Watershed stroke
Encyclopedia
A watershed stroke 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
" refers to those border zone regions in the brain supplied by the major cerebral arteries
where blood supply
is decreased.
In general, a stroke
occurs when there is some form of interruption or occlusion
of blood flow to or within the brain. This is typically categorized as a cerebral vascular accident
(CVA). Strokes can be classified into two major categories: ischemic and hemorrhagic. In ischemic strokes, blood flow
to the brain is blocked by blood clots
or fatty deposits called plaque
in blood vessel
linings. In hemorrhagic strokes, a blood vessel bursts in the brain. Specifically, watershed strokes are a type of ischemic stroke because they are characterized by reduced blood flow and not by blood vessel rupture. These events are localized to two primary regions of the brain, and are referred to as cortical watersheds (CWS) or external borderzone infarcts
and internal watersheds (IWS) or internal boarderzone infarcts. Watershed strokes make up approximately 10% of all ischemic stroke cases. However, because watershed strokes are seldom fatal and therefore can go unnoticed, this is probably an underestimate. Furthermore, 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 carotid artery narrowing, or stenosis
.
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
.
As mentioned above, these events are localized to two primary regions of the brain:
Nonetheless, within the literature itself, there exists confusion over terminology used to describe cortical
(outer brain) and subcortical (inner brain) infarcts located between two vascular regions. 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 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. Patients 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:
which represents Facial weakness, Arm weakness, Speech difficulty, and Time to act.
is affected symptoms could include, numbness, reduced sensory sensation, and hyperreflexia.
Most often, the side of the brain damaged results in body defects on the opposite side. Furthermore, since the cranial nerves are located within the brainstem, damage to this area can lead to defects in the function of these nerves. Symptoms could 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.
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.
remains controversial. It may involve various mechanisms such as systemic hypotension
, microemboli
, severe arterial stenosis
(ICA
occlusion) or a combination of these.
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 watershed stroke. With watershed strokes, platelet
aggregates block the small meningeal arteries
in watershed regions creating a microembolism. This process is referred to as atherosclerosis
. Microemboli usually form as thrombi
, and can block arteries outright. On the other hand, they often detach, move into the 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 an carotidendarterectomy
.
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.
at the split of the carotid artery in the neck may cause watershed infarcts between the territories of the anterior and the middle cerebral arteries. The resulting watershed infarcts in carotid occlusions have mostly been considered to be due to a reduced blood flow, similar to that of hypotension.
However, a different possible explanation has emerged. Alternatively, the vascular blockages could be the result of microemboli resulting from the carotid thrombi before the lumen becomes completely blocked. 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 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.
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.
, 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.
. 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.
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.
, 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.
, antioxidants
, B-group vitamins
, and zinc, have been shown to increase the recovery of neurocognitive function after a stroke. Antiplatelet drug
s, such as aspirin, as well as anticoagulant
s, are used to help prevent blood clots and therefore embolisms, which can cause watershed strokes. Statin
drugs are also used to control hypertension, another risk factor for watershed stroke.
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.
stenting may help to improve parallel, accessory blood flow. The stent may also lead to termination of recurrent middle cerebral artery (MCA)
strokes.
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 BBB
diffusion characteristics. Many advantages of these drugs include:
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.
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. "Watershed
Watershed area (medical)
Watershed area is the medical term referring to regions of the body that receive dual blood supply from the most distal branches of two large arteries, such as the splenic flexure of the large intestine....
" refers to those border zone regions in the brain supplied by the major cerebral arteries
Cerebral arteries
Cerebral arteries describe three main pairs of arteries and their branches, which irrigate the cerebrum of the brain. The three main arteries consist of the:*Anterior cerebral artery *Middle cerebral artery...
where blood supply
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
is decreased.
In general, a stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
occurs when there is some form of interruption or occlusion
Vascular occlusion
Vascular occlusion is a sudden blockage of a blood vessel, usually with a clot. It differs from thrombosis in that it can be used to describe any form of blockage, not just one formed by a clot. When it occurs in a major vein, it can, in some cases, cause deep vein thrombosis. The condition is...
of blood flow to or within the brain. This is typically categorized as a cerebral vascular accident
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
(CVA). Strokes can be classified into two major categories: ischemic and hemorrhagic. In ischemic strokes, blood flow
Blood flow
Blood flow is the continuous running of blood in the cardiovascular system.The human body is made up of several processes all carrying out various functions. We have the gastrointestinal system which aids the digestion and the absorption of food...
to the brain is blocked by blood clots
Thrombus
A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...
or fatty deposits called plaque
Atheroma
In pathology, an atheroma is an accumulation and swelling in artery walls that is made up of macrophage cells, or debris, that contain lipids , calcium and a variable amount of fibrous connective tissue...
in blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
linings. In hemorrhagic strokes, a blood vessel bursts in the brain. Specifically, watershed strokes are a type of ischemic stroke because they are characterized by reduced blood flow and not by blood vessel rupture. These events are localized to two primary regions of the brain, and are referred to as cortical watersheds (CWS) or external borderzone infarcts
Infarction
In medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
and internal watersheds (IWS) or internal boarderzone infarcts. Watershed strokes make up approximately 10% of all ischemic stroke cases. However, because watershed strokes are seldom fatal and therefore can go unnoticed, this is probably an underestimate. Furthermore, imaging studies in severe internal carotid artery
Internal carotid artery
In human anatomy, the internal carotid arteries are two major arteries, one on each side of the head and neck. They arise from the common carotid arteries where these bifurcate into the internal and external carotid artery, and they supply the brain....
(ICA) disease report an incidence of watershed stroke ranging from 19% to 64%. Almost 40% of these watershed infarcts are attributed to carotid artery narrowing, or stenosis
Stenosis
A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
.
Terminology and Location
Simply, watershed strokes are named because they affect the distal watershedWatershed area (medical)
Watershed area is the medical term referring to regions of the body that receive dual blood supply from the most distal branches of two large arteries, such as the splenic flexure of the large intestine....
areas of the brain. The original terminology came from the German literature, which used the analogy of an irrigation
Irrigation
Irrigation may be defined as the science of artificial application of water to the land or soil. It is used to assist in the growing of agricultural crops, maintenance of landscapes, and revegetation of disturbed soils in dry areas and during periods of inadequate rainfall...
system. The German scholars compared the blood flow
Blood flow
Blood flow is the continuous running of blood in the cardiovascular system.The human body is made up of several processes all carrying out various functions. We have the gastrointestinal system which aids the digestion and the absorption of food...
in distal arterial
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
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
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
.
As mentioned above, these events are localized to two primary regions of the brain:
- CorticalCerebral cortexThe cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
watershed strokes (CWS), or outer brain infarctsInfarctionIn medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
, are located between the cortical territories of the anterior cerebral artery (ACA), middle cerebral arteryMiddle cerebral artery-External links:*...
(MCA), and posterior cerebral arteryPosterior cerebral artery-External links: - Posterior Cerebral Artery Stroke* at strokecenter.org* at State University of New York Upstate Medical University* at psyweb.com* at neuropat.dote.hu...
(PCA). - Internal watershed Strokes (IWS), or subcortical brain infarcts, are located in the white matterWhite matterWhite matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
along and slightly above the lateral ventricleLateral ventriclesThe lateral ventricles are part of the ventricular system of the brain. Classified as part of the telencephalon, they are the largest of the ventricles....
, between the deep and the superficial arterial systems of the MCAMiddle cerebral artery-External links:*...
, or between the uperficial systems of the MCAMiddle cerebral artery-External links:*...
and ACA.
Nonetheless, within the literature itself, there exists confusion over terminology used to describe cortical
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
(outer brain) and subcortical (inner brain) infarcts located between two vascular regions. Besides watershed
Watershed area (medical)
Watershed area is the medical term referring to regions of the body that receive dual blood supply from the most distal branches of two large arteries, such as the splenic flexure of the large intestine....
, 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
Anatomy
Anatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy , and plant anatomy...
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 a blood flow to the brain. There are several causes of ischemia, including embolismEmbolism
In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
and atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. 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. Patients with many different cardiovascular diseases
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
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 ability 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
- AngiopathyAngiopathyAngiopathy is the generic term for a disease of the blood vessels . The best known and most prevalent angiopathy is diabetic angiopathy, a common complication of chronic diabetes.-By caliber:...
, a disease of the blood vessels - Arterial hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, or low blood pressure in the arteries - HypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, or high blood pressure - HyperlipidemiaHyperlipidemiaHyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
, or excessive cholesterol build up in the blood vessels - Diseases such as sickle cell anemiaSickle-cell diseaseSickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
, which can lead to deformed red blood cells clogging blood vessels and impeding blood flow - Carotid artery stenosisCarotid artery stenosisCarotid stenosis is a narrowing or constriction of the inner surface of the carotid artery, usually caused by atherosclerosis .-Signs and symptoms:...
, or narrowing of the carotid artery which can decrease the volume of blood flow to the brain
Initial symptoms
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 Stoke Association, are FAST (stroke)FAST (stroke)
FAST is an acronym used as a mnemonic to help detect and enhance responsiveness to stroke victim needs. The acronym stands for Facial weakness, Arm weakness, Speech difficulty, and Time to act....
which represents Facial weakness, Arm weakness, Speech difficulty, and Time to act.
Progressive symptoms
After the initial stroke, other symptoms depend on the area of the brain affected. If one of the three central nervous system pathwaysNeural pathway
A neural pathway, neural tract, or neural face, connects one part of the nervous system with another and usually consists of bundles of elongated, myelin-insulated neurons, known collectively as white matter...
is affected symptoms could include, numbness, reduced sensory sensation, and hyperreflexia.
Most often, the side of the brain damaged results in body defects on the opposite side. Furthermore, since the cranial nerves are located within the brainstem, damage to this area can lead to defects in the function of these nerves. Symptoms could include, altered breathing, problems with balance, drooping of eyelids, and decreased sensation in the face.
Damage to the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
may lead to aphasia or confusion and damage to the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
may lead to lack of motor movement.
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 (DWI), 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 (OCSP, also known as the Bamford or Oxford 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 infarctTotal anterior circulation infarctA Total Anterior Circulation Infarct is a type of cerebral infarction affecting the entire anterior circulation supplying one side of the brain....
(TACI), partial anterior circulation infarctPartial anterior circulation infarctPartial Anterior Circulation Infarct is a type of cerebral infarction affecting part of the anterior circulation supplying one side of the brain....
(PACI), lacunar infarct (LACI) or posterior circulation infarctPosterior circulation infarctA Posterior Circulation Infarct is a type of cerebral infarction affecting the posterior circulation supplying one side of the brain....
(POCI). These four entities predict the extent of the stroke, the area of the brain affected, the underlying cause, and the prognosis.
- The TOAST (Trial of Org 10172DanaparoidDanaparoid sodium is an anticoagulant that works by inhibiting activated factor X .Danaparoid is considered a "low molecular weight heparin" by some sources, but is chemically distinct from heparin and thus has little cross-reactivity in heparin-intolerant patients.It consists of a mixture of...
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
- ThrombosisThrombosisThrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
or embolism due to atherosclerosis of a large artery - EmbolismEmbolismIn medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
of cardiac origin - Occlusion of a small blood vessel
Pathogenesis
Although many imaging techniques are used to document watershed strokes, their pathogenesisPathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
remains controversial. It may involve various mechanisms such as systemic hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, microemboli
Embolism
In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
, severe arterial stenosis
Carotid artery stenosis
Carotid stenosis is a narrowing or constriction of the inner surface of the carotid artery, usually caused by atherosclerosis .-Signs and symptoms:...
(ICA
Internal carotid artery
In human anatomy, the internal carotid arteries are two major arteries, one on each side of the head and neck. They arise from the common carotid arteries where these bifurcate into the internal and external carotid artery, and they supply the brain....
occlusion) or a combination of these.
Hypotension
A sharp drop in blood pressureBlood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
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
Middle cerebral artery
-External links:*...
. These events caused by hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
do not usually cause the blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
to rupture.
Microemboli
microemboliEmbolism
In medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
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
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
aggregates block the small meningeal arteries
Middle meningeal artery
The middle meningeal artery is typically the third branch of the first part of the maxillary artery, one of the two terminal branches of the external carotid artery...
in watershed regions creating a microembolism. This process is referred to as atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
. Microemboli usually form as thrombi
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
, and can block arteries outright. On the other hand, they often detach, move into the circulation and eventually block smaller downstream branches of arteries causing a thromboembolism
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
. 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
Infarction
In medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:...
rather than secondary events. Nevertheless, secondary thrombi
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
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 an carotidendarterectomy
Carotid endarterectomy
Carotid endarterectomy is a surgical procedure used to prevent stroke, by correcting stenosis in the common carotid artery...
.
Microemboli can be common in some high-risk patients, such as those with carotid stenosis
Carotid artery stenosis
Carotid stenosis is a narrowing or constriction of the inner surface of the carotid artery, usually caused by atherosclerosis .-Signs and symptoms:...
. However, in healthier patients strokes do not usually result from microemboli.
ICA occlusions
ThrombiThrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
at the split of the carotid artery in the neck may cause watershed infarcts between the territories of the anterior and the middle cerebral arteries. The resulting watershed infarcts in carotid occlusions have mostly been considered to be due to a reduced blood flow, similar to that of hypotension.
However, a different possible explanation has emerged. Alternatively, the vascular blockages could be the result of microemboli resulting from the carotid thrombi before the lumen becomes completely blocked. 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 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
Thrombus
A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...
, thrombi adherent to the vessel wall, rather than by blood flow disturbances.
Carotid endarterectomy
Often considered one of the safest ways to treat symptomatic carotid stenosis, carotid endarterectomyCarotid endarterectomy
Carotid endarterectomy is a surgical procedure used to prevent stroke, by correcting stenosis in the common carotid artery...
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 angioplastyAngioplasty
Angioplasty is the technique of mechanically widening a narrowed or obstructed blood vessel, the latter typically being a result of atherosclerosis. An empty and collapsed balloon on a guide wire, known as a balloon catheter, is passed into the narrowed locations and then inflated to a fixed size...
, 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 (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.Long-term care and rehabilitation
Watershed strokes are seldom fatal, but they can lead to neuromuscular degeneration, as well as dementiaDementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
. 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.Winter, Jackie; Hunter, Susan; Sim, Julius; Crome, Peter "Hands-on therapy interventions for upper limb motor dysfunction following stroke", "The Cochrane Stroke Group", 23 Aug 2010 Occupational therapiesOccupational therapy
Occupational therapy is a discipline that aims to promote health by enabling people to perform meaningful and purposeful activities. Occupational therapists work with individuals who suffer from a mentally, physically, developmentally, and/or emotionally disabling condition by utilizing treatments...
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
Aphasia
Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....
resulting from stroke.
Surgical interventions
Endovascular interventions, including surgical revascularizationRevascularization
Revascularization is "a surgical procedure for the provision of a new, additional, or augmented blood supply to a body part or organ." The term derives from the prefix re-, in this case meaning "restoration" and vasculature, which refers to the circulatory structures of an organ.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 acidsAmino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
, antioxidants
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
, B-group vitamins
B vitamins
B vitamins are a group of water-soluble vitamins that play important roles in cell metabolism. The B vitamins were once thought to be a single vitamin, referred to as vitamin B . Later research showed that they are chemically distinct vitamins that often coexist in the same foods...
, and zinc, have been shown to increase the recovery of neurocognitive function after a stroke. Antiplatelet drug
Antiplatelet drug
An antiplatelet drug is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation...
s, such as aspirin, as well as anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s, are used to help prevent blood clots and therefore embolisms, which can cause watershed strokes. Statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
drugs are also used to control hypertension, another risk factor for watershed stroke.
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.Deep watershed infarcts
HemodynamicHemodynamics
Hemodynamics, meaning literally "blood movement" is the study of blood flow or the circulation.All animal cells require oxygen for the conversion of carbohydrates, fats and proteins into carbon dioxide , water and energy in a process known as aerobic respiration...
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 (BA) stenting
While intracranial artery stenting is used for same side stoke prevention, basilar arteryBasilar artery
In human anatomy, the basilar artery is one of the arteries that supplies the brain with oxygen-rich blood.The two vertebral arteries and the basilar artery are sometimes together called the vertebrobasilar system, which supplies blood to the posterior part of circle of Willis and anastomoses with...
stenting may help to improve parallel, accessory blood flow. The stent may also lead to termination of recurrent middle cerebral artery (MCA)
Middle cerebral artery
-External links:*...
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
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
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 BBB
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
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
Liposome
Liposomes are artificially prepared vesicles made of lipid bilayer. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules...
drugs seem to be well suited.