Subtypes and Causes

A detective trying to solve a crime searches for physical clues that will help identify a suspect. In a similar way, a doctor diagnosing a stroke searches for anatomical and biological aberrations — the underlying pathology — in order to determine exactly what type of stroke has occurred and what caused it. Pathology is the medical version of a set of fingerprints left at a crime scene: It helps to identify the culprit.

The first challenge is to decide whether the stroke is ischemic or hemorrhagic. The doctor will ask about your symptoms, perform a physical examination, and order blood, urine, and imaging tests (see "Diagnosing a stroke"). Next the doctor must find out precisely what pathological process in the affected artery might have caused a blockage (leading to ischemia) or a blood vessel rupture (leading to hemorrhage). Ischemic stroke and TIAs have four subtypes, based on four distinct pathologies. Hemorrhagic strokes are first defined by location (either intracerebral or extracerebral intracranial hemorrhage), and then by pathological subtype.

Ischemic strokes and TIAs

Each year about 560,000 people in the United States have ischemic strokes. But not all ischemic strokes are alike: Each subtype develops for different reasons and poses particular challenges (see "Ischemic stroke subtypes"). Although the exact treatment will depend on the type of ischemic stroke you have, clot-busting drugs and anticoagulants (antithrombotics), followed by preventive medications, make up the most common treatment regimen (see "Treating ischemic stroke").

Ischemic stroke subtypes Large-artery atherothrombotic stroke (A) most often occurs when a blood clot forms in an artery supplying blood to the brain and breaks off, traveling downstream to lodge in an area where the artery is already narrowed by plaque. These account for roughly 15% of ischemic strokes. Large-artery atherothrombotic stroke Small-artery or lacunar stroke is caused by the blockage of one of the smaller blood vessels that arise from the main arteries at the base of the brain. A small hole made of scar tissue may result. These account for about 25% of ischemic strokes. Embolic stroke (B) occurs when a clot that has formed elsewhere in the body — typically in the heart or the ascending part of the aorta — breaks off and travels through the bloodstream until it blocks an artery to the brain. Embolic stokes account for almost 60% of ischemic strokes. Embolic stroke Dissection stroke occurs because of a tearing, or dissection, of the carotid artery. This is one of several other types of pathologies that account for less than 3% of ischemic strokes.

Large-artery atherothrombotic strokes

Atherosclerosis is a medical term for the buildup of fatty deposits in the arteries. When this process occurs in arteries feeding the heart, it accounts for more than 90% of heart attacks. But when the same process affects arteries in the brain, it accounts for only 15% of ischemic strokes. That is because the brain has a rich supply of collateral blood vessels, the most significant being the Circle of Willis. These other blood vessels take over and compensate for the vessel that becomes clogged with plaque through the atherosclerotic process.

Strokes that are caused by atherosclerosis are known as large-artery atherothrombotic strokes. These types of stroke are often heralded by a TIA. Although atherosclerotic plaque can form in any artery, it may lead to stroke when it occurs at any of four strategically focal locations: the origin of the internal carotid artery, the siphon portion of the internal carotid artery, the middle cerebral artery stem, and the junction of the distal vertebral arteries and the basilar artery (see Figure 5).

Figure 5: Blood vessels affected by ischemic stroke ischemic stroke " src="http://assets.disaboom.com/Images/HarvardImages/103646.jpg" border="0" /> Blood vessels affected by ischemic stroke Large-artery atherothrombotic strokes generally occur at the origin of the internal carotid artery, the siphon portion of the internal carotid artery, the middle cerebral artery stem, or the junction of the distal vertebral arteries and the basilar artery. Small-vessel lacunar strokes typically result from obstruction of a single blood vessel that branches off from the Circle of Willis, the middle cerebral artery stem, the basilar artery, or the distal vertebral arteries. Embolic strokes are caused when a blood clot obstructs a major blood vessel at the base of the brain, such as the basilar artery or the middle cerebral stem. Dissection strokes occur after a large extracranial artery, such as the carotid or vertebral artery, tears.

Sometimes atherosclerotic plaques cause stroke or a TIA by producing a critical narrowing in the artery, limiting blood flow to the specific area of the brain that is supplied by that artery. This is known as a low-flow stroke and generally occurs when collateral flow to the same area through other vessels, such as the Circle of Willis, is limited. These strokes are usually progressive.

But atherosclerotic plaques are not just passive plugs that block arteries like a cork in a bottle. They are active, dynamic lesions teaming with cholesterol and inflammatory cells. The most common type of large-artery atherothrombotic stroke occurs when a plaque deposit ruptures and develops a blood clot (thrombus). Although the blood clot may not plug the artery completely, it can break off (embolize) and travel from the site of origin to the part of the brain being supplied by that particular artery. This is known as artery-to-artery embolic stroke. At other times, the blood clot may grow large enough to obstruct the blood vessel at the site of the atherosclerotic process, and then extend up into the brain to precipitate a stroke. This occurs mainly in the basilar artery and somewhat less commonly in the carotid artery or middle cerebral artery stem.

Damage from large artery-to-artery embolic stroke may grow worse for three reasons. First, the same underlying mechanism, atherosclerosis, may trigger a second stroke and expand the area of blocked blood flow. Second, brain swelling can occur as a result of the initial stroke and expand pressure inside the skull. In this case, the surgeons may have to remove part of the skull to relieve pressure caused by the swelling. Third, the blood clot that broke off and triggered an artery-to-artery embolic stroke can further fragment. Although this restores blood flow to the damaged brain, the sudden increase in blood flow can also give rise to little points of bleeding in smaller blood vessels such as arterials and capillaries. When this occurs, it is known as hemorrhagic conversion of an ischemic stroke. When the bleeding is severe and forms a large clot, brain compression results.

As might be expected, the advice about how to prevent large-artery atherothrombotic stroke is the same advice given to people at risk for heart attack: Most important, keep blood pressure and cholesterol levels within healthy parameters, stop smoking, and lose excess weight. For more information, and other advice about prevention, see "Preventing stroke."

Small-vessel lacunar stroke

Lacunar strokes, sometimes known as small-vessel strokes, account for 25% of ischemic strokes. This type of stroke is often heralded by a TIA. A lacunar stroke results from the obstruction of a single blood vessel that branches off from the Circle of Willis, the middle cerebral artery stem, the basilar artery, or the distal vertebral arteries (see Figure 5). These arteries are single vessels that penetrate into the brain. They do not branch. Such vessels may become obstructed in several ways.

Sometimes a small penetrating vessel becomes damaged by a unique pathologic process known as lipohyalinosis, in which endothelial cells (cells that line the blood vessel walls) are injured and degenerate as a result of persistent hypertension. Less commonly, atherosclerotic plaque can originate at the penetrating artery origin and obstruct it. In rare instances, a tiny embolic fragment may break away from a blood clot elsewhere and then travel down the arterial tree to block a tiny penetrating vessel.

However it occurs, the blockage starves a small part of the brain of blood flow, leaving a tiny area of scar tissue. Because the area of the damaged or infarcted brain is small, recovery is often significant. But some lacunar strokes can lead to disabling paralysis or a painful sensory syndrome.

Fortunately, in some cases prevention is possible. The lipohyalinotic process responsible for many lacunar strokes is directly related to hypertension and diabetes, which can damage blood vessel walls. Controlling blood pressure is the most important step you can take to help prevent this type of lacunar stroke (see "Preventing stroke").

Embolic stroke

Embolic strokes account for almost 60% of all ischemic strokes in the United States. This type of stroke occurs when an embolic fragment, usually a blood clot, breaks away from the heart, aorta, or an unknown source. When the blood clot is small, it travels to a more distant vessel in the brain and blocks it, resulting in a smaller stroke and limited area of brain damage. Larger clots, however, can block larger blood vessels and cause more damage. If the clot is between 2½ and 3 millimeters (about the size of the tip of a pencil), it can block major blood vessels at the base of the brain, such as the basilar artery or the middle cerebral stem (see Figure 5). The result can be a devastating and disabling stroke. The clots can develop out of the blue, changing a person's life forever. Prevention, whenever possible, is vital.

Treatment of embolic stroke may involve clot-busting agents such as tissue plasminogen activator, anticoagulation therapy with heparin and warfarin (Coumadin), and antiplatelet therapy with aspirin or other agents (see "Treating ischemic stroke").

Although not all embolic strokes can be prevented, some can. Although it has not yet been proved, strokes that occur because of atherosclerosis in the aorta possibly may be prevented by taking some of the same steps to reduce your risk of heart disease: controlling high blood pressure, keeping cholesterol levels healthy, and not smoking.

It is also possible to prevent embolic strokes that are caused by fragments originating inside the heart, particularly in the atria and the left atrial appendage. This type of stroke is most likely to occur in people with a heart rhythm disturbance known as atrial fibrillation (the most common cause of embolic stroke, accounting for fully 15% of all ischemic strokes). Studies at Massachusetts General Hospital and elsewhere have clearly demonstrated that, in people with atrial fibrillation who are over 65, anticoagulation therapy with warfarin (Coumadin) can be highly protective against embolic strokes. The MGH study, for example, found that people with atrial fibrillation who took warfarin were 86% less likely than others with this heart condition to suffer an embolic stroke.

The use of warfarin and other anticoagulants to prevent other types of cardiac-source embolic strokes is less well studied. However, warfarin may also be used in people who have recently received a heart-valve replacement, suffered a heart attack, or have poor cardiac output or a clot inside the heart.

People with other types of heart conditions may also be at increased risk of embolic stroke, but it is unclear whether the best approach is to use anticoagulation or antiplatelet therapy, or to recommend invasive therapies such as surgery. One example: People with a hole in the heart between the right and left atrial chambers, a condition called patent foramen ovale, are at increased risk for an embolic stroke. Possible treatments include antiplatelet therapy with aspirin, anticoagulant therapy with warfarin (Coumadin), or a surgical procedure to close the hole. The issue is under study, but until more is known, doctors must make their therapy decisions based on each patient.

Other subtypes of ischemic stroke

Other subtypes of ischemic stroke include inflammation of small blood vessels known as arteritides, genetic factors affecting small blood vessels, or trauma leading to dissection (tearing) of a large extracranial artery, such as the carotid or vertebral artery (see Figure 5). These other subtypes account for less than 3% of ischemic strokes. The likelihood of experiencing one of these stroke subtypes can vary, depending on your risk for developing the specific pathologic processes that can trigger them. Age, race, and some as yet unknown genetic factors all play a role.

Dissection lesions are extremely important because they involve major arteries, and therefore may cause major damage. In this type of stroke, the blood vessel tears (dissects), damaging the inside of the artery. A blood clot, or thrombus, develops, which may then break off and travel to the brain. Low-flow or embolic TIAs often herald a more devastating stroke.

A dissection stroke can occur out of the blue and often affects younger people. In fact, it is one of the most significant causes of devastating ischemic stroke in children and young adults who are very active. This type of stroke can be caused by arterial injury due to whiplash, chiropractic neck manipulation, or a trauma suffered during vigorous exercise (such as a skiing accident or strenuous weightlifting). Even serious retching or coughing may be enough to tear a blood vessel.

The best way to prevent a dissection stroke is to prevent trauma to the arteries. Anticoagulation therapy may help prevent further clots or embolism (see "Treating ischemic stroke").

Hemorrhagic strokes

Less than 20% of all strokes are hemorrhagic. A blood vessel in or around the brain bursts, spilling blood into the surrounding tissue. This type of stroke generally occurs in two different anatomical settings: inside the brain (intracerebral hemorrhage) or outside the brain, but inside the skull (extracerebral hemorrhage). Different subtypes of hemorrhagic stroke can occur at each location. Treatment is aimed at stopping the hemorrhage and repairing any damage, and generally involves an inter-arterial procedure, surgery, or medication.

Intracerebral hemorrhage

There are two basic types of intracerebral hemorrhages. The first, deep (hypertensive) hemorrhage, occurs in the deep structures of the brain (see Figure 6). The second type, lobar hemorrhage, occurs in the lobes of the right and left brain hemispheres.

Figure 6: Intracerebral hemorrhagic strokes Intracerebral hemorrhagic strokes Hemorrhage means bleeding. When the bleeding takes place within the interior of the brain, as shown in these two examples, the stroke is known as an intracerebral hemorrhage. A hypertensive hemorrhage (A) occurs deep within the brain, often when blood pressure is particularly high. A lobar hemorrhage (B) is generally not caused by hypertension but occurs when blood leaks into one of the four lobes of the brain.

Deep hypertensive hemorrhages. This type of hemorrhage usually strikes people with a history of high blood pressure (hypertension). Symptoms such as headache and vomiting are relentless over a period of minutes. Deep hypertensive hemorrhages can occur at four basic locations: the basal ganglia, thalamus, pons (brainstem), and cerebellum. Cerebellar hemorrhages are often severe enough to result in brainstem compression, coma, and death.

If diagnosed early, a deep hypertensive cerebellar hemorrhage can be treated with surgical removal of the hematoma. Following surgery, chances of rapid recovery are excellent. Surgery is also possible for other subtypes of deep hypertensive hemorrhage, but in these situations, recovery is more limited because the hemorrhage has already caused significant brain damage by the time the problem is diagnosed. Small hemorrhages are better left to heal on their own, and good recovery is possible with careful medical and nursing care through the acute phase.

Lobar hemorrhage. This type of intracerebral hemorrhage takes place when blood leaks into one of the four lobes of the brain: the frontal, parietal, temporal, or occipital lobe. Unlike hypertensive intracerebral hemorrhages, lobar hemorrhages are not necessarily caused by high blood pressure. These strokes generally affect people over 60. Other than age, there are no known risk factors for this type of stroke.

Most people with a lobar hemorrhage have headaches at the site of the bleeding, and more than half vomit or feel drowsy at the onset. Other symptoms depend on which lobe is affected. For instance, a hemorrhage in the occipital lobe can cause vision impairment, whereas bleeding in the frontal lobe can cause weakness in the arm or leg.

There are three types of lobar hemorrhage. The two with known causes often recur and have a genetic basis, so they tend to run in families. The last type, which develops for unknown reasons, does not usually recur.

The first type of lobar hemorrhage is caused by a protein deposited in the blood vessels of the frontal, parietal, occipital, and temporal lobes. The protein deposit weakens the blood vessels so much that they rupture, giving rise to the hemorrhage. Physicians at Massachusetts General Hospital and other institutions are studying ways to prevent this subtype through medical therapy, or treat it once it occurs.

A second type of lobar hemorrhage originates either in an entanglement of blood vessels, particularly between arteries and veins, known as an arteriovenous malformation (AVM), or in tiny angiomas, noncancerous tumors made up of blood vessels. Although many of these lesions are harmless, others may rupture and hemorrhage, causing a stroke. It is possible to eliminate or at least reduce the size of an AVM or angioma with microsurgery, an intra-arterial procedure, or radiation therapy. The method used will depend on the location and nature of the AVM or angioma.

With increased use of CT and MRI imaging in diagnosis, some AVMs are discovered by chance when a doctor has ordered a brain scan for some other reason. It is not clear whether such AVMs pose a high risk of rupture; they may actually pose less of a risk than previously thought. If so, surgery may pose a greater risk than leaving an accidentally discovered AVM untreated.

The third type of lobar hemorrhage is the kind that occurs for some unknown reason and is diagnosed when the other two mechanisms are excluded. This type of lobar hemorrhage does not often recur.

Extracerebral hemorrhage

The brain is covered by three membranes, collectively known as meninges. The dura mater (outer membrane) is tough and fibrous. The pia (innermost layer) is soft, as it is in direct contact with the brain. In between is the arachnoid layer, which is filled with multiple blood vessels and cerebrospinal fluid.

Extracerebral hemorrhages are those that occur in or around one of these three membranes. These hemorrhages cause a stroke when the bleeding is large enough to compress brain tissue or arteries supplying the brain with blood. Several types of extracerebral hemorrhages exist, defined by where they occur.

Subarachnoid hemorrhage. These hemorrhages occur just under the arachnoid membrane. Two types of subarachnoid hemorrhages exist: those caused by berry aneurysms and those caused by infectious aneurysms. As mentioned earlier in this report, aneurysms are bulges in blood vessel walls that can burst, creating the heavy bleeding that is referred to as a hemorrhage.

Berry aneurysms most often occur where major arteries divide at the base of the brain. The blood vessel walls weaken and bulge, forming a berry-shaped aneurysm, and then grow to a point where they become likely candidates for a rupture. The rupture can cause a devastating hemorrhage around the brain, compressing it and damaging tissue. At other times, the rupture may cause a devastating spasm of the vessels at the base of the brain, blocking blood flow and leading to ischemia and ischemic infarction. Berry aneurysms are best eliminated by intra-arterial catheter techniques or surgery (see "Treating hemorrhagic stroke"). They are best treated at institutions that are centers for interventional arterial procedures.

Infectious aneurysms occur in blood vessels located over the surface of the brain, not at its base. They generally result from a tiny embolus from an infected heart valve, in people with bacterial endocarditis. The infectious embolic particle lodges in a blood vessel on the surface of the cortex and infects it. As the blood vessel weakens, an aneurysm develops. Infectious aneurysms are best treated with antibacterial therapy. Occasionally they may have to be surgically excised.

If an aneurysm causes pain or other symptoms, a doctor may be able to diagnose it before it ruptures and does serious damage. An MRI or CT scan may reveal an aneurysm in a large blood vessel, although cerebral angiography, an invasive imaging test, provides more detailed information. An aneurysm is managed best when a team of neurosurgeons, interventional neuroradiologists, and neurologists work together to decide on the most appropriate treatment.

In about 45% of cases, a severe headache is the first major symptom of a subarachnoid hemorrhage. People often characterize the headache as the worst headache they have ever had, using words such as "explode" and "burst" to describe it. About half of people lose consciousness. Other early symptoms may include a stiff neck, nausea and vomiting, trouble concentrating and other kinds of mental impairment, and seizures.

Other extracerebral hemorrhages. Bleeding may also occur in the space underneath the dural lining, known as the subdural space, or above the dural lining, known as the epidural space. Subdural and epidural hemorrhages result from trauma and tear of blood vessels in these areas. Elderly people often have a large subdural space, which develops as a natural aspect of aging. The little venous connections in the subdural space often break, resulting in a slow oozing of blood. Surgical drainage of the blood, to prevent brain compression, may be required in subdural hemorrhages and is usually necessary in epidural hemorrhage.

Source: from Harvard Health Publications, Copyright © 2008 Harvard University. All rights reserved. Harvard Medical School does not endorse products.
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