Cerebrovascular Disease

Question 1

_______________ is the third leading cause of death (after heart disease and cancer) in
the United States; it is also the most prevalent neurologic disorder in terms of both morbidity
and mortality.

Answer 1

Cerebrovascular disease

Question 2

Cerebrovascular diseases include the expected three major categories,
________________ with patient management differing between groups.

Answer 2

• thrombosis,
• embolism,
• and hemorrhage,

Question 3

___________ is the clinical designation that applies to all these conditions, particularly when
symptoms begin acutely.

Answer 3

“Stroke”

Question 4

From the standpoint of pathophysiology and pathologic anatomy, it is
convenient to consider cerebrovascular disease as two processes:

Answer 4

1. • Hypoxia, ischemia, and infarction resulting from impairment of blood supply and oxygenation of CNS tissue
2. • Hemorrhage resulting from rupture of CNS vessels

Question 5

The most common cerebrovascular disorders are__________

Answer 5

1. global ischemia,
2. embolism,
3. hypertensive intraparenchymal hemorrhage,
4. and ruptured aneurysm

Question 6

The brain requires a constant supply of glucose and oxygen, which is delivered by the blood.
Although the brain accounts for only __________ of body weight, it receives______ of the resting
cardiac output and accounts for__________ of the total body oxygen consumption.

Answer 6

1. 1% to 2%
2. 15%
3. 20%

Question 7

The brain may be deprived of oxygen by
several mechanisms:

Answer 7

• hypoxia caused by a low partial pressure of oxygen (Po2),
• impairment of the blood’s oxygen-carrying capacity,
• or inhibition of oxygen use in the tissue;
• or ischemia, either transient or permanent, after interruption of the normal circulatory flow. Cessation of
• blood flow can result from a reduction in perfusion pressure (as in hypotension), small- or largevessel
• obstruction, or both.

Question 8

When blood flow to a portion of the brain is reduced, the survival of the tissue at risk depends
on the________________

These factors determine, in turn, the precise anatomic site and
size of the lesion and, consequently, the clinical deficit.

Answer 8

presence of collateral circulation, the duration of ischemia, and the magnitude and
rapidity of the reduction of flow.

Question 9

Two principal types of acute ischemic
injury are recognized:

Answer 9

1. Global cerebral ischemia
2. Focal cerebral ischemia

Question 10

Global cerebral ischemia (ischemic/hypoxic encephalopathy) occurs when

Answer 10

there is a
generalized reduction of cerebral perfusion, as in cardiac arrest, shock, and severe
hypotension.

Question 11

Focal cerebral ischemia follows reduction or cessation of blood flow to a localized area
of the brain due to:

Answer 11

1. large-vessel disease (such as embolic or thrombotic arterial
2. occlusion, often in a setting of atherosclerosis)
3. or to small-vessel disease (such as vasculitis or occlusion secondary to arteriosclerotic lesions seen in hypertension).

Question 12

The general biochemical changes that attend cellular ischemia are discussed in Chapter 1 .
Here we describe several special responses to ischemia in the CNS. [14] [15] [16] The
metabolic depletion of energy associated with ischemia can result in ____________________.

Answer 12

• inappropriate release of excitatory amino acid neurotransmitters such as glutamate, initiating cell damage by allowing excessive influx of calcium ions through NMDA-type glutamate receptors.

Note :This elevation of cellular calcium ions can, in turn, trigger a wide range of processes including inappropriate
activation of signaling cascades, free radical generation, and mitochondrial injury. All told, these together result in cell death, mostly through necrosis.

Question 13

In the region of transition between** necrotic tissue** and the normal brain, there is an area of “at-risk” tissue, referred to as the
________.

Note :This region can be rescued from injury in many animal models with a variety of antiapoptotic
interventions, implying that it may undergo damage by apoptosis as well.

Answer 13

penumbra

Question 14

The clinical outcome of a severe hypotensive episode that produces_____________ varies with the severity of the insult. In mild cases there may be only a transient post-ischemic confusional state followed by complete recovery
and no irreversible tissue damage.

Answer 14

global cerebral ischemia
(diffuse hypoxic/ischemic encephalopathy)

Note :** However, irreversible damage to CNS tissue may occur in
some individuals who suffer mild or transient global ischemic insults.**

Question 15

There is a hierarchy of
sensitivity among CNS cells:______________ are the most sensitive, although glial cells
(oligodendrocytes and astrocytes) are also vulnerable.

Answer 15

neurons

Question 16

There is also variability in the
susceptibility of populations of neurons in different regions of the CNS (selective vulnerability),
based in part on differences in regional cerebral blood flow and cellular metabolic requirements.
With severe global cerebral ischemia, widespread neuronal death occurs, irrespective of
regional vulnerability.

Question 17

Patients who survive this injury often remain in a persistent vegetative
state.

Question 18

​Other patients meet the current clinical criteria for “brain death,” including

Answer 18

• evidence of irreversible diffuse cortical injury (isoelectric, or “flat,” electroencephalogram)
• and brainstem damage, such as absent reflexes and respiratory drive,
• and absent cerebral perfusion

Question 19

When individuals with this pervasive form of injury are maintained on mechanical ventilation, the brain gradually undergoes an autolytic process—so-called ___________________

Answer 19

“respirator brain.”

Question 20

Border zone (“watershed”) infarcts occur in the regions of the brain or spinal cord that lies where?.

Answer 20

lie at the
most distal reaches of the arterial blood supply, the border zones between arterial territories

Question 21

In
the cerebral hemispheres, the border zone between the_____________ and ____________
distributions is at greatest risk

Answer 21

anterior and the middle cerebral artery

Question 22

. Damage to this region ( andterior and middle cerebral artery) produces a ___________________ over the cerebral convexity a few centimeters lateral to the interhemispheric fissure.

Answer 22

sickle-shaped band of
necrosis

Question 23

Border zone infarcts are usually seen after_____________

Answer 23

hypotensive episodes.

Question 24

In the setting of global ischemia, what is the appearance of the brain?

Answer 24

swollen,

Question 25

In the setting of global ischemia, , the gyri are____________,

Answer 25

widened

Question 26

In the setting of global ischemia,
and the sulci are___________ The cut surface shows poor demarcation between gray and
white matter.

Answer 26

narrowed.

In the setting of global ischemia, the brain is swollen, the gyri are widened,
and the sulci are narrowed.

Question 27

The microscopic changes of irreversible ischemic injury (infarction) are
grouped into three categories

Answer 27

• Early changes
• Subacute changes,\
• Repair

Question 28

Early changes, occurring 12 to 24 hours after the insult,
include ________________

Answer 28

• acute neuronal changes (red neurons; Figs. 28-13A and Figs. 28-13B )
• characterized at first by microvacuolization, then eosinophilia of the neuronal cytoplasm, and
• **later nuclear pyknosis and karyorrhexis. **

Question 29

Similar acute changes occur somewhat later in what type of cell
______________.

Answer 29

astrocytes and oligodendroglia

Question 30

What are the most susceptible to
global ischemia of short duration. After the acute injury, the reaction to tissue damage begins
with infiltration by neutrophils

Answer 30

• Pyramidal cells in CA1 of the hippocampus (Sommer sector),
• Purkinje cells of the cerebellum,
• and cortical pyramidal neurons

Question 31

Subacute changes, occurring at 24 hours to
2 weeks,include:

Answer 31

• necrosis of tissue,
• influx of macrophages,
• vascular proliferation, and
• reactive gliosis ( Fig. 28-13D ).

Question 32

Repair, robust after approximately 2 weeks, is characterized
by e_____________________( Fig. 28-13E ).

Answer 32

• ventual removal of all necrotic tissue,
• loss of normally organized CNS structure, and
• gliosis

Question 33

what is ** pseudolaminar necrosis.?**

Answer 33

In the cerebral cortex the** neuronal loss and gliosis **produce an

• *uneven destruction of the neocortex, with preservation of some layersandinvolvement of**
• others*,a pattern termed** pseudolaminar necrosis.**

Question 34

Cerebral arterial occlusion may lead to focal ischemia and, if sustained, to infarction of a
specific region within the territory of distribution of the compromised vessel.

The size, location,
and shape of the infarct and the extent of tissue damage that results are determined by
modifying factors mentioned earlier, the most impt _______________

Answer 34

collateral flow

Question 35

The major source of collateral flow is the________________(supplemented by the external carotidophthalmic
pathway)

Answer 35

circle of Willis

Question 36

. Partial and inconstant reinforcement is available over the surface of the brain for the distal branches of the anterior, middle, and posterior cerebral arteries through
___________.

Answer 36

cortical-leptomeningeal anastomoses

Question 37

In contrast, there is little if any collateral flow for the deep
penetrating vessels supplying structures such as the_________________________

Answer 37

• thalamus,
• basal ganglia, and
• deep white
• matter.

Question 38

Partial and inconstant reinforcement is available over the surface of the
brain for the distal branches of the anterior, middle, and posterior cerebral arteries through
____________________

Answer 38

cortical-leptomeningeal anastomoses.

Question 39

Occlusive vascular disease of severity sufficient to lead to cerebral infarction may be due to ______________; the basic
pathology of these conditions is discussed in Chapters 4 and 11 .

Answer 39

• in situ thrombosis,
• embolization from a distant source,
• or various forms of vasculitides

Question 40

The majority of thrombotic occlusions are due to ______________.

Answer 40

atherosclerosis

Question 41

The most common sites of
primary thrombosis causing cerebral infarction are the ___________, _________ and ________.

Answer 41

• carotid bifurcation,
• the origin of the** middle cerebral artery,**
• and either end of the basilar artery

Question 42

The evolution of arterial stenosis
varies from progressive narrowing of the lumen and thrombosis, which may be accompanied by
anterograde extension, to fragmentation and distal embolization.

Another important aspect of
occlusive cerebrovascular disease is its frequent association with systemic diseases such as
_______________ and _____________

Answer 42

hypertension and diabetes.

Question 43

Embolism to the brain occurs from a wide range of origins. _______________ are among
the most common sources;

Answer 43

Cardiac mural thrombi

Question 44

What are the important predisposing factor of cardiac mural emboli?

Answer 44

• myocardial infarct,
• valvular disease, and
• atrial fibrillation.

Question 45

Next in importance in emboli are thromboemboli arising in arteries, most often originating over atheromatous plaques within the _____________.

Answer 45

carotid arteries

Question 46

Other sources of emboli
include_________, particularly in children with cardiac anomalies; ___________ and ___________.

Answer 46

• paradoxical emboli
• emboli associated
  with cardiac surgery;
• and emboli of other material (tumor, fat, or air)

Question 47

The territory of distribution
of the _______________—the direct extension of the internal carotid artery—is most
frequently affectedbyembolic infarction; the incidence is aboutequal in the two hemispheres.
E

Answer 47

middle cerebral artery

Question 48

Emboli tend to lodge where blood vessels _____________

Answer 48

branch or in areas of preexisting luminal stenosis.

Question 49

**______________ **as in fat embolism, may occur after fractures;

Answer 49

“Shower embolization,”

Question 50

What are the manifestation of shower emobolism?

Answer 50

affected individuals
manifest generalized cerebral dysfunction with disturbances of higher cortical function and
consciousness, often without localizing signs.

Question 51

• *Widespread hemorrhagic lesions** involving the
• *white matter** are characteristic of embolization of _______________

Answer 51

bone marrow after trauma

Question 52

Answer 52

Widespread white-matter hemorrhages are characteristic of bone marrow
embolization.

Question 53

A variety of inflammatory processes that involve blood vessels may also lead to luminal
narrowing and cerebral infarcts.

Question 54

While infectious vasculitis of small and large vessels was once
most commonly associatedwithsyphilis and tuberculosis,it is nowmore common in the setting
of __________________________.

Answer 54

immunosuppression and opportunistic infection (such as aspergillosis or CMV encephalitis)

Question 55

____________________may involve cerebral vessels and
cause single or multiple infarcts throughout the brain.

Answer 55

**Polyarteritis nodosa and other non-infections vasculitides **

Question 56

____________ is an
inflammatory disorder that involves multiple small- to medium-sized parenchymal and
subarachnoid vessels and is

Answer 56

Primary angiitis of the CNS

Question 57

Primary angitis of the CNS characterize as:

Answer 57

characterized by chronic inflammation, multinucleated giant cells,
and destruction of the vessel wall.

Question 58

Granulomas may be found in association with the giant cells,
leading to the alternative name of granulomatous angiitis of the nervous system.

Affected
individuals manifest a ________________

Answer 58

diffuse encephalopathic or multifocal clinical picture, often with cognitive
dysfunction; patients improve with steroid and immunosuppressive treatment.

Question 59

Other conditions
that may cause thrombosis and infarction (and intracranial hemorrhage) include
_____________________

Answer 59

• hypercoagulable states,
• dissecting aneurysm of extracranial arteries in the neck supplying the brain,
• and drug abuse (amphetamines, heroin, cocaine)

Question 60

Infarcts are subdivided into two broad groups based on the presence of_____________.

Answer 60

hemorrhage

Question 61

Hemorrhagic (red) infarction, characterized by ____________.

Answer 61

• multiple,
• sometimes confluent,
• petechial hemorrhages,
• is typically associated with embolic events ( Fig. 28-15A )

Question 62

The hemorrhage is
presumed to be secondary to reperfusion of damaged vessels and tissue, either through
collaterals or directly after dissolution of intravascular occlusive material.

Question 63

In contrast,
nonhemorrhagic (pale, bland, anemic) infarcts are usually associated with _____________ Fig. 28-
15B ).

Answer 63

thrombosis

Question 64

The clinical management of patients with these two types of infarcts differs greatly as
thrombolytic therapy may be used in cases of thrombosis but is contraindicated in_______________

Answer 64

• • hemorrhagic
    infarcts. **

Question 65

Thrombolytic therapy is beneficial only during a ________________ after onset of
symptoms; therefore,rapid medical attention is essential

Answer 65

narrow time window

Question 66

Answer 66

A hemorrhagic infarction is present in the inferior temporal lobe of the left
side of this brain.

Question 67

Answer 67

B, A bland infarct with punctate hemorrhages, consistent with ischemiareperfusion
injury, is present in the temporal lobe.

Question 68

The macroscopic appearance of a nonhemorrhagic infarct varies with the
time after loss of blood supply.

During the first 6 hours of irreversible injury, little can be
observed.

By 48 hours the tissue becomes______________

Answer 68

pale, soft, and swollen, and the corticomedullary
junction becomes indistinct.

Question 69

In nonhemorrhagic infarct ,From 2 to 10 days, the brain becomes _____________

Answer 69

gelatinous and friable,
and the previously ill-defined boundary between normal and abnormal tissue becomes more
distinct as edema resolves in the adjacent tissue that has survived

Question 70

. From 10 days to 3
weeks of NONHEMORRHAGIC INFARCT, the ___________________________

Answer 70

tissue liquefies, eventually leaving a fluid-filled cavity lined by dark gray tissue,
which gradually expands as dead tissue is removed

Question 71

On microscopic examination of NONHEMORRHAGIC INFARCT the tissue reaction evolves along the following sequence:

Answer 71

• After the first 12 hours, ischemic neuronal change (red neurons; see earlier) and both cytotoxic and vasogenic edema predominate.
• There is loss of the usual tinctorial characteristics of white- and gray-matter structures.
• Endothelial and glial cells, mainly astrocytes, swell, and myelinated fibers begin to disintegrate.
• Up to 48 hours, neutrophilic emigration progressively increases and then falls off. Phagocytic cells, derived from circulating monocytes and activated microglia, are evident at 48 hours and become the predominant celltype in the ensuing 2 to 3 weeks.
• The macrophages become stuffed with the products of myelin breakdown or blood and may persist in the lesion for months to years. As the process of liquefaction and phagocytosis proceeds, astrocytes at the edges of the lesion progressively enlarge, divide, and develop a prominent network of cytoplasmic extensions
• . Reactive astrocytes can be seen as early as 1 week after the insult.
• After several months , the astrocytic response recedes, leaving behind a dense meshwork of
  glial fibers admixed with new capillaries and some perivascular connective tissue. In the
  cerebral cortex, the cavity is separated from the meninges and subarachnoid space by a
  gliotic layer of tissue, derived from the molecular layer of the cortex. The pia and arachnoid are not affected and do not contribute to the healing process. Infarcts undergo these reactive and reparative stages from the edges inward; thus, different areas of a lesion may look different, particularly during the early stages, revealing the natural progression of the response.

Question 72

In the nonhemorrhagic infarct microscopic exam, what predominates in the first 12 hours?

Answer 72

• ischemic neuronal change (red neurons; see earlier) and
• both cytotoxic and vasogenic edema predominate.

Question 73

In the nonhemorrhagic infarct microscopic exam, what predominates after 48 hrs?

Answer 73

neutrophilic emigration progressively
increases and then falls off.

Phagocytic cells, derived from circulating monocytes and
activated microglia, are evident at 48 hours and become the predominant celltype in the
ensuing 2 to 3 weeks.

Question 74

What is the microscopic picture of hemorrhagic infarction?

Answer 74

The microscopic picture and evolution of hemorrhagic infarction parallel ischemic
infarction,with theaddition of blood extravasation and resorption

. In individuals receiving
anticoagulant treatment, hemorrhagic infarcts may be associated with extensive intracerebral
hematomas.

Question 75

__________are often hemorrhagic and may occur after thrombotic
occlusion of the superior sagittal sinus or other sinuses or occlusion of the deep cerebral
veins.

Answer 75

**​Venous infarcts **

Question 76

What increases the state of ________________venous thrombosis.

Answer 76

• Carcinoma,
• localized infections,
• and other conditions leading to a hypercoagulable state

Question 77

Spinal cord infarction may be seen in the setting of_____________ or _______________

Answer 77

hypoperfusion or as a consequence of
interruption of the feeding tributaries derived from the aorta.

Question 78

Occlusion of the anterior spinal
arteryisrarer and may occur as a result of _____________

Answer 78

embolism or vasculitis.

Question 79

Deficits associated with infarction are determined by the ___________ involved rather than the
underlying pathologic process.

Neurologic symptoms referable to the area of injury often
develop rapidly, over minutes, and may continue to evolve over hours.

There can be
improvement in severity of symptoms associated with reversal of injury in the ischemic
penumbra as well as with resolution of associated local edema.

In general, there is often a
degree of slow improvement during a period of months.

Answer 79

brain region

Question 80

Because strokes are frequently
associated with atherosclerosis, many of the genetic and lifestyle risk factors are the same as
those for atherosclerotic disease.