Ischemic Stroke

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Practice Essentials

Ischemic stroke (see the image below) is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. Acute ischemic stroke is caused by thrombotic or embolic occlusion of a cerebral artery and is more common than hemorrhagic stroke.



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Maximum intensity projection (MIP) image from a computed tomography angiogram (CTA) demonstrates a filling defect or high-grade stenosis at the branch....

See Acute Stroke, a Critical Images slideshow, for more information on incidence, presentation, intervention, and additional resources.

Signs and symptoms

Consider stroke in any patient presenting with acute neurologic deficit or any alteration in level of consciousness. Common stroke signs and symptoms include the following:

Although such symptoms can occur alone, they are more likely to occur in combination. No historical feature distinguishes ischemic from hemorrhagic stroke, although nausea, vomiting, headache, and sudden change in level of consciousness are more common in hemorrhagic strokes. In younger patients, a history of recent trauma, coagulopathies, illicit drug use (especially cocaine), migraines, or use of oral contraceptives should be elicited.

With the availability of reperfusion options (fibrinolytic and endovascular therapies) for acute ischemic stroke in selected patients, the physician must be able to perform a brief but accurate neurologic examination on patients with suspected stroke syndromes. The goals of the neurologic examination include the following:

Essential components of the neurologic examination include the following evaluations:

The skull and spine also should be examined, and signs of meningismus should be sought.

See Clinical Presentation for more detail.

Diagnosis

Emergent brain imaging is essential for evaluation of acute ischemic stroke. Noncontrast computed tomography (CT) scanning is the most commonly used form of neuroimaging in the acute evaluation of patients with apparent acute stroke. The following neuroimaging techniques may also be used emergently:

Lumbar puncture

A lumbar puncture is required to rule out meningitis or subarachnoid hemorrhage when the CT scan is negative but the clinical suspicion remains high

Laboratory studies

Laboratory tests performed in the diagnosis and evaluation of ischemic stroke include the following:

See Workup for more detail.

Management

The goal for the emergent management of stroke is to complete the following within 60 minutes or less of patient arrival:[1]

Critical treatment decisions focus on the following:

Involvement of a physician with a special interest and training in stroke is ideal. Stroke care units with specially trained nursing and allied healthcare personnel have clearly been shown to improve outcomes.

Ischemic stroke therapies include the following:

Treatment of comorbid conditions may include the following:

Stroke prevention

Primary stroke prevention refers to the treatment of individuals with no previous history of stroke. Measures may include use of the following:

Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may include use of the following:

See Treatment and Medication for more detail.

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.)



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Maximum intensity projection (MIP) image from a computed tomography angiogram (CTA) demonstrates a filling defect or high-grade stenosis at the branch....

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 billion in annual cost.[4]  Between 2012 and 2030, total direct medical stroke-related costs are projected to triple, to $184.1 billion, with the majority of the projected increase in costs arising from those 65 to 79 years of age.[5]

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:[2]

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.[6] (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

See also Hemorrhagic Stroke.

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.)



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Lateral view of a cerebral angiogram illustrates the branches of the anterior cerebral artery (ACA) and Sylvian triangle. The pericallosal artery has ....

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.)



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The supratentorial vascular territories of the major cerebral arteries are demonstrated superimposed on axial (left) and coronal (right) T2-weighted i....



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Frontal view of a cerebral angiogram with selective injection of the left internal carotid artery (ICA) illustrates the anterior circulation. The ante....

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:

Table 1. Vascular Supply to the Brain



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See Table

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.[7, 8, 9]

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.[10]

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.[10]

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.[11] 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.[12, 13]

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.[11] 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.)



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Vascular distributions: Middle cerebral artery (MCA) infarction. Noncontrast computed tomography (CT) scanning demonstrates a large acute infarction i....



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Vascular distributions: Anterior cerebral artery (ACA) infarction. Diffusion-weighted image on the left demonstrates high signal in the paramedian fro....



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Vascular distributions: Posterior cerebral artery (PCA) infarction. The noncontrast computed tomography (CT) images demonstrate PCA distribution infar....



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Vascular distributions: Anterior choroidal artery infarction. The diffusion-weighted image (left) demonstrates high signal with associated signal drop....

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.[7, 14, 15]

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.[3, 7, 16] Hemorrhagic transformation is also more likely following administration of rt-PA in patients whose baseline noncontrast CT (NCCT) scans demonstrate areas of hypodensity.[17, 18, 19]

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%).[1] 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.[1] A fraction of patients who have experienced stroke develop chronic seizure disorders.

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):

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.[21]

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:[22]

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:[24, 25]

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:

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.[29]

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.[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.[31]

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.[32]

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.[33]

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.[34]

Large-vessel stroke has been associated with variations in HDAC9, PITX2, and ZFHX3.[35] 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.[36] An additional study suggested an association between ischemic stroke and a locus on 12p13.[37]

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.)



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Noncontrast computed tomography (CT) scan in a 52-year-old man with a history of worsening right-sided weakness and aphasia demonstrates diffuse hypod....



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Magnetic resonance angiogram (MRA) in a 52-year-old man demonstrates occlusion of the left precavernous supraclinoid internal carotid artery (ICA, red....



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Maximum intensity projection (MIP) image from a computed tomography angiogram (CTA) demonstrates a filling defect or high-grade stenosis at the branch....

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.)



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Axial noncontrast computed tomography (CT) scan demonstrates a focal area of hypodensity in the left posterior limb of the internal capsule in a 60-ye....

Causes of lacunar infarcts include the following:

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.[38] 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.[39] 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.)[40, 41]



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Cardioembolic stroke: Axial diffusion-weighted images demonstrate scattered foci of high signal in the subcortical and deep white matter bilaterally i....

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:[7, 42]

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.)[43, 44, 45]



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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-si....

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.

Epidemiology

Stroke is the leading cause of disability and the fifth leading cause of death in the United States.[46, 47] Each year, approximately 795,000 people in the United States experience new (610,000 people) or recurrent (185,000 people) stroke.[4] 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.[48]

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.[49] Hispanics have a lower overall incidence of stroke than whites and blacks but more frequent lacunar strokes and stroke at an earlier age.

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.[47] Risk of stroke increases with age, especially in patients older than 64 years, in whom 75% of all strokes occur.

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.[2]

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.[50] 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.[51]

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).[3, 52, 53] 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.[54, 55, 56]

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.

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:

In the spring of 2013, 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:

For patient education information, see the Stroke Health Center and the Brain and Nervous System Health Center, as well as Stroke, Transient Ischemic Attack (TIA, Mini-stroke),and Stroke-Related Dementia.

History

A focused medical history for patients with ischemic stroke aims to identify risk factors for atherosclerotic and cardiac disease, including the following (see Etiology):

In younger patients, elicit a history of the following:

Stroke should be considered in any patient presenting with an acute neurologic deficit (focal or global) or altered level of consciousness. No historical feature distinguishes ischemic from hemorrhagic stroke, although nausea, vomiting, headache, and a sudden change in the patient’s level of consciousness are more common in hemorrhagic strokes.

Consider stroke in any patient presenting with acute neurologic deficit or any alteration in level of consciousness. Common signs and symptoms of stroke include the abrupt onset of any of the following:

Although such symptoms can occur alone, they are more likely to occur in combination.

Establishing the time at which the patient was last without stroke symptoms, or last known to be normal, is especially critical when fibrinolytic therapy is an option. Unfortunately, the median time from symptom onset to emergency department (ED) presentation ranges from 4-24 hours in the United States.[1]

Multiple factors contribute to delays in seeking care for symptoms of stroke. Many strokes occur while patients are sleeping and are not discovered until the patient wakes (this phenomenon is also known as "wake-up" stroke). Stroke can leave some patients too incapacitated to call for help. Occasionally, a stroke goes unrecognized by patients or their caregivers.[4, 57]

If the patient awakens with symptoms, then the time of onset is defined as the time at which the patient was last seen to be without symptoms or last known normal time. Input from family members, coworkers, and bystanders may be required to help establish the exact time of onset, especially in right hemispheric strokes accompanied by neglect or left hemispheric strokes with aphasia.

Physical Examination

The goals of the physical examination are as follows:

The physical examination always includes a careful head and neck examination for signs of trauma, infection, and meningeal irritation. A careful search for the cardiovascular causes of stroke requires examination of the following:

The physical examination must encompass all of the major organ systems, starting with airway, breathing, and circulation (ABCs) and the vital signs. Patients with a decreased level of consciousness should be assessed to ensure that they are able to protect their airway. Patients with stroke, especially hemorrhagic stroke, can suffer quick clinical deterioration; therefore, constant reassessment is critical.

Ischemic strokes, unless large or involving the brainstem, do not tend to cause immediate problems with airway patency, breathing, or circulation compromise. On the other hand, patients with intracerebral or subarachnoid hemorrhage frequently require intervention for airway protection and ventilation.

Vital signs, while nonspecific, can point to impending clinical deterioration and may assist in narrowing the differential diagnosis. Many patients with stroke are hypertensive at baseline, and their blood pressure may become more elevated after stroke. While hypertension at presentation is common, blood pressure decreases spontaneously over time in most patients.

Head and neck, cardiac, and extremities examination

A careful examination of the head and neck is essential. Contusions, lacerations, and deformities may suggest trauma as the etiology for the patient's symptoms. Auscultation of the neck may elicit a bruit, suggesting carotid disease as the cause of the stroke.

Cardiac arrhythmias, such as atrial fibrillation, are found commonly in patients with stroke. Similarly, strokes may occur concurrently with other acute cardiac conditions, such as acute myocardial infarction and acute heart failure; thus, auscultation for murmurs and gallops is recommended.

Carotid or vertebrobasilar dissections and, less commonly, thoracic aortic dissections may cause ischemic stroke. Unequal pulses or blood pressures in the extremities may reflect the presence of aortic dissections.

Neurologic examination

With the availability of fibrinolytic and endovascular therapies for acute ischemic stroke in selected patients, the physician must be able to perform a brief but accurate neurologic examination on patients with suspected stroke syndromes. The goals of the neurologic examination include the following:

Essential components of the neurologic examination include the following evaluations:

The skull and spine also should be examined, and signs of meningismus should be sought.

National Institutes of Health Stroke Scale

A useful tool in quantifying neurologic impairment is the National Institutes of Health Stroke Scale (NIHSS) (see Table 2, below). The NIHSS enables the healthcare provider to rapidly determine the severity and possible location of the stroke. NIHSS scores are strongly associated with outcome and can help to identify those patients who are likely to benefit from reperfusion therapies and those who are at higher risk of developing complications from the stroke itself and potential reperfusion strategies.

The NIHSS is easily performed; it focuses on the following 6 major areas of the neurologic examination:

The NIHSS is a 42-point scale. Patients with minor strokes usually have a score of less than 5. An NIHSS score of greater than 10 correlates with an 80% likelihood of proximal vessel occlusions (as identified on CT or standard angiograms). However, discretion must be used in assessing the magnitude of the clinical deficit and resulting disability; for instance, if a patient's only deficit is mutism or blindness, the NIHSS score will be 3. Additionally, the scale does not measure some deficits associated with posterior circulation strokes (ie, vertigo, ataxia).[58]

Table 2. National Institutes of Health Stroke Scale



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Middle cerebral artery stroke

Middle cerebral artery (MCA) occlusions commonly produce the following:

The MCA supplies the upper extremity motor strip. Consequently, weakness of the arm and face is usually worse than that of the lower limb.

Anterior cerebral artery stroke

Anterior cerebral artery (ACA) occlusions primarily affect frontal lobe function. Findings in ACA stroke may include the following:

Posterior cerebral artery stroke

Posterior cerebral artery (PCA) occlusions affect vision and thought. Manifestations include the following:

Vertebrobasilar artery occlusions are particularly difficult to localize because they may cause a wide variety of cranial nerve, cerebellar, and brainstem deficits, and may be vague in nature. These include the following:

A hallmark of posterior circulation stroke is the presence of crossed findings: ipsilateral cranial nerve deficits and contralateral motor deficits. This contrasts with anterior stroke, which produces only unilateral findings.

Lacunar stroke

Lacunar strokes result from occlusion of the small, perforating arteries of the deep subcortical areas of the brain. The infarcts are generally from 2-20 mm in diameter. The most common lacunar syndromes include pure motor, pure sensory, and ataxic hemiparetic strokes. By virtue of their small size and well-defined subcortical location, lacunar infarcts do not lead to impairments in cognition, memory, speech, or level of consciousness.

Approach Considerations

Imaging studies

Emergent brain imaging is essential for excluding mimics (SAH, ICH, masses) and potentially confirming the diagnosis of ischemic stroke. Noncontrast CT scanning is the most commonly used form of neuroimaging in the acute evaluation of patients with apparent acute stroke. A lumbar puncture is required to rule out meningitis or subarachnoid hemorrhage when the CT scan is negative but the clinical suspicion remains high. Multimodal CT imaging with the addition of CT angiography and CT perfusion to NCCT has the potential to identify large vessel occlusions and areas of salvagable tissue.

MRI with magnetic resonance angiography (MRA) has been a major advance in the neuroimaging of stroke. MRI not only provides great structural detail but also can demonstrate early cerebral edema. In addition, MRI has proved to be sensitive for detection of acute intracranial hemorrhage. However, MRI is not as available as CT scanning is in emergencies, many patients have contraindications to MRI imaging (eg, pacemakers, implants), and interpretation of MRI scans may be more difficult.

Carotid duplex scanning is one of the most useful tests in evaluating patients with stroke. Increasingly, it is being performed earlier in the evaluation, not only to define the cause of the stroke but also to stratify patients for either medical management or carotid intervention if they have carotid stenoses.

Digital subtraction angiography is considered the definitive method for demonstrating vascular lesions, including occlusions, stenoses, dissections, and aneurysms.

For more information, see Cerebral Revascularization Imaging.

Laboratory studies

Extensive laboratory testing is not routinely required before decisions are made regarding fibrinolysis. Testing can often be limited to blood glucose, plus coagulation studies if the patient is on warfarin, heparin, or one of the newer antithrombotic agents (eg, dabigatran, rivaroxaban). A complete blood count (CBC) and basic chemistry panel can be useful baseline studies. 

Additional laboratory tests are tailored to the individual patient and may include the following:

A urine pregnancy test should be obtained for all women of childbearing age with stroke symptoms. The safety of the fibrinolytic agent recombinant tissue-type plasminogen activator (rt-PA) in pregnancy has not been studied in humans (ie, the agent is in the FDA pregnancy category C).

Brain Imaging With CT Scanning and MRI

CT scanning

Imaging with CT scanning has multiple logistic advantages for patients with acute stroke. Image acquisition is faster with CT scanning than with MRI, allowing for assessment with an examination that includes noncontrast CT scanning, CT angiography (CTA), and CT perfusion scanning in a short amount of time. Expedient acquisition is of the utmost importance in acute stroke imaging because of the narrow window of time available for definitive ischemic stroke treatment with pharmacologic agents and mechanical devices.

CT scanning can also be performed in patients who are unable to tolerate an MR examination or who have contraindications to MRI, including implantable pacemakers, some aneurysm clips, or other ferromagnetic materials in their bodies. Additionally, CT scanning is more easily accessible and commonly located in the ED, which is helpful for patients who require special equipment for monitoring or life support.[65, 66]

MRI

Previously, conventional (spin echo) MRI may take hours to produce discernible findings in acute ischemic stroke. Diffusion-weighted imaging (DWI) is highly sensitive to early cellular edema, which correlates well with the presence of cerebral ischemia. For this reason, many centers include DWI in their standard brain MRI protocol. DWI MRI can detect ischemia much earlier than standard CT scanning or spin echo MRI can and provides useful data in patients with stroke or transient ischemic attack (TIA). (See the image below.)[1, 67, 68, 69]  



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Magnetic resonance imaging (MRI) scan in a 70-year-old woman with a history of left-sided weakness for several hours. An axial T2 fluid-attenuated inv....

The most commonly used technique for perfusion MRI is dynamic susceptibility, which involves generating maps of brain perfusion by monitoring the first pass of a rapid bolus injection of contrast through the cerebral vasculature. Susceptibility-related T2 effects create signal loss in capillary blood vessels and parenchyma perfused by contrast.

For more information on MRI and MRA in this setting, see Magnetic Resonance Imaging in Acute Stroke.

Based on the central volume principle, dynamic brain perfusion data can be obtained. Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) can be calculated using either perfusion MRI or CT scanning. (See the image below.)



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Regions of interest are selected for arterial and venous input (image on left) for dynamic susceptibility-weighted perfusion magnetic resonance imagin....

An evidence-based guideline from the American Academy of Neurology advises that DWI is more useful than noncontrast CT scanning for the diagnosis of acute ischemic stroke within 12 hours of symptom onset and should be performed for the most accurate diagnosis of acute ischemic stroke (level A). No recommendations were made regarding the use of perfusion-weighted imaging (PWI) in diagnosing acute ischemic stroke, as evidence to support or refute its value in this setting is insufficient.[70]

Intra-arterial contrast enhancement may be seen secondary to slow flow during the first or second day after onset of infarction. This finding has been correlated with increased infarct volume size.[71]

Other Imaging Studies in Ischemic Stroke

Transcranial Doppler ultrasonography is useful for evaluating more proximal vascular anatomy—including the middle cerebral artery (MCA), intracranial carotid artery, and vertebrobasilar artery—through the infratemporal fossa.[72] Echocardiography is obtained in all patients with acute ischemic stroke in whom cardiogenic embolism is suspected.

Chest radiography has potential utility for patients with acute stroke. However, obtaining a chest radiograph should not delay the administration of rt-PA, as radiographs have not been shown to alter the clinical course or decision-making in most cases.[73]

The use of single-photon emission CT (SPECT) scanning in stroke is still experimental and is available only at select institutions. Theoretically, it can define areas of altered regional blood flow.[74]

Conventional angiography is the gold standard in evaluating for cerebrovascular disease as well as for disease involving the aortic arch and great vessels in the neck. Conventional angiography can be performed to clarify equivocal findings or to confirm and treat disease seen on MRA, CTA, transcranial Doppler, or ultrasonography of the neck. (See the images below.)



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A 48-year-old man presented with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference. Angiogram with selective injection of the....



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Follow-up imaging after mechanical embolectomy in 48-year-old man with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference demo....



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Cerebral angiogram performed approximately 4.5 hours after symptom onset in a 31-year-old man demonstrates an occlusion of the distal basilar artery (....



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Image on the left demonstrates deployment of a clot retrieval device (older generation device) in a 31-year-old man. Followup angiogram after embolect....

Blood Studies

A CBC serves as a baseline study and may reveal a cause for the stroke (eg, polycythemia, thrombocytosis, thrombocytopenia, leukemia), identify evidence of concurrent illness (eg, anemia), or issues that may affect reperfusion strategies (thrombocytopenia). The basic chemistry panel serves as a baseline study and may reveal a stroke mimic (eg, hypoglycemia, hyponatremia) or provide evidence of concurrent illness (eg, diabetes, renal insufficiency).

Coagulation studies may reveal a coagulopathy and are useful when fibrinolytics or anticoagulants are to be used. In patients who are not taking anticoagulants or antithrombotics and in whom there is no suspicion for coagulation abnormality, administration of rt-PA should not be delayed while awaiting laboratory results.

Cardiac biomarkers are important because of the association of cerebral vascular disease and coronary artery disease. Additionally, several studies have indicated a link between elevations of cardiac enzyme levels and poor outcome in ischemic stroke.

Toxicology screening may be useful in selected patients in order to assist in identifying intoxicated patients with symptoms/behavior mimicking stroke syndromes or to identify sympathomemetic (cocaine) use, which may be the cause of the ischemic or hemorrhagic stroke . In patients with suspected hypoxemia, arterial blood gas studies define the severity of hypoxemia and may detect acid-base disturbances. However, arterial punctures should be avoided unless absolutely necessary in patients being considered for fibrinolytic therapy.

Approach Considerations

The central goal of therapy in acute ischemic stroke is to preserve tissue in the ischemic penumbra, where perfusion is decreased but sufficient to stave off infarction. Tissue in this area of oligemia can be preserved by restoring blood flow to the compromised area and optimizing collateral flow.

Recanalization strategies, including the administration of intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial approaches, attempt to establish revascularization so that cells in the penumbra can be rescued before irreversible injury occurs. Restoring blood flow can mitigate the effects of ischemia only if performed quickly.

Many surgical and endovascular techniques have been studied in the treatment of acute ischemic stroke. Carotid endarterectomy has been used with some success in the acute management of internal carotid artery occlusions, but no evidence supports its use acutely in ischemic stroke.

In addition to limiting the duration of ischemia, an alternative strategy is to limit the severity of ischemic injury (ie, neuronal protection). Neuroprotective strategies are intended to preserve the penumbral tissues and to extend the time window for revascularization techniques. At the present time, however, no neuroprotective agents have been shown to impact clinical outcomes in ischemic stroke.

Palliative care

Palliative care is an important component of comprehensive stroke care. Some patients with severe strokes die during the initial hospitalization,  others will be severely disabled and palliative care can begin to address the patient's and family's short- and long-term needs. Some patients have advance directives providing instructions for medical providers in the event of severe medical illness or injury.

Clinical education

Prehospital care providers are essential to timely stroke care. Course curricula for prehospital care providers are beginning to include more information on stroke than ever before. Through certification and Acute Cardiac Life Support (ACLS) instruction, as well as continuing medical education classes, prehospital care providers can remain current on stroke warning signs, prehospital stroke tools, and triage protocols in their region, and can promote stroke awareness in their own communities.

Physician and nursing staff involved in the care of stroke patients, in the Emergency Department (ED) and in the hospital, should participate in scheduled stroke education. This will help them to maintain the skills required to treat stroke patients effectively and to remain current on medical advances for all stroke types.

Emergency Response and Transport

Recognition that a stroke may have occurred, activation of 911, and rapid transport to the appropriate receiving facility are necessary to provide stroke patients with the best chance for acute interventions. Of patients with signs or symptoms of stroke, 29–65% utilize some facet of the emergency medical services (EMS) system.[75, 76]

Most of the patients who call EMS are those who present within 3 hours of symptom onset. Calls to 911 and the use of EMS are associated with shorter time periods from symptom onset to hospital arrival.[77, 78]

Stroke should be a priority dispatch with prompt EMS response. EMS responders should perform a brief H&P, obtain time of symptom onset or last known normal, perform a prehospital stroke assessment, determine blood glucose levels, and provide advance notice to their ED destination in as timely a manner as possible so as to allow preparation and marshalling of personnel and resources. With the development of stroke center designation, which is currently in progress, such centers would then become the preferred destination for patients with acute stroke symptoms who utilize EMS.

Data supporting the use of emergency air transport for patients with acute stroke symptoms are limited. Further evaluation of this transportation modality is necessary to minimize the potentially high number of stroke mimics and to maximize the appropriate use of transport resources. Telemedicine is also a technology that can provide timely expert advice to rural and underserved clinics and hospitals.[1]

Acute Management of Stroke

The goal for the emergent management of stroke is to assess the patient’s airway, breathing, and circulation (ABCs); stabilize the patient as necessary; and complete initial evaluation and assessment, including imaging and laboratory studies, within 60 minutes of patient arrival.[1] A Finnish study demonstrated that time to treatment with fibrinolytics can be decreased with changes in EMS and ED coordination and in ED procedures for treating acute stroke patients.[79]

A US study in which a multidisciplinary team used value stream analysis to assess the steps required to treat acute ischemic stroke with IV rt-PA found several inefficiencies in the protocol (eg, in patient routing) that were slowing treatment. Use of a revised protocol that targeted those inefficiencies reduced door-to-needle times from 60 to 39 minutes and increased the percentage of patients treated in 60 minutes or less after hospital arrival from 52% to 78%, with no change in symptomatic hemorrhage rate.[80]

Critical decisions focus on the need for airway management, establishment of optimal blood pressure control, and identification of potential reperfusion therapies (IV fibrinolysis with rt-PA or intra-arterial approaches). Involvement of a physician with stroke expertise is ideal. Stroke care units with specially trained personnel exist and improve outcomes.

Comorbidities

Comorbid medical conditions also need to be addressed. Hyperthermia is infrequently associated with stroke but can increase morbidity. Administration of acetaminophen, by mouth or per rectum, is indicated in the presence of fever (temperature > 100.4°F).

Oxygen supplementation

Supplemental oxygen is recommended when the patient has a documented oxygen requirement (ie, oxygen saturation < 95%). In the small proportion of patients with stroke who are relatively hypotensive, administration of IV fluid, vasopressor therapy, or both may improve flow through critical stenoses.

Hypoglycemia and hyperglycemia

Hypoglycemia needs to be identified and treated early in the evaluation. In contrast, the management of hyperglycemia in acute stroke remains an area of uncertainty.[81]  Extreme hyperglycemia is detrimental in the setting of acute stroke.

Hyperglycemia is common after acute ischemic stroke, even in patients without diabetes. A Cochrane review found that the use of IV insulin to maintain serum glucose in the range of 4–7.5 mmol/L (72-135 mg/dL) in the first 24 hours of ischemic stroke did not improve functional outcome, death rates, or final neurologic deficit and significantly increased the risk of hypoglycemia.[82]

Fibrinolytic Therapy

The only fibrinolytic agent that has been shown to benefit selected patients with acute ischemic stroke is alteplase (rt-PA). While streptokinase may benefit patients with acute MI, in patients with acute ischemic stroke it has been shown to increase the risk of intracranial hemorrhage and death.

Fibrinolytics (ie, rt-PA) restore cerebral blood flow in some patients with acute ischemic stroke and may lead to improvement or resolution of neurologic deficits. Unfortunately, fibrinolytics may also cause symptomatic intracranial hemorrhage. Other complications include potentially extracranial hemorrhage and angioedema or allergic reactions.[1]

Inclusion/exclusion criteria

Therefore, if the patient is a candidate for fibrinolytic therapy, a thorough review of the inclusion and exclusion criteria must be performed. The exclusion criteria largely focus on identifying risk of hemorrhagic complications associated with fibrinolytic use. The American Heart Association/American Stroke Association (AHA/ASA) inclusion guidelines for the administration of rt-PA are as follows:[1]

Whereas these inclusion/exclusion criteria are from the original FDA approval, a more recent revision by the FDA of the product insert has reclassified many prevous absolute contraindications to now relative contraindications. Furthermore, subsequent data and experience have allowed some patients with what were previously considered relative contraindications to be safely treated. Involvement of a physician with stroke expertise is critical for assessing the risk/benefit consideration for these groups of patients.

Time to therapy

An rt-PA stroke study group from the National Institute of Neurologic Disorders and Stroke (NINDS) first reported that the early administration of rt-PA benefited carefully selected patients with acute ischemic stroke.[3] The FDA subsequently approved the use of rt-PA in patients who met NINDS criteria. In particular, rt-PA had to be given within 3 hours of stroke onset and only after CT scanning had ruled out hemorrhagic stroke.

Subsequently, fibrinolytic therapy administered 3–4.5 hours after symptom onset was found to improve neurologic outcomes in the European Cooperative Acute Stroke Study III (ECASS III), suggesting a wider time window for fibrinolysis in carefully selected patients.[83] On the basis of these and other data, in May 2009 the AHA/ASA revised the guidelines for the administration of rt-PA after acute stroke, expanding the window of treatment from 3 hours to 4.5 hours to provide more patients with an opportunity to benefit from this therapy.[83, 84, 85, 86]

Eligibility criteria for treatment during this later period are similar to those for earlier treatment but are more stringent, with any 1 of the following serving as an additional exclusion criterion:

In a meta-analysis of nine major trials of fibrinolysis treatment involving a total of 6756 patients with acute ischemic stroke, researchers found that administration of alteplase within 4.5 hours of stroke onset significantly improved outcomes, irrespective of age or stroke severity, with earlier treatment providing the greatest benefit. Good outcome was defined as modified Rankin score of 0 or 1, which indicates little or no residual disability at 3–6 months. The odds of a good stroke outcome were 75% higher for patients who received alteplase within 3 hours of symptom onset compared with those who did not. Patients given alteplase 3 to 4.5 hours after symptom onset had a 26% increased chance of a good outcome, and patients with a delay of more than 4.5 hours in receiving alteplase treatment had a nonsignificant 15% increase in the chance of a good recovery.[87, 88]

A 10-center European study of nearly 6900 patients found IV rt-PA to be most effective when given within 90 minutes of the onset of stroke symptoms.[89, 90] Patients scoring in the 7–12 range on the NIHSS had better outcomes when fibrinolytic therapy was provided within 90 minutes of symptom onset than when it was provided 90–270 minutes after onset. For patients with minor stroke or moderate-to-severe stroke, however, treatment within the initial 90-minute window provided no additional advantage.

Hemorrhage risk

Although antiplatelet therapy may increase the risk for symptomatic intracerebral hemorrhage with fibrinolysis, a study by Diedler et al that included 3782 patients who had received 1 or 2 antiplatelet drugs found that the risk of intracerebral hemorrhage was small compared with the documented benefit of fibrinolysis.[91] These researchers concluded that antiplatelet treatment should not be considered a contraindication to fibrinolysis, although caution is warranted in patients receiving the combination of aspirin and clopidogrel.

A 2015 study, the largest of its kind, provides data supporting the use of fibrinolysis for stroke in patients taking antiplatelet therapy. Researchers analyzed a cohort of more than 85,000 stroke patients who had received tPA, approximately half of whom were taking antiplatelet medication at the time of their stroke. Results show that among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for hemorrhage but better functional outcomes than those who were not receiving antiplatelet therapy.[92]

Data regarding the safety of fibrinolytic therapy in patients taking dabigatran, rivaroxaban, or apixaban are not available. Extreme caution should be used when considering fibrinolytic therapy in such patients.

Caution should also be exercised in the administration of rt-PA to patients with evidence of low attenuation (edema or ischemia) involving more than a third of the distribution of the middle cerebral artery (MCA) on their initial noncontrast CT scan; such patients are less likely to have a favorable outcome after fibrinolytic therapy and are at higher risk for hemorrhagic transformation of their ischemic stroke.[52]

Ultrasound therapy

Researchers have studied the use of transcranial ultrasound as a means of assisting rt-PA in fibrinolysis.[93, 94] By delivering mechanical pressure waves to the thrombus, ultrasound can theoretically expose more of the thrombus’s surface to the circulating fibrinolytic agent. Further research is necessary to determine the exact role of transcranial Doppler ultrasound in assisting fibrinolytics in acute ischemic stroke.

For more information, see Thrombolytic Therapy in Stroke and Reperfusion Injury in Stroke.

Intra-arterial Reperfusion

Theoretically, intra-arterial delivery may produce higher local concentrations of the fibrinolytic agent at lower total doses (and thus possibly lower the risk of a systemic bleed) and allow a longer therapeutic window. However, the longer time for initiating intra-arterial administration may mitigate some of this advantage and earlier phase II studies did not show a statistically significant difference in clinical outcomes.[1]

The Interventional Management of Acute Stroke Study (IMS-III) was halted for futility after showing no additional benefit from intra-arterial therapies (rt-PA, mechanical thrombectomy with mostly first-generation devices, or both) compared with intravenous rt-PA in patients with large-vessel occlusions. Additional analyses of the IMS III data are under way to better understand the results and potentially identity subsets of patients who may benefit from the combined approach.[95]

Intra-arterial fibrinolysis has been the traditional approach for patients with stroke from basilar artery occlusion. However, results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry study in 592 patients, did not support unequivocal superiority of intra-arterial fibrinolysis over intravenous fibrinolysis.[96]

A meta-analysis of case studies involving a total of 420 patients with basilar artery occlusion did indicate that recanalization was achieved more frequently with intra-arterial fibrinolysis than with intravenous fibrinolysis (65% vs 53%), but the report also found that death and long-term disability were equally common with the 2 techniques.[97] These researchers concluded that intravenous fibrinolysis represents probably the best treatment that can be offered to these patients in hospitals without a 24-hour interventional neuroradiologic service.[97]

Antiplatelet Agents

AHA/ASA guidelines recommend giving aspirin, 325 mg orally, within 24–48 hours of ischemic stroke onset. The benefit of aspirin is modest but statistically significant and appears principally to involve the reduction of recurrent stroke.[86]

The International Stroke Trial and the Chinese Acute Stroke Trial (CAST) demonstrated modest benefit from the use of aspirin in the setting of acute ischemic stroke. The International Stroke Trial randomized 19,435 patients within 48 hours of stroke onset to treatment with aspirin 325 mg, subcutaneous heparin in 2 different dose regimens, aspirin with heparin, and a placebo. The study found that aspirin therapy reduced the risk of stroke recurrence within 14 days (2.8% vs 3.9%), with no significant excess of hemorrhagic strokes.[98, 99]

In CAST, which included 21,106 patients, aspirin treatment (160 mg/day) that was started within 48 hours of the onset of suspected acute ischemic stroke and was continued in hospital for up to 4 weeks reduced mortality to 3.3%, compared with 3.9% with placebo. A separate study also found that the combination of aspirin and low–molecular-weight heparin did not significantly improve outcomes.[98]

Other antiplatelet agents have also been under evaluation for use in the acute presentation of ischemic stroke. In a preliminary pilot study, abciximab given within 6 hours showed a trend toward improved outcome at 3 months.[100] However, the phase 3 Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II) was terminated prematurely after 808 patients because of lack of efficacy and an increased rate of symptomatic or fatal intracranial hemorrhage in patients receiving abciximab.[101]

Blood Pressure Control

Although hypertension is common in acute ischemic stroke and is associated with poor outcome, studies of antihypertensive treatment in this setting have produced conflicting results. A theoretical drawback of blood pressure reduction is that elevated blood pressure may counteract dysfunctional cerebral autoregulation from stroke, but limited evidence suggests that antihypertensive treatment in acute stroke does not change cerebral perfusion.[102]

Calcium channel blockers did not alter outcome after ischemic stroke in some trials. Possible adverse effects of antihypertensive treatment have been reported in certain trials, especially those using intravenous calcium channel blockers or oral beta blockers. In the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) trial, early lowering of blood pressure with labetalol and lisinopril slightly improved outcome and did not increase serious adverse events. However, CHHIPS had a small sample size.[103]

A study in 339 patients with ischemic stroke found that oral candesartan reduced combined vascular events but had no effect on disability.[102] However, the Scandinavian Candesartan Acute Stroke Trial (SCAST), a randomized, placebo-controlled, double-blind study involving 2029 patients, found no indication of benefit from candesartan but did find some suggestion of harm.[104]

In the single-blind, randomized China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) study, which included 4,071 patients with acute ischemic stroke and elevated blood pressure, immediate blood pressure reduction with antihypertensive medication within 48 hours of symptom onset did not reduce the risk for death or major disability. CATIS excluded patients who received fibrinolytic therapy. Mean systolic blood pressure was reduced from 166.7 to 144.7 mm Hg within 24 hours in the antihypertensive treatment group.[105, 106]

Among the 2038 patients who received antihypertensive treatment, 683 reached the primary endpoint of death or major disability at 14 days or hospital discharge, compared with 681 of the 2,033 patients who received no antihypertensive treatment. At 3-month follow-up, 500 patients in the antihypertensive treatment group and 502 patients in the control group reached the secondary endpoint of death or major disability.[105, 106]

For patients who are not candidates for fibrinolytic therapy, current guidelines recommend permitting moderate hypertension in most patients with acute ischemic stroke. Most patients will experience spontaneous reduction in blood pressure over the first 24 hours without treatment.[86] The exceptions would be patients who have active comorbidities (eg, aortic dissection, acute myocardial infarction [MI], decompensated heart failure, hypertensive emergency) that require emergent blood pressure management.

Thresholds for antihypertensive treatment in acute ischemic stroke patients who are not fibrinolysis candidates, according to the 2013 ASA guidelines, are systolic blood pressure higher than 220 mm Hg or diastolic blood pressure above 120 mm Hg.[86] In those patients, a reasonable goal is to lower blood pressure by 15% during the first 24 hours after onset of stroke. Care must be taken to not lower blood pressure too quickly or aggressively, since this could worsen perfusion in the penumbra.

Mechanical Thrombectomy

Mechanical clot disruption is an alternative for patients in whom fibrinolysis is ineffective or contraindicated.

The 2018 American Heart Association/American Stroke Association guidelines for the emergency treatment of patients with acute ischemic stroke extend the time limit on mechanical clot removal from 6 hours to up to 24 hours in select patients. The new guidelines recommend thrombectomy in eligible patients 6 to 16 hours after a stroke.[107] They also broaden the eligibility criteria for IV tPA.

Currently, 4 devices are approved by the FDA for the endovascular treatment of acute ischemic stroke, as follows:

Successful recanalization occurred in 12 of 28 patients in the Mechanical Embolus Retrieval in Cerebral Ischemia (MERCI) 1 pilot trial, a study of the Merci Retrieval System.[108] In a second MERCI study, recanalization was achieved in 48% of patients in whom the device was deployed. Clot was successfully retrieved from all major cerebral arteries; however, the recanalization rate for the MCA was lowest.[109]

The Multi MERCI trial used the newer-generation Concentric retrieval device (L5). Recanalization was demonstrated in approximately 55% of patients who did not receive t-PA and in 68% of those to whom t-PA was given. Of patients who failed intravenous t-PA therapy, 73% had recanalization following mechanical embolectomy.[110] On the basis of these results, the FDA cleared the use of the MERCI device in patients who are either ineligible for or who have failed intravenous fibrinolytics.

In a trial of the Penumbra System in 23 patients who presented within 8 hours of symptom onset, revascularization to a Thrombolysis in Myocardial Infarction (TIMI) grade of 2 or 3 was accomplished in all 21 treated vessels. Vessel tortuosity prevented access by the device in 3 patients.[111]

More recent trials of the stent-retriever systems demonstrated superiority in reperfusion over the original Merci systems. In the Solitaire Flow Restoration Device Versus the Merci Retriever in Patients with Acute Ischaemic Stroke (SWIFT) study, which enrolled 113 subjects with moderate or severe strokes within 8 hours after symptom onset, the Solitaire FR system demonstrated successful revascularization (TIMI 2-3 flow) in 61% of patients, compared with 24% of patients treated with the Merci system. Patients in the Solitaire FR group also had a higher rate of good 90-day clinical outcomes than did those in the Merci group (58% versus 33%, respectively).[112]

A similar study, the Trevo Versus Merci Retrievers for Thrombectomy Revascularisation of Large Vessel Occlusions in Acute Ischaemic Stroke (TREVO 2) trial, reported successful reperfusion (TIMI 2-3 flow) in 86% of patients using the Trevor stent retriever, compared with 60% in the Merci group. The rate of good clinical outcomes at 90 days was also higher in the Trevo group than in the Merci group (40% vs 22%, respectively).[113] Ongoing studies will better define the role of intra-arterial therapies with and without intravenous fibrinolysis.

For more information, see Mechanical Thrombolysis in Acute Stroke.

Fever Control

Antipyretics are indicated for febrile stroke patients, since hyperthermia accelerates ischemic neuronal injury. Substantial experimental evidence suggests that mild brain hypothermia is neuroprotective. The use of induced hypothermia is currently being evaluated in phase II clinical trials.[114, 115, 116]

High body temperature in the first 12–24 hours after stroke onset has been associated with poor functional outcome. However, results from the Paracetamol (Acetaminophen) in Stroke (PAIS) trial did not support the routine use of high-dose acetaminophen (6 g daily) in patients with acute stroke, although post-hoc analysis suggested a possible beneficial effect on functional outcome in patients admitted with a body temperature of 37–39° C.[117]

Cerebral Edema Control

Significant cerebral edema after ischemic stroke is thought to be somewhat rare (10–20%). Maximum severity of edema is typically reached 72–96 hours after the onset of stroke.

Early indicators of ischemia on presentation and on noncontrast CT (NCCT) scans are independent indicators of potential swelling and deterioration (see the image below). Mannitol and other therapies to reduce intracranial pressure (ICP) may be used in emergency situations, although their usefulness in swelling secondary to ischemic stroke is unknown. No evidence exists supporting the use of corticosteroids to decrease cerebral edema in acute ischemic stroke. Prompt neurosurgical assistance should be sought when indicated.[1]



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Axial noncontrast computed tomography (NCCT) scan demonstrates diffuse hypodensity in the right lentiform nucleus with mass effect upon the frontal ho....

Patient position, hyperventilation, hyperosmolar therapy, and, rarely, barbiturate coma may be used, as in patients with increased ICP secondary to closed head injury. Hemicraniectomy has been shown to decrease mortality and disability among patients with large hemispheric infarctions associated with life-threatening edema.[118, 119, 120, 121]

The American Heart Association and the American Stroke Association have released a guideline for the management of cerebral and cerebellar infarction with brain swelling; recommendations include the following:[122, 123]

Seizure Control

Seizures occur in 2–23% of patients within the first days after ischemic stroke. These seizures are usually focal, but they may be generalized. Although primary prophylaxis for poststroke seizures is not indicated, secondary prevention of subsequent seizures with standard antiepileptic therapy is recommended.[1]

A fraction of patients who have experienced stroke develop chronic seizure disorders. Seizure disorders secondary to ischemic stroke should be managed in the same manner as other seizure disorders that arise as a result of neurologic injury.[1]

Acute Decompensation

In the case of the rapidly decompensating patient or the patient with deteriorating neurologic status, reassessment of the ABCs as well as hemodynamics and reimaging are indicated. Many patients who develop hemorrhagic transformation or progressive cerebral edema will demonstrate acute clinical decline. Rarely, a patient may have escalation of symptoms secondary to increased size of the ischemic penumbra. Careful observation for hemorrhagic transformation (especially in the first 24 hours postreperfusion) and cerebral edema in patients with hemispheric or posterior fossa strokes in the first 24–36 hours is warranted.

Anticoagulation and Prophylaxis

Currently, data are inadequate to justify the routine use of heparin or other anticoagulants in the acute management of ischemic stroke.[124] Patients with embolic stroke who have another indication for anticoagulation (eg, atrial fibrillation) may be placed on anticoagulation therapy nonemergently, with the goal of preventing further embolic disease; however, the potential benefits of that intervention must be weighed against the risk of hemorrhagic transformation.[1] For more information, see Stroke Anticoagulation and Prophylaxis.

Immobilized stroke patients in particular are at increased risk of developing deep venous thrombosis (DVT) and should receive early efforts to reduce the occurrence of DVT. The use of low-dose, subcutaneous unfractionated or low–molecular-weight heparin may be appropriate in these cases.[1] The CLOTS (Clots in Legs Or sTockings after Stroke) trial demonstrated that intermittent pneumatic compression of the lower extremities, started in the first 3 hospital days, reduced the risk of DVT in immobile patients with acute stroke.[125]

Neuroprotective Agents

The rationale for the use of neuroprotective agents is that reducing the release of excitatory neurotransmitters by neurons in the ischemic penumbra may enhance the survival or these neurons. Despite very promising results in several animal studies, however, no single neuroprotective agent in ischemic stroke has as yet been supported by randomized, placebo-controlled human studies. Nevertheless, substantial research is under way evaluating different neuroprotective strategies.

Hypothermia was very promising for the ongoing treatment of patients surviving cardiac arrest from ventricular tachycardia or ventricular fibrillation. However, no major clinical study has demonstrated a role for hypothermia in the early treatment of ischemic stroke.[1]  

For more information, see Neuroprotective Agents in Stroke.

Stroke Prevention

Primary prevention refers to the management of individuals with no history of stroke. Preventative measures may include the use of antiplatelet agents, statins, smoking cessation and exercise. The 2011 AHA/ASA guidelines for the primary prevention of stroke emphasize the importance of lifestyle changes to reduce well-documented modifiable risk factors, citing an 80% lower risk of a first stroke in people who follow a healthy lifestyle compared with those who do not.[22]

Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may include the use of anitplatelet agents,[126] anticoagulants (warfarin or newer novel oral anticoagulants) antihypertensives, statins,[127] and lifestyle interventions. A study by the Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators concluded that in stroke patients who have significant intracranial arterial stenosis, aspirin should be used in preference to warfarin for secondary prevention.[128]

Smoking cessation, blood pressure control, diabetes control, a low-fat low-salt diet, weight loss, and regular exercise should be encouraged as strongly as the medications described above. The 2011 AHA/ASA guidelines recommend ED-based smoking cessation interventions, and consider it reasonable for EDs to screen patients for hypertension and drug abuse.[22]

Written prescriptions for exercise and medications for smoking cessation (ie, nicotine patch, bupropion, varenicline) increase the likelihood of success with these interventions. In addition, the 2011 AHA/ASA guidelines for primary stroke prevention indicate that it is reasonable to avoid exposure to environmental tobacco smoke, despite a lack of stroke-specific data.

Aspirin for primary prevention

Overall, the value of aspirin in primary prevention appears uncertain,[129] and its use for this purpose is not recommended for patients at low risk. Aspirin is recommended for primary prevention only in persons with at least a 6–10% risk of cardiovascular events over 10 years.[22]

On the other hand, low-dose aspirin may be beneficial for primary prevention of stroke in women. A randomized, placebo-controlled trial in 39,876 initially healthy women aged 45 years or older demonstrated that 100 mg of aspirin on alternate days resulted in a 24% reduction in the risk of ischemic stroke, with a nonsignificant increase in the risk of hemorrhagic stroke.[130]

Secondary prevention guidelines

Guidelines issued in 2014 by the American Heart Association (AHA)/American Stroke Association (ASA) on the secondary prevention of stroke emphasize nutrition and lifestyle and include a new section on aortic atherosclerosis. New recommendations include the following:[131, 132]

Based on research results, the guidelines also recommend that, in patients without deep venous thrombosis (DVT), a patent foramen ovale not be closed. In addition, because there is little data to suggest that niacin or fibrate drugs, as a means to raise high-density lipoprotein (HDL) cholesterol, reduce secondary stroke risk, the guidelines no longer recommend their use.

Dual antiplatelet therapy for secondary prevention

A systematic review and meta-analysis of 12 randomized trials involving 3766 patients concluded that, compared with aspirin alone, dual antiplatelet therapy with aspirin plus either dipyridamole or clopidogrel appears to be safe and effective in reducing stroke recurrence and other vascular events (ie, transient ischemic attack [TIA], acute coronary syndrome, MI), in patients with acute ischemic stroke or TIA.[133] Dual therapy was also associated with a nonsignificant trend toward increased major bleeding.

The European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) showed that the combination of aspirin and dipyridamole was preferable to aspirin alone as antithrombotic therapy for cerebral ischemia of arterial origin.[134] In ESPRIT, secondary prevention was started within 6 months of a TIA or minor stroke of presumed arterial origin.

The addition of extended-release dipyridamole to aspirin therapy appears to be equally safe and effective whether started early or late after stroke. A German study in 543 patients found no significant difference in disability at 90 days, regardless of whether dipyridamole was started within 24 hours of stroke or TIA onset or after 7 days of aspirin monotherapy.[135]

In contrast, the Management of AtheroThrombosis with Clopidogrel in High-risk patients with recent transient ischaemic attack or ischaemic stroke (MATCH) trial, which included 7599 patients, found that adding aspirin to clopidogrel did not significantly reduce major vascular events. However, the risk of life-threatening or major bleeding was increased by the addition of aspirin.[136]

Research shows that aspirin combined with rivaroxaban cuts the ischemic stroke rate by almost half without significantly increasing the risk for intracerebral hemorrhage (ICH) compared with aspirin alone. The COMPASS trial studied 27,395 patients with stable atherosclerotic vascular disease divided into three treatment groups: aspirin 100 mg a day, rivaroxaban 5 mg twice daily, and a combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg per day. The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction and occurred in 379 patients in the combination group compared to 496 patients taking aspirin alone. However, bleeding events occurred in more patients in the combination group (3.1% vs 1.9%; HR, 1.70; 95% CI, 1.40 - 2.05; P< .001).[51]

Carotid artery stenosis

For patients at risk for stroke from asymptomatic carotid artery stenosis, the 2011 AHA/ASA primary prevention guidelines state that older studies that showed revascularization surgery as more beneficial than medical treatment may now be obsolete because of improvements in medical therapies. Therefore, individual patient comorbidities, life expectancy, and preferences should determine whether medical treatment alone or carotid revascularization is selected.[22]

Atrial fibrillation

Atrial fibrillation (AF) is a major risk factor for stroke. The 2011 AHA/ASA primary stroke prevention guideline recommends that EDs screen for AF and assess patients for anticoagulation therapy if AF is found.[22]

In the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W), oral anticoagulation with warfarin proved superior to clopidogrel plus aspirin for prevention of vascular events in patients with AF who were at high risk of stroke.[137] The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy.

Interestingly, in ACTIVE W, the rate of vascular events was significantly higher in patients who switched from warfarin to clopidogrel plus aspirin as a result of randomization than in patients who had been on warfarin before study enrollment and remained on warfarin during the study. The benefit of anticoagulation therapy over dual antiplatelet therapy was much more modest in patients who had not been on warfarin before study initiation and were then randomized to warfarin.

The 2011 ACC Foundation (ACCF)/AHA/Heart Rhythm Society (HRS) AF guideline update states that the new anticoagulant dabigatran is useful as an alternative to warfarin in patients with AF who do not have a prosthetic heart valve or hemodynamically significant valve disease.[138] However, a 2012 meta-analysis found an increased risk for MI or acute coronary syndrome with dabigatran.[139]  With the advent of other novel anticoagulants, the American Academy of Neurology (AAN) produced guidelines for the prevention of stroke in nonvalvuar atrial fibrillation in 2014.[140] The guidelines recommend that clinicians should administer dabigatran, rivaroxaban, or apixaban to patients who have nonvalvular atrial fibrillation requiring anticoagulant medication and are at higher risk of intracranial bleeding; they also suggest that clinicians might offer apixaban to patients with nonvalvular atrial fibrillation and GI bleeding risk who require anticoagulant medication. The AAN guidelines recommend that where oral anticoagulants are unavailable, clinicians might offer a combination of aspirin and clopidogrel. This combination was found to be more effective than aspirin for reducting strokes in atrial fibrillation in the ACTIVE trial although it did increase major hemorrhage risk.[141]

Specialized Stroke Centers

The concept of the specialized stroke center has evolved in response to the multitude of factors involved in the care of patients with acute stroke. The American Heart Association and the Brain Attack Coalition provided recommendations for the establishment of 3 tiers of stroke centers: acute stroke ready hospitals (ASRHs), primary stroke centers (PSCs), and comprehensive stroke centers (CSCs).[1] The Joint Commission for the Accreditation of Hospital Organizations (JC) and others now provide accreditation for ASRH, PSCs and CSCs. These centers are characterized as follows:

ASRHs, PSCs, and CSCs work most effectively when integrated into a regional stroke system of care so that patients are treated at the most appropriate hospital based on factors such as severity, comorbidities, and timing. Integrating regional prehospital services (911 and EMS) into this system of care ensures the most appropriate triage from the field.

Coordination of care

Once patients have been identified as potential stroke patients, their ED evaluation must be fast-tracked to allow for the completion of required laboratory tests and requisite noncontrast head CT scanning, as well as for the notification and involvement of neurologic consultants. These requirements have led to the development of "code stroke" protocols for the ED. In addition, EMS personnel are trained to identify possible stroke patients and arrange for their speedy, preferential transport to a PSC or CSC.[80]

Hospitals with specialized stroke teams have demonstrated significantly increased rates of fibrinolytic administration, decreased door-to-needle (DTN) times, and decreased mortality. Cumulatively, the center should identify performance measures and include mechanisms for evaluating the effectiveness of the system, as well as its component parts. The acute care of the stroke patient is more than anything a systems-based team approach requiring the cooperation of the ED, radiology, pharmacy, neurology, and intensive care unit (ICU) staff.

A stroke system should ensure effective interaction and collaboration among the agencies, services, and people involved in providing prevention and the timely identification, triage to the most appropriate hospital, rapid transport, treatment, and rehabilitation of stroke patients. For more information, see Stroke Team Creation and Primary Stroke Center Certification.

Consultations

A stroke team or an experienced professional who is sufficiently familiar with stroke should be available within 15 minutes of the patient's arrival in the ED. Other consultations are tailored to individual patient needs. Often, occupational therapy, physical therapy, speech therapy, and physical medicine and rehabilitation experts are consulted within the first day of hospitalization.

Consultation of cardiology, vascular surgery, or neurosurgery may be warranted based on the results of carotid duplex scanning , neuroimaging, transthoracic and transesophageal echocardiography, and clinical course. During hospitalization, additional useful consultations include the following:

Diet

Ischemic stroke is associated with vascular dementia; stroke survivors have almost double the rate of dementia than the general population. Patients may be helped by following the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, according to a 2018 study.[142] The diet may help prevent dementia as well.[143]

The MIND diet recommends at least three servings of whole grains a day and six servings of green leafy vegetables and two servings of berries a week, and it encourages regular consumption of other vegetables, fish, poultry, beans, and nuts. As well, it recommends olive oil as the primary oil and alcohol once per day. The diet restricts intake of red meats, fast foods, cheese, desserts, and butter.

Guidelines Summary

American Heart Association/American Stroke Association

Updated guidelines from the American Heart Association (AHA) and the American Stroke Association (ASA) extend the time limit on mechanical clot removal from 6 hours to up to 24 hours in select patients.[107]  The new guidelines recommend thrombectomy in eligible patients 6 to 16 hours after a stroke.[144, 145] They also broaden the eligibility criteria by allowing patients who are ineligible for IV tPA to undergo mechanical thrombectomy within 6 hours.

Patients should be considered for thrombectomy in under 6 hours after stroke onset if they have a large clot in one of the large vessels at the base of the brain and meet the following criteria:

The AHA and ASA also issued guidelines for the reduction of stroke risk specifically in women. These gender-specific recommendations include the following:[24, 25]

European Stroke Organisation

The European Stroke Organisation published guidelines on mechanical thrombectomy (MT) in acute ischemic stroke.[146] Recommendations include the following:

Evaluating and managing stroke in patients with COVID-19

Because patients with COVID-19 infection have high risk of developing acute stroke, an international panel of stroke experts from 18 countries issued a set of recommendations for managing acute ischemic stroke patients with either suspected or confirmed infection with the virus.[147, 148] Their recommendations include the following:

Medication Summary

While only 1 drug, recombinant tissue-type plasminogen activator (alteplase or generically referred to as rt-PA), has demonstrated efficacy and effectiveness in treating acute ischemic stroke and is approved by the FDA, other medications are equally important. National consensus panels have included the use of antihypertensives, anticonvulsants, and osmotic agents in their recommendations. Additional agents may be required for comorbid illnesses in many patients with stroke.

Medications for the management of ischemic stroke can be distributed into the following categories:

Alteplase (Activase)

Clinical Context:  Alteplase is a t-PA used in management of acute myocardial infarction (MI), acute ischemic stroke, and pulmonary embolism. Safety and efficacy with concomitant administration of heparin or aspirin during the first 24 hours after symptom onset have not been investigated.

Class Summary

Thrombolytic—more accurately, fibrinolytic—agents convert entrapped plasminogen to plasmin and initiate local fibrinolysis by binding to fibrin in a clot.

Diazepam (Valium)

Clinical Context:  Diazepam acts on the gamma-aminobutyric acid (GABA) receptor complex in the limbic system and thalamus, producing a calming effect. The drug is useful in controlling active seizures and should be augmented by longer-acting anticonvulsants, such as phenytoin or phenobarbital.

Lorazepam (Ativan)

Clinical Context:  Lorazepam is a short-acting benzodiazepine with a moderately long half-life. It has become the drug of choice in many centers for treating active seizures.

Class Summary

While seizures associated with stroke are relatively uncommon, recurrent seizures may be life threatening. Generally, agents used for treating recurrent convulsive seizures are also used in patients with seizures after stroke. Benzodiazepines, typically diazepam and lorazepam, are the first-line drugs for ongoing seizures.

Aspirin (ASA)

Clinical Context:  Aspirin blocks prostaglandin synthetase action, which in turn inhibits prostaglandin synthesis and prevents the formation of platelet-aggregating thromboxane A2. It also acts on the hypothalamic heat-regulating center to reduce fever.

Dipyridamole and aspirin (Aggrenox)

Clinical Context:  The combination of extended-release dipyridamole and aspirin reduces the relative risk of stroke, death, and myocardial infarction (MI). It is used for the secondary prevention of ischemic stroke and TIAs.

Clopidogrel (Plavix)

Clinical Context:  Clopidogrel inhibits platelet aggregation and is used for secondary stroke prevention. It is indicated for the reduction of atherothrombotic events following a recent stroke.

Class Summary

Although antiplatelet agents have proved useful for preventing recurrent stroke or stroke after transient ischemic attacks (TIAs), efficacy in the treatment of acute ischemic stroke has not been demonstrated. Early aspirin therapy is recommended within 48 hours of the onset of symptoms but should be delayed for at least 24 hours after rt-PA administration. Aspirin should not be considered as an alternative to intravenous fibrinolysis or other therapies aimed at improving outcomes after stroke.

Warfarin (Coumadin, Jantoven)

Clinical Context:  Warfarin is an anticoagulant used to reduce the risk of death, recurrent MI, and thromboembolic events such as stroke or systemic embolization after MI.

Dabigatran (Pradaxa)

Clinical Context:  Dabigatran is a competitive, direct inhibitor of thrombin that can prevent thrombus development. This agent inhibits free and clot-bound thrombin and thrombin-induced platelet aggregation. It may be used as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal to permanent atrial fibrillation and risk factors for stroke or systemic embolization.

Rivaroxaban (Xarelto)

Clinical Context:  Rivaroxaban is a Factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The dose is adjusted according to estimated creatinine clearance.

Apixaban (Eliquis)

Clinical Context:  Apixaban is a factor Xa inhibitor that inhibits platelet activation by selectively and reversibly blocking the active site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity. It inhibits free and clot-bound factor Xa and prothrombinase activity. Although this agent has no direct effect on platelet aggregation, it does indirectly inhibit platelet aggregation induced by thrombin. Apixaban is indicated to reduce risk of stroke and systemic embolism associated with nonvalvular atrial fibrillation.

Edoxaban (Savaysa)

Clinical Context:  Edoxaban is a Factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. A lower dose is needed with CrCl < 50 mL/min. Do not use with CrCL >95 mL/min. In the ENGAGE AF-TIMI 48 study, patients with NVAF with CrCL >95 mL/min had an increased rate of ischemic stroke with edoxaban 60 mg/day compared with patients treated with warfarin.

Class Summary

Anticoagulants such as warfarin are used for secondary stroke prevention.

Acetaminophen (Tylenol, Feverall, Aspirin Free Anacin)

Clinical Context:  Acetaminophen reduces fever by acting directly on hypothalamic heat-regulating centers, which increases the dissipation of body heat via vasodilation and sweating.

Class Summary

Hyperthermia in acute stroke is potentially harmful and should be treated. Agents with potential bleeding risk should be avoided, if possible.

Labetalol (Normodyne, Trandate)

Clinical Context:  Labetalol is an adrenergic receptor-blocking agent with nonselective beta-adrenergic and selective alpha1 competitive receptor-blocking actions. It produces dose-related decreases in blood pressure without inducing reflex tachycardia.

Class Summary

Optimal blood pressure management in acute stroke remains subject to some debate. Treatment parameters depend largely on whether the patient is a candidate for fibrinolytic therapy. While the target blood pressures may differ, the therapeutic agents are primarily the same.

Enalapril (Vasotec)

Clinical Context:  An ACE inhibitor, enalapril decreases circulating angiotensin II levels and suppresses the renin-angiotensin-aldosterone system, lowering overall blood pressure.

Class Summary

Angiotensin-converting enzyme (ACE) inhibitors prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Nicardipine (Cardene)

Clinical Context:  A calcium channel blocker, nicardipine inhibits calcium ion influx into vascular smooth muscle and myocardium.[92]

Class Summary

Optimal blood pressure management in acute stroke remains subject to some debate. Treatment parameters depend largely on whether the patient is a candidate for fibrinolytic therapy. While the target blood pressures may differ, the therapeutic agents are largely the same.

Nitroprusside sodium (Nipride, Nitropress, Sodium Nitroprusside)

Clinical Context:  Nitroprusside sodium is a vasodilator that decreases peripheral vascular resistance by relaxing arteriolar smooth muscle. It also decreases venous return through venous dilation.

Class Summary

Vasodilators lower blood pressure through direct vasodilation and relaxation of the vascular smooth muscle. They are used more for blood pressure lowering in severe or refractory situations and should be used with caution.

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ischemic stroke?What is the role of cytotoxic edema in the pathogenesis of ischemic stroke?What is the role of cerebral ischemia in the pathogenesis of stroke?What causes increased inflammation and microcirculatory compromise in the pathophysiology of ischemic stroke?What is the role of infarction in the pathophysiology of ischemic stroke?What is the role of hemorrhagic transformation in the pathophysiology of ischemic stroke?What are the mechanisms for hemorrhagic transformation in the pathophysiology of ischemic stroke?When is hemorrhagic transformation most likely to occur in the pathophysiology of ischemic stroke?What is the role of cerebral edema in the pathophysiology of ischemic stroke?What is the role of large-artery occlusion in the etiology of ischemic stroke?What is the pathogenesis of lacunar ischemic stroke?What is the etiology of ischemic stroke?What are the risk factors for ischemic stroke?Which nonmodifiable factors increase the risk for ischemic stroke?Are migraines with aura a significant risk factor for ischemic stroke?Which modifiable factors increase the risk for ischemic stroke?What are the AHA/ASA recommendations for reduction of stroke risk in women?What is the role of atherosclerosis in the etiology of ischemic stroke?Which genetic factors increase susceptibility to ischemic stroke?What is the role of homocysteine in the pathogenesis of ischemic stroke?What is the role of amyloid angiopathies in the etiology of ischemic stroke?What is the role of CADASIL in the etiology of ischemic stroke?Which genetic mutations are associated with ischemic stroke?What causes lacunar infarcts in ischemic stroke?What are the causes of cardiogenic emboli in ischemic stroke?What is the etiology of thrombotic stroke?What is the role of vascular watershed infarcts in the etiology of ischemic stroke?What is the role of cerebral blood flow disturbances in the etiology of ischemic stroke?What is the incidence of ischemic stroke in the US and globally?What are the race-related variances in the incidence of ischemic stroke?How does the incidence of ischemic stroke differ between males and females?How does the incidence and risk for ischemic stroke vary among age groups?What is the mortality rate of ischemic stroke and which factors affect the prognosis after acute ischemic stroke (AIS)?What is the strongest predictor of early mortality risk in patients with ischemic stroke?Which factors are associated with poor outcome in ischemic stroke?Which factors in patients with acute ischemic stroke (AIS) are associated with poor outcomes?What is the degree of recovery for patients with ischemic stroke?What should public health education about ischemic stroke include and which venues can be used to reach an audience with a higher stroke risk?According to the ASA, what are the easily recognizable symptoms of stroke?What are the warning signs of stroke?Which risk factors for atherosclerotic and cardiac disease should be identified in the medical history of patients with suspected ischemic stroke?What history should be elicited in younger patients with suspected ischemic stroke?What are signs and symptoms of stroke?What is the median time from symptom onset of ischemic stroke to emergency department (ED) presentation?Which factors contribute to delays in seeking care for ischemic stroke?How is the time of onset defined if the patient awakens with symptoms of stroke?What are the goals of the physical exam in suspected ischemic stroke?What should be included in the physical exam for suspected ischemic stroke?Why is constant reassessment necessary for patients with suspected ischemic stroke?What is the role of vital sign monitoring in the assessment of suspected ischemic stroke?Which physical findings from a head exam may suggest trauma or carotid disease as the etiology of ischemic stroke?Which cardiac conditions may be concurrent with ischemic stroke?How might aortic dissection be identified in patients with ischemic stroke?What are the goals of the neurologic exam for ischemic stroke?Which evaluations should be included in the neurologic exam for ischemic stroke?What is the NIH Stroke Scale (NIHSS) and how is it performed?What is the clinical presentation of middle cerebral artery (MCA) occlusions in ischemic stroke?What is the clinical presentation of anterior cerebral artery (ACA) occlusions in ischemic stroke?What is the clinical presentation of posterior cerebral artery (PCA) occlusions in ischemic stroke?What is the clinical presentation of vertebrobasilar artery occlusions in ischemic stroke?How is a posterior circulation stroke differentiated from an anterior circulation stroke?What is the clinical presentation of lacunar ischemic stroke?Which conditions should be included in the differential diagnoses of ischemic stroke?What is a transient ischemic attack (TIA) and what is the likelihood it will lead to ischemic stroke?What clinical findings help differentiate hemorrhagic stroke from ischemic stroke?What is cerebral venous thrombosis (CVT)?What are the differential diagnoses for ischemic stroke?What is the role of brain imaging studies in the workup of ischemic stroke?What is the role of MRI in the workup of ischemic stroke?What is the role of carotid duplex scanning in the workup of ischemic stroke?What is the role of digital subtraction angiography in the workup of ischemic stroke?What is the role of lab testing in the workup of ischemic stroke?Which lab tests may be useful in the workup of select patients with suspected ischemic stroke?When is a pregnancy test indicated in the workup of ischemic stroke?What is the role of CT scanning in the workup of ischemic stroke?What is the role of diffusion-weighted imaging (DWI) in the workup of ischemic stroke?What is the role of dynamic susceptibility contrast MRI (DSC-MRI) in the workup of ischemic stroke?What is calculated using either perfusion MRI or CT scanning in the workup of ischemic stroke?What are the AAN recommendations for imaging studies in the workup of ischemic stroke?Which imaging findings have been correlated with increased infarct volume size in ischemic stroke?What are the roles of transcranial Doppler ultrasonography and echocardiography in the workup of ischemic stroke?What is the role of chest radiography in the workup of ischemic stroke?What is the role of SPECT scanning in the workup of ischemic stroke?What is the role of angiography in the workup of ischemic stroke?What is the role of a CBC and a basic chemistry panel in the workup of ischemic stroke?What is the role of coagulation studies in the workup of ischemic stroke?What is the role of cardiac biomarkers in the workup of ischemic stroke?What is the role of toxicology screening and arterial blood gas studies in the workup of ischemic stroke?When is a pregnancy test performed in the workup of ischemic stroke?What is the central goal of therapy in acute ischemic stroke (AIS)?What is the goal of recanalization strategies in the treatment for 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stroke?Which fibrinolytic agent has been shown to benefit patients with acute ischemic stroke (AIS)?What is the role of fibrinolytics in the treatment of ischemic stroke and what are possible complications?What are the AHA/ASA inclusion guidelines for fibrinolytic therapy with rt-PA for ischemic stroke?What are the AHA/ASA inclusion guidelines for fibrinolytic therapy 3-4.5 hours after symptom onset in ischemic stroke?How effective is fibrinolytic therapy 3-4.5 hours after symptom onset in ischemic stroke?What is the risk of intracerebral hemorrhage with fibrinolysis therapy for ischemic stroke?When should caution be used in the administration of fibrinolytic therapy in the treatment of ischemic stroke?What is the role of ultrasound in fibrinolysis therapy in the treatment of ischemic stroke?What is the role of intra-arterial delivery of fibrinolytic agents in the treatment for ischemic stroke?What are the AHA/ASA guidelines for the administration of aspirin in the treatment of 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Retrieval System for endovascular treatment of ischemic stroke?How effective is the Penumbra System for the endovascular treatment of acute ischemic stroke (AIS)?How effective are the Solitaire FR Revascularization Device and Trevo systems for the endovascular treatment of acute ischemic stroke?When are antipyretics indicated in the treatment of ischemic stroke?What is role of high-dose acetaminophen in the treatment of ischemic stroke?What is the occurrence of cerebral edema after ischemic stroke?What does the presence of ischemia on presentation suggest in ischemic stroke?What are the treatment options for patients with increased intracranial pressure (ICP) secondary to closed head injury?What are the AHA/ASA guidelines for the management of cerebral and cerebellar infarction with brain swelling in ischemic stroke?What is the occurrence of seizures and seizure disorders in ischemic stroke and how are they treated?What treatment is indicated for a patient with rapidly decompensating ischemic stroke?What is the role of anticoagulation in the treatment of ischemic stroke?What is the role of neuroprotective agents in the treatment of ischemic stroke?What is the role of hypothermia in the early treatment of ischemic stroke?What are the AHA/ASA guidelines for the primary prevention of ischemic stroke?What is secondary prevention of ischemic stroke?What may increase the success of interventions for prevention of ischemic stroke?When is aspirin recommended for primary prevention of ischemic stroke?What do the AHA/ASA guidelines emphasize for secondary prevention of stroke?How effective is dual antiplatelet therapy for secondary prevention of ischemic stroke?What are the AHA/ASA recommendations for primary prevention in patients at risk for ischemic stroke from asymptomatic carotid artery stenosis?What are the AHA/ASA recommendations for primary prevention of stroke due to atrial fibrillation (AF)?What is the role of warfarin in the treatment of atrial fibrillation (AF) in patients at high risk of ischemic stroke?What are the AAN guidelines for prevention of ischemic stroke in patients with nonvalvular atrial fibrillation (AF)?What are the AHA and the Brain Attack Coalition recommendations for the establishment of specialized stroke centers?What is the code stroke ED protocol for treatment of possible ischemic stroke?What performance measures should be evaluated in hospitals with specialized stroke teams?What are the benefits of a stroke system for the management of ischemic stroke?Which specialists should be available in the ED within 15 minutes of the arrival of a patient with a possible ischemic stroke?Which specialist consultations may be warranted for ischemic stroke?What dietary guidelines should survivors of ischemic stroke follow?What are the AHA and ASA treatment guidelines for ischemic stroke?Which medications are used in the treatment of ischemic stroke?What categories of medications are used in the treatment of ischemic stroke?Which medications in the drug class Vasodilators are used in the treatment of Ischemic Stroke?Which medications in the drug class Calcium Channel Blockers are used in the treatment of Ischemic Stroke?Which medications in the drug class ACE Inhibitors are used in the treatment of Ischemic Stroke?Which medications in the drug class Beta Blockers, Alpha Activity are used in the treatment of Ischemic Stroke?Which medications in the drug class Analgesics, Other are used in the treatment of Ischemic Stroke?Which medications in the drug class Anticoagulants, Hematologic are used in the treatment of Ischemic Stroke?Which medications in the drug class Antiplatelet Agents are used in the treatment of Ischemic Stroke?Which medications in the drug class Anticonvulsants, Other are used in the treatment of Ischemic Stroke?Which medications in the drug class Thrombolytics are used in the treatment of Ischemic Stroke?

Author

Edward C Jauch, MD, MS, FAHA, FACEP, Chief of System Research, Mission Research Institute, Mission Health; Adjunct Professor, Department of Bioengineering, Clemson University

Disclosure: Received grant/research funds from Genentech for site pi.

Coauthor(s)

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.

Sami Al Kasab, MD, House Staff, Department of Neurology, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

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

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; Consultant, Abbott Vascular, Inc. .

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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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.

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.

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 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).

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).

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).

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.

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.

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.

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.

Magnetic resonance imaging (MRI) scan in a 70-year-old woman with a history of left-sided weakness for several hours. An axial T2 fluid-attenuated inversion recovery (FLAIR) image (left) demonstrates high signal in the lentiform nucleus with mass effect. The axial diffusion-weighted image (middle) demonstrates high signal in the same area, with corresponding low signal on the apparent diffusion coefficient (ADC) maps, consistent with true restricted diffusion and an acute infarction. Maximum intensity projection from a 3-dimensional (3-D) time-of-flight magnetic resonance angiogram (MRA, right) demonstrates occlusion of the distal middle cerebral artery (MCA) trunk (red circle).

Regions of interest are selected for arterial and venous input (image on left) for dynamic susceptibility-weighted perfusion magnetic resonance imaging (MRI). Signal-time curves (image on right) obtained from these regions of interest demonstrate transient signal drop following the administration of intravenous contrast. The information obtained from the dynamic parenchymal signal changes postcontrast is used to generate maps of different perfusion parameters.

A 48-year-old man presented with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference. Angiogram with selective injection of the right internal carotid artery demonstrates occlusion of the M1 segment of the right middle cerebral artery (MCA) and A2 segment of the right anterior cerebral artery (ACA; images courtesy of Concentric Medical).

Follow-up imaging after mechanical embolectomy in 48-year-old man with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference demonstrates complete recanalization of the right middle cerebral artery (MCA) and partial recanalization of the right A2 segment (images courtesy of Concentric Medical).

Cerebral angiogram performed approximately 4.5 hours after symptom onset in a 31-year-old man demonstrates an occlusion of the distal basilar artery (images courtesy of Concentric Medical).

Image on the left demonstrates deployment of a clot retrieval device (older generation device) in a 31-year-old man. Followup angiogram after embolectomy demonstrates recanalization of the distal basilar artery with filling of the superior cerebellar arteries and posterior cerebral arteries. The patient had complete resolution of symptoms following embolectomy (images courtesy of Concentric Medical).

Axial noncontrast computed tomography (NCCT) scan demonstrates diffuse hypodensity in the right lentiform nucleus with mass effect upon the frontal horn of the right lateral ventricle in a 70-year-old woman with a history of left-sided weakness for several hours.

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.

Axial noncontrast computed tomography (NCCT) scan demonstrates diffuse hypodensity in the right lentiform nucleus with mass effect upon the frontal horn of the right lateral ventricle in a 70-year-old woman with a history of left-sided weakness for several hours.

Magnetic resonance imaging (MRI) scan in a 70-year-old woman with a history of left-sided weakness for several hours. An axial T2 fluid-attenuated inversion recovery (FLAIR) image (left) demonstrates high signal in the lentiform nucleus with mass effect. The axial diffusion-weighted image (middle) demonstrates high signal in the same area, with corresponding low signal on the apparent diffusion coefficient (ADC) maps, consistent with true restricted diffusion and an acute infarction. Maximum intensity projection from a 3-dimensional (3-D) time-of-flight magnetic resonance angiogram (MRA, right) demonstrates occlusion of the distal middle cerebral artery (MCA) trunk (red circle).

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.

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.

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.

A 48-year-old man presented with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference. Angiogram with selective injection of the right internal carotid artery demonstrates occlusion of the M1 segment of the right middle cerebral artery (MCA) and A2 segment of the right anterior cerebral artery (ACA; images courtesy of Concentric Medical).

Follow-up imaging after mechanical embolectomy in 48-year-old man with acute left-sided hemiplegia, facial palsy, and right-sided gaze preference demonstrates complete recanalization of the right middle cerebral artery (MCA) and partial recanalization of the right A2 segment (images courtesy of Concentric Medical).

Cerebral angiogram performed approximately 4.5 hours after symptom onset in a 31-year-old man demonstrates an occlusion of the distal basilar artery (images courtesy of Concentric Medical).

Image on the left demonstrates deployment of a clot retrieval device (older generation device) in a 31-year-old man. Followup angiogram after embolectomy demonstrates recanalization of the distal basilar artery with filling of the superior cerebellar arteries and posterior cerebral arteries. The patient had complete resolution of symptoms following embolectomy (images courtesy of Concentric Medical).

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.

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.

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).

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).

Regions of interest are selected for arterial and venous input (image on left) for dynamic susceptibility-weighted perfusion magnetic resonance imaging (MRI). Signal-time curves (image on right) obtained from these regions of interest demonstrate transient signal drop following the administration of intravenous contrast. The information obtained from the dynamic parenchymal signal changes postcontrast is used to generate maps of different perfusion parameters.

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 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).

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.

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.

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
  Category Description Score
1alevel of consciousness (LOC)Alert



Drowsy



Stuporous



Coma



0



1



2



3



1bLOC questions (month, age)Answers both correctly



Answers 1 correctly



Incorrect on both



0



1



2



1cLOC commands (open and close eyes,



grip and release nonparetic hand)



Obeys both correctly



Obeys 1 correctly



Incorrect on both



0



1



2



2Best gaze (follow finger)Normal



Partial gaze palsy



Forced deviation



0



1



2



3Best visual (visual fields)No visual loss



Partial hemianopia



Complete hemianopia



Bilateral hemianopia



0



1



2



3



4Facial palsy (show teeth, raise brows,



squeeze eyes shut)



Normal



Minor



Partial



Complete



0



1



2



3



5Motor 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



6Motor 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



7Motor leg left* (raise 30°, hold 5 seconds)No drift



Drift



Cannot resist gravity



No effort against gravity



No movement



0



1



2



3



4



8Motor leg right* (raise 30°, hold 5 seconds)No drift



Drift



Cannot resist gravity



No effort against gravity



No movement



0



1



2



3



4



9Limb ataxia (finger-nose, heel-shin)Absent



Present in 1 limb



Present in 2 limbs



0



1



2



10Sensory (pinprick to face, arm, leg)Normal



Partial loss



Severe loss



0



1



2



11Extinction/neglect (double simultaneous testing)No neglect



Partial neglect



Complete neglect



0



1



2



12Dysarthria (speech clarity to "mama,



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



Normal articulation



Mild to moderate dysarthria



Near to unintelligible or worse



0



1



2



13Best 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)