Lecture 24; Ischemic Brain Injury 1 Flashcards
What is Brian ischemia?
Loss of blood supply to the brain
No oxygen or glucose delivery
Focal or global (CV failure)
Can occur at any stage of life
What is the epidemiology of ischemic stroke in NZ?
3rd biggest killer -2500 people/ year
24 New Zealanders every day, a quarter < 65 years old
The leading cause of adult disability
Currently 60,000 stroke survivors in NZ, many with disability
What are the causes of ischemic stroke?
- Atherosclerosis –fatty deposits lining vessel walls –restrict blood flow and clots can break off
- Thrombus -blood clot develops in a vessel in brain
- Embolism -blood clot develops elsewhere, usually in the heart or large arteries of the chest -breaks off and blocks small artery in brain
- Atrial fibrillation -clots form in the atria, dislodge and travel to the brain
What is Neonatal arterial ischemic stroke observed?
symptoms observed after birth. MRI shows stroke occurred recently
However, is not normally diagnosed at the time until developmental stages are not met.
- Therefore less treatment options
Are there treatments for pediatric ischemic stroke?
- No treatment
- Respond well to rehab b/c brain is very plastic
What are causes 1-4 of PIS?
Congenital heart defects
sickle cell disease
immune disorders
diseases of the arteries
What are causes 5-9 of PIS?
blood clotting abnormalities head or neck trauma intrauterine infection premature rupture of membranes maternal hypertension
What feeds blood supply to the brain?
basilar or cerebral artery
What are the two boundries of a stroke affected tissue?
- Ischemic core (infarcted tissue)
- Ischemic Penumbra (salvageable)
How is the core and penumbra differentiated?
MRI –Use diffusion weighted imaging to calculate the apparent diffusion coefficient
What happens to an MRI after stroke?
In acute cerebral infarction, the decrease in ADC values is the result of:Water moving into the intracellular compartment (diffusion is impeded by organelles)
Cellular swelling narrowing the extracellular space
What is the penumbra?
Penumbra –reduced perfusion surrounding infarct
Suppressed protein synthesis, constrained ATP production (Injury progresses through the penumbra as ATP decreases)
Fundamentally reversible but time-limited
What does penumbra injury or recovery depend on?
Depends on reperfusion and/or collateral perfusion
What is collateral perfusion?
Other smaller arteries…
What are two major collateral perfusion structures?
Circle of Willis: redistribute blood supply during extracranialvascular occlusion between carotid and vertebral arteries
Heubner’sanastomoses: determines volume and severity of focal ischemia during constriction of artery distal to Circle of Willis. Individual variability –number and diameter determines collateral supply
What can be used to image the penumbra?
MRI Perfusion Weighted Imaging (PWI)
- Inject contrast (gadolinium)
- Measured parameters such as time to peak (TTP) or mean transit time (MTT)
- Measure of cerebral blood flow
- Reduced in penumbra and ischemic core
- PWI/DWI mismatch region approximately corresponds to the ischemic penumbra
Whats a clot buster drug and when must it be used by?
TPA
- Must be used to treat within 3-4hrs to clear clot and restore blood flow
depends on collateral circulation
Why is imaging important?
Ischemic vs haemorrhagic stroke
Clot busters (tPA)
Better response to clot busters when there is a large penumbra
Can administer TPA after 3 h if significant diffusion/perfusion mismatch
Infarcted tissue can’t be salvaged
Important for future therapies
What is normal CBF and when does it become supressed?
Adult CBF ~ 50-70 ml/100 g/min CBF
~8 -18 ml/100 g/min = threshold for ion pump failure
Brain activity is suppressed before threshold for ion failure
At what point of CBF does fuel production change to anaerobic?
Anaerobic glycolysis
Glucose utilisation increases at 0.35mL/g/min (switching to anaerobic increases utilisation)
Declines below 0.25 mL/g/min
Accumulation of lactate and acidosis
At what point CBF does Energy failure occur?
Energy Failure below 0.26 mL/g/min
When does anoxic depolarisation occur?
Anoxic depolarisation below 0.10 mL/g/min
What is anoxic depolarisation and how does it all fit in?
- Cells depolarise because of the lack of ATP to maintain membrane gradients.
- Tissues start to infarct at this point because cells swell and membranes become disrupted
- Release of neurotransmitters propagates this injury.
What is happening in the penumbra?
Peri-infarct spreading depression:
- Depolarisation initiated in infarct core
- Spreads to peripheral zone
- Increased metabolic rate due to activated ion exchange pumps
- Reduced haemodynamic capacity of penumbra -mismatch between blood supply and demand
- Transient hypoxia and lactate production
Describe the relationship between infarct size and depolarisations;
- Linear relationship between number of depolarisations and infarct volume
What happens in global cerebral ischemia?
The whole brain becomes ischemic May be the result of whole-body ischemia Can occur at any stage of life Perinatal asphyxia Cardiac arrest Severe hypotension (shock)
What is the common cause of global adult ischemia?
Most often:
Primary ischemia + secondary hypoxia
Cardiac Arrest: 1/1000/year (20-75 y); only 20% of patients survive, and most survivors are disabled;
Shock—-hypotension/hypoperfusion
Heart stops (arrests)
no cardiac output, hypotension
No blood flow to brain
AND no blood flow to lungs hypoxiaBrain ischemia + hypoxia
What are the causes of global ischemia in the fetus?
Knot in umbilical cord Compression of cord during labour Umbilical cord around the neck Maternal hypotension Placental insufficiency Cardiovascular collapse after birth
What is the evolution of the global ischemia damage?
Evolves slowly over time after focal or global ischaemia
No core and penumbra pattern
Therapeutic windows of opportunity for treatment
Therapeutic hypothermia for HIE
