Primer on Cerebrovascular Diseases

Primer on Cerebrovascular Diseases, Second Edition, is a handy reference source for scientists, students, and physicians needing reliable, up-to-date information on basic mechanisms, physiology, pathophysiology, and medical issues related to brain vasculature. The book consists of short, specific chapters written by international experts on cerebral vasculature, presenting the information in a comprehensive and easily accessible manner.

Numerous changes have occurred in the field since the publication of the first edition in 1997, particularly our understanding of the genetic aspects of cerebrovascular disease. This updated edition reflects the advances made over the last two decades, not only demonstrating the promise for therapy, but also for a molecular understanding of cerebrovascular diseases. The new edition includes new and expanded topics, including carotid stenting, Iatrogenic causes of stroke, axonal transport and injury, RNAIs, proteomics, and more.

2018 BMA Medical Book Awards Highly Commended in Neurology.

• Provides concise chapters on topics in cerebral blood flow and metabolism, pathogenesis of cerebrovascular disorders, diagnostic testing, and management in a comprehensive and accessible format
• Written by international leading authorities on cerebral vasculature
• Provides up-to-date information on practical applications of basic research and the main clinical issues facing the community, such as axonal transport and proteomics

Advanced graduate students, researchers, and clinicians in the fields of neuroscience, neurology, neurosurgery, and pharmacology and physiology

Section I. Anatomy and Physiology

Chapter 1. Cerebrovascular Anatomy and Hemodynamics

• Introduction
• Anatomical Considerations
• Overview of Cerebral Hemodynamics
• Conclusion

Chapter 2. Cerebral Microcirculation

• Introduction
• Anatomy and Physiology of Microcirculation
• Neurovascular Unit and Coupling
• Microcirculation After Stroke and Thrombolysis
• Microvascular Dysfunction and Dementia
• Capillary Transit Time Heterogeneity as a Measure of Capillary Dysfunction

Chapter 3. The Glymphatic System and Brain Interstitial Fluid Homeostasis

• Introduction
• Interstitial Solute Clearance
• Perivascular Bulk Flow and the Glymphatic System
• Terminal Efflux Routes
• Physiological Roles of Perivascular Exchange and Cerebral Lymphatics
• Pathological Roles of Perivascular Cerebrospinal Fluid–Interstitial Fluid Exchange
• Conclusion

Chapter 4. Cerebrospinal Fluid: Formation, Absorption, Markers, and Relationship to Blood–Brain Barrier

• Introduction
• Blood–Brain Interfaces
• Blood–CSF Interface
• CSF–Blood Interface
• CSF Pressure
• Blood–Brain Barrier Interface
• Pathological Changes in the Capillary
• Conclusion

Chapter 5. Anatomy of Cerebral Veins and Dural Sinuses

• Introduction
• Dural Venous Sinuses
• Cerebral Veins

Chapter 6. Cerebral Vasa Vasorum

• Introduction
• Structure, Function, and Localization
• Cerebral Vasa Vasorum Neovascularization
• Molecular Imaging and Detection
• Clinical Significance in Disease

Chapter 7. Cerebral Vascular Muscle

• Introduction
• Myogenic Tone: Role of TRP Channels
• Mechanisms Underlying Vasodilation
• CADASIL: A Vascular Muscle Defect That Reduces Cerebral Blood Flow and Impairs Cognitive Function
• Summary

Chapter 8. Endothelium

• Introduction
• Endothelium and Vascular Tone
• Endothelium and Thrombosis
• Endothelium and Oxidative Stress
• Endothelium and Inflammation
• Endothelium and the RhoA/Rho-Kinase Pathway
• Endothelium and Angiogenesis
• Therapeutic Strategies to Maintain Cerebral Endothelial Function
• Funding Statement

Chapter 9. Development and Maintenance of the Blood–Brain Barrier

• Introduction
• Cell Types of the Neurovascular Unit
• Development
• Conclusion

Chapter 10. Cerebral Autoregulation

• Introduction: From Static to Dynamic
• Mechanisms Underlying Cerebral Autoregulation
• Cerebral Autoregulation in Hypertension and Neurological Diseases

Chapter 11. Cerebral Blood Flow Regulation (Carbon Dioxide, Oxygen, and Nitric Oxide)

• Introduction
• Physiological Responses of CO2
• Mechanisms of Action of CO2
• Conclusion
• Physiological Responses of O2
• Mechanisms of Action of O2
• Conclusion
• Physiological Responses of Nitric Oxide
• Conclusion

Chapter 12. CBF–Metabolism Coupling

• Introduction
• CBF Measurements
• CBF and Metabolism Coupling
• Neuronal Coupling to CBF and Metabolism
• Role of Astrocytes
• Uncoupling Between CBF and Metabolism

Chapter 13. Perivascular Neurotransmitter Regulation of Cerebral Blood Flow

• Introduction
• Sensory Nervous System

Chapter 14. Adenosine and Its Receptors Update: Influence on Cerebral Blood Flow (CBF)

• Introduction
• Adenosine Background
• Data Supporting Ado’s Role in Cerebral Blood Flow Regulation
• Conclusion

Chapter 15. Cerebrovascular Activity of Peptides Generated by Central Nervous System

• Introduction
• Endothelins
• The Kallikrein–Kinin System

Chapter 16. Eicosanoids in Cerebrovascular Diseases

• Introduction
• Production of Eicosanoids
• The Eicosanoid-Producing Enzymes
• Contributions to Stroke Injury
• Conclusion and Outlook

Chapter 17. Neurogenesis in Cerebrovascular Disease

• Introduction
• Adult Neurogenesis
• Cerebrovascular Disease and Neurogenesis
• Functional Significance of Neurogenesis in Cerebrovascular Disease
• Mechanisms of Neurogenesis-Mediated Repair
• Conclusion

Chapter 18. Gliogenesis

• Introduction
• Radial Glia Gives Rise to Neurons and Glial Cells During Development
• Adult Neurogenesis and Gliogenesis Take Place in SVZ or SGZ in Adult Brain
• Intrinsic Factors for Gliogenesis Regulation
• Gliogenesis After Brain Injury
• Conclusion

Chapter 19. Vascular Remodeling After Cerebral Ischemia

• Neovascularization After Cerebral Ischemia and Hypoxia
• Angiogenesis After Ischemia and Hypoxia
• Vasculogenesis and the Role of Endothelial Progenitor Cells
• Arteriogenesis and the Remodeling of Collateral Vessels After Stroke or Cerebral Hypoperfusion
• Therapies to Promote Poststroke Neovascularization

Section II. Pathophysiology

Chapter 20. An Overview of Atherosclerosis

• Introduction
• Cellular and Molecular Mechanisms in Atherosclerosis
• Pathology

Chapter 21. Thrombosis

• Introduction
• Physiology: Homeostatic System
• Role of Platelets
• Role of Vascular Endothelium
• Fibrinolysis
• Thrombotic Mechanisms
• Antithrombotic Treatment of Ischemic Stroke

Chapter 22. Histopathology of Cerebral Ischemia and Stroke

• Introduction
• Cerebral Infarction
• Astrocyte and Vascular Changes
• Inflammatory Events
• White Matter Changes
• Ischemic Penumbra
• Selective Ischemic Cell Death
• Summary

Chapter 23. Histopathology of Intracerebral Hemorrhage

• Introduction
• Histopathological Changes
• Summary

Chapter 24. Pathophysiology of Ischemia-Reperfusion Injury and Hemorrhagic Transformation in the Brain

• Introduction
• Cellular and Molecular Mechanisms of Ischemia-Reperfusion Injury and Hemorrhagic Transformation
• Intervention Strategies for Ischemia-Reperfusion Injury
• Conclusion

Chapter 25. Pathophysiology of Subarachnoid Hemorrhage, Early Brain Injury, and Delayed Cerebral Ischemia

• Introduction
• Aneurysm Formation
• Etiology of SAH
• Early Brain Injury
• Delayed Cerebral Ischemia
• Conclusion

Chapter 26. Pathophysiology of Ischemic White Matter Injury

• Cellular Anatomy of White Matter

Chapter 27. Central Neuroinflammation in Cerebral Ischemia: The Role of Glia

• Introduction
• Neuroinflammatory Response of Microglia to Cerebral Ischemia
• Neuroinflammatory Response of Astrocytes to Cerebral Ischemia
• Astrocyte–Microglia Cross Talk Following Cerebral Ischemia
• Conclusions

Chapter 28. Pathophysiology of the Peripheral Immune Response in Acute Ischemic Stroke

• Cerebral Ischemia and Inflammation
• Immune Cells Participating in Ischemic Injury and Tissue Repair
• Immune Cell Entry Into the Ischemic Brain
• Alterations of the Peripheral Immune System After Stroke
• Conclusion

Chapter 29. Cytotoxic and Vasogenic Brain Edema

• Introduction
• Normal Fluid Movement in the Brain
• Cerebral Edema
• Imaging and Monitoring Brain Edema
• Treatment
• Conclusion

Chapter 30. Spreading Depolarizations

• Basic Characteristics
• Impact on Injury Outcome
• Natural History of SDs in Injured Brain
• Trigger Factors and Modulators
• Detection of SDs
• Therapeutic Targeting of SDs
• Conclusion

Chapter 31. Hypertension

• Introduction
• Vascular Function
• Blood–Brain Barrier
• Vascular Structure
• Consequences of Vascular Disease During Hypertension

Chapter 32. Risk Factors: Diabetes

• Introduction
• Diabetes and Stroke
• Diabetes and Cognitive Impairment
• Cerebrovascular Function and Structure in Diabetes—Lessons From Preclinical Models
• A Unifying Hypothesis: Relevance of Microcerebrovascular Disease to Ischemic Stroke and Cognitive Impairment
• Conclusion

Chapter 33. Risk Factors: Aging

• Introduction
• Aged Blood–Brain Barrier and Neuroinflammation-aging
• Stroke
• Vascular Dementia
• Therapeutic Targets
• Research Disconnect
• Conclusion

Chapter 34. Risk Factors: Gender and Sex

• Introduction
• Examples of Traditional, Well-Studied Risk Factors: Hypertension and Hyperlipidemia
• Clinical Risk Factors More Prevalent in Women: Atrial Fibrillation, Diabetes Mellitus, Migraine With Aura, and Depression
• Female-Specific Clinical Risk Factors: Menopause, Hormone Replacement Therapy, Oral Contraceptives, and Pregnancy
• Role of Sex in Fundamental Stroke Pathobiology

Chapter 35. Mechanisms of Stroke Recovery

• Introduction
• Timeline for Stroke Recovery
• Excitatory Neuronal Signaling
• Promotion of Growth Programs
• Conclusions

Section III. Neuroprotection

Chapter 36. N-Methyl-D-Aspartate Receptors Remain Viable Therapeutic Targets for Stroke

• Introduction
• N-Methyl-d-Aspartate Subtype Glutamate Receptors at the Acute Phase of Stroke
• N-Methyl-d-Aspartate Subtype Glutamate Receptors and the Late Consequences of Stroke
• Conclusion

Chapter 37. Neuroprotectants: Reactive Oxygen Species (ROS) Based

• Introduction
• Sources of Reactive Oxygen Species in Cerebral Ischemia and SAH
• Basics of Free-Radical-Induced Lipid Peroxidation
• Mechanisms for Pharmacologic Inhibition of Oxidative Damage in Acute Ischemic or Hemorrhagic Stroke
• New Antioxidant Approaches
• Conclusion

Chapter 38. Neuroprotectants: Cell-Death Based

• Introduction
• Caspase
• Mitochondrial Pathway
• Bcl-2 Family
• Extrinsic Pathway
• Inhibitor of Apoptosis
• Caspase-Independent Cell Death
• Conclusion

Chapter 39. Comprehensive Concept of Regenerative Medicine for Ischemic Stroke With Bone Marrow Stromal Cells

• Introduction
• BMSC Transplantation for Ischemic Stroke
• Muse Cell Transplantation for Ischemic Stroke
• Conclusion

Chapter 40. Neuroprotectants: Temperature

• Introduction
• Therapeutic Hypothermia for Ischemia
• Therapeutic Hypothermia for Intracerebral Hemorrhage
• Conclusion

Chapter 41. Drug Delivery to the Central Nervous System

• Introduction
• Crossing the BBB
• Circumventing the BBB
• Conclusion

Chapter 42. Ischemic Tolerance: In Situ and Remote Pre- and Postconditioning

• Introduction
• In Situ PreC and PostC
• Cross-tolerance Induced by Heterologous Conditioning
• Remote Conditioning
• The Underlying Protective Mechanisms of In Situ and Remote Conditioning
• In Situ PreC
• In Situ PostC
• Remote PreC and PostC
• Conclusion

Section IV. Molecular Mechanisms

Chapter 43. Mechanisms of Neuron Death (Necrosis, Apoptosis, Autophagy) After Brain Ischemia

• Introduction
• Apoptosis, Necrosis, and Autophagy After Brain Ischemia
• Mechanisms of Selective Neuronal Death After Brain Ischemia

Chapter 44. Mechanisms of Glial Death and Protection

• Introduction
• Glia Metabolism
• Oligodendrocytes Are Vulnerable to Excitotoxicity Following Ischemia
• Mechanisms of Oligodendrocyte Damage, Protection, and Repair in Stroke
• Mechanisms of Astrocyte Damage and Protection in Stroke
• Conclusion

Chapter45. Mechanisms of Endothelial Injury and Blood–Brain Barrier Dysfunction in Stroke

• Introduction
• Disruption of the Blood–Brain Barrier in Ischemic Stroke
• Pathological Mechanisms of Endothelial Injury in Ischemic Stroke
• Therapeutic Opportunities
• Summary

Chapter 46. The Neurovascular Unit

• Introduction
• The Neurovascular Unit in CNS Function
• The Neurovascular Unit in Acute Stroke
• The Neurovascular Unit in Stroke Recovery
• Summary

Chapter 47. Mitochondrial Mechanisms During Ischemia and Reperfusion

• Introduction
• Adenosine Triphosphate and Energy Metabolisms
• Ion Channel Regulation of Mitochondrial Calcium
• Cell Death and Mitophagy
• Mitochondrial Transfer and Biogenesis
• Overview
• Abbreviations

Chapter 48. Excitotoxicity and Stroke

• Introduction
• What Is Excitotoxicity?
• How Excitotoxicity Kills Neurons
• Ischemia Initiates Excitotoxicity
• Clinical Disappointment—and Possible Explanations
• Possible Paths Forward—Maybe Still Starting With NMDA Antagonists

Chapter 49. Oxidative and Nitrosative Stress

• Oxidative Stress in Ischemic Stroke
• The Superoxide Radical
• Hydrogen Peroxide: A Superoxide Dismutant
• Nitric Oxide
• Peroxynitrite
• Iron and Oxidative Stress
• Reactive Oxygen Species and Cell Signaling Pathways
• Glutamate Excitotoxicity
• Sex Differences in Oxidative Stress and Stroke
• Oxidative Stress During Various Stages of Ischemia
• Antioxidants: Defense Against Reactive Oxygen Species

Chapter 50. Protein Kinases in Cerebral Ischemia

• Introduction
• Conclusion

Chapter 51. Ischemia Regulated Transcription Factors: Hypoxia Inducible Factor 1 and Activating Transcription Factor 4

• Introduction
• Hypoxia-Mediated Transcription Changes During Stroke
• Hypoxia Regulates Hypoxia-Inducible Factor System
• Regulation of Adaptive Transcription by HIF–Prolyl Hydroxylases
• Inhibiting HIF-PHDs as a Therapeutic Strategy
• HIF-PHD Inhibition to Prevent Oxidative Stress
• ATF4 is an Oxidative Stress–Inducible Transcription Factor Regulated by HIF-PHDs
• Glucose Deprivation and HIF Activity
• Conclusion

Chapter 52. Lipid Mediators

• Platelet-Activating Factor and Other Bioactive Lipids
• Platelet-Activating Factor Contributes to Excitotoxicity by Enhancing Glutamate Release
• Omega-3 Polyunsaturated Fatty Acids
• Docosahexaenoic Acid is Neuroprotective in Cerebral Ischemia
• Docosanoids: Neuroprotectin D1
• Concluding Remarks

Chapter 53. Mitogen-Activated Protein Kinase Signaling in Cerebrovascular Disease

• Mitogen-Activated Protein Kinase Signaling
• Ischemic Stroke
• Hemorrhagic Stroke
• Summary

Chapter 54. Rho-Associated Kinases in Cerebrovascular Disease

• Introduction
• Rho-Associated Kinases
• Rho-Associated Kinase Inhibitors
• Rho-Associated Kinase Inhibition in Experimental Models of Cerebrovascular Diseases
• Rho-Associated Kinase Inhibitors in Clinical Use for Cerebrovascular Diseases
• Conclusion

Chapter 55. Akt-GSK3β Pro-survival Signaling Pathway in Cerebral Ischemic Injury

• Introduction
• Akt Activation and Regulation
• Activation and Regulation of Akt in Cerebral Ischemic Injury
• Akt Regulates Transcriptional Machinery Leading to an Environment Supporting Cell Survival
• Glycogen Synthase Kinase 3β
• Other Akt Targets Impacting Transcription
• Summary

Chapter 56. Heat Shock Proteins and the Stress Response

• Introduction
• Heat Shock Proteins
• The Heat Shock Response
• Hsp70 in Ischemic Stroke
• Other Heat Shock Proteins
• Conclusion

Chapter 57. Noncoding RNAs and Stroke

• Introduction
• Noncoding RNAs
• miRNAs and Ischemic Brain Damage
• LncRNAs in the Post-Ischemic Brain
• piRNAs in the Post-Ischemic Brain
• Concluding Remarks

Chapter 58. Cytokines and Chemokines in Stroke

• Introduction
• Cytokines as Signaling Molecules in the Innate Immune Response of the Ischemic Brain
• Cytokines and Neuroinflammation
• The Role of Chemokines After Stroke
• Implication of Chemokines and Cytokines in Neurorepair Mechanisms After Stroke: Focus on Neurogenesis and Angiogenesis
• Therapeutic Approaches and Future Directions

Chapter 59. Growth Factors and Cerebrovascular Diseases

Chapter 60. Tissue Plasminogen Activator Signaling in the Normal and Diseased Brain

• Signaling in the Normal CNS
• Signaling in the Diseased CNS
• Conclusion

Chapter 61. Matrix Metalloproteinases and Extracellular Matrix in the Central Nervous System

• Introduction
• Basal Lamina and Endothelial Cells
• Common Features of the MMPs in Nervous Tissues and Cerebral Blood Vessels
• Enzymes and ECM
• Conclusion

Section V. Models and Methods

Chapter 62. Animal Models of Focal Ischemia

• Approaches to Inducing Focal Ischemia
• Induction of Middle Cerebral Artery Occlusion: Considerations for Anesthesia and Monitoring Physiological Variables
• Monitoring Cerebral Blood Flow During Middle Cerebral Artery Occlusion and Reperfusion
• Common Outcome Measures
• Use of Stroke Models for Understanding Pathophysiology Versus Treatments
• Comorbidities and Sex Differences

Chapter 63. Animal Models: Global Ischemia

• Introduction
• Rodent Models: Mice, Rats, Gerbils, and the Arctic Ground Squirrel
• Larger Animals: Dogs, Cats, and Monkeys
• Comparing Global Cerebral Ischemia With Cardiac Arrest
• Conclusion and Outlook

Chapter 64. Animal Models: Cerebral Hemorrhage

• Introduction
• Blood Injection Model
• Collagenase Injection Model
• Comparison of Blood and Collagenase Models
• Conclusion

Chapter 65. Animal Models of Neonatal Stroke/Ischemia

• Introduction
• Developmental Patterns of Ischemia-Associated Brain Damage in Preterm and Term Infants
• Large Animal Models of Ischemia-Related Injury
• Rodent Models of At-Term/Neonatal Focal Stroke and Hypoxia-Ischemia
• Method for Induction of tMCAO in P7 Rats
• Method for Induction of tMCAO in P10 Rats
• Method for Induction of tMCAO in P9–P10 Mice
• Model-Specific Oxidative and Inflammatory Mechanisms of Ischemic Injury in Neonates

Chapter 66. Animal Models: Vascular Models of Cognitive Dysfunction

• Introduction
• Cognitive Dysfunction of Vascular Origin in Human
• Animal Models: Advantages and Limitations
• Commonalities and Pathophysiology
• Conclusion

Chapter 67. Animal Models: Nonhuman Primates

• Introduction
• The Choice of Species
• Methods of Stroke Creation
• Assessment of Functional Outcome
• Surrogate Outcome Measures
• Conclusion

Chapter 68. Cerebral Blood Flow Methods

• Introduction
• Methods Requiring Brain Penetration
• Methods Requiring the Injection of a Radioactive Tracer
• Optical Techniques
• Conclusion

Chapter 69. Magnetic Resonance Imaging of Stroke

• Introduction
• T1-, T2-, and T2∗-Weighted MRI
• Diffusion-Weighted MRI
• MR Angiography and Perfusion MRI
• Perfusion-Diffusion Mismatch
• Tissue Classification and Prediction

Chapter 70. Principles and Methods of Molecular Imaging in Stroke

• Imaging Agents and Modalities
• Imaging Plaque Vulnerability
• Imaging Thrombus
• Imaging Apoptonecrosis
• Imaging Neuroinflammation
• Imaging Stem Cells
• Conclusion

Chapter 71. Experimental Methods for Measuring Blood Flow in Brain Capillaries

• Two-Photon Microscopy of Fluorescent Signals
• Line-Scans Overcome Limitations of Measurement Speed
• Analysis Methods
• Viewing Stalled Vessels
• Other Methods and Future Outlook

Chapter 72. Genomic Tools

• Introduction
• Ischemic Stroke Versus Controls and Intracerebral Hemorrhage
• mRNA Profiles for Causes of Stroke
• Transient Ischemic Attacks
• Hemorrhagic Transformation
• micro RNA Regulation of mRNA
• Alternative Splicing of mRNA and the Future

Chapter 73. Proteomes and Biomarkers of the Neurovascular Unit

• Introduction
• Neurovascular Unit “Carta”
• Brain Endothelial Cell “Carta”
• Proteome of Cerebral Vessels
• Translational Proteomics: Biomarkers for Cardiovascular Diseases
• Quantitative Targeted Proteomics: From Discovery to Application
• Conclusion

Chapter 74. Blood Biomarkers in Acute Stroke

• Introduction
• Methodological Aspects
• Identification of Patients With Ischemic Stroke
• Differentiation Between Intracerebral Hemorrhage and Ischemic Stroke
• Predicting Bleeding Complications After Thrombolysis
• Identifying Ischemic Stroke Etiology
• Predicting Recurrent-Events in Patients With Transitory Ischemic Attack
• Summary

Chapter 75. Rodent Behavioral Tests Sensitive to Functional Recovery and Compensation

• Introduction
• Forelimb Function Tasks
• Hind Limb Function Tasks
• Cognitive Tasks Overview
• Conclusion

Clinical Chapters

Section VI. Clinical Aspects: Medical and Surgical

Chapter 76. Transient Focal Neurological Events

• Transient Ischemic Attacks
• Seizures
• Migraine
• Transient Global Amnesia
• Vertigo
• Hypoglycemia
• Functional Neurological Disorders
• Neuromuscular Conditions
• Brain Tumors, Subdural Hematomas, and Space-Occupying Lesions
• Syncope and Vertebrobasilar Insufficiency
• Primary Ophthalmologic Conditions
• Demyelinating Conditions

Chapter 77. Types of Stroke and Their Differential Diagnosis

• Introduction
• Ischemic Stroke
• Hemorrhagic Stroke

Chapter 78. Small Artery Occlusive Diseases

• Introduction
• Characteristics of Small Artery Occlusive Diseases on Specific Arteries

Chapter 79. Anterior Circulation: Large Artery Occlusive Disease and Embolism

• Introduction
• Vascular Anatomy and Pathology

Chapter 80. Carotid Artery Disease

• Introduction
• Pathology
• Mechanisms of Symptoms From Carotid Occlusive Disease
• Cerebral Hemispheric Syndromes
• Retinal Ischemia
• The Carotid Bruit
• Other Less Common Clinical Features of Carotid Artery Occlusive Disease
• Carotid Dissection and Moyamoya Disease

Chapter 81. Posterior Circulation: Large Artery Occlusive Disease and Embolism

• Introduction
• Vascular Anatomy of the Posterior Circulation
• Subclavian Artery Disease
• Vertebral Artery Origin Disease
• Extracranial Vertebral Artery Dissection
• Intracranial Vertebral Occlusion
• Basilar Artery Disease
• Cerebellar Infarction
• Thalamic Infarction
• Posterior Cerebral Artery Territory Infarction
• Posterior Circulation Embolism
• Imaging Studies

Chapter 82. Primer in Cerebrovascular Disease: Innominate and Subclavian Disease

• Introduction
• Evaluation and Workup
• Subclavian and Innominate Stenosis
• Subclavian and Innominate Aneurysmal Disease

Chapter 83. Vertebral Artery Disease

• Vascular Anatomy
• Extracranial Vertebral Artery
• Intracranial Vertebral Artery

Chapter 84. Basilar Artery Disease

• Anatomy
• Pathology and Pathophysiology
• Other Less Common Pathophysiologic Findings of the Basilar Artery
• Clinical Syndromes of Basilar Artery Ischemia
• Clinical Presentation and Outcomes From the Registry Data: NEMC-PCR and BASICS

Chapter 85. The Heart and Stroke

• Overview
• Stroke Classification
• Direct Cardiogenic Brain Embolism
• Brain Hypoperfusion Due to Cardiac Pump Failure
• Neurological Effects From Cardiac Drugs
• Neurological Complication From Endovascular Cardiac Procedure
• Cardiac Complications Associated With Brain Lesions
• Coexistent Vascular Diseases Affecting Both Heart and Brain

Chapter 86. Aortic Arch Artherosclerotic Disease

• Introduction
• Complex Atheromatous Plaques in the Descending Aorta and Stroke
• Stroke Prevention in Patients With Aortic Arch Atherosclerosis
• Conclusion

Chapter 87. Brain Injury From Cerebral Hypoperfusion

• Introduction
• Syncope
• Watershed Territory Infarcts
• Hypoxic-Ischemic Encephalopathy

Chapter 88. Stroke and Eye Findings

• Introduction
• Conclusion

Chapter 89. Spinal Cord Strokes

• Spinal Cord Vascular Supply
• Spinal Cord Ischemia and Infarction
• Causes of Spinal Ischemia
• Spinal Vascular Malformations
• Diagnostic Evaluation of Patients Presenting With Spinal Cord Ischemia
• Spinal Hemorrhages

Chapter 90. Unique Features of Aneurysms by Location

• Introduction
• Internal Carotid Artery Aneurysms
• Anterior Communicating Artery Aneurysms
• Middle Cerebral Artery Aneurysms
• Vertebrobasilar and Cerebellar Artery Aneurysms
• Conclusions

Chapter 91. Clinical Aspects of Subarachnoid Hemorrhage

• Introduction
• Epidemiology
• Diagnosis
• Clinical Course
• Vasospasm
• Treatment of Cerebral Aneurysms
• Conclusion

Chapter 92. Clinical Aspects of Intracerebral Hemorrhage

• Introduction
• Classification
• Clinical Presentation
• Radiologic Findings
• Management
• Conclusion

Chapter 93. Clinical Aspects of Intraventricular Hemorrhage

• Introduction
• Etiology of Intraventricular Hemorrhage in Infants
• Clinical Presentation of Intraventricular Hemorrhage in Infants
• Grading of Intraventricular Hemorrhage in Infants
• Diagnosis of Intraventricular Hemorrhage in Infants
• Treatment of Intraventricular Hemorrhage in Infants
• Etiology of Intraventricular Hemorrhage in Adults
• Symptoms of Intraventricular Hemorrhage in Adults
• Diagnosis of Intraventricular Hemorrhage in Adults
• Grading of Intraventricular Hemorrhage in Adults
• Treatment of Intraventricular Hemorrhage in Adults
• Prognosis

Chapter 94. Clinical Aspects of Subdural Hemorrhage (SDH)

• Acute Subdural Hematoma
• Chronic Subdural Hematomas

Chapter 95. Cerebral Venous Thrombosis

• Introduction
• Epidemiology
• Etiology
• Clinical Presentation
• Diagnosis
• Treatment
• Prognosis

Chapter 96. Developmental Venous Anomalies

• Introduction
• Radiopathological Characteristics
• Classification and Key Descriptive Attributes
• Presentation and Natural History
• Treatment Options
• Considerations for Management

Chapter 97. Vein of Galen Arteriovenous Malformations

• Embryology
• Anatomy and Classification
• Clinical Presentation
• Prognosis
• Goals of Treatment
• Treatment Options
• Ongoing Challenges

Chapter 98. Carotid Cavernous and Other Dural Arteriovenous Fistulas

• Introduction
• Carotid Cavernous Fistulas
• Other Dural Arteriovenous Fistulas

Chapter 99. Cavernous Malformations

• Introduction
• Genetics
• Pathology
• Clinical Presentation
• Natural History
• Diagnosis
• Indications for Treatment
• Timing of Surgical Treatment
• Choice of Operative Approach
• Radiosurgery
• Principles of Surgical Treatment
• Cavernous Malformations Associated With Seizures
• Future Directions

Chapter 100. Spinal Vascular Malformations

• Spinal Vascular Anatomy
• Classification and Epidemiology
• Pathophysiology, Hemodynamics, and Natural History
• Radiological Features
• Treatment
• Conclusion

Chapter 101. Reversible Cerebral Vasoconstriction Syndromes

• Introduction
• Epidemiology
• Risk Factors and Pathophysiology
• Clinical Features
• Laboratory Test Results
• Brain Imaging Results
• Diagnostic Approach
• Management
• Prognosis and Counseling

Chapter 102. Spontaneous Dissections of Cervicocephalic Arteries

• Etiology and Physiopathology
• Epidemiology
• Clinical Presentation
• Diagnosis
• Management

Chapter 103. Stroke Secondary to Trauma

• Introduction
• Ischemic Stroke
• Decreased Cerebral Perfusion Pressure
• Vasospasm
• Vascular Injury
• Hemorrhagic Stroke
• Delayed Traumatic Intracerebral Hemorrhage
• Hemorrhagic Progression
• Conclusion

Chapter 104. Vascular Cognitive and Behavioral Disorders

• Introduction

Section VII. Medical Conditions and Stroke

Chapter 105. Stroke in Children

• Introduction
• Epidemiology
• Perinatal and Neonatal Stroke
• Stroke in Children
• Work-Up
• Stroke Mimics
• Treatment
• Conclusion

Chapter 106. Ischemic Stroke in the Young

• Introduction
• Epidemiology of Stroke in the Young
• Causes of Ischemic Stroke in the Young
• Clinical Clues Suggesting Specific Causes of Stroke
• An Approach to Diagnostic Testing in Young Stroke Patients
• Treatment and Prognosis in Young Stroke Patients

Chapter 107. Rare Genetic Causes of Stroke

• Introduction
• Monogenic Diseases
• Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS)
• Hereditary Endotheliopathy With Retinopathy, Nephropathy, and Stroke (HERNS)
• Type IV Collagen α1-Chain Mutation (COL4A1)
• Homocystinuria
• Marfan Syndrome and Vascular Ehlers–Danlos Syndrome
• Moyamoya Disease
• Polygenic Diseases
• Conclusions

Chapter 108. Stroke in Fabry Disease

• Epidemiology
• Pathophysiology
• Clinical Features
• Stroke Pathogenesis
• Neuroimaging
• Diagnosis
• Treatment

Chapter 109. Moyamoya Disease and Syndrome

• Introduction
• Epidemiology
• Pathology and Pathogenesis
• Clinical Features
• Diagnosis
• Prognosis and Treatment

Chapter 110. Varicella Zoster Virus and Stroke

• Introduction
• Epidemiology
• Clinical Features, Laboratory Abnormalities, and Diagnosis of VZV Vasculopathy
• Treatment of VZV Vasculopathy
• VZV in Giant Cell Arteritis
• Pathogenesis
• Conclusions

Chapter 111. Stroke and Migraine

• Introduction
• What Is Migraine?
• What Is the Relationship of Migraine to Stroke?
• Diagnosis and Prevention

Chapter 112. Cerebrovascular Complications of Cancer

• Stroke Directly Due to Tumor
• Stroke Due to Remote Effects of Tumor: Coagulopathy
• Hypercoagulability and Thrombosis
• Combined Hypercoaguability/Bleeding Diathesis
• Stroke in the Setting of Tumor, But Not Related to Tumor
• Sequelae of Cancer Treatment

Chapter 113. Radiation Vasculopathy

• Introduction
• Pathophysiology
• Incidence
• Radiological Manifestations
• Monitoring
• Treatment Options
• Cerebrovascular Complications of Cardiac Radiation
• Therapeutic Effects of Radiation on Cerebral Blood Vessels
• Future Prospects

Chapter 114. Aortic Dissection and Stroke

• Introduction

Chapter 115. Coagulopathies and Ischemic Stroke

• Introduction
• Antithrombin
• Protein C and Protein S
• Activated Protein C Resistance
• Fibrinogen and Fibrinolytic Abnormalities
• Homocyst(e)inemia
• Other Coagulation Abnormalities
• Who Should Be Evaluated for Coagulopathies?
• Summary

Chapter 116. Antiphospholipid Antibody Syndrome

• Introduction
• What Are Antiphospholipid Antibodies?
• Clinical and Laboratory Features of Antiphospholipid Antibody Syndrome
• Diagnosis of Antiphospholipid Antibody Syndrome
• Epidemiology
• When to Screen for aPL in Patients with Cerebrovascular Disease
• Predicting Thrombosis Risk in APS and aPL-Positive Patients
• Mechanisms of Antiphospholipid Antibody-Associated Disease
• Treatment

Chapter 117. Primary Platelet Disorders

• Introduction
• Thrombocytosis and Ischemic Stroke
• Thrombocytopenia and Ischemic Stroke
• Platelet Disorders and Hemorrhagic Stroke
• Conclusion

Chapter 118. Stroke and Sickle Cell Disease

• Introduction
• Silent Cerebral Infarctions
• Overt Cerebral Ischemic Infarction
• Intracranial Hemorrhage
• Other Neurological Problems
• Conclusion

Chapter 119. Pregnancy, Hormonal Contraception, and Postmenopausal Estrogen Replacement Therapy

• Stroke in Pregnancy
• Hormonal Contraception
• Hormone Replacement Therapy

Chapter 120. Toxicity/Substance Abuse

• Introduction
• Cannabis
• Amphetamines
• Cocaine
• Heroin
• Alcohol
• Cigarettes
• Conclusion

Chapter 121. Functional Disorders Presenting to the Stroke Service

• Introduction
• Etiology
• Diagnosis
• Management
• Prognosis
• Conclusion

Chapter 122. CADASIL

• Introduction
• Clinical Manifestations
• Imaging
• Pathological Data
• Diagnosis
• Treatment

Chapter 123. Stroke and Infection: Tuberculosis, Brucellosis, Syphilis, Lyme Disease and Listeriosis

• Neurosyphilis
• Neurobrucellosis
• Neuroborreliosis
• Neurotuberculosis
• Neuroinvasive Listeriosis

Chapter 124. HIV and Stroke

• Introduction
• Causes of Stroke in HIV Infection
• Cerebral Infections
• Cardiac Embolism
• Prothrombotic States
• Substance Abuse
• HIV-Associated Vasculopathy and Vasculitis
• Small Vessel HIV-Associated Vasculopathy
• Large- and Medium-Vessel HIV-Associated Vasculopathy
• Accelerated Atherosclerosis
• Approach to Stroke Therapy in the HIV-Positive Patient

Chapter 125. Stroke-Induced Immunodepression and Clinical Consequences

• Introduction
• Pathways of Stroke-Induced Immunodepression Syndrome
• Laboratory Markers for Stroke-Induced Immunodepression
• Sense and Nonsense of Stroke-Induced Immunodepression
• Therapeutic Implications
• Conclusions

Chapter 126. Cerebrovascular Complications of Cardiac Surgery

• Background
• Cardiac Surgical Procedures
• Minimally Invasive Cardiac Surgical Procedures
• Percutaneous Cardiac Surgical Procedures
• Mechanism of Stroke in Cardiac Surgery
• Acute Ischemic Stroke Treatment in Cardiac Surgery Patients
• Other Cerebrovascular Complications and Stroke Mimics

Section VIII. Diagnostic Testing

Chapter 127. Clinical Stroke Diagnosis

• Information Used for Stroke Diagnosis
• The Inductive Method—Sequential Hypothesis Generation and Testing and Pattern Matching
• Impact of Various Findings on the “What” Diagnosis
• Localization and Detection of the Vascular Lesion
• Stroke Localization
• Imaging and Laboratory Evaluation

Chapter 128. Cardiac Electrophysiology in Stroke Investigation: Holter, Event Monitor, and Long-Term Monitoring

• Background
• Optimizing Detection
• Relevance of Monitor Findings
• Evaluation
• Summary

Chapter 129. Cardiac Ultrasound in Stroke Investigation

• Major Sources of Emboli
• Imaging Procedures

Chapter 130. Overview of Neuroimaging of Stroke

• Introduction
• Commonly Used Imaging Modalities
• Ischemic Stroke
• Angiographic Assessment of Cerebral Vasculature
• Imaging Utilized for Endovascular Intervention
• Imaging Modalities to Assess Collateral Circulation
• Neuroimaging to Assess Cerebral Perfusion
• Intracerebral Hemorrhage
• Distinct Cases Associated With Ischemia/Infarction

Chapter 131. CT, CT-Angiography, and Perfusion-CT Evaluation of Stroke

• Introduction
• Hemorrhagic Stroke
• Arterio-occlusive Ischemic Stroke
• Veno-occlusive Ischemic Stroke

Chapter 132. MRI and MRA of Ischemic Stroke

• Introduction
• MRI of Brain Ischemia
• Diffusion MRI
• Magnetic Susceptibility Imaging
• FLAIR/T2- and T1-Weighted Imaging
• Contrast-Enhanced T1-Weighted Imaging
• MR Angiography
• Time-of-Flight and Phase-Contrast MRA
• Perfusion MRI
• MR in Acute Ischemic Stroke Triage
• The MGH Stroke Imaging Algorithm
• Conclusions

Chapter 133. Transcranial and Cervical Ultrasound in Stroke

• Introduction
• Transcranial Doppler Ultrasonography
• Cervical Duplex Ultrasonography
• Summary

Chapter 134. Conventional Cerebral Arteriography

• Introduction
• Indications
• Basic Concepts
• Safety
• Present and Future

Chapter 135. Ultrasound Examination of the Aortic Arch in Stroke

• Introduction
• Transesophageal Echocardiography
• Proximal Aortic Atheromas and Ischemic Stroke
• Arch Atheromas and Stroke After Cardiac Surgery or Aortic Procedures
• Considerations on Therapy and Prevention of Recurrent Events

Section IX. Management

Chapter 136. Thrombolysis for Acute Ischemic Stroke

• Intravenous Tissue Plasminogen Activator
• Extended Time Window to 4.5h
• Time to Treatment Effects
• Large Vessel Occlusion Strokes
• Mechanical Thrombectomy
• Conclusions

Chapter 137. General Treatment of Stroke in Intensive Care Setting

• Introduction
• General Critical Care
• Neurocritical Care
• Decompressive Craniectomy

Chapter 138. Physiological Monitoring of Stroke in the Intensive Care Setting

• Noninvasive Monitoring
• Oximetry
• End-Tidal CO2 Monitoring
• Blood Pressure
• Temperature Management
• Water Hemostasis
• Glycemic Control
• Invasive Monitoring
• Pulmonary Artery Catheterization
• Cerebrovascular Physiology and Intracranial Pressure Monitoring
• Conclusion

Chapter 139. Hypertensive Encephalopathy

• Introduction
• Pathophysiology
• Imaging Characteristics
• Management of Hypertensive Encephalopathy
• Conclusion

Chapter 140. Management of Cerebral Edema/Intracranial Pressure in Ischemic Stroke

• Introduction
• Pathophysiology
• Assessment of Cerebral Edema
• Conclusion

Chapter 141. Surgery for Ischemic Strokes

• Introduction

Chapter 142. Clinical Status of Neuroprotection in Cerebral Ischemia

• Introduction
• Primary Stroke Prevention During Interventions
• Penumbra Salvage
• Prevention of Secondary Brain Injury
• Neuroprotection From Vasospasm-Related Ischemia
• Conclusion

Chapter 143. Cardiac Complications and ECG Abnormalities After Stroke

• Introduction
• Ischemia and Heart Failure
• ECG Abnormalities and Arrhythmias
• Summary

Chapter 144. Management of Hypertension in Stroke

• Introduction
• Management of Hypertension in the Acute Stroke Period
• Management of Chronic Hypertension in Patients With Cerebrovascular Disease

Chapter 145. Management of Diabetes in Stroke

• Introduction
• Diabetes as a Risk Factor for Stroke
• Pathophysiology of Stroke in Diabetes
• Diabetes and Stroke Outcomes
• Management

Chapter 146. Management of Atrial Fibrillation

• Frequency and Pathogenesis
• The Role of Echocardiography in Estimating Stroke Risk
• Ischemic Stroke Risk Factors and Bleeding Risk
• Antithrombotic Strategies for Stroke Prevention
• Evaluation and Management of Patients With Ischemic Stroke
• Summary

Chapter 147. Depression, Psychosis, and Agitation in Stroke

• Introduction
• Poststroke Depression
• Poststroke Psychosis
• Poststroke Anxiety and Agitation
• Summary

Chapter 148. Treatment of Vasculitis

• Introduction
• Large-Vessel Vasculitis
• Medium-Vessel Vasculitis
• Small-Vessel Vasculitis
• Variable Vessel Vasculitis
• Single-Organ Vasculitis
• Vasculitis Associated With Systemic Disease

Chapter 149. Endovascular Therapy for the Treatment of Cerebrovascular Disease

• Introduction
• Stroke
• Intracranial Aneurysms
• Intracranial Arteriovenous Malformations
• Conclusion

Chapter 150. Surgery for Ischemic Infarcts

• Introduction
• Malignant MCA Stroke
• Cerebellar Stroke

Chapter 151. Carotid Endarterectomy and Carotid Angioplasty and Stenting

• Introduction
• Carotid Endarterectomy
• Carotid Angioplasty and Stenting
• Carotid Endarterectomy or Carotid Angioplasty and Stenting

Chapter 152. Management of Asymptomatic Extracranial Carotid Artery Disease

• Introduction
• Epidemiology
• Revascularization
• Official Guidelines and Current Status of Practice
• Subgroup Analyses, Pitfalls, and Other Limitations of Published Randomized CEA Trials in ACS
• Risk Stratification: Identifying Patients at High Risk
• Conclusion
• List of Commonly Used Abbreviations

Chapter 153. Management of Cerebellar Hematomas and Infarcts

• Cerebellar Hemorrhage
• Diagnosis
• Treatment
• Cerebellar Infarction

Chapter 154. Surgical and Endovascular Management of Ruptured Posterior Circulation Aneurysms

• Introduction
• Presentation and Diagnosis
• Natural History
• Treatment Options
• Surgical Approaches
• Endovascular Treatments
• Endovascular Technique
• Stent-Assisted Coiling
• Balloon Remodeling
• Flow Diversion
• Multidisciplinary Approaches
• Clip Versus Coiling

Chapter 155. Surgical and Endovascular Management of Patients With Unruptured Aneurysm

• Introduction
• Epidemiology
• Clinical Presentation
• Imaging
• Risk Factors for Rupture
• Management
• Follow-Up

Chapter 156. Surgical and Endovascular Management of Patients With Giant Cerebral Aneurysms

• Introduction
• Microsurgery
• Endovascular Surgery
• Conclusion

Chapter 157. Surgical and Endovascular Management of Aneurysms in the Pediatric Age Group

• Introduction
• Epidemiology and Pathophysiology
• Presentation and Evaluation
• Treatment and Surgical/Endovascular Indications
• Initial Management of Ruptured Aneurysm Cases (Surgical and Endovascular)
• Complications
• Posttreatment Care and Follow-Up
• Outcomes
• Common Clinical Questions
• Conclusions

Chapter 158. Surgical Management of Pituitary Apoplexy

• Introduction
• Pathophysiology
• Clinical Presentation
• Management
• Surgical Technique
• Postoperative Management and Outcome
• Conclusion

Chapter 159. Surgical and Endovascular Management of Acutely Ruptured Arteriovenous Malformations

• Introduction
• AVM Grading Systems
• Microsurgical Resection
• Endovascular Embolization
• Stereotactic Radiosurgery
• Conclusions

Chapter 160. Surgical and Endovascular Management of Unruptured Arteriovenous Malformations

• Introduction
• Epidemiology and Natural History
• Management
• Conclusions

Chapter 161. Surgical and Endovascular Management of Vertebrobasilar Atherosclerosis

• Introduction
• General Features of Vertebrobasilar Atherosclerosis
• Management of Vertebrobasilar Atherosclerosis
• Endovascular Revascularization
• Microsurgical Revascularization
• Conclusion

Chapter 162. Extracranial–Intracranial Bypass Procedures

• Introduction
• EC–IC Bypass for Flow Replacement
• EC–IC Bypass for Flow Augmentation
• Conclusion

Chapter 163. Surgical Aspects of Moyamoya Disease

• Surgical Management
• Operative Technique: Direct STA–MCA Bypass
• Indirect Bypass Technique
• Operative Results
• Conclusion

Chapter 164. Prevention of Ischemic Stroke

• Introduction
• AHA/ASA Guideline Recommendations for Management of Lifestyle and Vascular Risks for Ischemic Stroke Prevention
• AHA/ASA Guideline Recommendations for Management of Antithrombotics, Oral Anticoagulants, PFO Closure and Related Surgery, Carotid Endarterectomy, and Prevention
• Conclusion

Chapter 165. Management of Lipid Metabolism

• Introduction
• Pathophysiology of Lipid Metabolism in Cerebrovascular Disease
• Lipids and Atherosclerosis and Their Interaction With Other Risk Factors
• Recommendation for Prevention and Treatment of Lipid-Associated Cerebrovascular Disease

Chapter 166. Antiplatelet Agents: Mechanisms and Their Role in Stroke Prevention

• Introduction
• Pathogenesis of Stroke and Contributing Disease States
• Antiplatelet Agents: Mechanisms and Role in Stroke Prevention

Chapter 167. Anticoagulants in Stroke Treatment

• Introduction
• Anticoagulants for Secondary Stroke Prevention
• Ischemic Stroke
• Initiation and Discontinuation of Anticoagulation After Stroke
• Anticoagulation: Intracranial Hemorrhage and Microbleeds

Chapter 168. Rehabilitation for Disabling Stroke

• Scientific Bases
• Rehabilitation Outcome Measures
• Stages of Rehabilitation
• Specific Interventions
• Conclusion

Chapter 169. Magnetic and Direct Current Stimulation for Stroke

• Introduction
• Historical Background
• Brain Plasticity in Stroke
• Transcranial Magnetic Stimulation
• Repetitive TMS
• Transcranial Direct Current Stimulation
• Safety Considerations for NIBS
• Limitations of NIBS
• Future Directions

Chapter 170. Management of Aneurysms and Vascular Malformations During Pregnancy and Puerperium

• Neurosurgical Procedures During Pregnancy
• Radiation Exposure
• Recommendations for the Management of Vascular Malformations
• Conclusion