Cerebrovascular Disease Basics Flashcards
What is stroke?
Focal disturbance of blood flow into or out of brain
- Ischaemic (87%)
- Haemorrhagic (13%)
What is transient ischaemic attack (TIA)
- Definition
- Timing and resolution (standard vs contemporary)
- Pathophysiology
Abrupt onset neurological deficit due to interruption of blood flow to portion of the brain, with subsequent resolution of symptoms within 24 hours
- Contemporary definition defines as lasting under 1 hour
- Mostly resolves within 5 to 15 minutes
Normal imaging following TIA DOES NOT rule out TIA
If infarct identified on brain imaging -> classified as stroke regardless of druation of symptoms
Pathophysiology
Cause: same as stroke, commonly emboli, in-situ thrombosis
Occluded blood vessel reopens and function restored
Why is prompt recognition of TIA important?
(Epidemiology of TIA)
TIA - possibility of completed stroke
- Appropriate intervention prevent stroke and permanent disability (loading and treatment with DAPT)
- 90-day stroke rates >10-15% (highest within 48 hours to 7 days)
- Longer symptoms duration and large cerebral artery stenosis associated with higher risk of stroke
In the United States:
- > 795,000 cases of stroke per year
- > 250,000 cases of TIA per year
Risk factors for stroke
Non-modifiable
- Age (2nd biggest predictor)
- Sex, race
Modifiable
- Prior stroke (biggest predictor)
- Diabetes
- Hypertension
- Hyperlipidaemia
- Smoking
- Cardiac disease - AF, valvular disease
- Homocysteinaemia
Etiologies of Ischaemic Stroke
(TOAST -> CISS)
- Large vessel disease - intracranial (ICAD) , extracranial (ECAD)
- Plaque rupture resulting in large in-situ thrombosis or artery-to-artery thromboembolism - Small vessel disease - arteriolosclerosis, lipohyalinosis
- Strong association with diabetes, hypertension - Cardioembolic
- Embolic stroke of undetermine source (ESUS)
What are the classical clinical feature of large vessel disease?
(uncorrelated to real life)
Large vessel disease
- Occurs early in the morning hours or on waking up
- History of prior TIAs in same vascular distribution
- Symptoms fluctuate
What are the classical clinical feature of small vessel disease?
(uncorrelated to real life)
Small vessel disease
- History of diabetes, hypertension
- Diameter < 1.5cm (subcortical / lacunar)
- Occurs in subcortical regions - basal ganglia, thalamus, brainstem
- Lacking in cortical findings (aphasia, neglect)
- Symptoms fluctuate dramatically
- May have TIA with similar symptoms
What are the classical clinical feature of cardioembolic disease?
(uncorrelated to real life)
Cardioembolic disease (20%)
- History or features of heart disease
- Stoke symptoms maximal at onset (clot preformed already)
- TIA differing symptoms and embolism to different distributions
(fragment and lysed quickly)
- Associated with Valsalva
- Strokes of different ages in different vascular territories
- With reperfusion following prolonged ischaemia, development of petechial haemorrhages in ischaemic territory
Sites of lodge: intracranial ICA, MCA, PCA or their branches, rarely ACA
What cardiac conditions are considered source of cardioembolic stroke?
- Atrial fibrillation or flutter
- Mechanical valves
- Septic emboli
- Marantic endocarditis (sterile vegetations)
- PFO with left-to-right shunt and venous clot
What are rarer/other causes (ESUS) of stroke?
- Dissection of cervical vessels -> neck/face pain, history of trauma
- Carotid injury -> Horner’s syndrome
- Illicit drug (cocaine, stimulant-induced spasms)
- Hypercoagulable state - cancer, genetic clotting disorder, autoimmune (lupus/ALPS)
What is haemorrhagic transformation?
(Haemorrhagic conversion)
- Occurs in large or severe degree of ischaemia
- Most likely in first days to a week post-stroke
- Look out for clinical worsening -> immediate re-evalation with CT brain
- Tissues downstream becomes ischaemic - brain and vasculature
- Blood flow returns via weakened, damaged vessels
- Vessel leak -> petechial haemorrhage, or burst into haematoma
Stroke activation
- Onset and duration, time-to-needle
- Symptoms and signs
- Blood glucose - hypo or hyperglycaemia
- ECG, troponin
- Coagulation profile, FBC, RP
- NIHSS - at least 4 to 24
- CT brain - ASPECT (>5 for EVT, >7 for rtPA), ruled out intracranial bleeding and tumour
- Assess indications and contraindications for thrombolysis
- Blood pressure control if SBP > 185 for thrombolysis
What are the contraindications to rTPA?
Absolute Contraindications
1. > 4.5 hours from time patient last seen normal (not valid anymore with Trace III trial)
2. Initial CT brain suggests time of onset inaccurate
3. Intracranial haemorrhage - SAH, ICH
4. Intracranial neoplasm or AVM
5. Active internal bleeding
6. Uncontrolled hypertension > 185/110mmHg despite antihypertensive
7. Current bacterial endocarditis
8. Head trauma, recent intracranial/intraspinal surgery within 3 months
9. Recent AMI within 3 months
10. Known coagulopathy - INR > 1.7, Plt < 100, elevated PTT
- DOAC within 24 hours (48 hours in CKD)
- Warfarin if reversible with vitamin K or PCC
- IV heparin within 48 hours with APTT > normal range
Relative Contraindications
1. Minor or rapidly resolving deficits
2. Seizure
3. Major surgery in previous 2 weeks
4. GI or urinary haemorrhage within 3 weeks
5. Puncture at non-compressible sites within 1 week (biospy, LP)
Pathophysiology of Ischaemic Stroke
- Acute occlusion of intracranial vessel and degree of cerebral occlusion resulting in brain tissue death
- Complete occlusion: tissue death within 4-10 mins
- <16-18mL/100g: within 1 hour
- > 20mL/100g: ischaemia without infarct unless prolonged for several hours to days - Infarction via 2 pathways:
A. Necrotic pathway - cellular cytoskeletal breakdown
B. Apoptotic pathway - programmed cell death - Rise in intracellular calcium
- Energy failure (starvation of glucose, oxygen resulting in failure of ATP production)
> Membrane ion pump dysfunction (lack of ATP) causes neurons depolarisation, increases intracellular calcium
- Glutamate release from synaptic terminals, excessive glutamate ->neurotoxic
> activation of postynaptic glutamate receptors further increases calcium influx - Free radials generation
- Degradation of membrane lipids and mitochondrial dysfunction
- Damages vital functions of cells, axons ,dentrites, glia - Additional insults
- Fever, hyperglycaemia - Formation of ischaemic penumbra
- Ischaemic but reversible dysfunctional tissue surroinding core area of infarct
> Progresses to infarct if no restoration of flow
(Goal of revascularisation therapy to reverse penumbra)
What are the complications of acute ischaemic stroke?
- Haemorrhagic transformation
- Alteplase-related orolingual oedema
- Cerebral oedema -> obtundation and herniation
- Cerebellar oedema -> hydrocephalus, brainstem compression
- Post-stroke depression
- Fatigue
- Aspiration pneumonia
- Bedridden complications - DVT, PE
Cerebral oedema occurs in 5-10% of stroke and may cause ___ and ___
- Dependent on ___ of infarct - __ and __
Oedema peaks on __-__ day, mass effect up to __ days
Herniation upward or downward through __ or __
Clinical features of herniation: (3)
Treatment with ___, __and ___ to raise serum osmolarity
Avoid ___ as it may worsen hypotension and infarct
Definitive treatment: __
Cerebral oedema occurs in 5-10% of stroke and may cause obtundation and cerebral herniation
- Dependent on size of infarct - large hemispheric infarct and cerebellar infarct
Oedema peaks on 2nd-3rd day, mass effect up to 10 days
Herniation upward or downward through tentorium or under falx cerebri
Clinical features of herniation: somnolence, pupils dilatation (CN3 compression), increased ICP (nausea, vomiting)
Treatment with fluid restriction, hyperventilation and IV mannitol to raise serum osmolarity
Avoid hypovolaemia as it may worsen hypotension and infarct
Definitive treatment: surgical decompression
- Dosing and administration of IV rtPA
- Management of hypertension during rtPA
- Management of hypotension during rtPA
IV rtPA alteplase 0.9mg/kg up to 90mg maximum
- 10% given as bolus over 30-60 seconds
- 90% infusion over 60 minutes
Keep BP below 185/110 prior to rtPA and at least 24 hours after rtPA initiation
- Every Q15 mins for 2 hours after therapy
- Every Q30 mins for next 6 hours
- Every Q1 H until 24 hours post-rtPA
If BP >180/105 or higher
- Increase vitals monitoring to Q5 mins
- Continue IV rtPA
- Choice of antihypertensives:
A. IV Labetalol 10mg over 1-2 minutes, repeatable or doubled every 10-20 minutes, up to total 150mg
(10-20-40-80)
B. IV GTN 2.5 up to 400 mcg/min
If BP >230/140
- Stop rtPA infusion, give IV antihypertensives
- Consider other agents if poor response
- Resume rtPA only if BP within acceptable limits
If SBP < 100
- Give fluid challenge IV NS 100-500mL fast bolus
- If no response, start IV dopamine at 5 mcg/kg/min, titrate upwards until BP > 120, do not start below 5
- Monitor for signs of major haemorrhage
- KIV 4-6 units FFP
What happens if NIHSS worsens by 4 or more points from baseline during rtPA
- Stop rtPA immediately if still infusing
- Send FBC, coagulation panel, fibrinogen, GXM, antibody screen
- Urgent CT brain
- In the event of ICB, consider 4-6 units FFP/platelet/cryo/EACA
National Institute of Neurological Disorders and Stroke (NINDS) Stroke Study
Regime: IV rTPA 0.9mg/kg max 90mg
Timing: within 3 hours of onset
Haemorrhage: 5.8% increased incidence
6.4% rtPA vs 0.6% placebo
Resolution: 12% absolute increase
44% rtPA vs 32% placebo
Mortality: 4% non-significance reduction
17% rtPA vs 21% placebo
–> Benefits and improved clinical outcomes outweighs risks if given within 3 hours of stroke onset
European Cooperative Acute Stroke Study III (ECASS III)
Timing: 0 - 4.5 hours
Exclusion: > 80 years old, diabetic patients with previous stroke
Haemorrhage: 2.2% increased incidence
2.4% rtPA vs 0.2% placebo
Resolution: 7.2% absolute increase (lower than NINDS)
52.4% rtPA vs 45.2% placebo
–> rtPA approved for 3-4.5H window in Europe and Canada, however only 0-3H in USA
Japan Trial on IV rtPA
Dosing: 0.6mg/kg
Rationality: Asian descent higher propensity to bleed
Observation of > 600 patients
- Similar outcomes to historical controls
- Lower rate of ICB
Tenecteplase trials
- Bolus trial
- TRACE III Chinese trial
Bolus Trial
Dosing: IV tenecteplase 0.25mg/kg bolus over 5 seconds
Not directly tested against IV rtPA
Benefits: Given bolus. No need for 1 hour infusion
- Improved efficiency of transfer to stroke centre
- Trials found tenecteplase prior to EVT to be safe
TRACE III trial
Treatment of ischaemic stroke onset 4.5 - 24 hours with tenecteplase 0.25mg/kg max 25mg
- Less disability and similar survival as compared with standard medical treatment
- Higher incidence of symptomatic intracranial hemorrhage
Alteplase induced anaphylaxis or peri-oral/orolingual angioedema
Features:
- Swelling of tongue/lips
- Airway tightening - wheeze/stridor/bronchospasm
- Dyspnoea
- Rash/urticaria
Management:
1. Stop rtPA immediately
2. ABC
3. Early activation of airway team
4. IV hydrocortisone 100-200mg STAT
5. IV diphenhydramine 10-50mg STAT
6. SC adrenaline 0.5-1mL (1:1000 dilution)
7. Salbutamol inhalers
Endovascular therapy (EVT) in large vesel occlusion
Large vessel: basilar artery, intracranial ICA, MCA
- Often large clot volume and fails to open with IV rtPA
Overall meta-analysis: odds ratio 2.49, CI 95%
Timing studies:
- Good outcomes under 6H from stroke with/without pre-treatment with IV rtPA
- OR > 3 within 2 hours; OR 2 if 8 hours elapse
- >80% EVT within 1 hour of arrival to ED had good outcome, 1/3 if 6 hours elapsed
Outcome studies:
- EVT discharge 2 months earlier than medical
- Recovery to mRS 0-2: 46% EVT vs 26.5% medical
- Mortality benefits
EVT beyond 6 hours - clinical trials
Imaging: CT or MR perfusion studies
- must demonstrate good vascular collaterals
- can be treated up to 24 hours
A. Clinical Mismatch in Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) trial
- 47% EVT vs 13% medical
B. Endovascular Therapy Following Imaging Evaluation for Ischaemia Stroke 3 (DEFUSE-3) Trial
- 45% EVT vs 17% medical up to 16 hours from onset
C. Non-randomised data for basilar occlusion
- Safe up to 24 hours
- Lower mRS score in 3 months
What is the appearance of bacterial endocarditis infarcts?
- Multifocal symptoms and signs
- Infarcts microscopic size
- May develop into brain abscess or cause haemorrhage
- Mycotic aneurysms -> SAH, ICH
North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST)
(Management of carotid stenosis with endarterectomy)
Symptomatic: retinal or hemispheric symptoms
- Symptomatic + 70% carotid stenosis: reduces recurrent stroke risk in 2 years by half (absolute benefit of 14%)
- Symptomatic + 50-69% carotid stenosis: only reduces 3 year recurrent stroke risk by 6%, with similar surgical risk
- Asymptomatic patient: little to no recurrent stroke risk reduction, with similar surgical risk
(Natural history of ~2% stroke rate per year) - Most beneficial when endarterectomy performed within 2 weeks of symptoms onset, men > women
What are the causes of stroke?
Risk of Paradoxical Embolism (RoPE) Score
- Evaluation of stroke-related PFO in patients with cryptogenic stroke
- No hypertension
- No diabetes
- No previous stroke or TIA
- Non-moker
- Cortical infarct on imaging
- Younger age higher risk
Score of 4 and above warrants PFO closure
