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Cerebral vascular disease: Pathology review

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Pathology

Nervous system

Central nervous system disorders
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Nervous system pathology review

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Cerebral vascular disease: Pathology review

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Questions

USMLE® Step 1 style questions USMLE

19 questions
Preview

A 78-year-old right-handed man is brought to the emergency department following sudden-onset weakness in his right arm and inability to speak for twenty four hours. The patient’s daughter states she initially became concerned when he dropped his cup of coffee while walking to the kitchen table last night. The daughter states he has had a similar episode in the past that resolved spontaneously. He has a history of hypertension, for which he takes lisinopril. His temperature is 37°C (98.6°F), pulse is 92/min, and blood pressure is 158/104 mmHg. The patient is alert and visibly frustrated by not being able to speak. Physical examination reveals 2/5 strength in the right upper extremity and 4/5 strength in the right lower extremity. He follows written and verbal commands but is unable to speak or write. MRI of the head demonstrates ischemic changes in the cerebral territory supplied by the left middle cerebral artery. Which of the following histopathological findings are most likely to be observed in this patient’s brain at the present time?

Transcript

At the emergency department, 30-year-old Lydia presents with severe headache and confusion. Clinical examination reveals low grade fever and nuchal rigidity. Past medical history reveals she has polycystic kidney disease. Non-contrast CT reveals blood between the arachnoid and the pia mater. Lydia is treated supportively and sent home. Three days later she suddenly develops a severe headache, vomiting, and confusion.

Later that day, 70-year-old Amanda presents with left-sided weakness and numbness, with her foot and leg more affected than her arm. She can speak fluently and understands everything being said to her. Past medical history includes hypertension, hyperlipidemia, and a myocardial infarction last year.

Based on their presentation, the diagnosis is that both Lydia and Amanda had a cerebral vascular disease, most often referred to as a stroke. A stroke is when there’s a sudden focal neurological deficit due to a part of the brain losing its blood supply. Now, to safeguard the brain from hypoxia, the brain has a dual circulation called the circle of Willis, divided into an anterior and posterior circulation. The anterior circulation starts in the neck, where the common carotid artery splits into the external and internal branches. The internal carotid passes through the carotid canal of the temporal bone of the skull and into the cranial cavity. Once inside, the internal carotid artery gives off branches. First are the middle cerebral arteries that supply the lateral portions of the frontal, parietal, and temporal lobes. It’s also important to remember that the middle cerebral arteries supply the two language areas, Broca’s and Wernicke’s.

From the initial segment of the middle cerebral arteries, small perforating arteries called lenticulostriate arteries arise to supply a part of the basal ganglia called the striatum, which includes the caudate and putamen, as well as the internal capsule. And that’s something you absolutely must remember for the exams! The internal carotid artery also gives rise to the anterior cerebral artery, which supplies the medial portion of the frontal and parietal lobes. The two anterior arteries connect with one another via a short blood vessel called the anterior communicating artery, forming the anterior portion of the circle of Willis. An important area supplied by the anterior circulation is the cortical homunculus, which is kind of a neurological map of the areas and proportions of the brain that are in charge of the motor and sensory functions for different parts of the body.

The motor homunculus belongs to the frontal lobe, while the sensory homunculus is right behind it in the parietal lobe. Knowing the distribution of the cortical homunculus is important because the stroke will manifest as symptoms involving the body area that is controlled by the affected brain area, and this gives us a clue to where the stroke occurred. The cortical homunculus can be represented as a body lying on top of the brain like this, where each body part lies on top of its corresponding brain area. The toes are represented first, and then as one moves down, progressively higher parts of the body are represented, until the last part is the face. These representations on each side of the brain control the corresponding opposite side of the body.

Now, the medial area of the homunculus, representing the lower body, is supplied by the anterior cerebral artery, while the lateral area representing the upper body and face is supplied by the middle cerebral artery.

Moving on, the posterior circulation starts with the vertebral arteries, which head up through the transverse foramina of the cervical vertebrae and then through the foramen magnum into the cranial cavity. The vertebral arteries send branches that form the anterior spinal artery, which supplies the medial medulla and the anterior portion of the spinal cord above the level of T8. Below that level, the spinal cord is supplied by the artery of Adamkiewicz, which is a branch of the aorta. In addition, the vertebral arteries give off the posterior inferior cerebellar artery, or PICA, which supplies the lateral medulla and part of the cerebellum.

Then, at the base of the medulla, both vertebral arteries join into a single artery called the basilar artery. As the basilar artery ascends, it first gives off the anterior inferior cerebellar artery, or AICA, which supplies the lateral pons and part of the cerebellum. Then, the basilar artery sends small branches called pontine arteries to supply the mid-pons. Now, going up towards the midbrain, the basilar artery also gives off a few pontine branches, which supply much of the pons medially; as well as the right and left superior cerebellar arteries, which supply a part of the pons laterally and the superior part of the cerebellum.

The basilar artery also gives off the right and left posterior cerebral arteries, which supply the occipital lobe. Both of these arteries give the left and right posterior communicating arteries, which merge with the internal carotid arteries, thereby closing the posterior portion of the Circle of Willis. In general, the brain can get by on diminished blood flow when it happens gradually, because that allows enough time for collateral circulation to develop. But when blood supply is reduced suddenly, it causes tissue damage, which we call a stroke. After 5 minutes of hypoxia, neurons start to die and the damage becomes irreversible. The cells that are most vulnerable to hypoxia and get damaged first are the pyramidal cells of the hippocampus; the cells of the neocortex; and the Purkinje cells of the cerebellum. And that’s something you have to know for the exams!

All right, now let’s dive deeper into strokes. There are two main types of stroke, ischemic and hemorrhagic. Most strokes are ischemic, where a blocked artery reduces blood flow to the brain. Ischemic strokes can be classified into thrombotic, embolic, and hypoxic.

Thrombotic strokes usually occur when a clot forms over an atherosclerotic plaque, but they can also develop in non-inflammatory diseases like fibromuscular dysplasia. They’re more common in large vessels like the middle cerebral artery. But there’s a type of stroke that affects small vessels, called lacunar strokes and these are very high yield! Lacunar refers to “lake.” It receives its name because, after a lacunar stroke, the damaged brain tissue develops fluid-filled cysts, which look like little lakes under a microscope. Lacunar strokes typically involve the lenticulostriate arteries that supply the striatum and internal capsule.

Now, lacunar strokes can be associated with conditions like hypertension and diabetes that can lead to a type of arteriosclerosis called hyaline arteriolosclerosis where the arteriole wall gets filled with protein. This can make the arteriole wall thicker, reducing the size of the lumen and leading to lacunar strokes. Next, embolic strokes occur when a blood vessel is blocked by an embolus. If it arises from the heart, it’s called cardioembolic, and that usually occurs in the setting of an atrial fibrillation, where blood pools in the atria and can become clotted. That clot can then travel up to the blood vessels supplying the brain. Now, another cause of embolic stroke that gets frequently tested is infective endocarditis! Vegetations can detach from the infected valve to float through the bloodstream, and these are called septic emboli. Mind that septic emboli from the left side of the heart can lodge in the arterial circulation of the brain, causing a stroke, while right-sided ones usually lodge in the pulmonary circulation.

More rarely, there might be a paradoxical embolus that dislodges from the right side, and then slips through an atrial septal defect or patent foramen ovale. It enters the left atrium, and from there it can head off to the brain, causing a stroke. Now, an embolus can also dislodge from a thrombus or atherosclerotic plaque in the carotid arteries, and that results in a thromboembolic or atheroembolic stroke. Rarely, there might be a paradoxical embolus, which dislodges from a thrombus in the veins, like a deep vein thrombosis, and then slips through an atrial septal defect or patent foramen ovale, enters the left atrium, and from there, to the brain.

Finally, there’s hypoxic stroke, aka hypoxic ischemic encephalopathy, or global cerebral ischemia, which develops when there’s systemic hypoperfusion or hypoxemia. This can occur in cardiovascular surgeries, during cardiac arrest, due to ischemia during birth, and things like septic shock, or drowning. In these cases, the pattern of injury is called a watershed infarct or watershed stroke, where 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 and as a result, the tissues that are the furthest downstream are affected the most. The “furthest downstream” tissues are the watershed areas, which are at the border of blood supply from two separate groups of cerebral arteries, making them more vulnerable to ischemia. There are three main watershed areas where watershed infarcts typically occur; between the anterior cerebral and the middle cerebral arteries, as well as between the posterior cerebral and the middle cerebral arteries, and between the external and internal branches of the middle cerebral arteries.

All right, now let’s switch gears and talk about hemorrhagic strokes, in which a blood vessel bursts and bleeds out, creating a pool of blood that increases pressure in the skull and on nearby tissue and blood vessels. In addition, less oxygen-rich blood is flowing downstream to the cells that need it. Healthy tissue can die from both the direct pressure and the lack of oxygen within a few hours. Increased pressure within the skull can lead to brain herniation, which is when the brain moves acro