Stroke

Stroke follows heart disease and cancer as the third leading cause of death in developed countries, accounting for 10% of overall mortality in the UK. It is defined clinically as an acute neurological deficit of vascular origin that lasts more than 24 hours or causes death.

Types of stroke

Stroke is caused by inadequate tissue perfusion or ischaemia (Greek: isch-, restriction; haema, blood). The brain is particularly sensitive to ischaemia because neurons have a high metabolic rate and can only survive a few minutes without oxygen and glucose. Tissue death as a result of inadequate blood flow (e.g. due to an occluded blood vessel) is called infarction (Latin: infarctus, stuffed). The area of dead tissue is referred to as ‘an infarct’. There are two main types of stroke (Figs 10.1 and 10.2):

Fig. 10.1 Ischaemic stroke.
**(A)** Photograph taken during a post-mortem examination in a patient with an old (‘healed’) left hemisphere ischaemic infarct in the territory of the middle cerebral artery. Extensive resorption of brain tissue (leaving only a fluid-filled cyst cavity) indicates a prolonged period of survival after the stroke; **(B)** Coronal section of a fixed (preserved) brain slice in a different patient showing an old ischaemic stroke, also in the territory of the middle cerebral artery. From Ellison and Love: Neuropathology 2e (Mosby 2003) with permission.

Ischaemic stroke (85% of cases) is caused by reduced blood flow to a particular part of the brain, usually following occlusion of a cerebral artery.

Haemorrhagic stroke (15% of cases) is due to a ruptured blood vessel. This is commonly associated with high blood pressure and diseases that weaken the arterial wall.

In both types of stroke the brain tissue normally supplied by the vessel is suddenly deprived of blood and its function is lost. This causes focal neurological deficits that develop very rapidly (e.g. sudden weakness or loss of speech) and abrupt onset is the clinical hallmark of stroke. In haemorrhagic stroke, there may also be mechanical damage, such as tearing and compression of brain tissue, caused by blood escaping under arterial pressure.

Key Points

Stroke follows heart disease and cancer as the third leading cause of death in developed countries, accounting for 10% of overall mortality in the UK.

It is defined as an acute neurological deficit of vascular origin that lasts more than 24 hours or causes death. Abrupt onset is the clinical hallmark of stroke.

The two main types of stroke are ischaemic (85%) and haemorrhagic (15%); in most cases, inadequate tissue perfusion (ischaemia) leads to death of brain tissue (infarction).

Ischaemic stroke

Ischaemic stroke can be divided into five groups based on cause: (i) large-artery atherosclerosis; (ii) cardioembolism; (iii) small vessel occlusion; (iv) other defined cause; and (v) unknown cause (cryptogenic stroke). This classification is derived from a multicentre trial of acute stroke treatment (‘TOAST’) in the 1990s and continues to be widely used in UK stroke trials. The ‘other defined cause’ category incorporates many uncommon and rare causes of stroke including abnormalities of blood coagulation, infectious diseases, arterial damage and inflammatory disorders.

Large vessel and cardioembolic stroke

Cerebral blood vessels may be occluded by an embolus (Greek: embolos, wedge or plug). This is a small piece of coagulated blood (or occasionally some other material such as fat) that travels in the circulation and lodges in the vascular tree of the brain. Emboli often originate from the heart (cardioembolic stroke) in association with valve disease or an abnormal heart rhythm (Clinical Box 10.1). Disease in the neck vessels or aortic arch may also give rise to emboli.

Clinical Box 10.1: Atrial fibrillation

This is the most common type of abnormal heart rhythm, affecting 1% of people over the age 65 and 10% of those over 80. It is characterized by disorganized atrial contraction (fibrillation) with an irregular heartbeat. There may be palpitations, fainting episodes or chest pain, but it is often asymptomatic. Blood tends to pool and coagulate in the poorly contracting atria, increasing the risk of cardioembolic stroke (from the left atrium to the brain) up to ten-fold. Predisposing factors for atrial fibrillation include hypertension, heart disease, hyperthyroidism and excessive alcohol consumption. It can be treated with anticoagulants (e.g. warfarin or newer agents such as the direct thrombin inhibitor dabigatran). Alternatively, drugs may be given to control the heart rate if it is fast (which can compromise cardiac output) or a defibrillator can be used to restore a normal heart rhythm (called cardioversion).

Some ischaemic strokes are caused by coagulation of blood within a cerebral vessel, termed in situ thrombosis (Greek: thrombos, blood clot) or large artery intracranial occlusive disease. This is more common in people of Asian and African origin, but is increasingly recognized in Caucasians.

Small vessel disease

Small vessel disease is particularly common in patients with arterial hypertension together with other vascular risk factors (e.g. diabetes, cigarette smoking, elevated cholesterol). High blood pressure damages the arterial wall and its smooth muscle is gradually replaced by collagen, termed hyaline arteriosclerosis. In some cases there is vessel wall necrosis with accumulation of lipid-laden foam cells, which is referred to as lipohyalinosis.

Both types of pathology cause arteriosclerosis or ‘hardening’ of the arteries (Greek: sklerōs, hard). Sclerotic vessels are unable to dilate in response to reduced flow, leading to lacunar infarcts (see Ch. 12, Figs 12.18 and 12.19). These are small areas of ischaemic tissue damage (often in the basal ganglia or internal capsule) measuring less than 1 cm in diameter (Latin: lacūna, hole or gap). Small vessel disease is also an important cause of vascular cognitive impairment and dementia (Ch. 12).

Transient ischaemic attacks

A brief period of cerebral ischaemia may cause a reversible neurological deficit that resolves when the blood flow is restored. This is a transient ischaemic attack (TIA). Involvement of the retinal blood supply causes temporary blindness in one eye, termed amaurosis fugax (Greek: amaurosis, dark; Latin: fugax, fleeting). Symptoms usually resolve within minutes (and never last more than 24 hours, by definition) but neuroimaging evidence suggests that permanent damage occurs in 10–20% of cases. TIAs are associated with increased risk of both stroke and heart attack.

Haemorrhagic stroke

Spontaneous intracerebral haemorrhage is more common in people with high blood pressure and frequently occurs in the basal ganglia, cerebellum or pons (Fig. 10.2A). However, the incidence of hypertensive intracerebral haemorrhage is declining in the UK and USA and an increasingly important cause is cerebral amyloid angiopathy, particularly in the elderly (see Ch. 12, Clinical Box 12.5). This is caused by deposition of amyloid beta peptide in the walls of cortical and meningeal arteries, leading to atypical (or lobar) haemorrhages that are close to the cortical surface (Fig. 10.2B).

Up to a third of spontaneous intracranial haemorrhages are caused by rupture of an aneurysm (a dilatation in the wall of an artery). Since the cerebral blood vessels travel and branch within the subarachnoid space, this results in subarachnoid haemorrhage (Clinical Box 10.2). Aneurysms that rupture in the substance of the brain may cause devastating brain damage or sudden death.

Clinical Box 10.2: Subarachnoid haemorrhage

Bleeding into the subarachnoid space accounts for a third of intracranial haemorrhages. Although this does not necessarily cause a focal neurological deficit, subarachnoid haemorrhage is normally regarded as a type of stroke, accounting for 5% of cases overall. It classically presents with a severe headache (‘the worst headache I have ever had’). The most common cause is a ruptured berry aneurysm, a medical emergency with a high mortality rate (Fig. 10.3). Berry aneurysms are small vascular swellings which develop at congenital weak spots in the arterial wall. They are usually found at points where blood vessels branch, especially in the circle of Willis at the base of the brain. Ischaemic stroke may occur as a late complication. This is due to blood in the subarachnoid space acting as an irritant and triggering vasospasm. Unruptured berry aneurysms are found incidentally in up to 2% of post-mortem examinations.

Fig. 10.3 Subarachnoid haemorrhage.
Post-mortem photograph of the brain (ventral aspect) in a patient who collapsed and died after a sudden, severe headache. The subarachnoid space at the base of the brain is filled with fresh blood, obscuring the circle of Willis. *Inset*: after removal of the blood a ruptured berry aneurysm was found in the region of the anterior communicating artery, indicated by the pointer. From Ellison and Love: Neuropathology 2e (Mosby 2003) with permission.

Key Points

Cerebral blood vessels are most commonly occluded by emboli. These are often cardiogenic (e.g. due to atrial fibrillation or valve disease) but may also arise from the aortic arch or neck vessels.

Small vessel disease is associated with hypertension and other cardiovascular risk factors. In addition to stroke, it is an important cause of vascular cognitive impairment and dementia.

Large artery intracranial occlusive disease (in situ thrombosis) is often associated with vessel wall disease, leading to a regional infarct. It is more common in people of African and Asian origin.

Brief periods of cerebral ischaemia cause transient ischaemic attacks which usually resolve within a few minutes and never last more than 24 hours (by definition).

Spontaneous intracerebral haemorrhage is more common in people with arterial hypertension and frequently occurs in the basal ganglia, cerebellum or pons. Cerebral amyloid angiopathy is an increasingly recognized cause, leading to ‘atypical’ (superficial/lobar) haemorrhages.

Subarachnoid haemorrhage usually presents with a sudden, severe headache and is most often due to a ruptured berry aneurysm. It is a medical emergency with a high mortality rate.

Blood supply to the brain

The brain is supplied by two pairs of arteries that arise from branches of the aortic arch (Fig. 10.4):

Fig. 10.4 MRI-angiogram showing the aorta and neck vessels. Note that the right common carotid and right subclavian arteries [seen here on the left side of the image, following radiological convention] both arise from a single brachiochephalic artery. In contrast, the left common carotid and left subclavian arteries each arise separately as direct branches of the aortic arch. Courtesy of Dr Andrew MacKinnon.

The internal carotid arteries ascend in the anterior part of the neck, arising from the bifurcation of the common carotid arteries.

The vertebral arteries arise from the subclavian arteries and ascend in the lateral cervical region, passing through foramina in the transverse processes of the upper six cervical vertebrae.

The arteries at the base of the brain are linked by communicating vessels to form the circle of Willis. This gives rise to anterior, middle and posterior cerebral arteries on each side, which supply most of the cerebral hemisphere. The cerebral blood supply can be divided into anterior and posterior circulations (Fig. 10.5A).

Fig. 10.5 The anterior and posterior circulations and their origins from the circle of Willis.
**(A)** Schematic, two-dimensional, representation of the circle of Willis, showing the anterior (internal carotid) and posterior (vertebrobasilar) circulations; **(B)** Illustration of the three-dimensional arrangement of the circle of Willis.

Anterior circulation

The internal carotid artery divides at the base of the brain, giving rise to the middle cerebral artery (MCA) and the anterior cerebral artery (ACA). The MCA is the larger of the two and receives 80% of the internal carotid blood flow. For this reason, cardiogenic emboli are much more likely to enter the MCA than the ACA. The middle cerebral artery continues laterally between the frontal and temporal lobes and emerges from the lateral sulcus to supply most of the hemispheric convexity (Figs 10.6A and 10.7).

Fig. 10.6 The anterior, middle, posterior and lenticulostriate arteries.
**(A)** Coronal view of the cerebral hemisphere showing the anterior and middle cerebral arteries. The lenticulostriate (deep perforating) vessels can be seen arising at right-angles from the middle cerebral artery; **(B)** Midsagittal view of the cerebral hemisphere showing the anterior and posterior cerebral arteries.

The anterior cerebral artery passes forward and medially to meet its partner between the cerebral hemispheres. It winds around the corpus callosum and supplies the medial aspect of the hemisphere as far back as the parieto-occipital sulcus (Figs 10.6 and 10.8). Posterior to this point the posterior cerebral artery takes over to supply the occipital lobe. Perforating branches of the anterior circulation supply the optic radiations, so that anterior circulation strokes may cause a contralateral visual field defect.

Fig. 10.8 Medial view of the cerebral hemisphere showing the vascular territories of the middle, anterior and posterior cerebral arteries.
The dashed line indicates the arterial watershed zone between the main vascular territories.

Posterior circulation

The posterior circulation supplies the remainder of the cerebral hemisphere and the posterior fossa contents (brain stem and cerebellum). The two vertebral arteries unite in front of the brain stem, at the junction between pons and medulla, to become the basilar artery. For this reason, the posterior circulation is also known as the vertebrobasilar circulation. The basilar artery ascends along the basal pons to reach the midbrain where it splits into the two posterior cerebral arteries (PCA). These vessels wind around the midbrain and pass posteriorly, above the tentorium cerebelli, to supply the occipital lobe and the inferior surface of the temporal lobe (Figs 10.6B, 10.7 and 10.8).

Circle of Willis

The circle of Willis is a polygonal arrangement of blood vessels surrounding the optic chiasm and pituitary stalk. It connects the anterior and posterior circulations via the single anterior communicating artery and the paired posterior communicating arteries (Figs 10.5B and 10.9). The circle of Willis shows considerable anatomical variation and is incomplete in 50% of people. It is an example of a collateral circulation, an arrangement of interconnected vascular channels permitting blood flow via an alternative route in the event of an obstruction. Interconnections between vessels exist elsewhere (e.g. between the distal territories of the three main cerebral blood vessels) but are not always effective, particularly in the elderly. Some structures do not have a collateral blood supply (e.g. the internal capsule and basal ganglia) and are therefore more vulnerable to stroke.