Stroke — ischaemic thrombolysis, thrombectomy, haemorrhagic stroke, SAH and secondary prevention

Definition / Overview

Ischaemic stroke accounts for approximately 85% of all strokes and results from focal cerebral ischaemia due to arterial occlusion. It is a medical emergency where time-to-treatment is the dominant determinant of outcome, "time is brain." From a consultant physician perspective, the long case demands synthesis across the acute intervention window, underlying aetiology (cardioembolic, large-vessel atherosclerotic, small-vessel lacunar, cryptogenic), and a comprehensive secondary prevention and rehabilitation strategy tailored to the individual patient.

Pathophysiology

• Arterial occlusion leads to a core infarct (irreversibly infarcted tissue within minutes) surrounded by an ischaemic penumbra (hypoperfused but potentially salvageable tissue).
• The penumbra is the therapeutic target: reperfusion within the treatment window can rescue penumbral tissue and improve functional outcomes.
• Cardioembolic strokes (atrial fibrillation being the most common cause) tend to produce cortical territory infarcts; large-vessel atherosclerosis causes territorial or watershed infarcts; small-vessel lipohyalinosis causes lacunar infarcts ($< 15\,\text{mm}$, in deep perforator territories).
• Thrombus composition, clot burden, and collateral circulation all influence likelihood of spontaneous or pharmacological recanalisation.

Clinical Features and Initial Assessment

Bedside Recognition

• Sudden-onset focal neurological deficit, weakness, speech disturbance, visual field loss, neglect, ataxia, is the hallmark.
• Use a structured tool (NIHSS) to quantify severity: scores $\geq 6$ generally indicate moderate-to-severe stroke; higher scores correlate with large-vessel occlusion (LVO).
• Establish the time of last known well (not time of discovery): patients waking with stroke are considered as last known well at time of going to sleep unless imaging can refine this.

Mimics to Exclude

• Hypoglycaemia (always check BSL immediately), complex migraine, Todd's paresis, functional neurological disorder, hypertensive encephalopathy, intracranial mass with acute decompensation.

Investigation

Immediate (within minutes of arrival)

Extended Imaging

• CT perfusion (CTP): maps core infarct, penumbra, and mismatch; essential for thrombectomy selection beyond 6 hours.
• MRI DWI/FLAIR mismatch: DWI-positive but FLAIR-negative lesion suggests onset $< 4.5$ hours, useful for wake-up stroke thrombolysis decisions.

Aetiological Workup (after acute phase)

• Prolonged cardiac monitoring (minimum 24-hour Holter, ideally 2-4 weeks implantable monitor if no cause found), detects paroxysmal AF.
• Echocardiography (transthoracic ± transoesophageal), patent foramen ovale, intracardiac thrombus, valvular disease.
• Fasting lipids, HbA1c, renal function.
• Vasculitis screen, thrombophilia screen in young patients or cryptogenic stroke.
• Carotid duplex ultrasound, quantify stenosis at ICA origin.

Acute Management

Step 1, Stabilisation and Supportive Care

1. Airway, breathing, circulation; place in monitored bed.
2. Do not lower blood pressure before thrombolysis unless $\text{SBP} > 185\,\text{mmHg}$ or $\text{DBP} > 110\,\text{mmHg}$ (thrombolysis eligibility threshold). Permissive hypertension up to $220/120\,\text{mmHg}$ is acceptable in non-thrombolysis candidates in the first 24 hours, aggressive BP reduction in this window is harmful.
3. Correct hypoglycaemia; treat fever; maintain $\text{SpO}_2 > 94\%$ (supplemental oxygen only if hypoxic).
4. Nil by mouth pending formal swallow assessment.
5. IV access and fluid resuscitation with isotonic saline (avoid hypotonic solutions).

Step 2, Reperfusion: Intravenous Thrombolysis

Alteplase ($0.9\,\text{mg/kg}$ IV, maximum $90\,\text{mg}$; 10% as bolus over 1 minute, remainder over 60 minutes) remains the only TGA-approved thrombolytic for acute ischaemic stroke. Treatment must commence within 4.5 hours of last known well; the earlier within this window, the greater the benefit.

Eligibility Essentials

• Confirmed ischaemic stroke with measurable deficit.
• No haemorrhage or large completed infarct on CT.
• $\text{SBP} \leq 185\,\text{mmHg}$ and $\text{DBP} \leq 110\,\text{mmHg}$ at time of treatment.
• Blood glucose $3-22\,\text{mmol/L}$.

Key Contraindications

• Intracranial haemorrhage, structural vascular lesion (AVM, aneurysm), or intracranial neoplasm.
• Active bleeding or significant coagulopathy: platelets $< 100 \times 10^9/\text{L}$, INR $> 1.7$, therapeutic anticoagulation within appropriate timeframe.
• Recent major surgery or non-compressible arterial/venous puncture (within 14 days).
• Stroke or serious head injury within the preceding 3 months.
• Rapidly improving or minor non-disabling deficit.
• Seizure at stroke onset (with concern deficit represents Todd's paresis).
• Severe liver disease with coagulopathy.

Wake-up and Unknown Onset Stroke

• MRI DWI/FLAIR mismatch or CT perfusion can identify patients likely within 4.5 hours of symptom onset who may benefit from thrombolysis, select patients can be treated on this imaging basis.

Post-Thrombolysis Monitoring

• Hourly neurological observations and BP monitoring for 24 hours.
• Non-contrast CT at 24 hours to identify haemorrhagic transformation.
• Hold all antiplatelets and anticoagulants for the first 24 hours after alteplase.
• Symptomatic intracranial haemorrhage complicates approximately 6% of treated patients; suspect if neurological deterioration occurs post-infusion, stop infusion, urgent CT, haematology review.

Tenecteplase

• Single IV bolus ($0.25\,\text{mg/kg}$, maximum $25\,\text{mg}$) is increasingly used at centres where it simplifies logistics for bridging to thrombectomy transfer; evidence supports non-inferiority to alteplase in selected patients.

Step 3, Reperfusion: Endovascular Thrombectomy (EVT)

EVT is indicated for LVO (ICA, MCA M1/M2, basilar, vertebral) and delivers superior outcomes to medical therapy alone in eligible patients.

Within 6 Hours of Onset

• Confirmed LVO on CTA.
• No haemorrhage or large completed infarct (ASPECTS $\geq 6$).
• Premorbid functional independence (modified Rankin Scale $< 2$).
• EVT should be pursued in addition to IV alteplase if eligible; do not withhold alteplase to facilitate EVT.

Extended Window (6-24 Hours)

• 6-16 hours (DEFUSE-3 criteria): Core infarct $\leq 70\,\text{mL}$; perfusion mismatch volume $\geq 15\,\text{mL}$; mismatch ratio $\geq 1.8$.
• 16-24 hours (DAWN criteria): Stricter core volume thresholds, $\leq 30\,\text{mL}$ if age $< 80$ years; $\leq 20\,\text{mL}$ if age $\geq 80$ years. Clinical-imaging mismatch (significant deficit but small core).

EVT Contraindications

• Active uncontrolled coagulopathy (INR $> 3$, platelets $< 30 \times 10^9/\text{L}$).
• $\text{SBP} > 185\,\text{mmHg}$ or $\text{DBP} > 110\,\text{mmHg}$ refractory to treatment.
• Pre-existing disability (mRS $\geq 2$) that significantly limits recovery potential.
• Haemorrhage, mass, or significant mass effect as cause of deficits.

Outcome Expectations

• Probability of good outcome declines steeply with time; groin puncture within 2 hours of symptom onset gives an odds ratio for good outcome exceeding 3, falling to approximately 2 by 8 hours.
• Basilar artery thrombectomy is pursued in appropriately selected patients given the otherwise catastrophic natural history, though evidence is less robust than for anterior circulation.

Secondary Prevention

Antithrombotic Therapy

Antiplatelet therapy (non-cardioembolic stroke/TIA):

• Aspirin $325\,\text{mg}$ loading dose within 24-48 hours of stroke onset (or at 24 hours post-thrombolysis); maintenance $81\,\text{mg}$ daily.
• Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel for minor stroke (NIHSS $\leq 5$) or high-risk TIA for 21-30 days, then revert to monotherapy, reduces early recurrent stroke risk but increases bleeding with prolonged use.
• For intracranial atherosclerosis, aspirin plus clopidogrel for 3 months, then aspirin monotherapy.
• Aspirin plus dipyridamole is an alternative to clopidogrel monotherapy for non-cardioembolic stroke.

Anticoagulation (cardioembolic stroke):

• Atrial fibrillation (valvular or non-valvular) is the dominant indication.
• Direct oral anticoagulants (DOACs) are preferred over warfarin for non-valvular AF, dabigatran, apixaban, and rivaroxaban have all demonstrated non-inferiority or superiority to warfarin for stroke prevention with favourable bleeding profiles.
• Apixaban $5\,\text{mg}$ twice daily (or $2.5\,\text{mg}$ twice daily if $\geq 2$ of: age $\geq 80$, weight $\leq 60\,\text{kg}$, creatinine $\geq 133\,\mu\text{mol/L}$).
• Rivaroxaban $20\,\text{mg}$ daily with evening meal.
• Dabigatran $150\,\text{mg}$ twice daily (or $110\,\text{mg}$ twice daily in specific high-risk-for-bleeding populations); requires no dietary modification or routine INR monitoring.
• Warfarin (target INR $2-3$) remains appropriate for valvular AF (mechanical valves, rheumatic mitral disease) and when DOACs are not tolerated or contraindicated.
• Timing of anticoagulation initiation post-stroke: generally delayed 2 weeks for large territorial infarcts; TIA or minor stroke may be anticoagulated within 1-3 days. Individualise based on haemorrhagic transformation risk.
• Venous sinus thrombosis: anticoagulate with heparin/LMWH bridging to warfarin regardless of the presence of haemorrhagic infarct.

Risk Factor Modification

Carotid Intervention

• Symptomatic carotid stenosis ≥50% (ipsilateral to TIA or non-disabling stroke): carotid endarterectomy (CEA) is the preferred intervention, ideally within 2 weeks of the index event when risk of recurrence is highest.
• Stenosis 70-99% gains greatest absolute benefit from surgery.
• Carotid artery stenting is an alternative in patients at high surgical risk.
• Intracranial atherosclerosis: aggressive medical management (DAPT for 3 months, high-intensity statin, BP control) is superior to intracranial stenting, which carries unacceptable early procedural risk.

Complications and Special Considerations

In-Hospital Complications

• Cerebral oedema and raised ICP: peaks 24-72 hours in large hemispheric infarcts (malignant MCA syndrome). Decompressive hemicraniectomy within 48 hours reduces mortality in patients $\leq 60$ years with malignant MCA infarct; discuss goals of care carefully given post-operative disability.
• Haemorrhagic transformation: monitor with 24-hour CT post-thrombolysis; petechial transformation generally does not worsen outcome.
• Dysphagia: formal swallow assessment before oral intake; aspiration pneumonia is a leading cause of post-stroke death.
• DVT/PE: use pneumatic compression devices from admission; avoid routine heparin prophylaxis in the first 24-48 hours post-thrombolysis or in haemorrhagic transformation.
• Urinary retention and infection: avoid indwelling catheters where possible.
• Depression: affects up to 30% post-stroke; screen routinely and treat, influences rehabilitation engagement and long-term outcomes.
• Seizures: occur in ~5% of ischaemic strokes; treat with standard antiepileptic therapy if they occur, but do not use prophylactic antiepileptics.

Atrial Fibrillation Detected After Stroke

• Screen all ischaemic stroke patients with at least 24 hours of cardiac monitoring.
• If AF detected, initiate anticoagulation as soon as safely feasible.
• Consider implantable cardiac monitor for cryptogenic stroke, prolonged monitoring detects paroxysmal AF in a substantial proportion over 2-3 years.

Young Stroke (Age < 50 years)

• Broaden aetiology workup: patent foramen ovale (PFO), thrombophilia, vasculitis, illicit drug use, cervical artery dissection, CADASIL, antiphospholipid syndrome.
• PFO closure may be appropriate in selected young patients with cryptogenic stroke (NIHSS-defined embolic pattern, $< 60$ years, no alternative aetiology), refer to cardiology.

Rehabilitation and Long-Term Care

Principles

• Admission to a dedicated stroke unit is one of the highest-impact interventions, reducing death and disability independent of reperfusion therapy.
• Multidisciplinary team: neurology/medicine, physiotherapy, occupational therapy, speech pathology, social work, neuropsychology.
• Early mobilisation (within 24-48 hours for most patients, with caution in those with severe deficits or haemodynamic instability) improves outcomes.

Rehabilitation Domains

Prognostic Communication

• The modified Rankin Scale (mRS) is the standard outcome measure; mRS $0-2$ represents functional independence.
• Factors associated with poor outcome: advanced age, high NIHSS at presentation, large core infarct, early haemorrhagic transformation, baseline comorbidities, delayed reperfusion.
• Be explicit with patients and families that stroke recovery can continue for 6-12 months and beyond, with the greatest gains in the first 3 months, set realistic but not nihilistic expectations.

Nimodipine Note

• Nimodipine (calcium channel blocker) is used in subarachnoid haemorrhage to improve outcomes, it does not prevent vasospasm but reduces rates of cerebral infarction. It has no role in acute ischaemic stroke management; do not conflate these indications in the exam.

Key Consultant Reasoning Points for the Long Case

• Always determine the stroke mechanism, the aetiology drives secondary prevention; anticoagulation for AF, antiplatelet for atherosclerotic/lacunar, carotid intervention for symptomatic stenosis.
• Weigh thrombolysis risk-benefit explicitly, older age, mild deficit, and anticoagulant use require individual reasoning, not automatic exclusion.
• Frame EVT eligibility as a parallel pathway, eligible patients should go directly to a comprehensive stroke centre; do not allow thrombolysis administration to significantly delay transfer.
• Communicate blood pressure management rationale, permissive hypertension in the first 24 hours (non-thrombolysis) is counterintuitive to many physicians; be ready to explain the physiological basis (maintaining perfusion pressure to the penumbra).
• Multimorbidity considerations: renal impairment affects DOAC dosing; falls risk influences anticoagulation decisions; cognitive impairment affects consent and rehabilitation goals, synthesise all these in the long case.

Sources

• Therapeutic Guidelines (eTG)
• NHMRC clinical practice guidelines
• National Heart Foundation of Australia clinical guidelines