BOOK
Swaiman's Pediatric Neurology E-Book
Kenneth F. Swaiman | Stephen Ashwal | Donna M Ferriero | Nina F Schor | Richard S Finkel | Andrea L Gropman | Phillip L Pearl | Michael Shevell
(2017)
Additional Information
Book Details
Abstract
Since 1975, Dr. Kenneth Swaiman’s classic text has been the reference of choice for authoritative guidance in pediatric neurology, and the 6th Edition continues this tradition of excellence with thorough revisions that bring you fully up to date with all that’s new in the field. Five new sections, 62 new chapters, 4 new editors, and a reconfigured format make this a comprehensive and clearly-written resource for the experienced clinician as well as the physician-in-training.
- Nearly 3,000 line drawings, photographs, tables, and boxes highlight the text, clarify key concepts, and make it easy to find information quickly.
- New content includes 12 new epilepsy chapters, 5 new cerebrovascular chapters, and 13 new neurooncology chapters, as well as new chapters on neuroimmunology and neuromuscular disorders, as well as chapters focused on clinical care (e.g., Counseling Families, Practice Guidelines, Transitional Care, Personalized Medicine, Special Educational Law, Outcome Measurements, Neurorehabilitation, Impact of Computer Resources, and Training Issues).
- Additional new chapters cover topics related to the developmental connectome, stem cell transplantation, and cellular and animal models of neurological disease.
- Greatly expanded sections to increase your knowledge of perinatal acquired and congenital disorders, neurodevelopmental disabilities, pediatric epilepsy, and nonepileptiform paroxysmal disorders and disorders of sleep.
- Coverage of new, emerging, or controversial topics includes developmental encephalopathies, non-verbal learning disorders, and the pharmacological and future genetic treatment of neurodevelopmental disabilities.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Half title page | e1 | ||
| Online_Dedication | e2 | ||
| Swaiman’s Pediatric Neurology | e3 | ||
| Online_Copyright page | e4 | ||
| Table Of Contents | e5 | ||
| 1 General Aspects of the Patient’s Neurologic History | e11 | ||
| References | e20 | ||
| 2 Neurologic Examination of the Older Child | e21 | ||
| Observation/Mental Status | e21 | ||
| Screening Gross Motor Function | e21 | ||
| Physical Examination | e21 | ||
| Cranial Nerve Examination | e21 | ||
| Olfactory Nerve: Cranial Nerve I | e21 | ||
| Optic Nerve: Cranial Nerve II | e22 | ||
| Oculomotor, Trochlear, and Abducens Nerves: Cranial Nerves III, IV, and VI | e23 | ||
| Trigeminal Nerve: Cranial Nerve V | e24 | ||
| Facial Nerve: Cranial Nerve VII | e25 | ||
| Auditory Nerve: Cranial Nerve VIII | e26 | ||
| Glossopharyngeal and Vagus Nerves: Cranial Nerves IX and X | e26 | ||
| Spinal Accessory Nerve: Cranial Nerve XI | e26 | ||
| Hypoglossal Nerve: Cranial Nerve XII | e26 | ||
| Skeletal Muscles | e27 | ||
| Muscle Testing | e27 | ||
| Deep Tendon Reflexes | e29 | ||
| Other Reflexes | e33 | ||
| Sensory System | e35 | ||
| Cerebellar Function | e37 | ||
| Gait Evaluation | e37 | ||
| References | e37 | ||
| 3 Neurologic Examination after the Newborn Period Until 2 Years of Age | e39 | ||
| Approach to the Evaluation | e39 | ||
| Evaluation of the Patient | e39 | ||
| Stage 1 | e39 | ||
| Head | e40 | ||
| Cranial Nerves | e41 | ||
| Motor Evaluation | e41 | ||
| Sensory Testing and Cutaneous Examination | e43 | ||
| Stage 2 | e43 | ||
| Motor Performance Instruments | e44 | ||
| Developmental Reflexes | e44 | ||
| Stage 3 | e46 | ||
| Stage 4 | e47 | ||
| General Considerations | e47 | ||
| References | e48 | ||
| 4 Neurologic Examination of the Term and Preterm Infant | e49 | ||
| The Infant | e49 | ||
| Observation | e49 | ||
| Cranial Vault Evaluation | e49 | ||
| Developmental Reflexes | e50 | ||
| Motor Function | e50 | ||
| Cranial Nerve Examination | e52 | ||
| The Preterm Infant | e53 | ||
| General Examination | e53 | ||
| Neurologic Examination | e53 | ||
| Environmental Interaction | e54 | ||
| Formal Scale of Gestational Assessment | e54 | ||
| Deep Tendon Reflex Assessment | e54 | ||
| Body Attitude | e54 | ||
| Muscle Tone | e54 | ||
| Cranial Nerves | e56 | ||
| Developmental Reflexes | e60 | ||
| Assessment of Head Growth Patterns | e61 | ||
| References | e63 | ||
| 5 Muscular Tone and Gait Disturbances | e64 | ||
| Tone | e64 | ||
| Pathology | e64 | ||
| Evaluation of the Patient | e65 | ||
| History | e65 | ||
| Examination | e65 | ||
| Diagnosis | e67 | ||
| Clinical Laboratory Studies | e67 | ||
| Gait Impairment | e70 | ||
| Physiologic Considerations | e70 | ||
| Evaluation of the Patient | e71 | ||
| Differential Diagnosis | e72 | ||
| Spastic Hemiplegic Gait | e72 | ||
| Spastic Diplegic Gait | e72 | ||
| Cerebellar Gait | e73 | ||
| Extrapyramidal Gait | e74 | ||
| Other Dyskinetic Gaits | e74 | ||
| Steppage Gait | e74 | ||
| Hip Weakness Gait | e74 | ||
| Gait Apraxia | e74 | ||
| Antalgic Gait (Painful Gait) | e75 | ||
| Conversion Disorder | e75 | ||
| References | e75 | ||
| 6 Vision Loss | e78 | ||
| Visual Development | e78 | ||
| Assessment and Quantification of Visual Acuity | e78 | ||
| Vision Assessment in Infancy | e78 | ||
| Vision Assessment in Children | e79 | ||
| Assessment of Color Vision | e79 | ||
| Assessment of Visual Fields | e79 | ||
| Assessment of Ocular Motility | e79 | ||
| Assessment of Optic Nerve and Retinal Nerve Fiber Layer Integrity | e80 | ||
| Clinical Features Associated with Vision Loss | e80 | ||
| Examination of Children with Vision Loss | e81 | ||
| Vision Loss in Infants | e81 | ||
| Clinical Manifestations | e81 | ||
| Differential Diagnosis of Vision Loss in Infants | e83 | ||
| Structural Anomalies | e83 | ||
| Retinopathy of Prematurity. | e83 | ||
| Congenital Cataracts. | e83 | ||
| Corneal Opacity. | e83 | ||
| Ocular Coloboma. | e84 | ||
| Congenital Glaucoma. | e84 | ||
| Retinal Dysplasia. | e84 | ||
| Optic Nerve Hypoplasia. | e85 | ||
| Aniridia. | e85 | ||
| Ocular or Oculocutaneous Albinism. | e85 | ||
| Leber Congenital Amaurosis. | e85 | ||
| Vision Loss Caused by Cortical Visual Impairment | e86 | ||
| Structural Cerebral Anomalies Causing Cortical Visual Impairment | e87 | ||
| Hydrocephalus. | e87 | ||
| Structural Brain Anomalies. | e87 | ||
| Vision Loss Associated with Epilepsy. | e87 | ||
| Delayed Visual Maturation. | e87 | ||
| Diagnostic Evaluation of Infants with Poor Vision | e87 | ||
| Vision Loss in Children | e87 | ||
| Symptoms and Signs of Vision Loss | e87 | ||
| Differential Diagnosis of Vision Loss in Children | e88 | ||
| Amblyopia | e88 | ||
| Ocular Anomalies Causing Vision Loss | e88 | ||
| Eyelid Abnormalities: Ptosis. | e88 | ||
| Corneal Anomalies. | e88 | ||
| Anomalies of the Iris. | e88 | ||
| Anomalies of the Retina. | e88 | ||
| Retinitis Pigmentosa. | e89 | ||
| Neurometabolic Retinal Dysfunction. | e89 | ||
| Optic Nerve Disorders | e90 | ||
| Papilledema. | e90 | ||
| Pseudopapilledema. | e90 | ||
| Optic Neuritis. | e90 | ||
| Optic Atrophy. | e91 | ||
| Cerebral Vision Impairment | e91 | ||
| Nystagmus in Infancy | e91 | ||
| Nystagmus Caused by Visual Deprivation | e92 | ||
| Nystagmus Caused by Cerebral Disease | e92 | ||
| Congenital Motor Nystagmus | e92 | ||
| Transient Episodic Vision Loss in Children | e93 | ||
| References | e95 | ||
| 7 Hearing Impairment | e99 | ||
| Introduction | e99 | ||
| Anatomy and Physiology of the Ear and Auditory System | e99 | ||
| The External Ear | e101 | ||
| The Middle Ear | e101 | ||
| The Cochlea | e102 | ||
| The Central Auditory Nervous System | e103 | ||
| HI Classification | e104 | ||
| Classification by Definition of Impairment Site | e104 | ||
| 1. Conductive HI. | e104 | ||
| 2. Sensorineural HL. | e104 | ||
| 3. Auditory Neuropathy Spectrum Disorder. | e104 | ||
| 4. Central HL. | e104 | ||
| Classification by Severity and Profile of Thresholds Elevation | e104 | ||
| Functional and Structural Evaluation of Auditory Function | e105 | ||
| The Cross-Check Principle | e105 | ||
| Behavioral Methods | e105 | ||
| Auditory Thresholds | e105 | ||
| Supra-Threshold Testing | e106 | ||
| Objective Methods | e107 | ||
| Tympanometry | e107 | ||
| Objective Audiometry | e107 | ||
| Otoacoustic Emissions. | e107 | ||
| Evoked Potentials | e107 | ||
| Imaging | e109 | ||
| Hearing Problems in the Pediatric Population | e109 | ||
| Conductive HL and External Ear Malformations | e109 | ||
| Sensorineural HL | e109 | ||
| Ototoxicity | e110 | ||
| Traumatic HL | e110 | ||
| Auditory Neuropathy Spectrum Disorders | e110 | ||
| Genetic Hearing Loss | e110 | ||
| Nonsyndromic Hearing Loss | e111 | ||
| Autosomal Recessive Inheritance | e111 | ||
| Autosomal Dominant Inheritance. | e111 | ||
| X-linked and Mitochondrial Inheritance. | e111 | ||
| Genetic Diagnostics for Nonsyndromic Hearing Loss. | e111 | ||
| Syndromic Hearing Loss | e112 | ||
| Syndromic Genetic Hearing Loss | e112 | ||
| Consequences of Hearing Impairment | e114 | ||
| Diagnostic Evaluation of Suspected HI: Clinical Evaluation and Specialized Testing | e115 | ||
| Patient and Family Histories | e115 | ||
| Clinical Evaluation and Specialized Testing | e115 | ||
| Audiological Evaluation | e116 | ||
| Clinical Examples | e116 | ||
| Management | e116 | ||
| Reconstructive Surgery for External and Middle Ears Malformation | e119 | ||
| Choice of Communication Mode for Severe to Profound HI | e119 | ||
| Assistive Devices | e120 | ||
| Cochlear Implants | e120 | ||
| Brainstem Implants | e121 | ||
| Accessory Devices | e121 | ||
| Constraints on Speech and Language Learning | e121 | ||
| Future Developments | e121 | ||
| Electrophysiology | e121 | ||
| Imaging | e121 | ||
| Conventional Hearing Aids | e121 | ||
| Hearing Restoration Therapies | e121 | ||
| References | e121 | ||
| 8 Vertigo | e126 | ||
| Introduction | e126 | ||
| Physiologic Basis of Balance | e126 | ||
| Evaluation of Patients with Dizziness | e126 | ||
| History | e126 | ||
| Chief Complaint | e126 | ||
| Physical Examination | e127 | ||
| Videonystagmography | e127 | ||
| Caloric Testing | e129 | ||
| Rotational Testing | e129 | ||
| Computerized Dynamic Platform Posturography | e130 | ||
| Posturography and Vestibular Disorders— Results from the Medical Literature | e131 | ||
| Vestibular-Evoked Myogenic Potentials | e131 | ||
| Disorders Producing Vertigo | e131 | ||
| Acute Nonrecurring Spontaneous Vertigo | e131 | ||
| Head Trauma | e131 | ||
| Vestibular Neuritis | e131 | ||
| Recurrent Vertigo | e132 | ||
| Migraine-Related Dizziness | e132 | ||
| Ménière’s Disease | e132 | ||
| Seizure Disorders | e132 | ||
| Familial Episodic Ataxia | e132 | ||
| Nonvertiginous Disequilibrium | e132 | ||
| Bilateral Peripheral Vestibular Loss | e132 | ||
| Central Nervous System Disorders | e132 | ||
| Drug-Induced Dizziness | e133 | ||
| Nonneurologic Disorders | e133 | ||
| Treatments | e133 | ||
| References | e133 | ||
| 9 Taste and Smell | e134 | ||
| Chemical Senses | e134 | ||
| Taste, Smell, and Flavor | e134 | ||
| The Taste System | e134 | ||
| The Olfactory System | e134 | ||
| Flavor | e135 | ||
| Clinical Disorders of Taste and Smell | e135 | ||
| The Ontogeny of Taste Perception and Preferences | e138 | ||
| Fetus and Preterm Infants | e138 | ||
| Newborns, Infants, and Young Children | e139 | ||
| Sweet Taste | e139 | ||
| Umami Taste | e140 | ||
| Sour Taste | e140 | ||
| Bitter Taste | e140 | ||
| Salty Taste | e141 | ||
| Clinical Significance of Taste in Infants and Children | e141 | ||
| The Ontogeny of Olfactory and Flavor Perception | e142 | ||
| The Fetus | e142 | ||
| Newborns | e142 | ||
| Infants | e143 | ||
| Young Children | e144 | ||
| Clinical Significance of Olfaction in Infants and Children | e145 | ||
| Summary | e145 | ||
| Acknowledgments | e146 | ||
| References | e146 | ||
| 10 Neuropsychological Assessment | e150 | ||
| Introduction | e150 | ||
| Neuropsychological Assessment | e150 | ||
| What is a Neuropsychological Assessment? | e150 | ||
| Multicultural Factors | e151 | ||
| Neuropsychological Testing | e151 | ||
| When to Refer for Neuropsychological Evaluation | e152 | ||
| The Neuropsychological Report | e152 | ||
| Conclusion | e158 | ||
| References | e158 | ||
| 11 Spinal Fluid Examination | e160 | ||
| Introduction | e160 | ||
| History | e160 | ||
| Cerebrospinal Fluid Formation, Flow, and Absorption | e160 | ||
| Cerebrospinal Fluid Function | e162 | ||
| Diagnostic Sampling of Cerebrospinal Fluid | e162 | ||
| Indications | e162 | ||
| Contraindications and Cautions | e163 | ||
| Procedure | e163 | ||
| Complications | e164 | ||
| Cerebrospinal Fluid Analysis | e165 | ||
| Appearance | e165 | ||
| Cells | e166 | ||
| Microorganisms | e166 | ||
| Glucose | e167 | ||
| Protein | e167 | ||
| Immunologic Analysis | e169 | ||
| Neurometabolic Studies | e169 | ||
| References | e170 | ||
| 12 Pediatric Neuroimaging | e173 | ||
| Cranial Ultrasound | e173 | ||
| Computed Tomography | e176 | ||
| Magnetic Resonance Imaging | e179 | ||
| Magnetic Resonance Spectroscopy | e186 | ||
| Spectral Metabolites Using Proton Magnetic Resonance Spectroscopy | e188 | ||
| Diseases Studied with Proton Magnetic Resonance Spectroscopy | e189 | ||
| Diffusion-Weighted Imaging | e193 | ||
| Diffusion Tensor Imaging | e194 | ||
| Perfusion Magnetic Resonance Imaging | e198 | ||
| Susceptibility-Weighted Imaging | e199 | ||
| Functional Magnetic Resonance Imaging | e200 | ||
| Magnetic Source Imaging | e201 | ||
| Spinal Imaging | e202 | ||
| Angiography | e202 | ||
| Single-Photon Emission Computed Tomography and Positron Emission Tomography | e202 | ||
| Acknowledgments | e204 | ||
| References | e204 | ||
| 13 Pediatric Neurophysiologic Evaluation | e212 | ||
| Utility of Pediatric Neurophysiological Studies | e212 | ||
| Training in Clinical Neurophysiology | e212 | ||
| Instrumentation and Recording Techniques | e213 | ||
| Polarity Localization | e213 | ||
| Instrumental Control Settings | e213 | ||
| Sensitivity Settings | e213 | ||
| Filter Settings | e213 | ||
| Paper Speed | e214 | ||
| Physiologic Noncerebral Channels | e214 | ||
| Artifact Recognition | e214 | ||
| Recording Setting | e215 | ||
| Neurophysiological Basis for Electroencephalography | e215 | ||
| Potential Fields and Neuronal Networks | e218 | ||
| Neurophysiologic Basis of Abnormal Electrical Patterns | e219 | ||
| Abnormal Suppression or Slowing of Electroencephalographic Activity | e219 | ||
| Significance of Normal Variation in Electroencephalography: Maturational Patterns | e220 | ||
| Guidelines for Interpretation | e220 | ||
| Newborn Electroencephalographic Patterns | e221 | ||
| Ontogeny of Electroencephalographic Features | e222 | ||
| Gestational Age of Younger Than 28 Weeks | e226 | ||
| Gestational Age of 28 to 31 Weeks | e226 | ||
| Gestational Age of 32 to 34 Weeks | e227 | ||
| Gestational Age of 34 to 37 Weeks | e227 | ||
| Gestational Age of 38 to 42 Weeks | e228 | ||
| Normal Electroencephalographic Patterns in Infancy Through Adolescence | e229 | ||
| Waking Patterns | e229 | ||
| Mu Rhythm | e230 | ||
| Beta Activity | e230 | ||
| Theta and Delta Slowing | e230 | ||
| Lambda Waves | e231 | ||
| Hyperventilatory Response | e231 | ||
| Photic Stimulation | e231 | ||
| Drowsy Patterns | e231 | ||
| Sleep Activation Procedures | e232 | ||
| Sleep Patterns | e233 | ||
| Electroencephalographic Neonatal Sleep as an Ultradian Rhythm | e233 | ||
| Infant and Childhood Sleep | e234 | ||
| Vertex Waves and Sleep Spindles | e234 | ||
| Occipital Sharp Transients | e235 | ||
| Frequency Distribution During Sleep | e235 | ||
| Arousal Patterns | e235 | ||
| Patterns of Uncertain Significance | e235 | ||
| Abnormal Electroencephalographic Patterns | e236 | ||
| Abnormal Neonatal Electroencephalographic Patterns | e236 | ||
| Assessment of Prognosis | e236 | ||
| Focal Abnormalities | e238 | ||
| Neonatal Seizures | e239 | ||
| Focal Periodic Patterns | e241 | ||
| Spikes and Sharp Waves | e241 | ||
| Epileptiform Abnormalities | e241 | ||
| Generalized Epileptiform Patterns | e242 | ||
| Spike-and-Wave Patterns. | e242 | ||
| Sharp-Wave and Slow-Wave Complexes. | e243 | ||
| Hypsarrhythmia. | e243 | ||
| Generalized Periodic Discharges. | e244 | ||
| Secondary Bilateral Synchrony. | e244 | ||
| Focal Epileptiform Patterns | e244 | ||
| Rolandic Spikes. | e244 | ||
| Occipital Spikes. | e244 | ||
| Other Idiopathic Focal Epilepsies of Childhood | e245 | ||
| Temporal Spikes and Sharp Waves | e245 | ||
| Multiple Independent Spike Foci | e245 | ||
| Spike Discharges Associated With Specific Neurologic Conditions | e246 | ||
| Periodic Discharges | e246 | ||
| Abnormal Nonepileptiform Patterns | e247 | ||
| Role of Pediatric Electroencephalography in Specific Neurologic Situations | e247 | ||
| Febrile Seizures | e247 | ||
| Head Trauma | e247 | ||
| Headaches | e248 | ||
| Prognosis After Hypoxic-Ischemic Insults | e248 | ||
| Determination of Brain Death | e248 | ||
| Central Nervous System Infections | e248 | ||
| Degenerative Diseases | e249 | ||
| Reye Syndrome | e249 | ||
| Nonepileptic Paroxysmal Disorders | e249 | ||
| Monitoring Strategies and Computer Analyses of Electrographic Data | e250 | ||
| Synchronized Video-Electroencephalographic Recordings | e250 | ||
| Pediatric Neurointensive Care | e250 | ||
| Electroencephalography and Functional Neuroimaging | e251 | ||
| Magnetoencephalography | e251 | ||
| Computer Strategies for Electroencephalographic Sleep Analyses | e251 | ||
| Evoked Potential Analysis | e252 | ||
| Auditory-Evoked Potentials | e253 | ||
| Visual-Evoked Responses | e254 | ||
| Electroretinography | e255 | ||
| Somatosensory-Evoked Potentials | e256 | ||
| Event-Related Potentials | e257 | ||
| References | e257 | ||
| 14 Microstructural and Functional Connectivity in the Developing Brain | e266 | ||
| Abbreviations | e266 | ||
| Introduction | e266 | ||
| Assessment Strategies for Connectivity | e266 | ||
| Microstructural Connectivity | e266 | ||
| Functional Connectivity | e267 | ||
| Effective Connectivity | e268 | ||
| Anatomic Covariance | e268 | ||
| Tools of Network Science | e268 | ||
| Intrinsic Connectivity Networks | e269 | ||
| Categorization of Disorders of Connectivity | e270 | ||
| Fetal Development | e270 | ||
| Microstructural Studies | e270 | ||
| Fetal Functional Imaging | e270 | ||
| Environmental Perturbations | e271 | ||
| Connectivity in Typically Developing Children | e271 | ||
| Maturation of Microstructural Networks: Increases in Anisotropy, Decreases in Diffusivity | e271 | ||
| Functional Maturation: Increases in Both Integration and Segregation | e272 | ||
| Influence of Genes and the Environment | e272 | ||
| Preterm Birth Results in Long-Term Alterations in Connectivity | e273 | ||
| dMRI Studies Provide Evidence of Widespread Microstructural Abnormalities | e273 | ||
| Functional Studies: Alterations in Neural Networks in the Prematurely Born | e273 | ||
| Graph Theory Supports Both Widespread and Long-Lasting Changes in Connectivity in the Prematurely Born | e273 | ||
| Environmental Factors Alter Connectivity in the Prematurely Born | e274 | ||
| Autism Spectrum Disorder | e274 | ||
| Tourette Syndrome | e275 | ||
| Attention-Deficit/Hyperactivity Disorder | e276 | ||
| Sports-Related Concussion | e277 | ||
| Epilepsy | e278 | ||
| Childhood Absence Epilepsy | e278 | ||
| Rolandic Epilepsy | e278 | ||
| Localization-Related Epilepsy | e278 | ||
| Intractable Localization-Related Epilepsy | e279 | ||
| Perinatal Stroke | e279 | ||
| Imaging Genetics | e279 | ||
| Undiagnosed Developmental Disorders: The Role of Connectivity | e280 | ||
| Current Clinical Applications | e280 | ||
| Challenges for the Assessment of Connectivity | e280 | ||
| Feasibility | e280 | ||
| In-Scanner Head Motion | e280 | ||
| Age-Specific Atlases | e281 | ||
| Imaging during Natural Sleep | e281 | ||
| Conclusions | e281 | ||
| Acknowledgments | e281 | ||
| References | e281 | ||
| 15 Stem Cell Transplantation for Childhood Neurologic Disorders | e287 | ||
| Neural Stem Cell Biology | e287 | ||
| Definition of Neural Stem Cells | e287 | ||
| Stem Cell Niche and Function of Neural Stem Cells in the Developing Central Nervous System | e287 | ||
| Isolation and Propagation of Neural Stem Cells in Vitro | e287 | ||
| Generation of Human and Murine Neural Stem Cells from Embryonic Stem Cells | e288 | ||
| Generation of Neural Stem Cells from Induced Pluriporent Stem Cells | e288 | ||
| Transplantation of Neural Stem Cells | e289 | ||
| Detection of Donor Neural Stem Cells in the Host Mouse Brain | e289 | ||
| Homing of Neural Stem Cells | e289 | ||
| Bystander Effects of Engrafted Neural Stem Cells | e290 | ||
| Therapeutic Potential of Neural Stem Cells | e290 | ||
| Lysosomal Storage Disorders | e290 | ||
| Bystander Effects of Neural Stem Cells in Lysosomal Storage Disorders | e291 | ||
| Cell Replacement of NSCs in LSD | e291 | ||
| Hypoxic Ischemic Brain Injury and Stroke | e292 | ||
| Summary | e292 | ||
| Future Applications | e292 | ||
| References | e293 | ||
| 16 Cellular and Animal Models of Neurologic Disease | e296 | ||
| Introduction | e296 | ||
| Spontaneously Occurring Mutant Animals | e296 | ||
| Genetically Engineered Mouse Models | e297 | ||
| Transgenic Mice | e297 | ||
| Knock-out and Knock-in Mice | e299 | ||
| Genome Engineering Using CRISPR-Cas9 Technology | e302 | ||
| Cellular Model Systems: Cell Lines and Primary Neuronal Cultures | e303 | ||
| Induced Pluripotent Stem Cells: A Novel Human Cell Model for Neurologic Diseases | e305 | ||
| Current Limitations of Induced Pluripotent Stem Cells as a Disease Modeling Approach | e305 | ||
| Insights from Induced Pluripotent Stem Cells to Model Neurodevelopmental Disorders | e306 | ||
| Using iPSCs for Drug Screening | e306 | ||
| References | e306 | ||
| 17 Neonatal Neurointensive Care | e309 | ||
| Introduction | e309 | ||
| Establishing a Multidisciplinary Neurointensive Care Nursery | e309 | ||
| Work Flow in the Neurointensive Care Nursery | e311 | ||
| Clinical Scenarios Demonstrating Approach to Neurointensive Care | e311 | ||
| Neonatal Encephalopathy | e311 | ||
| Premature Neonate with Seizures | e311 | ||
| Resuscitation and Supportive Care to Prevent Brain Injury | e312 | ||
| Current Treatment Options for Neonates with Hypoxic-Ischemic Encephalopathy | e312 | ||
| Brain Monitoring and Seizure Management | e313 | ||
| Brain Imaging | e315 | ||
| Palliative Care | e315 | ||
| Continuity of Care: Neonatal Neurology and High-Risk Infant Follow-up Programs | e316 | ||
| References | e316 | ||
| 18 Neonatal Seizures | e318 | ||
| Introduction | e318 | ||
| Pathophysiology | e318 | ||
| Mechanisms of Excitability in the Developing Brain | e318 | ||
| The Effect of Seizures on Early Brain Development | e318 | ||
| Epidemiology | e318 | ||
| Incidence of Neonatal Seizures | e318 | ||
| Risk Factors for Neonatal Seizures | e319 | ||
| Etiology | e319 | ||
| Acute Symptomatic Seizures | e320 | ||
| Developmental Brain Abnormalities | e321 | ||
| Epilepsy Syndromes | e321 | ||
| Diagnosis | e322 | ||
| Neonatal Electroencephalogram Monitoring | e323 | ||
| Conventional Video Electroencephalogram | e323 | ||
| Indications for Electroencephalogram Monitoring | e323 | ||
| Duration of Electroencephalogram Recording | e323 | ||
| Diagnostic Considerations for Neonates with Seizures | e324 | ||
| Treatment | e325 | ||
| Acute Treatment | e325 | ||
| Treatment of Acute Symptomatic Seizures | e325 | ||
| Discontinuation of Medication for Acute Symptomatic Seizures | e327 | ||
| Treatment of Early Onset Epilepsy Syndromes | e327 | ||
| Outcomes After Neonatal Seizures | e327 | ||
| Mortality After Neonatal Seizures | e327 | ||
| Cognitive Outcomes After Neonatal Seizures | e327 | ||
| Cerebral Palsy After Neonatal Seizures | e327 | ||
| Postneonatal Epilepsy | e327 | ||
| Conclusions | e328 | ||
| References | e328 | ||
| 19 Hypoxic-Ischemic Brain Injury in the Term Newborn | e331 | ||
| Scope of the Problem | e331 | ||
| Etiology of Brain Injury in the Term Newborn | e331 | ||
| Clinical Syndrome and Natural History | e331 | ||
| Clinical Syndrome | e331 | ||
| Neonatal Encephalopathy | e331 | ||
| Management of Neonatal Encephalopathy | e332 | ||
| Clinical Management | e332 | ||
| Brain Imaging of Newborns With Encephalopathy | e333 | ||
| Advanced Magnetic Resonance Techniques. | e334 | ||
| Magnetic Resonance Spectroscopy. | e334 | ||
| Diffusion Imaging. | e334 | ||
| Brain Perfusion. | e334 | ||
| Patterns of Brain Injury | e334 | ||
| Progression of Neonatal Brain Injury | e335 | ||
| Outcomes | e335 | ||
| Motor Function | e335 | ||
| Vision and Hearing | e336 | ||
| Cognition | e336 | ||
| Outcome and Therapeutic Hypothermia | e336 | ||
| Outcome Prediction | e337 | ||
| Pathophysiology of Neonatal Hypoxic-Ischemic Brain Injury and Neuroprotection | e337 | ||
| Cerebral Blood Flow and Energy Metabolism | e337 | ||
| Excitotoxicity | e339 | ||
| Oxidative Stress | e340 | ||
| Neuroinflammation | e341 | ||
| Cell Death | e341 | ||
| Other Neuroprotection Strategies | e341 | ||
| Neurotrophic Factors | e342 | ||
| Stem Cells | e342 | ||
| Hypoxic-Ischemic Brain Injury in the Preterm Infant | e343 | ||
| Future Directions | e343 | ||
| Conclusions | e343 | ||
| References | e344 | ||
| 20 Cerebrovascular Disorders in the Newborn | e349 | ||
| Introduction | e349 | ||
| Definitions and Terminology | e349 | ||
| Acute Symptomatic Perinatal Arterial Ischemic Stroke (PAIS) | e349 | ||
| Epidemiology | e349 | ||
| Pathophysiology and Potential Risk Factors | e349 | ||
| Placental Disease | e349 | ||
| Maternal and Antepartum Factors | e350 | ||
| Intrapartum Risk Factors | e350 | ||
| Prothrombotic | e351 | ||
| Cardiac | e351 | ||
| Infection | e351 | ||
| Genetics | e351 | ||
| PAIS in the Preterm Infant | e351 | ||
| Clinical Presentation | e351 | ||
| Diagnosis: Neuroimaging | e352 | ||
| Acute Management: Investigations and Treatment | e352 | ||
| Outcomes and Rehabilitation. | e353 | ||
| Motor: Cerebral Palsy | e353 | ||
| Somatosensory | e354 | ||
| Visuospatial | e354 | ||
| Cognition | e354 | ||
| Executive Function and Attention | e354 | ||
| Language | e354 | ||
| Epilepsy | e355 | ||
| Outcome Prediction | e355 | ||
| Recurrence | e355 | ||
| Psychology and Mental Health | e355 | ||
| Presumed Perinatal Stroke (PPS) | e355 | ||
| Arterial Presumed Perinatal Stroke | e356 | ||
| Periventricular Venous Infarction (PVI) | e357 | ||
| Neonatal Cerebral Sinovenous Thrombosis (CSVT) | e358 | ||
| Epidemiology | e358 | ||
| Pathophysiology and Risk Factors | e358 | ||
| Clinical Presentation and Diagnosis | e358 | ||
| Management | e359 | ||
| Outcomes | e360 | ||
| Perinatal Intracerebral Hemorrhage | e360 | ||
| Definitions and Epidemiology | e360 | ||
| Pathophysiology and Risk Factors | e361 | ||
| Clinical Presentation and Diagnosis | e361 | ||
| Management | e362 | ||
| Outcomes | e362 | ||
| Synopsis | e362 | ||
| References | e363 | ||
| 21 Neonatal Nervous System Trauma | e369 | ||
| Introduction | e369 | ||
| Intrauterine Trauma | e369 | ||
| Penetrating Trauma | e369 | ||
| Blunt Trauma | e370 | ||
| Trauma Associated with Birth, by Location | e370 | ||
| Caput Succedaneum | e370 | ||
| Cephalohematoma | e370 | ||
| Subgaleal Hematoma | e371 | ||
| Skull Fractures | e371 | ||
| Intracranial Hemorrhage | e372 | ||
| Epidural Hemorrhage | e372 | ||
| Subdural Hemorrhage | e372 | ||
| Posterior Fossa Hemorrhage | e372 | ||
| Subarachnoid Hemorrhage | e372 | ||
| Intraparenchymal Hemorrhage and Cerebral Contusions | e372 | ||
| Intraventricular Hemorrhage | e373 | ||
| Spinal Cord Injury | e373 | ||
| Facial Nerve Injury | e373 | ||
| Brachial Plexus Injury | e374 | ||
| Phrenic Nerve Injury | e375 | ||
| Radial Nerve Palsy | e375 | ||
| Trauma Associated with Specific Obstetric Maneuvers | e375 | ||
| Vacuum Delivery | e375 | ||
| Vacuum Extraction and Prematurity | e375 | ||
| Extracranial Complications of Vacuum Extraction | e376 | ||
| Intracranial Complications of Vacuum Extraction | e376 | ||
| Forceps | e376 | ||
| Fetal Scalp Electrodes | e376 | ||
| Perinatal Counseling for Avoidance of Birth-Associated Trauma | e376 | ||
| Nervous System Trauma during the Newborn Period | e376 | ||
| Abusive Head Trauma in the Neonatal Period | e376 | ||
| Accidental Falls | e377 | ||
| Iatrogenic Trauma | e377 | ||
| Central Nervous System Iatrogenic Trauma | e377 | ||
| Peripheral Nervous System Iatrogenic Trauma | e377 | ||
| Trauma Mimics | e378 | ||
| Bone Disease | e378 | ||
| Bleeding Disorders | e378 | ||
| Nervous System Vascular Malformations | e379 | ||
| References | e379 | ||
| 22 Injury to the Developing Preterm Brain | e382 | ||
| Introduction | e382 | ||
| Intraventricular Hemorrhage | e382 | ||
| Pathophysiology | e382 | ||
| Intraventricular Hemorrhage Is a Complex Disorder | e382 | ||
| Clinical Risk Factors | e383 | ||
| Maternal Race and Healthcare Disparities Influence Risk for IVH in Preterm Neonates | e383 | ||
| Anatomic Factors Are Permissive for Hemorrhage | e383 | ||
| Alterations in Cerebral Blood Flow Contribute to IVH | e385 | ||
| Candidate Genes for IVH | e385 | ||
| Preclinical Studies Suggest Variants in Microvascular Proteins | e385 | ||
| Clinical Studies Implicate Candidate Genes in Coagulation, Inflammatory and Vascular Pathways | e386 | ||
| Coagulation Candidates. | e386 | ||
| Inflammatory Factors. | e386 | ||
| Vascular Genes. | e387 | ||
| Gene-by-Environment Interactions. | e387 | ||
| Neuropathology | e387 | ||
| Neuroimaging | e388 | ||
| Intraventricular Hemorrhage | e388 | ||
| Intraparenchymal Echodensities | e389 | ||
| Porencephaly | e389 | ||
| Clinical Findings | e389 | ||
| Incidence | e389 | ||
| Timing of IVH | e390 | ||
| Clinical Manifestations | e390 | ||
| Cerebrospinal Fluid Studies | e390 | ||
| Neonatal Outcome | e390 | ||
| Posthemorrhagic Hydrocephalus | e391 | ||
| Long-Term Outcome | e392 | ||
| Cerebral Palsy | e392 | ||
| Cognitive Outcome in Neonates With Intraventricular Hemorrhage | e392 | ||
| Alterations in Brain Development | e392 | ||
| Prevention of Intraventricular Hemorrhage | e393 | ||
| Environmental Prevention Strategies | e393 | ||
| Pharmacologic Prevention | e393 | ||
| Antenatal Corticosteroid Exposure | e393 | ||
| Indomethacin | e393 | ||
| Other Pharmacologic Prevention Strategies | e394 | ||
| Combined Environmental and Pharmacologic Strategies | e394 | ||
| Cerebellar Hemorrhage | e394 | ||
| White Matter Injury of the Premature Newborn | e394 | ||
| Neuropathology | e395 | ||
| Pathogenesis | e396 | ||
| Hypoxia-Ischemia | e396 | ||
| Inflammation/Infection | e396 | ||
| Vulnerability of Immature White Matter, Particularly Immature Oligodendrocytes | e397 | ||
| Additional Risk Factors | e397 | ||
| Intraventricular Hemorrhage. | e397 | ||
| Postnatal Corticosteroid Use. | e397 | ||
| Nutrition. | e397 | ||
| Clinical Presentation | e397 | ||
| EEG | e398 | ||
| Neuroimaging | e398 | ||
| Ultrasound | e398 | ||
| Magnetic Resonance Imaging | e399 | ||
| Recommendations for Imaging the Preterm Neonate and Child Born Preterm | e400 | ||
| Outcome | e400 | ||
| Cognitive | e401 | ||
| Social/Behavioral | e402 | ||
| Motor | e402 | ||
| Visual | e402 | ||
| Epilepsy | e402 | ||
| Prevention and Management | e402 | ||
| NICU Management | e403 | ||
| Management after NICU Discharge | e403 | ||
| Acknowledgments | e403 | ||
| References | e404 | ||
| 23 Perinatal Metabolic Encephalopathies | e411 | ||
| Introduction | e411 | ||
| General Approach | e411 | ||
| Correctable Disturbances of Glucose and Salt Balance | e412 | ||
| Hypoglycemia | e412 | ||
| Disturbances of Sodium Balance | e414 | ||
| Hyponatremia | e414 | ||
| Hypernatremia | e415 | ||
| Inborn Errors of Metabolism | e415 | ||
| Acute Fulminant Metabolic Diseases | e415 | ||
| Maple Syrup Urine Disease | e415 | ||
| Other Organic Acidopathies | e419 | ||
| Primary Lactic Acidosis Resulting From Defects in Oxidative Phosphorylation | e420 | ||
| Glutamine Synthetase Deficiency | e422 | ||
| Fructose-1,6-Biphosphatase Deficiency | e422 | ||
| Fatty Acid Oxidation Defects | e422 | ||
| Urea Cycle Disorders | e423 | ||
| Subacute Epileptic Encephalopathies | e423 | ||
| Glycine Cleavage Defects | e423 | ||
| Pyridoxine-Dependent and Pyridoxal Phosphate-Dependent Epileptic Encephalopathies | e424 | ||
| Sulfite Oxidase and Molybdenum Cofactor Deficiency | e425 | ||
| Menkes’ Disease | e426 | ||
| Glucose Transporter Defects | e426 | ||
| Serine Biosynthesis Defects | e427 | ||
| Purine Biosynthesis Defects | e427 | ||
| l-Amino Acid Decarboxylase Deficiency | e427 | ||
| Asparagine Synthetase Deficiency | e428 | ||
| Chronic Encephalopathies Without Multiorgan Involvement | e428 | ||
| Hyperphenylalaninemia | e428 | ||
| Succinic Semialdehyde Dehydrogenase Deficiency | e428 | ||
| Glutaric Aciduria | e428 | ||
| Chronic Encephalopathies With Multiorgan Involvement | e429 | ||
| Congenital Disorders of Glycosylation | e429 | ||
| Peroxisomal Disorders | e429 | ||
| Cholesterol Biosynthesis Defects (Smith–Lemli–Opitz Syndrome) | e429 | ||
| References | e429 | ||
| 24 Overview of Human Brain Malformations | e432 | ||
| Introduction | e432 | ||
| Epidemiology | e432 | ||
| Classification | e432 | ||
| Brain Imaging Recognition | e432 | ||
| Relationships to Other Neurologic Disorders | e434 | ||
| Relationship to Environmental Factors | e434 | ||
| Genetic Counseling | e434 | ||
| References | e435 | ||
| 25 Disorders of Neural Tube Development | e437 | ||
| Introduction | e437 | ||
| Anatomy and Embryology | e437 | ||
| Formation of the Neural Tube | e437 | ||
| Molecular Patterning of the Neural Tube | e439 | ||
| Epidemiology and Pathogenesis | e440 | ||
| Incidence | e440 | ||
| Complex Genetic Contributions | e440 | ||
| Gene-Environment Interactions Influencing Neural Tube Defects | e441 | ||
| Gene-Diet Interactions in Neural Tube Defects: Role of Metabolism of Folic Acid and Other Nutrients | e441 | ||
| Teratogens | e441 | ||
| Classification of Neural Tube Defects | e442 | ||
| Nomenclature | e442 | ||
| Embryologic Classification of Neural Tube Defects | e442 | ||
| Myelomeningocele | e442 | ||
| Antenatal Diagnosis | e442 | ||
| Prevention | e443 | ||
| Clinical Features | e444 | ||
| Secondary Abnormalities | e444 | ||
| Central Nervous System Complications | e444 | ||
| Bladder and Bowel Dysfunction | e444 | ||
| Orthopedic Problems | e444 | ||
| Chiari II Malformation | e445 | ||
| Classification. | e445 | ||
| Pathophysiology. | e445 | ||
| Clinical Features. | e445 | ||
| Management | e446 | ||
| Fetal Repair of Myelomeningocele | e446 | ||
| Management in the Newborn Period | e447 | ||
| Treatment of Chiari II Malformation | e447 | ||
| Outcome | e447 | ||
| Counseling | e447 | ||
| Anencephaly | e447 | ||
| Pathogenesis | e448 | ||
| Differential Diagnosis | e448 | ||
| Pathology | e448 | ||
| Encephalocele | e448 | ||
| Etiology | e448 | ||
| Clinical Characteristics | e448 | ||
| Management | e449 | ||
| Occult Forms of Spinal Dysraphism | e449 | ||
| Spinal Cord Lipoma | e450 | ||
| Dermal Sinus Tract | e450 | ||
| Spina Bifida Occulta | e451 | ||
| Meningocele | e451 | ||
| Split Cord Malformations | e451 | ||
| Embryology | e451 | ||
| Clinical Characteristics | e452 | ||
| Disorders of Secondary Neurulation | e453 | ||
| Fibrofatty Filum Terminale | e453 | ||
| Sacral Agenesis | e453 | ||
| References | e455 | ||
| 26 Disorders of Forebrain Development | e459 | ||
| Introduction | e459 | ||
| Prosencephalon Patterning | e459 | ||
| Prosencephalic Cleavage | e459 | ||
| Holoprosencephaly | e459 | ||
| Historical Background | e459 | ||
| Epidemiology | e459 | ||
| Definition and Subtypes of Holoprosencephaly | e460 | ||
| Neuropathological Findings | e460 | ||
| Etiology | e462 | ||
| Clinical Manifestations and Outcomes | e462 | ||
| Management | e463 | ||
| Prenatal Diagnosis and Imaging | e463 | ||
| Genetic Counseling and Testing | e463 | ||
| Agenesis of the Corpus Callosum | e463 | ||
| Historical Background | e465 | ||
| Epidemiology | e465 | ||
| Prenatal Diagnosis and Prediction of Outcomes | e465 | ||
| Development of the Corpus Callosum | e466 | ||
| Imaging and the Corpus Callosum | e466 | ||
| Etiology | e467 | ||
| Genetic | e467 | ||
| Nongenetic | e469 | ||
| Clinical Manifestations | e469 | ||
| Association of Agenesis of the Corpus Callosum With Autism and Related Neurodevelopmental Disorders | e469 | ||
| Management | e470 | ||
| Septooptic Dysplasia | e471 | ||
| Definition and Subtypes | e471 | ||
| Epidemiology | e471 | ||
| Etiology | e471 | ||
| Clinical Manifestations | e471 | ||
| Management | e471 | ||
| Isolated Septum Pellucidum Dysplasias | e472 | ||
| Absence of the Septum Pellucidum | e472 | ||
| Cavum Septum Pellucidum | e472 | ||
| References | e472 | ||
| 27 Disorders of Cerebellar and Brainstem Development | e476 | ||
| Introduction | e476 | ||
| Clinical Features | e476 | ||
| Approach to Neuroimaging | e476 | ||
| Approach to Genetic Testing | e476 | ||
| Disorders Primarily Affecting Cerebellum | e480 | ||
| Cerebellar Hypoplasia | e480 | ||
| Cerebellar Hypoplasias Primarily Affecting Vermis | e480 | ||
| Dandy-Walker Malformation | e480 | ||
| Joubert Syndrome | e480 | ||
| Global Cerebellar Hypoplasia with Involvement of Both Vermis and Hemispheres | e482 | ||
| Unilateral Cerebellar Hypoplasia | e482 | ||
| Cerebellar Atrophy | e483 | ||
| Cerebellar Dysplasias | e483 | ||
| Cerebellar Hyperplasia and Chiari Type I Malformation | e485 | ||
| Cerebellar Hyperplasia | e485 | ||
| Chiari I Malformation | e485 | ||
| Rhombencephalosynapsis | e487 | ||
| Disorders Affecting Cerebellum and Brainstem | e488 | ||
| Pontocerebellar Hypoplasias | e488 | ||
| Congenital Muscular Dystrophies Due to Defective α-Dystroglycan Glycosylation | e488 | ||
| Tubulinopathies | e490 | ||
| Pontine Tegmental Cap Dysplasia | e490 | ||
| Cerebellar Agenesis | e490 | ||
| Disorders Primarily Affecting Brainstem | e490 | ||
| Horizontal Gaze Palsy and Progressive Scoliosis | e490 | ||
| Brainstem Disconnection | e490 | ||
| Other Disorders with Predominantly Brainstem Involvement | e491 | ||
| References | e491 | ||
| 28 Disorders of Brain Size | e494 | ||
| Introduction | e494 | ||
| Microcephaly | e494 | ||
| Pathology | e494 | ||
| Neuroimaging | e495 | ||
| Clinical Features | e496 | ||
| Etiology | e498 | ||
| Genetics | e503 | ||
| Antenatal Diagnosis | e503 | ||
| Genetic Counseling | e503 | ||
| Summary | e503 | ||
| Megalencephaly (and Macrocephaly) | e503 | ||
| Definition and Classification | e503 | ||
| Pathology and Pathogenesis | e510 | ||
| Clinical Features | e510 | ||
| Etiology | e511 | ||
| References | e514 | ||
| 29 Malformations of Cortical Development | e520 | ||
| Introduction | e520 | ||
| Embryology | e520 | ||
| Classic Studies | e520 | ||
| Neurogenesis | e521 | ||
| Neuronal Migration | e521 | ||
| Cortical Organization | e522 | ||
| Further Reading | e522 | ||
| Biologic Pathways | e522 | ||
| Lissencephaly and Subcortical Band Heterotopia | e522 | ||
| Neuropathology | e522 | ||
| Brain Imaging | e524 | ||
| Clinical Features | e525 | ||
| Epilepsy | e525 | ||
| Survival | e527 | ||
| Syndromes, Genetics, and Molecular Basis | e527 | ||
| Miller-Dieker Syndrome | e527 | ||
| Isolated Lissencephaly Sequence | e527 | ||
| Subcortical Band Heterotopia | e528 | ||
| Lissencephaly With Cerebellar Hypoplasia | e528 | ||
| Baraitser-Winter Syndrome. | e529 | ||
| LIS Variants. | e529 | ||
| LCH RELN-Type. | e529 | ||
| MLIS MOPD1-Type. | e529 | ||
| MLIS Barth-Type. | e529 | ||
| X-Linked Lissencephaly With Abnormal Genitalia. | e529 | ||
| Genetic Counseling | e529 | ||
| Tubulinopathies | e529 | ||
| Neuropathology | e530 | ||
| Brain Imaging | e530 | ||
| Clinical Features | e530 | ||
| Syndromes, Genetics, and Molecular Basis | e530 | ||
| Lissencephaly With Cerebellar Hypoplasia | e530 | ||
| Lissencephaly (Classic) | e530 | ||
| Common Tubulinopathy | e530 | ||
| Developmental Encephalopathy | e531 | ||
| Genetic Counseling | e531 | ||
| Cobblestone Malformations | e531 | ||
| Neuropathology | e531 | ||
| Brain Imaging | e532 | ||
| Clinical Features | e534 | ||
| Prognosis and Management | e534 | ||
| Syndromes, Genetics, and Molecular Basis | e534 | ||
| Walker-Warburg Syndrome. | e535 | ||
| Muscle-Eye-Brain Disease. | e535 | ||
| Fukuyama Congenital Muscular Dystrophy. | e535 | ||
| Frontoparietal Cobblestone Malformation. | e535 | ||
| Congenital Disorders of Glycosylation. | e535 | ||
| Lamininopathies. | e535 | ||
| Genetic Testing | e535 | ||
| Antenatal Diagnosis | e535 | ||
| Neuronal Heterotopia | e536 | ||
| Periventricular Nodular Heterotopia. | e536 | ||
| Pathology | e536 | ||
| Brain Imaging | e536 | ||
| Clinical Features | e537 | ||
| Syndromes, Genetics, and Molecular Basis | e537 | ||
| FLNA-Associated PNH. | e537 | ||
| Unilateral PNH. | e537 | ||
| Other Syndromes. | e537 | ||
| Molecular Basis. | e537 | ||
| Genetic Testing | e537 | ||
| Antenatal Diagnosis | e537 | ||
| Subcortical Nodular and Other Types of Heterotopia | e539 | ||
| Polymicrogyria and Schizencephaly | e539 | ||
| Pathology | e539 | ||
| Brain Imaging | e542 | ||
| Clinical Features | e542 | ||
| Perisylvian Polymicrogyria. | e542 | ||
| Other Patterns. | e543 | ||
| Epilepsy. | e543 | ||
| Schizencephaly. | e543 | ||
| Etiology, Genetics, and Molecular Basis | e543 | ||
| Focal Cortical Dysplasia and Hemimegalencephaly | e544 | ||
| Pathology | e544 | ||
| Brain Imaging | e546 | ||
| Clinical Features | e548 | ||
| Etiology, Genetic, and Molecular Basis | e548 | ||
| Treatment | e549 | ||
| Summary | e549 | ||
| References | e549 | ||
| 30 Hydrocephalus and Arachnoid Cysts | e561 | ||
| Hydrocephalus | e561 | ||
| Definition | e561 | ||
| Classification | e561 | ||
| Epidemiology | e561 | ||
| Cerebrospinal Fluid Production, Circulation, and Absorption | e562 | ||
| Etiology and Pathophysiology | e563 | ||
| Congenital Causes in Infants and Children | e564 | ||
| Acquired Causes in Infants and Children | e565 | ||
| Clinical Characteristics | e565 | ||
| Symptoms and Signs in Infants | e565 | ||
| Symptoms and Signs in Older Children | e566 | ||
| Genetics | e566 | ||
| Neuroimaging | e567 | ||
| Cranial Ultrasound | e567 | ||
| Computed Tomography | e568 | ||
| Magnetic Resonance Imaging | e568 | ||
| Radiography | e568 | ||
| Diagnosis | e568 | ||
| Differential Diagnosis | e568 | ||
| Pathology | e569 | ||
| Management | e569 | ||
| Shunts | e569 | ||
| Endoscopic Third Ventriculostomy | e570 | ||
| Management of Hydrocephalus in Preterm Infants | e570 | ||
| Complications | e570 | ||
| Prognosis | e571 | ||
| Intracranial Arachnoid Cysts | e572 | ||
| Definition | e572 | ||
| Clinical Characteristics | e572 | ||
| Sylvian Fissure/Middle Cranial Fossa | e572 | ||
| Sellar Region | e573 | ||
| Posterior Fossa | e573 | ||
| Complications | e573 | ||
| Epilepsy | e573 | ||
| Subdural Hematoma and Hygroma | e573 | ||
| Neuropsychiatric Disorders | e573 | ||
| Management | e573 | ||
| Conclusions | e573 | ||
| References | e573 | ||
| 31 Congenital Anomalies of the Skull | e577 | ||
| Introduction | e577 | ||
| Craniosynostosis Versus Deformational Plagiocephaly | e577 | ||
| Sutural Anatomy and Head Shape | e578 | ||
| Epidemiology of Craniosynostosis | e581 | ||
| Kleeblattschädel (Cloverleaf Skull) | e582 | ||
| Treatment and Outcomes of Craniosynostosis | e583 | ||
| Nonsyndromic Craniosynostosis Neurocognitive Development | e583 | ||
| Wide Cranial Sutures | e584 | ||
| Anomalies of Fontanels | e584 | ||
| Cranial Dermal Sinus | e585 | ||
| Parietal Foramina (Including Cranium Bifidum) | e586 | ||
| Wormian Bones | e587 | ||
| Scalp Vertex Aplasia | e587 | ||
| Thin Cranial Bones | e588 | ||
| Undermineralization of the Skull | e589 | ||
| Craniotabes | e589 | ||
| Thick Cranial Bones | e589 | ||
| Sclerosis and Hyperostosis of the Skull | e589 | ||
| Anomalies of the Sella Turcica | e591 | ||
| Anomalies of Temporal Bone | e591 | ||
| Anomalies of Foramen Magnum | e592 | ||
| Anomalies of the Other Basal Foramina and Canals | e592 | ||
| Basilar Impression | e592 | ||
| Miscellaneous Anomalies of the Skull | e593 | ||
| Paracondylar Process | e593 | ||
| Bathrocephaly | e593 | ||
| Occipital Horns | e593 | ||
| References | e593 | ||
| 32 Developmental Encephalopathies | e597 | ||
| Definition of Developmental Encephalopathies | e597 | ||
| Relationship to Epileptic Encephalopathies | e597 | ||
| Relationship to Disorders With Prominent Brain Malformations | e597 | ||
| Relationship to Autism Spectrum Disorders | e597 | ||
| Biological Pathways Involved | e598 | ||
| Specific Developmental Encephalopathies | e599 | ||
| Rett Syndrome | e599 | ||
| CDKL5 Disorder | e599 | ||
| FOXG1 Disorders | e599 | ||
| MEF2C Disorder | e600 | ||
| Pitt-Hopkins Syndrome | e600 | ||
| Mowat-Wilson Syndrome | e601 | ||
| Chromosome 15q Disorders | e601 | ||
| Angelman Syndrome | e601 | ||
| Prader-Willi Syndrome | e602 | ||
| Duplication of Maternal 15q11q13 | e602 | ||
| CNTNAP2 and NRXN1 Disorders | e602 | ||
| DYRK1A Disorder | e602 | ||
| PURA Disorder | e602 | ||
| Conclusions | e602 | ||
| References | e603 | ||
| 33 Prenatal Diagnosis of Structural Brain Anomalies | e607 | ||
| Introduction | e607 | ||
| Prenatal Assessment of Normal Brain Development in the First Trimester | e607 | ||
| Prenatal Assessment of Normal Development of the Cortex | e607 | ||
| Prenatal Assessment of Normal Development of the Corpus Callosum | e610 | ||
| Prenatal Assessment of Normal Development of the Posterior Fossa | e610 | ||
| Prenatal Diagnosis of Ventriculomegaly | e612 | ||
| Prenatal Diagnosis of Abnormalities of the Corpus Callosum | e613 | ||
| Prenatal Diagnosis of Malformations of Cortical Development | e613 | ||
| Prenatal Diagnosis of Lissencephaly Type I | e614 | ||
| Prenatal Diagnosis of Cobblestone Complex | e614 | ||
| Prenatal Diagnosis of Periventricular Nodular Heterotopia | e614 | ||
| Prenatal Diagnosis of Polymicrogyria | e616 | ||
| Prenatal Diagnosis of Complex Cortical Malformations | e616 | ||
| Prenatal Diagnosis of Schizencephaly | e616 | ||
| Prenatal Diagnosis of Posterior Fossa Anomalies | e617 | ||
| Prenatal Diagnosis of Chiari Type II Malformation | e617 | ||
| Prenatal Diagnosis of Dandy–Walker Malformation | e617 | ||
| Prenatal Diagnosis of Mega Cisterna Magna, Posterior Fossa Arachnoid Cyst, and Blake’s Pouch Cyst | e617 | ||
| Prenatal Diagnosis of Vermis Hypoplasia/Agenesis | e619 | ||
| Prenatal Diagnosis of Cerebellar Hypoplasia | e619 | ||
| Prenatal Diagnosis of Rhombencephalosynapsis | e619 | ||
| Prenatal Diagnosis of Molar Tooth-Related Syndromes | e619 | ||
| Prenatal Diagnosis of Brainstem Anomalies | e620 | ||
| References | e620 | ||
| 34 Neurogenetics in the Genome Era | e623 | ||
| Introduction to the Human Genome | e623 | ||
| Genomic Variation | e623 | ||
| Chromosomal Structural Rearrangements | e623 | ||
| History of Cytogenetics | e623 | ||
| Chromosome Analysis | e624 | ||
| Karyotype | e626 | ||
| Fluorescence in Situ Hybridization | e626 | ||
| Copy Number Variations | e627 | ||
| Indels | e627 | ||
| Short Tandem Repeats | e627 | ||
| Mutations, Single Nucleotide Variants, and Single Nucleotide Polymorphisms | e628 | ||
| Diagnostic Technologies | e628 | ||
| Methods of General Mutation Detection | e628 | ||
| DNA Sequence Analysis | e628 | ||
| Sanger Sequencing. | e628 | ||
| Deletion/Duplication Analysis. | e629 | ||
| Methylation Studies. | e629 | ||
| Chromosomal Microarray. | e630 | ||
| Sanger Sequencing. | e631 | ||
| Southern Blot. | e632 | ||
| Next-Generation Sequencing. | e632 | ||
| Resources for Interpreting Genomic Testing | e633 | ||
| Somatic Mosaicism and Challenges of Tissue of Origin for DNA | e635 | ||
| Genetic Counseling | e636 | ||
| Standards of Genomic Care | e637 | ||
| Looking Toward the Future | e638 | ||
| Example of Principles in Practice | e638 | ||
| References | e640 | ||
| 35 Chromosomes and Chromosomal Abnormalities | e644 | ||
| Methods of Chromosome Analysis | e644 | ||
| Chromosome Preparation | e644 | ||
| Chromosome Banding | e644 | ||
| Molecular Cytogenetics | e645 | ||
| Chromosomal Abnormalities | e647 | ||
| Numerical Abnormalities | e647 | ||
| Structural Abnormalities | e647 | ||
| Deletions and Duplications | e647 | ||
| Translocations | e647 | ||
| Inversions | e647 | ||
| Insertions | e648 | ||
| Marker and Ring Chromosomes | e648 | ||
| Isochromosomes | e648 | ||
| Cytogenetic Nomenclature | e648 | ||
| Incidence of Chromosomal Abnormalities | e648 | ||
| Clinical Indications for Cytogenetic Analysis | e648 | ||
| Multiple Congenital Anomalies | e648 | ||
| Developmental Delay and/or Intellectual Disability | e648 | ||
| Fertility Problems | e650 | ||
| Unexplained Stillbirth/Neonatal Death | e650 | ||
| Prenatal Diagnosis | e650 | ||
| Malignancy | e650 | ||
| Specific Cytogenetic Syndromes | e650 | ||
| Polyploidy | e650 | ||
| Cytogenetics | e650 | ||
| Clinical Features | e650 | ||
| 36 Approach to the Patient with a Metabolic Disorder | e667 | ||
| Introduction | e667 | ||
| Inheritance | e667 | ||
| Laboratory Evaluation | e667 | ||
| Classification | e667 | ||
| Part 1: Clinical Presentation of IEMs in the Neonate or Infant Less Than 2 Years of Age | e668 | ||
| Acute Encephalopathy | e668 | ||
| Epilepsy | e669 | ||
| Abnormal Development Associated With Congenital Anomalies and/or Dysmorphic Physical Features | e672 | ||
| Abnormal Development in the Absence of Congenital Anomalies or Dysmorphic Physical Features | e673 | ||
| Associated Neurologic Symptoms | e673 | ||
| Associated Nonneurologic Symptoms | e674 | ||
| Neuroimaging | e674 | ||
| Neuromuscular Weakness | e674 | ||
| Miscellaneous Presentations of IEMs in the Neonatal and Infantile Period | e675 | ||
| Clinical Presentation of IEMs in Childhood (Older Than 2 Years of Age) and Adolescence | e675 | ||
| Ataxia | e675 | ||
| Dystonia | e675 | ||
| Recurrent Rhabdomyolysis | e676 | ||
| Vascular Stroke | e676 | ||
| Cognitive and Motor Regression | e677 | ||
| Psychiatric Symptoms | e677 | ||
| Dysautonomia | e677 | ||
| Conclusions | e678 | ||
| References | e678 | ||
| 37 Aminoacidemias and Organic Acidemias | e681 | ||
| Signs and Symptoms | e681 | ||
| Physical Findings | e681 | ||
| Laboratory Approaches to Diagnosis | e681 | ||
| Treatment | e682 | ||
| Inheritance and Genetic Counseling | e682 | ||
| Aminoacidemias | e683 | ||
| Phenylketonuria | e683 | ||
| Classification | e684 | ||
| Clinical Manifestations | e684 | ||
| Maternal Phenylketonuria Syndrome | e684 | ||
| Diagnosis | e684 | ||
| Genetics | e685 | ||
| Pathogenesis | e685 | ||
| Genotype–Phenotype Correlations | e685 | ||
| Genetic Counseling | e686 | ||
| Treatment | e686 | ||
| Additional and Novel Therapies | e687 | ||
| Biopterin Disorders | e687 | ||
| Clinical Manifestations | e688 | ||
| Diagnosis | e688 | ||
| Treatment | e688 | ||
| Hepatorenal Tyrosinemia | e688 | ||
| Pathophysiology | e689 | ||
| Clinical Manifestations | e689 | ||
| Laboratory Tests | e689 | ||
| Management | e689 | ||
| Other Categories of Tyrosinemia | e689 | ||
| Maple Syrup Urine Disease | e689 | ||
| Clinical Manifestations | e690 | ||
| Classic Maple Syrup Urine Disease. | e690 | ||
| Intermediate Maple Syrup Urine Disease. | e690 | ||
| Intermittent Maple Syrup Urine Disease. | e690 | ||
| Thiamine-Responsive Maple Syrup Urine Disease. | e690 | ||
| Dihydrolipoyl Dehydrogenase–Deficient Maple Syrup Urine Disease. | e692 | ||
| Laboratory Tests | e692 | ||
| Genetics | e692 | ||
| Treatment | e692 | ||
| Glycine Encephalopathy | e693 | ||
| Sulfur Amino Acid Metabolism and the Homocystinurias | e695 | ||
| Cystathionine β-Synthase Deficiency | e696 | ||
| 38 Inborn Errors of Urea Synthesis | e720 | ||
| The Urea Cycle | e720 | ||
| Clinical Description of Urea Cycle Disorders | e721 | ||
| N-Acetylglutamate Synthase Deficiency | e721 | ||
| Carbamoyl-Phosphate Synthase 1 Deficiency | e721 | ||
| Ornithine Transcarbamylase Deficiency | e721 | ||
| Citrullinemia | e722 | ||
| Citrullinemia Type I or ASS1 Deficiency | e722 | ||
| Citrullinemia Type II or Citrin Deficiency | e722 | ||
| Argininosuccinic Aciduria | e723 | ||
| Argininemia | e723 | ||
| Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome | e724 | ||
| Common Clinical Presentations of Urea Cycle Disorders | e724 | ||
| Associated Medical Conditions | e724 | ||
| Histopathologic Features of Urea Cycle Disorders | e724 | ||
| Mechanism of Neuropathology | e725 | ||
| Downregulation of Astrocytic Glutamate Transporters | e725 | ||
| Elevated Glutamine Levels | e725 | ||
| Altered Water Transport Through Aquaporin 4 Water Channels | e725 | ||
| Altered Glucose Metabolism/Disturbed Energy Metabolism | e725 | ||
| Interference With the Normal Flux of Potassium Ions | e725 | ||
| Oxidative and Nitrosative Stress | e725 | ||
| Differential Diagnosis | e726 | ||
| Treatment | e726 | ||
| Hemodialysis | e727 | ||
| Liver Transplantation | e728 | ||
| Protein Restriction | e728 | ||
| Alternative-Pathway Therapy | e728 | ||
| N-Carbamyl-L-Glutamate | e728 | ||
| Management of Intercurrent Hyperammonemic Crises | e728 | ||
| Therapies Under Investigation | e729 | ||
| Cell Therapy | e729 | ||
| Hepatocyte Transfer | e729 | ||
| Gene Therapy | e729 | ||
| Neuroprotection | e729 | ||
| Nitric Oxide Supplementation Therapy | e729 | ||
| Outcome | e729 | ||
| Summary | e729 | ||
| Acknowledgment | e729 | ||
| References | e730 | ||
| 39 Diseases Associated with Primary Abnormalities in Carbohydrate Metabolism | e733 | ||
| Introduction | e733 | ||
| Abnormalities of Galactose Metabolism | e733 | ||
| Galactosemia | e733 | ||
| Galactose-1-Phosphate Uridyltransferase Deficiency | e733 | ||
| Pathology. | e733 | ||
| Biochemistry. | e733 | ||
| Clinical Characteristics. | e734 | ||
| Clinical Laboratory Tests. | e735 | ||
| Management. | e735 | ||
| Uridine Diphosphogalactose Epimerase Deficiency | e735 | ||
| Galactokinase Deficiency | e736 | ||
| Biochemistry. | e736 | ||
| Clinical Characteristics. | e736 | ||
| Management. | e736 | ||
| Abnormalities of Fructose Metabolism | e736 | ||
| Hereditary Fructose Intolerance | e736 | ||
| Biochemistry | e736 | ||
| Clinical Characteristics and Differential Diagnosis | e736 | ||
| Clinical Laboratory Tests and Diagnosis | e736 | ||
| Management | e737 | ||
| Fructose-1,6-Diphosphatase Deficiency | e737 | ||
| Glycogen Storage Diseases | e737 | ||
| Glucose-6-Phosphatase Deficiency (Von Gierke Disease, Glycogen Storage Disease Type I, Hepatorenal Glycogenosis) | e738 | ||
| Pathology | e738 | ||
| Biochemistry | e738 | ||
| Clinical Characteristics | e741 | ||
| Clinical Laboratory Tests | e741 | ||
| Management | e741 | ||
| Acid α-Glucosidase (GAA, Acid Maltase) Deficiency, Infantile Type (Pompe’s Disease, Idiopathic Generalized Glycogenosis, Glycogen Storage Disease Type II) | e742 | ||
| Pathology | e742 | ||
| Biochemistry | e742 | ||
| Clinical Characteristics | e742 | ||
| 40 Disorders of Glycosylation | e759 | ||
| Defining Types of Glycosylation | e759 | ||
| N-Linked Glycosylation | e759 | ||
| Overview | e759 | ||
| Biosynthesis | e759 | ||
| N-Linked Glycan Biosynthesis | e759 | ||
| Congenital Disorders of Glycosylation | e760 | ||
| Diagnosis | e760 | ||
| General Clinical Features | e761 | ||
| Specific Disorders | e761 | ||
| Defects in Protein N-Glycosylation | e761 | ||
| PMM2-CDG (Ia) | e761 | ||
| MPI-CDG (Ib) | e761 | ||
| ALG6-CDG (Ic) | e770 | ||
| ALG3-CDG (Id) | e770 | ||
| ALG12-CDG (Ig) | e770 | ||
| ALG8-CDG (Ih) | e770 | ||
| ALG2-CDG (Ii) | e770 | ||
| DPAGT1-CDG (Ij) | e771 | ||
| ALG1-CDG (Ik) | e771 | ||
| ALG9-CDG (Il) | e771 | ||
| RFT1-CDG (In) | e771 | ||
| MOGS-CDG (IIb) | e771 | ||
| TUSC3-CDG | e771 | ||
| SRD5A3-CDG (Iq) | e771 | ||
| ALG13-CDG/CMS (Is) | e772 | ||
| MAN1B1- CDG | e772 | ||
| NGLY1-CDG | e772 | ||
| Defects in Protein O-Glycosylation | e772 | ||
| Defects in Glycosphingolipids (GSL) | e772 | ||
| Glycosylphosphatidylinositol Glycosylation | e772 | ||
| Defects in Multiple Glycosylation and Other Pathways | e772 | ||
| DPM1-CDG (Ie) | e772 | ||
| DPM2-CDG | e773 | ||
| DPM3-CDG (Io) | e773 | ||
| MPDU1-CDG (If) | e774 | ||
| B4GALT1-CDG (IId) | e774 | ||
| SLC35A1-CDG (IIf) | e774 | ||
| SLC35A2-CDG | e774 | ||
| SLC35C1-CDG (IIc) | e775 | ||
| COG Complex | e775 | ||
| COG7-CDG (IIe). | e775 | ||
| COG8-CDG (IIh). | e775 | ||
| COG4-CDG (IIj). | e775 | ||
| COG5-CDG. | e775 | ||
| COG6-CDG. | e775 | ||
| When to Suspect and Test for Congenital Disorders of Glycosylation | e775 | ||
| Summary | e776 | ||
| References | e776 | ||
| 41 Lysosomal Storage Diseases | e781 | ||
| Overview and General Concepts | e781 | ||
| Sphingolipidoses | e785 | ||
| Gangliosidoses | e788 | ||
| GM1 Gangliosidoses | e789 | ||
| GM2 Gangliosidoses | e790 | ||
| Fabry Disease | e793 | ||
| Gaucher Disease | e795 | ||
| Niemann–Pick Disease, Including Types A and B | e798 | ||
| Niemann–Pick Disease, Including Types C and D | e800 | ||
| Farber Disease (Lipogranulomatosis) | e801 | ||
| Krabbe Disease (Globoid Cell Leukodystrophy) | e802 | ||
| Metachromatic Leukodystrophy (Sulfatide Lipidosis) | e805 | ||
| Multiple Sulfatase Deficiency (Austin Disease) | e807 | ||
| Wolman Disease and Cholesteryl Ester Storage Disorder | e808 | ||
| Mucopolysaccharidoses | e809 | ||
| Mucopolysaccharidosis Type I (MPS I) | e811 | ||
| Mucopolysaccharidosis Type II (MPS II) | e813 | ||
| Mucopolysaccharidosis Type III (MPS III) | e814 | ||
| Mucopolysaccharidosis Type IV (MPS IV) | e815 | ||
| Mucopolysaccharidosis Type VI (MPS VI) | e816 | ||
| Mucopolysaccharidosis Type VII (MPS VII) | e816 | ||
| Mucopolysaccharidosis Type IX (MPS IX) | e817 | ||
| Glycoproteinoses | e817 | ||
| Mannosidosis | e817 | ||
| Fucosidosis | e818 | ||
| Aspartylglycosaminuria | e819 | ||
| Sialidosis | e820 | ||
| Galactosialidosis | e821 | ||
| Schindler–Kanzaki Disease (α-N-Acetylgalactosaminidase Deficiency) | e822 | ||
| Mucolipidoses | e822 | ||
| Mucolipidosis Type I (Sialidosis Type II) | e822 | ||
| Mucolipidosis Type II (I-Cell Disease) and Type III (Pseudo-Hurler Polydystrophy) | e823 | ||
| Mucolipidosis Type IV | e824 | ||
| Glycogen Storage Disease Type II (Pompe Disease) | e825 | ||
| Danon Disease | e827 | ||
| Sialic Acid Storage Disorders | e827 | ||
| Cystinosis | e828 | ||
| Neuronal Ceroid Lipofuscinoses | e829 | ||
| References | e831 | ||
| 42 Mitochondrial Diseases | e849 | ||
| History and Mitochondrial Genetics | e849 | ||
| Classification of Mitochondrial Diseases | e849 | ||
| Metabolic Disturbances | e851 | ||
| Histopathologic Disturbances | e851 | ||
| Defects of Pyruvate Metabolism and of the Krebs Cycle | e853 | ||
| Defects of the Krebs Cycle | e855 | ||
| Mendelian Defects of the Respiratory Chain | e855 | ||
| Respiratory Chain “Direct Hits” | e855 | ||
| 43 Peroxisomal Disorders | e868 | ||
| Historical Overview | e868 | ||
| Structure and Function of Peroxisomes | e868 | ||
| Metabolic Function of Peroxisomes | e869 | ||
| Peroxisomal Fatty Acid Oxidation | e870 | ||
| Long-Chain Acyl-Coenzyme a Ligase and Lignoceroyl-Coenzyme a Ligase | e870 | ||
| Acyl-Coenzyme a Oxidases | e870 | ||
| Bifunctional or Multifunctional Enzymes | e870 | ||
| Thiolases | e870 | ||
| Oxidation of Unsaturated Fatty Acids | e870 | ||
| Branched-Chain Fatty Acid Oxidation and Phytanic Acid α-Oxidation | e870 | ||
| Bile Acid Synthesis | e870 | ||
| Plasmalogen Synthesis | e871 | ||
| Prostaglandin Degradation | e871 | ||
| Amino Acid Metabolism | e871 | ||
| D-Amino Acid Oxidase. | e871 | ||
| Alanine-Glyoxalate Aminotransferase. | e871 | ||
| Pipecolic Acid Oxidase. | e871 | ||
| Classification of Peroxisomal Disorders | e871 | ||
| Conditions Resulting From Defective Peroxisome Biogenesis | e872 | ||
| Molecular Etiology of Disorders of Peroxisome Assembly | e872 | ||
| Zellweger Spectrum Disorders | e872 | ||
| Clinical and Pathologic Features | e873 | ||
| Zellweger Syndrome | e873 | ||
| Neonatal Adrenoleukodystrophy and Infantile Refsum Disease | e873 | ||
| Clinical Features | e874 | ||
| Laboratory Diagnosis | e874 | ||
| Prenatal Diagnosis | e875 | ||
| Therapy | e875 | ||
| Rhizomelic Chondrodysplasia Punctata | e875 | ||
| Defects of Single Peroxisomal Enzymes | e876 | ||
| Defects of Single Peroxisomal β-Oxidation Enzymes | e876 | ||
| Adrenoleukodystrophy | e876 | ||
| Biochemical and Molecular Basis | e876 | ||
| Clinical and Pathologic Features of X-Linked Adrenoleukodystrophy and Adrenomyeloneuropathy | e877 | ||
| Childhood Cerebral Adrenoleukodystrophy (ALD). | e877 | ||
| Adolescent Cerebral Form of Adrenoleukodystrophy. | e877 | ||
| Adult Cerebral Form of Adrenoleukodystrophy. | e877 | ||
| Adrenomyeloneuropathy. | e877 | ||
| Adrenoleukodystrophy With Addison Disease Only. | e877 | ||
| Asymptomatic Patients With the Biochemical Defect of Adrenoleukodystrophy. | e877 | ||
| Symptomatic Heterozygotes. | e877 | ||
| Pathogenesis of Adrenoleukodystrophy | e879 | ||
| Therapies for Adrenoleukodystrophy. | e879 | ||
| Newborn Screening for ALD | e879 | ||
| Contiguous Deletion of the XALD Gene | e880 | ||
| Acyl-CoA Oxidase Deficiency | e880 | ||
| Bifunctional Enzyme Deficiency | e880 | ||
| Peroxisomal α-Methylacyl-CoA Racemase Defect | e880 | ||
| Single-Enzyme Defects of Plasmalogen Synthesis | e880 | ||
| Classic Adult Refsum Disease | e880 | ||
| Mulibrey Nanism | e880 | ||
| Current and Future Outlook | e881 | ||
| References | e881 | ||
| 44 Neurotransmitter-Related Disorders | e885 | ||
| Monoaminergic Neurotransmitter Deficiency States With Hyperphenylalaninemia | e885 | ||
| Overview | e885 | ||
| Role of BH4 in the Central Nervous System | e885 | ||
| 6-Pyruvoyltetrahydropterin Synthase Deficiency | e887 | ||
| Dihydropteridine Reductase Deficiency | e887 | ||
| Autosomal-Recessive Guanosine Triphosphate Cyclohydrolase Deficiency | e888 | ||
| Pterin-4a-Carbinolamine Dehydratase Deficiency (Primapterinuria) | e888 | ||
| Monoaminergic Neurotransmitter Deficiency States Without Hyperphenylalaninemia | e888 | ||
| Overview | e888 | ||
| Segawa Disease or Autosomal-Dominant Dopa-Responsive Dystonia | e888 | ||
| Aromatic L-Amino Acid Decarboxylase or Dopa-Decarboxylase Deficiency | e889 | ||
| Sepiapterin Reductase Deficiency | e890 | ||
| Tyrosine Hydroxylase Deficiency or Autosomal-Recessive Dopa-Responsive Dystonia | e890 | ||
| Tryptophan Hydroxylase Deficiency | e891 | ||
| Dopamine Beta-Hydroxylase Deficiency | e891 | ||
| Monoamine Oxidase Deficiency | e891 | ||
| Monoamine Oxidase A Deficiency | e891 | ||
| Monoamine Oxidase B Deficiency | e892 | ||
| Monoamine Oxidase A and B Deficiency | e892 | ||
| Dopamine Transporter Deficiency | e892 | ||
| Vesicular Monoamine Transporter 2 Deficiency | e892 | ||
| Disorders of Amino Acid Neurotransmitters | e892 | ||
| Gamma-Aminobutyric Acid Transaminase Deficiency | e892 | ||
| Succinic Semialdehyde Dehydrogenase Deficiency | e893 | ||
| Secondary Neurotransmitter Deficiency States | e893 | ||
| Undefined Neurotransmitter Deficiency States | e893 | ||
| Approach to Treatment in Patients With Neurotransmitter Deficiency States | e894 | ||
| Neurologic Disorders Characterized by Excess Neurotransmitter Levels | e894 | ||
| Glycine Encephalopathy | e894 | ||
| Leukoencephalopathy With Vanishing White Matter | e894 | ||
| References | e894 | ||
| 45 Phakomatoses and Allied Conditions | e897 | ||
| The Neurofibromatoses | e897 | ||
| Neurofibromatosis Type 1 | e897 | ||
| Clinical Characteristics | e897 | ||
| Pathology | e901 | ||
| Genetics | e901 | ||
| Management | e902 | ||
| Neurofibromatosis Type 2 | e902 | ||
| Clinical Characteristics and Pathology | e902 | ||
| Genetics | e903 | ||
| Management | e903 | ||
| Schwannomatosis | e903 | ||
| Tuberous Sclerosis Complex | e904 | ||
| Clinical Characteristics | e904 | ||
| Clinical Laboratory Testing | e906 | ||
| Pathology | e908 | ||
| Genetics | e908 | ||
| Management | e908 | ||
| Von Hippel-Lindau Disease | e908 | ||
| Clinical Characteristics | e908 | ||
| Pathology | e909 | ||
| Genetics | e909 | ||
| Management | e910 | ||
| Sturge-Weber Syndrome (Encephalofacial Angiomatosis) | e910 | ||
| Clinical Characteristics | e910 | ||
| Pathology | e912 | ||
| Management | e912 | ||
| Maffucci Syndrome | e912 | ||
| Epidermal Nevus Syndrome | e913 | ||
| Parry-Romberg Syndrome (Facial Hemiatrophy) | e914 | ||
| Neurocutaneous Melanosis | e914 | ||
| Klippel-Trénaunay-Weber Syndrome | e915 | ||
| Incontinentia Pigmenti (Bloch-Sulzberger Syndrome) | e915 | ||
| Incontinentia Pigmenti Achromians (Hypomelanosis of Ito) | e916 | ||
| Wyburn-Mason Syndrome (Retinocephalic Angiomatosis) | e916 | ||
| References | e917 | ||
| 46 Disorders of Vitamin Metabolism | e927 | ||
| Vitamin A (Retinol) | e927 | ||
| Vitamin A Deficiency | e927 | ||
| Vitamin A Intoxication | e927 | ||
| Vitamin A Teratogenesis | e929 | ||
| THIAMINE (VITAMIN B1) | e929 | ||
| Thiamine Deficiency | e929 | ||
| Diagnosis and Laboratory Findings | e929 | ||
| Inborn Errors of Thiamine Metabolism | e930 | ||
| Rogers Syndrome (THTR1 Deficiency) | e930 | ||
| Biotin- or Thiamine-Responsive Basal Ganglia Disease | e930 | ||
| Thiamine Pyrophosphokinase Deficiency | e930 | ||
| Amish Lethal Microcephaly and Bilateral Striatal Necrosis Resulting From SLC25A19 Mutations | e930 | ||
| RIBOFLAVIN (VITAMIN B2) | e931 | ||
| Riboflavin Deficiency | e931 | ||
| Riboflavin-Dependent Enzymatic Reactions | e931 | ||
| Disorders of riboflavin transport | e931 | ||
| Introduction | e931 | ||
| Riboflavin Deficiency (OMIM 615026) | e932 | ||
| Riboflavin Transporter Deficiency Neuronopathy | e932 | ||
| Clinical Findings | e932 | ||
| Biochemical Findings | e932 | ||
| Therapy and Outcome | e932 | ||
| NIACIN (VITAMIN B3) | e932 | ||
| Niacin Deficiency (Pellagra) | e932 | ||
| Niacin Dependency | e932 | ||
| VITAMIN B6 | e932 | ||
| Pyridoxine Deficiency | e933 | ||
| Vitamin B6 Dependency | e933 | ||
| Pyridoxine-Dependent Epilepsy | e933 | ||
| Pyridox(am)ine 5′-Phosphate Oxidase Deficiency | e934 | ||
| Pyridoxine Versus PLP and Potential Side Effects | e936 | ||
| Hyperprolinemia Type II | e936 | ||
| Congenital Hypophosphatasia | e936 | ||
| Vitamin B6–Responsive Disorders | e936 | ||
| Gyrate Atrophy | e936 | ||
| Classical Homocystinuria | e936 | ||
| Vitamin B12 (Cobalamin) | e936 | ||
| Cobalamin Deficiency | e937 | ||
| Cobalamin Dependency | e937 | ||
| CblC, CbD-MMA/HC, CbF, and CblJ Deficiency (Combined Defects of Ado- and MetCbl) | e938 | ||
| CblE, CblG, and CblD-HC Deficiency (Defects of MetCbl; Remethylation Defects) | e938 | ||
| CblA-MMA, CblB-MMA, and CblD-MMA Deficiency (Defects of AdoCbl) | e938 | ||
| Vitamin C (Ascorbic Acid) | e938 | ||
| Vitamin C Deficiency | e938 | ||
| Vitamin D | e938 | ||
| Vitamin D Deficiency | e939 | ||
| Vitamin D Intoxication | e939 | ||
| Vitamin E | e939 | ||
| Nutritional Vitamin E Deficiency | e939 | ||
| Disorders of Vitamin E Metabolism | e939 | ||
| Biotin (Vitamin H) | e939 | ||
| Biotin Deficiency | e940 | ||
| Biotin Dependency | e940 | ||
| Biotinidase Deficiency | e940 | ||
| Biotin-Dependent Holocarboxylase Synthetase Deficiency (Multiple Carboxylase Deficiency) | e940 | ||
| Biotin-Responsive Basal Ganglia Disease | e940 | ||
| FOLATE (VITAMIN B9) | e940 | ||
| Nutritional Folate Deficiency | e941 | ||
| Folate and Pregnancy | e942 | ||
| Disorders of Folate Metabolism | e942 | ||
| Dihydrofolate Reductase Deficiency | e942 | ||
| Disease Characteristics | e942 | ||
| Clinical and Biochemical Findings | e942 | ||
| 47 Nutrition and the Developing Brain | e952 | ||
| Protein-Calorie Malnutrition | e952 | ||
| Micronutrients | e954 | ||
| Minerals | e954 | ||
| Iron | e954 | ||
| Zinc | e955 | ||
| Iodine | e955 | ||
| Vitamins | e955 | ||
| Folate | e956 | ||
| Cobalamin (Vitamin B12) | e956 | ||
| Vitamin D | e956 | ||
| Other Vitamins | e957 | ||
| Long-Chain Polyunsaturated Fatty Acids | e957 | ||
| References | e958 | ||
| 48 The Neuronal Ceroid Lipofuscinosis Disorders | e960 | ||
| Introduction | e960 | ||
| Historical Clinical Characterization | e960 | ||
| Nomenclature | e960 | ||
| Clinical Description and Characterization | e960 | ||
| Molecular Genetics | e963 | ||
| Pathology | e963 | ||
| Pathobiology | e963 | ||
| NCL Models | e966 | ||
| Animal | e966 | ||
| Human Models | e967 | ||
| Clinical Trials | e967 | ||
| Diagnosis | e967 | ||
| CLN1 (PPT1; OMIM | e967 | ||
| Clinical Description | e967 | ||
| Other Presentations | e969 | ||
| Genetics and Pathology | e969 | ||
| Diagnostic Evaluation | e969 | ||
| Clinical Trials | e969 | ||
| CLN2 (TPP1; OMIM | e970 | ||
| Clinical Description | e970 | ||
| Other Presentations | e970 | ||
| Genetics and Pathology | e970 | ||
| Diagnostic Evaluation | e970 | ||
| Clinical Trials | e971 | ||
| CLN3 (CLN3; OMIM | e971 | ||
| Clinical Description | e971 | ||
| Other Presentations | e971 | ||
| Genetics and Pathology | e971 | ||
| Diagnostic Evaluation | e971 | ||
| Clinical Trials | e972 | ||
| CLN4 (DNAJC5; Autosomal Dominant Kufs; OMIM | e972 | ||
| Clinical Description | e972 | ||
| Genetics and Pathology | e972 | ||
| 49 Channelopathies | e987 | ||
| Introduction | e987 | ||
| Epilepsy Syndromes | e987 | ||
| Dravet Syndrome | e987 | ||
| Clinical Features | e987 | ||
| Genetics/Pathophysiology | e988 | ||
| Clinical Laboratory Tests | e988 | ||
| Treatment | e989 | ||
| Generalized Epilepsy with Febrile Seizures Plus | e989 | ||
| Clinical Features | e989 | ||
| Genetics/Pathophysiology | e989 | ||
| 50 Neurodevelopmental Disabilities | e996 | ||
| General Conceptions and Considerations When Approaching a Child with Suspected Developmental Disabilities | e996 | ||
| Basic Principles in Human Brain Development | e996 | ||
| The Embryonic Period | e996 | ||
| The Fetal Period | e996 | ||
| Postnatal Period Into Adolescence | e997 | ||
| Brain Plasticity | e998 | ||
| Nature and Nurture—Inseparable Twinning | e998 | ||
| Spectrum of Neurodevelopmental Disabilities | e999 | ||
| Overview and Scope of the Problem | e999 | ||
| Determinants and Risk Factors | e1000 | ||
| Commonalities | e1000 | ||
| Overlap in Neurodevelopment Disorders | e1000 | ||
| Approach to the Evaluation of a Child with Suspected Neurodevelopmental or Intellectual Disability | e1001 | ||
| The Developmental History | e1001 | ||
| Birth History | e1001 | ||
| Social History | e1001 | ||
| Family History | e1001 | ||
| Physical Examination | e1001 | ||
| Testing | e1002 | ||
| Multidisciplinary Approach to the Care of the Child with a Neurodevelopmental Disorder | e1002 | ||
| Policy | e1002 | ||
| Early Intervention | e1003 | ||
| Source: Individuals with Education Act of 2004 | e1004 | ||
| Education of the School-Aged Child with Disabilities: Individualized Educational Plans and 504 Plans | e1004 | ||
| Health Insurance, the Affordable Care Act (ACA), and Children with Disabilities | e1004 | ||
| References | e1004 | ||
| 51 Global Developmental Delay and Intellectual Disability | e1007 | ||
| Definitions | e1007 | ||
| Epidemiology | e1007 | ||
| History and Ethics | e1008 | ||
| Diagnosis | e1009 | ||
| Definitions and Testing | e1009 | ||
| Advances in Diagnostic Testing | e1010 | ||
| Genomic Microarray | e1010 | ||
| Advances in Imaging | e1016 | ||
| Proteomics in Disease Analysis | e1016 | ||
| Etiology | e1016 | ||
| General Considerations | e1016 | ||
| Genetic Causes | e1017 | ||
| Fragile X Syndrome | e1017 | ||
| Other X-Linked ID Conditions | e1017 | ||
| Nonsyndromic Inherited Autosomal GDD and ID | e1018 | ||
| De Novo Dominant GDD and ID | e1018 | ||
| Other Etiologic Considerations | e1018 | ||
| Evaluation of the Patient | e1018 | ||
| History | e1018 | ||
| Physical Examination | e1019 | ||
| Laboratory Testing | e1020 | ||
| Consultation and Follow-Up | e1022 | ||
| Medical Management of Coexisting Conditions | e1022 | ||
| Outcome and Prognosis | e1022 | ||
| Acknowledgments | e1024 | ||
| References | e1024 | ||
| 52 Cognitive and Motor Regression | e1029 | ||
| Introduction | e1029 | ||
| Definition | e1029 | ||
| Epidemiology | e1029 | ||
| Etiology | e1029 | ||
| Diagnostic Evaluation | e1032 | ||
| History | e1032 | ||
| Developmental History | e1032 | ||
| Family History | e1033 | ||
| Maternal History | e1033 | ||
| Neonatal History | e1033 | ||
| Environmental History | e1033 | ||
| General Medical History | e1033 | ||
| Examination | e1034 | ||
| Laboratory Testing | e1034 | ||
| Brain Biopsy | e1036 | ||
| Diagnostic Approach | e1037 | ||
| Management | e1038 | ||
| References | e1058 | ||
| 53 Developmental Language Disorders | e1061 | ||
| Introduction | e1061 | ||
| Neural Substrates of Language | e1061 | ||
| Neuroanatomy of Specific Language Impairment | e1061 | ||
| Factors Associated With Developmental Language Disorders | e1062 | ||
| Genetics | e1062 | ||
| Diagnosis | e1063 | ||
| Nosology of Developmental Language Disorders | e1064 | ||
| Articulation and Expressive Fluency Disorders | e1064 | ||
| Pure Articulation Disorders | e1064 | ||
| Stuttering and Cluttering | e1064 | ||
| Phonological Programming Disorder | e1065 | ||
| Verbal Dyspraxia | e1065 | ||
| Disorders of Receptive and Expressive Language | e1065 | ||
| Phonological Syntactic Syndrome | e1065 | ||
| Verbal Auditory Agnosia | e1065 | ||
| Higher-Order Language Disorders | e1065 | ||
| Semantic Pragmatic Syndrome | e1065 | ||
| Lexical Syntactic Syndrome | e1065 | ||
| Outcome of Developmental Language Disorders | e1066 | ||
| Evaluation of the Child With a Suspected Developmental Language Disorder | e1066 | ||
| Treatment | e1067 | ||
| References | e1067 | ||
| 54 Nonverbal Learning Disabilities and Associated Disorders | e1070 | ||
| Introduction | e1070 | ||
| What Are Nonverbal Learning Disabilities? | e1070 | ||
| Coexistent Issues | e1070 | ||
| Neuropsychological Findings | e1071 | ||
| Verbal–Performance IQ Split | e1071 | ||
| Language. | e1071 | ||
| Achievement. | e1071 | ||
| Visual–Spatial Skills | e1072 | ||
| Executive Functioning | e1072 | ||
| Social Perception and Psychopathology | e1072 | ||
| Neuroimaging Findings in NLD and AS/ASD | e1073 | ||
| fMRI | e1074 | ||
| Neurologic Aspects of Nonverbal Learning Disabilities | e1074 | ||
| References | e1076 | ||
| 55 Dyslexia | e1078 | ||
| Evolution of Dyslexia as an Unexpected Difficulty in Relation to Intelligence | e1078 | ||
| Dyslexia Is Specific—Learning Disabilities Are Not | e1078 | ||
| Definition of Dyslexia | e1078 | ||
| Epidemiology and Etiology | e1078 | ||
| Phonologic Model of Dyslexia | e1079 | ||
| Neurobiological Evidence Supporting Dyslexia | e1079 | ||
| Making a Hidden Disability Visible | e1079 | ||
| Implications of Brain Imaging Studies | e1080 | ||
| Diagnosis | e1080 | ||
| Tests Helpful in the Evaluation of Children for Dyslexia | e1082 | ||
| Phonological Processing | e1082 | ||
| Letter Knowledge | e1082 | ||
| Academic Achievement | e1082 | ||
| Physical and Neurologic Examination and Laboratory Tests | e1082 | ||
| Outcome: Phonologic Deficit in Adolescence and Adult Life | e1082 | ||
| Essential Components of Diagnosis in Adolescents and Young Adults | e1082 | ||
| Lack of Automaticity | e1082 | ||
| Measure of Intelligence | e1082 | ||
| Treatment | e1082 | ||
| Attentional Mechanisms in Reading and Dyslexia | e1083 | ||
| Accommodations | e1083 | ||
| Summary | e1084 | ||
| Acknowledgments | e1084 | ||
| References | e1084 | ||
| 56 Attention Deficit–Hyperactivity Disorder | e1086 | ||
| Diagnosis and Controversies in the Diagnosis of Attention Deficit–Hyperactivity Disorder | e1086 | ||
| Coexisting Conditions | e1088 | ||
| Neurobiology of Attention Deficit–Hyperactivity Disorder | e1088 | ||
| Structural Imaging | e1089 | ||
| Functional Imaging | e1090 | ||
| Clinical Neurophysiology | e1090 | ||
| Genetic Studies | e1091 | ||
| Other Potential Causes of Attention Deficit–Hyperactivity Disorder | e1092 | ||
| Coexisting Conditions | e1092 | ||
| Diagnostic Evaluation | e1093 | ||
| Laboratory Studies | e1093 | ||
| Electroencephalography | e1093 | ||
| Sleep Studies | e1093 | ||
| Imaging Studies | e1093 | ||
| Treatment | e1093 | ||
| Nonpharmacologic Therapies | e1093 | ||
| Sleep | e1093 | ||
| Biofeedback Programs | e1093 | ||
| Pharmacologic Therapy | e1094 | ||
| Stimulant Medications | e1094 | ||
| Methylphenidate | e1095 | ||
| Dexmethylphenidate | e1095 | ||
| Dextroamphetamine | e1096 | ||
| Noradrenergic Potentiation | e1096 | ||
| Atomoxetine | e1096 | ||
| Nonstimulant Medications | e1096 | ||
| Tricyclic Antidepressants | e1096 | ||
| Desipramine | e1096 | ||
| Alpha-Adrenergic Agonists | e1096 | ||
| Complementary and Alternative Medications | e1097 | ||
| Outcome | e1097 | ||
| Conclusions | e1099 | ||
| References | e1099 | ||
| 57 Autistic Spectrum Disorders | e1104 | ||
| Historical Perspective of the Diagnostic and Statistical Manual of Mental, Disorders in Relation to Autism | e1104 | ||
| Clinical Features of ASD | e1104 | ||
| Persistent Deficits in Social Communication and Social Interaction | e1104 | ||
| Restricted, Repetitive Patterns of Behavior, Interests, or Activities | e1106 | ||
| Onset Patterns in ASD | e1106 | ||
| Epidemiology | e1107 | ||
| Sibling Studies | e1108 | ||
| Neonatal Intensive Care and Prematurity | e1108 | ||
| Parental Age and Socioeconomic Factors | e1108 | ||
| Autoimmune and Other Factors | e1108 | ||
| Vaccines | e1109 | ||
| Animal Models of Autism | e1109 | ||
| Neuropathology in ASD | e1110 | ||
| New Insights | e1110 | ||
| Neurotransmitters and ASD | e1110 | ||
| Neuroimaging in ASD | e1111 | ||
| Genetics of ASD | e1111 | ||
| Screening and Diagnostic Evaluation for ASD | e1112 | ||
| Screening and Diagnostic Instruments | e1113 | ||
| Diagnostic Instruments for ASD | e1114 | ||
| Speaking with Parents about a New Diagnosis of ASD | e1115 | ||
| Recommendations for a Child with Newly Diagnosed ASD | e1115 | ||
| The Neurologic Evaluation in Autism | e1116 | ||
| Large HC and Somatic Overgrowth | e1116 | ||
| Motor Disturbances in Tone, Gait, Praxis, and Stereotypies | e1116 | ||
| Self-Injurious Behaviors (SIB) | e1117 | ||
| Clinical Testing | e1117 | ||
| Definitive Evaluation of Hearing and Vision | e1117 | ||
| Lead Level | e1117 | ||
| Electroencephalography | e1117 | ||
| Neuroimaging Studies | e1117 | ||
| Metabolic Testing | e1118 | ||
| Tests of Unproven Value | e1118 | ||
| Coexistent Medical Conditions | e1118 | ||
| Gastrointestinal Problems | e1118 | ||
| Sleep Disturbances | e1118 | ||
| Epilepsy | e1118 | ||
| Pharmacologic Therapy | e1118 | ||
| Neuroleptic Agents | e1120 | ||
| Opiate Antagonists | e1121 | ||
| Serotonin Reuptake Inhibitors | e1121 | ||
| Stimulants and Drugs to Treat Hyperactivity | e1121 | ||
| Antiseizure Drugs | e1122 | ||
| Cholinesterase Inhibitors | e1122 | ||
| Glutaminergic and Gamma-aminobutyric Acidergic Agents | e1122 | ||
| Summary | e1122 | ||
| Complementary and Alternative Medicine | e1122 | ||
| Educational and Behavioral Interventions | e1123 | ||
| Resources for Families and Practitioners | e1125 | ||
| Disclaimer | e1126 | ||
| References | e1126 | ||
| 58 Management of Common Comorbidities Associated with Neurodevelopmental Disorders | e1137 | ||
| Hypertonia | e1137 | ||
| Assessment | e1137 | ||
| Interventions | e1137 | ||
| Spasticity Interventions | e1137 | ||
| 1. Nonpharmacologic Rehabilitation Strategies | e1138 | ||
| 2. Oral Medications for Spasticity: | e1138 | ||
| 3. Neurosurgical Procedures | e1138 | ||
| 4. Botulinum Toxin Injections | e1139 | ||
| Treatment of Dystonia | e1139 | ||
| Musculoskeletal (MSK) Deformities | e1139 | ||
| Muscle Contractures | e1139 | ||
| Hips Subluxation/Dislocation | e1139 | ||
| Scoliosis | e1139 | ||
| Atlanto-Axial Instability | e1140 | ||
| Feeding and Gastrointestinal Issues | e1140 | ||
| Assessment of Feeding and Nutrition | e1140 | ||
| History | e1140 | ||
| Observation | e1140 | ||
| Physical Examination | e1140 | ||
| Additional Investigations | e1141 | ||
| Management of Feeding and Nutritional Issues | e1141 | ||
| Gastroesophageal Reflux | e1141 | ||
| Constipation | e1141 | ||
| Need for Gastrostomy Feeding Tubes | e1141 | ||
| Seizures and Special Considerations in Neurodevelopmental Disorders | e1141 | ||
| Diagnosis of Seizures in Children with Neurodevelopmental Disorders | e1141 | ||
| Treatment of Seizures in Children with Neurodevelopmental Disorders | e1142 | ||
| Antiepileptic Drug Adverse Effects | e1142 | ||
| Polypharmacy | e1142 | ||
| Withdrawal of Antiepileptic Drugs | e1142 | ||
| Drug-Resistant Epilepsy | e1142 | ||
| Treating Seizures in Children with Attention-Deficit/Hyperactivity Disorder | e1142 | ||
| Treating Seizures in Children with Cerebral Palsy | e1142 | ||
| Fragility Fractures (Osteopenia/Osteoporosis) | e1143 | ||
| Sleep Disorders | e1143 | ||
| Behavior | e1143 | ||
| Assessment of Behavior | e1143 | ||
| Antecedents of Behavior | e1144 | ||
| Behavior Description | e1144 | ||
| Consequences of Behavior | e1144 | ||
| Additional Elements of Assessment | e1144 | ||
| General Principles of Management of Behavior Problems | e1144 | ||
| Psychopharmacology | e1144 | ||
| References | e1145 | ||
| 59 Treatment of Neurodevelopmental Disorders | e1147 | ||
| Introduction | e1147 | ||
| Rett Syndrome, Down Syndrome, Tuberous Sclerosis, and Fragile X Syndrome | e1147 | ||
| General Concepts Surrounding Treatments | e1147 | ||
| Rett Syndrome | e1148 | ||
| Down Syndrome | e1149 | ||
| Tuberous Sclerosis | e1150 | ||
| Fragile X Syndrome | e1151 | ||
| Generalization of Treatment From Single-Gene Disorders to Neurodevelopmental Disorders and Autism Spectrum Disorder | e1155 | ||
| Inborn Errors of Metabolism | e1155 | ||
| Introduction | e1155 | ||
| Intellectual Developmental Disabilities | e1155 | ||
| Conditions and Treatments | e1155 | ||
| Outcomes | e1161 | ||
| Evidence and Clinical Practice | e1161 | ||
| Signs and Symptoms | e1161 | ||
| Diagnostic Approach to Treatable Inborn Errors of Metabolism | e1162 | ||
| Frequency of Treatable Inborn Errors of Metabolism in Neurodevelopmental Disorders | e1162 | ||
| Treatable Inborn Errors of Metabolism Presenting With Other Neurodevelopmental Disorder Phenotypes | e1163 | ||
| Epilepsy | e1163 | ||
| Atypical Cerebral Palsy | e1163 | ||
| Psychiatric Disease | e1164 | ||
| Newborn Screening | e1164 | ||
| Congenital Hypothyroidism | e1164 | ||
| Conclusions and Future Directions | e1165 | ||
| References | e1165 | ||
| 60 Neuropsychopharmacology | e1168 | ||
| Introduction | e1168 | ||
| Stimulants | e1168 | ||
| Clinical Applications | e1168 | ||
| Pharmacology | e1171 | ||
| Clinical Management | e1171 | ||
| Assessment. | e1171 | ||
| Initiating Medication and Dose Titration. | e1172 | ||
| Monitoring Stimulants. | e1172 | ||
| Adverse Effects | e1172 | ||
| Drug Interactions | e1173 | ||
| Nonstimulant Medications | e1173 | ||
| Atomoxetine | e1173 | ||
| Clinical Applications | e1173 | ||
| Pharmacology | e1173 | ||
| Clinical Management | e1174 | ||
| Adverse Effects | e1174 | ||
| Drug Interactions | e1174 | ||
| Alpha2-Agonists | e1174 | ||
| Clinical Applications | e1174 | ||
| Pharmacology | e1174 | ||
| Clinical Management | e1175 | ||
| Adverse Effects | e1175 | ||
| Drug Interactions | e1175 | ||
| Antidepressants | e1175 | ||
| Tricyclic Antidepressants | e1175 | ||
| Clinical Applications | e1175 | ||
| Pharmacology | e1176 | ||
| Clinical Management | e1176 | ||
| Assessment. | e1176 | ||
| Initiation and Titration of Tricyclic Antidepressants. | e1176 | ||
| Adverse Effects | e1177 | ||
| Drug Interactions | e1177 | ||
| Selective Serotonin Reuptake Inhibitors | e1177 | ||
| Clinical Applications | e1177 | ||
| Pharmacology | e1177 | ||
| Pharmacodynamics. | e1177 | ||
| Pharmacokinetics | e1178 | ||
| Citalopram. | e1178 | ||
| Escitalopram. | e1178 | ||
| Fluoxetine. | e1178 | ||
| Fluvoxamine. | e1178 | ||
| Paroxetine. | e1179 | ||
| Sertraline. | e1179 | ||
| Clinical Management | e1179 | ||
| Assessment. | e1179 | ||
| Initiation and Titration of Dose. | e1179 | ||
| Adverse Effects | e1179 | ||
| Common Effects. | e1179 | ||
| Antidepressants and Risk for Suicidal Behavior. | e1180 | ||
| Drug Interactions | e1181 | ||
| Serotonin–Norepinephrine Reuptake Inhibitors | e1181 | ||
| Clinical Applications | e1181 | ||
| Pharmacology | e1181 | ||
| Venlafaxine. | e1181 | ||
| Adverse Effects | e1182 | ||
| Drug Interactions | e1182 | ||
| Other Antidepressants | e1182 | ||
| Bupropion | e1182 | ||
| 61 Overview of Seizures and Epilepsy in Children | e1207 | ||
| Introduction | e1207 | ||
| An Ancient Disease in Modern Times | e1207 | ||
| New Conceptual and Practical Definitions | e1207 | ||
| Conceptual Evolution and a New Lexicon for the Epilepsies | e1209 | ||
| Epidemiology | e1209 | ||
| Diagnosis | e1209 | ||
| Overview and Summary | e1210 | ||
| Acknowledgment | e1210 | ||
| References | e1210 | ||
| 62 Principles of Management and Outcome | e1212 | ||
| Starting Antiseizure Treatment | e1212 | ||
| With Which Medicine to Start? | e1212 | ||
| “Rescue” Home Benzodiazepines | e1213 | ||
| Routines of Care | e1213 | ||
| Prediction of Seizure Outcome | e1214 | ||
| Intractability | e1215 | ||
| When to Stop Antiseizure Medicines | e1216 | ||
| Social Outcome | e1216 | ||
| References | e1217 | ||
| 63 Neurophysiology of Seizures and Epilepsy | e1220 | ||
| Classification of Seizures | e1220 | ||
| Cellular Electrophysiology | e1220 | ||
| Excitation–Inhibition Balance | e1220 | ||
| Structural Correlates of Epilepsy: Hippocampus and Neocortex | e1220 | ||
| Overview of Ion Channels | e1221 | ||
| Voltage-Dependent Membrane Conductances | e1221 | ||
| Depolarizing Conductances | e1221 | ||
| Hyperpolarizing Conductances | e1222 | ||
| Synaptic Physiology | e1222 | ||
| Inhibitory Synaptic Transmission | e1222 | ||
| Excitatory Synaptic Transmission | e1224 | ||
| Abnormal Neuronal Firing | e1224 | ||
| Paroxysmal Depolarization Shift | e1224 | ||
| Synchronizing Mechanisms | e1225 | ||
| Glial Mechanisms for Modulating Epileptogenicity | e1226 | ||
| Physiology of Absence Epilepsy | e1227 | ||
| Increased Seizure Susceptibility of the Developing Brain | e1228 | ||
| Development of Ionic Channels and Membrane Properties | e1228 | ||
| Development of Neurotransmitters, Receptors, and Transporters | e1229 | ||
| Structural Maturation of the Brain and Seizure Susceptibility | e1230 | ||
| Regulation of the Ionic Environment | e1230 | ||
| Epileptogenesis in the Developing Brain | e1230 | ||
| Antiseizure Drug Mechanisms | e1231 | ||
| Procedures for Antiseizure Drug Testing | e1231 | ||
| Antiseizure Drug Mechanisms of Action | e1231 | ||
| Summary | e1233 | ||
| References | e1233 | ||
| 64 Epilepsy Genetics | e1236 | ||
| Introduction | e1236 | ||
| Epilepsies With Onset in Neonatal Period | e1236 | ||
| Benign Familial Neonatal Epilepsy | e1236 | ||
| KCNQ2 Encephalopathy | e1236 | ||
| Ohtahara Syndrome (Early Infantile Epileptic Encephalopathy) | e1237 | ||
| Benign Familial Neonatal-Infantile Epilepsy | e1238 | ||
| Epileptic Encephalopathy Associated With SCN2A | e1238 | ||
| Epilepsies With Onset in Infancy | e1238 | ||
| Benign Familial Infantile Epilepsy | e1238 | ||
| Epileptic Encephalopathy Associated With Cyclin-Dependent Kinase-Like 5 | e1238 | ||
| Epilepsy of Infancy With Migrating Focal Seizures | e1239 | ||
| West Syndrome | e1239 | ||
| Dravet Syndrome and Genetic Epilepsy With Febrile Seizures Plus | e1242 | ||
| Epileptic Encephalopathy Associated With SCN8A | e1243 | ||
| Epilepsy Associated With Protocadherin 19 (PCDH19) | e1243 | ||
| Other Early-Onset Epilepsies | e1243 | ||
| Syndromes With Onset in Childhood and Adolescence | e1243 | ||
| Epilepsy-Aphasia Syndromes | e1243 | ||
| Idiopathic Generalized Epilepsies | e1243 | ||
| Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy | e1244 | ||
| Autosomal-Dominant Focal Epilepsy With Auditory Features | e1244 | ||
| Familial Focal Epilepsy With Variable Foci and DEPDC5-Related Epilepsies | e1244 | ||
| References | e1245 | ||
| 65 Febrile Seizures | e1250 | ||
| Definitions | e1250 | ||
| Epidemiology | e1250 | ||
| Initial Evaluation | e1250 | ||
| Pathophysiology | e1251 | ||
| Related Morbidity and Mortality | e1251 | ||
| Recurrent Febrile Seizures | e1252 | ||
| Febrile Seizures and Subsequent Epilepsy | e1252 | ||
| Febrile Seizures, Mesial Temporal Sclerosis, and Temporal Lobe Epilepsy | e1253 | ||
| Genetics | e1253 | ||
| Treatment | e1253 | ||
| Terminating a Febrile Seizure | e1254 | ||
| In-Hospital Management | e1254 | ||
| Home Management | e1254 | ||
| Preventing a Febrile Seizure | e1254 | ||
| Intermittent Medications at Time of Fever | e1254 | ||
| Antipyretics. | e1254 | ||
| Benzodiazepines. | e1254 | ||
| Barbiturates. | e1254 | ||
| Daily Medications | e1254 | ||
| Preventing Epilepsy | e1254 | ||
| Guidelines for Therapy | e1254 | ||
| Counseling and Education | e1254 | ||
| Acknowledgments | e1255 | ||
| References | e1255 | ||
| 66 Generalized Seizures | e1257 | ||
| Generalized Tonic-Clonic Seizures | e1257 | ||
| Clinical Features | e1257 | ||
| Differential Diagnosis | e1257 | ||
| Electroencephalographic Findings | e1258 | ||
| Etiology | e1259 | ||
| Initial Evaluation | e1259 | ||
| Comorbidities Associated with Generalized Seizures | e1259 | ||
| Medical Treatment | e1259 | ||
| Valproate | e1260 | ||
| Lamotrigine | e1260 | ||
| Levetiracetam | e1260 | ||
| Topiramate | e1261 | ||
| Absence Seizures | e1261 | ||
| Clinical Features | e1261 | ||
| Childhood Absence Epilepsy | e1262 | ||
| Juvenile Absence Epilepsy | e1262 | ||
| Myoclonic Absence and Eyelid Myoclonia | e1262 | ||
| Juvenile Myoclonic Epilepsy | e1262 | ||
| Differential Diagnosis | e1262 | ||
| Etiology | e1263 | ||
| Initial Evaluation | e1263 | ||
| Electroencephalographic Findings | e1263 | ||
| Pathophysiology | e1264 | ||
| Treatment | e1266 | ||
| Prognosis | e1266 | ||
| Myoclonic Seizures | e1266 | ||
| Clinical Features | e1266 | ||
| Etiology and Prognosis | e1266 | ||
| Electroencephalographic Findings | e1266 | ||
| Tonic Seizures | e1267 | ||
| 67 Focal and Multifocal Seizures | e1272 | ||
| Introduction | e1272 | ||
| Types of Focal Seizures in Children | e1272 | ||
| Alteration of Consciousness | e1272 | ||
| Semiologic Classification Schemes | e1273 | ||
| Auras | e1274 | ||
| Autonomic | e1275 | ||
| Automotor | e1275 | ||
| Behavioral Arrest or Hypomotor | e1275 | ||
| Clonus or Myoclonus—Focal | e1275 | ||
| Dialeptic or Dyscognitive | e1275 | ||
| Epileptic Spasms With Asymmetric Features | e1275 | ||
| Gelastic | e1275 | ||
| Hypermotor | e1275 | ||
| Tonic | e1276 | ||
| Versive | e1276 | ||
| Ontogeny of Focal Seizures | e1277 | ||
| Management | e1277 | ||
| References | e1282 | ||
| 68 Epileptic Spasms and Myoclonic Seizures | e1283 | ||
| Introduction | e1283 | ||
| Epilepsy Syndromes With Prominent Myoclonic Seizures | e1283 | ||
| Benign Myoclonic Epilepsy of Infancy (BMEI) | e1283 | ||
| EEG | e1283 | ||
| Treatment and Outcome | e1283 | ||
| Dravet Syndrome | e1283 | ||
| Myoclonic-Astatic Epilepsy of Doose (MAE) | e1284 | ||
| Etiology | e1284 | ||
| Seizure Semiologies | e1284 | ||
| EEG | e1284 | ||
| Treatment | e1284 | ||
| Outcome | e1285 | ||
| Juvenile Myoclonic Epilepsy (JME) | e1285 | ||
| Seizure Semiologies | e1285 | ||
| EEG | e1285 | ||
| Pathophysiology | e1285 | ||
| Imaging | e1285 | ||
| Treatment | e1286 | ||
| Outcomes | e1286 | ||
| Progressive Myoclonic Epilepsies (PME) | e1286 | ||
| Unverricht-Lundborg Disease (ULD) | e1287 | ||
| Lafora Disease (LD) | e1287 | ||
| Myoclonic Epilepsy With Ragged-Red Fibers (MERRF) | e1287 | ||
| Neuronal Ceroid Lipofuscinoses (NCL) | e1287 | ||
| Infantile Spasms | e1288 | ||
| Electroclinical Features. | e1288 | ||
| Spasms | e1288 | ||
| Hypsarrhythmia and the Ictal EEG | e1288 | ||
| Classification. | e1289 | ||
| Etiologic Factors. | e1289 | ||
| Diagnostic Evaluation. | e1290 | ||
| Course and Prognosis. | e1291 | ||
| Pathophysiology. | e1292 | ||
| Treatment. | e1292 | ||
| Hormonal Therapy | e1294 | ||
| Acth. | e1294 | ||
| Corticosteroids | e1294 | ||
| Vigabatrin | e1295 | ||
| Surgical Therapy | e1295 | ||
| Other Treatments | e1296 | ||
| Emerging Therapies | e1296 | ||
| Late-Onset Epileptic Spasms | e1297 | ||
| References | e1297 | ||
| 69 Status Epilepticus | e1302 | ||
| Epidemiology | e1302 | ||
| Economic Burden of Status Epilepticus | e1302 | ||
| Pathophysiology | e1302 | ||
| Neurotransmitter Receptor Changes Promoting Self-Sustaining Seizures | e1302 | ||
| Pathologic Changes Secondary to SE | e1304 | ||
| Physiologic Changes With SE | e1304 | ||
| Age Dependent Effects of SE on the Brain | e1304 | ||
| Definitions | e1304 | ||
| Etiology | e1305 | ||
| Clinical Presentation and Initial Management | e1305 | ||
| Laboratory Testing | e1306 | ||
| EEG Monitoring | e1306 | ||
| Time to Treatment | e1306 | ||
| Rationale Behind the Need for a Rapid Treatment | e1306 | ||
| Changes in Neurotransmitter Receptors in the Seizing Brain | e1307 | ||
| Time Elapsed From Seizure Onset to Treatment Administration in SE | e1307 | ||
| Treatment Options | e1307 | ||
| Treatment Guidelines for SE | e1307 | ||
| Benzodiazepines as First-Line Treatment | e1307 | ||
| Lorazepam as the Preferred First-Line Drug for SE | e1308 | ||
| Alternatives to the Intravenous Route of Administration | e1309 | ||
| Nonbenzodiazepine Antiseizure Drugs | e1309 | ||
| Refractory SE | e1310 | ||
| Super-Refractory SE | e1310 | ||
| Autoimmune SE and Immune Therapies | e1311 | ||
| Outcome | e1311 | ||
| Neonatal Status Epilepticus | e1311 | ||
| Nonconvulsive Status Epilepticus | e1312 | ||
| Summary | e1313 | ||
| References | e1313 | ||
| 70 Electroclinical Syndromes | e1318 | ||
| 1.0 Introduction | e1318 | ||
| 2.0 Benign Neonatal Seizures | e1318 | ||
| 2.1 Clinical Features | e1318 | ||
| 2.2 Etiology | e1318 | ||
| 2.3 Diagnosis | e1318 | ||
| 2.4 Differential Diagnosis | e1318 | ||
| 2.5 Prognosis | e1318 | ||
| 2.6 Management | e1318 | ||
| 3.0 Benign Familial Neonatal Epilepsy (BFNE) | e1319 | ||
| 3.1 Clinical Features | e1319 | ||
| 3.2 Etiology | e1319 | ||
| 3.3 Diagnosis | e1319 | ||
| 3.4 Differential Diagnosis | e1319 | ||
| 3.5 Prognosis | e1320 | ||
| 3.6 Management | e1320 | ||
| 4.0 Ohtahara Syndrome | e1320 | ||
| 4.1 Clinical Features | e1320 | ||
| 4.2 Etiology | e1320 | ||
| 4.3 Diagnosis | e1322 | ||
| 4.4 Differential Diagnosis | e1323 | ||
| 4.5 Prognosis | e1323 | ||
| 4.6 Treatment | e1323 | ||
| 5.0 Early Myoclonic Encephalopathy (EME) | e1323 | ||
| 5.1 Clinical Features | e1323 | ||
| 5.2 Etiology | e1323 | ||
| 5.3 Diagnosis | e1323 | ||
| 5.4 Differential Diagnosis | e1324 | ||
| 5.5 Prognosis | e1324 | ||
| 5.6 Management | e1324 | ||
| 6.0 Conclusion | e1324 | ||
| References | e1324 | ||
| 71 Electroclinical Syndromes | e1326 | ||
| Introduction | e1326 | ||
| Generalized Syndromes | e1326 | ||
| Myoclonic Epilepsy in Infancy | e1326 | ||
| Seizures | e1326 | ||
| Other Neurologic Findings | e1326 | ||
| Etiology | e1326 | ||
| EEG Findings | e1326 | ||
| Neuroimaging | e1326 | ||
| Other Laboratory Studies | e1326 | ||
| Differential Diagnosis | e1326 | ||
| Treatment | e1326 | ||
| Outcome | e1327 | ||
| Myoclonic Encephalopathies in Nonprogressive Disorders | e1327 | ||
| Etiology | e1327 | ||
| Seizures and EEG | e1327 | ||
| Neuroimaging | e1328 | ||
| Other Neurologic Findings | e1328 | ||
| Other Laboratory Studies | e1328 | ||
| Differential Diagnosis | e1334 | ||
| Treatment | e1334 | ||
| 72 Electroclinical Syndromes | e1346 | ||
| Introduction | e1346 | ||
| Childhood Generalized Epilepsy Syndromes | e1346 | ||
| Childhood Absence Epilepsy (CAE) | e1346 | ||
| Clinical Characteristics | e1346 | ||
| EEG Findings | e1346 | ||
| Etiology | e1346 | ||
| Treatment | e1347 | ||
| Prognosis | e1347 | ||
| Generalized Epilepsy With Eyelid Myoclonia (Jeavons Syndrome) | e1348 | ||
| 73 Electroclinical Syndromes | e1359 | ||
| Introduction | e1359 | ||
| Ontogenesis and Classification | e1359 | ||
| Epidemiology and Psychosocial and Cognitive Implications of Adolescent Epilepsy | e1359 | ||
| Compliance and Behavioral Issues | e1360 | ||
| Sports, Concussion, and Traumatic Brain Injury | e1360 | ||
| The Cost of Adolescent Epilepsy | e1360 | ||
| Adolescent Generalized Epilepsies | e1361 | ||
| Juvenile Myoclonic Epilepsy | e1361 | ||
| Juvenile Absence Epilepsy | e1363 | ||
| Genetic Generalized Epilepsies With Convulsions | e1364 | ||
| Rare Genetic Syndromes That May Present in Adolescence | e1364 | ||
| Adolescent Focal Epilepsies | e1366 | ||
| Mesial Temporal Lobe Epilepsy Resulting From Hippocampal Sclerosis | e1366 | ||
| Autosomal-Dominant Partial Epilepsy With Auditory Features | e1367 | ||
| Autosomal-Dominant Nocturnal Frontal Lobe Epilepsy | e1369 | ||
| Additional Diagnostic Considerations | e1369 | ||
| Chronobiology | e1369 | ||
| Biomarkers | e1369 | ||
| Treatment | e1370 | ||
| Antiseizure Drugs—Tackling an Old Problem With New Solutions | e1370 | ||
| Pharmacogenetics—The Horizon of Epilepsy Treatment | e1370 | ||
| Conclusion | e1371 | ||
| References | e1371 | ||
| 74 Focal Structural Epilepsy | e1374 | ||
| Introduction | e1374 | ||
| Focal Structural Epilepsy With Focal Malformations of Cortical Development | e1374 | ||
| Focal Cortical Dysplasia | e1374 | ||
| Pathology | e1374 | ||
| Imaging Features | e1374 | ||
| Clinical Features | e1374 | ||
| Etiology | e1374 | ||
| Management | e1374 | ||
| Hemimegalencephaly | e1375 | ||
| Neurologic Features | e1375 | ||
| Neuroimaging | e1375 | ||
| Nonneurologic Features | e1375 | ||
| Etiology | e1375 | ||
| Focal Structural Epilepsy With Neurocutaneous Syndromes | e1376 | ||
| Tuberous Sclerosis Complex | e1376 | ||
| Sturge–Weber Syndrome | e1376 | ||
| Genetic | e1378 | ||
| Neuroimaging | e1378 | ||
| 75 Other Acquired Epilepsies | e1383 | ||
| Posttraumatic Epilepsy | e1383 | ||
| Early Versus Late Posttraumatic Seizures | e1384 | ||
| Epidemiology | e1384 | ||
| Risk Factors | e1384 | ||
| Natural History and Treatment | e1385 | ||
| Poststroke Epilepsy | e1385 | ||
| Early Versus Late Poststroke Seizures | e1385 | ||
| Epidemiology | e1385 | ||
| 76 Inherited Metabolic Epilepsies | e1390 | ||
| Introduction | e1390 | ||
| General Principles | e1390 | ||
| Small Molecule Disorders | e1390 | ||
| Amino and Organic Acid Disorders | e1390 | ||
| Fatty Acid Oxidation Disorders | e1393 | ||
| Mitochondrial Diseases | e1393 | ||
| Urea Cycle Disorders | e1394 | ||
| Disorders of Glucose Homeostasis | e1394 | ||
| Vitamin Dependency States | e1395 | ||
| Neurotransmitter Disorders | e1395 | ||
| Purine and Pyrimidine Defects | e1395 | ||
| Large Molecule Disorders | e1396 | ||
| Disorders of Glycosylation | e1396 | ||
| Lysosomal Storage Disorders | e1396 | ||
| Peroxisomal Diseases | e1397 | ||
| Leukodystrophies | e1397 | ||
| Conclusion | e1397 | ||
| References | e1398 | ||
| Abbreviations | e1398 | ||
| 77 Antiseizure Drug Therapy in Children | e1401 | ||
| Pharmacokinetic Principles | e1401 | ||
| Absorption | e1401 | ||
| Volume of Distribution | e1405 | ||
| Protein Binding | e1406 | ||
| Metabolism and Elimination | e1407 | ||
| Specific Antiseizure Drugs | e1408 | ||
| Barbiturates | e1408 | ||
| Benzodiazepines | e1408 | ||
| Carbamates | e1408 | ||
| Carbamazepine | e1408 | ||
| Oxcarbazepine | e1409 | ||
| Eslicarbazepine | e1409 | ||
| Felbamate | e1409 | ||
| Gamma-Aminobutyric Acid Analogs | e1410 | ||
| Gabapentin | e1410 | ||
| Pregabalin | e1410 | ||
| Hydantoins | e1410 | ||
| Phenytoin | e1410 | ||
| Fosphenytoin | e1411 | ||
| Ezogabine | e1411 | ||
| Lacosamide | e1411 | ||
| Lamotrigine | e1411 | ||
| Levetiracetam | e1412 | ||
| Perampanel | e1412 | ||
| Rufinamide | e1412 | ||
| Tiagabine | e1412 | ||
| Topiramate | e1412 | ||
| Valproic Acid | e1413 | ||
| Vigabatrin | e1413 | ||
| Zonisamide | e1413 | ||
| Generic Formulations | e1413 | ||
| Pharmacodynamics | e1414 | ||
| Dose–Response or Concentration–Response Concept | e1414 | ||
| Tolerance | e1414 | ||
| Physiologic Factors Affecting Drug Disposition in Children | e1414 | ||
| General Considerations | e1414 | ||
| Neonates | e1415 | ||
| Infants and Children | e1415 | ||
| Drug Interactions | e1415 | ||
| Absorption | e1415 | ||
| Protein Binding | e1415 | ||
| Metabolism | e1415 | ||
| Mechanism of Action of Antiseizure Drugs | e1415 | ||
| Dosage Formulations and Routes of Administration | e1416 | ||
| Intravenous and Intramuscular Administration | e1416 | ||
| Rectal Administration | e1416 | ||
| Intranasal Administration | e1416 | ||
| Monitoring Antiseizure Drug Therapy | e1417 | ||
| Monitoring of Drug Therapy | e1417 | ||
| Clinical Monitoring of Adverse Effects | e1418 | ||
| Monitoring of Drug Concentrations | e1418 | ||
| Interpretation of “Optimal Therapeutic Ranges” | e1418 | ||
| When to Obtain Drug Concentrations | e1418 | ||
| What to Measure | e1418 | ||
| Laboratory Tests for Idiosyncratic Reactions | e1419 | ||
| Adverse Drug Reactions to Antiseizure Drugs | e1419 | ||
| Central Nervous System Adverse Reactions | e1419 | ||
| Gastrointestinal Effects | e1420 | ||
| Weight Gain | e1420 | ||
| Weight Loss | e1420 | ||
| Gastric Irritation | e1420 | ||
| Gingival Hyperplasia | e1420 | ||
| Increased Seizures | e1420 | ||
| Osteomalacia | e1420 | ||
| Tremor and Movement Disorders | e1420 | ||
| Other Effects | e1421 | ||
| Anticonvulsant Hypersensitivity Syndrome in Children | e1421 | ||
| Clinical Features | e1421 | ||
| Pathogenesis | e1421 | ||
| Prevention | e1421 | ||
| Managing Adverse Effects | e1421 | ||
| Discontinuation of Antiseizure Drug Therapy | e1422 | ||
| Benefits of Drug Discontinuation | e1422 | ||
| Risks of Drug Discontinuation | e1422 | ||
| References | e1422 | ||
| 78 Epilepsy Surgery in the Pediatric Population | e1427 | ||
| Historical Background | e1428 | ||
| Indications for Epilepsy Surgery | e1428 | ||
| Preoperative Evaluation | e1430 | ||
| Seizure Semiology | e1430 | ||
| Physical Examination | e1431 | ||
| Electroencephalography | e1431 | ||
| Magnetic Resonance Imaging | e1431 | ||
| Single-Photon Emission Computed Tomography | e1431 | ||
| Positron Emission Tomography | e1434 | ||
| Magnetic Resonance Spectroscopy | e1435 | ||
| Magnetoencephalography | e1435 | ||
| Functional Mapping | e1436 | ||
| Concept of Congruence | e1438 | ||
| Invasive Intracranial Electroencephalography Monitoring | e1439 | ||
| Types of Surgery | e1439 | ||
| Goals of Surgery | e1441 | ||
| Research Issues: Trends for the Future | e1441 | ||
| References | e1441 | ||
| 79 Neuromodulation in Epilepsy | e1446 | ||
| Introduction | e1446 | ||
| Vagus Nerve Stimulation | e1446 | ||
| Anterior Nucleus of the Thalamus Deep-Brain Stimulation | e1447 | ||
| Responsive Neurostimulation | e1447 | ||
| Trigeminal Nerve Stimulation | e1448 | ||
| Repetitive Transcranial Magnetic Stimulation for Seizure Suppression | e1448 | ||
| Diagnostic Transcranial Magnetic Stimulation | e1448 | ||
| Transcranial Direct Current Stimulation | e1449 | ||
| Conclusion | e1449 | ||
| References | e1450 | ||
| 80 Ketogenic Diets | e1452 | ||
| History | e1452 | ||
| Efficacy | e1452 | ||
| Efficacy of the Classic Ketogenic Diet | e1452 | ||
| Efficacy of the Ketogenic Diet for Adults | e1456 | ||
| Efficacy of Alternative Ketogenic Diets | e1457 | ||
| Mechanisms of Action | e1458 | ||
| Oxidation of Fatty Acids: Ketogenesis | e1459 | ||
| Clinical Studies of Ketosis | e1460 | ||
| Experimental Studies of Diets in Animal Models | e1461 | ||
| Selection of Candidates for the Diet | e1461 | ||
| Value of the EEG in Ketogenic Diet Prediction | e1462 | ||
| Initiation and Maintenance | e1463 | ||
| Prehospital Evaluation | e1463 | ||
| Hospitalization | e1463 | ||
| Side Effects | e1464 | ||
| Advantages (and Disadvantages) Compared With Other Treatments for Epilepsy | e1466 | ||
| Advantages | e1466 | ||
| Disadvantages | e1466 | ||
| The Ketogenic Diet in the 21st Century | e1467 | ||
| References | e1467 | ||
| Resources | e1474 | ||
| Websites | e1474 | ||
| 81 Pediatric Psychogenic Nonepileptic Seizures and Psychiatric Disorders | e1475 | ||
| 1. Overview | e1475 | ||
| 2. Evaluation of the Patient | e1475 | ||
| Risk Factors | e1475 | ||
| History | e1476 | ||
| Differential Diagnosis Between Epilepsy and PNES | e1476 | ||
| Multidisciplinary Assessment Including Psychiatric Evaluation | e1476 | ||
| 3. Psychopathology in Children With PNES | e1476 | ||
| 4. Multidisciplinary Treatment Model | e1477 | ||
| The Role of the Neurologist | e1477 | ||
| Basic Principles of Psychiatric PNES Treatment | e1478 | ||
| 5. Outcome | e1478 | ||
| Summary | e1478 | ||
| References | e1479 | ||
| 82 Behavioral, Cognitive, and Social Aspects of Childhood Epilepsy | e1481 | ||
| Cognitive and Behavioral Disorders | e1481 | ||
| Cognitive Disabilities in Children With Epilepsy | e1481 | ||
| Cognitive Function in Self-Limited Childhood Epilepsy Syndromes | e1481 | ||
| Learning Disabilities and Academic Underachievement | e1481 | ||
| Attention Deficit, Impulsivity, and Overactivity | e1481 | ||
| Autism and Autistic Spectrum Disorders | e1482 | ||
| Psychiatric Disorders in Childhood Epilepsy | e1482 | ||
| Behavioral Problems, Conduct Disorders, and Delinquency | e1482 | ||
| Cognitive and Behavioral Outcome of Specific Epilepsy Syndromes: | e1482 | ||
| Epileptic Encephalopathy, a Model System of Epilepsy | e1482 | ||
| Infantile Spasms | e1482 | ||
| Epileptic Encephalopathies of Infancy | e1483 | ||
| Lennox–Gastaut Syndrome | e1483 | ||
| Electrical Status Epilepticus in Sleep and Landau–Kleffner Syndrome | e1483 | ||
| Self-Limited Focal Epilepsies of Childhood | e1483 | ||
| Family, Community, and Cultural Perceptions of Epilepsy | e1483 | ||
| Social Adjustment of Adults With Childhood-Onset Epilepsy | e1483 | ||
| Effects of Antiseizure Drugs on Behavior, Attention, and Mood | e1483 | ||
| General Effects of Antiseizure Drugs | e1483 | ||
| Psychotropic Effects and Adverse Psychiatric Effects of Antiseizure Drugs | e1484 | ||
| Forced Normalization | e1484 | ||
| Mood Disorders | e1484 | ||
| Psychosis | e1484 | ||
| Fear of Side Effects and Effective Antiseizure Medication Use | e1484 | ||
| Behavioral and Cognitive Effects of the Older vs. Newer Antiseizure Medicines | e1485 | ||
| Phenobarbital | e1485 | ||
| Phenytoin | e1485 | ||
| Valproic Acid | e1485 | ||
| Carbamazepine | e1485 | ||
| Oxcarbazepine | e1485 | ||
| Lamotrigine | e1485 | ||
| Felbamate | e1485 | ||
| Topiramate | e1485 | ||
| Zonisamide | e1486 | ||
| Levetiracetam | e1486 | ||
| Clobazam | e1486 | ||
| Gabapentin | e1486 | ||
| Vigabatrin | e1486 | ||
| Lacosamide | e1486 | ||
| Perampanel | e1487 | ||
| Retigabine | e1487 | ||
| Treatment of Cognitive, Social, Academic, and Behavioral Problems Associated With Epilepsy | e1487 | ||
| School Inclusion and Academic Planning | e1487 | ||
| Behavior Problems and Discipline | e1487 | ||
| Treatment of Attention-Deficit Disorders in Children With Epilepsy | e1487 | ||
| Peer Relationships, Teasing, and Social Isolation | e1487 | ||
| Occupational Planning and Adjustment | e1487 | ||
| References | e1488 | ||
| 83 Mortality in Children with Epilepsy | e1492 | ||
| Introduction | e1492 | ||
| Epidemiology | e1492 | ||
| Sudden Unexpected Death in Epilepsy—Definition | e1493 | ||
| Sudden Unexpected Death in Epilepsy—Risk Factors | e1493 | ||
| Seizure Type, Duration, and Severity | e1493 | ||
| Sleep/Awake State | e1494 | ||
| Body Position | e1494 | ||
| Proposed Mechanisms for Sudden Unexpected Death in Epilepsy | e1494 | ||
| Discussions About Sudden Unexpected Death in Epilepsy With Families and Patients | e1496 | ||
| Prevention of Mortality Related to Seizures | e1496 | ||
| Prevention of Mortality Not Related to Seizures | e1497 | ||
| Conclusions | e1497 | ||
| References | e1497 | ||
| 84 Headache in Children and Adolescents | e1500 | ||
| Introduction | e1500 | ||
| Classification | e1500 | ||
| Migraine Without Aura | e1500 | ||
| Migraine With Aura | e1500 | ||
| Chronic Migraine | e1501 | ||
| Migraine Variants | e1501 | ||
| Tension-Type Headache | e1501 | ||
| Trigeminal Autonomic Cephalalgia | e1501 | ||
| Paroxysmal Hemicrania | e1501 | ||
| Epidemiology | e1501 | ||
| Migraine Pathophysiology | e1502 | ||
| Evaluation of the Child With Headaches | e1502 | ||
| Neuroimaging | e1502 | ||
| Lumbar Puncture | e1503 | ||
| Clinical Laboratory Testing | e1503 | ||
| Electroencephalogram | e1503 | ||
| Management of Pediatric Migraine | e1503 | ||
| Pharmacologic Therapies for Migraine Headache | e1504 | ||
| Acute Therapy/Outpatient Abortive Therapy | e1504 | ||
| Emergency Room Management of Migraine Exacerbation | e1505 | ||
| Antidopaminergic Drugs—Prochlorperazine and Metoclopramide. | e1505 | ||
| Nonsteroidal Anti-Inflammatory Drugs—Ketorolac. | e1505 | ||
| Antiepileptic Drugs—Sodium Valproate. | e1506 | ||
| Triptan Compounds. | e1506 | ||
| Dihydroergotamine Use in the Emergency Department. | e1506 | ||
| Inpatient Therapy for Severe Debilitating Acute Exacerbation of Primary Headache | e1506 | ||
| Dihydroergotamine Use in the Inpatient Setting. | e1506 | ||
| Sodium Valproate. | e1506 | ||
| Preventive Treatment | e1506 | ||
| Antidepressants. | e1507 | ||
| Antiepileptic Drugs. | e1507 | ||
| Antihistamines. | e1509 | ||
| Beta Blockers. | e1509 | ||
| Botulinum Toxin. | e1509 | ||
| Nutraceuticals for Headache Prevention. | e1509 | ||
| Nonpharmacologic Treatment for Chronic Headaches | e1510 | ||
| Specific Secondary Headache Syndromes | e1510 | ||
| Posttraumatic Headache | e1510 | ||
| Idiopathic Intracranial Hypertension | e1511 | ||
| Intracranial Hypotension | e1512 | ||
| Headache Secondary to a Brain Tumor | e1512 | ||
| Chiari Malformation | e1512 | ||
| Metabolic Causes of Headache in Children | e1512 | ||
| MELAS | e1512 | ||
| CADASIL | e1513 | ||
| Conclusion | e1513 | ||
| References | e1513 | ||
| 85 Breath-Holding Spells and Reflex Anoxic Seizures | e1516 | ||
| Breath-Holding Spells | e1516 | ||
| Clinical Features | e1516 | ||
| Clinical Laboratory Tests | e1516 | ||
| Pathophysiology | e1516 | ||
| Cyanotic Spells | e1516 | ||
| Pallid Spells | e1517 | ||
| Genetics | e1518 | ||
| Treatment | e1518 | ||
| Reflex Anoxic Seizures | e1519 | ||
| Clinical Features | e1519 | ||
| Pathophysiology | e1519 | ||
| Clinical Laboratory Tests | e1519 | ||
| Treatment | e1519 | ||
| References | e1520 | ||
| 86 Syncope and Postural Orthostatic Tachycardia Syndrome | e1522 | ||
| Syncope | e1522 | ||
| Epidemiology | e1522 | ||
| Etiology | e1522 | ||
| Cardiovascular-Mediated Syncope | e1522 | ||
| Neurocardiogenic Syncope | e1522 | ||
| Clinical Features | e1522 | ||
| Pathophysiology | e1523 | ||
| Diagnostic Evaluation | e1524 | ||
| Tilt-Table Testing | e1524 | ||
| Treatment | e1525 | ||
| Prognosis | e1525 | ||
| Convulsive Syncope | e1525 | ||
| Reflex Syncope | e1526 | ||
| Situational Syncope | e1526 | ||
| Hyperventilation Syncope | e1526 | ||
| Suffocation or Strangulation Syncope | e1526 | ||
| Drug-Induced Syncope | e1526 | ||
| Psychogenic Syncope | e1526 | ||
| Postural Orthostatic Tachycardia Syndrome | e1526 | ||
| Introduction | e1526 | ||
| Clinical Features | e1527 | ||
| Pathophysiology | e1527 | ||
| I. Hypovolemic and Deconditioned POTS | e1528 | ||
| II. Hyperadrenergic POTS | e1528 | ||
| III. Neuropathic POTS | e1528 | ||
| Coexistent Conditions Associated With POTS | e1528 | ||
| I. Visceral Pain and Dysmotility | e1528 | ||
| II. Chronic Fatigue, Neurocognitive Disorders, Insomnia, and Fibromyalgia | e1528 | ||
| III. Nutritional Deficiencies | e1528 | ||
| IV. Headaches | e1528 | ||
| V. Ehlers-Danlos Syndrome (EDS) | e1528 | ||
| Clinical and Laboratory Evaluation. | e1528 | ||
| Treatment | e1529 | ||
| Conclusions | e1530 | ||
| References | e1530 | ||
| 87 Nocturnal Paroxysmal Disorders | e1533 | ||
| A. Parasomnias | e1533 | ||
| I. Disorders of Arousal from NREM Sleep | e1533 | ||
| Sleepwalking | e1533 | ||
| Confusional Arousals | e1534 | ||
| Sleep Terrors | e1534 | ||
| Sleep-Related Eating Disorder | e1535 | ||
| Diagnosis | e1535 | ||
| II. Parasomnias Associated with REM Sleep | e1535 | ||
| Nightmares | e1535 | ||
| REM Sleep Behavior Disorder | e1535 | ||
| Recurrent Isolated Sleep Paralysis | e1535 | ||
| III. Other Parasomnias | e1535 | ||
| Nocturnal Enuresis | e1535 | ||
| Exploding Head Syndrome | e1535 | ||
| Sleep-Related Hallucinations | e1535 | ||
| IV. Normal Variants | e1535 | ||
| Sleep Talking | e1535 | ||
| Sleep Starts | e1535 | ||
| V. Other Disorders | e1536 | ||
| Catathrenia | e1536 | ||
| Hypnic Headaches | e1536 | ||
| Head Banging | e1536 | ||
| B. Nocturnal Panic Attacks | e1536 | ||
| C. Sandifer Syndrome | e1537 | ||
| References | e1537 | ||
| 88 Disorders of Excessive Sleepiness | e1539 | ||
| Assessment of Sleepiness | e1539 | ||
| Clinical Assessment | e1539 | ||
| History | e1539 | ||
| Physical Examination | e1539 | ||
| Subjective Evaluation Tools | e1539 | ||
| Objective Evaluation Tools | e1539 | ||
| Actigraphy | e1539 | ||
| Nocturnal Polysomnography | e1539 | ||
| Multiple Sleep Latency Test (MSLT) | e1540 | ||
| The Maintenance of Wakefulness Test (MWT) | e1540 | ||
| Cerebrospinal Fluid Hypocretin-1 Levels | e1540 | ||
| Histocompatibility Antigen (HLA) Subtypes | e1541 | ||
| Narcolepsy Type 1 (Narcolepsy with Cataplexy) | e1541 | ||
| Other Associations | e1541 | ||
| Pathophysiology | e1542 | ||
| Diagnosis | e1542 | ||
| Treatment | e1542 | ||
| Treatment of Daytime Sleepiness | e1543 | ||
| Wake-Promoting Agents | e1543 | ||
| Stimulants | e1543 | ||
| Treatment of Cataplexy | e1543 | ||
| Treatment of Nocturnal Sleep Fragmentation | e1543 | ||
| Sodium Oxybate | e1543 | ||
| Future Treatments | e1543 | ||
| Narcolepsy Type 2 | e1543 | ||
| Kleine-Levin Syndrome (KLS) | e1544 | ||
| Idiopathic Hypersomnia (IH) | e1544 | ||
| Hypersomnia Due to Medical Disorders, Medications, or Substance Abuse | e1544 | ||
| Traumatic Brain Injury (TBI) | e1544 | ||
| Cancer | e1544 | ||
| Prader-Willi Syndrome (PWS) | e1545 | ||
| Myotonic Dystrophy 1 (MD1) | e1545 | ||
| Norrie Disease | e1545 | ||
| Coffin-Lowry Syndrome (CLS) | e1545 | ||
| Neiman Pick Disease Type C | e1545 | ||
| ROHHAD (Rapid Onset Obesity with Hypothalamic Dysfunction and Autonomic Dysregulation) Syndrome | e1545 | ||
| Encephalopathies/Encephalitis | e1545 | ||
| Encephalitis Lethargica | e1545 | ||
| Voltage-gated Potassium Channel (VGKC) Complex Autoimmunity | e1545 | ||
| Anti-NMDA Receptor Encephalitis | e1545 | ||
| Insufficient Sleep Syndrome (ISS) | e1546 | ||
| References | e1546 | ||
| 89 Restless Legs Syndrome and Periodic Limb Movement Disorder in Children and Adolescents | e1549 | ||
| Introduction | e1549 | ||
| Prevalence | e1549 | ||
| Symptoms | e1549 | ||
| Presentation | e1549 | ||
| Diagnosis | e1549 | ||
| Iron Deficiency | e1551 | ||
| Iron and Neuroimaging | e1551 | ||
| Family History and Genetics | e1551 | ||
| Coexistent Conditions | e1551 | ||
| Treatment | e1552 | ||
| Conclusions | e1553 | ||
| References | e1553 | ||
| 90 Apparent Life-Threatening Event and Sudden Infant Death Syndrome | e1555 | ||
| Introduction | e1555 | ||
| Apparent Life-Threatening Events | e1555 | ||
| Definition | e1555 | ||
| Epidemiology | e1555 | ||
| Risk Factors | e1555 | ||
| Etiology/Differential Diagnosis | e1555 | ||
| Evaluation | e1556 | ||
| History | e1556 | ||
| Physical Examination | e1556 | ||
| Diagnostic Testing | e1557 | ||
| Inpatient Versus Outpatient Management | e1557 | ||
| Home Monitoring | e1557 | ||
| Risk of SIDS | e1557 | ||
| Risk of Death | e1557 | ||
| Sudden Infant Death Syndrome | e1557 | ||
| Introduction | e1557 | ||
| Definition | e1557 | ||
| Pathogenesis | e1558 | ||
| The Triple-Risk Model | e1558 | ||
| Disease Mechanisms Contributing to SIDS | e1558 | ||
| Cardiac Abnormalities | e1558 | ||
| Infection | e1559 | ||
| Metabolic/Genetics | e1559 | ||
| The Brainstem and the 5-Hydroxytryptamine System | e1559 | ||
| Epidemiology | e1559 | ||
| Risk Factors | e1560 | ||
| Prone and Side Sleep Position | e1560 | ||
| Bed-Sharing | e1560 | ||
| Soft Bedding and Bedding Accessories | e1560 | ||
| Overheating | e1560 | ||
| Maternal Smoking | e1560 | ||
| Prematurity | e1560 | ||
| Prevention | e1560 | ||
| References | e1561 | ||
| 91 The Cerebellum and the Hereditary Ataxias | e1564 | ||
| Introduction | e1564 | ||
| Basic Cerebellar Structure, Function, and Dysfunction | e1564 | ||
| Cerebellar Structure | e1564 | ||
| Cerebellar Function | e1565 | ||
| Cerebellar Dysfunction | e1566 | ||
| Nonhereditary Causes of Ataxia | e1567 | ||
| The Hereditary Ataxias | e1567 | ||
| Autosomal Recessive Inherited Syndromes | e1569 | ||
| Friedreich Ataxia (FRDA MIM 229300) | e1569 | ||
| Clinical Manifestations. | e1569 | ||
| Pathology. | e1574 | ||
| Genetics. | e1574 | ||
| Treatment. | e1575 | ||
| Friedreich Ataxia 2 (MIM 601992) | e1575 | ||
| Vitamin E Deficiency and Related Syndromes | e1575 | ||
| Ataxia-Telangiectasia (Louis-Bar Syndrome— MIM 208900) | e1575 | ||
| Clinical Manifestations. | e1575 | ||
| Laboratory Findings. | e1576 | ||
| Pathology. | e1576 | ||
| Genetics. | e1576 | ||
| Treatment. | e1577 | ||
| Ataxia-Telangiectasia-Like Disorder 1 (MIM 604391) | e1577 | ||
| Ataxia-Telangiectasia–Like Disorder 2 (MIM 615919) | e1577 | ||
| Early Onset Ataxia with Ocular Motor Apraxia and Hypoalbuminemia (Ataxia-Oculomotor Apraxia 1, AOA1—MIM 208920) | e1577 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 1 (MIM 606002); Ataxia-Oculomotor Apraxia 2 | e1577 | ||
| Ataxia-Oculomotor Apraxia 3; (AOA3—MIM 615217) | e1577 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 2 (MIM 213200); Cerebellar Hypoplasia, Nonprogressive Norman Type | e1577 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 3 (MIM 271250); Spinocerebellar Ataxia with Blindness and Deafness | e1578 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 4 (MIM 607317); Spinocerebellar Ataxia with Saccadic Intrusions (Formerly Spinocerebellar Ataxia 24) | e1578 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 5 (MIM 606937); Nonprogressive Congenital Cerebellar Ataxia with Mental Retardation, Optic Atrophy, and Skin Abnormalities | e1578 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 6 (MIM 608029); Norwegian Nonprogressive Infantile Cerebellar Ataxia | e1578 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 7 (MIM 609270) | e1578 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 8 (MIM 610743); Cerebellar Ataxia, Autosomal Recessive, Type 1; Recessive Ataxia of Beauce | e1578 | ||
| Coenzyme Q10 Deficiency Primary, 4 (MIM 612016); Spinocerebellar Ataxia, Autosomal Recessive 9 | e1578 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 10 (MIM 613728) | e1578 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 11 (MIM 614229) | e1578 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 12 (MIM 614322) | e1579 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 13 (MIM 614831) | e1579 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 14 (MIM 615386) | e1579 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 15 (MIM 615705) | e1579 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 16 (MIM 615768) | e1579 | ||
| Spinocerebellar Ataxia, Autosomal Recessive 17 (MIM 616127) | e1579 | ||
| Cerebellar Ataxia, Cayman Type (MIM 601238) | e1579 | ||
| Mitochondrial DNA Depletion Syndrome 7 (Hepatocerebral Type) (MIM 271245); Infantile-Onset Spinocerebellar Ataxia; Formerly Spinocerebellar Ataxia 8 | e1579 | ||
| Ramsay Hunt Syndrome: Progressive Myoclonic Ataxia and Progressive Myoclonic Epilepsy (Baltic Myoclonus, Mediterranean Myoclonus, Unverricht-Lundborg Syndrome) (MIM 159700) | e1579 | ||
| Other Childhood-Onset Ataxias | e1580 | ||
| Autosomal Dominant Inherited Ataxias (Spinocerebellar Ataxias) | e1580 | ||
| Spinocerebellar Ataxia Type 1; Olivopontocerebellar Atrophy 1 (MIM 164400) | e1580 | ||
| Spinocerebellar Ataxia Type 2 (MIM 183090) | e1581 | ||
| Machado-Joseph Disease and Spinocerebellar Ataxia Type 3 (MIM 109150) | e1581 | ||
| Spinocerebellar Ataxia Type 4 (MIM 600223) | e1582 | ||
| Spinocerebellar Ataxia Type 5 (MIM 600224) | e1582 | ||
| Spinocerebellar Ataxia Type 6 (MIM 183086) | e1582 | ||
| Spinocerebellar Ataxia Type 7 (MIM 164500) | e1582 | ||
| Spinocerebellar Ataxia Type 8 (MIM 608768) | e1583 | ||
| Spinocerebellar Ataxia Type 10 (MIM 603516) | e1583 | ||
| Spinocerebellar Ataxia Type 11 (MIM 604432) | e1584 | ||
| Spinocerebellar Ataxia Type 12 (MIM 604326) | e1584 | ||
| Spinocerebellar Ataxia Type 13 (MIM 605259) | e1584 | ||
| Spinocerebellar Ataxia Type 14 (MIM 605361) | e1584 | ||
| Spinocerebellar Ataxia Types 15 and 16 (MIM 606658 and 606364) | e1584 | ||
| Spinocerebellar Ataxia Type 17; Huntington Disease-Like 4 (MIM 607136) | e1584 | ||
| Spinocerebellar Ataxia Type 18 (Sensory/Motor Neuropathy with Ataxia—MIM 607458) | e1585 | ||
| Spinocerebellar Ataxia Type 19 (MIM 607346) | e1585 | ||
| Spinocerebellar Ataxia Type 20 (MIM 608687) | e1585 | ||
| Spinocerebellar Ataxia Type 21 (MIM 607454) | e1585 | ||
| Spinocerebellar Ataxia Type 23 (MIM 610245) | e1585 | ||
| Spinocerebellar Ataxia Type 24 (MIM 608703) | e1585 | ||
| Spinocerebellar Ataxia Type 25 (MIM 608703) | e1585 | ||
| Spinocerebellar Ataxia Type 26 (MIM 609306) | e1586 | ||
| Spinocerebellar Ataxia Type 27 (MIM 609307); Fibroblast Growth Factor 14-SCA | e1586 | ||
| Spinocerebellar Ataxia Type 28 (MIM 610246) | e1586 | ||
| Spinocerebellar Ataxia Type 29 (MIM 117360) Cerebellar Ataxia, Congenital, Nonprogressive, Autosomal Dominant | e1586 | ||
| Spinocerebellar Ataxia Type 30 (MIM 613371) | e1586 | ||
| Spinocerebellar Ataxia Type 31 (MIM 117210) | e1586 | ||
| Spinocerebellar Ataxia Type 32 (MIM 613909) | e1586 | ||
| Spinocerebellar Ataxia Type 34 (MIM 133190) | e1586 | ||
| Spinocerebellar Ataxia Type 35 (MIM 613908) | e1587 | ||
| Spinocerebellar Ataxia Type 36 (MIM 614153) Asidan/Costa Da Morte Ataxia | e1587 | ||
| Spinocerebellar Ataxia Type 37 (MIM 615945) | e1587 | ||
| Spinocerebellar Ataxia Type 38 (MIM 615957) | e1587 | ||
| Spinocerebellar Ataxia Type 40 (MIM 616053) | e1587 | ||
| Dentatorubral-Pallidoluysian Atrophy (MIM 125370). | e1587 | ||
| Episodic Ataxias | e1588 | ||
| Hereditary Spastic Ataxia | e1588 | ||
| Spastic Ataxia 1, Autosomal Dominant (MIM 108600) | e1588 | ||
| Spastic Ataxia 2, Autosomal Recessive (MIM 611302) | e1589 | ||
| Spastic Ataxia 3, Autosomal Recessive (MIM 611390) or Autosomal Recessive Spastic Ataxia with Leukoencephalopathy; ARSAL | e1589 | ||
| Spastic Ataxia 4, Autosomal Recessive (MIM 613672) | e1589 | ||
| Spastic Ataxia 5, Autosomal Recessive (MIM 614487) | e1589 | ||
| Spastic Ataxia Charlevoix-Saguenay Type; (MIM 270550) Spastic Ataxia 6, Autosomal Recessive (SPAX6); Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay | e1589 | ||
| Spastic Ataxia 7, Autosomal Dominant (MIM 108650); Spastic Ataxia with Congenital Miosis | e1589 | ||
| Spastic Paraplegia, Ataxia and Mental Retardation (MIM 607565). | e1589 | ||
| X-Linked Spinocerebellar Ataxia | e1589 | ||
| Diagnostic Approach to the Hereditary Ataxias | e1590 | ||
| Management of Cerebellar Dysfunction and Ataxia | e1590 | ||
| References | e1590 | ||
| 92 Acute Cerebellar Ataxia | e1595 | ||
| Clinical Evaluation of Acute Ataxia | e1595 | ||
| Causes of Acute Cerebellar Ataxia | e1595 | ||
| Inflammatory Cerebellitis | e1595 | ||
| Infectious/Postinfectious | e1595 | ||
| Demyelinating | e1595 | ||
| Paraneoplastic | e1596 | ||
| Intoxication | e1597 | ||
| Mass Lesions | e1597 | ||
| Trauma | e1597 | ||
| Vascular | e1597 | ||
| Metabolic/Genetic | e1597 | ||
| Other Neurologic Disorders | e1598 | ||
| Psychogenic | e1598 | ||
| Investigations in Acute Ataxia | e1598 | ||
| Computed Tomography and Magnetic Resonance Imaging | e1598 | ||
| Cerebrospinal Fluid | e1598 | ||
| Electromyography and Electroencephalography | e1598 | ||
| Toxicology | e1599 | ||
| Urinary Catecholamines/Metaiodobenzylguanidine Scintigraphy | e1599 | ||
| Others Tests | e1599 | ||
| Treatment and Prognosis | e1599 | ||
| References | e1601 | ||
| 93 Movement Disorders | e1603 | ||
| Introduction | e1603 | ||
| Characteristic Features of Pediatric Movement Disorders | e1603 | ||
| Diagnosis of Movement Disorders | e1603 | ||
| The Role of the Basal Ganglia in Movement Disorders | e1604 | ||
| Basal Ganglia Pathophysiology in Movement Disorders | e1606 | ||
| Etiologies of Movement Disorders in Children | e1606 | ||
| Classification of Childhood Movement Disorders | e1607 | ||
| Ataxia | e1607 | ||
| Athetosis | e1607 | ||
| Ballismus | e1608 | ||
| Chorea | e1608 | ||
| Dystonia | e1608 | ||
| Myoclonus | e1609 | ||
| Parkinsonism | e1609 | ||
| Stereotypies | e1609 | ||
| Tics | e1609 | ||
| Tremor | e1610 | ||
| Approach to Treatment | e1610 | ||
| Chorea | e1610 | ||
| Sydenham Chorea | e1610 | ||
| Benign Hereditary Chorea | e1611 | ||
| Ataxia-Telangiectasia | e1612 | ||
| Fahr Syndrome | e1612 | ||
| Medication-Induced Chorea | e1612 | ||
| Chorea Associated With Systemic Illness | e1613 | ||
| Ballism | e1613 | ||
| Treatment of Chorea | e1613 | ||
| Dystonia | e1613 | ||
| Genetic Dystonias (DYTx Classifications) | e1613 | ||
| DYT1 Dystonia | e1615 | ||
| DYT2 Dystonia | e1615 | ||
| DYT4 Dystonia | e1616 | ||
| DYT5 (Dopa-Responsive) Dystonia | e1616 | ||
| DYT6 Dystonia | e1616 | ||
| Paroxysmal Dyskinesia (DYT8, DYT9, DYT10) | e1616 | ||
| DYT11 Dystonia (Myoclonus-Dystonia Syndrome) | e1616 | ||
| DYT12 Dystonia | e1617 | ||
| DYT16 Dystonia | e1617 | ||
| Dystonias Associated With Neurodegenerative Disorders | e1617 | ||
| Pantothenate Kinase-Associated Neurodegeneration (PKAN) | e1617 | ||
| PLA2G6-Associated Neurodegeneration (PLAN) | e1618 | ||
| Lesch-Nyhan Disease | e1618 | ||
| Spinocerebellar Ataxia Type 3 | e1618 | ||
| Organic Acidemias | e1619 | ||
| Neuroacanthocytosis | e1619 | ||
| Dystonia Due to Nonprogressive Disorders | e1619 | ||
| Cerebral Palsy | e1619 | ||
| Kernicterus | e1619 | ||
| Medication-Induced Dystonias | e1620 | ||
| Dystonic Storm | e1620 | ||
| Treatments for Dystonia | e1620 | ||
| Tremor | e1621 | ||
| Classification of Tremor | e1621 | ||
| Primary Tremor | e1622 | ||
| Secondary Tremor | e1622 | ||
| Treatment of Tremor | e1622 | ||
| Parkinsonism | e1623 | ||
| Parkinson Disease | e1623 | ||
| PARK2 | e1624 | ||
| PARK6 | e1624 | ||
| Other Genetic Disorders Causing Parkinsonism | e1624 | ||
| PARK19 | e1624 | ||
| Neuronal Intranuclear Inclusion Disease | e1624 | ||
| Pallido-Pyramidal Syndrome | e1624 | ||
| Kufor-Rakeb Syndrome | e1624 | ||
| Huntington Disease | e1625 | ||
| Other Causes of Parkinsonism | e1625 | ||
| Treatment of Parkinsonism | e1625 | ||
| Myoclonus | e1625 | ||
| Classification of Myoclonus | e1626 | ||
| Physiologic and Developmental Myoclonus | e1626 | ||
| Symptomatic Myoclonus | e1626 | ||
| Dyssynergia Cerebellaris Myoclonica (Ramsay-Hunt Syndrome) | e1627 | ||
| Dentato-Rubral-Pallido-Luysian Atrophy | e1627 | ||
| Postanoxic Myoclonus | e1627 | ||
| Treatment of Myoclonus | e1627 | ||
| Stereotypy | e1627 | ||
| Other Movement Disorders | e1627 | ||
| Restless Legs Syndrome and Periodic Leg Movements of Sleep | e1627 | ||
| Hyperekplexia | e1627 | ||
| Bobble-Head Doll Syndrome | e1628 | ||
| Functional (Psychogenic) Movement Disorders | e1628 | ||
| References | e1629 | ||
| 94 Paroxysmal Dyskinesias | e1637 | ||
| Introduction | e1637 | ||
| Historical Context and Terminology | e1637 | ||
| Classic Phenotypes of Paroxysmal Dyskinesia | e1638 | ||
| Paroxysmal Kinesigenic Dyskinesia | e1638 | ||
| Clinical Features | e1638 | ||
| Genetics | e1639 | ||
| Diagnosis | e1639 | ||
| Treatment | e1639 | ||
| Paroxysmal Nonkinesigenic Dyskinesia | e1639 | ||
| Clinical Features | e1639 | ||
| 95 Movement Disorders of Infancy | e1646 | ||
| Benign Neonatal Sleep Myoclonus | e1646 | ||
| Benign Myoclonus of Early Infancy | e1646 | ||
| Jitteriness | e1646 | ||
| Shuddering | e1647 | ||
| Paroxysmal Tonic Upgaze of Infancy | e1647 | ||
| Spasmus Nutans | e1648 | ||
| Head Nodding | e1648 | ||
| Benign Paroxysmal Torticollis | e1648 | ||
| Benign Idiopathic Dystonia of Infancy | e1649 | ||
| Posturing during Masturbation | e1649 | ||
| References | e1649 | ||
| 96 Drug-Induced Movement Disorders in Children | e1651 | ||
| Introduction and Overview | e1651 | ||
| Definition of Drug-Induced Movement Disorders | e1651 | ||
| Clinical Characteristics—Phenomenology of Drug-Induced Movement Disorders in Children | e1651 | ||
| Drug-Induced Movement Disorders | e1651 | ||
| Drug-Induced Movement Disorders Associated With Dopamine Receptor Blockade: Typical Antipsychotics, Atypical Antipsychotics | e1651 | ||
| Epidemiology | e1651 | ||
| Clinical Features of Drug-Induced Movement Disorders Induced by Dopamine Receptor Blocking Agents | e1654 | ||
| Pathophysiology | e1655 | ||
| Diagnosis of Acute, Chronic, Tardive, and Withdrawal Emergent Syndromes | e1655 | ||
| Treatment of Drug-Induced Movement Disorders Related to Use of Dopamine Receptor Blocking Agents | e1655 | ||
| Acute Drug-Induced Movement Disorders. | e1655 | ||
| Chronic Drug-Induced Movement Disorders. | e1655 | ||
| Tardive Movement Disorders. | e1655 | ||
| Neuroleptic Malignant Syndrome | e1656 | ||
| Drug-Induced Movement Disorders Associated With Treatment of Attention Deficit Disorder | e1656 | ||
| Epidemiology of Psychostimulant Use in Children | e1656 | ||
| Clinical Features | e1656 | ||
| Pathophysiology | e1656 | ||
| Diagnosis | e1656 | ||
| Treatment | e1656 | ||
| Drug-Induced Movement Disorders Associated With Other Medications | e1656 | ||
| Serotonin Reuptake Inhibitors | e1656 | ||
| Antiseizure Medications | e1657 | ||
| Drug-Induced Movement Disorder Associated With Chemotherapeutic, Immunomodulatory, and Anti-infectious Medications | e1657 | ||
| DIMDs Associated With Vitamin Administration | e1657 | ||
| Conclusion | e1657 | ||
| References | e1657 | ||
| 97 Cerebral Palsy | e1660 | ||
| Outline | e1660 | ||
| I. Introduction | e1660 | ||
| II. History | e1660 | ||
| III. Current Definition | e1661 | ||
| IV. Presentation and Diagnostic Assessment | e1661 | ||
| V. Epidemiology | e1663 | ||
| A. Prevalence | e1663 | ||
| B. Life Expectancy | e1663 | ||
| VI. Etiologic Spectrum | e1663 | ||
| VII. Classification | e1664 | ||
| A. Common Cerebral Palsy Syndromes | e1664 | ||
| 1. Spastic Hemiplegia | e1664 | ||
| 2. Spastic Quadriplegia | e1665 | ||
| 3. Spastic Diplegia | e1665 | ||
| 4. Extrapyramidal CP | e1665 | ||
| 4.1. Choreoathetotic CP. | e1665 | ||
| 4.2. Dystonic CP. | e1665 | ||
| 5. Hypotonic (Atonic) CP | e1666 | ||
| 6. Ataxic CP | e1666 | ||
| 7. Mixed CP | e1666 | ||
| B. Functional Classification | e1666 | ||
| VIII. Comorbidity Spectrum | e1669 | ||
| IX. Quality of Life | e1669 | ||
| X. Conclusion | e1670 | ||
| References | e1670 | ||
| 98 Tics and Tourette Syndrome | e1673 | ||
| Tic Phenomenology | e1673 | ||
| Definition | e1673 | ||
| Simple Versus Complex Tics | e1673 | ||
| Characteristics | e1673 | ||
| Misdiagnoses | e1674 | ||
| Tic Assessment Scales | e1674 | ||
| Tic Disorders | e1674 | ||
| Provisional Tic Disorder | e1674 | ||
| Chronic (Motor or Vocal) Tic Disorder | e1674 | ||
| Tourette Syndrome/Tourette Disorder | e1674 | ||
| Substance-Induced Tic Disorder | e1675 | ||
| Tic Disorder Due to a Generalized Medical Condition | e1675 | ||
| Tic Disorder Not Otherwise Specified | e1675 | ||
| Course | e1675 | ||
| Epidemiology | e1675 | ||
| Associated (Comorbid) Behaviors | e1675 | ||
| Attention Deficit Hyperactivity Disorder | e1675 | ||
| Obsessive-Compulsive Disorder | e1676 | ||
| Anxiety and Depression | e1676 | ||
| Disruptive Behaviors, Episodic Outbursts (Rage), and Self-Injurious Behavior | e1676 | ||
| Other Psychopathologies | e1676 | ||
| Academic Difficulties | e1676 | ||
| Sleep Disorders | e1677 | ||
| Etiology | e1677 | ||
| Genetic Basis | e1677 | ||
| Autoimmune Disorder | e1677 | ||
| Neurobiology of Tic Disorders | e1678 | ||
| Neuroanatomic Localization | e1678 | ||
| Striatum | e1678 | ||
| Cortex | e1679 | ||
| Other Regions | e1679 | ||
| Neurotransmitter Abnormalities | e1679 | ||
| Dopamine | e1679 | ||
| Serotonin | e1679 | ||
| Glutamate | e1680 | ||
| GABA | e1680 | ||
| Treatment | e1680 | ||
| Nonpharmacologic Treatments | e1680 | ||
| Pharmacotherapy | e1681 | ||
| Tier 1 Medications | e1681 | ||
| Tier 2 Medications | e1681 | ||
| Other Medications and Botulinum Toxin | e1681 | ||
| Surgical Approaches | e1681 | ||
| References | e1682 | ||
| 99 Genetic and Metabolic Disorders of the White Matter | e1690 | ||
| Introduction | e1690 | ||
| Part I. Hypomyelinating White Matter Disorders | e1690 | ||
| 1. Pelizaeus-Merzbacher Disease | e1693 | ||
| 2. Pelizaeus–Merzbacher-Like Disease | e1696 | ||
| 3. 4H Syndrome | e1696 | ||
| 4. Hypomyelination Related to Cytoplasmic tRNA Synthetase Defects | e1697 | ||
| 5. Oculodentodigital Dysplasia | e1698 | ||
| 6. Hypomyelination With Congenital Cataract | e1698 | ||
| 7. Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum | e1698 | ||
| 8. Sialic Acid Storage Disorders | e1699 | ||
| 9. Fucosidosis | e1699 | ||
| 10. Serine Synthesis Defects | e1699 | ||
| 11. Cockayne Syndrome and Trichothiodystrophy | e1700 | ||
| 12. 18q Minus Syndrome | e1700 | ||
| 13. SOX10-Associated Disorders | e1700 | ||
| Part II. White Matter Disorders With Demyelination | e1701 | ||
| A. Primary Demyelinating Leukodystrophies | e1701 | ||
| 1. Alexander Disease | e1701 | ||
| 2. X-Linked Adrenoleukodystrophy | e1703 | ||
| 3. Other Peroxisomal Disorders | e1703 | ||
| Peroxisome Biogenesis Disorders (PBD). | e1703 | ||
| Single Enzyme Deficiencies of Peroxisomal Fatty-Acid β- Oxidation. | e1704 | ||
| 4. Metachromatic Leukodystrophy | e1704 | ||
| 5. Metachromatic Leukodystrophy-Like Variants | e1705 | ||
| 6. Krabbe Disease or Globoid Cell Leukodystrophy | e1705 | ||
| 7. Saposin A Deficiency | e1705 | ||
| 8. Sjögren-Larsson Syndrome | e1705 | ||
| B. White Matter Disorders With White Matter Vacuolization and Intramyelinic Edema | e1706 | ||
| 1. Canavan Disease | e1706 | ||
| 2. eIF2B-Related Disorder (Vanishing White Matter) | e1706 | ||
| 3. Megalencephalic Leukoencephalopathy With Subcortical Cysts | e1707 | ||
| 4. ClC-2-Related Leukoencephalopathy | e1707 | ||
| C. Calcifying Leukoencephalopathies | e1708 | ||
| 1. Aicardi-Goutières Syndrome | e1708 | ||
| 2. Cerebroretinal Microangiopathy With Calcifications and Cysts | e1709 | ||
| 3. Leukoencephalopathy With Calcifications and Cysts | e1709 | ||
| 4. Bandlike Intracranial Calcification With Simplified Gyration and Polymicrogyria | e1709 | ||
| 5. Cockayne Syndrome | e1709 | ||
| 6. Spondyloenchondrodysplasia | e1709 | ||
| 7. Cytomegalovirus (CMV) | e1709 | ||
| 8. Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL, OMIM 125310) | e1709 | ||
| 9. Intracranial Calcification Associated With Leukoencephalopathy | e1710 | ||
| 10. Dihydropterine Reductase Deficiency | e1710 | ||
| 11. 27-Hydroxylase Deficiency or CTX (OMIM 213700) | e1710 | ||
| 12. Bilateral Occipital Calcifications With Leukoencephalopathy, Seizures, and Clinical or Subclinical Celiac Disease | e1710 | ||
| 13. Familial Hemophagocytic Lymphohistiocytosis (FHLH) | e1710 | ||
| D. Cystic Leukoencephalopathies | e1710 | ||
| E. MLC | e1710 | ||
| F. RNAse T2-Deficient Leukoencephalopathy | e1711 | ||
| G. Congenital Cytomegalovirus (CMV) Infection | e1711 | ||
| H. CRMCC | e1711 | ||
| I. Leukoencephalopathies With Brainstem, Cerebellum, and Spinal Cord Involvement | e1711 | ||
| 1. Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation | e1711 | ||
| 2. Alexander Disease (AxD) | e1711 | ||
| 3. Polyglucosan Body Disease (PGBD, OMIM 263570) | e1713 | ||
| 4. ADLD (LaminB1) | e1713 | ||
| E. Adult-Onset Leukoencephalopathies | e1713 | ||
| 1. Neuroaxonal Leukodystrophy With Spheroids | e1714 | ||
| 2. Leukoencephalopathy Due to Mutations in AARS2 | e1714 | ||
| Part III. Secondary Leukoencephalopathies to Inborn Errors of Metabolism Excluding the Classical Lysosomal and Peroxisomal Disorders | e1714 | ||
| 1. Defects of O-Glycan Synthesis or Dystroglycanopathies | e1714 | ||
| 2. L2-Hydroxyglutaric Aciduria (L2HGA, OMIM 236792) | e1714 | ||
| 3. Biotinidase Deficiency (OMIM 253260) | e1714 | ||
| 4. Menkes Disease (OMIM 309400) | e1715 | ||
| 5. Molybdenum Cofactor Deficiency and Isolated Sulfite Oxidase Deficiency (OMIM 252150) | e1715 | ||
| 6. GM1 Gangliosidosis | e1716 | ||
| 7. GM2 Gangliosidoses | e1717 | ||
| 8. Mucopolysaccharidoses (MPS) | e1717 | ||
| 9. Mucolipidosis Type IV | e1717 | ||
| 10. Neuronal Ceroid Lipofuscinoses (NCL) | e1717 | ||
| 11. Mitochondrial Leukoencephalopathies | e1717 | ||
| Acknowledgments | e1718 | ||
| References | e1718 | ||
| 100 Acquired Disorders Affecting the White Matter | e1725 | ||
| Acute Central Nervous System Demyelination | e1725 | ||
| Optic Neuritis | e1725 | ||
| Transverse Myelitis | e1725 | ||
| Polyfocal Demyelination/Acute Disseminated Encephalomyelitis | e1725 | ||
| Other Clinical Presentations | e1726 | ||
| Investigation of a Child with Acute Demyelination | e1726 | ||
| Laboratory Investigations | e1726 | ||
| Magnetic Resonance Imaging | e1726 | ||
| Management of Acute Demyelination | e1727 | ||
| Relapsing Demyelinating Disorders | e1728 | ||
| Multiple Sclerosis | e1728 | ||
| Demographics and Epidemiology of Pediatric Multiple Sclerosis | e1728 | ||
| Diagnostic Criteria for Pediatric Multiple Sclerosis | e1728 | ||
| Clinical Course of Pediatric Multiple Sclerosis | e1729 | ||
| Magnetic Resonance Imaging Features of Pediatric Multiple Sclerosis | e1729 | ||
| Pathobiological Insights Into Pediatric MS | e1730 | ||
| Genetic and Environmental Risk Factors. | e1730 | ||
| Serum Autoantibodies. | e1732 | ||
| Cerebrospinal Fluid Proteomics. | e1732 | ||
| T-Cell Responses. | e1732 | ||
| Immunomodulatory Therapy in Pediatric Multiple Sclerosis | e1732 | ||
| Principles of Immunomodulatory Therapy. | e1732 | ||
| Second-Line Therapies. | e1733 | ||
| General Care Issues | e1733 | ||
| Recurrent and Multiphasic Acute Disseminated Encephalomyelitis | e1734 | ||
| Neuromyelitis Optica | e1734 | ||
| Demographics and Epidemiology of Childhood Neuromyelitis Optica | e1734 | ||
| Clinical Features of Pediatric Neuromyelitis Optica | e1734 | ||
| Symptomatic Brain Involvement in Neuromyelitis Optica | e1734 | ||
| Diagnostic Criteria for Pediatric Neuromyelitis Optica | e1734 | ||
| Systemic Autoimmunity in Neuromyelitis Optica | e1734 | ||
| Laboratory Features of Neuromyelitis Optica | e1734 | ||
| Magnetic Resonance Imaging in Neuromyelitis Optica | e1735 | ||
| Treatment of Pediatric Neuromyelitis Optica | e1735 | ||
| Conclusions | e1736 | ||
| Resources | e1736 | ||
| References | e1736 | ||
| 101 Disorders of Consciousness in Children | e1741 | ||
| Historical Perspective | e1741 | ||
| Neural Correlates of Consciousness | e1742 | ||
| Approaches to Studying the NCC | e1742 | ||
| Neuroimaging | e1743 | ||
| Neurophysiology | e1745 | ||
| Neural Correlates of Consciousness in DOC Patients | e1745 | ||
| Definitions | e1746 | ||
| Impairment of Consciousness With Activated Mental State | e1747 | ||
| Impairment of Consciousness With Reduced Mental State | e1747 | ||
| Vegetative State, Minimally Conscious State, and Related Conditions | e1747 | ||
| Vegetative State/Unresponsive Wakefulness Syndrome | e1747 | ||
| Minimally Conscious State | e1749 | ||
| Locked-in Syndrome | e1750 | ||
| Akinetic Mutism | e1750 | ||
| Brain Death | e1750 | ||
| Consciousness Rating Scales | e1750 | ||
| Pathophysiology | e1753 | ||
| Etiologies | e1753 | ||
| Evaluation | e1753 | ||
| Clinical Evaluation | e1754 | ||
| Identification of Cause | e1754 | ||
| History | e1755 | ||
| General Physical Examination | e1755 | ||
| Neurologic Examination | e1755 | ||
| Brain Herniation | e1757 | ||
| Historical Perspective | e1757 | ||
| Herniation Syndromes | e1757 | ||
| Uncal Herniation | e1758 | ||
| Central or Transtentorial Downward Herniation | e1758 | ||
| Infratentorial (Cerebellar) Herniation Syndromes | e1758 | ||
| Diagnostic Testing | e1759 | ||
| Treatment | e1759 | ||
| 1. Maintain Airway, Oxygenation, and Ventilation | e1759 | ||
| 2. Maintain Circulation | e1760 | ||
| 3. Administer Glucose | e1760 | ||
| 4. Correct Acid-Base and Electrolyte Imbalance | e1760 | ||
| 5. Consider Specific Antidotes | e1760 | ||
| 6. Reduce Increased Intracranial Pressure | e1760 | ||
| 7. Stop Seizures | e1760 | ||
| 8. Treat Infection | e1760 | ||
| 9. Adjust Body Temperature | e1760 | ||
| 10. Manage Agitation | e1761 | ||
| 11. Treatment of Chronic Impairments | e1761 | ||
| Monitoring of the Comatose Patient | e1761 | ||
| Outcome Measurement | e1763 | ||
| Prognosis | e1764 | ||
| Traumatic Injury | e1764 | ||
| Nontraumatic Injury | e1766 | ||
| Clinical Neurophysiology | e1766 | ||
| Neuroimaging | e1766 | ||
| Conclusions | e1767 | ||
| Acknowledgment | e1767 | ||
| References | e1767 | ||
| 102 Traumatic Brain Injury in Children | e1774 | ||
| Introduction and Background | e1774 | ||
| Epidemiology of Pediatric Traumatic Brain Injury | e1774 | ||
| Anatomy | e1774 | ||
| Biomechanics | e1775 | ||
| Injury Types | e1775 | ||
| Pathophysiology of Traumatic Brain Injury | e1776 | ||
| Distinctions of Injury to the Developing Brain | e1776 | ||
| Biomechanical Factors | e1776 | ||
| Changes in Cerebral Metabolism | e1776 | ||
| Distinct Neurovascular Regulation | e1776 | ||
| Increased Excitatory Neurotransmission | e1777 | ||
| Ongoing Cerebral Maturation | e1777 | ||
| The Posttraumatic Neurometabolic Cascade | e1777 | ||
| Glutamate Release and Ionic Flux | e1777 | ||
| Dynamic Changes in Cerebral Metabolism | e1777 | ||
| Cerebral Blood Flow: Hyperemia? Hypoperfusion? | e1777 | ||
| Altered Neurotransmission | e1778 | ||
| Axonal Disconnection | e1779 | ||
| Cell Death: Necrosis and Apoptosis | e1779 | ||
| Impaired Plasticity | e1779 | ||
| Patient History | e1779 | ||
| Examination | e1780 | ||
| Immediate Management | e1781 | ||
| Acute Clinical Syndromes | e1781 | ||
| Herniation Syndromes | e1781 | ||
| Diffuse Cerebral Swelling | e1782 | ||
| Diffuse Axonal Injury | e1782 | ||
| Paroxysmal Sympathetic Hyperactivity | e1782 | ||
| Abusive Head Trauma | e1783 | ||
| Subarachnoid Hemorrhage | e1784 | ||
| Subdural Hematoma | e1784 | ||
| Epidural Hematoma | e1785 | ||
| Cerebral Contusion and Laceration | e1786 | ||
| Traumatic Arterial Dissection and Traumatic Aneurysms | e1786 | ||
| Concussion | e1786 | ||
| Acute Postconcussive Syndromes | e1787 | ||
| Sports Concussion/Repeated Concussion | e1787 | ||
| Epidemiology | e1787 | ||
| Pathophysiology | e1787 | ||
| Symptomatology | e1788 | ||
| Sequelae | e1788 | ||
| Second-Impact Syndrome | e1788 | ||
| Skull Fractures | e1789 | ||
| Scalp Lacerations and Hematomas | e1789 | ||
| Diagnostic Evaluation | e1790 | ||
| Neuroimaging | e1790 | ||
| Skull X-Rays | e1790 | ||
| Computed Tomography | e1790 | ||
| Magnetic Resonance Imaging | e1792 | ||
| Angiography | e1792 | ||
| Ultrasound | e1792 | ||
| Lumbar Puncture | e1792 | ||
| Neurophysiological Testing | e1792 | ||
| General Management Principles for Severe Pediatric TBI | e1794 | ||
| Stabilization and Prevention of Secondary Injury | e1794 | ||
| Intracranial Pressure Management | e1794 | ||
| Sedation and Neuromuscular Blockade | e1794 | ||
| Hyperventilation | e1795 | ||
| Hyperosmolar Therapy | e1795 | ||
| Intracranial Pressure Monitoring—Indications and Treatment Threshold | e1795 | ||
| Cerebral Perfusion Pressure | e1796 | ||
| Cerebrospinal Fluid Drainage | e1797 | ||
| Barbiturates | e1797 | ||
| Temperature Control and Hypothermia | e1797 | ||
| Surgical Management of ICP | e1797 | ||
| Early Posttraumatic Seizures and Seizure Prophylaxis | e1798 | ||
| Acute Anticonvulsant Therapy | e1798 | ||
| Prevention of Posttraumatic Epilepsy | e1799 | ||
| Supportive Care | e1799 | ||
| Treatment Algorithm for Increased Intracranial Pressure in Severe Pediatric Traumatic Brain Injury | e1799 | ||
| General Management of Mild Traumatic Brain Injury/Concussion | e1799 | ||
| Mild TBI Without Loss of Consciousness in Children Over Age 2 Years | e1802 | ||
| Mild Traumatic Brain Injury With Brief Loss of Consciousness in a Child Over Age 2 Years | e1802 | ||
| Mild Traumatic Brain Injury in Children Under 2 Years Old | e1802 | ||
| Guidelines for Return to Play Following Sports Concussion | e1803 | ||
| Prognosis and Outcome | e1803 | ||
| Clinical Predictors of Outcome | e1803 | ||
| Demographics—Age and Gender | e1804 | ||
| Injury Characteristics | e1804 | ||
| Physiologic Measurements | e1804 | ||
| Intracranial Pressure. | e1804 | ||
| Cerebral Blood Flow and Cerebral Perfusion Pressure. | e1804 | ||
| Neuroimaging and Prognosis | e1805 | ||
| Computed Tomography | e1805 | ||
| Structural Magnetic Resonance Imaging | e1805 | ||
| Diffusion-Weighted Imaging and Diffusion Tensor Imaging | e1805 | ||
| Magnetic Resonance Spectroscopy | e1805 | ||
| Neurophysiological Testing and Prognosis | e1805 | ||
| Electroencephalogram | e1805 | ||
| Somatosensory-Evoked Potentials | e1806 | ||
| Late Clinical Syndromes | e1806 | ||
| Vegetative and Minimally Conscious States | e1806 | ||
| Cognitive Impairment and Behavioral Disorders | e1806 | ||
| Sleep Disorders | e1807 | ||
| Spasticity and Motor Impairment | e1807 | ||
| Posttraumatic Hydrocephalus | e1807 | ||
| Posttraumatic Epilepsy | e1808 | ||
| Subacute and Chronic Subdural Hematoma | e1808 | ||
| Posttraumatic Headache | e1809 | ||
| Postconcussive Syndrome | e1809 | ||
| Late Complications of Skull Fractures | e1810 | ||
| Experimental Models of Pediatric Traumatic Brain Injury for Future Research | e1810 | ||
| Conclusions | e1810 | ||
| References | e1810 | ||
| 103 Abusive Head Trauma | e1821 | ||
| Introduction | e1821 | ||
| Historical Perspective | e1821 | ||
| Terminology | e1821 | ||
| Developmental Differences Predisposing the Immature Neuraxis to Injury | e1821 | ||
| Mechanical Factors | e1821 | ||
| Biologic Factors | e1822 | ||
| Responses to Injury | e1822 | ||
| Mechanisms of Injury | e1822 | ||
| Contribution of Hypoxia-Ischemia | e1822 | ||
| Clinical Features | e1823 | ||
| Acute Presentation | e1823 | ||
| Early Posttraumatic Seizures | e1823 | ||
| Subacute and Chronic Presentation | e1823 | ||
| Predictors of Outcome | e1823 | ||
| Mortality Predictors. | e1824 | ||
| Sequelae of Abusive Head Injury | e1824 | ||
| Posttraumatic Epilepsy | e1824 | ||
| Cognitive and Executive Function | e1824 | ||
| Behavioral Sequelae | e1824 | ||
| Visual Sequelae | e1824 | ||
| Motor Sequelae | e1825 | ||
| Neuropathology | e1825 | ||
| Pathologic Features | e1825 | ||
| Extracranial Injuries | e1825 | ||
| Scalp. | e1825 | ||
| Skull Fractures. | e1825 | ||
| Intracranial Injuries | e1825 | ||
| Subdural Hematomas. | e1825 | ||
| Mixed-Density or “Hyperacute” Subdural Hematoma. | e1827 | ||
| Chronic Subdural Hematomas. | e1827 | ||
| Chronic Subdural Effusions. | e1827 | ||
| Subarachnoid Hemorrhage. | e1827 | ||
| Epidural Hematoma. | e1828 | ||
| Brain Injuries | e1828 | ||
| White-Matter Contusional Tears. | e1830 | ||
| Ocular Pathology | e1832 | ||
| Retinal Hemorrhages. | e1832 | ||
| Optic Nerve Sheath Hemorrhage. | e1833 | ||
| Spinal Injuries | e1833 | ||
| Differential Diagnosis | e1833 | ||
| Unintentional Injury | e1834 | ||
| Falls. | e1834 | ||
| Birth Trauma. | e1835 | ||
| Neurometabolic Disease. | e1835 | ||
| Differential of Specific Findings | e1835 | ||
| Retinal and Optic Nerve Sheath Hemorrhages | e1835 | ||
| Extensive Subarachnoid Hemorrhage | e1835 | ||
| Clinical Assessment | e1836 | ||
| History | e1836 | ||
| General Examination | e1836 | ||
| Neurologic Examination | e1836 | ||
| Autonomic and Neuroendocrine Responses | e1836 | ||
| Laboratory and Radiographic Evaluation | e1837 | ||
| Laboratory Evaluation | e1837 | ||
| Biochemical Markers. | e1837 | ||
| Neuroimaging and Radiographic Evaluation | e1838 | ||
| Postmortem Examination | e1839 | ||
| Making the Diagnosis of Abusive Head Injury | e1839 | ||
| General Considerations | e1839 | ||
| Evaluating the History | e1840 | ||
| Timing | e1840 | ||
| Lucid Interval | e1840 | ||
| Dating by Neuroimaging | e1840 | ||
| Medicolegal Issues | e1841 | ||
| Conclusions | e1841 | ||
| References | e1841 | ||
| 104 Hypoxic-Ischemic Encephalopathy in Infants and Older Children | e1849 | ||
| Cardiac Arrest: Etiology, Survival, and Neurologic Outcome | e1849 | ||
| Postcardiac-Arrest Syndrome | e1849 | ||
| Response to Inadequate Oxygen Delivery: Mechanisms of Brain Injury | e1850 | ||
| Brain Energy Failure | e1850 | ||
| Calcium-Mediated Injury | e1851 | ||
| Excitotoxic Injury | e1851 | ||
| Activation of Intracellular Enzymes | e1851 | ||
| Phospholipase Release of Free Fatty Acids | e1852 | ||
| Activation of Nitric Oxide Synthesis | e1852 | ||
| Formation of Oxygen Radicals | e1853 | ||
| Neuroinflammation, Glia, and the Neurovascular Unit | e1854 | ||
| Genetic Damage and Regulation | e1854 | ||
| Autophagy | e1854 | ||
| Clinical Pathophysiology | e1854 | ||
| Cerebral Blood Flow and Metabolism After Resuscitation | e1854 | ||
| Major Disorders Causing Cardiac Arrest | e1855 | ||
| Abusive Head Trauma | e1855 | ||
| Sudden Infant Death Syndrome | e1855 | ||
| Epidemiology | e1855 | ||
| Incidence and Age at Death. | e1855 | ||
| Drowning (Submersion Injury) | e1856 | ||
| Epidemiology | e1856 | ||
| Management. | e1856 | ||
| Strangulation Injury | e1856 | ||
| Lightning and Electrical Injuries | e1856 | ||
| Electrical Shock | e1857 | ||
| Sudden Cardiac Arrest in Children and Adolescents | e1857 | ||
| Neurologic Complications After Cardiac Arrest | e1857 | ||
| Delayed Posthypoxic Injury | e1857 | ||
| Postischemic Seizures | e1857 | ||
| Delayed Postanoxic Myoclonic Seizures | e1857 | ||
| Paroxysmal Sympathetic Hyperactivity | e1858 | ||
| Neurologic Prognosis After Cardiac Arrest | e1858 | ||
| Electroencephalography Following Cardiac Arrest | e1858 | ||
| Somatosensory- and Auditory-Evoked Potentials | e1859 | ||
| Neuroimaging, Injury, and Outcome Assessment | e1859 | ||
| Treatment | e1860 | ||
| Resuscitation | e1860 | ||
| Postresuscitation Interventions | e1861 | ||
| Intracranial Pressure Monitoring and Control | e1861 | ||
| Glucose Homeostasis | e1861 | ||
| Cardiovascular Support | e1862 | ||
| Extracorporeal Membrane Oxygenation and Cardiopulmonary Resuscitation | e1862 | ||
| Temperature Control | e1863 | ||
| Postcardiac-Arrest Brain Injury—Potential Therapies | e1863 | ||
| Dilemma of Neurologic Morbidity | e1864 | ||
| References | e1864 | ||
| 105 Disorders of Intracranial Pressure | e1868 | ||
| Introduction | e1868 | ||
| Normal Intracranial Pressure | e1868 | ||
| Pathophysiology of Raised Intracranial Pressure | e1868 | ||
| Compliance Changes with Age | e1868 | ||
| Effects of Intracranial Hypertension on Cerebral Perfusion | e1868 | ||
| Cerebral Autoregulation | e1868 | ||
| Effects of Intracranial Hypertension on Autoregulation | e1869 | ||
| Regulation of Cerebral Blood Flow | e1869 | ||
| Intracranial Pressure Monitoring | e1870 | ||
| History | e1870 | ||
| Indications for Intracranial Pressure Monitoring | e1870 | ||
| Methods of Intracranial Pressure Monitoring | e1870 | ||
| Noninvasive Approaches to Intracranial Pressure Monitoring | e1871 | ||
| Thresholds and Doses of Raised Intracranial Pressure | e1872 | ||
| Duration of Physiologic Derangement and Outcome | e1872 | ||
| Application of Receiver Operating Characteristic Curves to Determining Thresholds | e1872 | ||
| Evidence Supporting Age-Dependent Physiologic Thresholds | e1872 | ||
| Area Under the Curve Analyses of Intracranial Pressure and Cerebral Perfusion Pressure Insults | e1872 | ||
| Combining High-Frequency Data Collection with Calculation of ICP and CPP Dose | e1873 | ||
| Similar Thresholds Affect Outcome in Other Forms of Severe Brain Injury | e1873 | ||
| Lessons and Limitations of These Studies | e1873 | ||
| Intracranial Hypertension Related to Compromise of Autoregulation | e1873 | ||
| Calculation of Cerebrovascular Reactivity | e1873 | ||
| Autoregulation-Directed Therapy in Pediatric Neurotrauma | e1873 | ||
| Linking Intracranial Pressure and Cerebral Metabolism | e1873 | ||
| Utility of Measurement of Intracranial Pressure | e1874 | ||
| Effects of Gender on Increased Intracranial Pressure | e1874 | ||
| Clinical Manifestations of Raised Intracranial Pressure | e1874 | ||
| Physical Examination Findings | e1874 | ||
| Herniation Syndromes | e1874 | ||
| Lumbar Puncture in Patients with Raised Intracranial Pressure | e1874 | ||
| Management of Acutely Elevated Intracranial Pressure | e1875 | ||
| Initial Assessment, Imaging, and Surgical Intervention | e1875 | ||
| General Principles of Medical Management | e1876 | ||
| Evidence in Support of Guideline-Directed Management of Intracranial Pressure | e1877 | ||
| Intracranial Pressure-Directed Therapy | e1877 | ||
| Spontaneous Intracranial Hypotension | e1877 | ||
| Diagnosis and Management | e1878 | ||
| Chronic Intracranial Hypertension | e1878 | ||
| Idiopathic Intracranial Hypertension | e1878 | ||
| Treatment of Idiopathic Intracranial Hypertension | e1878 | ||
| Conclusions | e1878 | ||
| References | e1879 | ||
| 106 Spinal Cord Injury | e1882 | ||
| Epidemiology | e1882 | ||
| Anatomy | e1883 | ||
| Bony Spine and Ligaments | e1883 | ||
| Spinal Cord | e1883 | ||
| Pathogenesis: Mechanisms of Spinal Cord Injury | e1884 | ||
| Clinical Assessment | e1885 | ||
| History | e1885 | ||
| General Physical Examination | e1885 | ||
| Neurologic Examination | e1885 | ||
| Laboratory Studies | e1887 | ||
| Radiographic Evaluation | e1887 | ||
| Electrophysiologic Evaluation | e1889 | ||
| Lumbar Puncture | e1890 | ||
| Clinical Syndromes | e1890 | ||
| Intraspinal Intramedullary Injuries | e1890 | ||
| Complete Spinal Cord Injuries | e1890 | ||
| Incomplete Spinal Cord Injuries | e1890 | ||
| Cervical Nerve Root/Brachial Plexus Neuropraxia | e1890 | ||
| Cervical Cord Neuropraxia | e1890 | ||
| Cervicomedullary Syndrome | e1891 | ||
| Central Spinal Syndrome | e1891 | ||
| Anterior Spinal Cord Syndrome | e1891 | ||
| Posterior Spinal Cord Syndrome | e1891 | ||
| Brown-Séquard Syndrome | e1891 | ||
| Conus Medullaris Syndrome | e1891 | ||
| Intraspinal Extramedullary Injuries | e1891 | ||
| Spinal Epidural Hematoma | e1891 | ||
| Spinal Subdural Hematoma | e1892 | ||
| Spinal Subarachnoid Hemorrhage | e1892 | ||
| Spinal Epidural Abscess | e1892 | ||
| Spinal Arachnoid Cysts | e1893 | ||
| Spinal Epidermoid Tumor | e1893 | ||
| Herniation of Nucleus Pulposus | e1893 | ||
| Cauda Equina Injuries | e1893 | ||
| Catastrophic Spinal Cord Injuries | e1893 | ||
| Supraspinal Changes | e1893 | ||
| Management | e1893 | ||
| Short-Term Management | e1893 | ||
| Spine Immobilization and Supportive Care | e1893 | ||
| Completed Randomized Controlled Clinical Trials | e1894 | ||
| Methylprednisolone, Naloxone, and Tirilazad | e1894 | ||
| GM1 Ganglioside | e1895 | ||
| Nimodipine | e1895 | ||
| Lithium | e1895 | ||
| Additional Pharmacologic Clinical Trials | e1895 | ||
| Minocycline | e1895 | ||
| Riluzole | e1896 | ||
| Erythropoietin (EPO) | e1896 | ||
| Nonpharmacologic Clinical Trials | e1896 | ||
| Hypothermia | e1896 | ||
| Oscillating Field Stimulation (OFS) | e1896 | ||
| Molecular Mechanisms and Therapeutic Approaches | e1896 | ||
| Myelin-Associated Inhibitors | e1897 | ||
| Glial Scar-Associated Inhibitors | e1897 | ||
| Cell Transplantation Therapies | e1897 | ||
| Activated Autologous Macrophages (AAM). | e1897 | ||
| Schwann Cells. | e1897 | ||
| Olfactory Ensheathing Cells (OECs). | e1897 | ||
| Stem Cell Therapy. | e1898 | ||
| Bone Marrow Stromal Cells (BMSCs). | e1898 | ||
| Therapeutic Approaches Currently Undergoing Human Investigation | e1898 | ||
| Nogo | e1898 | ||
| Rho Pathway Antagonists | e1898 | ||
| Gene Therapy for Spinal Cord Injury | e1899 | ||
| The Future and Concerns | e1899 | ||
| Additional Beneficial Treatments | e1899 | ||
| Long-Term Management | e1899 | ||
| Cervical Spine Immobilization | e1899 | ||
| Supportive Medical Care | e1899 | ||
| Physical Therapy | e1900 | ||
| Functional Electrical Stimulation (FES) | e1901 | ||
| Gait Training | e1901 | ||
| Adaptive Technology | e1901 | ||
| Psychological Therapy | e1902 | ||
| The Multidisciplary Needs of the Child With a Spinal Cord Injury | e1902 | ||
| Surgical Management | e1902 | ||
| Prognosis | e1903 | ||
| Prevention | e1904 | ||
| References | e1904 | ||
| 107 Determination of Brain Death in Infants and Children | e1910 | ||
| Historical Perspective | e1910 | ||
| Legal Definition of Brain Death | e1912 | ||
| Epidemiology | e1912 | ||
| Incidence of Brain Death | e1912 | ||
| Etiologies of Brain Death | e1912 | ||
| Outcome after Diagnosis of Brain Death | e1912 | ||
| Neurologic Evaluation | e1914 | ||
| Clinical Examination | e1914 | ||
| Cerebral Unresponsivity | e1914 | ||
| Brainstem Examination | e1914 | ||
| Number of Examinations, Examiners, and Observation Periods | e1915 | ||
| Number of Examinations and Examiners. | e1915 | ||
| Duration of Observation Periods. | e1915 | ||
| Apnea Testing | e1915 | ||
| Technique for Performing Apnea Testing. | e1917 | ||
| Ancillary Neurodiagnostic Studies | e1917 | ||
| Electroencephalogram | e1918 | ||
| Electroencephalogram in Pediatric Brain Death | e1919 | ||
| Measurements of Cerebral Perfusion | e1920 | ||
| Cerebral Angiography | e1920 | ||
| Radionuclide Imaging | e1920 | ||
| Computed Tomographic Angiography and Perfusion | e1921 | ||
| Magnetic Resonance Imaging and Magnetic Resonance Angiography | e1922 | ||
| Transcranial Doppler | e1922 | ||
| Digital Subtraction Angiography | e1922 | ||
| Xenon Computed Tomography | e1922 | ||
| Positron Emission Tomography | e1922 | ||
| Magnetic Resonance Spectroscopy | e1923 | ||
| Comparison of Electroencephalogram and Cerebral Blood Flow Studies | e1923 | ||
| Evoked Potentials | e1923 | ||
| Brain Tissue Oxygenation | e1923 | ||
| Brain Death in Newborns | e1924 | ||
| Epidemiology | e1924 | ||
| Clinical Examination | e1924 | ||
| Duration of Observation | e1924 | ||
| Apnea Testing | e1924 | ||
| Ancillary Studies | e1924 | ||
| Determination of Brain Death in the Comatose Pediatric Patient | e1925 | ||
| Discussions with Family Members and Staff | e1926 | ||
| Organ Donation | e1926 | ||
| References | e1927 | ||
| 108 Development and Function of the Cerebrovascular System | e1931 | ||
| Introduction | e1931 | ||
| Brain Vascular Formation and Differentiation | e1931 | ||
| Vasculogenesis and Angiogenesis | e1931 | ||
| Smooth Muscle Differentiation | e1931 | ||
| Endothelial Differentiation and the Blood-brain Barrier | e1932 | ||
| Fetal and Neonatal Cerebrovascular Contractility | e1933 | ||
| Calcium Handling and the Contractile Apparatus | e1934 | ||
| Ion Pumps and Channels | e1934 | ||
| Vasoactive Ligands and Receptors | e1934 | ||
| Fetal and Neonatal Whole Brain Cerebrovascular Reactivity | e1935 | ||
| Flow-Metabolism Coupling | e1935 | ||
| Hypercapnic Vasodilatation | e1935 | ||
| Hypoxic Vasodilatation | e1935 | ||
| Autoregulation | e1935 | ||
| Neurovascular Mechanisms | e1936 | ||
| Conclusions | e1936 | ||
| References | e1937 | ||
| 109 Arterial Ischemic Stroke in Infants and Children | e1941 | ||
| Overview and Definitions | e1941 | ||
| Epidemiology, Mortality, and Burden of Pediatric Stroke | e1941 | ||
| Incidence | e1941 | ||
| Stroke Mortality | e1941 | ||
| Economic and Social Burden of Stroke | e1941 | ||
| Pathophysiology | e1941 | ||
| Arterial Circulation: Anatomy and Vascular Patterns of AIS | e1941 | ||
| Mechanisms of Thromboembolism | e1941 | ||
| Mechanisms of Infarction | e1943 | ||
| Risk Factors | e1943 | ||
| Infection | e1944 | ||
| Arteriopathies | e1944 | ||
| Focal or Transient Cerebral Arteriopathy. | e1944 | ||
| Primary Angiitis of the Central Nervous System and Other Conditions Associated with Cerebral Arteriopathy. | e1945 | ||
| Dissection and Other Physical Injury. | e1945 | ||
| Moyamoya Disease and Moyamoya Syndrome. | e1947 | ||
| Congenital or Genetic Arteriopathies. | e1949 | ||
| Cardiac | e1949 | ||
| Prothrombotic Disorders | e1950 | ||
| Sickle Cell Disease | e1951 | ||
| Additional Considerations | e1951 | ||
| Clinical Features and Diagnostic Delays | e1951 | ||
| Diagnosis: Neuroimaging | e1953 | ||
| Computed Tomography | e1953 | ||
| Magnetic Resonance Imaging | e1953 | ||
| Conventional Angiography | e1953 | ||
| Treatment | e1953 | ||
| Emergent: Stroke Unit Care and Neuroprotection | e1953 | ||
| Emergent: Thrombolysis | e1954 | ||
| Urgent: Antithrombotic Therapies | e1954 | ||
| Anticoagulation. | e1955 | ||
| Antiplatelet Therapy. | e1955 | ||
| Urgent: Malignant Cerebral Edema | e1955 | ||
| Outcomes and Chronic Management | e1956 | ||
| Sequelae of AIS | e1956 | ||
| Stroke Recurrence | e1957 | ||
| References | e1957 | ||
| 110 Sinovenous Thrombosis in Infants and Children | e1963 | ||
| Introduction | e1963 | ||
| Epidemiology | e1963 | ||
| Pathogenesis | e1963 | ||
| Sinovenous Circulation: Anatomy and Vascular Patterns | e1963 | ||
| Intracranial Venous Physiology | e1963 | ||
| Mechanisms of Thrombosis | e1964 | ||
| Mechanisms of Brain Injury | e1965 | ||
| Clinical Features | e1965 | ||
| Risk Factors | e1965 | ||
| Infection | e1966 | ||
| Anemia | e1966 | ||
| Prothrombotic Disorders | e1967 | ||
| Acute Systemic Conditions | e1967 | ||
| Chronic Systemic Conditions | e1969 | ||
| Diagnosis: Neuroimaging | e1970 | ||
| Computed Tomography (CT) | e1971 | ||
| Magnetic Resonance Imaging | e1971 | ||
| Treatment | e1973 | ||
| Anticoagulation | e1973 | ||
| Endovascular Treatment and Thrombolysis | e1974 | ||
| Nonantithrombotic Therapies | e1974 | ||
| Increased Intracranial Pressure | e1974 | ||
| Infection | e1974 | ||
| Seizures | e1974 | ||
| Steroids | e1974 | ||
| Other | e1974 | ||
| Outcome | e1975 | ||
| References | e1975 | ||
| 111 Vascular Malformations, Intracerebral Hemorrhage, and Subarachnoid Hemorrhage in Infants and Children | e1978 | ||
| Introduction and Epidemiology | e1978 | ||
| Presentation | e1978 | ||
| Differential Diagnosis | e1978 | ||
| Initial Studies | e1978 | ||
| Initial Management | e1979 | ||
| Acute Medical and Surgical Monitoring and Management | e1979 | ||
| Increased Intracranial Pressure: Signs, Symptoms, and Monitoring | e1979 | ||
| Increased ICP: Medical Management | e1979 | ||
| Increased ICP: Surgical Management | e1979 | ||
| Evacuation of Intraparenchymal Hemorrhage | e1979 | ||
| Hemicraniectomy | e1979 | ||
| Seizures: Monitoring and Treatment | e1979 | ||
| Recurrent Hemorrhage | e1980 | ||
| Outcomes | e1980 | ||
| High Flow Lesions | e1980 | ||
| Arteriovenous Malformations | e1980 | ||
| Epidemiology | e1980 | ||
| Associated Conditions and Genetic Syndromes | e1981 | ||
| Evaluation | e1981 | ||
| Treatment | e1982 | ||
| Outcome | e1983 | ||
| Arteriovenous Fistulas | e1983 | ||
| Pathogenesis | e1983 | ||
| Epidemiology | e1983 | ||
| Associated Conditions and Genetic Syndromes | e1983 | ||
| Presentation | e1984 | ||
| Evaluation | e1984 | ||
| Treatment | e1984 | ||
| Outcome | e1985 | ||
| Vein of Galen Malformations | e1985 | ||
| Pathogenesis | e1985 | ||
| 112 Cerebral Arteriopathies in Children | e1996 | ||
| Introduction | e1996 | ||
| Classification Schemes | e1996 | ||
| Focal Cerebral Arteriopathy/Transient Cerebral Arteriopathy | e1996 | ||
| Moyamoya Arteriopathy | e1996 | ||
| Arteriopathy of Sickle Cell Disease | e1999 | ||
| Cervicocephalic Arterial Dissection | e1999 | ||
| Central Nervous System Vasculitis | e2001 | ||
| Primary Central Nervous Systems Vasculitis | e2001 | ||
| Secondary Vasculitis | e2001 | ||
| Fibromuscular Dysplasia | e2002 | ||
| Diagnosis of Cerebral Arteriopathy | e2003 | ||
| Follow Up | e2003 | ||
| Conclusion | e2003 | ||
| References | e2003 | ||
| 113 Coagulation Disorders and Cerebrovascular Disease in Children | e2007 | ||
| Introduction | e2007 | ||
| Coagulation Disorders in Pediatric Arterial Ischemic Stroke | e2007 | ||
| Acquired Thrombophilia | e2007 | ||
| Presentation | e2007 | ||
| Vascular Thrombus. | e2007 | ||
| Positive APAs as Follows. | e2008 | ||
| Evaluation | e2010 | ||
| Treatment | e2010 | ||
| Genetic Thrombophilia | e2011 | ||
| 114 Bacterial Infections of the Nervous System | e2018 | ||
| Acute Bacterial Meningitis | e2018 | ||
| Epidemiology | e2018 | ||
| Pathogenesis | e2018 | ||
| Clinical Manifestations | e2019 | ||
| Clinical Presentations of Neonatal Meningitis | e2020 | ||
| Infection of Implantable Devices | e2020 | ||
| Diagnostic Evaluation | e2021 | ||
| Cerebrospinal Fluid Analysis | e2021 | ||
| Other Laboratory Testing | e2022 | ||
| Neuroimaging | e2022 | ||
| Clinical Prediction Models for Bacterial Meningitis | e2022 | ||
| Complications | e2023 | ||
| Pathophysiologic Changes | e2023 | ||
| Blood–Brain Barrier Disruption. | e2023 | ||
| Brain Edema. | e2023 | ||
| Hyponatremia, Dehydration, and Inappropriate Secretion of Antidiuretic Hormone. | e2023 | ||
| Intracranial Hypertension. | e2024 | ||
| Cerebral Blood Flow Changes. | e2024 | ||
| Seizures | e2024 | ||
| Deafness and Cranial Nerve Damage | e2024 | ||
| Neuronal Damage | e2024 | ||
| Hydrocephalus | e2024 | ||
| Septic Shock and Disseminated Intravascular Coagulation | e2025 | ||
| Extraaxial Fluid Collections | e2025 | ||
| Brain Abscess | e2025 | ||
| Pathology | e2025 | ||
| Treatment | e2025 | ||
| General Care | e2025 | ||
| Antibiotics | e2026 | ||
| Antiinflammatory Therapy | e2027 | ||
| Fluid Therapy | e2028 | ||
| Prognosis | e2028 | ||
| Prevention | e2028 | ||
| Immunization | e2028 | ||
| Chemoprophylaxis | e2029 | ||
| Recurrent Acute Bacterial Meningitis | e2029 | ||
| Chronic (Subacute) Bacterial Meningitis | e2029 | ||
| Tuberculous Meningitis | e2030 | ||
| Epidemiology and Pathogenesis | e2030 | ||
| Clinical Characteristics | e2030 | ||
| Diagnosis | e2030 | ||
| Treatment | e2030 | ||
| Syphilis | e2031 | ||
| Epidemiology and Pathogenesis | e2031 | ||
| Clinical Characteristics | e2031 | ||
| Diagnosis | e2031 | ||
| Treatment | e2032 | ||
| Lyme Disease (Lyme Neuroborreliosis) | e2032 | ||
| Clinical Characteristics | e2032 | ||
| Diagnosis | e2032 | ||
| Treatment and Outcome | e2032 | ||
| Leptospir5osis | e2032 | ||
| Aseptic Meningitis | e2033 | ||
| Other Bacterial Infections of the Nervous System | e2033 | ||
| Bartonella | e2033 | ||
| Mycoplasma pneumoniae | e2034 | ||
| Leprosy (Hansen’s Disease) | e2034 | ||
| Central Nervous System Abscess | e2035 | ||
| Brain Abscess | e2035 | ||
| Epidemiology, Pathogenesis, and Pathology | e2035 | ||
| Clinical Manifestations and Diagnosis | e2035 | ||
| Neurosurgical Management and Antimicrobial Therapy | e2036 | ||
| Complications and Outcomes | e2036 | ||
| Epidural Abscesses | e2037 | ||
| Cranial Epidural Abscess | e2037 | ||
| Spinal Epidural Abscess | e2037 | ||
| References | e2037 | ||
| 115 Viral Infections of the Nervous System | e2041 | ||
| General Considerations | e2041 | ||
| Epidemiology of Viral Infections | e2041 | ||
| Clinical Features of Virus-Induced Neurologic Disorders | e2043 | ||
| Meningitis | e2044 | ||
| Encephalitis | e2044 | ||
| Other Conditions | e2044 | ||
| Intrauterine and Perinatal Viral Infections | e2045 | ||
| Diagnosis | e2045 | ||
| Cerebrospinal Fluid | e2045 | ||
| Neuroimaging | e2046 | ||
| Microbiological Evaluation | e2046 | ||
| Treatment | e2047 | ||
| Supportive Care | e2047 | ||
| Antiviral Therapy | e2048 | ||
| Specific Viral Infections | e2048 | ||
| Herpesviruses | e2048 | ||
| Herpes Simplex Viruses (HSVs), Types 1 and 2 | e2048 | ||
| Clinical Manifestations | e2048 | ||
| Diagnosis | e2049 | ||
| Treatment and Outcome | e2049 | ||
| Cytomegalovirus | e2050 | ||
| Clinical Manifestations | e2050 | ||
| Diagnosis | e2050 | ||
| Treatment and Outcome | e2051 | ||
| Varicella Zoster Virus | e2051 | ||
| Clinical Manifestations | e2051 | ||
| Diagnosis | e2052 | ||
| Treatment and Outcome | e2052 | ||
| Epstein-Barr Virus | e2052 | ||
| Clinical Manifestations | e2052 | ||
| Diagnosis, Treatment, and Outcome | e2052 | ||
| Human Herpesviruses Types 6 and 7 | e2052 | ||
| Adenoviruses | e2053 | ||
| Picornaviruses | e2053 | ||
| Clinical Features | e2053 | ||
| Diagnosis | e2054 | ||
| Treatment and Outcome | e2054 | ||
| Alphaviruses | e2055 | ||
| Eastern Equine Encephalitis Virus | e2055 | ||
| Western Equine Encephalitis Virus | e2055 | ||
| Venezuelan Equine Encephalitis Virus | e2055 | ||
| Rubella Virus | e2056 | ||
| Clinical Features | e2056 | ||
| Diagnosis | e2056 | ||
| 116 Fungal, Rickettsial, and Parasitic Diseases of the Nervous System | e2075 | ||
| Fungal Diseases | e2075 | ||
| Cryptococcosis | e2075 | ||
| Epidemiology, Environmental Reservoir, and Pathogenesis | e2075 | ||
| Clinical Characteristics, Clinical Laboratory Tests, and Diagnosis | e2075 | ||
| Management | e2075 | ||
| Coccidioidomycosis | e2075 | ||
| Epidemiology, Microbiology, and Pathology | e2075 | ||
| Clinical Characteristics, Clinical Laboratory Tests, and Diagnosis | e2076 | ||
| 117 Neurologic Complications of Immunization | e2132 | ||
| Assessing Causality | e2132 | ||
| Vaccine Injury Compensation Program | e2132 | ||
| Types of Vaccines | e2133 | ||
| Vaccines Composed of Whole-Killed Organisms | e2133 | ||
| Inactivated Polio Vaccine | e2133 | ||
| Influenza Virus Vaccine | e2133 | ||
| Guillain–Barré Syndrome. | e2133 | ||
| Seizures. | e2134 | ||
| Multiple Sclerosis. | e2134 | ||
| Acute Disseminated Encephalomyelitis. | e2135 | ||
| Narcolepsy. | e2135 | ||
| Bell’s Palsy. | e2135 | ||
| Rabies Vaccine | e2135 | ||
| Whole-Cell Pertussis Vaccine | e2135 | ||
| Hepatitis A Vaccine | e2135 | ||
| Vaccines Composed of Live-Attenuated Viruses | e2135 | ||
| Measles: Rubeola | e2135 | ||
| Mumps | e2136 | ||
| Rubella | e2136 | ||
| Oral Polio Vaccine | e2136 | ||
| Varicella | e2136 | ||
| Smallpox | e2137 | ||
| Rotavirus | e2137 | ||
| Component Vaccines | e2137 | ||
| Acellular Pertussis Vaccine | e2137 | ||
| Meningococcal Conjugate Vaccine | e2137 | ||
| Haemophilus Influenzae Type b | e2137 | ||
| Pneumococcal Conjugated Vaccine | e2137 | ||
| Human Papillomavirus Vaccine | e2138 | ||
| Tetanus and Diphtheria | e2138 | ||
| Recombinant Vaccines | e2138 | ||
| Hepatitis B Vaccine | e2138 | ||
| Combination Vaccines and Additives | e2138 | ||
| Mumps, Measles, and Rubella Vaccine and Autism | e2138 | ||
| Thimerosal-Containing Vaccines and Developmental Disorders of Childhood | e2138 | ||
| Vaccine Injection–Related Outcomes | e2138 | ||
| Deltoid Bursitis | e2139 | ||
| Syncope | e2139 | ||
| References | e2139 | ||
| 118 Paraneoplastic Neurologic Syndromes | e2142 | ||
| Introduction | e2142 | ||
| History of Paraneoplastic Syndromes | e2142 | ||
| Definition | e2142 | ||
| Diagnosis | e2142 | ||
| Treatment | e2143 | ||
| Classical PNS | e2143 | ||
| Lambert–Eaton Myasthenic Syndrome | e2143 | ||
| OMA Syndrome | e2144 | ||
| Subacute Sensory Neuronopathy | e2145 | ||
| Nonclassical PNS | e2145 | ||
| Paraneoplastic Cerebellar Degeneration | e2145 | ||
| Stiff-Person Syndrome | e2146 | ||
| Limbic Encephalitis | e2146 | ||
| Cancer-Associated Retinopathy | e2147 | ||
| Autoimmune Encephalitides | e2147 | ||
| Anti-N-methyl-D-aspartate Receptor Encephalitis | e2147 | ||
| Chapter Summary and Future Perspective | e2147 | ||
| References | e2148 | ||
| 119 Immune-Mediated Epilepsy, Movement Disorders, and Hashimoto’s Encephalopathy in Children | e2150 | ||
| Introduction | e2150 | ||
| Background | e2150 | ||
| Definitions: Immune Activation, Immune Mediation, Autoimmune | e2150 | ||
| Autoantibody: The Cell-Surface Paradigm | e2150 | ||
| Autoantibody Methodology | e2150 | ||
| Autoantibody Pathogenic Mechanisms | e2150 | ||
| Immune-Mediated Epilepsy | e2151 | ||
| Autoimmune Encephalitis Syndromes | e2151 | ||
| Autoantibody Associations with Epilepsy | e2151 | ||
| Guidelines for Identification of Autoimmune Epilepsy | e2152 | ||
| Autoimmune Movement Disorders | e2153 | ||
| Background | e2153 | ||
| Autoimmune Encephalitis Associated with Movement Disorders (Table 119-2) | e2153 | ||
| Sydenham Chorea | e2155 | ||
| PANDAS, PANS, and Tourette Syndrome | e2155 | ||
| Hashimoto Encephalopathy or SREAT | e2155 | ||
| Background | e2155 | ||
| Clinical Syndrome | e2155 | ||
| Etiology | e2156 | ||
| Treatment of Autoimmune CNS Disease and Therapeutic Decision Making | e2156 | ||
| References | e2156 | ||
| 120 Opsoclonus Myoclonus Syndrome | e2158 | ||
| Introduction | e2158 | ||
| Clinical Aspects | e2158 | ||
| Presentation and Course | e2158 | ||
| Differential Diagnosis | e2158 | ||
| Genetics | e2158 | ||
| Etiology | e2159 | ||
| Epidemiology | e2159 | ||
| Diagnostic Testing | e2159 | ||
| Tumor Detection | e2159 | ||
| Neuroinflammation Detection | e2159 | ||
| Ancillary Testing | e2160 | ||
| Pretreatment Immune Health | e2160 | ||
| ACTH Challenge Test | e2160 | ||
| Standard of Care and Quality of Life | e2160 | ||
| Immunopathogenesis | e2161 | ||
| Tumor Immunology | e2163 | ||
| CNS Inflammatory Mediators | e2163 | ||
| Immune Dysregulation. | e2163 | ||
| Inflammatory Proteins. | e2163 | ||
| Brain-Related Proteins. | e2163 | ||
| The Effect of Immunotherapy on Brain Inflammation. | e2163 | ||
| Autoantibodies. | e2163 | ||
| Treatment | e2163 | ||
| Treatment Strategy | e2163 | ||
| The Front-Loaded Approach. | e2163 | ||
| The Staggered Approach. | e2163 | ||
| Integrating Neuroinflammation with Clinical Assessment. | e2164 | ||
| Antitumor Therapy | e2164 | ||
| Immunotherapy | e2164 | ||
| IVIg and SCIg. | e2164 | ||
| Corticosteroids. | e2165 | ||
| ACTH1-39. | e2165 | ||
| Synthetic ACTH1-24. | e2165 | ||
| Monoclonal Antibody Therapy. | e2166 | ||
| Cyclophosphamide. | e2166 | ||
| Steroid Sparers. | e2167 | ||
| Methotrexate. | e2167 | ||
| Plasmapheresis. | e2167 | ||
| Inadequate Response | e2167 | ||
| Potential Treatment Side Effects/ Adverse Events | e2167 | ||
| Safety Monitoring and Measures | e2167 | ||
| Supportive Therapy | e2167 | ||
| Management of Relapse and Progression | e2167 | ||
| Relapse | e2167 | ||
| Progression | e2167 | ||
| Immunization Issues | e2168 | ||
| Future Directions | e2169 | ||
| Acknowledgments | e2169 | ||
| References | e2169 | ||
| 121 Neurologic Manifestations of Rheumatic Disorders of Childhood | e2172 | ||
| Juvenile Idiopathic Arthritis (Chronic Arthropathies) | e2172 | ||
| Neurologic Manifestations | e2172 | ||
| Systemic Juvenile Idiopathic Arthritis | e2172 | ||
| Acute Encephalopathy. | e2172 | ||
| Neuropathies. | e2173 | ||
| Mood Disturbances. | e2174 | ||
| Myositis. | e2174 | ||
| Polyarticular Juvenile Idiopathic Arthritis (Poly JIA) | e2174 | ||
| Myelopathy. | e2174 | ||
| Pauciarticular Juvenile Idiopathic Arthritis (Pauci JIA) | e2175 | ||
| Iridocyclitis and Uveitis. | e2175 | ||
| Psoriatic, Enthesitis-Related, and Undifferentiated Syndromes | e2175 | ||
| Neuropathology | e2175 | ||
| Management | e2175 | ||
| Periodic Fever Syndromes | e2175 | ||
| Neonatal-Onset Multisystem Inflammatory Disease or Chronic Infantile Neurologic Cutaneous and Articular Syndrome | e2175 | ||
| Familial Mediterranean Fever | e2176 | ||
| Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome | e2176 | ||
| Hyper-IgG (Autoimmune Lymphoproliferative) Syndrome | e2176 | ||
| Arthritis Associated with Infectious Agents | e2176 | ||
| Acute Rheumatic Fever | e2176 | ||
| Neurologic Manifestations | e2176 | ||
| Sydenham Chorea | e2176 | ||
| Clinical Manifestations. | e2176 | ||
| Laboratory Findings. | e2177 | ||
| Neuropathology | e2177 | ||
| Treatment | e2177 | ||
| Postinfectious Tourette Syndrome and PANDAS | e2177 | ||
| Other Central Nervous System Manifestations | e2177 | ||
| Lyme Disease | e2177 | ||
| Reactive Arthritis (formerly called Reiter Syndrome) | e2178 | ||
| Connective Tissue Disorders | e2178 | ||
| Systemic Lupus Erythematosus | e2178 | ||
| Neurologic Manifestations | e2179 | ||
| Seizures. | e2179 | ||
| Neuropsychiatric Lupus. | e2179 | ||
| Headache. | e2179 | ||
| Chorea. | e2179 | ||
| Reye-like Syndrome. | e2180 | ||
| Cerebrovascular Disease. | e2180 | ||
| Hypertensive Encephalopathy. | e2180 | ||
| Cranial Nerve, Brainstem, and Spinal Cord Dysfunction. | e2180 | ||
| Central Nervous System Infections. | e2180 | ||
| Lupus Aseptic Meningitis. | e2180 | ||
| Peripheral Nervous System Involvement. | e2180 | ||
| Myopathy. | e2180 | ||
| Drug-Induced Lupus Syndrome. | e2180 | ||
| Laboratory Findings | e2181 | ||
| Neuroimaging Evaluation | e2181 | ||
| Treatment of Neurologic Manifestations | e2182 | ||
| Neuropathology | e2183 | ||
| Scleroderma | e2184 | ||
| Neurologic Manifestations | e2184 | ||
| Laboratory Findings | e2185 | ||
| 122 Pediatric Neuro-oncology: | e2202 | ||
| Introduction | e2202 | ||
| Incidence | e2202 | ||
| Etiology | e2202 | ||
| Pathology and Classification | e2203 | ||
| Staging and Stratification | e2204 | ||
| Clinical Presentation | e2205 | ||
| General Aspects of Treatment | e2205 | ||
| Surgery | e2205 | ||
| Radiation Therapy | e2206 | ||
| Chemotherapy | e2207 | ||
| Biologic Therapy, Immunotherapy, Vaccines, and Gene Therapy | e2207 | ||
| Immunotherapy | e2207 | ||
| Gene Therapy | e2208 | ||
| Prognosis | e2208 | ||
| References | e2208 | ||
| 123 Medulloblastoma | e2211 | ||
| Introduction | e2211 | ||
| Etiology | e2211 | ||
| Biology | e2211 | ||
| Clinical Presentation and Diagnosis | e2213 | ||
| Clinical Features | e2213 | ||
| Imaging Features | e2213 | ||
| Management and Outcome | e2214 | ||
| Surgery | e2214 | ||
| Staging and Stratification | e2214 | ||
| Postsurgical Management | e2215 | ||
| Relapsed Medulloblastoma | e2217 | ||
| Future Therapy | e2217 | ||
| Sequelae in Medulloblastoma Survivors | e2218 | ||
| References | e2218 | ||
| 124 Other Embryonal and Pineal Malignancies of the Central Nervous System | e2221 | ||
| Introduction | e2221 | ||
| Clinical Presentation | e2221 | ||
| Types of CNS Embryonal Tumors | e2221 | ||
| Embryonal Tumors with Multilayered Rosettes | e2221 | ||
| Medulloepithelioma | e2221 | ||
| CNS Embryonal Tumors Not Otherwise Specified | e2222 | ||
| Treatment and Outcomes | e2222 | ||
| Pineal Tumors | e2223 | ||
| Pineocytomas | e2223 | ||
| Pineoblastomas | e2223 | ||
| Treatment and Outcomes | e2224 | ||
| Summary | e2224 | ||
| References | e2224 | ||
| 125 Ependymoma | e2225 | ||
| Introduction | e2225 | ||
| Incidence and Epidemiology | e2225 | ||
| Location | e2225 | ||
| Pathology | e2225 | ||
| Diagnostic Evaluation | e2225 | ||
| Imaging Studies | e2225 | ||
| Prognostic Factors | e2225 | ||
| Tumor Grade | e2226 | ||
| Genetics of Ependymoma | e2227 | ||
| Cytogenetics | e2228 | ||
| Epigenetic Phenomena | e2229 | ||
| Genetics of Spinal Ependymoma | e2229 | ||
| Biomarkers | e2229 | ||
| RTKI Family of Proteins Including ERBB2 | e2230 | ||
| Treatment of Ependymoma | e2230 | ||
| Chemotherapy | e2230 | ||
| Radiation Therapy | e2231 | ||
| Experimental Therapy | e2232 | ||
| Recurrence and Patterns of Failure | e2232 | ||
| Summary | e2233 | ||
| Conclusion | e2233 | ||
| References | e2233 | ||
| 126 Pediatric Brain Tumors – High-Grade Glioma | e2236 | ||
| Introduction | e2236 | ||
| Clinical Presentation | e2236 | ||
| Diagnosis and Initial Management | e2236 | ||
| Histopathology and Molecular Pathology | e2236 | ||
| Imaging | e2238 | ||
| Metabolic Imaging | e2238 | ||
| Perfusion Magnetic Resonance Imaging | e2238 | ||
| Therapy | e2239 | ||
| Current Therapy | e2239 | ||
| Future Directions | e2240 | ||
| Targeted Therapies for Children With High-Grade Gliomas | e2240 | ||
| CNS-Directed Delivery Strategies | e2241 | ||
| Convection-Enhanced Delivery | e2241 | ||
| Intranasal Delivery | e2241 | ||
| References | e2241 | ||
| 127 Pediatric Low-Grade Glioma | e2245 | ||
| Introduction | e2245 | ||
| Clinical Presentation | e2245 | ||
| Classification and Histologic Features | e2245 | ||
| Pilocytic Astrocytoma (WHO Grade I) | e2246 | ||
| Pilomyxoid Astrocytoma (WHO Grade II) | e2246 | ||
| Dysembryoplastic Neuroepithelial Tumor (WHO Grade I) | e2246 | ||
| Ganglioglioma (WHO Grade I) | e2246 | ||
| Pleomorphic Xanthroastrocytoma (WHO Grade II) | e2246 | ||
| Diffuse Fibrillary Astrocytoma | e2247 | ||
| Pediatric Low-Grade Glioma; Not Otherwise Specified | e2247 | ||
| Evaluation and Diagnosis | e2247 | ||
| Differential Diagnosis | e2247 | ||
| Pathogenesis | e2247 | ||
| Treatment | e2248 | ||
| Surgery | e2248 | ||
| Chemotherapy | e2248 | ||
| Radiation Therapy | e2250 | ||
| Supportive Care | e2250 | ||
| Seizures | e2250 | ||
| Genetic Features of Pediatric Low-Grade Glioma | e2250 | ||
| Current Clinical Trials | e2250 | ||
| Targeting the RAS/MAP-Kinase Pathway | e2250 | ||
| mTOR Pathway Inhibition | e2250 | ||
| Antiangiogenic Therapy | e2251 | ||
| Immunomodulatory Therapy | e2251 | ||
| Consideration for Patients with Neurofibromatosis Type 1 | e2251 | ||
| Outcome | e2251 | ||
| Conclusions | e2252 | ||
| References | e2252 | ||
| 128 Diffuse Intrinsic Pontine Glioma | e2254 | ||
| Background | e2254 | ||
| Developmental Context of DIPG | e2254 | ||
| Molecular Characteristics of DIPG | e2254 | ||
| Epidemiology | e2255 | ||
| Clinical Presentation | e2255 | ||
| Diagnostic Workup: Imaging and Pathology Studies | e2255 | ||
| Differential Diagnosis | e2256 | ||
| Treatment | e2256 | ||
| Emerging Therapeutic Strategies | e2257 | ||
| Prognosis | e2258 | ||
| Acknowledgment | e2258 | ||
| References | e2258 | ||
| 129 Atypical Teratoid/Rhabdoid Tumors | e2261 | ||
| Introduction | e2261 | ||
| Historical Background and Incidence | e2261 | ||
| Clinical Presentation and Radiographic Findings | e2261 | ||
| Histopathology | e2262 | ||
| Genetics of AT/RT | e2263 | ||
| Staging and Therapeutic Interventions | e2264 | ||
| Chemotherapy | e2264 | ||
| Radiation | e2265 | ||
| Toxicity of Therapy | e2265 | ||
| Future Directions | e2265 | ||
| Conclusions | e2265 | ||
| References | e2266 | ||
| 130 Central Nervous System Germinoma and Other Germ Cell Tumors | e2267 | ||
| Introduction | e2267 | ||
| Epidemiology | e2267 | ||
| Pathology and Etiology of Germ Cell Tumors | e2267 | ||
| Germinoma | e2268 | ||
| Clinical Presentation | e2268 | ||
| Radiology | e2268 | ||
| Tumor Markers | e2268 | ||
| S-Kit in Germinoma | e2269 | ||
| Staging | e2269 | ||
| Treatment | e2269 | ||
| Role of Radiation and Chemotherapy | e2269 | ||
| Radiation Therapy | e2269 | ||
| Chemotherapy | e2269 | ||
| Combined Chemotherapy and Radiation Therapy | e2270 | ||
| Choices of Chemotherapeutic Agents | e2270 | ||
| Role of Surgery | e2270 | ||
| The Need for Biopsy and Second-Look Surgery | e2270 | ||
| Prognosis and Summary | e2271 | ||
| References | e2271 | ||
| 131 Craniopharyngioma, Meningiomas, and Schwannomas | e2274 | ||
| Craniopharyngiomas | e2274 | ||
| Epidemiology | e2274 | ||
| Clinical Presentation | e2274 | ||
| Neuroimaging | e2274 | ||
| Histopathology | e2274 | ||
| Treatment | e2276 | ||
| Radical Surgical Resection | e2276 | ||
| Subtotal Resection With Irradiation | e2277 | ||
| Aspiration | e2277 | ||
| Intracystic Therapy | e2277 | ||
| Intracavitary Irradiation. | e2277 | ||
| Intracystic Bleomycin. | e2277 | ||
| Intracystic Interferon. | e2277 | ||
| Outcomes and Quality of Life | e2278 | ||
| Overview | e2278 | ||
| Meningiomas | e2278 | ||
| Epidemiology | e2279 | ||
| Clinical Presentation | e2279 | ||
| Molecular Genetics | e2279 | ||
| Meningiomas and Genetic Conditions | e2279 | ||
| Radiation-Induced Meningiomas | e2279 | ||
| Neuroimaging | e2279 | ||
| Histopathology | e2280 | ||
| Treatment | e2280 | ||
| Observation | e2280 | ||
| Surgery | e2281 | ||
| Radiation | e2281 | ||
| Overview | e2281 | ||
| Schwannomas | e2281 | ||
| Clinical Presentation | e2281 | ||
| Schwannomas and Genetic Conditions | e2282 | ||
| Neuroimaging | e2282 | ||
| Histopathology | e2282 | ||
| Treatment | e2282 | ||
| Overview | e2282 | ||
| References | e2282 | ||
| 132 Pediatric Intradural Spinal Cord Tumors | e2286 | ||
| Introduction | e2286 | ||
| Epidemiology | e2286 | ||
| Presentation | e2286 | ||
| Diagnosis | e2286 | ||
| Tumor Subtypes | e2287 | ||
| Extramedullary Spinal Cord Tumors (EMSCTs) | e2287 | ||
| Spinal Meningiomas | e2287 | ||
| Peripheral Nerve Tumors (Neurofibromas, Schwannomas) | e2288 | ||
| Ependymomas of the Conus-Cauda Region | e2288 | ||
| Intramedullary Spinal Cord Tumors (IMSCTs) | e2288 | ||
| Glial Tumors | e2288 | ||
| Intramedullary Ependymomas | e2288 | ||
| Low-Grade Astrocytomas | e2289 | ||
| Malignant Spinal Gliomas | e2289 | ||
| Surgery and Complications of Spinal Tumor Surgery | e2289 | ||
| Operative Technique | e2290 | ||
| For Extramedullary Tumors | e2290 | ||
| For Intramedullary Tumors | e2290 | ||
| Surgical Risks and Complications | e2290 | ||
| References | e2291 | ||
| 133 System Cancer and the Central Nervous System Involvement | e2292 | ||
| Central Nervous System Leukemia | e2292 | ||
| Lymphoma | e2293 | ||
| Histiocytosis | e2293 | ||
| Neuroblastoma | e2294 | ||
| Sarcoma | e2294 | ||
| Osteosarcoma | e2294 | ||
| Ewing’s Sarcoma | e2295 | ||
| Rhabdomyosarcoma | e2295 | ||
| Conclusions | e2295 | ||
| Acknowledgment | e2295 | ||
| References | e2295 | ||
| 134 Posttreatment Neurologic Sequelae of Pediatric Central Nervous System Tumors | e2297 | ||
| Introduction | e2297 | ||
| Tools With Which to Study Sequelae | e2297 | ||
| Mortality in Long-Term Survivors | e2297 | ||
| Central Nervous System Posttreatment Sequelae | e2298 | ||
| Weakness | e2298 | ||
| Seizures | e2298 | ||
| Posttreatment Encephalopathy | e2299 | ||
| Posterior Reversible Encephalopathy | e2299 | ||
| Pseudoprogression | e2300 | ||
| Cerebrovascular Events | e2300 | ||
| Postoperative Cerebellar Mutism Syndrome | e2300 | ||
| Chronic Leukoencephalopathy | e2300 | ||
| Cognitive Impairment | e2301 | ||
| Definition and Measurement of Neurocognitive Effects | e2301 | ||
| Risk Factors for Neurocognitive Deficits | e2303 | ||
| Neurosensory Deficits | e2304 | ||
| Visual Impairment | e2304 | ||
| Hearing Loss | e2305 | ||
| Peripheral Nervous System Impairment | e2305 | ||
| Growth and Other Sequelae With a Neuroendocrine Component | e2305 | ||
| Conclusions | e2306 | ||
| References | e2306 | ||
| 135 Muscle and Nerve Development in Health and Disease | e2309 | ||
| Embryology and Development | e2309 | ||
| Skeletal Muscle | e2309 | ||
| Peripheral Nerve | e2310 | ||
| Neuromuscular Junction | e2311 | ||
| General Anatomy and Structure of Skeletal Muscle | e2311 | ||
| Morphology | e2311 | ||
| Sarcomere | e2311 | ||
| Contractile and Sarcomeric Proteins | e2311 | ||
| Sarcotubular System | e2313 | ||
| Cytoskeletal Proteins | e2314 | ||
| Dystrophin | e2314 | ||
| Dystrophin-Glycoprotein Complex | e2315 | ||
| Sarcoglycans | e2316 | ||
| Utrophin | e2316 | ||
| Dysferlin | e2316 | ||
| Caveolin | e2317 | ||
| Merosin (Laminin-α2) | e2317 | ||
| Intermediate Filaments | e2317 | ||
| Nuclear Membrane Proteins | e2317 | ||
| Muscle Fiber Types | e2317 | ||
| General Anatomy and Structure of Peripheral Nerves | e2318 | ||
| Neuromuscular Function: From the Central Nervous System to the Sarcomere | e2319 | ||
| Neural Control of Movement | e2319 | ||
| Neuromuscular Transmission | e2320 | ||
| Excitation-Contraction Coupling | e2321 | ||
| Gamma Efferent System | e2322 | ||
| Muscle Metabolism | e2323 | ||
| References | e2323 | ||
| 136 Laboratory Assessment of the Child with Suspected Neuromuscular Disorders | e2326 | ||
| Introduction | e2326 | ||
| Laboratory Chemistries and Serologies | e2326 | ||
| Nerve Conduction Studies and Electromyography | e2328 | ||
| Motor Unit Number Estimation | e2329 | ||
| Electrical Impedance Myography | e2329 | ||
| Imaging Studies | e2329 | ||
| Genetic Testing | e2330 | ||
| Conclusions | e2331 | ||
| References | e2331 | ||
| 137 Clinical Assessment of Pediatric Neuromuscular Disorders | e2336 | ||
| Definition, Classification, and Epidemiology of Pediatric Neuromuscular Disorders | e2336 | ||
| Evaluation of the Child With a Suspected Neuromuscular Disorder | e2338 | ||
| Localization and Classification | e2340 | ||
| History | e2340 | ||
| Examination | e2342 | ||
| Quality of Life and Disability Scales | e2348 | ||
| Conclusions | e2348 | ||
| References | e2349 | ||
| 138 The Floppy Infant | e2351 | ||
| Defining Hypotonia | e2351 | ||
| Muscle Tone | e2351 | ||
| Localization of Hypotonia | e2351 | ||
| History | e2351 | ||
| Examination | e2352 | ||
| Central Hypotonia | e2354 | ||
| Peripheral Hypotonia | e2354 | ||
| Specific Causes of Central Hypotonia | e2355 | ||
| Chromosomal Abnormalities | e2355 | ||
| MeCP2-Related Disorders | e2357 | ||
| Canavan Disease | e2357 | ||
| Peroxisomal Disorders | e2357 | ||
| Smith-Lemli-Opitz | e2357 | ||
| Pelizaeus-Merzbacher Disease | e2357 | ||
| Creatine Deficiency Disorders | e2357 | ||
| Congenital Disorders of N-Glycosylation | e2358 | ||
| Specific Causes of Peripheral Hypotonia | e2358 | ||
| Anterior Horn Cell Disease | e2358 | ||
| Myotonic Dystrophy | e2358 | ||
| Peripheral Neuropathies | e2358 | ||
| Disorders of the Neuromuscular Junction | e2359 | ||
| Congenital Myopathies | e2359 | ||
| Barth Syndrome | e2360 | ||
| Pompe Disease | e2360 | ||
| Carnitine Palmitoyltransferase Deficiency Type II | e2360 | ||
| Connective Tissue Disorders (Loeys-Dietz Syndrome, Marfan Syndrome) | e2361 | ||
| Specific Causes of Combined Central and Peripheral Hypotonia | e2361 | ||
| Congenital Muscular Dystrophies | e2361 | ||
| Mitochondrial Respiratory Chain Disorders | e2361 | ||
| Marinesco-Sjögren Syndrome | e2362 | ||
| References | e2362 | ||
| 139 Genetic Disorders Affecting the Motor Neuron | e2365 | ||
| Epidemiology | e2365 | ||
| Clinical Characteristics | e2365 | ||
| Type I SMA | e2365 | ||
| Type II SMA | e2367 | ||
| Type III SMA | e2367 | ||
| Outliers | e2367 | ||
| Other “Spinal Muscular Atrophies” | e2368 | ||
| Genetics | e2368 | ||
| The SMN Gene | e2368 | ||
| Genetic Diagnosis | e2369 | ||
| Newborn Screening | e2370 | ||
| Other Diagnostic Tests | e2370 | ||
| Molecular Function of SMN | e2371 | ||
| Differential Diagnosis | e2372 | ||
| Non-5q Spinal Muscular Atrophies | e2372 | ||
| Congenital Neuropathies | e2372 | ||
| Hexosaminidase A Deficiency | e2372 | ||
| Juvenile Muscular Atrophy of Distal Upper Extremity (Hirayama Disease) | e2373 | ||
| Other Disorders | e2373 | ||
| The Pathology of SMA | e2374 | ||
| Animal Models | e2375 | ||
| Worm, Fly, and Fish Models of SMA | e2375 | ||
| Murine Models of SMA: Additional Insights Into Disease Pathology | e2375 | ||
| Murine Models of SMA: Revealing the Cellular and Temporal Requirements of SMN | e2375 | ||
| Treatment | e2375 | ||
| Clinical Trials in SMA: Outcome Measures | e2376 | ||
| Clinical Trials in SMA: Therapeutics | e2377 | ||
| Agents That Upregulate SMN2 Gene Expression and Promote Exon 7 Inclusion | e2377 | ||
| Small Molecules | e2377 | ||
| Neuroprotective, SMN Protein Stabilization Agents | e2378 | ||
| Other Small Molecules | e2378 | ||
| Other Approaches | e2378 | ||
| SMN2 Splicing Modifiers | e2378 | ||
| Antisense Oligonucleotides. | e2378 | ||
| Small Molecule Drugs. | e2379 | ||
| Stem Cells | e2379 | ||
| Gene Therapy | e2379 | ||
| Care of the Patient With SMA | e2379 | ||
| Pulmonary | e2379 | ||
| Gastrointestinal | e2380 | ||
| Nutrition | e2380 | ||
| Orthopedic | e2380 | ||
| Fatigue | e2380 | ||
| Case Example: SMA Type III | e2380 | ||
| Conclusions | e2381 | ||
| Acknowledgments | e2381 | ||
| References | e2381 | ||
| 140 Other Motor Neuron Diseases of Childhood | e2384 | ||
| Anatomy: The Anterior Horn Cells of the Spinal Cord | e2384 | ||
| Clinical Features | e2384 | ||
| Diagnostic Workup | e2384 | ||
| Hereditary Diseases Affecting Spinal Motor Neurons | e2384 | ||
| SMA-Like Motor Neuron Disorders | e2384 | ||
| Motor Neuron Disease With Central Nervous System Manifestations | e2390 | ||
| Motor Neuron Diseases With Predominant Bulbar Weakness | e2390 | ||
| Motor Neuron Disease With Arthrogryposis | e2391 | ||
| Motor Neuron Disease With Distal Weakness | e2391 | ||
| Amyotrophic Lateral Sclerosis With Onset in the First Two Decades of Life | e2392 | ||
| Möbius’s Syndrome | e2392 | ||
| Other Atypical and Acquired Motor Neuron Disorders | e2393 | ||
| Infections | e2393 | ||
| Poliovirus | e2393 | ||
| West Nile Virus | e2394 | ||
| Enterovirus | e2394 | ||
| Other | e2394 | ||
| Vascular Etiologies | e2394 | ||
| Trauma | e2395 | ||
| Unknown Etiologies | e2395 | ||
| Treatment | e2395 | ||
| References | e2396 | ||
| 141 Genetic Peripheral Neuropathies | e2400 | ||
| Definition | e2400 | ||
| Prevalence and Classification | e2400 | ||
| Clinical Sequelae of Inherited Neuropathy | e2400 | ||
| Pathophysiology | e2403 | ||
| Neurophysiology | e2403 | ||
| Genetic Testing and Diagnostic Strategies | e2404 | ||
| Specific Forms of CMT | e2406 | ||
| CMT1: Autosomal-Dominant Demyelinating Neuropathies | e2406 | ||
| CMT1A | e2406 | ||
| CMT1B | e2407 | ||
| CMT1C | e2407 | ||
| CMT1D | e2407 | ||
| CMT1E | e2407 | ||
| CMT1F | e2407 | ||
| See CMT2E | e2407 | ||
| HNPP. | e2407 | ||
| CMTX: X-Linked CMT | e2407 | ||
| CMT2: Autosomal-Dominant Axonal Neuropathies | e2408 | ||
| CMT2A | e2408 | ||
| CMT2B | e2408 | ||
| CMT2C | e2408 | ||
| CMT2D | e2408 | ||
| CMT2E | e2408 | ||
| CMT2F | e2408 | ||
| CMT2L | e2408 | ||
| CMT2K | e2408 | ||
| CMT2M | e2409 | ||
| CMT2O | e2409 | ||
| CMT4: Autosomal-Recessive Neuropathies | e2409 | ||
| CMT4A | e2409 | ||
| CMT4B1 | e2409 | ||
| CMT4B2 | e2409 | ||
| CMT4B3 | e2409 | ||
| CMT4C | e2409 | ||
| CMT4F | e2409 | ||
| CMT4J | e2409 | ||
| CMT4: Autosomal-Recessive Axonal Neuropathies (Also Known as AR-CMT2). | e2409 | ||
| A: Lamin A/C | e2409 | ||
| Intermediate CMT | e2409 | ||
| Distal Hereditary Motor Neuropathies. | e2410 | ||
| AD dHMN Type I | e2410 | ||
| AD dHMN Type II | e2410 | ||
| AR dHMN Type III and AR dHMN Type IV | e2410 | ||
| AD dHMN V | e2410 | ||
| AR dHMN VI | e2410 | ||
| AD dHMN VII | e2410 | ||
| AR dHMN-J | e2411 | ||
| Hereditary Sensory Neuropathies. | e2411 | ||
| HSN I | e2411 | ||
| HSN IA-IF | e2411 | ||
| HSN II, IIB, IIC, IID | e2412 | ||
| HSN III | e2412 | ||
| HSN IV | e2412 | ||
| HSN V | e2412 | ||
| HSN VI | e2412 | ||
| HSN VII | e2412 | ||
| Neuropathies Associated With Inherited Metabolic Disease. | e2412 | ||
| Other Inherited Neuropathies | e2413 | ||
| Giant Axonal Neuropathy. | e2413 | ||
| Neuroaxonal Dystrophy. | e2413 | ||
| Differential Diagnosis. | e2413 | ||
| Treatment Strategies. | e2413 | ||
| Conclusion | e2415 | ||
| References | e2415 | ||
| 142 Acquired Peripheral Neuropathies | e2419 | ||
| Anatomy | e2419 | ||
| Facial Nerve Paralysis (Bell’s Palsy) | e2419 | ||
| Clinical Features | e2419 | ||
| Laboratory Findings | e2420 | ||
| Treatment and Prognosis | e2422 | ||
| Recurrent Facial Paralysis | e2422 | ||
| Brachial Plexus | e2422 | ||
| Injury | e2422 | ||
| Metabolic Neuropathies | e2422 | ||
| Diabetes Mellitus | e2422 | ||
| Uremic Neuropathy | e2422 | ||
| Acute Intermittent Porphyria | e2423 | ||
| Vitamin Deficiency | e2424 | ||
| Congenital Pernicious Anemia | e2424 | ||
| Abetalipoproteinemia | e2424 | ||
| Pathology | e2424 | ||
| 143 Inflammatory Neuropathies | e2436 | ||
| Guillain-Barré Syndrome | e2436 | ||
| Epidemiology | e2436 | ||
| Antecedent Events | e2437 | ||
| Clinical Features of AIDP (GBS) | e2438 | ||
| Other Subtypes of Guillain-Barré Syndrome | e2439 | ||
| Acute Motor Axonal Neuropathy | e2439 | ||
| Acute Motor and Sensory Axonal Neuropathy | e2439 | ||
| Miller Fisher Syndrome | e2440 | ||
| Rare Childhood Guillain-Barré Syndrome Variants | e2440 | ||
| Diagnostic Challenges of GBS in Childhood | e2440 | ||
| GBS Diagnostic Criteria | e2440 | ||
| Differential Diagnosis | e2440 | ||
| Laboratory Findings Supportive of GBS | e2440 | ||
| Cerebrospinal Fluid | e2440 | ||
| Electrodiagnosis | e2441 | ||
| Magnetic Resonance Imaging | e2442 | ||
| Pathogenesis | e2442 | ||
| GBS Treatment | e2443 | ||
| Supportive Care | e2443 | ||
| GBS Immunotherapy | e2443 | ||
| Corticosteroids in GBS | e2444 | ||
| Potential GBS Therapies | e2444 | ||
| Childhood GBS Outcome | e2444 | ||
| Chronic Inflammatory Demyelinating Polyradiculoneuropathy | e2444 | ||
| Epidemiology | e2444 | ||
| Antecedent Events | e2444 | ||
| Diagnostic Criteria and Clinical Features | e2444 | ||
| CIDP Laboratory Evaluation | e2445 | ||
| Cerebrospinal Fluid and Electrodiagnosis | e2445 | ||
| CIDP Pathology | e2445 | ||
| Pathogenesis | e2446 | ||
| CIDP Magnetic Resonance Imaging | e2446 | ||
| Childhood CIDP Immunotherapy | e2446 | ||
| First-Line CIDP Treatments | e2446 | ||
| Corticosteroids. | e2446 | ||
| Intravenous Immunoglobulin. | e2446 | ||
| Plasmaphereis/Plasma exchange (PE). | e2446 | ||
| Potential Second-Line Immunosuppressants for Treatment-Resistant CIDP | e2446 | ||
| Methotrexate. | e2446 | ||
| Azathioprine. | e2447 | ||
| Cyclosporine A. | e2447 | ||
| Monoclonal Antibody. | e2447 | ||
| Interferons. | e2447 | ||
| Other Agents. | e2447 | ||
| Current Practice in Childhood CIDP Immunotherapy. | e2447 | ||
| Differentiating Abrupt-Onset CIDP from GBS Fluctuations. | e2447 | ||
| Clinical Variants Not Meeting CIDP Research Criteria. | e2447 | ||
| Childhood CIDP Outcome | e2447 | ||
| Other Causes of Immune-Mediated Neuropathies in Children | e2448 | ||
| References | e2448 | ||
| 144 Congenital Myasthenic Syndromes | e2451 | ||
| Introduction | e2451 | ||
| Basic Concepts | e2451 | ||
| Clinical Manifestations | e2451 | ||
| Diagnosis | e2451 | ||
| Classification | e2453 | ||
| Presynaptic Congenital Myasthenic Syndromes | e2453 | ||
| 1. Endplate Choline Acetyltransferase (ChAT) Deficiency | e2453 | ||
| 2. SNAP25B Myasthenia | e2454 | ||
| 3. Synaptotagmin-2 Myasthenia | e2454 | ||
| Synaptic Basal Lamina Associated Congenital Myasthenic Syndromes | e2454 | ||
| 1. Endplate Acetylcholinesterase Deficiency | e2454 | ||
| 2. Congenital Myasthenic Syndrome Associated With β2-Laminin Deficiency | e2455 | ||
| Postsynaptic Congenital Myasthenic Syndromes | e2455 | ||
| 1. Primary Acetylcholine Receptor Deficiency | e2455 | ||
| 2. Kinetic Defects in Acetylcholine Receptor | e2455 | ||
| 2.1 Slow-channel myasthenia | e2455 | ||
| 2.2 Fast-channel myasthenia | e2456 | ||
| 3. Prenatal Congenital Myasthenic Syndrome Caused by Mutations in Acetylcholine Receptor Subunits and Other Endplate Specific Proteins | e2456 | ||
| 4. Sodium-channel Myasthenia | e2456 | ||
| 5. Congenital Myasthenic Syndrome Caused by Plectin Deficiency | e2456 | ||
| Congenital Myasthenic Syndromes Caused by Defects in Endplate Development or Maintenance | e2456 | ||
| 1. Agrin Myasthenia | e2456 | ||
| 2. LRP4 Myasthenia | e2457 | ||
| 3. MuSK Myasthenia | e2457 | ||
| 4. Dok-7 Myasthenia | e2457 | ||
| 5. Rapsyn Myasthenia | e2457 | ||
| Congenital Myasthenic Syndromes Associated With Congenital Defects of Glycosylation | e2457 | ||
| 1. GFPT1 Myasthenia | e2457 | ||
| 2. DPAGT1 Myasthenia | e2457 | ||
| 3. ALG2 and ALG14 Myasthenia | e2458 | ||
| Other Myasthenic Syndromes | e2458 | ||
| 1. PREPL Deletion Syndrome | e2458 | ||
| 2. Myasthenic Syndrome Associated With Defects in the Mitochondrial Citrate Carrier SLC25A1 | e2458 | ||
| 3. Myasthenic Syndromes Associated With Congenital Myopathies | e2458 | ||
| Treatment | e2458 | ||
| References | e2459 | ||
| 145 Acquired Disorders of the Neuromuscular Junction | e2462 | ||
| Acquired Diseases of the Neuromuscular Junction | e2462 | ||
| The Neuromuscular Junction | e2462 | ||
| Autoimmune Myasthenia Gravis | e2462 | ||
| Clinical Features | e2463 | ||
| Clinical Classification | e2464 | ||
| Categories of Myasthenia Gravis in Childhood | e2464 | ||
| Neurologic Examination | e2465 | ||
| Clinical and Laboratory Tests | e2465 | ||
| Edrophonium (Tensilon) Test | e2465 | ||
| Electrophysiologic Testing | e2467 | ||
| Repetitive Nerve Stimulation. | e2467 | ||
| Single-Fiber Electromyography. | e2468 | ||
| Antibody Testing | e2468 | ||
| Anti-AChR Antibodies. | e2468 | ||
| Anti-MuSK Antibodies. | e2470 | ||
| Striated Muscle Antibodies and Other Laboratory Studies. | e2470 | ||
| Treatment | e2470 | ||
| Neonatal Myasthenia Gravis. | e2470 | ||
| Juvenile Myasthenia Gravis | e2470 | ||
| Acetylcholinesterase Inhibitors. | e2470 | ||
| Thymectomy. | e2471 | ||
| Corticosteroids. | e2472 | ||
| Azathioprine. | e2473 | ||
| Cyclosporine. | e2473 | ||
| Mycophenolate Mofetil. | e2473 | ||
| Cyclophosphamide. | e2474 | ||
| Plasmapheresis. | e2474 | ||
| Tacrolimus. | e2474 | ||
| Intravenous Immunoglobulin. | e2474 | ||
| Drugs to Avoid. | e2475 | ||
| Lambert–Eaton Myasthenic Syndrome. | e2475 | ||
| Clinical Features. | e2475 | ||
| Diagnostic Tests. | e2475 | ||
| Treatment. | e2476 | ||
| Botulism | e2477 | ||
| Infant Botulism | e2477 | ||
| Foodborne Botulism | e2477 | ||
| Wound Botulism | e2478 | ||
| References | e2478 | ||
| 146 Duchenne and Becker Muscular Dystrophies | e2482 | ||
| The Dystrophin Protein | e2482 | ||
| The “Reading Frame Rule” | e2482 | ||
| Clinical Features | e2483 | ||
| Duchenne Muscular Dystrophy | e2483 | ||
| Becker Muscular Dystrophy | e2485 | ||
| Laboratory Features | e2485 | ||
| Molecular Genetic Testing | e2485 | ||
| DMD Mutation Analysis. | e2485 | ||
| Genotype-Phenotype Correlations | e2486 | ||
| Muscle Biopsy | e2487 | ||
| Management of DMD and BMD | e2487 | ||
| Pharmacologic Management | e2487 | ||
| Corticosteroids. | e2487 | ||
| Cardiac. | e2487 | ||
| Pulmonary. | e2488 | ||
| Non-pharmacologic Management | e2488 | ||
| Spine/Scoliosis. | e2488 | ||
| Contractures. | e2488 | ||
| Recent Advances in Dystrophinopathy Therapeutics | e2488 | ||
| References | e2489 | ||
| 147 Congenital, Limb Girdle and Other Muscular Dystrophies | e2493 | ||
| Dystrophinopathies (Duchenne and Becker Muscular Dystrophies and Clinical Variants) | e2493 | ||
| Limb-Girdle Muscular Dystrophies | e2493 | ||
| Historical Background and Definition | e2493 | ||
| Autosomal-Recessive Limb-Girdle Muscular Dystrophies | e2494 | ||
| Sarcoglycanopathies (LGMD 2C-F) | e2495 | ||
| Pathophysiology | e2495 | ||
| Dystrophin-Associated Proteins. | e2495 | ||
| Intracellular DAPs. | e2495 | ||
| Transmembrane DAPs | e2495 | ||
| Dystroglycan Complex. | e2495 | ||
| Sarcoglycan Complex. | e2496 | ||
| Genetics and Mutations. | e2496 | ||
| Clinical Features. | e2498 | ||
| Time Course and Distribution of Motor Symptoms. | e2498 | ||
| Cardiac Features. | e2498 | ||
| Pulmonary Features. | e2499 | ||
| Contractures and Other Signs and Symptoms. | e2499 | ||
| Diagnosis. | e2499 | ||
| Treatment. | e2499 | ||
| Disorders of α-Dystroglycan Glycosylation | e2500 | ||
| Limb-Girdle Muscular Dystrophy 2I: Fukutin-Related Protein Deficiency | e2500 | ||
| Pathophysiology and Genetics. | e2500 | ||
| Clinical Features. | e2500 | ||
| Diagnosis. | e2500 | ||
| Management. | e2500 | ||
| Other α-Dystroglycanopathies | e2500 | ||
| Calpainopathy (LGMD2A) | e2501 | ||
| Background and Epidemiology. | e2501 | ||
| Pathophysiology, Genetics, and Mutations. | e2501 | ||
| Clinical Features. | e2501 | ||
| Time Course and Distribution of Motor Symptoms. | e2501 | ||
| Cardiac Features. | e2502 | ||
| Pulmonary Features. | e2502 | ||
| Contractures and Other Signs and Symptoms. | e2502 | ||
| Diagnosis. | e2502 | ||
| Treatment. | e2502 | ||
| Dysferlinopathy (LGMD 2B) | e2502 | ||
| Pathophysiology. | e2502 | ||
| Genetics and Mutations. | e2502 | ||
| Clinical Features. | e2502 | ||
| Time Course and Distribution of Motor Symptoms. | e2502 | ||
| 148 Congenital Myopathies | e2529 | ||
| Introduction | e2529 | ||
| Diagnostics | e2529 | ||
| Infancy (0 to 12 Months) | e2529 | ||
| Early Childhood (Age 1 to 5 Years) | e2533 | ||
| Diagnostic Testing for Congenital Myopathies | e2533 | ||
| Muscle Biopsy | e2533 | ||
| Genetics | e2534 | ||
| Muscle Imaging (MRI or Ultrasonography) | e2534 | ||
| Specific Subtypes of Congenital Myopathies | e2535 | ||
| Centronuclear Myopathies | e2535 | ||
| Specific Centronuclear Myopathies: Myotubular Myopathy | e2535 | ||
| Specific Centronuclear Myopathies: DNM2-Related CNM | e2537 | ||
| Nemaline Myopathies | e2538 | ||
| Actinopathies | e2538 | ||
| NEB-Related Nemaline Myopathy | e2539 | ||
| Core Myopathies | e2540 | ||
| RYR1-Related Myopathies | e2540 | ||
| SEPN1-Related Myopathies | e2542 | ||
| Other Core Myopathies: MYH7-Related Myopathies | e2542 | ||
| Other Core Myopathies: TTN-Related Myopathies | e2542 | ||
| Congenital Fiber-Type Disproportion | e2542 | ||
| General Management of Congenital Myopathies | e2542 | ||
| Respiratory | e2542 | ||
| Nutrition, Gastrointestinal, and Oromotor Management | e2543 | ||
| Cardiac | e2543 | ||
| Orthopedic | e2543 | ||
| Physical Therapy/Exercise | e2543 | ||
| Summary | e2543 | ||
| References | e2543 | ||
| 149 Metabolic Myopathies | e2547 | ||
| Utilization of Bioenergetic Substrates in Exercise | e2547 | ||
| Myoglobinuria | e2548 | ||
| Glycogenoses | e2548 | ||
| Pathophysiology | e2549 | ||
| Glycolytic/Glycogenolytic Defects | e2549 | ||
| Acid Maltase Deficiency | e2549 | ||
| Clinical Features. | e2549 | ||
| Laboratory Tests. | e2551 | ||
| Pathology and Pathophysiology. | e2551 | ||
| Inheritance. | e2551 | ||
| Biochemistry, Molecular Genetics, and Diagnostic Testing. | e2551 | ||
| Treatment. | e2552 | ||
| Phosphorylase B Kinase Deficiency | e2552 | ||
| Clinical Features. | e2552 | ||
| Laboratory Features. | e2553 | ||
| Biochemistry and Molecular Genetics. | e2553 | ||
| Treatment. | e2553 | ||
| Phosphorylase Deficiency | e2553 | ||
| Clinical Features. | e2553 | ||
| Laboratory Data. | e2553 | ||
| Inheritance. | e2553 | ||
| Muscle Biopsy. | e2553 | ||
| Biochemical Considerations. | e2553 | ||
| Pathophysiology. | e2553 | ||
| Molecular Genetics. | e2553 | ||
| Treatment. | e2554 | ||
| Debrancher Deficiency | e2554 | ||
| Clinical Features. | e2554 | ||
| Laboratory Data. | e2554 | ||
| Inheritance. | e2554 | ||
| Pathology. | e2554 | ||
| Biochemistry. | e2554 | ||
| 150 Inflammatory Myopathies | e2595 | ||
| Idiopathic Inflammatory Myopathies | e2595 | ||
| Dermatomyositis | e2595 | ||
| Clinical Features | e2595 | ||
| Associated Manifestations. | e2595 | ||
| Laboratory Features | e2596 | ||
| Blood Tests. | e2596 | ||
| Electromyography. | e2596 | ||
| Muscle Biopsy. | e2597 | ||
| Pathogenesis | e2597 | ||
| Treatment | e2598 | ||
| Corticosteroids. | e2598 | ||
| Other Agents. | e2598 | ||
| Polymyositis | e2599 | ||
| Clinical Features | e2599 | ||
| Overlap Syndromes. | e2599 | ||
| Laboratory Features | e2599 | ||
| Muscle Biopsy. | e2599 | ||
| Pathogenesis | e2600 | ||
| Treatment | e2600 | ||
| Congenital Inflammatory Myopathy | e2600 | ||
| Other Idiopathic Inflammatory Myopathies | e2600 | ||
| Inflammatory Myopathy Associated With Infections | e2600 | ||
| Influenza Myositis | e2600 | ||
| Clinical Features | e2600 | ||
| 151 Channelopathies | e2605 | ||
| The Myotonic Dystrophies | e2605 | ||
| Mode of Inheritance of DM1 and DM2 | e2605 | ||
| Myotonic Dystrophy Type 1 | e2605 | ||
| Clinical Features | e2605 | ||
| Myotonic Dystrophy Type 2 (Formerly Proximal Myotonic Myopathy) | e2606 | ||
| Clinical Features | e2606 | ||
| DM1 and DM2: Genotype–Phenotype Correlations | e2606 | ||
| Disease Mechanisms for DM1 and DM2 | e2607 | ||
| DM1 and DM2 Are RNA-Mediated Diseases | e2607 | ||
| Human Studies Supporting RNA-Mediated Pathomechanism for DM1 and DM2 | e2608 | ||
| Animal Models | e2609 | ||
| Current Human Research | e2609 | ||
| Diagnostic Approach | e2609 | ||
| Laboratory Testing for DM1 and DM2 | e2612 | ||
| DM1 Testing | e2612 | ||
| DM2 Testing | e2612 | ||
| Treatment of DM1 and DM2 | e2612 | ||
| DM1 Treatment | e2612 | ||
| DM2 Treatment | e2612 | ||
| Experimental Therapeutics in Myotonic Dystrophy | e2612 | ||
| Autosomal-Dominant and Autosomal-Recessive Myotonia Congenita | e2613 | ||
| Clinical Features | e2613 | ||
| Genetics | e2613 | ||
| Pathophysiology | e2613 | ||
| Clinical Laboratory Tests | e2614 | ||
| Treatment | e2615 | ||
| Acetazolamide-Responsive Sodium Channel Myotonia and Myotonia Fluctuans | e2615 | ||
| Clinical Features | e2615 | ||
| Genetics | e2616 | ||
| Pathophysiology | e2616 | ||
| Clinical Laboratory Tests | e2616 | ||
| Treatment | e2616 | ||
| The Periodic Paralyses | e2616 | ||
| Hyperkalemic Periodic Paralysis | e2618 | ||
| 152 Management of Children with Neuromuscular Disorders | e2626 | ||
| Therapeutic Exercise | e2626 | ||
| Orthotics and Adaptive Devices | e2626 | ||
| Scoliosis Management | e2628 | ||
| Respiratory Management | e2629 | ||
| Cardiac Management | e2631 | ||
| Duchenne Muscular Dystrophy | e2631 | ||
| Becker Muscular Dystrophy | e2631 | ||
| Limb-Girdle Muscular Dystrophy | e2631 | ||
| Myotonic Dystrophy | e2631 | ||
| Emery-Dreifuss Muscular Dystrophy | e2631 | ||
| Congenital Myopathies | e2632 | ||
| Kearns-Sayre Syndrome | e2632 | ||
| Andersen-Tawil Syndrome | e2632 | ||
| Gastrointestinal and Nutrition Management | e2632 | ||
| Bone Health | e2632 | ||
| Endocrine Management | e2633 | ||
| Psychosocial Management | e2633 | ||
| Transition and Aging | e2633 | ||
| References | e2634 | ||
| 153 Endocrine Disorders of the Hypothalamus and Pituitary in Childhood and Adolescence | e2637 | ||
| Introduction | e2637 | ||
| Anatomic and Physiologic Aspects | e2637 | ||
| Hypothalamic/Pituitary Disorders of Pubertal Development | e2638 | ||
| Normal Physiology of Puberty and Adrenarche | e2638 | ||
| Sexual Precocity | e2639 | ||
| Management | e2639 | ||
| Delayed or Arrested Puberty | e2640 | ||
| Isolated Congenital Hypogonadotropic Hypogonadism | e2640 | ||
| Hypogonadotropic Hypogonadism Associated with Multiple Hypothalamic/Pituitary Hormone Deficiencies | e2640 | ||
| Functional Hypogonadotropic Hypogonadism | e2641 | ||
| Evaluation of Delayed or Arrested Puberty | e2641 | ||
| Management | e2641 | ||
| Disorders of Prolactin Secretion | e2641 | ||
| Normal Biochemistry and Physiology of Prolactin | e2641 | ||
| Clinical Features and Management of Hyperprolactinemia | e2642 | ||
| Hypothalamic/Pituitary Disorders of Glucocorticoid Production | e2642 | ||
| Adrenocorticotropic Excess | e2642 | ||
| Adrenocorticotropic Hormone Deficiency | e2642 | ||
| Hypothalamic/Pituitary Disorders of Statural Growth | e2643 | ||
| Growth Hormone Deficiency | e2644 | ||
| Growth Hormone Excess | e2644 | ||
| Hypothalamic/Pituitary Disorders of Thyroid Function | e2644 | ||
| Normal Thyroid Physiology | e2644 | ||
| Central Hypothyroidism | e2645 | ||
| Central Hyperthyroidism | e2645 | ||
| Hypothalamic Disorders of Appetite Regulation and Energy Balance | e2645 | ||
| Hypothalamic/Pituitary Disorders of Water Balance | e2646 | ||
| Diabetes Insipidus | e2647 | ||
| Syndrome of Inappropriate Antidiuretic Hormone Secretion | e2647 | ||
| References | e2648 | ||
| 154 Disorders of the Autonomic Nervous System: | e2652 | ||
| Introduction | e2652 | ||
| Anatomy and Physiology of the Autonomic Nervous System | e2652 | ||
| Embryologic Development | e2652 | ||
| Anatomy of the Autonomic Nervous System | e2652 | ||
| Efferent Autonomic Pathways | e2652 | ||
| Sympathetic Efferent Pathways. | e2652 | ||
| Parasympathetic Efferent Pathways. | e2653 | ||
| Efferent Neurotransmission. | e2653 | ||
| Afferent Autonomic Pathways | e2654 | ||
| Central Nervous System Integration | e2654 | ||
| Clinical Approach to the Diagnosis of Pediatric Autonomic Disorders | e2655 | ||
| Clinical History Taking | e2655 | ||
| Orthostatic Intolerance | e2655 | ||
| Syncope. | e2655 | ||
| Orthostatic Intolerance. | e2656 | ||
| Abnormal Gastrointestinal Motility. | e2656 | ||
| Urinary Symptoms. | e2656 | ||
| Thermoregulatory Abnormalities. | e2656 | ||
| Ocular Symptoms. | e2656 | ||
| Respiratory Symptoms. | e2656 | ||
| Clinical Examination and Autonomic Testing | e2656 | ||
| Measurements of Vascular Sympathetic Function | e2656 | ||
| Measurements of Cardiac Parasympathetic Function | e2657 | ||
| Measurements of Sudomotor Sympathetic Function | e2658 | ||
| Additional Tests | e2658 | ||
| Pediatric Autonomic Disorders | e2658 | ||
| Functional Disorders of Unknown Origin | e2658 | ||
| Reflex (Vasovagal) Syncope | e2658 | ||
| Postural Tachycardia Syndrome | e2660 | ||
| Orthostatic Intolerance without Tachycardia | e2660 | ||
| Metabolic Disorders | e2660 | ||
| Obesity | e2660 | ||
| Eating Disorders | e2661 | ||
| Diabetes Mellitus | e2661 | ||
| Other Metabolic Disorders | e2661 | ||
| Autonomic Dysfunction Secondary to Focal Disease | e2661 | ||
| Acquired Afferent Baroreflex Failure | e2661 | ||
| Catecholamine-Secreting Tumors | e2661 | ||
| Autoimmune Autonomic Disorders | e2661 | ||
| Guillain-Barré Syndrome | e2661 | ||
| Autoimmune Autonomic Ganglionopathy | e2662 | ||
| Acute Autonomic and Sensory Neuropathy | e2662 | ||
| Anti-NMDA Receptor Encephalitis | e2662 | ||
| Lambert-Eaton Myasthenic Syndrome | e2662 | ||
| Dipeptidyl-Peptidase-Like Protein-6 (DPPX) Potassium Channel Antibody Encephalitis | e2662 | ||
| Genetic Autonomic Disorders | e2662 | ||
| Hereditary Sensory and Autonomic Neuropathies | e2662 | ||
| HSAN Type 1. | e2662 | ||
| HSAN Type 2. | e2662 | ||
| HSAN Type 3 (Familial Dysautonomia). | e2662 | ||
| HSAN Type 4 (Congenital Insensitivity to Pain with Anhidrosis). | e2664 | ||
| HSAN Type 5. | e2664 | ||
| HSAN Type 6. | e2664 | ||
| HSAN Type 7. | e2664 | ||
| Other Syndromes with Sensory and Autonomic Involvement. | e2664 | ||
| Inborn Errors of Metabolism | e2665 | ||
| Dopamine Beta-Hydroxylase Deficiency. | e2665 | ||
| Aromatic L-Amino Acid Decarboxylase Deficiency. | e2665 | ||
| Menkes Disease. | e2665 | ||
| Fabry Disease. | e2665 | ||
| Porphyrias. | e2666 | ||
| Hirschsprung Disease | e2666 | ||
| Congenital Central Hypoventilation Syndrome and Related Ventilatory Disorders | e2666 | ||
| Allgrove Syndrome and Related Disorders | e2666 | ||
| Other Genetic Disorders with Autonomic Dysfunction | e2666 | ||
| Rett Syndrome. | e2666 | ||
| Alexander Disease. | e2666 | ||
| Hyperbradykininism. | e2666 | ||
| Panayiotopoulos Syndrome. | e2666 | ||
| Congenital Alacrima. | e2667 | ||
| Cold-Induced Sweating Syndrome. | e2667 | ||
| References | e2667 | ||
| 155 Disorders of Micturition and Defecation | e2670 | ||
| Introduction | e2670 | ||
| Disorders of Micturition: | e2670 | ||
| Epidemiology | e2670 | ||
| Neuropsychiatric Comorbidity | e2671 | ||
| Anatomy of the Lower Urinary Tract (LUT) | e2671 | ||
| Afferent Mechanisms | e2672 | ||
| Periaqueductal Gray (PAG) and Pontine Micturition Center (PMC) | e2674 | ||
| Cortex | e2675 | ||
| Insula | e2676 | ||
| Anterior Cingulate Cortex (ACC) | e2676 | ||
| Prefrontal Cortex | e2676 | ||
| Other Brain Areas | e2676 | ||
| Efferent Mechanisms—Peripheral | e2678 | ||
| Efferent Mechanisms—Central | e2679 | ||
| Diagnosis | e2680 | ||
| History and Physical Examination | e2680 | ||
| Physical Examination | e2681 | ||
| Clinical Testing | e2681 | ||
| Disorders of Defecation | e2682 | ||
| Normal Defecation Patterns | e2682 | ||
| Functional Anatomy of Large Intestine, Rectum, and Anus | e2682 | ||
| Colorectal Motility and Defecation | e2682 | ||
| The Intrinsic Nervous System | e2682 | ||
| The Extrinsic Nervous System | e2683 | ||
| Muscle Contractions and Colorectal Motility | e2683 | ||
| CNS and the Gut | e2683 | ||
| Patient Evaluation | e2684 | ||
| History. | e2684 | ||
| Neurologic Examination | e2684 | ||
| Clinical Studies | e2684 | ||
| Differential Diagnosis | e2684 | ||
| Management | e2685 | ||
| References | e2685 | ||
| 156 Poisoning and Drug-Induced Neurologic Diseases | e2689 | ||
| Introduction | e2689 | ||
| Emergency Evaluation | e2689 | ||
| Management | e2690 | ||
| Testing | e2690 | ||
| Other Ancillary Testing | e2691 | ||
| Neurologic Examination | e2691 | ||
| Common Toxidromes | e2693 | ||
| Specific Agents | e2696 | ||
| Poisons and Environmental Toxins | e2696 | ||
| Biologic Toxins | e2696 | ||
| Snake Venom. | e2696 | ||
| Scorpion Envenomation. | e2696 | ||
| Tick Bites. | e2696 | ||
| Botulism. | e2696 | ||
| Tetanus. | e2697 | ||
| Insecticides | e2697 | ||
| Nerve Agents | e2697 | ||
| Lindane. | e2697 | ||
| Insect Repellents. | e2698 | ||
| Metals | e2698 | ||
| Lead. | e2698 | ||
| Mercury. | e2698 | ||
| Thallium. | e2698 | ||
| Arsenic. | e2699 | ||
| Drugs of Abuse | e2699 | ||
| Cocaine | e2699 | ||
| Opiates | e2699 | ||
| Cannabis | e2699 | ||
| Gamma-Hydroxybutyrate | e2700 | ||
| Hydrocarbons | e2700 | ||
| Nitrous Oxide | e2700 | ||
| Hallucinogens | e2700 | ||
| Emerging Drugs of Abuse | e2700 | ||
| Amphetamines | e2700 | ||
| “Ecstasy” | e2701 | ||
| Ethanol | e2701 | ||
| Barbiturates | e2701 | ||
| Benzodiazepines | e2701 | ||
| Baclofen | e2701 | ||
| Other Sedatives | e2701 | ||
| Antipsychotic Agents (Neuroleptics) | e2701 | ||
| Antidepressants | e2702 | ||
| Lithium | e2702 | ||
| Salicylates | e2702 | ||
| Acetaminophen | e2703 | ||
| Stimulants | e2703 | ||
| Theophylline | e2703 | ||
| Diphenhydramine | e2703 | ||
| Atropine and Related Alkaloids | e2703 | ||
| Drugs Used in Organ Transplantation | e2704 | ||
| Cyclosporine | e2704 | ||
| Muromonab-CD3 (OKT3) | e2704 | ||
| Tacrolimus (FK-506) | e2704 | ||
| Antibiotics | e2704 | ||
| Chloramphenicol | e2704 | ||
| Nitrofurantoin | e2704 | ||
| Aminoglycosides | e2704 | ||
| Beta-Lactam Antibiotics | e2704 | ||
| Antiviral Agents | e2704 | ||
| Antineoplastic Drugs | e2705 | ||
| Vinca Alkaloids | e2705 | ||
| Methotrexate | e2705 | ||
| L-Asparaginase | e2705 | ||
| Platinum Agents | e2705 | ||
| Cytosine Arabinoside | e2706 | ||
| Cyclophosphamide and Ifosfamide | e2706 | ||
| Other Agents Used in Cancer Chemotherapy | e2706 | ||
| Steroids | e2706 | ||
| Adverse Drug Reactions | e2706 | ||
| Method of Preparation | e2706 | ||
| Technique of Drug Administration | e2706 | ||
| Pharmacogenetic Susceptibility | e2707 | ||
| Drug Interactions | e2707 | ||
| Neuroteratology | e2707 | ||
| Concluding Remarks and Additional Sources | e2709 | ||
| Internet Sites | e2710 | ||
| References | e2710 | ||
| 157 Neurologic Disorders in Children with Heart Disease | e2723 | ||
| List of Abbreviations | e2723 | ||
| Introduction | e2723 | ||
| Anatomic Considerations | e2723 | ||
| Fetal Circulation | e2723 | ||
| Assessment of Fetal Circulation | e2726 | ||
| Transitional Circulation | e2727 | ||
| Postnatal Circulation | e2728 | ||
| Heart Surgeries | e2728 | ||
| Perioperative Considerations | e2728 | ||
| White Matter Injury | e2728 | ||
| Arterial Ischemic Stroke | e2729 | ||
| Intracranial Hemorrhage | e2730 | ||
| Infectious Endocarditis | e2730 | ||
| Cerebral Sinovenous Thrombosis | e2731 | ||
| Seizures | e2731 | ||
| Neurologic Sequelae of Heart Failure | e2731 | ||
| Mechanical Circulatory Support Devices | e2732 | ||
| Extracorporeal Membrane Oxygenation (ECMO) | e2732 | ||
| Neurologic Management Specific to Cardiac Care | e2732 | ||
| Peripheral Neuromuscular Injury | e2732 | ||
| Plexopathies | e2732 | ||
| Mononeuropathies | e2733 | ||
| Polyneuropathy and Myopathy | e2733 | ||
| Neurologic Conditions Associated With Acquired Heart Disease | e2733 | ||
| Inherited Disorders of Heart, Muscle, and Nervous System | e2733 | ||
| Genetic Disorders Associated With Cardiac Defects | e2733 | ||
| Inborn Errors of Metabolism | e2733 | ||
| Disorders of Energy Production | e2735 | ||
| Mitochondrial Fatty Acid Oxidation Defects | e2735 | ||
| Disorders of Oxidative Phosphorylation | e2735 | ||
| Storage Disorders of the Heart and Nervous System | e2735 | ||
| Glycogen Storage Diseases | e2735 | ||
| Lysosomal and Peroxisomal Storage Diseases | e2735 | ||
| Inherited Neuromuscular Disorders With Cardiac Complications | e2736 | ||
| X-Linked Muscular Dystrophies | e2736 | ||
| Myotonic Dystrophy | e2736 | ||
| Short- and Long-Term Outcomes | e2736 | ||
| Preoperative Neurologic Status | e2736 | ||
| Postoperative Neurologic Findings | e2737 | ||
| Assessment of Neurodevelopmental Outcome During Childhood | e2738 | ||
| Short-Term Outcome | e2738 | ||
| Neuromotor Development | e2740 | ||
| Cognitive Development | e2740 | ||
| Language Development | e2740 | ||
| Behavioral Outcome | e2740 | ||
| Long-Term Outcome | e2741 | ||
| Motor and Visuomotor Outcome | e2741 | ||
| Intellectual Outcome | e2741 | ||
| Language Outcome | e2741 | ||
| Higher Order Intellectual Outcome and Academic Achievement | e2742 | ||
| Behavior and Social Functions | e2742 | ||
| Adolescent and Adult Outcome | e2742 | ||
| Summary | e2743 | ||
| References | e2743 | ||
| 158 Neurologic Disorders Associated with Renal Diseases | e2748 | ||
| Renal Diseases Secondarily Affecting the Nervous System | e2748 | ||
| Acute Kidney Injury | e2748 | ||
| Sodium and Water Disorders | e2748 | ||
| Potassium Abnormalities | e2750 | ||
| Calcium and Magnesium Abnormalities | e2750 | ||
| Chronic Kidney Disease | e2752 | ||
| Uremic Encephalopathy | e2752 | ||
| Clinical Features of Uremia. | e2752 | ||
| Pathophysiology of Uremia. | e2752 | ||
| Diagnostic Considerations in Patients With Uremia. | e2753 | ||
| Management of Uremic Encephalopathy. | e2755 | ||
| Congenital Uremic Encephalopathy | e2755 | ||
| Stroke and Vasculopathy | e2756 | ||
| Dialysis-Associated Complications | e2756 | ||
| Dialysis Disequilibrium Syndrome | e2757 | ||
| Dialysis-Associated Seizures | e2757 | ||
| Aluminum Toxicity and Encephalopathy (Including Dialysis Dementia) | e2757 | ||
| Vitamin and Cofactor Deficiencies | e2758 | ||
| Intracranial Hemorrhage | e2758 | ||
| Milder Forms of Encephalopathy | e2758 | ||
| Uremic Peripheral Polyneuropathy | e2759 | ||
| Uremic Myopathy (Myopathy of Chronic Kidney Disease) | e2760 | ||
| Malnutrition | e2761 | ||
| Endocrinopathy | e2761 | ||
| Complications Associated With Renal Transplantation | e2761 | ||
| Infection | e2761 | ||
| Malignancy | e2762 | ||
| Drugs | e2762 | ||
| Hypertension | e2763 | ||
| Hypertensive Encephalopathy | e2763 | ||
| Clinical Features of Hypertensive Encephalopathy. | e2763 | ||
| Pathophysiology of Hypertensive Encephalopathy. | e2763 | ||
| Diagnostic Considerations in Patients With Hypertensive Encephalopathy. | e2764 | ||
| Outcomes From Hypertensive Encephalopathy. | e2764 | ||
| Posterior Reversible Encephalopathy Syndrome | e2764 | ||
| Clinical Features of Posterior Reversible Encephalopathy Syndrome. | e2764 | ||
| Diagnostic Considerations in Patients With Posterior Reversible Encephalopathy Syndrome. | e2765 | ||
| Management of Posterior Reversible Encephalopathy Syndrome. | e2765 | ||
| Diseases Affecting Both Kidney and Nervous System | e2766 | ||
| Thrombotic Thrombocytopenic Purpura | e2766 | ||
| Hemolytic-Uremic Syndrome | e2767 | ||
| Treatment | e2768 | ||
| Vasculitic Diseases With Neurologic-Renal Presentations | e2768 | ||
| Hepatorenal Syndrome | e2768 | ||
| Amyloidosis | e2769 | ||
| Metabolic Diseases Producing Generalized Renal and Neurologic Dysfunction | e2771 | ||
| Selective Tubular Dysfunction | e2771 | ||
| Proximal Renal Tubular Acidosis | e2771 | ||
| Nephropathic Cystinosis | e2772 | ||
| Neurologic Drugs That May Affect Renal Function in Individuals With Normal Kidneys | e2773 | ||
| Drug Therapy in Renal Disease | e2775 | ||
| Drug-Induced Encephalopathy in Renal Failure | e2776 | ||
| Treatment of Seizures Associated With Renal Disease | e2776 | ||
| Concerns About Specific Antiseizure Medication Use in the Setting of Renal Failure | e2776 | ||
| Phenytoin. | e2776 | ||
| Valproate. | e2777 | ||
| Barbiturates. | e2777 | ||
| Carbamazepine. | e2777 | ||
| Oxcarbazepine. | e2777 | ||
| Ethosuximide. | e2777 | ||
| Levetiracetam. | e2777 | ||
| Zonisamide. | e2777 | ||
| Lamotrigine. | e2777 | ||
| Gabapentin. | e2777 | ||
| Benzodiazepines. | e2778 | ||
| Kidney Stones | e2778 | ||
| Other Neurologic Drugs | e2778 | ||
| References | e2778 | ||
| 159 Neurologic Disorders Associated with Gastrointestinal Diseases | e2785 | ||
| Introduction | e2785 | ||
| Disorders Associated With Gastrointestinal Disease | e2785 | ||
| The Enteric Nervous System | e2785 | ||
| Dysphagia. | e2786 | ||
| Episodic Gastrointestinal Disease | e2786 | ||
| Neurologic Mechanisms of Recurrent Abdominal Pain and Irritable Bowel Syndrome | e2786 | ||
| Cyclic Vomiting Syndrome and Recurrent Abdominal Pain | e2787 | ||
| Irritable Bowel Syndrome | e2787 | ||
| Infantile Colic | e2788 | ||
| Anatomic Gastrointestinal Disorders | e2788 | ||
| Gastroesophageal Reflux | e2788 | ||
| Intestinal Pseudoobstruction | e2789 | ||
| Hirschsprung Disease | e2790 | ||
| Other Neurocristopathy Syndromes | e2791 | ||
| Other Pseudoobstruction Syndromes | e2792 | ||
| Mitochondrial Neurogastrointestinal Encephalopathy. | e2792 | ||
| Intussusception. | e2792 | ||
| Malabsorption Syndromes | e2792 | ||
| Celiac Disease | e2793 | ||
| Short Bowel Syndrome | e2794 | ||
| Inflammatory Bowel Disease | e2794 | ||
| Enteric Infections | e2795 | ||
| Escherichia coli | e2795 | ||
| Campylobacter jejuni | e2795 | ||
| Nipah Virus | e2796 | ||
| Infant Botulism | e2796 | ||
| Shigellosis | e2796 | ||
| Rotavirus Infection | e2797 | ||
| The Human Microbiome and Neurologic Disorders in Children | e2797 | ||
| Development and Role of the Human Microbiota | e2797 | ||
| The Prenatal Period. | e2797 | ||
| The Postnatal Period. | e2797 | ||
| Childhood/Adolescence. | e2797 | ||
| Disease States and the Influences of the Microbiota and Microbiome | e2798 | ||
| The Microbiota and Immune-Mediated Nervous System Disorders. | e2798 | ||
| Multiple Sclerosis. | e2798 | ||
| Guillain–Barré Syndrome. | e2798 | ||
| The Microbiota and Nonimmune-Mediated CNS Disorders | e2798 | ||
| Autistic Spectrum Disorder. | e2798 | ||
| Attention Deficit Hyperactivity Disorder. | e2798 | ||
| Cerebral Palsy. | e2799 | ||
| Epilepsy. | e2799 | ||
| Intellectual Disability. | e2799 | ||
| Depression, Anxiety, Stress, and Schizophrenia. | e2799 | ||
| Therapeutic Implications | e2799 | ||
| Other Gastrointestinal Diseases | e2799 | ||
| Whipple’s Disease | e2799 | ||
| Turcot’s Syndrome | e2800 | ||
| Porphyria | e2800 | ||
| Neurologic Disorders Associated With Hepatobiliary Diseases | e2801 | ||
| Hepatitis | e2801 | ||
| Hepatic Encephalopathy | e2802 | ||
| Neurologic Abnormalities | e2802 | ||
| Fulminant Liver Failure | e2802 | ||
| Cognitive and Behavioral Abnormalities | e2803 | ||
| Minimal Hepatic Encephalopathy | e2803 | ||
| Laboratory Tests | e2803 | ||
| Neuropathology and Pathophysiology | e2804 | ||
| Treatment | e2805 | ||
| Prognosis | e2806 | ||
| Neurologic Abnormalities Associated With Liver Transplantation | e2806 | ||
| Neurologic Abnormalities in Primary Biliary Cirrhosis | e2806 | ||
| Reye’s Syndrome | e2807 | ||
| Hepatolenticular Degeneration: Wilson’s Disease | e2807 | ||
| Progressive Hepatocerebral Disease | e2810 | ||
| Bilirubin Encephalopathy: Kernicterus | e2810 | ||
| Pathophysiology of Hyperbilirubinemia. | e2810 | ||
| Neuropathology. | e2811 | ||
| Clinical Manifestations. | e2811 | ||
| Laboratory Testing. | e2812 | ||
| Management. | e2812 | ||
| References | e2812 | ||
| 160 Counseling Children with Neurologic Disorders and Their Families | e2823 | ||
| Introduction | e2823 | ||
| The Clinician–Patient Relationship | e2823 | ||
| Communication Skills | e2823 | ||
| Nonverbal Communication | e2823 | ||
| Conveying Empathy | e2824 | ||
| Providing Information | e2824 | ||
| Specific Challenges | e2827 | ||
| Low Health Literacy | e2827 | ||
| Family Discord | e2827 | ||
| Alternate Belief Systems | e2827 | ||
| Spirituality | e2827 | ||
| Difficult Patients | e2828 | ||
| Uncertain Test Results | e2828 | ||
| Terminal Illnesses | e2829 | ||
| Conclusion | e2829 | ||
| References | e2829 | ||
| 161 Approaches to Personalized Medicine in Pediatric Neurology | e2831 | ||
| Introduction | e2831 | ||
| Genomic Diagnosis | e2831 | ||
| Genetic Contribution to Disease | e2831 | ||
| Genetic and Genomic Variants and Disease | e2832 | ||
| Therapeutics | e2833 | ||
| Targeted Treatment | e2833 | ||
| Treatment of Rare Mendelian Disorders | e2833 | ||
| Disease Stratification | e2834 | ||
| Pharmacogenetics | e2834 | ||
| Prevention | e2835 | ||
| Newborn Screening | e2835 | ||
| Risk Assessment | e2835 | ||
| Future Prospects | e2836 | ||
| Genome Sequencing | e2836 | ||
| Patient Engagement | e2837 | ||
| Final Comments | e2837 | ||
| References | e2837 | ||
| 162 Pediatric Neurorehabilitation Medicine | e2839 | ||
| Introduction | e2839 | ||
| Mechanisms Underlying Functional Recovery in the Nervous System | e2839 | ||
| Resolution of Temporary Dysfunction | e2840 | ||
| Plasticity of the Nervous System | e2840 | ||
| Reorganization of Neuronal Connections | e2840 | ||
| Functional Recovery Through Adaptation | e2840 | ||
| Principles of Pediatric Neurorehabilitation | e2841 | ||
| Medical Aspects of Acute Pediatric Rehabilitation Management | e2841 | ||
| Comprehensive Pediatric Rehabilitation Programs | e2842 | ||
| Rehabilitation Treatment of Motor Impairment | e2843 | ||
| Overview | e2843 | ||
| Treatment of Spasticity | e2843 | ||
| Rehabilitation Therapy | e2843 | ||
| Oral Medications | e2844 | ||
| Neuromuscular Blockade: Alcohol, Phenol, and Botulinum Toxin Injections | e2846 | ||
| Intrathecal Baclofen Therapy | e2846 | ||
| Selective Dorsal Rhizotomy | e2847 | ||
| Orthopedic Surgery | e2847 | ||
| Treatment of Dystonia and Other Hyperkinetic Movement Disorders | e2847 | ||
| Acquired Brain Injury | e2848 | ||
| Behavioral Disturbances | e2848 | ||
| Communication and Cognitive Deficits | e2848 | ||
| Postinjury Seizures | e2849 | ||
| Pediatric Stroke | e2849 | ||
| Novel Rehabilitation Strategies—Overview | e2849 | ||
| Practice-Based Therapies—Constraint Induced Movement Therapy(CIMT) and Robot-Assisted Therapy | e2849 | ||
| Practice-Based Therapies to Improve Nonmotor Function | e2850 | ||
| Stimulation of the Nervous System to Improves Stroke Recovery | e2850 | ||
| Medications to Improve Stroke Recovery | e2850 | ||
| Spinal Cord Injury | e2851 | ||
| Medical Issues | e2851 | ||
| Rehabilitation Strategies | e2852 | ||
| Future Directions | e2853 | ||
| References | e2853 | ||
| 163 Pain Management and Palliative Care | e2856 | ||
| Pain Management | e2856 | ||
| Introduction | e2856 | ||
| Historical Background | e2856 | ||
| Physiology | e2856 | ||
| Developmental Differences | e2856 | ||
| Clinical Assessment | e2857 | ||
| Management | e2857 | ||
| Types of Pain Medications | e2858 | ||
| Aspirin, Acetaminophen, and NSAIDs | e2858 | ||
| Opioids | e2859 | ||
| Procedural Sedation and Analgesia | e2859 | ||
| Analgesia | e2860 | ||
| Sedation | e2860 | ||
| Types of Pain | e2860 | ||
| Neuropathic Pain | e2860 | ||
| Pain in Children With Significant Neurologic Impairment | e2861 | ||
| Migraine and Headache | e2861 | ||
| Summary | e2861 | ||
| Palliative Care | e2861 | ||
| Introduction | e2861 | ||
| Historical Background | e2861 | ||
| Definitions of Palliative Care | e2862 | ||
| Components of Palliative Care | e2862 | ||
| Identifying the Need | e2862 | ||
| Transition in Goals of Care | e2863 | ||
| Levels of Care | e2863 | ||
| Communication | e2864 | ||
| Healthcare Decision Making | e2864 | ||
| Persistent Vegetative State | e2865 | ||
| Environment for Death and Dying | e2865 | ||
| Support During Dying | e2865 | ||
| Assessment and Treatment of Symptoms | e2865 | ||
| Developmental, Emotional, and Spiritual Concerns | e2865 | ||
| Bereavement | e2865 | ||
| Follow-Up Conference | e2867 | ||
| Barriers to Palliative Care | e2867 | ||
| Summary | e2867 | ||
| References | e2867 | ||
| 164 Ethical Issues in Child Neurology | e2869 | ||
| Introduction | e2869 | ||
| Theoretical Approaches to Ethics | e2869 | ||
| Utilitarianism | e2869 | ||
| Deontology | e2870 | ||
| Common Morality and Natural Law | e2870 | ||
| Principlism | e2870 | ||
| Virtue or Character Ethics | e2871 | ||
| Ethics of Care | e2872 | ||
| Casuistry | e2872 | ||
| Spirituality | e2872 | ||
| Ethical Responsibilities | e2873 | ||
| Duties as a Physician | e2873 | ||
| Duties as a Pediatrician | e2874 | ||
| Duties as a Neurologist | e2875 | ||
| Research | e2875 | ||
| Ethical Problems | e2875 | ||
| Personhood | e2875 | ||
| Euthanasia | e2876 | ||
| Organ Donation | e2877 | ||
| Perfection and Neuroethics | e2877 | ||
| Synthesis | e2878 | ||
| References | e2879 | ||
| 165 Transitional Care for Children with Neurologic Disorders | e2881 | ||
| Introduction | e2881 | ||
| Barriers to Effective Transition | e2881 | ||
| Disorders that May be Dangerous to Society if Untreated | e2882 | ||
| Disorders that are Potentially Lethal but Have Emerging Treatments Leading to Increased Survival Well into Adulthood | e2883 | ||
| Disorders that Are Problematic and “Static” in Childhood but Progress in Adulthood | e2884 | ||
| Disorders Diagnosed in Childhood with Their Most Serious Manifestations in Adulthood | e2884 | ||
| Disorders that are Cured in Childhood but have Neurologic Sequelae that Persist into Adulthood | e2884 | ||
| Disorders that May/May Not Remit in Childhood but Have Persistent Effects on Adult Social Function | e2885 | ||
| Disorders that May be Uncomfortable for Adult Care | e2885 | ||
| Disorders in Childhood Treated in a Way that is Difficult to Replicate in Adult Medicine | e2885 | ||
| What Happens if Transition/Transfer is Poorly Managed? | e2885 | ||
| Models of Care for Transition | e2886 | ||
| 1. Abandonment of Specialized Care or “Fend for Yourself” | e2886 | ||
| 2. Referral to an Adult Rehabilitation Program | e2886 | ||
| 3. Referral to an Adult Neurologist or Other Specialist | e2886 | ||
| 4. Referral to the United States Model of an Internal Medicine/Pediatric Subspecialist | e2887 | ||
| 5. Referral to a Nurse-Run Transition Clinic | e2887 | ||
| 6. A Joint Pediatric/Adult Transition Clinic | e2887 | ||
| 7. Internet-Based Support Groups | e2887 | ||
| Conclusions | e2887 | ||
| References | e2888 | ||
| 166 Practice Guidelines in Pediatric Neurology | e2890 | ||
| Introduction | e2890 | ||
| History | e2890 | ||
| Development Process | e2891 | ||
| The American Academy of Neurology Process | e2894 | ||
| Choosing Topics and Panelists | e2894 | ||
| Collecting and Grading Evidence | e2894 | ||
| Drawing Conclusions | e2896 | ||
| Writing Recommendations | e2896 | ||
| Processes Used by Other Groups | e2897 | ||
| Law and Ethics | e2899 | ||
| Guideline Utilization | e2899 | ||
| Conclusion | e2899 | ||
| References | e2900 | ||
| 167 Special Education Law as it Relates to Children with Neurologic Disorders | e2903 | ||
| History | e2903 | ||
| Special Education Case Law | e2903 | ||
| Federal Legislation | e2905 | ||
| Individuals with Disabilities Education Act (IDEA) | e2905 | ||
| Health Insurance Portability and Accountability Act of 1996 (HIPAA) | e2906 | ||
| No Child Left Behind Act (NCLB) | e2906 | ||
| Case Studies and the Law | e2907 | ||
| International Special Education | e2907 | ||
| Canada | e2907 | ||
| China | e2907 | ||
| India | e2908 | ||
| Israel | e2908 | ||
| Italy | e2908 | ||
| Japan | e2908 | ||
| References | e2908 | ||
| 168 Measurement of Health Outcomes in Pediatric Neurologic Disorders | e2910 | ||
| Outcome Measures: Purpose, Properties, Prioritizing | e2910 | ||
| ICF as a Framework for Outcome Measurement | e2911 | ||
| Child’s Age and Stage as a Determinant of Measurement Focus | e2913 | ||
| New Directions in Outcome Measurement | e2915 | ||
| References | e2916 | ||
| 169 The Influence of Computer Resources on Child Neurology | e2918 | ||
| Clinical Discussions and Groups | e2918 | ||
| Authoritative Narrative Content | e2923 | ||
| Wikis | e2924 | ||
| Diagnostic Decision Support | e2924 | ||
| Treatment Decision Support | e2925 | ||
| Interoperability | e2926 | ||
| Education | e2926 | ||
| Dissemination of Original Research | e2927 | ||
| Hardware | e2927 | ||
| Perspectives | e2927 | ||
| Conflict of Interest | e2928 | ||
| References | e2928 | ||
| 170 Education and Training of Child Neurologists and Workforce Issues | e2929 | ||
| Introduction | e2929 | ||
| Historical Aspects | e2929 | ||
| Current Approaches | e2930 | ||
| Education and Training Preceding Child Neurology | e2932 | ||
| Current Workforce Issues | e2933 | ||
| Future Workforce Issues | e2934 | ||
| References | e2934 | ||
| Appendix B | e2935 | ||
| Vanderbilt Assessment Scales | e2935 | ||
| Examples of Local Guidelines for Hypothermia and Stroke Management | e2945 |