BOOK
Volpe's Neurology of the Newborn E-Book
Joseph J. Volpe | Terrie E Inder | Basil T. Darras | Linda S. de Vries | Adre J du Plessis | Jeffrey Neil | Jeffrey M Perlman
(2017)
Additional Information
Book Details
Abstract
A clear, engaging writing style, hundreds of full-color images, and new information throughout make Volpe’s Neurology of the Newborn, 6th Edition, an indispensable resource for those who provide care for neonates with neurological conditions. World authority Dr. Joseph Volpe, along with Dr. Terrie E. Inder and other distinguished editors, continue the unparalleled clarity and guidance you’ve come to expect from the leading reference in the field – keeping you up to date with today’s latest advances in diagnosis and management, as well as the many scientific and technological advances that are revolutionizing neonatal neurology.
- Features a brand new, full-color design with hundreds of new figures, tables, algorithms, and micrographs.
- Includes two entirely new chapters: Neurodevelopmental Follow-Up and Stroke in the Newborn; a new section on Neonatal Seizures; and an extensively expanded section on Hypoxic-Ischemia and Other Disorders.
- Showcases the experience and knowledge of a new editorial team, led by Dr. Joseph Volpe and Dr. Terrie E. Inder, Chair of the Department of Pediatric Newborn Medicine at Brigham and Women’s Hospital, all of whom bring a wealth of insight to this classic text.
- Offers comprehensive updates from cover to cover to reflect all of the latest information regarding the development of the neural tube; prosencephalic development; congenital hydrocephalus; cerebellar hemorrhage; neuromuscular disorders and genetic testing; and much more.
- Uses an improved organization to enhance navigation.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| IFC_Expert Consult page | IFC-1 | ||
| Volpe's Neurology of the Newborn | i | ||
| Copyright Page | iv | ||
| Dedication | v | ||
| Contributors | vi | ||
| Preface to the Sixth Edition | viii | ||
| Preface to the First Edition | xi | ||
| Acknowledgments | xii | ||
| Table Of Contents | xiii | ||
| Video Contents | xv | ||
| Unit I Human Brain Development | 1 | ||
| 1 Neural Tube Development | 3 | ||
| Normal Development of the Fundamental Central Neuroaxis | 3 | ||
| Milestones of Major Events | 3 | ||
| Formation of the Neural Tube | 4 | ||
| Primary Neurulation | 4 | ||
| Cellular and Molecular Mechanisms of Primary Neurulation. | 5 | ||
| Secondary Neurulation (Caudal Neural Tube Formation) | 6 | ||
| Disorders of Craniospinal Development | 6 | ||
| Craniocerebral Dysraphism (Box 1.3) | 6 | ||
| Craniorachischisis Totalis | 6 | ||
| Anatomical Abnormality. | 6 | ||
| Anencephaly | 7 | ||
| Anatomical Abnormality. | 7 | ||
| Timing and Clinical Aspects. | 7 | ||
| Diagnosis. | 8 | ||
| Encephaloceles | 9 | ||
| Anatomical Abnormality. | 9 | ||
| Timing and Clinical Aspects. | 9 | ||
| Diagnosis. | 10 | ||
| Management and Outcome. | 10 | ||
| Spinal Dysraphism | 10 | ||
| Disorders of Primary Neurulation in the Spine | 11 | ||
| Myelomeningocele | 12 | ||
| Anatomical Abnormality. | 12 | ||
| Timing. | 13 | ||
| Etiological Considerations. | 13 | ||
| Clinical Aspects. | 14 | ||
| Neurological Features. | 14 | ||
| Associated Anomalies and Putative Mechanisms | 15 | ||
| Chiari Type II Malformation. | 15 | ||
| Hydrocephalus. | 16 | ||
| Other Central Nervous System Anomalies. | 17 | ||
| Diagnosis. | 17 | ||
| Management. | 18 | ||
| Primary Prevention. | 18 | ||
| Management After Fetal Diagnosis. | 20 | ||
| Management of Labor and Delivery. | 22 | ||
| Postnatal Management. | 22 | ||
| Early Postnatal Management. | 22 | ||
| Long-Term Management of Associated Lesions | 22 | ||
| Management of Hydrocephalus. | 22 | ||
| Management of Brain Stem Dysfunction Associated With the Chiari Type II Malformation. | 22 | ||
| Management of Orthopedic, Bowel, and Urinary Tract Complications. | 23 | ||
| Results of Therapy. | 23 | ||
| Conclusions. | 24 | ||
| Myeloschisis. | 24 | ||
| Anatomical Abnormality. | 24 | ||
| Timing. | 25 | ||
| Disorders of Secondary Neurulation | 25 | ||
| Occult (Closed) Spinal Dysraphism | 25 | ||
| Anatomical Abnormality. | 25 | ||
| Timing. | 26 | ||
| Myelocystocele | 26 | ||
| Anatomical Abnormality. | 26 | ||
| Meningoceles | 27 | ||
| Anatomical Abnormality. | 27 | ||
| Diastematomyelia. | 28 | ||
| Other Lesions (See Box 1.9). | 28 | ||
| Relative Frequency. | 29 | ||
| Clinical Aspects. | 29 | ||
| Management. | 29 | ||
| Key References | 30 | ||
| References | 33.e1 | ||
| 2 Prosencephalic Development | 34 | ||
| Normal Prosencephalic Development | 34 | ||
| Disorders of Prosencephalic Development | 35 | ||
| Disorders of Prosencephalic Formation | 37 | ||
| Aprosencephaly and Atelencephaly | 37 | ||
| Unit II Neurological Evaluation | 189 | ||
| 9 Neurological Examination | 191 | ||
| Normal Neurological Examination | 191 | ||
| Estimation of Gestational Age | 191 | ||
| Head: External Characteristics and Rate of Growth | 192 | ||
| External Characteristics | 192 | ||
| Skin: Sturge-Weber Syndrome. | 192 | ||
| Head Size and Shape. | 192 | ||
| Rate of Head Growth | 194 | ||
| Level of Alertness | 197 | ||
| Cranial Nerves | 198 | ||
| Olfaction (I) | 198 | ||
| Olfactory Discriminations. | 198 | ||
| Vision (II) | 198 | ||
| Visual Acuity, Color, and Other Discriminations. | 198 | ||
| Optic Fundi (II) | 199 | ||
| Pupils (III) | 199 | ||
| Extraocular Movements (III, IV, VI) | 199 | ||
| Facial Sensation and Masticatory Power (V) | 200 | ||
| Facial Motility (VII) | 200 | ||
| Audition (VIII) | 200 | ||
| Auditory Acuity, Localization, and Discriminations. | 200 | ||
| Sucking and Swallowing (V, VII, IX, X, XII) | 201 | ||
| Sternocleidomastoid Function (XI) | 201 | ||
| Tongue Function (XII) | 201 | ||
| Taste (VII, IX) | 201 | ||
| Motor Examination | 201 | ||
| Tone and Posture | 202 | ||
| Developmental Aspects. | 202 | ||
| Preference of Head Position. | 202 | ||
| Motility and Power | 202 | ||
| Tendon Reflexes and Plantar Response | 203 | ||
| Tendon Reflexes. | 203 | ||
| Plantar Response. | 203 | ||
| Primary Neonatal Reflexes | 204 | ||
| Moro Reflex | 204 | ||
| Palmar Grasp | 204 | ||
| Tonic Neck Response | 204 | ||
| Placing and Stepping | 205 | ||
| Sensory Examination | 205 | ||
| Abnormal Neurological Features | 205 | ||
| Abnormalities of Level of Alertness | 205 | ||
| Abnormalities of Cranial Nerves | 206 | ||
| Olfaction | 206 | ||
| Vision | 206 | ||
| Optic Fundi | 206 | ||
| Optic Disc Hypoplasia or Atrophy. | 206 | ||
| Retinal and Preretinal Hemorrhages. | 206 | ||
| Chorioretinitis. | 207 | ||
| Retinopathy of Prematurity. | 207 | ||
| Retinoblastoma. | 207 | ||
| Pupils | 207 | ||
| Bilateral Increase in Pupillary Size. | 207 | ||
| Bilateral Decrease in Pupillary Size. | 207 | ||
| Unilateral Decrease in Pupillary Size. | 207 | ||
| Unilateral Increase in Pupillary Size. | 207 | ||
| Extraocular Movements | 208 | ||
| Abnormal Eye Position. | 208 | ||
| Limitation of Eye Movement. | 209 | ||
| Abnormal Eye Movements. | 209 | ||
| Facial Sensation and Masticatory Power | 209 | ||
| Facial Motility | 210 | ||
| Cerebrum. | 210 | ||
| Nucleus. | 210 | ||
| Nerve. | 210 | ||
| Neuromuscular Junction. | 211 | ||
| Muscle. | 211 | ||
| Audition | 211 | ||
| Genetic Deafness. | 211 | ||
| Bilirubin and Other Toxins. | 211 | ||
| Congenital and Neonatal Infections. | 212 | ||
| Defects of Head and Neck. | 212 | ||
| Low Birth Weight. | 212 | ||
| Term Infant, Hypoxia-Ischemia. | 213 | ||
| Sucking and Swallowing | 213 | ||
| Cerebrum. | 213 | ||
| Nuclei. | 214 | ||
| Nerve. | 214 | ||
| Neuromuscular Junction. | 214 | ||
| Muscle Involvement. | 214 | ||
| Sternocleidomastoid Function | 214 | ||
| Tongue Function | 214 | ||
| Abnormalities of the Motor Examination | 214 | ||
| Hypertonia | 214 | ||
| Hypotonia and Weakness | 215 | ||
| Focal Cerebral. | 215 | ||
| Parasagittal Cerebral. | 215 | ||
| Periventricular Cerebral (Bilateral). | 215 | ||
| Spinal Cord. | 215 | ||
| Lower Motor Neuron. | 215 | ||
| Nerve Roots. | 215 | ||
| Peripheral Nerve. | 215 | ||
| Neuromuscular Junction. | 215 | ||
| Muscle. | 215 | ||
| Tendon Reflexes and Plantar Response | 215 | ||
| Abnormal Movements | 215 | ||
| Myotonia. | 216 | ||
| Fasciculation. | 216 | ||
| Jitteriness. | 216 | ||
| Excessive Startles. | 216 | ||
| Movement Disorder With Bronchopulmonary Dysplasia. | 216 | ||
| Abnormalities of Primary Neonatal Reflexes | 216 | ||
| Moro Reflex | 216 | ||
| Tonic Neck Reflex | 216 | ||
| Palmar Grasp | 216 | ||
| Abnormalities of the Sensory Examination | 216 | ||
| Value of the Neonatal Neurological Examination | 217 | ||
| Evaluation of Cerebral Function | 217 | ||
| Role in Estimating Prognosis | 217 | ||
| Key References | 218 | ||
| References | 221.e1 | ||
| 10 Specialized Neurological Studies | 222 | ||
| Cerebrospinal Fluid Examination | 222 | ||
| White Blood Cell, Protein, and Glucose Concentrations | 222 | ||
| Red Blood Cell Counts in High-Risk Newborns | 222 | ||
| Neurophysiological Studies | 223 | ||
| Brain-Stem Auditory Evoked Responses | 223 | ||
| Major Waveforms and Anatomical Correlates | 224 | ||
| Developmental Changes | 224 | ||
| Detection of Disorders of the Auditory Pathways | 224 | ||
| Hearing Screening | 225 | ||
| Visual Evoked Responses | 225 | ||
| Cortical Response | 225 | ||
| Developmental Changes | 226 | ||
| Detection of Disorders of the Visual Pathway | 226 | ||
| Electroencephalogram | 227 | ||
| Normal Development | 227 | ||
| 27 to 28 Weeks. | 227 | ||
| 29 to 30 Weeks. | 227 | ||
| 31 to 33 Weeks. | 229 | ||
| 34 to 35 Weeks. | 229 | ||
| 36 to 37 Weeks. | 230 | ||
| 38 to 40 Weeks. | 230 | ||
| Clinical Application | 230 | ||
| Disordered Development. | 230 | ||
| Depression and Lack of Differentiation. | 231 | ||
| Excessively Discontinuous Activity. | 231 | ||
| Electrocerebral Silence. | 233 | ||
| Unilateral Depression of Background Activity. | 233 | ||
| Periodic Discharges. | 233 | ||
| Multifocal Sharp Waves. | 234 | ||
| Central Positive Sharp Waves. | 234 | ||
| Rhythmic Generalized or Focal Alpha Frequency Activity. | 234 | ||
| Hypsarrhythmia. | 234 | ||
| Value of Serial EEG. | 235 | ||
| Amplitude-Integrated Electroencephalogram | 235 | ||
| Methodology and Rationale | 235 | ||
| Recording | 235 | ||
| Clinical Applications | 238 | ||
| Assessment of Asphyxiated Term Infants. | 238 | ||
| Detection of Seizures. | 238 | ||
| Other Applications. | 238 | ||
| Structural Brain Imaging | 238 | ||
| Ultrasonography | 239 | ||
| Computed Tomography | 239 | ||
| Magnetic Resonance Imaging | 239 | ||
| T1- and T2-Weighted Imaging | 239 | ||
| Myelination. | 239 | ||
| Volumetry. | 241 | ||
| Cartography. | 243 | ||
| Sensitivity to Injury. | 244 | ||
| Diffusion Imaging. | 244 | ||
| Apparent Diffusion Coefficient. | 245 | ||
| Diffusion Tractography. | 246 | ||
| MR Angiography. | 246 | ||
| Susceptibility-Weighted Imaging. | 246 | ||
| Fetal Imaging. | 246 | ||
| MR Spectroscopy. | 246 | ||
| Functional MRI. | 247 | ||
| Near-Infrared Spectroscopy | 248 | ||
| Basic Principles and Determinations | 248 | ||
| Clinical Application | 250 | ||
| Quantitative Determinations of Oxygenated Hemoglobin, Deoxygenated Hemoglobin, and Cerebral Blood Volume in the Newborn. | 250 | ||
| Value of NRI in Specific Clinical Situations. | 250 | ||
| Magnetoencephalography | 250 | ||
| Key References | 251 | ||
| References | 254.e1 | ||
| 11 Neurodevelopmental Follow-Up | 255 | ||
| Principles and Concepts of Child Development | 255 | ||
| Life Course Development | 255 | ||
| Domains of Development | 256 | ||
| Importance of a Child’s Postnatal Experiences | 257 | ||
| Which Infants Need Follow-Up? | 257 | ||
| Models of Neurodevelopmental Follow-Up | 258 | ||
| The Timing of Follow-Up Assessments | 258 | ||
| Duration of Follow-Up | 259 | ||
| Neurodevelopmental Domains to Assess | 259 | ||
| Staff Training | 259 | ||
| Family and Cultural Considerations | 259 | ||
| Choice of Assessment Setting | 261 | ||
| Deciding Which Measure to Use | 261 | ||
| Minimizing Measurement Bias | 261 | ||
| Child Characteristics | 262 | ||
| Physical Health/Growth | 262 | ||
| Neurological | 262 | ||
| Vision and Hearing | 262 | ||
| Growth | 262 | ||
| Feeding Problems | 262 | ||
| Daily Functioning | 262 | ||
| Brain Development. | 262 | ||
| Neuromotor Function | 263 | ||
| Language Development | 267 | ||
| Cognition and Learning | 267 | ||
| Emotional and Behavioral Well-Being or Mental Health | 268 | ||
| Social Development | 269 | ||
| Parental Well-Being and Family Situation | 269 | ||
| References | 269 | ||
| Unit III Neonatal Seizures | 273 | ||
| 12 Neonatal Seizures | 275 | ||
| Pathophysiology | 275 | ||
| Mechanisms | 275 | ||
| Neuroanatomical and Neurophysiological Substrates | 275 | ||
| Neuroanatomical Features | 276 | ||
| Neurophysiological Features | 276 | ||
| Energy Metabolism | 278 | ||
| Mechanisms of Brain Injury With Seizures | 279 | ||
| Prolonged Seizures | 279 | ||
| Recurrent Seizures | 282 | ||
| Clinical Aspects | 283 | ||
| Seizure Classification | 283 | ||
| Seizure Types | 283 | ||
| Subtle Seizures. | 285 | ||
| Clonic Seizures. | 286 | ||
| Tonic Seizures. | 287 | ||
| Myoclonic Seizures. | 287 | ||
| Electroencephalographic-Only (Subclinical, Nonconvulsive, Occult) Seizures | 288 | ||
| Nonepileptic Movements | 288 | ||
| Jitteriness. | 288 | ||
| Tremors. | 289 | ||
| Nonepileptic Myoclonus. | 289 | ||
| Hyperekplexia. | 289 | ||
| Other Normal Motor Activities. | 290 | ||
| Does Absence of Electroencephalographic Seizure Activity Indicate That a Clinical Event Is Nonepileptic? | 290 | ||
| Seizure Etiology | 290 | ||
| Hypoxic-Ischemic Encephalopathy | 291 | ||
| Ischemic Stroke | 292 | ||
| Intracranial Hemorrhage | 292 | ||
| Intracranial Infection | 293 | ||
| Developmental Defects | 293 | ||
| Metabolic Disturbances | 293 | ||
| Hypoglycemia. | 294 | ||
| Hypocalcemia. | 294 | ||
| Local Anesthetic Intoxication. | 294 | ||
| Other Metabolic Disturbances. | 295 | ||
| Drug Withdrawal | 297 | ||
| Neonatal Epilepsy Syndromes | 297 | ||
| Benign Familial Neonatal Epilepsy. | 297 | ||
| Benign Nonfamilial Neonatal Convulsions. | 298 | ||
| Early Myoclonic Encephalopathy and Early Infantile Epileptic Encephalopathy (Ohtahara Syndrome). | 298 | ||
| Malignant Migrating Partial Seizures of Infancy. | 299 | ||
| Diagnosis | 299 | ||
| Electroencephalogram and Electroencephalographic Monitoring | 300 | ||
| Amplitude-Integrated EEG | 300 | ||
| Prognosis | 302 | ||
| General Outcomes | 302 | ||
| Predicting Outcome in Individual Patients | 302 | ||
| Relation of Neurological Disease to Outcome. | 302 | ||
| Relation of Electroencephalographic to Outcome. | 302 | ||
| Management | 306 | ||
| Selection of Whom to Treat | 306 | ||
| Adequacy of Treatment | 308 | ||
| Usual Sequence of Therapy | 308 | ||
| Glucose | 310 | ||
| Anticonvulsant Medications | 311 | ||
| Phenobarbital. | 311 | ||
| Phenytoin and Fosphenytoin. | 313 | ||
| Benzodiazepines (Lorazepam, Diazepam, Midazolam). | 314 | ||
| Lidocaine. | 314 | ||
| Levetiracetam. | 315 | ||
| Topiramate. | 315 | ||
| Other Drugs and Treatments. | 315 | ||
| Other Modes of Therapy | 315 | ||
| Calcium and Magnesium. | 315 | ||
| Metabolic Strategies. | 316 | ||
| Maintenance Therapy | 317 | ||
| Duration of Therapy | 317 | ||
| Key References | 318 | ||
| References | 321.e1 | ||
| Unit IV Hypoxic-Ischemic and Related Disorders | 323 | ||
| 13 Pathophysiology: | 325 | ||
| Definitions | 325 | ||
| Mode of Cell Death—Necrosis, Apoptosis, and Autophagy | 325 | ||
| Importance of the Reperfusion Period | 327 | ||
| Initiating Role of Energy Failure | 327 | ||
| Primary Mediators of Hypoxic-Ischemic Injury in the Newborn Brain—Physiological and Biochemical | 328 | ||
| Major Pathogenetic Themes | 328 | ||
| Physiological Mediators: Cerebral Blood Flow | 329 | ||
| Importance of Cerebral Blood Flow and Regulation | 329 | ||
| Cerebral Blood Flow: Knowledge From Experimental Studies in Animal Models | 329 | ||
| Fetal Circulation | 329 | ||
| Regulation of Cerebral Blood Flow: General Principles | 330 | ||
| Autoregulation. | 330 | ||
| Coupling of Cerebral Function, Metabolism, and Blood Flow. | 330 | ||
| Cerebral Blood Flow in the Perinatal Period | 331 | ||
| Ontogenetic Effects. | 331 | ||
| Regional Effects. | 331 | ||
| Cerebral Autoregulation. | 331 | ||
| Cerebral Blood Flow During and After Perinatal Asphyxia or Other Hypoxic-Ischemic Insults in Experimental Animal Models | 334 | ||
| Redistribution of Fetal Circulation. | 334 | ||
| Increase in Cerebral Blood Flow. | 335 | ||
| Loss of Vascular Autoregulation. | 335 | ||
| Hypotension and Diminished Cerebral Blood Flow. | 335 | ||
| Postasphyxial-Postischemic Effects. | 336 | ||
| Cerebral Blood Flow in the Human Newborn | 337 | ||
| Methodology | 337 | ||
| Development and Normal Values of Cerebral Blood Flow in the Human Newborn | 337 | ||
| Changes Immediately After Delivery. | 337 | ||
| Changes Beyond the Immediate Postpartum Period. | 338 | ||
| Normal Values. | 338 | ||
| Regulation in the Human Newborn. | 338 | ||
| Autoregulation. | 338 | ||
| Carbon Dioxide. | 341 | ||
| Oxygen. | 341 | ||
| Glucose. | 342 | ||
| Neuronal Activity (Seizure). | 342 | ||
| Pharmacological Agents. | 342 | ||
| Perinatal Asphyxia, Autoregulation of Cerebral Blood Flow, and Cerebral Hyperemia in the Human Newborn Infant | 342 | ||
| Impaired Autoregulation. | 342 | ||
| Impaired Vascular Reactivity and Cerebral Hyperemia. | 342 | ||
| Biochemical Mediators of Hypoxic-Ischemic Cerebral Injury—Human Newborn and Relevant Experimental Models | 343 | ||
| Normal Carbohydrate and Energy Metabolism | 343 | ||
| Glucose Uptake | 343 | ||
| Formation of Glucose-6-Phosphate | 343 | ||
| Glycogen Metabolism | 344 | ||
| Glycolysis | 344 | ||
| Citric Acid Cycle and Electron Transport Chain | 345 | ||
| Summary | 345 | ||
| Effects of Hypoxemia on Carbohydrate and Energy Metabolism | 345 | ||
| Major Changes | 345 | ||
| Maturational Vulnerability. | 346 | ||
| Regional Vulnerability. | 346 | ||
| Mechanisms | 346 | ||
| Effects of Hypoxia-Ischemia on Carbohydrate and Energy Metabolism | 347 | ||
| Major Changes | 347 | ||
| Secondary Energy Failure | 348 | ||
| Effects of Asphyxia on Carbohydrate and Energy Metabolism | 349 | ||
| Major Changes | 349 | ||
| Additional Effects of Asphyxia (vs. Solely Hypoxemia or Ischemia or Both) | 350 | ||
| Influence of Carbohydrate Status on Hypoxic-Ischemic Brain Injury | 351 | ||
| Deleterious Role of Low Brain Glucose in Perinatal Animals | 351 | ||
| Importance of Endogenous Brain Glucose Reserves. | 351 | ||
| Summary. | 351 | ||
| Deleterious Role of Abundant Brain Glucose in Adult Animals | 352 | ||
| Importance of Severe Lactic Acidosis in Brain. | 352 | ||
| Beneficial(?) Role of Abundant Brain Glucose in Perinatal Animals | 353 | ||
| Summary. | 354 | ||
| Influence of Maturation on Glucose and Energy Metabolism With Hypoxia-Ischemia | 355 | ||
| Birth as an Additive or Potentiating Factor in Hypoxic Injury | 355 | ||
| Biochemical Mechanisms of Cellular Injury in Hypoxic-Ischemic Cerebral Injury: Beyond Glucose and Energy Metabolism | 356 | ||
| Role of Accumulation of Cytosolic Calcium | 356 | ||
| Mechanisms. | 356 | ||
| Role of Free Radicals: Reactive Oxygen and Nitrogen Species | 357 | ||
| Free Radicals. | 357 | ||
| Reactive Oxygen Species. | 359 | ||
| Nitric Oxide and Reactive Nitrogen Species. | 360 | ||
| Role of Excitatory Amino Acids | 361 | ||
| Normal Features. | 361 | ||
| Role of Glutamate in Hypoxic-Ischemic Cell Death in Cultured Neurons. | 363 | ||
| Relevance of Glutamate-Induced Excitotoxicity to Hypoxic-Ischemic Injury in Vivo. | 365 | ||
| Role of Inflammation | 366 | ||
| Adult Models of Hypoxic-Ischemic Injury. | 366 | ||
| Perinatal Models of Hypoxic-Ischemic Injury. | 366 | ||
| Potentiation of Perinatal Hypoxic-Ischemic Brain Injury by Inflammation Provoked by Infection. | 367 | ||
| Inflammation and Brain Injury in Human Infants. | 368 | ||
| Rationale for Neuroprotective Approaches to Hypoxic-Ischemic Brain Injury Based on Timing and Mechanisms | 368 | ||
| Interventions for Prevention of Neurons From Hypoxic-Ischemic Injury | 368 | ||
| Decrease in Energy Depletion. | 369 | ||
| Inhibition of Glutamate Release. | 369 | ||
| Amelioration of Impairment in Glutamate Uptake. | 370 | ||
| Blockade of Glutamate Receptors. | 370 | ||
| Blockade of Free Radical Generation. | 371 | ||
| Removal of Free Radicals. | 372 | ||
| Blockade of Downstream Effects. | 372 | ||
| Inhibition of Inflammatory Effects. | 373 | ||
| The Preterm Infant—Biochemical Mechanisms of Oligodendroglial Death With Hypoxia-Ischemia | 374 | ||
| Intrinsic Vulnerability of Early Differentiating Oligodendroglia to Hypoxic-Ischemic Injury | 374 | ||
| Infection or Inflammation as an Additional or Potentiating Mechanism | 375 | ||
| Gram-Negative Infection, Endotoxin (Lipopolysaccharide), and White Matter Injury. | 375 | ||
| Innate Immunity and the Relation of Systemic Inflammation to the Brain. | 375 | ||
| Central Role of Microglia. | 376 | ||
| Hypoxia-Ischemia and Maternal/Fetal Infection: Potentiating Insults | 376 | ||
| Potentiation of Adverse Systemic and Cerebral Circulatory Effects by Combined Infection or Inflammation and Hypoxia-Ischemia. | 376 | ||
| Microglia as a Convergence Point in the Potentiation of White Matter Injury by Infection or Inflammation and Hypoxia-Ischemia. | 376 | ||
| Maturation-Dependent Intrinsic Vulnerability of Premyelinating Oligodendrocytes in Cerebral White Matter | 377 | ||
| Reactive Oxygen and Nitrogen Species Toxicity | 377 | ||
| Reactive Oxygen Species Toxicity. | 377 | ||
| Reactive Nitrogen Species Toxicity. | 379 | ||
| Excitotoxicity | 379 | ||
| Elevated Glutamate Levels in Vivo. | 379 | ||
| Sources of Glutamate. | 379 | ||
| Glutamate Receptors. | 380 | ||
| Relation of Excitotoxicity to Reactive Oxygen Species/Reactive Nitrogen Species Toxicity. | 382 | ||
| Interventions for Prevention of Oligodendrocytes From Hypoxic-Ischemic and Inflammatory Injury | 382 | ||
| Prevention of Hypoxia-Ischemia. | 382 | ||
| Prevention of Infection or Inflammation. | 382 | ||
| Prevention of Excitotoxicity. | 382 | ||
| Prevention of Free Radical Generation. | 383 | ||
| Scavenging of Free Radicals. | 383 | ||
| Blockade of Downstream Effects. | 383 | ||
| Key References | 384 | ||
| References | 388.e1 | ||
| 14 Encephalopathy of Prematurity | 389 | ||
| Neuropathological Features of the Encephalopathy of Prematurity | 389 | ||
| Periventricular Leukomalacia | 389 | ||
| Gray Matter Lesions in Encephalopathy of Prematurity | 390 | ||
| Thalamus | 390 | ||
| Cerebral Cortex | 391 | ||
| Late Migrating GABAergic Neurons | 392 | ||
| Subplate Neurons | 392 | ||
| Deficit of Neurons in the Subplate Zone and White Matter in the Encephalopathy of Prematurity. | 392 | ||
| Radial Glial Fibers | 393 | ||
| Development of Radial Glial Fibers and Astrocytes in the Cerebral White Matter in the Preterm Period. | 393 | ||
| White Matter Axons | 394 | ||
| Diffuse Axonal Injury in the Cerebral White Matter in the Encephalopathy of Prematurity. | 394 | ||
| Neural Repair | 394 | ||
| Plasticity of the Neocortex Following Hemorrhagic and Hypoxic-Ischemic Encephalopathies. | 395 | ||
| Cerebellum | 398 | ||
| Encephalopathy of Prematurity—Neuropathology in Living Infants | 398 | ||
| Cerebral White Matter Injury | 398 | ||
| Neuronal-Axonal Abnormalities | 399 | ||
| Potential Sequences of Events in the Encephalopathy of Prematurity | 399 | ||
| Preoligodendrocyte Injury, Primary | 400 | ||
| Axonal Injury, Primary | 401 | ||
| Thalamic Injury, Primary | 401 | ||
| Subplate Neuronal Injury, Primary | 402 | ||
| Late Migrating GABAergic Neuronal Injury, Primary | 402 | ||
| Cerebral Cortical Neuronal Injury, Primary | 402 | ||
| Conclusion | 402 | ||
| References | 402 | ||
| 15 Encephalopathy of Prematurity | 405 | ||
| Overview of Pathogenesis | 405 | ||
| Ischemia | 405 | ||
| Periventricular Vascular Anatomical and Physiological Factors | 405 | ||
| Cerebral Ischemia, Impaired Cerebrovascular Autoregulation, and Pressure-Passive Cerebral Circulation | 406 | ||
| Factors That Predispose to a Pressure Passive Circulation | 408 | ||
| Factors That Influence the Timing and Distribution of White Matter Injury | 409 | ||
| Clinical Factors Supporting a Role for Hypoxia-Ischemia in the Pathogenesis of White Matter Injury | 410 | ||
| Infection/Inflammation | 412 | ||
| Clinical/Epidemiological Observations | 412 | ||
| Potential Role of Proinflammatory Cytokines in White Matter Injury | 413 | ||
| Cellular Mediators of Inflammation | 414 | ||
| Infection and Hypoxia-Ischemia- Potentiating Insults | 414 | ||
| Inflammation-Induced Sensitization of White Matter Injury | 414 | ||
| Intrinsic Vulnerability of the Premature Newborn to Acute Cerebral White Matter Injury | 415 | ||
| Vulnerability to Free Radical Attack | 415 | ||
| Vulnerability to Excitotoxicity | 417 | ||
| Other Potentially Vulnerable White Matter–Associated Cellular Elements | 418 | ||
| Factors Related to the Progression of Chronic White Matter Injury | 419 | ||
| Glial Cell Proliferative Responses | 420 | ||
| Disrupted preOL Maturation in Chronic Lesions | 420 | ||
| Molecular Mechanisms of Arrested Maturation of preOLs and Myelination Disturbances | 420 | ||
| Key References | 421 | ||
| References | 424.e1 | ||
| 16 Encephalopathy of Prematurity: | 425 | ||
| Clinical Settings | 425 | ||
| NeurologicAL Syndrome | 426 | ||
| Diagnosis | 427 | ||
| Electroencephalogram | 427 | ||
| Neuroimaging | 427 | ||
| Neuroimaging of Cerebral White Matter in the Encephalopathy of Prematurity | 427 | ||
| Relevant Neuropathology. | 427 | ||
| Cranial Ultrasonography. | 429 | ||
| Magnetic Resonance Imaging. | 430 | ||
| Neuroimaging of Neuronal/Axonal Components in the Encephalopathy of Prematurity | 432 | ||
| Prognosis and Clinicopathological Correlations | 432 | ||
| Difficulties of Delineating Prognosis and Clinicopathological Correlations in Premature Infants | 432 | ||
| Clinicopathological Correlates | 435 | ||
| Motor Deficits | 435 | ||
| Spastic Diplegia. | 435 | ||
| Other Motor Disturbances. | 436 | ||
| Neurodevelopmental (Nonmotor) Deficits | 437 | ||
| Cognitive Deficits. | 437 | ||
| Behavioral Disturbances. | 440 | ||
| Socialization Deficits—Autism Spectrum Disorders. | 440 | ||
| Visual Deficits. | 440 | ||
| Management | 440 | ||
| Antenatal Interventions | 440 | ||
| Prevention of Premature Birth | 440 | ||
| Antenatal Magnesium | 441 | ||
| Antenatal Steroids | 441 | ||
| Antenatal Antibiotics and Other Antiinflammatory Agents | 441 | ||
| Antibiotics. | 441 | ||
| N-Acetylcysteine. | 442 | ||
| Optimal Management of Labor and Delivery | 442 | ||
| Delayed Cord Clamping/Umbilical Cord Milking | 442 | ||
| Newborn Resuscitation | 442 | ||
| Ventilation | 442 | ||
| Oxygen | 442 | ||
| Hypoxemia. | 443 | ||
| Hyperoxia. | 443 | ||
| Is the Optimal Oxygen Saturation in Premature Infants Age-Dependent? | 443 | ||
| Carbon Dioxide | 444 | ||
| Hypercarbia. | 444 | ||
| Hypocarbia. | 444 | ||
| Perfusion | 445 | ||
| Recognition of Pressure-Passive Cerebral Circulation | 445 | ||
| Recognition of Normal Arterial Blood Pressure Levels in the Newborn | 447 | ||
| Avoidance of Systemic Hypotension | 448 | ||
| Avoidance of Systemic Hypertension | 449 | ||
| Glucose | 449 | ||
| Seizures | 449 | ||
| Indomethacin | 449 | ||
| Neuroprotective Interventions | 450 | ||
| Erythropoietin | 450 | ||
| Epidermal Growth Factor, Insulin-Like Growth Factor | 451 | ||
| Hypothermia | 451 | ||
| Neurorestorative Interventions | 451 | ||
| Nutrition | 451 | ||
| Experiential | 452 | ||
| Visual. | 452 | ||
| Auditory. | 452 | ||
| Pain, Stress. | 452 | ||
| Individualized Care | 453 | ||
| Early Intervention Programs | 453 | ||
| Parenting/Educational/Social Factors | 453 | ||
| Stem Cells | 453 | ||
| Key References | 454 | ||
| References | 457.e1 | ||
| 17 Intrauterine, Intrapartum Assessments in the Term Infant | 458 | ||
| Antepartum Assessment | 458 | ||
| Fetal Movement and Behavioral States | 458 | ||
| Maturational Changes | 458 | ||
| Relation to Fetal Well-Being | 459 | ||
| Fetal Neurological Examination | 460 | ||
| Fetal Heart Rate: Nonstress and Stress Tests | 460 | ||
| Nonstress Test | 460 | ||
| Contraction Stress Test | 460 | ||
| Fetal Biophysical Profile | 461 | ||
| Fetal Growth | 461 | ||
| Doppler Measurements of Blood Flow Velocity in Maternal Umbilical and Fetal Cerebral and Ductus Venosus Vessels | 462 | ||
| Umbilical Artery | 462 | ||
| Fetal Cerebral Vessels | 465 | ||
| Ductus Venosus | 466 | ||
| Sequence of Changes in Doppler Parameters in the Fetus With Intrauterine Growth Restriction | 466 | ||
| Intrapartum Assessment | 467 | ||
| Relationship Between Intrapartum Asphyxia and Cerebral Palsy | 468 | ||
| Meconium Passage in Utero | 468 | ||
| Fetal Heart Rate Alterations | 469 | ||
| Rate | 469 | ||
| Beat-to-Beat Variability | 470 | ||
| Accelerations | 470 | ||
| Decelerations | 470 | ||
| Early Type. | 470 | ||
| Late Type. | 471 | ||
| Variable Type. | 472 | ||
| Taxonomy of Fetal Heart Rate Patterns | 473 | ||
| Relation of Fetal Heart Rate Abnormalities to Neonatal Neurological Course and Subsequent Outcome | 473 | ||
| Fetal Electrocardiogram | 474 | ||
| Fetal Acid-Base Status | 474 | ||
| Alterations in Fetal Acid-Base Measurements and Neonatal Outcome | 475 | ||
| Alterations in Fetal Acid-Base Measurements and Later Neurological Outcome | 476 | ||
| Other Techniques for Monitoring Fetal Well-Being Intrapartum | 477 | ||
| Fetal Pulse Oximetry | 477 | ||
| Fetal Electroencephalogram | 477 | ||
| Doppler Measurements of Blood Flow Velocity | 477 | ||
| Near-Infrared Spectroscopy | 478 | ||
| Techniques Evaluating Fetal Brain Development and Placental Development | 478 | ||
| Placental Evaluation | 478 | ||
| Fetal Cerebral Evaluation | 479 | ||
| Key References | 481 | ||
| References | 483.e1 | ||
| 18 Hypoxic-Ischemic Injury in the Term Infant | 484 | ||
| Neuropathology | 484 | ||
| Brain Swelling and Brain Necrosis | 484 | ||
| Pathological Aspects in Human Infants | 484 | ||
| Experimental Aspects in Perinatal Animals | 485 | ||
| Intrauterine Partial Asphyxia in the Fetal Monkey. | 485 | ||
| Intrauterine Partial Asphyxia in the Fetal Lamb. | 485 | ||
| Hypoxic-Ischemic Insult in the Neonatal Rat and Piglet. | 485 | ||
| Selective Neuronal Necrosis: Patterns of Injury | 485 | ||
| Cellular Aspects | 486 | ||
| Regional Aspects (Autopsied Infants) | 486 | ||
| Diffuse Neuronal Injury. | 486 | ||
| Cerebral Cortex. | 486 | ||
| Deep Nuclear Structures. | 488 | ||
| Brain Stem. | 488 | ||
| Cerebellum. | 488 | ||
| Spinal Cord. | 488 | ||
| Cerebral–Deep Nuclear Neuronal Injury. | 489 | ||
| Deep Nuclear–Brain-Stem Neuronal Injury. | 489 | ||
| Pontosubicular Neuronal Necrosis. | 489 | ||
| Cerebellar Injury. | 490 | ||
| Regional Aspects (Living Infants) | 491 | ||
| Parasagittal Cerebral Injury | 491 | ||
| Cellular and Regional Aspects (Autopsied Infants) | 491 | ||
| Unit V Intracranial Hemorrhage | 591 | ||
| 22 Intracranial Hemorrhage | 593 | ||
| Overview | 593 | ||
| Classification | 593 | ||
| Recognition of Hemorrhage | 593 | ||
| Three Major Steps | 593 | ||
| Neuroimaging in the Recognition of Intracranial Hemorrhage | 594 | ||
| Cerebrospinal Fluid in the Recognition of Intracranial Hemorrhage | 595 | ||
| Traumatic Lumbar Puncture. | 595 | ||
| Cerebrospinal Fluid Findings of Intracranial Hemorrhage. | 595 | ||
| Subdural Hemorrhage | 596 | ||
| Neuropathology | 597 | ||
| Anatomy of Major Veins and Sinuses | 597 | ||
| Major Varieties of Subdural Hemorrhage | 597 | ||
| Tentorial Laceration. | 597 | ||
| Occipital Osteodiastasis. | 598 | ||
| Falx Laceration. | 598 | ||
| Superficial Cerebral Vein Rupture. | 600 | ||
| Pathogenesis | 600 | ||
| Clinical Features | 601 | ||
| Tentorial Laceration, Occipital Diastasis, and Syndromes Associated With Posterior Fossa Subdural Hematoma | 601 | ||
| Rapidly Lethal Syndromes. | 601 | ||
| Less Malignant Syndromes Associated With Posterior Fossa Subdural Hematoma. | 601 | ||
| Falx Laceration | 601 | ||
| Cerebral Convexity Subdural Hemorrhage | 601 | ||
| Diagnosis | 602 | ||
| Clinical Syndromes | 602 | ||
| Computed Tomography, Magnetic Resonance Imaging, and Ultrasound Scans | 602 | ||
| Skull Radiographs | 603 | ||
| Prognosis | 603 | ||
| Management | 605 | ||
| Tentorial and Falx Lacerations, Occipital Osteodiastasis, and Posterior Fossa Subdural Hematoma | 605 | ||
| Cerebral Convexity Subdural Hematoma | 605 | ||
| Primary Subarachnoid Hemorrhage | 605 | ||
| Neuropathology | 606 | ||
| Pathogenesis | 606 | ||
| Clinical Features | 606 | ||
| Diagnosis | 606 | ||
| Prognosis | 606 | ||
| Management | 607 | ||
| Intraventricular Hemorrhage of the Term Infant | 607 | ||
| Neuropathology | 607 | ||
| Pathogenesis | 609 | ||
| Clinical Features | 609 | ||
| Diagnosis | 609 | ||
| Prognosis | 609 | ||
| Management | 611 | ||
| Miscellaneous Examples of Neonatal Intracranial Hemorrhage | 611 | ||
| Trauma | 611 | ||
| Hemorrhagic Infarction | 611 | ||
| Coagulation Defect | 612 | ||
| Thrombocytopenia | 612 | ||
| Neonatal Isoimmune Thrombocytopenia. | 612 | ||
| Deficiency of Coagulation Factors | 612 | ||
| Congenital Deficiency of Coagulation Factors. | 612 | ||
| Vitamin K Deficiency. | 613 | ||
| Vascular Defect | 613 | ||
| Aneurysm | 614 | ||
| Arteriovenous Malformation | 614 | ||
| Coarctation of the Aorta | 615 | ||
| Cerebral Tumor | 615 | ||
| Unknown Cause | 616 | ||
| Extracorporeal Membrane Oxygenation | 616 | ||
| Patient Selection and Technique | 616 | ||
| Intracranial Hemorrhage | 616 | ||
| Mechanisms of Hemorrhagic and Ischemic Brain Injury With Extracorporeal Membrane Oxygenation | 617 | ||
| Cerebral Hemodynamics in Infants Treated With Extracorporeal Membrane Oxygenation. | 617 | ||
| Pathogenesis of Intracranial Hemorrhage With Extracorporeal Membrane Oxygenation. | 618 | ||
| Outcome in Infants Treated With Extracorporeal Membrane Oxygenation. | 618 | ||
| Key References | 620 | ||
| References | 622.e1 | ||
| 23 Cerebellar Hemorrhage | 623 | ||
| Cerebellar Hemorrhage: Preterm Infants | 623 | ||
| Prevalence | 623 | ||
| Neuropathology | 623 | ||
| Cerebellar Hemorrhage: Term Infant | 627 | ||
| Pathogenesis | 627 | ||
| Intravascular Factors | 628 | ||
| Pressure-Passive Cerebellar Circulation. | 628 | ||
| Increased Venous Pressure, Compliant Skull. | 630 | ||
| Disturbed Coagulation. | 631 | ||
| Vascular Factors | 632 | ||
| Tenuous Vascular Integrity. | 632 | ||
| Subependymal and Subpial Germinal Matrix Vessels. | 632 | ||
| Internal Granule Cell Layer. | 632 | ||
| Hypoxia-Ischemia. | 632 | ||
| Extravascular Factors | 632 | ||
| Tear of Cerebellar Parenchyma and Vessels: Compliant Skull. | 632 | ||
| Poor Vascular Support: Subependymal and Subpial Germinal Matrix Regions. | 632 | ||
| Extension From Intraventricular Hemorrhage. | 632 | ||
| Clinical Features | 632 | ||
| Diagnosis | 633 | ||
| Prognosis | 633 | ||
| Management | 635 | ||
| References | 635 | ||
| 24 Preterm Intraventricular Hemorrhage/Posthemorrhagic Hydrocephalus | 637 | ||
| Neuropathology | 638 | ||
| Arterial Supply to Subependymal Germinal Matrix | 638 | ||
| Capillary Network | 638 | ||
| Venous Drainage of Subependymal Germinal Matrix | 639 | ||
| Site of Origin and Spread of Intraventricular Hemorrhage | 641 | ||
| Site of Origin | 641 | ||
| Spread of Intraventricular Hemorrhage | 642 | ||
| Neuropathological Consequences of Intraventricular Hemorrhage | 642 | ||
| Germinal Matrix Destruction | 642 | ||
| Cerebral White Matter Injury/Dysmaturation | 642 | ||
| Cerebral Gray Matter Dysmaturation | 642 | ||
| Cerebellar Dysmaturation | 643 | ||
| Periventricular Hemorrhagic Infarction | 644 | ||
| Hydrocephalus | 648 | ||
| Neuropathological Accompaniments of Intraventricular Hemorrhage | 649 | ||
| Periventricular Leukomalacia | 649 | ||
| Selective Neuronal Necrosis | 649 | ||
| Pathogenesis | 649 | ||
| Intravascular Factors | 649 | ||
| Fluctuating Cerebral Blood Flow | 649 | ||
| Increases in Cerebral Blood Flow: Importance of Pressure-Passive Circulation | 651 | ||
| Elevations of Arterial Blood Pressure and Pressure-Passive Cerebral Circulation. | 652 | ||
| Causes of Increased Arterial Blood Pressure in the Human Newborn. | 653 | ||
| Relevant Experimental Studies: Role of Hypertension. | 655 | ||
| Rapid Volume Expansion. | 655 | ||
| Hypercarbia. | 656 | ||
| Decreased Hemoglobin. | 656 | ||
| Blood Glucose. | 657 | ||
| Increases in Cerebral Venous Pressure | 657 | ||
| Importance of Venous Anatomy. | 657 | ||
| Labor and Delivery. | 657 | ||
| Hypoxic-Ischemic Injury. | 658 | ||
| Respiratory Disturbances. | 658 | ||
| Decreases in Cerebral Blood Flow | 659 | ||
| Importance of Pressure-Passive Cerebral Circulation. | 659 | ||
| Perinatal Hypoxic-Ischemic Events. | 659 | ||
| Postnatal Ischemic Events. | 661 | ||
| Platelet and Coagulation Disturbances | 662 | ||
| Platelet-Capillary Function. | 662 | ||
| Coagulation. | 662 | ||
| Potential Role of Drugs. | 662 | ||
| Vascular Factors | 663 | ||
| Tenuous Vascular Integrity | 663 | ||
| Vulnerability to Hypoxic-Ischemic Injury | 663 | ||
| Extravascular Factors | 663 | ||
| Deficient Vascular Support | 664 | ||
| Fibrinolytic Activity | 664 | ||
| Postnatal Decrease in Extravascular Tissue Pressure | 664 | ||
| Interaction of Pathogenetic Factors | 665 | ||
| Clinical Features | 665 | ||
| Three Basic Syndromes | 665 | ||
| Catastrophic Syndrome | 665 | ||
| Saltatory Syndrome | 665 | ||
| Clinically Silent Syndrome | 666 | ||
| Diagnosis | 666 | ||
| Initial Approach | 666 | ||
| Ultrasound Scan | 666 | ||
| Identification of the Hemorrhage | 666 | ||
| Grading the Severity of Hemorrhage | 666 | ||
| Timing of Hemorrhage | 667 | ||
| Severity of Hemorrhage | 668 | ||
| Computed Tomography Scan | 669 | ||
| Magnetic Resonance Imaging Scan | 669 | ||
| Prognosis | 669 | ||
| Short-Term Outcome: Mortality Rates and Progressive Ventricular Dilation | 669 | ||
| Long-Term Outcome: Neurological Sequelae | 670 | ||
| Periventricular Hemorrhagic Infarction—Major Determinant of Long-Term Outcome | 671 | ||
| Management | 672 | ||
| Prevention | 673 | ||
| Perinatal Interventions | 673 | ||
| Prevention of Premature Birth. | 673 | ||
| Transportation in Utero. | 674 | ||
| Prenatal Pharmacological Interventions. | 674 | ||
| Optimal Management of Labor and Delivery—Delivery Mode. | 675 | ||
| Delayed Cord Clamping. | 675 | ||
| Umbilical Cord Milking. | 676 | ||
| Temperature Stabilization. | 676 | ||
| Newborn Resuscitation. | 676 | ||
| Postnatal Interventions | 677 | ||
| Correction of Fluctuating Cerebral Blood Flow Velocity. | 677 | ||
| Correction or Prevention of Other Major Hemodynamic Disturbances. | 678 | ||
| Correction of Abnormalities of Coagulation. | 679 | ||
| Pharmacological Interventions | 679 | ||
| Indomethacin. | 679 | ||
| Other Pharmacological Approaches | 681 | ||
| Etamsylate. | 681 | ||
| Phenobarbital. | 681 | ||
| Vitamin E. | 681 | ||
| Conclusions | 681 | ||
| Acute Management of Intraventricular Hemorrhage | 682 | ||
| Maintenance of Cerebral Perfusion | 682 | ||
| Prevention of Cerebral Hemodynamic Disturbances | 682 | ||
| Serial Ultrasound Scans | 682 | ||
| Posthemorrhagic Hydrocephalus | 682 | ||
| Incidence and Definition | 682 | ||
| Pathogenesis | 683 | ||
| Evolution | 683 | ||
| Reasons for Ventricular Dilation Before Rapid Head Growth | 684 | ||
| Relation of Ventricular Dilation to Brain Injury | 684 | ||
| Experimental Studies. | 684 | ||
| Human Studies. | 685 | ||
| Prevention | 687 | ||
| Management of Progressive Posthemorrhagic Ventricular Dilation | 688 | ||
| Natural History. | 688 | ||
| Basic Groups for Management | 689 | ||
| Rapidly Progressive Ventricular Dilation | 689 | ||
| Slowly Progressive Ventricular Dilation | 690 | ||
| Serial Lumbar Punctures. | 690 | ||
| Drugs That Decrease Cerebrospinal Fluid Production. | 691 | ||
| Ventricular Drainage. | 691 | ||
| DRIFT. | 692 | ||
| Direct External Ventricular Drains. | 692 | ||
| Tunneled External Ventricular Drains. | 692 | ||
| Subcutaneous Ventricular Catheter With a Reservoir. | 693 | ||
| Subcutaneous Ventricular Cather With a Subgaleal Pouch (Ventricular-Subgaleal Shunt). | 693 | ||
| Conclusion Concerning Temporizing Ventricular Drainage Procedures. | 694 | ||
| Ventriculoperitoneal Shunt. | 694 | ||
| Endoscopic Third Ventriculostomy. | 694 | ||
| Key References | 695 | ||
| References | 698.e1 | ||
| Unit VI Metabolic Encephalopathies | 699 | ||
| 25 Glucose | 701 | ||
| Definition | 701 | ||
| Postnatal Changes | 701 | ||
| Statistical Thresholds | 701 | ||
| Operational Thresholds | 701 | ||
| Neurophysiological Threshold | 702 | ||
| Neurological Outcome Thresholds | 703 | ||
| Normal Metabolic Aspects | 703 | ||
| Brain as the Primary Determinant of Glucose Production | 703 | ||
| Glucose Metabolism in the Brain | 704 | ||
| Glucose Uptake | 704 | ||
| Hexokinase | 704 | ||
| Major Fates of Glucose-6-Phosphate | 704 | ||
| Phosphofructokinase | 705 | ||
| Pyruvate | 705 | ||
| Acetyl-Coenzyme A | 705 | ||
| Citric Acid Cycle | 705 | ||
| Glucose as the Primary Metabolic Fuel for Brain | 705 | ||
| Alternative Substrates for Glucose in Brain Metabolism | 707 | ||
| Overview | 707 | ||
| Ketone Bodies | 707 | ||
| Energy Production. | 707 | ||
| Limitations of Hepatic Ketone Synthesis. | 707 | ||
| Lactate | 708 | ||
| Biochemical Aspects of Hypoglycemia | 708 | ||
| Major Initial Biochemical Effects of Hypoglycemia on Brain Metabolism | 708 | ||
| Major Biochemical Changes | 708 | ||
| Dissociation of Impaired Brain Function and Energy Metabolism | 709 | ||
| Major Later Biochemical Effects of Hypoglycemia on Brain Metabolism | 710 | ||
| Glucose and Energy Metabolism | 710 | ||
| Biochemical Changes in the Mature Animal | 710 | ||
| Glucose and Energy Metabolism. | 710 | ||
| Metabolic Responses to Preserve Brain Energy Levels. | 710 | ||
| Intracellular Calcium and Cell Injury With Hypoglycemia. | 710 | ||
| Role of Excitotoxic Amino Acids in Hypoglycemic Neuronal Death. | 711 | ||
| Biochemical Changes in the Newborn Animal | 711 | ||
| Similarities and Differences in Changes in the Newborn and Adult Brain. | 711 | ||
| Reasons for the Relative Resistance of the Newborn Brain to Hypoglycemia. | 711 | ||
| Role for Excitotoxic Amino Acids in Hypoglycemic Neuronal Death. | 712 | ||
| Glutathione Depletion and Oxidative Stress. | 712 | ||
| Hypoglycemia and Hypoxemia or Asphyxia | 713 | ||
| Hypoglycemia and Hypoxemia | 713 | ||
| Hypoglycemia and Asphyxia | 713 | ||
| Summary | 714 | ||
| Hypoglycemia and Ischemia | 714 | ||
| Enhanced Vulnerability of the Hypoglycemic Brain to Ischemic Insult | 714 | ||
| Impaired Vascular Autoregulation and the Likelihood of Ischemic Insult in Hypoglycemia | 714 | ||
| Summary | 715 | ||
| Hypoglycemia and Seizures | 715 | ||
| Neuropathology | 715 | ||
| Experimental Observations | 715 | ||
| Human Observations | 716 | ||
| Neonatal Neuropathology | 716 | ||
| Neuropathological Sequelae | 717 | ||
| Unresolved Issues | 717 | ||
| Clinical Aspects | 717 | ||
| Incidence | 717 | ||
| Clinical Categorization of Neonatal Hypoglycemia | 718 | ||
| Early Transitional-Adaptive Hypoglycemia | 718 | ||
| Hypoglycemia Associated With Impaired Metabolic Adaptation | 719 | ||
| Neonatal Hypoglycemia Associated With Intrauterine Growth Restriction | 719 | ||
| Severe Recurrent Hypoglycemia | 719 | ||
| Neurological Features | 720 | ||
| Major Neurological Features | 720 | ||
| Seizures: Importance of Duration of Hypoglycemia | 720 | ||
| Brain Imaging in Neonatal Hypoglycemia | 720 | ||
| Prognosis | 720 | ||
| Relation of Neurological Outcome to Neonatal Neurological Features | 721 | ||
| Relation of Brain Imaging to Outcome | 722 | ||
| Neurocognitive Outcome in Infants With Moderate Hypoglycemia (Blood Sugar < 47 mg/dL) | 723 | ||
| Management | 724 | ||
| Prevention | 724 | ||
| Therapy | 724 | ||
| When to Treat. | 724 | ||
| How to Treat. | 725 | ||
| Conclusions | 726 | ||
| Key References | 726 | ||
| References | 729.e1 | ||
| 26 Bilirubin | 730 | ||
| Normal Bilirubin Structure and Metabolism | 730 | ||
| Bilirubin Structure and Properties | 730 | ||
| Bilirubin Metabolism | 730 | ||
| Production | 730 | ||
| Transport | 730 | ||
| Hepatic Uptake | 731 | ||
| Conjugation | 731 | ||
| Excretion | 731 | ||
| Enterohepatic Circulation | 731 | ||
| Pathophysiology | 731 | ||
| Hyperbilirubinemia | 731 | ||
| Major Causes | 731 | ||
| Physiological Hyperbilirubinemia | 732 | ||
| Definition. | 732 | ||
| Mechanisms. | 733 | ||
| Important Determinants of Neuronal Injury by Bilirubin | 733 | ||
| Interrelationships of Bilirubin, Albumin, and Hydrogen Ion | 733 | ||
| Concentration of Serum Unconjugated and Free Bilirubin | 734 | ||
| Unconjugated Bilirubin. | 734 | ||
| Free Bilirubin. | 734 | ||
| Concentration of Serum Albumin | 735 | ||
| Bilirubin Binding by Albumin | 735 | ||
| Affinity of Newborn Albumin for Bilirubin. | 736 | ||
| Endogenous Anions. | 736 | ||
| Exogenous Anions. | 736 | ||
| Concentration of Hydrogen Ions: Acidosis | 736 | ||
| Blood-Brain Barrier | 737 | ||
| Bilirubin Transport Across an Intact Blood-Brain Barrier. | 737 | ||
| Bilirubin Transport Across a Disrupted Blood-Brain Barrier. | 738 | ||
| Neuronal Susceptibility | 739 | ||
| Mechanisms of Bilirubin Neurotoxicity | 740 | ||
| Spectrum of Effects of Bilirubin on Cellular Functions | 740 | ||
| Potential Sequence for Bilirubin Neurotoxicity | 741 | ||
| Plasma Membrane and Excitotoxicity. | 741 | ||
| Importance of the Mitochondrion. | 743 | ||
| Final Common Pathway to Cell Death. | 743 | ||
| Implications for Therapy | 743 | ||
| Neuropathology | 743 | ||
| Acute Bilirubin Encephalopathy-Kernicterus | 743 | ||
| Bilirubin Staining | 744 | ||
| Neuronal Injury | 745 | ||
| Topography. | 745 | ||
| Cytopathology. | 745 | ||
| Relation to Hypoxic-Ischemic Injury. | 745 | ||
| Secondary Bilirubin Staining of Brain of Premature Infants | 745 | ||
| Clinical Aspects of Acute and Chronic Bilirubin Encephalopathies | 745 | ||
| Clinical Features | 746 | ||
| Acute Bilirubin Encephalopathy-Kernicterus | 746 | ||
| Initial Phase. | 746 | ||
| Intermediate Phase. | 746 | ||
| Advanced Phase. | 747 | ||
| Chronic Postkernicteric Bilirubin Encephalopathy Following Marked Neonatal Hyperbilirubinemia | 747 | ||
| Major Features and Temporal Evolution. | 747 | ||
| Extrapyramidal Movement Abnormalities. | 748 | ||
| Gaze Abnormalities. | 748 | ||
| Auditory Abnormalities. | 748 | ||
| Intellectual Deficits. | 749 | ||
| Relationship of Neurological Sequelae in Term Infants to Degree of Hyperbilirubinemia. | 749 | ||
| Chronic Bilirubin Encephalopathies Without Marked Neonatal Hyperbilirubinemia | 750 | ||
| Neurological Sequelae in Term Infants Without Marked Hyperbilirubinemia. | 750 | ||
| Neurological Sequelae in Premature Infants Without Marked Hyperbilirubinemia. | 751 | ||
| Diagnosis | 752 | ||
| Serum Bilirubin Measurements | 752 | ||
| Brain Stem Auditory Evoked Responses and Other Electrophysiological Measures | 752 | ||
| Magnetic Resonance Imaging | 754 | ||
| Management | 755 | ||
| Prevention | 755 | ||
| Surveillance and Early Detection | 755 | ||
| Phototherapy | 757 | ||
| Phototherapy in the Premature Infant. | 758 | ||
| Intravenous Immunoglobulin. | 758 | ||
| Exchange Transfusion | 758 | ||
| Other Therapies | 758 | ||
| Key References | 759 | ||
| References | 762.e1 | ||
| 27 Amino Acids | 763 | ||
| Overview of Aminoacidopathies With Neonatal Neurological Manifestations | 763 | ||
| Maple Syrup Urine Disease | 763 | ||
| Normal Metabolic Aspects | 763 | ||
| Transamination | 763 | ||
| Oxidative Decarboxylation | 763 | ||
| Biochemical Aspects of Disordered Metabolism | 763 | ||
| Enzymatic Defect and Essential Consequences | 763 | ||
| Biochemical Effects of Excess Branched-Chain Amino Acids, Ketoacids, or Both | 763 | ||
| Importance of Branched-Chain Ketoacids | 765 | ||
| Clinical Features | 765 | ||
| Neurodiagnostic Studies | 766 | ||
| Genetics | 768 | ||
| Metabolic Features | 768 | ||
| Neuropathology | 768 | ||
| Management | 769 | ||
| Prevention | 769 | ||
| Early Detection | 769 | ||
| Acute Therapy | 769 | ||
| Long-Term Therapy | 769 | ||
| Nonketotic Hyperglycinemia (Glycine Encephalopathy) | 769 | ||
| Normal Metabolic Aspects | 770 | ||
| Biochemical Aspects of Disordered Metabolism | 770 | ||
| Enzymatic Defect and Essential Consequences | 770 | ||
| Biochemical Effects of Excessive Brain Glycine | 771 | ||
| Clinical Features | 772 | ||
| Distinction From Ketotic Hyperglycinemia | 775 | ||
| Genetics | 775 | ||
| Metabolic Features | 775 | ||
| Neuropathology | 775 | ||
| Management | 775 | ||
| Prevention | 775 | ||
| Early Detection | 775 | ||
| Therapeutic Attempts | 776 | ||
| Sodium Benzoate. | 776 | ||
| Strychnine. | 777 | ||
| Benzodiazepines. | 777 | ||
| Excitatory Amino Acid Antagonists. | 777 | ||
| Conclusions. | 777 | ||
| Hyperammonemia | 777 | ||
| Normal Metabolic Aspects | 778 | ||
| Major Sources and Fates of Ammonia | 778 | ||
| Urea Cycle | 778 | ||
| Ammonia Disposal in Brain | 778 | ||
| Biochemical Aspects of Disordered Metabolism | 778 | ||
| Enzymatic Defects and Essential Consequences | 778 | ||
| Biochemical Effects of Excessive Ammonia | 779 | ||
| Urea Cycle Defects | 780 | ||
| Carbamyl Phosphate Synthetase Deficiency (Congenital Hyperammonemia Type I) | 780 | ||
| Clinical Features. | 780 | ||
| Metabolic Features. | 781 | ||
| Neuropathology. | 781 | ||
| Ornithine Transcarbamylase Deficiency (Congenital Hyperammonemia Type II) | 782 | ||
| Unit VII Degenerative Disorders | 821 | ||
| 29 Degenerative Disorders of the Newborn | 823 | ||
| Major Disorders | 823 | ||
| Disorders Primarily Affecting Gray Matter | 823 | ||
| No Visceral Storage | 823 | ||
| Tay-Sachs Disease | 823 | ||
| Congenital Neuronal Ceroid-Lipofuscinosis | 826 | ||
| Alpers Disease | 827 | ||
| Menkes Disease | 827 | ||
| Disorders Mimicking Gray Matter Degeneration | 831 | ||
| Glucose Transporter Defect | 831 | ||
| Gray Matter Degenerations With Visceral Storage | 831 | ||
| GM1 Gangliosidosis | 831 | ||
| GM2 Gangliosidosis (Sandhoff Variant) | 832 | ||
| Niemann-Pick Disease | 832 | ||
| Gaucher Disease | 832 | ||
| Farber Disease | 833 | ||
| Infantile Sialic Acid Storage Disease (and Sialidoses) | 833 | ||
| Disorders Primarily Affecting White Matter | 833 | ||
| Canavan Disease | 834 | ||
| Alexander Disease | 835 | ||
| Krabbe Disease | 837 | ||
| Pelizaeus-Merzbacher Disease | 840 | ||
| Leukodystrophy With Cerebral Calcifications (Aicardi-Goutieres Syndrome) | 842 | ||
| Disorders Affecting Both Gray and White Matter | 843 | ||
| Peroxisomal Disorders | 845 | ||
| Zellweger Syndrome | 845 | ||
| Neonatal Adrenoleukodystrophy | 846 | ||
| Mitochondrial Disorders | 848 | ||
| Leigh Syndrome and Other Mitochondrial Encephalopathies | 848 | ||
| Serine Synthesis Deficiency | 850 | ||
| Disorders With Cerebellar and Pontine Hypoplasia | 850 | ||
| Congenital Disorders of Glycosylation Type 1a (Carbohydrate-Deficient Glycoprotein Syndromes) | 850 | ||
| Pontocerebellar Hypoplasia Type 2 | 853 | ||
| Neurotransmitter Disorders | 854 | ||
| Rett Syndrome | 855 | ||
| Key References | 855 | ||
| References | 858.e1 | ||
| Unit VIII Neuromuscular Disorders | 859 | ||
| 30 Evaluation, Special Studies | 861 | ||
| Motor System | 861 | ||
| Levels Above the Lower Motor Neuron | 861 | ||
| Corticospinal and Corticobulbar Tracts | 861 | ||
| Basal Ganglia | 861 | ||
| Cerebellum | 861 | ||
| Other Components | 861 | ||
| Rubrospinal Tract. | 862 | ||
| Reticulospinal Tracts. | 862 | ||
| Vestibulospinal Tract. | 862 | ||
| Lower Motor Neuron | 862 | ||
| Peripheral Nerve | 862 | ||
| Neuromuscular Junction | 862 | ||
| Muscle | 862 | ||
| Development | 862 | ||
| Premyoblastic Stage. | 863 | ||
| Myoblastic Stage. | 863 | ||
| Myotubular Stage. | 863 | ||
| Myocytic Stage. | 863 | ||
| Early Histochemical Differentiation. | 863 | ||
| Intermediate Histochemical Differentiation. | 863 | ||
| Late Histochemical Differentiation. | 864 | ||
| Mature Myocytic Stage. | 864 | ||
| Importance of Motor Innervation. | 864 | ||
| Contractile Elements | 864 | ||
| Excitation and Contraction Coupling | 865 | ||
| Biochemical Features | 865 | ||
| Carbohydrate Metabolism. | 865 | ||
| Fatty Acid Utilization. | 865 | ||
| Evaluation of Disorders of the Motor System | 866 | ||
| History | 866 | ||
| Physical Examination | 866 | ||
| Laboratory Studies | 866 | ||
| Cerebrospinal Fluid | 866 | ||
| Serum Enzyme Levels | 866 | ||
| Creatine Kinase. | 866 | ||
| Aldolase. | 867 | ||
| Aspartate and Alanine Aminotransferases. | 867 | ||
| Nerve Conduction Studies | 867 | ||
| Electromyography | 867 | ||
| Basic Features. | 867 | ||
| Anterior Horn Cell Disorders. | 867 | ||
| Peripheral Nerve Disorders. | 868 | ||
| Muscle Disorders. | 868 | ||
| Myotonia. | 869 | ||
| Myasthenia. | 869 | ||
| Muscle Biopsy | 870 | ||
| Value and Indications. | 870 | ||
| Technique. | 870 | ||
| Major Abnormalities. | 870 | ||
| Genetic Testing | 872 | ||
| Chromosomal Microarrays. | 872 | ||
| Single-Gene Testing. | 872 | ||
| Gene Panels. | 872 | ||
| Whole-Exome or Genome Sequencing. | 873 | ||
| References | 873 | ||
| 31 Arthrogryposis Multiplex Congenita | 874 | ||
| Clinical Features | 874 | ||
| Pathogenesis | 874 | ||
| Relation to Impaired Intrauterine Motility | 874 | ||
| Two Major Subgroups—Genetic and Nongenetic | 875 | ||
| Distal Arthrogryposes | 876 | ||
| Pathology | 876 | ||
| Cerebrum or Brain Stem | 876 | ||
| Anterior Horn Cell | 877 | ||
| Peripheral Nerve | 880 | ||
| Neuromuscular Junction | 880 | ||
| Muscle | 881 | ||
| Primary Disorder of Joint or Connective Tissue | 882 | ||
| Intrauterine Mechanical Obstruction | 882 | ||
| Diagnosis | 882 | ||
| Management | 883 | ||
| Acknowledgement | 884 | ||
| Key References | 884 | ||
| References | 886.e1 | ||
| 32 Levels Above Lower Motor Neuron to Neuromuscular Junction | 887 | ||
| Levels Above the Lower Motor Neuron | 887 | ||
| Congenital Encephalopathies | 887 | ||
| Hypoxia-Ischemia | 887 | ||
| Intracranial Hemorrhage and Infection | 887 | ||
| Metabolic Disorders | 887 | ||
| Endocrine Disorders | 887 | ||
| Trauma | 888 | ||
| Developmental Disturbance | 888 | ||
| Degenerative Encephalopathies | 889 | ||
| Spinal Cord Disorders | 889 | ||
| Level of the Lower Motor Neuron | 889 | ||
| Spinal Muscular Atrophy Type 1 (Werdnig-Hoffmann Disease) | 889 | ||
| Pathogenesis and Etiology | 889 | ||
| Clinical Features | 890 | ||
| Onset. | 890 | ||
| Neurological Features. | 891 | ||
| Course. | 893 | ||
| Laboratory Studies | 893 | ||
| Serum Enzymes. | 893 | ||
| Electromyography. | 893 | ||
| Nerve Conduction Studies. | 893 | ||
| Muscle Biopsy. | 893 | ||
| Other Studies. | 895 | ||
| Neuropathology | 895 | ||
| Essential Cellular Changes. | 895 | ||
| Topography. | 895 | ||
| Management. | 895 | ||
| Spinal Muscular Atrophy Variants | 897 | ||
| Neurogenic Arthrogryposis Multiplex Congenita | 898 | ||
| Generalized and Localized Types | 898 | ||
| Cervical Form. | 898 | ||
| Caudal Form. | 898 | ||
| Unit IX Intracranial Infections | 971 | ||
| 34 Viral, Protozoan, and Related Intracranial Infections | 973 | ||
| Destructive Versus Teratogenic Effects | 973 | ||
| TORCH Infections | 973 | ||
| Cytomegalovirus Infection | 973 | ||
| Pathogenesis | 974 | ||
| Fetal Infection. | 974 | ||
| Parturitional and Postnatal Infections. | 975 | ||
| Neuropathology | 975 | ||
| Meningoencephalitis. | 976 | ||
| Microcephaly. | 977 | ||
| Disturbances of Neuronal Migration. | 977 | ||
| Cerebellar Hypoplasia. | 977 | ||
| Other Findings. | 977 | ||
| Clinical Aspects | 977 | ||
| Incidence of Clinically Apparent Infection. | 977 | ||
| Clinical Features. | 977 | ||
| Clinical Diagnosis. | 978 | ||
| Laboratory Evaluation | 978 | ||
| Diagnosis During Pregnancy. | 978 | ||
| Diagnosis of Cytomegalovirus Infection in the Newborn | 979 | ||
| Serological Studies. | 979 | ||
| Isolation of Virus. | 979 | ||
| Diagnostic Studies. | 979 | ||
| Prognosis | 984 | ||
| Relation to Time of Onset of Fetal Infection and Antenatal Neuroimaging Findings. | 984 | ||
| Relation to Neonatal Clinical Syndrome. | 985 | ||
| Outcome With Asymptomatic Congenital Infection. | 986 | ||
| Management | 987 | ||
| Prevention. | 987 | ||
| Supportive Therapy. | 987 | ||
| Antimicrobial Therapy. | 987 | ||
| Toxoplasmosis | 989 | ||
| Pathogenesis | 989 | ||
| Fetal Infection. | 989 | ||
| Importance of Time of Maternal Infection. | 989 | ||
| Neuropathology | 990 | ||
| Meningoencephalitis. | 990 | ||
| Porencephaly and Hydranencephaly. | 990 | ||
| Hydrocephalus. | 990 | ||
| Microcephaly. | 990 | ||
| Clinical Aspects | 990 | ||
| Incidence of Clinically Apparent Infection. | 990 | ||
| Clinical Features. | 991 | ||
| Clinical Diagnosis. | 992 | ||
| Laboratory Evaluation | 992 | ||
| Isolation of Toxoplasma. | 992 | ||
| Serological Studies. | 992 | ||
| Neurodiagnostic Studies. | 993 | ||
| Prognosis | 993 | ||
| Relation to the Neonatal Clinical Syndrome. | 993 | ||
| Outcome With Asymptomatic Congenital Infection. | 995 | ||
| Management | 995 | ||
| Prevention. | 995 | ||
| Supportive Therapy. | 997 | ||
| Antimicrobial Therapy. | 997 | ||
| Rubella | 997 | ||
| Pathogenesis | 997 | ||
| Fetal Infection. | 997 | ||
| Importance of Time of Maternal Infection. | 997 | ||
| Neuropathology | 998 | ||
| Meningoencephalitis. | 998 | ||
| Vasculopathy. | 998 | ||
| Microcephaly and Impaired Myelination. | 998 | ||
| Clinical Aspects | 999 | ||
| Incidence of Clinically Apparent Infection. | 999 | ||
| Clinical Features. | 999 | ||
| Clinical Diagnosis. | 1000 | ||
| Laboratory Evaluation | 1000 | ||
| Isolation of Virus. | 1000 | ||
| Serological Studies. | 1001 | ||
| Neurodiagnostic Studies. | 1001 | ||
| Prognosis | 1001 | ||
| Relation to Neonatal Clinical Syndrome. | 1001 | ||
| Long-Term Hearing Deficits and Other Sequelae. | 1001 | ||
| Late Progressive Panencephalitis. | 1002 | ||
| Management | 1002 | ||
| Prevention. | 1002 | ||
| Supportive Therapy. | 1002 | ||
| Antimicrobial Therapy. | 1002 | ||
| Herpes Simplex | 1003 | ||
| Pathogenesis | 1003 | ||
| Parturitional and Ascending Infection. | 1003 | ||
| Fetal (Transplacental) Infection. | 1004 | ||
| Postnatal Infection. | 1005 | ||
| Role of Host Factors. | 1005 | ||
| Neuropathology | 1005 | ||
| Meningoencephalitis. | 1006 | ||
| Neuropathological Sequelae. | 1006 | ||
| Clinical Aspects | 1006 | ||
| Incidence of Clinically Apparent Infection. | 1006 | ||
| Clinical Features of Disseminated Disease. | 1007 | ||
| Clinical Features of Localized Disease. | 1008 | ||
| Clinical Diagnosis. | 1008 | ||
| Laboratory Evaluation | 1008 | ||
| Cytological Techniques. | 1008 | ||
| Isolation of Virus and Detection of Viral DNA. | 1009 | ||
| Importance of Maternal Evaluation. | 1009 | ||
| Serological Studies. | 1009 | ||
| Neurodiagnostic Studies. | 1009 | ||
| Prognosis | 1012 | ||
| Relation to the Neonatal Clinical Syndrome. | 1012 | ||
| Management | 1012 | ||
| Prevention. | 1012 | ||
| Supportive Therapy. | 1014 | ||
| Antimicrobial Therapy. | 1014 | ||
| Congenital Syphilis | 1015 | ||
| Pathogenesis | 1015 | ||
| Fetal Infection. | 1015 | ||
| Importance of Stage and Timing of Maternal Infection. | 1015 | ||
| Neuropathology | 1016 | ||
| Acute and Subacute Meningitis. | 1016 | ||
| Chronic Meningovascular Syphilis. | 1016 | ||
| Juvenile General Paresis and Tabes Dorsalis. | 1016 | ||
| Clinical Aspects | 1016 | ||
| Incidence of Clinically Apparent Infection. | 1016 | ||
| Clinical Features: Early Congenital Syphilis. | 1016 | ||
| Clinical Features: Late Congenital Syphilis. | 1017 | ||
| Clinical Diagnosis. | 1017 | ||
| Laboratory Evaluation | 1017 | ||
| Identification of Treponema. | 1017 | ||
| Serological Studies. | 1018 | ||
| Neurodiagnostic Studies. | 1018 | ||
| Prognosis | 1018 | ||
| Management | 1018 | ||
| Prevention. | 1018 | ||
| Supportive Therapy. | 1019 | ||
| Antimicrobial Therapy. | 1019 | ||
| Other Viruses | 1019 | ||
| Human Immunodeficiency Virus | 1019 | ||
| Pathogenesis | 1020 | ||
| Fetal and Parturitional Infection. | 1020 | ||
| Postnatal Infection. | 1020 | ||
| Neuropathology | 1021 | ||
| Meningoencephalitis. | 1021 | ||
| Cerebral Atrophy. | 1021 | ||
| Calcific Vasculopathy. | 1022 | ||
| Spinal Cord Myelin Loss. | 1022 | ||
| Central Nervous System Lymphoma, Opportunistic Infections, Stroke. | 1023 | ||
| Clinical Aspects | 1023 | ||
| Incidence of Clinically Apparent Infection. | 1023 | ||
| Clinical Features. | 1023 | ||
| Laboratory Evaluation | 1024 | ||
| Isolation of Virus. | 1024 | ||
| Serological Studies. | 1024 | ||
| Neurodiagnostic Studies. | 1024 | ||
| Prognosis | 1024 | ||
| Management | 1025 | ||
| Prevention. | 1025 | ||
| Supportive Therapy. | 1026 | ||
| Antimicrobial Therapy. | 1026 | ||
| Entero- and Parechoviruses | 1027 | ||
| Pathogenesis | 1027 | ||
| Fetal Infection. | 1027 | ||
| Parturitional Infections. | 1027 | ||
| Postnatal Infection. | 1027 | ||
| Role of Host Factors. | 1028 | ||
| Neuropathology | 1028 | ||
| Clinical Aspects | 1029 | ||
| Clinical Diagnosis. | 1029 | ||
| Laboratory Evaluation | 1030 | ||
| Isolation of Virus. | 1030 | ||
| Serological Studies. | 1030 | ||
| Neurodiagnostic Studies. | 1030 | ||
| Prognosis | 1032 | ||
| Management | 1032 | ||
| Prevention. | 1032 | ||
| Supportive Care. | 1032 | ||
| Antimicrobial Therapy. | 1032 | ||
| Prevention. | 1033 | ||
| Varicella | 1033 | ||
| Perinatal Varicella | 1033 | ||
| Pathogenesis. | 1033 | ||
| Neuropathology. | 1034 | ||
| Clinical Aspects. | 1034 | ||
| Laboratory Evaluation. | 1034 | ||
| Prognosis. | 1034 | ||
| Management. | 1034 | ||
| Congenital Varicella Syndrome | 1034 | ||
| Pathogenesis. | 1035 | ||
| Neuropathology. | 1035 | ||
| Clinical Aspects. | 1035 | ||
| Laboratory Evaluation. | 1036 | ||
| Prognosis. | 1036 | ||
| Management. | 1036 | ||
| Rotavirus | 1036 | ||
| Pathogenesis | 1036 | ||
| Clinical Aspects | 1037 | ||
| Clinical Features. | 1037 | ||
| Laboratory Evaluation | 1038 | ||
| Isolation of Virus. | 1038 | ||
| Neuroimaging Studies. | 1038 | ||
| Prognosis | 1039 | ||
| Management | 1039 | ||
| Prevention. | 1039 | ||
| Parvovirus | 1039 | ||
| Transmission to the Fetus | 1039 | ||
| Fetal Infection | 1039 | ||
| Hydrops. | 1039 | ||
| Central Nervous System Involvement. | 1039 | ||
| Prognosis | 1040 | ||
| Management | 1040 | ||
| Prevention. | 1040 | ||
| Lymphocytic Choriomeningitis | 1041 | ||
| Clinical Aspects | 1041 | ||
| West Nile Virus | 1041 | ||
| Maternal-Fetal Transmission | 1041 | ||
| Diagnosis | 1041 | ||
| Prognosis | 1041 | ||
| Chikungunya Virus | 1042 | ||
| Perinatal Transmission | 1042 | ||
| Clinical Aspects | 1042 | ||
| Management | 1042 | ||
| Zika Virus | 1042 | ||
| Pathogenesis | 1042 | ||
| Transmission to Fetus and Newborn. | 1042 | ||
| Fetal Infection. | 1042 | ||
| Clinical Aspects | 1043 | ||
| Neuropathology. | 1043 | ||
| Clinical Diagnosis. | 1044 | ||
| Laboratory Diagnosis. | 1044 | ||
| Neurodiagnostic Studies | 1044 | ||
| Postnatal Infection. | 1046 | ||
| Prognosis | 1046 | ||
| Relation to Time of Infection. | 1046 | ||
| Management. | 1046 | ||
| Key References | 1046 | ||
| References | 1049.e1 | ||
| 35 Bacterial and Fungal Intracranial Infections | 1050 | ||
| Bacterial Meningitis | 1050 | ||
| Early-Onset and Late-Onset Bacterial Sepsis and Meningitis | 1050 | ||
| Etiology | 1050 | ||
| Pathogenesis | 1051 | ||
| Factors Related to Pregnancy and Delivery | 1052 | ||
| Factors Related to the Infant | 1052 | ||
| Innate Immunity. | 1052 | ||
| Adaptive Immunity. | 1052 | ||
| Immunological Aspects of Group B Streptococcal Infection. | 1053 | ||
| Factors Related to the Neonatal Environment | 1053 | ||
| Factors Related to the Microorganism | 1053 | ||
| Specific Serotypes Related to Meningitis. | 1053 | ||
| Importance of Capsular Polysaccharides. | 1054 | ||
| Neuropathology | 1054 | ||
| Major Features | 1054 | ||
| Acute Changes | 1054 | ||
| Arachnoiditis. | 1054 | ||
| Ventriculitis. | 1055 | ||
| Vasculitis. | 1056 | ||
| Cerebral Edema. | 1057 | ||
| Infarction. | 1057 | ||
| Associated Encephalopathy. | 1058 | ||
| Subdural Effusion and Empyema. | 1058 | ||
| Long-Term Changes | 1058 | ||
| Hydrocephalus. | 1058 | ||
| Multicystic Encephalomalacia and Porencephaly. | 1058 | ||
| Cerebral Cortical and White Matter Atrophy. | 1059 | ||
| Possible Cerebral Cortical Developmental (Organizational) Defects. | 1059 | ||
| Neuropathological Changes Characteristic of Specific Microorganisms | 1059 | ||
| Citrobacter species, Serratia marcescens, Proteus, Pseudomonas, Enterobacter, and Bacillus cereus species. | 1059 | ||
| Listeria monocytogenes. | 1059 | ||
| Mechanisms of Brain Injury | 1059 | ||
| Clinical Features | 1061 | ||
| Two Basic Syndromes | 1061 | ||
| Early-Onset Disease | 1061 | ||
| Dominance of Nonneurological Signs. | 1062 | ||
| Late-Onset Disease | 1062 | ||
| Dominance of Neurological Signs. | 1063 | ||
| Major Neurological Complications | 1063 | ||
| Increased Intracranial Pressure. | 1063 | ||
| Ventriculitis With Localization of Infection. | 1064 | ||
| Acute Hydrocephalus. | 1064 | ||
| Intracerebral Mass or Extracerebral Collection. | 1064 | ||
| Diagnosis | 1064 | ||
| Clinical Evaluation | 1064 | ||
| Laboratory Evaluation | 1064 | ||
| Cerebrospinal Fluid Findings. | 1064 | ||
| Identification of the Microorganism in Cerebrospinal Fluid. | 1066 | ||
| Identification of the Microorganism From Other Sites. | 1066 | ||
| Adjunct Tests. | 1066 | ||
| Neurodiagnostic Studies | 1066 | ||
| Cerebrospinal Fluid Pressure. | 1066 | ||
| Ventricular Puncture. | 1067 | ||
| Ultrasound Scan. | 1067 | ||
| Magnetic Resonance Imaging. | 1067 | ||
| Prognosis | 1069 | ||
| Reservations Concerning Available Data | 1069 | ||
| Group B Streptococcal Infection | 1069 | ||
| Gram-Negative Enteric Infections | 1072 | ||
| Selected Prognostic Factors | 1072 | ||
| Management | 1074 | ||
| Prevention (Group B Streptococcal Infection) | 1074 | ||
| Chemoprophylaxis. | 1074 | ||
| Immunoprophylaxis. | 1075 | ||
| Supportive Care | 1075 | ||
| Neurological Disturbances | 1075 | ||
| Seizures. | 1075 | ||
| Inappropriate Antidiuretic Hormone Secretion. | 1075 | ||
| Cerebral Edema. | 1075 | ||
| Acute Hydrocephalus. | 1076 | ||
| Subdural Effusion. | 1076 | ||
| Brain Abscess. | 1076 | ||
| Pneumocephalus. | 1076 | ||
| Antibiotics | 1076 | ||
| Initial Treatment. | 1076 | ||
| Specific Treatment. | 1076 | ||
| Duration of Treatment. | 1077 | ||
| Treatment Failure. | 1077 | ||
| Ventriculitis | 1077 | ||
| Inadequacy of Intrathecal Therapy. | 1077 | ||
| Inadequacy of Routine Intraventricular Therapy. | 1077 | ||
| Indications for Diagnostic Ventricular Puncture. | 1078 | ||
| Ventriculostomy. | 1078 | ||
| Brain Abscess | 1078 | ||
| Etiology | 1079 | ||
| Pathogenesis | 1079 | ||
| Neuropathology | 1079 | ||
| Clinical Features | 1079 | ||
| Diagnosis | 1079 | ||
| Clinical Evaluation | 1079 | ||
| Laboratory Evaluation | 1080 | ||
| Peripheral White Blood Cell Count. | 1080 | ||
| Cerebrospinal Fluid. | 1080 | ||
| Brain Imaging. | 1080 | ||
| Identification of the Organism. | 1080 | ||
| Prognosis | 1080 | ||
| Management | 1080 | ||
| Disseminated Fungal Infection | 1081 | ||
| Pathogenesis | 1082 | ||
| Neuropathology | 1083 | ||
| Clinical Features | 1083 | ||
| Diagnosis | 1083 | ||
| Prognosis | 1084 | ||
| Management | 1086 | ||
| Tetanus Neonatorum | 1086 | ||
| Pathogenesis | 1086 | ||
| Clinical Features | 1086 | ||
| Diagnosis | 1087 | ||
| Clinical Evaluation | 1087 | ||
| Laboratory Evaluation | 1087 | ||
| Prognosis | 1087 | ||
| Management | 1087 | ||
| Prevention | 1087 | ||
| Treatment | 1087 | ||
| Supportive Care. | 1087 | ||
| Antitoxin and Antimicrobial Therapy. | 1088 | ||
| Acknowledgment | 1088 | ||
| Key References | 1088 | ||
| References | 1089.e1 | ||
| Unit X Perinatal Trauma | 1091 | ||
| 36 Injuries of Extracranial, Cranial, Intracranial, Spinal Cord, and Peripheral Nervous System Structures | 1093 | ||
| Major Varieties of Perinatal Trauma | 1093 | ||
| Injury to Extracranial, Cranial, and Central Nervous System Structures | 1093 | ||
| Extracranial Hemorrhage | 1093 | ||
| Caput Succedaneum | 1093 | ||
| Subgaleal Hemorrhage | 1093 | ||
| Cephalhematoma | 1095 | ||
| Incidence. | 1095 | ||
| Pathology. | 1095 | ||
| Pathogenesis. | 1096 | ||
| Clinical Features. | 1096 | ||
| Management. | 1096 | ||
| Skull Fracture | 1096 | ||
| Linear Fracture | 1097 | ||
| Incidence. | 1097 | ||
| Pathology. | 1097 | ||
| Pathogenesis. | 1097 | ||
| Unit XI Intracranial Mass Lesions | 1125 | ||
| 37 Brain Tumors and Vein of Galen Malformations | 1127 | ||
| Brain Tumors | 1127 | ||
| Neuropathology | 1127 | ||
| Histological Types | 1127 | ||
| Location | 1128 | ||
| Clinical Features | 1129 | ||
| Diagnosis | 1129 | ||
| Prognosis | 1131 | ||
| Management | 1133 | ||
| Major Modalities of Treatment | 1133 | ||
| Treatment of Specific Tumors | 1134 | ||
| Vein of Galen Malformation | 1135 | ||
| Neuropathology | 1135 | ||
| Clinical Features | 1138 | ||
| Diagnosis | 1139 | ||
| Prognosis | 1139 | ||
| Management | 1140 | ||
| Arachnoid Cysts | 1141 | ||
| Pathology | 1141 | ||
| Clinical Features | 1142 | ||
| Management | 1142 | ||
| Key References | 1144 | ||
| References | 1146.e1 | ||
| Unit XII Drugs and The Developing Nervous System | 1147 | ||
| 38 Passive Addiction and Teratogenic Effects | 1149 | ||
| Major Factors Involved in Neurologic Disturbances Associated With Intrauterine Drug Exposure | 1149 | ||
| Developmental Consequences for the Infant | 1149 | ||
| Alcohol | 1150 | ||
| Prevalence | 1150 | ||
| Clinical Features | 1151 | ||
| Neurodevelopmental Consequences | 1153 | ||
| Cognition and Executive Functioning | 1153 | ||
| Language Development | 1154 | ||
| Behavior and Regulatory Problems | 1154 | ||
| Motor and Visual Function | 1154 | ||
| Neuropathology | 1154 | ||
| Pathogenesis | 1155 | ||
| Fetal Blood Flow | 1155 | ||
| Fetal Malnutrition | 1155 | ||
| Molecular Effects | 1156 | ||
| Genetic and Epigenetic Alterations | 1157 | ||
| Prevention | 1157 | ||
| Treatment | 1158 | ||
| Antiepileptic Drugs | 1158 | ||
| Prevalence | 1158 | ||
| Clinical Features | 1158 | ||
| Maternal-Fetal Effects | 1158 | ||
| Major Congenital Malformations | 1158 | ||
| Neonatal Effects | 1159 | ||
| Neurodevelopmental Consequences | 1162 | ||
| Cognition and Executive Functioning | 1162 | ||
| Language Development | 1162 | ||
| Behavior and Regulatory Problems | 1163 | ||
| Motor and Visual Function | 1163 | ||
| Neuropathology | 1163 | ||
| Pathogenesis | 1163 | ||
| Fetal Blood Flow | 1163 | ||
| Fetal Malnutrition | 1164 | ||
| Molecular Effects | 1164 | ||
| Genetic Factors | 1165 | ||
| Prevention | 1165 | ||
| Treatment | 1165 | ||
| Stimulants | 1166 | ||
| Prevalence | 1166 | ||
| Clinical Features | 1167 | ||
| Maternal-Fetal Effects | 1167 | ||
| Neonatal Effects | 1167 | ||
| Destructive Effects on the Central Nervous System | 1168 | ||
| Cerebral Infarction and Intracranial Hemorrhage. | 1168 | ||
| Teratogenic Effects on the Central Nervous System | 1169 | ||
| Microcephaly. | 1169 | ||
| Disturbances of Midline Prosencephalic Development and Neuronal Migration. | 1169 | ||
| Neurodevelopmental Consequences | 1169 | ||
| Cognition and Executive Functioning | 1170 | ||
| Language Development | 1170 | ||
| Behavior and Regulatory Problems | 1170 | ||
| Motor and Visual Function | 1171 | ||
| Neuropathology | 1171 | ||
| Pathogenesis | 1171 | ||
| Fetal Blood Flow | 1171 | ||
| Fetal Nutrition | 1171 | ||
| Molecular Effects | 1172 | ||
| Genetic and Epigenetic Alterations | 1173 | ||
| Prevention | 1174 | ||
| Treatment | 1174 | ||
| Opioids | 1174 | ||
| Prevalence | 1174 | ||
| Clinical Features | 1175 | ||
| Maternal-Fetal Effects | 1175 | ||
| Neonatal Abstinence Syndrome | 1176 | ||
| Neurodevelopmental Consequences | 1179 | ||
| Cognition and Executive Function | 1179 | ||
| Behavior and Regulatory Problems | 1179 | ||
| Motor and Visual Function | 1179 | ||
| Neuropathology | 1179 | ||
| Pathogenesis | 1180 | ||
| Pathogenesis of Neonatal Abstinence | 1180 | ||
| Pathogenesis of Potential Long-Term Consequences | 1180 | ||
| Prevention | 1180 | ||
| Treatment | 1181 | ||
| Recognition | 1181 | ||
| Supportive Therapy | 1181 | ||
| Drug Therapy | 1181 | ||
| Antidepressants | 1181 | ||
| Prevalence | 1182 | ||
| Clinical Features | 1182 | ||
| Maternal-Fetal Effects | 1182 | ||
| Neonatal Effects | 1182 | ||
| Neurodevelopmental Consequences | 1182 | ||
| Cognition and Executive Functioning | 1182 | ||
| Language Development | 1182 | ||
| Behavior | 1182 | ||
| Motor Function | 1183 | ||
| Neuropathology | 1183 | ||
| Pathogenesis | 1183 | ||
| Pathogenesis of Poor Neonatal Adaptation Syndrome | 1183 | ||
| Pathogenesis of Potential Long-Term Effects | 1183 | ||
| Prevention | 1183 | ||
| Treatment | 1183 | ||
| Sedatives | 1184 | ||
| Prevalence | 1184 | ||
| Clinical Features | 1184 | ||
| Maternal-Fetal Effects | 1184 | ||
| Neonatal Effects | 1184 | ||
| Neurodevelopmental Consequences | 1184 | ||
| Neuropathology | 1184 | ||
| Pathogenesis | 1185 | ||
| Prevention | 1185 | ||
| Treatment | 1185 | ||
| Anesthetics | 1185 | ||
| Prevalence | 1185 | ||
| Clinical Features | 1185 | ||
| Maternal and Neonatal Effects | 1185 | ||
| Neurodevelopmental Consequences | 1186 | ||
| Neuropathology and Pathophysiology | 1186 | ||
| Prevention | 1186 | ||
| Marijuana | 1186 | ||
| Prevalence | 1186 | ||
| Clinical Features | 1187 | ||
| Maternal-Fetal Effects | 1187 | ||
| Neonatal Effects | 1187 | ||
| Neurodevelopmental Consequences | 1188 | ||
| Cognition, Executive Functioning, and Language Development | 1188 | ||
| Behavior and Regulatory Problems | 1188 | ||
| Motor and Visual Function | 1188 | ||
| Pathophysiology | 1188 | ||
| Prevention | 1189 | ||
| Drug Use and the Preterm Infant | 1189 | ||
| Conclusions | 1189 | ||
| References | 1189.e1 | ||
| Index | 1191 | ||
| A | 1191 | ||
| B | 1193 | ||
| C | 1195 | ||
| D | 1199 | ||
| E | 1200 | ||
| F | 1201 | ||
| G | 1202 | ||
| H | 1204 | ||
| I | 1207 | ||
| J | 1209 | ||
| K | 1209 | ||
| L | 1209 | ||
| M | 1210 | ||
| N | 1213 | ||
| O | 1214 | ||
| P | 1215 | ||
| Q | 1218 | ||
| R | 1218 | ||
| S | 1219 | ||
| T | 1221 | ||
| U | 1222 | ||
| V | 1222 | ||
| W | 1223 | ||
| X | 1224 | ||
| Z | 1224 | ||
| IBC_Clinical Key ad | IBC-1 |