Cerebral Ischaemia and Stroke

Question 1

What is the circle of Willis?

Answer 1

The blood supply system to the brain, which has different arteries that supply different areas of the brain. The system allows collateral circulation in the case of a major artery occlusion

Question 2

What is a stroke?

Answer 2

A stroke is a loss of brain function caused by a disruption of blood supply, usually leading to a permanent sensory, motor/cognitive deficit. AKA cerebrovascular accident. Defined as a rapidly developing focal (localised) disturbance of brain function of presumed vascular origin and of >24hr duration.

Question 3

What are the neurological deficits that result from a stroke?

Answer 3

Hemiplegia (paralysis on one side), balance problems, loss of sensation, visual field, language, motor planning skills, personality change. Manifestation depends on the affected area but severity doesnt equal tissue loss

Question 4

What is an ischaemic stroke?

Answer 4

A stroke that results due to a restriction of blood supply (>20% of normal flow). Can be focal or global. Responsible for 85% of strokes. Focal eg. occlusion in a cerebral vessel. Global eg. Blood flow to brain is halted or drastically reduced eg. by cardiac arrest.

Question 5

What is the difference between a thrombosis and an embolism?

Answer 5

A thrombosis is a platelet plug in the vessel itself, and an embolism is a blood clot/other material (fat/air) that originates elsewhere.

Question 6

What determines the degree of tissue damage in a stroke?

Answer 6

The extent and duration of the occlusion, and the degree of blood supply from other vessels.

Question 7

Describe the tissue that results from a stroke ie. core and penumbra

Answer 7

The core is tissue that undergoes irreversible damage due to the ischaemia - called an infarct. Cells suffer necrotic death very quickly. The penumbra is the area surrounding the core that has undergone damage but not irreversible because it receives collateral flow from surrounding vessels. Over hours the infarct can spread from the core to the penumbra

Question 8

Which area of the ischaemic tissue is the target of therapy?

Answer 8

The penumbra because it offers a window of oppurtunity to preserve tissue. The more collateral vessels surround the region means there is more penumbra because more tissues receive O2 and glucose.

Question 9

What is a transient ischaemic attack?

Answer 9

A rapidly developing focal disturbance of presumed vascular origin that completely resolves within 24hr. Occurs when blood flow is briefly interrupted. The symptoms are similar to a stroke but don’t last as long.

Question 10

What is the importance of a TIA and what are the risk factors?

Answer 10

Often a warning sign for risk of a more serious and debilitating stroke. Most important factors are high BP, smoking, heart disease, carotid artery disease, diabetes, heavy alcohol use.

Question 11

What is a haemorrhagic stroke?

Answer 11

A stroke that results from bleeding in the brain

Question 12

What is an intracerebral haemorrhagic stroke?

Answer 12

An intracerebral haemorrhagic stroke is when the vessel inside the brain bursts and leaks blood into the surrounding tissue. It is often caused by an aneurysm (sac-like malformation of a vessel, protruding from vessel wall and weakening it)

Question 13

What is a subarachnoid haemorrhagic stroke?

Answer 13

Bleeding between the brain and the tissue covering the brain (subarachnoid space). It causes brain cells to die and affected parts of the brain to stop working properly. Cells in the area suffer from: lack of blood, compression by blood leaking out of the vessel and forming a clot, causing secondary inflammation and toxicity. High BP and ageing blood vessels are the most common causes

Question 14

Explain the risk factors for a stroke

Answer 14

Hypertension - Main risk factor for haemorrhagic stroke but contributes to atherosclerosis which can lead to ischaemic
Age - Stroke risk increases with age
Cardiac disease - Left atrial dysfunction including fibrillation is associated with a risk of thromboembolism which can cause a stroke
Smoking - Contributes to 15% of annual stroke deaths
Diabetes - Stroke causes 20% of diabetic deaths
High LDL cholesterol - Can promote atherosclerotic build up
Sedentary behaviour, diet, obesity - Affect all the others, so impact is secondary.

Question 15

What is global ischaemia?

Answer 15

Results from temporary blockage of blood flow to the brain eg. cardiac arrest.

Question 16

Which neuronal cell types are particularly vulnerable to global ischaemia?

Answer 16

Pyramidal cells of CA1 hippocampus area, pyramidal neurons of neocortex (layers 3, 5, 6), Purkinje cells of cerebellum, striatum neurons. They die after 10-20 mins.

Question 17

What happens to the neurons in the CA1 hippocampus during global isachemia?

Answer 17

They die quickly and lesions in this area commonly manifest as memory loss. The cell death isn’t immediate, and while the cells appear to recover and resume normal function, global ischaemia has triggered delayed neuronal death

Question 18

Why does the brain use so much glucose?

Answer 18

Uses 20% of total glucose and up consumption (up to 50% in intense activity) mainly to maintain transmembrane ion gradients and restoring them after each action potential

Question 19

Why does the brain need a continuous supply of glucose?

Answer 19

Because it cannot store or synthesise glucose and can’t utilise other energy sources. Glucose can be supplemented (but not replaced) by lactate or ketone bodies in extreme circumstances eg. starvation

Question 20

What are the effects of hypoglycaemia?

Answer 20

Disorientation, slurred speech, impaired motor function. Glucose < 2mM can lead to loss of consciousness, coma, or death

Question 21

Why does the brain need a continuous supply of O2?

Answer 21

It needs to produce ATP via oxidative phosphorylation. Because the energy demand of the brain is so high, in hypoxic condition, anaerobic respiration is only sufficient for a couple of minutes to keep cells alive. Complete lack of O2 to the brain is called anoxia

Question 22

How does limited blood flow affect the brain?

Answer 22

If blood flow is < 50%, functions significantly impaired. If total blood flow is interrupted for 4 seconds, there’s loss of consciousness. After a few minutes, irreversible damage occurs to the brain

Question 23

What are the differences between the different types of cell death that occur during ischaemia?

Answer 23

In the focal core, all cells die rapidly due to a lack of energy to maintain function and integrity. This passive unregulated cell death is necrosis.
The delayed neuronal cell death occuring in global ischaemia is programmed cell death, the most well known being apoptosis.

Question 24

How can ischaemic strokes be treated with drugs?

Answer 24

Tissue-type plasminogen activator, a thrombolytic agent, helps to dissolve the clot to restore blood flow

Question 25

Why is tPA not given to all patients?

Answer 25

There are risks of complications so it is only given to a small minority of patients, and not to haemmorrhagic stroke patients.

Question 26

How can surgery be used to treat ischaemic stroke?

Answer 26

Can use a catheter into an artery and surgically remove the clot.

Question 27

How does hypothermia treat ischaemic stroke?

Answer 27

It slows the pathological process, resulting in a smaller infarct, however mortality rates and disability levels are the same

Question 28

What are the most common treatments for stroke?

Answer 28

Combination therapies and prevention