L4- Stroke: Cerebrovascular Disease

How many neurons and connections does the brain contain?

Contains >80 billion neurons and >1 trillion connections

How much does the brain weigh? (In grams)

Weighs approximately 1500–1800 g.

What two things does the brain require to function?

blood supply and glucose

Why is the brain highly vascularised?

To deliver its metabolic requirements

How much glucose is delivered per day by the brain? (In grams)

150 g of glucose per day

Are redundancies of cerebral blood supply built in?

Yes- the cerebral circulation contains alternative/interconnected vascular routes rather than relying on one simple vessel.

What is another term for stroke?

Cerebrovascular accident (CVA).

Define stroke

A sudden neurological event of vascular origin with clinical symptoms and signs that last more than 24 hours or may lead to death

How is a TIA (Transient ischaemic attack, also called a “mini-stroke”) defined?

A neurological event of vascular origin in which symptoms and signs last <24 hours, although in most cases they last approximately 1–2 hours

What 5 part spectrum of cerebrovascular disorders is presented which is possibly considered as a representation of the stages of one continuous disease process?

• TIA: effects <24 hours.

• Reversible Ischaemic Neurologic Deficit (RIND): >24 hours but subsequently resolves.

• Partial, non-progressing stroke.

• Progressing stroke: also called stroke in evolution.

• Completed stroke: completely irreversible.

How important is stroke as a cause of death worldwide?

It is the second most common cause of mortality worldwide.

How important is stroke as a cause of disability, what is the global burden of stroke?

It is the third most common cause of disability, and the global burden of stroke-related disability is high.

What are the 2 unmodifiable risk factors for stroke?

• Age

• Family history

What are the 6 potentially modifiable risk factors?

• Hyperlipidaemia

• Hypertension

• Diabetes

• Obesity

• Smoking

• Heart disease and impaired cardiac function such as atrial fibrillation (AF), LVH and valvular disease

What 4 vessel-wall or blood-cell disorders are particularly considered in stroke patients younger than 50?

• Dissection

• Vasculitis

• Sickle cell anaemia

• Antiphospholipid syndrome

What 4 cardiac conditions are considered in stroke patients younger than 50?

• Congenital heart disease and its complications

• Valve prolapse

• Patent foramen ovale (PFO) causing paradoxical embolism

• Ventricular septal defect (VSD) causing paradoxical embolism

What medication-related risk factor is listed in patients younger than 50?

Oral contraceptives.

How can atrial fibrillation (AF) lead to stroke

AF → out-of-sync contraction of the atria → ventricles in escape rhythm → blood stasis → thrombus formation → thrombus embolises to the brain.

What is a thrombus?

In situ coagulation of blood components into a solid form.

What is an embolus?

Anything that travels through the blood system; it is usually a thrombus, but does not necessarily have to be one.

What term combines a thrombus and an embolus?

Thromboembolic disease.

What are the three components of Virchow’s triad?

1. Hypercoagulable state

2. Stasis of blood/lack of laminar flow

3. Endothelial injury in the vascular wall

What 3 examples of hypercoagulable states

• Factor V Leiden disease/clotting disorder

• Metastatic cancer states

• OCP use

Which component of Virchow’s triad explains thrombus formation in AF particularly well?

Stasis/loss of normal laminar blood flow

Name one likely artery of origin pathology for stroke

Internal carotid thrombosis.

What exposure/intervention can be carried out on the carotid artery to deal with carotid vascular disease?

Carotid endarterectomy

Name the two main types of stroke

1. Ischaemic

2. Haemorrhagic

What is the difference in the aetiology of ischaemic stroke vs a haemorrhagic stroke?

• Ischaemic- A stroke caused by an alteration or problem with blood flow.

• Haemorrhagic- A stroke caused by bleeding from a vessel/aneurysm within the brain.

Are ischaemic and haemorrhagic processes necessarily mutually exclusive?

No- an ischaemic infarct can undergo haemorrhagic transformation

What is ischaemic-to-haemorrhagic transformation?

After a period of ischaemia, changes in the brain blood vessels can cause breakdown of the vascular wall, resulting in haemorrhage

What proportion of cerebral infarcts are haemorrhagic versus non-haemorrhagic?

Approximately 20% haemorrhagic and 80% non-haemorrhagic.

How do cerebral infarcts often begin- haemorrhagic or non-haemorrhagic?

They are often initially non-haemorrhagic

How can secondary haemorrhage subsequently occur?

Through ischaemia-reperfusion injury.

Why is distinguishing haemorrhagic from non-haemorrhagic/ischaemic stroke crucial?

Because their treatment is completely different.

What determines the clinical manifestations of a stroke?

The anatomical region affected.

What ate the three classical stroke signs?

• Unilateral facial weakness/drooping

• Unilateral limb weakness

• Slurred speech

What does the FAST stand for?

Recognition of Face, Arms, Speech and Time: facial asymmetry, inability to maintain arm elevation, speech abnormality and the need to seek urgent help

How may a TIA be managed?

Conservatively.

What drug approach can be used for appropriate stroke patients? Give an example

Thrombolytics eg Alteplase

When must thrombolytics not be used?

In a haemorrhagic stroke- Whether the patient has an appropriate ischaemic stroke rather than a haemorrhage- hence the need for urgent imaging.

What should be done about an underlying cause such as AF?

Treat the underlying condition.

Can surgery have a role?

Yes. Surgical intervention can be performed in some rare cases of stroke in evolution.

What investigation is emphasised for differentiating stroke type?

CT of the head.

What two types of stroke are compared on the CT images?

If a CT scanner is booked for a routine assessment such as advanced/metastatic cancer while a suspected acute stroke requires imaging, who should be assessed?

Acute stroke assessment is time-critical- rapid door-to-needle time.

What is the target door-to-needle time?

<60 minutes.

• Hospital is pre-notified of an incoming stroke.

• Stroke team is activated by a single call.

• A rapid registration process is used.

• Patient is moved to the scanner on the EMS stretcher.

• Laboratory results are not required unless indicated, or point-of-care analysis can be used.

• Alteplase is administered in the scanner area.

What non-thrombotic embolus can cause an embolic ischaemic stroke?

A fat/bone marrow embolus.

When can fat emboli occur?

Following a (long) bone fracture.

Does ischaemia have to result from a focal embolus/thrombus leading into systemic hypoperfusion?

No.

What is systemic hypoperfusion in the brain equivalent to?

Diffuse ischaemic/hypoxic encephalopathy

What type of cerebral ischaemia does systemic hypoperfusion cause?

Global cerebral ischaemia.

Are the neurological signs usually focal in diffuse ischaemic/hypoxic encephalopathy (systemic hypoperfusion)?

No. They are diffuse, non-focal and bilateral.

What 3 situations can cause systemic cerebral hypoperfusion?

• Cardiac arrest

• Shock

• Severe hypotension

Which 3 neurons are especially sensitive to systemic hypoperfusion?

• Neurons of the pyramidal layer of the hippocampus

• Cerebellar Purkinje cells

• Pyramidal neurons of the cerebral cortex

What are watershed infarcts?

Infarcts usually occurring after hypotensive episodes at the border zones between arterial territories

What general pathological response is important after an ischaemic stroke?

Inflammation.

Does the body have an infinite number of ways of responding to injury/insult?

No- The body has only a limited number of ways of responding to injury/insult, and inflammation is a common response

What are the 5 classical manifestations of inflammation depicted by the “pillars”?

• Heat

• Pain

• Swelling

• Redness

• Loss of function

Are all classical signs of inflammation always apparent in the brain?

No

What occurs in the brain after injury?

Cerebral oedema.

What 2 macroscopic changes indicate cerebral oedema?

• Widened gyri

• Flattened sulci

What microscopic neuronal change is associated with early ischaemic injury?

Red dead neurons.

How quickly can neurons die following the ischaemic insult?

<24 hours.

What does the body attempt to do after the noxious cerebral insult?

It attempts to remove/take down the damaged area.

What 2 pathological processes/ 1 cell type are associated with the removal of damaged tissue?

• Neutrophils

• Gliosis

• Necrosis

What type of necrosis occurs in cerebral infarction?

Liquefactive necrosis.

What time period is given for these changes?

Approximately 24 hours to 2 weeks.

What does the body normally use to replace damaged tissue?

Scar tissue.

Can the brain replace damaged tissue with scar tissue as effectively as many other tissues?

No- it cannot do so effectively

What happens to the infarcted brain tissue over time?

It is remodelled, with macrophages removing debris over time.

Does a haemorrhagic stroke look different grossly from a non-haemorrhagic infarct?

Yes. The specimens show prominent blood/haemorrhagic discolouration within the brain tissue.

What are the 2 major causes of haemorrhagic stroke

• Hypertension, associated with dissection/rupture

• Vascular disease, including:

  • Vasculitis

  • Medial degeneration

  • Aneurysm rupture

Is the order tunica “adventitia, intima, media” correct from inner to outer?

No- Tunica intima, media, adventitious is correct

What are the four most important effects of hypertension on the brain?

1. Lacunar infarcts

2. Slit haemorrhages

3. Hypertensive encephalopathy

4. Intracerebral haemorrhage/haemorrhagic stroke

In what two locations are the lacunar infarcts illustrated?

In the caudate and putamen.

Which vessels are particularly affected by hypertension in lacunar disease?

Deep penetrating arteries and arterioles.

What 3 structures do these deep penetrating arteries and arterioles supply?

• Basal ganglia

• Hemispheric white matter

• Brainstem

What vascular change develops in the Deep penetrating arteries and arterioles with hypertension in lacunar disease?

Arteriolar sclerosis → They may become occluded → Single or multiple small cavitary infarcts called lacunes (lake-like spaces)

How do hypertensive slit haemorrhages evolve?

There is rupture of small-calibre penetrating vessels, producing small haemorrhages → They resolve and leave a slit-like cavity → A slit haemorrhage with surrounding brownish discolouration.

What is hypertensive encephalopathy?

A clinicopathological syndrome arising in the setting of malignant hypertension **a medical emergency

What neurological dysfunction occurs in hypertensive encephalopathy?

Diffuse cerebral dysfunction.

What 5 symptoms can occur in hypertensive encephalopathy?

• Headaches

• Confusion

• Vomiting

• Convulsions

• Progression to coma

Where does hypertensive intracerebral haemorrhage typically occur? 4

• Deep white matter

• Deep grey matter

• Brainstem

• Cerebellum

What hallmark feature is associated with hypertensive intracerebral haemorrhage?

Charcot–Bouchard microaneurysms

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