Ischaemic stroke

Contents

Overview

Stroke is the second leading cause of death and the leading cause of adult disability worldwide. Ischaemic stroke accounts for approximately 85% of all strokes. The fundamental principle of acute management is time — "time is brain." Every minute of complete ischaemia results in the death of approximately 1.9 million neurons. Reperfusion by thrombolysis or mechanical thrombectomy is the cornerstone of treatment in eligible patients.

Pathophysiology

Ischaemic stroke results from occlusion of a cerebral artery, causing ischaemia in the territory it supplies.

Causes:

  • Large artery atherosclerosis: thrombosis or artery-to-artery embolism from unstable carotid or intracranial plaque
  • Cardioembolic: AF (most common cardiac cause), intracardiac thrombus, endocarditis, patent foramen ovale with paradoxical embolism
  • Small vessel disease (lacunar stroke): occlusion of deep penetrating arteries from hypertensive lipohyalinosis. Causes lacunar syndromes (pure motor, pure sensory, ataxic hemiparesis).
  • Cryptogenic: no identified cause after standard workup; may represent undetected paroxysmal AF or evolving atherosclerosis

In the ischaemic core (no flow), neurones die within minutes. Surrounding the core, a penumbra of potentially salvageable tissue survives on collateral flow but is at risk of irreversible injury if flow is not restored. Reperfusion therapies aim to rescue the penumbra.

Clinical Assessment

Stroke presents with sudden-onset focal neurological deficits. Common presentations:

  • Hemiparesis, hemiplegia, hemisensory loss
  • Dysphasia (dominant hemisphere — left in most right-handers)
  • Hemianopia
  • Gaze deviation towards the side of the lesion (frontal eye field damage) — contralateral gaze palsy is less common
  • Neglect (non-dominant hemisphere)
  • Cerebellar signs: ataxia, dysarthria, diplopia, vertigo, nystagmus (posterior circulation)

FAST (Face, Arm, Speech, Time) is widely used for public recognition. The clinical scoring for stroke severity is NIHSS (National Institute of Health Stroke Scale, 0–42), which guides treatment decisions and prognosis.

Posterior circulation stroke (PICA, basilar artery) requires attention: it may present with non-specific symptoms (vertigo, vomiting, headache), progress to locked-in syndrome or death from basilar artery occlusion, and may not be detected on early CT.

Investigations

CT brain without contrast: Immediately available; primarily used to exclude haemorrhage before thrombolysis. May be normal in the first 6 hours or show early ischaemic changes (loss of grey-white differentiation, cortical swelling, hyperdense artery sign indicating clot).

CT angiography (CTA head and neck): Identifies the site of arterial occlusion, assesses the intracranial and extracranial vessels, and identifies large vessel occlusion (LVO) amenable to mechanical thrombectomy.

CT perfusion: Assesses infarct core and penumbra. Used to select patients for extended-window thrombectomy (6–24 hours) using DAWN or DEFUSE-3 criteria.

MRI DWI (diffusion-weighted imaging): More sensitive than CT for early ischaemic change, especially posterior fossa and small lacunar infarcts. Restricted diffusion confirms acute ischaemia. Ideally performed when CT is non-diagnostic, but not if it delays treatment.

ECG: Identifies AF as a cause. Stroke-related ECG changes (QT prolongation, T-wave changes) may also occur from CNS injury.

Echocardiography: TTE (or TOE for better visualisation of left atrial appendage and atrial septum) to identify cardioembolic source.

Blood tests: FBC, coagulation, glucose, renal function, lipids, ESR/CRP. Blood cultures if endocarditis is suspected.

Reperfusion Treatment

Intravenous Thrombolysis

Alteplase (recombinant tPA) 0.9 mg/kg (maximum 90 mg), 10% as IV bolus, remainder over 60 minutes.

Time window: up to 4.5 hours from symptom onset in eligible patients. Beyond 4.5 hours, benefit does not clearly outweigh haemorrhagic transformation risk.

Absolute contraindications: haemorrhage on CT, recent surgery (within 14 days), major trauma, active bleeding, blood pressure >185/110 mmHg unresponsive to treatment, prior intracranial haemorrhage, known bleeding diathesis or anticoagulation.

Tenecteplase 0.25 mg/kg IV bolus (maximum 25 mg): single-bolus fibrinolytic. NICE TA990 recommends tenecteplase, within its marketing authorisation, as an option for thrombolytic treatment of acute ischaemic stroke in adults within 4.5 hours of symptom onset once intracranial haemorrhage has been excluded. Alteplase remains an alternative; local stroke network protocols determine which agent is used.

Mechanical Thrombectomy

Mechanical thrombectomy (MT) is the extraction of a clot from an intracranial artery using a stent retriever or aspiration catheter under fluoroscopic guidance.

Indicated for LVO (ICA, M1, M2 segment of MCA, basilar artery) within 6 hours of onset in eligible patients. Extended time window to 24 hours using CT perfusion selection (DAWN and DEFUSE-3 trials).

MT is superior to thrombolysis alone for LVO — multiple RCTs (MR CLEAN, ESCAPE, SWIFT-PRIME, EXTEND-IA, DAWN, DEFUSE-3) demonstrate significantly improved functional outcomes, with NNT of approximately 2.6 to reduce disability.

MT and thrombolysis are not mutually exclusive: eligible patients receive thrombolysis and proceed to MT simultaneously ("drip and ship").

ICU Management

Most ischaemic stroke patients are managed on a stroke unit. ICU admission is required for:

  • Mechanical ventilation (reduced GCS, airway compromise, aspiration)
  • Haemodynamic monitoring and vasoactive support
  • Post-thrombectomy monitoring
  • Malignant MCA infarction

Blood pressure: In the acute phase, permissive hypertension (allowing BP up to 220/120 mmHg) is recommended in patients not receiving reperfusion therapy — this maintains perfusion through collateral vessels. If thrombolysis has been given, maintain BP below 180/105 mmHg. Antihypertensives: IV labetalol, nicardipine.

Blood glucose: NICE recommends maintaining blood glucose between 4 and 11 mmol/L in acute stroke. Both hypoglycaemia and hyperglycaemia worsen outcome.

Temperature: Hyperthermia is harmful — treat fever aggressively with antipyretics and cooling.

Oxygenation: Supplemental oxygen only if oxygen saturation drops below 95%; routine oxygen does not improve outcomes.

Antiplatelet: Aspirin 300 mg (oral or NG) within 24–48 hours of thrombolysis (do not give aspirin for 24 hours post-thrombolysis), or immediately if thrombolysis not given.

DVT prophylaxis: Intermittent pneumatic compression from day 1. LMWH can be started within 24–48 hours of thrombolysis, balancing thrombosis vs haemorrhagic transformation risk.

Nutrition: Early NG feeding if swallow unsafe. SLT assessment should not delay nutrition.

Malignant MCA Infarction

Malignant MCA infarction is a complete or near-complete infarction of the MCA territory, affecting approximately 10% of MCA strokes. It causes severe cerebral oedema and transtentorial herniation, with mortality of 50–80% without surgical intervention.

Onset of herniation is typically at 2–5 days. Warning signs: declining consciousness, worsening hemiplegia, ipsilateral pupil dilatation.

Medical management: Head-of-bed elevation 30°, pain and agitation control, normothermia, normoglycaemia, avoiding hyponatraemia. Osmotherapy (mannitol, hypertonic saline) as a bridge.

Decompressive hemicraniectomy: Surgical removal of a large bone flap to allow brain swelling without herniation. The DECIMAL, HAMLET, and DESTINY trials demonstrated a significant mortality reduction with hemicraniectomy within 48 hours of stroke onset in patients under 60 years. DESTINY-II extended this benefit to patients up to 80 years, though functional outcomes are poorer in older patients and the decision must consider quality of life.

Patient and family discussions must address acceptable functional outcomes before surgery — hemicraniectomy significantly reduces mortality but does not prevent severe disability.

Secondary Prevention

  • Antiplatelet: Aspirin 75 mg + clopidogrel 75 mg for 21 days (POINT/CHANCE trials) after non-cardioembolic TIA or minor stroke; then single antiplatelet long-term.
  • Anticoagulation: For cardioembolic stroke (AF) — direct oral anticoagulants (DOACs) are preferred over warfarin. Timing of anticoagulation initiation after ischaemic stroke depends on stroke size and haemorrhagic transformation risk.
  • Carotid endarterectomy: For symptomatic 70–99% carotid stenosis (NASCET criteria), within 2 weeks of TIA or minor stroke.
  • Statin: Atorvastatin 80 mg — SPARCL trial demonstrated reduced stroke recurrence with high-intensity statin regardless of baseline LDL.
  • Blood pressure reduction: Lowering BP reduces recurrent stroke risk; initiated after the acute phase.

Viva Questions

What are the indications for and contraindications to IV thrombolysis in ischaemic stroke?

IV alteplase at 0.9 mg/kg (maximum 90 mg) is indicated for ischaemic stroke within 4.5 hours of symptom onset in eligible patients. Before giving thrombolysis, haemorrhage must be excluded on CT. The patient should have a measurable neurological deficit, blood pressure below 185/110 mmHg at the time of treatment, and no absolute contraindications. Key absolute contraindications include any intracranial haemorrhage on CT, major surgery or serious trauma within 14 days, gastrointestinal or urinary haemorrhage within 21 days, any prior intracranial haemorrhage, suspected or confirmed endocarditis, and known bleeding diathesis (including INR >1.7 or APTT above normal range with active anticoagulation). Patients on direct oral anticoagulants require thrombin or factor Xa levels to be within acceptable limits before thrombolysis can be given. Time is critical — "time is brain" — so the aim is to give thrombolysis within 60 minutes of hospital arrival (door-to-needle time). Beyond 4.5 hours, the risk of haemorrhagic transformation outweighs the benefit in unselected patients.

What is the evidence base for mechanical thrombectomy in ischaemic stroke and who is eligible?

Mechanical thrombectomy (MT) involves retrieval of an intracranial clot under fluoroscopic guidance using stent retrievers or aspiration catheters. It is the most effective intervention for ischaemic stroke when a large vessel occlusion (ICA, M1 or M2 MCA, basilar artery) is identified. Five landmark RCTs published in 2015 — MR CLEAN, ESCAPE, SWIFT-PRIME, EXTEND-IA, and THRACE — demonstrated consistent and substantial benefit, with a number needed to treat to prevent one additional dependent patient of approximately 2.6. MT is indicated within 6 hours of onset for patients with confirmed LVO on CTA, a clinical deficit consistent with the occlusion site (NIHSS ≥6), and a small ischaemic core relative to penumbra on perfusion imaging. The time window extends to 24 hours using CT perfusion-guided patient selection: the DAWN trial (using clinical-imaging mismatch) and DEFUSE-3 trial (using perfusion mismatch) demonstrated benefit in late-presenting patients with salvageable tissue. Thrombolysis and MT are complementary, not competing — eligible patients receive both. Basilar artery occlusion is associated with very high mortality without MT, and should be treated even beyond standard time windows given the severity of outcome.

How do you manage a patient with malignant MCA infarction?

Malignant MCA infarction involves near-complete territory infarction causing massive cerebral oedema, transtentorial herniation, and rapid neurological decline, typically over 2–5 days. In the ICU, initial management focuses on optimising conditions for brain recovery: elevating the head of the bed to 30°, ensuring normothermia, normoglycaemia, normonatraemia, and adequate oxygenation. Osmotherapy with hypertonic saline (3% NaCl targeting sodium 145–155 mmol/L) or mannitol provides temporary reduction in cerebral oedema as a bridge to definitive intervention. The definitive treatment is decompressive hemicraniectomy — surgical removal of a large unilateral bone flap to allow the oedematous brain to herniate outward rather than inward. Evidence from the pooled analysis of the DECIMAL, HAMLET, and DESTINY trials shows substantial mortality reduction (from approximately 70% to 30%) when hemicraniectomy is performed within 48 hours of stroke onset in patients under 60. DESTINY-II extended this benefit to patients up to 80, but functional outcomes in older patients are worse and the decision requires careful discussion with the family about acceptable quality of life. Many survivors have severe persistent disability — this should be central to shared decision-making about surgery.