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دانلود کتاب Swaiman's pediatric neurology : principles and practice
دانلود کتاب عصب شناسی کودکان سوایمن: اصول و عمل
مشخصات کتاب
Swaiman's pediatric neurology : principles and practice
ویرایش: [6 ed.]
نویسندگان: Kenneth F. Swaiman (editor)
سری:
ISBN (شابک) : 9780323371018, 0323371019
ناشر: Elsevier
سال نشر: 2018
تعداد صفحات: [1412]
زبان: English
فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود)
حجم فایل: 130 Mb
قیمت کتاب (تومان) : 43,000
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توجه داشته باشید کتاب عصب شناسی کودکان سوایمن: اصول و عمل نسخه زبان اصلی می باشد و کتاب ترجمه شده به فارسی نمی باشد. وبسایت اینترنشنال لایبرری ارائه دهنده کتاب های زبان اصلی می باشد و هیچ گونه کتاب ترجمه شده یا نوشته شده به فارسی را ارائه نمی دهد.
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فهرست مطالب
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
