Cerebrovascular Disease Pathology Guide

Timings come from the Stony Brook neuropathology chapter for perfusion failure and from The Autopsy Book stroke guide for gross appearance.

Cerebrovascular disease pathology divides into ischemic infarction and hemorrhage. Each lesion has a recognizable vessel-level cause and a gross appearance that changes with time.

This guide sorts lesions by vessel type and mechanism. It sits within the neuropathology course, which places stroke alongside other tissue-level patterns.

Sorting lesions by mechanism

Start with the question of whether tissue died from lack of flow or from blood escaping a vessel. Infarction is death of tissue in a region of brain due to lack of blood flow through the supplying vessel, according to the Stony Brook neuropathology chapter. That chapter names four main processes behind focal ischemic infarction: atherosclerosis, embolism, arteriosclerosis and hypotension.

Vessel size predicts which process is likely. Superficial vessels are most commonly occluded by emboli, whereas deep penetrating vessels are most commonly affected by hypertension. That split lets you guess the mechanism from where a lesion sits before you look at the microscopy.

The Stroke Manual puts ischemic stroke at about 80-85% of strokes, with intracranial hemorrhage at about 15%. Medscape reports that nearly 800,000 people have a stroke each year in the United States and that 82-92% of those strokes are ischemic. Ischemic disease therefore dominates, but hemorrhage has distinct pathology.

• Ischemic stroke: arterial occlusion or hypoperfusion causes infarction. Border zones, also called watershed regions, are the most vulnerable to poor perfusion.
• Intracerebral hemorrhage: bleeding into brain parenchyma, usually from a diseased small vessel.
• Subarachnoid hemorrhage: bleeding into the space around the brain, listed with intracerebral and intraventricular hemorrhage as intracranial hemorrhage types.
• Vascular malformations: abnormal vessels such as arteriovenous malformations, which are a separate etiologic category.

Ischemic infarct in the first minutes and hours

Early ischemic injury is biochemical, so the brain looks normal while neurons are already failing. Average cerebral blood flow is 50 mL/100 g/min, and gray matter has greater blood flow than white matter, per the Stony Brook chapter. The same source notes that glutamate released in ischemia causes an overwhelming influx of calcium into dendrites, resulting in neuronal death.

Not all underperfused tissue is lost at once. The Stroke Manual gives a functional threshold of about 20 mL/100 g/min and a morphologic threshold of about 10-12 mL/100 g/min. Further decline or prolonged ischemia leads to irreversible membrane damage. Tissue between those two thresholds is the penumbra, which is why timing matters for what survives.

Territory helps you recognize which artery was involved. Medscape describes the middle cerebral artery as supplying the lateral frontal and parietal lobes, the anterior temporal lobes, the insula and the basal ganglia. This is why the large wedge-shaped middle cerebral artery infarct in the lead image is the classic lesion of the field.

Reading infarct age at the cut surface

Gross findings change slowly at first, so use them as a rough clock and not a precise one. The Autopsy Book records no visible alteration at 0-6 hours, then edematous swelling and softening of tissue with discoloration and loss of gray-white distinction at 8-48 hours. A cystic scar lined by leptomeninges replaces the injured tissue after more than 2-3 months. The stretch between those two points is the period in which swollen, softened tissue is converted to scar.

1. Check the territory first. Match the lesion to a named artery, since superficial branches suggest embolism and deep branches suggest hypertensive disease.
2. Judge swelling and borders. Swelling with indistinct gray-white borders points to a lesion in the early window of about 8-48 hours. A slice that looks entirely normal does not rule out an infarct under about 6 hours old.
3. Look for a cavity in old lesions. A cystic scar lined by leptomeninges fits a lesion older than about 2-3 months.
4. Examine the supplying arteries. Serial cross sections of the circle of Willis document the presence or absence of occlusive lesions, and the same dissection checks for aneurysm.

Small vessel disease and lacunar infarcts

Lacunar infarcts belong to the deep penetrating vessels, not the large surface arteries. Those deep vessels are the ones most commonly affected by hypertension, per the Stony Brook chapter. The Stroke Manual adds that small penetrating arteries and arterioles are more often affected by arteriolopathy, characterized by medial hypertrophy and fibrinoid deposition.

When you see a small deep infarct, look at the vessels beside it. Hyalinized wall thickening supports a small vessel mechanism and argues against an embolic one, which tends to occlude superficial branches.

Hypertensive and amyloid intracerebral hemorrhage

Intracerebral hemorrhage has two common vessel-wall explanations, and location is the quickest way to tell them apart. The Autopsy Book describes acute hemorrhage as a red-brown mass that can exert mass effect on surrounding brain.

Hypertensive brain hemorrhage

Hypertension most commonly affects deep penetrating vessels, so the bleed lies deep in the hemisphere. The putamen is the typical site in the coronal slice below. Pair a deep bleed with arteriolopathy in the neighboring small vessels to support a hypertensive cause.

Cerebral amyloid angiopathy

Cerebral amyloid angiopathy differs from hypertensive hemorrhage in which vessels carry the disease. It involves vessel walls in the cortex and is confirmed by Congo red staining, where amyloid shows apple-green birefringence under polarized light. Deep arteriolopathy is not the defining feature here.

The practical rule is to ask where the bleed sits and what stain the vessel wall takes. A deep bleed with fibrinoid arteriolopathy suggests hypertension. Cortical vessel walls with Congo red birefringence indicate amyloid.

Subarachnoid hemorrhage and berry aneurysm

Subarachnoid hemorrhage is a hemorrhagic stroke subtype, grouped by the Stroke Manual with intracerebral and primary intraventricular hemorrhage. Its characteristic source is the berry aneurysm, which arises on the arteries of the circle of Willis at the base of the brain. Blood then spreads through the subarachnoid space around that arterial ring.

This is why the circle of Willis gets its own dissection step. The Autopsy Book notes that serial cross sections of the circle can document occlusive lesions, and the same careful examination is how an aneurysm is found. When subarachnoid blood is present, look at the base of the brain before assuming any other source.

Arteriovenous malformation pathology

An arteriovenous malformation is a developmental vascular abnormality, and the Autopsy Book lists arteriovenous malformations among the vascular abnormalities that cause stroke. Its recognizable gross and angiographic pattern is a tangle of vessels, not a single diseased artery or one saccular outpouching.

Consider a malformation when a hemorrhage lacks the deep location of hypertensive disease and the cortical amyloid pattern. Documenting the tangled vessel architecture separates it from those causes.

Related lesion patterns

Cerebrovascular lesions can overlap with other causes of brain damage, so compare patterns across diagnoses. For mechanical injury, see the guide on traumatic brain injury neuropathology. For infective lesions, see suppurative meningitis pathology.

Frequently asked questions