and external resources
of an ischemic stroke in the brain without (left)
and with (right) contrast.
watershed stroke or watershed infarct is defined
as an ischemia,
or blood flow blockage, that is localized to the border
zones between the territories of two major arteries
in the brain. Watershed
locations are those border-zone regions in the brain supplied
by the major cerebral
arteries where blood
supply is decreased. Watershed strokes are a concern
because they comprise approximately 10% of all ischemic
strokes are localized to two primary regions of the brain,
and are termed cortical watersheds (CWS) and internal watersheds
Patients with many different cardiovascular
diseases have a higher likelihood of experiencing a
or loss of blood
flow in border-zone regions of the brain. The resulting
symptoms differ based on the affected area of the brain.
scan and MRI
are used for diagnosis, and afterward several treatment
options are available, including the removal of atherosclerotic
plaque and a physical widening of the clogged blood
vessel. Long-term care is focused around three areas:
rehabilitative therapy, surgical interventions, and prevention
of future watershed strokes. Going forward, research to
combat watershed strokes is focusing on various topics,
such as stem
strokes are named because they affect the distal watershed
areas of the brain. The original terminology came from the
German literature, which used the analogy of an irrigation
system. The German scholars compared the blood flow in distal
of the brain to the last field on a farm, which was the
area with the least supply of water and therefore most vulnerable
to any reduction in flow.
In a medical context, the term “watershed” refers to those
areas of the brain that receive dual blood supply from the
branching ends of two large arteries.
events are localized to two primary regions of the brain:
within the literature itself, there exists confusion over
the terminology used to describe cortical (outer brain)
infarcts and subcortical (inner brain) infarcts. Besides
watershed, border-zone is another common term used to refer
to areas of the brain between the ends of two adjacent arteries.
Other less used terms include: borderland, end zone, boundary
zone, and terminal zone. These varying terms have arisen
from the considerable anatomic
variability both in the cerebral vascular structure and
the territories of the brain that they supply.
and risk factors
strokes are caused by ischemia or a lack a blood flow to
There are several causes of ischemia, including embolism
There are several conditions that can predispose someone
to watershed stroke by increasing the likelihood that insufficient
blood supply will be able to reach the brain. People with
many different cardiovascular
diseases have a higher likelihood of experiencing a
clot or a plaque that impedes flow through a blood
Cardiovascular diseases that increase the risk of ischemia
heart failure, which can lead to an inability to
pump sufficient amounts of blood to the brain
which can cause a buildup of cholesterol plaques in
the blood vessels, thereby decreasing the volume of
blood that can flow through the vessel and reach the
a disease of the blood vessels
or low blood pressure in the arteries
or high blood pressure
or excessive cholesterol buildup in the blood vessels
such as sickle
cell anemia, which can lead to deformed red blood
cells clogging blood vessels and impeding blood flow
artery stenosis, or narrowing of the carotid artery
which can decrease the volume of blood flow to the brain
signs and symptoms in general
stroke symptoms are due to the reduced blood flow to all
parts of the body, specifically the brain, thus leading
to brain damage. Initial symptoms, as promoted by the American
Stroke Association, are FAST
(stroke), representing F = Facial weakness (droop),
A = Arm weakness (drift), S = Speech difficulty (slur),
and T = Time to act (priority of intervention).
strokes are considered a medical emergency. Any one of these
symptoms, whether seen alone or in combination, should be
assumed to be stroke until proven otherwise. Emergency medical
help should be sought IMMEDIATELY if any or all of these
symptoms are seen or experienced. Early diagnosis and timely
medical intervention can drastically reduce the severity
of a stroke, limit damage to the brain, improve the chances
of a full recovery and reduce recovery times massively.
the initial stroke, other symptoms depend on the area of
the brain affected. If one of the three central
nervous system pathways is affected, symptoms can include
numbness, reduced sensation, and hyperreflexia.
often, the side of the brain damaged results in body defects
on the opposite side. Since the cranial nerves originate
from the brainstem,
damage to this area can lead to defects in the function
of these nerves. Symptoms can include altered breathing,
problems with balance, drooping of eyelids, and decreased
sensation in the face.
to the cerebral cortex may lead to aphasia
or confusion and damage to the cerebellum
may lead to lack of motor movement.
stroke signs and symptoms
presentations which are particularly suggestive of a watershed
stroke include bilateral visual loss, stupor, and weakness
of the proximal limbs, sparing the face hands and feet.
of a cerebral vascular accident begins with a general neurological
examination, used to identify specific areas of resulting
injury. A CT
scan of the brain is then used to identify any cerebral
hemorrhaging. An MRI with special sequences called diffusion-weighted
MR imaging (DWI), is very sensitive for locating areas of
an ischemic based stroke, such as a watershed stroke.
diagnosis and evaluation of a stroke includes evaluation
of the blood vessels in the neck using either Doppler ultrasound,
MR-angiography or CT-angiography, or formal angiography.
An echocardiogram may be performed looking for a cardiac
source of emboli. Blood tests for risk factors also may
be ordered, including cholesterol levels, triglyceride levels,
homocysteine levels, and blood coagulation tests.
TOAST (Trial of Org
10172 in Acute Stroke Treatment) classification
is based on clinical symptoms as well as results of
further investigations. In this diagnostic system, a
stroke is classified as being due to
or embolism due to atherosclerosis of a large artery
of cardiac origin
of a small blood vessel
many imaging techniques are used to document watershed strokes,
remains controversial. It may involve various mechanisms
such as systemic hypotension, microemboli,
severe etarial stenosis, ICA occlusion or a combination
sharp drop in blood
pressure is the most frequent cause of watershed infarcts.
The most frequent location for a watershed stroke is the
region between the anterior cerebral artery and middle cerebral
artery. These events caused by hypotension do not usually
cause the blood vessel to rupture.
have not been experimentally proven to cause watershed strokes.
It is unclear whether they are a cause or an effect of a
With watershed strokes, platelet
aggregates block the small meningeal
arteries in watershed regions creating a microembolism.
Microemboli usually form as thrombi, and can block arteries
outright. On the other hand, they often detach, move into
blood circulation, and eventually block smaller downstream
branches of arteries causing a thromboembolism. Generally,
emboli travel as far outward as their size permits along
the vascular branches of the brain. Using this hypothesis,
microemboli are viewed as the cause of the infarct rather
than secondary events. Nevertheless, secondary thrombi do
form after infarcts, and therefore it has been difficult
to distinguish between emboli and thrombi in watershed locations.
The best supporting evidence is correlative; patients display
subcortical abnormalities on CT scans and present more microembolic
signals during a carotid
can be common in some high-risk patients, such as those
with carotid stenosis. However, in healthier patients strokes
do not usually result from microemboli.
Internal carotid artery
of the neck. The internal carotid arteries arise from
carotid arteries - labeled Common caroti
on the figure.
at the split of the internal carotid artery in the neck
may cause watershed infarcts between the territories of
the anterior cerebral artery and the middle cerebral artery.
The resulting watershed infarcts in carotid artery blockages
have mostly been considered to be due to a reduced blood
flow, similar to that of hypotension.
Imaging studies in severe internal
carotid artery (ICA) disease report an incidence of
watershed stroke ranging from 19% to 64%.
Almost 40% of these watershed infarcts are attributed to
narrowing of the carotid artery, which produces the reduced
a different possible explanation has emerged. Alternatively,
the vascular occlusion could be the result of microemboli
from the carotid thrombi before the lumen
becomes completely blocked.
In this scenario, the clotting becomes too severe and the
clot breaks free. The resulting traveling clot is known
as an embolus (plural emboli). The wall of internal carotid
artery just distal to the bifurcation (split) is a common
site of atherosclerosis because of the unique hemodynamic
effects caused by the blood flow divider. As a result, thrombi
formation is more prevalent there.
In general, researches have observed that this microembolization
is a frequent phenomenon during the build-up of cerebral
The resulting emboli are pieces of calcified plaque. If
these microemboli are 0.1 mm in diameter, they might
pass into the small branches of the vascular system. There
they may be destroyed by protective cellular defenses, or
they may cause a stroke.
Altogether, these considerations suggest that the watershed
infarcts in carotid thrombosis are caused by microembolization
from mural thrombi, thrombi adherent to the vessel wall,
rather than by blood flow disturbances.
considered one of the safest ways to treat symptomatic carotid
stenosis, carotid endarterectomy is a procedure by which
a surgeon gently removes atherosclerotic plaque. Blood flow
hopefully then returns to normal, increasing oxygen concentration
to normal amounts in watershed areas of the brain.
is the potential for complications, including disturbing
portions of the plaque leading to a stroke or heart attack
during or after surgery. Small risks of bleeding and infection
exist as well.
treatments of carotid stenosis
this type of procedure, a narrowed blood vessel is expanded
via angioplasty or stenting. A thin angiography catheter
is inserted in a large groin blood vessel and advanced to
the stenosis. Percutaneous treatment is less invasive than
endarterectomy, usually requiring only local anesthesia.
Endarterectomy is still considered safer though, as percutaneous
treatments can lead to accidental dislodging of plaque or
even arterial rupturing.
an angiography cather with a small deflated balloon attached
on the tip is advanced to a carotid stenosis. The ballon
is then inflated slowly, forcing the narrowed portion of
the vessel to expand.
stenting follows a similar procedure. Rather than using
a balloon, a stent (metal mesh-like tube) is placed over
the atherosclerotic plaque in the hopes of stabilizing it
and allowing for increased blood flow to watershed portions
of the brain.
care and rehabilitation
strokes are seldom fatal, but they can lead to neuromuscular
degeneration, as well as dementia.
This degeneration at the watershed regions of the brain
can lead to difficulties with movement and motor coordination,
as well as speech. Long-term care is focused around three
areas: rehabilitative therapy, surgical interventions, and
prevention of future watershed strokes.
rehabilitative therapy for watershed stroke patients involves
physical, occupational, and speech and language therapies.
Physical therapy can be used to enhance motor function in
the legs and arms that has been impacted by stroke.
therapies can be provided to help to alleviate cognitive
impairments that result from watershed stroke,
as well as to improve fine motor function that was damaged
as a result of the stroke.
Stroke can also cause impairments in speech production secondary
to neurocognitive and neuromuscular impairments, and therefore
speech and language therapies are often a component of long-term
care for stroke patients. Intensive speech and language
therapy has been shown to improve speech deficits associated
resulting from stroke.
interventions, including surgical revascularization,
can increase blood flow in the area of the stroke, thereby
decreasing the likelihood that insufficient blood flow to
the watershed regions of the brain will result in subsequent
Neuroscientists are currently researching stem cell transplantation
therapies to improve recovery of cebreral tissue in affected
areas of the brain post-stroke. Should this intervention
be proven effective, it will greatly increase the number
of neurons in the brain that can recover from a stroke.
of future strokes
are several interventions that are often used to help prevent
the recurrence of a watershed stroke; namely, nutritional
interventions, as well as antiplatelet, anticoagulant, and
statin drug use. Nutritional interventions, including increased
consumption of certain amino
and zinc, have been shown to increase the recovery of neurocognitive
function after a stroke.
drugs, such as aspirin, as well as anticoagulants,
are used to help prevent blood clots and therefore embolisms,
which can cause watershed strokes. Statin
drugs are also used to control hyperlipidemia, another risk
factor for watershed stroke.
and future research
stroke is still a major health concern and studies are being
conducted to determine the pathway in which brain damage
occurs to identify targets for intervention. Stem cell transplantation
may help in intervention to improve cell recovery and regeneration.
after cardiac surgery
the mechanism is not entirely understood, the likelihood
of a watershed stroke increases after cardiac surgery. An
experiment conducted in a five year span studied the diagnosis,
etiology, and outcome of these postoperative strokes. It
was observed that intraoperative decrease in blood pressure
may lead to these strokes and patients who have undergone
aortic procedures are more likely to have bilateral watershed
infarcts. Furthermore, bilateral watershed strokes are associated
with poor, short-term outcomes and are most reliably observed
by diffusion-weighted imaging MRI. Thus future clinical
research and practice should focus on the identification
of bilateral stroke characteristics. This identification
can help discover affected areas and increase correct diagnosis.
impairment is thought to be the cause of deep watershed
infarcts, characterized by a rosary-like pattern. However
new studies have shown that microembolism might also contribute
to the development of deep watershed infarcts. The dual
contribution of hemodynamic impairment and microembolism
would result in different treatment for patients with these
artery (BA) stenting
intracranial artery stenting is used for same side stoke
artery stenting may help to improve parallel, accessory
blood flow. The stent may also lead to termination of recurrent
middle cerebral artery (MCA) strokes.
area around the damaged ischemia is known as the penumbra.
This viable area has the ability to regenerate with the
help of pharmacological treatment however most patients
with penumbra are left untreated. New research is being
conducted in metabolic suppression, direct energy delivery,
and selective drug delivery to help salvage this area of
the brain after a stroke.
new drug has been shown to home to ischemic stroke tissue
as well as apoptotic
neuronal cells of the penumbra region. This discovery may
help in creating selective drug delivery for stroke patients.
are currently being researched for specific drug delivery
due to their ph-sensitive and high blood–brain
barrier diffusion characteristics. Many advantages of
these drugs include:
can be maintained in the active state while encapsulated.
encapsulated provides direct access to target tissue
of non-specific binding
for a high concentration of drug
to the fact that acidic environment and low blood flow are
prominent characteristic of the penumbra area, liposomal
drugs seem to be well suited.