Ischemic Stroke Practice Essentials Stroke is characterized by the sudden loss of blood circulation to an area of the brain, resulting

in a corresponding loss of neurologic function. Strokes are classified as either hemorrhagic or ischemic. Acute ischemic stroke refers to stroke caused by thrombosis or embolism and is more common than hemorrhagic stroke. Essential update: Thrombolysis within 90 minutes yields excellent results in patients with mild to moderate ischemic stroke Administration of intravenous recombinant tissue-type plasminogen activator (rt-PA) is most effective within 90 minutes of the onset of stroke symptoms, according to a 10center European study of nearly 6900 patients. The investigators found that patients who scored in the 7-12 range on the National Institutes of Health Stroke Scale (NIHSS) had better outcomes when thrombolytic therapy was provided within the first hour and a half of symptom onset than did those treated between 90 and 270 minutes after onset, with the earlier-treated patients demonstrating little or no disability 3 months after thrombolysis. For patients with minor stroke or moderate to severe stroke, however, treatment within the 90-minute window provided no additional advantage.[1, 2] Signs and symptoms Although signs and symptoms of stroke can occur alone, they are more likely to occur in combination. Common stroke signs and symptoms include the following: Abrupt onset of hemiparesis, monoparesis, or quadriparesis Acute hemisensory loss Complete or partial hemianopia, monocular or binocular visual loss, or diplopia Visual field deficits Diplopia Dysarthria Ataxia Vertigo Nystagmus Aphasia Sudden decrease in the level of consciousness In younger patients, a history of recent trauma, coagulopathies, illicit drug use (especially cocaine), migraines, or use of oral contraceptives should be elicited. See Clinical Presentation for more detail. Diagnosis With the availability of thrombolytic therapy 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. Essential components of the neurologic examination include evaluations of the following: Cranial nerves Motor function Sensory function Cerebellar function Gait

Deep tendon reflexes Mental status level of consciousness The patients skull and spine also should be examined, and signs of meningismus should be sought.

Laboratory studies

Laboratory tests performed in the diagnosis and evaluation of ischemic stroke include the following: Complete blood cell count: The CBC count serves as a baseline study and may reveal a cause for the stroke (eg, polycythemia, thrombocytosis, thrombocytopenia, leukemia) or provide evidence of concurrent illness (eg, anemia) Basic chemistry panel: The 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: Coagulation studies may reveal a coagulopathy and are useful when thrombolytics or anticoagulants are to be used Cardiac biomarkers: Cardiac biomarkers are important because of the association of cerebral vascular disease and coronary artery disease Toxicology screening: Toxicology screening may assist in identifying intoxicated patients with symptoms/behavior mimicking stroke syndromes Pregnancy testing: A urine pregnancy test should be obtained for all women of childbearing age with stroke symptoms; recombinant tissue-type plasminogen activator (rt-PA) is a pregnancy class C agent Arterial blood gas analysis: Although infrequent in patients with suspected hypoxemia, arterial blood gas defines the severity of hypoxemia and may be used to detect acid-base disturbances

Imaging studies

Imaging in ischemic stroke can involve the following modalities: Several types of magnetic resonance imaging Several types of computed tomography scanning Angiography Ultrasonography Radiology Echocardiography Nuclear imaging

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 See Workup for more detail. Management Ischemic stroke therapies include the following: Thrombolytic therapy: Thrombolytics restore cerebral blood flow among some patients with acute ischemic stroke and may lead to improvement or resolution of neurologic deficits Antiplatelet agents: 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[3, 4]

Stroke prevention

Mechanical thrombolysis: Involves treatment of acute ischemic stroke

the

endovascular

Primary stroke prevention refers to the treatment of individuals with no previous history of stroke. Measures may include use of the following: Platelet antiaggregants 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (ie, statins) Exercise Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may include use of the following: Platelet antiaggregants Antihypertensives HMG-CoA reductase inhibitors (statins) Lifestyle interventions See Treatment and Medication for more detail. Image library

Vascular distributions: 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 MCA distributions), greater on the left indicating multivessel involvement suggesting emboli. Background Stroke is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. Also previously called cerebrovascular accident (CVA) or stroke syndrome, stroke is a nonspecific term encompassing a heterogeneous group of pathophysiologic causes. Broadly, however, strokes are classified as either hemorrhagic or ischemic. Acute ischemic stroke refers to stroke caused by thrombosis or embolism and is more common than hemorrhagic stroke. (Prior literature indicated that only 8-18% of strokes are hemorrhagic, but a retrospective review from a stroke center found that 40.9% of 757 strokes included in the study were hemorrhagic.[5] ) Based on the system of categorizing stroke developed in the multicenter Trial of Org 10172 in Acute Stroke Treatment (TOAST), ischemic strokes may be divided into the following 3 major subtypes[6] : Large artery infarction: Thrombotic strokes are caused by in situ occlusions on atherosclerotic lesions in the carotid, vertebrobasilar, and cerebral arteries, typically proximal to major branches. Small-vessel, or lacunar, infarction

Cardioembolic infarction: Cardiogenic emboli are a common source of recurrent stroke. They may account for up to 20% of acute strokes and have been reported to have the highest 1-month mortality. (See Pathophysiology.) The National Institute of Neurologic Disorders and Stroke (NINDS) recombinant tissue-type plasminogen activator (rtPA) stroke study group first reported that the early administration of rt-PA benefited carefully selected patients with acute ischemic stroke.[7] The trials outcome led to the long-standing goal of t-PA administration within a 3-hour window for a patient deemed likely to benefit from thrombolytic intervention. Encouraged by this breakthrough study and the subsequent approval by the US Food and Drug Administration (FDA) of the use of t-PA in acute ischemic stroke, many medical professionals now consider acute ischemic stroke to be a medical emergency that may be amenable to treatment. Thrombolytic therapy administered between 3 and 4.5 hours after the onset of symptoms was found to be efficacious in improving neurologic outcomes in the European Cooperative Acute Stroke Study III (ECASS III), suggesting a wider time window for the administration of thrombolytics.[8] Based on this and other data, in May 2009, the American Heart Association and the American Stroke Association guidelines for the administration of rt-PA were revised to expand the treatment window from 3 to 4.5 hours.[9] This indication has not yet been FDA approved. Understanding of the pathophysiology, clinical presentation, and evaluation of the stroke patient is essential, as is knowledge of the therapeutic armamentarium currently available to treat acute ischemic stroke, which includes supportive care, treatment of neurologic complications, antiplatelet therapy, glycemic control, blood pressure control, prevention of hyperthermia, and thrombolytic therapy. (See Treatment and Management.) See the images below.

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

duration. Magnetic Resonance Imaging (MRI) was subsequently obtained in the

same patient as in the above image. An axial T2 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 3D time-offlight magnetic resonance angiogram (MRA, right) demonstrates occlusion of the distal middle cerebral artery (MCA) trunk (red circle). 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. See the Cardiac Output calculator. Knowledge of cerebrovascular arterial anatomy and the territories supplied by each is useful in determining which vessels are involved in acute stroke. Atypical patterns that do not conform to a vascular distribution may indicate a diagnosis other than ischemic stroke, such as venous infarction. Arterial distributions 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. 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 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. The cerebellar hemispheres are supplied inferiorly by the posterior inferior cerebellar artery (PICA) arising from the vertebral artery, superiorly by the superior cerebellar artery, and anterolaterally by the anterior inferior cerebellar artery (AICA) from the basilar artery. The cerebral vasculature is seen in the images below. The images after Table 1 demonstrate cerebral artery infarction.

Frontal view of a cerebral angiogram with selective injection of the left internal carotid artery illustrates the anterior circulation. The anterior cerebral artery consists of the A1 segment proximal to the anterior communicating artery with the A2 segment distal to it. The MCA can be divided into 4 segments: the M1 (horizontal segment) extends to 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).

Lateral view of a cerebral angiogram illustrates the branches of the anterior cerebral artery 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 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 MCA with the apex representing the Sylvian point. Table 1. Vascular Supply to the Brain (Open Table in a new window) VASCULAR TERRITORY Anterior Circulation (Carotid) Anterior Artery Cerebral Cortical branches: medial frontal and parietal lobe Structures Supplied

Medial

lenticulostriate

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

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.

Middle Artery

Cerebral

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

Lateral lenticulostriate branches: globus pallidus and putamen, internal capsule

Anterior Artery

Choroidal

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

Posterior Circulation (Vertebrobasilar) Posterior Artery Cerebral Cortical branches: occipital lobes, medial and posterior temporal and parietal lobes

Vascular distributions: MCA infarction. Noncontrast CT 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 (ACA territory), thalami and paramedian occipital lobe (PCA

Perforating branches: brainstem, posterior thalamus and midbrain

Posterior Inferior Cerebellar Artery Anterior Inferior Cerebellar Artery Superior Artery Cerebellar

Inferior vermis; posterior inferior cerebellar hemispheres Anterolateral cerebellum

and

territory). Vascular distributions: 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 MCA distributions), greater on the left indicating multivessel involvement suggesting emboli.

Superior vermis; superior cerebellum

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 MCA (red) supplies the lateral aspects of the hemispheres, including the lateral frontal, parietal and anterior temporal lobes, insula and basal ganglia. The ACA (blue) supplies the medial frontal and parietal lobes. The PCA (green) supplies the thalami and occipital and inferior

Vascular distributions: PCA infarction. The noncontrast 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 before bifurcating into the anterior and middle cerebral arteries. The anterior choroidal artery may also arise from the MCA. Pathophysiology Acute ischemic strokes are the result of vascular occlusion secondary to thromboembolic disease (see Etiology). Ischemia results in cell hypoxia and depletion of cellular adenosine triphosphate (ATP). Without ATP, energy failure results in an inability to maintain ionic gradients across the cell membrane and cell depolarization. With an influx of sodium and calcium ions and passive inflow of water into the cell, cytotoxic edema results.[10, 11, 12] Ischemic core and penumbra An acute vascular occlusion produces heterogeneous regions of ischemia in the affected vascular territory. The quantity of local blood flow is made up of any residual flow in the major arterial source and the collateral supply, if any. Regions of the brain with CBF lower than 10 mL/100g of tissue/min are referred to collectively as the core, and these cells are presumed to die within minutes of stroke onset. Zones of decreased or marginal perfusion (CBF < 25 mL/100g of tissue/min) are collectively called the ischemic penumbra. Tissue in the penumbra can remain viable for several hours because of marginal tissue perfusion. Ischemic cascade On the cellular level, the ischemic neuron becomes depolarized as ATP is depleted and membrane ion-transport systems fail. 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-Daspartate (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.[13] 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 barriers breakdown, proteins and water flood into the extracellular space, leading to vasogenic edema. Vasogenic edema produces greater levels of brain swelling and mass

effect that peaks at 3-5 days and resolves over the next several weeks with resorption of water and proteins.[14, 15] 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.[13] 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 oligodendroglia and microglia 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 fluidlike low density is eventually seen, consisting of encephalomalacia and cystic change. The evolution of these chronic changes may be seen in the weeks to months following the infarction. Hemorrhagic transformation of ischemic stroke Hemorrhagic transformation represents the conversion of a bland infarction into an area of hemorrhage. This is estimated to occur in 5% of uncomplicated ischemic strokes, in the absence of thrombolytics. Hemorrhagic transformation is not always associated with neurologic decline and ranges from small petechial hemorrhages to hematomas requiring evacuation. 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 bloodbrain barrier. With disruption of the blood-brain barrier, red blood cells extravasate from the weakened capillary bed producing petechial hemorrhage or more frank [10, 16, 17] intraparenchymal hematoma. Hemorrhagic transformation of an ischemic infarct occurs within 2-14 days post ictus, usually within the first week. It is more commonly seen following cardioembolic strokes and is more likely with larger infarct size.[10, 18, 7]Hemorrhagic transformation is also more likely following administration of t-PA, with noncontrast computed tomography (NCCT) scanning demonstrating areas of hypodensity.[19, 20, 21] Poststroke cerebral edema and seizures Although significant cerebral edema can occur after anterior circulation ischemic stroke, it is thought to be somewhat rare (10-20%).[22] 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 stroke.[22] 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 thrombosis embolism, thrombosis in situ, or relative hypoperfusion. As blood flow decreases, neurons cease functioning, and irreversible neuronal ischemia and injury begin at blood flow rates of less than 18 mL/100 g of tissue/min. Risk factors

Risk factors for ischemic stroke include modifiable and nonmodifiable etiologies. 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: Age Race Sex Ethnicity History of migraine headaches Sickle cell disease Fibromuscular dysplasia Heredity 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.[23] 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.[23] 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 for ischemic stroke include the following: Hypertension (the most important) Diabetes mellitus Cardiac disease - Atrial fibrillation, valvular disease, mitral stenosis, and structural anomalies allowing right to left shunting, such as a patent foramen ovale and atrial and ventricular enlargement Hypercholesterolemia Transient ischemic attacks (TIAs) Carotid stenosis Hyperhomocystinemia Lifestyle issues - Excessive alcohol intake, tobacco use, illicit drug use, obesity, physical inactivity Oral contraceptive use Among the types of cardiac disease that increase stroke risk are atrial fibrillation, valvular disease, mitral stenosis, and structural anomalies allowing right-to-left shunting, such as a patent foramen ovale and atrial and ventricular enlargement. TIA is a transient neurologic deficit with no evidence of an ischemic lesion on neuroimaging. Roughly 80% resolve within 60 minutes.[24] TIA can result from the aforementioned mechanisms of stroke. Data suggest that roughly 10% of patients with TIA suffer stroke within 90 days and half of these patients suffer stroke within 2 days.[25, 26]

stroke risk. Dosage size, older age and/or the presence of dementia, and the use of antipsychotics with a high binding affinity for alpha-2-adrenergic and M1-muscarinic receptors contributed to the stroke risk.[27] According to the investigators, the stroke risk in persons taking antipsychotic medications was 1.6-fold higher in the 2 weeks before the stroke occurred. However, this association was observed only in the initial 28 days of antipsychotic use, after which the drugs were no longer a contributing factor in stroke. Genetic and inflammatory mechanisms Evidence continues to accumulate to suggest important roles for inflammation and genetic factors in the process 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) 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. For more information, see Genetic and Inflammatory Mechanisms in Stroke. In addition, complete information on the following metabolic disease and stroke can be found in the main articles: Metabolic Disease and Stroke - Methylmalonic Acidemia Metabolic Disease and Stroke Homocystinuria/Homocysteinemia Metabolic Disease and Stroke - Fabry Disease Metabolic Disease and Stroke MELAS Metabolic Disease and Stroke Hyperglycemia/Hypoglycemia Flow disturbances Stroke symptoms can result from inadequate cerebral blood flow due to decreased blood pressure (and specifically, decreased cerebral perfusion pressure) or as a result of hematologic hyperviscosity due to 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. 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.)

Antipsychotic medications

An analysis of 14,584 stroke patients who had at least 1 antipsychotic prescription during the year before their first hospitalization for stroke indicated that in the first few weeks of use, antipsychotics are associated with an increased

Noncontrast CT in this 52year-old male with a history of worsening right-sided weakness and aphasia demonstrates diffuse hypodensity and sulcal effacement 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

Axial noncontrast CT demonstrates a focal area of hypodensity in the left posterior limb of the internal capsule in this 60-year-old male with new onset of right-sided weakness. The lesion demonstrates high signal on the FLAIR sequence (middle image) and diffusion-weighted MRI (right image), with low signal on the ADC maps indicating an acute lacunar infarction. Lacunar infarcts are typically no more than 1.5 cm in size and can occur in the deep gray matter structures, corona radiata, brainstem and cerebellum. Causes of lacunar infarcts include the following: Microatheroma Lipohyalinosis Fibrinoid necrosis secondary to hypertension or vasculitis Hyaline arteriosclerosis Amyloid angiopathy The great majority are related to hypertension. Embolic strokes

area of infarction. MRA in the same patient as in the above image (left) demonstrates occlusion of the left precavernous supraclinoid internal carotid artery (ICA, red circle), occlusion or high-grade stenosis of the distal MCA trunk and attenuation of multiple M2 branches. The diffusion-weighted image (right) demonstrates high signal confirmed to be true restricted diffusion on the ADC map consistent with acute infarction.

MIP image from a CTA demonstrates a filling defect or high-grade stenosis at the branching point of the right MCA trunk (red circle), suspicious for thrombus or embolus. CTA is highly accurate in detecting large vessel stenosis and occlusions, which account for approximately one third of ischemic strokes. Lacunar strokes Lacunar strokes represent 13-20% of all ischemic strokes. They occur when the penetrating branches of the MCA, the lenticulostriate arteries, or the penetrating branches of the circle of Willis, vertebral artery, or basilar artery become occluded. (See the image below.)

Cardiogenic emboli may account for up to 20% of acute strokes. Emboli may arise from the heart, the extracranial arteries, or, rarely, the right-sided circulation (paradoxical emboli) with subsequent passage through a patent foramen ovale. The sources of cardiogenic emboli include the following: Valvular thrombi (eg, in mitral stenosis or endocarditis or from use of a prosthetic valve) Mural thrombi (eg, in myocardial infarction [MI], atrial fibrillation [AF], dilated cardiomyopathy, or severe congestive heart failure [CHF]) Atrial myxoma MI is associated with a 2-3% incidence of embolic strokes, of which 85% occur in the first month after MI.[28] Embolic strokes tend to have a sudden onset, and neuroimaging may demonstrate previous infarcts in several vascular territories or calcific emboli. Risk factors include atrial fibrillation and recent cardiac surgery. 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.[29, 30] (See the image below.)

Cardioembolic stroke: Axial diffusion-weighted images demonstrate scattered foci of high signal in the subcortical and deep white matter bilaterally in a patient with a known cardiac source for

embolization. An area of low signal in the left gangliocapsular region may be secondary to prior hemorrhage or subacute to chronic lacunar infarct. Recurrent strokes are most commonly secondary to cardioembolic phenomenon. For more information, see Cardioembolic Stroke. Thrombotic strokes Thrombogenic factors may include injury to and loss of endothelial cells, exposing the subendothelium, and 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 increase the risk for 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 in patients with widespread atherosclerosis. In other patients, especially younger patients, other causes should be considered, including the following[31, 10] : Hypercoagulable states (eg, antiphospholipid antibodies, protein C deficiency, protein S deficiency, pregnancy) Sickle cell disease Fibromuscular dysplasia Arterial dissections Vasoconstriction associated with substance abuse 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 due to severe hypoperfusion, such as in carotid occlusion or prolonged hypotension.[32, 33, 34]

trends continue, this number is projected to reach 1 million per year by the year 2050.[36] The global incidence of stroke is unknown. Stroke incidence by race and sex In the United States, blacks have an age-adjusted risk of death from stroke that is 1.49 times that of whites.[37] 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 males 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%. Stroke and age Although stroke often is considered a disease of elderly persons, one third of strokes occur in persons younger than 65 years.[36] Risk of stroke increases with age, especially in patients older than 64 years, in whom 75% of all strokes occur. Prognosis The prognosis after acute ischemic stroke varies greatly, depending on the stroke severity and on the patients premorbid condition, age, and poststroke complications.[6] Some patients experience hemorrhagic transformation of their infarct (See Pathophysiology). This is estimated to occur in 5% of uncomplicated ischemic strokes, in the absence of thrombolytics. Hemorrhagic transformation is not always associated with neurologic decline and ranges from small petechial hemorrhages to hematomas requiring evacuation. 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%. In the United States, 20% of individuals die within the first year after a first-time stroke, as previously mentioned. Cardiogenic emboli are associated with the highest 1-month mortality in patients with acute stroke. 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 longterm follow-up. The presence of CT scan evidence of infarction early in presentation has been associated with poor outcome and with an increased propensity for hemorrhagic transformation after thrombolytics.[7, 38, 39] 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 thrombolysis, as well as extension of the infarcted territory.[40, 41, 42] To see complete information on Motor Recovery in Stroke, please go to the main article by clicking here.

MRI was obtained to evaluate this 62-year-old hypertensive and diabetic male with a history of transient episodes of right-sided weakness and aphasia. The 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 MCA watershed areas. The left sided infarcts have corresponding low signal on the ADC map (right), signifying acuity. An old left posterior parietal infarct is noted as well. Epidemiology Stroke is the leading cause of disability and the third leading cause of death in the United States.[35] More than 700,000 persons per year suffer a first-time stroke in the United States, with 20% of these individuals dying within the first year after the stroke. If current

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 include using local churches, employers, and senior organizations to promote stroke awareness. The American Stroke Association advises the public to be aware of the symptoms of stroke that are easily recognized and to call 911 immediately. These symptoms include the following: Sudden numbness or weakness of face, arm, or leg, especially on 1 side of the body Sudden confusion Sudden difficulty in speaking or understanding Sudden deterioration of vision in 1 or both eyes Sudden difficulty in walking, dizziness, and loss of balance or coordination Sudden, severe headache with no known cause History A focused medical history for patients with ischemic stroke aims to identify risk factors for atherosclerotic and cardiac disease, including hypertension, diabetes mellitus, tobacco use, high cholesterol, and a history of coronary artery disease, coronary artery bypass, or atrial fibrillation (see Etiology). Consider stroke in any patient presenting with acute neurologic deficit or any alteration in level of consciousness. Common signs of stroke include the following: Acute hemiparesis or hemiplegia Acute hemisensory loss Complete or partial hemianopia, monocular or binocular visual loss, or diplopia Dysarthria or aphasia Ataxia, vertigo, or nystagmus Sudden decrease in consciousness In younger patients, elicit a history of recent trauma, coagulopathies, illicit drug use (especially cocaine), migraines, or use of oral contraceptives. Establishing the time at which the patient was last without stroke symptoms is especially critical when thrombolytic therapy is an option. 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. 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 include detecting extracranial causes of stroke symptoms, distinguishing stroke from stroke mimics, determining and documenting for future comparison the degree of deficit, and localizing the lesion. The physical examination always includes a careful head and neck examination for signs of trauma, infection, and meningeal irritation. 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 change in level of consciousness are more common in hemorrhagic strokes. Common symptoms of stroke include the following: Abrupt onset of hemiparesis, monoparesis, or quadriparesis Hemisensory deficits Monocular or binocular visual loss Visual field deficits Diplopia Dysarthria Ataxia Vertigo Aphasia Sudden decrease in the level of consciousness Although such symptoms can occur alone, they are more likely to occur in combination. A careful search for the cardiovascular causes of stroke requires examination of the ocular fundi (retinopathy, emboli, hemorrhage), heart (irregular rhythm, murmur, gallop), and peripheral vasculature (palpation of carotid, radial, and femoral pulses, auscultation for carotid bruit). Patients with a decreased level of consciousness should be assessed to ensure that they are able to protect their airway. The physical examination must encompass all of the major organ systems, starting with the airway, breathing, and circulation (ABC) and the vital signs. Patients with stroke, especially hemorrhagic stroke, can clinically deteriorate quickly; 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. Acutely lowering blood pressure has not proven to be beneficial in these stroke patients in the absence of signs and symptoms of associated malignant hypertension, acute myocardial infarction, CHF, or aortic dissection. Head and neck 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 examination 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 CHF; thus, auscultation for murmurs and gallops is recommended. Examination of the extremities 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 thrombolytic therapy 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: Confirming the presence of a stroke syndrome (to be defined further by cranial computed tomography [CT] scanning) Distinguishing stroke from stroke mimics Establishing a neurologic baseline should the patient's condition improve or deteriorate Essential components of the neurologic examination include the evaluation of cranial nerves, motor function, sensory function, cerebellar function, gait, and deep tendon reflexes, as well as of mental status and level of consciousness. The skull and spine also should be examined, and signs of meningismus should be sought. Central facial weakness from a stroke should be differentiated from the peripheral weakness of Bell palsy. With peripheral lesions (Bell palsy), the patient is unable to lift the eyebrows, wrinkle the forehead, or or close the eye on the affected side. A useful tool in quantifying neurological impairment is the National Institutes of Health Stroke Scale (NIHSS). The NIHSS (see Table 2, below and the NIH Stroke Score calculator) is used mostly by stroke teams. It enables the consultant to rapidly determine the severity and possible location of the stroke. A patient's score on the NIHSS is strongly associated with outcome, and it can help to identify those patients who are likely to benefit from thrombolytic therapy and those who are at higher risk of developing hemorrhagic complications of thrombolytic use. This scale is easily used and focuses on the following 6 major areas of the neurologic examination: level of consciousness Visual function Motor function Sensation and neglect Cerebellar function Language The NIHSS is a 42-point scale, with minor strokes usually being considered to have a score less than 5. An NIHSS score greater than 10 correlates with an 80% likelihood of visual flow deficits on angiography. However, discretion must be used in assessing the magnitude of the clinical deficit; for instance, if a patient's only deficit is being mute, the NIHSS score will be 3. Additionally, the scale does not measure some deficits associated with posterior circulation strokes (ie, vertigo, ataxia).[43]

Table 2. NIH Stroke Scale (Open Table in a new window) Category 1a level of consciousness (LOC) Description Alert Score 0

Drowsy

Stuporous

Coma

1b

LOC questions (month, age)

Answers correctly

both

Answers correctly

2 Incorrect both on

1c

Answers both correctly Answers 1 correctly Incorrect on both

Obeys correctly

both 0

Obeys correctly

2 Incorrect both on

Best gaze (follow finger)

Normal

Partial palsy

gaze

Forced deviation 6 Motor arm right* (raise 90, hold 10 seconds)

No

movement

Best visual (visual fields)

No visual loss

No

drift 0

Partial hemianopia

Drift

2 Complete hemianopia 3 Bilateral hemianopia

Cannot gravity

resist 2

No effort against gravity

4 No movement

Facial palsy (show teeth, raise brows, squeeze eyes shut)

Normal

Minor

0 7 Motor leg left* (raise 30, hold 5 seconds) No drift 0

Partial Complete

1 Drift 2 Cannot gravity 3 3 resist 2 1

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

No

drift 0

No effort against gravity

4 Drift 1 No movement

Cannot gravity

resist

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

No

drift 0

3 No effort against gravity 4

Drift

Cannot gravity

resist 2

dysarthria 3 No effort against gravity 4 No movement 13 9 Limb ataxia (finger-nose, heel- Absent shin) 0 Mild moderate aphasia to 1 Best language** (name items, describe pictures) No aphasia 0 Near to unintelligible or worse 2

Present limb

in

2 2 Severe aphasia 3 Mute 10 Sensory (pinprick arm, leg) to face, Normal 0 Total Partial loss 1 0-42

Present limbs

in

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

Severe

loss 2

11

Extinction/neglect simultaneous testing)

(double No

neglect

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

Middle cerebral artery stroke Partial neglect 1 MCA occlusion commonly produces contralateral hemiparesis, contralateral hypesthesia, ipsilateral hemianopsia, and gaze preference toward the side of the lesion. Agnosia is common, and receptive or expressive aphasia may result if the lesion occurs in the dominant hemisphere. Neglect, inattention, and extinction of double simultaneous stimulation may occur in nondominant hemisphere lesions. Since the MCA supplies the upper extremity motor strip, weakness of the arm and face is usually worse than that of the lower limb. Anterior cerebral artery stroke ACA occlusions primarily affect frontal lobe function and can result in disinhibition and speech perseveration, producing primitive reflexes (eg, grasping, sucking reflexes), altered mental status, impaired judgment, contralateral weakness (greater in legs than arms), contralateral cortical sensory deficits gait apraxia, and urinary incontinence.

Complete neglect

12

Dysarthria (speech clarity to Normal "mama, baseball, huckleberry, articulation tip-top, fifty-fifty")

1 Mild moderate to

Posterior cerebral artery stroke PCA occlusions affect vision and thought, producing contralateral homonymous hemianopsia, cortical blindness, visual agnosia, altered mental status, and impaired memory. Vertebrobasilar artery occlusions are notoriously difficult to detect because they cause a wide variety of cranial nerve, cerebellar, and brainstem deficits. These include the following: Vertigo Nystagmus Diplopia Visual field deficits Dysphagia Dysarthria Facial hypesthesia Syncope Ataxia A hallmark of posterior circulation stroke is that there are crossed findings: ipsilateral cranial nerve deficits and contralateral motor deficits. This is contrasted to 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. Diagnostic Considerations Stroke mimics commonly confound the clinical diagnosis of stroke. One study reported that 19% of patients diagnosed with acute ischemic stroke by neurologists before cranial CT scanning actually had noncerebrovascular causes for their symptoms. The most frequent stroke mimics include the following: Seizure (17%) Systemic infection (17%) Brain tumor (15%) Toxic-metabolic cause, such as hyponatremia and hypoglycemia (13%) Positional vertigo (6%). A critical masquerading metabolic derangement not to be missed by providers is hypoglycemia.[44, 45] For more information, see Metabolic Disease and Stroke Hyperglycemia/Hypoglycemia. Diagnosis and management of a rare form of stroke, cerebral venous thrombosis (CVT), was the subject of a 2011 AHA/ASA statement for healthcare professionals. According to the statement, diagnosing CVT requires a high degree of clinical suspicion. Most people diagnosed with CVT present with headache, often of increasing severity, usually but not always accompanied by focal neurological signs.[46] Differential Diagnoses Acute Coronary Syndrome Atrial Fibrillation

Bell Palsy Benign Positional Vertigo Brain Abscess Epidural Hematoma Hemorrhagic Stroke in Emergency Medicine Inner Ear Labyrinthitis Myocardial Infarction Neoplasms, Brain Subarachnoid Hemorrhage Syncope Transient Ischemic Attack Approach Considerations Laboratory evaluation of the patient with ischemic stroke should be driven by comorbid illnesses as well as the potential acute stroke. Additional laboratory tests are tailored to the individual patient. They may include rapid plasma reagent (RPR), toxicology screen, fasting lipid profile, sedimentation rate, pregnancy test, antinuclear antibody (ANA), rheumatoid factor, and homocysteine. CT is the most commonly used form of neuroimaging in the acute evaluation of patients with apparent acute stroke. 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 impaired metabolism. 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. Complete Blood Cell Count CBC count serves as a baseline study and may reveal a cause for the stroke (eg, polycythemia, thrombocytosis, thrombocytopenia, leukemia) or provide evidence of concurrent illness (eg, anemia). Basic Chemistry Panel 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 Coagulation studies may reveal a coagulopathy and are useful when thrombolytics or anticoagulants are to be used. In patients who are not anticoagulated and in whom there is no suspicion for coagulation abnormality, administration of recombinant tissuetype plasminogen activator (rt-PA) should not be delayed awaiting laboratory studies. Cardiac Biomarkers

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 Toxicology screening may be useful in selected patients in order to assist in identifying intoxicated patients with symptoms/behavior mimicking stroke syndromes. Urine pregnancy test should be obtained for all women of childbearing age with stroke symptoms. The agent rt-PA is Pregnancy Class C. Arterial Blood Gas Analysis Although infrequent in patients with suspected hypoxemia, arterial blood gas defines the severity of hypoxemia and may detect acid-base disturbances. If considering thrombolytics, arterial punctures should be avoided unless absolutely necessary. Imaging in Stroke Imaging in ischemic stroke can involve several types of MRI, several types of CT scanning, angiography, ultrasonography, radiology, echocardiography, and nuclear imaging studies. Magnetic resonance imaging Conventional MRI may take hours to produce discernable findings, well after the diffusionweighted images have become positive. For this reason, many centers always include diffusionweighted images in their standard brain MRI protocol. Diffusion-weighted MRI can detect ischemia much earlier than can standard CT scanning or MRI and provides useful data in stroke and TIA patients outside of the initial management window.[22, 47, 48] 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 that can be measured and is proportional to the CBV. (See the image below.)

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

An evidence-based guideline from the American Academy of Neurology recommends that diffusionweighted imaging (DWI) is more useful than noncontrast CT 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.[49] A study by Bhattacharya et al concluded that the early use of MRI helps to prevent emergency departments from misdiagnosing ischemic stroke in young adults presenting with signs of stroke. Reviewing a prospective database of patients aged 16-49 years with ischemic stroke, the investigators found that the chance of misdiagnosis was lower in patients who had undergone MRI within 48 hours.[50] The study also found that, in general, there is a particular risk that emergency departments will misdiagnose ischemic stroke in patients younger than 35 years, indicating that early MRI studies would be especially beneficial in young adults with signs of stroke. Intra-arterial contrast enhancement may be seen secondary to slow flow during the first or second day after onset of infarction and has been correlated with increased infarct volume size.[51] The 3 different techniques used to produce MRA images are 3-dimensional time of flight (3D TOF), phase-contrast (PC), and contrast-enhanced MRA (CEMRA). Three-dimensional TOF takes advantage of the higher signal from protons in flowing blood, compared with protons in stationary tissue, which become partially saturated and lose signal when exposed to a radiofrequency (RF) pulse. Areas of signal loss and narrowing correspond to stenosis and occlusions. PC involves tagging the spins of moving protons using bidirectional gradients and marking their changes in position when each gradient is applied. PC is exquisitely sensitive to flow, which the operator can choose the velocity threshold for, and gives excellent background suppression. CEMRA utilizes the intraluminal signal produced by a timed bolus of paramagnetic contrast material to evaluate vessel patency. Images may be single phase (i.e. arterial) or time resolved. For more information, see Magnetic Resonance Imaging in Acute Stroke. CT scanning Imaging with computed tomography (CT) scanning has multiple logistic advantages for patients with acute stroke. CT scanning is able to more rapidly acquire images than MRI, allowing for assessment with an examination that includes noncontrast CT scanning, CT angiography, CT perfusion scanning in less than 10 minutes. 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 pacemakers, aneurysm clips, or other ferromagnetic materials in their bodies. Additionally, CT scanning is more easily accessible for patients who require special equipment for maintaining and monitoring life support.[52, 53] The 2011 AHA/ASA CVT statement notes that MRI is more sensitive for the detection of CVT than CT. However, these modalities do not always accurately reveals positive findings of intraluminal thrombus, which is key to the diagnosis of CVT. Therefore, although a plain CT or MRI is useful in the initial evaluation, a negative finding should not rule out CVT.[46] Other imaging studies in ischemic stroke

Transcranial Doppler ultrasonography is useful for evaluating more proximal vascular anatomy through the infratemporal fossa, including the MCA, intracranial carotid artery, and vertebrobasilar artery.[54] 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 recombinant tissue-type plasminogen activator (rtPA); these radiographs have not been shown to alter the clinical course or decision-making in most cases.[55] The use of SPECT scanning in stroke is still relatively experimental and available only at select institutions; it can theoretically define areas of altered regional blood flow. 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; it also provides for less invasive endovascular interventions. 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. 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. Approach Considerations Multiple factors contribute to delays in seeking care for symptoms of stroke. Many strokes occur while patients are sleeping (also known as "wake-up" stroke) and are not discovered until the patient wakes. Stroke can leave some patients too incapacitated to call for help. Occasionally, a

stroke goes unrecognized by the patient or their caregivers. (See Diagnostic Considerations).[36, 56] The median time from symptom onset to ED presentation ranges from 4-24 hours in the United States.[22] 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 ACLS instruction, as well as continuing medical education classes, prehospital care providers can remain current on stroke and promote stroke awareness in their own communities. Physician and nursing staff involved in the care of patients who have had a stroke, in the 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. Establishing the time at which stroke symptoms first occurred is of paramount importance when considering patients for possible thrombolytic therapy. An essential question is, "When was the patient last seen to be normal?" It is advisable for emergency clinicians to rapidly enlist the assistance of family members or relatives to establish time of symptom onset and to identify other pertinent components of the patient's presentation history. The central goal of therapy in acute ischemic stroke is to preserve the area of oligemia in the ischemic penumbra. The area of oligemia can be preserved by limiting the severity of ischemic injury (ie, neuronal protection) or by reducing the duration of ischemia (ie, restoring blood flow to the compromised area). Recanalization strategies, including IV recombinant tissuetype 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. Neuroprotective strategies are intended to preserve the penumbral tissues and to extend the time window for revascularization techniques; however, at the present time, no neuroprotective agents are available and approved for use in ischemic stroke. The ischemic cascade offers many points at which such interventions could be attempted. Multiple strategies and interventions for blocking this cascade are currently under investigation. The timing of the restoration of cerebral blood flow appears to be a critical factor. Time may also prove to be a key factor in neuronal protection. It is expected that neuroprotective agents, which block the earliest stages of the ischemic cascade (eg, glutamate receptor antagonists, calcium channel blockers), will be effective only in the proximal phases of presentation. The American Heart Association (AHA) and American Stroke Association (ASA) released new guidelines for the early management of acute ischemic stroke in January 2013. New features of the guidelines include a focus on the importance of stroke systems of care, a recommendation for the use of tissue plasminogen activator (t-PA) in selected patients presenting within 3 to 4.5 hours of symptom onset, and a

recommendation for door-to-needle times within 60 minutes of hospital arrival in patients eligible for thrombolysis.[27, 3] A registry study involving 58,353 patients with acute ischemic stroke who underwent t-PA treatment within 4.5 hours of symptom onset confirmed that earlier treatment yielded better outcomes.[57, 58] For every 1000 patients, the investigators found that with each 15-minute reduction in time to therapy, an additional 18 patients had improved ambulation at discharge, an additional 13 patients were discharged to a more independent environment, and an additional 4 patients survived to discharge. Emergency Response and Transport Recognition that a stroke may have occurred and rapid transport to the appropriate receiving facility are necessary after addressing the ABCs. Of patients with signs or symptoms of stroke, 29-65% utilize some facet of the emergency medical services (EMS) system.[59, 60] Furthermore, most patients who call EMS are those who present within 3 hours of symptom onset. EMS use is associated with shorter time periods from symptom onset to hospital arrival.[61, 62] Stroke should be a priority dispatch with prompt EMS response. EMS responders should provide in as timely a manner as possible advance notice to their emergency department destination so as to allow preparation and marshaling of personnel and resources. There is now ongoing development of stroke center designation that would then become the preferred destination for patients with acute stroke symptoms utilizing 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 has the potential to provide timely expert advice to rural and underserved clinics and hospitals.[22] Acute Management of Stroke The goal for the acute management of patients with stroke is to stabilize the patient and to complete initial evaluation and assessment, including imaging and laboratory studies within 60 minutes of patient arrival.[22] A Finnish study demonstrated that time to treatment with thrombolytics can be decreased with changes in EMS and ED coordination and in ED procedures for treating acute stroke patients.[63] Critical decisions focus on blood pressure control, the need for intubation, and determination of risk-to-benefit profile for thrombolytic intervention. Referral to a physician with a special interest in stroke is ideal. Stroke care units exist and improve outcomes with specially trained personnel. Comorbid medical problems need to be addressed. Hypoglycemia and hyperglycemia need to be identified and treated early in the evaluation. 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 >100.4F). Supplemental oxygen is recommended when the patient has a documented oxygen requirement. In the small proportion of

patients with stroke who are relatively hypotensive, pharmacologically increasing blood pressure may improve flow through critical stenoses. An area of continued interest in acute stroke is glucose management. A Cochrane review found that the use of intravenous insulin to maintain serum glucose within the first few hours of ischemic stroke did not improve functional outcome, death, or final neurological deficit and significantly increased the risk of hypoglycemia.[64] The 2011 AHA/ASA statement on CVT notes that appropriate acute therapy should focus on preventing complications and anticoagulation therapy. The recommended tests were MRI and MR venography (MRV) because they are the most sensitive. Blood workup should be performed later based on the underlying causes.[46] Thrombolytic Therapy Thrombolytics restore cerebral blood flow among some patients with acute ischemic stroke and may lead to improvement or resolution of neurologic deficits. Unfortunately, thrombolytics can also cause symptomatic intracranial hemorrhage, defined as radiographic evidence of hemorrhage combined with escalation of the NIHSS score by 4 or more points (see the NIH Stroke Scorecalculator). Therefore, if the patient is a candidate for thrombolytic therapy, a thorough review of the inclusion and exclusion criteria must be performed. The exclusion criteria largely focus on identifying risk of hemorrhagic complication associated with thrombolytic use. While streptokinase and rt-PA have been shown to benefit patients with acute MI, only alteplase (rt-PA) has been shown to benefit selected patients with acute ischemic stroke. In May 2009, the American Heart Association/American Stroke Association (AHA/ASA) guidelines for the administration of rt-PA following acute stroke were revised to expand the window of treatment from 3 hours to 4.5 hours to provide more patients with an opportunity to receive benefit from this effective therapy.[8, 9, 65] Eligibility criteria for treatment in the 3-4.5 hours after acute stroke are similar to those for treatment at earlier time periods, with any 1 of the following additional exclusion criteria: Patients older than 80 years All patients taking oral anticoagulants are excluded regardless of the international normalized ratio (INR) Patients with baseline NIHSS greater than 25 Patients with a history of stroke and diabetes Caution should be exercised in the administration of rt-PA to patients with major deficits. Patients with evidence of low attenuation (edema or ischemia) involving more than a third of the distribution of the MCA on their initial NCCT scan are less likely to have favorable outcome after thrombolytic therapy and are thought to be at higher risk for hemorrhagic transformation of their ischemic stroke.[38] In addition to the risk of symptomatic intracranial hemorrhage (6.4% in the NINDS trial), other complications include potentially hemodynamically significant hemorrhage and angioedema or allergic reactions.[22]

Streptokinase has not been shown to benefit patients with acute ischemic stroke, but it has been shown to increase their risk of intracranial hemorrhage and death. Researchers have studied the use of transcranial ultrasound as a means of assisting rt-PA in thrombolysis. By delivering mechanical pressure waves to the thrombus, ultrasound can theoretically expose more of its surface to the circulating thrombolytic agent. Further research is necessary to determine the exact role of transcranial Doppler ultrasound in assisting thrombolytics in acute ischemic stroke. No human trials comparing the IV versus intra-arterial administration of thrombolytics exist. Theoretic advantages to intra-arterial delivery may include the possibility that higher local concentrations of thrombolytic would allow lower total doses of the agent (and theoretically less risk of systemic bleed) and a longer therapeutic window; however, the longer time to administration via the intra-arterial approach versus the IV approach may mitigate some of this advantage. For more information, see Thrombolytic Therapy. For more information, see Reperfusion Injury in Stroke. Antiplatelet Agents 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 20,000 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 early stroke recurrence.[3, 4] CAST evaluated 21,106 patients and had a 4-week mortality reduction of 3.3% contrasted to 3.9%. A separate study also found that the combination of aspirin and lowmolecularweight heparin did not significantly improve outcomes.[3] The early initiation of aspirin plus extended-release dipyridamole is likely to be as safe and effective in preventing disability as is later initiation after 7 days following stroke onset, according to a German study. The studys authors attempted to assess the precise time to initiate dipyridamole following ischemic stroke or TIA.[66] Patients from 46 stroke units who presented with an NIHSS score of 20 or less were randomly assigned to receive aspirin 25 mg plus extended-release dipyridamole 200 mg bid (early dipyridamole regimen) (n=283) or aspirin monotherapy (100 mg once daily) for 7 days (n=260). Therapy in either group was initiated within 24 hours of stroke onset. After 2 weeks, all patients received aspirin plus dipyridamole for up to 90 days. At day 90, 154 (56%) patients in the early dipyridamole group and 133 (52%) in the aspirin plus later dipyridamole group had no or mild disability (P = .45). Other antiplatelet agents are also under evaluation for use in the acute presentation of ischemic stroke. In a preliminary pilot study, abciximab was given within 6 hours to establish a safety profile. A trend toward improved outcome at 3 months for the treatment versus the placebo group was noted.[67] Further clinical trials are necessary. Neuroprotective Agents

Despite very promising results in several animal studies, as of yet no single neuroprotective agent in ischemic stroke is supported by randomized, placebo-controlled human studies. Nevertheless, substantial research is underway evaluating different neuroprotective strategies, including hypothermia. For more information, see Neuroprotective Agents in Stroke. Mechanical Thrombolysis Studies have evaluated the efficacy of mechanical clot disruption in the setting of acute stroke. In most cases, these technologies were used in combination with thrombolysis. In an investigation by Berlis et al, mechanical disruption via an endovascular photoacoustic device was found to be more effective than thrombolysis alone in recanalization rates.[68] There are currently 2 FDA-approved devices for the endovascular treatment of acute ischemic stroke: the Concentric Retriever, which is mainly a grasping device, and the Penumbra device, which employs an aspiration function to remove clots.[69, 70, 71] The Penumbra trial demonstrated 82% recanalization in patients when using the aspiration function of the Penumbra device. 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.[72] In a second MERCI study, recanalization was achieved in 48% of those in which the device was deployed. Clot was successfully retrieved from all major cerebral arteries; however, the recanalization rate for the MCA was lowest. A further study of clot extraction, the Prolyse in Acute Cerebral Thromboembolism II (PROACT II) study, identified a recanalization rate of 66%.[73, 74] 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 for whom t-PA was given in a group of patients with acute ischemic stroke presenting within 8 hours of onset of symptoms. Seventy-three percent of patients who failed IV t-PA therapy had recanalization following mechanical embolectomy.[75] However, based on these results, the FDA has cleared the use of the MERCI device in patients who are either ineligible for or who have failed IV thrombolytics. According to the 2011 AHA/ASA statement on CVT, evidence is insufficient to draw conclusions about the value of endovascular thrombolysis in patients with CVT. For that reason, the statement recommends this therapy only in patients with progressive neurological deterioration that persists despite medical treatment.[46] For more information, see Mechanical Thrombolysis in Acute Stroke. For more information, see Cerebral Revascularization. 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 I clinical trials.[76, 77, 78]

High body temperature in the first 12-24 hours after stroke onset has been associated with poor functional outcome. Results from the Paracetamol (Acetaminophen) In Stroke (PAIS) trial did not support the routine use of high-dose acetaminophen in patients with acute stroke. The study assessed whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever. Patients (n=1400) were randomly assigned to receive acetaminophen (6 g daily) or placebo within 12 hours of symptom onset. After 3 months, improvement on the modified Rankin scale was not beyond what was expected.[79] Cerebral Edema Control Significant cerebral edema after ischemic stroke is thought to be somewhat rare (10-20%); maximum severity of edema is reached 72-96 hours after the onset of stroke. Early indicators of ischemia on presentation and on NCCT scans are independent indicators of potential swelling and deterioration. Mannitol and other therapies to reduce 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.[22] 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 shown to decrease mortality and disability among patients with large hemispheric infarctions associated with life-threatening edema.[80, 81, 82, 83] Seizure Control Seizures occur in 2-23% of patients within the first days after stroke. Although seizure prophylaxis is not indicated, prevention of subsequent seizures with standard antiepileptic therapy is recommended.[22] The 2011 AHA/ASA CVT statement notes a lack of clinical trials on the use of anticonvulsants to control seizures, which occur in 37% of adults, 48% of children, and 71% of newborns who present with CVT. Therefore, opinions on their use vary greatly. However, because seizures increase the risk of anoxic damage, anticonvulsant treatment after even a single seizure is reasonable.[46] Post-ischemia strokes are usually focal, but they may be generalized. A fraction of patients who have experienced stroke develop chronic seizure disorders. Seizures secondary to ischemic stroke should be managed in the same manner as other seizure disorders that arise as a result of neurologic injury.[22] Acute Decompensation or Escalation In the case of the rapidly decompensating patient or the patient with deteriorating neurologic status, reassessment of 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. Some advocate resetting the time window to zero in this

circumstance and encourage consideration of reperfusion strategies. Anticoagulation and Prophylaxis Heparin is known to prolong the lytic state caused by t-PA. Currently, data are inadequate to justify the utilization of heparin or other anticoagulants in the acute management of patients with ischemic stroke. Patients with embolic stroke who have another indication for anticoagulation (eg, atrial fibrillation) may be placed on anticoagulation therapy with the goal of preventing further embolic disease; however, the potential beneficial effects from that decision must be weighted against the risk of hemorrhagic transformation.[22] Immobilized stroke patients who are not receiving anticoagulants, such as IV heparin or an oral anticoagulant, may benefit from the administration of low-dose, subcutaneous unfractionated or lowmolecular-weight heparin, which reduces the risk of deep venous thrombosis.[22] For more information, see Stroke Anticoagulation and Prophylaxis. Induced Hypothermia Hypothermia is fast becoming the standard of care for the ongoing treatment of patients surviving cardiac arrest due to ventricular tachycardia or ventricular fibrillation. However, no major clinical study has demonstrated a role for hypothermia in the early treatment of ischemic stroke.[22] Carotid Endarterectomy 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 in acute stroke. Stroke Prevention Primary prevention refers to the treatment of individuals with no previous history of stroke. Measures may include the use of platelet antiaggregants; 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (ie, statins); and exercise. In February 2011, AHA/ASA guidelines for the primary prevention of stroke were published. The guideline emphasizes 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.[84] Secondary prevention refers to the treatment of individuals who have already had a stroke. Measures may include the use of platelet antiaggregants, antihypertensives, HMG-CoA reductase inhibitors (statins), and lifestyle interventions. Smoking cessation, blood pressure control, diabetes control, a low-fat diet, weight loss, and regular exercise should be encouraged as strongly as the medications described above. Written prescriptions for exercise and medications for smoking cessation (nicotine patch, bupropion, varenicline) increase the likelihood of success with these interventions. In addition to these well-documented factors, 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.

The use of aspirin for primary stroke prevention is not recommended for persons at low risk. Aspirin is recommended for this purpose only in persons with at least a 6-10% risk of cardiovascular events over 10 years.[84] For patients with stroke risk due to 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 due to improvements in medical therapies. Therefore, individual patient comorbidities, life expectancy, and preferences should determine whether medical treatment alone or carotid revascularization is selected.[84] Atrial fibrillation is a major risk factor for stroke. The 2011 ACC Foundation (ACCF)/AHA/Heart Rhythm Society (HRS) atrial fibrillation guideline update on dabigatran states that the new anticoagulant dabigatran is useful as an alternative to warfarin in patients with atrial fibrillation who do not have a prosthetic heart valve or hemodynamically significant valve disease.[85] The 2011 AHA/ASA primary stroke prevention guideline recommends that EDs screen for AF and assess patients for anticoagulation therapy if AF is found.[84] For patients with atrial fibrillation after stroke or TIA, the 2010 AHA/ASA secondary stroke prevention guideline is in accord with the standard recommendation of warfarin, with aspirin as an alternative for patients who cannot take oral anticoagulants. However, clopidogrel should not be used in combination with aspirin for such patients because the bleeding risk of the combination is comparable to that of warfarin. The guideline states that the benefit of warfarin after stroke or TIA in patients without atrial fibrillation has not been established.[86] The 2011 AHA/ASA guideline recommends ED-based smoking cessation interventions, and considers it reasonable for EDs to screen patients for hypertension and drug abuse.[84] Periprocedural use of antithrombotic medications In May 2013, the American Academy of Neurology issued guidelines on the periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease.[87, 88] The guidelines list all the procedures for which there are data on stopping or continuing aspirin or warfarin and give recommendations. Key recommendations include the following: Stroke patients who are undergoing dental procedures should continue aspirin Stroke patients who are undergoing invasive ocular anesthesia, cataract surgery, dermatologic procedures, spinal/epidural procedures, transrectal ultrasound-guided prostate biopsy, or carpal tunnel surgery should probably continue aspirin Stroke patients receiving warfarin should routinely continue treatment when undergoing dental procedures and should probably continue treatment during dermatologic procedures Neurologists should counsel patients that bridging therapy is probably associated with increased bleeding risks, as

compared with stopping warfarin; the risks compared with continuing warfarin are unknown Specialized Stroke Centers Given the multitude of factors that go into the care of a patient with acute stroke, the concept of the specialized stroke center has evolved. The Brain Attack Coalition provided recommendations for the establishment of 2 tiers of stroke centers: primary stroke centers (PSCs) and comprehensive stroke centers (CSCs).[22] The Joint Commission for the Accreditation of Hospital Organizations (JCAHO) now provides accreditation for PSC, and efforts to establish the requirements that distinguish CSC are currently ongoing. The PSC is designed to maximize the timely provision of stroke-specific therapy, including the administration of rtPA, and is also capable of providing care to patients with uncomplicated stroke. The CSC shares the commitment that the PSC has to acute delivery of rt-PA and also provides care to patients with hemorrhagic stroke and intracranial hemorrhage and all patients with stroke requiring ICU level of care.[22] 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 the notification and involvement of neurologic consultation. These requirements have led to the development of "stroke codes" or "stroke activations" in which EMS crews have been trained to identify possible stroke patients and arrange for their speedy, preferential transport to a PSC or CSC. Additionally, Stroke Centers should have personnel versed at monitoring stroke vital signs, which include the following: Blood pressure Glucose levels Temperature Oxygenation Change in neurologic status Hospitals with specialized stroke teams have demonstrated significantly increased rates of thrombolytic administration 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 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, transport, treatment, and rehabilitation of stroke patients. For more information, see Stroke Team Creation and Primary Stroke Center Certification. Palliative Care Palliative care is an important component of comprehensive stroke care. Some stroke patients will simply not recover, and others will be in a state of debilitation such that the most humane and appropriate therapeutic concern is the comfort of the patient. Some patients have advanced

directives providing instructions for medical providers in the event of severe medical illness or injury. Consultations Consultations are tailored to individual patient needs. An experienced professional who is sufficiently familiar with stroke or a stroke team should be available within 15 minutes of the patient's arrival in the ED. Often, occupational therapy, physical therapy, speech therapy, and physical medicine and rehabilitation experts are consulted within the first day of hospitalization. Consultation of cardiology and 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: Home health care coordinator Rehabilitation coordinator Social worker Psychiatrist (commonly for depression) Dietitian Medication Summary While only 1 drug, tissue plasminogen activator (t-PA), has demonstrated efficacy and effectiveness in treating acute ischemic stroke (AIS) and is approved by the US Food and Drug Administration (FDA), other medications are equally important. National consensus panels have included 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: Anticoagulation Reperfusion Antiplatelet Neuroprotective Fibrinolytic Agents Class Summary Fibrinolytic agents convert entrapped plasminogen to plasmin and initiate local fibrinolysis by binding to fibrin in a clot. View full drug information Alteplase (Activase) Alteplase is a t-PA used in management of acute 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. Anticonvulsant Agents 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. View full drug information Diazepam (Valium)

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. View full drug information Lorazepam (Ativan) Lorazepam is a short-acting benzodiazepine with a moderately long half-life. It has become drug of choice in many centers for treating active seizures. Antiplatelet Agents Class Summary Although antiplatelet agents have been shown 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 IV thrombolysis or other therapies aimed at improving outcomes after stroke. View full drug information Aspirin (Bayer Aspirin, Anacin, Bufferin) 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. View full drug information Ticlopidine (Ticlid) Ticlopidine is a second-line antiplatelet therapy for patients who cannot tolerate aspirin or in whom aspirin is not effective. View full drug information Dipyridamole and aspirin (Aggrenox) The combination of extended-release dipyridamole and aspirin reduces the relative risk of stroke, death, and MI. It is used for the secondary prevention of ischemic stroke and TIAs. View full drug information Clopidogrel (Plavix) Clopidogrel inhibits platelet aggregation and is used for secondary stroke prevention. It is indicated for the reduction of atherothrombotic events following a recent stroke. Anticoagulants Class Summary Anticoagulants such as warfarin are used for secondary stroke prevention. View full drug information Warfarin (Coumadin, Jantoven)

Warfarin is a coumarin anticoagulant used to reduce the risk of death, recurrent MI, and thromboembolic events such as stroke or systemic embolization after MI. Antipyretic Agents Class Summary Hyperthermia in acute stroke is potentially harmful and should be treated. Agents with potential bleeding risk should be avoided if possible. View full drug information Acetaminophen (Tylenol, Feverall, Aspirin Free Anacin) Acetaminophen reduces fever by acting directly on hypothalamic heat-regulating centers, which increases the dissipation of body heat via vasodilation and sweating. Antihypertensive Agents Class Summary Optimal blood pressure management in acute stroke remains subject to some debate. Treatment parameters largely depend on whether the patient is a candidate for thrombolytic therapy. While the target blood pressures may differ, the therapeutic agents are largely the same. View full drug information Labetalol (Normodyne) 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. View full drug information Enalapril (Vasotec) An ACE inhibitor, enalapril decreases circulating angiotensin II levels and suppresses the renin-angiotensin-aldosterone system, lowering overall blood pressure. View full drug information Nicardipine (Cardene) A calcium-channel blocker, nicardipine inhibits calcium ion influx into vascular smooth muscle and myocardium.[89] View full drug information Sodium nitroprusside (Nitropress) Sodium nitroprusside is a vasodilator that decreases peripheral vascular resistance by direct action of arteriolar smooth muscle. It also decreases venous return through venous dilation.