Primer on Cerebrovascular Diseases

2nd Edition - February 10, 2017
Imprint: Academic Press
Editors: Louis R. Caplan, Jose Biller, Megan C. Leary, Eng H. Lo, Ajith J Thomas, Midori Yenari, John H. Zhang
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 0 3 0 5 8 - 5
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 0 3 0 5 9 - 2

Primer on Cerebrovascular Diseases, Second Edition, is a handy reference source for scientists, students, and physicians needing reliable, up-to-date information on basic mechanism… Read more

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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.

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

Louis R. Caplan

Louis R. Caplan, M.D. (Editor)

Beth Israel Deaconess Medical Center, Harvard University, Boston, MA

Dr. Caplan is a world-renowned neuroscientist and a senior member of the Division of Cerebrovascular Disease at Beth Israel Deaconess Medical Center, Boston. He is a Professor of Neurology at Harvard Medical School, Boston, and the founder of the Harvard Stroke Registry. Dr. Caplan is the author or editor of 45 books and more than 700 articles in medical journals. He is a member of many professional societies, serving as an officer on committees for the American Heart Association, the American Academy of Neurology, and the American Neurological Association. He has served as the Chair of both the Boston Society of Neurology and the Chicago Neurological Society.

Affiliations and expertise

Neurology, Harvard University, Beth Israel Deaconess Medical Center, Boston, MA, USA

Jose Biller

José Biller, M.D., FACP, FAAN, FANA, FAHA

Loyola University Chicago, Maywood, IL, USA

Dr. José Biller is Professor of Neurology and Neurological Surgery and Chairperson of the Department of Neurology at Loyola University Chicago Stritch School of Medicine. Dr. Biller served as Director of the American Board of Psychiatry and Neurology (ABPN) from 1994 to 2001, and President of the ABPN in 2001. He is Chief Editor of the Journal of Stroke and Cerebrovascular Diseases , and an editorial board member and reviewer for an array of other national and international journals and publications. He is a Fellow of the American Academy of Neurology, American Neurological Association, American College of Physicians, and the Stroke Council of the American Heart Association. He has published more than 370 peer-reviewed articles, more than 150 book chapters, and numerous books.

Affiliations and expertise

Neurology, Professor and Chairman, Department of Neurology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA

Megan C. Leary

Megan Carroll Leary, M.D. (Editor)

Department of Neurology, Lehigh Valley Hospital and Health Network, Allentown, PA USA

Dr. Leary is a neurologist with 15 years clinical experience, who specializes in Neurology and Vascular Neurology. She currently is the Neurology Residency Program Director for Lehigh Valley Hospital and Health Network in Allentown, PA, and is an Assistant Professor of Neurology in affiliation with Morsani College of Medicine at the University of South Florida. Dr. Leary is also a consulting neurologist at Harvard Clinical Research Institute at Harvard Medical School. Additionally, Dr. Leary is a member of many professional societies and serves on the American Board of Psychiatry and Neurology's Vascular Neurology Examination Committee. Her interests include cryptogenic stroke, acute ischemic stroke, and the association between cardiac disease and stroke.

Affiliations and expertise

Neurology, Lehigh Valley Hospital and Health Network, Allentown, PA, USA

Eng H. Lo

Eng H. Lo is a basic neurovascular scientist. He helped develop the neurovascular unit concept (Lo, Nat Rev Neurosci 2003; Tiedt et al, Nat Rev Neurol 2022).

Affiliations and expertise

Professor of Neurology and Radiology, Harvard Medical School, Research Staff, Mass General Hospital, Massachusetts General Hospital, Neuroprotection Research Lab, Charlestown, MA, USA

Ajith J Thomas

Ajith J. Thomas, M.D.

Beth Israel Deaconess Medical Center, Harvard University, Boston, MA

Dr. Thomas is a Neurosurgeon Co- Director of the Brain Aneurysm Institute at Beth Israel Deaconess Medical Center. He is also an Assistant Professor of Neurosurgery at Harvard University Medical School. He is the Program director for the Cerebrovascular fellowship for cranial and endovascular neurosurgery and site director for the Beth Israel Deaconess Center Neurosurgery Residency program. He has authored more than 100 peer reviewed papers in neurosurgery and several book chapters. His clinical interests are Subarachnoid Hemorrhage; Aneurysms; Stroke; Arteriovenous Malformations; Trigeminal Neuralgia; Peripheral Nerve Disorders. He is board certified from the American Board of Neurological Surgery.

Affiliations and expertise

Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA

Midori Yenari

Midori A. Yenari, M.D.

University of California, San Francisco, San Francisco, CA

Dr. Yenari specializes in vascular neurology, and is on the faculty in the Department of Neurology at the University of California, San Francisco. She is also a staff neurologist and stroke program director at the San Francisco Veterans Affairs Medical Center. Her research focuses on the cellular and molecular mechanisms of stroke and potential therapies particularly as they pertain to immune modulation and therapeutic hypothermia. Dr. Yenari is a fellow of the American Academy of Neurology, a fellow of the American Heart Association and has served on editorial boards for Stroke, Journal of Cerebral Blood Flow and Metabolism, Neurobiology of Disease and Translational Stroke Research.

Affiliations and expertise

Neurology, University of California, San Francisco, San Francisco, CA, USA

John H. Zhang

John H. Zhang, M.D., Ph.D. (Editor)

Loma Linda University Medical School, Loma Linda, CA

Dr. Zhang is currently Professor of Anesthesiology, Neurosurgery, Neurology, Basic Sciences (Physiology & Pharmacology), Pathology & Human Anatomy, and Nursing at Loma Linda University Medical Center. He also serves as Director of Center for Brain Hemorrhage Research, Vice-Chair, Department of Basic Sciences (Chief of Division of Physiology) and Director of Physiology Graduate Training Program, Director of Basic Science Research Division in Neurosurgery and Anesthesiology. Dr. Zhang’s research efforts have been supported by grants from American Heart Association, National Institute of Health, and Department of Defense as well as other Regional foundations and Industry with more than 23 million US dollars. Dr. Zhang has published more than 600 peer reviewed articles and has been invited to speak in meetings, seminars, and grand rounds more than 300 times.

Affiliations and expertise

Loma Linda University School of Medicine, Loma Linda, CA, USA

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Primer on Cerebrovascular Diseases

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Louis R. Caplan

Jose Biller

Megan C. Leary

Eng H. Lo

Ajith J Thomas

Midori Yenari

John H. Zhang

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