ABSTRACT
A. The Aortic Arch and Its Three Major Vessels (Fig. 11-1) 1. The aortic arch gives rise to 3 major branches: the
brachiocephalic, left common carotid, and left subclavian arteries
2. The brachiocephalic artery gives rise to the right common carotid and right subclavian arteries
3. The vertebral arteries branch off the subclavian artery
B. The Carotid Artery (Fig. 11-2) 1. The common carotid artery bifurcates into the internal
and external carotid arteries at approximately the cervical vertebral level 3-4
2. The main branches of the internal carotid artery are listed in Table 11-1
3. The internal carotid artery is composed of several segments a. Cervical: no branches arise from this segment b. Petrous: internal carotid artery enters the carotid canal
of the temporal bone; a few minor branches (vidian, caroticotympanic) arise from this segment
c. Cavernous: traverses the cavernous sinus along with cranial nerves III, IV, VI, and V1 and V2; a few minor branches (meningohypophyseal trunk, inferolateral trunk, capsular arteries) arise from this segment
d. Clinoid: small segment; no branches e. Ophthalmic: most commonly intradural; gives rise to
ophthalmic artery (supplies the retina) and superior hypophyseal artery
f. Communicating segment: begins proximal to the origin of the posterior communicating artery and ends where the carotid terminates; the two major branches are the
Table 11-1. Main Branches of Internal Carotid Artery System
Branch Supplies
posterior communicating artery and anterior choroidal artery
g. At the carotid terminus, the artery bifurcates into the anterior and middle cerebral arteries
C. Anterior Cerebral Artery (ACA) (Fig. 11-3) 1. Composed of perforating vessels and cortical vessels
a. Perforating or penetrating arteries (including recurrent artery of Heubner) supply deep structures: head of caudate nucleus, corpus callosum, part of fornix
b. Cortical branches supply the medial aspect of the cerebral hemisphere
D. Middle Cerebral Artery (MCA) (Fig. 11-4) 1. Has both perforating branches and cortical branches 2. Perforating branches
a. Arise from segment M1 (extends from carotid terminus to MCA bifurcation) and
b. Are called the lateral lenticulostriate arteries
c. Supply the basal ganglia and internal capsule 3. Cortical branches: supply lateral aspect of cerebral
hemisphere and anterior temporal lobe
E. Anastomoses 1. Collateral circulation: refers to alternative paths of
blood supply (should one artery be impaired or occluded)
2. Several anastomoses supply collateral circulation to the brain a. Circle of Willis (Fig. 11-5)
1) An anastomotic ring connecting the anterior circulation (carotid artery system) and posterior circulation (vertebrobasilar system)
2) Less than 35% of people have a complete circle of Willis 3) Components of the circle of Willis are shown in
Figure 11-5 b. Leptomeningeal collaterals: refers to anastomoses of
distal cortical arteries
c. External carotid or extracranial vertebral artery-tointracranial artery anastomoses 1) External carotid artery commonly anastomoses with
ophthalmic artery, serving as collateral circulation for distal internal carotid artery
F. Vertebral Artery (Fig. 11-6) 1. The right and left vertebral arteries arise from the
respective subclavian arteries 2. The vertebral arteries ascend through the transverse
foramina of vertebral bodies C6 to the axis; minor meningeal branches arise from these segments
3. Vertebral arteries enter the foramen magnum and pierce the dura mater
4. Intracranial vertebral arteries extend the length of the medulla and join at the pontomedullary junction to form the basilar artery
5. Important branches of the intracranial vertebral arteries include the following: a. Anterior spinal artery-supplies midline medulla,
including the pyramids, and extends caudally to supply ventrolateral spinal cord
b. Posterior spinal artery-supplies a portion of lateral medulla and extends caudally to supply posterior funiculus of spinal cord
c. Paramedian perforating arteries-supply the paramedian aspect of the medulla
d. Posterior inferior cerebellar artery (PICA)—supplies lateral medulla and inferior aspect of the cerebellum (Fig. 11-7 A)
G. Basilar Artery (Fig. 11-6) 1. Formed by union of left and right vertebral arteries at
pontomedullary junction 2. Extends to the interpeduncular fossa where it ends by
branching into the posterior cerebral arteries (PCAs) 3. Median and paramedian perforating branches supply
their respective areas (Fig. 11-7 B) 4. Two long circumferential branches, anterior inferior
cerebellar artery (AICA) and superior cerebellar artery (SCA), supply lateral pons inferiorly and superiorly, respectively, and a portion of the cerebellum
5. SCA also supplies part of midbrain
H. Posterior Cerebral Artery (PCA) (Fig. 11-6) 1. Basilar artery bifurcates into right and left PCAs at the
interpeduncular fossa 2. Each PCA gives rise to both perforating and cortical
arteries 3. Perforating branches arise from segments P1 and P2 of
PCA a. Supply the thalamus b. Supply portions of the midbrain (Fig. 11-7 C)
4. Cortical branches a. Medial occipital artery gives rise to parieto-occipital and
calcarine branches (supply visual cortex) b. Lateral occipital artery gives rise to temporal artery (sup-
plies inferior temporal lobe)
I. Blood Supply to Deep Structures and Cerebellum (Tables 11-2 and 11-3)
J. Arterial Vascular Supply: borders of the arterial vascular supply are shown in Figure 11-8
K. Cerebral Venous System (Fig. 11-9) 1. Venous drainage occurs from pial venous plexuses that
form within the substance of brain and drain into larger cerebral veins that, in turn, pass through subarachnoid space to empty into dural venous sinuses; small veins of the scalp communicate with dural venous sinuses via emissary veins
2. Dural venous sinuses are formed where periosteal and meningeal layers separate; these venous structures have no valves
3. Important dural venous sinuses: superior sagittal, inferior sagittal, straight (rectus), transverse, and sigmoid sinuses
4. Cavernous sinus: important venous structure composed of network of venous channels; situated on either side of sella turcica, with some interconnecting channels
5. Ophthalmic veins drain into the cavernous sinus, from which blood drains to superior and inferior petrosal veins to transverse and jugular veins, respectively
6. Deep cerebral veins a. Drain deep structures (e.g., basal ganglia, deep white
matter, diencephalon) into the internal cerebral vein and great cerebral vein
b. Internal cerebral veins c. Basal vein of Rosenthal d. Great cerebral vein of Galen
7. Superficial cerebral veins a. Superficial veins drain cerebral cortex and superficial
subcortical white matter into venous sinuses b. Superior cerebral veins c. Inferior cerebral veins d. Superficial middle cerebral vein e. Superior anastomotic vein (Trolard) f. Inferior anastomotic vein (Labbé)
L. Spinal Cord Vasculature 1. Blood supply to the spinal cord emerges from anterior
and posterior spinal arteries (branches of vertebral arteries) and from spinal branches of segmental arteries
2. Anterior spinal artery a. Paired anterior spinal arteries branch from vertebral
arteries and join to form a single artery that descends along the anterior (ventral) aspect of the medulla and spinal cord
Table 11-2. Blood Supply to Basal Ganglia and Thalamus
Structure Supply
Table 11-3. Blood Supply to Cerebellum
Artery Supplies
The middle meningeal artery enters the skull via the foramen spinosum
b. As anterior spinal artery descends along spinal cord, anastomotic branches from the anterior radicular arteries contribute to the vessel’s continuity
c. Supplies midline medulla (including pyramids) and provides sulcal branches that enter anterior median fissure of the spinal cord to supply anterior and lateral funiculi (Fig. 11-10 A)
3. Posterior spinal artery a. Paired posterior spinal arteries arise from vertebral arter-
ies (and occasionally PICA) and descend on posterior surface of spinal cord, medial to dorsal roots
b. Like the anterior spinal artery, these arteries receive contributions from radicular arteries as they descend
c. These arteries supply posterior third of spinal cord, including the posterior columns
4. Segmental arteries and radicular arteries a. Maintain continuity of anterior and posterior spinal
arteries at each level of spinal cord b. Include ascending cervical, intercostal, and lumbar
arteries c. Contribute branches that further divide into anterior
and posterior radicular arteries d. May be up to 31 pairs of radicular arteries: not every
radicular artery contributes to spinal cord vascularization e. Cervical cord has the most contributions; thoracic and
lumbar segments have fewer (perhaps 2-4) arteries that contribute to spinal cord blood supply, making the region more vulnerable to ischemia
f. Blood supply to mid-thoracic (T4-T6) cord is relatively tenuous: the vascular watershed zone of spinal cord, most vulnerable to ischemic insults
The blood supply to the mid-thoracic (T4-T6) spinal cord is relatively tenuous: the vascular watershed zone of the spinal cord, most vulnerable to ischemic insults
g. Artery of Adamkiewicz: large anterior radicular artery at level T12, L1, or L2; major source of blood to lower thoracic and upper lumbar cord (Fig. 11-10 B)
5. Veins of spinal cord a. Anterolateral and anteromedian veins drain anterior
cord b. Posterolateral and posteromedian veins drain posterior
cord c. These veins drain into radicular veins, which empty into
the epidural venous plexus d. The epidural venous plexus has longitudinal connections
with other veins of central nervous system (extending all the way to the brainstem region) and can drain into segmental veins and systemic venous system
A. Principles of Cellular Injury and Vascular Biology 1. Cellular injury and ischemia
a. Normal cerebral blood flow in humans is approximately 50 to 60 mL/100 g of brain tissue per minute to supply oxygen and glucose to tissues and remove lactic acid
b. When flow decreases to 20 to 40 mL/100 g per minute, neuronal dysfunction occurs
c. When flow is less than 10 to 15 mL/100 g per minute, irreversible tissue damage occurs
d. Because of extensive collateral circulation, there is variability in perfusion changes within an ischemic lesion
e. In the central core of the infarction, severity of hypoperfusion results in irreversible cellular damage
f. Around this core is a region of decreased flow in which either the critical flow threshold for cell death has not been reached or the duration of ischemia has been insufficient to cause irreversible damage, the so-called ischemic penumbra
g. If flow is not restored, this penumbra may result in permanent and irreversible damage
h. Secondary effects of ischemia 1) In addition to lack of energy supply to the tissue,
other mechanisms contribute to cell death 2) Excess glutamate release and impaired glutamate
reuptake during ischemia results in prolonged elevations of calcium in the cytosol; this elevated calcium in turn triggers proteases, lipases, endonucleases, and cytokines, which result in neuronal cell death
2. Pathology (Fig. 11-11 and 11-12) a. Acute (1 day-1 week)
1) Gross: affected area is edematous 2) Microscopic
a) Acutely, there are eosinophilic pyknotic neurons; there is neuropil vacuolation, often most prominent at the edge of the infarct
b) Within 1 to 3 days, an inflammatory response is seen, followed by mononuclear cell influx by days 3 to 5; the latter phagocytize dying cells
b. Subacute (1 week-1 month) 1) Gross: tissue destruction, liquefactive necrosis 2) Microscopic: reactive astrocytes and prominent
macrophage infiltration and phagocytosis are often seen
c. Chronic (>1 month) 1) Gross: cavitation of affected area with surrounding
gliosis 2) Microscopic: cystic cavity forms, surrounded by
gliosis; there may be residual macrophage infiltration (Fig. 11-12)
B. Atherogenesis 1. Is an important pathologic lesion responsible for
cerebral infarction 2. Atherosclerotic plaque formation requires several
sequential steps that are set into motion by certain triggers: hypertension, diabetes mellitus, obesity, chronic inflammation or infection, oxidized lipoproteins
3. Triggers result in activation of endothelial cells and expression of white blood cell adhesion protein
4. Certain adhesion molecules allow migration of white
blood cells into the intima, and these monocytes transform into macrophages
5. Subsequently, macrophages engulf specific lipoproteins and become “foam” cells, which can secrete mediators that allow continued accumulation of other monocytes, promote smooth muscle cell proliferation in the vessel, and change the extracellular matrix, degrading the collagen protective structure
6. The plaque is dynamic and may change over time because of continued triggers and risk factors: increased lipid content, intramural hemorrhage, calcification
7. The artery may show progressive narrowing of the lumen to occlusion or endothelial integrity may become vulnerable from proliferation of metalloproteinases degrading stability of the plaque
8. If the plaque become unstable and ruptures, the subendothelium is exposed, and platelets can adhere and aggregate, resulting in thrombus formation
9. Atherosclerosis is most common at arterial bifurcations (Fig. 11-13)
A. Large-Artery Disease: clinical syndromes (Table 11-4)
B. Small-Vessel Disease (lacunar stroke): clinical syndromes
1. Lacunar stroke refers to a 1.5-cm (greatest diameter) or smaller ischemic stroke within the distribution of a penetrating end artery (Additional information is given below, but the clinical-anatomic descriptions are provided here)
2. More than 20 lacunar syndromes have been described; the most common syndromes are listed in Table 11-5
A. Mechanisms and Causes of Ischemia 1. Definitions
a. Ischemic stroke: a fixed focal neurologic deficit attributable to an arterial or venous territory and lasting longer than 24 hours
b. Transient ischemic attack (TIA): a transient focal neurologic deficit attributable to an arterial territory and lasting less than 24 hours (by definition), most last less than 20 minutes
c. Reversible ischemic neurologic deficit (RIND): a focal neurologic deficit that lasts longer than 24 hours, but resolves by 3 weeks
2. Mechanisms a. Hypoperfusion: may be global or focal, the latter in the
setting of a single-vessel fixed stenosis b. Thrombosis (e.g., thrombus at site of atherosclerotic
plaque rupture) c. Embolism
1) Cardiac: thrombus, myxomatous emboli, vegetation 2) Artery to artery: cholesterol, platelet, thrombotic emboli 3) Rare: air, fat, or amniotic fluid emboli
3. Causes a. Etiology of thrombosis or emboli can be divided into
several categories (from proximal to distal) 1) Cardioembolic source 2) Large-vessel disease of extracranial vessels (aorta,
carotid arteries, vertebral arteries) 3) Large-vessel disease of intracranial vessels 4) Small-vessel disease (lacunar)
5) Abnormalities intrinsic to blood itself, i.e., coagulation defects
6) Venous infarction 7) Other
b. Desite thorough diagnostic evaluation, 15% to 35% of cerebral infarctions remain cryptogenic, i.e., no definable source
4. Prevalence: overall prevalence of selected cerebral infarction causes in a general population of patients is approximately a. Cardioembolic in 30% b. Large-vessel disease in 20% c. Small-vessel disease in 20% d. Other in 3% e. Cryptogenic in 27%
5. Differential diagnosis of ischemic stroke is listed in Table 11-6
6. General approach to ischemic stroke evaluation a. First goal: determine if patient is a candidate for acute
therapy, such as thrombolytic agents b. Second goal: prevent recurrent ischemic stroke
1) This involves diagnostic investigations to determine cause of ischemic stroke, specifically a cause that would require treatment other than an antiplatelet agent, such as surgery or anticoagulation
2) Identify risk factors such as hyperlipidemia, hypertension, others
c. Third goal: prevent early and late complications of ischemic stroke 1) Poststroke depression 2) Myocardial infarction (MI) 3) Pulmonary emboli/deep venous thrombosis 4) Aspiration pneumonia
7. General approach to ischemic stroke evaluation is shown in Fig. 11-14 a. Localizing a stroke requires knowledge of neuroanatomy
and typical clinical presentations (Tables 11-4 and 11-5) b. Localization can be aided by cross-sectional imaging
studies such as computed tomography (CT) and magnetic resonance imaging (MRI)
c. CT 1) May be negative early in ischemic stroke 2) Cortical ischemia may take 24 hours to evolve 3) Early signs of cortical ischemia may include
a) Sulcal effacement (most apparent with side-to-side comparison)
b) Loss of distinction between gray and white matter c) Dense MCA sign or hyperdense basilar artery may
also be seen, suggesting clot within the arteries d. MRI (Fig. 11-15)
Table 11-4. Large-Vessel Clinical Syndromes*
Vessel Clinical presentation
Table 11-5. Lacunar Syndromes
Typical clinical Typical Syndrome presentation localization
1) Random diffusion of water molecules: relatively free in extracellular space and restricted in intracellular space in normal state; best measured by diffusionweighted imaging (DWI)
2) Rapid dysfunction of cellular metabolism and ion exchange pumps cause massive shift of water from extracellular to intracellular compartment: cytotoxic edema
3) Cytotoxic edema forming early in ischemic stroke restricts diffusion of water molecules, resulting in increased signal on DWI and decreased signal on apparent diffusion coefficient (ADC) map
4) Diffusion signal increases very early (within minuteshours) and remains positive for about 2 weeks, then normalizes so that acute to subacute infarcts can be distinguished from old infarcts and background ischemic white matter changes
5) Patients with transient symptoms may also have abnormalities on DWI
6) FLAIR and T2-weighted images are also helpful for ischemic stroke
7) Caution: not all diffusion hyperintensity is an ischemic stroke; positive diffusion abnormalities have been described in neoplastic, infectious, and demyelinating processes
8. Special situation: stroke in the young-atherosclerosis is a common cause in younger patients, but nonathero-
sclerotic arteriopathies such as dissection and cardioembolic sources are frequent
9. Special situation: stroke during pregnancy a. Ischemic stroke and hemorrhage may occur during
pregnancy b. Pregnancy represents a special situation in which the
body is preparing for an event that requires rapid coagulation at the time of birth
c. Coagulation changes during pregnancy and postpartum period 1) When the placenta separates, maternal blood flows at
700 mL/min and is reduced by myometrial compression and thrombotic occlusion of the vessels
2) Coagulation is activated and fibrinogen is increased and coagulation inhibitors are decreased; coagulation system and fibrinolytic systems are important in controlling fibrin deposition in uteroplacental circulation while simultaneously preventing fibrin deposition in rest of vascular system
3) Changes typically begin in first trimester and increase maximally by late pregnancy
4) Erythrocyte mass increases at about 10 weeks and increases progressively until term
5) Plasma volume increases at about 10 weeks’ gestation and increases progressively until 30 to 34 weeks, after which it plateaus
6) Mean increase in plasma volume by 30 to 34 weeks is 50%
7) Because volume increases by 50% and erythrocyte mass increases only by 18% to 30%, the hematocrit decreases: anemia (30-34-week nadir)
8) Changes of the specific coagulation factors in pregnancy are noted in Table 11-7
d. Pregnancy and postpartum-associated cerebrovascular complications can include 1) Subarachnoid hemorrhage
a) Incidence: 20 per 100,000 pregnancies b) Etiology: aneurysmal rupture, arteriovenous
malformation (AVM) rupture, trauma c) More common to occur during pregnancy than
postpartum period 2) Intraparenchymal hemorrhage
a) Incidence: 4 per 100,000 b) Etiology: AVM rupture, cavernous malformation
rupture, eclampsia, venous thrombosis c) More common during postpartum period than
during pregnancy 3) Venous thrombosis (with ischemia and/or hemorrhage)
a) Incidence: 10 to 20 per 100,000 (higher in underdeveloped countries)
Table 11-6. Differential Diagnosis of Ischemic Stroke
b) Most common in postpartum period (80%) c) Often associated with predisposing factor for
thrombosis such as factor V Leiden mutation, dehydration, concurrent infection, sickle cell anemia
4) Pituitary apoplexy (Sheehan’s syndrome) 5) Arterial stroke
a) Incidence: 3.5 to 5 per 100,000
b) Highest risk in postpartum period c) Causes vary, with some pregnancy-specific and
some not pregnancy-specific d) Pregnancy-specific causes: eclampsia (common),
choriocarcinoma (rare), amniotic fluid embolism (rare), postpartum cerebral angiopathy (rare), peripartum cardiomyopathy (rare)
A. Cardioembolic Ischemic Stroke 1. Approximately 20% to 30% of cerebral infarctions in a
general population are result of a cardioembolic source 2. “Major cardiac risk sources” are established as causative
risk factors for TIA and cerebral infarction 3. “Minor risk sources” are established as potential sources
and carry an uncertain risk of recurrent stroke because of inconclusive data in epidemiologic literature (Table 11-8)
4. Nonvalvular atrial fibrillation a. Prevalence: 1% of general population, 10% of popula-
tion older than 75 years b. Risk factors for thromboembolism in patients with atrial
fibrillation include 1) Previous stroke or TIA 2) History of hypertension 3) Congestive heart failure or impaired left ventricular
dysfunction 4) Advanced age 5) Diabetes mellitus 6) Coronary artery disease 7) Left atrial thrombus or spontaneous echo contrast
c. Risk of stroke: may be as high as 10% to 12% per year with associated risk factors
d. Treatment 1) Anticoagulation with warfarin is superior to aspirin in
secondary prevention of stroke in patients with atrial fibrillation
2) Practice guidelines recommend adjusted dose anticoagulation in high-risk patients a) High-risk patients: those older than 75 years,
patients older than 60 with diabetes or coronary artery disease, all patients with risk factors for thromboembolism
b) Risk factors for thromboembolism: heart failure, left ventricular ejection fraction less than 0.35, history of hypertension, previous thromboembolism, rheumatic heart disease, prosthetic heart valves, thrombus detected on echocardiography
c) Goal international normalized ratio (INR) is 2.0 to 3.0 except for patients with rheumatic heart disease or prosthetic valves who may require a higher INR
d) Low-risk patients without risk factors for thromboembolism younger than 75 years can be treated with aspirin alone if they have not had a previous ischemic stroke or TIA
5. Impaired myocardial function and cardiomyopathy a. Can result in cardioembolic ischemic stroke b. Cardiomyopathy with left ventricular ejection fraction
less than 30% increases risk of ischemic stroke c. Anticoagulation is recommended for patients with
thromboembolic events related to cardiomyopathy 6. Myocardial infarction
a. Risk factors for ischemic stroke after MI: older age, apical or anterior wall MI, coexistence of left ventricular dysfunction or atrial fibrillation, echocardiographic evidence of mural thrombi or severe wall motion abnormalities, previous history of stroke, history of hypertension before MI, history of systemic or pulmonary embolism
b. Most cardioembolic events occur within first 2 weeks after acute MI, and one-third occur within the first
Table 11-7. Changes in Specific Coagulation Factors in Pregnancy
Increased Decreased No change
Table 11-8. Major and Minor Cardiac Risk Sources
Major risk sources Minor risk sources
month; stroke risk is greatest in the first week and persists for 4 to 6 months
c. In absence of aforementioned risk factors, old MI is not usually responsible for acute cerebrovascular ischemic event
d. Treatment: short-term anticoagulation in addition to aspirin may be recommended for high-risk patients with recent MI
7. Left atrial spontaneous echo contrast a. Echocardiographic finding b. May represent local blood stasis; often seen with atrial
fibrillation or left atrial thrombus c. Unclear whether patients with this finding (by itself)
benefit from antiplatelet or anticoagulation therapy d. This finding should lead to further evaluation with
Holter monitor or telemetry for paroxysmal atrial fibrillation
8. Infectious endocarditis a. Typical sources
1) Staphylococcus aureus 2) Streptococcus viridans
b. Risk factors 1) Intravenous drug use (generally involving the right-
sided heart valves) 2) Prosthetic heart valves 3) Structural heart valve or other cardiac disease
c. Neurologic complications 1) Ischemic stroke due to emboli 2) Mycotic aneurysm formation with potential rupture 3) Intracranial abscesses
d. Diagnosis 1) Transesophageal echocardiography (TEE) 2) Blood cultures
e. Clinical picture: new cardiac murmur, fever, Janeway lesions, Osler’s nodes, Roth’s spots
f. Treatment 1) Appropriate antibiotics depending on culture results 2) Surgery may be needed for ruptured mycotic
aneurysm or asymptomatic large or enlarging mycotic aneurysm
9. Nonbacterial thrombotic endocarditis (NBTE) a. Libman-Sacks endocarditis
1) May be associated with systemic lupus erythematosus 2) Valvular vegetations consist of immune complexes,
white blood cells, fibrin and platelet thrombi, fibrosis 3) Mitral, aortic, and tricuspid valves are usually affected
b. Marantic endocarditis 1) This term usually refers to NBTE in patients with
malignancy 2) The pathology is very similar to that of Libman-Sacks
endocarditis
3) Often, platelet and fibrin thrombi, usually of aortic and mitral valves
c. Sources 1) Systemic lupus erythematosus 2) Human immunodeficiency virus (HIV) infection 3) Antiphospholipid antibody syndrome 4) Malignancies (usually adenocarinomas)
d. Neurologic complications 1) Ischemic stroke 2) Systemic emboli are also common
e. Diagnosis 1) TEE 2) Blood cultures to rule out infection 3) Other systemic findings to suggest specific source
(e.g., known malignancy, HIV infection, lupus) f. Treatment
1) Anticoagulation is generally considered 2) If heart valve is damaged, surgery or valvuloplasty
may be considered 10. Osler-Weber-Rendu disease (see also Chapter 13)
a. Autosomal dominant condition characterized by numerous telangiectasias in multiple organs, including lung, liver, kidney, skin, brain
b. Neurologic manifestations due most commonly to cerebral ischemia from pulmonary fistulae
c. Treatment: treat pulmonary fistulae 11. Valvular heart disease and prosthetic (mechanical)
heart valves a. Valvular heart disease and mechanical, prosthetic valves
increase risk for ischemic stroke b. Risk factors for ischemic stroke with prosthetic valves:
advanced age, previous thromboembolic event, left ventricular dysfunction, associated atrial fibrillation, left atrial thrombus, mitral position of valve, tilting disk valve, and caged-ball valves
c. Risk of thromboembolism is also higher with multiple (rather than single) prosthetic valves
d. Anticoagulation is preferred over antiplatelet agents for prosthetic valves; level of anticoagulation depends on type of prosthetic valve
12. Patent foramen ovale (PFO) a. Association between PFO and cerebral infarction has
been controversial, with varying results from epidemiologic studies; population-based echocardiographic study suggests prevalence of 25% in general population
b. Risk factors thought to increase probability that PFO is associated with cerebral infarction: size, shunting characteristics (right to left), associated atrial septal aneurysm, known deep venous thrombosis, cortical stroke
c. Treatment is controversial
d. Treatment options for secondary prevention: antiplatelet drugs, anticoagulation, closure of PFO with endovascular device, or open heart surgery and PFO repair
e. No definitive data on which treatment is better than aspirin and each has its own associated risks
f. Studies on both device closure and surgery suggest recurrent stroke risk is 3% to 4% per year; this suggests other mechanisms may have a role and appropriate selection needs to be refined
13. Diagnostic testing for cardioembolic ischemic mechanisms
a. Electrocardiography (ECG) (electrocardiogram)—all patients should have ECG to evaluate for dysrhthymia, MI, or suggestion of ventricular dysfunction
b. Echocardiography 1) May be used to confirm major sources and to detect
minor sources of cardioembolism 2) TEE vs. transthoracic echocardiography (TTE)
a) Sensitivity and specificity for left ventricular thrombi similar for TEE and TTE
b) Advantages of TTE: noninvasive, provides a better estimate of left ventricular function than TEE
c) Disadvantage of TTE: difficulty in achieving adequate window in larger patients
d) Advantages of TEE i) Far superior to TTE for left atrial thrombus ii) More sensitive than TTE for detecting other
potential sources of cardioembolism: aortic atheromatous disease or dissection, spontaneous echo contrast, PFO, atrial septal aneurysm
c. Blood cultures: if endocarditis is suspected d. Laboratory tests: consider additional tests such as anti-
nuclear antibody (ANA), ds-DNA, erythrocyte sedimentation rate, HIV, malignancy screen if NBTE is discovered
B. Extracranial Large-Artery Disease 1. Differential diagnosis of extracranial large-vessel disease
is listed in Table 11-6 2. Prevalence: approximately 15% to 20% of strokes are
secondary to large-vessel disease 3. Aortic atherosclerosis
a. Epidemiologic data suggest that aortic plaque 4 mm or larger is independent risk factor for ischemic stroke
b. Stroke risk is greater for complex, mobile plaques larger than 5 mm
c. Diagnosis: TEE is preferred test for diagnosis of aortic atherosclerosis; however, because optimal treatment is unclear, it may not be necessary to perform TEE only to look for aortic disease
d. Treatment 1) Currently, best antithrombotic management is not
defined, with conflicting data on anticoagulation vs. antiplatelet agents
2) The only randomized clinical trial suggests anticoagulation is not superior to antiplatelet agents
4. Aortic dissection a. Pathology and pathophysiology
1) Result of spontaneous medial hemorrhage and cleavage creating a false lumen that communicates with true lumen via an intimal tear
2) Two-thirds of aortic dissections involve the ascending aorta
b. Clinical 1) Clues to diagnosis on history: chest and/or back pain
(although may not be elicited in patients with aphasia or altered mental status)
2) Clues to diagnosis on examination: aortic regurgitation murmur, hypotension, reduced peripheral pulses, different blood pressure recordings between upper limbs
3) Neurologic complications of aortic dissection: TIA, cerebral infarction, spinal artery syndrome, syncope, ischemic peripheral neuropathy
c. Diagnosis 1) Chest X-ray may show widened mediastinum, but
sensitivity is only moderate 2) Definitive diagnosis can be made by TEE or chest CT
d. Treatment 1) Management of aortic dissection complicated by
stroke is controversial 2) Many series suggest poor prognosis for patients with
aortic dissection and stroke whether treated medically or surgically
5. Internal carotid artery stenosis: atherosclerosis (Fig. 11-16) a. Epidemiology: extracranial atherosclerosis of carotid
bifurcation is more common than intracranial stenosis b. Clinical (see section above on large-vessel syndromes
involving internal carotid artery) c. Diagnosis (discussed below) d. Treatment of symptomatic internal carotid artery steno-
sis and occlusion 1) Term “symptomatic stenosis or occlusion” refers to
cerebral infarction or TIA symptoms in anterior circulation ipsilateral to atheromatous diseased internal carotid artery
2) Symptomatic internal carotid artery stenosis 70% to 99% a) Northern American Symptomatic Carotid
Endarterectomy Trial (NASCET): the 2-year ipsilateral stroke rate was 26% in medically treated vs. 9% in carotid endarterectomy (CEA) group
3) Symptomatic internal carotid artery stenosis 50% to 69% a) 5-Year risk of fatal or nonfatal ipsilateral stroke was
22% in medically treated group and 15.7% in the surgically treated group
b) Greater benefit of surgery for i) Men than for women ii) Patients who have had stroke than for those with
TIAs iii) Patients with hemispheric symptoms than for
those with retinal symptoms c) Increased risk of perioperative stroke or death in
patients with diabetes, increased blood pressure, contralateral occlusion, or left-sided carotid disease
4) Internal carotid artery stenosis <50%: no data suggest CEA is beneficial over medical management
5) Symptomatic internal carotid artery occlusion (100% blockage) a) Best medical management (anticoagulation vs.
