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Ischemic Stroke

Updated: Feb 21, 2024
  • Author: Edward C Jauch, MD, MBA, MS, FAHA, FACEP; Chief Editor: Helmi L Lutsep, MD
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Overview

Background

Acute ischemic stroke (AIS) is characterized by the sudden loss of blood circulation to an area of the brain, typically in a vascular territory, resulting in a corresponding loss of neurologic function. Also previously called cerebrovascular accident (CVA) or stroke syndrome, stroke is a nonspecific state of brain injury with neuronal dysfunction that has several pathophysiologic causes. Strokes can be divided into 2 types: hemorrhagic or ischemic. Acute ischemic stroke is caused by thrombotic or embolic occlusion of a cerebral artery. (See the image below.)

Maximum intensity projection (MIP) image from a computed tomography angiogram (CTA) demonstrates a filling defect or high-grade stenosis at the branching point of the right middle cerebral artery (MCA) trunk (red circle), suspicious for thrombus or embolus. CTA is highly accurate in detecting large- vessel stenosis and occlusions, which account for approximately one third of ischemic strokes.

Nearly 800,000 people suffer strokes each year in the United States; 82–92% of these strokes are ischemic. Stroke is the fifth leading cause of adult death and disability, resulting in over 72ドル billion in annual cost. [] Between 2012 and 2030, total direct medical stroke-related costs are projected to triple, to 184ドル.1 billion, with the majority of the projected increase in costs arising from those 65 to 79 years of age. []

Ischemic and hemorrhagic stroke cannot be reliably differentiated on the basis of clinical examination findings alone. Further evaluation, especially with brain imaging tests (ie, computed tomography [CT] scanning or magnetic resonance imaging [MRI]), is required. (See Workup.)

Stroke categories

The system of categorizing stroke developed in the multicenter Trial of ORG 10172 in Acute Stroke Treatment (TOAST) divides ischemic strokes into the following 3 major subtypes: []

  • Large-artery

  • Small-vessel, or lacunar

  • Cardioembolic infarction

Large-artery infarctions often involve thrombotic in situ occlusions on atherosclerotic lesions in the carotid, vertebrobasilar, and cerebral arteries, typically proximal to major branches; however, large-artery infarctions may also be cardioembolic.

Cardiogenic emboli are a common source of recurrent stroke. They may account for up to 20% of acute strokes and have been reported to have the highest 1-month mortality. [] (See Pathophysiology.)

Small vessel or lacunar strokes are associated with small focal areas of ischemia due to obstruction of single small vessels, typically in deep penetrating arteries, that generate a specific vascular pathology.

In many patients the exact etiology of their stroke is not identified and these are classified as cryptogenic strokes.

Treatment

Recanalization strategies, including intravenous recombinant tissue-type plasminogen activator (alteplase or rt-PA) and intra-arterial approaches, attempt to establish revascularization so that cells within the ischemic penumbra (a metabolically active region, peripheral to the ischemic area, where blood flow is reduced and the cells are potentially viable) can be rescued before irreversible injury occurs. Restoring blood flow can mitigate the effects of ischemia only if performed quickly.

The US Food and Drug Administration (FDA) has approved the use of rt-PA in patients who meet criteria set forth by the National Institute of Neurologic Disorders and Stroke (NINDS). In particular, rt-PA must be given within 3 hours of stroke onset and only after CT scanning has ruled out hemorrhagic stroke.

On the basis of recent European data, the American Heart Association and American Stroke Association recommended expanding the window of treatment from 3 hours to 4.5 hours, with more stringent exclusion criteria for the later period (see Treatment). The FDA has not approved rt-PA for this expanded indication, but this has become the community standard in many institutions.

Other aspects of treatment for acute ischemic stroke include the following:

Optimization of physiologic parameters and prevention of neurologic complications

  • Supplemental oxygen as required (> 94% SaO2)

  • Glycemic control

  • Optimal blood pressure control (with consideration for reperfusion therapies)

  • Prevention of hyperthermia

See also Hemorrhagic Stroke.

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Anatomy

The brain is the most metabolically active organ in the body. While representing only 2% of the body's mass, it requires 15–20% of the total resting cardiac output to provide the necessary glucose and oxygen for its metabolism.

Knowledge of cerebrovascular arterial anatomy and the territories supplied by the cerebral arteries is useful in determining which vessels are involved in acute stroke. Atypical patterns of brain ischemia that do not conform to specific vascular distributions may indicate a diagnosis other than ischemic stroke, such as venous infarction.

Arterial distributions

In a simplified model, the cerebral hemispheres are supplied by 3 paired major arteries, specifically, the anterior, middle, and posterior cerebral arteries.

The anterior and middle cerebral arteries carry the anterior circulation and arise from the supraclinoid internal carotid arteries. The anterior cerebral artery (ACA) supplies the medial portion of the frontal and parietal lobes and anterior portions of basal ganglia and anterior internal capsule. (See the image below.)

Lateral view of a cerebral angiogram illustrates the branches of the anterior cerebral artery (ACA) and Sylvian triangle. The pericallosal artery has been described to arise distal to the anterior communicating artery or distal to the origin of the callosomarginal branch of the ACA. The segmental anatomy of the ACA has been described as follows: the A1 segment extends from the internal carotid artery (ICA) bifurcation to the anterior communicating artery; A2 extends to the junction of the rostrum and genu of the corpus callosum; A3 extends into the bend of the genu of the corpus callosum; A4 and A5 extend posteriorly above the callosal body and superior portion of the splenium. The Sylvian triangle overlies the opercular branches of the middle cerebral artery (MCA), with the apex representing the Sylvian point.

The middle cerebral artery (MCA) supplies the lateral portions of the frontal and parietal lobes, as well as the anterior and lateral portions of the temporal lobes, and gives rise to perforating branches to the globus pallidus, putamen, and internal capsule. The MCA is the dominant source of vascular supply to the hemispheres. (See the images below.)

The supratentorial vascular territories of the major cerebral arteries are demonstrated superimposed on axial (left) and coronal (right) T2-weighted images through the level of the basal ganglia and thalami. The middle cerebral artery (MCA; red) supplies the lateral aspects of the hemispheres, including the lateral frontal, parietal, and anterior temporal lobes; insula; and basal ganglia. The anterior cerebral artery (ACA; blue) supplies the medial frontal and parietal lobes. The posterior cerebral artery (PCA; green) supplies the thalami and occipital and inferior temporal lobes. The anterior choroidal artery (yellow) supplies the posterior limb of the internal capsule and part of the hippocampus extending to the anterior and superior surface of the occipital horn of the lateral ventricle.
Frontal view of a cerebral angiogram with selective injection of the left internal carotid artery (ICA) illustrates the anterior circulation. The anterior cerebral artery (ACA) consists of the A1 segment proximal to the anterior communicating artery, with the A2 segment distal to it. The middle cerebral artery (MCA) can be divided into 4 segments: the M1 (horizontal segment) extends to the anterior basal portion of the insular cortex (the limen insulae) and gives off lateral lenticulostriate branches, the M2 (insular segment), M3 (opercular branches), and M4 (distal cortical branches on the lateral hemispheric convexities).

The posterior cerebral arteries arise from the basilar artery and carry the posterior circulation. The posterior cerebral artery (PCA) gives rise to perforating branches that supply the thalami and brainstem and the cortical branches to the posterior and medial temporal lobes and occipital lobes. (See Table 1, below.)

The cerebellar hemispheres are supplied as follows:

  • Inferiorly by the posterior inferior cerebellar artery (PICA), arising from the vertebral artery (see the image below)

    Frontal projection from a right vertebral artery angiogram illustrates the posterior circulation. The vertebral arteries join to form the basilar artery. The posterior inferior cerebellar arteries (PICAs) arise from the distal vertebral arteries. The anterior inferior cerebellar arteries (AICAs) arise from the proximal basilar artery. The superior cerebellar arteries (SCAs) arise distally from the basilar artery prior to its bifurcation into the posterior cerebral arteries (PCAs).

  • Superiorly by the superior cerebellar artery

  • Anterolaterally by the anterior inferior cerebellar artery (AICA), from the basilar artery

Table 1. Vascular Supply to the Brain

VASCULAR TERRITORY

Structures Supplied

Anterior Circulation (Carotid)

Anterior Cerebral Artery

Cortical branches: medial frontal and parietal lobe

Medial lenticulostriate branches: caudate head, globus pallidus, anterior limb of internal capsule

Middle Cerebral Artery

Cortical branches: lateral frontal and parietal lobes, lateral and anterior temporal lobe

Lateral lenticulostriate branches: globus pallidus and putamen, internal capsule

Anterior Choroidal Artery

Optic tracts, medial temporal lobe, ventrolateral thalamus, corona radiata, posterior limb of the internal capsule

Posterior Circulation (Vertebrobasilar)

Posterior Cerebral Artery

Cortical branches: occipital lobes, medial and posterior temporal and parietal lobes

Perforating branches: brainstem, posterior thalamus and midbrain

Posterior Inferior Cerebellar Artery

Inferior vermis; posterior and inferior cerebellar hemispheres

Anterior Inferior Cerebellar Artery

Anterolateral cerebellum

Superior Cerebellar Artery

Superior vermis; superior cerebellum

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Pathophysiology

Acute ischemic strokes result from vascular occlusion secondary to thromboembolic disease (see Etiology). Ischemia causes cell hypoxia and depletion of cellular adenosine triphosphate (ATP). Without ATP, there is no longer the energy to maintain ionic gradients across the cell membrane and cell depolarization. Influx of sodium and calcium ions and passive inflow of water into the cell lead to cytotoxic edema. [, , ]

Ischemic core and penumbra

An acute vascular occlusion produces heterogeneous regions of ischemia in the affected vascular territory. Local blood flow is limited to any residual flow in the major arterial source plus the collateral supply, if any.

Affected regions with cerebral blood flow of lower than 10 mL/100 g of tissue/min are referred to collectively as the core. These cells are presumed to die within minutes of stroke onset. []

Zones of decreased or marginal perfusion (cerebral blood flow < 25 mL/100g of tissue/min) are collectively called the ischemic penumbra. Tissue in the penumbra can remain viable for several hours because of marginal tissue perfusion. []

Ischemic cascade

On the cellular level, the ischemic neuron becomes depolarized as ATP is depleted and membrane ion-transport systems fail. Disruption of cellular metabolism also impairs normal sodium-potassium plasma membrane pumps, producing an intracellular increase in sodium, which in turns increases intracellular water content. This cellular swelling is referred to as cytotoxic edema and occurs very early in cerebral ischemia.

Cerebral ischemia impairs the normal sodium-calcium exchange protein also found on cell plasma membranes. The resulting influx of calcium leads to the release of a number of neurotransmitters, including large quantities of glutamate, which in turn activates N-methyl-D-aspartate (NMDA) and other excitatory receptors on other neurons.

These neurons then become depolarized, causing further calcium influx, further glutamate release, and local amplification of the initial ischemic insult. This massive calcium influx also activates various degradative enzymes, leading to the destruction of the cell membrane and other essential neuronal structures. [] Free radicals, arachidonic acid, and nitric oxide are generated by this process, which leads to further neuronal damage.

Ischemia also directly results in dysfunction of the cerebral vasculature, with breakdown of the blood-brain barrier occurring within 4-6 hours after infarction. Following the barrier’s breakdown, proteins and water flood into the extracellular space, leading to vasogenic edema. This produces greater levels of brain swelling and mass effect that peak at 3–5 days and resolve over the next several weeks with resorption of water and proteins. [, ]

Within hours to days after a stroke, specific genes are activated, leading to the formation of cytokines and other factors that, in turn, cause further inflammation and microcirculatory compromise. [] Ultimately, the ischemic penumbra is consumed by these progressive insults, coalescing with the infarcted core, often within hours of the onset of the stroke.

Infarction results in the death of astrocytes, as well as the supporting oligodendroglial and microglial cells. The infarcted tissue eventually undergoes liquefaction necrosis and is removed by macrophages, with the development of parenchymal volume loss. A well-circumscribed region of cerebrospinal fluid–like low density, resulting from encephalomalacia and cystic change, is eventually seen. The evolution of these chronic changes may be seen in the weeks to months following the infarction. (See the images below.)

Vascular distributions: Middle cerebral artery (MCA) infarction. Noncontrast computed tomography (CT) scanning demonstrates a large acute infarction in the MCA territory involving the lateral surfaces of the left frontal, parietal, and temporal lobes, as well as the left insular and subinsular regions, with mass effect and rightward midline shift. There is sparing of the caudate head and at least part of the lentiform nucleus and internal capsule, which receive blood supply from the lateral lenticulostriate branches of the M1 segment of the MCA. Note the lack of involvement of the medial frontal lobe (anterior cerebral artery [ACA] territory), thalami, and paramedian occipital lobe (posterior cerebral artery [PCA] territory).
Vascular distributions: Anterior cerebral artery (ACA) infarction. Diffusion-weighted image on the left demonstrates high signal in the paramedian frontal and high parietal regions. The opposite diffusion-weighted image in a different patient demonstrates restricted diffusion in a larger ACA infarction involving the left paramedian frontal and posterior parietal regions. There is also infarction of the lateral temporoparietal regions bilaterally (both middle cerebral artery [MCA] distributions), greater on the left indicating multivessel involvement and suggesting emboli.
Vascular distributions: Posterior cerebral artery (PCA) infarction. The noncontrast computed tomography (CT) images demonstrate PCA distribution infarction involving the right occipital and inferomedial temporal lobes. The image on the right demonstrates additional involvement of the thalamus, also part of the PCA territory.
Vascular distributions: Anterior choroidal artery infarction. The diffusion-weighted image (left) demonstrates high signal with associated signal dropout on the apparent diffusion coefficient (ADC) map involving the posterior limb of the internal capsule. This is the typical distribution of the anterior choroidal artery, the last branch of the internal carotid artery (ICA) before bifurcating into the anterior and middle cerebral arteries. The anterior choroidal artery may also arise from the middle cerebral artery (MCA).

Hemorrhagic transformation of ischemic stroke

Hemorrhagic transformation represents the conversion of an ischemic infarction into an area of hemorrhage. This is estimated to occur in 5% of uncomplicated ischemic strokes, in the absence of fibrinolytic treatment. Hemorrhagic transformation is not always associated with neurologic decline, with the conversion ranging from the development of small petechial hemorrhages to the formation of hematomas that produce neurologic decline and may necessitate surgical evacuation or decompressive hemicraniectomy.

Proposed mechanisms for hemorrhagic transformation include reperfusion of ischemically injured tissue, either from recanalization of an occluded vessel or from collateral blood supply to the ischemic territory or disruption of the blood-brain barrier. With disruption of the blood-brain barrier, red blood cells extravasate from the weakened capillary bed, producing petechial hemorrhage or more frank intraparenchymal hematoma. [, , ]

Spontaneous hemorrhagic transformation of an ischemic infarct occurs within 2–14 days postictus, usually within the first week. It is more commonly seen following cardioembolic strokes and is more likely to occur with larger infarct volumes. [, , ] Hemorrhagic transformation is also more likely following administration of rt-PA in patients whose baseline noncontrast CT (NCCT) scans demonstrate areas of hypodensity. [, , ]

Poststroke cerebral edema and seizures

Although clinically significant cerebral edema can occur after anterior circulation ischemic stroke, it is thought to be somewhat rare (10-20%). [] Edema and herniation are the most common causes of early death in patients with hemispheric stroke.

Seizures occur in 2-23% of patients within the first days after ischemic stroke. [] A fraction of patients who have experienced stroke develop chronic seizure disorders.

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Etiology

Ischemic strokes result from events that limit or stop blood flow, such as extracranial or intracranial thrombotic embolism, thrombosis in situ, or relative hypoperfusion. As blood flow decreases, neurons cease functioning. Although a range of thresholds has been described, irreversible neuronal ischemia and injury is generally thought to begin at blood flow rates of less than 18 mL/100 g of tissue/min, with cell death occurring rapidly at rates below 10 mL/100 g of tissue/min

Risk factors

Risk factors for ischemic stroke include modifiable and nonmodifiable conditions. Identification of risk factors in each patient can uncover clues to the cause of the stroke and the most appropriate treatment and secondary prevention plan.

Nonmodifiable risk factors include the following (although there are likely many others):

  • Age

  • Race

  • Sex

  • Ethnicity

  • History of migraine headaches []

  • Fibromuscular dysplasia

  • Heredity: Family history of stroke or transient ischemic attacks (TIAs)

In a prospective study of 27,860 women aged 45 years or older who were participating in the Women's Health Study, Kurth et al found that migraine with aura was a strong risk factor for any type of stroke. The adjusted incidence of this risk factor per 1000 women per year was similar to those of other known risk factors, including systolic blood pressure 180 mm Hg or higher, body mass index 35 kg/m2 or greater, history of diabetes, family history of myocardial infarction, and smoking. []

For migraine with aura, the total incidence of stroke in the study was 4.3 per 1000 women per year, the incidence of ischemic stroke was 3.4 per 1000 per year, and the incidence of hemorrhagic stroke was 0.8 per 1000 per year.

Modifiable risk factors include the following: []

  • Hypertension (the most important)

  • Diabetes mellitus

  • Cardiac disease: Atrial fibrillation, valvular disease, heart failure, mitral stenosis, structural anomalies allowing right-to-left shunting (eg, patent foramen ovale), and atrial and ventricular enlargement

  • Hypercholesterolemia

  • Transient ischemic attacks (TIA)

  • Carotid stenosis

  • Hyperhomocystinemia

  • Lifestyle issues: Excessive alcohol intake, tobacco use, illicit drug use, physical inactivity []

  • Obesity

  • Oral contraceptive use/postmenopausal hormone use

  • Sickle cell disease

In 2014, the American Heart Association and the American Stroke Association issued guidelines for the reduction of stroke risk specifically in women. These gender-specific recommendations include the following: [, ]

  • A stroke risk score should be developed specifically for women

  • Women with a history of high blood pressure before pregnancy should be considered for low-dose aspirin and/or calcium supplement treatment to reduce the risk of preeclampsia

  • Blood pressure medication may be considered for pregnant women with moderately high blood pressure (150-159 mmHg/100-109 mmHg), and pregnant women with severe high blood pressure (160/110 mmHg or above) should be treated

  • Women should be screened for high blood pressure before they start using birth control pills because of an increased risk of stroke

  • Women with migraine headaches with aura should be encouraged to quit smoking to reduce the risk of stroke

  • Women over age 75 should be screened for atrial fibrillation

Genetic and inflammatory mechanisms

Evidence continues to accumulate that inflammation and genetic factors have important roles in the development of atherosclerosis and, specifically, in stroke. According to the current paradigm, atherosclerosis is not a bland cholesterol storage disease, as previously thought, but a dynamic, chronic, inflammatory condition caused by a response to endothelial injury.

Traditional risk factors, such as oxidized low-density lipoprotein (LDL) cholesterol and smoking, contribute to this injury. It has been suggested, however, that infections may also contribute to endothelial injury and atherosclerosis.

Host genetic factors, moreover, may modify the response to these environmental challenges, although inherited risk for stroke is likely multigenic. Even so, specific single-gene disorders with stroke as a component of the phenotype demonstrate the potency of genetics in determining stroke risk.

A number of genes are known to increase susceptibility to ischemic stroke. Mutations to the F2 and F5 genes are relatively common in the general population and increase the risk of thrombosis. Mutations in the following genes also are known to increase the risk of stroke:

  • NOS3: A nitric oxide synthetase gene; involved in vascular relaxation []

  • ALOX5AP: Involved in the metabolism of arachidonic acid []

  • PRKCH: Involved in major signal transduction systems []

Hyperhomocysteinemia and homocystinuria

Hyperhomocysteinemia is implicated in the pathogenesis of ischemic stroke. The most common concern is mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. In many populations, the mutant allele frequency reaches polymorphic proportions, and the risk factor for cerebrovascular disease is related to the serum level of homocysteine. Furthermore, in persons who are compound heterozygotes for MTHFR mutation, if elevated homocysteine is found it can be lowered with oral folic acid therapy.

In addition, hyperhomocysteinemia can be seen in cystathione beta synthetase (CBS) deficiency, which is generally referred to as homocystinuria. This disorder is inherited in an autosomal recessive manner. Symptoms usually manifest early in life. Patients have a marfanoid habitus, ectopia lentis, and myopia and generally have intellectual disability. []

Thromboembolic events are the most common cause of death for patients with homocystinuria and may be of any type, including myocardial infarction. The risk of having a vascular event in homocystinuria is 50% by age 30. [] It was previously suggested that persons who are heterozygous for mutations in the CBS gene may have an increased risk of cerebrovascular disease as well, but several more recent studies on this subject failed to replicate this finding.

Amyloid angiopathies

Amyloid angiopathies are also known to increase risk for stroke and dementia. Mutations in the CST3 gene are causative and are inherited in an autosomal dominant manner. Sufferers will have diffuse deposition of amyloid, including in the brain. The onset of symptoms is typically in the third or fourth decade of life, with death occurring before age 60 years. These angiopathies appear to be most common in the Icelandic population. []

CADASIL

Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy (CADASIL), is caused by mutations in the NOTCH3 gene. It affects the small arteries of the brain. Strokelike episodes typically occur at a mean age of 46 years, with an age range of 19–67 years. White-matter changes in the brain are typically evident by young adulthood and progress over time. []

Migraine headaches occur in 30–40% of people with CADASIL. Approximately 60% of symptomatic individuals have cognitive deficits, which can start as early as age 35 years, and many develop multi-infarct dementia. []

Other mutations

Genome-wide association studies have revealed additional loci that are commonly associated with ischemic stroke. Early onset ischemic stroke has been found to be associated with 2 single-nucleotide polymorphisms on 2q23.3. []

Large-vessel stroke has been associated with variations in HDAC9, PITX2, and ZFHX3. [] HDAC9 is located on7p21.1, while PITX2 and ZFHX3 are located on 9p21. It is of note that the 9p21 locus has also been associated with cardiovascular disease.

A polymorphism at 2q36.3 was found in which adenosine substitution conferred a lower risk of ischemic stroke in an additive fashion. [] An additional study suggested an association between ischemic stroke and a locus on 12p13. []

For more information, see Genetic and Inflammatory Mechanisms in Stroke. In addition, complete information on the following metabolic diseases and stroke can be found in the following main articles:

Large-artery occlusion

Large-artery occlusion typically results from embolization of atherosclerotic debris originating from the common or internal carotid arteries or from a cardiac source. A smaller number of large-artery occlusions may arise from plaque ulceration and in situ thrombosis. Large-vessel ischemic strokes more commonly affect the MCA territory, with the ACA territory affected to a lesser degree. (See the images below.)

Noncontrast computed tomography (CT) scan in a 52-year-old man with a history of worsening right-sided weakness and aphasia demonstrates diffuse hypodensity and sulcal effacement with mass effect involving the left anterior and middle cerebral artery territories consistent with acute infarction. There are scattered curvilinear areas of hyperdensity noted suggestive of developing petechial hemorrhage in this large area of infarction.
Magnetic resonance angiogram (MRA) in a 52-year-old man demonstrates occlusion of the left precavernous supraclinoid internal carotid artery (ICA, red circle), occlusion or high-grade stenosis of the distal middle cerebral artery (MCA) trunk and attenuation of multiple M2 branches. The diffusion-weighted image (right) demonstrates high signal confirmed to be true restricted diffusion on the apparent diffusion coefficient (ADC) map consistent with acute infarction.
Maximum intensity projection (MIP) image from a computed tomography angiogram (CTA) demonstrates a filling defect or high-grade stenosis at the branching point of the right middle cerebral artery (MCA) trunk (red circle), suspicious for thrombus or embolus. CTA is highly accurate in detecting large- vessel stenosis and occlusions, which account for approximately one third of ischemic strokes.

Lacunar strokes

Lacunar strokes represent 13–20% of all ischemic strokes. They result from occlusion of the penetrating branches of the MCA, the lenticulostriate arteries, or the penetrating branches of the circle of Willis, vertebral artery, or basilar artery. The great majority of lacunar strokes are related to hypertension. (See the image below.)

Axial noncontrast computed tomography (CT) scan demonstrates a focal area of hypodensity in the left posterior limb of the internal capsule in a 60-year-old man with acute onset of right-sided weakness. The lesion demonstrates high signal on the fluid-attenuated inversion recovery (FLAIR) sequence (middle image) and diffusion-weighted magnetic resonance imaging (MRI) scan (right image), with low signal on the apparent diffusion coefficient (ADC) maps indicating an acute lacunar infarction. Lacunar infarcts are typically no more than 1.5 cm in size and can occur in the deep gray matter structures, corona radiata, brainstem, and cerebellum.

Causes of lacunar infarcts include the following:

  • Microatheroma

  • Lipohyalinosis

  • Fibrinoid necrosis secondary to hypertension or vasculitis

  • Hyaline arteriosclerosis

  • Amyloid angiopathy

  • Microemboli

Embolic strokes

Cardiogenic emboli may account for up to 20% of acute strokes. Emboli may arise from the heart, the extracranial arteries, including the aortic arch or, rarely, the right-sided circulation (paradoxical emboli) with subsequent passage through a patent foramen ovale. [] Sources of cardiogenic emboli include the following:

Acute myocardial infarction is associated with a 2-3% incidence of embolic strokes, of which 85% occur in the first month after the infarction. [] Embolic strokes tend to have a sudden onset, and neuroimaging may demonstrate previous infarcts in several vascular territories or may show calcific emboli.

Cardioembolic strokes may be isolated, multiple and in a single hemisphere, or scattered and bilateral; the latter 2 types indicate multiple vascular distributions and are more specific for cardioembolism. Multiple and bilateral infarcts can be the result of embolic showers or recurrent emboli. Other possibilities for single and bilateral hemispheric infarctions include emboli originating from the aortic arch and diffuse thrombotic or inflammatory processes that can lead to multiple small-vessel occlusions. (See the image below.) [, ]

Cardioembolic stroke: Axial diffusion-weighted images demonstrate scattered foci of high signal in the subcortical and deep white matter bilaterally in a patient with a known cardiac source for embolization. An area of low signal in the left gangliocapsular region may be secondary to prior hemorrhage or subacute to chronic lacunar infarct. Recurrent strokes are most commonly secondary to cardioembolic phenomenon.

For more information, see Cardioembolic Stroke.

Thrombotic strokes

Thrombogenic factors may include injury to and loss of endothelial cells; this loss exposes the subendothelium and results in platelet activation by the subendothelium, activation of the clotting cascade, inhibition of fibrinolysis, and blood stasis. Thrombotic strokes are generally thought to originate on ruptured atherosclerotic plaques. Arterial stenosis can cause turbulent blood flow, which can promote thrombus formation; atherosclerosis (ie, ulcerated plaques); and platelet adherence. All cause the formation of blood clots that either embolize or occlude the artery.

Intracranial atherosclerosis may be the cause of thrombotic stroke in patients with widespread atherosclerosis. In other patients, especially younger patients, other causes should be considered, including the following: [, ]

  • Hypercoagulable states (eg, antiphospholipid antibodies, protein C deficiency, protein S deficiency, pregnancy)

  • Sickle cell disease

  • Fibromuscular dysplasia

  • Arterial dissections

  • Vasoconstriction associated with substance abuse (eg, cocaine, amphetamines)

Watershed infarcts

Vascular watershed, or border-zone, infarctions occur at the most distal areas between arterial territories. They are believed to be secondary to embolic phenomenon or to severe hypoperfusion, as occurs, for example, in carotid occlusion or prolonged hypotension. (See the image below.) [, , ]

Magnetic resonance imaging (MRI) scan was obtained in a 62-year-old man with hypertension and diabetes and a history of transient episodes of right-sided weakness and aphasia. The fluid-attenuated inversion recovery (FLAIR) image (left) demonstrates patchy areas of high signal arranged in a linear fashion in the deep white matter, bilaterally. This configuration is typical for deep border-zone, or watershed, infarction, in this case the anterior and posterior middle cerebral artery (MCA) watershed areas. The left-sided infarcts have corresponding low signal on the apparent diffusion coefficient (ADC) map (right), signifying acuity. An old left posterior parietal infarct is noted as well.

Flow disturbances

Stroke symptoms can result from inadequate cerebral blood flow because of decreased blood pressure (and specifically, decreased cerebral perfusion pressure) or as a result of hematologic hyperviscosity from sickle cell disease or other hematologic illnesses, such as multiple myeloma and polycythemia vera. In these instances, cerebral injury may occur in the presence of damage to other organ systems. For more information, see Blood Dyscrasias and Stroke.

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Epidemiology

Stroke is the leading cause of disability and the fifth leading cause of death in the United States. [, ] Each year, approximately 795,000 people in the United States experience new (610,000 people) or recurrent (185,000 people) stroke. [] Epidemiologic studies indicate that 82–92% of strokes in the United States are ischemic.

According to the World Health Organization (WHO), 15 million people suffer stroke worldwide each year. Of these, 5 million die, and another 5 million are left permanently disabled. []

Race-, sex-, and age-related demographics

In the United States, Blacks have an age-adjusted risk of death from stroke that is 1.49 times that of Whites. [] Hispanics have a lower overall incidence of stroke than Whites and Blacks but more frequent lacunar strokes and stroke at an earlier age. Indigenous people in high-income countries have higher incidence of stroke than non-indigenous people. []

Men are at higher risk for stroke than women; White men have a stroke incidence of 62.8 per 100,000, with death being the final outcome in 26.3% of cases, while women have a stroke incidence of 59 per 100,000 and a death rate of 39.2%.

Although stroke often is considered a disease of elderly persons, one third of strokes occur in persons younger than 65 years. [] Risk of stroke increases with age, especially in patients older than 64 years, in whom 75% of all strokes occur.

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Prognosis

In the Framingham and Rochester stroke studies, the overall mortality rate at 30 days after stroke was 28%, the mortality rate at 30 days after ischemic stroke was 19%, and the 1-year survival rate for patients with ischemic stroke was 77%. However, the prognosis after acute ischemic stroke varies greatly in individual patients, depending on the stroke severity and on the patient’s premorbid condition, age, and poststroke complications. []

A study utilizing the large national Get With The Guidelines - Stroke registry found that the baseline National Institutes of Health Stroke Scale (NIHSS) score was the strongest predictor of early mortality risk, even more so than currently used mortality prediction models incorporating multiple clinical data. [] Cardiogenic emboli are associated with the highest 1-month mortality in patients with acute stroke.

In late 2018, a new clinical score was developed to identify patients with a high risk of early mortality after an ischemic stroke. Researchers examined data on 77,653 ischemic stroke patients from the Austrian national stroke unit registry, who were treated between 2006 and 2017. They analyzed a comprehensive list of variables on these patients and compared characteristics in patients who died within the first 7 days after the stroke to those who survived. Multivariate analysis was then performed to ascertain which factors were increasingly associated with early stroke death. Key factors included age, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), pre-stroke functional disability (modified Rankin Scale > 0), pre-existing heart disease, diabetes mellitus, posterior circulation stroke syndrome, and non-lacunar stroke cause. Results showed that patients with a score ≥ 10 had a 35% risk of dying within the first few days at the stroke unit. []

The presence of computed tomography (CT) scan evidence of infarction early in presentation has been associated with poor outcome and with an increased propensity for hemorrhagic transformation after fibrinolytic therapy (see Pathophysiology). [, , ] Hemorrhagic transformation is estimated to occur in 5% of uncomplicated ischemic strokes in the absence of fibrinolytic therapy, although it is not always associated with neurologic decline. Indeed, hemorrhagic transformation ranges from the development of small petechial hemorrhages to the formation of hematomas requiring evacuation.

Acute ischemic stroke has been associated with acute cardiac dysfunction and arrhythmia, which then correlate with worse functional outcome and morbidity at 3 months. Data suggest that severe hyperglycemia is independently associated with poor outcome and reduced reperfusion in fibrinolysis, as well as extension of the infarcted territory. [, , ]

In stroke survivors from the Framingham Heart Study, 31% needed help caring for themselves, 20% needed help when walking, and 71% had impaired vocational capacity in long-term follow-up. For more information, see the Medscape Reference article Motor Recovery in Stroke.

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Patient Education

Public education must involve all age groups. Incorporating stroke into basic life support (BLS) and cardiopulmonary resuscitation (CPR) curricula is just one way to reach a younger audience. Avenues to reach an audience with a higher stroke risk could include local churches, employers, and senior organizations to promote stroke awareness.

The American Stroke Association (ASA) advises the public to be aware of the symptoms of stroke that are easily recognized, including the sudden onset of any of the following, and to call 911 immediately:

  • Numbness or weakness of face, arm, or leg, especially on 1 side of the body

  • Confusion

  • Difficulty in speaking or understanding

  • Deterioration of vision in 1 or both eyes

  • Difficulty in walking, dizziness, and loss of balance or coordination

  • Severe headache with no known cause

The ASA launched a stroke public education campaign that uses the acronym FAST to teach the warning signs of stroke and the importance of calling 911, as follows:

  • F: Face drooping

  • A: Arm weakness

  • S: Speech difficulty

  • T: Time to call 911

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References

  1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015 Jan 27. 131 (4):e29-322. [QxMD MEDLINE Link].

  2. Ovbiagele B, Goldstein LB, Higashida RT, Howard VJ, Johnston SC, Khavjou OA, et al. Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke. 2013 Aug. 44 (8):2361-75. [QxMD MEDLINE Link].

  3. Adams HP Jr, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999 Jul 13. 53(1):126-31. [QxMD MEDLINE Link].

  4. Sacco RL, Shi T, Zamanillo MC, Kargman DE. Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community: the Northern Manhattan Stroke Study. Neurology. 1994 Apr. 44(4):626-34. [QxMD MEDLINE Link].

  5. Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet. 2008 May 10. 371(9624):1612-23. [QxMD MEDLINE Link].

  6. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999 Sep. 22(9):391-7. [QxMD MEDLINE Link].

  7. Yuan J, Yankner BA. Apoptosis in the nervous system. Nature. 2000 Oct 12. 407(6805):802-9. [QxMD MEDLINE Link].

  8. Latchaw RE, Yonas H, Hunter GJ, Yuh WT, Ueda T, Sorensen AG, et al. Guidelines and recommendations for perfusion imaging in cerebral ischemia: A scientific statement for healthcare professionals by the writing group on perfusion imaging, from the Council on Cardiovascular Radiology of the American Heart Association. Stroke. 2003 Apr. 34(4):1084-104. [QxMD MEDLINE Link].

  9. Kasner SE, Grotta JC. Emergency identification and treatment of acute ischemic stroke. Ann Emerg Med. 1997 Nov. 30(5):642-53. [QxMD MEDLINE Link].

  10. Gotoh O, Asano T, Koide T, Takakura K. Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin. Stroke. 1985 Jan-Feb. 16(1):101-9. [QxMD MEDLINE Link].

  11. Bell BA, Symon L, Branston NM. CBF and time thresholds for the formation of ischemic cerebral edema, and effect of reperfusion in baboons. J Neurosurg. 1985 Jan. 62(1):31-41. [QxMD MEDLINE Link].

  12. Mullins ME, Lev MH, Schellingerhout D, Gonzalez RG, Schaefer PW. Intracranial hemorrhage complicating acute stroke: how common is hemorrhagic stroke on initial head CT scan and how often is initial clinical diagnosis of acute stroke eventually confirmed?. AJNR Am J Neuroradiol. 2005 Oct. 26(9):2207-12. [QxMD MEDLINE Link].

  13. Lyden PD, Zivin JA. Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence. Cerebrovasc Brain Metab Rev. 1993 Spring. 5(1):1-16. [QxMD MEDLINE Link].

  14. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995 Dec 14. 333(24):1581-7. [QxMD MEDLINE Link].

  15. Nighoghossian N, Hermier M, Adeleine P, Blanc-Lasserre K, Derex L, Honnorat J, et al. Old microbleeds are a potential risk factor for cerebral bleeding after ischemic stroke: a gradient-echo T2*-weighted brain MRI study. Stroke. 2002 Mar. 33(3):735-42. [QxMD MEDLINE Link].

  16. González RG. Imaging-guided acute ischemic stroke therapy: From "time is brain" to "physiology is brain". AJNR Am J Neuroradiol. 2006 Apr. 27(4):728-35. [QxMD MEDLINE Link].

  17. Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep. 126(3 Suppl):483S-512S. [QxMD MEDLINE Link].

  18. Dubey N, Bakshi R, Wasay M, Dmochowski J. Early computed tomography hypodensity predicts hemorrhage after intravenous tissue plasminogen activator in acute ischemic stroke. J Neuroimaging. 2001 Apr. 11(2):184-8. [QxMD MEDLINE Link].

  19. [Guideline] Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007 May. 38(5):1655-711. [QxMD MEDLINE Link].

  20. Brooks M. Migraine Linked to Double Risk for Silent Stroke. Medscape Medical News. Available at https://www.medscape.com/viewarticle/825451. Accessed: May 27, 2014.

  21. Anderson P. Migraine with aura 'major' contributor to all stroke types. Medscape Medical News. June 27, 2013. [Full Text].

  22. [Guideline] Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011 Feb. 42(2):517-84. [QxMD MEDLINE Link]. [Full Text].

  23. Kurl S, Laukkanen JA, Rauramaa R, Lakka TA, Sivenius J, Salonen JT. Cardiorespiratory fitness and the risk for stroke in men. Arch Intern Med. 2003 Jul 28. 163(14):1682-8. [QxMD MEDLINE Link].

  24. Bushnell C, McCullough LD, Awad IA, Chireau MV, Fedder WN, Furie KL, et al. Guidelines for the Prevention of Stroke in Women: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014 Feb 6. [QxMD MEDLINE Link].

  25. Hughes S. First AHA/ASA Guidelines to Reduce Stroke Risk in Women. Medscape [serial online]. Available at https://www.medscape.com/viewarticle/820277. Accessed: February 11, 2014.

  26. Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993 Aug 15. 268(23):17478-88. [QxMD MEDLINE Link].

  27. Miller DK, Gillard JW, Vickers PJ, Sadowski S, Léveillé C, Mancini JA, et al. Identification and isolation of a membrane protein necessary for leukotriene production. Nature. 1990 Jan 18. 343(6255):278-81. [QxMD MEDLINE Link].

  28. Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, et al. A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat Genet. 2007 Feb. 39(2):212-7. [QxMD MEDLINE Link].

  29. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet. 1985 Jan. 37(1):1-31. [QxMD MEDLINE Link]. [Full Text].

  30. Testai FD, Gorelick PB. Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders. Arch Neurol. 2010 Feb. 67(2):148-53. [QxMD MEDLINE Link].

  31. Jensson O, Gudmundsson G, Arnason A, Blöndal H, Petursdottir I, Thorsteinsson L, et al. Hereditary cystatin C (gamma-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage. Acta Neurol Scand. 1987 Aug. 76(2):102-14. [QxMD MEDLINE Link].

  32. Oberstein SA. Diagnostic strategies in CADASIL. Neurology. 2003 Jun 24. 60(12):2020; author reply 2020. [QxMD MEDLINE Link].

  33. Dichgans M. Cognition in CADASIL. Stroke. 2009 Mar. 40(3 Suppl):S45-7. [QxMD MEDLINE Link].

  34. Cheng YC, O'Connell JR, Cole JW, Stine OC, Dueker N, McArdle PF, et al. Genome-wide association analysis of ischemic stroke in young adults. G3 (Bethesda). 2011 Nov. 1(6):505-14. [QxMD MEDLINE Link]. [Full Text].

  35. The International Stroke Genetics Consortium (ISGC); the Wellcome Trust Case Control Consortium 2 (WTCCC2), Bellenguez C, Bevan S, Gschwendtner A, Spencer CC, et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet. 2012 Feb 5. 44(3):328-33. [QxMD MEDLINE Link]. [Full Text].

  36. Arregui M, Fisher E, Knüppel S, Buijsse B, di Giuseppe R, Fritsche A, et al. Significant associations of the rs2943634 (2q36.3) genetic polymorphism with adiponectin, high density lipoprotein cholesterol and ischemic stroke. Gene. 2012 Feb 25. 494(2):190-5. [QxMD MEDLINE Link].

  37. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, et al. Genomewide association studies of stroke. N Engl J Med. 2009 Apr 23. 360(17):1718-28. [QxMD MEDLINE Link]. [Full Text].

  38. Arboix A, Alio J. Acute cardioembolic cerebral infarction: answers to clinical questions. Curr Cardiol Rev. 2012 Feb. 8(1):54-67. [QxMD MEDLINE Link]. [Full Text].

  39. Witt BJ, Ballman KV, Brown RD Jr, Meverden RA, Jacobsen SJ, Roger VL. The incidence of stroke after myocardial infarction: a meta-analysis. Am J Med. 2006 Apr. 119(4):354.e1-9. [QxMD MEDLINE Link].

  40. Wessels T, Wessels C, Ellsiepen A, Reuter I, Trittmacher S, Stolz E. Contribution of diffusion-weighted imaging in determination of stroke etiology. AJNR Am J Neuroradiol. 2006 Jan. 27(1):35-9. [QxMD MEDLINE Link].

  41. Roh JK, Kang DW, Lee SH, Yoon BW, Chang KH. Significance of acute multiple brain infarction on diffusion-weighted imaging. Stroke. 2000 Mar. 31(3):688-94. [QxMD MEDLINE Link].

  42. Adams H, Adams R, Del Zoppo G, Goldstein LB. Guidelines for the early management of patients with ischemic stroke: 2005 guidelines update a scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke. 2005 Apr. 36(4):916-23. [QxMD MEDLINE Link].

  43. Derdeyn CP, Khosla A, Videen TO, Fritsch SM, Carpenter DL, Grubb RL Jr. Severe hemodynamic impairment and border zone--region infarction. Radiology. 2001 Jul. 220(1):195-201. [QxMD MEDLINE Link].

  44. Pollanen MS, Deck JH. Directed embolization is an alternate cause of cerebral watershed infarction. Arch Pathol Lab Med. 1989 Oct. 113(10):1139-41. [QxMD MEDLINE Link].

  45. Waterston JA, Brown MM, Butler P, Swash M. Small deep cerebral infarcts associated with occlusive internal carotid artery disease. A hemodynamic phenomenon?. Arch Neurol. 1990 Sep. 47(9):953-7. [QxMD MEDLINE Link].

  46. U.S. Centers for Disease Control and Prevention and the Heart Disease and Stroke Statistics - 2007 Update, published by the American Heart Association. Available at https://www.strokecenter.org/patients/stats.htm. Accessed: September 2008.

  47. Towfighi A, Saver JL. Stroke declines from third to fourth leading cause of death in the United States: historical perspective and challenges ahead. Stroke. 2011 Aug. 42(8):2351-5. [QxMD MEDLINE Link].

  48. MacKay J, Mensah GA. World Health Organization. Global Burden of Stroke. The Atlas of Heart Disease and Stroke. Available at https://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.pdf.

  49. Schneider AT, Kissela B, Woo D, Kleindorfer D, Alwell K, Miller R, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites. Stroke. 2004 Jul. 35(7):1552-6. [QxMD MEDLINE Link].

  50. Balabanski AH, Dos Santos A, Woods JA, et al. The Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index: A Systematic Review Protocol. Front Neurol. 2021. 12:661570. [QxMD MEDLINE Link].

  51. Fonarow GC, Saver JL, Smith EE, Broderick JP, Kleindorfer DO, Sacco RL, et al. Relationship of national institutes of health stroke scale to 30-day mortality in medicare beneficiaries with acute ischemic stroke. J Am Heart Assoc. 2012 Feb. 1(1):42-50. [QxMD MEDLINE Link]. [Full Text].

  52. Gattringer T, Posekany A, Niederkorn K, Knoflach M, Poltrum B, Mutzenbach S, et al. Predicting Early Mortality of Acute Ischemic Stroke. Stroke. 2019 Feb. 50 (2):349-356. [QxMD MEDLINE Link].

  53. von Kummer R, Allen KL, Holle R, Bozzao L, Bastianello S, Manelfe C, et al. Acute stroke: usefulness of early CT findings before thrombolytic therapy. Radiology. 1997 Nov. 205(2):327-33. [QxMD MEDLINE Link].

  54. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995 Oct 4. 274(13):1017-25. [QxMD MEDLINE Link].

  55. Bruno A, Levine SR, Frankel MR, Brott TG, Lin Y, Tilley BC, et al. Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial. Neurology. 2002 Sep 10. 59(5):669-74. [QxMD MEDLINE Link].

  56. Bruno A, Biller J, Adams HP Jr, Clarke WR, Woolson RF, Williams LS, et al. Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Neurology. 1999 Jan 15. 52(2):280-4. [QxMD MEDLINE Link].

  57. Baird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, et al. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke. 2003 Sep. 34(9):2208-14. [QxMD MEDLINE Link].

  58. Mandelzweig L, Goldbourt U, Boyko V, Tanne D. Perceptual, social, and behavioral factors associated with delays in seeking medical care in patients with symptoms of acute stroke. Stroke. 2006 May. 37(5):1248-53. [QxMD MEDLINE Link].

  59. National Institutes of Health Stroke Scale. Available at https://www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf. Accessed: October 2008.

  60. Huff JS. Stroke mimics and chameleons. Emerg Med Clin North Am. 2002 Aug. 20(3):583-95. [QxMD MEDLINE Link].

  61. Libman RB, Wirkowski E, Alvir J, Rao TH. Conditions that mimic stroke in the emergency department. Implications for acute stroke trials. Arch Neurol. 1995 Nov. 52(11):1119-22. [QxMD MEDLINE Link].

  62. Runchey S, McGee S. Does this patient have a hemorrhagic stroke?: clinical findings distinguishing hemorrhagic stroke from ischemic stroke. JAMA. 2010 Jun 9. 303(22):2280-6. [QxMD MEDLINE Link].

  63. Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurolo... Stroke. 2009 Jun. 40(6):2276-93. [QxMD MEDLINE Link].

  64. Tintinalli J, Kellen G, Stapczynski J. American College of Emergency Physicians. Emergency Medicine: A Comprehensive Study Guide. 6th. New York: McGraw Hill; 2004. 1382-1390.

  65. Leira EC, Chang KC, Davis PH, Clarke WR, Woolson RF, Hansen MD, et al. Can we predict early recurrence in acute stroke?. Cerebrovasc Dis. 2004. 18(2):139-44. [QxMD MEDLINE Link].

  66. Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005 Sep 3-9. 366(9488):809-17. [QxMD MEDLINE Link].

  67. Byrne JV. The aneurysm "clip or coil" debate. Acta Neurochir (Wien). 2006 Feb. 148(2):115-20. [QxMD MEDLINE Link].

  68. Sorensen AG, Buonanno FS, Gonzalez RG, Schwamm LH, Lev MH, Huang-Hellinger FR, et al. Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging. Radiology. 1996 May. 199(2):391-401. [QxMD MEDLINE Link].

  69. González RG, Schaefer PW, Buonanno FS, Schwamm LH, Budzik RF, Rordorf G, et al. Diffusion-weighted MR imaging: diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset. Radiology. 1999 Jan. 210(1):155-62. [QxMD MEDLINE Link].

  70. Marks MP, Olivot JM, Kemp S, Lansberg MG, Bammer R, Wechsler LR, et al. Patients with acute stroke treated with intravenous tPA 3-6 hours after stroke onset: correlations between MR angiography findings and perfusion- and diffusion-weighted imaging in the DEFUSE study. Radiology. 2008 Nov. 249(2):614-23. [QxMD MEDLINE Link]. [Full Text].

  71. Schellinger PD, Bryan RN, Caplan LR, Detre JA, Edelman RR, Jaigobin C, et al. Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010 Jul 13. 75(2):177-85. [QxMD MEDLINE Link].

  72. Sorensen AG, Copen WA, Ostergaard L, Buonanno FS, Gonzalez RG, Rordorf G, et al. Hyperacute stroke: simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow, and mean tissue transit time. Radiology. 1999 Feb. 210(2):519-27. [QxMD MEDLINE Link].

  73. Camerlingo M, Casto L, Censori B, Ferraro B, Gazzaniga GC, Mamoli A. Transcranial Doppler in acute ischemic stroke of the middle cerebral artery territories. Acta Neurol Scand. 1993 Aug. 88(2):108-11. [QxMD MEDLINE Link].

  74. Sagar G, Riley P, Vohrah A. Is admission chest radiography of any clinical value in acute stroke patients?. Clin Radiol. 1996 Jul. 51(7):499-502. [QxMD MEDLINE Link].

  75. Meerwaldt R, Slart RH, van Dam GM, Luijckx GJ, Tio RA, Zeebregts CJ. PET/SPECT imaging: from carotid vulnerability to brain viability. Eur J Radiol. 2010 Apr. 74(1):104-9. [QxMD MEDLINE Link].

  76. Handschu R, Poppe R, Rauss J, Neundörfer B, Erbguth F. Emergency calls in acute stroke. Stroke. 2003 Apr. 34(4):1005-9. [QxMD MEDLINE Link].

  77. Williams JE, Rosamond WD, Morris DL. Stroke symptom attribution and time to emergency department arrival: the delay in accessing stroke healthcare study. Acad Emerg Med. 2000 Jan. 7(1):93-6. [QxMD MEDLINE Link].

  78. Zweifler RM, Mendizabal JE, Cunningham S, Shah AK, Rothrock JF. Hospital presentation after stroke in a community sample: the Mobile Stroke Project. South Med J. 2002 Nov. 95(11):1263-8. [QxMD MEDLINE Link].

  79. Lacy CR, Suh DC, Bueno M, Kostis JB. Delay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes Knowledge and Epidemiology (S.T.R.O.K.E.). Stroke. 2001 Jan. 32(1):63-9. [QxMD MEDLINE Link].

  80. Puolakka T, Väyrynen T, Häppölä O, Soinne L, Kuisma M, Lindsberg PJ. Sequential analysis of pretreatment delays in stroke thrombolysis. Acad Emerg Med. 2010 Sep. 17(9):965-9. [QxMD MEDLINE Link].

  81. Ford AL, Williams JA, Spencer M, McCammon C, Khoury N, Sampson TR, et al. Reducing door-to-needle times using Toyota's lean manufacturing principles and value stream analysis. Stroke. 2012 Dec. 43(12):3395-8. [QxMD MEDLINE Link]. [Full Text].

  82. Bruno A, Kent TA, Coull BM, Shankar RR, Saha C, Becker KJ, et al. Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial. Stroke. 2008 Feb. 39(2):384-9. [QxMD MEDLINE Link].

  83. Bellolio MF, Gilmore RM, Stead LG. Insulin for glycaemic control in acute ischaemic stroke. Cochrane Database Syst Rev. 2011 Sep 7. 9:CD005346. [QxMD MEDLINE Link].

  84. Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25. 359(13):1317-29. [QxMD MEDLINE Link].

  85. [Guideline] Del Zoppo GJ, Saver JL, Jauch EC, Adams HP Jr. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. Stroke. 2009 Aug. 40(8):2945-8. [QxMD MEDLINE Link]. [Full Text].

  86. Wahlgren N, Ahmed N, Dávalos A, Hacke W, Millán M, Muir K, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008 Oct 11. 372(9646):1303-9. [QxMD MEDLINE Link].

  87. Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2013 Jan 31. [QxMD MEDLINE Link].

  88. Brooks M. Stroke a Race Against the Clock, Review Confirms. Medscape Medical News. Available at https://www.medscape.com/viewarticle/830611. Accessed: September 2, 2014.

  89. Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Aug 5. [QxMD MEDLINE Link].

  90. Strbian D, Ringleb P, Michel P,et al. Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?. Stroke. 2013 Aug 22. [QxMD MEDLINE Link].

  91. Brooks M. Ultra-Early' Thrombolysis Cuts Disability in Mild Stroke. Medscape Medical News. Aug 28 2013. [Full Text].

  92. Diedler J, Ahmed N, Sykora M, Uyttenboogaart M, Overgaard K, Luijckx GJ, et al. Safety of intravenous thrombolysis for acute ischemic stroke in patients receiving antiplatelet therapy at stroke onset. Stroke. 2010 Feb. 41(2):288-94. [QxMD MEDLINE Link].

  93. Xian Y, Federspiel JJ, Grau-Sepulveda M, Hernandez AF, Schwamm LH, Bhatt DL, et al. Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator. JAMA Neurol. 2015 Nov 9. 1-10. [QxMD MEDLINE Link].

  94. Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004 Nov 18. 351(21):2170-8. [QxMD MEDLINE Link].

  95. Tsivgoulis G, Eggers J, Ribo M, Perren F, Saqqur M, Rubiera M, et al. Safety and efficacy of ultrasound-enhanced thrombolysis: a comprehensive review and meta-analysis of randomized and nonrandomized studies. Stroke. 2010 Feb. 41(2):280-7. [QxMD MEDLINE Link].

  96. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013 Mar 7. 368(10):893-903. [QxMD MEDLINE Link]. [Full Text].

  97. Schonewille WJ, Wijman CA, Michel P, Rueckert CM, Weimar C, Mattle HP, et al. Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study. Lancet Neurol. 2009 Aug. 8(8):724-30. [QxMD MEDLINE Link].

  98. Lindsberg PJ, Mattle HP. Therapy of basilar artery occlusion: a systematic analysis comparing intra-arterial and intravenous thrombolysis. Stroke. 2006 Mar. 37(3):922-8. [QxMD MEDLINE Link].

  99. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997 Jun 7. 349(9066):1641-9. [QxMD MEDLINE Link].

  100. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997 May 31. 349(9065):1569-81. [QxMD MEDLINE Link].

  101. Abciximab in acute ischemic stroke: a randomized, double-blind, placebo-controlled, dose-escalation study. The Abciximab in Ischemic Stroke Investigators. Stroke. 2000 Mar. 31(3):601-9. [QxMD MEDLINE Link].

  102. Adams HP Jr, Effron MB, Torner J, Dávalos A, Frayne J, Teal P, et al. Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II). Stroke. 2008 Jan. 39(1):87-99. [QxMD MEDLINE Link].

  103. Sare GM, Geeganage C, Bath PM. High blood pressure in acute ischaemic stroke--broadening therapeutic horizons. Cerebrovasc Dis. 2009. 27 Suppl 1:156-61. [QxMD MEDLINE Link].

  104. Potter JF, Robinson TG, Ford GA, Mistri A, James M, Chernova J, et al. Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial. Lancet Neurol. 2009 Jan. 8(1):48-56. [QxMD MEDLINE Link].

  105. Sandset EC, Bath PM, Boysen G, Jatuzis D, Kõrv J, Lüders S, et al. The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial. Lancet. 2011 Feb 26. 377(9767):741-50. [QxMD MEDLINE Link].

  106. Jeffrey S. CATIS: No Benefit of BP Reduction in Acute Phase of Stroke. Medscape Medical News. Available at https://www.medscape.com/viewarticle/814531. Accessed: November 24, 2013.

  107. He J, Zhang Y, Xu T, Zhao Q, Wang D, Chen CS, et al. Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke: The CATIS Randomized Clinical Trial. JAMA. 2013 Nov 17. [QxMD MEDLINE Link].

  108. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Jan 24. [QxMD MEDLINE Link].

  109. Gobin YP, Starkman S, Duckwiler GR, Grobelny T, Kidwell CS, Jahan R, et al. MERCI 1: a phase 1 study of Mechanical Embolus Removal in Cerebral Ischemia. Stroke. 2004 Dec. 35(12):2848-54. [QxMD MEDLINE Link].

  110. Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005 Jul. 36(7):1432-8. [QxMD MEDLINE Link].

  111. Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, et al. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke. 2008 Apr. 39(4):1205-12. [QxMD MEDLINE Link].

  112. Bose A, Henkes H, Alfke K, Reith W, Mayer TE, Berlis A. The Penumbra System: a mechanical device for the treatment of acute stroke due to thromboembolism. AJNR Am J Neuroradiol. 2008 Aug. 29(7):1409-13. [QxMD MEDLINE Link].

  113. Saver JL, Jahan R, Levy EI, Jovin TG, Baxter B, Nogueira RG, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial. Lancet. 2012 Oct 6. 380(9849):1241-9. [QxMD MEDLINE Link].

  114. Nogueira RG, Lutsep HL, Gupta R, Jovin TG, Albers GW, Walker GA, et al. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012 Oct 6. 380(9849):1231-40. [QxMD MEDLINE Link].

  115. Marion DW. Controlled normothermia in neurologic intensive care. Crit Care Med. 2004 Feb. 32(2 Suppl):S43-5. [QxMD MEDLINE Link].

  116. Olsen TS, Weber UJ, Kammersgaard LP. Therapeutic hypothermia for acute stroke. Lancet Neurol. 2003 Jul. 2(7):410-6. [QxMD MEDLINE Link].

  117. Hemmen TM, Raman R, Guluma KZ, Meyer BC, Gomes JA, Cruz-Flores S, et al. Intravenous thrombolysis plus hypothermia for acute treatment of ischemic stroke (ICTuS-L): final results. Stroke. 2010 Oct. 41(10):2265-70. [QxMD MEDLINE Link].

  118. den Hertog HM, van der Worp HB, van Gemert HM, Algra A, Kappelle LJ, van Gijn J, et al. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial. Lancet Neurol. 2009 May. 8(5):434-40. [QxMD MEDLINE Link].

  119. Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol. 2009 Apr. 8(4):326-33. [QxMD MEDLINE Link].

  120. Jüttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke. 2007 Sep. 38(9):2518-25. [QxMD MEDLINE Link].

  121. Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A, et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007 Mar. 6(3):215-22. [QxMD MEDLINE Link].

  122. Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke. 2007 Sep. 38(9):2506-17. [QxMD MEDLINE Link].

  123. Wijdicks EF, Sheth KN, Carter BS, Greer DM, Kasner SE, Kimberly WT, et al. Recommendations for the Management of Cerebral and Cerebellar Infarction With Swelling: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014 Jan 30. [QxMD MEDLINE Link].

  124. Hughes S. AHA/ASA Guideline on Stroke With Brain Swelling. Medscape [serial online]. Available at https://www.medscape.com/viewarticle/820481. Accessed: February 25, 2014.

  125. Padma V, Fisher M, Moonis M. Role of heparin and low-molecular-weight heparins in the management of acute ischemic stroke. Expert Rev Cardiovasc Ther. 2006 May. 4(3):405-15. [QxMD MEDLINE Link].

  126. CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Dennis M, Sandercock P, Reid J, Graham C, Forbes J, Murray G. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet. 2013 Aug 10. 382(9891):516-24. [QxMD MEDLINE Link].

  127. Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ. 1994 Jan 8. 308(6921):81-106. [QxMD MEDLINE Link]. [Full Text].

  128. Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006 Aug 10. 355(6):549-59. [QxMD MEDLINE Link].

  129. Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005 Mar 31. 352(13):1305-16. [QxMD MEDLINE Link].

  130. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009 May 30. 373(9678):1849-60. [QxMD MEDLINE Link]. [Full Text].

  131. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005 Mar 31. 352(13):1293-304. [QxMD MEDLINE Link].

  132. [Guideline] Hughes S. New AHA/ASA Stroke Secondary Prevention Guidelines. Medscape Medical News. May 2 2014. [Full Text].

  133. [Guideline] Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2014 May 1. [QxMD MEDLINE Link]. [Full Text].

  134. Geeganage CM, Diener HC, Algra A, Chen C, Topol EJ, Dengler R, et al. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials. Stroke. 2012 Apr. 43(4):1058-66. [QxMD MEDLINE Link].

  135. Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20. 367(9523):1665-73. [QxMD MEDLINE Link].

  136. Dengler R, Diener HC, Schwartz A, Grond M, Schumacher H, Machnig T, et al. Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial. Lancet Neurol. 2010 Feb. 9(2):159-66. [QxMD MEDLINE Link].

  137. Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004 Jul 24-30. 364(9431):331-7. [QxMD MEDLINE Link].

  138. Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006 Jun 10. 367(9526):1903-12. [QxMD MEDLINE Link].

  139. [Guideline] Wann LS, Curtis AB, Ellenbogen KA, Estes NA 3rd, Ezekowitz MD, Jackman WM, et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on Dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011 Mar 15. 123(10):1144-50. [QxMD MEDLINE Link]. [Full Text].

  140. Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med. 2012 Mar 12. 172(5):397-402. [QxMD MEDLINE Link].

  141. Culebras A, Messé SR, Chaturvedi S, Kase CS, Gronseth G. Summary of evidence-based guideline update: prevention of stroke in nonvalvular atrial fibrillation: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014 Feb 25. 82 (8):716-24. [QxMD MEDLINE Link].

  142. ACTIVE Investigators., Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009 May 14. 360 (20):2066-78. [QxMD MEDLINE Link].

  143. Anderson P. MIND Diet May Slow Cognitive Decline in Stroke Survivors. Medscape Medical News. Available at https://www.medscape.com/viewarticle/891957 . January 30, 2018; Accessed: February 15, 2018.

  144. Morris MC, Tangney CC, Wang Y, Sacks FM, Barnes LL, Bennett DA, et al. MIND diet slows cognitive decline with aging. Alzheimers Dement. 2015 Sep. 11 (9):1015-22. [QxMD MEDLINE Link].

  145. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018 Jan 24. [QxMD MEDLINE Link].

  146. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018 Jan 4. 378 (1):11-21. [QxMD MEDLINE Link].

  147. Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, et al. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischemic Stroke. J Neurointerv Surg. 2019 Feb 26. [QxMD MEDLINE Link].

  148. Qureshi AI, Abd-Allah F, Alsenani F, et al. Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel. Int J Stroke. 2020 May 3. 1747493020923234. [QxMD MEDLINE Link].

  149. Yasgur BS. New Guidance to Protect Providers, Manage Stroke in COVID-19. Medscape Medical News. Available at https://www.medscape.com/viewarticle/930973. May 21, 2020; Accessed: May 27, 2020.

  150. Schönenberger S, Möhlenbruch M, Pfaff J, Mundiyanapurath S, Kieser M, Bendszus M, et al. Sedation vs. Intubation for Endovascular Stroke TreAtment (SIESTA) - a randomized monocentric trial. Int J Stroke. 2015 Aug. 10 (6):969-78. [QxMD MEDLINE Link].

Media Gallery
of 21
Tables
Table 1. Vascular Supply to the Brain

VASCULAR TERRITORY

Structures Supplied

Anterior Circulation (Carotid)

Anterior Cerebral Artery

Cortical branches: medial frontal and parietal lobe

Medial lenticulostriate branches: caudate head, globus pallidus, anterior limb of internal capsule

Middle Cerebral Artery

Cortical branches: lateral frontal and parietal lobes, lateral and anterior temporal lobe

Lateral lenticulostriate branches: globus pallidus and putamen, internal capsule

Anterior Choroidal Artery

Optic tracts, medial temporal lobe, ventrolateral thalamus, corona radiata, posterior limb of the internal capsule

Posterior Circulation (Vertebrobasilar)

Posterior Cerebral Artery

Cortical branches: occipital lobes, medial and posterior temporal and parietal lobes

Perforating branches: brainstem, posterior thalamus and midbrain

Posterior Inferior Cerebellar Artery

Inferior vermis; posterior and inferior cerebellar hemispheres

Anterior Inferior Cerebellar Artery

Anterolateral cerebellum

Superior Cerebellar Artery

Superior vermis; superior cerebellum

Table 2. National Institutes of Health Stroke Scale

Category

Description

Score

1a

level of consciousness (LOC)

Alert

Drowsy

Stuporous

Coma

0

1

2

3

1b

LOC questions (month, age)

Answers both correctly

Answers 1 correctly

Incorrect on both

0

1

2

1c

LOC commands (open and close eyes,

grip and release nonparetic hand)

Obeys both correctly

Obeys 1 correctly

Incorrect on both

0

1

2

2

Best gaze (follow finger)

Normal

Partial gaze palsy

Forced deviation

0

1

2

3

Best visual (visual fields)

No visual loss

Partial hemianopia

Complete hemianopia

Bilateral hemianopia

0

1

2

3

4

Facial palsy (show teeth, raise brows,

squeeze eyes shut)

Normal

Minor

Partial

Complete

0

1

2

3

5

Motor arm left* (raise 90°, hold 10 seconds)

(preferably with the palm facing up)

No drift

Drift

Cannot resist gravity

No effort against gravity

No movement

0

1

2

3

4

6

Motor arm right* (raise 90°, hold 10 seconds)

(preferably with the palm facing up)

No drift

Drift

Cannot resist gravity

No effort against gravity

No movement

0

1

2

3

4

7

Motor leg left* (raise 30°, hold 5 seconds)

No drift

Drift

Cannot resist gravity

No effort against gravity

No movement

0

1

2

3

4

8

Motor leg right* (raise 30°, hold 5 seconds)

No drift

Drift

Cannot resist gravity

No effort against gravity

No movement

0

1

2

3

4

9

Limb ataxia (finger-nose, heel-shin)

Absent

Present in 1 limb

Present in 2 limbs

0

1

2

10

Sensory (pinprick to face, arm, leg)

Normal

Partial loss

Severe loss

0

1

2

11

Extinction/neglect (double simultaneous testing)

No neglect

Partial neglect

Complete neglect

0

1

2

12

Dysarthria (speech clarity to "mama,

baseball, huckleberry, tip-top, fifty-fifty")

Normal articulation

Mild to moderate dysarthria

Near to unintelligible or worse

0

1

2

13

Best language** (name items,

describe pictures)

No aphasia

Mild to moderate aphasia

Severe aphasia

Mute

0

1

2

3

Total

-

0-42

* For limbs with amputation, joint fusion, etc, score 9 and explain

** For intubation or other physical barriers to speech, score 9 and explain. Do not add 9 to the total score. NIH Stroke Scale (PDF)

Contributor Information and Disclosures
Author

Edward C Jauch, MD, MBA, MS, FAHA, FACEP Chair, Department of Research, University of North Carolina Health Sciences at MAHEC; Professor (Adjunct), Departments of Emergency Medicine and Neurology, University of North Carolina at Chapel Hill School of Medicine

Edward C Jauch, MD, MBA, MS, FAHA, FACEP is a member of the following medical societies: American Heart Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: RAPID.AI.

Coauthor(s)

Sami Al Kasab, MD Assistant Professor of Neurology and Neurosurgery, Department of Neurosurgery, Medical University of South Carolina College of Medicine

Sami Al Kasab, MD is a member of the following medical societies: American Academy of Neurology, American College of Physicians, American Heart Association

Disclosure: Nothing to disclose.

Brian Stettler, MD Assistant Professor, Program Director, Emergency Medicine Residency Program, Department of Emergency Medicine, and Faculty Greater Cincinnati/Northern Kentucky Stroke Team, University of Cincinnati

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Abbott Laboratories, advisory group.

Acknowledgements

Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Joseph U Becker, MD Fellow, Global Health and International Emergency Medicine, Stanford University School of Medicine

Joseph U Becker, MD is a member of the following medical societies: American College of Emergency Physicians, Emergency Medicine Residents Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Salvador Cruz-Flores, MD, MPH, FAHA, FCCM Professor of Neurology and Epidemiology, Sidney W Souers Endowed Chair, Director of Souers Stroke Institute, Cerebrovascular and Neurointensive Care Section, Director, Vascular Neurology Fellowship Training Program, Interim Chairman, Department of Neurology and Psychiatry, St Louis University School of Medicine; Director, Neuroscience Intensive Care Unit (5ICU), St Louis University Hospital

Salvador Cruz-Flores, MD, MPH, FAHA, FCCM is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Academy of Neurology, American College of Physicians, American Heart Association, American Society of Neuroimaging, American Stroke Association, National Stroke Association, Neurocritical Care Society, and Society of Critical Care Medicine

Disclosure: Axio inc Honoraria Review panel membership; Roche Honoraria Review panel membership; Lilly Honoraria Review panel membership; Biotronik Honoraria Review panel membership

J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Richard S Krause, MD Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Charles R Wira III, MD Assistant Professor, Section of Emergency Medicine, Yale University School of Medicine; DEM Liaison and Attending Physician, Yale Acute Stroke Service, Department of Neurology, Yale-New Haven Hospital

Charles R Wira III, MD is a member of the following medical societies: American College of Emergency Physicians, American Heart Association, American Stroke Association, Neurocritical Care Society, Society for Academic Emergency Medicine, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

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