Acute Ischaemic Stroke

Summary

Acute ischaemic stroke (AIS) is a medical emergency caused by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. It accounts for approx. 85% of all strokes. The primary pathophysiology involves occlusion of a cerebral artery by a thrombus (local formation) or embolus (from a distant source). Management has been revolutionised by reperfusion therapies: intravenous thrombolysis (IVT) within 4.5 hours and mechanical thrombectomy (MT) within 24 hours for large vessel occlusions. "Time is brain" - rapid assessment and treatment are critical to minimise neuronal loss. [1,2]

Key Facts

Clinical Pearls

Time is Brain: Approx. 1.9 million neurons are lost per minute in untreated acute ischaemic stroke. Every 15-minute delay in reperfusion is associated with reducing disability-free life by one month.

Wake-Up Stroke: Patients waking up with symptoms are now eligible for treatment! DWI-FLAIR mismatch on MRI or CTP core/penumbra ratios can identify patients within the therapeutic window despite unknown time of onset (DAWN and DEFUSE-3 trials).

Mimics: Always check GLUCOSE! Hypoglycaemia is the most common reversible stroke mimic. Others include migraine (aura), seizure (Todd's paresis), and functional disorders.

Blood Pressure: Permissive hypertension is allowed (up to 220/120 mmHg) in non-thrombolysed patients to maintain perfusion to the penumbra. If thrombolysing, BP must be <185/110 mmHg.

Posterior Circulation: "The Five Ds" of posterior circulation stroke: Dizziness, Diplopia, Dysarthria, Dysphagia, Dysmetria (ataxia). Often missed by FAST screening.

Why This Matters Clinically

Stroke is the second leading cause of death and third leading cause of disability globally. Neurological outcomes are time-dependent. Junior doctors are often the first responders to "Stroke Calls" and must rapidly differentiate stroke from mimics, assess eligibility for lysis/thrombectomy, manage blood pressure, and initiate secondary prevention. Failure to recognise LVO (Large Vessel Occlusion) or "wake-up stroke" eligibility denies patients potentially life-changing interventions. [3,4]

National Institutes of Health Stroke Scale (NIHSS)

Validated tool to quantify severity. Vital for thrombolysis decisions.

1a. Level of Consciousness:

• 0: Alert.
• 1: Drowsy.
• 2: Obtunded.
• 3: Coma.

1b. LOC Questions (Month, Age):

• 0: Both correct.
• 1: One correct.
• 2: Neither.

1c. LOC Commands (Open/Close eyes, Grip):

• 0: Both correct.
• 1: One correct.
• 2: Neither.

2. Best Gaze:

• 0: Normal.
• 1: Partial gaze palsy.
• 2: Forced deviation (Total gaze palsy).

3. Visual Fields:

• 0: No visual loss.
• 1: Partial hemianopia.
• 2: Complete hemianopia.
• 3: Bilateral hemianopia (blindness).

4. Facial Palsy:

• 0: Normal symmetry.
• 1: Minor paralysis (flattened nasolabial fold).
• 2: Partial paralysis (lower face).
• 3: Complete paralysis (upper and lower).

5. Motor Arm (Left & Right):

• 0: No drift (holds 10s).
• 1: Drift.
• 2: Some effort against gravity.
• 3: No effort against gravity.
• 4: No movement.

6. Motor Leg (Left & Right):

• 0: No drift (holds 5s).
• 1-4: As above.

7. Limb Ataxia:

• 0: Absent.
• 1: Present in one limb.
• 2: Present in two limbs.

8. Sensory:

• 0: Normal.
• 1: Mild-moderate loss.
• 2: Severe to total loss.

9. Best Language:

• 0: No aphasia.
• 1: Mild-moderate aphasia.
• 2: Severe aphasia.
• 3: Mute / Global aphasia.

10. Dysarthria:

• 0: Normal.
• 1: Mild-moderate slurring.
• 2: Severe (unintelligible).

11. Extinction/Inattention (Neglect):

• 0: No abnormality.
• 1: Visual, tactile, auditory, spatial, or personal inattention.
• 2: Profound hemi-inattention.

NIHSS Interpretation:

• <5: Minor stroke (usually no lysis).
• 5-15: Moderate stroke (ideal lysis candidate).
• >20: Severe stroke (high risk of haemorrhage with lysis).

Supplementary Scores (Risk Stratification)

ABCD2 Score (TIA Prognosis) Used to predict early stroke risk after TIA.

• Age ≥ 60 years: 1 point
• Blood Pressure ≥ 140/90 mmHg: 1 point
• Clinical Features:
  • Unilateral weakness: 2 points
  • Speech impairment without weakness: 1 point
• Duration:
  • ≥ 60 minutes: 2 points
  • 10-59 minutes: 1 point
• Diabetes: 1 point Interpretation: Score 6-7 = High Risk (8% 2-day stroke risk).

CHA2DS2-VASc Score (AF Stroke Risk) Determines indication for anticoagulation in AF.

• Congestive Heart Failure: 1
• Hypertension: 1
• Age ≥ 75: 2
• Diabetes: 1
• Stroke/TIA/Thromboembolism: 2
• Vascular disease (MI, PAD, Aortic plaque): 1
• Age 65-74: 1
• Sex Category (Female): 1 Recommendation: Male ≥1, Female ≥2 → Offer Anticoagulation (DOAC).

HAS-BLED Score (Bleeding Risk)

• Hypertension (>160mmHg): 1
• Abnormal Renal/Liver function: 1 each
• Stroke history: 1
• Bleeding history/predisposition: 1
• Labile INRs: 1
• Elderly (>65): 1
• Drugs (Antiplatelets/NSAIDs) / Alcohol: 1 each Note: High score is not a contraindication, but prompts regular review and risk factor modification.

Cranial Nerve Assessment in Stroke

Localising the lesion using CN findings is critical.

General Examination Findings

• Pulse: Irregularly irregular (AF).
• Blood Pressure: Often acutely elevated ("Reactive hypertension"). Check both arms (Dissection).
• Heart Sounds: Murmurs (Mitral stenosis, Regurgitation).
• Carotids: Bruits (Stenosis/Turbulence).
• Fundoscopy: Hypertensive/Diabetic changes, Papilloedema (Tumour mimic).
• Skin: Vasculitic rash, Endocarditis stigmata (Janeway lesions/Osler nodes).

Modified Rankin Scale (mRS): The global standard for functional outcome measurement.

• 0 - No symptoms.
• 1 - No significant disability: Able to carry out all usual activities.
• 2 - Slight disability: Unable to carry out all previous activities but able to look after own affairs without assistance.
• 3 - Moderate disability: Requires some help, but able to walk without assistance.
• 4 - Moderately severe disability: Unable to walk without assistance and unable to attend to own bodily needs without assistance.
• 5 - Severe disability: Bedridden, incontinent and requiring constant nursing care and attention.
• 6 - Dead.

Prognostic Indicators:

• Age: Strongest non-modifiable predictor.
• Stroke Severity (NIHSS): High score = poor outcome.
• Recanalisation: TICI 2b/3 (successful opening) in thrombectomy is strongest predictor of good outcome.
• Time to Treatment: Every 30 min delay reduces chance of good outcome by ~10%.
• Glucose: Hyperglycaemia (>8 mmol/L) associated with infarct expansion.
• Body Temperature: Pyrexia associated with worse outcomes.

Mortality Statistics:

• 30-day mortality: ~15-20%.
• 1-year mortality: ~30%.
• Recurrence rate: ~10% in first year (highest in first month).

Key Guidelines Summary

NICE NG128 (2019):

• Admit all suspected strokes directly to Hyperacute Stroke Unit (HASU).
• Brain imaging within 1 hour.
• Alterplase within 4.5h.
• Thrombectomy within 6h (standard) or 24h (mismatch).
• Aspirin 300mg within 24h.
• High intensity statin.

ESO (European Stroke Organisation) Guidelines:

• Strong recommendation for Thrombectomy.
• Recommendations for dual antiplatelet therapy in minor stroke.
• BP management post-thrombectomy (Target <140mmHg usually recommended).

Landmark Trials Checklist

1. NINDS (National Institute of Neurological Disorders and Stroke) - 1995

• Question: Does IV rtPA (Alteplase) within 3 hours of onset improve outcome?
• Design: RCT (n=624). rtPA vs Placebo.
• Result: 30% relative increase in patients with minimal/no disability (mRS 0-1) at 3 months. No increase in mortality despite increased ICH risk (6.4% vs 0.6%).
• Impact: Established thrombolysis as the first effective treatment for AIS (0-3h window).

2. ECASS III (European Cooperative Acute Stroke Study III) - 2008

• Question: Is the window extendable to 3 - 4.5 hours?
• Design: RCT (n=821). rtPA (3 - 4.5h) vs Placebo.
• Result: Significant benefit in good outcome (mRS 0-1): 52% vs 45%. SICH rate 2.4%.
• Impact: Extended the lysis window to 4.5h. (Excluded age >80 and severe stroke NIHSS >25).

3. IST-3 (Third International Stroke Trial) - 2012

• Question: Is lysis safe/effective in patients >80 years?
• Design: Mega-trial (n=3035). Open label.
• Result: Benefit of lysis was maintained in the >80 age group.
• Impact: Removed the upper age limit for thrombolysis.

4. MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment) - 2015

• Question: Is Intra-arterial treatment (Thrombectomy) better than medical therapy alone for anterior circulation LVO?
• Design: RCT (n=500). Proximal occlusion (ICA/M1/M2). Within 6 hours.
• Result: Absolute increase in functional independence (mRS 0-2) of 13.5% (NNT 7).
• Impact: The "Big Bang" of stroke care. Established MT as standard of care. Followed by HERMES meta-analysis confirming benefit across 5 trials.

5. DAWN / DEFUSE-3 - 2018 (The Late Window)

• Question: Can we treat beyond 6 hours if tissue is salvageable?
• Design:
  • DAWN: 6-24h. Clinical-Core Mismatch (Severe deficit but small core on CTP/DWI).
  • DEFUSE-3: 6-16h. Perfusion Mismatch (Core <70ml, Ratio >1.8).
• Result:
  • DAWN: Functional independence 49% vs 13% (NNT 2.8!).
  • DEFUSE-3: Functional independence 45% vs 17%.
• Impact: Extended thrombectomy window to 24 hours for selected patients. Paradigm shift from "Clock-based" to "Tissue-based" selection.

6. WAKE-UP - 2018

• Question: Can we thrombolyse patients with unknown onset (specifically wake-up strokes)?
• Design: RCT. MRI selection (DWI Positive / FLAIR Negative).
• Result: Better functional outcome with Alteplase vs Placebo.
• Impact: Enabled IVT for wake-up strokes if MRI suggests onset <4.5h.

7. CHANCE / POINT - 2013 / 2018

• Question: Does Dual Antiplatelet Therapy (DAPT) reduce recurrence in minor stroke?
• Design:
  • CHANCE (China): High risk TIA or Minor Stroke (NIHSS ≤3). Aspirin + Clopidogrel vs Aspirin. Day 1-21.
  • POINT (International): Similar design.
• Result: Reduced risk of recurrent stroke at 90 days. Slightly higher haemorrhage risk in POINT (longer duration).
• Impact: Standardised DAPT (21 days) for minor stroke/TIA.

8. AcT (Alteplase compared to Tenecteplase) - 2022

• Question: Is Tenecteplase non-inferior to Alteplase?
• Design: Pragmatic registry-linked RCT (n=1600).
• Result: Tenecteplase non-inferior for functional outcome.
• Impact: accelerating shift to Tenecteplase (easier to administer).

9. INTERSTROKE - 2016

• Question: What causes stroke globally?
• Design: Case-control (32 countries).
• Result: 10 modifiable risk factors account for 90% of PAR (Population Attributable Risk).
• Factors: Hypertension (biggest), Inactivity, Lipids, Diet, Obesity, Smoking, Cardiac causes, Alcohol, Stress, Diabetes.

10. HAMLET / DESTINY II / DECIMAL

• Question: Effectiveness of Hemicraniectomy in malignant MCA infarction?
• Result: Survival benefit increased (mortality reduced from ~70% to ~30%). However, most survivors have mRS 3-4 (moderately severe disability).
• Impact: Life-saving procedure, but quality of life discussion essential with family.

"A stroke is often called a 'brain attack'. It happened because a blood clot blocked one of the main pipes (arteries) supplying blood to a specific part of your brain. Instead of oxygen and sugar reaching the brain cells, the supply was cut off.

Think of it like a garden hose being kinked—the plants (brain cells) beyond the kink stop getting water and start to wilt. The symptoms you experienced (like weakness or speech trouble) happened because that part of the brain stopped working.

What we did: We [gave a strong clot-busting drug / performed a procedure] to unkink the hose and restore blood flow. This gives the brain cells the best chance to recover.

What happens now:

1. Monitoring: We will watch you closely in the Stroke Unit to prevent complications.
2. Prevention: We are starting medications to thin your blood, lower your cholesterol, and control your blood pressure so this doesn't happen again.
3. Rehabilitation: The brain heals slowly. Our team of physiotherapists and speech therapists will work with you to retrain the brain pathways. Recovery is a marathon, not a sprint."

Common Exam Questions

1. "Describe the Bamford Classification."

• Key: Know the criteria for TACS, PACS, POCS, and LACS precisely. Don't forget visual fields and higher function.
• Trap: Calling a Lacunar stroke "symptoms only" - remember the anatomical correlates (internal capsule/pons).

2. "Contraindications to Thrombolysis (Absolute vs Relative)."

• Key: BP >185/110, Recent surgery, Anticoagulation (INR >1.7), Hx of ICH.
• Scenario: "Patient on Warfarin, INR 1.3... Lysis is OK!" (Cutoff is 1.7). "Patient on Apixaban last dose 4h ago... Lysis is NO! (Unless levels checked/reversed - usually mechanical thrombectomy preferred)".
• Relative: Recent minor surgery, seizure at onset, pregnancy.

3. "Management of malignant MCA syndrome."

• Key: Decompressive Hemicraniectomy. Timing <48h. Age usually <60.
• Rationale: Reduces mortality from 80% to 30%, but high morbidity risk remains (survival with disability).

4. "Secondary prevention with AF (1-3-6-12 Rule)."

• Key: DOAC (not warfarin) usually. Timing of start depends on NIHSS/Severity.
• Why delay? Risk of haemorrhagic transformation in friable tissue.

5. "Interpretation of CT Head."

• Key: "Loss of grey-white differentiation at the insular ribbon" (Early sign). "Hyperdense MCA sign". Exclude bleed. Calculate ASPECTS.

Viva Points

Scenario 1: The Wake-Up Stroke Examiner: "A 65M wakes up at 07:00 with right hemiplegia. Last seen well at 23:00. Fast positive. What do you do?" Candidate: "Activate Stroke Call. ABCs/Glucose. Non-con CT head to exclude bleed. Time of onset >4.5h by definition (using 'last seen well'). Eligibility for IVT is standard NO, BUT... I would request CT Perfusion or MRI (DWI-FLAIR mismatch). If mismatch present (small core, large penumbra) → Eligible for Thrombectomy (up to 24h) or potentially Lysis (WAKE-UP trial criteria). Refer to stroke centre."

Scenario 2: The BP Dilemma Examiner: "Acute Stroke, Left Hemiplegia. BP 210/110. CT: Ischaemic. Nurse asks if she should start GTN patch." Candidate: "Stop! Are we thrombolysing?

• If YES (candidate for lysis): We MUST lower BP <185/110 first. Use IV Labetalol 10-20mg bolus. If refractory despite treatment, we cannot lyse.
• If NO (too late / contraindication): Permissive Hypertension. Do NOT lower BP unless >220/120. Brain needs perfusion pressure to save the penumbra. Dropping BP will extend the infarct."

Scenario 3: The Young Stroke Examiner: "A 35F presents with TACS. No vascular risk factors. What is your differential for Aetiology?" Candidate: "In a young patient, I would look beyond atherosclerosis:

1. Dissection: Carotid/Vertebral (History of neck trauma/pain?).
2. Cardioembolic: PFO (Paradoxical embolus), Endocarditis.
3. Hypercoagulable: APLS, Factor V Leiden, OCP use.
4. Vasculitis: SLE, Takayasu.
5. Drugs: Cocaine. Investigation: Need TOE (for PFO), Vasculitis screen, Thrombophilia screen."

OSCE Station: Stroke Thrombolysis Call

Task: Take focused history from wife of patient with suspected stroke and determine eligibility for lysis. Crucial Questions:

1. Exact time "Last Seen Well"? (Not when found).
2. Any recent surgery / trauma / head injury (<3 months)?
3. Any history of brain bleeds?
4. Medications? (Blood thinners - Warfarin/DOACs?)
5. Recent GI bleed (<21 days)?
6. Pre-morbid function (mRS)? (Would we treat aggressively?)
7. Any seizure at onset?
8. Any suggestion of mimics (hypoglycaemia, migraine history)?

Common Mistakes

• Missed Hypoglycaemia: Creating a "Stroke Call" without checking BM.
• Treating Hypertension: Lowering BP in non-thrombolysed stroke (worsens ischaemia).
• Aspirin Loading: Giving 300mg Aspirin before CT excludes bleed (dangerous).
• NBM: Feeding a patient before swallow screen (aspiration risk).
• Glucose: Giving Dextrose fluids (worsens outcomes). Use Saline only.

MCQ Practice

Q1: Which of the following is an ABSOLUTE contraindication to thrombolysis? A. Age > 80 B. Seizure at onset C. BP 175/100 mmHg D. Platelet count 90,000 E. Previous ischaemic stroke 6 months ago Answer: D. Platelet count <100,000 is an absolute contraindication. Age >80 is NOT (IST-3). Seizure is relative/caution. BP <185/110 is acceptable. Previous stroke <3 months is absolute, >3 months is relative/allowed.

Q2: A patient has a right-sided hemiparesis (face/arm > leg) and Broca's aphasia. Which artery is occluded? A. Left ACA B. Right MCA C. Left MCA Superior Division D. Left MCA Inferior Division E. Left PCA Answer: C. Left hemisphere (Aphasia). MCA (Face/Arm>Leg). Broca's (Expressive) is Superior Division. Wernicke's is Inferior Division.

Q3: According to the ECASS III trial, what is the extended time window for IV thrombolysis? A. 3 hours B. 4.5 hours C. 6 hours D. 12 hours E. 24 hours Answer: B. 4.5 hours. NINDS established 3 hours. ECASS III extended to 4.5 hours.

Q4: A 60M presents with 'Locked-in Syndrome'. Which vessel is occluded? A. Basilar Artery (mid-pons) B. PCA C. PICA D. AICA E. Vertebral Artery Answer: A. Basilar artery occlusion causes infarction of the ventral pons, damaging corticospinal and corticobulbar tracts but sparing the reticular activating system (consciousness) and vertical eye movements (midbrain).

Q5: Which of the following is NOT part of the ABCD2 score? A. Age B. Blood Pressure C. Clinical Features D. Duration E. Echo findings Answer: E. ABCD2 includes Age, BP, Clinical features, Duration, Diabetes. It stratifies TIA risk.

Q6: What is the target blood pressure before thrombolysis? A. <220/120 B. <185/110 C. <160/90 D. <140/90 E. <130/80 Answer: B. <185/110 mmHg is the rigid cutoff for rtPA safety.

Q7: A patient with stroke develops fever (38.5C) on day 2. Most likely cause? A. Central fever B. Aspiration Pneumonia C. Drug reaction D. DVT E. UTI Answer: B. Aspiration pneumonia is the commonest cause of fever and death in the first week. Dysphagia screening is critical.

Q8: Management of symptomatic 80% carotid stenosis in a fit 70-year-old? A. Medical management only B. Carotid Endarterectomy within 2 weeks C. Carotid Endarterectomy within 3 months D. Carotid Stenting immediately E. Warfarin Answer: B. CEA within 2 weeks (ideally 48h) offers max benefit (NASCET).

Q9: Which thrombophilia is most associated with arterial stroke in young patients? A. Factor V Leiden B. Protein C deficiency C. Antiphospholipid Syndrome D. G20210A mutation E. Antithrombin deficiency Answer: C. APLS is a major cause of arterial thrombosis. Others are primarily venous.

Q10: Mechanism of Action of Alteplase? A. Direct Thrombin Inhibitor B. Factor Xa Inhibitor C. Tissue Plasminogen Activator (converts plasminogen to plasmin) D. Antiplatelet E. Vitamin K Antagonist Answer: C. tPA converts plasminogen to plasmin, which degrades fibrin clots.

• LVO: Large Vessel Occlusion (ICA, M1, Basilar). Target for thrombectomy.
• TICI: Thrombolysis in Cerebral Infarction score. Measures reperfusion success (2b/3 is goal).
• ASPECTS: Alberta Stroke Program Early CT Score. CT grading system.
• DWI: Diffusion Weighted Imaging. Sensitive MRI sequence for acute ischemia.
• ADC: Apparent Diffusion Coefficient. Differentiates acute stroke (dark) from shine-through.
• Penumbra: Salvageable brain tissue at risk.
• HASU: Hyperacute Stroke Unit.
• CEA: Carotid Endarterectomy.
• DAPT: Dual Antiplatelet Therapy.
• SICH: Symptomatic Intracranial Haemorrhage.

Last Reviewed: 2025-12-27 | MedVellum Editorial Team

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and current guidelines.