#90284: Ischemic Stroke

Hemorrhagic stroke is associated with a higher risk of fatality than ischemic stroke, and roughly one-third of patients die within 30 days after the event [1,24]. Hemorrhagic strokes are categorized by the location of the hemorrhage, either intracerebral or subarachnoid, with the former being more common.

The majority of hemorrhagic strokes are caused by ICH, and because of this, discussion of hemorrhagic stroke often refers to ICH [1,25]. ICH is defined as bleeding directly into the brain parenchyma [25,26]. Intraventricular hemorrhage refers to extension of bleeding into the brain ventricles [26,27]. Nontraumatic ICH is categorized as primary (unrelated to congenital or acquired lesions), secondary (caused by a congenital or acquired condition), or spontaneous (unrelated to trauma or surgery) [26]. Hypertension, congenital arterial aneurysm, thrombocytopenia (platelet counts <20,000), and depletion of intravascular clotting factors (e.g., hypothrombinemia) are conditions that elevate the risk of sustaining a hemorrhagic stroke, important because risk can be anticipated and treated.

The clinical features of ICH include sudden, intense headache, vomiting, seizures, depressed consciousness, meningeal irritation, and blood-tainted cerebrospinal fluid. Onset of symptoms may occur within seconds to minutes after the start of an ICH. Individuals with this type of stroke often feel more ill than those with an ischemic stroke.

ICH is the least treatable type of stroke [28]. Functional independence is regained within 6 months in approximately 20% of survivors [29]. The morbidity and mortality depend on the volume and location of the hematoma. The 1-year mortality rate varies according to anatomic location, with the highest mortality rate (65%) associated with ICH in the brain stem; the rate is 57% for lobar hemorrhage, 51% for deep hemorrhage, and 42% for cerebellar hemorrhage [30]. Overall, 46% of patients with ICH survive one year and 29% survive five years [31].

As many as 80% of primary ICHs occur after small vessels are compromised by chronic hypertension [32]. Hypertension is associated with ICH originating in the periventricular deep white matter, deep subcortical structures, pons, and cerebellum [33]. In individuals older than 70 years of age, cerebral amyloid angiopathy, a condition that leads to amyloid protein infiltration into the cortical arterioles, is responsible for approximately 20% of ICHs [34]. Other causes of ICH include anticoagulant and antiplatelet use, drug use (e.g., cocaine, phenylpropanolamine), and other bleeding diathesis [28,35]. Fewer than 15% of all cases of ICH are secondary to congenital vascular abnormalities and malignant brain lesions [26].

Subarachnoid hemorrhages occur less frequently than ICHs. The hallmark of subarachnoid hemorrhage is the immediate onset of a severe headache with signs of meningeal irritation [36]. Individuals may describe this headache as their "worst ever." Nausea, vomiting, neck pain, and photophobia are also classic symptoms, although they are not always present [36]. Neurologic deficits may be acute or may manifest hours to days after the onset of bleeding.

Nontraumatic subarachnoid hemorrhages are subcategorized as aneurysmal or non-aneurysmal [37]. Aneurysmal subarachnoid hemorrhage is associated with higher rates of morbidity and mortality than non-aneurysmal hemorrhage. Among patients who live 3 months after the event, the risk of death is 8.7% within 5 years and 17.9% within 10 years [38]. In contrast, non-aneurysmal subarachnoid hemorrhages are associated with better outcomes and are less likely to cause death [39].

Most nontraumatic subarachnoid hemorrhages involve rupture of an intracranial aneurysm or cerebral arteriovenous malformation. Congenital arteriovenous anomalies are more likely to cause stroke in adolescents and young adults [40]. The incidence of perimesencephalic subarachnoid hemorrhage, a non-aneurysmal type, is increasing. Although the cause remains unknown, increased use of antithrombotic medications may be a factor [41,42].

Guidelines for the management of spontaneous ICH have been published by AHA/ASA [28]. Rapid diagnosis and assessment are crucial, as early deterioration is common in the hours after onset. Prehospital management objectives are maintenance of the airway, cardiovascular support, and rapid transport to the nearest facility prepared to care for patients with acute stroke. Advanced notice to the ED of impending arrival is key to expediting assessment and shortening the time to neuroimaging. Any combination of severe headache, vomiting, systolic blood pressure >220 mm Hg, decreased level of consciousness, and rapid symptom progression suggests ICH, although none are specific and neuroimaging is required to distinguish ICH from ischemic stroke. Computed tomography (CT) is sensitive and usually readily available. Key components of initial evaluation include time of symptom onset, progression of symptoms, vascular risk factors, medications (e.g., anticoagulant medication, illicit drug use), and a focused neurologic examination to assess severity. Laboratory studies should include complete blood count, prothrombin time, partial thromboplastin time, and toxicology screen to detect cocaine and other sympathomimetic drugs associated with ICH. Medical management and follow-up imaging is predicated on initial findings and the underlying vascular abnormalities identified [28].

TIAs are sometimes referred to as "ministrokes" because, like ischemic strokes, they are caused by inadequate cerebral blood flow. TIAs are also called warning strokes, as they often precede an ischemic stroke [43]. The superseded definition of a TIA was "a sudden, focal neurologic deficit that lasts for less than 24 hours, is presumed to be of vascular origin, and is confined to an area of the brain or eye perfused by a specific artery" [44]. The 24-hour time limit was an arbitrary remnant of the time interval used in prospective surveys in the early 1970s [45]. Magnetic resonance imaging (MRI) and computed tomography (CT) have demonstrated that one-third of TIAs, including those that last only minutes, cause infarcts [46].

Because TIA and ischemic stroke are less distinct from one another than once believed, a new TIA definition was proposed, revised, and endorsed in 2009. The proposed definition states that TIA is "a brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than 1 hour, and without evidence of acute infarction" [44]. This definition was thought to better reflect the ischemic pathogenesis of TIA, promote its early management, and support the use of diagnostic imaging techniques to ensure that the patient does not have infarction [44]. The definition was endorsed by the 2009 AHA/ASA guideline, with the omission of "typically less than 1 hour" (as infarction is not necessarily bound by a set period of time) and reads, "Transient ischemic attack (TIA): a transient episode of neurologic dysfunction caused by focal brain, spinal-cord, or retinal ischemia, without acute infarction" [10,47]. A 2023 AHA scientific statement on diagnosis and management of TIA stipulates no evidence of tissue infarction determined by diffusion-weighted (DW) MRI. Resolution of symptoms combined with MRI demonstrating acute infarction should be diagnosed as an ischemic stroke [402].

TIAs are caused by similar conditions as those leading to ischemic stroke [10]. Among the common causes are embolic platelet thrombi shed from atherosclerotic plaque within large vessels and cardioembolism from mural thrombi related to atrial fibrillation (AF) or valvular heart disease. Other conditions complicated by TIAs include hypercoagulable states, arterial dissection, sympathomimetic drugs (e.g., cocaine), and arteritis (caused by noninfectious necrotizing vasculitis, drugs, irradiation, or local trauma) [53].

Research shows that TIA should be considered a dire event, a herald sign of sustained risk for adverse cardiovascular events in subsequent years. Prompt intervention is necessary for prevention of more potent ischemic stroke. The risk of stroke is 1.2% at 2 days and increases to 7.4% within 90 days after TIA [1]. A large multicenter TIA registry study found that the risk of stroke within one year was 5.1% and the five-year risk 9.5%; the combined risk of stroke, acute coronary syndrome, or death attributable to cardiovascular disease was 6.2% at one year and 12.9% at five years (398). Approximately 15% of ischemic strokes are preceded by a TIA [3]. However, there are several challenges to immediate treatment of TIAs [10]:

As with any stroke, the symptoms of TIA depend on the affected vascular territory. For instance, involvement of the carotid artery causes disturbances in the ipsilateral eye or brain [49]. Although the most common focal neurologic signs of TIA are sudden-onset unilateral weakness and numbness or tingling in a limb, a TIA can cause any of the following symptoms [49,50]:

Transient graying or blurring of vision is also common. Occasionally, the line of sight will be shaded. Vertebrobasilar TIAs reflect vestibulocerebellar symptoms such as ataxia, dizziness, vertigo, dysarthria, vision abnormalities (e.g., double vision, hemianopia, bilateral vision loss), and unilateral or bilateral motor and sensory dysfunctions [10]. Clinicians should bear in mind that patients may appear asymptomatic on initial evaluation. This is because TIAs often resolve within 5 minutes [51]. The possibility of TIA should be considered if the patient says, "I don't know why I'm here. Whatever it was, it is all better now" [52].

The risk factors for TIA are similar to those for ischemic stroke and include many modifiable factors, such as hyperhomocysteinemia, hyperlipidemia, smoking, obesity, and diabetes [10]. Risk is substantially reduced by treatment of vascular disorders such as hypertension and AF, two conditions commonly associated with older age. Younger individuals (18 to 45 years of age) who have a TIA or ischemic stroke often have no detectable vascular risk factors [54].

As noted, the risk of ischemic stroke is high in the period following a TIA. A meta-analysis found that approximately 5% of patients who have a TIA will have an ischemic stroke within the next 7 days [11,43]. The risk of stroke within three months after a TIA is approximately 10%; the cumulative risk approaches 25% over the ensuing 5 years [11]. Prompt initiation of secondary prevention strategies for TIA and minor stroke with existing therapies has been shown to reduce the risk of early recurrent stroke by 80% [48]. AHA/ASA guidelines support the concept that, with few exceptions, secondary prevention in patients who present with TIA is the same as that for those with ischemic stroke [10]. A 2020 clinical practice review and 2023 AHA published statement on diagnosis and management of TIA provide updated clinical guidance [399,402]. Selected key principles are as follows:

Within minutes of the onset of ischemic stroke, the core of an infarct can begin to form at the least-perfused site. This site is encircled by an area partially altered metabolically and ionically by cytotoxic edema [55]. This area, the ischemic penumbra, is structurally intact and generally salvageable if reperfusion is achieved promptly. Because cerebral function deficits develop rapidly (within minutes to hours) as an ischemic stroke progresses, these brain attacks are a medical emergency. Each minute that passes results in an average loss of 1.9 million neurons and 14 billion synapses; an ischemic brain ages 3.6 years for every hour that passes after the onset of stroke [56]. For this reason, stroke specialists use the mantra, "time is brain." Although irreversible damage occurs, most individuals with stroke have recoverable penumbral tissue for at least three hours following the onset of symptoms [16].

The physical signs, symptoms, and sequelae of ischemic stroke are usually unilateral because of the circulatory anatomy of the brain (Table 3). Anterior circulation is composed of the paired internal carotid arteries and vessels that supply blood to the cerebral hemispheres. Each common carotid artery bifurcates into the internal and external carotid arteries. The ophthalmic artery, posterior communicating artery, and anterior choroidal artery are supplied by the internal carotid artery (Figure 1). Most importantly, the internal carotid artery provides blood to the middle cerebral artery, the largest intracerebral vessel. The middle cerebral artery provides oxygen to the lateral, frontal, parietal, and temporal lobes and the basal ganglia. It also supplies the anterior cerebral artery, which is responsible for the medial part of the frontal and parietal lobes, most of the corpus callosum, the frontobasal cerebral cortex, deep structures, and the anterior diencephalon. The anterior choroidal artery supplies a portion of the thalamus and the posterior limb of the internal capsule.

CORONAL SECTION OF THE CEREBRUM ILLUSTRATING ARTERIAL TERRITORIES

Figure 1

Source : [60] Reprinted from Blumenfeld H. Neuroanatomy Through Clinical Cases. 2nd ed. Boston, MA: Sinauer Associates, Inc.; 2013, with permission from Sinauer Associates, Inc.

Posterior circulation is primarily composed of the vertebrobasilar artery, the posterior cerebral artery, which it supplies, and other branching vessels. The posterior cerebral artery provides blood to the occipital and medial temporal lobes, as well as regions of the midbrain, subthalamic nucleus, basal nucleus, thalamus, mesial inferior temporal lobe, and occipitoparietal cortices. The two main segments of the posterior cerebral artery (P1 and P2) are connected by the posterior communicating artery. The Circle of Willis links the anterior and posterior circulation at the base of the brain.

In general, ischemic strokes are categorized according to etiology: thrombotic and embolic [61]. In addition, they are classified into five subtypes according to a system developed by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) [62].

A thrombotic stroke results from progressive atherosclerosis that impairs cerebral arterial blood flow. The stroke event takes two forms: atherosclerotic plaque formation leads to critical stenosis of an artery supplying blood to a region of the brain, or when a fragment of unstable plaque (embolus) breaks loose and lodges in a branch point downstream. The stenosed or occluded artery may be a large vessel (e.g., carotid artery systems, vertebral arteries, the Circle of Willis) or a small vessel (e.g., branches of the Circle of Willis, the posterior circulation). Approximately 21% to 27% of ischemic strokes arise from atherosclerotic disease of the large vessels [63,64]. The cerebral artery branch points, especially those of the internal carotid artery, are the most vulnerable [65]. Small-vessel disease is associated with 21% to 25% of ischemic strokes [63,64]. Thrombotic strokes caused by small-vessel disease are traditionally associated with lacunar infarcts, small, deep, subcortical lesions of 15 mm or less in diameter resulting from occlusion of a single penetrating artery [62,66]. As many as 20% of older individuals who are otherwise healthy have asymptomatic lacunar infarcts unrelated to an ictal event [67]. These silent infarctions were previously believed to be benign with a good long-term prognosis. However, they now have been linked to increased risks of stroke and death and can lead to debilitating cognitive impairments such as vascular dementia [67,68].

Independent risk factors for lacunar infarcts include hypertension, gender, age, diabetes, smoking, and a history of TIA [67]. Although hypertension is strongly associated with the development of small-vessel occlusion, lacunar infarcts also occur in individuals without hypertension. However, normotensive individuals with lacunar infarcts are typically 85 years of age or older, suggesting that hypertension accelerates the arteriopathy underpinning small-vessel disease. Diabetes is an independent risk factor for lacunar infarcts [69].

An embolic stroke occurs when an embolus (i.e., any circulating clot or particle originating from a distal point) lodges in a cerebral arterial vessel, interrupting blood supply to the brain. Stroke registries indicate that 14% to 30% of ischemic strokes are embolic [70,71,72,73,74]. Arterial emboli may originate from the heart (chamber or diseased valves), from the carotid or intracranial arteries (atheromatous plaque), aortic arch, or peripheral venous system by way of a right-to-left shunt (paradoxical embolus). Emboli may be composed of thrombus, fatty deposits, atherosclerotic plaque fragments, or cellular debris emanating from intravascular infections (e.g., endocarditis) or tumors (e.g., atrial myxoma). Clinical symptoms of the resulting infarct correspond to the location of the embolus, not its type. The region of the middle cerebral artery is most frequently blocked by emboli [75].

AF is the most common cardiogenic cause of embolic stroke, and the proportion of strokes caused by AF increases with increasing patient age. The presence of AF increases the risk of embolic stroke fivefold and doubles the risk of death [76,77]. Atrial fibrillation is associated with blood stasis and thrombus formation within the left atrial appendage. Other cardiogenic sources of brain embolism include valvular thrombi (e.g., rheumatic disease, endocarditis, prosthetic valves), mural thrombi from myocardial infarction (MI) or severe heart failure, and paradoxical embolization across a patent foramen ovale [78,79]. MI is associated with a 2% to 3% incidence of embolic stroke, 70% of which occur in the first week after the event [77,79].

The subtype of ischemic stroke influences treatment decisions, prognosis, and risk of recurrent stroke. The TOAST system was designed to facilitate decision making and standardize ischemic stroke research (Table 4) [62]. Most strokes are subclassified as a large-artery atherosclerosis (caused by either a thrombus or an embolus), a cardioembolism, or an occlusion of a small vessel (lacuna) [62]. Approximately 4% of individuals with stroke have coexisting large-vessel and small-vessel disease [61,80]. Other determined causes are rare (approximately 3%), and registries have classified up to 33% of ischemic strokes as being of "undetermined etiology" [81].

Age, gender, and race/ethnicity play major roles in the prevalence of stroke and its associated mortality.

Age

Prolonged damage of the aging cardiovascular system by various risk factors for stroke doubles the risk of ischemic stroke for each decade of life after 55 years of age [9]. Thus, clinicians should be sensitive to their patients' modifiable risk factors, most notably hypertension, starting at an early age [1]. As many as 70% of strokes occur in individuals older than 65 years of age, and the average age at the time of ischemic stroke is 71 years in men and 75 years in women [1]. Stroke patients 85 years of age and older comprise 17% of all stroke patients [1]. Clinicians should be particularly aware of silent cerebral infarctions in older individuals, as these infarctions occur more commonly in this population [89].

Although stroke risk increases with age, strokes can occur at any age; hospital surveillance data from 2014 found that 38% of people hospitalized for stroke were younger than 65 years of age [25]. Approximately 10% to 15% of all strokes occur in adults 18 to 50 years of age, and the underlying pathogenesis and risk factors are more diverse [1,401]. The common types of ischemic stroke in older persons are large vessel atherosclerosis and small vessel occlusions; these two subtypes account for only 10% to 20% of stroke in younger adults. Studies of subtypes have reported a higher prevalence (20% to 47%) of cardioembolism among younger patients with stroke [1,401].

Gender

Women have a higher lifetime risk of stroke than men [90,91,92]. According to estimates from the Framingham Heart Study, among people 55 to 75 years of age, the risk of stroke is 1 in 5 for women and 1 in 6 for men [93]. About 55,000 more women than men have a stroke each year; stroke is the cause of death for about 80,000 women each year [3]. Age-specific stroke incidence rates are substantially lower among women than men, except in those 80 years of age and older, in which the incidence rate in women is approximately equal to or higher than the rate in men [90,91,94,95,96]. Risk factors unique to women or more common in young women include estrogen-containing oral contraceptives, pregnancy, and migraine with aura. The combination of migraine with aura, oral contraceptive use, and cigarette smoking increases stroke ninefold compared with women who do not have any of these three risk factors [401]. The underlying conditions associated with stroke in women with these risk factors include cardioembolism, patent foreman ovale, and prothrombotic states. Pregnancy itself is a prothrombotic state, which in addition to hypertensive disorders of pregnancy increases the risk for ischemic stroke, ICH, and cerebral venous thrombosis. The approximate incidence of stroke is 30 per 100,000 pregnancies, which is three times higher than the incidence of stroke in nonpregnant young adults of comparable age [401]. The complication may occur during the antepartum, peripartum, or postpartum periods.

Among individuals 65 years of age and older, the median survival time after a first stroke is typically longer for women than for men. For both men and women, the median survival decreases with age (Table 5) [97]. However, the possibility of gender disparities in how health care is provided to individuals who present with stroke symptoms is also being evaluated.

Studies suggest that, compared with men, women are evaluated less frequently following a stroke and that any evaluation is more likely to be delayed [98,99,100]. This pattern results from women's presentation with nontraditional symptoms or without traditional symptoms and inappropriate worry by both clinician and patient about treatment-related risks (Table 6) [98,99,101,102,103]. Although studies to evaluate differences in strokes between men and women are in early stages, preliminary results indicate that emergency medical service (EMS) personnel and clinicians need an accurate understanding of symptom presentation patterns for men and women. The prevalence of nontraditional symptoms is higher among women than men; nontraditional stroke symptoms include headache, face and limb pain, nausea, and hiccups as well as symptoms typically believed to be unrelated to neurologic deficits (e.g., chest pain, shortness of breath, palpitations) [102].

Race/Ethnicity

The decline in stroke mortality has reduced, but not eliminated, the racial/ethnic gap in stroke mortality [88]. Racial/ethnic disparities in the incidence of stroke and its related mortality are substantial, and the factors contributing to the disparities are complex and poorly understood [1,5,6,7,8,104]. The risk of first-time stroke among Black individuals is 1.5 times higher than that for White individuals in the United States, and the incidence of first-ever stroke is increasing among Hispanic Americans compared to White Americans [1]. The Northern Manhattan Study (NOMAS) showed that the age-adjusted incidence of first ischemic stroke per 100,000 individuals was 191 in the Black population, 149 in the Hispanic population, and 88 in the White population [1,104]. Another study showed that the prevalence of stroke among these three groups also varied according to age [6]. In the Black population, the prevalence was 4.8% for individuals 45 to 64 years of age and 10% for individuals 65 years of age and older; the corresponding prevalences were 2.3% and 10% for Hispanic individuals and 2% and 9% for White individuals [6]. Intracranial atherosclerotic strokes were the most common type of strokes among the Black and Hispanic populations [1,104]. Higher rates of hypertension, obesity, and diabetes among Black Americans might account for some of this disparity [400].

According to the AHA 2019 update on statistics for heart disease and stroke, the prevalence of stroke is highest for American Indian/Alaskan Natives and lowest for Asian/Pacific Islanders (Table 7) [1]. Data indicate variation among stroke-related mortality rates as well and show that stroke deaths have increased in minority populations while decreasing in the White population. Projections indicate a 20.5% increase in stroke by 2030, with the greatest increase (29%) in Hispanic men [1].

Data from 2016 demonstrated an overall rate of 37.3 deaths per 100,000, with a rate of 51.9 for the Black (non-Hispanic) population, 36.1 for the White (non-Hispanic) population, 32.1 for the Hispanic population, 31.0 for the Asian/Pacific Islander population, and 30.7 for the American Indian/Alaskan Native population [1]. Risk factors, such as hypertension, diabetes, and obesity, vary among these populations as well, but increased risks alone cannot completely explain increased prevalence or mortality [9].

Consumption of fruits and vegetables reduces the risk of stroke in a dose-dependent manner. Risk is reduced 6% for each serving of fruits and vegetables per day [105]. Reducing sodium intake and increasing antioxidants, potassium, and calcium also mitigates the risk of stroke [9,106,107]. The AHA/ASA recommend that individuals with stroke residing in long-term care facilities be evaluated for calcium and vitamin D supplementation [21]. The Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in fruits, vegetables, and low-fat dairy products and which limits saturated and total fat intake, has been shown to lower blood pressure and likely reduce the risk of stroke [106,107].

Overwhelming evidence shows an undeniable association between cigarette smoking and stroke [9,108]. Smoking doubles the risk for ischemic stroke and increases the risk of hemorrhagic stroke 2 to 4 times [109]. The stroke risk for Black Americans who smoke is more than double that for nonsmokers in the same racial/ethnic group. A cohort study found stroke risk was 2.5 times higher for current smokers compared with never smokers [400]. The stroke risk was dose-dependent, according to smoking intensity; the risk increased 2.3 times for individuals who smoked 1 to 19 cigarettes per day and 2.8 times for those who smoked more than 20 cigarettes per day. Recurring exposure to environmental ("secondhand") smoke almost doubles the risk of stroke [110]. Secondhand smoke exposure is a contributing factor in more than 8,000 stroke deaths each year [111]. Using data from the National Health Interview Survey and death certificate data for 2000 through 2004, the Centers for Disease Control and Prevention estimated that smoking resulted in an annual average of 61,616 stroke deaths among men and 97,681 stroke deaths among women [112].

Individuals who smoke should be prescribed smoking cessation medications and be informed about cessation programs, counseling, and nicotine-replacement products. Epidemiologic studies show that, following smoking cessation, stroke risk decreases over time [9]. Individuals who do not smoke should be encouraged not to start.

One study has found that in the body mass index (BMI) range of 25 to 50 kg/m2, each 5 kg/m2 increase in BMI was associated with a 40% increased risk of stroke mortality; in the BMI range of 15 to 25 kg/m2, there was no relationship between BMI and stroke mortality [113]. Another large epidemiologic study showed that the risk almost doubled for overweight and obese men [114]. A meta-analysis of data from 25 studies involving more than 2.2 million people showed an increased risk of ischemic stroke of 22% in overweight individuals and 64% in obese individuals [115]. Studies have not yet addressed if losing weight reduces this risk [9]. However, it is well-documented that weight loss lowers blood pressure and cholesterol and positively affects other risk factors for stroke. Clinicians should encourage overweight patients to begin a weight-loss program that includes a healthful diet and exercise and provide patients with safe weight-loss strategies, such as those recommended by the AHA [9].

Body fat distribution has proven to be a fairly reliable indicator of stroke risk [116,117]. While some studies support abdominal adiposity as a significant risk factor for stroke only in men, other research indicates that a high concentration of abdominal fat is a significant risk factor in both men and women, independent of BMI [9]. On the other hand, gynoid adiposity in women appears to be associated with a lower risk for stroke, even for women with a higher BMI [117]. A high hip-to-waist ratio may be a more important risk factor for vascular disease, including stroke, than BMI score alone [118].

A large and generally consistent body of evidence indicates that routine physical activity prevents stroke [9]. A habitually sedentary lifestyle increases an individual's chance of stroke. Physically active men and women generally have a 25% to 30% lower risk of stroke or death than the least active people [119]. Individuals should be strongly encouraged to engage in aerobic exercise at moderate intensity for 150 minutes or more weekly, at vigorous intensity for 75 minutes or more per week, or a combination of both that fulfills these requirements [9]. It should be noted that only moderate-to-vigorous intensity exercise has been found to reduce the incidence of stroke [104].

For most individuals with nonmodifiable stroke risks, the probability of stroke can be decreased substantially with rigorous preventive measures and the treatment of modifiable risks [9,16]. The AHA recommends addressing lifestyle risk factors, as discussed, and medically managing several risk factors, including hypertension, diabetes, AF, other cardiac conditions, dyslipidemia, and asymptomatic carotid stenosis [9].

Hypertension

Hypertension is perhaps the most significant risk factor for stroke, and risk increases as blood pressure increases [9]. Sustained elevation in blood pressure has adverse effects on small and large arteries throughout the cerebrovascular system, increasing risk for multiple stroke types (ICH, aneurysmal subarachnoid hemorrhage, and ischemic stroke). Fortunately, the prevalence of hypertension has plateaued over the past decade and remained stable, at 29%, between 2008 and 2017 [121,122]. Control of hypertension (defined as blood pressure less than 140/90 mm Hg) also has improved, with rates of control increasing from 27.3% in 1988–1994 to 50.1% in 2007–2008 [9]. These improvements are likely attributable to heightened awareness and treatment, with awareness among U.S. residents increasing from 69% in 1988–1994 to 81% in 2007–2008 [9]. Still, more than two-thirds of people 65 years of age and older are hypertensive [123].

Treatment of hypertension is effective for primary and secondary prevention of stroke. The AHA and other professional organizations recommend that all adults 18 years of age and older be screened for high blood pressure [124]. The U.S. Preventive Services Task Force (USPSTF) recommends screening for all adults 18 years of age and older and annual screening for adults 40 years of age and older who are at increased risk for high blood pressure. Increased risk is defined as [124]:

Individuals 18 to 39 years of age with normal blood pressure (<130/85 mm Hg) who do not have other risk factors should be screened every 3 to 5 years. The USPSTF additionally recommends rescreening with properly measured office blood pressure. If the blood pressure is elevated, the diagnosis should be confirmed with ambulatory blood pressure monitoring [124].

The 2017 Guideline for High Blood Pressure in Adults recommends screening every 2 years for adults with a blood pressure less than 120/80 mm Hg and screening every 3 to 6 months for people with systolic blood pressure of 120 to 129 mm Hg or with diastolic blood pressure greater than 80 mm Hg [125]. The AHA/ASA recommends that women be screened for high blood pressure before taking birth control pills, as the combination increases the risk of stroke [126].

Appropriate management of hypertension may also include dietary changes, other lifestyle modifications, and pharmacologic therapy. There is no evidence that any particular class of antihypertensives offers special protection against stroke in all patients; the desired result is more important than the choice of treatment. Treatment should be individualized on the basis of other clinical characteristics and medication tolerance. Among patients with other cardiovascular risk factors, more intensive control (systolic blood pressure <130 mm Hg) reduces risk of stroke more than usual control (<140 mm Hg) (9). Studies have shown that management is possible for the majority of patients, but most will require treatment that includes two or more drugs [9].

Diabetes

Diabetes, if untreated, leads to enhanced atherogenesis and microvascular disease within small arterioles. The risk for stroke is 2 times higher among individuals with diabetes. In 2017, after adjusting for population age differences, hospitalization rates for stroke were more than three times higher among adults 20 years of age and older with diagnosed diabetes compared with those without diagnosed diabetes [127]. Type 2 diabetes is associated with an increased prevalence of atherogenic risk factors, such as hypertension, obesity, and dyslipidemia. The combination of hyperglycemia and hypertension is thought to increase the risk of stroke [9]. The AHA recommends that the target blood pressure for individuals with diabetes be less than 140/90 mm Hg [9]. Pharmacologic therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) has been shown to be safe and effective in this population [9]. In addition, lipid-lowering statins reduce the risk of first-time strokes in patients with diabetes, irrespective of the baseline lipid levels, pre-existing vascular conditions, and glycemic control [128].

Atrial Fibrillation

AF is associated with a fourfold to fivefold increased risk of ischemic stroke, and approximately 60,000 strokes occur among the 2.3 million individuals with AF annually [9]. According to the AHA/ASA, women older than 75 years of age should be screened for AF risk due to its link to greater stroke risk [126]. All patients with AF should be considered for anticoagulant therapy. Whether to use warfarin (a vitamin K antagonist) or a non-vitamin K-dependent, direct-acting anticoagulant depends on underlying predisposition, age, patient comorbidities and concomitant medications, bleeding risk, and stroke risk. High-risk factors for stroke include previous TIA/stroke, mitral stenosis, prosthetic heart valves, and systemic embolism. Moderate-risk factors include age older than 75 years, heart failure, hypertension, and diabetes. AHA guidelines recommend that eligible patients with nonvalvular AF be treated with warfarin or one of the direct non-vitamin-K oral anticoagulants [195]. Patients with AF and mechanical heart valves or mitral stenosis should only receive treatment with warfarin, as the direct non-vitamin K oral agents are contraindicated. The individual's preferences and access to high-quality anticoagulation monitoring should be considered. Warfarin therapy to maintain an international normalized ratio (INR) of 2.0 to 3.0 (target: 2.5) is strongly recommended for high-risk individuals (those with more than a 4% annual risk of stroke) with AF and no significant contraindications to oral anticoagulants [9,129]. Despite the effectiveness of such treatments, anticoagulant therapy continues to remain underprescribed due to overestimation of the associated risks of warfarin (e.g., intracranial, extracranial hemorrhage) and underestimation of stroke risk [129]. Some physicians err on the side of caution and aim for an INR greater than the recommended target, with a corresponding reduction in therapeutic effectiveness.

Other Cardiac Conditions

The management of valvular heart disease, unstable angina, chronic stable angina, acute MI, and other cardiac conditions is a critical factor in stroke prevention. Strategies to prevent postoperative neurologic injury and stroke in patients undergoing surgical revascularization for atherosclerotic heart disease can be found in the American College of Cardiology coronary artery bypass graft surgery guidelines, which are approved by the AHA [9,130]. The AHA states that it is "reasonable" to use warfarin for patients who have had ST-elevation MI and left ventricular dysfunction with extensive regional wall-motion abnormalities [9].

Dyslipidemia

The AHA recommends that statin therapy for individuals with known coronary heart disease or high-risk hypertension (e.g., patients with diabetes), including those with normal low-density lipoprotein (LDL) cholesterol levels [9]. In addition, these individuals should be encouraged at every interaction to exercise, eat a healthful diet, and quit smoking. Niacin, bile acid sequestrants, ezetimibe, or fibric acid derivatives may also be considered for individuals with known coronary heart disease and low levels of high-density lipoprotein cholesterol, such as people in whom target cholesterol levels cannot be achieved with statins or people who cannot tolerate statin therapy; however, their effectiveness in decreasing stroke risk has not been established [9].

Asymptomatic Carotid Stenosis

The U.S. Preventive Services Task Force (USPSTF) recommends against screening for asymptomatic carotid artery stenosis in the general adult population.

(https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/carotid-artery-stenosis-screening Last Accessed: March 22, 2023)

Strength of Recommendation/Level of Evidence: D (The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.)

Individuals with asymptomatic carotid artery stenosis should be screened for other modifiable risk factors, and any risk factors identified should be controlled as soon as possible. Antiplatelet therapy with aspirin is recommended, unless contraindicated [9]. Carotid revascularization (endarterectomy or vascular stent) for stroke prevention is an option for asymptomatic patients with >70% stenosis of the internal carotid artery if the risk of perioperative stroke and other adverse outcomes is low (<3%). However, the effectiveness compared with best medical management is not well established [9,10]. Comorbidities and life expectancy should be considered when determining if surgery is appropriate. In addition, thorough discussion with the patient and his or her family/caregivers is a necessity. Topics should include the possibility of surgery-related death, the risks and benefits associated with the procedure, and the patient's preferences. For patients with a high surgical risk, carotid angioplasty/stenting may be considered. However, the periprocedural and overall 1-year event rates in some studies have dampened the AHA's enthusiasm for the stenting option [9,10].

Depressive Symptoms

After publication of the AHA guidelines, the findings of a large study showed that depressive symptoms are an independent risk factor for stroke, especially for patients younger than 65 years of age [131]. Clinicians may consider managing depressive symptoms and mood disorders as aggressively as hypertension or diabetes, because mood disorders appear to increase risk for all types of stroke [132].

Conventional catheter angiography is invasive and requires a nephrotoxic contrast medium [169]. It is particularly valuable for the detection of vasculopathies associated with cerebral complications, including aneurysm, vasculitis, arteriovenous malformation, atherosclerosis, and arterial dissection [10,16]. Digital subtraction angiography (DSA), a type of catheter angiography, remains the standard against which newer technologies for detection of many types of cerebrovascular lesions and diseases are measured [170,171,172,173,174]. Its sensitivity and specificity equal or exceed those of noninvasive techniques; however, because of time considerations and procedural difficulties, it is not recommended in initial evaluation of stroke patients [16].

Unlike catheter angiography, MRA creates a map of blood flow rather than a true image of the vasculature anatomy. Noninvasive time-of-flight MRA is performed without contrast medium, and like phase-contrast (gadolinium) MRA is minimally invasive (catheter insertion required). Although MRA provides a high-resolution image of many vessels, it cannot reliably resolve distal or branch occlusions of the intracranial vasculature [16]. MRA also tends to overestimate the degree and length of high-grade stenosis (compared with DSA) by signaling loss of flow when blood flow is turbulent, in-plane, or slow [175]. MRA is helpful for detecting uncommon causes of ischemic stroke or TIAs (e.g., arterial dissection, venous thrombosis) [172]. The 2019 AHA/ASA guideline recommends the use of MRA with DW-MRI when selecting candidates for mechanical thrombectomy between 6 and 24 hours after last known well time [16]. DW-MRI is sensitive to acute cellular injury in cerebral ischemia and can be used to assess ischemic lesions in the first few hours [177].

CTA also permits noninvasive, rapid screening of intracranial and extracranial vasculature for stenosis and occlusion. Preliminary data suggest that CTA effectively detects large-vessel intracranial occlusions when compared with ultrasound and DSA; however, because it provides a static image of vascular anatomy, it is inferior to DSA for demonstrating flow rates and direction [16,178]. Although CTA is fast and can be adapted to conventional CT, contrast medium is required, and patients are exposed to additional radiation [16]. The 2019 AHA/ASA guideline recommends the use of CTA with CTP or MRA/DW-MRI for selecting candidates for mechanical thrombectomy between 6 and 24 hours after last known well time [16].

Doppler ultrasonography is a noninvasive imaging technique used to measure arterial blood flow and determine the site and degree of stenosis/occlusion of the external carotid and cerebral vasculature. A common use of transcranial Doppler ultrasonography is for primary and secondary stroke prevention in patients presenting with TIA and stroke. It can be used to monitor progress of vascular recovery during the early post-acute thrombolysis treatment phase of stroke care [10,16,166]. Additional uses of transcranial Doppler ultrasonography in patients with stroke include [16,166,167]:

Despite the usefulness of this technique, its performance is highly operator-dependent [166]. Considerable anatomic and physiologic knowledge of the cerebral vasculature is required, as vessel images are not produced, and skill and experience are prerequisites for data interpretation. Data acquisition and interpretation tend to be time-consuming and may delay treatment [166,168]. While these reasons suggest that vascular imaging is not practical for the diagnosis of ischemic stroke in most cases, it may be useful in some. A recommendation in the 2019 AHA/ASA guidelines states that noninvasive imaging of the cervical carotid arteries should be routinely performed within 24 hours of admission in patients with nondisabling acute ischemic stroke in the carotid territory who are candidates for carotid endarterectomy [16]. Additionally, intracranial vessel imaging is recommended to guide selection of appropriate secondary stroke prevention treatments [16].

Transcranial Doppler (TCD) ultrasonography has been used to detect intracranial vessel abnormalities and to evaluate occlusions and stenoses in intracranial vessels. It is less accurate than CTA or MRA for steno-occlusive disease but can detect microembolic signals that indicate extracranial or cardiac sources of embolism [152]. TCD has been shown to predict and enhance outcomes with IV rt-PA [179].

Because the time between the onset of stroke and treatment should be limited, catheter angiography is not recommended by the AHA for the diagnosis of a suspected stroke [152]. In the case of a stroke, the utility of the imaging tool increases after a diagnosis has been made. As with transcranial Doppler ultrasonography, cerebral angiography is particularly useful for confirming the diagnosis, monitoring the progression of thrombolytic therapy, and assisting with the prognosis, particularly during the first 72 hours after a stroke [152].

With a goal to improve functional outcomes, the American College of Emergency Physicians recommends that intravenous tPA should be offered and may be given to selected patients with acute ischemic stroke within three hours after symptom onset at institutions where systems are in place to safely administer the medication. The increased risk of symptomatic intracerebral hemorrhage should be considered when deciding whether to administer tPA.

(https://www.acep.org/globalassets/new-pdfs/clinical-policies/tpa-for-stroke_new.pdf Last Accessed: March 22, 2023)

Strength of Recommendation: B (Recommendation based on moderate clinical certainty)

The IV administration of alteplase (rt-PA) has been FDA-approved for the treatment of stroke since 1996. Rapid administration of rtPA to appropriate patients remains the mainstay of early treatment of acute ischemic stroke [18]. Treatment with rt-PA is highly effective if administered within 3 hours. The earlier treatment is initiated, the higher the probability of a full recovery. Treatment within 90 minutes has been associated with a higher rate of favorable outcome at 3 months compared with treatment administered within 180 minutes [185]. For patients who meet national and international eligibility guidelines, IV rtPA improves functional outcomes at 3 to 6 months when given within 4.5 hours after ischemic stroke onset and should be administered [18]. However, the therapeutic window may extend to 6 hours [186,187]. Studies to determine the threshold of rt-PA benefits are ongoing. The AHA/ASA recommend that health systems set a goal of increasing their percentage of stroke patients treated within 60 minutes of presenting to hospital (i.e., door-to-needle time of 60 minutes) to at least 80% [152]. Tenectaplase is a newer tissue plasminogen activator investigated for treatment of ischemic stroke; it appears to be as effective as alteplase and may have a better safety profile [16].

The AHA/ASA have changed some of their recommendations regarding rt-PA treatment since their 2013 guidelines (Table 13) [16]. Administration of rt-PA is not recommended for patients who have a systolic blood pressure greater than 185 mm Hg or a diastolic blood pressure greater than 110 mm Hg [16].

Between 31% and 50% of patients treated with rt-PA have a 4-point or greater improvement on the NIHSS by 3 months after the stroke [152]. These clinical improvements do not recede for at least 1 year after the stroke. In general, the best response to rt-PA has been found for patients who are younger than 75 years of age, with a baseline NIHSS score of less than 20, and no history of diabetes or pre-existing disability [152].

The most common serious medical complication of rt-PA is secondary brain hemorrhage, which occurs in 6% of patients [188]. Yet, the risk does not outweigh the benefits of rt-PA. Three months following rt-PA therapy, approximately 30% of patients are neurologically normal or near normal; 30% have mild-to-moderate neurologic deficits; 20% have moderate-to-severe deficits; and 20% have died [189]. Other dangerous complications of rt-PA, although rare, are angioedema, anaphylaxis, systemic hemorrhage, and, if rt-PA is administered soon after an acute MI, myocardial rupture [16,190].

The AHA/ASA Task Force reviewed and discussed several studies addressing the use of heparin or low-molecular-weight heparin (LMWH) as an adjunct to a thrombolytic agent in the treatment of stroke [16]. In general, the Task Force concluded that early administration of heparin or LMWH is inadvisable partly due to the increased risk of bleeding complications, especially the hemorrhagic transformation of ischemic strokes. Additionally, early administration has not been shown to prevent recurrent stroke, lessen the risk of neurologic worsening, or improve patient outcome [16].

Although no new data regarding antiplatelet treatment have emerged since the 2003 version of the AHA/ASA guideline for ischemic stroke management, the AHA/ASA recommendations for antiplatelet therapy have changed (Table 14) [16]. Data combined from two large clinical trials suggest that administration of aspirin (325 mg) within 24 to 48 hours after the onset of stroke slightly reduces mortality and morbidity by preventing early recurrent stroke in some patients [191,192]. The findings of these trials do not suggest the use of aspirin within 24 hours of thrombolytic administration or as a substitute for thrombolytic therapy. A 2014 Cochrane review confirmed the results of these trials [193]. A review that summarized the results of nine randomized controlled trials also confirmed these findings and demonstrated increased odds of complete recovery [194]. In patients presenting with minor (NIHSS ≤3) noncardioembolic stroke who are not treated with rt-PA, dual antiplatelet therapy (aspirin and clopidogrel) started within 24 hours after symptom onset and continued for 21 days is effective in reducing risk of recurrent stroke for a period up to 90 days [16].

In patients with acute ischemic stroke or transient ischemic attack, the American Heart Association/American Stroke Association recommends early (within 48 hours) aspirin therapy at a dose of >60–325 mg.

(https://www.ahajournals.org/doi/10.1161/STR.0000000000000211 Last Accessed: March 22, 2023)

Strength of Recommendation/Level of Evidence: 1A (Strong recommendation, high-quality evidence)

Ticagrelor is a reversible, short-acting P2Y12 agonist. The Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial tested the efficacy of ticagrelor (18-mg loading dose, then 90 mg twice daily) to aspirin in 13,199 patients with acute ischemic stroke or high-risk TIA [196]. The primary outcome (i.e., time to stroke occurrence, MI, or death within 90 days) occurred in 6.7% of patients treated with ticagrelor versus 7.5% treated with aspirin. Ischemic stroke occurred in 5.8% in the ticagrelor arm versus 6.7% in the aspirin arm. There were no differences in major bleeding, intracranial hemorrhage, or fatal bleeding. A subgroup analysis of the SOCRATES trial found that ticagrelor was effective at preventing the primary outcome in patients with a background history of aspirin use [197]. Ticagrelor versus placebo was the subject of the THALES (Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death) trial, which was completed in December 2019. As of 2020, the results have not yet been published [198].

Several trials have examined the efficacy of clopidogrel plus low-dose aspirin [199,200,201,202,203,204]. While the data from two of these trials suggest a benefit from dual antiplatelet therapy (i.e., clopidogrel/aspirin), the results of the other trials suggest a lack of benefit and possibly harm in the longer term. The combination dipyridamole plus aspirin for ischemic stroke management has been studied in several trials involving more than 17,000 patients [205,206,207,208,209,210]. The combination was found to be an acceptable antiplatelet therapy for patients with ischemic stroke or TIA and probably superior to aspirin alone. However, twice-daily dosing and headache cause many patients to discontinue the regimen [207,208,209,210].

The efficacy of IV glycoprotein IIb/IIIa receptor blockers (GP IIb/IIIa inhibitors), such as abciximab, in combination with other interventions or alone is under investigation. Preliminary results from the Abciximab in Emergent Stroke Treatment Trial (AbESTT) indicate that IV GP IIb/IIIa inhibitors may accelerate spontaneous recanalization, improve microvascular patency, and offer an adequate safety profile [211,212]. However, a systematic review of GP IIb/IIIa inhibitors as well as results of the AbESTT-II (a phase III trial of abciximab) did not demonstrate either safety or efficacy of the drug for treatment of acute ischemic stroke and found an increased rate of symptomatic or fatal intracranial hemorrhage, with no reduction in death or disability in survivors [213,214]. The 2019 AHA/ASA guideline contains both revised and new recommendations regarding the use of IV GP IIb/IIIa inhibitors, including abciximab (Table 14) [16].

Although emergent angioplasty and stenting are high-risk procedures, progressing strokes, which occur when patients' moderate neurologic deficits deteriorate significantly within 72 hours after onset, are associated with very poor outcomes and high mortality rates [215]. Therefore, some case studies suggest that emergency angioplasty followed by immediate or delayed stenting is appropriate for patients with a progressing stroke caused by carotid artery occlusion or stenosis, respectively [216,217]. However, the safety and efficacy of emergency carotid artery stenting are not established, and the procedure remains controversial [218,219].

Angioplasty and stenting may be appropriate for patients with acute stroke secondary to carotid artery dissection [220,221]. In one study, emergency angioplasty and stenting of the internal carotid artery performed in conjunction with intra-arterial thrombolysis was associated with more favorable outcomes than pharmacologic treatment alone in patients with acute carotid artery occlusion and secondary artery-to-artery embolism to the middle cerebral artery [222]. In a larger study by the same group of investigators, treatment with urokinase followed by angioplasty and stenting increased recanalization [223]. Another study found that angioplasty and stenting of the proximal occlusion and stent-based thrombectomy of the intracranial occlusion may be feasible, effective, and safe in selected patients with acute internal carotid artery occlusion and concomitant major vessel embolic stroke [221].

The AHA/ASA assert that the use of angioplasty and intra-arterial thrombolytics in the emergency management of stroke should be limited to comprehensive stroke centers, which have the resources and physician expertise to perform them safely, and in the setting of clinical trials [18].

In addition to use in emergent angioplasty and stenting, mechanical thrombectomy is both a primary reperfusion strategy and an adjunct to pharmacologic fibrinolysis for achieving recanalization in patients with acute ischemic stroke [16]. Mechanical treatments include the use of catheters during angiography to directly deliver either a clot-disrupting or retrieval device to an artery-occluding thromboembolus [224].

The primary advantage of mechanical devices is their ability to remove a clot in a matter of minutes, compared with pharmacologic thrombolytics (even those delivered intra-arterially) that may take as long as two hours to dissolve the clot [225,226]. A second advantage is that newer devices (e.g., retrievable stents) have shown higher recanalization rates and better outcomes than those seen with older devices (e.g., the Merci Retriever) [224]. The primary disadvantage of endovascular therapy is the delay in initiation of treatment because of the time required to mobilize the interventional team and, in many cases, the need to transfer the patient to another hospital [227,228]. In the absence of sufficient trial data, it had been uncertain whether endovascular therapy, with or without the previous use of IV rt-PA, would be more effective than IV rt-PA alone [229]. However, newer trials (i.e., MR CLEAN, EXTEND-IA, ESCAPE, and SWIFT-PRIME) have demonstrated the efficacy of endovascular therapy using the newer, retrievable stents [230,231,232].

In addition to reviewing the results of these four trials, the AHA/ASA also reviewed the results of the REVASCAT trial [18,233]. Of the five stent retriever trials, MR CLEAN, ESCAPE, and SWIFT-PRIME permitted use of salvage intra-arterial fibrinolytic drugs, whereas EXTEND-IA and REVASCAT did not [18]. Every or nearly every patient in the trials first received IV rt-PA. All five studies enrolled participants 18 years of age and older. Four of the trials used NIHSS scores (>2, >5, and 8–29) as eligibility criteria, and the fifth trial enrolled patients with a similar distribution of NIHSS scores. Four of the five trials used a prestroke function eligibility criterion. All five trials required baseline nonenhanced CT or MRI and used different strategies of an imaging-based selection criterion in addition to nonenhanced CT or MRI. A large majority of patients in the trials had ICA or proximal MCA (M1) occlusion. All five trials allowed the inclusion of patients with proximal cervical carotid stenosis, and all but one trial (SWIFT-PRIME) allowed the inclusion of patients with complete atherosclerotic cervical carotid occlusion. General anesthesia and conscious sedation were the two most frequently used anesthetic approaches for patients with acute ischemic stroke receiving endovascular therapy. None of the trials established the usefulness of mechanical thrombectomy devices other than stent retrievers [18].

The AHA/ASA analysis of and conclusions about these five stent retriever trials form the basis of their 2015 focused update to the guidelines on the management of patients with acute ischemic stroke (Table 15) [18].

In the setting of acute ischemic stroke, justification for emergent (within the first 24 hours) or early revascularization with carotid endarterectomy (CEA) is based on reports of increased risk of recurrent stroke in patients undergoing medical therapy while awaiting revascularization. Some studies have found that CEA is most beneficial when performed within 2 weeks of the last cerebrovascular symptom and that the benefits decline rapidly after 3 weeks [194,234]. However, the risk associated with emergency CEA is believed to be high, for several reasons, particularly in patients with an unstable neurologic status [235]. First, embolic and hemodynamic injuries can occur [236]. Second, detection of an arterial lesion and mobilization of an operating room staff is time-intensive. Lastly, hyperperfusion, which occurs in 0.3% to 1.2% of patients who have CEA, can lead to brain edema and hemorrhagic transformation [236]. Other complications may also develop.

For some patients, however, the benefit of CEA may outweigh the risk. For instance, patients with acute ischemic stroke who have already had previous CEA may be successfully treated with surgical revascularization. Some studies indicate that early CEA may also be appropriate for patients with small, nondisabling stroke in whom the goal is to reduce ongoing thromboembolism or flow-limiting ischemia [235,237,238,239,240,241]. Results of other small studies have suggested that administration of an anticoagulant and delaying surgery until after the patient is stabilized is a better option [242]. Due to the limited and conflicting data, high perceived risk, and unestablished usefulness, the AHA/ASA have a Class II, Level of Evidence B recommendation regarding the use of carotid endarterectomy for treatment of acute ischemic stroke [16].

As stated, the stroke survivor's family members and caregivers are integral to the post-stroke treatment plan [21]. However, 12% to 55% of caregivers suffer from emotional distress, most commonly depression [21,263,264]. Untreated depression is associated with a lower quality of life for both the caregiver and the stroke survivor [21,265]. A growing body of research is focused on treatment strategies to benefit both the caregiver and the stroke survivor and on educational programs that target issues such as supportive problem solving, physical care needs, financial and domestic assistance, respite, reassurance, and counseling [21,266,267,268,269,270].

When a patient is medically stabilized, a rehabilitation physician is consulted to assess the patient's rehabilitative needs and recommend the proper rehabilitation setting (Table 18) [17]. Additionally, the patient's complete medical history is provided to the rehabilitation physician. If indicated, other rehabilitation specialists may perform specialized or more intensive assessments. Overall, rehabilitation assessments should be [21]:

The NIHSS is a strong prognosticator of functional outcome, rendering it a valuable tool for determining rehabilitation needs [271,272]. It is the most widely used global assessment of impairment in the United States. It is a good predictor of short- and long-term morbidity and mortality and has been found to be sensitive to change in numerous studies [21]. Multiple assessments with the scale provide the rehabilitation team with a sense of the patient's recovery trajectory as he or she enters the rehabilitation stage.

The NIHSS provides detailed information in addition to an overall stroke severity score. A score of less than 5 indicates minor or no functional disability, whereas a score of more than 16 suggests severe disability and an increased probability of death [273]. With the advent of stroke treatment, patients with a score of 5 to 15 are likely to benefit from rehabilitation without the need for a nursing facility [274]. Patients with a score of more than 15 may improve with rehabilitation; however, these patients will likely require long-term care. More than one-half of survivors with a baseline score greater than 20 are initially sent to some form of rehabilitation facility rather than directly discharged to a nursing facility or home [274].

Because the type of stroke affects the usefulness of the NIHSS, its results should be qualified by medical history, examination, and brain imaging data [275]. Specifically, the scale is better suited for predicting functional outcomes at 3 and 6 months after stroke for patients with subcortical lesions than for patients with cortical lesions [21,276,277]. Additionally, the reliability of the scale in predicting depressive symptoms and cognitive dysfunctions depends on the hemisphere affected [21,277]. Because the NIHSS does not include evaluation of weakness of the distal part of the upper extremity, which is common in patients with stroke, a finger extension evaluation should be conducted in addition to the scale [278,279]. The presence of finger extension or partial shoulder abduction within 72 hours after stroke onset can help predict the patient's functional recovery at six months [280,281].

Although new measurement tools are being developed, they are difficult to evaluate with the traditional criteria (e.g., validity, reliability) normally used in evidence-based reviews [21]. The AHA/ASA recommendations for the assessment of rehabilitation needs (Table 19) are based on traditional measurement models, such as the FIM [21].

Soon after patient assessment, family/caregivers should be educated about and referred to community resources [21,282]. If it is recommended that the patient be discharged from an acute care facility to a nursing facility or the patient's home, relevant contact and background information for nursing home facilities, assisted-living services, social support groups, and stroke-related organizations should be provided to facilitate familial decision-making. Viable options should be presented to the family, especially information about long-term care placement if a severely disabled patient is not a candidate for rehabilitation [21]. If the family/caregivers will be taking care of the patient at a private residence (with or without professional assistance), it is essential to foster discussions about the needs of the patient, challenges the patient and family/caregivers may face, and the benefits of social support programs for the patient and family/caregivers. Whenever possible, written materials should be provided, and they should be in the primary language of the family. Among the important topics to discuss and provide education about include [21]:

Education about and referral to appropriate community resources can help to support the needs and priorities of the patient and the family or caregiver [21]. A systematic review and meta-analysis demonstrated that functional outcomes (i.e., motor, cognitive, and psychosocial function) can be improved or, at a minimum, maintained in stroke survivors when community interventions are available [21,283,284].

The patient's psychosocial status will influence his or her willingness and approach to participating in a rehabilitation program. A psychosocial assessment enables the rehabilitation team to incorporate family/caregivers more effectively into the rehabilitation process [285]. In addition, how the team manages the patient's care may be contingent on the patient's life circumstances and personality profile. Some patients and their caregivers fail to discuss psychosocial issues with their providers [21,264]. Cultural differences may also play a part in a patient's willingness to discuss these issues [21]. Areas of emphasis for the psychosocial assessment should include:

When designing and implementing the patient's treatment plan, the rehabilitation team should also take into account the residual effects of any difficulties the patient may have had before the stroke, such as drug or alcohol addiction; stress from recent life events, such as divorce, a loved one's death, or retirement; or clinical depression [21]. Individual patients will vary in how well they respond to challenging and demanding therapeutic approaches. After a patient's unique needs and circumstances are determined, relevant specialists will be incorporated into the team. All members of the rehabilitation team should be sensitive to the patient's psychosocial needs.

Medical complications related to illness, being bedridden, or lack of proper care/attention can prolong hospitalization, impede rehabilitation, increase disability, or result in death. Living in an inappropriate post-stroke environment also substantially increases a patient's risk for complications. Complications may develop in as many as 85% of hospitalized patients who have had a stroke [286]. Thus, medical examinations before and during a patient's rehabilitation program should assess the most common risks of complications: skin breakdown, deep vein thrombosis (DVT), swallowing dysfunction, bowel and bladder incontinence, falls, and pain [21].

Skin Breakdown and Contractures

Pressure ulcers are a commonly encountered complication in hospital and long-term care facilities, occurring in approximately 10% and 25% of patients in those settings, respectively [286]. According to the National Pressure Ulcer Advisory Panel, a pressure ulcer is a "localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in combination with shear" [287,288]. Although ulcers typically occur proximal to osseous prominences (e.g., the sacrum, hips, ankles), skin breakdown at the ears is also common in certain settings [289,290]. Most pressure ulcers are associated with deep tissue injury [291]. Regular assessment of skin and the use of objective risk scales (e.g., the Braden scale) may help prevent skin injury and should be followed by regular skin inspection with documentation [21,292]. Risk factors for pressure ulcers include [286]:

Conditions secondary to pressure ulcers include pain, localized infection, cellulitis, osteomyelitis, sepsis, and even death [293,294]. However, not all pressure ulcers, even those that are severe, will elicit a pain sensation [295].

Ulcers can be prevented or minimized with several measures, including proper positioning, turning, and transferring techniques; good hygiene; proper nutrition and hydration; and the use of barrier sprays, special mattresses, and protective dressings [21,292]. Good pain management may be necessary to perform correct positioning and frequent turning. Patients should be monitored daily for skin breakdown [21]. Any sign of a pressure ulcer warrants daily treatment [21].

Following stroke with hemiparesis, contracture on the affected side will develop in approximately 60% of patients within the first year, with wrist contractures occurring most commonly in patients who do not recover functional hand use [21,296,297]. Contractures are painful and can make self-care difficult. Many clinicians recommend daily stretching of the affected limb(s); families and patients should be taught proper stretching technique [21]. The effectiveness of resting hand splints is not well established [21]. Contractures of the ankle/foot can affect gait quality and patient safety. Ankle-foot orthosis and the nighttime use of a resting ankle splint may be beneficial in preventing ankle contracture [21].

Deep Vein Thrombosis

DVT affects only 2% of patients with stroke; yet, its prevention is critical [286]. The American Academy of Family Physicians recommends that DVT risk be calculated with use of the Well's DVT prediction model, and the results of this model will dictate subsequent DVT testing (Table 20) [298,299]. For patients with symptoms in both legs, the more symptomatic leg should be tested. A score of 3 or more on the Well's test indicates a high clinical probability of DVT; the probability is intermediate for a score of 1 or 2.

The D-dimer test alone is not recommended to rule out DVT in patients who have had a stroke. Patients with intermediate-to-high risk for DVT should be screened with use of ultrasonography. This imaging modality may not detect DVT in the calf, however, and repeat ultrasonography or venography should be used when DVT in the calf is suspected. Contrast venography was previously the most definitive test for the diagnosis of DVT, but today, Doppler ultrasound is the diagnostic study of choice [299].

Measures such as early mobilization and anticoagulation therapy are recommended to decrease the incidence of DVT after stroke. A patient's risk can be substantially reduced by 50-foot walks daily (with assistance, if necessary), administration of subcutaneous, low-dose unfractionated heparin (5,000 units twice a day, unless contraindicated), and the use of graduated compression stockings (GCS) as an adjunct to medication [300]. GCS and intermittent pneumatic compression may be considered for prevention of post-stroke DVT, but their routine prophylactic use requires further study. The benefit of treatment should be weighed against the increased risk of skin complications [21,301,302].

Swallowing Dysfunction

Based on instrumental testing results, dysphagia may develop in 42% to 78% of patients within three days after stroke [21,303]. This disorder is strongly linked to the development of malnutrition and pneumonia if not identified early and managed properly [21,303,304]. The AHA/ASA guidelines include a Class I recommendation for early dysphagia screening in patients with acute stroke [21]. Patients with dysphagia often have problems with aspiration, which can cause serious consequences if the stroke has suppressed cough sensations [21]. Although cerebral and cortical strokes can cause dysphagia, swallowing is most severely compromised by brain stem strokes [303].

The speech and language pathologist on the rehabilitation team should perform a brief swallow assessment on all patients with stroke before oral intake of food and fluids [21,305]. A dysfunctional swallow should be further examined using a complete bedside swallow examination. If bedside swallow screenings indicate an affected swallow, or if the patient has a high risk for aspiration and/or dysphagia, performing a videofluoroscopy swallowing study or fiberoptic endoscopic examination is recommended [21,305,306]. The grade of dysphagia correlates with dysarthria, aphasia, low functional independence, and level of cognitive functioning [306]. The speech and language pathologist may best identify the specific physiologic problem and recommend the necessary management and interventions for treatment. A Cochrane review assessing the effectiveness of a variety of interventions (e.g., acupuncture, neuromuscular electrical stimulation, physical stimulation) on functional outcome found that behavioral interventions and acupuncture reduced dysphagia, and pharyngeal electrical stimulation reduced pharyngeal transit time. However, the authors concluded that data are insufficient to determine the effect of these and other interventions (e.g., nutritional/fluid supplementation) on functional outcome and death. [304]. Authors of another review found that acupuncture may be effective for treatment of post-stroke dysphagia, but concluded that the reported benefits should be verified with further studies [307].

Bladder and Bowel Dysfunction

Upon admission to community-based facilities, approximately 50% of stroke survivors have urinary incontinence and 30% have fecal incontinence [308,309]. Almost all patients with fecal incontinence (98%) suffer from urinary incontinence. Urinary and fecal incontinence can lead to patient discomfort, skin breakdown, and sepsis. Fecal incontinence, in particular, reduces patient and family morale.

Large infarcts, aphasia, cognitive impairment, functional disability, lesions in the frontal cortex or frontoparietal lobes, and advanced age are associated with post-stroke urinary dysfunction [310]. Medications such as diuretics, alpha-adrenoreceptor blockers, and anticholinergic drugs can cause or exacerbate this complication [311,312]. Hyper-reflexia and hyporeflexia are the most common mechanisms of urinary incontinence in stroke survivors [313]. Detrusor sphincter dyssynergia, a cause of incomplete bladder voiding, is uncommon because its pathogenesis involves lesions between the brain stem and spine [312]. When assessing bladder function in patients with acute stroke, it is important to evaluate urinary retention with use of a bladder scanner or an in-and-out catheterization; urinary frequency, volume, and control; and the presence of dysuria. Patients who have urinary incontinence may benefit from bladder-training regimens and scheduled voiding [311,314].

Fecal incontinence can be due to neurogenic impairments or leakage around a fecal impaction (overflow incontinence) [315]. If the underlying cause of fecal incontinence is neurogenic, the signs and symptoms would likely include reduced rectal sensation and tone, inability to voluntarily contract the rectal sphincter, and stool in the rectal vault [315]. A diagnosis of constipation with overflow incontinence is more likely if the patient has rectal sensation and tone.

Risk factors for impaction and constipation include immobility, inactivity, dehydration, some medications, mood disorders, and cognitive deficits [316,317]. Multivariate analysis has shown that advanced age and diabetes are risk factors for fecal incontinence [317]. Patients with persistent constipation or fecal incontinence may benefit from bowel-management programs and psychosocial support [318]. Because of the risk of skin breakdown, the social stigma, and the burden of care associated with bowel and bladder incontinence, management is an essential component of the rehabilitation process [21].

Falls

Within 12 weeks after a stroke, approximately 25% of patients will fall [286]. Up to 70% of individuals with a stroke fall during the first six months after discharge from the hospital or rehabilitation facility [21,319]. Individuals with stroke are also at risk of repeated falls that include injury [21,320]. One study found that most falls occur at home in the first 3 months following post-stroke risk assessment [320]. Falls are a common complication for several reasons, including [315,321,322]:

The Berg Balance Scale may be the most appropriate screen for patients who are likely to fall [21,323,324]. This scale tests 14 specific functional movements of daily living of increasing difficulty [325]. The 56-point maximum score indicates adequate balance and low risk of a fall. A score of less than 45 is associated with a proclivity for falling [323,325]. The score at 2 months post-stroke is useful for informing a patient's risk of falls, but it does not account for the multifactorial nature of the problem and should not preclude risk management provided in conjunction with exercise interventions, such as rehabilitation that targets gait coordination, to improve mobility [320,326]. If the patient is able to walk, the Stops Walking When Talking test may further help to identify the risk for a fall [323]. With this test, the examiner initiates a conversation with the patient while walking; if the patient stops walking to respond, the risk of a fall is increased [327]. St. Thomas' Risk Assessment Tool in Falling Elderly Inpatients (known as STRATIFY), a tool used commonly in the rehabilitation setting, has been shown to be a poor predictor of the risk for fall when screening patients with stroke [328].

In addition to the physical consequences associated with falls, there are also psychologic and social consequences. Impairments in balance, gait, motor control, perception, and vision contribute to a heightened fear of falling in the stroke survivor, with 30% to 80% reporting various levels of fear associated with falling and mobility [21]. This fear can cascade into reduced levels of physical activity and deconditioning, resulting in greater physical decline, loss of ability to perform activities of daily living, loss of independence, social isolation, and depression. Education in fall prevention and balance training are essential components of the rehabilitation process [21].

Pain

Pain is one of the most frequently experienced complications. Almost one-half of all stroke survivors experience chronic pain, 65% of whom have shoulder pain [286]. Whether chronic or periodic, pain can delay functional recovery by masking motor function improvement, diminishing a patient's motivation or willingness to perform rehabilitative tasks, or limiting the patient's movement or requiring the use of a cane or wheelchair for ambulation [17]. Pain most often results from joint immobilization and the fixation of tendons and ligaments in one position [85]. In some patients, however, stroke-induced sensorimotor pathway damage leads to the sensation of pain in an affected extremity or side of the body. The most common pain syndrome of this type is central post-stroke pain, which affects 8% of patients, or at least 56,000 stroke patients in the United States each year [21,329,330]. Four percent of patients with central post-stroke pain experience it as shoulder pain. Central post-stroke pain can be difficult to manage, even with medications. Only amitriptyline and lamotrigine have been shown to be effective in placebo-controlled studies [331].

The evidence from randomized controlled trials so far does not confirm or refute that electrical stimulation around the shoulder after stroke influences reports of pain, but there do appear to be benefits for passive humeral lateral rotation.

(https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001698/full Last Accessed: March 22, 2023)

Level of Evidence: Meta-Analysis

The AHA/ASA recommend patient and family education (i.e., range of motion, positioning) about shoulder pain and care following stroke [21]. A clinical assessment of the pain that includes musculoskeletal evaluation, evaluation of spasticity, identification of any subluxation, and testing for regional sensory changes is also recommended. Ultrasound may be considered for diagnosis of shoulder soft tissue injury [21]. Botulinum toxin injection or a trial or neuromodulating pain medications may be useful to reduce severe hypertonicity in hemiplegic shoulder muscles. Positioning and the use of supportive devices may help reduce pain [21].

Use of diagnostic criteria for central post-stroke pain can be helpful [21]. Additionally, initial medical examinations should thoroughly document suspected etiology of any pain, its location and characteristics (e.g., burning, tingling, stabbing, dull), its duration and intensity, and what aggravates or relieves the pain. Any pain that interferes with the rehabilitation process should be identified and treated accordingly. There is limited evidence on the efficacy of proposed treatments for central post-stroke pain. Combined pharmacotherapy (e.g., amitriptyline, lamotrigine) and therapeutic exercise may be reasonable. Few nonpharmacologic options exist [21].

Approximately 45% of stroke survivors have residual neurologic deficits that impair mobility, which is one of the most devastating sequelae of stroke [21,87]. At 6 months, about half of ischemic stroke survivors who are 65 years of age or older have hemiparesis, nearly one-third require assistance with walking, and more than one-quarter need assistance with activities of daily living [87]. Although functional outcome primarily depends on the patient's post-stroke neurologic damage and compensatory capacity, the multidisciplinary rehabilitation team plays a major role in recovery [246]. The team's coordinated and customized efforts can help many stroke survivors adopt an active and social lifestyle. To tailor services to a patient's needs, the team should assess his or her functional abilities during the immediate post-acute stroke phase before hospital discharge. Assessment relies on a physical examination and a systematic battery of tests that measure a patient's ability to complete activities of daily living and that screens for cognitive/communication skills as well as visual/spatial neglect disorders [21]. Knowledge of the patient's preferred activities is also helpful.

Several functions/activities are typically measured to assess comprehensive functional status initially and during the rehabilitation process (Table 21). Although many measurement tools can be used to objectively record a patient's comprehensive functional acuity, the most widely used and trusted instrument in the stroke rehabilitation setting is the FIM [332,333]. Throughout the rehabilitation process, FIM-supported systematic screening can help the rehabilitation team to [21,332]:

As stated, loss of mobility is a devastating post-stroke outcome and restoration of gait-related activities (e.g., rising to stand, sitting down, climbing stairs) is often one of the primary goals of rehabilitation. Additionally, many patients will require assistive devices, adaptive equipment, and other items to maximize independent functioning after stroke [21].

In general, major rehabilitation goals are for patients to regain safe ambulation in the home and community and to regain the ability to perform activities of daily living with minimal or no assistance. Thus, patients should be reassessed for daily tasks that are appropriate to their expected level of dependency [21]. If a return to independent community or home living is possible, domestic functioning should be evaluated [17,334]. Skills needed to stay home alone include preparing a meal, using safety precautions, properly taking medications, and obtaining emergency services. Patients who wish to resume driving should be assessed thoroughly for driving-related physical, cognitive, and behavioral functions [21]. Driving is an instrumental activity of daily living for many individuals due to its impact on their ability to participate in activities outside the home. Between one- and two-thirds of post-stroke survivors resume driving after one year, but because it is a highly complex activity requiring skills in cognition, perception, and emotional and motor control, the ability to drive is often affected by stroke. The AHA/ASA recommend that [21]:

Healthy cognition and communication are essential to an individual's sense of well-being. Unfortunately, stroke has an adverse effect on cognitive and communicative abilities.

Cognition

Calculation, executive functioning (the integration of multiple and complex processes), and visual perception/construction are the cognitive arenas most often affected during the first several weeks after a stroke [335,336]. Up to 88% of patients with a cerebellar stroke have cognitive deficits, such as impairments in abstract thought, attention, control, memory, planning, and speech [337]. In many cases, patients with stroke-associated right brain damage have anosognosia, a condition in which patients are rendered unaware of their contralateral sensory and motor neurologic deficits (hemiplegia, hemianesthesia, and hemianopia) [338]. Although many survivors regain some or all cognitive skills soon following a stroke, up to 38% remain cognitively impaired at 3 months [339]. Recovery rates may be as high as 80% within 6 months for stroke survivors, with visual perception and visual memory showing the most improvement and language and abstract reasoning showing the least [340,341]. At 1 and 3 years after a stroke, cognitive impairment is one of the factors most strongly linked with poor physical and mental health status [342]. Cognitive status is an important determinant of post-stroke success. The AHA/ASA recommend that all stroke patients be screened for cognitive deficits before being discharged to home [21].

Stroke-induced damage to the brain's cognition centers is second only to Alzheimer disease as the leading cause of dementia. Stroke-associated dementia manifests with the following symptoms [343]:

The National Guideline Centre recommends that patients should be screened for cognitive deficits after stroke. Where a cognitive deficit is identified, carry out a detailed assessment using valid, reliable, and responsive tools before designing a treatment program.

(https://www.nice.org.uk/guidance/CG162 Last Accessed: March 22, 2023)

Level of Evidence: Expert Opinion/Consensus Statement

Areas of cognitive and arousal ability that should be assessed before and during rehabilitation are learning and memory, attention, visual/spatial neglect and impairments, executive functioning, and apraxia (loss of the ability to execute skilled movements despite having the desire and the physical ability to perform them) [21]. In addition to its use in assessing functional ability, the FIM is effective as an initial screen of cognitive and functional communication deficits [344]. Because stroke-related cognition deficits are independently associated with left hemispheric stroke, visual field defect, and urinary incontinence, the presence of any of these conditions should heighten awareness of the possibility of the presence of the others [339].

Visual and spatial dysfunctions may be particularly difficult to identify during the initial post-stroke examination because multiple neuroanatomic systems can be affected to varying degrees. When a standard medical examination does not include the brief, systematic screening for visual and spatial neglects, more than 60% of these dysfunctions remain undiagnosed. However, the use of the FIM may increase their early identification [344]. Patients with neglect deficits are unknowingly inattentive to specific body parts and/or spaces in the external environment. For instance, patients may brush half of their teeth or only eat food on half of their tray. Unilateral neglect is present in almost 50% of patients with right hemispheric stroke [345]. Patients with unilateral neglect are also unaware of limbs contralateral to the site of the brain lesion(s). Neglect disorders are strongly associated with poor functional outcomes and safety issues. Patients with neglect are prone to falls and injuries as well as burns to the affected limbs [322]. Addressing visual and spatial deficits as early as possible in the rehabilitation process using multiple functional adaptation techniques (e.g., visual scanning, external cues) and patient/caregiver education may decrease a patient's risk for injury [21].

Communication

As with cognitive difficulties, communication problems strain relationships between stroke survivors and their social system, impede rehabilitation, and lead to poor quality of life. Common communication-related stroke sequelae are aphasia, dysarthria, and apraxia (a speech disorder in which there is incoordination of muscles required for speech). Patients with communication deficits may also have dysphagia. How these disorders are manifested as well as their severity depends on the location and degree of the stroke. Interventions for apraxia of speech should be individually tailored and may include behavioral techniques and strategies that target [21]:

Augmentative and alternative communication devices and modalities should be used to supplement speech [21].

Aphasia affects one-third of stroke survivors and is one of the most common stroke-associated communication deficits [21,346].

The three types of aphasia are expressive, receptive, and global (Table 22) [347]. Patients with expressive aphasia have difficulties using words and sentences, whereas patients with receptive aphasia struggle to understand what others are communicating to them. Global aphasia is a combination of these two types. Aphasia is typically related to lesions on the left side of the brain, as the language center is located within this hemisphere in most individuals [348]. In many cases, aphasia (mild aphasia in particular) can be an elusive diagnosis because patients may [347]:

A variety of treatment approaches for aphasia have been developed, but no conclusions can yet be made about the effectiveness of one treatment over another [21].

An additional challenge in assessment is that members of the rehabilitation team typically do not have a clear sense of the patient's communication skills before the stroke. Lastly, reading and writing skills are usually more affected than oral communication.

Well-trained, organized rehabilitation teams can use alternative methods of communicating to mitigate the effects of cognitive and communication disorders. Ideally, these problems should be recognized and managed early. However, arriving at a diagnosis can be challenging. The speech and language pathologist on the rehabilitation team is best suited to evaluate the patient for cognitive/communication disorders. In some cases, problems are initially undetected or develop after the evaluation. Training the rehabilitation team to recognize symptoms of cognitive and communication deficits early (especially those that are subtle) and report findings to the speech and language pathologist can serve as a "safety net" for patients [21]. For proper diagnosis, the speech and language pathologist should also seek the help of the patient's family to gain an understanding of the patient's cognition and communication history.

Through interviews, conversation, structured observations and other formal tests, the speech and language pathologist can evaluate the individual's cognition and communication skills, including speech, expression, social communication, and reading/writing (Table 23) [21,349].

If necessary, the speech and language pathologist can formulate remediation strategies to accelerate recovery of the affected communication skills, development of compensatory techniques, or use of residual skills [21,349]. In many cases, patients with stroke-induced attention deficits, visual neglect, memory deficits, executive function deficits, and problem-solving difficulties can be retrained or taught compensation techniques [350]. Strategies to enhance communication with the patient should be taught to the rehabilitation team as well as the family/caregivers [21]. Any interventions should be individually tailored and designed to target the overt communication deficit as well as any deficits that accompany or underlie the communication deficit, including attention, memory, and executive functions. The use of drugs to improve cognitive impairments is not well established [21].

Following a stroke, it is understandable that patients and their families experience intense emotions. In many cases, the staff's kindness and helpfulness, familial support, and the passage of time allow patients and their families to deal with the grief and other feelings precipitated by the stroke without medication or psychologic therapy. However, approximately 33% of patients experience post-stroke depression, and other mood disorders also manifest in stroke survivors [1,351,352]. In general, psychologic conditions can have a significant impact on the success of rehabilitation. Thus, all patients should be thoroughly evaluated for psychologic disorders as early as possible and on an ongoing basis [21].

Detecting post-stroke depression can be particularly challenging, as symptoms often appear to be typical post-stroke symptoms or are subtle. Patients may experience fatigue, sleeping difficulties, loss of appetite, tearfulness, and feelings of hopelessness. They may refuse to participate in therapy [21]. Additionally, cognitive deficits may prevent the patient from recognizing or having the ability to communicate depressive symptoms. Patients with an acquired flat affect may "sound sad" or indifferent to their situation without having post-stroke depression. Although several screening tools for depression in the older population are available (Table 24), a single, universally accepted evaluation tool for post-stroke depression has not been developed. Because little research in this area is available and the condition is underdiagnosed by nonpsychiatric physicians, the diagnosis of post-stroke depression should be based on information from multiple sources, including medical evaluation, patient self-report, observation of patient behavior, patient history, and staff reports of changes in behavior and motivation.

The accompaniment of post-stroke depression with other psychologic disorders is not uncommon [21]. Therefore, the medical evaluation should also screen for other categories of psychiatric symptoms [21]. Generalized anxiety disorder, which affects 20% of survivors, often coexists with post-stroke depression [356]. Generalized anxiety disorder delays the recovery of the ability to carry out activities of daily living and negatively affects social functioning [21]. Additionally, up to 15% of stroke survivors have pseudobulbar affect, characterized by uncontrollable laughing/crying [21].

Both post-stroke depression and pseudobulbar affect respond well to selective serotonin reuptake inhibitors [357]. Although these drugs carry some risk, they are safe in most patients who have had a stroke. However, these medications should not be administered prophylactically [358,359]. Although studies are limited, the use of cognitive-behavioral therapy techniques and brief supportive therapy in conjunction with medication may be beneficial to those with post-stroke depression and other neuropsychiatric sequelae of stroke [21].

The results of meta-analyses have indicated that lowering blood pressure reduces the risk of stroke 30% to 40% [376,377]. The findings of longitudinal studies suggest that treatment with antihypertensive medications in hypertensive and normotensive patients reduces the incidence of recurrent strokes, MI, and other vascular events [378]. In particular, diuretics or diuretics combined with ACE inhibitors (e.g., ramipril, perindopril) most significantly reduce the risk of recurrent ischemic stroke [10,378]. However, lifestyle modifications that include weight loss; increased intake of fruits, vegetables, and low-fat dairy products; habitual aerobic physical activity; and limited alcohol consumption are crucial components of controlling blood pressure [123]. Although most studies address the prevention of additional ischemic strokes, hypertension management has also been shown to reduce the risk of recurrent hemorrhagic stroke and is included in guideline recommendations published by the AHA/ASA [10,378]. In the context of secondary stroke prevention, the target blood pressure is <130 mm Hg systolic, <80 mm Hg diastolic.

AHA Recommendations

Diabetes is a well-documented independent risk factor for recurrent stroke [379,380]. Aggressive control of hypertension in diabetic patients, with a lower target of 130/80 mm Hg, has been shown to reduce the risk of stroke as well as other cardiovascular events [123]. Including ACE inhibitors in the treatment regimen of patients with diabetes effectively lowers blood pressure, slows the progression of renal disease, and reduces albuminuria [10,381].

AHA Recommendations

Smoking doubles the risk of stroke [382]. Its cessation eliminates the elevated risk after 5 years and reduces the overall risk of stroke-related hospitalization [10,382,383]. Exposure to secondhand smoke also appears to increase the risk of stroke [10,384]. The most effective combination of therapies for smoking cessation is nicotine replacement, social support, and counseling [10,385].

AHA Recommendations

The results of a meta-analysis suggest that the risk of stroke is increased 69% for individuals who have more than five drinks (with one drink defined as 12 ounces of beer, 4 ounces of wine, or 1.5 ounces of liquor) per day compared with nondrinkers [386].

AHA Recommendations

Habitual exercise clearly prevents stroke [365]. In addition, a sedentary lifestyle impedes functional recovery and places patients at a higher risk for stroke recurrence.

AHA Recommendations

Extracranial carotid stenosis is an important and treatable cause of stroke. Patients with severe stenosis ipsilateral to a disabling stroke or TIA who are candidates for intervention should be treated early after presentation. The choice between carotid endarterectomy and carotid artery stenting should be determined by specific patient comorbidities and vascular anatomy [10].

AHA Recommendations

The rate of stroke recurrence for patients with symptomatic intracranial atherosclerosis is approximately 9% [10]. The findings of retrospective studies have suggested that the greatest rate of recurrence is found among patients with this condition who do not have a response to antithrombotic therapy [387]. Although the results of some studies have indicated that angioplasty or stenting should be considered for such patients, the usefulness of these surgical interventions is unknown and considered investigational [10]. AHA/ASA recommends that patients with severe intracranial stenosis in the territory of stroke or TIA should not receive angioplasty and stenting as the first-line therapy for stroke prevention; aggressive medical management and short-term dual antiplatelet therapy are preferred [10].

AHA Recommendations

With regard to patients with stroke or TIA due to 50% to 99% stenosis of a major intracranial artery:

With regard to patients with stroke or TIA due to 70% to 99% stenosis of a major intracranial artery, the addition of clopidogrel 75 mg/day to aspirin for 90 days might be reasonable.

The anticoagulant warfarin has a narrow therapeutic margin and numerous food and drug interactions, and these factors (which necessitate frequent INR testing and dose adjustment), combined with the associated significant bleeding risks, have led to the underutilization of this drug despite having been shown to prevent recurrent stroke substantially in patients with ischemic stroke or TIA and AF and despite the adoption of performance measures and guidelines advocating its use in these patients [10,388,389]. Easy-to-use alternative therapies are required and include dabigatran, rivaroxaban, and apixaban [390,391,392]. Significant adverse effects (i.e., serious, sometimes fatal bleeding, acute coronary events) have been associated with some of these agents, making their use inappropriate for some patients [393,394]. However, a 2011 focused update on dabigatran published by the American College of Cardiology, the AHA, and the Heart Rhythm Society recommends this agent as a useful alternative to warfarin for select patients [395].

Between 35% to 45% of patients with stroke and AF have coexisting conditions that may have caused the stroke [396]. In many cases, both the AF and the other condition (usually stenosis) will require treatment [10].

AHA Recommendations

The use of certain antiplatelet therapies rather than oral anticoagulation for noncardioembolic ischemic strokes and TIAs has been shown to reduce the overall risk of recurrent stroke and decrease the incidence of fatal recurrent strokes [10]. Clopidogrel is appropriate for patients who are allergic to aspirin or for patients in whom dipyridamole-associated headaches occur.

AHA Recommendation

Aspirin (50 mg to 325 mg per day) monotherapy, the combination of aspirin 25 mg and extended-release dipyridamole 200 mg twice daily, or clopidogrel 75 mg monotherapy are all acceptable options for initial therapy. The selection of an antiplatelet agent should be individualized on the basis of patient risk factor profiles, cost, tolerance, and other clinical characteristics.