Stroke: Etiology, classification, and epidemiology

INTRODUCTION — The two broad categories of stroke, hemorrhage and ischemia, are diametrically opposite conditions: hemorrhage is characterized by too much blood within the closed cranial cavity, while ischemia is characterized by too little blood to supply an adequate amount of oxygen and nutrients to a part of the brain [1].

Each of these categories can be divided into subtypes that have somewhat different causes, clinical pictures, clinical courses, outcomes, and treatment strategies. As an example, intracranial hemorrhage can be caused by intracerebral hemorrhage (ICH, also called parenchymal hemorrhage), which involves bleeding directly into brain tissue, and subarachnoid hemorrhage (SAH), which involves bleeding into the cerebrospinal fluid that surrounds the brain and spinal cord [1].

This topic will review the classification of stroke. The clinical diagnosis of stroke subtypes and an overview of stroke evaluation are discussed separately. (See "Clinical diagnosis of stroke subtypes" and "Overview of the evaluation of stroke".)

DEFINITIONS — Stroke is classified into two major types:

●Brain ischemia due to thrombosis, embolism, or systemic hypoperfusion

●Brain hemorrhage due to intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH)

A stroke is the acute neurologic injury that occurs as a result of one of these pathologic processes. Approximately 80 percent of strokes are due to ischemic cerebral infarction and 20 percent to brain hemorrhage. (See 'Epidemiology' below.)

An infarcted brain is pale initially. Within hours to days, the gray matter becomes congested with engorged, dilated blood vessels and minute petechial hemorrhages. When an embolus blocking a major vessel migrates, lyses, or disperses within minutes to days, recirculation into the infarcted area can cause a hemorrhagic infarction and may aggravate edema formation due to disruption of the blood-brain barrier.

Transient ischemic attack (TIA) is defined clinically by the temporary nature of the associated neurologic symptoms, which last less than 24 hours by the classic definition. The definition is changing with recognition that transient neurologic symptoms are frequently associated with permanent brain tissue injury. The definition of TIA is discussed in more detail separately. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Definition of TIA'.)

A primary ICH damages the brain directly at the site of the hemorrhage by compressing the surrounding tissue. Physicians must initially consider whether the patient with suspected cerebrovascular disease is experiencing symptoms and signs suggestive of ischemia or hemorrhage.

The great majority of ischemic strokes are caused by a diminished supply of arterial blood, which carries sugar and oxygen to brain tissue. Another cause of stroke that is difficult to classify is stroke due to occlusion of veins that drain the brain of blood. Venous occlusion causes a backup of fluid resulting in brain edema, and in addition it may cause both brain ischemia and hemorrhage into the brain. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)

BRAIN ISCHEMIA — There are three main subtypes of brain ischemia [2]:

●Thrombosis (see 'Thrombosis' below) generally refers to local in situ obstruction of an artery. The obstruction may be due to disease of the arterial wall, such as arteriosclerosis, dissection, or fibromuscular dysplasia; there may or may not be superimposed thrombosis.

●Embolism (see 'Embolism' below) refers to particles of debris originating elsewhere that block arterial access to a particular brain region [3]. Since the process is not local (as with thrombosis), local therapy only temporarily solves the problem; further events may occur if the source of embolism is not identified and treated.

●Systemic hypoperfusion (see 'Systemic hypoperfusion' below) is a more general circulatory problem, manifesting itself in the brain and perhaps other organs.

Blood disorders (see 'Blood disorders' below) are an uncommon primary cause of stroke. However, increased blood coagulability can result in thrombus formation and subsequent cerebral embolism in the presence of an endothelial lesion located in the heart, aorta, or large arteries that supply the brain.

Thrombosis — Thrombotic strokes are those in which the pathologic process giving rise to thrombus formation in an artery produces a stroke either by reduced blood flow distally (low flow) or by an embolic fragment that breaks off and travels to a more distant vessel (artery-to-artery embolism). Thrombotic strokes can be divided into either large or small vessel disease (table 1). These two subtypes of thrombosis are worth distinguishing since the causes, outcomes, and treatments are different.

Large vessel disease — Large vessels include both the extracranial (common and internal carotids, vertebral) and intracranial arterial system (Circle of Willis and proximal branches) (figure 1 and figure 2).

Intrinsic lesions in large extracranial and intracranial arteries cause symptoms by reducing blood flow beyond obstructive lesions, and by serving as the source of intra-arterial emboli. At times a combination of mechanisms is operant. Severe stenosis promotes the formation of thrombi which can break off and embolize, and the reduced blood flow caused by the vascular obstruction makes the circulation less competent at washing out and clearing these emboli.

Pathologies affecting large extracranial vessels include:

●Atherosclerosis

●Dissection

●Takayasu arteritis

●Giant cell arteritis

●Fibromuscular dysplasia

Pathologies affecting large intracranial vessels include:

●Atherosclerosis

●Dissection

●Arteritis/vasculitis

●Noninflammatory vasculopathy

●Moyamoya syndrome

●Vasoconstriction

Atherosclerosis is by far the most common cause of in situ local disease within the large extracranial and intracranial arteries that supply the brain. White platelet-fibrin and red erythrocyte-fibrin thrombi are often superimposed upon the atherosclerotic lesions, or they may develop without severe vascular disease in patients with hypercoagulable states. Vasoconstriction (eg, with migraine) is probably the next most common, followed in frequency by arterial dissection (a disorder much more common than previously recognized) and traumatic occlusion. Fibromuscular dysplasia is an uncommon arteriopathy, while arteritis is frequently mentioned in the differential diagnosis, but it is an extremely rare cause of thrombotic stroke.

Aortic disease is really a form of proximal extracranial large vessel disease, but it is often considered together with cardioembolic sources because of anatomic proximity. (See 'Aortic atherosclerosis' below.)

Identification of the specific focal vascular lesion, including its nature, severity, and localization, is important for treatment since local therapy may be effective (eg, surgery, angioplasty, intraarterial thrombolysis). It should be possible clinically in most patients to determine whether the local vascular disease is within the anterior (carotid) or posterior (vertebrobasilar) circulation and whether the disorder affects large or penetrating arteries. (See "Clinical diagnosis of stroke subtypes", section on 'Neurologic examination'.)

Delivery of adequate blood through a blocked or partially blocked artery depends upon many factors, including blood pressure, blood viscosity, and collateral flow. Local vascular lesions also may throw off emboli, which can cause transient symptoms. In patients with thrombosis, the neurologic symptoms often fluctuate, remit, or progress in a stuttering fashion (figure 3). (See "Clinical diagnosis of stroke subtypes", section on 'Clinical course of symptoms and signs' and "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Mechanisms and clinical manifestations'.)

Small vessel disease — Small vessel disease affects the intracerebral arterial system, specifically penetrating arteries that arise from the distal vertebral artery, the basilar artery, the middle cerebral artery stem, and the arteries of the circle of Willis. These arteries thrombose due to:

●Lipohyalinosis (a lipid hyaline build-up distally secondary to hypertension) and fibrinoid degeneration

●Atheroma formation at their origin or in the parent large artery

The most common cause of obstruction of the smaller arteries and arterioles that penetrate at right angles to supply the deeper structures within the brain (eg, basal ganglia, internal capsule, thalamus, pons) is lipohyalinosis (ie, blockage of an artery by medial hypertrophy and lipid admixed with fibrinoid material in the hypertrophied arterial wall). A stroke due to obstruction of these vessels is referred to as a lacunar stroke (see "Lacunar infarcts"). Lipohyalinosis is most often related to hypertension, but aging may play a role.

Microatheromas can also block these small penetrating arteries, as can plaques within the larger arteries that block or extend into the orifices of the branches (called atheromatous branch disease) [1].

Penetrating artery occlusions usually cause symptoms that develop during a short period of time, hours or at most a few days (figure 4), compared with large artery-related brain ischemia, which can evolve over a longer period.

Embolism — Embolic strokes are divided into four categories (table 1) [3].

●Those with a known source that is cardiac

●Those with a possible cardiac or aortic source based upon transthoracic and/or transesophageal echocardiographic findings

●Those with an arterial source (artery to artery embolism)

●Those with a truly unknown source in which tests for embolic sources are negative

The symptoms depend upon the region of brain rendered ischemic [4,5]. The embolus suddenly blocks the recipient site so that the onset of symptoms is abrupt and usually maximal at the start (figure 5). Unlike thrombosis, multiple sites within different vascular territories may be affected when the source is the heart (eg, left atrial appendage or left ventricular thrombus) or aorta. Treatment will depend upon the source and composition of the embolus. (See "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack".)

Cardioembolic strokes usually occur abruptly, although they occasionally present with stuttering, fluctuating symptoms. The symptoms may clear entirely since emboli can migrate and lyse, particularly those composed of thrombus. When this occurs, infarction generally also occurs but is silent; the area of infarction is smaller than the area of ischemia that gave rise to the symptoms. This process is often referred to as a TIA due to embolism, although it is more correctly termed an embolic infarction or stroke in which the symptoms clear within 24 hours.

High-risk cardiac source — The diagnosis of embolic strokes with a known cardiac source is generally agreed upon by physicians (table 2) [6,7]; included in this category are those due to:

●Atrial fibrillation and paroxysmal atrial fibrillation

●Rheumatic mitral or aortic valve disease

●Bioprosthetic and mechanical heart valves

●Atrial or ventricular thrombus

●Sinus node dysfunction

●Sustained atrial flutter

●Recent myocardial infarction (within one month)

●Chronic myocardial infarction together with ejection fraction <28 percent

●Symptomatic congestive heart failure with ejection fraction <30 percent

●Dilated cardiomyopathy

●Fibrous nonbacterial endocarditis as found in patients with systemic lupus (ie, Libman-Sacks endocarditis), antiphospholipid syndrome, and cancer (marantic endocarditis)

●Infective endocarditis

●Papillary fibroelastoma

●Left atrial myxoma

●Coronary artery bypass graft (CABG) surgery

With CABG, for example, the incidence of postoperative neurologic sequelae is approximately 2 to 6 percent, most of which is due to stroke [8]. Atheroemboli associated with ascending aortic atherosclerosis is probably the most common cause. (See "Neurologic complications of cardiac surgery".)

Potential cardiac source — Embolic strokes considered to have a potential cardiac source (table 2) are ones in which a possible source is detected (usually) by echocardiographic methods [6,7,9], including:

●Patent foramen ovale

●Atrial septal aneurysm

●Atrial septal aneurysm with patent foramen ovale

●Atrial cardiopathy (large or malfunctioning left atrium)

●Left ventricular aneurysm without thrombus

●Isolated left atrial smoke on echocardiography (no mitral stenosis or atrial fibrillation)

●Complex atheroma in the ascending aorta or proximal arch (see 'Aortic atherosclerosis' below)

In this group, the association of the cardiac or aortic lesion and the rate of embolism is often uncertain, since some of these lesions do not have a high frequency of embolism and are often incidental findings unrelated to the stroke event [10]. Thus, they are considered potential sources of embolism. A truly unknown source represents embolic strokes in which no clinical evidence of heart disease is present (table 1).

Aortic atherosclerosis — In longitudinal population studies with nonselected patients, complex aortic atherosclerosis does not appear to be associated with any increased primary ischemic stroke risk [11-13]. However, most studies evaluating secondary stroke risk have found that complex aortic atherosclerosis is a risk factor for recurrent stroke [14-17].

The range of findings is illustrated by the following studies:

●A prospective case-control study examined the frequency and thickness of atherosclerotic plaques in the ascending aorta and proximal arch in 250 patients admitted to the hospital with ischemic stroke and 250 consecutive controls, all over the age of 60 years [15]. Atherosclerotic plaques ≥4 mm in thickness were found in 14 percent of patients compared with 2 percent of controls, and the odds ratio for ischemic stroke among patients with such plaques was 9.1 after adjustment for atherosclerotic risk factors. In addition, aortic atherosclerotic plaques ≥4 mm were much more common in patients with brain infarcts of unknown cause (relative risk 4.7).

●In contrast, a population-based study of 1135 subjects who had transesophageal echocardiography (TEE) found that complex atherosclerotic plaque (>4 mm with or without mobile debris) in the ascending and transverse aortic arch was not a significant risk factor for cryptogenic ischemic stroke or TIA after adjusting for age, sex, and other clinical risk factors [12]. However, there was an association between complex aortic plaque and noncryptogenic stroke. The investigators concluded that complex aortic arch debris is a marker for the presence of generalized atherosclerosis.

Methodologic differences are a potential explanation for the discrepant results of these reports assessing the risk of ischemic stroke related to aortic atherosclerosis, as the earlier case-control studies may have been skewed by selection and referral bias. However, many patients with aortic atherosclerosis also have cardiac or large artery lesions, a problem that may confound purely epidemiologic studies.

In the author's opinion, there is no question that large protruding plaques in the ascending aorta and arch, particularly mobile plaques, are an important cause of stroke [18]. (See "Thromboembolism from aortic plaque".)

Systemic hypoperfusion — Reduced blood flow is more global in patients with systemic hypoperfusion and does not affect isolated regions. The reduced perfusion can be due to cardiac pump failure caused by cardiac arrest or arrhythmia, or to reduced cardiac output related to acute myocardial ischemia, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia may further reduce the amount of oxygen carried to the brain.

Symptoms of brain dysfunction typically are diffuse and nonfocal in contrast to the other two categories of ischemia. Most affected patients have other evidence of circulatory compromise and hypotension such as pallor, sweating, tachycardia or severe bradycardia, and low blood pressure. The neurologic signs are typically bilateral, although they may be asymmetric when there is preexisting asymmetrical craniocerebral vascular occlusive disease.

The most severe ischemia may occur in border zone (watershed) regions between the major cerebral supply arteries since these areas are most vulnerable to systemic hypoperfusion. The signs that may occur with borderzone infarction include cortical blindness, or at least bilateral visual loss; stupor; and weakness of the shoulders and thighs with sparing of the face, hands, and feet (a pattern likened to a "man-in-a-barrel").

Blood disorders — Blood and coagulation disorders are an uncommon primary cause of stroke and TIA, but they should be considered in patients younger than age 45, patients with a history of clotting dysfunction, and in patients with a history of cryptogenic stroke [10]. The blood disorders associated with arterial cerebral infarction include:

●Sickle cell anemia

●Polycythemia vera

●Essential thrombocytosis

●Heparin induced thrombocytopenia

●Protein C or S deficiency, acquired or congenital

●Prothrombin gene mutation

●Factor V Leiden (resistance to activated protein C)

●Antithrombin III deficiency

●Antiphospholipid syndrome

●Hyperhomocysteinemia

●Thrombotic thrombocytopenic purpura (TTP)

Factor V Leiden mutation and prothrombin 20210 mutations are associated mostly with venous rather than arterial thrombosis. They can result in cerebral venous thrombosis or deep venous thrombosis with paradoxical emboli. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)

Infectious and inflammatory disease such as pneumonia, urinary tract infections, Crohn disease, ulcerative colitis, HIV/AIDS, and cancers result in a rise in acute phase reactants such as fibrinogen, C-reactive protein, and coagulation factors VII and VIII. In the presence of an endothelial cardiac or vascular lesion, this increase can promote active thrombosis and embolism.

CLASSIFICATION SYSTEMS FOR ISCHEMIC STROKE

TOAST classification — The TOAST classification scheme for ischemic stroke is widely used and has good interobserver agreement [19]. The TOAST system (table 3) attempts to classify ischemic strokes according to the major pathophysiologic mechanisms that are recognized as the cause of most ischemic strokes (table 1). It assigns ischemic strokes to five subtypes based upon clinical features and the results of ancillary studies including brain imaging, neurovascular evaluations, cardiac tests, and laboratory evaluations for a prothrombotic state.

The five TOAST subtypes of ischemic stroke are:

●Large artery atherosclerosis

●Cardioembolism

●Small vessel occlusion

●Stroke of other determined etiology

●Stroke of undetermined etiology

The last subtype, stroke of undetermined etiology, involves cases where the cause of a stroke cannot be determined with any degree of confidence, and by definition includes those with two or more potential causes identified, those with a negative evaluation, and those with an incomplete evaluation. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)".)

SSS-TOAST and CCS classification — Since the original TOAST classification scheme was developed in the early 1990s, advances in stroke evaluation and diagnostic imaging have allowed more frequent identification of potential vascular and cardiac causes of stroke [6]. These advances could cause an increasing proportion of ischemic strokes to be classified as "undetermined" if the strict definition of this category (cases with two or more potential causes) is applied.

As a result, an evidenced-based modification of the TOAST criteria called SSS-TOAST was developed [6]. The SSS-TOAST system divides each of the original TOAST subtypes into three subcategories as "evident," "probable," or "possible" based upon the weight of diagnostic evidence as determined by predefined clinical and imaging criteria. In a further refinement, an automated version of the SSS-TOAST called the Causative Classification System (CCS) was devised (table 4) to improve its usefulness and accuracy for stroke subtyping [20]. The CCS is a computerized algorithm that consists of questionnaire-style classification scheme. The CCS appears to have good inter-rater reliability among multiple centers [21]. It is available online at https://ccs.mgh.harvard.edu/ccs_title.php.

The overall agreement between the original TOAST and CCS classification systems appears to be moderate at best, suggesting that two methods often classify stroke cases into different categories despite having categories with similar names [22].

BRAIN HEMORRHAGE — There are two main subtypes of brain hemorrhage [2]:

●Intracerebral hemorrhage (ICH) refers to bleeding directly into the brain parenchyma

●Subarachnoid hemorrhage (SAH) refers to bleeding into the cerebrospinal fluid within the subarachnoid space that surrounds the brain

Intracerebral hemorrhage — Bleeding in ICH is usually derived from arterioles or small arteries. The bleeding is directly into the brain, forming a localized hematoma that spreads along white matter pathways. Accumulation of blood occurs over minutes or hours; the hematoma gradually enlarges by adding blood at its periphery like a snowball rolling downhill. The hematoma continues to grow until the pressure surrounding it increases enough to limit its spread or until the hemorrhage decompresses itself by emptying into the ventricular system or into the cerebrospinal fluid (CSF) on the pial surface of the brain [23,24].

The most common causes of ICH are hypertension, trauma, bleeding diatheses, amyloid angiopathy, illicit drug use (mostly amphetamines and cocaine), and vascular malformations [23,24] (see "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis"). Less frequent causes include bleeding into tumors, aneurysmal rupture, and vasculitis.

The earliest symptoms of ICH relate to dysfunction of the portion of the brain that contains the hemorrhage [23,24]. As examples:

●Bleeding into the right putamen and internal capsule region causes left limb motor and/or sensory signs

●Bleeding into the cerebellum causes difficulty walking

●Bleeding into the left temporal lobe presents as aphasia

The neurologic symptoms usually increase gradually over minutes or a few hours. In contrast to brain embolism and SAH, the neurologic symptoms related to ICH may not begin abruptly and are not maximal at onset (figure 6) (and see below).

Headache, vomiting, and a decreased level of consciousness develop if the hematoma becomes large enough to increase intracranial pressure or cause shifts in intracranial contents (figure 7) [23,24]. These symptoms are absent with small hemorrhages; the clinical presentation in this setting is that of a gradually progressing stroke.

ICH destroys brain tissue as it enlarges. The pressure created by blood and surrounding brain edema is life threatening; large hematomas have a high mortality and morbidity. The goal of treatment is to contain and limit the bleeding. Recurrences are unusual if the causative disorder is controlled (eg, hypertension or bleeding diathesis).

Subarachnoid hemorrhage — The two major causes of SAH are rupture of arterial aneurysms that lie at the base of the brain and bleeding from vascular malformations that lie near the pial surface. Bleeding diatheses, trauma, amyloid angiopathy, and illicit drug use are less common. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

Rupture of an aneurysm releases blood directly into the CSF under arterial pressure. The blood spreads quickly within the CSF, rapidly increasing intracranial pressure. Death or deep coma ensues if the bleeding continues. The bleeding usually lasts only a few seconds but rebleeding is very common. With causes of SAH other than aneurysm rupture, the bleeding is less abrupt and may continue over a longer period of time.

Symptoms of SAH begin abruptly in contrast to the more gradual onset of ICH. The sudden increase in pressure causes a cessation of activity (eg, loss of memory or focus or knees buckling). Headache is an invariable symptom and is typically instantly severe and widespread; the pain may radiate into the neck or even down the back into the legs. Vomiting occurs soon after onset. There are usually no important focal neurologic signs unless bleeding occurs into the brain and CSF at the same time (meningocerebral hemorrhage). Onset headache is more common than in ICH, and the combination of onset headache and vomiting is infrequent in ischemic stroke (figure 7) [25]. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

Approximately 30 percent of patients have a minor hemorrhage manifested only by sudden and severe headache (the so-called sentinel headache) that precedes a major SAH (figure 7) [25]. The complaint of the sudden onset of severe headache is sufficiently characteristic that SAH should always be considered. In a prospective study of 148 patients presenting with sudden and severe headache, for example, SAH was present in 25 percent overall and 12 percent in patients in whom headache was the only symptom [26].

EPIDEMIOLOGY — Globally, ischemia accounts for 62 percent, intracerebral hemorrhage 28 percent, and subarachnoid hemorrhage 10 percent of all incident strokes, reflecting a higher incidence of hemorrhagic stroke in low- and middle-income countries [27,28]. In the United States, the proportion of all strokes due to ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage is 87, 10, and 3 percent, respectively [29].

The lifetime risk of stroke for adult men and women (25 years of age and older) is approximately 25 percent [30]. The highest risk of stroke is found in East Asia, Central Europe, and Eastern Europe. Worldwide, stroke is the second most common cause of mortality and the second most common cause of disability [31]. In China, which has the greatest burden of stroke in the world, the age-standardized prevalence, incidence, and mortality rates are estimated to be 1115, 247, and 115 per 100,000 person-years, respectively [32]. These data suggest that the stroke prevalence in China is relatively low compared with the prevalence in high-income countries, but the stroke incidence and mortality rates in China are among the highest in the world. While the incidence of stroke is decreasing in high-income countries, including the United States [33-35], the incidence is increasing in low-income countries [36]. The overall rate of stroke-related mortality is decreasing in high and low income countries, but the absolute number of people with stroke, stroke survivors, stroke-related deaths, and the global burden of stroke-related disability is high and increasing [37].

In the United States, the annual incidence of new or recurrent stroke is about 795,000, of which about 610,000 are first-ever strokes, and 185,000 are recurrent strokes [29]. There is a higher regional incidence and prevalence of stroke and a higher stroke mortality rate in the southeastern United States (sometimes referred to as the "stroke belt") than in the rest of the country [38-42].

The lifetime risk of stroke is higher for females compared with males [29].

Black and Hispanic Americans have an increased risk of stroke compared with White Americans, as illustrated by the following observations:

●The Northern Manhattan Study reported that the age-adjusted incidence of first ischemic stroke among White, Hispanic, and Black Americans was 88, 149, and 191 per 100,000 respectively [43]. Among Black compared with White Americans, the relative rate of stroke attributed to intracranial atherosclerosis, extracranial atherosclerosis, lacunes, and cardioembolism was 5.85, 3.18, 3.09, and 1.58 respectively. Among Hispanic compared with White Americans, the relative rate of stroke attributed to intracranial atherosclerosis, extracranial atherosclerosis, lacunes, and cardioembolism was 5.00, 1.71, 2.32, and 1.42.

●The Greater Cincinnati/Northern Kentucky Stroke Study showed that small vessel strokes and strokes of undetermined origin were nearly twice as common, and large vessel strokes were 40 percent more common, among Black compared with White patients [44]. The incidence of cardioembolic strokes was not significantly different.

●An increased incidence of stroke has also been found among Mexican Americans compared with non-Hispanic White Americans [45].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Intracerebral hemorrhage (The Basics)" and "Patient education: Stroke (The Basics)")

●Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)")

SUMMARY

●Classification – Stroke is classified into two major types (see 'Definitions' above):

•Brain ischemia due to thrombosis, embolism, or systemic hypoperfusion

•Brain hemorrhage due to intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH)

●Ischemia - There are three main subtypes of brain ischemia (table 1):

•Thrombosis generally refers to local in situ obstruction of an artery. The obstruction may be due to disease of the arterial wall, such as atherosclerosis, arteriosclerosis, dissection, or fibromuscular dysplasia; there may or may not be superimposed thrombosis. Thrombotic strokes can be divided into either large or small vessel disease. These two subtypes of thrombosis are worth distinguishing since the causes, outcomes, and treatments are different. (See 'Thrombosis' above.)

•Embolism refers to particles of debris originating elsewhere that block arterial access to a particular brain region. The source of embolism is most often from the heart or from an artery (artery-to-artery embolism). (See 'Embolism' above.)

•Systemic hypoperfusion is a more general circulatory problem, manifesting itself in the brain and perhaps other organs. (See 'Systemic hypoperfusion' above.)

Blood disorders are an uncommon primary cause of stroke. However, increased blood coagulability can result in thrombus formation and subsequent cerebral embolism in the presence of an endothelial lesion located in the heart, aorta, or large arteries that supply the brain. (See 'Blood disorders' above.)

●Ischemic stroke classification – The TOAST classification scheme for ischemic stroke (table 3) is widely used and has good interobserver agreement. The SSS-TOAST system divides each of the original TOAST subtypes into three subcategories as "evident," "probable," or "possible" based upon the weight of diagnostic. The Causative Classification System (CCS) (table 4) is an automated version of the SSS-TOAST. (See 'Classification systems for ischemic stroke' above.)

●Brain hemorrhage – There are two main subtypes of brain hemorrhage:

•ICH refers to bleeding directly into the brain parenchyma. Accumulation of blood occurs over minutes or hours. The most common causes of ICH are hypertension, trauma, bleeding diatheses, amyloid angiopathy, illicit drug use (mostly amphetamines and cocaine), and vascular malformations. Less frequent causes include bleeding into tumors, aneurysmal rupture, and vasculitis. (See 'Intracerebral hemorrhage' above.)

•SAH refers to bleeding into the cerebrospinal fluid within the subarachnoid space that surrounds the brain. The two major causes of SAH are rupture of arterial aneurysms that lie at the base of the brain and bleeding from vascular malformations that lie near the pial surface. Bleeding diatheses, trauma, amyloid angiopathy, and illicit drug use are less common. Rupture of an aneurysm releases blood directly into the cerebrospinal fluid (CSF) under arterial pressure. The blood spreads quickly within the CSF, rapidly increasing intracranial pressure. Death or deep coma ensues if the bleeding continues. (See 'Subarachnoid hemorrhage' above.)

●Epidemiology – Globally, ischemia accounts for 62 percent, intracerebral hemorrhage 28 percent, and subarachnoid hemorrhage 10 percent of all incident strokes, reflecting a higher incidence of hemorrhagic stroke in low- and middle-income countries. In the United States, the proportion of all strokes due to ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage is 87, 10, and 3 percent, respectively. (See 'Epidemiology' above.)