Cerebrovascular Disease- INTRACRANIAL HEMORRHAGE

Question 1

INTRACRANIAL HEMORRHAGE

Hemorrhages may occur at any site within the CNS. In some instances they may be a secondary phenomenon occurring, for example, within infarcts in arterial border zones or in infarcts caused
by only partial or transient vascular obstruction.

Question 2

Primary hemorrhages within the_______________ are typically related to trauma and were discussed earlier with traumatic
lesions.

Answer 2

epidural or
subdural space

Question 3

Hemorrhages within the brain parenchyma and subarachnoid space, in contrast, are
more often a manifestation of underlying cerebrovascular disease, although trauma may also
cause hemorrhage in these sites.

Question 4

Spontaneous (nontraumatic) intraparenchymal hemorrhages occur most commonly in middle to
late adult life, with apeak incidence at about age __________.

Answer 4

60 years

Question 5

What is the Most are caused of intracerebral ( intraparenchymal hemorrhage? ________________

Answer 5

by rupture of a
small intraparenchymal vessel.

Question 6

When the hemorrhages occur in the basal ganglia and
thalamus, they are designated _______________to distinguish them from those that
occur in the lobes of the cerebral hemispheres, which are called lobar hemorrhages.

Answer 6

ganglionic hemorrhages

Question 7

In ganglionic hemorrhages the two
major underlying etiologies of this form of cerebrovascular disease are___________ and ___________.

In addition, other local and systemic factors may cause or
contribute to nontraumatic hemorrhage, including systemic coagulation disorders, neoplasms,
vasculitis, aneurysms, and vascular malformations.

Answer 7

hypertension and
cerebral amyloid angiopathy (CAA)

Question 8

_____________is the most common underlying cause of primary brain parenchymal hemorrhage ,
accounting for more than 50% of clinically significant hemorrhages and for roughly 15% of
deaths among individuals with chronic hypertension.

Answer 8

Hypertension

Question 9

Hypertension causes a number of
abnormalities in vessel walls, including ________________.

Answer 9

• accelerated atherosclerosis in larger arteries;
• hyaline arteriolosclerosis in smaller vessels;
• and, in severe cases, proliferative changes
• and frank necrosis of arterioles

Question 10

_____________ affected by hyaline change are presumably weaker than
are normal vesselsand are thereforemore vulnerable to rupture.

Answer 10

Arteriolar walls

Question 11

In some instances chronic
hypertensionis associated with thedevelopment of minute aneurysms, termed______________ which may be the site of rupture.

Answer 11

Charcot-
Bouchard microaneurysms,

Question 12

Charcot-Bouchard aneurysms,
not to be confused with saccular aneurysms of larger intracranial vessels, occur in vessels that
are less than 300 μm in diameter, most commonly within the _____________

Answer 12

basal ganglia.

Question 13

Hypertensive intraparenchymal hemorrhage may originate in the \_\_\_\_\_\_\_\_\_
(50% to 60% of cases), **thalamus, pons, cerebellar hemispheres (rarely)**, and other regions of
the brain ( Fig. 28-18A ).

Answer 13

putamen

Question 14

Acute hemorrhages, independent of etiology, are characterized by
_______________.

Answer 14

extravasation of blood with compression of the adjacent parenchyma

Question 15

Old hemorrhages show
an area of _____________.

Answer 15

cavitary destruction of brain with a rim of brownish discoloration

Question 16

On microscopic
examination the early lesion consists of a central core of ___________________-Eventually the
edema resolves, pigment- and lipid-laden macrophages appear, and proliferation of reactive
astrocytesis seen at the periphery of the lesion.

The cellular events then follow the same time
course that is observed after cerebral infarction.

Answer 16

clotted blood surrounded by a rim of
brain tissue showing anoxic neuronal and glial changes as well as edema.

Question 17

___________ is a condition in which amyloidogenic peptides, nearly always the same one found in
Alzheimer disease (Aβ40; see the discussion below), deposit in the walls of medium- and smallcaliber
meningeal and cortical vessels.

This deposition can result in weakening of the vessel
wall and risk of hemorrhage

.

Answer 17

CAA

Question 18

As with Alzheimer disease, in which there is a relationship between
a polymorphism in the gene that encodes apolipoprotein E (ApoE) and risk of disease, there is
an effect of the ApoE genotype on the risk of recurrence of hemorrhage from sporadic CAA.

The presence of either an____________ allele increases the risk of repeat bleeding.

Answer 18

ε2 or ε4

Question 19

While some
mutations in the precursor protein for the________________) cause
familial Alzheimer disease, others result in autosomal dominant forms of CAA.

Answer 19

Aβ peptide (amyloid precursor protein, APP

Question 20

The underlying vascular abnormality of CAA is typically restricted to the
_______________although involvement of the
molecular layer of the cerebellum can be observed as well.

Answer 20

• leptomeningeal
• and cerebral cortical arterioles
• and capillaries,

Question 21

What is the microscopic finding in CAA____________

Answer 21

Involved vessels appear “stiff” on
microscopic sections, remaining open with round lumens through tissue processing.

Question 22

What is distinguishing feature of CAA to aretiolar sclerosis?

Answer 22

Unlike
with arteriolar sclerosis, there is no fibrosis; rather, dense and uniform deposits of amyloid
are present

Question 23

_________________ is a rare hereditary form of stroke caused by mutations in the gene encoding the
Notch3 receptor. [17]

Answer 23

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL)

Question 24

What is the characteristic of CADASIL?

Answer 24

The disease is characterized clinically by recurrent strokes (usually
infarcts, less often hemorrhages) and dementia.

Question 25

What is the histopathologic study has shown abnormalities
of white matter and leptomeningeal arteries (also involving non-CNS vessels) consisting of
__________________.

Answer 25

• **concentric thickening **of the media and adventitia.
• Basophilic, PAS-positive deposits, which appear as osmiophilic compact granular material by electron microscopy, have been consistently detected in the walls of affected vessels,
• as has loss of smooth muscle cells ( Fig. 28-18C )

Question 26

How is the diagnosis can be made in CADASIL?

Answer 26

through the identification of these deposits in other
tissues, such as skin or muscle biopsies, or through genetic approaches.

Many of the causative
mutations disrupt the normal folding of the extracellular domain of Notch3, and the
characteristic deposits appear to be comprised of Notch3 ectodomains. How these deposits
relate to the disease is not understood; a toxic gain-of-function mechanism affecting vascular
smooth muscle has been proposed

Question 27

Intracerebral hemorrhage, independent of cause, can be clinically devastating if it affects large
portions of the brain and extends into the ventricular system, or it can affect small regions and
either be clinically silent or evolve like an infarct.

Over weeks or months there is a gradual
resolution of the hematoma, sometimes with considerable clinical improvement.

Again, the
______________________ determines the clinical manifestations.

Answer 27

location of the hemorrhage

Question 28

The most frequent cause of clinically significant subarachnoid hemorrhage is rupture of a
____________.

Subarachnoid hemorrhage may also result from extension of a
traumatic hematoma, rupture of a hypertensive intracerebral hemorrhage into the ventricular
system, vascular malformation, hematologic disturbances, and tumors.

Answer 28

saccular (berry) aneurysm

Question 29

__________ is the most common type of intracranial aneurysm.

Answer 29

Saccular aneurysm

Question 30

Other aneurysm types
include a_____________ These latter three, like saccular aneurysms, are most often found in the anterior
circulation, but differ in that they more often cause cerebral infarction rather than subarachnoid
hemorrhage.

Answer 30

• atherosclerotic (fusiform; mostly of the basilar artery),
• mycotic,
• traumatic,
• and dissecting.

Question 31

mycotic, traumatic, and dissecting, like saccular aneurysms, are most often found in the___________, but differ in that they more often cause cerebral infarction rather than subarachnoid
hemorrhage.

Answer 31

anterior circulation

Question 32

Saccular aneurysms are found in about 2% of the population according to recent data from
community-based radiologic studies.

About 90% of saccular aneurysms are found near major
arterial branch points in the ___________ ( Fig. 28-19 ); multiple aneurysms exist in 20%
to 30% of cases in autopsy series.

Answer 32

anterior circulation

Question 33

Question 34

Pathogenesis of Saccular Aneurysms.

The etiology of saccular aneurysms is unknown.

Although the majority occur_____________,
genetic factors may be important in their pathogenesis, since there is an increased incidence of
aneurysms in first-degree relatives of those affected.

There is also an increased incidence in
individuals with certain mendelian disorders (such as autosomal dominant polycystic kidney
disease,Ehlers-Danlos syndrome type IV,neurofibromatosis type 1 [NF1],andMarfan
syndrome), Marfan

**syndrome **fibromuscular dysplasia **neurofibromatosis type 1 [NF1], **of extracranial arteries, and coarctation of the aorta.

Answer 34

sporadically

Question 35

What are the major predisposing factors of saccular aneurysm?

Answer 35

The predisposing factors include :

• cigarette smoking and
• hypertension (estimated to be present in about half of these patients).

Although they are sometimes referred to as congenital,
theaneurysms are not present at birth but develop over time because of an underlying defect in
the media of the vessel.

Question 36

An unruptured saccular aneurysm is a ______________, usually at an
arterial branch pointalong thecircle of Willis or a major vessel just beyond..

Answer 36

thin-walled outpouching

Question 37

Describe the morphology of saccular aneurysms ?

Answer 37

• 2 or 3 cm in diameter
• and have a bright red shiny surface
• and a thin, translucent wall ( Fig. 28-20 ).
• Atheromatous plaques,
• calcification,
• or thrombotic occlusion of the sac may be found in the wall or lumen of the aneurysm.
• Brownish discoloration of the adjacent brain and meninges is evidence of prior hemorrhage.
• The neck of the aneurysm may be either **wide or narrow. **
• The arterial wall adjacent to the neck of the aneurysm often shows some intimal thickening and gradual attenuation of the media as it approaches the neck.
• At the neck of the aneurysm, the muscular wall and intimal elastic lamina stop short and are absent from
• the aneurysm sac itself.
• The sac is made up of thickened hyalinized intima. T
• he adventitia covering the sac is continuous with that of the parent artery

Question 38

Where does aneursym Rupture usually occurs?

Answer 38

at the apex
of the sacwith extravasation of blood into the subarachnoid space, the substance of the
brain, or both.

Question 39

Clinical Features.

Rupture of an aneurysm with clinically significant subarachnoid hemorrhage is most frequent in
the _________________

Answer 39

fifth decade and is slightly more frequent in females.

Question 40

Overall, the rate of bleeding is roughly
1.3% per year, with the probability of rupture increasing with the size of the lesion.

Question 41

Aneurysms
greater than___________in diameter have a roughly 50% risk of bleeding per year.

Rupture may
occur at any time, but in about one third of cases it is associated with acute increases in
intracranial pressure, such as with straining at stool or sexual orgasm.

Blood under arterial
pressure is forced into the subarachnoid space and affected individuals are stricken with a
sudden, excruciating headache (“the worst headache I’ve ever had”), rapidly losing
consciousness.

Answer 41

10 mm

Question 42

Between **____________ **of patients die with the first rupture, but patients who
survive often improve and recover consciousness in minutes. Repeat bleeding is common in
survivors, and it is currently not possible to predict in which patients repeat bleeding will occur.
With each episode of bleeding, the prognosis is worse.

Answer 42

25% and 50%

Question 43

The clinical consequences of blood in the subarachnoid space can be separated into acute
events,occurring within hours to days after the hemorrhage, andlate sequelae associated with
the healing process.

Question 44

In the first few days after a subarachnoid hemorrhage, regardless of the
etiology, there is an increased risk of additional ischemic injury from vasospasm affecting
vessels bathed in the extravasated blood.

This problem is of greatest significance in cases of
basal subarachnoid hemorrhage, in which vasospasm can involve major vessels of the circle of
Willis.
Various mediators have been proposed to have a role in this reactive process, including
endothelins, nitric oxide, and arachidonic acid metabolites. In the healing phase of
subarachnoid hemorrhage, meningeal fibrosis and scarring occur, sometimes leading to
obstruction of CSF flow as well as interruption of the normal pathways of CSF resorption.

Question 45

Vascular malformations of the brain are classified into four principal groups: _____________

Answer 45

1. arteriovenous malformations,
2. cavernous malformations,
3. capillary telangiectasias,
4. and venous angiomas.

Question 46

Which among the fou types of vascular malformations are associated with risk of hemorrhage and development of
neurologic symptom

Answer 46

• arteriovenous malformations,
• cavernous malformations,

Question 47

Morphology.

Arteriovenous malformations (AVM) **involve vessels i**n the **subarachnoid
space****extending into brain parenchyma**or may occur**exclusively within the brain.**

This tangled network of wormlike vascular channels has ________________________

They are composed of greatly enlarged blood vessels
separated by gliotic tissue, often with evidence of prior hemorrhage. Some vessels can be
recognized as arteries with duplication and fragmentation of the internal elastic lamina, while
others show marked thickening or partial replacement of the media by hyalinized connective
tissue.

Answer 47

prominent, pulsatile arteriovenous
shunting with high blood flow.

Question 48

Cavernous malformations consist of____________

They occur most often in the cerebellum,
pons, and subcortical regions, in decreasing order of frequency, and have a low flow without
arteriovenous shunting. Foci of old hemorrhage, infarction, and calcification frequently
surround the abnormal vessels.

Answer 48

• greatly distended,
• loosely organized vascular channels with
• thin, collagenized walls
• and are devoid of intervening nervous tissue (thus
• distinguishing them from capillary telangiectasias).

Question 49

How to distinguish cavernous malformationfrom capilary talengiactia?

Answer 49

devoid of intervening nervous tissue

(thus distinguishing them from capillary telangiectasias).

Question 50

Where does cavernous malformation mostly occurs?

Answer 50

They occur most often in the cerebellum,
pons, and subcortical regions, indecreasing order of frequency, and have a low flow without
arteriovenous shunting.
Foci of old hemorrhage, infarction, and calcification frequently
surround the abnormal vessels.

Question 51

Venous angiomas (varices) consist of ______________

Answer 51

aggregates of
ectatic venous channels.

Question 52

________________ is a venous angiomatous malformation of the spinal cord and overlying
meninges,most often in thelumbosacral region,associated withischemic myelomalacia and
slowly progressive neurologic symptoms.

Answer 52

Foix-Alajouanine disease (angiodysgenetic necrotizing
myelopathy)

Question 53

_______________ are the most common type of clinically significant vascular malfor
mation.

Males are affected twice as frequently as females, and the lesion is often recognized
clinically between the ages of 10 and 30 years, presenting as a seizure disorder, an
intracerebral hemorrhage, or a subarachnoid hemorrhage.

Answer 53

Arteriovenous malformations

Question 54

Where is th most common site in arteriovenous malformation?

Answer 54

The most common site is the
territory of the middle cerebral artery, particularly its posterior branches.

Large arteriovenous
malformations occurring in the newborn period can lead to congestive heart failure because of
shunt effects,especiallyif the malformationinvolves the vein of Galen.

Question 55

Cavernous
malformations are unique among this class of lesion in that **familial forms are relatively common,**
with a **variety of identified genetic loci**. [18]

________________ is an additional hallmark of
these autosomal dominant disorders with high penetrance.

Answer 55

Multiplicity of lesions