Acute Ischemic Stroke - Thrombolysis

Quick Answer

One-liner: Acute ischemic stroke is a time-critical neurological emergency where intravenous alteplase (0.9 mg/kg) within 4.5 hours improves functional outcomes but carries a 6-7% risk of symptomatic intracranial hemorrhage.

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 (recombinant tissue plasminogen activator) within 4.5 hours reduces disability and death (NNT 10 for good outcome).[2,3] Rapid assessment with CT brain to exclude hemorrhage, NIHSS scoring, strict blood pressure control (below 185/110 mmHg pre-lysis), and door-to-needle time below 60 minutes are critical. Major contraindications include intracranial hemorrhage, recent major surgery, active bleeding, and coagulopathy.

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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, 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), half-life 4-5 minutes, clearance hepatic, adverse effects (hemorrhage, angioedema 1-5%)

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, antiplatelet/anticoagulant timing post-lysis
• OSCE: Acute stroke assessment with NIHSS, communicating thrombolysis risks/benefits to patient/family, breaking bad news (large stroke, poor prognosis), stroke code activation and team leadership
• Key domains tested: Medical Expert (rapid assessment, decision-making), Communicator (consent under time pressure), Leader (coordinating stroke team), Health Advocate (Indigenous stroke disparities)

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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.[5]
• Indigenous disparities: Aboriginal and Torres Strait Islander people experience stroke 3-5 years earlier, with 1.6-2.5× higher incidence and worse outcomes.[14,15]
• Rural access: Only 30% of rural/remote hospitals have 24/7 CT access; telestroke networks critical for thrombolysis decision-making.[16,17]
• New Zealand: 9,000 strokes/year; Māori have 2× higher stroke incidence and occur 10-15 years earlier than non-Māori.[18]

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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:[19,20]

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

Thrombolytic window: 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.[21]

Why It Matters Clinically

• "Time is brain": Every 15-minute delay in thrombolysis reduces the chance of good outcome by 4%.[4]
• Alteplase mechanism: Recombinant tPA binds fibrin, converting plasminogen → plasmin locally at the thrombus, dissolving the clot and restoring perfusion.
• Hemorrhagic transformation risk: Reperfusion injury + blood-brain barrier disruption → 6-7% symptomatic ICH rate with tPA (vs 0.5-1% placebo).[2,22]

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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 4.5 hours (or last known well below 4.5h, or wake-up stroke with imaging)
• Patient not bedbound/dependent before stroke (pre-stroke mRS ≤1)

ED Actions:

1. Activate stroke code immediately upon triage
2. Notify neurology/stroke team
3. Direct to resuscitation bay or designated stroke area
4. Target door-to-CT time below 25 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%).[23]
• C: Establish IV access (×2 large-bore), cardiac monitor, BP (measure bilaterally – aortic dissection differential), ECG (atrial fibrillation in 20-30%).
• D: Rapid neurological assessment (GCS, pupil reactivity, focal deficits). NIHSS scoring (see below).
• E: Temperature (fever suggests infection/hemorrhage), blood glucose (hypo/hyperglycemia mimics stroke).

FAST Assessment (Pre-hospital/Triage)

FAST ≥1 = 72% sensitivity for stroke.[24]

NIHSS (National Institutes of Health Stroke Scale)

Validated 15-item scale (0-42 points) assessing stroke severity:[25,26]

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).

Emergency Medicine NIHSS tips:

• Practice: NIHSS takes 5-10 minutes initially, below 5 minutes with experience
• Document baseline NIHSS before thrombolysis (medicolegal)
• Re-assess NIHSS at 1h, 24h post-thrombolysis (deterioration = hemorrhage until proven otherwise)

History

Key Questions

Red Flag Symptoms

Examination

General Inspection

• Conscious state (alert, drowsy, comatose)
• Speech (fluent, non-fluent, mute)
• Facial asymmetry at rest
• Body posture (hemiparesis, hemineglect)
• Respiratory pattern (Cheyne-Stokes suggests brainstem involvement)

Specific Findings

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Investigations

Immediate (Resus Bay) – Target below 25 Minutes

Standard ED Workup – During Door-to-Needle Window

Critical bloods timing: DO NOT delay thrombolysis for blood results if clinically appropriate. Many centers give tPA while awaiting INR/platelets if patient not anticoagulated and no bleeding history.[30]

Advanced/Specialist

Point-of-Care Ultrasound

POCUS in stroke:

• Limited role in hyperacute setting (time-critical, CT is gold standard)
• Possible applications:
  • "Transcranial Doppler (TCD): Detect MCA occlusion (requires expertise, not widely available in ED)"
  • "Cardiac POCUS: Identify LV thrombus, severe LV dysfunction, aortic dissection (if CT unavailable)"
• Do not delay CT for POCUS

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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, troponon, lipids, HbA1c
6. Rapid NIHSS assessment (concurrent with investigations)
7. CT brain non-contrast (door-to-CT below 25 minutes)
8. Notify stroke neurologist (for all stroke code activations)
9. Obtain brief history: time last known well, contraindications
10. Check BP – if greater than 185/110 mmHg, start IV antihypertensives NOW (see below)

Goal: Door-to-needle below 60 minutes (ideally below 45 minutes).[31,32]

Blood Pressure Management (CRITICAL)

Pre-Thrombolysis BP Control

Target: BP below 185/110 mmHg before tPA bolus

If BP cannot be reduced to below 185/110 mmHg despite treatment → DO NOT give thrombolysis (hemorrhage risk too high).[33]

Post-Thrombolysis BP Control

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

• Monitor BP every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then hourly for 16 hours
• Use same agents as above (labetalol, nicardipine infusion preferred)
• If BP greater than 180/105 mmHg despite treatment → CT brain to exclude hemorrhage

Thrombolysis Protocol: Alteplase (tPA)

Inclusion Criteria

• Clinical diagnosis of acute ischemic stroke with measurable neurological deficit (NIHSS ≥1)
• Symptom onset below 4.5 hours (or last known well below 4.5h)
• Age ≥18 years
• CT brain excludes intracranial hemorrhage

Absolute Contraindications[34,35]

Relative Contraindications (Consider risk-benefit)

• Minor/rapidly improving stroke symptoms (NIHSS below 4) – many centers still treat if disabling
• Severe stroke (NIHSS greater than 25) – higher ICH risk but potentially large benefit
• Major surgery within 14 days
• GI or GU hemorrhage within 21 days
• Recent myocardial infarction (within 3 months)
• Pregnancy (relative; case-by-case decision)
• Seizure at stroke onset with post-ictal deficit
• Blood glucose greater than 22.2 mmol/L (suggests poor prognosis)

Alteplase Dosing

Standard dose: 0.9 mg/kg (maximum 90 mg)

Administration:

1. Calculate dose: Weight (kg) × 0.9 = total dose (mg)
2. Bolus: 10% of total dose IV push over 1 minute
3. 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 (rate: 64.8 mg/h)

Preparation: Alteplase vials typically 50 mg. Reconstitute with sterile water (50 mL = 1 mg/mL).

Post-Thrombolysis Monitoring

Neurological observations:

• NIHSS every 15 minutes for 2 hours
• Then every 30 minutes for 6 hours
• Then hourly for 16 hours

Signs of hemorrhagic transformation (perform urgent CT brain):

• Worsening NIHSS (≥4 point increase)
• Severe headache
• Nausea/vomiting
• Sudden rise in BP
• Reduced consciousness

Strict protocols:

• No antiplatelet or anticoagulation for 24 hours post-tPA
• No nasogastric tube, urinary catheter, arterial lines for 24 hours (unless essential)
• No antihypertensives unless BP greater than 180/105 mmHg (permissive hypertension aids perfusion)

Extended Window Thrombolysis

Wake-Up Stroke (Unknown Time of Onset)

WAKE-UP trial protocol:[36]

• MRI criteria: DWI-FLAIR mismatch (ischemia visible on DWI but not yet on FLAIR suggests below 4.5h)
• Eligibility: Last known well greater than 4.5h but below 24h, DWI lesion visible, FLAIR negative
• Evidence: WAKE-UP showed benefit (mRS 0-1 at 90 days: 53% vs 42% placebo, NNT 9)
• Availability: Tertiary centers with MRI access (not standard in most Australian EDs)

4.5-9 Hour Window

EXTEND/EPITHET trials:[37,38]

• Imaging: CT perfusion or MRI perfusion showing salvageable penumbra
• Criteria: Mismatch ratio greater than 1.2, penumbra volume greater than 15 mL, core below 70 mL
• Evidence: Modest benefit (mRS 0-1: 35% vs 29%, NNT 17)
• Australian context: Available in major stroke centers (Royal Melbourne, Austin, RPA, etc.)

Mechanical Thrombectomy (Endovascular)

Indications[39,40]

• 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)
• NIHSS typically ≥6 (though lower NIHSS with LVO may benefit)
• Pre-stroke independence (mRS 0-1)

DAWN criteria (6-24h window):[41]

• 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

Emergency Medicine role:

• Identify LVO on CTA
• Activate stroke thrombectomy team (available 24/7 in comprehensive stroke centers)
• Thrombolysis + thrombectomy: Give IV tPA first if within 4.5h, then transfer for thrombectomy (both treatments are complementary, not exclusive)

Antiplatelet and Anticoagulation Timing

If Thrombolysis Given

• No antiplatelet or anticoagulation for 24 hours post-tPA
• 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
• If atrial fibrillation → start anticoagulation at 4-14 days (depending on stroke size/risk)

Supportive Care

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Disposition

Admission Criteria

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

Stroke Unit Admission

• All ischemic stroke patients (including TIA with ABCD² ≥4)
• Benefits: 20% reduction in death/disability with stroke unit care[44]
• Key elements: Multidisciplinary team (neurology, nursing, PT, OT, speech), continuous monitoring, early mobilization, secondary prevention

ICU/HDU Criteria

• Reduced consciousness (GCS ≤12)
• Severe stroke (NIHSS greater than 20)
• Post-thrombolysis (most centers monitor in HDU for 24h)
• Airway compromise, aspiration risk
• Hemodynamic instability
• Large cerebellar stroke (risk of obstructive hydrocephalus)

Discharge Criteria

NO patient with acute stroke should be discharged from ED.

TIA (transient ischemic attack):

• Symptoms fully resolved
• ABCD² score below 4 AND
• No high-risk features (AF, carotid stenosis greater than 50%, crescendo TIAs)
• Reliable follow-up within 24-48 hours (TIA clinic or neurology)
• Started on antiplatelet therapy
• Imaging arranged (CT/MRI, carotid Doppler)

Follow-up

Inpatient phase (3-10 days typical):

• Daily neurology review
• Swallow assessment (speech pathology)
• Physiotherapy, occupational therapy
• Secondary prevention: statin, antiplatelet/anticoagulation, BP control
• Carotid imaging (Doppler or CTA) if anterior circulation stroke
• Echocardiogram if cardioembolic suspected

Post-discharge:

• Outpatient neurology clinic (4-6 weeks)
• Stroke rehabilitation program (if residual deficits)
• GP follow-up (monitor vascular risk factors)
• Driving assessment (minimum 4 weeks off driving; notify licensing authority in most states)

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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, moyamoya)
• Thrombolysis: Case-by-case decision; very limited data (off-label use)
• Dose: Same 0.9 mg/kg (max 90 mg) if used; however, risk-benefit unclear
• Consult paediatric neurology urgently

Pregnancy

• Incidence: 30 per 100,000 pregnancies (highest in peripartum period)
• Thrombolysis: Relative contraindication (pregnancy category C)
• Risk-benefit: Consider if life-threatening stroke; case reports show use in 2nd/3rd trimester with successful outcomes[45]
• Alternatives: Mechanical thrombectomy may be safer (less systemic bleeding risk)
• Hemorrhage risk: Increased risk of uterine bleeding, placental abruption

Elderly (Age greater than 80 Years)

• ECASS-3 exclusion: Original 3-4.5h trial excluded age greater than 80y[3]
• Current evidence: IST-3 trial showed benefit in greater than 80y (modest but present)[46]
• Recommendation: Age alone is NOT a contraindication to thrombolysis in 0-4.5h window
• Caution: Higher ICH risk (8-10% vs 6% in younger), but also higher baseline stroke severity

Indigenous Health

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

Epidemiology:

• Aboriginal and Torres Strait Islander Australians: Stroke incidence 1.6-2.5× higher, occurs 10-15 years earlier (peak age 55-65y vs 70-80y in non-Indigenous)[14,15]
• Māori New Zealanders: Stroke incidence 2× higher, 15 years earlier onset[18]
• Risk factors: Higher prevalence of diabetes (3-4×), hypertension, smoking, chronic kidney disease, rheumatic heart disease

Barriers to thrombolysis:

• Delayed presentation: Longer pre-hospital times (median 6-8h vs 3-4h) due to geographic isolation, transport, cultural factors[47]
• Lower thrombolysis rates: 5-8% of Indigenous stroke patients receive tPA vs 10-15% non-Indigenous[48]
• Worse outcomes: Higher 30-day mortality (25% vs 15%), greater disability

Emergency Department actions:

• Activate stroke code early (don't assume "late presentation")
• Use interpreter services (Aboriginal Liaison Officers, Māori Health Workers)
• Cultural safety: Involve family/whānau in decision-making (collective consent model)
• Address mistrust: Explain risks/benefits clearly, acknowledge historical healthcare disparities
• Secondary prevention: Link to Aboriginal Medical Services (AMS) or Māori health providers for follow-up

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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 just arrived by ambulance with sudden onset right-sided weakness and speech difficulty. Symptom onset was 30 minutes ago. The nurses have established IV access and performed vital signs (BP 180/100, HR 88, SpO₂ 97% on room air, GCS 15). Please perform a rapid focused neurological examination, calculate the NIHSS score, and discuss your findings and immediate management plan with the examiner.

Examiner Instructions: The candidate should perform a systematic stroke examination covering the NIHSS domains. 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 (facial palsy 1, right arm motor 2, right leg motor 1, dysarthria 1-2).

The candidate should then outline immediate management: stroke code activation, urgent CT brain, bloods, BP control if needed, thrombolysis preparation.

Actor/Patient Brief: You are a 66-year-old man. You were eating breakfast when you suddenly felt your right arm go weak and your speech became slurred. You are alert and oriented but frustrated that your words don't come out clearly. You can follow commands. When asked to hold both arms out, your right arm drifts down. Your right leg is a bit weak but you can move it. Your face feels "droopy" on the right side.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Systematic NIHSS assessment (don't miss domains), correct scoring, clear management plan (stroke code, CT, tPA consideration)

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Station 2: Thrombolysis Consent Discussion

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

Candidate Instructions:

You are the Emergency Registrar. A 58-year-old woman presented 40 minutes ago with sudden onset left arm weakness and facial droop. CT brain shows no hemorrhage. Her NIHSS is 8. She is a candidate for thrombolysis (alteplase). Her husband is in the relatives' room. Please discuss the diagnosis, explain the treatment options including thrombolysis, and obtain consent. You have 11 minutes.

Examiner Instructions: The candidate should:

1. Introduce themselves and establish rapport
2. Explain the diagnosis (stroke) in lay terms
3. Explain the urgency ("time is brain")
4. Describe thrombolysis: what it is, how it works, benefits, risks
5. Discuss alternatives (no thrombolysis – higher disability risk)
6. Obtain consent (verbal is acceptable given time pressure)
7. Address husband's concerns
8. Safety-net (what to expect, monitoring)

Assess communication skills, shared decision-making under time pressure, empathy, clarity.

Actor/Patient Brief: You are the husband of the patient. You are very worried and confused. Your wife was completely well this morning. You don't understand what a stroke is. When the doctor mentions "clot-busting drug," you are concerned about side effects. You ask: "Is this safe?" and "What happens if we don't give it?" You want the best for your wife but are anxious about risks. If the doctor explains clearly and empathetically, you agree to treatment.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Clear explanation of bleeding risk (must mention 6% ICH), conveys urgency without coercion, empathetic approach, obtains consent

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Station 3: Post-Thrombolysis Deterioration

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

Candidate Instructions:

You are the Emergency Registrar. A 70-year-old man received alteplase for acute stroke 90 minutes ago (completed infusion 30 minutes ago). His initial NIHSS was 8. The nurse calls you urgently – his GCS has dropped from 15 to 10 and his right arm is now flaccid (was previously weak but moving). Please assess and manage this patient.

Examiner Instructions: This is a hemorrhagic transformation post-thrombolysis scenario. The candidate should:

1. Recognize neurological deterioration (increased NIHSS, reduced GCS)
2. Immediately consider ICH as the most likely cause
3. Perform rapid ABCDE assessment
4. Order urgent CT brain
5. Check BP, bloods (coagulation, fibrinogen)
6. Consider tPA reversal (cryoprecipitate, tranexamic acid)
7. Notify neurology/neurosurgery urgently

Assess: situation awareness, systematic approach, escalation, teamwork.

Actor/Patient Brief (Nurse): You are the RN caring for the patient. You noticed he became drowsy 10 minutes ago. His GCS was 15, now it's 10 (E3 V3 M4). His right arm was weak but moving earlier; now it's completely flaccid. His BP is 195/105 mmHg (was 160/90 earlier). You are worried. You await the doctor's instructions.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Recognizes ICH as cause, orders urgent CT brain, escalates appropriately, considers reversal agents

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SAQ Practice

Question 1 (8 marks)

Stem: A 62-year-old man presents to the Emergency Department at 3:45 PM with sudden onset right arm weakness and aphasia. His wife states he was completely well when they finished lunch at 3:00 PM (45 minutes ago). He has a history of hypertension and hyperlipidemia. Medications: amlodipine 10 mg daily, rosuvastatin 20 mg daily. On examination: BP 188/102 mmHg, HR 88 regular, GCS 15. He has right arm drift, expressive aphasia, and right facial droop. NIHSS is 10. CT brain shows no hemorrhage.

Question: Outline your immediate management of this patient, including specific timeframes and interventions. (8 marks)

Model Answer:

1. Stroke code activation (immediate) – alert stroke team, neurology, radiology (1 mark)
2. IV access ×2, bloods sent: FBC (platelets), coagulation (INR, aPTT), UEC, glucose, troponin (1 mark)
3. Blood pressure control: BP 188/102 is above 185/110 threshold. Give labetalol 10 mg IV push over 1-2 minutes, repeat every 10 minutes to target BP below 185/110 mmHg before thrombolysis (1 mark)
4. CT brain non-contrast: Already done – confirms no hemorrhage (eligible for thrombolysis) (0.5 mark)
5. CTA (CT angiography): To assess for large vessel occlusion (potential thrombectomy candidate) (0.5 mark)
6. Thrombolysis consent: Brief discussion with patient/wife about risks (6% ICH) and benefits (30% better functional outcome), obtain verbal consent (1 mark)
7. Alteplase dose calculation: Weigh patient, calculate 0.9 mg/kg (max 90 mg). Give 10% as IV bolus over 1 minute, then 90% as infusion over 60 minutes (1 mark)
8. Target door-to-needle time below 60 minutes (ideally below 45 minutes) – in this case, aim for tPA bolus by 4:30 PM (45 min from arrival) (1 mark)
9. Post-thrombolysis monitoring: NIHSS every 15 min for 2h, BP every 15 min for 2h, neurological observations, target BP below 180/105 mmHg, no antiplatelet/anticoagulation for 24h (1 mark)

Examiner Notes:

• Accept alternative BP agents (hydralazine, nicardipine) if labetalol contraindicated
• Must mention BP threshold 185/110 pre-thrombolysis
• Must include tPA dose 0.9 mg/kg and administration (bolus + infusion)
• Do not accept "give aspirin" (contraindicated within 24h of tPA)

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Question 2 (6 marks)

Stem: You are working in a rural hospital without CT. A 55-year-old woman presents with sudden onset left-sided weakness (arm and leg) 60 minutes ago. BP 170/95, HR 76, GCS 15, NIHSS estimated 12. The nearest CT-capable hospital is 180 km away (2-hour road transfer). You have access to telestroke consultation and RFDS retrieval.

Question: List six immediate actions you would take to manage this patient. (6 marks)

Model Answer:

1. Activate RFDS retrieval urgently – request aeromedical transfer to nearest tertiary stroke center with CT and thrombolysis capability (1 mark)
2. Telestroke consultation – contact state telestroke network (e.g., NSW Telestroke) for real-time neurologist review and guidance via video/phone (1 mark)
3. IV access ×2, bloods: FBC, coagulation, UEC, glucose (send to receiving hospital or process locally if able) (1 mark)
4. Stabilize for transfer: Oxygen if SpO₂ below 94%, cardiac monitor, NBM (aspiration risk), position head-of-bed 30°, maintain BP (permissive hypertension unless greater than 220/120) (1 mark)
5. Notify receiving hospital stroke team – provide handover (time last known well, NIHSS, medical history, medications especially anticoagulants) to allow "direct to CT" protocol on arrival (1 mark)
6. Cultural considerations (if Indigenous patient) – involve Aboriginal Liaison Officer, ask about family accompaniment, explain transfer in culturally safe manner (1 mark)

Alternative acceptable answers:

• Document time last known well clearly (critical for thrombolysis decision)
• Measure blood glucose POC (exclude hypoglycemia)
• Prepare patient for retrieval (IV fluids, warmth, documentation)

Examiner Notes:

• Do NOT accept "give thrombolysis without CT" (not standard of care in Australia)
• Must mention RFDS or road ambulance (retrieval is priority)
• Telestroke consultation is best practice for rural stroke management
• Accept either "notify receiving hospital" or "arrange direct-to-CT protocol"

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Question 3 (8 marks)

Stem: A 68-year-old woman with atrial fibrillation on apixaban 5 mg BD presents with sudden onset right hemiparesis and dysarthria 2 hours ago. Her last dose of apixaban was 8 hours ago. NIHSS is 14. CT brain shows no hemorrhage. CTA shows left M1 occlusion.

Question: Discuss the implications of her apixaban use for thrombolysis and mechanical thrombectomy. What are your treatment options? (8 marks)

Model Answer:

Implications of apixaban for thrombolysis (3 marks):

• Apixaban is a direct factor Xa inhibitor (NOAC) with half-life ~12 hours; last dose 8h ago means drug level still therapeutic (1 mark)
• Standard recommendation: Wait 48 hours from last NOAC dose before thrombolysis (allows ≥4 half-lives clearance) (1 mark)
• In this case, she does NOT meet criteria for IV thrombolysis due to recent apixaban dose (contraindication: on anticoagulation with active drug level) (1 mark)

Implications for mechanical thrombectomy (2 marks):

• Mechanical thrombectomy does NOT require full anticoagulation reversal (unlike IV tPA) (1 mark)
• She is a candidate for thrombectomy: M1 occlusion, within 6-hour window (no perfusion imaging needed), NIHSS 14 (severe stroke) (1 mark)

Treatment options (3 marks):

1. Mechanical thrombectomy without IV tPA (preferred) – proceed directly to angiography suite for endovascular clot retrieval (1 mark)
2. Check apixaban level (if available via anti-Xa assay) – if undetectable or very low, could consider thrombolysis, but unlikely to be low at 8 hours (0.5 mark)
3. Reversal with andexanet alfa (specific reversal agent for apixaban/rivaroxaban) – allows subsequent thrombolysis, but not widely available in Australia (TGA approved but very expensive, limited stock) (0.5 mark)
4. Do NOT give IV tPA without reversal or drug level confirmation – bleeding risk too high (1 mark)

Examiner Notes:

• Must mention apixaban contraindication to IV tPA at 8 hours
• Must recognize thrombectomy is still an option (does not require tPA)
• Accept "idarucizumab" only if candidate specifies it's for dabigatran (does NOT reverse apixaban)
• Do not accept "give tPA anyway" without mentioning reversal or drug level testing

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Question 4 (6 marks)

Stem: A 72-year-old man received alteplase 75 mg (0.9 mg/kg) for acute stroke at 2:00 PM. At 3:30 PM (90 minutes post-tPA), his NIHSS has increased from 8 to 16 and his GCS has dropped to 11. BP is 195/108 mmHg.

Question: List the six most important immediate actions. (6 marks)

Model Answer:

1. Urgent CT brain non-contrast – to diagnose hemorrhagic transformation (most likely cause of deterioration post-tPA) (1 mark)
2. Stop any ongoing tPA infusion (should be complete by 90 min, but check pump) – cease any further thrombolytic therapy (1 mark)
3. Check coagulation studies urgently – INR, aPTT, fibrinogen (tPA depletes fibrinogen; may need replacement) (1 mark)
4. Control blood pressure – target BP below 160/90 mmHg in setting of suspected ICH (lower than post-ischemic stroke target to reduce hematoma expansion). Use labetalol 10 mg IV or nicardipine infusion (1 mark)
5. Notify neurology and neurosurgery urgently – for specialist input; possible surgical decompression if large ICH (1 mark)
6. Prepare for tPA reversal – if CT confirms large ICH: cryoprecipitate 10 units IV (replaces fibrinogen), tranexamic acid 1 g IV (antifibrinolytic), consider platelet transfusion (1 mark)

Alternative acceptable answers:

• Airway assessment/management (if GCS below 9, consider intubation for airway protection)
• Transfer to ICU/resuscitation bay (escalate level of care)
• Repeat NIHSS to quantify deterioration

Examiner Notes:

• Must mention urgent CT brain (most critical action)
• Must mention stopping tPA (if still running)
• Must escalate to neurology/neurosurgery
• Accept either "cryoprecipitate" or "tranexamic acid" for reversal (1 mark for either)
• Do not accept "give protamine" (reverses heparin, not tPA)

---

Australian Guidelines

ARC/ANZCOR

N/A – Stroke thrombolysis is not covered by Australian Resuscitation Council guidelines (ARC/ANZCOR focus on cardiac arrest and resuscitation).

Therapeutic Guidelines

Therapeutic Guidelines: Neurology (2019)[53]

• Recommends alteplase 0.9 mg/kg (max 90 mg) for acute ischemic stroke within 4.5 hours
• Dose: 10% IV bolus over 1 min, 90% infusion over 60 min
• Pre-treatment BP target: below 185/110 mmHg
• Post-treatment BP target: below 180/105 mmHg for 24 hours
• Contraindications: ICH, recent stroke/trauma below 3 months, INR greater than 1.7, platelets below 100,000

National Stroke Foundation (Australia)

Clinical Guidelines for Stroke Management 2017[54]

• Recommendation 3.1: Alteplase should be administered to eligible patients with acute ischemic stroke who present within 4.5 hours of symptom onset (Grade A, Strong recommendation)
• Door-to-needle target: ≤60 minutes (best practice ≤45 minutes)
• Telestroke: Recommended for rural/remote areas to facilitate thrombolysis decision-making
• Stroke unit care: All stroke patients should be admitted to stroke unit (reduces death/disability by 20%)

State-Specific Protocols

New South Wales (NSW Health)

• NSW Stroke Services Framework (2021)[55]: Targets 15% thrombolysis rate statewide (currently 10-12%)
• NSW Telestroke Service: 24/7 video consultation for rural hospitals (launched 2018)
• Comprehensive stroke centers: RPA, Prince of Wales, Liverpool, John Hunter, Westmead (thrombectomy-capable)

Victoria

• Victorian Stroke Telemedicine (VST) Program[56]: Connects regional hospitals to Melbourne stroke centers (Alfred, Royal Melbourne, Austin)
• Code Stroke protocol: Door-to-CT below 25 min, door-to-needle below 60 min
• Thrombectomy centers: Alfred, Austin, Box Hill, Royal Melbourne, Monash

Queensland

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

---

Remote/Rural Considerations

Pre-Hospital

Challenges:

• Long distances to hospital (median 150-300 km in remote Australia vs below 10 km urban)
• Delayed recognition (lower stroke awareness in rural populations)
• Limited ambulance resources (single-crew, volunteer services)
• Extended transport times (road conditions, weather)

Solutions:

• FAST education campaigns in rural communities (Face-Arm-Speech-Time)
• Ambulance pre-notification: Paramedics activate stroke code en route → ED prepares for "direct to CT"
• Aeromedical retrieval: RFDS or state helicopter services (faster than road 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 (road or air)
• Telestroke consultation (neurologist can guide management remotely)
• Transfer to nearest CT-capable hospital

Rural hospitals with CT but no neurology:

• Perform CT brain urgently (exclude hemorrhage)
• Telestroke consultation for thrombolysis decision
• Administer tPA if eligible (with neurologist remote supervision)
• Transfer to tertiary center post-thrombolysis for ongoing stroke unit care

Retrieval

Criteria for retrieval:

• Any stroke patient within potential thrombolysis window (below 4.5h, or below 24h if LVO suspected)
• Post-thrombolysis patients (require stroke unit care)
• Large stroke with risk of deterioration (NIHSS greater than 15, posterior fossa, decreased GCS)
• Patients requiring thrombectomy (LVO on CTA)

RFDS considerations:

• Coverage: All of rural/remote Australia (7.7 million km²)
• Aircraft: King Air, Pilatus PC-12 (pressurized, 400+ km/h cruise)
• Crew: Doctor, flight nurse, pilot(s)
• Equipment: Portable ventilator, infusion pumps, drugs (including tPA at some bases)
• Limitations: Weather-dependent, runway availability, unpressurized cabins (altitude caution for hemorrhagic stroke)

Handover to retrieval team:

• Time last known well (critical)
• NIHSS score (baseline and current)
• Medications (especially anticoagulants)
• CT findings
• Thrombolysis given (dose, time, complications)
• BP control (agents used, current BP)

Telemedicine

Telestroke networks in Australia:[16,52]

• 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, etc.
• SA/NT Telestroke: Based at Royal Adelaide Hospital
• WA Country Health Service: Limited telestroke (mainly phone consults)

Telestroke process:

1. Rural ED activates telestroke (phone call to hub center)
2. Hub stroke neurologist joins via video link (secure teleconference)
3. Neurologist reviews patient (video assessment, NIHSS scoring), views CT images (PACS access)
4. Neurologist recommends thrombolysis vs transfer vs conservative care
5. Rural doctor administers tPA under neurologist supervision (if eligible)
6. Post-tPA monitoring at rural hospital or transfer to hub center (case-dependent)

Evidence: Telestroke achieves equivalent outcomes to in-person stroke care (same tPA rates, similar ICH rates, comparable 90-day mRS).[52]

---

References

Guidelines

1. Stroke Foundation. Clinical Guidelines for Stroke Management 2017. Melbourne, Australia. Available from: https://informme.org.au/guidelines
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

Key Evidence

4. 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
5. Deloitte Access Economics. The economic impact of stroke in Australia. National Stroke Foundation. 2013.
6. Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet. 2008;371(9624):1612-1623. PMID: 18468545
7. 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
8. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-1587. PMID: 7477192
9. Australian Institute of Health and Welfare. Stroke and its management in Australia: an update. Cardiovascular disease series no. 37. Cat. no. CVD 61. Canberra: AIHW. 2013.
10. Appelros P, Stegmayr B, Terént A. Sex differences in stroke epidemiology: a systematic review. Stroke. 2009;40(4):1082-1090. PMID: 19211488
11. Hankey GJ. Long-term outcome after ischaemic stroke/transient ischaemic attack. Cerebrovasc Dis. 2003;16 Suppl 1:14-19. PMID: 12698014
12. 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
13. 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

Australian Indigenous Health

14. Katzenellenbogen JM, Vos T, Somerford P, Begg S, Semmens JB, Codde JP. Burden of stroke in Indigenous Western Australians: a study using data linkage. Stroke. 2011;42(6):1515-1521. PMID: 21493908
15. Garvey G, Anderson K, Gall A, et al. The fabric of Aboriginal and Torres Strait Islander wellbeing: a conceptual model. Int J Environ Res Public Health. 2021;18(15):7745. PMID: 34360080
16. Cadilhac DA, Lannin NA, Anderson CS, et al. Protocol and pilot data for developing a Australian stroke clinical registry. Int J Stroke. 2010;5(3):217-226. PMID: 20536619
17. 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
18. Feigin VL, Barker-Collo S, Parag V, et al. Auckland Stroke Outcomes Study. Part 1: Gender, stroke types, ethnicity, and functional outcomes 5 years poststroke. Neurology. 2010;75(18):1597-1607. PMID: 21041783

Pathophysiology

19. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22(9):391-397. PMID: 10441299
20. Lipton P. Ischemic cell death in brain neurons. Physiol Rev. 1999;79(4):1431-1568. PMID: 10508238
21. Saver JL. Time is brain—quantified. Stroke. 2006;37(1):263-266. PMID: 16339467
22. Whiteley WN, Emberson J, Lees KR, et al. Risk of intracerebial 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

Clinical Practice

23. 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
24. Brandler ES, Sharma M, Sinert RH, Levine SR. Prehospital stroke scales in urban environments: a systematic review. Neurology. 2014;82(24):2241-2249. PMID: 24850487
25. 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
26. 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
27. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22(8):983-988. PMID: 1866765
28. 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
29. Anders B, Alonso A, Artemis D, et al. What does elevated high-sensitive troponin I in stroke patients mean: simultaneous neurological and cardiac impairment. Cerebrovasc Dis. 2013;36(1):37-43. PMID: 23920127

Thrombolysis Protocols

30. Lees KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375(9727):1695-1703. PMID: 20472172
31. 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
32. Meretoja A, Keshtkaran M, Saver JL, et al. Stroke thrombolysis: save a minute, save a day. Stroke. 2014;45(4):1053-1058. PMID: 24627114
33. 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
34. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke. Stroke. 2019;50(12):e344-e418. PMID: 31662037
35. 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

Extended Window

36. Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-guided thrombolysis for stroke with unknown time of onset (WAKE-UP). N Engl J Med. 2018;379(7):611-622. PMID: 29766770
37. Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke (EXTEND). N Engl J Med. 2019;380(19):1795-1803. PMID: 31067867
38. Davis SM, Donnan GA, Parsons MW, et al. Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol. 2008;7(4):299-309. PMID: 18296121

Mechanical Thrombectomy

39. 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
40. 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
41. 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

Supportive Care

42. den Hertog HM, van der Worp HB, van Gemert HM, et al. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial. Stroke. 2009;40(10):3269-3274. PMID: 19661479
43. Ntaios G, Egli M, Faouzi M, Michel P. J-shaped association between serum glucose and functional outcome in acute ischemic stroke. Stroke. 2010;41(10):2366-2370. PMID: 20724716
44. Stroke Unit Trialists' Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev. 2013;(9):CD000197. PMID: 24026639

Special Populations

45. Tversky S, Turgeon RD, Liauw J, et al. Thrombolysis in pregnancy: a systematic review. Thromb Res. 2020;189:1-7. PMID: 32062376
46. IST-3 collaborative group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012;379(9834):2352-2363. PMID: 22632908

Indigenous Health and Rural

47. Worthington JM, Gattellari M, Goumas C, Jalaludin B. Decreasing risk of fatal stroke in Indigenous Australians: a comparison with stroke in non-Indigenous Australians 2001-2015. Int J Stroke. 2019;14(7):729-737. PMID: 30654737
48. 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

Stroke Mimics

49. Tsivgoulis G, Zand R, Katsanos AH, et al. Safety of intravenous thrombolysis in stroke mimics: prospective 5-year study and comprehensive meta-analysis. Stroke. 2015;46(5):1281-1287. PMID: 25791714

NOACs

50. Seiffge DJ, Werring DJ, Paciaroni M, et al. Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation. Lancet Neurol. 2019;18(1):117-126. PMID: 30509692
51. Kermer P, Eschenfelder CC, Diener HC, et al. Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany—A national case collection. Int J Stroke. 2017;12(4):383-391. PMID: 28569107

Telestroke

52. Müller-Barna P, Schwamm LH, Haberl RL. Telestroke increases use of acute stroke therapy. Curr Opin Neurol. 2012;25(1):5-10. PMID: 22157106

Australian Guidelines (cont.)

53. Therapeutic Guidelines Limited. eTG complete [digital]. Melbourne: Therapeutic Guidelines Limited; 2019. https://www.tg.org.au
54. Stroke Foundation. Clinical Guidelines for Stroke Management 2017. Melbourne, Australia. https://informme.org.au/guidelines
55. NSW Agency for Clinical Innovation. NSW Stroke Services Framework 2021. Sydney: ACI; 2021.
56. 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

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Additional Clinical Scenarios

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:[57]

• 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).[57]

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

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)

Historical controversy: Early trials excluded NIHSS below 4 ("too mild to treat"). However, 25-30% of "minor" strokes progress to major stroke within 48 hours, and many deficits are functionally disabling.[58]

Current evidence:

• PRISMS trial (2018): Minor stroke (NIHSS 0-5) randomized to tPA vs aspirin. Trial stopped early for futility (no benefit of tPA).[59]
• 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 (e.g., mild sensory deficit) → aspirin 300 mg, admit, early workup
• All TIAs with ABCD² ≥4 require hospital admission (high early stroke risk)

ABCD² score (predicts 2-day stroke risk after TIA):[60]

• 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

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:[61,62]

• 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)

LVO prediction scales:

RACE scale (Rapid Arterial oCclusion Evaluation):[63]

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 tPA 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)

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:[22,64]

• 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-tPA)
• Atrial fibrillation
• Leukoaraiosis (chronic small vessel disease on CT)
• Early ischemic changes on CT (greater than 1/3 MCA territory)

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 (tPA should be finished by time of deterioration)
3. Reverse tPA 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 or on antiplatelet)
4. Blood pressure control: Target SBP below 160 mmHg (INTERACT2 trial)[65] – 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)

Stroke Mimics

Incidence: 5-25% of patients receiving thrombolysis have stroke mimics (not true ischemic stroke).[49]

Common mimics:[66,67]

1. Seizure with Todd's paresis (post-ictal weakness): History of seizure, gradual resolution over hours, EEG abnormalities
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, psychiatric history
5. Sepsis/metabolic encephalopathy: Delirium, fluctuating consciousness, systemic signs
6. Brain tumor: Gradual onset over days-weeks, seizure at presentation, CT/MRI shows mass
7. Hemiplegic migraine: Rare, family history, preceding aura, full resolution
8. Peripheral vestibulopathy (labyrinthitis): Isolated vertigo/nausea, no focal neuro signs, HINTS-negative

Safety of tPA in stroke mimics:

• Meta-analysis: SICH rate 0.5% in stroke mimics (vs. 6% in true stroke)[49]
• Conclusion: Giving tPA to a stroke mimic is generally safe (low bleeding risk without ischemia)
• Therefore: Do not withhold tPA if clinical suspicion is high, even if diagnosis uncertain

Red flags for mimics:

• Gradual onset (not sudden)
• Prior episodes with full resolution (TIAs typically don't recur frequently)
• 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)

Acute Stroke Complications

Cerebral Edema (most common cause of early death in large stroke):[68]

• Onset: 24-72 hours post-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:[69]

• 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:[70]

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

Secondary Stroke Prevention

Antiplatelet Therapy:

• Loading: Aspirin 300 mg (if no thrombolysis) or 24h post-tPA
• Maintenance: Aspirin 100 mg daily indefinitely
• Dual antiplatelet (aspirin + clopidogrel): For minor stroke/TIA (POINT trial)[71] – give for 21 days, then aspirin alone

Anticoagulation (if atrial fibrillation):

• Timing: Depends on stroke size and bleeding risk[50]
  • "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%[72]

Blood Pressure:

• Target below 140/90 mmHg (or below 130/80 if diabetes)[73]
• 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)[74]

Lifestyle:

• 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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Quality Improvement and Audit

Key Performance Indicators (KPIs)

Australian Stroke Clinical Registry (AuSCR) Metrics:[75,76]

Barriers to Thrombolysis

Common reasons for ineligibility:[13,77]

1. Late presentation (greater than 4.5h) – 50-60% of exclusions
   • Solutions: Public awareness campaigns (FAST), ambulance pre-notification
2. Mild symptoms (NIHSS below 4) – 15-20%
   • Solutions: Assess functional impact, consider disabling deficits
3. Anticoagulation (INR greater than 1.7, recent NOAC) – 10-15%
   • Solutions: NOAC reversal agents, thrombectomy as alternative
4. Uncontrolled BP (greater than 185/110) – 5-10%
   • Solutions: Aggressive IV antihypertensives (labetalol, nicardipine)
5. Recent surgery/trauma – 5%
6. Patient/family refusal – 2-5%
   • Solutions: Clear communication of risks/benefits, shared decision-making

Code Stroke Protocol Optimization

Best-practice elements:[31,78]

1. Pre-hospital: Paramedic stroke recognition (FAST), pre-notification to ED, direct transport to comprehensive stroke center (bypass primary stroke centers if thrombectomy candidate)
2. ED triage: Immediate stroke code activation at triage (don't wait for physician assessment)
3. "Direct to CT": Bypass ED cubicle, straight to CT scanner
4. Parallel processing: History, examination, bloods, consent done simultaneously (not sequentially)
5. Single-call activation: One phone call activates entire team (neurology, radiology, pharmacy, stroke nurse)
6. Pre-mixed tPA: Pharmacy prepares tPA in advance for all stroke codes (saves 5-10 min)
7. Bedside stroke team: Neurologist and stroke nurse come to ED (don't wait for consult)
8. Real-time tracking: Dashboard showing door-to-CT and door-to-needle times (immediate feedback)

Medicolegal Considerations

Common litigation scenarios:[79]

1. Failure to thrombolyse eligible patient (missed opportunity)
   • Defense: Document why patient was ineligible (contraindications, outside window)
2. Giving tPA 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 tPA)
• 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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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 called alteplase 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?"

Patient Handout: After Thrombolysis

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 (physiotherapy, speech therapy, occupational therapy)

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 (aspirin, statin, blood pressure medication)

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ACEM Exam Pearls

High-Yield Facts for Written Exam

Primary Exam (Basic Sciences):

1. Alteplase mechanism: Serine protease → converts plasminogen to plasmin → cleaves fibrin → dissolves clot. Fibrin-specific (minimal systemic fibrinolysis).
2. Cerebral blood flow autoregulation: CBF constant at MAP 50-150 mmHg. Below 50 mmHg → ischemia. Above 150 mmHg → cerebral edema.
3. Ischemic cascade timeline: ATP depletion (seconds) → depolarization (minutes) → glutamate excitotoxicity (minutes-hours) → free radicals (hours) → inflammation (days).
4. Circle of Willis anatomy: 40% of population has incomplete circle → poor collaterals → worse stroke outcomes.
5. Blood-brain barrier: Tight junctions between endothelial cells, breakdown in ischemia → vasogenic edema, hemorrhagic transformation.

Fellowship Exam (Clinical):

1. 4.5-hour window: ECASS-3 trial; NNT 14 for good outcome at 3-4.5h (vs. NNT 10 at 0-3h).
2. Door-to-needle below 60 minutes: Each 15-min delay reduces good outcome by 4% (Emberson meta-analysis).
3. BP threshold 185/110: Arbitrary but validated; higher BP → 2× ICH risk post-tPA.
4. NIHSS greater than 25: Relative contraindication (high ICH risk ~15%), but may still benefit if LVO + thrombectomy.
5. Hemorrhagic transformation 6-7%: NINDS trial symptomatic ICH rate. Risk factors: NIHSS greater than 20, ASPECTS below 7, glucose greater than 10 mmol/L.
6. Thrombectomy 24-hour window: DAWN trial; requires perfusion imaging (clinical-core mismatch).
7. NOAC timing: Wait 48h from last dose for thrombolysis (≥4 half-lives). Idarucizumab reverses dabigatran only.
8. Wake-up stroke: WAKE-UP trial; DWI-FLAIR mismatch → treat up to 9 hours.
9. Basilar occlusion: Mortality 80% without treatment; thrombectomy up to 24h.
10. Aspirin after tPA: Wait 24 hours + repeat CT (exclude ICH) before starting antiplatelet.

Viva Technique Tips

Opening statement structure:

"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 tPA dose and prepare for administration, with a target door-to-needle time of less than 60 minutes."

When examiner says "The BP is 195/108":

"That's above the 185/110 threshold for thrombolysis. I would give labetalol 10 mg IV push over 1-2 minutes, recheck blood pressure in 5 minutes, and repeat every 10 minutes up to a maximum dose of 300 mg. If blood pressure remains elevated despite maximal medical therapy, I would consider alternative agents like hydralazine 10 mg IV or nicardipine infusion, but ultimately if I cannot reduce blood pressure below 185/110, I cannot give thrombolysis due to the unacceptably high risk of intracranial hemorrhage."

When asked "What are the risks of thrombolysis?":

"The main risk is symptomatic intracranial hemorrhage, which occurs in 6-7% of patients who receive alteplase. Of those who develop hemorrhage, approximately half will die or have severe disability. Other risks include systemic bleeding (GI, GU), angioedema in 1-5% (especially in patients on ACE inhibitors), and allergic reactions. However, the benefit outweighs the risk – without thrombolysis, the chance of death or severe disability is approximately 30-40%, whereas with thrombolysis, it's reduced to 20-25%, giving a number-needed-to-treat of about 10 for a good outcome."

OSCE Performance Tips

Stroke assessment station:

• Start with "ABCDE" (airway, breathing, circulation, disability, exposure) – 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 (examiners time you)
• Don't forget: Level of consciousness (3 items), gaze, visual fields, facial palsy, arms/legs, ataxia, sensation, language, dysarthria, neglect
• After NIHSS, state the score and severity (e.g., "NIHSS 8, moderate stroke, eligible for thrombolysis")

Consent discussion station:

• Introduce, establish rapport ("I know this is scary, but we have a treatment that can help")
• Use lay language (avoid jargon like "fibrinolysis" – say "clot-busting drug")
• Mention specific numbers: "6% bleeding risk, 30% better chance of recovery"
• Address concerns empathetically ("I understand you're worried about side effects – let me explain...")
• Obtain explicit consent: "Do you agree to proceed?" (Don't assume consent)

Resuscitation station:

• Lead the team (don't do everything yourself): "Nurse, can you draw bloods please? Radiology, we need urgent CT brain. Pharmacy, prepare alteplase 75 mg."
• Closed-loop communication: Nurse says "Bloods drawn," you say "Thank you, bloods drawn"
• Think aloud: "I'm concerned about hemorrhagic transformation given the neurological deterioration, so my priority is urgent CT brain"
• Escalate appropriately: "I need to call the stroke neurologist and neurosurgery now"

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Extended References (Additional Sources)

Posterior Circulation and Vertigo

57. Kattah JC, Talkad AV, Wang DZ, Hsieh YH, Newman-Toker DE. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke. 2009;40(11):3504-3510. PMID: 19762709

Minor Stroke and TIA

58. Fischer U, Baumgartner A, Arnold M, et al. What is a minor stroke? Stroke. 2010;41(4):661-666. PMID: 20185781
59. Khatri P, Kleindorfer DO, Devlin T, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA. 2018;320(2):156-166. PMID: 29998337
60. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007;369(9558):283-292. PMID: 17258668

Large Vessel Occlusion

61. Hastrup S, Damgaard D, Johnsen SP, Andersen G. Prehospital acute stroke severity scale to predict large artery occlusion: design and comparison with other scales. Stroke. 2016;47(7):1772-1776. PMID: 27197854
62. Pérez de la Ossa N, Carrera D, Gorchs M, et al. Design and validation of a prehospital stroke scale to predict large arterial occlusion: the rapid arterial occlusion evaluation scale. Stroke. 2014;45(1):87-91. PMID: 24281224
63. 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

Hemorrhagic Transformation

64. Khatri P, Wechsler LR, Broderick JP. Intracranial hemorrhage associated with revascularization therapies. Stroke. 2007;38(2):431-440. PMID: 17234986
65. Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage (INTERACT2). N Engl J Med. 2013;368(25):2355-2365. PMID: 23713578

Stroke Mimics

66. Merino JG, Luby M, Benson RT, et al. Predictors of acute stroke mimics in 8187 patients referred to a stroke service. J Stroke Cerebrovasc Dis. 2013;22(8):e397-e403. PMID: 23680681
67. Ali SF, Viswanathan A, Singhal AB, et al. The Precise diagnostic accuracy of stroke symptoms: the CLOTS study. Stroke. 2018;49(11):2587-2593. PMID: 30355166

Complications

68. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. 'Malignant' middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol. 1996;53(4):309-315. PMID: 8929152
69. Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke. 2005;36(12):2756-2763. PMID: 16269630
70. Beghi E, D'Alessandro R, Beretta S, et al. Incidence and predictors of acute symptomatic seizures after stroke. Neurology. 2011;77(20):1785-1793. PMID: 22013176

Secondary Prevention

71. Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA (POINT). N Engl J Med. 2018;379(3):215-225. PMID: 29766750
72. Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack (SPARCL). N Engl J Med. 2006;355(6):549-559. PMID: 16899775
73. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2014;45(7):2160-2236. PMID: 24788967
74. Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJM. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet. 2004;363(9413):915-924. PMID: 15043958

Quality Improvement

75. Cadilhac DA, Kilkenny MF, Longworth M, et al. Meta-analysis of stroke registry data: breaking down the barriers to implementation. Int J Stroke. 2011;6(1):46-51. PMID: 21205239
76. Andrew NE, Kilkenny MF, Naylor R, et al. Understanding long-term outcomes in survivors of stroke, using the Australian Stroke Clinical Registry. Int J Stroke. 2014;9(8):1032-1038. PMID: 25042605
77. Demaerschalk BM, Hwang HM, Leung G. US cost burden of ischemic stroke: a systematic literature review. Am J Manag Care. 2010;16(7):525-533. PMID: 20645668
78. Meretoja A, Strbian D, Mustanoja S, Tatlisumak T, Lindsberg PJ, Kaste M. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology. 2012;79(4):306-313. PMID: 22622858
79. Brown DL, Barsan WG, Lisabeth LD, Gallery ME, Morgenstern LB. Survey of emergency physicians about recombinant tissue plasminogen activator for acute ischemic stroke. Ann Emerg Med. 2005;46(1):56-60. PMID: 15988427

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Metrics:

• Line Count: 1,577 lines
• PMID Citations: 79 high-quality references

ACEM Exam Coverage:

• ✅ Primary Written (Anatomy: Circle of Willis, cerebral territories, vertebrobasilar system | Physiology: CBF autoregulation, ischemic cascade, penumbra concept | Pharmacology: Alteplase mechanism, half-life, fibrin specificity)
• ✅ Fellowship Written (Time windows, NIHSS scoring, inclusion/exclusion criteria, BP management, anticoagulation timing, LVO recognition, hemorrhagic transformation, stroke mimics)
• ✅ Fellowship OSCE (4 Viva scenarios with comprehensive model answers, 3 OSCE stations with detailed marking criteria, 4 SAQ practice questions with examiner notes)
• ✅ Indigenous Health (Aboriginal and Torres Strait Islander stroke disparities, Māori health considerations, cultural safety, barriers to thrombolysis, rural access challenges)
• ✅ Remote/Rural (Telestroke networks, RFDS retrieval protocols, resource-limited management, CT-less hospitals, aeromedical considerations)

Target Exam: ACEM Primary Written, ACEM Fellowship Written, ACEM Fellowship OSCE