Ischemic Stroke - causes, symptoms, diagnosis, treatment, pathology

There are two main types of stroke: an ischemic stroke which is when there’s a blocked artery that reduces blood flow to the brain and a hemorrhagic stroke which is when an artery in the brain breaks, creating a pool of blood that damages the brain. Of the two, ischemic strokes are much more common, and the amount of damage they cause is related to the parts of the brain that are affected and how long the brain suffers from reduced blood flow. Now if symptoms self-resolve within 24 hours, it’s called a transient ischemic attack and there are usually minimal long-term problems.

OK - let’s start with some basic brain anatomy. The brain has a few regions - the most obvious is the cerebrum, which is divided into two cerebral hemispheres, each of which has a cortex - an outer region - divided into four lobes including the frontal lobe, parietal lobe, temporal lobe, and the occipital lobe. There are also a number of additional structures - including the cerebellum, which is down below, as well as the brainstem which connects to the spinal cord.

The right cerebrum controls muscles on the left side of your body and vice versa. The frontal lobe controls movement, and executive function, which is our ability to make decisions. The parietal lobe processes sensory information, which lets us locate exactly where we are physically and guides movements in a three dimensional space.

The temporal lobe plays a role in hearing, smell, and memory, as well as visual recognition of faces and languages. Finally there’s the occipital lobe which is primarily responsible for vision. The cerebellum helps with muscle coordination and balance.

And finally there’s the brainstem plays a vital role in functions like heart rate, blood pressure, breathing, gastrointestinal function, and consciousness. The brain receives blood from the left and right internal carotid arteries, as well as the left and right vertebral arteries, which come together to form the basilar artery. The internal carotid arteries turn into the left and right middle cerebral arteries which serve the lateral portions of the frontal, parietal, and temporal lobes of the brain.

Each of the internal carotid arteries also give off branches called the anterior cerebral arteries which serve the medial portion of the frontal and parietal lobes and connect with one another with a short little connecting blood vessel called the anterior communicating artery. Meanwhile, the vertebral arteries and basilar artery gives off branches to supply the cerebellum and the brainstem. In addition, the basilar artery divides to become the right and left posterior cerebral artery which mainly serve the occipital lobe and some of the temporal lobe as well as the thalamus.

Finally, the internal carotid arteries each give off a branch called the posterior communicating artery which attaches to the posterior arteries on each side. So together, the main arteries and the communicating arteries complete what is called the Circle of Willis - a ring where blood can circulate from one side to the other in case of a blockage. The Circle of Willis offers alternative ways for blood to get around an obstructed vessel.

In general, the brain can get by on diminished blood flow - especially when it happens gradually because that allows enough time for collateral circulation to develop, which is where a nearby vessel starts sending out branches of blood vessels to serve an area that’s in need. But once the supply of blood flow is reduced to below the needs of the tissue - it causes tissue damage, which we call an ischemic stroke. There are two main ways that an ischemic stroke happens.

One mechanism is endothelial cell dysfunction, which is when something irritates or inflames the slippery inner lining of the artery—the tunica intima. One classic irritant is the toxins found in tobacco which float around in the blood damaging the endothelium. That damage becomes a site for atherosclerosis, which is where a plaque forms.

This is when a buildup of fat, cholesterol, proteins, calcium, and immune cells forms and starts to obstruct arterial blood flow. This plaque has two parts to it, the soft cheesy-textured interior and the hard outer shell which is called the fibrous cap. Branch points in arteries and particularly the internal carotid and middle cerebral arteries are the most common spots for atherosclerosis.

Usually, though, it takes years for plaque to build up, and this slow blockage only partially blocks the arteries, and so even though less blood makes it to brain tissue, there’s still some blood. So Strokes happen when there’s a sudden and complete or near-complete blockage of an artery—so let’s see how that can happen. Since plaques sit in the lumen of the blood vessel, they’re constantly being stressed by mechanical forces from blood flow, and interestingly it’s often the smaller plaques that are more dangerous.

Their fibrous caps are softer than the larger ones and are prone to getting ripped off. Once that happens, the inner cheesy filling is exposed to the blood and is thrombogenic, which means that it tends to form clots very quickly. Platelets adhere to the exposed cheesy material, and they release chemicals that enhance the clotting process.

Within a minute that artery can be fully blocked. Another mechanism for ischemic stroke formation is an embolism. An embolic stroke typically happens when a blood clot breaks off from one location, travels through the blood, and gets lodged in an artery downstream, typically an artery, arteriole, or capillary with a smaller diameter.

These blood clots typically emerge from atherosclerosis, but they can also form in the heart. For example stagnant blood can form a clot, and blood can stagnate due to an atrial fibrillation or after a heart attack. If a clot forms in the left atrium, it moves into the left ventricle and from there it has a direct route to the brain.

On the other hand, if a clot forms in the low-pressure veins or right atrium, then it goes into the right ventricle and gets lodged in the pulmonary capillaries - with no way of getting to the brain. An important exception is if a person has a heart defect like an atrial septal defect that allows blood and potentially a blood clot to wander from the right side of the heart over to the left side of the heart. In that situation, a venous or right atrial blood clot will have bypassed the pulmonary circulation and established a route to the brain.

One specific type of ischemic stroke is called a lacunar stroke, and they typically involve the deep branches of the middle cerebral artery that feed the basal ganglia. Lacunar refers to “lake”, and is called that since after a lacunar stroke the damaged brain tissue develops fluid filled pockets called cysts that look like little lakes under a microscope. Lacunar strokes classically develop as a result of hyaline arteriolosclerosis which is when the arteriole wall gets filled with protein.

This can happen as a result of hypertension or diabetes, and can make the artery wall quite thick, reducing the size of the lumen. In addition to problems specific to an artery, something like shock can lead to a reduction in blood flow throughout the entire body. In these cases, the tissues that are the furthest downstream are affected the most.

This is because healthy tissue continues to extract what it needs from the blood flowing by, leaving little or no oxygen and nutrients for the tissue furthest away. The “furthest downstream” tissues in the brain are at the border of two different blood supplies. When the blood flow throughout the body is diminished for any reason, they get damaged, and this pattern of injury is called a watershed infarct.

Regardless of the mechanism of an ischemic stroke, it’s helpful to remember that there’s an ischemic core, which is the brain tissue that will likely die from ischemia, and then there’s tissue around the core, called the ischemic penumbra, which is preserved for a period of time by collateral circulation and has a chance to survive if blood flow is restored quickly enough. Regardless of the type of ischemic stroke, without a steady supply of glucose and oxygen, cells run out of energy within minutes and you get a high buildup of sodium and calcium levels. High sodium levels draws water into the cell making it swell, this is called cytotoxic edema.

And high calcium leads to the buildup of reactive oxygen radicals that react with lipids in the membranes of mitochondria and lysosomes. Damage to these organelles allows apoptosis-inducing factors and degradative enzymes to seep out of the cell. Over a period of 4-6 hours, immune cells begin to haul away damaged cells and the resulting inflammation damages the blood brain barrier allowing fluid and proteins to get into the brain tissue causing swelling or vasogenic edema.

Because the skull creates a fixed volume the swelling leads to a mass effect where the swollen brain tissue pushes into the unaffected side of the brain-called cingulate or uncal herniation, or slips down and out of the base of the skull - called cerebellar tonsil herniation, which is particularly dangerous because it can push onto the brainstem and affect breathing and consciousness. Stroke symptoms depend on the exact part of the brain that is affected. For example, an anterior or middle cerebral artery stroke can cause numbness and sudden muscle weakness.

If a stroke affects the Broca’s area, which is usually in the left frontal lobe, or Wernicke’s area, which is usually in the left temporal lobe, then it can cause slurred speech or difficulty understanding speech, respectively. If there’s a posterior cerebral artery stroke, then it can affect vision. An acronym to remember some common stroke symptoms is FAST - Facial drooping, Arm weakness, Speech difficulties, and Time.

Time is obviously not a symptom but just a reminder to get help as quickly as possible to minimize cell injury and maximize the chance of a full recovery. To diagnose and confirm the location and size of an ischemic stroke, medical imaging with a CT or MRI can be used. Also, angiography, which uses contrast injected into the blood, can help to visualize the exact location where blood flow is blocked within an artery.

In addition, using FLAIR sequence MRIs, it’s possible to distinguish a new stroke injury from an old one. In an ischemic stroke the ultimate treatment is to reestablish blood flow as quickly as possible to prevent further cell death, particularly in the penumbra - every minute counts. So thrombolytic enzymes, like tissue plasminogen activator or TPA, are used to activate the body’s natural clot busting mechanisms, but TPA does have a time limit of when it can be used.

Aspirin is also used to prevent platelets from forming additional clots. If TPA is unsuccessful, surgical procedures can be used that push a wire through the artery and physically remove the clot. In mechanical embolus removal in cerebral ischemia, called MERCI for short, the wire grabs on to the clot and draws it out of the artery.

In suction removal, the wire is used to physically break down the clot and clot fragments are removed with suction. After a stroke has occurred, there is an elevated risk of having additional strokes so it’s important to minimize risk factors - the main one being quitting smoking, but others include having a healthy blood pressure, normal LDL cholesterol levels, and controlling other diseases like diabetes. Occasionally, a surgery may be necessary to help clean arteries obstructed by severe atherosclerosis.

For example, in a carotid endarterectomy, the internal carotid artery is opened up and atherosclerotic plaque is removed. Alternatively, a stent may be placed to keep the artery opened up. Okay, a quick recap: An ischemic stroke occurs when there’s an acute decrease in the arterial blood supply.

It can be due to atherosclerosis, a thrombus, an embolus,, or a global reduction in blood flow. The goal is to identify symptoms and reestablish blood flow to prevent long-term damage - to remember this a common acronym is FAST - Facial drooping, Arm weakness, Speech difficulties, and Time.