A 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 stroke cases.
Watershed strokes are localized to two primary regions of the brain, and are
termed cortical watersheds and internal watersheds. Patients with many different
cardiovascular diseases have a higher likelihood of experiencing a blood clot
or loss of blood flow in border-zone regions of the brain. The resulting
symptoms differ based on the affected area of the brain. A CT 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 cell research.
Terminology and location Watershed 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 arterial territories 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.
These events are localized to two primary regions of the brain:
Cortical watershed strokes, or outer brain infarcts, are located between the
cortical territories of the anterior cerebral artery, middle cerebral artery,
and posterior cerebral artery. Internal watershed strokes, or
subcortical brain infarcts, are located in the white matter along and slightly
above the lateral ventricle, between the deep and the superficial arterial
systems of the MCA, or between the superficial systems of the MCA and ACA.
Nonetheless, within the literature itself, there exists confusion over the
terminology used to describe cortical infarcts and subcortical 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. Causes and risk factors
Watershed strokes are caused by ischemia or a lack of blood flow to the brain.
There are several causes of ischemia, including embolism and atherosclerosis.
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 vessel. Cardiovascular diseases that increase the risk of ischemia
include: Congestive heart failure, which can lead
to an inability to pump sufficient amounts of blood to the brain
Atherosclerosis, 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 brain Angiopathy, a disease of the blood
vessels Arterial hypotension, or low blood
pressure in the arteries Hypertension, or high blood pressure
Hyperlipidemia, or excessive cholesterol buildup in the blood vessels
Diseases such as sickle cell anemia, which can lead to deformed red blood
cells clogging blood vessels and impeding blood flow
Carotid artery stenosis, or narrowing of the carotid artery which can decrease
the volume of blood flow to the brain Signs and symptoms
= Stroke signs and symptoms in general= Watershed 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, representing F = Facial weakness, A =
Arm weakness, S = Speech difficulty, and T = Time to act.
All 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. After 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. Most 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.
Damage to the cerebral cortex may lead to aphasia or confusion and damage to
the cerebellum may lead to lack of motor movement.
= Watershed stroke signs and symptoms= Stroke 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.
Diagnosis Diagnosis 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, is very sensitive for locating
areas of an ischemic based stroke, such as a watershed stroke.
Further 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. = Classification systems=
The Oxfordshire Community Stroke Project classification relies primarily on the
patient's initial symptoms. Based on the extent of the symptoms, the stroke
episode is classified as total anterior circulation infarct, partial anterior
circulation infarct, lacunar infarct or posterior circulation infarct. These
four entities predict the extent of the stroke, the area of the brain affected,
the underlying cause, and the prognosis. The TOAST 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
Thrombosis or embolism due to atherosclerosis of a large artery
Embolism of cardiac origin Occlusion of a small blood vessel
Pathogenesis Although many imaging techniques are
used to document watershed strokes, their pathogenesis remains
controversial. It may involve various mechanisms such as systemic hypotension,
microemboli, severe arterial stenosis, ICA occlusion or a combination of these.
= Hypotension= A 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. = Microemboli=
Microemboli have not been experimentally proven to cause watershed strokes. It is
unclear whether they are a cause or an effect of a watershed stroke. 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 endarterectomy.
Microemboli 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. = ICA occlusions=
Thrombi 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 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 blood flow.
However, 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. The wall of internal carotid artery just
distal to the bifurcation 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 thrombi. 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. Treatment
= Carotid endarterectomy= Often 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.
There 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.
= Percutaneous treatments of carotid stenosis=
In 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.
Carotid angioplasty During carotid angioplasty, 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.
Carotid stenting Carotid stenting follows a similar
procedure. Rather than using a balloon, a stent is placed over the
atherosclerotic plaque in the hopes of stabilizing it and allowing for
increased blood flow to watershed portions of the brain.
Long-term care and rehabilitation Watershed 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 therapies=
Long-term 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. Occupational 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 with aphasia
resulting from stroke. = Surgical interventions=
Endovascular 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 strokes. 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. = Prevention of future strokes=
There 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 acids,
antioxidants, B-group vitamins, and zinc, have been shown to increase the
recovery of neurocognitive function after a stroke. Antiplatelet 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.
Current and future research = Stem cell transplantation=
Ischemic 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. = Strokes after cardiac surgery=
Although 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.
= Deep watershed infarcts= Hemodynamic 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 specific infarcts. = Basilar artery stenting=
While intracranial artery stenting is used for same side stoke prevention,
basilar artery stenting may help to improve parallel, accessory blood flow.
The stent may also lead to termination of recurrent middle cerebral artery
strokes. = Penumbra imaging=
The 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.
CLEVSRKNC peptide This 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. Liposomal drug delivery
Nanoliposomes 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:
Drugs can be maintained in the active state while encapsulated.
Being encapsulated provides direct access to target tissue
Prevention of non-specific binding Allows for a high concentration of drug
Due to the fact that acidic environment and low blood flow are prominent
characteristic of the penumbra area, liposomal drugs seem to be well suited.
References