Official reprint from UpToDate www.uptodate.com ©2015 UpToDate

AuthorLouis R Caplan,MD

Section EditorScott E Kasner,MD

Deputy EditorJohn F Dashe,MD, PhD

Etiology, classification, and epidemiology of stroke

All topics are updated as new evidence becomes availableand our peer review process is complete.Literature review current through: Oct 2015. | This topiclast updated: Nov 26, 2014.

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

Each of these categories can be divided into subtypes thathave somewhat different causes, clinical pictures, clinicalcourses, outcomes, and treatment strategies. As anexample, intracranial hemorrhage can be caused byintracerebral hemorrhage (ICH, also called parenchymalhemorrhage), which involves bleeding directly into braintissue, and subarachnoid hemorrhage (SAH), which involvesbleeding into the cerebrospinal fluid that surrounds the brainand spinal cord [1].

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

DEFINITIONS — Stroke is classified into two major types:

A stroke is the acute neurologic injury that occurs as a resultof one of these pathologic processes. Approximately 80percent of strokes are due to ischemic cerebral infarction and20 percent to brain hemorrhage.

An infarcted brain is pale initially. Within hours to days, thegray matter becomes congested with engorged, dilated bloodvessels and minute petechial hemorrhages. When anembolus blocking a major vessel migrates, lyses, ordisperses within minutes to days, recirculation into theinfarcted area can cause a hemorrhagic infarction and mayaggravate edema formation due to disruption of the blood­brain barrier.

A primary ICH damages the brain directly at the site of the

®®

Brain ischemia due to thrombosis, embolism, orsystemic hypoperfusion

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

hemorrhage by compressing the surrounding tissue.Physicians must initially consider whether the patient withsuspected cerebrovascular disease is experiencingsymptoms and signs suggestive of ischemia or hemorrhage.

The great majority of ischemic strokes are caused by adiminished supply of arterial blood, which carries sugar andoxygen to brain tissue. Another cause of stroke that isdifficult to classify is stroke due to occlusion of veins thatdrain the brain of blood. Venous occlusion causes a back­upof fluid resulting in brain edema, and in addition it may causeboth brain ischemia and hemorrhage into the brain.

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

Blood disorders (see 'Blood disorders' below) are anuncommon primary cause of stroke. However, increasedblood coagulability can result in thrombus formation andsubsequent cerebral embolism in the presence of anendothelial lesion located in the heart, aorta, or large arteriesthat supply the brain.

Transient ischemic attack (TIA) is defined clinically by thetemporary nature of the associated neurologic symptoms,which last less than 24 hours by the classic definition. Thedefinition is changing with recognition that transientneurologic symptoms are frequently associated withpermanent brain tissue injury. The definition of TIA isdiscussed in more detail separately. (See "Definition oftransient ischemic attack".)

Thrombosis — Thrombotic strokes are those in which thepathologic process giving rise to thrombus formation in anartery produces a stroke either by reduced blood flow distally(low flow) or by an embolic fragment that breaks off andtravels to a more distant vessel (artery­to­artery embolism).Thrombotic strokes can be divided into either large or smallvessel disease (table 1). These two subtypes of thrombosis

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

Embolism (see 'Embolism' below) refers to particles ofdebris originating elsewhere that block arterial accessto a particular brain region [3]. Since the process is notlocal (as with thrombosis), local therapy onlytemporarily solves the problem; further events mayoccur if the source of embolism is not identified andtreated.

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

are worth distinguishing since the causes, outcomes, andtreatments are different.

Large vessel disease — Large vessels include both theextracranial (common and internal carotids, vertebral) andintracranial arterial system (Circle of Willis and proximalbranches) (figure 1 and figure 2).

Intrinsic lesions in large extracranial and intracranial arteriescause symptoms by reducing blood flow beyond obstructivelesions, and by serving as the source of intra­arterial emboli.At times a combination of mechanisms is operant. Severestenosis promotes the formation of thrombi which can breakoff and embolize, and the reduced blood flow caused by thevascular obstruction makes the circulation less competent atwashing out and clearing these emboli.

Pathologies affecting large extracranial vessels include:

Pathologies affecting large intracranial vessels include:

Atherosclerosis is by far the most common cause of in situlocal disease within the large extracranial and intracranialarteries that supply the brain. White platelet­fibrin and rederythrocyte­fibrin thrombi are often superimposed upon theatherosclerotic lesions, or they may develop without severevascular disease in patients with hypercoagulable states.Vasoconstriction (eg, with migraine) is probably the nextmost common, followed in frequency by arterial dissection (adisorder much more common than previously recognized)and traumatic occlusion. Fibromuscular dysplasia is anuncommon arteriopathy, while arteritis is frequentlymentioned in the differential diagnosis, but it is an extremelyrare cause of thrombotic stroke.

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

Identification of the specific focal vascular lesion, includingits nature, severity, and localization, is important fortreatment since local therapy may be effective (eg, surgery,angioplasty, intraarterial thrombolysis). It should be possible

AtherosclerosisDissectionTakayasu arteritisGiant cell arteritisFibromuscular dysplasia

AtherosclerosisDissectionArteritis/vasculitisNoninflammatory vasculopathyMoyamoya syndromeVasoconstriction

clinically in most patients to determine whether the localvascular disease is within the anterior (carotid) or posterior(vertebrobasilar) circulation and whether the disorder affectslarge or penetrating arteries. (See "Clinical diagnosis ofstroke subtypes", section on 'Neurologic examination'.)

Delivery of adequate blood through a blocked or partiallyblocked artery depends upon many factors, including bloodpressure, blood viscosity, and collateral flow. Local vascularlesions also may throw off emboli, which can cause transientsymptoms. In patients with thrombosis, the neurologicsymptoms often fluctuate, remit, or progress in a stutteringfashion (figure 3). (See "Clinical diagnosis of strokesubtypes", section on 'Clinical course' and "Etiology andclinical manifestations of transient ischemic attack", sectionon 'Clinical manifestations'.)

Small vessel disease — Small vessel disease affectsthe intracerebral arterial system, specifically penetratingarteries that arise from the distal vertebral artery, the basilarartery, the middle cerebral artery stem, and the arteries of thecircle of Willis. These arteries thrombose due to:

The most common cause of obstruction of the smallerarteries and arterioles that penetrate at right angles to supplythe deeper structures within the brain (eg, basal ganglia,internal capsule, thalamus, pons) is lipohyalinosis (ie,blockage of an artery by medial hypertrophy and lipidadmixed with fibrinoid material in the hypertrophied arterialwall). A stroke due to obstruction of these vessels is referredto as a lacunar stroke. (See "Lacunar infarcts".)Lipohyalinosis is most often related to hypertension, butaging may play a role.

Microatheromas can also block these small penetratingarteries, as can plaques within the larger arteries that blockor extend into the orifices of the branches (calledatheromatous branch disease) [1].

Penetrating artery occlusions usually cause symptoms thatdevelop during a short period of time, hours or at most a fewdays (figure 4), compared with large artery­related brainischemia, which can evolve over a longer period.

Embolism — Embolic strokes are divided into fourcategories (table 1).

Lipohyalinosis (a lipid hyaline build­up distallysecondary to hypertension) and fibrinoid degeneration

Atheroma formation at their origin or in the parent largeartery

Those with a known source that is cardiac

Those with a possible cardiac or aortic source basedupon transthoracic and/or transesophagealechocardiographic findings

The symptoms depend upon the region of brain renderedischemic [4,5]. The embolus suddenly blocks the recipientsite so that the onset of symptoms is abrupt and usuallymaximal at the start (figure 5). Unlike thrombosis, multiplesites within different vascular territories may be affectedwhen the source is the heart (eg, left atrial appendage or leftventricular thrombus) or aorta. Treatment will depend uponthe source and composition of the embolus. (See "Secondaryprevention for specific causes of ischemic stroke andtransient ischemic attack".)

Cardioembolic strokes usually occur abruptly, although theyoccasionally present with stuttering, fluctuating symptoms.The symptoms may clear entirely since emboli can migrateand lyse, particularly those composed of thrombus. Whenthis occurs, infarction generally also occurs but is silent; thearea of infarction is smaller than the area of ischemia thatgave rise to the symptoms. This process is often referred toas a TIA due to embolism, although it is more correctlytermed an embolic infarction or stroke in which thesymptoms clear within 24 hours.

Cardioembolic strokes can be divided into those with aknown source and those with a possible cardiac orascending aortic source based upon transthoracic and/ortransesophageal echocardiographic findings [3].

High­risk cardiac source — The diagnosis of embolicstrokes with a known cardiac source is generally agreedupon by physicians (table 2) [6,7]; included in this categoryare those due to:

Those with an arterial source (artery to arteryembolism)

Those with a truly unknown source in which tests forembolic sources are negative

Atrial fibrillation and paroxysmal atrial fibrillationRheumatic mitral or aortic valve diseaseBioprosthetic and mechanical heart valvesAtrial or ventricular thrombusSick sinus syndromeSustained atrial flutterRecent myocardial infarction (within one month)Chronic myocardial infarction together with ejectionfraction <28 percent

Symptomatic congestive heart failure with ejectionfraction <30 percent

Dilated cardiomyopathyFibrous nonbacterial endocarditis as found in patientswith systemic lupus (ie, Libman­Sacks endocarditis),antiphospholipid syndrome, and cancer (maranticendocarditis)

Infective endocarditis

With CABG, for example, the incidence of postoperativeneurologic sequelae is approximately 2 to 6 percent, most ofwhich is due to stroke [8]. Atheroemboli associated withascending aortic atherosclerosis is probably the mostcommon cause. (See "Neurologic complications of cardiacsurgery".)

Potential cardiac source — Embolic strokes consideredto have a potential cardiac source (table 2) are ones in whicha possible source is detected (usually) by echocardiographicmethods [6,7], including:

In this group, the association of the cardiac or aortic lesionand the rate of embolism is often uncertain, since some ofthese lesions do not have a high frequency of embolism andare often incidental findings unrelated to the stroke event [9].Thus, they are considered potential sources of embolism. Atruly unknown source represents embolic strokes in which noclinical evidence of heart disease is present (table 1).

Aortic atherosclerosis — In longitudinal populationstudies with nonselected patients, complex aorticatherosclerosis does not appear to be associated with anyincreased primary ischemic stroke risk [10­12]. However,most studies evaluating secondary stroke risk have foundthat complex aortic atherosclerosis is a risk factor forrecurrent stroke [13­16].

The range of findings is illustrated by the following studies:

Papillary fibroelastomaLeft atrial myxomaCoronary artery bypass graft (CABG) surgery

Mitral annular calcificationPatent foramen ovaleAtrial septal aneurysmAtrial septal aneurysm with patent foramen ovaleLeft ventricular aneurysm without thrombusIsolated left atrial smoke on echocardiography (nomitral stenosis or atrial fibrillation)

Complex atheroma in the ascending aorta or proximalarch (see 'Aortic atherosclerosis' below)

A prospective case­control study examined thefrequency and thickness of atherosclerotic plaques inthe ascending aorta and proximal arch in 250 patientsadmitted to the hospital with ischemic stroke and 250consecutive controls, all over the age of 60 years [14].Atherosclerotic plaques ≥4 mm in thickness were foundin 14 percent of patients compared with 2 percent ofcontrols, and the odds ratio for ischemic stroke amongpatients with such plaques was 9.1 after adjustment foratherosclerotic risk factors. In addition, aorticatherosclerotic plaques ≥4 mm were much morecommon in patients with brain infarcts of unknown

Methodologic differences are a potential explanation for thediscrepant results of these reports assessing the risk ofischemic stroke related to aortic atherosclerosis, as theearlier case­control studies may have been skewed byselection and referral bias. However, many patients withaortic atherosclerosis also have cardiac or large arterylesions, a problem that may confound purely epidemiologicstudies.

In the author's opinion, there is no question that largeprotruding plaques in the ascending aorta and arch,particularly mobile plaques, are an important cause of stroke[17].

Systemic hypoperfusion — Reduced blood flow is moreglobal in patients with systemic hypoperfusion and does notaffect isolated regions. The reduced perfusion can be due tocardiac pump failure caused by cardiac arrest or arrhythmia,or to reduced cardiac output related to acute myocardialischemia, pulmonary embolism, pericardial effusion, orbleeding. Hypoxemia may further reduce the amount ofoxygen carried to the brain.

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

The most severe ischemia may occur in border zone(watershed) regions between the major cerebral supplyarteries since these areas are most vulnerable to systemichypoperfusion. The signs that may occur with borderzoneinfarction include cortical blindness, or at least bilateral visualloss; stupor; and weakness of the shoulders and thighs withsparing of the face, hands, and feet (a pattern likened to a"man­in­a­barrel").

Blood disorders — Blood and coagulation disorders are an

cause (relative risk 4.7).

In contrast, a population­based study of 1135 subjectswho had transesophageal echocardiography (TEE)found that complex atherosclerotic plaque (>4 mm withor without mobile debris) in the ascending andtransverse aortic arch was not a significant risk factorfor cryptogenic ischemic stroke or TIA after adjustingfor age, gender, and other clinical risk factors [11].However, there was an association between complexaortic plaque and noncryptogenic stroke. Theinvestigators concluded that complex aortic arch debrisis a marker for the presence of generalizedatherosclerosis.

uncommon primary cause of stroke and TIA, but they shouldbe considered in patients younger than age 45, patients witha history of clotting dysfunction, and in patients with ahistory of cryptogenic stroke [9]. The blood disordersassociated with arterial cerebral infarction include:

Factor V Leiden mutation and prothrombin 20210 mutationsare associated mostly with venous rather than arterialthrombosis. They can result in cerebral venous thrombosis ordeep venous thrombosis with paradoxical emboli. (See"Etiology, clinical features, and diagnosis of cerebral venousthrombosis".)

Infectious and inflammatory disease such as pneumonia,urinary tract infections, Crohn's disease, ulcerative colitis,HIV/AIDS, and cancers result in a rise in acute phasereactants such as fibrinogen, C­reactive protein, andcoagulation factors VII and VIII. In the presence of anendothelial cardiac or vascular lesion, this increase canpromote active thrombosis and embolism.

TOAST classification — The TOAST classification schemefor ischemic stroke is widely used and has goodinterobserver agreement [18]. The TOAST system (table 3)attempts to classify ischemic strokes according to the majorpathophysiologic mechanisms that are recognized as thecause of most ischemic strokes (table 1). It assignsischemic strokes to five subtypes based upon clinicalfeatures and the results of ancillary studies including brainimaging, neurovascular evaluations, cardiac tests, andlaboratory evaluations for a prothrombotic state.

The five TOAST subtypes of ischemic stroke are:

The last subtype, stroke of undetermined etiology, involvescases where the cause of a stroke cannot be determinedwith any degree of confidence, and by definition includesthose with two or more potential causes identified, those witha negative evaluation, and those with an incomplete

Sickle cell anemiaPolycythemia veraEssential thrombocytosisHeparin induced thrombocytopeniaProtein C or S deficiency, acquired or congenitalProthrombin gene mutationFactor V Leiden (resistance to activated protein C)Antithrombin III deficiencyAntiphospholipid syndromeHyperhomocysteinemia

Large artery atherosclerosisCardioembolismSmall vessel occlusionStroke of other determined etiologyStroke of undetermined etiology

evaluation. (See "Cryptogenic stroke".)

SSS­TOAST and CCS classification — Since the originalTOAST classification scheme was developed in the early1990s, advances in stroke evaluation and diagnostic imaginghave allowed more frequent identification of potentialvascular and cardiac causes of stroke [6]. These advancescould cause an increasing proportion of ischemic strokes tobe classified as "undetermined" if the strict definition of thiscategory (cases with two or more potential causes) isapplied.

As a result, an evidenced­based modification of the TOASTcriteria called SSS­TOAST was developed [6]. The SSS­TOAST system divides each of the original TOAST subtypesinto three subcategories as "evident," "probable," or"possible" based upon the weight of diagnostic evidence asdetermined by predefined clinical and imaging criteria. In afurther refinement, an automated version of the SSS­TOASTcalled the Causative Classification System (CCS) wasdevised (table 4) to improve its usefulness and accuracy forstroke subtyping [19]. The CCS is a computerized algorithmthat consists of questionnaire­style classification scheme.The CCS appears to have good inter­rater reliability amongmultiple centers [20]. It is available online athttps://ccs.mgh.harvard.edu/ccs_title.php.

The overall agreement between the original TOAST and CCSclassification systems appears to be moderate at best,suggesting that two methods often classify stroke cases intodifferent categories despite having categories with similarnames [21].

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

Intracerebral hemorrhage — Bleeding in ICH is usuallyderived from arterioles or small arteries. The bleeding isdirectly into the brain, forming a localized hematoma thatspreads along white matter pathways. Accumulation of bloodoccurs over minutes or hours; the hematoma graduallyenlarges by adding blood at its periphery like a snowballrolling downhill. The hematoma continues to grow until thepressure surrounding it increases enough to limit its spreador until the hemorrhage decompresses itself by emptying intothe ventricular system or into the cerebrospinal fluid (CSF)on the pial surface of the brain [22,23].

The most common causes of ICH are hypertension, trauma,bleeding diatheses, amyloid angiopathy, illicit drug use

Intracerebral hemorrhage (ICH) refers to bleedingdirectly into the brain parenchyma

Subarachnoid hemorrhage (SAH) refers to bleeding intothe cerebrospinal fluid within the subarachnoid spacethat surrounds the brain

(mostly amphetamines and cocaine), and vascularmalformations [22,23]. (See "Spontaneous intracerebralhemorrhage: 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 theportion of the brain that contains the hemorrhage [22,23]. Asexamples:

The neurologic symptoms usually increase gradually overminutes or a few hours. In contrast to brain embolism andSAH, the neurologic symptoms related to ICH may not beginabruptly and are not maximal at onset (figure 6) (and seebelow).

Headache, vomiting, and a decreased level ofconsciousness develop if the hematoma becomes largeenough to increase intracranial pressure or cause shifts inintracranial contents (figure 7) [22,23]. These symptoms areabsent with small hemorrhages; the clinical presentation inthis setting is that of a gradually progressing stroke.

ICH destroys brain tissue as it enlarges. The pressurecreated by blood and surrounding brain edema is life­threatening; large hematomas have a high mortality andmorbidity. The goal of treatment is to contain and limit thebleeding. Recurrences are unusual if the causative disorderis controlled (eg, hypertension or bleeding diathesis).

Subarachnoid hemorrhage — The two major causes ofSAH are rupture of arterial aneurysms that lie at the base ofthe brain and bleeding from vascular malformations that lienear the pial surface. Bleeding diatheses, trauma, amyloidangiopathy, and illicit drug use are less common. (See"Clinical manifestations and diagnosis of aneurysmalsubarachnoid hemorrhage".)

Rupture of an aneurysm releases blood directly into the CSFunder arterial pressure. The blood spreads quickly within theCSF, rapidly increasing intracranial pressure. Death or deepcoma ensues if the bleeding continues. The bleeding usuallylasts only a few seconds but rebleeding is very common.With causes of SAH other than aneurysm rupture, thebleeding is less abrupt and may continue over a longer periodof time.

Symptoms of SAH begin abruptly in contrast to the moregradual onset of ICH. The sudden increase in pressurecauses a cessation of activity (eg, loss of memory or focusor knees buckling). Headache is an invariable symptom andis typically instantly severe and widespread; the pain may

Bleeding into the right putamen and internal capsuleregion causes left limb motor and/or sensory signs

Bleeding into the cerebellum causes difficulty walkingBleeding into the left temporal lobe presents as aphasia

radiate into the neck or even down the back into the legs.Vomiting occurs soon after onset. There are usually noimportant focal neurologic signs unless bleeding occurs intothe brain and CSF at the same time (meningocerebralhemorrhage). Onset headache is more common than in ICH,and the combination of onset headache and vomiting isinfrequent in ischemic stroke (figure 7) [24]. (See "Clinicalmanifestations and diagnosis of aneurysmal subarachnoidhemorrhage".)

Approximately 30 percent of patients have a minorhemorrhage manifested only by sudden and severe headache(the so­called sentinel headache) that precedes a major SAH(figure 7) [24]. The complaint of the sudden onset of severeheadache is sufficiently characteristic that a minor SAHshould always be considered. In a prospective study of 148patients presenting with sudden and severe headache, forexample, subarachnoid hemorrhage was present in 25percent overall and 12 percent in patients in whom headachewas the only symptom [25].

The goal of treatment of SAH is to identify the cause andquickly treat it to prevent rebleeding. The other goal oftreatment is to prevent brain damage due to delayedischemia related to vasoconstriction of intracranial arteries;blood within the CSF induces vasoconstriction, which can beintense and severe. The treatment of SAH is discussedseparately. (See "Treatment of aneurysmal subarachnoidhemorrhage".)

EPIDEMIOLOGY — Globally, the incidence of stroke due toischemia is 68 percent, while the incidence of hemorrhagicstroke (intracerebral hemorrhage and subarachnoidhemorrhage combined) is 32 percent, reflecting a higherincidence of hemorrhagic stroke in low­ and middle­incomecountries [26]. In the United States, the proportion of allstrokes due to ischemia, intracerebral hemorrhage, andsubarachnoid hemorrhage is 87, 10, and 3 percent,respectively [27].

Worldwide, stroke is the second most common cause ofmortality and the third most common cause of disability [28].While the incidence of stroke is decreasing in high­incomecountries, including the United States [29], the incidence isincreasing in low­income countries [30]. The overall rate ofstroke­related mortality is decreasing in high and low incomecountries, but the absolute number of people with stroke,stroke survivors, stroke­related deaths, and the global burdenof stroke­related disability is high and increasing [30].

In the United States, the annual incidence of new orrecurrent stroke is about 795,000, of which about 610,000 arefirst­ever strokes, and 185,000 are recurrent strokes [27].There is a higher regional incidence and prevalence of strokeand a higher stroke mortality rate in the southeastern UnitedStates (sometimes referred to as the "stroke belt") than in

the rest of the country [31­35].

Men have a higher incidence of stroke than women atyounger but not older ages, with the incidence reversed andhigher for women by age 75 years and older [27].

Blacks and Hispanics have an increased risk of strokecompared with whites in the United States, as illustrated bythe following observations:

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The Northern Manhattan Study reported that the age­adjusted incidence of first ischemic stroke amongwhites, Hispanics, and blacks was 88, 149, and 191per 100,000 respectively [36]. Among blacks comparedwith whites, the relative rate of stroke attributed tointracranial atherosclerosis, extracranialatherosclerosis, lacunes, and cardioembolism was5.85, 3.18, 3.09, and 1.58 respectively. AmongHispanics compared with whites, the relative rate ofstroke attributed to intracranial atherosclerosis,extracranial atherosclerosis, lacunes, andcardioembolism was 5.00, 1.71, 2.32, and 1.42.

The Greater Cincinnati/Northern Kentucky Stroke Studyshowed that small vessel strokes and strokes ofundetermined origin were nearly twice as common, andlarge vessel strokes were 40 percent more common,among blacks compared with whites [37]. Theincidence of cardioembolic strokes was not significantlydifferent among blacks and whites.

An increased incidence of stroke has also been foundamong Mexican Americans compared with non­Hispanic whites [38].

Stroke prevalence rates (age 18 and older) for blacks,whites, Asians, and American Indian/Alaska nativesare 3.8, 3.0, 1.9, and 5.8 percent, respectively [27].

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Topic 1089 Version 17.0

Basics topics (see "Patient information: Hemorrhagicstroke (The Basics)" and "Patient information: Stroke(The Basics)")

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

GRAPHICS

Pathophysiologic ischemic strokeclassification

Large vessel atherothromboticstroke

More common

Bifurcation of the common carotid artery

Siphon portion of the common carotid artery

Middle cerebral artery stem

Intracranial vertebral arteries proximal tomiddle basilar artery

Origin of the vertebral arteries

Less common

Origin of the common carotid artery

Posterior cerebral artery stem

Origin of the major branches of the basilar­vertebral arteries

Origin of the branches of the anterior,middle, and posterior cerebral arteries

Small vessel (lacunar) stroke

Mechanism

Lipohyalinotic occlusion

Less frequently proximal atherothromboticocclusion

Least likely embolic occlusion

Most common locations

Penetrating branches of the anterior,middle, and posterior cerebral and basilararteries

Cardioaortic embolic stroke

Cardiac sources definite ­antithrombotic therapy generally used

Left atrial thrombus

Left ventricular thrombus

Atrial fibrillation and paroxysmal atrialfibrillation

Sustained atrial flutter

Recent myocardial infarction (within onemonth)

Rheumatic mitral or aortic valve disease

Bioprosthetic and mechanical heart valve

Chronic myocardial infarction with ejectionfraction <28 percent

Symptomatic heart failure with ejectionfraction <30 percent

Dilated cardiomyopathy

Cardiac sources definite ­anticoagulation hazardous

Bacterial endocarditis (exceptionnonbacterial)

Atrial myxoma

Cardiac sources possible

Mitral annular calcification

Patent foramen ovale

Atrial septal aneurysm

Atrial septal aneurysm with patent foramenovale

Left ventricular aneurysm withoutthrombus

Isolated left atrial smoke (no mitral stenosisor atrial fibrillation)

Mitral valve strands

Ascending aortic atheromatous disease(>4 mm)

True unknown source embolic stroke

Other

Dissection

Moyamoya

Binswanger's disease

Primary thrombosis

Cerebral mass

Graphic 55099 Version 3.0

Anatomy of the cerebral arterial circulation

Frontal view of the carotid arteries, vertebral arteries and intracranial vessels and theircommunication with each other via the Circle of Willis.

Reproduced with permission from: Uflacker R. Atlas Of Vascular Anatomy: An AngiographicApproach, Second Edition. Philadelphia: Lippincott Williams & Wilkins, 2006. Copyright © 2006Lippincott Williams & Wilkins.

Graphic 51410 Version 5.0

Major cerebral vascular territories

Representation of the territories of the major cerebral vessels shown ina coronal section of the brain.

Reproduced with permission from Kistler, JP, et al, Cerebrovascular Diseases.Harrison's Principles of Internal Medicine, 13th ed, McGraw­Hill, New York 1994.Copyright 1994 McGraw­Hill Companies, Inc.

Graphic 65199 Version 2.0

Stuttering time course of thrombotic stroke

The course of weakness of the right limb in a patient with athrombotic stroke reveals fluctuating symptoms, varying betweennormal and abnormal, progressing in a stepwise or stuttering fashionwith some periods of improvement.

Graphic 64107 Version 2.0

Time course of lacunar infarction

Penetrating artery occlusions usually cause symptoms that developover a short period of time, hours or at most a few days, compared tolarge artery­related brain ischemia which can evolve over a longerperiod. A stuttering course may ensue, as with large arterythrombosis. This patient had a pure motor hemiparesis.

Graphic 52246 Version 1.0

Time course of embolic stroke

Embolic stroke occurs suddenly, with symptoms maximal at onset.This patient had multiple embolic events with different clinicalsymptoms (initially weakness, followed by paresthesias).

Graphic 73261 Version 1.0

Cardioaortic sources of cerebralembolism

Sources withhigh primaryrisk forischemicstroke

Left atrialthrombus

Left ventricularthrombus

Atrial fibrillation

Paroxysmalatrial fibrillation

Sick sinussyndrome

Atrial flutter

Recentmyocardialinfarction(within onemonth prior tostroke)

Mitral stenosisor rheumaticvalve disease

Bioprostheticand mechanicalheart valves

Chronicmyocardialinfarctiontogether withlow ejectionfraction (<28percent)

Dilatedcardiomyopathy(priorestablisheddiagnosis or leftventriculardilatation withan ejectionfraction of <40percent or

Sources with low oruncertain primaryrisk for ischemicstroke

Cardiac sources ofembolism

Mitral annularcalcification

Patent foramen ovale

Atrial septal aneurysm

Atrial septal aneurysmand patent foramenovale

Left ventricularaneurysm withoutthrombus

Left atrial smoke

Congestive heart failurewith ejection fraction<30 percent

Apical akinesia

Wall motionabnormalities(hypokinesia, akinesia,dyskinesia) other thanapical akinesia

Hypertrophiccardiomyopathy

Left ventricularhypertrophy

Left ventricularhypertrabeculation/non­compaction

Aortic sources ofembolism

Complex atheroma inthe ascending aorta orproximal arch(protruding with >4mm thickness, ormobile debris, or plaqueulceration)

fractionalshortening of<25 percent)

Nonbacterialthromboticendocarditis

Infectiveendocarditis

Papillaryfibroelastoma

Left atrialmyxoma

The high and low risk cardioaortic sources inthis table are separated using an arbitrary 2percent annual or one­time primary stroke riskthreshold.

Data from:1. Ay H, Benner T, Arsava EM, et al. A

computerized algorithm for etiologicclassification of ischemic stroke: the CausativeClassification of Stroke System. Stroke 2007;38:2979.

2. Ay H, Furie KL, Singhal A, et al. An evidence­based causative classification system for acuteischemic stroke. Ann Neurol 2005; 58:688.

3. Arsava EM, Ballabio E, Benner T, et al. TheCausative Classification of Stroke system: aninternational reliability and optimization study.Neurology 2010; 75:1277.

Reproduced and modified with permission from: AyH, Furie KL, Singhal A, et al. An evidence­basedcausative classification system for acute ischemicstroke. Ann Neurol 2005; 58:688. Copyright © 2005American Neurological Association.

Graphic 60843 Version 8.0

TOAST classification of subtypesof acute ischemic stroke

Large­artery atherosclerosis

Cardioembolism

Small­vessel occlusion

Stroke of other determined etiology

Stroke of undetermined etiology

Two or more causes identified

Negative evaluation

Incomplete evaluation

Graphic 62571 Version 1.0

Causative Classification System(CCS) of ischemic stroke etiology

Strokemechanism

Level ofconfidence

Criteria

Large arteryatherosclerosis

Evident 1. Eitherocclusive orstenotic (≥50percentdiameterreduction or<50 percentdiameterreduction withplaqueulceration orthrombosis)vasculardisease judgedto be caused byatherosclerosisin the clinicallyrelevantextracranial orintracranialarteries

2. The absenceof acuteinfarction invascularterritories otherthan thestenotic oroccluded artery

Probable 1. History of ≥1transientmonocularblindness(TMB), TIA, orstroke from theterritory ofindex arteryaffected byatherosclerosiswithin the lastmonth

2. Evidence ofnear­occlusivestenosis ornonchronic

completeocclusionjudged to becaused byatherosclerosisin the clinicallyrelevantextracranial orintracranialarteries (exceptfor thevertebralarteries)

3. The presenceof ipsilateraland unilateralinternalwatershedinfarctions ormultiple,temporallyseparate,infarctionsexclusivelywithin theterritory of theaffected artery

Possible 1. The presenceof anatheroscleroticplaqueprotruding intothe lumen andcausing mildstenosis (<50percent) in theabsence of anydetectableplaqueulceration orthrombosis in aclinicallyrelevantextracranial orintracranialartery andhistory of ≥2TMB, TIA, orstroke from theterritory ofindex arteryaffected byatherosclerosis,

at least 1 eventwithin the lastmonth

2. Evidence forevident largearteryatherosclerosisin the absenceof completediagnosticinvestigationfor othermechanisms

Cardio­aorticembolism

Evident 1. The presenceof a high­riskcardiac sourceof cerebralembolism

Probable 1. Evidence ofsystemicembolism

2. The presenceof multipleacuteinfarctions thathave occurredclosely relatedin time withinboth right andleft anterior orboth anteriorand posteriorcirculations inthe absence ofocclusion ornear­occlusivestenosis of allrelevantvessels. Otherdiseases thatcan causemultifocalischemic braininjury such asvasculitides,vasculopathies,andhaemostatic orhemodynamicdisturbancesmust not bepresent.

Possible 1. The presenceof a cardiaccondition withlow oruncertainprimary risk ofcerebralembolism

2. Evidence forevident cardio­aortic embolismin the absenceof completediagnosticinvestigationfor othermechanisms

Small arteryocclusion

Evident 1. Imagingevidence of asingle andclinicallyrelevant acuteinfarction <20mm in greatestdiameter withinthe territory ofbasal orbrainstempenetratingarteries in theabsence of anyother pathologyin the parentartery at thesite of theorigin of thepenetratingartery (focalatheroma,parent vesseldissection,vasculitis,vasospasm,etc)

Probable 1. The presenceof stereotypiclacunartransientischemicattacks withinthe past week

2. The presenceof a classicallacunarsyndrome

Possible 1. Presentingwith a classicallacunarsyndrome inthe absence ofimaging that issensitiveenough todetect smallinfarctions

2. Evidence forevident smallartery occlusionin the absenceof completediagnosticinvestigationfor othermechanisms

Other causes Evident 1. The presenceof a specificdisease processthat involvesclinicallyappropriatebrain arteries

Probable 1. A specificdisease processthat hasoccurred inclear and closetemporal orspatialrelationship tothe onset ofbrain infarctionsuch as arterialdissection,cardiac orarterial surgery,andcardiovascularinterventions

Possible 1. Evidence foran evidentother cause inthe absence ofcomplete

diagnosticinvestigationfor mechanismslisted above

Undeterminedcauses

Unknown

Cryptogenicembolism:

1. Angiographicevidence ofabrupt cut­offconsistent witha blood clotwithinotherwiseangiographicallynormal lookingintracranialarteries

2. Imagingevidence ofcompleterecanalizationof previouslyoccluded artery

3. The presenceof multipleacuteinfarctions thathave occurredclosely relatedin time withoutdetectableabnormality inthe relevantvessels

Othercryptogenic:

1. Those notfulfilling thecriteria forcryptogenicembolism

Incompleteevaluation:

1. The absenceof diagnostictests that,under theexaminer'sjudgment, theirpresence wouldhave beenessential touncover theunderlyingetiology

Unclassified 1. The presence

of >1 evidentmechanism inwhich there iseither probableevidence foreach, or noprobableevidence to beable toestablish asingle cause

Reproduced with permission from: Ay H, Benner T,Arsava EM. A computerized algorithm for etiologicclassification of ischemic stroke: the CausativeClassification of Stroke System. Stroke 2007;38:2979.

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Time course of neurologic changes in intracerebralhemorrhage

Schematic representation of rapid downhill course in terms of unusualbehavior (green), hemimotor function (blue), and consciousness (red)in a patient with intracerebral (intraparenchymal) hemorrhage.

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Headache and vomiting in stroke subtypes

The frequency of sentinel headache, onset headache, and vomiting inthree subtypes of stroke: subarachnoid hemorrhage (SAH),intraparenchymal (intracerebral) hemorrhage (IPH), and ischemicstroke (IS). Onset headache was present in virtually all patients withSAH and about one­half of those with IPH; all of these symptoms wereinfrequent in patients with IS.

Data from: Gorelick PB, Hier DB, Caplan LR, et al, Neurology 1986; 36:1445.

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