystonia Due to Nonprogressive Disorders
Cerebral Palsy
Kernicterus
Medication-Induced Dystonias
Treatment of Dystonia
Tremor
Primary Tremor Disorders
Secondary Tremor Disorders
Treatment of Tremor
Parkinsonism
Juvenile Parkinson Disease
Secondary Parkinsonism
Treatment of Parkinsonism
Myoclonus
Classification of Myoclonus
Physiologic and Developmental Myoclonus
Essential Myoclonus
Symptomatic Myoclonus
Treatment of Myoclonus
Stereotypy
Other Movement Disorders
Restless Legs Syndrome and Periodic Leg Movements of Sleep
Hyperekplexia
Bobble-Head Doll Syndrome
References
Selected References
94 Paroxysmal Dyskinesias
Introduction
Historical Context and Terminology
Classic Phenotypes of Paroxysmal Dyskinesia
Paroxysmal Kinesigenic Dyskinesia
Clinical Features
Genetics
Diagnosis
Treatment
Paroxysmal Nonkinesigenic Dyskinesia
Clinical Features
Genetics
Diagnosis
Treatment
Paroxysmal Exertion-Induced Dyskinesia
Clinical Features
Genetics
Diagnosis
Treatment
Other Phenotypes
Paroxysmal Hypnogenic Dyskinesia
Genotype–Phenotype Association in Paroxysmal Dyskinesia
Acknowledgments
References
Selected References
95 Movement Disorders of Infancy
Benign Neonatal Sleep Myoclonus
Benign Myoclonus of Early Infancy
Jitteriness
Shuddering
Paroxysmal Tonic Upgaze of Infancy
Spasmus Nutans
Head Nodding
Benign Paroxysmal Torticollis
Benign Idiopathic Dystonia of Infancy
Posturing during Masturbation
References
Selected References
96 Drug-Induced Movement Disorders in Children
Introduction and Overview
Definition of Drug-Induced Movement Disorders
Clinical Characteristics—Phenomenology of Drug-Induced Movement Disorders in Children
Drug-Induced Movement Disorders
Drug-Induced Movement Disorders Associated with Dopamine Receptor Blockade: Typical Antipsychotics, Atypical Antipsychotics
Epidemiology
Clinical Features of Drug-Induced Movement Disorders Induced by Dopamine Receptor Blocking Agents
Pathophysiology
Diagnosis of Acute, Chronic, Tardive, and Withdrawal Emergent Syndromes
Treatment of Drug-Induced Movement Disorders Related to Use of Dopamine Receptor Blocking Agents
Acute Drug-Induced Movement Disorders.
Chronic Drug-Induced Movement Disorders.
Tardive Movement Disorders.
Neuroleptic Malignant Syndrome
Drug-Induced Movement Disorders Associated with Treatment of Attention Deficit Hyperactivity Disorder
Epidemiology of Psychostimulant Use in Children
Clinical Features
Pathophysiology
Diagnosis
Treatment
Drug-Induced Movement Disorders Associated with Other Medications
Serotonin Reuptake Inhibitors
Antiseizure Medications
Drug-Induced Movement Disorders Associated with Chemotherapeutic, Immunomodulatory, and Anti-infectious Medications
Conclusion
References
Selected References
97 Cerebral Palsy
Outline
I. Introduction
II. Current Definition
III. Presentation and Diagnostic Assessment
IV. Epidemiology
V. Etiologic Spectrum
VI. Classification
A. Common Cerebral Palsy Syndromes
B. Functional Classification
VII. Comorbidity Spectrum
IX. Conclusion
References
Selected References
98 Tics and Tourette Syndrome
Tic Phenomenology
Tic Disorders
Course
Epidemiology
Comorbid Disorders
Etiology
Neurobiology of Tic Disorders
Anatomic Abnormalities
Neurotransmitter Abnormalities
Treatment
References
Selected References
Part XI: White Matter Disorders
99 Genetic and Metabolic Disorders of the White Matter
Introduction
Part I. Hypomyelinating White Matter Disorders
1. Pelizaeus-Merzbacher Disease
2. Pelizaeus–Merzbacher-Like Disease
3. 4H Syndrome
4. Hypomyelination Related to Cytoplasmic tRNA Synthetase Defects
5. Oculodentodigital Dysplasia
6. Hypomyelination With Congenital Cataract
7. Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum
8. Sialic Acid Storage Disorders
9. Fucosidosis
10. Serine Synthesis Defects
11. Cockayne Syndrome and Trichothiodystrophy
12. 18q Minus Syndrome
13. SOX10-Associated Disorders
Part II. White Matter Disorders With Demyelination
A. Primary Demyelinating Leukodystrophies
1. Alexander Disease
2. X-Linked Adrenoleukodystrophy
3. Peroxisome Biogenesis Disorders
4. Metachromatic Leukodystrophy
5. Metachromatic Leukodystrophy-Like Variants
6. Krabbe Disease or Globoid Cell Leukodystrophy
7. Saposin A Deficiency
8. Sjögren-Larsson Syndrome
B. White Matter Disorders With White Matter Vacuolization and Intramyelinic Edema
1. Canavan Disease
2. eIF2B-Related Disorder (Vanishing White Matter)
3. Megalencephalic Leukoencephalopathy With Subcortical Cysts
4. ClC-2-Related Leukoencephalopathy
C. Calcifying Leukoencephalopathies
1. Aicardi-Goutières Syndrome
2. Cerebroretinal Microangiopathy With Calcifications and Cysts
3. Leukoencephalopathy With Calcifications and Cysts
4. Bandlike Intracranial Calcification With Simplified Gyration and Polymicrogyria
5. Cockayne Syndrome
6. Spondyloenchondrodysplasia
7. Cytomegalovirus
8. Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
9. Intracranial Calcification Associated With Leukoencephalopathy
10. Dihydropterine Reductase Deficiency
11. 27-Hydroxylase Deficiency or CTX
12. Bilateral Occipital Calcifications With Leukoencephalopathy, Seizures, and Clinical or Subclinical Celiac Disease
13. Familial Hemophagocytic Lymphohistiocytosis
D. Cystic Leukoencephalopathies
E. Leukoencephalopathies With Brainstem, Cerebellum, and Spinal Cord Involvement
1. Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation
2. Alexander Disease (AxD)
3. Polyglucosan Body Disease (PGBD, OMIM 263570)
4. Autosomal Dominant Leukodystrophy With Autonomic Disease (LaminB1)
F. Adult-Onset Leukoencephalopathies
Part III. Secondary Leukoencephalopathies to Inborn Errors of Metabolism, Excluding the Classical Lysosomal and Peroxisomal Disorders
Acknowledgments
References
Selected References
100 Acquired Disorders Affecting the White Matter
Acute Central Nervous System Demyelination
Optic Neuritis
Transverse Myelitis
Polyfocal Demyelination
Other Clinical Presentations
Investigation of a Child with Acute Demyelination
Laboratory Investigations
Magnetic Resonance Imaging
Management of Acute Demyelination
Relapsing Demyelinating Disorders
Multiple Sclerosis
Epidemiology of Pediatric Multiple Sclerosis
Diagnostic Criteria for Pediatric Multiple Sclerosis
Clinical Course of Pediatric Multiple Sclerosis
Magnetic Resonance Imaging Features of Pediatric Multiple Sclerosis
Pathobiological Insights Into Pediatric Multiple Sclerosis
Immunomodulatory Therapy in Pediatric Multiple Sclerosis
Principles of Immunomodulatory Therapy.
Second-Line Therapies.
General Care Issues
Multiphasic Acute Disseminated Encephalomyelitis
Neuromyelitis Optica
Epidemiology of Pediatric Neuromyelitis Optica
Clinical Features of Pediatric Neuromyelitis Optica
Symptomatic Brain Involvement in Neuromyelitis Optica
Diagnostic Criteria for Pediatric Neuromyelitis Optica
Systemic Autoimmunity in Neuromyelitis Optica
Laboratory Features of Neuromyelitis Optica
Magnetic Resonance Imaging in Neuromyelitis Optica
Treatment of Pediatric Neuromyelitis Optica
Conclusions
References
Resources
Selected References
Part XII: Brain Injury and Disorders of Consciousness
101 Disorders of Consciousness in Children
Historical Perspective
Neural Correlates of Consciousness
Approaches to Studying the NCC
Neuroimaging
Neurophysiology
Neural Correlates of Consciousness in DOC Patients
Definitions
Impairment of Consciousness With Activated Mental State
Impairment of Consciousness With Reduced Mental State
Vegetative State, Minimally Conscious State, and Related Conditions
Vegetative State/Unresponsive Wakefulness Syndrome
Minimally Conscious State
Locked-in Syndrome
Akinetic Mutism
Brain Death
Consciousness Rating Scales
Pathophysiology
Etiologies
Evaluation
Clinical Evaluation
Identification of Cause
History
General Physical Examination
Neurologic Examination
Brain Herniation
Historical Perspective
Herniation Syndromes
Uncal Herniation
Central or Transtentorial Downward Herniation
Infratentorial (Cerebellar) Herniation Syndromes
Diagnostic Testing
Treatment
1. Maintain Airway, Oxygenation. and Ventilation
2. Maintain Circulation
3. Administer Glucose
4. Correct Acid-Base and Electrolyte Imbalance
5. Consider Specific Antidotes
6. Reduce Increased Intracranial Pressure
7. Stop Seizures
8. Treat Infection
9. Adjust Body Temperature
10. Manage Agitation
11. Treatment of Chronic Impairments
Monitoring of the Comatose Patient
Outcome Measurement
Prognosis
Traumatic Injury
Nontraumatic Injury
Clinical Neurophysiology
Neuroimaging
Conclusions
Acknowledgment
References
Selected References
102 Traumatic Brain Injury in Children
Introduction and Background
Epidemiology of Pediatric Traumatic Brain Injury
Anatomy
Biomechanics
Pathophysiology of Traumatic Brain Injury
The Posttraumatic Neurometabolic Cascade
Patient History
Examination
Immediate Management
Acute Clinical Syndromes
Herniation Syndromes
Diffuse Cerebral Swelling
Diffuse Axonal Injury
Paroxysmal Sympathetic Hyperactivity
Abusive Head Trauma
Subarachnoid Hemorrhage
Subdural Hematoma
Epidural Hematoma
Cerebral Contusion and Laceration
Traumatic Arterial Dissection and Traumatic Aneurysms
Concussion
Sports Concussion/Repeated Concussion
Epidemiology
Symptomatology
Sequelae
Second-Impact Syndrome
Skull Fractures
Scalp Lacerations and Hematomas
Diagnostic Evaluation
Skull X-Rays
Computed Tomography
Magnetic Resonance Imaging and Angiography
Neurophysiological Testing
General Management Principles for Severe Pediatric TBI
Stabilization and Prevention of Secondary Injury
Intracranial Pressure Management
Sedation and Neuromuscular Blockade
Hyperventilation
Hyperosmolar Therapy
Intracranial Pressure Monitoring—Indications and Treatment Threshold
Cerebrospinal Fluid Drainage
Barbiturates
Temperature Control and Hypothermia
Surgical Management of ICP
Early Posttraumatic Seizures and Seizure Prophylaxis
Supportive Care
General Management of Mild Traumatic Brain Injury/Concussion
Guidelines for Return to Play Following Sports Concussion
Prognosis and Outcome
Late Clinical Syndromes
Vegetative and Minimally Conscious States
Cognitive Impairment and Behavioral Disorders
Sleep Disorders
Spasticity and Motor Impairment
Posttraumatic Hydrocephalus
Posttraumatic Epilepsy
Subacute and Chronic Subdural Hematoma
Posttraumatic Headache
Postconcussive Syndrome
Late Complications of Skull Fracture
Conclusions
References
Selected References
103 Abusive Head Trauma
Introduction
Historical Perspective
Terminology
Developmental Differences Predisposing the Immature Neuraxis to Injury
Mechanical Factors
Biologic Factors
Responses to Injury
Mechanisms of Injury
Contribution of Hypoxia-Ischemia
Clinical Features
Acute Presentation
Early Posttraumatic Seizures
Subacute and Chronic Presentation
Predictors of Outcome
Mortality Predictors.
Sequelae of Abusive Head Trauma
Posttraumatic Epilepsy
Cognitive and Executive Function
Behavioral Sequelae
Visual Sequelae
Motor Sequelae
Neuropathology
Pathologic Features
Extracranial Injuries
Scalp.
Skull Fractures.
Intracranial Injuries
Subdural Hematoma.
Mixed-Density or “Hyperacute” Subdural Hematoma.
Chronic Subdural Hematoma.
Chronic Subdural Effusions.
Subarachnoid Hemorrhage.
Epidural Hematomas.
Brain Injuries
Ocular Pathology
Retinal Hemorrhages (Table 103-1).
Optic Nerve Sheath Hemorrhage.
Spinal Injuries
Differential Diagnosis
Unintentional Injury
Falls.
Birth Trauma
Neurometabolic Disease
Differential of Specific Findings
Retinal and Optic Nerve Sheath Hemorrhages
Extensive Subarachnoid Hemorrhage
Clinical Assessment
General Examination
General Examination
Neurologic Examination
Autonomic and Neuroendocrine Responses
Laboratory and Radiographic Evaluation
Laboratory Evaluation
Biochemical Markers.
Neuroimaging and Radiographic Evaluation
Postmortem Examination
Making the Diagnosis of Abusive Head Injury
General Considerations
Evaluating the History
Timing
Lucid Interval
Dating by Neuroimaging
Medicolegal Issues
Conclusions
References
Selected References
104 Hypoxic-Ischemic Encephalopathy in Infants and Older Children
Cardiac Arrest: Etiology, Survival, and Neurologic Outcome
Postcardiac-Arrest Syndrome
Response to Inadequate Oxygen Delivery: Mechanisms of Brain Injury
Brain Energy Failure
Calcium-Mediated Injury
Excitotoxic Injury
Activation of Intracellular Enzymes
Phospholipase Release of Free Fatty Acids
Activation of Nitric Oxide Synthesis
Formation of Oxygen Radicals
Neuroinflammation, Glia, and the Neurovascular Unit
Genetic Damage and Regulation
Autophagy
Clinical Pathophysiology
Cerebral Blood Flow and Metabolism After Resuscitation
Major Disorders Causing Cardiac Arrest
Abusive Head Trauma
Sudden Infant Death Syndrome
Drowning (Submersion Injury)
Epidemiology
Management.
Strangulation Injury
Lightning and Electrical Injuries
Electrical Shock
Sudden Cardiac Arrest in Children and Adolescents
Neurologic Complications After Cardiac Arrest
Delayed Posthypoxic Injury
Postischemic Seizures
Delayed Postanoxic Myoclonic Seizures
Paroxysmal Sympathetic Hyperactivity
Neurologic Prognosis After Cardiac Arrest
Electroencephalography Following Cardiac Arrest
Somatosensory- and Auditory-Evoked Potentials
Neuroimaging
Treatment
Temperature Control
Resuscitation
Intracranial Pressure Monitoring and Control
Glucose Homeostasis
Cardiovascular Support
Extracorporeal Membrane Oxygenation-Cardiopulmonary Resuscitation
Postcardiac-Arrest Brain Injury—Potential Therapies
Dilemma of Neurologic Morbidity
References
Selected References
105 Disorders of Intracranial Pressure
Introduction
Pathophysiology of Raised Intracranial Pressure
Compliance and Cerebral Blood Flow Changes with Age
Cerebral Autoregulation
Effects of Intracranial Hypertension on Autoregulation
Regulation of Cerebral Blood Flow
Intracranial Pressure Monitoring
History
Methods of Intracranial Pressure Monitoring
Noninvasive Approaches to Intracranial Pressure Monitoring
Thresholds and Doses of Raised Intracranial Pressure
Evidence Supporting Age-Dependent Physiologic Thresholds
Lessons and Limitations of These Studies
Intracranial Hypertension Related to Compromise of Autoregulation
Calculation of Cerebrovascular Reactivity
Autoregulation-Directed Therapy in Pediatric Neurotrauma
Linking Intracranial Pressure and Cerebral Metabolism
Utility of Measurement of Intracranial Pressure
Clinical Manifestations of Raised Intracranial Pressure
Physical Examination Findings
Management of Acutely Elevated Intracranial Pressure
Initial Assessment, Imaging, and Surgical Intervention
General Principles of Medical Management
Evidence in Support of Guideline-Directed Management of Intracranial Pressure
Intracranial Pressure-Directed Therapy
Spontaneous Intracranial Hypotension
Chronic Intracranial Hypertension
Idiopathic Intracranial Hypertension
Treatment of Idiopathic Intracranial Hypertension
Conclusions
References
Selected References
106 Spinal Cord Injury
Epidemiology
Anatomy
Pathogenesis: Mechanisms of Spinal Cord Injury
Clinical Assessment
History
General Physical Examination
Neurologic Examination
Laboratory Studies
Radiographic Evaluation
Electrophysiologic Evaluation
Lumbar Puncture
Clinical Syndromes
Intraspinal Intramedullary Injuries
Complete Spinal Cord Injuries
Incomplete Spinal Cord Injuries
Cervical Nerve Root/Brachial Plexus Neuropraxia
Cervical Cord Neuropraxia
Cervicomedullary Syndrome
Central Spinal Cord Syndrome
Anterior Spinal Cord Syndrome
Posterior Spinal Cord Syndrome
Brown-Séquard Syndrome
Conus Medullaris Syndrome
Intraspinal Extramedullary Injuries
Spinal Epidural Hematoma
Spinal Subdural Hematoma
Spinal Subarachnoid Hemorrhage
Spinal Epidural Abscess
Spinal Arachnoid Cysts
Spinal Epidermoid Tumor
Herniation of Nucleus Pulposus
Cauda Equina Injuries
Catastrophic Spinal Cord Injuries
Supraspinal Changes
Management
Short-Term Management
Spine Immobilization and Supportive Care
Completed Randomized Controlled Clinical Trials
Methylprednisolone, Naloxone, and Tirilazad
Additional Beneficial Treatments
Long-Term Management
Cervical Spine Immobilization
Supportive Medical Care
Physical Therapy
Functional Electrical Stimulation (FES)
Gait Training
Adaptive Technology
Psychological Therapy
The Multidisciplary Needs of the Child With a Spinal Cord Injury
Surgical Management
Prognosis
Prevention
References
Suggested References
107 Determination of Brain Death in Infants and Children
Historical Perspective
Legal Definition of Brain Death
Epidemiology
Incidence of Brain Death
Etiologies of Brain Death
Outcome after Diagnosis of Brain Death
Neurologic Evaluation
Clinical Examination
Cerebral Unresponsivity
Brainstem Examination
Number of Examinations, Examiners, and Observation Periods
Number of Examinations and Examiners.
Duration of Observation Periods.
Apnea Testing
Technique for Performing Apnea Testing.
Ancillary Neurodiagnostic Studies
Electroencephalogram
Electroencephalogram in Pediatric Brain Death
Measurements of Cerebral Perfusion
Cerebral Angiography
Radionuclide Imaging
Computed Tomographic Angiography and Perfusion
Magnetic Resonance Imaging and Magnetic Resonance Angiography
Transcranial Doppler Ultrasonography
Digital Subtraction Angiography
Xenon Computed Tomography
Positron Emission Tomography
Magnetic Resonance Spectroscopy
Comparison of Electroencephalogram and Cerebral Blood Flow Studies
Evoked Potentials
Brain Tissue Oxygenation
Brain Death in Newborns
Epidemiology
Clinical Examination
Duration of Observation
Apnea Testing
Ancillary Studies
Determination of Brain Death in the Comatose Pediatric Patient
Discussions with Family Members and Staff
Organ Donation
References
Selected References
Part XIII: Cerebrovascular Disease in Children
108 Development and Function of the Cerebrovascular System
Introduction
Brain Vascular Formation and Differentiation
Vasculogenesis and Angiogenesis
Smooth Muscle Differentiation
Endothelial Differentiation and the Blood-brain Barrier
Fetal and Neonatal Cerebrovascular Contractility
Calcium Handling and the Contractile Apparatus
Ion Pumps and Channels
Vasoactive Ligands and Receptors
Fetal and Neonatal Whole Brain Cerebrovascular Reactivity
Flow-Metabolism Coupling
Hypercapnic Vasodilation
Hypoxic Vasodilation
Autoregulation
Neurovascular Mechanisms
Conclusions
References
Selected References
109 Arterial Ischemic Stroke in Infants and Children
Overview and Definitions
Epidemiology, Mortality, and Burden of Pediatric Stroke
Pathophysiology
Arterial Circulation: Anatomy and Vascular Patterns of AIS
Mechanisms of Thromboembolism
Mechanisms of Infarction
Risk Factors
Infection
Arteriopathies
Focal or Transient Cerebral Arteriopathy.
Primary Angiitis of the Central Nervous System and Other Conditions Associated with Cerebral Arteriopathy.
Dissection and Other Physical Injury.
Moyamoya Disease and Moyamoya Syndrome.
Congenital or Genetic Arteriopathies.
Cardiac
Prothrombotic and Hematological Disorders
Sickle Cell Disease
Additional Considerations
Clinical Features and Diagnostic Delays
Diagnosis: Neuroimaging
Treatment
Stroke Unit Care and Neuroprotection
Thrombolysis and Thrombectomy
Antithrombotic Therapies
Anticoagulation.
Antiplatelet Therapy.
Malignant Cerebral Edema
Outcomes and Chronic Management
Sequelae of AIS
Stroke Recurrence
References
References
110 Sinovenous Thrombosis in Infants and Children
Introduction
Epidemiology
Pathogenesis
Sinovenous Circulation: Anatomy and Vascular Patterns
Intracranial Venous Physiology
Mechanisms of Thrombosis
Mechanisms of Brain Injury
Clinical Features
Risk Factors
Infection
Anemia
Prothrombotic Disorders
Acute Systemic Conditions
Chronic Systemic Conditions
Diagnosis: Neuroimaging
Computed Tomography
Magnetic Resonance Imaging
Catheter Angiography
Treatment
Antithrombotic Therapy
Anticoagulation Therapy
Endovascular Treatment and Thrombolysis
Nonantithrombotic Therapies
Increased Intracranial Pressure
Seizures
Steroids
Risk Factor Management
Outcome
References
Selected References
111 Vascular Malformations, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage in Infants and Children
Introduction and Epidemiology
Initial Management
Acute Medical and Surgical Monitoring and Management
Increased Intracranial Pressure: Signs, Symptoms, and Monitoring
Increased ICP: Medical Management
Increased ICP: Surgical Management
Intraparenchymal Hemorrhage Evacuation
Hemicraniectomy
Seizures: Monitoring and Treatment
Recurrent Hemorrhage
Outcomes
High Flow Lesions
Arteriovenous Malformations
Evaluation
Treatment
Arteriovenous Fistulas
Definition
Presentation
Evaluation
Treatment
Outcome
Vein of Galen Malformations
Definition
Evaluation
Treatment
Outcome
Low Flow Lesions
Cavernous Malformations
Definition
Presentation
Evaluation
Treatment
Treatment
Outcome
Aneurysms
Definition
Presentation
Evaluation
Treatment
Outcome
References
Selected References
112 Cerebral Arteriopathies in Children
Cerebral Arteriopathies in Children
Focal Cerebral Arteriopathy/Transient Cerebral Arteriopathy
Moyamoya Arteriopathy
Arteriopathy of Sickle Cell Disease
Cervicocephalic Arterial Dissection
Central Nervous System Vasculitis
Primary Central Nervous System Vasculitis
Secondary Vasculitis
Fibromuscular Dysplasia
Diagnosis of Cerebral Arteriopathy
Follow Up
Conclusion
References
Selected References
113 Coagulation Disorders and Cerebrovascular Disease in Children
Introduction
Coagulation Disorders in Pediatric Arterial Ischemic Stroke
Acquired Thrombophilia (Bernard et al., 2011)
Presentation
Evaluation
Treatment
Genetic Thrombophilia (Bernard et al., 2011)
Presentation
Evaluation
Treatment
Sickle Cell Disease
Presentation
Evaluation and Treatment
Coagulation Disorders in Pediatric Cerebral Sinovenous Thrombosis
Acquired Thrombophilia
Presentation
Evaluation
Treatment
Genetic Thrombophilia
Presentation
Diagnosis
Treatment
Coagulation Disorders in Pediatric Hemorrhagic Stroke
Introduction
Evaluation
Treatment
Other Rare Bleeding Disorders
References
Selected References
Part XIV: Infections of the Nervous System
114 Bacterial Infections of the Nervous System
Acute Bacterial Meningitis
Epidemiology
Pathogenesis
Clinical Manifestations
Clinical Presentations of Neonatal Meningitis
Infection of Implantable Devices
Diagnostic Evaluation
Cerebrospinal Fluid Analysis and Other Laboratory Testing
Neuroimaging
Complications
Pathophysiologic Changes
Seizures
Deafness and Cranial Nerve Damage
Neuronal Damage
Hydrocephalus
Septic Shock and Disseminated Intravascular Coagulation
Extraaxial Fluid Collections
Brain Abscess
Pathology
Treatment
General Care
Antibiotics
Antiinflammatory Therapy
Fluid Therapy
Prognosis
Prevention
Immunization
Chemoprophylaxis
Recurrent Acute Bacterial Meningitis
Chronic (Subacute) Bacterial Meningitis
Tuberculous Meningitis
Epidemiology and Pathogenesis
Clinical Characteristics
Diagnosis
Treatment
Syphilis
Epidemiology and Pathogenesis
Clinical Characteristics
Diagnosis
Treatment
Lyme Disease (Lyme Neuroborreliosis)
Clinical Characteristics
Diagnosis
Treatment and Outcome
Leptospirosis
Aseptic Meningitis
Other Bacterial Infections of the Nervous System
Bartonella
Mycoplasma pneumoniae
Leprosy (Hansen’s Disease)
Central Nervous System Abscess
Brain Abscess
Epidemiology and Pathogenesis
Clinical Manifestations and Diagnosis
Neurosurgical Management and Antimicrobial Therapy
Epidural Abscesses
Spinal Epidural Abscess
References
Selected References
115 Viral Infections of the Nervous System
General Considerations
Epidemiology of Viral Infections
Clinical Features of Virus-Induced Neurologic Disorders
Meningitis
Encephalitis
Other Disorders
Intrauterine Viral Infections
Diagnosis
Cerebrospinal Fluid
Neuroimaging
Microbiological Evaluation
Treatment
Supportive Care
Specific Medications
Selected Viral Infections
Herpesviruses
Herpes Simplex Viruses Types 1 and 2
Clinical Manifestations
Diagnosis
Treatment and Outcome
Cytomegalovirus
Clinical Manifestations
Diagnosis
Treatment and Outcome
Epstein-Barr Virus
Clinical Manifestations
Diagnosis, Treatment, and Outcome
Flaviviruses
West Nile Virus
Clinical Features
Diagnosis, Treatment, and Outcome
Paramyxoviruses
Measles and Subacute Sclerosing Panencephalitis
Clinical Features
Diagnosis
Treatment and Outcome
Rhabdoviruses
Rabies Virus
Clinical Features
Diagnosis
Treatment and Outcome
Arenaviruses
Lymphocytic Choriomeningitis Virus
Influenza viruses
Retroviruses
Human Immunodeficiency Virus
Clinical Features
Diagnosis
Treatment and Outcome
Emerging Viral Infections
Nipah Virus
Dengue Virus
Parechoviruses
Chikungunya Virus
Zika Virus
References
Selected References
116 Fungal, Rickettsial, and Parasitic Diseases of the Nervous System
Fungal Diseases
Cryptococcosis
Coccidioidomycosis
North American Blastomycosis
South American Blastomycosis
Histoplasmosis
Nocardia
Actinomycosis
Aspergillosis
Clinical Characteristics, Clinical Laboratory Tests, and Diagnosis
Candidiasis
Zygomycosis
Scedosporium spp. Infection
Rickettsial Diseases
Rocky Mountain Spotted Fever
Parasitic Diseases
Protozoal Infections of the Central Nervous System
Amebic Infections of the Central Nervous System
Primary Amebic Meningoencephalitis: Naegleria fowleri
Granulomatous Amebic Encephalitis: Acanthamoeba spp. and Balamuthia mandrillaris
Granulomatous Amebic Encephalitis: Balamuthia mandrillaris
Toxoplasmosis
Malaria
Trypanosomal Infections of the Nervous System
Chagas Disease
African Sleeping Sickness
Helminths
Baylisascaris Procyonis Infection
Angiostrongylus Infection
Gnathostomiasis
Cestodes
Sparganosis
Echinococcosis
Cysticercosis
Coenurosis
Schistosomiasis
Paragonimiasis
References
Selected References
117 Neurologic Complications of Immunization
Assessing Causality
Vaccine Injury Compensation Program
Types of Vaccines
Vaccines Composed of Whole-Killed Organisms
Inactivated Polio Vaccine
Influenza Virus Vaccine
Guillain–Barré Syndrome.
Multiple Sclerosis.
Acute Disseminated Encephalomyelitis.
Bell’s Palsy.
Narcolepsy.
Rabies Vaccine
Whole-Cell Pertussis Vaccine
Hepatitis A Vaccine
Vaccines Composed of Live-Attenuated Viruses
Measles: Rubeola
Mumps
Rubella
Oral Polio Vaccine
Varicella
Smallpox
Rotavirus
Component Vaccines
Acellular Pertussis Vaccine
Meningococcal Conjugate Vaccine
Haemophilus Influenzae Type b
Pneumococcal Conjugated Vaccine
Human Papillomavirus Vaccine
Tetanus and Diphtheria
Recombinant Vaccines
Hepatitis B Vaccine
Combination Vaccines and Additives
Mumps, Measles, and Rubella Vaccine and Autism
Thimerosal-Containing Vaccines and Developmental Disorders of Childhood
Vaccine Injection–Related Outcomes
Deltoid Bursitis
Syncope
References
Selected References
Part XV: Immune Mediated Disorders of the Nervous System
118 Paraneoplastic Neurologic Syndromes
Introduction
History of Paraneoplastic Syndromes
Definition
Diagnosis
Treatment
Classical PNDs
Lambert–Eaton Myasthenic Syndrome
Opsoclonus Myoclonus Ataxia Syndrome
Subacute Sensory Neuronopathy
Nonclassical PNS
Paraneoplastic Cerebellar Degeneration
Stiff-Person Syndrome
Limbic Encephalitis
Cancer-Associated Retinopathy
Autoimmune Encephalitides
Anti-N-methyl-D-aspartate Receptor Encephalitis
Chapter Summary and Future Perspective
References
Selected References
119 Immune-Mediated Epilepsy, Movement Disorders, and Hashimoto’s Encephalopathy in Children
Introduction
Background
Definitions: Immune Activation, Immune Mediation, Autoimmune
Autoantibody: The Cell-Surface Paradigm
Autoantibody Methodology
Autoantibody Pathogenic Mechanisms
Immune-Mediated Epilepsy
Autoimmune Encephalitis Syndromes
Autoantibody Associations with Epilepsy
Guidelines for Identification of Autoimmune Epilepsy
Autoimmune Movement Disorders
Background
Autoimmune Encephalitis Associated with Movement Disorders (Table 119-2)
Sydenham Chorea
PANDAS, PANS, and Tourette Syndrome
Hashimoto Encephalopathy or SREAT
Background
Clinical Syndrome
Etiology
Treatment of Autoimmune CNS Disease and Therapeutic Decision Making
References
Selected References
120 Opsoclonus Myoclonus Syndrome
Introduction
Clinical Aspects
Presentation and Course
Differential Diagnosis
Genetics
Etiology
Epidemiology
Diagnostic Testing
Tumor Detection
Neuroinflammation Detection
Ancillary Testing
Pretreatment Immune Health
ACTH or Dexamethasone Challenge Test
Standard of Care and Quality of Life
Immunopathogenesis
Tumor Immunology
CNS Inflammatory Mediators
Immune Dysregulation.
Inflammatory Proteins.
Brain-Related Proteins.
The Effect of Immunotherapy on Brain Inflammation.
Autoantibodies.
Treatment
Treatment Strategy
The Front-Loaded Approach.
The Staggered Approach.
Integrating Neuroinflammation with Clinical Assessment.
Antitumor Therapy
Immunotherapy
IVIg.
Corticosteroids.
ACTH 1-39.
Monoclonal Antibody Therapy.
Cyclophosphamide.
Steroid Sparers.
Methotrexate.
Plasmapheresis.
Inadequate Response
Potential Side Effects and Safety Monitoring
Supportive Therapy
Management of Relapse and Progression
Relapse
Progression
Immunization Issues
Future Directions
References
Selected References
121 Neurologic Manifestations of Rheumatic Disorders of Childhood
Juvenile Idiopathic Arthritis (Chronic Arthropathies)
Neurologic Manifestations
Systemic Juvenile Idiopathic Arthritis
Acute Encephalopathy.
Neuropathies.
Mood Disturbances.
Myositis.
Polyarticular Juvenile Idiopathic Arthritis (Poly JIA)
Myelopathy.
Pauciarticular Juvenile Idiopathic Arthritis (Pauci JIA)
Iridocyclitis and Uveitis.
Psoriatic, Enthesitis-Related, and Undifferentiated Syndromes
Neuropathology
Management
Periodic Fever Syndromes
Neonatal-Onset Multisystem Inflammatory Disease or Chronic Infantile Neurologic Cutaneous and Articular Syndrome
Familial Mediterranean Fever
Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome
Hyper-IgG (Autoimmune Lymphoproliferative) Syndrome
Arthritis Associated with Infectious Agents
Acute Rheumatic Fever
Neurologic Manifestations
Sydenham Chorea
Clinical Manifestations.
Laboratory Findings.
Neuropathology
Treatment
Postinfectious Tourette Syndrome and PANDAS
Other Central Nervous System Manifestations
Lyme Disease
Reactive Arthritis (formerly called Reiter Syndrome)
Connective Tissue Disorders
Systemic Lupus Erythematosus
Neurologic Manifestations
Seizures.
Neuropsychiatric Lupus.
Headache.
Chorea.
Reye-like Syndrome.
Cerebrovascular Disease.
Hypertensive Encephalopathy.
Cranial Nerve, Brainstem, and Spinal Cord Dysfunction.
Central Nervous System Infections.
Lupus Aseptic Meningitis.
Peripheral Nervous System Involvement.
Myopathy.
Drug-Induced Lupus Syndrome.
Laboratory Findings
Neuroimaging Evaluation
Treatment of Neurologic Manifestations
Neuropathology
Scleroderma
Neurologic Manifestations
Laboratory Findings
Treatment
Mixed Connective Tissue Disease
Neurologic Manifestations
Treatment
Sjögren Syndrome
Neurologic Manifestations
Laboratory Findings
Treatment
Primary Vasculitic Diseases
Necrotizing Vasculitis
Polyarteritis Nodosa
Neurologic Manifestations.
Laboratory Findings.
Neuropathology.
Treatment.
Kawasaki Disease
Neurologic Manifestations.
Neuropathology.
Treatment.
Cogan Syndrome
Leukocytoclastic Vasculitis
Henoch-Schönlein Purpura
Neurologic Characteristics.
Treatment.
Hypersensitivity Angiitis
Granulomatous Angiitis
Churg-Strauss Syndrome
Neurologic Manifestations.
Treatment.
Granulomatosis with Polyangiitis (formerly called Wegener’s Granulomatosis)
Neurologic Manifestations.
Treatment.
Primary Angiitis of the Central Nervous System
Neurologic Manifestations.
Laboratory Findings.
Treatment.
Necrotizing Sarcoid Granulomatosis
Sarcoidosis
Neurologic Manifestations.
Treatment.
Giant Cell Arteritis
Temporal Arteritis
Takayasu Arteritis
Miscellaneous Vasculitic Disorders
Behçet Disease
Neurologic Manifestations.
Treatment.
Miscellaneous Disorders
Thrombotic Thrombocytopenic Purpura
Neurologic Manifestations.
Laboratory Findings.
Treatment.
Antiphospholipid Antibody Syndrome
Erythromelalgia and Erythermalgia
References
Selected References
Part XVI: Pediatric Neurooncology
122 Pediatric Neuro-oncology: An Overview
Introduction
Incidence
Etiology
Pathology and Classification
Staging and Stratification
Clinical Presentation
General Aspects of Treatment
Surgery
Radiation Therapy
Chemotherapy
Biologic Therapy, Immunotherapy, Vaccines, and Gene Therapy
Immunotherapy
Gene Therapy
Prognosis
References
Selected References
123 Medulloblastoma
Introduction
Etiology
Biology
Clinical Presentation and Diagnosis
Clinical Features
Radiographic Features
Management and Outcome
Surgery
Staging and Stratification
Postsurgical Management
Relapsed Medulloblastoma
Future Therapy
Sequelae in Medulloblastoma Survivors
References
Selected References
124 Other Embryonal and Pineal Malignancies of the Central Nervous System
Introduction
Clinical Presentation
Types of CNS Embryonal Tumors
Embryonal Tumors with Multilayered Rosettes
Medulloepithelioma
CNS Embryonal Tumors Not Otherwise Specified
Treatment and Outcomes
Pineal Tumors
Pineocytomas
Pineoblastoma
Treatment and Outcomes
Summary
References
Selected References
125 Ependymoma
Introduction
Incidence and Epidemiology
Location
Pathology
Diagnostic Evaluation
Imaging Studies
Prognostic Factors
Tumor Grade
Genetics
Cytogenetics
Epigenetic Phenomena
Biomarkers
Treatment of Ependymoma
Chemotherapy
Radiation Therapy
Experimental Therapy
Recurrence and Patterns of Failure
Summary
References
Selected References
126 Pediatric Brain Tumors – High-Grade Glioma
Introduction
Clinical Presentation
Diagnosis and Initial Management
Histopathology and Molecular Pathology
Imaging
Metabolic Imaging
Perfusion Magnetic Resonance Imaging
Therapy
Current Therapy
Future Directions
Targeted Therapies for Children With High-Grade Gliomas
CNS-Directed Delivery Strategies
Convection-Enhanced Delivery
Intranasal Delivery
References
Selected References
127 Pediatric Low-Grade Glioma
Introduction
Clinical Presentation
Classification and Histologic Features
Pilocytic Astrocytoma (WHO Grade I)
Pilomyxoid Astrocytoma (WHO Grade II)
Dysembryoplastic Neuroepithelial Tumor (WHO Grade I)
Ganglioglioma (WHO Grade I)
Pleomorphic Xanthroastrocytoma (WHO Grade II)
Diffuse Fibrillary Astrocytoma
Pediatric Low-Grade Glioma; Not Otherwise Specified
Evaluation, Diagnosis, and Management
Differential Diagnosis
Pathogenesis
Treatment
Surgery
Chemotherapy
Radiation Therapy
Supportive Care
Seizures
Genetic Features of Pediatric Low-Grade Glioma
Current Clinical Trials
Targeting the RAS/MAP-Kinase Pathway
mTOR Pathway Inhibition
Antiangiogenic Therapy
Immunomodulatory Therapy
Outcome
Conclusions
References
Selected References
128 Diffuse Intrinsic Pontine Glioma
Background
Epidemiology
Presentation and Diagnosis
Prognosis
Histopathology
Extent of Spread
Developmental Context of DIPG
Molecular Characteristics of DIPG
Current Treatment
Emerging Therapeutic Strategies
Acknowledgment
References
Selected References
129 Atypical Teratoid/Rhabdoid Tumors
Introduction
Historical Background and Incidence
Clinical Presentation and Radiographic Findings
Histopathology
Genetics of AT/RT
Staging and Therapeutic Interventions
Chemotherapy
Radiation
Toxicity of Therapy
Future Directions
Conclusions
References
Selected References
130 Central Nervous System Germinoma and Other Germ Cell Tumors
Introduction
Epidemiology
Pathology and Etiology of Germ Cell Tumors
Germinoma
Clinical Presentation
Radiology
Tumor Markers
S-Kit in Germinoma
Staging
Treatment
Role of Radiation and Chemotherapy
Radiation Therapy
Chemotherapy
Combined Chemotherapy and Radiation Therapy
Role of Surgery
The Need for Biopsy and Second-Look Surgery
Prognosis and Summary
References
Selected References
131 Craniopharyngioma, Meningiomas, and Schwannomas
Craniopharyngiomas
Epidemiology
Clinical Presentation
Neuroimaging
Histopathology
Treatment
Radical Surgical Resection
Subtotal Resection With Irradiation
Aspiration
Intracystic Therapy
Intracavitary Irradiation.
Intracystic Bleomycin.
Intracystic Interferon.
Outcomes and Quality of Life
Overview
Meningiomas
Epidemiology
Clinical Presentation
Molecular Genetics
Meningiomas and Genetic Conditions
Radiation-Induced Meningiomas
Neuroimaging
Histopathology
Treatment
Observation
Surgery
Radiation
Overview
Schwannomas
Clinical Presentation
Schwannomas and Genetic Conditions
Neuroimaging
Histopathology
Treatment
Overview
Selected References
132 Pediatric Intradural Spinal Cord Tumors
Introduction
Epidemiology
Presentation
Diagnosis
Tumor Subtypes
Extramedullary Spinal Cord Tumors
Spinal Meningiomas
Peripheral Nerve Tumors (Neurofibromas, Schwannomas)
Ependymomas of the Conus-Cauda Region
Intramedullary Spinal Cord Tumors (IMSCTs)
Glial Tumors
Intramedullary Ependymomas
Low-Grade Astrocytomas
Malignant Spinal Gliomas
References
Selected References
133 System Cancer and the Central Nervous System Involvement
Central Nervous System Leukemia
Lymphoma
Histiocytosis
Neuroblastoma
Sarcoma
Osteosarcoma
Ewing’s Sarcoma
Rhabdomyosarcoma
Conclusions
Acknowledgment
References
Selected References
134 Posttreatment Neurologic Sequelae of Pediatric Central Nervous System Tumors
Introduction
Mortality in Long-Term Tumor Survivors
Central Nervous System Posttreatment Sequelae
Weakness
Seizures
Posttreatment Encephalopathy With Neurologic Impairment
Posterior Reversible Encephalopathy
Pseudoprogression
Cerebrovascular Events
Postoperative Cerebellar Mutism Syndrome
Chronic Leukoencephalopathy
Cognitive Impairment
Definition and Measurement of Neurocognitive Effects
Risk Factors for Neurocognitive Deficits
Neurosensory Deficits
Visual Impairment
Hearing Loss
Peripheral Nervous System Impairment
Growth and Other Sequelae With a Neuroendocrine Component
Conclusions
References
Selected References
Part XVII: Neuromuscular Disorders
135 Muscle and Nerve Development in Health and Disease
Embryology and Development
Skeletal Muscle
Peripheral Nerve
Neuromuscular Junction
General Anatomy and Structure of Skeletal Muscle
Morphology
Sarcomere
Contractile and Sarcomeric Proteins
Sarcotubular System
Cytoskeletal Proteins
Dystrophin
Dystrophin-Glycoprotein Complex
Sarcoglycans
Utrophin
Dysferlin
Caveolin
Merosin (Laminin-α2)
Intermediate Filaments
Nuclear Membrane Proteins
Muscle Fiber Types
General Anatomy and Structure of Peripheral Nerves
Neural Control of Movement
References
Selected References
136 Laboratory Assessment of the Child with Suspected Neuromuscular Disorders
Introduction
Laboratory Chemistries and Serologies
Nerve Conduction Studies and Electromyography
Motor Unit Number Estimation
Electrical Impedance Myography
Imaging Studies
Genetic Testing
Conclusions
References
Selected References
137 Clinical Assessment of Pediatric Neuromuscular Disorders
Definition, Classification, and Epidemiology of Pediatric Neuromuscular Disorders
Evaluation of the Child With a Suspected Neuromuscular Disorder
Localization and Classification
History
Examination
Quality of Life and Disability Scales
References
Selected References
138 The Floppy Infant
Defining Hypotonia
Muscle Tone
Localization of Hypotonia
History
Examination
Central Hypotonia
Peripheral Hypotonia
References
Selected References
139 Genetic Disorders Affecting the Motor Neuron
Epidemiology
Clinical Characteristics
Type I SMA
Type II SMA
Type III SMA
Outliers
Other “Spinal Muscular Atrophies”
Genetics
The SMN Gene
Genetic Diagnosis
Newborn Screening
Other Diagnostic Tests
Molecular Function of SMN
Differential Diagnosis
The Pathology of SMA
Treatment
Clinical Trials in SMA: Therapeutics
Agents That Upregulate SMN2 Gene Expression and Promote Exon 7 Inclusion
Small Molecules
Neuroprotective, SMN Protein Stabilization Agents
Other Small Molecules
Other Approaches
SMN2 Splicing Modifiers
Antisense Oligonucleotides.
Small Molecule Drugs.
Stem Cells
Gene Therapy
Care of the Patient With SMA
Pulmonary
Gastrointestinal
Nutrition
Orthopedic
Fatigue
Conclusions
Acknowledgments
References
Selected References
140 Other Motor Neuron Diseases of Childhood
Anatomy: The Anterior Horn Cells of the Spinal Cord
Diagnostic Workup
Hereditary Diseases Affecting Spinal Motor Neurons
SMA-like Motor Neuron Disorders
Motor Neuron Disease With Central Nervous System Manifestations
Motor Neuron Diseases With Predominant Bulbar Weakness
Motor Neuron Disease With Arthrogryposis
Motor Neuron Disease With Distal Weakness
Amyotrophic Lateral Sclerosis With Onset in the First Two Decades of Life
Other Atypical and Acquired Motor Neuron Disorders
Infections
Vascular Etiologies
Trauma
Unknown Etiologies
Treatment
References
Selected References
141 Genetic Peripheral Neuropathies
Definition
Prevalence and Classification
Clinical Sequelae of Inherited Neuropathy
Pathophysiology
Neurophysiology
Genetic Testing and Diagnostic Strategies
Specific Forms of CMT
CMT1: Autosomal-Dominant Demyelinating Neuropathies
CMT1A
CMT1B
CMT1C
CMT1D
CMT1E
HNPP
CMTX: X-Linked CMT
CMT2: Autosomal-Dominant Axonal Neuropathies
CMT2A
CMT4: Autosomal-Recessive Neuropathies
CMT4A
CMT4B1/B2/B3
CMT4C
CMT4F
CMT4: Autosomal-Recessive Axonal Neuropathies (Also Known as AR-CMT2).
Distal Hereditary Motor Neuropathies.
Hereditary Sensory Neuropathies.
Neuropathies Associated With Inherited Metabolic Disease.
Differential Diagnosis.
Treatment Strategies.
Conclusion
References
Selected References
142 Acquired Peripheral Neuropathies
Anatomy
Facial Nerve Paralysis (Bell’s Palsy)
Clinical Features
Laboratory Findings
Treatment and Prognosis
Brachial Plexus
Metabolic Neuropathies
Diabetes Mellitus
Uremic Neuropathy
Acute Intermittent Porphyria
Vitamin Deficiency
Congenital Pernicious Anemia
Abetalipoproteinemia
Pathology
Clinical Characteristics
Alpha-Lipoprotein Deficiency (Tangier Disease)
Clinical Characteristics
Krabbe’s Disease (Globoid Cell Leukodystrophy)
Metachromatic Leukodystrophy
Refsum’s Disease (Heredopathia Atactica Polyneuritiformis) and Peroxisome Biogenesis Disorders
Toxic Neuropathies
Diphtheria
Neuropathy of Serum Sickness
Antibiotic-Induced Neuropathy
Pyridoxine-Induced Polyneuropathy
Nitrous Oxide–Induced Polyneuropathy
Chemotherapeutic Agent–Induced Neuropathy
Vaccine-Induced Polyneuropathy
Heavy Metal Neuropathy
Vasculitic Neuropathies
References
Selected References
143 Inflammatory Neuropathies
Guillain-Barré Syndrome
Epidemiology
Antecedent Events
Clinical Features of AIDP (GBS)
Acute Motor Axonal Neuropathy
Other Subtypes and Variants of GBS
Diagnostic Challenges of GBS in Childhood
GBS Diagnostic Criteria
Differential Diagnosis
Laboratory Findings Supportive of GBS
Cerebrospinal Fluid
Electrodiagnosis
Magnetic Resonance Imaging
GBS Pathogenesis
GBS Treatment
Supportive Care
GBS Immunotherapy
Corticosteroids in GBS
Potential GBS Therapies
Childhood GBS Outcome
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Epidemiology
Antecedent Events
Diagnostic Criteria and Clinical Features
CIDP Laboratory Evaluation
Cerebrospinal Fluid and Electrodiagnosis
CIDP Pathology and Pathogenesis
CIDP Magnetic Resonance Imaging
Childhood CIDP Immunotherapy
First-Line CIDP Treatments
Corticosteroids.
Intravenous Immunoglobulin.
Plasmaphereis/Plasma exchange (PE).
Potential Second-Line Immunosuppressants for Treatment Resistant CIDP
Current Practice in Childhood CIDP Immunotherapy.
Differentiating Abrupt-Onset CIDP From GBS Fluctuations.
Clinical Variants Not Meeting CIDP Research Criteria.
Childhood CIDP Outcome
Other Causes of Immune-Mediated Neuropathies in Children
References
Selected References
144 Congenital Myasthenic Syndromes
Introduction
Clinical Manifestations
Diagnosis
Presynaptic Congenital Myasthenic Syndromes
1. Endplate Choline Acetyltransferase (ChAT) Deficiency
2. SNAP25B Myasthenia
3. Synaptotagmin-2 Myasthenia
Synaptic Basal Lamina Associated Congenital Myasthenic Syndromes
1. Endplate Acetylcholinesterase Deficiency
2. Congenital Myasthenic Syndrome Associated With β2-Laminin Deficiency
Postsynaptic Congenital Myasthenic Syndromes
1. Primary Acetylcholine Receptor Deficiency
2. Kinetic Defects in Acetylcholine Receptor
2.1 Slow-channel Myasthenia
2.2 Fast-channel Myasthenia
3. Prenatal Congenital Myasthenic Syndrome Caused by Mutations in Acetylcholine Receptor Subunits and Other Endplate Specific Proteins
4. Sodium-channel Myasthenia
5. Congenital Myasthenic Syndrome Caused by Plectin Deficiency
Congenital Myasthenic Syndromes Caused by Defects in Endplate Development or Maintenance
1. Agrin Myasthenia
2. LRP4 Myasthenia
3. MuSK Myasthenia
4. Dok-7 Myasthenia
5. Rapsyn Myasthenia
Congenital Myasthenic Syndromes Associated With Congenital Defects of Glycosylation
1. GFPT1 Myasthenia
2. DPAGT1 Myasthenia
3. ALG2 and ALG14 Myasthenia
Other Myasthenic Syndromes
1. PREPL Deletion Syndrome
2. Myasthenic Syndrome Associated With Defects in the Mitochondrial Citrate Carrier SLC25A1
3. Myasthenic Syndromes Associated With Congenital Myopathies
Treatment
References
Selected References
145 Acquired Disorders of the Neuromuscular Junction
Acquired Diseases of the Neuromuscular Junction
Autoimmune Myasthenia Gravis
Clinical Features
Categories of Myasthenia Gravis in Childhood
Clinical and Laboratory Tests
Edrophonium (Tensilon) Test
Electrophysiologic Testing
Repetitive Nerve Stimulation
Single-Fiber Electromyography
Antibody Testing
Anti-AChR Antibodies
Anti-MuSK Antibodies
Treatment.
Acetylcholinesterase Inhibitors
Thymectomy
Corticosteroids
Azathioprine
Cyclosporine
Mycophenolate Mofetil
Cyclophosphamide
Plasmapheresis
Intravenous Immunoglobulin
Drugs to Avoid
Lambert–Eaton Myasthenic Syndrome
Clinical Features
Diagnostic Tests
Treatment
Botulism
Infantile Botulism
Foodborne Botulism
Wound Botulism
References
Selected References
146 Duchenne and Becker Muscular Dystrophies
The Dystrophin Protein
The “Reading Frame Rule”
Clinical Features
Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
Laboratory Features
Molecular Genetic Testing
DMD Mutation Analysis.
Genotype-Phenotype Correlations
Muscle Biopsy
Management of DMD and BMD
Pharmacologic Management
Corticosteroids.
Cardiac.
Pulmonary.
Non-pharmacologic Management
Spine/Scoliosis.
Contractures.
Recent Advances in Dystrophinopathy Therapeutics
Selected References
147 Congenital, Limb Girdle and Other Muscular Dystrophies
Dystrophinopathies (Duchenne and Becker Muscular Dystrophies and Clinical Variants)
Limb-Girdle Muscular Dystrophies
Definition
Autosomal-Recessive Limb-Girdle Muscular Dystrophies
Sarcoglycanopathies (LGMD 2C-F)
Pathophysiology.
Genetics and Mutations.
Clinical Features.
Time Course and Distribution of Motor Symptoms.
Cardiac Features.
Pulmonary Features.
Contractures and Other Signs and Symptoms.
Diagnosis.
Treatment.
Disorders of α-Dystroglycan Glycosylation
Limb-Girdle Muscular Dystrophy 2I: Fukutin-Related Protein Deficiency
Clinical Features.
Diagnosis.
Management.
Other α-Dystroglycanopathies
Calpainopathy (LGMD2A)
Background and Epidemiology.
Pathophysiology, Genetics, and Mutations.
Clinical Features.
Time Course and Distribution of Motor Symptoms.
Cardiac Features.
Pulmonary Features.
Contractures and Other Signs and Symptoms.
Diagnosis.
Treatment.
Dysferlinopathy (LGMD 2B)
Pathophysiology.
Genetics and Mutations.
Clinical Features.
Time Course and Distribution of Motor Symptoms.
Cardiac and Pulmonary Features.
Contractures and Other Signs and Symptoms.
Diagnosis.
Treatment.
Anoctaminopathy (LGMD2L)
Other Rare Autosomal-Recessive Limb-Girdle Muscular Dystrophies
Autosomal-Recessive Conditions Presenting as LGMD
Partial Laminin α2 Deficiency.
X-Linked Recessive Conditions Presenting as LGMD
Autosomal-Dominant Limb-Girdle Muscular Dystrophies
Autosomal-Dominant LGMDs Without Cardiac Involvement
Myotilinopathy-LGMD 1A.
Pathophysiology and Mutations.
Clinical Features.
Diagnosis.
Treatment.
Caveolinopathy (LGMD 1C)
Pathophysiology and Genetics.
Clinical Features.
Diagnosis.
Treatment.
LGMD 1D.
Autosomal-Dominant LGMDs With Cardiac Involvement
Laminopathy (LGMD 1B).
Pathophysiology and Genetics.
Clinical Features.
Cardiac Features.
Diagnosis.
Treatment.
Autosomal-Dominant Conditions That May Present as LGMD
Facioscapulohumeral Dystrophy (FSHD, See Below).
Myotonic Dystrophy (DM) Types 1 and 2.
Collagen VI–Related Dystrophies.
Emery-Dreifuss Muscular Dystrophy
Pathophysiology and Genetics
Clinical Features
Diagnosis
Management
Summary and Approach to LGMD Patients
Clinical Features
Muscle Biopsy and Protein Studies
Molecular Genetic Testing
Diagnostic Algorithm
Facioscapulohumeral Muscular Dystrophy
Molecular Genetics
Clinical Features
Laboratory Findings
Diagnosis
Treatment
Oculopharyngeal Muscular Dystrophy
Congenital Muscular Dystrophies
Abnormalities of α-Dystroglycan
Clinical Presentations of the Dystroglycanopathies
Muscle Biopsy Features
Fukuyama Congenital Muscular Dystrophy
MDC1C (Fukutin-Related Protein Deficiency)
Muscle-Eye-Brain Disease
Walker-Warburg Syndrome
MDC1D: LARGE
Congenital Muscular Dystrophy With Integrin α7 Deficiency
Abnormalities of Extracellular Matrix Proteins
MDC1A: Laminin-α2 (Merosin)–Negative Congenital Muscular Dystrophy (“Nonsyndromic Congenital Muscular Dystrophy”)
Genetics.
Clinical Features.
Diagnosis.
Merosin-Positive, Nonsyndromic Congenital Muscular Dystrophies
Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy
Congenital Muscular Dystrophy With Early Rigid Spine Syndrome
Diagnosis.
Treatment.
Lamin A/C-Associated Congenital Muscular Dystrophy
Nesprin-Associated Congenital Muscular Dystrophy
Approach to the Patient With an LGMD, FSHD, EDMD, and CMD
Clinical Assessment
Diagnostic Studies
Treatment
Acknowledgments
References
Selected References
148 Congenital Myopathies
Diagnostics
Diagnostic Testing for Congenital Myopathies
Muscle Biopsy
Genetics
Muscle Imaging (MRI or Ultrasonography)
Specific Subtypes of Congenital Myopathy
Centronuclear Myopathies
Nemaline Myopathies
Core Myopathies
RYR1-Related Myopathies
SEPN1-Related Myopathies
Congenital Fiber-Type Disproportion
General Management of Congenital Myopathies
Respiratory
Nutrition, Gastrointestinal, and Oromotor Management
Cardiac
Orthopedic
Physical Therapy/Exercise
Summary
References
Selected References
149 Metabolic Myopathies
Utilization of Bioenergetic Substrates in Exercise
Myoglobinuria
Glycogenoses
Pathophysiology (see online version for details)
Glycolytic/Glycogenolytic Defects
Fatty Acid Oxidation Disorders
Historical Background
Fasting Adaptation
Increased Susceptibility of the Child
Normal Pathway of Fatty Acid Oxidation
Clinical and Biochemical Features of Identified Defects
Common Features of Fatty Acid Oxidation Disorders
Involvement of Fatty Acid Oxidation–Dependent Tissues
Hypoketotic Hypoglycemia.
Alterations in Plasma and Tissue Concentrations of Carnitine.
Additional Laboratory Findings
Specific Features of Individual Genetic Defects (see online version of this chapter for details)
Differentiating Laboratory Features
Diagnostic Approaches and Screening Methods
History and Physical Examination
Treatment
Avoidance of Precipitating Factors
High-Carbohydrate, Low-Fat Diet
Uncooked Cornstarch
Other Treatments
Clinical Monitoring
Genetics and Presymptomatic Recognition
Mitochondrial Encephalomyopathies (also refer to Chapter 42)
Morphologic Considerations
Clinical Considerations
Biochemical Classification
Physiologic Considerations (see online version of this chapter for details)
Genetic Classification (see Chapter 42)
Therapeutic Approaches in Mitochondrial Diseases
Myoadenylate Deaminase Deficiency
Clinical Presentation
Laboratory Tests
Pathology
Biochemistry and Molecular Genetics
Acknowledgments
References
Selected References
150 Inflammatory Myopathies
Idiopathic Inflammatory Myopathies
Dermatomyositis
Clinical Features
Associated Manifestations.
Laboratory Features
Blood Tests.
Electromyography.
Muscle Biopsy.
Pathogenesis (see online chapter)
Treatment.
Corticosteroids.
Other Agents.
Polymyositis
Clinical Features
Overlap Syndromes.
Laboratory Features
Muscle Biopsy.
Pathogenesis (see online chapter)
Treatment.
Congenital Inflammatory Myopathy
Other Idiopathic Inflammatory Myopathies
Inflammatory Myopathy Associated With Infections
Influenza Myositis
Clinical Features
Laboratory Features
Pathogenesis (see online chapter)
Treatment.
Other Viral Myositides
Trichinosis
Clinical Features
Laboratory Features
Treatment
Toxoplasmosis
Clinical and Laboratory Features
Treatment
Cysticercosis
Bacterial Infections
Fungal Myositides
References
Selected References
151 Channelopathies
The Myotonic Dystrophies
Mode of Inheritance of Myotonic Dystrophy Types 1 and 2
Myotonic Dystrophy Type 1
Clinical Features
Myotonic Dystrophy Type 2 (Formerly Proximal Myotonic Myopathy)
Clinical Features
DM1 and DM2: Genotype–Phenotype Correlations
Diagnostic Approach
Laboratory Testing for DM1 and DM2
DM1 Testing
DM2 Testing
Treatment of DM1 and DM2
DM1 Treatment
DM2 Treatment
Autosomal-Dominant and Autosomal-Recessive Myotonia Congenita
Clinical Features
Genetics
Pathophysiology
Clinical Laboratory Tests
Treatment
Acetazolamide-Responsive Sodium Channel Myotonia and Myotonia Fluctuans
Clinical Features
Genetics
Pathophysiology
Clinical Laboratory Tests
Treatment
The Periodic Paralyses
Hyperkalemic Periodic Paralysis
Clinical Features
Genetics
Pathophysiology
Clinical Laboratory Tests
Treatment
Paramyotonia Congenita
Clinical Features
Genetics
Clinical Laboratory Tests
Pathophysiology
Treatment
Hypokalemic Periodic Paralysis
Clinical Features
Genetics
Pathophysiology
Clinical Laboratory Tests
Treatment
Periodic Paralysis With Cardiac Arrhythmia: Andersen–Tawil Syndrome
Clinical Features
Genetics
Pathophysiology
Clinical Laboratory Tests
Treatment
Thyrotoxic Periodic Paralysis
Clinical Features
Pathophysiology
Genetics
Clinical Laboratory Tests
Treatment
References
Selected References
152 Management of Children with Neuromuscular Disorders
References
Selected References
Part XVIII: Systemic and Autonomic Nervous System Diseases
153 Endocrine Disorders of the Hypothalamus and Pituitary in Childhood and Adolescence
Introduction
Anatomic and Physiologic Aspects
Hypothalamic/Pituitary Disorders of Pubertal Development
Normal Physiology of Puberty and Adrenarche
Sexual Precocity
Management
Delayed or Arrested Puberty
Isolated Congenital Hypogonadotropic Hypogonadism
Hypogonadotropic Hypogonadism Associated with Multiple Hypothalamic/Pituitary Hormone Deficiencies
Functional Hypogonadotropic Hypogonadism
Evaluation of Delayed or Arrested Puberty
Management
Disorders of Prolactin Secretion
Normal Biochemistry and Physiology of Prolactin
Clinical Features and Management of Hyperprolactinemia
Hypothalamic/Pituitary Disorders of Glucocorticoid Production
Adrenocorticotropic Excess
Adrenocorticotropic Hormone Deficiency
Hypothalamic/Pituitary Disorders of Statural Growth
Growth Hormone Deficiency
Growth Hormone Excess
Hypothalamic/Pituitary Disorders of Thyroid Function
Normal Thyroid Physiology
Central Hypothyroidism
Central Hyperthyroidism
Hypothalamic Disorders of Appetite Regulation and Energy Balance
Hypothalamic/Pituitary Disorders of Water Balance
Diabetes Insipidus
Syndrome of Inappropriate Antidiuretic Hormone Secretion
References
Selected References
154 Disorders of the Autonomic Nervous System:
Introduction
Anatomy and Physiology of the Autonomic Nervous System
Anatomy of the Autonomic Nervous System
Efferent Autonomic Pathways
Sympathetic Efferent Pathways.
Parasympathetic Efferent Pathways.
Efferent Neurotransmission.
Afferent Autonomic Pathways
Central Nervous System Integration
Clinical Approach to the Diagnosis of Pediatric Autonomic Disorders
Clinical History Taking
Orthostatic Intolerance
Syncope.
Orthostatic Intolerance with Orthostatic Tachycardia.
Abnormal Gastrointestinal Motility.
Genitourinary Symptoms.
Thermoregulatory Abnormalities.
Ocular Symptoms.
Respiratory Symptoms.
Pediatric Autonomic Disorders
Functional Disorders of Unknown Origin
Reflex (Vasovagal) Syncope
Postural Tachycardia Syndrome
Metabolic Disorders
Obesity
Eating Disorders
Diabetes Mellitus
Other Metabolic Disorders
Autonomic Dysfunction Secondary to Focal Disease
Acquired Afferent Baroreflex Failure
Catecholamine-Secreting Tumors
Autoimmune Autonomic Disorders
Guillain-Barré Syndrome
Autoimmune Autonomic Ganglionopathy
Acute Autonomic and Sensory Neuropathy
Anti-NMDA Receptor Encephalitis
Lambert-Eaton Myasthenic Syndrome
Dipeptidyl-Peptidase-Like Protein-6 (DPPX) Potassium Channel Antibody Encephalitis
Genetic Autonomic Disorders
Hereditary Sensory and Autonomic Neuropathies
HSAN Type 1.
HSAN Type 2.
HSAN Type 3 (Familial Dysautonomia).
HSAN Type 4 (Congenital Insensitivity to Pain with Anhidrosis).
HSAN Type 5.
HSAN Type 6.
HSAN Type 7.
Other Syndromes with Sensory and Autonomic Involvement.
Inborn Errors of Metabolism
Dopamine Beta-Hydroxylase Deficiency.
Aromatic L-Amino Acid Decarboxylase Deficiency.
Menkes Disease.
Fabry Disease.
Porphyrias.
Hirschsprung Disease
Congenital Central Hypoventilation Syndrome and Related Ventilatory Disorders
Allgrove Syndrome and Related Disorders
Other Genetic Disorders with Autonomic Dysfunction
Rett Syndrome.
Alexander Disease.
Hyperbradykininism.
Panayiotopoulos Syndrome.
Congenital Alacrima.
Cold-Induced Sweating Syndrome.
References
Selected References
155 Disorders of Micturition and Defecation
Introduction
Disorders of Micturition
Epidemiology
Neuropsychiatric Comorbidity
Anatomy of the Lower Urinary Tract (LUT)
Afferent Mechanisms
Periaqueductal Gray (PAG) and Pontine Micturition Center (PMC)
Insula
Anterior Cingulate Cortex (ACC)
Prefrontal Cortex
Diagnosis
History and Physical Examination
Physical Examination
Clinical Testing
Disorders of Defecation
Normal Defecation Patterns
Functional Anatomy of Colon, Rectum, and Anus
Colorectal Motility and Defecation
The Intrinsic Nervous System
The Extrinsic Nervous System
Muscle Contractions and Colorectal Motility
CNS and the Gut
Patient Evaluation
History
Neurologic Examination
Clinical Studies
Differential Diagnosis
Management
References
Selected References
156 Poisoning and Drug-Induced Neurologic Diseases
Introduction
Emergency Evaluation
Management
Testing
Other Ancillary Testing
Neurologic Examination
Common Toxidromes
Poisons and Environmental Toxins
Biologic Toxins
Snake Venom
Tick Bites.
Botulism.
Tetanus.
Insecticides
Organophosphate and Carbamate Insecticides.
Insect Repellents.
Metals
Lead.
Mercury.
Thallium.
Arsenic.
Drugs of Abuse
Cocaine
Opiates
Cannabis
Gamma-Hydroxybutyrate
Hydrocarbons
Hallucinogens
Amphetamines
“Ecstasy”
Emerging Drugs of Abuse
Barbiturates
Benzodiazepines
Baclofen
Antipsychotic Agents (Neuroleptics)
Antidepressants
Lithium
Salicylates
Stimulants
Diphenhydramine
Drugs Used in Organ Transplantation
Cyclosporine
Muromonab-CD3 (OKT3)
Tacrolimus (FK-506)
Antibiotics
Chloramphenicol
Nitrofurantoin
Aminoglycosides
Beta-Lactam Antibiotics
Antineoplastic Drugs
Vinca Alkaloids
Methotrexate
L-Asparaginase
Platinum Agents
Cytosine Arabinoside
Cyclophosphamide and Ifosfamide
Neuroteratology
Concluding Remarks and Additional Sources
Internet Sites
References
Selected References
157 Neurologic Disorders in Children with Heart Disease
List of Abbreviations
Introduction
Anatomic Considerations
Fetal Circulation
Postnatal Circulation
Heart Surgeries
Perioperative Considerations
White Matter Injury
Arterial Ischemic Stroke
Intracranial Hemorrhage
Cerebral Sinovenous Thrombosis
Seizures
Neurologic Sequelae of Heart Failure
Mechanical Circulatory Support Devices
Extracorporeal Membrane Oxygenation (ECMO)
Neurologic Management Specific to Cardiac Care
Short and Long-Term Outcomes
Postoperative Neurologic Findings
Short-Term Outcome
Long-Term Outcome
Adolescent and Adult Outcome
Summary
References
Selected References
158 Neurologic Disorders Associated With Renal Diseases
Renal Diseases Secondarily Affecting the Nervous System
Acute Kidney Injury
Sodium and Water Disorders
Potassium Abnormalities
Calcium and Magnesium Abnormalities
Chronic Kidney Disease
Uremic Encephalopathy
Clinical Features of Uremia.
Pathophysiology of Uremia.
Diagnostic Considerations in Patients With Uremia.
Management of Uremic Encephalopathy.
Congenital Uremic Encephalopathy
Stroke and Vasculopathy
Dialysis-Associated Complications
Dialysis Disequilibrium Syndrome
Dialysis-Associated Seizures
Aluminum Toxicity and Encephalopathy (Including Dialysis Dementia)
Vitamin and Cofactor Deficiencies
Intracranial Hemorrhage
Milder Forms of Encephalopathy
Uremic Peripheral Polyneuropathy
Uremic Myopathy (Myopathy of Chronic Kidney Disease)
Malnutrition
Endocrinopathy
Complications Associated With Renal Transplantation
Infection
Malignancy
Drugs
Hypertension
Hypertensive Encephalopathy
Clinical Features of Hypertensive Encephalopathy.
Pathophysiology of Hypertensive Encephalopathy.
Diagnostic Considerations in Patients With Hypertensive Encephalopathy.
Outcomes From Hypertensive Encephalopathy
Posterior Reversible Encephalopathy Syndrome
Clinical Features of Posterior Reversible Encephalopathy Syndrome.
Diagnostic Considerations in Patients With Posterior Reversible Encephalopathy Syndrome.
Management of Posterior Reversible Encephalopathy Syndrome.
Diseases Affecting Both Kidney and Nervous System
Thrombotic Thrombocytopenic Purpura
Hemolytic-Uremic Syndrome
Treatment
Vasculitic Diseases With Neurologic-Renal Presentations
Hepatorenal Syndrome
Amyloidosis
Metabolic Diseases Producing Generalized Renal and Neurologic Dysfunction
Selective Tubular Dysfunction
Proximal Renal Tubular Acidosis
Nephropathic Cystinosis
Neurologic Drugs That May Affect Renal Function in Individuals With Normal Kidneys
Drug Therapy in Renal Disease
Drug-Induced Encephalopathy in Renal Failure
Treatment of Seizures Associated With Renal Disease
Concerns About Specific Antiseizure Medication Use in the Setting of Renal Failure
Phenytoin.
Valproate.
Barbiturates.
Carbamazepine.
Oxcarbazepine.
Ethosuximide.
Levetiracetam.
Zonisamide.
Lamotrigine.
Gabapentin.
Benzodiazepines.
Kidney Stones
Other Neurologic Drugs
References
Selected References
159 Neurologic Disorders Associated with Gastrointestinal Diseases
Introduction
Disorders Associated With Gastrointestinal Disease
The Enteric Nervous System
Dysphagia.
Episodic Gastrointestinal Disease
Recurrent Abdominal Pain and Irritable Bowel Syndrome
Cyclic Vomiting Syndrome and Recurrent Abdominal Pain
Irritable Bowel Syndrome
Infantile Colic
Anatomic Gastrointestinal Disorders
Gastroesophageal Reflux
Intestinal Pseudoobstruction
Hirschsprung Disease
Other Neurocristopathy Syndromes
Other Pseudoobstruction Syndromes
Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE)
Intussusception
Malabsorption Syndromes
Celiac Disease
Short Bowel Syndrome
Inflammatory Bowel Disease
Enteric Infections
The Human Microbiome and Neurologic Disorders in Children
Development and Role of the Human Microbiota
Disease States and the Influences of the Microbiota and Microbiome
The Microbiota and Immune-Mediated Nervous System Disorders.
Multiple Sclerosis.
Guillain–Barré Syndrome.
The Microbiota and Nonimmune-Mediated CNS Disorders
Autistic Spectrum Disorder.
Attention Deficit Hyperactivity Disorder.
Cerebral Palsy.
Epilepsy.
Intellectual Disability.
Depression, Anxiety, Stress and Schizophrenia.
Therapeutic Implications
Other Gastrointestinal Diseases
Whipple’s Disease
Turcot’s Syndrome
Porphyria
Neurologic Disorders Associated With Hepatobiliary Diseases
Hepatitis
Hepatic Encephalopathy
Neurologic Abnormalities
Fulminant Liver Failure
Cognitive and Behavioral Abnormalities
Minimal Hepatic Encephalopathy
Laboratory Tests
Neuropathology and Pathophysiology
Treatment
Prognosis
Neurologic Abnormalities Associated With Liver Transplantation
Neurologic Abnormalities in Primary Biliary Cirrhosis
Reye’s Syndrome
Hepatolenticular Degeneration: Wilson’s Disease
Progressive Hepatocerebral Disease
Bilirubin Encephalopathy: Kernicterus
Pathophysiology of Hyperbilirubinemia.
Neuropathology.
Clinical Manifestations.
Laboratory Testing.
Management.
References
Selected References
Part XIX: Care of the Child with Neurologic Disorders
160 Counseling Children with Neurologic Disorders and Their Families
Introduction
The Clinician–Patient Relationship
Communication Skills
Nonverbal Communication
Conveying Empathy
Providing Information
Specific Challenges
Low Health Literacy
Family Discord
Alternate Belief Systems
Spirituality
Difficult Patients
Uncertain Test Results
Terminal Illnesses
References
Selected References
161 Approaches to Personalized Medicine in Pediatric Neurology
Introduction
Genomic Diagnosis
Therapeutics
Targeted Treatment
Disease Stratification
Pharmacogenetics
Prevention
Newborn Screening
Risk Assessment
Future Prospects
Genome Sequencing
Patient Engagement
Final Comments
References
Selected References
162 Pediatric Neurorehabilitation Medicine
Introduction
Mechanisms Underlying Functional Recovery in the Nervous System
Resolution of Temporary Dysfunction
Plasticity of the Nervous System
Reorganization of Neuronal Connections
Functional Recovery Through Adaptation
Principles of Pediatric Neurorehabilitation
Medical Aspects of Acute Pediatric Rehabilitation Management
Comprehensive Pediatric Rehabilitation Programs
Rehabilitation Treatment of Motor Impairment
Overview
Treatment of Spasticity
Rehabilitation Therapy
Oral Medications
Neuromuscular Blockade: Alcohol, Phenol, and Botulinum Toxin Injections
Intrathecal Baclofen Therapy
Selective Dorsal Rhizotomy
Orthopedic Surgery
Treatment of Dystonia and Other Hyperkinetic Movement Disorders
Acquired Brain Injury
Behavioral Disturbances
Communication and Cognitive Deficits
Postinjury Seizures
Pediatric Stroke
Novel Rehabilitation Strategies-Overview
Practice Based Therapies—Constraint Induced Movement Therapy and Robot Assisted Therapy
Stimulation of the Nervous System to Improve Stroke Recovery
Medications to Improve Stroke Recovery
Spinal Cord Injury
Medical Issues
Rehabilitation Strategies
Future Directions
References
Selected References
163 Pain Management and Palliative Care
Pain Management
Introduction
Historical Background
Physiology
Developmental Differences
Clinical Assessment
Management
Types of Pain Medications
Aspirin, Acetaminophen, and NSAIDs
Opioids
Procedural Sedation and Analgesia
Analgesia
Sedation
Types of Pain
Neuropathic Pain
Pain in Children With Significant Neurological Impairment
Migraine and Headache
Summary
Palliative Care
Introduction
Historical Background
Definitions of Palliative Care
Components of Palliative Care
Identifying the Need
Transition in Goals of Care
Levels of Care
Communication
Healthcare Decision Making
Persistent Vegetative State
Environment for Death and Dying
Support During Dying
Assessment and Treatment of Symptoms
Developmental, Emotional and Spiritual Concerns
Bereavement
Follow-Up Conference
Barriers to Palliative Care
Summary
References
Selected References
164 Ethical Issues in Child Neurology
Introduction
Theoretical Approaches to Ethics
Utilitarianism
Deontology
Common Morality and Natural Law
Principlism
Virtue or Character Ethics
Ethics of Care
Casuistry
Spirituality
Ethical Responsibilities
Duties as a Physician
Duties as a Pediatrician
Duties as a Neurologist
Research
Synthesis
References
Selected References
165 Transitional Care for Children with Neurologic Disorders
Introduction
Barriers to Care
Disorders that May be Dangerous to Society if Untreated
Disorders that are Potentially Lethal in Childhood and Young Adulthood and Have Emerging Treatments Leading to Increased Survival Well into Adulthood
Disorders that Are Problematic and “Static” in Childhood but Progress in Adulthood
Disorders Diagnosed in Childhood with Their Most Serious Manifestations in Adulthood
Disorders that Are Cured in Childhood but Have Neurologic Sequelae that Persist into Adulthood
Disorders that May/May Not Remit in Childhood but Have Persistent Effects on Adult Social Function
Disorders that May Be Uncomfortable for Adult Care
Disorders in Childhood Treated in a Way that is Difficult to Replicate in Adult Medicine
Poor or Little Development of the Transition Process Yields Poor Outcome
Models of Care for Transition
1. Abandonment of Specialized Care or “Fend for Yourself”
2. Referral to an Adult Rehabilitation Program
3. Referral to an Adult Neurologist or Internist
4. Referral to an Internal Medicine/Pediatric Subspecialist
5. Referral to a Nurse-Run Transition Clinic
6. A Joint Pediatric/Adult Transition Clinic
7. Internet-Based Support Groups
Conclusions
References
Selected References
166 Practice Guidelines in Pediatric Neurology
Introduction
History
Development Process
The American Academy of Neurology Process
Choosing Topics and Panelists
Collecting and Grading Evidence
Drawing Conclusions
Writing Recommendations
Law and Ethics
Guideline Utilization
Conclusion
References
References
167 Special Education Law as it Relates to Children with Neurologic Disorders
History
Special Education Case Law
Federal Legislation
Individuals with Disabilities Education Act (IDEA)
Health Insurance Portability and Accountability Act of 1996 (HIPAA)
No Child Left Behind Act (NCLB)
International Special Education
Canada
China
India
Israel
Italy
Japan
References
Selected References
168 Measurement of Health Outcomes in Pediatric Neurologic Disorders
Outcome Measures: Purpose, Properties, Prioritizing
ICF as a Framework for Outcome Measurement
Child’s Age and Stage as a Determinant of Measurement Focus
New Directions in Outcome Measurement
References
Selected References
169 The Influence of Computer Resources on Child Neurology
Clinical Discussions and Groups
Wikis
Diagnostic Decision Support
Treatment Decision Support
Education
Perspectives
Conflict of Interest
References
Selected References
170 Education and Training of Child Neurologists and Workforce Issues
Introduction
Historical Aspects
Current Approaches
Education and Training Preceding Child Neurology
Current Workforce Issues
Future Workforce Issues
References
Selected References
Appendix A
Denver II
Checklist for Documentation of Brain Death Examination in Infants and Children
Index
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z