Stroke and Neurodegeneration

Question 1

What is stroke?

Answer 1

Acute onset of neurological deficits; lasting for more than 24 hours, due to a disturbance in blood supply to the brain.

Question 2

Why is stroke defined as an onset of neurological deficits that lasts more than 24 hours?

Answer 2

Less than 24 hours = TIA (precursor)

Question 3

What are the neurological symptoms of stroke?

Answer 3

• Aphasia (difficulty making speech/understanding it)
• Dysphasia (difficulty swallowing)
• Apraxia (control of speech)
• Hemiparesis; hemi = half = half paralysed (motor/sensory)
• Facial weakness
• Confusion, dizziness, vision impairments (nonspecific)
• Thunderclap headache; associated w/subarachnoid/intracerebral haemorrhage ‘worst headache ever’
• F.A.S.T.

Question 4

How prevalent is stroke?

Answer 4

• 15 million suffer strokes worldwide each year
• 5 million die (1/3)
• 5 million and permanently disabled (1/3; assistance needed for rest of life)
  »> LEADING cause of disability

Question 5

What are the non-modifiable risk factors for stroke?

Answer 5

• Age (#1); risk doubles every 10 years after 65 (Avg = 73)
• Race; Afro-Carribean risk
• Genetics
• Gender; pre-menopausal women less likely to have stroke due to estrogen’s protective properties, whilst post-menopausal women are equally likely

Question 6

What are the modifiable risk factors of stroke?

Answer 6

• Hypertension
• Smoking
• Diabetes
• High cholesterol
• Obesity
• Activity levels

Question 7

How is atherosclerosis implicated in stroke?

Answer 7

• Build-up of fatty deposits in arteries
• Results in harder, narrower, less elasticity
• Fatty plaques may break off; primary cause of blood clots

Question 8

What are the different types/subtypes of stroke?

Answer 8

Two different types: ischaemic or haemorrhagic:

Ischaemic (88%):
- Thrombotic (57%); Forms in situ (inside the brain) e.g. atherosclerosis
> Lacunar occlusion (26%); small infarcts 2-20mm, from the occlusion of a single small perforating artery supplying the subcortical areas of the brain
> Large vessel occlusion (31%); major cerebral arteries e.g. middle

• Embolic (31%); Clot/plaque formed from the body e.g. AF, DVT
  > Large vessel occlusion (31%); major cerebral arteries e.g. middle

OR

Haemorrhagic (12%); bleeding in the brain e.g. ruptured vessel, 40% mortality, build-up of blood increases intracranial pressure = pressure on stem etc.
> Intracerebral (7%, middle)
> Subarachnoid (5%, meninges)

Question 9

Describe the acronym, FAST.

Answer 9

Facial weakness
Arm weakness
Speech difficulty
Time to call 999

> Time is imperative

Question 10

How is blood supplied to the brain?

Answer 10

Two main pairs of arteries that supply the brain:

• Carotid arteries
• Vertebral arteries

Question 11

Describe the cerebral blood supply WRT the 4 major pairs of cerebral arteries and the anastomosis mechanism.

Answer 11

Diagram P.265
- Basilar arteries (brain stem), vertebral arteries merge together to basilar, supplies most of the brain
- Posterior cerebral arteries; supply hippocampus, medial occipital and inferior temporal lobes
- Middle cerebral arteries; supply lateral temporal and parietal lobes, and posterior frontal lobe (motor/sensory cortex = stroke symptoms, supplies loads of blood = strokes most likely to occur here)
- Anterior cerebral arteries; supply medial frontal and superior parietal lobe, corpus callosum
»> Circle of Willis; anastomosis (cross-connection) circuit around brain; can compensate for lack of blood flow. collateral circulation
> Carotid arteries join Circle of Willis between Anterior cerebral arteries and the MIddle cerebral arteries

Question 12

What are the Lenticulostriate arteries?

Answer 12

• Branched from the Middle cerebral arteries
• Feeds basal ganglia, internal capsule
• Prime spot for a lacunar occlusion; no collateral Circle of Willis to back it up

Question 13

What is the most common cause for a haemorrhage in the brain?

Answer 13

• Rupture of a saccular (berry) aneurysm
• Common at junctions of vessels (pressure differences )
  E.g. anterior, middle, internal, basilar

Question 14

How are brain aneurysms treated?

Answer 14

• Aneurism clipping

- Aneurism coiling; fill w/wire, prevents blood going in

Question 15

How is stroke diagnosed?

Answer 15

• ROSIER (RecOgnition of Stroke In the Emergency Room; acute classification)
• ABCD (Age, Blood pressure, Clinical features, Duration, Diabetes; risk of stroke after a TIA)
• Hunt and Hess (haemorrage)

Question 16

Where do CT scans fit in the diagnosis of stroke?

Answer 16

• CT (computed tomography) is used to rule out haemorrhage
  > 40-60% effective at detecting acute ischaemia otherwise
  > Ischaemic tissue becomes more dense (darker on CT) with time

Question 17

When is diffusion weighted imaging used in stroke diagnosis?

Answer 17

• MRI technique
• 95% effective at detecting acute ischaemic stroke
  »> More reliable for acute ischaemic stroke than CT (which only serves to rule out haemorrhagic stroke)

Question 18

What is the most common type of stroke?

Answer 18

• Middle cerebral artery territorial (hemiplegia; paralysis of one side of the body) infarction
• Lacunar infarctions are strategic and prevalent

Question 19

What is the concept of the penumbra?

Answer 19

A Hallmark of stroke:
- Represents potentially salvageable tissue (fate not decided)
- Cerebral blood flow thresholds define tissue death:
• Core infarct = <12 ml/100g/min (rapid tissue death)
• Penumbra = 12-22mL/100g/min (likely surrounding tissue will die, but needs time to do so; thus time is brain for stroke)
• Without rapid treatment, the Core (dead tissue) takes over Penumbra region too

Question 20

What is the only treatment for ischaemic stroke? What is the time window of its efficacy?

Answer 20

• Recombinant tissue plasminogen activator (rt-PA; Alteplase)
• Time window is 3 hours from symptom onset; showing a 30% improvement after 3 months
• Breaks up fibrinogen in clot
  »> Less than 10% of patients receive it (in time?)

Question 21

What is the time course of events in stroke?

Answer 21

• Excitotoxicity occurs; cells depolarising constantly (tissue death)
• Peri-infarct depolarisations from build-up of ions from excitotoxicity
• Inflammatory response
• Apoptosis

Question 22

What is the pathophysiological overview of stroke?

Answer 22

Ischaemia from stroke = energy failure = decreased blood flow/glucose delivery:

Excitotoxicity:

• Cell depolarisation results in Na+ and Ca2+ influx, K+ efflux
• Failure of ion pumps; excessive Na+/Ca2+
• Leads to Glu release and activation of NMDA and AMPA
• Voltage-gated NMDA permeable to Ca2+, Na+ and K+
• XS Glu and Ca2+ displace the Mg2+ ion, leading to further influx
• AMPA voltage-gated channel permeable to Ca2+, Na+ and K+
• Water influx from high Na+/Ca2+ etc.; cell swells (oedema)
• K+ efflux starts to stimulate neighbouring cells (Glu too); resulting in peri-infarct depolarisations
• Metabotropic Glu receptors (mGluR) G protein mediate Ca2+ release too

Inflammation:

• Inflammatory mediators released from cell recruit leukocytes, activate microglia, astrocytes
• BBB breakdown; disrupted tight junctions due to astroglia/leukocytes etc.
• Influx of leukocytes (neutrophils, lymphocytes, monocytes) from periphery

> > > Apoptosis.