Stroke Definition and Causes Transcript
Stroke Definition and Causes
This is Dr. Cal Shipley and today we’re going to be looking at the question: What is a stroke and how does it happen? Simply stated, stroke occurs when there is rapid death of brain tissue due to a disturbance in blood supply. Disturbances in blood flow to the brain may be divided into ischemic varieties, in which there is a loss of blood flow to brain tissue, and hemorrhagic varieties, in which there is bleeding into the brain or onto the surface of the brain. I’ll return to the causes of stroke in a moment, but first, let’s look at the anatomy of the blood supply to the brain.
Blood supply to the brain
Blood is supplied to the brain by two pairs of arteries. The anterior supply supplies blood primarily to the middle and front portions of the brain, and consists of the left and right carotid arteries. The posterior supply supplies blood primarily to the brain stem, and back portions of the brain, and consists of the right and left vertebral arteries, which then join together to form the single basilar artery.
Rotating the brain so that we have a view from the left side, we can now more clearly see how the anterior supply originating from the carotid arteries distributes blood primarily to the middle and front portions of the brain.
And the posterior supply, originating from the basilar artery, supplies mostly the brain stem and the rear portions of the brain. And in a prime example of nature’s wonderful design, there is a communicating artery which joins the two systems. Known as the posterior communicating artery, this vessel is part of the Circle of Willis. In the event that there is sudden impairment of blood flow to the brain from either the anterior or posterior system, the communicating arteries allow for crossover flow, which may help to prevent damage to the portion of the brain affected by the impaired flow.
Stroke: Ischemic causes
Now let’s return to the causes of stroke, starting with ischemia, or loss of blood flow to the brain. Ischemic causes account for 80% of all strokes. The first type of ischemia we’re going to look at is thrombosis.
Stroke: Ischemic causes – Thrombosis
Thrombosis refers to a local obstruction of an artery, and may be due to disease of the arterial wall, such as hardening of the arteries or arteriosclerosis, dissection or fibromuscular dysplasia, in which abnormal thickening of the artery wall causes obstruction. Thrombosis may occur in large arteries or small arteries.
Stroke: Thrombosis of large arteries
Let’s take a look at large arteries first. Large arteries that may be affected by thrombosis include the carotid, vertebral or basilar arteries, or any of their major branches, including the anterior, middle, and posterior cerebral arteries, or their larger branches.
As an example, let’s take a look at a large artery thrombosis occurring in the left middle cerebral artery. In a typical scenario, atherosclerotic plaque, which has built up over many years along the artery wall, eventually undergoes degenerative change which causes rupture of the plaque surface. Once ruptured, the interior of the plaque releases chemical substances which promote clot formation in the blood vessel. The resulting combination of blood clot and plaque leads to thrombosis, with complete obstruction to blood flow within the vessel.
The subsequent loss of blood flow in arteries that are beyond the point of thrombosis starves the brain of critical nutrients, including oxygen and glucose, and eventually leads to rapid death of brain tissue, also known as stroke. The further upstream the thrombosis occurs, that is, the larger the artery affected by obstruction, the greater the potential devastation to brain tissue. The human brain is exquisitely sensitive to even brief periods of ischemia. Changes in brain cells may be observed within two to three hours of interruption of nutrient flow, with complete death of brain tissue occurring within 6 to 24 hours after the onset of ischemia.
Stroke: Thrombosis of small arteries
Now let’s take a look at the other variety of thrombosis, that is thrombosis affecting small arteries. Stroke occurring as a result of this type of thrombosis is also known as lacunar stroke or lacunar infarct.
Lacunar infarct occurs as a result of disease in small arteries which are coming directly off larger arteries, such as the carotid, basilar, and anterior, middle, and posterior cerebral arteries. These small branches, or penetrating arteries as they are called, supply blood flow to the central portions of the brain and the brainstem. As a result of the very specific anatomic location of these penetrating arteries, lacunar infarct commonly involves the structures of the central brain, particularly the basal ganglia, and the pons in the brainstem.
The thrombosis which occurs in the small arteries involved in lacunar infarcts appears to be primarily caused by prolonged elevation of blood pressure, also known as hypertension. In a typical scenario, prolonged hypertension results in a process known as lipohyalinosis. The process of lipohyalinosis as depicted here consists of damage to the inner wall of the small artery with progressive accumulation of debris within the vessel, ultimately leading to complete obstruction to blood flow.
Lacunar infarcts are typically small, affecting areas of brain tissue up to 15 millimeters in size. Long-term uncontrolled elevations in blood pressure affect all the arteries in the human body, and the vessels responsible for lacunar infarcts are no exception to this rule. As a result, the number of areas of lacunar stroke in affected individuals tends to increase over time. It should be noted that in recent years, there has been some controversy over the classification of small vessel disease of the brain, and subsequent lacunar infarcts, as distinct entities in the causes of stroke.
Many of the opponents of the theory of lacunar infarct feel that these strokes are simply caused by clots which have traveled to these arteries from elsewhere, also known as emboli. We will be discussing the concept of emboli and embolism in our next segment. Now we’ve looked at the most common cause of ischemic strokes in the brain thrombosis.
Stroke due to Embolism
The second most common cause is embolism. Embolism occurs when clots or particles originating from upstream of a particular artery travel to that artery and obstruct it. This is, of course, in contrast to thrombosis whereby thrombus forms at the point of obstruction in the artery. The heart is a common source of emboli to the brain.
Let’s take a look at a little bit of cardiac anatomy to set things up. Here we see the left ventricle and the left atrium, the small chamber on top, with the atrial appendage. And in cross-section, we see the left atrium, and we’ve unfolded the atrium here for clarity to show how the atrial appendage is kind of an extended chamber off the atrium itself. The blood flow goes from the left atrium into the left ventricle, and then the left ventricle pushes blood up into the aorta and hence to the brain via the carotid, and vertebral, and basilar arteries as we discussed previously.
The anatomy and flow characteristics make clear that any clots or particles which are formed in or enter into the heart have a really good chance of being pumped right up into the vessels of the brain. Two common conditions that can result in formation of clot in the left ventricle and then embolization of clot to the brain are congestive heart failure and myocardial infarction, also known as heart attack. The physiological mechanism which gives rise to clot formation in both conditions is similar. Let’s take a look at our heart model to better understand how this occurs.
Taking a look at the heart in cross-section, we can isolate the left ventricle and then freeze it at its point of maximum contraction. The percentage of blood ejected from the left ventricle with each contraction is known as the ejection fraction. A normal ejection fraction is 50 to 65 percent. In other words, 50 to 65 percent of the blood contained in the left ventricle just prior to each contraction is ejected into the aorta.
In both congestive heart failure and myocardial infarction, also known as heart attack, there may be marked impairment of left ventricular contraction and, therefore, a marked reduction in ejection fraction. This impairment and contraction can lead to a condition known as blood stasis. Stasis refers to pooling of blood in the base, also known as the apex of the left ventricle. When blood pools anywhere in the human body, and the left ventricle is no exception, it tends to form clots. The medical term for a clot is a thrombus. Immediately after formation, a thrombus may be adherent to the wall of the left ventricle.
Unpredictably, a thrombus may break free and be ejected into the aorta. A thrombus has now become an embolus. Once in motion, an embolus has a tendency to break up into smaller pieces. The tiniest pieces may not cause significant impairment of blood flow to the brain. However, larger fragments may cause significant obstruction of blood flow to brain tissue resulting in a stroke. In this example, a significantly sized embolus has lodged in a branch of the right middle cerebral artery. On CT scan, the area of stroke can be readily viewed as this dark oval area.
This particular patient had had a previous stroke as noted here on the right side of the screen. Another common condition in which thrombi may form and embolize to the brain is atrial fibrillation. Unlike normal heart rhythm, in atrial fibrillation, the atrial chamber quivers, or fibrillates, at a much higher rate than the ventricles. Moreover, the fibrillating atrium is much less effective in injecting blood into the ventricle just prior to ventricular contraction, also known as systole. The beating left ventricle continues to draw blood through the main chamber of the atrium.
However, in the appendage, blood movement is much slowed, a condition known as blood stasis. Stasis in the left atrial appendage greatly increases the chance for clot formation. As demonstrated here, many clots are initially adherent to the wall of the f fibrillating atrium. An adherent clot, also known as a thrombus, may unpredictably detach itself from the wall of the atrium, enter the left ventricle, and then be ejected up into the aorta and hence to the brain.
The tendency for thrombus detachment and ejection increases if the atrium suddenly reverts to a normal rhythm. Once detached, the thrombus now travels, or embolizes, to the arteries of the brain. Along the way, the embolus, as it is now known, may fragment into many smaller pieces with only those of significant size causing obstruction to blood flow. In this example, one embolus has lodged in the right middle cerebral artery resulting in a stroke as noted on this CT scan. The dark oval shape indicates the area of stroke.
Another condition in which embolization may occur from the heart to the brain is endocarditis. Endocarditis can occur when there is fungal or, more commonly, bacterial infection in the bloodstream, a condition known as septicemia or sepsis. As the organisms travel through the heart, they attach themselves to the valve leaflets between the heart chambers. The oxygen and nutrient-rich environment found in the left side of the heart results in rapid growth of organisms, which form clumps known as vegetations.
Unpredictably the vegetations may detach from the valve leaflets. The vegetation’s are then injected into the aorta or they may travel up into the arteries of the brain causing obstruction to blood flow and subsequent stroke.
Stroke due to Global Ischemia
The final category of ischemic stroke which we’re going to look at is global loss of blood flow to the brain. Global blood flow loss may occur at any condition in the body in which there is a generalized loss of blood flow to all organs.
Conditions which can lead to global blood flow loss include severe loss of blood volume as in hemorrhagic shock, rhythm disturbances of the heart such as ventricular fibrillation or cardiac arrest, infectious states with blood-borne infection, also known as septicemia, and narcotics overdose. The typical brain injury that occurs with a global loss of blood flow is known as a watershed stroke. To better understand how this occurs, let’s take a look at the blood flow patterns in the brain.
Here’s a view of the brain in cross-section looking from above. The arterial blood flow to the brain is such that there is flow from the outer edge towards the center of each cerebral hemisphere, as well as a flow from the inner edge towards the center of each cerebral hemisphere. Where the inner and outer flows meet is known as the watershed area. It therefore follows that when there is a generalized loss of blood flow to the brain, such as in narcotic overdosage, the watershed areas of each hemisphere are particularly susceptible to ischemia and stroke.
Seen from above in both our animation and in an MRI, watershed stroke has a very characteristic appearance.
Stroke due to hemorrhage
As you may recall from the beginning of this review, the second major classification of stroke causes is hemorrhagic. Hemorrhagic causes account for 20% of all strokes. Hemorrhagic causes may be further subdivided into intracerebral hemorrhage, that is bleeding within the substance of the brain itself, and the subarachnoid hemorrhage, or bleeding onto the surface of the brain.
The frequency of occurrence is equally split between the two different forms of hemorrhage. Amongst the causes of interest cerebral hemorrhage are uncontrolled high blood pressure, also known as hypertension, trauma, bleeding disorders such as hemophilia, vascular malformation such as aneurysms and arteriovenous malformations, amyloid angiopathy, which is an acquired disease resulting in weakness of blood vessel walls, and drug abuse, primarily involving the use of cocaine or amphetamines.
Hemorrhagic Stroke due to Arteriovenous Malformation (AVM)
The mechanism of brain tissue damage in intracerebral hemorrhage is very similar irrespective of the specific cause. For purposes of illustration today, let’s take a look at intracerebral hemorrhage occurring as a result of an arteriovenous malformation.
An arteriovenous malformation represents a dramatic abnormality between the arterial, or feeder side of the vascular system, and the venous or drainage side of the vascular system.
As this segment demonstrates, prior to interfacing with the venous side of the system, arteries divide into smaller and smaller branches with the very smallest branches being capillaries. The size of the capillaries is such that red blood cells may only flow through them in single file. This branching structure from largest to smallest vessels results in a steady decrease in the blood pressure at each level, until by the time one gets to the capillaries, the blood pressure is only a fraction of that in the major arteries. This reduction in pressure as vessels become smaller is critically important. If capillaries were to be exposed to the much higher pressures present in the larger arteries, they would immediately rupture.
On the venous side of the system, capillaries interface with tiny venules which join together to form larger and larger veins. In an arteriovenous malformation, this normal branching structure is absent. Instead, we see a large feeder artery entering a nest or nidus of small abnormal arterioles. On the venous side, the normal branching structure is also absent with one large vein draining the nidus.
Here is a view of the AVM as seen on angiogram. The lack of a normal branching structure in the AVM results in extremely high flows and pressures across the abnormal small vessels of the nidus. As a consequence, AVMs have a high potential for rupture and hemorrhage of nidus vessels. As mentioned previously, intracerebral hemorrhage takes place within the substance of the brain tissue itself.
The accumulation of blood, also known as a hematoma, continues to grow until the pressure surrounding it limits expansion or until it decompresses itself by rupturing into the cerebral spinal fluid system either into the ventricles of the brain or onto the surface of the brain. As seen here on an MRI image, the size of the hematoma could be very significant. Intracerebral hemorrhage can have a devastating effect on brain function in affected individuals.
The hemorrhage occurs within the brain substance where billions of neurons are densely packed together. As the hematoma grows, it twists and ruptures neurons along its path, causing massive irreversible damage. One neurosurgeon has likened the process to turning on a fire hose in a bowl of jello. Switching from the microscopic to the macroscopic level, we see how the hematoma fragments brain tissue as it continues to expand.
Hemorrhagic Stroke due to Subarachnoid Hemorrhage
Let’s take a look now at the other common cause of hemorrhagic stroke, subarachnoid hemorrhage. Unlike intracerebral hemorrhage in which bleeding occurs within the brain itself, subarachnoid hemorrhage occurs on the surface of the brain. The most common cause of subarachnoid hemorrhage is rupture of an aneurysm. 85% of aneurysms in the brain occur in the anterior circulation, predominantly in the Circle of Willis.
The risk factors for both formation and rupture of aneurysms overlap and include cigarette smoking, moderate to heavy use of alcohol, high blood pressure, genetic risk, use of sympathomimetic drugs such as diet pills, cold remedies, and cocaine, and amphetamine abuse, estrogen deficiency, particularly in menopausal females, anticoagulation therapy, and possibly, the use of cholesterol-lowering medications known as statins.
As an example of subarachnoid hemorrhage, we’re going to look at a ruptured berry aneurysm occurring in the Circle of Willis. To begin, let’s take a look at the anatomy of the Circle of Willis. The Circle of Willis is best seen by examining the underside of the brain.
The Circle of Willis is really a beautiful piece of anatomy, and represents a central hub from which radiates the entire blood flow to the brain. Inflow is primarily via the internal carotids and vertebral arteries. Outflow of blood from the Circle occurs via anterior, middle, and posterior cerebral arteries, each with left and right branches on either side of the circle. The basilar, posterior communicating, and anterior communicating arteries complete the Circle by merging the inflow of blood to the brain from the carotid and vertebral arteries. The chance is minimized that an obstruction or impairment in flow in any one of these arteries will result in a significant impairment of blood supply to the outflowing arteries.
Now that we have a better understanding of the anatomy of the Circle of Wills, let’s take a look at how it contributes to subarachnoid hemorrhage in the brain. While beautiful in design and function, the Circle of Willis is also the location of 85% of all aneurysms within the brain. One common site for the occurrence of an aneurysm is the junction between the anterior communicating and anterior cerebral arteries. Aneurysms form as a result of an acquired structural weakness in the blood vessel wall. Arteries which carry very high flows such as those in the Circle of Willis are thought to be particularly susceptible to mechanical damage in the vessel wall.
The previously mentioned contributory factors such as cigarette smoking or high blood pressure may accelerate the process of damage to the vessel wall. The strength of the aneurysm wall is inversely proportional to its size. Lesions one centimeter or larger are particularly susceptible to sudden increase in growth and rupture. With rupture, blood spreads rapidly across the surface of the brain via the cerebral spinal fluid.
Bleeding generally only last a few seconds. However, re-bleeding may occur, and is most likely within 24 hours of rupture and initial hemorrhage. The most common cause of death and disability after subarachnoid hemorrhage is vasospasm, extreme narrowing of the arteries, with impairment of blood flow to brain tissue and subsequent stroke. Vasospasm usually occurs within the first three days after a hemorrhage and generally peaks in effect about one week out.
Vasospasm occurs as a result of chemical irritation of blood vessel walls by breakdown products of hemorrhaged blood. The duration of vasospasm and the location of the vessels affected determines the size and depth of subsequent strokes.
Cal Shipley, M.D. copyright 2020