Primer on Cerebrovascular Diseases

Primer on Cerebrovascular Diseases

Second Edition

Editors

Louis R. Caplan

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

José Biller

Department of Neurology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, United States

Megan C. Leary

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

Morsani College of Medicine, University of South Florida, Tampa, FL, United States

Eng H. Lo

Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

Ajith J. Thomas

Division of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard Medical School,Boston, MA, United States

Midori Yenari

Department of Neurology, University of California, San Francisco, San Francisco Veterans Affairs Medical School, San Francisco, CA, United States

John H. Zhang

Departments of Anesthesiology and Neurosurgery, Loma Linda University School of Medicine, Loma Linda, CA, United States

Table of Contents

Cover image

Title page

Copyright

List of Contributors

Introduction

Basic Sciences

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