Cerebrovascular pathology

ABEL B. (MD)
Pathology lectures, NMEI, DBU

cerebrovascular
The term cerebrovascular disease denotes
any abnormality of the brain caused by a
pathologic process of blood vessels
They cause 200,000 deaths each year in the
United States (expected to double in 2030)
Stroke is clinically defined as an abrupt
onset of a neurologic deficit that is
attributable to a focal vascular cause that
persists for > 24 hours

 Cerebrovascular diseases
TIA (transient ischemic attach) was
originally defined as a sudden onset
of a focal neurologic symptom and/or
sign lasting less than 24 hours
TIA is now defined as a transient
episode of neurologic dysfunction
caused by focal brain, spinal cord, or
retinal ischemia, without acute
infarction

Classification of CVD
Based on pathophysiology and pathologic
anatomy, it is convenient to consider
cerebrovascular disease as two processes:
1. Impairment of blood supply and
oxygenation of CNS tissue (Hypoxia,
ischemia, and infarction)
2. Hemorrhage resulting from rupture of CNS
vessels

Physiologic perfusion & O2 supply of

the brain tissue
The brain is 1.5% by weight of the
total body weight & receives 15% of
cardiac output & 20% of body
oxygen consumption
Brain oxygen consumption (CMRO2,
cerebral metabolic rate for oxygen) is
about 3.5 ml/100g/min !!! (highly
aerobic organ)

Brain perfusion
The brain has increased blood flow
(55ml/min/100gm tissue),
with marked variations of oxygen demand
between the different parts of the brain:
white Vs Grey matter
different parts of the grey mater
Pyramidal cells (level 3 &5), hippocampus,
purkinje cells of cerebellum

The brain relies on blood borne glucose

for 90% of its energy requirements

Brain Ischemia

Ischemia
Two principal types of acute ischemic
injury are recognized (based on the
anatomic involvement)
1. Global cerebral ischemia
(ischemic/hypoxic encephalopathy)
occurs when there is a generalized
reduction of cerebral perfusion.
- such as in cardiac arrest, shock,
and severe hypotension.

Ischemia
2. Focal cerebral ischemia: follows
reduction or cessation of blood flow to a
localized area of the brain due to:
- large-vessel disease (such as embolic or
thrombotic arterial occlusion, often in a
setting of atherosclerosis) or
- small-vessel disease (such as vasculitis
or occlusion secondary to arteriosclerotic
lesions seen in hypertension).

Global Cerebral Ischemia

The clinical picture diffuse hypoxic/ischemic
encephalopathy varies with the severity of
the insult.
In mild cases, there may be only a transient
postischemic confusional state, with
eventual complete recovery and no irreversible
tissue damage. (e.g. syncopal attacks)
From the cells of the CNS Neurons are the
most sensitive to hypoxia, although glial
cells (oligodendrocytes and astrocytes) are
also vulnerable.

Global Cerebral
Ischemia
In severe global cerebral ischemia,
widespread neuronal death, irrespective of
regional vulnerability, occurs.
Patients who survive in this state often remain
severely impaired neurologically and deeply
comatose (persistent vegetative state).
Other patients meet the current clinical
criteria for "brain death," including persistent
evidence of diffuse cortical injury (isoelectric,
or "flat," electroencephalogram)

Morphological changes of
ischemia
The morphological changes after
irreversible ischemia are:
A. Early changes: occurring 12 to
24 hours after the insult, include
acute neuronal cell change (red
neurons) characterized at first by
microvacuolization, then
eosinophilia of the neuronal
cytoplasm, and later nuclear
pyknosis and karyorrhexis

Morphological changes of
ischemia
B. Subacute changes: occurring
at 24 hours to 2 weeks, include
necrosis of tissue, influx of
macrophages, vascular proliferation,
and reactive gliosis

Morphological changes of
ischemia
C. Repair: seen after approximately
2 weeks, is characterized by eventual
removal of all necrotic tissue, loss of
normally organized CNS structure,
and gliosis

Focal Cerebral Ischemia

Causes of focal ischemia

These are caused by vascular occlusion
secondary to:
- Atherosclerosis & thrombosis
- Embolization (arterio-arteriolar, cardiac,
paradoxical embolization)
- Infections (vasculitis by: syphilis, TB, CMV,
toxoplasmosis, HSV I, aspergillosis)
- Drugs (amphetamines, heroin, cocaine)
- Others (CADASIL, CAA)

The outcomes of ischemia

When blood flow to a portion of the brain is
reduced, the survival of the tissue at risk
depends on a number of modifying factors:
1. the availability of collateral circulation
(water shed areas)
2. the duration of ischemia
3. the magnitude and rapidity of the reduction
of flow (thrombosis Vs Embolization)
4. The selective vulnerability of the brain tissue

The duration of the ischemia Vs the

severity of ischemia
Decrease in cerebral blood flow to
zero causes death of brain tissue
within 410 minutes
values <1618 mL/100 g/min cause
infarction within an hour
values <20 mL/100 g/min cause
ischemia without infarction unless
prolonged for several hours or
days

Focal Cerebral Ischemia

Cerebral arterial occlusion may lead to
focal ischemia and ultimately, if it is
sustained, to infarction.
The size, location, and shape of the
infarct and the extent of tissue damage
that results from focal cerebral ischemia
brought about by occlusion of a blood vessel
are determined by:
- the involved arteries &
- the adequacy of collateral flow.

Collateral blood flow

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 cortical leptomeningeal
anastomoses.
In contrast, there is little if any collateral
flow for the deep penetrating vessels
supplying structures such as the thalamus,
basal ganglia, and deep white matter.

Clinical features of ischemia

Depends of the:
- Site
- Size
- Severity
- Duration
Of the infarction

Intracranial hemorrhages

Intracranial hemorrhages

Include:
Epidural hemorrhages
Subdural hemorrhages
Subarachnoid hemorrhages
Intraparenchymal hemorrhages
Intraventricular hemorrhages

Intracranial hemorrhages
Can be classified as traumatic and
non-traumatic.
Epidural & subdural hemorrhages
are usually traumatic
Intracerebral, subarachnoid &
interaventricular could be
spontaneous

Intracerebral
(Intraparenchymal) Hemorrhage
Is on common form of CVD / stroke.
If spontaneous is also known as
hemorrhagic stroke.
Hypertension is a well defined risk
factor for hemorrhagic stroke.
Others include: vasculitis,
coagulopathies, neoplasms,
vascular malformations &
aneurysms, amyloidosis

Intracerebral hemorrhage
Ganglionic hemorrhages are highly
associated with hypertension.
The commonest site of bleeding in
hypertensive individuals are: putamen,
thalamus, pons, and cerebral
hemispheres (in decreasing frequency)
Lobar hemorrhages are highly
associated with: infections, bleeding
tendencies, tumors

Morphology of hemorrhages
Acute hemorrhages are
characterized by extravasation of
blood with compression of the
adjacent parenchyma.
Old hemorrhages show an area of
cavitary destruction of brain with a
rim of brownish discoloration

Complications of intracranial
hemorrhages

Compressive effects
Ischemic effects
Edema
Midline shifts
Increased ICP
Herniation
Long term (ICP, rebleeding, permanent
morbidity)
Others

Subarachnoid hemorrhages
The most frequent cause of clinically significant
subarachnoid hemorrhage is rupture of a
saccular (berry) aneurysm. [excluding
trauma]
But it also result from extension of a traumatic
hematoma, rupture of a hypertensive
intracerebral hemorrhage into the
ventricular system, vascular malformation,
hematologic disturbances, and tumors.

Pathogenesis of Saccular
Aneurysms
The etiology of saccular aneurysms is
unknown.
But the common associated risk
factors are:
- PCKD (autosomal dominant)
- Marfans syndrome
- Ehlers-Danlos syndrome [type IV]
- neurofibromatosis type 1

C/F
Sever global headache & signs of
increased ICP
Death could occur in 25-50% of patients
Re-bleeding is common in the survivors
(20% in the first 2 weeks, 30% in the first
month, and about 3% per year afterwards)
LP findings (blood stained CSF,
Xanthochromic CSF in chronic cases)
communicating hydrocephalus

Hypertensive CVD
Hypertension causes:
-

Ischemic stroke
Hemorrhagic stroke
Lacunar infarcts
Slit hemorrhages
Hypertensive encephalopathy

Lacunar infarcts
Are small infarcts (<15mm), that
are caused by the atherosclerotic
occlusion of small vessels
Based on their location in the CNS,
lacunes can either be clinically silent
or cause severe neurologic
impairment

Hypertensive
Encephalopathy
Acute hypertensive
encephalopathy is a clinicopathologic syndrome arising in a
hypertensive patient characterized
by diffuse cerebral dysfunction
including:
headaches,
confusion,
vomiting, and convulsions,
sometimes leading to coma

Any questions?