6.8.

2 CEREBROVASCULAR DISEASES
Dr. Tilbe

CEREBROVASCULAR DISEASE
Any abnormality of the brain due to an underlying
pathology in the blood vessels
Impaired blood supply
rapidly developing loss of brain function.
Clinically present as "Stroke or CVA (cerebrovascular
accident)

STROKE
Medical emergency and can cause permanent neurological
damage, complications, and death.
Leading cause of adult disability in the US, Europe and Figure 2: Embolism may cause obstruction of CNS vessels resulting to
even in the Philippines. death of brain tissue due to lack of blood supply.
No. 2 cause of death worldwide
CEREBRAL BLOOD FLOW
TWO UNDERLYING PATHOLOGIC PROCESSES
CBF delivers a constant supply of glucose and oxygen
RESPONSIBLE FOR STROKE:
1) Impairment of blood supply of CNS tissue Brain:
hypoxia, ischemia, and infarction 1- 2% of BW,
2) Rupture of CNS vessels hemorrhage Receives 15% of the resting CO
Accounts for 20% of the total body O2
Impaired blood supply and hemorrhage will lead to consumption.
ischemia (lack of glucose and oxygen supply) Normal CBF: about 50 mL/ minute for each 100 gm of
Affected area is unable to function, leading to tissue
hemiplegia and other neurologic deficits
regional variations between white and gray matter
and among different portions of the gray matter
COMMON CEREBROVASCULAR DISORDERS:
1) Thrombosis CBF remains constant over a wide range of BP and ICP
2) Embolism Ischemic stroke because of auto-regulation of vascular resistance.
3) Intraparenchymal Causes of decreased oxygen to the brain:
hemorrhage due to HPN A low partial pressure of oxygen (pO2) (functional
4) Subarachnoid Hemorrhagic hypoxia),
hemorrhage secondary to stroke Impaired oxygen-carrying capacity of the blood,
ruptured aneurysm inhibition of oxygen use by tissue
Ischemia after interruption of the normal blood flow.
A. Ischemic Stroke is due to a reduction of blood flow most
Special responses to ischemia in the CNS.
commonly due to occlusion (an obstruction) brought
Excitatory amino acid neurotransmitters (e.g. Glutamate)
about by thrombosis or embolism.
released overstimulates and result in persistent opening
B. Hemorrhagic stroke (or intracranial hemorrhage) of specific membrane channels including N-methyl-D-
due to rupture of blood vessel in the brain aspartate and kainate receptors.
spilling blood into the spaces surrounding the Cell death results from
brain cells 1) Uncontrolled influx of calcium ions or
due to rupture of cerebral aneurysm 2) Toxic effects of nitrous oxide

The mortality and long-term morbidity prognosis is

generally worse for hemorrhagic strokes than for
ischemic strokes.

Figure 1: Two processes in CVS: (1) Hypoxia, ischemia and infarction

resulting from impairment of blood supply and oxygenation if CNS
tissue. (2) Hemorrhage resulting from rupture of CNS vessels.
Figure 3: This diagram shows how the CNS responds to ischemia.

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TWO TYPES OF ACUTE ISCHEMIC INJURY
A. GLOBAL CEREBRAL ISCHEMIA
Due to severe hypotensive episode leading to a
generalized reduction of cerebral perfusion (cardiac arrest,
shock, and severe hypotension.)
Clinical outcome: Diffuse hypoxic/ischemic
encephalopathy:
o Mild cases: no irreversible tissue damage
Eventual complete recovery
o Severe cases: can result in irreversible damage to
CNS tissue.
Occur in parts of the brain that lie at the boundary
between zones of arterial distribution from different
arteries.
Normally, border zones are hypoperfused because they
are the last to receive blood from main arterial trunk.
With hypotension watershed areas are more
susceptible to damage than other areas of the brain.
PATHOLOGIC CONSEQUENCES:
Focal neuronal death that follows pattern of
selective vulnerability. Preferentially affects
Sommer Sector of Hippocampus and Purkinje cells
Watershed infarcts
Laminar necrosis
Figure 4: Bilaterally symmetric dark discolored areas (superior
and just lateral to the midline) representing recent infarction in
the watershed zone (overlapping area) supplied by ACA and
MCA circulation
CORTICAL LAMINAR NECROSIS
A specific type of cortical infarction, which
usually develops as a result of generalized
ischemia
Typically affects the deep layers of the cerebral
cortex (area receiving blood from blood vessels
entering the cortex from the surface of the brain
(short penetrators)
Figure 5: Gross picture of laminar necrosis. The gray matter
has six layers. The third layer is the most vulnerable to
depletion of oxygen and glucose.
Mattus Medina Pamintuan Panday Parabuac Rejante
Figure 6: Gross picture of global cerebral ischemia. Brain is
swollen. Gyri are widened, and the sulci are narrowed. Poor
demarcation between gray and white matter.
Microscopic Findings:
Mild global ischemia : neurons(most sensitive
cells ) are affected first
Severe global cerebral ischemia: widespread
neuronal death
B. FOCAL CEREBRAL ISCHEMIA/INFARCTION
Due to reduction or cessation of blood flow to a localized
area of the brain
Focal ischemia: obstruction of local blood supplies not
enough to cause necrosis.
Infarction: tissue necrosis due to sustained, obstruction
of local blood supply (further discussed below);
CAUSES:
a) Large-vessel disease (such as embolic or
thrombotic arterial occlusion)
i. Thrombotic Arterial Occlusion - causes
bland/white type of infarct
ii. Embolic Arterial Occlusion - causes
hemorrhagic type of infarct
b) Small-vessel disease (such as vasculitis or
occlusion secondary to arteriosclerotic lesions seen
in HPN)
CEREBRAL INFARCTS
Focal brain necrosis due to complete and prolonged
ischemia that affects all tissue elements
CAUSES:
A. THROMBOTIC INFARCTS
Are due to atherosclerosis
The most common sites:
Carotid bifurcation,
the origin of the middle cerebral artery,
either end of the basilar artery.
Frequently associated with hypertension and diabetes.
Figure 7: Majority of thrombotic occlusions is due to atherosclerosis.
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 Due arteriolar sclerosis (due to HPN) of
deep penetrating arterioles of Basal
ganglia and brainstem.
Maybe clinically silent or cause severe
neurologic impairment depending on
location.

Figure 8: Progressive narrowing of the lumen may be accompanied Figure 10: Lakelike spaces (<15 mm), in the lenticular nucleus,
by embolization resulting to obstruction = stroke. thalamus, internal capsule, deep white matter, caudate
nucleus, and pons.

Figure 9: Thrombosis of the internal carotid artery (black

arrow). .
Figure 11: Cystic spaces from resolved liquefactive necrosis
B. EMBOLIC INFARCTS with scattered fat-laden macrophages and surrounding gliosis.
Embolism is the most frequent cause of ischemic
infarction. D. OTHER CAUSES OF ARTERIAL OCCLUSION AND
Embolic infarcts have an abrupt onset. INFARCTION
Origin: 1. Vasculitis
1) Cardiac mural thrombi are the most common o Inflammation of blood vessels luminal narrowing
sources. Predisposing factors: MI, valvular disease, infarcts
and AF. o Examples: PAN, giant cell (temporal) arteritis,
2) Thromboemboli arising in arteries, most often granulomatous arteritis, SLE, infectious vasculitis
originating over atheromatous plaques within the (pyogenic meningitis, tuberculous meningitis, CNS
carotid arteries. syphilis, fungal vasculitis); primary angitis of CNS
3) Other sources: Emboli of other material (tumor,
fat, or air). INFARCT: CLINICAL FEATURES
Clinical presentation depends on location and size of infarct.
C. SMALL VESSEL DISEASE Maybe asymptomatic
Primarily seen in HPN and DM Develops a hemiplegia, a sensory deficit,
Also known as: blindness, aphasia, or some other deficits
"small artery arteriosclerosis", Outcome:
"hyaline arteriolosclerosis Maybe fatal
"lipohyalinosis". May show slow improvement during a period of
Pathogenesis: months.
HPN: endothelial injury and leakage of plasma
proteins in and around vessels; INFARCTS: CLINICAL FINDINGS
DM: glycation of pr- and diffuse BM Embolic infarcts: abrupt onset
thickening. Atherothrombotic infarcts:
Vessels walls thicken, becomes Evolve over a period of time, usually hours.
homogenous and hyalinized Often preceded by transient ischemic attacks
Lumen becomes narrowed (TIAs).
Vessels become tortous TIA (focal neurological deficit that lasts less
Outcome: than 24 hours and resolves) - due to
SMALL INFARCTS (LACUNAR INFARCTS) temporary decrease of perfusion impairs
which affects small penetrating arteries and neurological function but not enough to cause
arterioles that supply the BG, thalamus, deep permanent damage (probably due to lysis of
white matter, and the BS emboli soon after occlusion)
Account for about 20% of all strokes.
Single or multiple, small, cavitary infarcts

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 An infarct has: 10 days to 3 weeks:
Central core of total ischemia and necrosis tissue liquefies, eventually leaving a fluid-filled
(irreversible). cavity lined by dark gray tissue
Ischemic penumbra: A zone of borderline ischemic
tissue surrounding the central core (reversible)

Window of opportunity for salvaging the

penumbra is very short therefore an ischemic
stroke is an emergency.
If within 3 hours adequate blood supply is not
restored necrosis extends to the penumbra.
Restoration of perfusion in the penumbra and
then to resorption of cerebral edema recovery
of function, after an infarct

TWO TYPES OF INFARCTS: Figure 14: Intermediate infarct of the frontal lobe: liquefactive
A. Hemorrhagic (red) infarction necrosis with formation of cystic spaces as resolution begins.
Multiple, sometimes confluent, petechial
hemorrhages
INFARCTION: MICROSCOPIC FEATURES
Hemorrhage is probably secondary to reperfusion
1. Early changes (12 to 24 hours after the insult)
of damaged vessels and tissue either via collaterals
Acute neuronal cell change (red neurons)
or direct clot dissolution.
Microvacuolization eosinophilia of the
neuronal cytoplasm nuclear pyknosis and
karyorrhexis
Neutrophilic emigration progressively increases
then decreases

Figure 15: Acute ischemic injury: diffuse eosinophilia of

neurons, which are beginning to shrink.
Figure 12: Hemorrhagic Infarct: edematous infarcted tissue
produces a mass effect decrease in size of the left ventricle
with shift of the midline. Arterial embolus often leads to a
hemorrhagic appearance.

B. Non-hemorrhagic (pale, bland, anemic) infarcts

usually associated with thrombosis

Figure 16: Infiltration of a cerebral infarct by neutrophils

begins at the edges of the lesion

2. Subacute changes (24 hours to 2 weeks)

Figure 13: A bland infarct with punctate hemorrhages,
consistent with ischemia-reperfusion injury
GROSS (Non-hemorrhagic infarct):
1st 6 hours of irreversible injury:
minimal change
48 hours:
the tissue becomes pale, soft, and swollen, and
the corticomedullary junction becomes indistinct.
2 to 10 days
brain becomes gelatinous and friable
Necrosis of tissue, influx of macrophages, vascular
proliferation, and reactive gliosis
Phagocytic cells (circulating monocytes and activated
microglia) are seen at 48 hours and become the
predominant cell type in the next 2 to 3 weeks.
3. Repair (after 2 weeks)
Macrophages (peak reaction: 3-4 weeks) stuffed with
the products of myelin breakdown or blood may
persist for months to years.
Removal of all necrotic tissue loss of normally
organized CNS structure Astrocytes from the
surrounding undamaged brain proliferate and form a
glial scar around the infarct (completed in approximately
2 months).

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 Histo: Focal tissue destruction, pigment-laden
macrophages, and gliosis.

HYPERTENSIVE INTRAPARENCHYMAL HEMORRHAGE

Putamen (50% to 60% of cases)
Thalamus, pons, cerebellar hemispheres (rarely), and
other regions of the brain .
Early lesion:
- Central core of clotted blood surrounded by a
rim of edematous brain tissue showing anoxic
neuronal and glial changes
Later lesion:
- Pigment and lipid-laden macrophages with
proliferated reactive astrocytes at the periphery
Figure 17: Resolution of the liquefactive necrosis in a cerebral
of clot.
infarction leads to the formation of a cystic space.
Clinical Features:
o Clinical symptoms depend on location and size
of the bleed
Large portions of the brain affected with
involvement of the ventricular system >>
fatal
Maybe clinically silent
May produce neurologic deficits
o Hemorrhage may gradually resolve over weeks or
months.

Figure 18: Cystic infarct showing destruction of the cortex with

cavitation.

HEMORRHAGIC STROKES
Accounts for 15% to 20% of strokes
Due to rupture of blood vessels with intracerebral or
subarachnoid hemorrhage. Figure 19: Massive hypertensive hemorrhage rupturing into a
3 major causes of hemorrhagic strokes are lateral ventricle.
1. Hypertensive bleed
2. Ruptured arterial aneurysms SUBARACHNOID HEMORRHAGE
3. Arteriovenous malformations
Common cause of hemorrhagic stroke
Most common cause: rupture of a saccular (berry)
INTRACEREBRAL (INTRAPARENCHYMAL)
aneurysm.
HEMORRHAGE
Other causes:
Spontaneous (nontraumatic) intraparenchymal - Extension of a traumatic hematoma
hemorrhages - Rupture of a hypertensive intracerebral
Most common cause of hemorrhage in middle to late hemorrhage into the ventricular system,
adult life - Vascular malformation,
Most are caused by rupture of a small intraparenchymal - Hematologic disturbances
vessel - Tumors
Hypertension : the most common underlying cause PATHOGENESIS OF SACCULAR ANEURYSMS
((Hypertensive Bleed) - Etiology: unknown.
- Accounts for more than 50% of clinically significant - Majority occur sporadically
hemorrhages - Genetic factors may play a role in their
Due to HPN induced vessel wall abnormalities: pathogenesis.
Hyaline arteriolosclerosis in small vessels - Predisposing factors:
Proliferative changes and frank necrosis of Cigarette smoking
arterioles HPN
Lipohyalinosis promoting the development of - Basic underlying defect: defect in the media of the
rupture prone Charcot-Burhard aneurysms vessel (maybe present since birth)

CHARCOT-BOUCHARD MICROANEURYSMS
o Minute aneurysms, which are prone to rupture seen in
patients with chronic HPN.
o CB aneurysms, occur in vessels that are less than 300 m
in diameter
o Most common within the basal ganglia.

HPN: SLIT HEMORRHAGES

Slit-like cavity (slit hemorrhages) surrounded by brownish
discoloration upon resorption
Due to rupture of the small-caliber penetrating vessels Figure 19: Common sites of saccular aneurysm in the
damaged by HPN.
circle of willis.

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Figure 20: Berry aneurysm: Outpouchings (few mm - 3cm in
diameter) at an arterial branch point along the circle of Willis.
Have bright red shiny surface and a thin translucent wall. The
wall or lumen may contain atheromatous plaques, calcification,
or thrombus.
SAH: Clinical Features:
- Most frequent in the 5th decade
- Slightly more frequent in females
- Aneurysms > 10 mm in diameter: 50% risk of bleeding
per year.
- 1/3 cases it is associated with acute increases in
intracranial pressure, such as with straining at stool or
sexual orgasm.
- Sx: sudden, excruciating headache, then rapidly lose
consciousness.
Complications of SAH:
1) Acute events ( hours to days)
Vasospasm increased risk of further
damage
2) Late sequelae
Meningeal fibrosis and scarring can lead
obstruction of CSF flow.
Figure 22: Vascular malformation: dilated, tortuous, worm-like
blood vessels separated by gliotic tissue
CEREBRAL EDEMA
Caused by the release of osmotically active substances
(arachidonic acid, electrolytes, lactic acid) from the
necrotic brain tissue
Vascular injury and leakage of proteins in the interstitial
space aggravates edema
By 3-4 days (most dangerous period for large infarct)
interstitial fluid accumulates in the infarct and around it.
Increase tissue volume ( edema or hemorrhage)
increase pressure inside fixed capacity of skull damage
to brain by:
Decreasing perfusion
Displace tissue across dural barriers or through
openings (herniation)

ARTERIOVENOUS MALFORMATION
Most common type of vascular malformation.
M:F ratio 2:1
Clinically presents between the ages of 10 and 30 years as:
Seizure disorder
Intracerebral hemorrhage
Subarachnoid hemorrhage
Most common site: territory of the MCA, particularly its Figure 23: Swelling of the left cerebral hemisphere a shift
posterior branches with herniation of the uncus of the hippocampus through the
Developmental abnormalities of cerebral vessels. Tangle tentorium uncal grooving (white arrow.)
of abnormal vessels interposed between a feeding artery
and a draining vein.
Chronic compression ischemia of brain tissue
seizures and neurologic deficits
HISTO: Greatly enlarged blood vessels separated by
gliotic tissue

Figure 24: Acute cerebral swelling producing herniation of the

cerebelllar tonsils into the foramen magnum.
Figure 21: GROSS morphology - tangled network of wormlike Acute brain swelling in the closed cranial cavity is serious
irregular, tortuous vessels with prominent, pulsatile can be fatal. Cause of death from a massive hemispheric
arteriovenous shunt. infarct:
Cerebral edema and herniations

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