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Clinical Scales to Assess Patients With Stroke

Key Points Several scales are used to assess patients with ischemic or hemorrhagic stroke. These scales ease communication among healthcare professionals, facilitate stroke care, and are crucial for stroke research. The scales are used in a variety of settings and include systems to screen for the presence of a stroke in an emergency setting, to describe the severity of neurologic impairments, to differentiate hemorrhagic and ischemic…

Classification of Ischemic Stroke

Key Points Extensive etiologic heterogeneity in ischemic stroke necessitates categorizing patients into classes with discrete phenotypic, pathophysiologic, therapeutic, and prognostic features. The primary purpose of etiologic classification is to establish a common language in the field for better scientific communication. Phenotypic classification provides a summary of abnormal test findings organized in major etiologic categories without weighting toward the most likely cause in the presence of multiple…

Genetic Basis of Stroke Occurrence, Prevention, and Outcome

Key Points Fabry disease is an X-linked recessive disorder caused by reduced α-galactosidase activity for which enzyme replacement therapy is available. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a small-vessel stroke disorder caused by mutations in the NOTCH3 gene. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy is a stroke disorder caused by mutations in the HTRA1 gene. Homocysteinemia, commonly due to…

Vascular Dementia and Cognitive Impairment

Key Points Vascular dementia (VaD), as conventionally defined, is one of the most frequent forms of dementia. Furthermore, when vascular contributions to other types of dementias are included, it is arguably the most common form of dementia. Criteria for the diagnosis of VaD have evolved to include a broader phenotype, and memory impairment is not required for a diagnosis of VaD. Vascular mild cognitive impairment (VaMCI)…

Prognosis After Stroke

Key Points Stroke is the second most common cause of death in the world and a leading cause of long-term disability. In the United States, stroke has declined from the third leading cause of death to the fifth cause of death. Despite this encouraging trend, there is a substantial ongoing race-ethnic and geographic disparity in stroke mortality and other outcomes. Strokes recur in 6%–13% of patients…

Risk Factors and Prevention

Key Points This chapter summarizes key evidence on the determinants of stroke, focusing on risk factors that are relatively common and modifiable, and interventions intended to reduce the risk of a first stroke. Data from large, prospective epidemiologic cohort studies and selected clinical trial data are summarized. Carotid bruits increase the risk of stroke two- to threefold, but should be considered as markers of systemic atherosclerotic…

Stroke Disparities

Key Points Despite dramatic temporal declines in stroke mortality for all race/ethnic groups, the black-white disparity in stroke has been persistent (or even perhaps growing). While the black-white disparity in mortality averages 40% across the age spectrum, this pooling across ages obscures a much larger (200%–300%) excess mortality for blacks aged 45–65. This excess mortality is largely attributable to a higher incidence of stroke in blacks…

Global Burden of Stroke

Key Points The Global Burden of Diseases (GBD) 2016 study shows that while mortality rates and mortality to incidence ratios for stroke have decreased, the global burden of stroke in terms of absolute numbers of incident strokes, survivors, stroke-related deaths, and disability adjusted life-years (DALYs) lost are high and have increased over the last three decades. While there has been a decline in stroke incidence, mortality,…

Gliovascular Mechanisms and White Matter Injury in Vascular Cognitive Impairment and Dementia

Key Points Vascular disease is a major cause of dementia in the elderly. White matter is vulnerable to ischemic damage with oligodendrocytes targeted by hypoxia. The neurovascular unit in the white matter includes the oligodendrocytes that myelinate axons. Microglia impact the health of the oligodendrocytes and influence the endothelial cells. Understanding the complex impact of cytokines, proteases, and growth factors on the oligodendrocytes could lead to…

Genetics and Vascular Biology of Brain Vascular Malformations

Key Points Cerebrovascular malformations are a major cause of intracranial hemorrhage in young adults and children, resource-intensive to manage, and poorly understood with respect to mechanisms and risk factors. Most cases of brain arteriovenous malformations (AVMs) are sporadic, but they can occur in Mendelian diseases, notably hereditary hemorrhagic telangiectasia (HHT) caused by autosomal dominant mutations in transforming growth factor beta (TGF-β)/bone morphogenetic protein 9 (BMP-9) signaling…

Mechanisms of Plasticity Remodeling and Recovery

Key Points Angiogenesis, neurogenesis, axonal plasticity, oligodendrogenesis, synaptogenesis, and inflammatory response are major interwoven brain repair processes during stroke recovery. microRNAs play an important role in mediating repair processes. Exosomes, by transferring select RNAs and proteins, are mediators of intercellular communication, and their generation and molecular cargo are affected by stroke. Cell-based and pharmacologically based therapies can amplify brain repair processes and lead to improvement of…

Inflammation and Immune Response

Key Points Inflammation is a predominant feature of clinical and experimental stroke. Brain resident and hematogenous immune cells participate in the inflammatory response. Local intravascular and parenchymal events initiate a sterile inflammatory response to ischemia. Postischemic immune response may be deleterious during the acute phase but contributes to brain repair during the subacute and chronic stages. Scavenger receptors and Toll-like receptors act as sensors for molecules…

White Matter Pathophysiology

Key Points Most ischemic strokes involve both white matter and gray matter, and 20% of strokes predominantly involve white matter. Mechanisms of white matter ischemic injury are less well understood than the mechanisms of gray matter ischemic injury and distinctly different from the latter. Axons and oligodendrocytes are most vulnerable to ischemic injury in white matter: axons suffer loss of their sodium gradient and accumulate toxic…

Mechanisms of Damage After Cerebral Hemorrhage

Key Points The mechanisms triggering brain damage after intracerebral hemorrhage (ICH) are pleiotropic and are in many respects distinct from those contributing to ischemic brain injury. The toxicity of extravasated blood toward all structural components of the neurovascular unit represents a unique feature of ICH-mediated brain damage. Inflammation and oxidative stress appear to play prominent roles in the pathobiology of ICH. The secondary injury after ICH…

The Neurovascular Unit and Responses to Ischemia

Key Points The neurovascular unit is a structural and functional concept that seeks to integrate microvessel events with those of the neurons, glia, and brain matrix and serves as a framework for fundamental and new findings (e.g., the glymphatic CSF transport network). Within each compartment, networks of cells, matrix, and membranes interact and are moderated by supportive cells. Coordinated changes in brain vascular and microvascular caliber…

Intracellular Signaling: Mediators and Protective Responses

Key Points Preconditioning of the brain and other organs is an adaptive response to a noxious but nonlethal experience that activates an intracellular reaction rendering the tissue resistant to a subsequent potentially lethal event. Preconditioning consists of an early and a delayed window of protection that are characterized not only by their temporal profiles of protection but also by the mechanisms of activation and the robustness…

Molecular and Cellular Mechanisms of Ischemia-Induced Neuronal Death

Key Points Cerebral ischemia induces neuronal death through necrosis, apoptosis, necroptosis, or ferroptosis. Calcium is a critical factor in ischemic neuronal death. Both glutamate excitotoxicity and nonexcitotoxic mechanisms trigger ischemic cell death through calcium. Oxidative stress contributes to ischemic neuronal death after ischemic stroke. Epigenetic dysregulation contributes to ischemic neuronal death. Acknowledgments This work was supported by NIH grants NS 46742 (to R.S.Z.); NS045048, NS062157, and…

Histopathology of Brain Tissue Response to Stroke and Injury

Key Points The four kinds of ischemia are transient focal, permanent focal, transient global, and permanent global. Small vessel disease of arterioles can involve either blockage or breakage, and in hypertension, both can occur simultaneously. Large vessel carotid artery pathology is comprised of endothelial ulceration, intramural hemorrhage into carotid plaque, and intraluminal thrombosis with detachment and embolization. Infarction is a well-demarcated tissue lesion and a pH…

Cerebral Blood Flow and Metabolism: Regulation and Pathophysiology in Cerebrovascular Disease

Key Points Since the storage of substrates for energy metabolism is minimal, the brain is normally highly dependent on a continuous supply of oxygen and glucose from the blood for its functional and structural integrity. Control of cerebral blood flow (CBF) under conditions of normal cerebral perfusion pressure is determined by the caliber of the resistance vessels, primarily arterioles but also larger intracranial and extracranial arteries,…

Mechanisms of Thrombosis and Thrombolysis

Key Points The fundamental processes involved in thrombus formation, thrombus dissolution, and thrombus stability and their relevance to the central nervous system (CNS) are described. The role(s) of endogenous plasminogen activators (PAs, including tissue-type plasminogen activator, urokinase-type plasminogen activator) in thrombus dissolution are presented, together with considerations of their regulation in vivo. Their relevance to derived therapeutics is emphasized. Fibrinolytic agents tested or used as pharmaceuticals including…