Stroke: Pathophysiology, Diagnosis, and Management, 5th Edition J. P. Mohr MS MD

Cover
Copyright
Dedication
Contributors
Preface
Section 1 - Pathophysiology
	Chapter 1 - Vascular Biology and Atherosclerosis of Cerebral Arteries
		Physiologic Regulation of Cerebrovascular Tone
			Nitric Oxide and Cyclic Guanosine ­Monophosphate–Mediated Mechanisms
			Cyclic Adenosine Monophosphate–Mediated Mechanisms
			K+ Channels and Endothelium-Derived ­Hyperpolarizing Factor (EDHF)
			Transient Receptor Potential Channels
			Reactive Oxygen Species
			Regulation of Myogenic Tone: TRP Channels and RhoA/Rho Kinase
		Pathophysiologic Alterations in Cerebral Vessel Function
			Platelets and Leukocytes
			Atherosclerosis
			Effects of Therapy to Lower Plasma Cholesterol Levels
			Chronic Hypertension
			K+ Channels
			Subarachnoid Hemorrhage
			Hyperhomocysteinemia
			Diabetes Mellitus
		Summary
			Acknowledgments
		REFERENCES
	Chapter 2 - The Cerebral Microvasculature and Responses to Ischemia
		Anatomy of the Cerebral Vasculature
		The Neurovascular Unit
		The Blood-Brain Barrier and Matrix Integrity
		Cerebral Microvessel Responses to Focal Ischemia
			Focal Cerebral Ischemia and Proteolysis of the Microvascular Matrix
			Focal Cerebral Ischemia and Microvessel Cell Adhesion
			Pharmacologic Modulation of Microvascular Matrix-Adhesion Interactions
			Initiation of Cellular Inflammation
			Fibrin Formation and Deposition
			Hemostasis and the Microvessel Wall
		Angiogenesis
		Amyloid Deposition and Lipohyalinosis
		Summary
		References
	Chapter 3 - Mechanisms of Thrombosis and Thrombolysis
		Thrombus Formation
		Fibrinolysis
			Plasminogen
			Plasminogen Activation
			Thrombus Dissolution
		Plasminogen Activators
			Endogenous Plasminogen Activators
			Exogenous Plasminogen Activators
			Plasminogen Activators Derived from Desmodus rotundus
			Novel Plasminogen Activators
		Regulation of Endogenous Fibrinolysis
			α  2-Antiplasmin and α  2-Macroglobulin
			Inhibitors of Plasminogen Activators and Fibrinolysis
		Impact of Plasmin Generation on Microvascular Integrity
		Consequences of Therapeutic Plasminogen Activation
		Limitations on the Clinical Use of Fibrinolytic Agents
		Plasminogen Activators in Cerebral Tissue
		Plasminogen Activators in Experimental Cerebral Ischemia
		Plasminogen Activators and Recanalization in Ischemic Stroke
		Plasminogen Activators and Cerebral Hemorrhage
		REFERENCES
	Chapter 4 - Cerebral Blood Flow and ­Metabolism in Human ­Cerebrovascular Disease
		Methods of Measurement
			Cerebral Blood Flow
			Cerebral Metabolism
		Energy Metabolism and Normal Cerebral Hemodynamics
			Normal Values of CBF and CMR
			Control of Cerebral Blood Flow
			Response of Cerebral Blood Flow and Metabolism to Changes in Metabolic Demand
			Response of Cerebral Blood Flow to Changes in Arterial Partial Pressure of CO2
			Response of Cerebral Blood Flow to Changes in Arterial Partial Pressure of Oxygen, Oxygen Content, Hemoglobin, and Blood Viscosi...
			Response of Cerebral Blood Flow to Changes in Blood Glucose Concentration
			Response of Cerebral Blood Flow to Changes in Cerebral Perfusion Pressure
		Hemodynamic Effects of Arterial Occlusive Disease
			Hemodynamic Effect of Arterial Stenosis
			Methods to Measure the Hemodynamic Effects of Large Artery Occlusive Disease
			Three-Stage Classification System of Cerebral Hemodynamics
			Correlation of Cerebral Hemodynamics with Stroke Risk
		Acute Ischemic Stroke
			Evolution of Infarction
			Autoregulation and Vasoreactivity
			Flow-Metabolism Thresholds of Tissue Function and Viability
			Thresholds for Ischemia in the Newborn Brain
		Remote Metabolic Effects of Ischemia
			Physiologic Basis
			Contralateral Cerebellar Hypometabolism
			Contralateral Cerebral Hypometabolism
			Ipsilateral Cerebral Hypometabolism
			Clinical Relevance
		Intracerebral Hemorrhage
			Cerebral Blood Flow and Metabolism
			Autoregulation
		Arteriovenous Malformations
		Aneurysmal Subarachnoid Hemorrhage
			Cerebral Blood Flow and Metabolism
			Autoregulation
			Transcranial Doppler Measurement of Cerebral Blood Flow Velocity
		Conclusions
			Acknowledgments
		REFERENCES
	Chapter 5 - Histopathology of Cerebral ­Ischemia
		The Biological Levels of Organization and Stroke
		Selective Neuronal Necrosis versus Infarction
		Selective Vulnerability
		Selective Neuronal Necrosis
			Neuronal Acidophilia
			Neurons Undergo a “Dendritic Death”
		Pannecrosis or Infarction
			Hypermetabolism and Acidosis in Central ­Nervous System Tissue
			Apoptosis in Ischemia
		Epilogue
		REFERENCES
	Chapter 6 - Molecular and Cellular ­Mechanisms of Ischemia-Induced Neuronal Death
		Global Ischemia
		Focal Ischemia
		Experimental Models of Global and Focal Ischemia
			In Vivo Models
			In Vitro Models
		Modalities of Ischemic Cell Death
			Necrosis
			Apoptosis
			Autophagy
			Cell Death Pathways in Global and Focal ­Ischemia
		Triggers of Ischemic Cell Death
			Glutamate Excitotoxicity
			Nonexcitotoxic Mechanisms
			Calcium
			Zinc
		Mechanisms of Ischemic Cell Death
			Metabolic Stress
			Mitochondrial Permeabilization
			Nitric Oxide
			Free Radicals and Lipid Peroxidation
			Epigenetic Mechanisms and Transcriptional Regulation
			Inflammation
			Acknowledgments
		REFERENCES
	Chapter 7 - Apoptosis and Related Mechanisms in Cerebral Ischemia
		Pathways of Ischemic Cell Death
		Molecular Mechanisms of Apoptosis
			Mitochondrial Pathway
			Death Receptor–Mediated Pathway
			Nuclear Pathway
			Endoplasmic Reticulum Pathway
			Cell Survival Pathways
		Apoptosis in Cerebral Ischemia
			Caspase Activation during Focal and Global Ischemia
		Apoptosis in Spinal Cord Ischemia
		Inhibition of Apoptotic Pathways Reduces Ischemic Damage
		Apoptosis in Human Brain
		REFERENCES
	Chapter 8 - Molecular Pathophysiology of White Matter Anoxic-Ischemic Injury
		White Matter Anatomy and Physiology
			Cell Culture
			In Vitro Tissue Models
			In Vivo Models
		Effects of Ischemia on White Matter
			Derangement of Transmembrane Ion ­Gradients
			The Ca2+ Hypothesis and Anoxic-Ischemic White Matter Injury
		Mechanisms of White Matter Injury
			Ca2+ Entry and Intracellular Ca2+ Release in Axons during Ischemia
			Reversal of Na+–Ca2+ Exchange
			Activation of Voltage-Gated Ca2+ Channels
			Activation of Intracellular Ca2+ Release
			Excitotoxic Pathways Injure Glia in White Matter
		Autoprotection in White Matter
			Strategies for Protecting White Matter from Anoxic-Ischemic Injury Are Diverse
			Acknowledgments
		REFERENCES
	Chapter 9 - Cerebral Ischemia and Inflammation
		Cerebral Ischemia, Cytokines, and Inflammation
		Mechanisms by Which Inflammation Contributes to Ischemic Brain Injury
		Nitric Oxide and Inducible Nitric Oxide Synthase
		Cyclooxygenase-2
		Danger Sensors: Scavenger Receptors and Toll-like Receptors
		Transcription Factors Involved in Postischemic Inflammation
		Inflammatory Mediators and Ischemic Preconditioning
		From Bench to Bedside
		Conclusions
			Acknowledgments
		REFERENCES
	Chapter 10 - Intracellular Signaling: Mediators and Protective Responses
		Preconditioning
			Induction of Preconditioning
			Cross-Tolerance
			Cellular Defense
		Cellular Maintenance
		Regeneration and Repair
		Clinical Implications
		REFERENCES
	Chapter 11 - Enhancing Brain Reorganization and Recovery of Function after Stroke
		Neurogenesis in the Subventricular Zone
		Proliferation of Neural Stem and Progenitor Cells after Stroke
		Migration and Survival of Neuroblasts after Stroke
		Angiogenesis
		Coupling of Neurogenesis and Angiogenesis
		Angiogenesis, Neurogenesis, and Functional Recovery
			The Effect of Cell-Based and Pharmacologically Based Therapies on Angiogenesis and ­Neurogenesis
			The Effect of Cell and Pharmacologically Based Therapies on Axonal Remodeling
		Conclusion
		REFERENCES
	Chapter 12 - Genetics and Vascular Biology of Brain Vascular Malformations
		Brain Arteriovenous Malformations
			Etiology and Pathogenesis
			Characterization of Lesional Tissue Removed at Surgery
			Genetic Considerations Relevant to AVMs
			Mendelian Disease
			Familial Aggregation
		Genetic Studies of Nonfamilial AVM
			Candidate Gene Studies in AVM Patients
			Beyond Candidate Gene Studies
			An Alternative Genetic Mechanism for ­Sporadic AVMs
			Experimental AVM Models
			Summary and Synthesis of Data Regarding Etiology and Pathogenesis of AVM
		Cerebral Cavernous Malformations
			Overview
			CCM Genetics
			CCM1/KRIT1
			CCM2/MGC4607
			CCM3/PDCD10
			CCM Pathogenesis
			Genotype–Phenotype Correlation
			Summary of CCM Biology and Pathogenesis
		Other Vascular Malformations
			Acknowledgments
		REFERENCES
Section 2 - Epidemiology and Prevention
	Chapter 13 - Distribution of Stroke: Heterogeneity by Age, Race, and Sex
		Indices of Stroke Heterogeneity
		Distribution of Disease
			Stroke Mortality
			Stroke Incidence
			Stroke Prevalence
		Conclusions
		REFERENCES
	Chapter 14 - Epidemiology of Stroke
		Magnitude of the Problem
		Mortality
		Cost
		Incidence of Stroke
		Frequency of Stroke by Type
			Silent Stroke
			Recurrent Stroke
		Risk Factors for Stroke
			Atherogenic Host Factors
			Heart Disease and Impaired Cardiac Function
			Other Host Factors
			Environmental Factors
			Acknowledgments
		REFERENCES
	Chapter 15 - Prognosis after Stroke
		Mortality after Ischemic Stroke
			Early Mortality after Ischemic Stroke
			Late Mortality after Ischemic Stroke
			Predictors of Death after Ischemic Stroke
		Recurrence after Ischemic Stroke
			Predictors of Recurrence after Ischemic Stroke
			Predictors of Early Stroke Recurrence
			Predictors of Late Stroke Recurrence
		Worsening after Ischemic Stroke
		Cardiac Events after Stroke
		Stroke Outcome Prediction Models
			Stroke Prognostic Risk Scores
		Functional Disability and Handicap after Stroke
		Quality of Life after Stroke
		Depression after Stroke
		REFERENCES
	Chapter 16 - Primary Prevention of Stroke
		Assessing the Risk for a First Stroke
		Lifestyle Modification
			Cigarette Smoking
			Physical Activity
			Weight Management and Diet
			Alcohol and Drug Abuse
		Management of Well-Documented Modifiable Risk Factors for Preventinga First Stroke
			Hypertension
			Diabetes
			Lipid-Lowering Therapy
			Atrial Fibrillation
			Aspirin
		REFERENCES
	Chapter 17 - Vascular Dementia and Vascular Cognitive Decline
		Historical Evolution of the Concept of Vascular Dementia
		Diagnostic Criteria for Vascular Dementia
		Dementia following Stroke
		Overlap of Vascular and Neurodegenerative Pathologies
		Epidemiology
		Clinical Diagnosis
			Vascular Mild Cognitive Impairment
		Neuropsychological Assessments of Vascular Cognitive Impairment
		Pathophysiology of Vascular Cognitive Impairment
			Changes in the Neurovascular Unit
		Imaging Correlates of Vascular Cognitive Impairment
			Prevalence of Cerebrovascular Brain Injury
			Association of Cerebrovascular Brain Injury with Cognitive Changes
			Summary
		Neuropathologic Aspects
			Other Vascular Pathologies
		Prevention of Vascular Cognitive Impairment
			Association of Vascular Risk Factors with Vascular Cognitive Impairment and Vascular Dementia
			Association of Vascular Disease Severity ­Measures with Vascular Cognitive Impairment
			Association of Common Clinical Disease States with Vascular Cognitive Impairment
		Treatment of Persons with Clinical Vascular Dementia
		Control of Vascular Risk Factors
		Pharmacologic Treatment of Cognitive Impairment
		Summary
		References
	Chapter 18 - Stroke Genetics
		Evidence for Heritability for Stroke and Its Subtypes
		Disorders Associated with Ischemic or Hemorrhagic Stroke
			Fabry Disease
			CADASIL
			CARASIL
			Homocystinuria
			MELAS
			Sickle Cell Anemia
			Fibromuscular Dysplasia
			Collagen Type IV Alpha 1 Mutations
			Hypercoagulable Disorders
			Moyamoya Disease
			Mendelian CAAs
			Mendelian Cerebral Cavernous Malformation Syndromes
			Autosomal Dominant Polycystic Kidney ­Disease
			Hereditary Hemorrhagic Telangiectasia
			HERNS
		Genome-wide Association Studies
		Apolipoprotein E and Intracerebral Hemorrhage
		Genetic Risk Factors for Common Ischemic Stroke
		Genetics for Optimizing Drug Therapy
		REFERENCES
	Chapter 19 - The Global Burden of Stroke
		The Global Burden of Disease Studies
		Methods for Assessing Cause-Specific Mortality in the GBD
		GBD Estimates of Stroke Mortality at Global, Regional, and Country Level
		Global Stroke Epidemiology: Data and Methods
		Assessing Disability Due to Stroke
		The Global Burden of Stroke in 2004
		Assessing the Contribution of Stroke Risk Factors
		Projections of Stroke Mortality and Burden from 2004 to 2030
		Discussion and Conclusions
			Acknowledgments
		REFERENCES
Section 3 - Clinical Manifestations
	Chapter 20 - Classification of Ischemic Stroke
		Forms of Infarction: Bland and Hemorrhagic
		Problems in the Diagnosis of Infarction
		Subtypes of Ischemic Stroke
			Infarct with Large Artery Thrombosis
			Clinical Features
			Results of Diagnostic Tests
		Embolism Attributed to Cardiac Sources
			Properties of Emboli
			Clinical Features
			Results of Diagnostic Tests
		Lacunar Infarction
			Clinical Features
			Results of Diagnostic Tests
		Cryptogenic Infarction or Infarct of Undetermined Cause
			Clinical Features
			Results of Diagnostic Tests
			Potential Explanations for Cryptogenic Stroke
		REFERENCES
	Chapter 21 - Clinical Scales to Assess Patients with Stroke
		Desired Qualities of Stroke Scales
		Emergency Medical Services Scales
		Scales to Differentiate Hemorrhagic Stroke from Ischemic Stroke
		Scales to Quantify the Severity of Hemorrhagic Stroke
		Scales to Quantify the Severity of Subarachnoid Hemorrhage
		Scales to Quantify the Severity of Ischemic Stroke
		Systems to Differentiate the Cause of Ischemic Stroke
		Measures to Assess Responses to Rehabilitation Interventions
		Scales to Rate Outcomes (Disability) after Stroke
		Scales to Rate Outcomes (Global or Handicap) after Stroke
		Scales to Assess the Quality of Life after Stroke
		REFERENCES
	Chapter 22 - Carotid Artery Disease
		Carotid Anatomy and Lesion Development
			Atherosclerosis of the Extracranial Common Carotid Bifurcation and Internal Carotid
			Intracranial Internal Carotid Artery Disease
		Pathophysiology of Carotid Artery Ischemia
			Collateral Pathways
			Mechanisms of Ischemic Stroke
		Clinical Syndromes
		Ischemic Stroke from Carotid Artery Disease
			Ocular Infarction
			The Anterior Choroidal Artery
			Cerebral Infarction
		Reversible Ischemic Neurologic Deficit
		Transient Ischemic Attacks
			Differential Diagnosis of Transient Ischemic Attacks
			Transient Ischemic Attacks with Intracranial Internal Carotid Artery Disease
			Transient Monocular Blindness
			Transient Hemispheric Attacks
			Nonsimultaneous Transient Monocular Blindness and Transient Hemispheric Attacks
			Stroke Risk Associated with Transient Monocular Blindness and Transient Hemispheric Attacks
			Angiographic Correlations with Transient ­Ischemic Attacks
			Transient Ischemic Attacks and Nonstenosing Carotid Lesions
		Asymptomatic Carotid Artery Disease
			Asymptomatic Carotid Artery Occlusion
			Asymptomatic Carotid Artery Stenosis
			Asymptomatic Carotid Ulceration
			Asymptomatic Bruit
			Postendarterectomy Doppler Ultrasonography Findings
		REFERENCES
	Chapter 23 - Anterior Cerebral Artery Disease
		Anatomy
			Anomalies and Species Differences
		Symptoms and Signs
			Weakness and Sensory Loss
			Callosal Disconnection Signs
			Akinetic Mutism (Abulia)
			Language Disturbance
			Other Mental Abnormalities
			Incontinence and Other Autonomic Changes
			Miscellaneous Symptoms
			Periventricular Leukomalacia of Infancy
		REFERENCES
	Chapter 24 - Middle Cerebral Artery Disease
		Descriptive Terms
			Names of Stem, Divisions, and Branches
		Histology
		Pathology
			Embolism
			Thrombosis
			Other Diseases
		Clinical Syndromes of Middle Cerebral Artery Territory Infarction
		Clinical Syndromes from Infarction of Either Hemisphere
			Loss of Consciousness
			Hemiplegia and Hemiparesis
			Movement Disorders
			Contraversive Eye and Head Deviation
			Dizziness and Vertigo
			Sensory Disturbances
			Visual Field Disturbances
		Syndromes Referable to ­Language-Dominant (Usually Left) Hemisphere Infarction
			Aphasia
			Apraxias
		Syndromes of Infarction in the Hemisphere Nondominant for Speech and Language
			Neglect and Extinction
			Anosognosia
			Impersistence
			Dressing Apraxia
			Loss of Topographic Memory and ­Disorientation for Place
			Disorders of Spatial Localization
			Confusion and Delirium
			Confabulation and Reduplicative Paramnesia
			Constructional Apraxia
			Allesthesia
			Amusia
			Aprosody and Affective Agnosia
			Treatment of Hemineglect
		References
	Chapter 25 - Posterior Cerebral Artery Disease
		Anatomy
			Brainstem and Thalamic Territory
			Cortical Territory
			Collateral Linkages
		Vascular Disease
			Embolism
			Thrombosis
			Other Causes of Infarction
		Clinical Syndromes
			Distal Basilar and Posterior Cerebral Artery Stem Occlusion
			Sensory Syndromes
			Motor Syndromes
			Oculomotor and Pupillary Disturbances
			Visual Field Disturbances
			Visual Agnosia
			Distortions of Visual Perception
			Topographical Disorientation
			Disorders of Reading
			Color Dysnomia and Dyschromatopsia
			Aphasia
			Memory Disorder Syndromes
			Klüver-Bucy Syndrome
		REFERENCES
	Chapter 26 - Vertebrobasilar Disease
		Anatomy
			Embryology
			Vascular Anatomy
		Pathology
			Atherosclerosis
			Lipohyalinosis
			Aneurysms
			Arterial Dissection
			Cervical Spondylosis
			Neck Rotation or Trauma
			Fibromuscular Dysplasia
			Temporal Arteritis
			Other Diseases
		Pathophysiology
			Intraarterial Embolism
			Worsening
		Clinical Findings in Patients with Vascular Lesions in Various Locations
			Occlusion or Severe Stenosis of the Basilar Artery
			Clinical Tempo and Course
		Clinical Syndromes of Basilar Occlusion
			Coma
			Weakness
			Decerebrate Responses
			Locked-in Syndrome
			Ataxia
			Palatal Myoclonus
			Neuroophthalmologic Observations
			Sensory Findings
			Abnormalities of Respiration
		Top of the Basilar Artery Occlusion
			Abnormalities of Alertness, Attention, and Behavior
			Pupillary Abnormalities
			Oculomotor Dysfunction
			Abnormalities of Convergence
			Hallucinations
			Confabulations
			Hemiballism and Abnormal Movements
		Basilar Branch and Lacunar Disease
		Occlusion of Long Circumferential Branches of the Basilar Artery
			Superior Cerebellar Artery Occlusions
			Anterior Inferior Cerebellar Artery Occlusions
			Posterior Inferior Cerebellar Artery Infarctions
		Intracranial Vertebral Artery Occlusive Disease
			Lateral Medullary Infarction
			Hemimedullary Infarction (Elements of Medial and Lateral Ischemia)
			Medial Medullary Infarction
			Transient Ischemic Attacks or No Deficit
		Extracranial Vertebral Artery Occlusive Disease
		Bilateral Vertebral Artery Occlusion
		Subclavian-Innominate Artery Disease and Subclavian Steal
		Mobile Thrombus in the Aortic Arch
		Multiple Infarcts in the Posterior Circulation
		Low-Flow States with Resultant Borderzone Ischemia in the Posterior Circulation
		Migraine
		REFERENCES
	Chapter 27 - Microangiopathies (Lacunes)
		Historical Aspects
		Definitions
		Pathoanatomy
			Size
			Location
			Vascular Territories Involved
		Arteriopathies Underlying Lacunes
			Microatheroma
			Lipohyalinosis and Fibrinoid Necrosis
			Charcot-Bouchard Aneurysms
			Other Causes
		General Clinical Features
		Clinical Syndromes
			Lacunar State
			Pure Motor Stroke
			Pure Sensory Stroke
			Sensorimotor Stroke
			Ataxic Hemiparesis
			Dysarthria-Clumsy Hand Syndrome
			Atypical Lacunar Syndromes
			Movement Disorders
			Speech and Language Disorders
			Infarcts in the Centrum Semiovale
			Microangiopathies in Vascular Dementia
			Strategic Infarcts
		Laboratory Studies
			Computed Tomography
			Magnetic Resonance Imaging
			Angiography
			Transcranial Doppler Ultrasonography
			Echocardiography
			Neurophysiologic Studies
			Genetic Study
		Prognosis
			Risk of Vascular Dementia
			Progression of Asymptomatic Small Vessel Disease
		Treatment
			Practical Approach
		REFERENCES
	Chapter 28 - Cerebral Venous Thrombosis
		Epidemiology
		Venous Anatomy
		Pathophysiology
		Etiology
		Clinical Aspects
		Diagnosis
			Computed Tomography
			CT Venography
			Magnetic Resonance Techniques
			Intraarterial Angiography
			Interobserver Agreement on Neuroimaging Diagnosis of Cerebral Venous Thrombosis
			Transcranial Doppler Ultrasonography
			D-Dimer Levels
		Prognosis
		Treatment
			Antithrombotic Treatment
			Thrombolysis
			Prevention of Thrombotic Events after the Acute Phase
			Symptomatic Treatment
		Contraception and Future Pregnancies
		REFERENCES
	Chapter 29 - Intracerebral Hemorrhage
		Genetics
			Familial Cerebral Amyloid Angiopathy
			Sporadic Cerebral Amyloid Angiopathy
		Pathologic Features and Pathogenesis
			Vascular Rupture
			Active Bleeding
			Gross Pathologic Anatomy
			Recurrence of Intracerebral Hemorrhage
			Histopathologic Studies
			Nonhypertensive Causes of Intracerebral Hemorrhage
		Brain Imaging
			Microhemorrhages
		General Clinical and Laboratory Features
		Supratentorial Intracerebral Hemorrhage
			Putaminal Hemorrhage
			Caudate Hemorrhage
			Thalamic Hemorrhage
			White Matter (Lobar) Hemorrhage
		Hemorrhage Affecting the Brainstem and Cerebellum
			Cerebellar Hemorrhage
			Midbrain Hemorrhage
			Pontine Hemorrhage
			Unilateral Basal or Basotegmental Hemorrhages
			Lateral Tegmental Brainstem Hematomas
			Medullary Hemorrhage
		References
	Chapter 30 - Aneurysmal Subarachnoid Hemorrhage
		Historical Aspects
		Epidemiology
			Risk Factors
			Causes of Subarachnoid Hemorrhage
		Pathophysiology
			Distribution and Types of Aneurysms
			Aneurysm Development
			Aneurysm Rupture
		Clinical Presentation
			Signs and Symptoms
			Misdiagnosis of Subarachnoid Hemorrhage
		Radiographic and Diagnostic Testing
		Searching for the Aneurysm
			Cerebral (Catheter) Angiography
			CT Angiography
			Magnetic Resonance Angiography
			Angiographically “Negative” Subarachnoid Hemorrhage
			Grading Scales for Subarachnoid Hemorrhage
		Management
			General Measures
			Securing the Aneurysm: Surgical versus Endovascular Treatment
			Neurologic Complications
			Medical Complications of Subarachnoid ­Hemorrhage
		Outcomes
		REFERENCES
	Chapter 31 - Arteriovenous Malformations and Other Vascular Anomalies
		Arteriovenous Malformations
			History
			Etiology
			Morphology
			Epidemiology
			Genetics
			Diagnosis and Classification
			Clinical Syndromes
			Physiologic Studies
		Other Vascular Malformations and Anomalies
			Acquired Arteriovenous Fistulas
		Ongoing Clinical Trials
		References
	Chapter 32 - Spinal Cord Ischemia
		Historical Aspects
		Blood Supply to the Spinal Cord
			Longitudinal Arteries
			Radicular Tributary Arteries
			Intrinsic Blood Supply of the Cord
			Venous System
		Physiology of Spinal Cord Blood Flow
		Pathology of Spinal Cord Infarction
		Etiology
			Dissection of an Aortic Aneurysm
			Coarctation of the Aorta
			Systemic Hypoperfusion
			Iatrogenic Ischemia of the Spinal Cord
			Anterior Spinal Artery Syndrome
			Posterior Spinal Artery Syndrome
			Venous Infarction
		Differential Diagnosis
		Diagnostic Tests
		Treatment and Prognosis
		References
Section 4 - Specific Medical Diseases and Stroke
	Chapter 33 - Arterial Dissections and Fibromuscular Dysplasia
		Arterial Dissections
			Epidemiology
			Pathology
			Clinical Manifestations
			Diagnosis
			Treatment
			Course and Prognosis
		Fibromuscular Dysplasia
			Epidemiology
			Pathology
			Pathogenesis
			Sites
			Clinical Manifestations and Diagnosis
			Treatment
		References
	Chapter 34 - Collagen Vascular and Infectious Diseases
		Giant Cell Arteritis
			General Clinical Features
			Diagnosis
			Treatment and Prognosis
			Pathology
			Clinical Features
			Treatment
		Takayasu’s Arteritis
		Polyarteritis Nodosa
		Systemic Lupus Erythematosus
		Wegener’s Granulomatosis
		Allergic Angiitis
		Lymphomatoid Granulomatosis
		Scleroderma
		Rheumatoid Arthritis
		Sjögren’s Syndrome
		Sneddon’s Syndrome
		Malignant Atrophic Papulosis
		Behçet’s Disease
		Cryoglobulinemia
		References
	Chapter 35 - Moyamoya Disease
		Guideline For Diagnosis
		Epidemiology
		Pathology
			The Circle of Willis and the Major Branches
			Perforating Arteries (Moyamoya Vessels)
			Leptomeningeal Vessels
			Aneurysm Formation
			Extracranial Cervical Arteries and Systemic Arteries
		Etiology and Pathogenesis
		Clinical Symptoms and Signs
		Laboratory Findings
		Clinical Examination
			Angiography
			Computed Tomography
			Magnetic Resonance Imaging and ­Angiography
			Ultrasonography
			Electroencephalography
			Other Clinical Examinations
		Disease Progression and Prognosis
		Treatment
			Medical Treatment
			Surgical Treatment
		Conclusion and Future Directions
		References
	Chapter 36 - Migraine and Stroke
		Clinical Features
		Classification
			Migraine-Induced Stroke
			Coexisting Stroke and Migraine
			Stroke with Clinical Features of Migraine
			Uncertain Classification
		Epidemiology
			Potential Factors Increasing the Risk of Stroke among Patients with Migraine
		Neuroimaging
			Magnetic Resonance Imaging
			Positron Emission Tomography
		Headache of Vascular Disease
			Drug-Induced Migraine–Related Stroke
		Migraine that Mimics Stroke
			Hemiplegic Migraine
			Basilar Artery Migraine
		Mechanisms
		Migraine and Patent Foramen Ovale
			Acknowledgments
		References
	Chapter 37 - Hypertensive Encephalopathy
		Pathogenesis
		Pathologic Features
		Clinical Features
		Neuroradiologic Features
		Causes
		Treatment
		References
	Chapter 38 - Atherosclerotic Disease of the Proximal Aorta
		Aortic Plaques and Ischemic Stroke
			Pathology Studies
			In Vivo Studies—Transesophageal ­Echocardiography
			Case-Control Studies
			Prospective Studies
			Plaque Morphology and Stroke Risk
		Natural History of Aortic Plaques
		Aortic Plaques and Atheroembolism
			Proximal Aortic Plaques and Cardiac Surgery
			Proximal Aortic Plaques and Cardiac ­Catheterization
		Treatment of Proximal Aortic Plaques
			Systemic Anticoagulation
			Antiplatelet Medications
			Thrombolysis
			Statins
			Surgery
		Future Directions
			Newer Imaging Modalities
			Identification of the Vulnerable (High-Risk) Plaque
		Summary
		REFERENCES
	Chapter 39 - CADASIL: Cerebral Autosomal ­Dominant Arteriopathy with ­Subcortical Infarcts and ­Leukoencephalopathy
		History
		Clinical Presentation
		Neuroimaging
		Pathology
		Genetics
		Diagnosis
		Conclusion
		REFERENCES
	Chapter 40 - Reversible Cerebral ­Vasoconstriction Syndromes
		Demographics and Clinical Features
		Laboratory Findings
		Brain Imaging
		Differential Diagnosis
		Etiology and Pathophysiology
		Management
		Outcome and Prognosis
		REFERENCES
	Chapter 41 - Coagulation Abnormalities in Stroke
		Pathogenesis of Thrombosis
			Vascular Injury
			Factor V Leiden, Antithrombin III, Protein C, Protein S, and Protein Z Deficiencies; Prothrombin G20210A Polymorphism; and von W...
			Activation of Hemostasis and Fibrin Formation
			Fibrinolysis
			Platelet Adhesion, Activation, and Aggregation
			Heparin-Induced Thrombocytopenia
			Antiphospholipid Antibodies
			Sneddon‘s Syndrome
		Homocystinuria and Homocystinemia
		Sickle Cell Disease
		References
	Chapter 42 - Stroke and Substance Abuse
		Opiates
		Amphetamine and Related Agents
		Cocaine
		Phencyclidine
		Lysergic Acid Diethylamide
		Marijuana
		Barbiturates
		Inhalants
		Alcohol
		Tobacco
		REFERENCES
	Chapter 43 - Cardiac Diseases
		Diagnostic Studies
		Approach to Management
			Structural Cardiac Defects
			Dysrhythmias
			Valvular Disease
			Cardiac Procedures
			Cardiac Embolism and the Hemostatic System
		REFERENCES
Section 5 -Diagnostic Studies
	Chapter 44 - Ultrasonography
		Ultrasound Technology
			Doppler Ultrasonography
			Imaging Techniques
		Monitoring Early Atherosclerosis
			Intima–Media Thickness
			IMT Sampling
			Serial Measurements of IMT
			Quality Control
			Pathophysiologic Correlates
			Clinical Studies of IMT
			Identifying Early Carotid Plaque
			Endothelium-Dependent Flow-Mediated Vasodilation
			Assessment of Advanced Atherosclerotic Disease
		Nonatherosclerotic Vascular Disease
			Carotid Artery Dissection
			Vertebral Artery Dissection
			Inflammatory Disease of the Carotid Arteries
			Intracranial Stenosis and Occlusion
			Assessment of Intracranial Collateralization
			Microembolic Signal Detection
			Definition of High-Intensity Transient Signals
			Differentiation
			Localizing the Source of Embolism in Patients with Stroke
			Predicting Cerebral Ischemia
			Interventional Trials Using MES Detection
			Future Aspects of Microembolic Signal Detection
			Dolichoectatic Arteries and Intracranial Vasculopathies
			Detection of Right-to-Left Cardiac Shunts
		Echocontrast Studies in Stroke Diagnosis
			Carotid Artery Stenosis
			Insufficient Transcranial Bone Windows
			Intracranial Vertebral and Basilar Arteries
			Intracranial Aneurysms
			Arteriovenous Malformations
			Venous Thrombosis
		Ultrasound Monitoring in Acute Stroke
			Monitoring of Thrombolysis
			Monitoring of Midline Shift
			Assessment of Vasospasm
			Increased Intracranial Pressure
			Functional Studies
			Ultrasonographic Brain Perfusion Imaging
			Contrast-Specific Imaging Techniques
			Power Modulation
			Power Modulated Pulse-Inversion Imaging
			High Mechanical Index Perfusion Studies
			Low Mechanical Index Perfusion Imaging
			Bolus, Destruction, and Refill Kinetics
			Safety of Ultrasound Perfusion Imaging
			Brain Perfusion Imaging in Acute Ischemic Stroke Patients
		Stroke Therapy with Ultrasound
			Sonothrombolysis
			Ultrasound-Enhanced t-PA Thrombolysis
			Microbubble-Enhanced Thrombolysis with t-PA
			Clot Lysis with Ultrasound and Microbubbles without Thrombolytic Drugs
		Emerging Applications
			Molecular Imaging
			Opening the Blood–Brain Barrier
			Ultrasound-Enhanced Gene Therapy
			Targeted Drug Delivery with Ultrasound
		REFERENCES
	Chapter 45 - Computed Tomography–Based ­Evaluation of Cerebrovascular ­Disease
		Noncontrast CT
			Feasibility and Technical Capacity
			Diagnostic Impact
			Therapeutic Impact
			Prognostic Impact
		CTA
			Feasibility and Technical Capacity
			Diagnostic Accuracy
			Diagnostic Impact
			Therapeutic Impact
		CT Perfusion Imaging
			Technical Capacity and Feasibility
			Diagnostic Accuracy
			Diagnostic Impact
			Therapeutic and Prognostic Impact
		Posterior Circulation CT Imaging
			Ischemic Stroke
		NCT and CTA in Acute Hemorrhagic Stroke
			Acknowledgment
		REFERENCES
	Chapter 46 - Magnetic Resonance Imaging of Cerebrovascular Diseases
		Conventional Pulse Sequences
			Advanced Stroke MRI
			Susceptibility-Weighted Imaging
			Spectroscopy
		Stroke MRI Examination
		Transient Ischemic Attacks
			Standard MRI
			Advanced MR Techniques: Diffusion-Weighted Imaging, Perfusion MRI
		Ischemic Stroke
			Tissue Metabolite Changes in Infarction
		Hemorrhage
			Intraparenchymal Hemorrhage
			Microbleeds
			Hemorrhagic Transformation
			Subarachnoid Hemorrhage
			Subdural and Epidural Hematomas
		Vascular Pathology
			Cerebral Venous Thrombosis
		MRI-Guided Acute Stroke Therapy
		References
	Chapter 47 - Cerebral Angiography
		Technique
		Risks
		Angiographic Cerebral Vasculature: Normal Anatomy
		Indications
			Intracranial Hemorrhage
			Ischemia
		REFERENCES
Section 6 -Therapy
	Part A - Medical Therapy
		Chapter 48 - Prehospital and Emergency ­Department Care of the Patient with Acute Stroke
			Prehospital Components
				Emergency Department
			First Contact with Medical Care
			Prehospital Evaluation and Management
			Prehospital Identification of Stroke
			Emergency Department Time Delays
			Emergency Department Triage
				Airway
				Breathing
				Circulation
				Other Issues
				Diagnostic Studies
				Stroke Mimics
				Ischemic Stroke
				Hemorrhagic Stroke
				Subarachnoid Hemorrhage
			Conclusion
			REFERENCES
		Chapter 49 - Intravenous Thrombolysis
			Thrombosis and Thrombolysis
				Endogenous Plasminogen Activators
				Novel Plasminogen Activators
				Exogenous Plasminogen Activators
				Feasibility Studies
				Large, Randomized, Multicenter, Placebo-Controlled Trials
				Treatment Protocol
				Expedited Treatment Protocol
				Early Computed Tomography Findings Are Not Contraindications to Treatment
				Effect of Time to Thrombolytic Treatment
				Generalized Efficacy of t-Pa for Acute Stroke
				Recanalization and Arterial Reocclusion after t-Pa Treatment
				Management During and After Thrombolytic Treatment77
				Predictors of Good Outcome with Thrombolytic Treatment
				Risks of Thrombolysis
				Cost-Effectiveness of Thrombolysis
			Combination Treatment
			Conclusion
			REFERENCES
		Chapter 50 - Antithrombotic Therapy for ­Treatment of Acute Ischemic Stroke
			Pharmacology
				Heparin, Low-Molecular-Weight Heparins, and Danaparoid
				Other Anticoagulants
				Antiplatelet Agents
				Heparin
				Low-Molecular-Weight Heparins and Danaparoid
				Other Antithrombotic Agents
				Antiplatelet Agents
				Conclusions
				Unfractionated Heparin
				Low-Molecular-Weight Heparins and Danaparoid
				Other Antithrombotic Agents
				Antiplatelet Agents
				Conclusions
			Prevention of Deep Vein Thrombosis
			Other Indications
			Current Status of Antithrombotic Therapy
			Future of Antithrombotic Therapy
			REFERENCES
		Chapter 51 - General Stroke Management and Stroke Units
			Short History of Stroke Units
			Stroke Unit Design
			Effectiveness of Stroke Unit Care
			Who Benefits?
			Availability of Stroke Unit Care
			General Stroke Management
				Vital Functions
				Recanalization
				Unstable Cerebral Ischemia and Progressing Stroke
				Prevention and Treatment of Infarct Edema and Elevated Intracranial Pressure
				Prevention of Acute Medical Complications
				Special Aspects
			Conclusions
			REFERENCES
		Chapter 52 - Critical Care of the Patient with Acute Stroke
			General Principles of Neurologic Critical Care
				Ancillary Tests
				Clinical Examinations
				Pulmonary Function and Mechanical Ventilation
				Sedation and Analgesia
				Fluid and Electrolyte Balance
				Nutrition
				Blood Pressure Control
				Invasive Monitoring Procedures
					Central Venous Line
					Pulse Contour Analysis
					Invasive Monitoring of Arterial Blood Pressure
					Invasive Monitoring of Intracranial Pressure
				Treatment of Raised Intracranial Pressure
					Basic Measures
					Specific Treatment
				Prevention of Deep Vein Thrombosis and Pulmonary Embolism
				Management of Blood Glucose
				Temperature Management
			Specific Treatment of Various Stroke Syndromes
				Acute Large Middle Cerebral Artery Stroke
				Acute Basilar Artery Occlusion
				Cerebellar Infarction
				Spontaneous Intracerebral Hemorrhage
					Medical Treatment
				Subarachnoid Hemorrhage
					General Management
					Rebleeding
					Antifibrinolytics
					Acute Hydrocephalus
					Vasospasm
					Extracranial Complications
					Invasive Neuromonitoring
			References
		Chapter 53 - Pharmacologic Modification of Acute Cerebral Ischemia
			Background: Preclinical and Clinical Cytoprotection
				The Definition and Role of Cytoprotection
				Targets of Cytoprotection: The Ischemic ­Cascade
				Preclinical Stroke Models
				Preclinical Testing of Cytoprotective Therapies
					The Need for Careful Physiologic Monitoring
					Penumbra as Target
					Reperfusion Injury
					Downstream Targets
					Multimodality Therapy
					Early Pharmacologic Intervention May Influence Functional Recovery
					Relevance of Animal Models
				Important Issues to Clarify in Design of Future Clinical Trials
					Standardization of Stroke
					Sample Size
					Time
					Coupling Cytoprotection with Reperfusion
					Dose
					More Sensitive Outcome Measures
					More Potent Therapies Are Needed
			Clinical Cytoprotective Therapy Trials
				Calcium Antagonists
				Glutamate Antagonists
				Agents Acting Indirectly on Glutamate
				Other Neurotransmitter Modulators
				Free Radical Scavengers, Adhesion ­Molecule Blockers, Steroids, and Other ­Anti-Inflammatory Strategies
				Membrane “Stabilizers” and Trophic Factors
				Hypothermia
				Caffeinol
				Blood Substitutes and Oxygen Delivery
			Conclusion
			Reference
		Chapter 54 - Treatment of “Other” Stroke ­Etiologies
			Vascular Disorders
				Noninflammatory Vasculopathies
					Arterial Dissection
					Fibromuscular Dysplasia
					Vasospasm after Subarachnoid Hemorrhage
					Reversible Cerebral Vasoconstriction Syndromes
					Radiation-Induced Vasculopathy
					Moyamoya Disease
					Hyperhomocyst(e)inemia and Homocystinuria
					Fabry Disease
				Inflammatory Vasculopathies
					Isolated Angiitis of the Central Nervous System
					Temporal (Giant Cell) Arteritis
					Cerebral Vasculitis Related to Collagen Vascular Disorders
					Cerebral Vasculitis Related to Infection
					Cerebral Vasculitis Related to Toxins
					Cerebral Vasculitis Related to Neoplasms
			Hematologic Disorders
				Prothrombotic Disorders
					Disorders of the Coagulation System
					Antiphospholipid Antibody Syndrome
				Disseminated Intravascular Coagulation
				Sickle Cell Disease
			Miscellaneous Disorders
				Migraine-Related Stroke
				Mitochondrial Encephalopathy, Lactic Acidosis, and Strokelike Episodes
				Cerebral Venous Thrombosis
			Reference
		Chapter 55 - Medical Therapy of Intracerebral and Intraventricular Hemorrhage
			Emergency Department Management
			The Importance of Aggressive Medical Therapies
				Stroke Units and Intensive Care Units
				Fever
				Hyperglycemia
				Hypertension
				Mechanical Ventilation
				Deep Vein Thrombosis
				Steroids
				Anticonvulsants
				Antiplatelets
				Other Therapies
			Prevention of Rebleeding
				Cerebral Edema
				Hydrocephalus and Intraventricular Hemorrhage
				Intracranial Pressure Considerations
			Selection of Patients for Surgery
			Conclusions
			Reference
		Chapter 56 - Rehabilitation and Recovery of the Patient with Stroke
			Neurologic Rehabilitation
				Specialized Assessment and Outcome ­Measures
				Mechanisms for Gains
				Organization of Services
				Overview of Practices
			Rehabilitation-Related Medical Complications
				Bladder Dysfunction
				Musculoskeletal and Central Pain
				Depression
				Fatigue
				Dysphagia
				Skin Ulcers
				Sexual Dysfunction
				Sleep Disorders
				Spasticity
			Cognitive Rehabilitation
				Memory Disorders
				Visuospatial and Attentional Disorders
				Pharmacotherapy
				Speech and Language Therapies
				Interventions
				Pharmacotherapy
			Mobility Training
				Natural History
				Interventions
				Task-Oriented Approaches
			Upper Extremity and Self-Care Skills
				Natural History
				Interventions
				Task-Oriented Approaches
				Pharmacotherapy
			Conclusions
			References
		Chapter 57 - Enhancing Stroke Recovery with Cellular Therapies
			What Are the Goals of Cell-Based Therapy for Stroke?
			The Complexity of Stroke for Cell Therapy
			The Complexity of Cells
				Embryonic Cells
				Neural Cells
					Neural Transplants
					Neural Stem Cells
					Neural Stem Cell Lines
					Summary of Neural Cells
				Alternative Sources of Adult Stem Cells
					Bone Marrow
			Mechanisms
				Tissue Replacement
				Trophicity and Paracrine Effects
				Peripheral Organs as Bioreactors
				Angiogenesis and Neurogenesis
				Upregulating Brain Plasticity
			Pilot Clinical Trials: Lessons Learned
				NT2N Cells
				Porcine Niemann Pick-C1s (NPCs)
			Recent and Ongoing Studies
				Mesenchymal Stem Cells
				Bone Marrow Mononuclear Cells
				Other Bone Marrow Studies
			Translational Barriers
				Delivery Routes
				Allogeneic versus Autologous
				Safety Issues
				When to Treat
				Surrogates of Activity and Biologic Potency Assays
				Labeling and Tracking of Cells
			Guidelines: Stem Cell Therapies as an Emerging Paradigm in Stroke
			Conclusion
				Disclosures
			Reference
		Chapter 58 - Antiplatelet Therapy for Secondary Prevention of Stroke
			Platelet Physiology in the Planning of Antiplatelet Therapy
				Normal Functions of Platelets in Hemostasis
				Participants in the Initial Platelet Response to Vascular Injury
				Platelet Membrane Components Mediating Platelet Activation
				Platelet Adhesion
				Platelet Aggregation
					Platelet Membrane Receptors in Aggregation
					Multiple Independent Pathways to Aggregation
				Platelet Release Reaction
				Platelet Synthesis of Vasoactive Lipid Mediators
				How Platelet Activation Promotes Blood Coagulation
				Platelet Participation in Fibrinolysis and Thrombolysis
				Physiologic Mechanisms That Limit Platelet Activation
				Platelet Activation as a Link between Hemostasis and Inflammation
			Platelet Function in Patients at Risk of Occlusive Stroke
				Factors Contributing to Platelet Hyperactivity
				Role of Platelet Count
				Chronic Changes in Platelet Reactivity
				Aspirin
				Clopidogrel, a Thienopyridine Inhibitor of ADP-Mediated Platelet Activation
				Antiplatelet Agents in Primary Prevention of Stroke
				Antiplatelet Agents in Secondary Prevention of Noncardioembolic Stroke
					Antiplatelets in Comparison with Warfarin
					Antiplatelets as Monotherapy and in Combination for Secondary Stroke Prevention
				Antiplatelet Agents in Secondary Prevention of Cardioembolic Stroke
			Combinations of Antiplatelet Agents
				Aspirin and Thienopyridines
					Ischemic Strokes
					Carotid Endarterectomy and Carotid Artery Stenting
				Antiplatelet Agents and Anticoagulants
			Other Antiplatelet Agents
			Antiplatelet and Cerebral Microbleeds
			Conclusions
			Reference
		Chapter 59 - Secondary Prevention of Cardioembolic Stroke
			Atrial Fibrillation
				Stroke Prevention in Atrial Fibrillation
			Cardiomyopathies
				Dilated Cardiomyopathy
			Myocardial Infarction
			Valvular Heart Disease
				Rheumatic Mitral Valve Disease
			Prosthetic Cardiac Valves
			Nonbacterial Thrombotic Endocarditis
			Infectious Endocarditis
			Cardiac Tumors
			Patent Foramen Ovale
			Aortic Arch Disease
			Anticoagulant Agents
				Heparin, Low-Molecular-Weight Heparin, and Heparinoids
				Warfarin
				Oral Anticoagulants Combined with ­Antiplatelet Agents
				New Antithrombotic Agents
			Summary
			References
		Chapter 60 - Conduct of Stroke-Related Clinical Trials
			Prevention Trials
			Therapeutic Trials
			The Three Phases of Clinical Trials
				Phase 1 Trials
				Phase 2 Trials
				Phase 3 Trials
			Outcome Measures
			Sample Size
				J-Shaped Distribution
				One-Tailed or Two-Tailed Tests
				Power and Alpha Level
				Equivalence or Noninferiority
				Adjusting for Drop-Outs and Drop-Ins
			Adaptive Designs
			Inclusion and Exclusion Criteria for Phase 3 Trials
			Randomization
				Stratification
				Blocking
			Blinding
			Recruitment
				Measuring Adherence to Treatment
			Data Collection and Quality Assurance
				Protocol and Manual of Procedures
				Training
			Data Analyses
				Intent to Treat
				General Approaches
				Global Tests
				Multiple Comparisons
				Clustering
				Missing Data
				Interim Analysis
				Analysis of Covariance
				Subgroup Analyses and Interactions
			Regulations and Guidelines
				Federal Regulations
				Ethics and the Protection of Human Subjects
				International Guidelines for Conducting Clinical Trials
			Reference
	Part B - Interventional Therapy
		Chapter 61 - Interventional Neuroradiologic Therapy of Atherosclerotic Disease and Vascular Malformations
			Acute Ischemic Stroke
				Thrombolysis of Acute Ischemic Stroke
				Intraarterial Thrombolysis Trials
				Mechanical Thrombolysis
				Physician and Patient Education
			Intracranial Atherosclerotic Disease
				Natural History and Medical Management
				Endoluminal Revascularization
			Extracranial Vertebral Artery Stenosis
			Subclavian Steal Syndrome
			Intracranial Aneurysms
				Subarachnoid Hemorrhage
				Mass Effect
				Ischemic Complications
				Technical Advances in Coil Treatment
				Fusiform Aneurysms
			Arteriovenous Malformations
				Definition, Pathology, and Epidemiology
				Classification
				Natural History
				Treatment
			Conclusion
				Disclosures
			References
		Chapter 62 - Intraarterial Thrombolysis in Acute Ischemic Stroke
			General Technique of Intraarterial Thrombolysis
				Thrombolytic Agents
				Adjunctive Therapy
			The Prolyse in Acute Cerebral Thromboembolism Trials
				Middle Cerebral Artery Embolism Local ­Fibrinolytic Intervention Trial
			Mechanical Thrombectomy in Acute Stroke
				The Mechanical Embolus Removal in Cerebral Ischemia and Multi MERCI Trials
				The Penumbra System
				Indications for and Drawbacks of Mechanical Thrombectomy
			Drawbacks of Intraarterial Thrombolysis
			Intraarterial versus Intravenous Thrombolysis
			Combined Intravenous and Intraarterial Thrombolysis
			Recanalization of Acute Internal Carotid Occlusion
			“Wake Up” Stroke
			Vertebrobasilar Intraarterial Thrombolysis
			Risk Factors for Hemorrhagic Transformation
			Other Factors Affecting Outcomes with Thrombolysis
			New Endovascular Therapies for Acute Stroke
			Current Status of Intraarterial Thrombolysis and Needfor More Evidence
			Reference
		Chapter 63 - Endovascular Treatment of Cerebral Aneurysms
			Endovascular Treatment of Ruptured Aneurysms: Evidence
			Endovascular Treatment of Unruptured Aneurysms: Evidence
			Techniques of Endovascular Aneurysm Treatment
				Embolic Coil Technology
				Liquid Embolics
				Adjunctive Devices
				Preprocedural Management
				Intraprocedural Management
				Postprocedural Management
			Management of Periprocedural Complications during Endovascular Aneurysm Treatment
				Thromboembolic Complications
				Perforation
			Future of the Endovascular Treatment of Brain Aneurysms
			Reference
		Chapter 64 - Interventional Therapy of Brain and Spinal Arteriovenous Malformations
			Brain Arteriovenous Malformations
				Classification of Vascular Malformations in General
				Classification of Pial Brain Arteriovenous Malformations in Particular
				Concepts of Treatment
				Specific Treatment Considerations
				Indications for and Contraindications to Endovascular Therapies
			Spinal Arteriovenous Malformations
				Spinal Cord Vascularization
				Angiomorphologic Classification
				Pathophysiologic Classification
				Concepts of Treatment
				Indications for and Contraindications to Endovascular Therapies
			Reference
		Chapter 65 - Dural Arteriovenous Malformations
			Clinical Presentation
			Pathophysiology and Lesion Evolution
			Diagnosis, Classification, and Indications for Treatment
				Diagnosis
				Classification
				Indications for Treatment
			Treatment Options
				Surgical Technique
				Endovascular Treatment
				Radiosurgical Treatment
				Comprehensive Management Strategy
			Summary
			Reference
	Part C - Surgical Therapy
		Chapter 66 - Genetics of Aneurysms and ­Arteriovenous Malformations
			Associated Heritable Disorders
			Arteriovenous Malformations of the Brain
				Associated Heritable Disorders
			Genetic Studies
				Linkage Studies
				Association Studies Using Candidate Genes
				Genome-Wide Association Studies
				Genome-Wide Gene Expression Studies
			Genetic Studies of Intracranial Aneurysms
				Linkage Studies
				Association Studies
				Genome-Wide Association Studies
				Genome-Wide Gene Expression Studies
			Genetic Studies of Arteriovenous Malformations of the Brain
				Linkage Studies
				Association Studies
				Genome-Wide Association Studies
				Genome-Wide Gene Expression Studies
			Conclusion
			Reference
		Chapter 67 - Anterior Circulation Aneurysms
			Historical Perspective
			Intracranial Aneurysms
			General Operative Considerations
				Operative Setup and Positioning
				Surgical Technique
				Pterional Approach
				Petrous Internal Carotid Artery Aneurysms
				Cavernous Internal Carotid Artery Aneurysms
				Paraclinoid ICA Aneurysms
				Posterior Communicating Artery Internal Carotid Artery Aneurysms
				Anterior Choroidal Internal Carotid Artery Aneurysms
				Carotid Bifurcation Aneurysms
				Anterior Communicating Artery Aneurysms
				Distal Anterior Cerebral Artery Aneurysms
				Middle Cerebral Artery Aneurysms
				Giant Aneurysms
				Postoperative Management
				Cerebrospinal Fluid Management
			Reference
		Chapter 68 - Surgical Management of Posterior Circulation Aneurysms
			Selection Criteria for Surgical Treatment
			Surgical Approaches to the Terminal Basilar Bifurcation (Basilar Apex)
				Transsylvian (Frontotemporal or Pterional) Approach
					Intradural Dissection
					Approaches to the Interpeduncular Cistern
					Modifications to Enhance Pterional Exposure
				Anterior Subtemporal Approach
				Temporopolar Approach
					Head Position and Fixation
					Scalp Incision and Craniotomy
					Intradural Dissection
					Approaches to the Interpeduncular Cistern
					Modifications to Enhance Temporopolar Exposure
				Selection of Surgical Approach
			Surgical Approaches to Distal Posterior Cerebral and Superior Cerebellar Artery Aneurysms
			Surgical Approaches to Vertebral Artery and Posterior Inferior Cerebellar Artery Aneurysms
				Far Lateral Suboccipital Craniotomy
					Positioning
					Scalp Incision and Craniotomy
					Intradural Dissection
				Suboccipital Craniotomy
			Surgical Approaches to Basilar Trunk Aneurysms
			Reference
		Chapter 69 - Surgery for Intracerebral Hemorrhage
			Imaging in the Diagnosis of Intracerebral Hemorrhage
				Computed Tomography
					Sites of Hemorrhage
				Magnetic Resonance Imaging
				Angiography
				Blood Flow Mapping with Single-­Photon ­Emission CT and Positron Emission ­Tomography
			Pathophysiology of the Penumbra
				Underlying Pathology
			Surgical Treatment
				Prospective Randomized Controlled Trials and Observational Studies
					Class I Evidence
					Class II and Class III Evidence
				Craniotomy
				Endoscopic Removal of Hematoma
				Ultrasonic Aspiration
				Intracavity Thrombolysis
			Treatment of Intracerebral Hemorrhage Associated with Specific Lesions
				Aneurysmal Intracerebral Hemorrhage
				Arteriovenous Malformation
				Cerebellar Hemorrhage
			Prognosis and Follow-Up
				Epilepsy
				Risk of Rebleeding
				Assessment of Dependence and Disability
			Reference
		Chapter 70 - Intraventricular Hemorrhage
			Primary Intraventricular Hemorrhage
			Hypertensive Brain Hemorrhage and Intraventricular Hemorrhage
			Aneurysmal Intraventricular Hemorrhage
			Clinical Features
			Diagnosis
			Treatment
			Prognosis
			Reference
		Chapter 71 - Surgical Decision Making, Techniques, and Periprocedural Care of Cerebral Arteriovenous Malformations
			Patient-Related Factors
			AVM Architecture
			Timing of Surgery
			Operative Risks
			Anesthetic Considerations for Microsurgery
			Microsurgical Resection
			Posterior Fossa Arteriovenous Malformations
			Associated Aneurysms
			Multimodality Treatment
			Postoperative Care
			Brain Edema and Hemorrhage
			Embolization
			Pediatric Lesions
			Pregnant Patients
			Other Vascular Malformations
			Conclusion
			References
		Chapter 72 - Spinal Arteriovenous Malformations
			Treatment Strategies
				Extradural Arteriovenous Fistulas
				Intradural Dorsal Arteriovenous Fistulas
				Intradural Ventral Arteriovenous Fistulas
				Extradural-Intradural Arteriovenous Malformations
				Intramedullary Arteriovenous Malformations
				Conus Medullaris Arteriovenous Malformations
			Conclusions
			References
		Chapter 73 - Radiosurgery for Arteriovenous Malformations
			Radiosurgery Technique
				Patient Selection
				Head Ring Application
				Stereotactic Image Acquisition
				Treatment Planning
				Dose Selection
				Radiation Delivery
				Follow-up
			Reported Efficacy of AVM Radiosurgery
				Gamma Knife Radiosurgery
				Particle Beam (Proton or Helium) Radiosurgery
				Linear Accelerator Radiosurgery
			Reasons for Radiosurgery Failure
			Complications
				Hemorrhage after Radiosurgery
				Radiation-Induced Complications
				Very Late Onset Complications
			Multimodality AVM Treatment
			Radiosurgery for Other Types of Vascular Malformation
				Venous Malformations
				Telangiectasia
				Dural Arteriovenous Malformations
			Conclusions
			Reference
		Chapter 74 - Cerebral Cavernous Malformations and Venous Anomalies: Diagnosis, Natural History, and Clinical Management
			Definition and Pathologic Features
			Epidemiology and Genetics
			Cerebral Cavernous Malformations
				Diagnostic Imaging
				Clinical Management
					Expectant Follow-up and Medical Management
					Stereotactic Radiosurgery
			Venous Anomalies
				Diagnostic Imaging
				Clinical Management
			Future Considerations
			Reference
		Chapter 75 - Indications for Carotid Endarterectomy in Patients with Symptomatic Stenosis
			Historical Overview
			Prospective Randomized Trials Using Carotid Endarterectomy for Symptomatic Carotid Stenosis
				Early Trials for Carotid Endarterectomy
				Carotid Endarterectomy Trial Meta-analyses and Other Post Hoc Analyses
				Summary of Trials for CEA and Proposed Indications for Intervention Options
			Recent Randomized Trials Comparing Carotid Endarterectomy with Carotid Angioplasty and Stenting
			Conclusions
			References
		Chapter 76 - Surgical Management of Asymptomatic Carotid Stenosis
			Natural History
				Effect of Stenosis Severity
				Effect of Stenosis Progression
				Effect of Plaque Ulceration
			Carotid Endarterectomy versus Medical Management
			Carotid Endarterectomy Versus Carotid Artery Stenting
			Decision Making and Patient Selection
				Age and Life Expectancy
				Gender
				Carotid Plaque Morphology
				Contralateral Carotid Artery Disease
				Concomitant Operations
			Anesthetic Technique and Neuroprotection
			Monitoring Techniques
			Intraoperative Carotid Shunting
			Carotid Patch Grafting
			Surgical Technique
			Complications and Postoperative Care
				Thromboembolic Events
				Wound Hematomas
				Hypertension and Hypotension
				Cerebral Hyperperfusion Syndrome
				Seizures
				Cranial and Sympathetic Nerve Injury
				Myocardial Infarction
			Concluding Remarks and Personal Biases
			References
		Chapter 77 - Extracranial to Intracranial Bypass for Cerebral Ischemia
			Historical Aspects
			Initial Experience with Extracranial to Intracranial Bypass in Acute Brain Ischemia
				Experience with Bypass for Ischemia from Cerebral Vasospasm
				Bypass for Occlusive Cerebrovascular Disease Not Amenable to Carotid Endarterectomy
			Current Trends in the Use of Extracranial to Intracranial Bypass
				Basic Surgical Technique
					Standard STA-MCA Bypass
					Short Saphenous Vein Graft
					Preparation of the Saphenous Vein Graft and Anastomosis
					Long Saphenous Vein Graft or Radial Artery Graft
				Acute Stroke and Emergency Cerebral ­Revascularization
				Occlusive Cerebrovascular Disease
				Moyamoya Disease
				Aneurysms and Tumors
			Conclusions
				Acknowledgments and Disclosure Statement
			References
		Chapter 78 - Cerebral Infarction: Surgical Treatment
			Pathology
			Diagnosis
				Computed Tomography
				Magnetic Resonance Imaging
				Single-Photon Emission Computed Tomography
				Positron Emission Tomography
				Invasive Neuromonitoring
				Animal Studies
				Technical Aspects
			Clinical Studies
				Clinical Case Series
				Clinical Randomized Trials
				Mortality and Functional Outcome
				Quality of Life
				Treatment of Patients with Dominant-­Hemisphere Infarction
				Timing of Hemicraniectomy
				Treatment of Elder Patients
			Related Disorders
				Decompressive Surgery in Space-Occupying Cerebellar Infarction
				Decompressive Surgery in Traumatic Brain Injury
				Decompressive Surgery in Subarachnoid Hemorrhage
				Decompressive Surgery for Spontaneous Intracerebral Hemorrhage
				Decompressive Surgery in Cerebral Venous Thrombosis
			Reference
		Chapter 79 - Cerebellar Infarction and Hemorrhage
			Anatomy of the Cerebellum
			Cerebellar Hemorrhage
				Clinical Features and Pathophysiology
				Indications for Surgery
				Surgical Procedure of Hematoma Evacuation
				Postoperative Management
				Illustrative Cases
					Case 1
					Case 2
					Case 3
			Cerebellar Infarction
				Clinical Features and Pathophysiology
				Indications for Surgery
				Surgical Procedure
				Illustrative Cases
					Case 4
					Case 5
			Conclusion
			Reference
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	X
	Z
Copyright
Title Page
Dedication
Contents
Chapter 1: ‘I’m thinking’ – Oh, but are you?
Chapter 2: Renegade perception
Chapter 3: The Pushbacker sting
Chapter 4: ‘Covid’: The calculated catastrophe
Chapter 5: There is no ‘virus’
Chapter 6: Sequence of deceit
Chapter 7: War on your mind
Chapter 8: ‘Reframing’ insanity
Chapter 9: We must have it? So what is it?
Chapter 10: Human 2.0
Chapter 11: Who controls the Cult?
Chapter 12: Escaping Wetiko
Postscript
Appendix: Cowan-Kaufman-Morell Statement on Virus Isolation
Bibliography
Index