Key Facts

Stroke thrombolysis has revolutionised the emergency management of ischaemic stroke since the landmark NINDS trial (1995). The addition of mechanical thrombectomy has further improved outcomes for large vessel occlusion. Time remains the most critical factor — 'time is brain'.

Epidemiology

Stroke affects approximately 100,000 people per year in the UK. Ischaemic stroke accounts for 85%, haemorrhagic stroke 15%. Approximately 12% of ischaemic stroke patients in the UK receive thrombolysis (SSNAP data). Stroke is the 4th leading cause of death and the leading cause of adult disability in the UK.

Aetiology

Ischaemic stroke results from:

• Large artery atherosclerosis (carotid, intracranial) — ~25%
• Cardioembolism (AF, valvular disease, LV thrombus) — ~25%
• Small vessel disease (lacunar) — ~25%
• Other/undetermined — ~25%

Pathophysiology

Acute vessel occlusion creates an ischaemic core (irreversibly damaged) surrounded by a penumbra (ischaemic but potentially salvageable tissue). The penumbra relies on collateral blood supply and is the target of reperfusion therapy. Without treatment, the penumbra progressively converts to infarct core — approximately 1.9 million neurones lost per minute of untreated large vessel occlusion.

Stroke Recognition (FAST)

• Face: Facial weakness (drooping)
• Arms: Arm weakness (drift)
• Speech: Slurred or absent speech
• Time: Time to call 999

NIHSS (National Institutes of Health Stroke Scale)

• Quantifies stroke severity (0-42)
• Score >5 — moderate stroke, consider thrombolysis
• Score >10 — moderate-severe, high likelihood of large vessel occlusion
• Score >20 — severe stroke

Large Vessel Occlusion (LVO) Signs

• Dense hemiplegia, hemisensory loss
• Neglect, gaze preference
• Aphasia (dominant hemisphere)
• NIHSS typically ≥6

Red Flags

• Rapidly improving symptoms — may still benefit from thrombolysis (don't assume TIA)
• Seizure at onset — difficult to distinguish from stroke; CT/MRI helps
• Posterior circulation stroke — may present with vertigo, ataxia, visual loss, dysphagia (often missed)
• Young stroke — consider dissection, PFO, thrombophilia, cocaine

Bedside

• CT head (non-contrast): IMMEDIATELY — to exclude haemorrhage (must be done before thrombolysis)
• Blood glucose: Exclude hypoglycaemia (stroke mimic)
• NIHSS score: Quantify severity, track response
• ECG: AF detection
• Observations: BP — must be <185/110 before thrombolysis

Bloods

• FBC, coagulation (INR, APTT): Must check before thrombolysis (but do NOT delay treatment for results unless on anticoagulants)
• U&Es, glucose: Baseline
• Troponin: Concurrent MI in some patients

Imaging

• CT angiography (CTA): Identify large vessel occlusion — essential for thrombectomy decision
• CT perfusion: Identify ischaemic penumbra — guides late thrombectomy (DAWN/DEFUSE-3 criteria)
• MRI (DWI/PWI): Most sensitive for early ischaemia; DWI-FLAIR mismatch can help time unknown-onset strokes

Special Tests

• Carotid USS/CTA: After acute phase — assess for carotid stenosis
• Echocardiography: Cardioembolic source (PFO, thrombus, valve disease)
• 24h/72h Holter or prolonged ECG: Paroxysmal AF detection

Non-pharmacological

• Stroke unit admission: All stroke patients — reduces mortality by 20% (Stroke Unit Trialists' Collaboration)
• Swallow screen: Before any oral intake — NIHSS, water swallow test; SALT assessment if concerns
• Early mobilisation: Within 24-48 hours (AVERT trial — avoid very early aggressive mobilisation)
• Multidisciplinary team: Physiotherapy, occupational therapy, SALT, nursing, psychology

Pharmacological

Thrombolysis (within 4.5 hours):

• Alteplase 0.9mg/kg IV (max 90mg): 10% as IV bolus, remaining 90% over 60 minutes
• BP must be <185/110 before treatment — use labetalol 10-20mg IV or GTN infusion
• Monitor for sICH: neuro obs every 15 min for 2h, every 30 min for 6h, hourly for 24h
• No antiplatelet or anticoagulant for 24 hours post-thrombolysis

If sICH occurs after thrombolysis:

• Stop alteplase infusion
• Urgent CT head
• Tranexamic acid 1g IV, cryoprecipitate 10 units, consider platelet transfusion

Secondary prevention (start at 24h post-thrombolysis or immediately if not thrombolysed):

• Aspirin 300mg OD for 14 days, then clopidogrel 75mg OD long-term
• Statin: Atorvastatin 20-80mg OD
• Anticoagulation for AF: DOAC (apixaban 5mg BD, rivaroxaban 20mg OD) — start at 2-14 days depending on infarct size
• Antihypertensive: Target <130/80 after acute phase

Surgical/Interventional

• Mechanical thrombectomy: For LVO (ICA/M1 MCA) within 6 hours (or up to 24h with favourable perfusion imaging)
• Decompressive craniectomy: For malignant MCA infarction with cerebral oedema (within 48h, age ≤60) — DECIMAL/DESTINY/HAMLET trials
• Carotid endarterectomy/stenting: For symptomatic carotid stenosis >50% (ECST criteria) — within 2 weeks of index event

Referral Criteria

• All suspected stroke — emergency ambulance to nearest HASU (Hyper-Acute Stroke Unit)
• LVO identified — refer to thrombectomy centre (neurosciences centre)
• Carotid stenosis >50% — vascular surgery within 2 weeks

• Thrombolysis at 3 hours: NNT 7 for favourable outcome; absolute benefit ~12%
• Thrombolysis at 4.5 hours: NNT 14; absolute benefit ~7%
• Thrombectomy: NNT 2.6 for reduced disability in LVO (MR CLEAN, ESCAPE, EXTEND-IA trials)
• sICH risk: ~6% with thrombolysis; mortality from sICH ~50%
• Overall stroke 30-day mortality: ~12%; 1-year mortality ~25%
• Stroke unit care: Reduces mortality by 20% and disability by 15% compared with general ward care

Thrombolysis Inclusion/Exclusion Criteria (Summary)

Key Stroke Thrombolysis/Thrombectomy Trials