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 layers**and**involvement 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 occlusion**s are due to \_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 40

atherosclerosis

Question 41

The **most common sites** of **primary thrombosi**s 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 affected**by**embolic infarction**; the incidence is about**equal 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 t**o luminal narrowing and cerebral infarcts**.

Question 54

While infectious vasculitis of small and large vessels **was once most commonly associated**with**syphilis and tuberculosis,**it is now**more 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 b**ased 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 b**ecome 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 the**addition 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 artery**is**rarer** 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 r**eversal of injury in the ischemic penumbra as well as with resolution of associated local edema.** **I**n 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.**