CEREBROVASCULAR DISEASES

Dr Noor ul Balqis Che Ibr ahim

Depar tment of Pathology

 DEFINITION OF CVD

• CVD refer to a variety of condition/group of disease that

affect the blood supply/vessel to the brain.
• Any condition that can prevent the brain cell from getting
enough oxygen and resulting in brain damage.
• Brain abnormality due to pathologic process of the blood
vessels and blood supply
• Stroke/brain attack/cerebrovascular accident refer to an
acute alteration in a neurology status last for more than
24hours and correlates with sudden disruption in blood
flow to areas in brain.
 OUTLINE

• CVD occur via two basic pathways

• Reduced blood flow or oxygenation
• Cerebral hypoxia-ischaemia (Global)
• Cerebral infarction (Focal)
• Vascular dementia
• CADASIL (Cerebral Autosominal Dominant Arteriopathy with
Subcortical Infarct and Leukoencepalopathy)

• Cerebral hemorrhage
• Hypertensive cerebrovascular disease
• Aneurysm
• Vascular malformation
• Vasculitis
• Cerebral Amyloid Angiopathy
 • Hypoxia, ischemia, and
infarction resulting from
IT IS CONVENIENT impairment of the blood
TO CONSIDER supply and oxygenation of
CEREBROVASCULAR CNS and tissue
DISEASE AS TWO
PROCESSES:
• Hemorrhage resulting
from rupture of CNS vessels
Reduced blood flow or oxygenation
Cerebral hypoxia-ischaemia Ischemia refers to the
Cerebral infarction
CADASIL (Cerebral autosomal
insufficiency of blood
dominant arterioathy with supply. It can be focal
subcortical infarct and
leukoencephalopathy)
or global.
Cerebral hemorrhage
Hypertensive cerebrovascular
disease
Hypoxia refers to the
Aneurysm reduced supply of
Vascular malformation oxygen while the blood
Vasculitis
Cerebral Amyloid Angiopathy flow is entirely normal
or even increased.

Reduced blood flow or oxygenation
Cerebral hypoxia-ischaemia
Cerebral infarction
CADASIL
Cerebral hemorrhage
Hypertensive cerebrovascular
disease
Aneurysm
Vascular malformation
Vasculitis
Cerebral Amyloid Angiopathy
Ischemia
• Reduction in perfusion pressure
(hypotension)
• Vessel obstruction
Functional hypoxia (low pO2)
• Impaired O2-carrying capacity of blood eg:
reduced blood oxygen content in
cardiopulmonary disease, carbon monoxide
poisoning
• Inhibition of O2 use by tissue, eg:cyanide
poisoning
Effects of ischemia -infarction
• Neurons can survive 4 - 5 minutes when no
perfusion
• Necrosis and inflammation
• Nitric oxide/free radical damage neurons
Reduced blood flow or oxygenation
Cerebral hypoxia-ischaemia
Cerebral infarction
CADASIL Global cerebral ischemia (hypoxic
ischaemic encephalopathy)
• Cardiac arrest
Cerebral hemorrhage • Shock and severe hypotension

Hypertensive cerebrovascular Focal cerebral ischemia (vessel

disease obstruction)

Aneurysm • Atherosclerosis in hypertension

• Embolism or thrombosis in atherosclerosis
Vascular malformation • Vasculitis
Vasculitis
Cerebral Amyloid Angiopathy
 CLINICAL PRESENTATION
• In mild cases ~ transient postischemic
confusional state

CEREBRAL
• In severe cases ~
H Y P OX I A -
ISCHAEMIA • Persistent vegetative state
(GLOBAL • Severe neurological impairment
CEREBRAL • Deeply comatose
ISCHEMIA)
• Brain death
• Persistent diffuse cortical injury
• Brainstem damage (absence of reflexes,
respiratory drive and cerebral perfusion)
 • Brain edema

• Widened gyri & narrowed sulci

• Poor demarcation between gray &

GROSS white matter
MORPHOLOGY
• Border zone (watershed) infarcts
• Sickle-shaped band of necrosis in border
zone between ant. & mid. cerebral art.
Distribution
• Wedge-shaped infarcts in brain & spinal
cord
GLOBAL HYPOXIC-ISCHEMIC
ENCEPHALOPATHY

Comatose
patient on
ventilator
after cardiac
arrest resus.
INFARCT OVER WATERSHED ZONE
(ANTERIOR & MIDDLE CEREBRAL
ART.) IN HYPOTENSION
 • Early changes ( 12 to 24 hrs )
• Cell necrosis
• red neurons
• Purkinje cells of cerebellum
• Neutrophilic infiltration

• Subacute changes ( 24 hrs to 2 wks )

• Tissue necrosis
MORPHOLOGY • Influx of macrophages
• Angiogenesis
• Starting reactive gliosis

• Repair ( > 2wks )

• Reactive gliosis
• Disorganized CNS structures
• Pseudolaminar necrosis
NORMAL NEURON VS DYING NEURON
 DYING RED
NEURON IN HYPOXIA

Fragmentation of nuclei

Anoxic shrunken neuron with pyknotic/condense

And eosinophilic cytoplasm.
DYING PURKINJE CELLS IN HYPOXIA

Relatively normal neuron

Eosinophilic changes

Pyknotic nuclei

Cerebral hypoxia-ischaemia
Cerebral infarction/focal
cerebral ischaemia
CADASIL
Hypertensive cerebrovascular
disease
Aneurysm
Vascular malformation
Vasculitis
Cerebral Amyloid Angiopathy
• A cerebral infarct in this setting is defined as focus/areas
of brain tissue that dies a result of localized hypoxia-
ischaemia caused by cessation of blood flow.
• This follows territory of distribution of compromised
vessels and depending on
• Adequate collateral
• Circle of Willis
• Partial or inconsistent collateral
• Distal branches of ant., mid & post. cerebral art.
• Little collateral flow
• Thalamus, basal ganglia & deep white matter
• Clinical features:
• May be asymptomatic
• Hemiplegia, sensory deficit, blindness and aphasia
• Atherothrombotic infarcts are often preceded by
transient ischemic attacks (TIAs).
• TIA is a focal neurological deficit that lasts less than 24
hours and resolves.They may be caused by:
• critical reduction of perfusion but resolves before
permanent tissue damage, or
• emboli that break up soon after occluding vessels.
 CEREBRAL INFARCTION/FOC AL
CEREBRAL ISCHAEMIA

• The main causes of infarction is atherosclerosis of large

vessel or embolic occlusion of distal vessel or both.
• Risk factor for cerebral infarction is similar with
atherosclerotic cardiovascular disease and this includes
diabetes, hpt, smoking, family history,hpl, truncal obesity.
• In embolic infarcts, these appear abruptly.
• In athero-thrombotic infarcts, they evolve over a period of
time, usually hours.
NORMAL DISTRIBUTION OF CEREBRAL ARTERIES
 • Caused by the pathological accumulation of
fluid in the brain intracellular and extracellular
spaces.
• Caused by both cytotoxic and vasogenic
edema.
BRAIN EDEMA • Release of osmotically active substances from
IN CEREBRAL the necrotic brain tissue.
INFARCT • Aggravated by vascular injury and leakage of
proteins in the interstitial space.
• By 3-4 days, interstitial fluid accumulates in the
infarct and around it.
• Death from massive infarct is caused by
cerebral edema and herniations.
ATHEROSCLEROSIS OF THE BASILAR
ARTERIES

Vertebral art
THROMBUS IN THE MIDDLE
CEREBRAL ARTERY
 Poorly demarcated area of congestion

Later, it becomes sharply demarcated but

softens progressively.
GROSS
APPEARANCE
> 2/52 onward, it begins to disintegrate
and is gradually replaced by a cavity.

The size and location of infarcts follows

the anatomy of vascular territories.
 MORPHOLOGY

• Pale infarct, usually dt thrombosis

• Gross
• No changes (<6hrs)
• Pale, soft & swollen (by 48hrs)
• Gelatinous & friable (2 to 10 days)
• Tissue liquefies (10 days to 3 wks)
• Fluid-filled cavity lined by dark gray tissue

• Microscopic
• Red neurons (after 12hrs)
• Neutrophilic emigration (up to 48hrs)
• Macrophages predominate (2 to 3 wks)
• Gliosis developing esp. around the cystic cavity
Acute infarct in the distribution of RMCA. Swelling and early disintegration of the
infarcted area.
INFARCTION (MID CEREBRAL ART. DISTR.)
FRONTAL LOBE INFARCT W EARLY
RESOLUTION
ORGANIZING INFARCT (WELL
DEMARCATED YELLOW AREA)
Old MCA infarct. A collapsed cavity.
CEREBRAL INFARCT W H’AGE & EDEMA
INFARCT WITH PUNCTATE HEMORRHAGE

This infarct was caused by an embolus.

 ACUTE CEREBRAL INFARCT
WITH EDEMA

Pale area represent edema

 MACROPHAGES IN
LIQUEFACTIVE NECROSIS
RESOLUTION OF NECROSIS
CYSTIC SPACES
MACROPHAGES IN ORGANIZING
INFARCT
REMOTE (C AVITARY) HEALED
INFARCT

Ventricle
 • Vascular (multi-infarct) dementia
• Over months & years, develop multiple
infarcts
• Dementia, gait abnormalities &
pseudobulbar signs
VA S C U L A R
DEMENTIA • Causes:
• Atherothrombotic/emboli
• Hypertensive CVD
• Coagulopathies
• Vasculitis
 • Pathological features:
• Cerebral atrophy
• Numerous lesion in the white matter and
deep nuclei structure
• Diffuse ventriculomegaly with
hydrocephalus dur to marked reduction in
white matter.
• Lacunar infarcts.

VA S C U L A R • Microscopically includes extensice

atherosclerosis and hyaline arteriosclerosis.
DEMENTIA

• Binswanger disease
• Subtype of subcortical vascular dementia
• A form of small vessel vascular dementia
• Atrophy of the subcortical white matter
(subcortical leukoencephalopathy)
• Insidious fluctuating dementia involving
memory, mood and cognition; seizures &
mild strokes.
 • This is cause by abnormalities of the
blood vessel
• Such causes includes
• Causes:
• Hypertensive cerebrovascular disease
• Aneurysm
I N T R AC R A N I A L / C E R E B R A L
H E M O R R H AG E • Vascular malformation
• Vasculitis
• Cerebral Amyloid Angiopathy
• Mechanism: rupture intraparenchymal
vessels
 • Hpt is major causes of intracerebral
Cerebral hypoxia-ischaemia hemorrhage
Cerebral infarction/focal cerebral
• Peak in 60 y/o
ischaemia
Vascular dementia • Effect of hypertension includes
CADASIL • Accelerated atherosclerosis in larger
Hypertensive arteries
• Hyaline arteriolosclerosis in smaller
cerebrovascular vessels

disease • Weakening and necrosis of arterioles

Aneurysm • Development of minute aneurysms called

Vascular malformation
Vasculitis
Cerebral Amyloid Angiopathy
Charcot-Bouchard aneurysm
• In small vessels: 100 to 300 μm
• Commonly in basal ganglia: putamen,
globus pallidus, and thalamus
 • Sites
• Putamen (50% to 60%)
HYPERTENSIVE
CVD • Others: thalamus, pons, cerebellar
hemispheres (rare)
 • Lacunar Infarcts
• Arteriolar sclerosis
• Lacunes - small cavitary infarcts
• Sites: lenticular nucleus, thalamus, internal
capsule, deep white matter, caudate
nucleus and pons
• HPE: cavities with foamy macrophages &
PATHOLOGIC surrounding gliosis
FEATURES
• Slit Hemorrhages
• Rupture of small penetrating vessels &
h’age gets absorbed
• Slitlike cavities - with surrounding brown
discoloration
• HPE: focal tissue destruction, pigment-
laden macrophages and gliosis
Hemorrhages involving the basal ganglia area (the putamen in particular) tend to be
non-traumatic and caused by hypertension, which damages and weakens the small
penetrating arteries. A mass effect with midline shift, often with secondary edema,
may lead to herniation.
THALAMIC H’AGE
PRIMARY PONTINE
HEMORRHAGE
LACUNAR INFARCTION IN THE
PONS

Thrombosis of the sclerotic

arterioles leading to small
lacunar infarcts,or "lacunes"
Charcot-Bouchard microaneurysm, Masson Trichrome stain: A Charcot-Bouchard
microaneurysm (arrow) is an ectatic outpouching of an abnormal small vessel.The wall of the
aneurysm is composed of a thin layer of collagen (blue), and a fresh mural thrombus is located
at the lower right (contrast to Berry aneurysm)
LACUNAR INFARCT WITH CYSTIC
SPACES
 • This is a clinical condition due to acute
increase in systemic pressure leading
to acute neurological syndromes.
• The symptom includes ;
• Diffuse cerebral dysfunction
• Headaches
H Y P E RT E N S I V E • Confusion
E N C E P H A L O PAT H Y
• Vomiting and convulsions
• Coma
• Morphology:
• Cerebral edema
• Petechiae
 • Most common intracranial aneurysm
• Other type of aneurysms includes fusiform,
atherosclerotic, mycotic, and dissecting(pseudo).

• 90% occur in the anterior circulation

BERRY • Majority solitary

ANEURYSM • 20 to 30% of cases are multiple in autopsy series

• Presentation
• Sudden, excruciating headache
• Rapid loss of consciousness
• Rupture occur anytime but 1/3 of cases occur
during acute increase ICP
 • Pathogenesis
• Sporadic
• Cigarette smoking
• Hypertension

• Genetic factor involvement

• Ehlers-Danlos syndrome & Marfan
BERRY syndrome
ANEURYSM • Fibromuscular dysplasia of extracranial
arteries
• Coarctation of aorta
• Neurofibromatosis type 1
• Polycystic kidney disease

• Congenital
 • Morphology
• Few mm to 2cm
• Bright red, shiny surface & thin,
translucent wall
• Rupture is usually at apex
• Brown discoloration of the adjacent
brain & meninges

BERRY
• Arterial adjacent to it shows intimal
ANEURYSM thickening
• Sac is made of thickened hyalinized
intima but no muscular wall or elastic
lamina
• Adventitia of sac is continuous with
parent artery
• Atheromatous plaques, calcification or
thrombus
Subarachnoid
Hemorrhage
extravasation of blood into the
subarachnoid space between the
Majority is caused/as a complication of berry
pial and arachnoid membrane
aneurysm.
Other causes includes extension of traumatic
hematoma, rupture of HPT intracerebral h’age into
ventricular system, vascular malformation, bleeding
diathesis, & tumours
BERRY/SACCULAR ANEURYSM OF VERTEBRAL
ART

Temporal Lobe

Rt vertebral artery
The white arrow on the
black card marks the site
of a ruptured
berr/saccular aneurysm
in the circle of Willis.
This is a major cause for
subarachnoid
hemorrhage.
• The circle of Willis has been dissected, and three berry
aneurysms are seen.
• Multiple aneurysms are seen in about 20-30% of cases of
berry aneurysm.
Cerebral hypoxia-ischaemia
Cerebral infarction/
focal cerebral ischaemia
Vascular dementia
• Four groups
CADASIL
Hypertensive cerebrovascular disease
• Arteriovenous
Aneurysm malformations
Vascular malformation • Cavernous angiomas
Vasculitis
Cerebral Amyloid Angiopathy • Capillary telangiectasias
• Venous angiomas
 • Male : female = 2:1
• Age: 10 to 30
• Presentation
• Seizure disorder
Arteriovenous • Intracerebral h’age

malformations • Subarachnoid h’age

Cavernous angiomas
Capillary telangiectasias • Site
Venous angiomas • Middle cerebral art. (esp. post.
branch)
• Others: midbrain, cerebellum or
spinal cord

• Large AVM in newborn can lead to

CHF due to shunt effects, esp. it
involves vein of Galen
A cause for hemorrhage, particularly in persons aged 10 to 30, is a vascular
malformation. Seen here is a mass of irregular, tortuous vessels over the left posterior
parietal region.
ARTERIO-VENOUS
MALFORMATION

Striatum

Amygdala
• The microscopic appearance of
this vascular malformation reveals
the dilated, tortuous, worm-like
vascular channels where arteries
shunt directly into veins with no
intervening capillary bed; high
pressure.
• Duplication & fragmentation of
elastic lamina
• Thickened and hyalinized tunica
media
• Gliotic stroma & background
Arteriovenous malformations

Cavernous angiomas
Capillary telangiectasias
Venous angiomas

Abnormal cluster of enlarged capillaries

with no significant feeding arteries or
veins; low pressure
Distended, loosely organized vascular
channels

Thin, collagenized, hyalinized wall

Devoid of intervening nervous tissue

Old h’age, infarction or calcification

around vessels
Arteriovenous malformations
Cavernous angiomas
Capillary telangiectasias

Venous angiomas

•Closely packed thick walled vessels, which are

variably dilated and commonly display
thrombosis with occasionally formation of
phleboliths (calcified thrombi)

Cerebral hypoxia-ischaemia
Cerebral infarction/
focal cerebral ischaemia
Vascular dementia
Hypertensive cerebrovascular disease
Aneurysm
Vascular malformation
Vasculitis
CADASIL
Cerebral Amyloid Angiopathy
• Inflammation of the blood vessel wall may
occur as a part of systemic disorder such as
in Giant Cell Arteritis and Polyarteritis
Nodosa or maybe localized to cerebral
blood vessel.
• Type
• Giant Cell Arteritis
• Polyarteritis Nodosa
• Primary angiitis of the central nervous
system
 GIANT CELL ARTERITIS

• Inflammatory disease affecting

the large blood vessels of the
scalp, neck and arms
• Transmural and perivascular
infiltrate of lymphocytes,
histiocytes and giant cells
POLYARTERITIS NODOSA

• Rare vasculitis affecting small and

medium-sized
• Characterized by necrotizing • Leukocytic infiltrate
inflammation
• Acute fever, muscle, joint pains, asymmetric polyarthritis, malaise,
rash and weight loss
• Neuropathy and kidney failure
• Pathology features
• Leukocytic infiltrate
• Fibrinoid necrosis

Fibrinoid necrosis
 PRIMARY ANGIITIS OF THE CNS
(PACNS)

• Severe inflammatory disease of unknown origin.

• The term PACNS unifies a group of
clinicopathological presentations of vasculitis affecting
the vessels of the brain and spinal cord without any
overt systemic vasculitis or underlying potential
cause.
• Patient can present either as ischaemic or
haemorrhagic infarction.
PATHOLOGY FEATURES
• Granulomatous vasculitis (most common pattern)
• Granulomas and multinucleated giant cells.
• There was at least focal vessel wall destruction

• Lymphocytic vasculitis
• predominantly lymphocytic inflammation with occasional plasma cells, extending
through the vascular wall with features of vascular distortion and destruction.

• Necrotizing vasculitis (least frequent pattern)

• characterized by acute necrotizing vasculitis, similar to the pattern seen in PAN,
with transmural fibrinoid necrosis.
THE END