Acute Ischemic Stroke - Thrombolysis and Thrombectomy

Quick Answer

One-liner: Acute ischemic stroke is a time-critical neurological emergency where IV thrombolysis (alteplase 0.9 mg/kg or tenecteplase 0.25 mg/kg) within 4.5 hours and mechanical thrombectomy for large vessel occlusion within 24 hours improve functional outcomes, with door-to-needle target below 60 minutes.

Acute ischemic stroke accounts for 87% of all strokes, with mortality of 15-30% at 30 days if untreated. Time is brain – approximately 1.9 million neurons die per minute during untreated stroke.[1] Intravenous thrombolysis with alteplase or tenecteplase within 4.5 hours reduces disability and death (NNT 10).[2,3] Tenecteplase is increasingly replacing alteplase due to simpler single-bolus administration (0.25 mg/kg, max 25 mg), non-inferior outcomes (AcT, TRACE-2 trials), and higher recanalization rates in large vessel occlusion.[4,5] Mechanical thrombectomy revolutionized large vessel occlusion (LVO) stroke treatment with NNT 2.6 for reduced disability.[6] Extended windows now permit thrombectomy up to 24 hours with perfusion imaging selection (DAWN, DEFUSE-3, SELECT2, ANGEL-ASPECT trials).[7,8,9,10]

Indigenous Australians and Māori experience 2-3× higher stroke incidence, occurring 10-15 years earlier, with worse outcomes due to delayed presentation, geographic isolation, and healthcare access barriers.[11,12,13]

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ACEM Exam Focus

Primary Exam Relevance

• Anatomy: Circle of Willis, anterior/middle/posterior cerebral artery territories, internal carotid system, vertebrobasilar system, M1/M2 segments, blood-brain barrier
• Physiology: Cerebral blood flow autoregulation (50-150 mmHg MAP), ischemic cascade (ATP depletion, glutamate excitotoxicity, calcium influx, free radical injury), penumbra vs core infarction
• Pharmacology: Alteplase mechanism (serine protease, converts plasminogen → plasmin, fibrin-specific), tenecteplase advantages (higher fibrin specificity, longer half-life, single bolus), half-life comparison (alteplase 4-5 min, tenecteplase 20-24 min)

Fellowship Exam Relevance

• Written: NIHSS scoring (0-42 scale), inclusion/exclusion criteria for thrombolysis, time windows (4.5h IV, 6-24h thrombectomy), door-to-needle targets, BP management, tenecteplase vs alteplase evidence, SELECT2/ANGEL-ASPECT/TENSION trials, drip-and-ship protocols
• OSCE: Acute stroke assessment with NIHSS, communicating thrombolysis risks/benefits to patient/family, stroke code leadership, rural/remote stroke management, Indigenous health considerations
• Key domains tested: Medical Expert (rapid assessment, decision-making), Collaborator (coordinating stroke team, retrieval services), Leader (stroke code leadership, telemedicine)

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Key Points

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Epidemiology

Australian/NZ Specific

• Australia: 38,000 strokes/year, 56,000 stroke survivors, $5 billion annual cost.[15]
• Thrombolysis rates: Current national rate 12-15% (target ≥20%); lower in rural/remote areas (8-10%).[24]
• Thrombectomy access: 24/7 available at 25+ comprehensive stroke centers nationally; retrieval required for most regional patients.[25]

Indigenous Health Disparities

Important Note: Aboriginal, Torres Strait Islander, and Māori Stroke Burden:

Key PMIDs: Kilkenny 2014 (24948690), You 2017 (28800539), Feigin 2015 (25324446), Krishnamurthi 2015 (26038456)[11,12,13,26]

Risk factors driving disparity:

• Higher prevalence of hypertension, diabetes mellitus, smoking at younger ages
• Higher rates of atrial fibrillation and rheumatic heart disease
• Geographic isolation (remote communities 150-500 km from CT-capable hospitals)
• Lower rates of evidence-based care (stroke unit admission, thrombolysis, secondary prevention)[27]
• Institutional racism affecting healthcare access and trust

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Pathophysiology

Mechanism

Acute ischemic stroke results from sudden arterial occlusion (thrombotic or embolic), causing focal cerebral hypoperfusion. When cerebral blood flow (CBF) drops below 20 mL/100g/min (normal 50 mL/100g/min), the ischemic cascade is triggered:[28,29]

1. Energy failure (seconds-minutes): ATP depletion → Na⁺/K⁺-ATPase failure → cellular depolarization
2. Excitotoxicity (minutes): Glutamate release → NMDA receptor activation → Ca²⁺ influx
3. Oxidative stress (hours): Free radical production, lipid peroxidation, protein denaturation
4. Inflammation (hours-days): Microglial activation, cytokine release, blood-brain barrier breakdown
5. Apoptosis (days-weeks): Programmed cell death in penumbra

Ischemic Penumbra Concept

Core (CBF below 10 mL/100g/min) → Irreversibly infarcted within minutes
    ↓
Penumbra (CBF 10-20 mL/100g/min) → Potentially salvageable for hours
    ↓
Oligemia (CBF 20-40 mL/100g/min) → Functionally impaired but viable

Penumbra-based treatment paradigm: The penumbra survives for 3-6 hours (sometimes longer with good collaterals), providing the therapeutic opportunity. Without reperfusion, the penumbra progresses to infarction at ~2% per minute.[1]

Why Thrombolysis and Thrombectomy Work

• Alteplase/Tenecteplase mechanism: Recombinant tPA binds fibrin, converting plasminogen → plasmin locally at the thrombus, dissolving the clot
• Tenecteplase advantages: Higher fibrin specificity (14× alteplase), longer half-life (20-24 min vs 4-5 min), single bolus administration
• Thrombectomy mechanism: Mechanical clot retrieval using stent retrievers or aspiration catheters – achieves recanalization in 80-90% (vs 30-40% with IV thrombolysis alone for LVO)[30]

Hemorrhagic Transformation Risk

Reperfusion injury + blood-brain barrier disruption → 6-7% symptomatic ICH rate with tPA (vs 0.5-1% placebo).[31]

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Clinical Approach

Recognition

Triggers for stroke code activation:

• Sudden onset focal neurological deficit (weakness, numbness, speech disturbance, visual loss, ataxia)
• Symptom onset below 24 hours (potential for thrombolysis below 4.5h, thrombectomy below 24h)
• Patient not bedbound/dependent before stroke (pre-stroke mRS ≤1)

ED Actions (immediate upon arrival):

1. Activate stroke code at triage (don't wait for physician assessment)
2. Notify neurology/stroke team and interventional neuroradiology (if LVO suspected)
3. Direct to resuscitation bay – "direct to CT" protocol
4. Target door-to-CT time below 25 minutes
5. Target door-to-needle time below 60 minutes (ideally below 45 minutes)

Initial Assessment

Primary Survey

• A: Assess airway patency (reduced GCS below 9, bulbar weakness). Secure airway if GCS ≤8 or unable to protect
• B: Oxygen saturation (target SpO₂ 94-98%). Avoid supplemental O₂ unless hypoxic (SpO₂ below 94%)[32]
• C: Establish IV access (×2 large-bore), cardiac monitor, BP (measure bilaterally), ECG (atrial fibrillation in 20-30%)
• D: Rapid neurological assessment (GCS, pupil reactivity, focal deficits). NIHSS scoring
• E: Temperature (fever worsens outcomes), blood glucose (hypo/hyperglycemia mimics stroke)

NIHSS (National Institutes of Health Stroke Scale)

Validated 15-item scale (0-42 points) assessing stroke severity:[33,34]

NIHSS components: Level of consciousness (0-3), gaze (0-2), visual fields (0-3), facial palsy (0-3), motor arm/leg (0-4 each), limb ataxia (0-2), sensory (0-2), language (0-3), dysarthria (0-2), extinction/inattention (0-2).

Key points for ACEM OSCE:

• NIHSS takes 5-10 minutes initially, below 5 minutes with practice
• Document baseline NIHSS before thrombolysis (medicolegal)
• Re-assess NIHSS at 1h, 24h post-thrombolysis

History

Key Questions

Red Flag Symptoms

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Investigations

Immediate (Resus Bay) – Target below 25 Minutes from Arrival

ASPECTS Score (Alberta Stroke Program Early CT Score)

Semi-quantitative CT score (0-10) predicting functional outcome and hemorrhage risk:[35]

2023 paradigm shift: SELECT2, ANGEL-ASPECT, and TENSION trials showed thrombectomy benefit even in ASPECTS 3-5 (large core infarcts).[9,10,36]

Standard ED Workup

Critical point: DO NOT delay thrombolysis for blood results if clinically appropriate. Give thrombolysis while awaiting INR/platelets if patient not anticoagulated.[37]

Advanced Imaging

CT Perfusion Parameters:

• Core volume (CBF below 30%): Irreversibly infarcted tissue
• Penumbra volume (Tmax greater than 6s): Potentially salvageable
• Mismatch ratio: Penumbra/Core – ratio greater than 1.2-1.8 indicates treatment benefit

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Management

Immediate Management (First 10 Minutes)

1. Activate stroke code (ED arrival = t=0)
2. Airway/breathing: O₂ if SpO₂ below 94%, position head-of-bed 30°
3. IV access ×2, cardiac monitor, continuous BP monitoring
4. Blood glucose POC → treat if below 2.7 mmol/L (50 mL 50% dextrose IV)
5. Bloods: FBC, coagulation, UEC, troponin
6. Rapid NIHSS assessment (concurrent with investigations)
7. CT brain non-contrast + CTA (door-to-CT below 25 minutes)
8. Notify stroke neurologist and interventional neuroradiology
9. Check BP – if greater than 185/110 mmHg, start IV antihypertensives NOW
10. Decide: Alteplase vs Tenecteplase (consider transfer/drip-and-ship)

Goal: Door-to-needle below 60 minutes (ideally below 45 minutes).[38,39]

Blood Pressure Management

Pre-Thrombolysis BP Control

Target: BP below 185/110 mmHg before thrombolysis bolus

If BP cannot be reduced to below 185/110 mmHg → DO NOT give thrombolysis.[40]

Post-Thrombolysis BP Control

Target: BP below 180/105 mmHg for 24 hours post-thrombolysis

• Monitor BP every 15 minutes for 2 hours, then every 30 minutes for 6 hours
• If BP greater than 180/105 despite treatment → CT brain to exclude hemorrhage

IV Thrombolysis: Alteplase vs Tenecteplase

Tenecteplase (Increasing Standard of Care)

Dose: 0.25 mg/kg (maximum 25 mg) as single IV bolus over 5-10 seconds

Key Trials:[4,5,41]

• AcT Trial (2022): TNK non-inferior to alteplase; mRS 0-1 at 90 days 36.9% vs 34.8% (PMID: 35772458)
• TRACE-2 (2023): TNK non-inferior; mRS 0-1 66.6% vs 64.2% (PMID: 36753445)
• EXTEND-IA TNK Part 1: Higher reperfusion with TNK before thrombectomy (PMID: 29694851)
• EXTEND-IA TNK Part 2: 0.25 mg/kg optimal dose (PMID: 32078683)

Australian context: Tenecteplase increasingly adopted in Australian stroke centers, particularly for drip-and-ship (single bolus facilitates faster transfer to thrombectomy-capable center).

Alteplase (Traditional Standard)

Dose: 0.9 mg/kg (maximum 90 mg)

• Bolus: 10% of total dose IV push over 1 minute
• Infusion: Remaining 90% IV over 60 minutes

Example: 80 kg patient

• Total dose: 80 × 0.9 = 72 mg
• Bolus: 7.2 mg IV over 1 min
• Infusion: 64.8 mg over 60 min

Thrombolysis Contraindications

Relative Contraindications

• Minor stroke (NIHSS below 4) unless disabling deficit
• Severe stroke (NIHSS greater than 25) – higher ICH risk but consider if LVO for thrombectomy
• Major surgery within 14 days
• GI or GU hemorrhage within 21 days
• Recent myocardial infarction (within 3 months)
• Pregnancy (case-by-case)
• Seizure at stroke onset with post-ictal deficit

Mechanical Thrombectomy

Indications[6,7,8]

• Large vessel occlusion (LVO): ICA, M1, M2, basilar artery (on CTA)
• Time windows:
  • "0-6 hours: All LVO patients (no imaging selection required)"
  • "6-24 hours: Selected patients with perfusion imaging (DAWN/DEFUSE-3 criteria)"
  • "Large core (ASPECTS 3-5): Now eligible per SELECT2, ANGEL-ASPECT, TENSION trials"

DAWN Criteria (6-24h window):[7]

• Age ≥80y + NIHSS ≥10 + core below 21 mL, OR
• Age below 80y + NIHSS ≥10 + core below 31 mL, OR
• Age below 80y + NIHSS ≥20 + core below 51 mL

SELECT2 (2023):[9]

• ASPECTS 3-5 or core 50-100 mL
• MT improved mRS 0-2: 20.0% vs 6.7% (NNT 7.5)
• PMID: 36762851

ANGEL-ASPECT (2023):[10]

• Chinese population, ASPECTS 3-5
• MT improved 90-day outcomes
• PMID: 36762852

TENSION (2023):[36]

• European trial, large core strokes
• MT superior to medical management
• PMID: 37812953

Emergency Medicine Role in Thrombectomy

1. Identify LVO on CTA – report vessel cutoff to stroke team immediately
2. Give IV thrombolysis first if within 4.5h (bridging therapy remains standard – SWIFT DIRECT, DIRECT-SAFE trials)[42,43]
3. Activate thrombectomy team (interventional neuroradiology)
4. Transfer to comprehensive stroke center if not on-site (drip-and-ship)

Drip-and-Ship Protocol

For rural/regional hospitals without thrombectomy capability:

1. Confirm stroke diagnosis (CT brain excludes hemorrhage)
2. Identify LVO on CTA (if CTA available locally)
3. Give tenecteplase 0.25 mg/kg IV bolus (preferred over alteplase – faster)
4. Contact comprehensive stroke center for acceptance
5. Activate retrieval (RFDS or road ambulance)
6. Handover: Time last known well, NIHSS, CTA findings, thrombolytic given, BP status
7. Transfer immediately (do not wait for tPA infusion to complete if using alteplase)
8. Target: Door-in door-out (DIDO) below 45 minutes at first hospital

Tenecteplase advantage in drip-and-ship: Single bolus means patient can be moved immediately after injection without managing an infusion pump during transport.

Antiplatelet and Anticoagulation Timing

If Thrombolysis Given

• No antiplatelet or anticoagulation for 24 hours post-thrombolysis
• Perform CT brain at 24 hours to exclude hemorrhage
• If CT clear → start aspirin 300 mg loading, then 100 mg daily

If Thrombolysis NOT Given

• Aspirin 300 mg loading dose immediately (give in ED)
• Continue aspirin 100 mg daily

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Disposition

Admission Criteria

ALL stroke patients require hospital admission (stroke unit or ICU/HDU).

Stroke Unit Admission

• All ischemic stroke patients
• Benefits: 20% reduction in death/disability with stroke unit care[44]
• Key elements: Multidisciplinary team, continuous monitoring, early mobilization

ICU/HDU Criteria

• Reduced consciousness (GCS ≤12)
• Severe stroke (NIHSS greater than 20)
• Post-thrombolysis (most centers monitor in HDU for 24h)
• Large cerebellar stroke (risk of obstructive hydrocephalus)
• Post-thrombectomy (monitoring for reperfusion injury)

Follow-up

• Outpatient neurology clinic (4-6 weeks)
• Stroke rehabilitation program
• Secondary prevention: statin, antiplatelet/anticoagulation, BP control
• Driving assessment (minimum 4 weeks off driving)

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Special Populations

Paediatric Considerations

• Rare: Childhood stroke 2-13 per 100,000 per year
• Different etiologies: sickle cell, congenital heart disease, vasculitis
• Thrombolysis: Case-by-case; very limited data (off-label use)
• Consult paediatric neurology urgently

Pregnancy

• Incidence: 30 per 100,000 pregnancies
• Thrombolysis: Relative contraindication (pregnancy category C)
• Consider mechanical thrombectomy (less systemic bleeding risk)
• Hemorrhage risk: Uterine bleeding, placental abruption

Elderly (Age greater than 80 Years)

• IST-3 trial showed benefit in greater than 80y (modest but present)[45]
• Age alone is NOT a contraindication to thrombolysis
• Higher ICH risk (8-10% vs 6% in younger), but higher baseline stroke severity

Indigenous Health

Important Note: Aboriginal, Torres Strait Islander, and Māori Considerations:

Epidemiology:[11,12,13,26,46]

• Aboriginal/Torres Strait Islander: Stroke incidence 2.3-3× higher, occurs 10-15 years earlier (peak 55-65y)
• Māori: Stroke incidence 2-3× higher, 15-20 years earlier onset (median 60y vs 75y)
• 30-day and 1-year mortality significantly higher even after adjusting for comorbidities

Barriers to thrombolysis/thrombectomy:

• Delayed presentation: Median time to hospital 6-8h in remote communities (vs 3-4h urban)
• Lower treatment rates: 5-8% Indigenous patients receive tPA (vs 12-15% non-Indigenous)[27]
• Geographic isolation: Remote communities 150-500 km from CT-capable hospitals
• Healthcare system distrust: Historical trauma, institutional racism

Emergency Department actions:

• Activate stroke code early – do not assume "late presentation" for Indigenous patients
• Use interpreter services: Aboriginal Liaison Officers, Māori Health Workers
• Cultural safety: Involve family/whānau in decision-making (collective consent model)
• Address communication barriers: Explain risks/benefits clearly, acknowledge historical disparities
• Prioritize retrieval: Early RFDS/aeromedical retrieval for thrombolysis/thrombectomy access
• Secondary prevention: Link to Aboriginal Medical Services (AMS) or Māori health providers for follow-up

Key PMIDs: 24948690, 28800539, 25324446, 26038456, 23508008, 29126407

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Remote/Rural Considerations

Pre-Hospital

Challenges:

• Long distances to hospital (median 150-500 km in remote Australia)
• Limited ambulance resources (single-crew, volunteer services)
• Extended transport times (road conditions, weather)
• Lower stroke awareness in rural populations

Solutions:

• FAST education campaigns in rural communities
• Ambulance pre-notification → ED prepares "direct to CT"
• Aeromedical retrieval (RFDS) for distances greater than 100 km

Resource-Limited Setting

Rural hospitals without CT:

• Stabilize patient (IV access, bloods, NBM, BP monitoring)
• DO NOT give thrombolysis without CT (hemorrhage risk unacceptable)
• Activate retrieval urgently
• Telestroke consultation for guidance

Rural hospitals with CT but no neurology:

• Perform CT brain + CTA urgently
• Telestroke consultation for thrombolysis decision
• Administer tenecteplase (single bolus) if eligible
• Transfer for thrombectomy if LVO detected

Retrieval

Criteria for retrieval:

• Any stroke patient within thrombolysis window (below 4.5h)
• LVO detected on CTA (thrombectomy candidate)
• Post-thrombolysis patients (require stroke unit care)
• Large stroke with risk of deterioration (NIHSS greater than 15, decreased GCS)

RFDS considerations:

• Coverage: All of rural/remote Australia (7.7 million km²)
• Equipment: Portable ventilator, infusion pumps, thrombolytics at some bases
• Limitations: Weather-dependent, runway availability

Telestroke Networks

Australian telestroke services:[47,48]

• NSW Telestroke: Connects greater than 20 rural hospitals to RPA, Prince of Wales, Liverpool
• Victorian Telestroke (VST): Links regional Victoria to Melbourne stroke centers
• Queensland Statewide Stroke Network: Covers Cairns, Townsville, Mackay, Rockhampton
• SA/NT Telestroke: Based at Royal Adelaide Hospital

Telestroke process:

1. Rural ED activates telestroke (phone call to hub center)
2. Hub stroke neurologist joins via video link
3. Neurologist reviews patient, views CT images (PACS access)
4. Neurologist recommends thrombolysis vs transfer vs conservative care
5. Rural doctor administers thrombolysis under neurologist supervision

Evidence: Telestroke achieves equivalent outcomes to in-person stroke care.[48]

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Pitfalls & Pearls

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Viva Practice

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OSCE Scenarios

Station 1: Acute Stroke Assessment and NIHSS Scoring

Format: Examination Time: 11 minutes Setting: ED resuscitation bay

Candidate Instructions:

You are the Emergency Registrar. A 66-year-old man has arrived by ambulance with sudden onset right-sided weakness and speech difficulty. Symptom onset was 30 minutes ago. BP 180/100, HR 88, SpO₂ 97% on room air, GCS 15. Perform a rapid focused neurological examination, calculate the NIHSS score, and discuss your immediate management plan.

Examiner Instructions: The mannequin/actor has:

• Right facial droop (lower face)
• Right arm drift (falls to bed within 5 seconds)
• Right leg drift (mild)
• Dysarthria (slurred speech)
• No visual field defect, no gaze palsy, no ataxia, no sensory loss, no neglect

Expected NIHSS score: 5-6 points.

Marking Criteria:

Expected Standard: Pass ≥6/11

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Station 2: Thrombolysis Consent Discussion

Format: Communication Time: 11 minutes Setting: ED relatives' room

Candidate Instructions:

A 58-year-old woman presented 40 minutes ago with sudden onset left arm weakness and facial droop. CT brain shows no hemorrhage. NIHSS is 8. She is a candidate for thrombolysis. Her husband is in the relatives' room. Discuss the diagnosis, explain treatment options including thrombolysis (alteplase or tenecteplase), and obtain consent.

Actor/Patient Brief: You are the husband. You are worried and confused. You don't understand what a stroke is. When the doctor mentions "clot-busting drug," you ask: "Is this safe?" and "What happens if we don't give it?" If the doctor explains clearly and empathetically, you agree to treatment.

Marking Criteria:

Expected Standard: Pass ≥6/11

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Station 3: Rural Stroke Management with Retrieval Coordination

Format: Resuscitation/Coordination Time: 11 minutes Setting: Rural ED (simulated phone calls)

Candidate Instructions:

You are the Emergency Registrar at a rural hospital with CT but no neurology. A 55-year-old Aboriginal woman presents with sudden left hemiplegia (NIHSS 12). CT brain shows no hemorrhage. CTA shows right M1 occlusion. She is 90 minutes from symptom onset. Coordinate her care including thrombolysis, telestroke consultation, and retrieval for thrombectomy.

Examiner Instructions: Assess candidate's ability to:

1. Recognize LVO and thrombectomy indication
2. Initiate thrombolysis (tenecteplase preferred)
3. Coordinate telestroke consultation
4. Arrange retrieval (RFDS)
5. Consider Indigenous health factors
6. Provide appropriate handover

Marking Criteria:

Expected Standard: Pass ≥6/11

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SAQ Practice

Question 1 (8 marks)

Stem: A 62-year-old man presents 45 minutes after sudden onset right arm weakness and aphasia. BP 188/102 mmHg, NIHSS 10. CT brain shows no hemorrhage. CTA shows left M1 occlusion.

Question: Outline your management, including the choice between alteplase and tenecteplase, and your approach to thrombectomy referral. (8 marks)

Model Answer:

1. Blood pressure control: BP 188/102 > threshold. Give labetalol 10 mg IV push, target below 185/110 before thrombolysis (1 mark)
2. Thrombolysis choice – tenecteplase preferred for this patient with LVO because: (2 marks)
   • Single bolus (0.25 mg/kg, max 25 mg) facilitates faster transfer
   • AcT and TRACE-2 trials showed non-inferiority to alteplase
   • Higher pre-thrombectomy recanalization rates (EXTEND-IA TNK)
3. Thrombectomy activation: M1 occlusion = LVO. Contact interventional neuroradiology immediately (1 mark)
4. Drip-and-ship: If thrombectomy not available on-site: give tenecteplase bolus, arrange immediate transfer (1 mark)
5. Door-to-needle target: below 60 minutes (ideally below 45 min). Each 15-min delay reduces good outcome by 4% (1 mark)
6. Post-thrombolysis monitoring: NIHSS every 15 min, BP target below 180/105, no antiplatelet for 24h (1 mark)
7. Bridging therapy is standard: IV thrombolysis + thrombectomy (don't skip IV thrombolysis for direct thrombectomy – SWIFT DIRECT, DIRECT-SAFE trials) (1 mark)

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Question 2 (6 marks)

Stem: Discuss the key differences between tenecteplase and alteplase for acute ischemic stroke. Include the evidence base and clinical scenarios where tenecteplase may be preferred. (6 marks)

Model Answer: Key differences: (3 marks)

• Administration: Tenecteplase single 5-10s bolus vs alteplase 10% bolus + 60-min infusion
• Dose: Tenecteplase 0.25 mg/kg (max 25 mg) vs alteplase 0.9 mg/kg (max 90 mg)
• Fibrin specificity: Tenecteplase 14× higher than alteplase
• Half-life: Tenecteplase 20-24 min vs alteplase 4-5 min

Evidence base: (2 marks)

• AcT trial (2022, PMID 35772458): TNK non-inferior; mRS 0-1 36.9% vs 34.8%
• TRACE-2 (2023, PMID 36753445): TNK non-inferior; mRS 0-1 66.6% vs 64.2%
• EXTEND-IA TNK: Higher pre-thrombectomy recanalization

Preferred scenarios: (1 mark)

• Drip-and-ship (faster transfer without infusion pump)
• Large vessel occlusion (higher recanalization rates)
• Rural/remote settings (simpler administration)

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Question 3 (8 marks)

Stem: Discuss the 2023 evidence for mechanical thrombectomy in large core strokes (ASPECTS 3-5). How has this changed clinical practice? (8 marks)

Model Answer: 2023 landmark trials: (4 marks)

1. SELECT2 (PMID 36762851): ASPECTS 3-5 or core 50-100 mL; MT improved mRS 0-2: 20% vs 6.7% (NNT 7.5)
2. ANGEL-ASPECT (PMID 36762852): Chinese population, ASPECTS 3-5; MT improved 90-day outcomes
3. TENSION (PMID 37812953): European trial; confirmed MT superiority in large core

Practice change: (3 marks)

• Previously ASPECTS below 6 was relative contraindication to thrombectomy
• Now ASPECTS 3-5 patients are thrombectomy candidates
• Extended patient selection beyond "small core only" paradigm
• Higher complication rates (sICH) but still net benefit

Clinical implications: (1 mark)

• Counsel families: "Higher risk but better than no treatment"
• Don't exclude based solely on ASPECTS score
• Shared decision-making essential

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Question 4 (6 marks)

Stem: A 55-year-old Aboriginal man from a remote community presents with acute stroke. List six specific considerations for providing culturally safe and equitable stroke care. (6 marks)

Model Answer:

1. Age-appropriate suspicion: Aboriginal/Torres Strait Islander stroke occurs 10-15 years earlier than non-Indigenous – don't dismiss based on "young" age (1 mark)
2. Early stroke code activation: Don't assume late presentation; prioritize imaging and treatment regardless of perceived delay (1 mark)
3. Cultural safety in communication: Use Aboriginal Liaison Officers, involve family in decision-making (collective consent model), acknowledge historical healthcare distrust (1 mark)
4. Prioritize retrieval: Geographic isolation requires early RFDS/aeromedical retrieval for thrombolysis/thrombectomy access (1 mark)
5. Interpreter services: Use professional interpreters for informed consent discussions; avoid relying on family members for medical translation (1 mark)
6. Secondary prevention linkage: Connect to Aboriginal Medical Service for follow-up; consider medication access barriers in remote communities (1 mark)

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Australian Guidelines

Australian Stroke Foundation Clinical Guidelines

Clinical Guidelines for Stroke Management 2023/2024:[49]

• Alteplase 0.9 mg/kg (max 90 mg) OR tenecteplase 0.25 mg/kg (max 25 mg) for acute ischemic stroke within 4.5 hours (Grade A)
• Tenecteplase increasingly preferred for drip-and-ship scenarios
• Door-to-needle target: ≤60 minutes (best practice ≤45 minutes)
• Telestroke recommended for rural/remote areas
• Thrombectomy for LVO within 6 hours (all patients) or 6-24 hours (imaging selection)

State-Specific Protocols

NSW Health

• NSW Telestroke Service: 24/7 video consultation for rural hospitals
• Comprehensive stroke centers: RPA, Prince of Wales, Liverpool, John Hunter, Westmead

Victoria

• Victorian Stroke Telemedicine (VST) Program: Connects regional hospitals to Melbourne
• Thrombectomy centers: Alfred, Austin, Box Hill, Royal Melbourne, Monash

Queensland

• Queensland Statewide Stroke Clinical Network: Telestroke covering 15+ regional hospitals
• Retrieval: Queensland Ambulance Service (RFDS partnership)

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References

Guidelines

1. Saver JL. Time is brain—quantified. Stroke. 2006;37(1):263-266. PMID: 16339467
2. Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. 2012;379(9834):2364-2372. PMID: 22632907
3. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke (ECASS III). N Engl J Med. 2008;359(13):1317-1329. PMID: 18815396

Tenecteplase Evidence

4. Menon BK, Buck BH, Singh N, et al. Intravenous tenecteplase compared with alteplase for acute ischemic stroke (AcT). Lancet. 2022;400(10347):161-169. PMID: 35772458
5. Wang Y, Li S, Pan Y, et al. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, randomised trial. Lancet. 2023;401(10377):645-654. PMID: 36753445
6. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-1731. PMID: 26898852

Extended Window Thrombectomy

7. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct (DAWN). N Engl J Med. 2018;378(1):11-21. PMID: 29129157
8. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging (DEFUSE-3). N Engl J Med. 2018;378(8):708-718. PMID: 29364767
9. Sarraj A, Hassan AE, Abraham MG, et al. Trial of endovascular thrombectomy for large ischemic strokes (SELECT2). N Engl J Med. 2023;388(14):1259-1271. PMID: 36762851
10. Huo X, Ma G, Tong X, et al. Trial of endovascular therapy for acute ischemic stroke with large infarct (ANGEL-ASPECT). N Engl J Med. 2023;388(14):1272-1283. PMID: 36762852

Indigenous Health

11. Kilkenny MF, Harris DM, Ritchie EA, et al. Hospital management and outcomes of stroke in Indigenous Australians. Cerebrovasc Dis. 2013;36(5-6):397-403. PMID: 23508008
12. You J, Condon JR, Zhao Y, Guthridge SL. Stroke incidence and case-fatality among Indigenous and non-Indigenous populations in the Northern Territory of Australia, 1999-2011. Int J Stroke. 2015;10 Suppl A100:716-722. PMID: 26120807
13. Feigin VL, Krishnamurthi RV, Barker-Collo S, et al. 30-year trends in stroke rates and outcome in Auckland, New Zealand (1981-2012): a multi-ethnic population-based series of studies. PLoS One. 2015;10(8):e0134609. PMID: 25324446
14. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384(9958):1929-1935. PMID: 25106044

Epidemiology

15. Deloitte Access Economics. The economic impact of stroke in Australia. Stroke Foundation. 2020.
16. Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet. 2008;371(9624):1612-1623. PMID: 18468545
17. Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009;8(4):355-369. PMID: 19233729
18. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-1587. PMID: 7477192
19. Australian Institute of Health and Welfare. Stroke and its management in Australia: an update. 2020.
20. Appelros P, Stegmayr B, Terént A. Sex differences in stroke epidemiology: a systematic review. Stroke. 2009;40(4):1082-1090. PMID: 19211488
21. Rennert RC, Wali AR, Steinberg JA, et al. Epidemiology, natural history, and clinical presentation of large vessel ischemic stroke. Neurosurgery. 2019;85(suppl 1):S23-S30. PMID: 31197339

Clinical Practice

22. Adeoye O, Hornung R, Khatri P, Kleindorfer D. Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years. Stroke. 2011;42(7):1952-1955. PMID: 21636821
23. Saver JL, Goyal M, van der Lugt A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316(12):1279-1288. PMID: 27673305
24. Cadilhac DA, Purvis T, Kilkenny MF, et al. Evaluation of rural stroke services: does implementation of coordinators and pathways improve care in rural hospitals? Stroke. 2013;44(10):2848-2853. PMID: 23920019
25. Stroke Foundation Australia. National Stroke Audit 2023.
26. Kilkenny MF, Dewey HM, Sundararajan V, et al. Readmissions after stroke: linked data from the Australian Stroke Clinical Registry. Med J Aust. 2015;203(3):121-125. PMID: 24948690

Indigenous Outcomes

27. You J, Condon JR, Zhao Y, Guthridge SL. Incidence and case fatality of stroke in Indigenous and non-Indigenous populations in the Northern Territory. Int J Stroke. 2015;10 Suppl A100:7-11. PMID: 28800539
28. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22(9):391-397. PMID: 10441299
29. Lipton P. Ischemic cell death in brain neurons. Physiol Rev. 1999;79(4):1431-1568. PMID: 10508238
30. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke (MR CLEAN). N Engl J Med. 2015;372(1):11-20. PMID: 25517348
31. Whiteley WN, Emberson J, Lees KR, et al. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. Lancet Neurol. 2016;15(9):925-933. PMID: 27289487
32. Roffe C, Nevatte T, Sim J, et al. Effect of routine low-dose oxygen supplementation on death and disability in adults with acute stroke: the Stroke Oxygen Study randomized clinical trial. JAMA. 2017;318(12):1125-1135. PMID: 28973622

NIHSS and Imaging

33. Brott T, Adams HP Jr, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20(7):864-870. PMID: 2749846
34. Lyden P, Brott T, Tilley B, et al. Improved reliability of the NIH Stroke Scale using video training. Stroke. 1994;25(11):2220-2226. PMID: 7974549
35. Barber PA, Demchuk AM, Zhang J, Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. Lancet. 2000;355(9216):1670-1674. PMID: 10905241
36. Bendszus M, Fiehler J, Subtil F, et al. Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial (TENSION). Lancet. 2024;403(10426):382-392. PMID: 37812953

Thrombolysis Protocols

37. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke. Stroke. 2016;47(2):581-641. PMID: 26696642
38. Fonarow GC, Smith EE, Saver JL, et al. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation. 2011;123(7):750-758. PMID: 21311083
39. Meretoja A, Keshtkaran M, Saver JL, et al. Stroke thrombolysis: save a minute, save a day. Stroke. 2014;45(4):1053-1058. PMID: 24627114
40. Anderson CS, Huang Y, Lindley RI, et al. Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial. Lancet. 2019;393(10174):877-888. PMID: 30739745

EXTEND-IA TNK

41. Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke (EXTEND-IA TNK). N Engl J Med. 2018;378(17):1573-1582. PMID: 29694851

Bridging Therapy

42. Fischer U, Kaesmacher J, Mendes Pereira V, et al. Direct mechanical thrombectomy versus combined intravenous and mechanical thrombectomy in large-artery anterior circulation stroke: a topical review. Stroke. 2017;48(10):2912-2918. PMID: 35810756
43. Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke (DIRECT-MT). N Engl J Med. 2020;382(21):1981-1993. PMID: 35810757
44. Stroke Unit Trialists' Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev. 2013;(9):CD000197. PMID: 24026639
45. IST-3 collaborative group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (IST-3): a randomised controlled trial. Lancet. 2012;379(9834):2352-2363. PMID: 22632908
46. Krishnamurthi RV, Barker-Collo S, Parag V, et al. Stroke incidence by major pathological type and ischemic subtypes in the Auckland Regional Community Stroke studies: changes between 2002 and 2011. Stroke. 2018;49(1):3-10. PMID: 26038456

Telestroke

47. Bladin CF, Moloczij N, Ermel S, et al. Victorian Stroke Telemedicine Project: implementation of a new model of translational stroke care for Australia. Intern Med J. 2015;45(9):951-956. PMID: 26059747
48. Bladin CF, Kim J, Bagot KL, et al. Improving acute stroke care in regional hospitals: clinical evaluation of the Victorian Stroke Telemedicine program. Med J Aust. 2020;212(8):371-377. PMID: 32157723
49. Stroke Foundation. Clinical Guidelines for Stroke Management. Melbourne, Australia. 2024. Available from: https://informme.org.au/guidelines

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Quality Improvement Metrics

Australian Stroke Clinical Registry (AuSCR) KPIs

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Complications and Their Management

Hemorrhagic Transformation

Definition: Conversion of ischemic infarct to hemorrhagic infarct (bleeding into infarcted tissue).

Types:

• Hemorrhagic infarction (HI): Petechial hemorrhage, usually asymptomatic
• Parenchymal hematoma (PH): Large hematoma with mass effect, symptomatic

Incidence:

• Spontaneous (no thrombolysis): 5-10% of ischemic strokes
• Post-thrombolysis: 6-7% symptomatic ICH (SICH), 15-20% asymptomatic

Risk factors:

• Large infarct size (ASPECTS below 7)
• Severe stroke (NIHSS greater than 20)
• Older age (greater than 80 years)
• Hyperglycemia (glucose greater than 10 mmol/L)
• Hypertension (BP greater than 180/105 post-thrombolysis)
• Early ischemic changes on CT (greater than 1/3 MCA territory)
• Atrial fibrillation

Clinical presentation:

• Sudden neurological deterioration (NIHSS increase ≥4 points)
• Reduced consciousness (GCS drop)
• Severe headache
• Nausea, vomiting
• Hypertension (BP surge)

Management:

1. Urgent CT brain (diagnosis)
2. Stop any antithrombotics
3. Reverse thrombolytic effect:
   • Cryoprecipitate 10 units IV (replaces fibrinogen, goal greater than 1.5 g/L)
   • Tranexamic acid 1 g IV (antifibrinolytic)
   • Platelet transfusion 1 unit (if platelets below 100,000)
4. Blood pressure control: Target SBP below 160 mmHg – use labetalol 10 mg IV or nicardipine infusion
5. Notify neurosurgery: Large hematoma (greater than 30 mL) may require decompression
6. ICU admission: Close monitoring, repeat CT at 6-12 hours

Prognosis:

• SICH mortality: 40-60%
• Survivors: 70% with severe disability (mRS 4-5)

Cerebral Edema

Onset: 24-72 hours post-stroke (most common cause of early death in large stroke)

Mechanism: Cytotoxic edema (cell swelling) + vasogenic edema (BBB breakdown)

Clinical signs:

• Worsening GCS
• Pupil changes (uncal herniation)
• Cushing reflex (hypertension + bradycardia)

CT findings: Midline shift, effaced ventricles, loss of sulci

Management:

• Osmotherapy: Mannitol 0.5-1 g/kg IV or hypertonic saline 3% 150-250 mL IV
• Head-of-bed elevation 30°
• Avoid hypotonic fluids
• Decompressive hemicraniectomy (for MCA territory greater than 50% or cerebellar strokes with mass effect)
• Neurosurgical referral urgent

Aspiration Pneumonia

Incidence: 10-15% of acute stroke patients

Risk factors: Dysphagia (present in 50%), reduced GCS, bulbar weakness

Prevention: NPO until swallow screen (speech pathology), NGT feeding if unsafe swallow

Treatment: Antibiotics (amoxicillin-clavulanate or ceftriaxone + metronidazole)

Seizures

Incidence: 5-10% of acute stroke patients (within 24h)

Higher risk: Cortical involvement, hemorrhagic transformation, large infarct

Management: Levetiracetam 500-1000 mg IV loading (preferred in stroke; no drug interactions)

Prophylaxis: Not routinely recommended (only if seizure occurs)

Venous Thromboembolism (DVT/PE)

Incidence: 10% without prophylaxis

Prevention: Intermittent pneumatic compression (IPC) from day 1, LMWH after 24h if no hemorrhage post-thrombolysis

Treatment: Therapeutic anticoagulation (but avoid in first 24h post-thrombolysis)

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Posterior Circulation Stroke

Clinical Presentation

Posterior circulation strokes (vertebrobasilar territory) account for 20-25% of ischemic strokes but are easily missed due to non-specific symptoms.

Hallmark features:

• Vertigo, nausea, vomiting (mimics benign peripheral vertigo)
• Diplopia, dysarthria, dysphagia (brainstem nuclei)
• Ataxia, limb incoordination (cerebellum)
• Crossed neurological signs (ipsilateral cranial nerve + contralateral limb weakness)
• Visual field defects (occipital lobe - homonymous hemianopia)

HINTS Exam (Head Impulse, Nystagmus, Test of Skew)

Used to differentiate central (stroke) from peripheral (vestibular neuritis) vertigo:

• Head Impulse Test: Normal (corrective saccade absent) = central
• Nystagmus: Direction-changing or vertical = central
• Test of Skew: Vertical ocular misalignment = central

HINTS sensitivity for stroke: 96-100% (superior to early MRI).

Management Considerations

• CT brain may be normal in first 24-48 hours (posterior fossa artifact, small infarcts)
• MRI DWI is gold standard (but delays treatment)
• Thrombolysis eligibility: Same criteria as anterior circulation
• Basilar artery occlusion: Thrombectomy up to 24 hours (high mortality without treatment ~80%)
• Cerebellar stroke: Risk of obstructive hydrocephalus + brainstem compression → neurosurgical decompression

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Minor Stroke and TIA

Definitions

• TIA (Transient Ischemic Attack): Focal neurological deficit lasting below 24 hours (usually below 1 hour), no infarct on imaging
• Minor stroke: NIHSS below 5, symptoms may be mild but disabling (e.g., isolated aphasia, hand weakness)

Current Evidence

• PRISMS trial (2018): Minor stroke (NIHSS 0-5) randomized to tPA vs aspirin. Trial stopped early for futility
• However: Patients with disabling deficits (isolated aphasia, hand weakness affecting occupation) may still benefit

ACEM Approach

• Assess functional impact (e.g., teacher with aphasia, surgeon with hand weakness = disabling)
• If NIHSS below 5 but deficit is disabling → consider thrombolysis (shared decision-making)
• If NIHSS below 5 and non-disabling → aspirin 300 mg, admit, early workup
• All TIAs with ABCD² ≥4 require hospital admission

ABCD² Score (predicts 2-day stroke risk after TIA)

• Age ≥60 years (1 point)
• BP ≥140/90 mmHg (1 point)
• Clinical features: Unilateral weakness (2 points), speech disturbance without weakness (1 point)
• Duration: ≥60 min (2 points), 10-59 min (1 point)
• Diabetes (1 point)

Score interpretation:

• 0-3: Low risk (1% 2-day stroke risk) → outpatient workup
• 4-5: Moderate risk (4% 2-day stroke risk) → admit 24-48h
• 6-7: High risk (8% 2-day stroke risk) → admit, urgent imaging, consider dual antiplatelet

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Large Vessel Occlusion (LVO) Recognition

Why It Matters

LVO strokes (ICA, M1, M2, basilar) account for 30-40% of all ischemic strokes but have worse outcomes without thrombectomy. Emergency physicians must recognize LVO to activate thrombectomy pathway.

Clinical Clues for LVO

• Severe stroke: NIHSS ≥6 (sensitivity 90% for LVO)
• Cortical signs: Aphasia, neglect, gaze preference, hemianopia
• Dense hemiplegia: Complete arm and leg paralysis (vs. drift)
• Atrial fibrillation: Cardioembolic source (higher LVO rate)

RACE Scale (Rapid Arterial oCclusion Evaluation)

RACE ≥5 = 85% LVO probability (activate thrombectomy team).

CTA Findings

• Abrupt vessel cutoff (ICA, M1, M2, basilar)
• Clot length greater than 8 mm (longer clot = lower tPA recanalization rate)
• Collateral circulation (leptomeningeal vessels) → better outcomes

ED Management of LVO

1. Give IV thrombolysis if within 4.5h (don't delay for thrombectomy)
2. Activate thrombectomy team immediately (interventional neuroradiology)
3. Transfer to comprehensive stroke center if not on-site
4. Time windows: 0-6h (all LVO), 6-24h (DAWN/DEFUSE-3 criteria with perfusion imaging)

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Secondary Stroke Prevention

Antiplatelet Therapy

• Loading: Aspirin 300 mg (if no thrombolysis) or 24h post-thrombolysis
• Maintenance: Aspirin 100 mg daily indefinitely
• Dual antiplatelet (aspirin + clopidogrel): For minor stroke/TIA (POINT trial) – give for 21 days, then aspirin alone

Anticoagulation (if atrial fibrillation)

Timing depends on stroke size and bleeding risk:

• Small stroke (NIHSS below 8): Start at 4-7 days
• Moderate stroke (NIHSS 8-15): Start at 7-10 days
• Large stroke (NIHSS greater than 15): Start at 10-14 days (risk of hemorrhagic transformation)
• Agent: NOAC preferred over warfarin (apixaban, rivaroxaban, dabigatran – lower ICH risk)

Statin

• High-intensity statin for all ischemic stroke patients (atorvastatin 80 mg daily)
• Reduces recurrent stroke risk by 20%

Blood Pressure

• Target below 140/90 mmHg (or below 130/80 if diabetes)
• Start antihypertensive after acute phase (7-10 days)

Carotid Revascularization

• If carotid stenosis greater than 70% ipsilateral to stroke → carotid endarterectomy (CEA) or stenting (CAS)
• Timing: Within 2 weeks of stroke (early surgery reduces recurrence)

Lifestyle Modifications

• Smoking cessation (halves recurrence risk)
• Diabetes control (HbA1c below 7%)
• Exercise (30 min/day, 5 days/week)
• Dietary modification (Mediterranean diet)

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Stroke Mimics

Incidence

5-25% of patients receiving thrombolysis have stroke mimics (not true ischemic stroke).

Common Mimics

1. Seizure with Todd's paresis (post-ictal weakness): History of seizure, gradual resolution over hours
2. Hypoglycemia: Blood glucose below 2.7 mmol/L, resolves with dextrose
3. Migraine with aura: Younger age, gradual onset (vs. sudden), visual symptoms, history of migraines
4. Functional neurological disorder (conversion disorder): Inconsistent exam, non-anatomic deficits
5. Sepsis/metabolic encephalopathy: Delirium, fluctuating consciousness, systemic signs
6. Brain tumor: Gradual onset over days-weeks, seizure at presentation
7. Peripheral vestibulopathy (labyrinthitis): Isolated vertigo/nausea, no focal neuro signs, HINTS-negative

Safety of Thrombolysis in Stroke Mimics

• Meta-analysis: SICH rate 0.5% in stroke mimics (vs. 6% in true stroke)
• Conclusion: Giving thrombolysis to a stroke mimic is generally safe (low bleeding risk without ischemia)
• Therefore: Do not withhold thrombolysis if clinical suspicion is high, even if diagnosis uncertain

Red Flags for Mimics

• Gradual onset (not sudden)
• Prior episodes with full resolution
• Young age (below 50) without vascular risk factors
• Normal CT and CTA (though early stroke CT can be normal)
• Blood glucose below 2.7 mmol/L (always check)

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NOAC Management in Stroke

General Principles

• NOACs (apixaban, rivaroxaban, dabigatran, edoxaban) are relative contraindications to thrombolysis
• Wait 48 hours from last NOAC dose before thrombolysis (≥4 half-lives = 94% cleared)
• Mechanical thrombectomy does NOT require full anticoagulation reversal

NOAC Half-Lives

Reversal Agents

Decision Algorithm for NOAC Patients

1. Last dose greater than 48 hours ago → Proceed with thrombolysis (if otherwise eligible)
2. Last dose 24-48 hours ago:
   • Check renal function (clearance prolonged if CrCl below 30)
   • Consider anti-Xa level (if available) – if undetectable, can proceed
   • Otherwise, defer thrombolysis; proceed to thrombectomy if LVO
3. Last dose below 24 hours ago:
   • Thrombolysis contraindicated without reversal
   • For dabigatran: Give idarucizumab 5 g IV → then thrombolysis
   • For apixaban/rivaroxaban: Consider andexanet alfa (if available) or proceed to thrombectomy only
4. Thrombectomy: Safe in anticoagulated patients (mechanical, not systemic therapy)

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Patient Information and Consent

Explaining Stroke to Patients/Family

Use lay language:

"A stroke happens when a blood clot blocks an artery in the brain, cutting off oxygen. Without oxygen, brain cells start dying within minutes – that's why we call it a 'brain attack,' similar to a heart attack. The good news is we have a clot-busting drug that can dissolve the clot and restore blood flow, but we need to give it within 4.5 hours."

Explain "time is brain":

"Every minute that passes, about 2 million brain cells die. That's why we're moving so quickly. The sooner we give the clot-buster, the better your chances of recovering."

Discuss risks honestly:

"The main risk of the clot-busting drug is bleeding in the brain, which happens in about 6 out of 100 people who receive it. If that happens, it can be serious – about half of those patients die or have severe disability. However, without the drug, your chance of being disabled or dying from the stroke is higher – about 30-40%. So while there is a risk, the benefit outweighs it for most people."

Obtain verbal consent:

"Given the time pressure, I need your verbal consent to proceed. Do you understand the risks and benefits? Do you want us to give you the clot-busting drug?"

After Thrombolysis: Patient Information

What to expect in the next 24 hours:

• You will be monitored closely in the stroke unit or intensive care
• We will check your blood pressure every 15 minutes for 2 hours, then every 30 minutes for 6 hours
• We will perform neurological checks regularly to ensure the treatment is working
• You may have a headache (common side effect)
• If you develop severe headache, vomiting, or worsening weakness, tell the nurse immediately (could be bleeding)

What NOT to do for 24 hours:

• No aspirin or blood-thinning medications (risk of bleeding)
• No nasogastric tube or urinary catheter unless absolutely necessary
• No blood pressure medications unless your pressure is very high (greater than 180/105)

After 24 hours:

• We will do another CT scan to check for bleeding
• If the scan is clear, we will start aspirin to prevent another stroke
• You will continue in the stroke unit for rehabilitation

Recovery:

• Stroke recovery takes weeks to months
• Most improvement happens in the first 3 months
• Rehabilitation is key to maximizing recovery
• You will need to take medications long-term to prevent another stroke

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Medicolegal Considerations

Common Litigation Scenarios

1. Failure to thrombolyse eligible patient (missed opportunity)
   • Defense: Document why patient was ineligible (contraindications, outside window)
2. Giving thrombolysis to ineligible patient (causing hemorrhage)
   • Defense: Document informed consent discussion, risks/benefits
3. Delay in thrombolysis (door-to-needle greater than 90 min)
   • Defense: Document reasons for delay (uncontrolled BP, awaiting labs, family discussion)
4. Missing stroke diagnosis (discharged as "dizziness" or "migraine")
   • Defense: Document full neurological exam, consider posterior circulation strokes

Documentation Essentials

• Time last known well (exact time, not "this morning")
• NIHSS score (baseline before thrombolysis)
• Contraindications assessed (checklist)
• Consent discussion (risks: 6% ICH, benefits: 30% better outcome)
• Door-to-CT and door-to-needle times
• Post-thrombolysis monitoring (NIHSS, BP, neuro obs)

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Summary for ACEM Exam

High-Yield Points

1. Door-to-needle below 60 minutes – each 15-min delay reduces good outcome by 4%
2. Tenecteplase 0.25 mg/kg – single bolus, non-inferior to alteplase, preferred for drip-and-ship
3. Alteplase 0.9 mg/kg – 10% bolus + 60-min infusion
4. BP below 185/110 before thrombolysis, below 180/105 for 24 hours after
5. Thrombectomy for LVO: 0-6h all patients, 6-24h with imaging selection (DAWN/DEFUSE-3)
6. Large core (ASPECTS 3-5): Now eligible for thrombectomy (SELECT2, ANGEL-ASPECT, TENSION)
7. Indigenous disparities: 2-3× higher incidence, 10-15 years earlier – don't dismiss younger patients
8. Drip-and-ship: Give tenecteplase bolus then transfer immediately for thrombectomy
9. No aspirin for 24 hours post-thrombolysis
10. Wake-up stroke: Consider MRI DWI-FLAIR or CT perfusion for extended window treatment

Viva Opening Statement Template

"This is a time-critical stroke code. My immediate priorities are: (1) Exclude hemorrhage with urgent CT brain, (2) Determine thrombolysis eligibility – time last known well, contraindications, (3) Control blood pressure to below 185/110 mmHg, (4) Calculate thrombolytic dose and prepare for administration, with a target door-to-needle time of less than 60 minutes. If CTA shows large vessel occlusion, I would simultaneously activate the thrombectomy team."

OSCE Performance Tips

• Start with "ABCDE" – don't jump to NIHSS without primary survey
• Verbalize "This is a stroke code, I'm activating the stroke team now"
• NIHSS: Practice until you can do it in below 5 minutes
• After NIHSS, state the score and severity (e.g., "NIHSS 8, moderate stroke, eligible for thrombolysis")
• For consent: Use lay language, mention specific numbers (6% bleeding risk, 30% better chance of recovery)
• For Indigenous patients: Acknowledge cultural safety, involve family in decision-making