Ischaemic Stroke (Adult)

1. Overview

Ischaemic stroke is the sudden onset of focal neurological deficit resulting from arterial occlusion, leading to cerebral infarction. It represents approximately 85% of all strokes, with the remaining 15% being haemorrhagic. Ischaemic stroke is a medical emergency where time-critical intervention can mean the difference between complete recovery and permanent disability or death. [1,2]

The fundamental principle underpinning acute stroke management is "Time is Brain". Experimental studies have demonstrated that during a large vessel occlusion, approximately 1.9 million neurons, 14 billion synapses, and 12 km of myelinated fibres are lost every minute that reperfusion is delayed. [3] This highlights the critical importance of rapid recognition, imaging, and treatment initiation.

Management strategy hinges on rapid differentiation from haemorrhagic stroke via emergency CT imaging, followed by immediate consideration of reperfusion therapy with either intravenous thrombolysis (alteplase) or endovascular thrombectomy, depending on time from onset and vascular anatomy. Alongside acute reperfusion, comprehensive stroke unit care and aggressive secondary prevention are essential to optimise outcomes and prevent recurrence. [4,5]

Clinical Pearls

The Wake-Up Stroke Dilemma: When a patient awakens with stroke symptoms, the "time of onset" is defined as the last time they were witnessed to be neurologically normal (typically when they went to sleep). This frequently places patients outside the conventional 4.5-hour thrombolysis window. However, advanced imaging with MRI DWI-FLAIR mismatch or CT perfusion may identify patients with viable penumbra who can benefit from treatment. Additionally, these patients may still be eligible for mechanical thrombectomy up to 24 hours if imaging criteria are met. [6]

The Aspirin Hazard: NEVER administer aspirin before neuroimaging has definitively excluded intracranial haemorrhage. Antiplatelet therapy given to a patient with haemorrhagic stroke significantly increases haematoma expansion and mortality. All stroke protocols mandate CT brain before any antithrombotic agent.

Permissive Hypertension Philosophy: Blood pressure is often markedly elevated (180-220 mmHg systolic) in acute ischaemic stroke. This represents a physiological compensatory response to maintain cerebral perfusion pressure (CPP) in the face of arterial occlusion and impaired autoregulation. Aggressive BP lowering is contraindicated unless systolic exceeds 220 mmHg or diastolic exceeds 120 mmHg (or > 185/110 if thrombolysis is planned). Overzealous BP reduction can extend infarct into the penumbra and worsen outcomes. [7]

The Golden Hour: Although the thrombolysis window extends to 4.5 hours, outcomes are time-dependent. Treatment within 90 minutes of onset (the "golden hour") yields dramatically better outcomes than treatment at 4 hours. Door-to-needle times should be minimised aggressively.

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2. Epidemiology

Global Burden

Stroke is the second leading cause of death worldwide and the third leading cause of disability-adjusted life years (DALYs). The Global Burden of Disease study estimated 101 million prevalent stroke cases globally in 2019, with 12.2 million incident strokes annually. [1] Ischaemic stroke accounts for 62.4% of all new stroke events.

Demographics

Age: Incidence doubles for each decade after age 55. However, approximately 10-15% of ischaemic strokes occur in adults under 45 years ("young stroke"), where aetiologies differ (cervical artery dissection, patent foramen ovale with paradoxical embolism, antiphospholipid syndrome, inherited thrombophilia). [2]

Sex: Men have 25% higher incidence than women at younger ages, but women experience higher lifetime risk due to greater longevity and very advanced age stroke risk. Stroke is the leading cause of disability in women. [1]

Ethnicity: Stroke incidence is highest in Black, Hispanic, and South Asian populations compared to White populations, partly attributable to higher prevalence of hypertension and diabetes. [8]

Risk Factors

Risk factors are traditionally divided into modifiable and non-modifiable:

Non-Modifiable:

• Age (strongest predictor)
• Male sex
• Family history
• Ethnicity
• Prior stroke or TIA

Modifiable - Dominant Contributors:

1. Hypertension - Single most important risk factor, present in 70% of stroke patients. Each 10 mmHg increase in systolic BP is associated with a 30% increase in stroke risk. [7]

2. Atrial Fibrillation - Increases stroke risk 5-fold. AF-related strokes are typically more severe due to larger embolic burden. CHA₂DS₂-VASc score quantifies risk. [10]

3. Diabetes Mellitus - Increases risk 2-fold through multiple mechanisms (accelerated atherosclerosis, endothelial dysfunction, hypercoagulability).

4. Dyslipidaemia - Elevated LDL and low HDL increase atherosclerotic stroke risk.

5. Smoking - Doubles stroke risk; effect is dose-dependent and reversible within 5 years of cessation.

6. Obesity and Physical Inactivity - Independent risk factors that also contribute via hypertension and diabetes.

7. Excessive Alcohol Consumption - Heavy drinking (> 2 drinks/day) increases risk, while light-moderate consumption may be protective.

Modifiable - Other Contributors:

• Obstructive sleep apnoea
• Hyperhomocysteinaemia
• Migraine with aura (particularly in young women on oestrogen)
• Inflammatory conditions (SLE, rheumatoid arthritis, vasculitis)
• Recent infection (transient prothrombotic state)

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3. Aetiology and Pathophysiology

TOAST Classification of Ischaemic Stroke Aetiology

The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification remains the most widely used aetiological classification system:

1. Large Artery Atherosclerosis (20-25%)

• Stenosis or occlusion of major intracranial or extracranial arteries
• Most commonly affects carotid bifurcation, carotid siphon, middle cerebral artery (MCA), basilar artery
• Mechanisms: artery-to-artery embolism, in-situ thrombosis, haemodynamic insufficiency
• Risk factors: hypertension, diabetes, smoking, hyperlipidaemia

2. Cardioembolism (20-25%)

• Embolus from cardiac source
• High-risk sources: atrial fibrillation (50% of cardioembolic strokes), mechanical prosthetic valve, recent MI with LV thrombus, dilated cardiomyopathy with EF less than 30%, infective endocarditis, atrial myxoma
• Medium-risk sources: patent foramen ovale (PFO), atrial septal aneurysm, mitral valve prolapse
• Typically produces larger infarcts with higher haemorrhagic transformation risk

3. Small Vessel Disease / Lacunar (20-25%)

• Occlusion of small penetrating arteries (lenticulostriate, pontine perforators, thalamoperforators)
• Pathology: lipohyalinosis or microatheroma affecting vessels 40-200 μm diameter
• Produces small (less than 15 mm) deep infarcts ("lacunes") in basal ganglia, internal capsule, thalamus, pons
• Classical lacunar syndromes: pure motor hemiparesis, pure sensory stroke, ataxic hemiparesis, dysarthria-clumsy hand syndrome
• Risk factors: hypertension (dominant), diabetes

4. Stroke of Other Determined Aetiology (5-10%)

• Arterial dissection (carotid or vertebral) - common in young adults, suspect with neck pain/trauma
• Vasculitis (primary CNS vasculitis, secondary to SLE, GCA, PAN)
• Prothrombotic states: antiphospholipid syndrome, protein C/S deficiency, factor V Leiden
• Haematological: sickle cell disease, polycythaemia, thrombocytosis
• Mitochondrial disorders: MELAS, Fabry disease
• CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
• Drug-related: cocaine, amphetamines, oral contraceptives

5. Cryptogenic / Undetermined Aetiology (25-35%)

• No cause identified despite comprehensive workup
• Embolic Stroke of Undetermined Source (ESUS) - subset with non-lacunar stroke, no proximal arterial stenosis, no major cardioembolic source
• Often attributed to undetected paroxysmal AF or paradoxical embolism through PFO

Pathophysiology of Cerebral Ischaemia

Exam Detail: Cerebral Blood Flow Thresholds:

Normal cerebral blood flow (CBF) is 50-60 mL/100g/min. The brain has limited glycogen stores and is exquisitely sensitive to ischaemia:

• Normal CBF: 50-60 mL/100g/min - normal neuronal function
• Oligaemia: 35-50 mL/100g/min - mild flow reduction, compensated by increased oxygen extraction
• Penumbra: 20-35 mL/100g/min - electrically silent but metabolically viable tissue; neurones cease firing but maintain membrane potential and can recover if reperfused
• Infarction threshold: less than 20 mL/100g/min - energy failure, loss of ionic homeostasis, irreversible injury within minutes
• Core infarct: less than 10 mL/100g/min - immediate necrosis

The Ischaemic Penumbra Concept:

The penumbra is the zone surrounding the infarct core where CBF is reduced below the threshold for electrical function but above the threshold for immediate cell death. It represents tissue that is:

• Functionally impaired (contributing to clinical deficits)
• Metabolically viable (salvageable)
• Destined to infarct without intervention
• Potentially recoverable with reperfusion

The penumbra can persist for several hours (sometimes up to 24 hours with good collaterals), creating the therapeutic window for reperfusion therapies. Advanced imaging (CT perfusion, MRI PWI-DWI mismatch) can identify penumbra and guide treatment beyond conventional time windows. [6]

Ischaemic Cascade:

1. Energy Failure (seconds-minutes): ATP depletion, failure of Na⁺-K⁺-ATPase pump
2. Ionic Imbalance: Cellular depolarisation, Na⁺ and Ca²⁺ influx, K⁺ efflux
3. Excitotoxicity: Excessive glutamate release, NMDA receptor overactivation, further Ca²⁺ influx
4. Oxidative Stress: Free radical generation, mitochondrial dysfunction
5. Inflammation: Microglial activation, cytokine release (IL-1, TNF-α), neutrophil infiltration
6. Blood-Brain Barrier Disruption: Vasogenic oedema, risk of haemorrhagic transformation
7. Apoptosis: Programmed cell death in penumbral zone over hours-days

Cerebral Oedema After Stroke:

Oedema evolves over 3-5 days post-stroke and is the primary cause of early neurological deterioration:

• Cytotoxic oedema (first 24 hours): Intracellular water accumulation from pump failure
• Vasogenic oedema (days 2-5): Extracellular water from BBB breakdown
• Malignant MCA Syndrome: Massive oedema from large MCA territory infarction (> 50% of MCA territory) causing midline shift, transtentorial herniation, and death in 80% of cases without decompressive hemicraniectomy

Collateral Circulation

The brain has remarkable collateral capacity that determines penumbra survival:

Circle of Willis: Anterior communicating artery connects ACAs; posterior communicating arteries connect anterior and posterior circulation. Anatomical variants are common (complete in only 40-50% of population).

Leptomeningeal Collaterals: Pial anastomoses between MCA, ACA, and PCA territories. Superior collaterals correlate with better outcomes and larger penumbra. [3]

Haemodynamic Stroke: In severe carotid stenosis or occlusion with poor collaterals, watershed infarcts occur at the border zones between vascular territories (ACA-MCA, MCA-PCA) during systemic hypotension.

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4. Clinical Presentation

The cardinal feature is sudden onset of focal neurological deficit. Unlike other neurological conditions that evolve gradually, stroke deficits are maximal at onset. Symptoms correspond to the vascular territory affected.

Vascular Territory Syndromes

Anterior Circulation (Carotid Territory):

Middle Cerebral Artery (MCA) - Most Common

Superior Division MCA:

• Contralateral face and arm weakness (hand > arm > leg)
• Contralateral sensory loss (face and arm)
• Gaze deviation toward the lesion (frontal eye field)
• Dominant hemisphere (usually left): Broca's aphasia (expressive, non-fluent)
• Non-dominant hemisphere (usually right): hemineglect, anosognosia, constructional apraxia

Inferior Division MCA:

• Dominant hemisphere: Wernicke's aphasia (receptive, fluent but meaningless speech)
• Contralateral superior quadrantanopia (temporal lobe)

Complete MCA:

• Global aphasia (if dominant)
• Contralateral hemiplegia (face, arm, leg)
• Contralateral hemisensory loss
• Contralateral homonymous hemianopia
• Gaze deviation
• High risk of malignant oedema

Anterior Cerebral Artery (ACA)

• Contralateral leg > arm weakness (motor cortex supplies leg on medial surface)
• Contralateral leg sensory loss
• Abulia, apathy (frontal lobe dysfunction)
• Urinary incontinence
• Grasp reflex, primitive reflexes

Internal Carotid Artery (ICA)

• May be asymptomatic if Circle of Willis complete
• If symptomatic: combination of MCA and ACA territory
• May have ipsilateral monocular visual loss (amaurosis fugax) from ophthalmic artery involvement
• Watershed infarcts in severe stenosis

Posterior Circulation (Vertebrobasilar Territory):

Posterior Cerebral Artery (PCA)

• Contralateral homonymous hemianopia with macular sparing (dual blood supply to occipital pole)
• Alexia without agraphia (if dominant hemisphere with splenium of corpus callosum)
• Visual agnosia, prosopagnosia (if bilateral)
• Memory impairment (hippocampus)
• Thalamic syndromes if proximal occlusion (thalamoperforators involved)

Vertebrobasilar System

• Diplopia, dysarthria, dysphagia, vertigo (brainstem cranial nerve nuclei)
• Crossed signs: ipsilateral cranial nerve deficits with contralateral limb weakness/sensory loss
• Ataxia (cerebellar)
• Locked-in syndrome (ventral pontine infarct): quadriplegia and anarthria with preserved consciousness and vertical eye movements
• Top of basilar syndrome: bilateral PCA infarcts, confusion, amnesia, visual deficits

Classic Brainstem Syndromes (Viva Favourites):

Lacunar Syndromes:

These result from small vessel occlusion and produce pure motor or sensory deficits without cortical signs (no aphasia, neglect, or visual field defects):

1. Pure Motor Hemiparesis (most common): Face, arm, and leg weakness from internal capsule or pons lacune
2. Pure Sensory Stroke: Hemisensory loss from thalamic lacune
3. Ataxic Hemiparesis: Weakness with ipsilateral limb ataxia (internal capsule or pons)
4. Dysarthria-Clumsy Hand Syndrome: Facial weakness, dysarthria, mild hand weakness (pons)
5. Sensorimotor Stroke: Combined motor and sensory deficit (thalamus and internal capsule)

Bamford (Oxford) Clinical Classification

This bedside classification predicts prognosis, vascular territory, and infarct size:

1. Total Anterior Circulation Stroke (TACS) - Requires ALL 3:

• Unilateral weakness AND/OR sensory deficit (face, arm, leg)
• Homonymous hemianopia
• Higher cortical dysfunction (aphasia in dominant hemisphere, neglect in non-dominant)
• Territory: Proximal MCA or ICA occlusion
• Prognosis: Worst (60% dead or dependent at 1 year)

2. Partial Anterior Circulation Stroke (PACS) - Requires 2 of 3 TACS criteria OR isolated higher cortical dysfunction:

• Territory: Branch MCA occlusion
• Prognosis: Intermediate (30% dead or dependent)

3. Lacunar Stroke (LACS) - Requires 1 of the 5 lacunar syndromes AND no cortical signs:

• Territory: Perforating arteries (basal ganglia, internal capsule, thalamus, pons)
• Prognosis: Best (10% dead or dependent at 1 year, but high recurrence risk)

4. Posterior Circulation Stroke (POCS) - Requires ANY 1:

• Cranial nerve palsy with contralateral motor/sensory deficit (crossed signs)
• Bilateral motor and/or sensory deficit
• Conjugate eye movement disorder (gaze palsy, internuclear ophthalmoplegia)
• Cerebellar dysfunction (ataxia, nystagmus, vertigo)
• Isolated homonymous hemianopia
• Territory: Vertebrobasilar
• Prognosis: Variable (20% dead or dependent, but high early recurrence risk)

FAST Recognition Tool (Prehospital)

A public health campaign mnemonic for recognising stroke:

• Face: Facial droop, ask to smile
• Arms: Arm drift, ask to raise both arms
• Speech: Slurred or garbled speech
• Time: Time to call emergency services (999/911)

FAST has 90% sensitivity for stroke recognition by paramedics and bystanders. However, it misses approximately 10% of strokes, particularly posterior circulation strokes (no arm weakness, facial droop, or speech disturbance).

Additional Clinical Clues

Sudden severe headache: Unusual in ischaemic stroke (less than 20% of cases) but can occur with:

• Posterior circulation stroke
• Carotid/vertebral dissection (neck pain too)
• Haemorrhagic transformation
• Large infarct with significant oedema

Seizure at onset: Occurs in less than 5% of ischaemic strokes but more common with cortical infarcts and cardioembolic aetiology. Increases risk of subsequent post-stroke epilepsy.

Level of consciousness: Typically preserved in ischaemic stroke unless:

• Basilar artery occlusion (coma, locked-in state)
• Large bihemispheric strokes
• Malignant MCA syndrome with herniation
• Unwitnessed fall with head injury

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5. Differential Diagnosis (Stroke Mimics)

Approximately 20-30% of suspected strokes admitted to hyperacute stroke units are ultimately diagnosed with stroke mimics. Accurate differentiation is critical because thrombolysis in stroke mimics exposes patients to unnecessary bleeding risk.

Major Stroke Mimics

Critical Differentiation Point - Bell's Palsy vs Stroke:

• UMN (Stroke): Forehead spared (can wrinkle forehead and close eye) due to bilateral corticobulbar innervation of upper face
• LMN (Bell's palsy): Entire hemiface affected including forehead (cannot wrinkle forehead or fully close eye)

ROSIER Score (Recognition of Stroke in Emergency Room):

Used in emergency departments to distinguish stroke from mimics:

Score > 0 suggests stroke (sensitivity 92%, specificity 86%).

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6. Investigations

The primary objective is immediate differentiation of ischaemic from haemorrhagic stroke, followed by identification of stroke mechanism and secondary prevention targets.

Immediate (Hyperacute - Within 10 Minutes of Arrival)

1. Capillary Blood Glucose

• Purpose: Exclude hypoglycaemia (can mimic stroke exactly)
• Action: If less than 4 mmol/L, give IV glucose and reassess neurology

2. ECG

• Purpose: Identify atrial fibrillation (present in 20% of ischaemic strokes)
• Also detects MI as stroke cause or complication

3. Blood Tests (do not delay imaging):

• FBC (polycythaemia, thrombocytosis, anaemia)
• Coagulation (INR if on warfarin - affects thrombolysis eligibility)
• U&Es, creatinine (renal function)
• Glucose (formal lab confirmation)
• Lipid profile
• Troponin (MI association)

Emergency Neuroimaging (Door-to-Scan Target: less than 30 Minutes)

Non-Contrast CT Brain - First-Line Gold Standard

Purpose:

• Excludes haemorrhage (absolute thrombolysis contraindication)
• Excludes stroke mimics (tumour, subdural)
• Identifies early ischaemic changes
• Estimates stroke age

Findings:

Haemorrhage: Hyperdense (white) - immediate exclusion from thrombolysis

Ischaemic stroke (time-dependent):

• 0-6 hours: CT may be normal (most common finding) or show subtle early signs:
  • Loss of grey-white matter differentiation
  • Insular ribbon sign (loss of definition of insular cortex)
  • Hyperdense MCA sign (thrombus in vessel appears bright)
  • Subtle sulcal effacement
• 6-24 hours: Hypodense (dark) area in vascular territory
• 24-48 hours: Well-defined hypodensity with mass effect
• Days-weeks: Hypodensity shrinks, encephalomalacia

ASPECTS (Alberta Stroke Program Early CT Score):

• 10-point scoring system for early ischaemic changes in MCA territory
• 1 point deducted for each region with hypoattenuation
• Score ≤7 predicts poor functional outcome and higher haemorrhagic transformation risk
• Used to guide thrombectomy decisions [11]

CT Angiography (CTA) - Performed Immediately After Non-Contrast CT

Purpose:

• Identifies large vessel occlusion (LVO) - determines thrombectomy candidacy
• Assesses collateral circulation
• Identifies carotid stenosis/dissection

Findings:

• Vessel cut-off sign (occlusion of ICA, M1, M2, basilar)
• Collateral grading (good collaterals = larger penumbra)

CTA is mandatory if thrombectomy is being considered (i.e., all patients presenting within 6-24 hours).

CT Perfusion (CTP) - Optional for Extended Window

Purpose:

• Identifies ischaemic penumbra (salvageable tissue)
• Guides treatment beyond conventional time windows
• Informs thrombectomy decisions 6-24 hours from onset [6]

Parameters:

• CBF (cerebral blood flow): Flow to tissue
• CBV (cerebral blood volume): Blood in tissue
• MTT (mean transit time): Time for blood to traverse tissue
• Ttp (time to peak): Time to peak enhancement

Penumbra identification: MTT/Tmax prolongation with preserved CBV

Mismatch ratio: Tmax > 6s volume / core infarct volume > 1.8 indicates significant penumbra

Advanced/Alternative Imaging

MRI Brain with Diffusion-Weighted Imaging (DWI)

Advantages over CT:

• Detects hyperacute ischaemia within minutes (appears bright on DWI)
• More sensitive for small infarcts (especially posterior fossa)
• Identifies stroke age (DWI-FLAIR mismatch: if DWI positive but FLAIR negative, stroke is less than 4.5 hours old - used for wake-up strokes) [6]
• Differentiates acute from chronic infarcts

Disadvantages:

• Takes longer (30-45 mins vs 5 mins for CT)
• Less available out-of-hours
• Contraindications (pacemakers, claustrophobia)

MRI is preferred for:

• Posterior circulation strokes (brainstem/cerebellum)
• Young stroke workup (higher resolution, better tissue characterisation)
• Wake-up stroke with DWI-FLAIR mismatch protocol

Gradient Echo (GRE) / Susceptibility-Weighted Imaging (SWI): Detects microhaemorrhages, helps assess bleeding risk before anticoagulation.

Secondary Prevention Workup (Within 48 Hours)

Identify Stroke Mechanism to Guide Prevention:

1. Vascular Imaging - Identify Large Artery Stenosis

Carotid Doppler Ultrasound:

• First-line for carotid artery assessment
• Measures stenosis severity (% stenosis by NASCET criteria)
• > 50% symptomatic stenosis warrants consideration for carotid endarterectomy or stenting
• > 70% symptomatic stenosis has strong evidence for surgery [12]

CT Angiography (neck to circle of Willis) or MR Angiography:

• More detailed vascular anatomy
• Identifies dissection (intimal flap, tapered narrowing, "string sign")
• Assesses intracranial stenosis

2. Cardiac Imaging - Identify Cardioembolic Source

Transthoracic Echocardiogram (TTE):

• Assesses LV function (thrombus risk if EF less than 30%)
• Valve pathology (stenosis, regurgitation, vegetations)
• Regional wall motion abnormalities (recent MI)

Transoesophageal Echocardiogram (TOE) with Bubble Study:

• Superior for:
  • Patent foramen ovale (PFO) detection in young stroke
  • Left atrial appendage thrombus (if AF present)
  • Aortic arch atheroma
  • Valve vegetations (endocarditis)
• Bubble study: Inject agitated saline, look for bubbles crossing from RA to LA (PFO)

Prolonged Cardiac Monitoring:

• 72-hour Holter monitor (detects paroxysmal AF in 5% additional patients)
• Implantable loop recorder (detects paroxysmal AF in 10-30% of cryptogenic strokes over months)
• Indicated in cryptogenic stroke to detect occult AF [13]

3. Haematological/Thrombophilia Screen (Selected Patients)

Only perform in:

• Young patients (less than 50 years)
• No obvious cause
• Family history of thrombosis
• Recurrent thrombotic events

Tests:

• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein)
• Protein C, Protein S, Antithrombin III
• Factor V Leiden, Prothrombin G20210A mutation
• Homocysteine level
• Sickle cell screen (if appropriate ethnicity)

4. Vasculitis/Inflammatory Screen (If Suspected)

• ESR, CRP
• ANA, ANCA, complement levels
• Cerebral angiography or high-resolution vessel wall MRI (if primary CNS vasculitis suspected)

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7. Classification/Staging

Stroke Severity - NIHSS (National Institutes of Health Stroke Scale)

The NIHSS is a 15-item standardised neurological examination score (0-42 points) that quantifies stroke severity. It is used to:

• Guide treatment decisions (thrombolysis, thrombectomy)
• Predict outcomes
• Monitor progression
• Standardise communication

Thrombolysis is indicated for NIHSS > 4 (disabling deficit) and generally avoided for NIHSS less than 4 (risk outweighs benefit).

Thrombectomy is considered for NIHSS ≥6 with confirmed large vessel occlusion.

Modified Rankin Scale (mRS) - Functional Outcome Measure

Used to assess disability at 90 days post-stroke (primary endpoint in trials):

Good outcome = mRS 0-2 (independent) Poor outcome = mRS 3-6 (dependent or dead)

CHA₂DS₂-VASc Score (Stroke Risk in Atrial Fibrillation)

Guides anticoagulation decisions in patients with AF:

Score 0 (male) or 1 (female): Consider no anticoagulation or aspirin Score 1 (male) or 2 (female): Consider anticoagulation Score ≥2 (male) or ≥3 (female): Anticoagulation recommended (DOAC or warfarin)

For stroke patients with AF, they automatically have a score ≥2, making anticoagulation mandatory for secondary prevention.

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8. Management

Acute stroke management follows a structured pathway focused on reperfusion (restore blood flow), stroke unit care (organised multidisciplinary management), and secondary prevention (prevent recurrence).

Management Algorithm

               SUSPECTED STROKE (FAST positive)
                         ↓
         EMERGENCY AMBULANCE (Pre-alert stroke team)
                         ↓
              ED ARRIVAL - Start clock
                         ↓
           ┌─────────────────────────────┐
           │  IMMEDIATE (Within 10 min)  │
           │  • Glucose (exclude hypo)   │
           │  • IV access                │
           │  • Bloods (FBC, U&E, INR)   │
           │  • ECG (AF?)                │
           │  • Brief history (onset     │
           │    time, anticoagulants)    │
           └──────────┬──────────────────┘
                      ↓
           ┌──────────────────────────────────┐
           │  CT BRAIN (Non-contrast)         │
           │  Target: Door-to-scan less than 30 min    │
           └──────────┬───────────────────────┘
                      ↓
         ┌────────────┴────────────┐
         │                         │
    HAEMORRHAGE              NO HAEMORRHAGE
         │                    (ISCHAEMIC)
         ↓                         ↓
   Neurosurgery          Confirm Time of Onset
   consultation          Calculate from last seen well
         │                         ↓
         │              ┌──────────┴──────────────┐
         │              │                         │
         │         less than 4.5 HOURS              4.5-24 HOURS
         │              ↓                         ↓
         │    ┌─────────────────────┐    CT ANGIOGRAPHY
         │    │ THROMBOLYSIS?       │    (LVO present?)
         │    │ Check eligibility:  │            ↓
         │    │ • No contraindic.   │    ┌───────┴────────┐
         │    │ • Disabling deficit │    │                │
         │    │ • BP less than 185/110       │   YES              NO
         │    │ • INR less than 1.7          │    ↓                ↓
         │    │ • Platelets > 100    │ THROMBECTOMY?   Aspirin 300mg
         │    └──────┬──────────────┘ (if 6-24
h:         ↓
         │           ↓                check CT          Supportive
         │    IV ALTEPLASE           perfusion for       Care
         │    0.9 mg/kg (max 90mg)   penumbra) [6]       │
         │    10% bolus, 90% over    Clot retrieval      │
         │    60 mins                device               │
         │           │                     ↓              │
         │           └──────────┬──────────┘              │
         │                      ↓                         │
         │              ┌───────────────────┐             │
         │              │  POST-REPERFUSION │             │
         │              │  Wait 24h before  │             │
         │              │  starting aspirin │             │
         │              │  (bleeding risk)  │             │
         │              └────────┬──────────┘             │
         │                       │                        │
         └───────────────────────┴────────────────────────┘
                                 ↓
                   ┌─────────────────────────────┐
                   │     STROKE UNIT CARE        │
                   │  • Swallow screen (NBM      │
                   │    until passed)            │
                   │  • Permissive hypertension  │
                   │    (allow up to 220/120)    │
                   │  • Aspirin 300mg x 14 days  │
                   │  • Statin 80mg              │
                   │  • VTE prophylaxis          │
                   │  • Early mobilisation       │
                   │  • MDT rehabilitation       │
                   │  • Secondary prevention     │
                   │    workup                   │
                   └─────────────────────────────┘

1. Acute Reperfusion Therapy

Exam Detail: A. Intravenous Thrombolysis (Alteplase - Recombinant Tissue Plasminogen Activator)

Mechanism: Converts plasminogen to plasmin, which degrades fibrin clot.

Eligibility Criteria:

• Clinical diagnosis of ischaemic stroke with measurable deficit
• Onset less than 4.5 hours (or wake-up stroke with DWI-FLAIR mismatch showing less than 4.5h) [6]
• Age: No upper age limit (benefit proven even > 80 years)
• NIHSS typically ≥4 (disabling deficit)
• CT brain excludes haemorrhage

Dose: 0.9 mg/kg (maximum 90 mg)

• 10% as IV bolus over 1 minute
• Remaining 90% as infusion over 60 minutes

Blood Pressure Requirements:

• Must be less than 185/110 mmHg before starting thrombolysis
• Maintain less than 180/105 mmHg for 24 hours after thrombolysis
• Use labetalol or nicardipine if needed to lower BP

Major Contraindications (Absolute):

• Intracranial haemorrhage on CT
• Significant head trauma or stroke within 3 months
• Intracranial or intraspinal surgery within 3 months
• GI bleed or major surgery within 21 days
• Arterial puncture at non-compressible site within 7 days
• Current anticoagulation with INR > 1.7 or PT > 15 seconds
• Current use of DOAC within 48 hours (unless normal coagulation tests)
• Platelets less than 100,000/mm³
• Glucose less than 2.7 mmol/L (treat hypoglycaemia first)
• Active bleeding or known bleeding diathesis
• Suspected aortic dissection
• Bacterial endocarditis

Relative Contraindications (Assess Risk-Benefit):

• Minor or rapidly improving symptoms
• Seizure at stroke onset
• Recent MI within 3 months
• Pregnancy
• NIHSS > 25 (very severe stroke - higher haemorrhage risk)

Efficacy: Thrombolysis increases odds of good outcome (mRS 0-1) by 75% if given within 90 minutes, decreasing to 20% increased odds at 4.5 hours. Absolute benefit is approximately 10-13% increase in independent survival (Number Needed to Treat = 8-10). [4]

Complications:

• Symptomatic intracranial haemorrhage (sICH): 6-7% (vs 1% without thrombolysis)
• Systemic bleeding: 2-3%
• Angioedema (orolingual): 1-5% (more common with ACE inhibitor use)
• Haemorrhagic transformation of infarct: 15% (usually asymptomatic)

Post-Thrombolysis Care:

• Neuro observations every 15 minutes for 2 hours, then 30 minutes for 6 hours, then hourly for 16 hours
• Any deterioration: Stop infusion, stat CT brain (to exclude haemorrhage)
• No antiplatelets or anticoagulants for 24 hours post-lysis
• Avoid NG tube, urinary catheter, arterial puncture for 24 hours
• CT brain at 24 hours to exclude haemorrhage before starting antiplatelet

Tenecteplase: Newer single-bolus thrombolytic agent showing non-inferiority to alteplase with easier administration. Increasingly used in some centres. [14]

Exam Detail: B. Mechanical Thrombectomy (Endovascular Clot Retrieval)

Revolution in Stroke Care: Five landmark trials in 2015 (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT) proved overwhelming benefit of thrombectomy for large vessel occlusion. [15] This is one of the most effective treatments in all of medicine: Number Needed to Treat = 2-3 for good functional outcome.

Indications:

• Large vessel occlusion (LVO) on CTA:
  • Internal carotid artery (ICA)
  • Middle cerebral artery M1 or proximal M2 segment
  • Basilar artery
• Presentation within 6 hours of onset (standard window), or
• Presentation within 6-24 hours with evidence of salvageable penumbra on CT/MR perfusion imaging [6]
• NIHSS typically ≥6
• Pre-stroke mRS ≤1 (previously independent)
• ASPECTS ≥6 (limited early ischaemic changes)

Procedure:

• Femoral artery puncture under local anaesthetic or sedation
• Catheter advanced to site of occlusion
• Stent-retriever device or aspiration catheter used to extract clot
• Goal: TICI 2b-3 reperfusion (≥50% territory reperfused)
• Procedure time typically 30-90 minutes

Efficacy:

• 71% achieve mRS 0-2 (good outcome) with thrombectomy vs 40% with medical therapy alone
• Absolute benefit: 31% increase in functional independence
• Benefit maintained even in patients > 80 years old
• NNT = 3 for one additional patient to achieve functional independence [15]

Complications:

• Symptomatic intracranial haemorrhage: 4-6%
• Vessel dissection/perforation: 1-2%
• Embolisation to new territory: 2-5%
• Groin haematoma: 2-3%

Thrombectomy PLUS Thrombolysis: If patient presents within 4.5 hours and has LVO, give IV thrombolysis immediately ("drip and ship") and proceed to thrombectomy. Combined therapy is superior to either alone. [15]

Extended Window Thrombectomy (6-24 Hours): The DAWN and DEFUSE-3 trials showed benefit up to 24 hours from onset IF perfusion imaging (CT or MR perfusion) demonstrates large penumbra (mismatch between ischaemic core and hypoperfused tissue). [6] This transformed care for wake-up strokes.

2. Hyperacute Medical Management (First 24-48 Hours)

Blood Pressure Management - Permissive Hypertension

• DO NOT lower BP acutely unless systolic > 220 or diastolic > 120 mmHg
• Rationale: Cerebral autoregulation is impaired in acute stroke; BP reduction decreases perfusion to penumbra
• Exception: If thrombolysing, must maintain less than 180/105 mmHg to reduce haemorrhage risk
• If BP lowering required: Use short-acting IV agents (labetalol, nicardipine)
• Restart chronic antihypertensives at 48-72 hours once stable [7]

Glucose Management

• Target 4-11 mmol/L
• Hyperglycaemia (> 11 mmol/L) worsens ischaemic injury and outcomes
• Hypoglycaemia must be treated immediately (mimics stroke and worsens injury)
• Use insulin sliding scale if persistently > 11 mmol/L

Temperature

• Treat fever aggressively (paracetamol, cooling)
• Pyrexia > 37.5°C worsens outcomes (increases metabolic demand)
• Hypothermia trials have not shown benefit (unlike cardiac arrest)

Dysphagia Screening - Critical Safety Measure

• Screen ALL patients before any oral intake ("Nil by mouth until swallow screen passed")
• 50% of acute stroke patients have dysphagia
• Aspiration pneumonia is the leading cause of death in first week post-stroke
• Use validated screening tool (e.g., water swallow test)
• If failed: NPO, IV fluids, urgent SALT (Speech and Language Therapy) assessment
• Consider NG tube if prolonged dysphagia (reduces pneumonia vs oral intake)

Venous Thromboembolism Prophylaxis

• Immobile stroke patients are at high risk of DVT/PE (10-20% develop DVT)
• Mechanical: Intermittent pneumatic compression devices or anti-embolic stockings (if legs not paralysed)
• Pharmacological: Low-dose LMWH (enoxaparin 40 mg SC daily) starting at 24-48 hours if:
  • No haemorrhagic transformation on 24h CT
  • Not anticoagulated already
  • Immobile
• Full treatment-dose anticoagulation if DVT/PE confirmed

Aspirin - Antiplatelet Therapy

• Dose: 300 mg daily for 14 days, then 75 mg daily (or switch to clopidogrel 75 mg)
• Timing: Start immediately if NOT thrombolysed. If thrombolysed, wait 24 hours (after CT excludes haemorrhage).
• Mechanism: Reduces early recurrence risk (10% at 1 week without treatment)
• Evidence: IST and CAST trials showed aspirin within 48 hours reduces recurrence and improves outcomes [9]
• Contraindications: Haemorrhagic stroke, active bleeding, severe thrombocytopaenia

Statin Therapy

• Start immediately: Atorvastatin 80 mg at night
• Rationale: Pleiotropic effects (plaque stabilisation, anti-inflammatory, endothelial function) beyond lipid-lowering
• Evidence: Reduces recurrent stroke by 30% (SPARCL trial) [16]
• Safe in acute phase: No increased haemorrhagic transformation risk

3. Stroke Unit Care

Organised Stroke Unit vs General Ward: Stroke unit care reduces death or dependency by 25% compared to general ward care. [5] This is one of the most powerful interventions in stroke medicine.

Components of Stroke Unit Care:

1. Specialised nursing staff trained in stroke care
2. Multidisciplinary team:
   • Stroke physicians
   • Physiotherapists (early mobilisation, gait re-education)
   • Occupational therapists (ADL assessment, home adaptations)
   • Speech and language therapists (dysphagia, aphasia)
   • Dietitians
   • Social workers
   • Psychologists (post-stroke depression, cognitive rehabilitation)
3. Protocols for dysphagia screening, mobilisation, VTE prophylaxis
4. Early rehabilitation (mobilise within 24 hours if safe)
5. Monitoring for complications
6. Education for patients and families
7. Discharge planning and secondary prevention

Length of Stay: Median 5-7 days for uncomplicated ischaemic stroke.

4. Complications and Their Management

Decompressive Hemicraniectomy - Critical Viva Topic:

• Indication: Malignant MCA syndrome (> 50% MCA territory infarct) with progressive decline in GCS
• Timing: Within 48 hours of symptom onset (benefit proven up to 48h, not beyond)
• Age: Most benefit in patients less than 60 years (DECIMAL, DESTINY, HAMLET trials) [17]
• Procedure: Large craniectomy, duraplasty
• Outcome: Reduces mortality from 80% to 30%, but survivors have moderate-severe disability (mRS 3-4); reduces very severe disability (mRS 5)
• Consent: Discuss with family early; decision must be made rapidly

5. Secondary Prevention (Prevent Recurrence)

Recurrence Risk Without Prevention: 10% at 1 week, 15% at 1 year, 30% at 5 years.

With Optimal Secondary Prevention: Risk reduced by 80%.

Exam Detail: A. Antiplatelet Therapy

First-Line: Clopidogrel 75 mg daily (lifelong)

• Superior to aspirin for long-term secondary prevention (CAPRIE trial: 8.7% relative risk reduction vs aspirin) [9]
• Start after initial 14 days of aspirin 300 mg
• Prodrug; requires CYP2C19 metabolism (20% of population are poor metabolisers with reduced efficacy)

Alternative: Aspirin 75 mg + Dipyridamole MR 200 mg BD

• Non-inferior to clopidogrel (ESPRIT trial)
• More side effects (headache from dipyridamole)
• Used if clopidogrel not tolerated

Dual Antiplatelet Therapy (Aspirin + Clopidogrel) - Short-Term Only

• Used for 21 days after high-risk TIA or minor stroke (NIHSS ≤3)
• CHANCE and POINT trials showed benefit in first 3 weeks, but increased bleeding beyond 21 days [18]
• NOT used long-term

Aspirin Alone (75 mg daily)

• Third-line if clopidogrel and aspirin-dipyridamole not tolerated
• Less effective than clopidogrel

Exam Detail: B. Anticoagulation (for Cardioembolic Stroke)

Indications:

• Atrial fibrillation (most common indication)
• Mechanical heart valve
• Left ventricular thrombus
• Dilated cardiomyopathy with EF less than 30%

First-Line: Direct Oral Anticoagulants (DOACs)

Preferred over warfarin due to:

• Superior efficacy (30% relative risk reduction vs warfarin for stroke prevention in AF)
• Lower intracranial haemorrhage risk
• No monitoring required
• Fewer drug interactions
• Fixed dosing

Options:

• Apixaban 5 mg BD (reduce to 2.5 mg BD if 2 of: age ≥80, weight ≤60 kg, creatinine ≥133 μmol/L)
• Rivaroxaban 20 mg daily (reduce to 15 mg if CrCl 30-49)
• Edoxaban 60 mg daily (reduce to 30 mg if CrCl 30-50, weight ≤60 kg, or on P-glycoprotein inhibitor)
• Dabigatran 150 mg BD (reduce to 110 mg BD if age > 80, high bleeding risk)

Warfarin:

• Second-line (if DOAC contraindicated or mechanical valve)
• Target INR 2-3 (2.5-3.5 for mechanical valve)
• Requires regular monitoring

Timing of Anticoagulation After Stroke - Critical Decision:

The risk of haemorrhagic transformation must be balanced against recurrent embolism risk.

General Rule (based on stroke size):

• Small stroke (less than 1.5 cm): Start at 3 days
• Moderate stroke: Start at 6 days
• Large stroke (> 1.5 cm or involving > 1/3 MCA territory): Start at 12-14 days
• Very large/haemorrhagic transformation: Delay further, individualise

1-3-6-12 Day Rule: Small (1 day), moderate (3-6 days), large (12 days) - commonly cited but evidence is limited. [13]

Bridging Anticoagulation: NOT recommended (LMWH while waiting to start warfarin/DOAC). Increases bleeding without reducing recurrent stroke.

C. Carotid Intervention (for Symptomatic Carotid Stenosis)

Indications (ECST and NASCET trials) [12]:

• Symptomatic carotid stenosis > 50% (moderate benefit)
• Symptomatic carotid stenosis > 70% (strong benefit - NNT = 6 for stroke prevention over 5 years)
• "Symptomatic" = stroke or TIA in carotid territory within 6 months

Timing: Operate within 2 weeks of index event (maximal benefit when recurrence risk highest). Waiting > 2 weeks loses much of the benefit.

Options:

1. Carotid Endarterectomy (CEA) - Gold Standard

   • Open surgical removal of plaque
   • Perioperative stroke/death risk: 3-5%
   • Highly effective: 65% relative risk reduction for recurrent ipsilateral stroke [12]
   • Preferred in younger patients, favourable anatomy

2. Carotid Artery Stenting (CAS)

   • Endovascular approach
   • Higher perioperative stroke risk than CEA in older patients (> 70 years)
   • Preferred in: hostile neck (previous surgery/radiotherapy), high surgical risk, tandem lesions

Contraindications to Surgery:

• Chronic total occlusion (no benefit)
• Asymptomatic stenosis in most patients (less clear benefit; guidelines vary)
• Life expectancy less than 5 years

D. Blood Pressure Control (Long-Term)

• Target: less than 130/80 mmHg (AHA/ASA 2021 guidelines) or less than 140/90 mmHg (NICE)
• Reduces recurrent stroke risk by 30% [7]
• Any antihypertensive is effective; ACE inhibitor + thiazide diuretic combination (perindopril + indapamide) has best evidence (PROGRESS trial)

E. Lipid Management

• Target: LDL-C less than 1.8 mmol/L (or > 50% reduction from baseline)
• Therapy: High-intensity statin (atorvastatin 80 mg)
• Reduces recurrent stroke by 30% (SPARCL trial) [16]
• Continue even if cholesterol "normal" (pleiotropic benefit)

F. Diabetes Control

• Target HbA1c less than 53 mmol/mol (7%)
• Intensive glucose control reduces microvascular but not macrovascular complications
• Address other risk factors aggressively (BP, lipids, antiplatelet)

G. Lifestyle Modification

• Smoking cessation: Halves stroke risk within 5 years
• Alcohol: Limit to ≤14 units/week
• Weight loss: Target BMI less than 25 kg/m²
• Exercise: ≥150 minutes moderate-intensity aerobic activity per week
• Diet: Mediterranean diet, low salt (less than 6 g/day)

H. Patent Foramen Ovale (PFO) Closure

• Consider in patients less than 60 years with cryptogenic stroke and PFO with atrial septal aneurysm or large shunt
• Percutaneous device closure reduces recurrent stroke by 50% compared to medical therapy (CLOSE, RESPECT, REDUCE trials)
• Not indicated in older patients or those with alternative stroke mechanism

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9. Prognosis and Outcomes

Mortality

Leading Causes of Death:

1. Pneumonia (aspiration)
2. Cardiac complications (MI, arrhythmia)
3. Recurrent stroke
4. Pulmonary embolism
5. Cerebral oedema/herniation (first week)

Functional Outcomes at 3-6 Months

Prognostic Factors

Poor Prognosis:

• Advanced age (> 80 years)
• Severe initial deficit (NIHSS > 20)
• Large infarct volume (> 50% MCA territory)
• Haemorrhagic transformation
• Posterior circulation location (basilar occlusion has 75% mortality)
• Atrial fibrillation (larger emboli, worse outcomes)
• Pre-existing disability
• Comorbidities (diabetes, heart failure, renal failure)

Good Prognosis:

• Young age (less than 65 years)
• Lacunar stroke (LACS subtype)
• Rapid treatment (thrombolysis less than 90 mins, thrombectomy)
• Good collaterals
• No comorbidities
• Strong social support

Recovery Timeline

• First 3 months: Most rapid recovery (80% of neuroplasticity occurs in this window)
• 3-6 months: Continued but slower improvement
• 6-12 months: Plateau for most patients
• Beyond 1 year: Minimal further motor recovery, but adaptive strategies continue to develop

Neuroplasticity: The brain's ability to reorganise and form new neural connections. Enhanced by:

• Early intensive rehabilitation
• Task-specific repetitive practice
• Constraint-induced movement therapy
• Enriched environment, social stimulation
• Pharmacotherapy (SSRIs may enhance recovery)

Recurrence Risk

Secondary Prevention Impact: Optimal medical therapy (antiplatelet/anticoagulation, statin, BP control) reduces 5-year recurrence risk from 40% to 8-10% (80% relative risk reduction).

Long-Term Complications

• Post-stroke depression: 30-50%; treat with SSRIs
• Post-stroke dementia: 10-30% develop dementia within 5 years (vascular dementia)
• Post-stroke epilepsy: 10% develop seizures (higher risk with cortical involvement, haemorrhagic transformation)
• Post-stroke pain (central post-stroke pain syndrome): 10%; neuropathic pain from thalamic lesions; treat with amitriptyline, gabapentin, or pregabalin
• Spasticity: 20-40%; treat with physiotherapy, baclofen, or botulinum toxin
• Shoulder subluxation: Common after hemiplegia; requires physiotherapy, supportive devices

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10. Prevention and Screening

Primary Prevention

For General Population:

• BP screening and treatment (target less than 140/90)
• Lipid screening in adults > 40 years; statin if 10-year CVD risk > 10%
• Diabetes screening and management
• Smoking cessation
• Maintain healthy weight (BMI less than 25)
• Regular physical activity (≥150 mins/week)
• Mediterranean diet

For High-Risk Populations (e.g., AF):

• Anticoagulation based on CHA₂DS₂-VASc score
• Aggressive risk factor modification

Screening for Asymptomatic Carotid Stenosis: NOT recommended in general population (low yield, unclear benefit of prophylactic surgery). Consider in high-risk individuals (e.g., pre-CABG).

Secondary Prevention

See Management Section 5 (above) - comprehensive strategy targeting all modifiable risk factors.

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11. Key Guidelines

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12. Examination Focus

Common MRCP Exam Questions

1. Imaging Question: "A CT brain shows a hyperdense structure in the right MCA. What does this indicate, and what is the next step?"

• Answer: Hyperdense MCA sign indicates acute thrombus in the middle cerebral artery. This suggests a large vessel occlusion. Next step is CT angiography to confirm and assess for thrombectomy candidacy if within the time window.

2. Management Question: "A 68-year-old presents 3 hours after sudden left hemiplegia. CT shows no haemorrhage. BP is 195/105. What is your management?"

• Answer: This patient is within the thrombolysis window. Blood pressure is elevated but less than 220/120, which is expected in acute stroke (permissive hypertension). However, for thrombolysis, BP must be less than 185/110. I would cautiously lower BP with IV labetalol to less than 185/110, then administer IV alteplase 0.9 mg/kg (10% bolus, 90% over 60 minutes) after confirming no contraindications. Simultaneously, perform CT angiography to assess for large vessel occlusion and thrombectomy candidacy.

3. Anatomy Question: "A patient has weakness affecting the left leg more than the left arm, with no facial involvement. Which vascular territory is affected?"

• Answer: Right anterior cerebral artery (ACA). The ACA supplies the motor cortex on the medial surface of the cerebral hemisphere, which controls the contralateral leg. MCA supplies the lateral surface (face and arm).

4. Classification Question: "A 72-year-old has right-sided weakness, right homonymous hemianopia, and expressive aphasia. Using the Bamford classification, how would you categorise this stroke?"

• Answer: Total Anterior Circulation Stroke (TACS). The patient has all three criteria: (1) unilateral weakness, (2) homonymous hemianopia, and (3) higher cortical dysfunction (expressive aphasia). This indicates proximal MCA or ICA occlusion and carries a poor prognosis.

5. Secondary Prevention Question: "A 55-year-old had an ischaemic stroke. Carotid Doppler shows 80% stenosis ipsilateral to the stroke. What is your recommendation?"

• Answer: This is symptomatic carotid stenosis > 70%, which has strong evidence for surgical intervention. I would recommend carotid endarterectomy within 2 weeks of the stroke (while recurrence risk is highest). The NASCET trial showed NNT = 6 to prevent one stroke over 5 years. Ensure patient is on optimal medical therapy (antiplatelet, statin, BP control) and assess surgical fitness.

6. Complication Question: "Day 3 post large MCA stroke, GCS drops from 15 to 9. What is the likely cause and management?"

• Answer: Malignant MCA syndrome with cerebral oedema causing raised intracranial pressure and herniation. This typically occurs 3-5 days post-stroke. Urgent CT brain to confirm midline shift. If age less than 60 and within 48 hours of deterioration, refer for decompressive hemicraniectomy (reduces mortality from 80% to 30%). Meanwhile, head elevation 30°, osmotherapy (mannitol or hypertonic saline), and supportive care.

7. Wake-Up Stroke Question: "A patient wakes at 7am with aphasia and right hemiplegia. They were last seen well at 11pm. Are they eligible for thrombolysis?"

• Answer: Time of onset is defined as last seen well (11pm), making it 8 hours from onset. This exceeds the conventional 4.5-hour window. However, the patient may still be eligible for treatment using advanced imaging. MRI with DWI-FLAIR mismatch (DWI positive but FLAIR negative indicates less than 4.5 hours) could identify thrombolysis candidates. Additionally, if CT perfusion or MR perfusion shows significant penumbra, the patient may be eligible for thrombectomy up to 24 hours (DAWN/DEFUSE-3 criteria).

Viva Points

Viva Point: Opening Statement: "Ischaemic stroke is the acute onset of focal neurological deficit due to arterial occlusion, leading to cerebral infarction. It accounts for 85% of all strokes and is the second leading cause of death globally. Time-critical reperfusion therapy with thrombolysis or thrombectomy can dramatically improve outcomes."

Key Facts to Mention:

1. Epidemiology: 12.2 million strokes annually worldwide; lifetime risk 1 in 4; 85% are ischaemic. [1]

2. Time is Brain: 1.9 million neurons die per minute during large vessel occlusion, hence the critical importance of rapid treatment. [3]

3. TOAST Classification: 5 aetiological subtypes - large artery atherosclerosis, cardioembolism, small vessel disease, other determined, and cryptogenic.

4. Thrombolysis: IV alteplase 0.9 mg/kg within 4.5 hours increases odds of good outcome by 75% if given within 90 minutes (NNT = 8-10 for functional independence). [4]

5. Thrombectomy: For large vessel occlusion within 6-24 hours (with imaging selection beyond 6h). NNT = 3 for functional independence - one of the most effective treatments in medicine. [6,15]

6. Stroke Unit Care: Reduces death or dependency by 25% compared to general ward. [5]

7. Secondary Prevention: Optimal medical therapy reduces 5-year recurrence from 40% to 8-10%. Includes antiplatelet/anticoagulation, high-dose statin, BP control, and carotid endarterectomy for symptomatic stenosis > 70%. [12,16]

8. Carotid Endarterectomy: For symptomatic stenosis > 70% within 2 weeks (NNT = 6 over 5 years). [12]

Management Algorithm: "I would approach a suspected stroke patient with ABC assessment, immediate glucose check to exclude hypoglycaemia, and stat CT brain within 30 minutes. If CT excludes haemorrhage and onset is within 4.5 hours with no contraindications, I would administer IV alteplase. Simultaneously, I would obtain CTA to identify large vessel occlusion and refer for thrombectomy if present and within 24 hours with perfusion imaging evidence of penumbra. Post-reperfusion, the patient would receive stroke unit care with dysphagia screening, permissive hypertension, aspirin (after 24 hours if thrombolysed), high-dose statin, VTE prophylaxis, and early mobilisation. Secondary prevention workup includes carotid Doppler, ECG, prolonged cardiac monitoring, and echocardiogram to identify mechanism and guide prevention."

Common Mistakes in Exams

❌ Giving aspirin before CT brain: NEVER give antiplatelet or anticoagulant before imaging excludes haemorrhage. This is a dangerous error.

❌ Aggressively lowering BP in acute stroke: Permissive hypertension (allow up to 220/120) is the standard approach unless thrombolysing. Dropping BP extends infarct.

❌ Confusing Bell's palsy with stroke: Bell's palsy is LMN (forehead involved, cannot close eye). Stroke is UMN (forehead spared, can close eye and wrinkle forehead).

❌ Starting oral anticoagulation immediately in AF-related stroke: Risk of haemorrhagic transformation. Delay based on infarct size (typically 3-14 days).

❌ Thrombolysis beyond 4.5 hours without advanced imaging: Standard thrombolysis window is 4.5 hours. Beyond this requires DWI-FLAIR mismatch or clinical trial enrolment.

❌ Missing indications for decompressive hemicraniectomy: Age less than 60, large MCA infarct, GCS drop, within 48 hours. This is life-saving. Delays are fatal.

❌ Not screening for dysphagia: Aspiration pneumonia is the leading cause of death. All stroke patients must be NBM until swallow screen passed.

❌ Stating "stroke" without specifying ischaemic vs haemorrhagic: Always differentiate. Management is completely different.

Model Answers

Q: Describe your approach to a patient presenting with sudden onset right arm weakness and slurred speech.

A: "I would approach this systematically as a suspected acute stroke. First, I would perform an ABC assessment to ensure airway patency and haemodynamic stability. Immediately, I would check capillary blood glucose to exclude hypoglycaemia, which can mimic stroke. I would obtain a focused history including exact time of onset (or last seen well), current medications (particularly anticoagulants), and stroke risk factors.

On examination, I would assess using the NIHSS to quantify deficit severity and FAST criteria for rapid stroke recognition. I would arrange urgent bloods (FBC, U&Es, coagulation, glucose, lipids), ECG to screen for atrial fibrillation, and stat non-contrast CT brain within 30 minutes to exclude haemorrhage.

If CT shows no haemorrhage and the patient is within 4.5 hours of onset with a disabling deficit (NIHSS ≥4) and no contraindications, I would administer IV alteplase 0.9 mg/kg after ensuring BP less than 185/110 mmHg. Simultaneously, I would obtain CT angiography to identify any large vessel occlusion suitable for thrombectomy.

Following acute treatment, I would admit to the stroke unit for specialist care including dysphagia screening (nil by mouth until passed), permissive hypertension (avoid lowering BP unless > 220/120), aspirin 300 mg daily (starting 24 hours after thrombolysis or immediately if not thrombolysed), atorvastatin 80 mg, VTE prophylaxis, and early mobilisation.

For secondary prevention, I would investigate stroke mechanism with carotid Doppler ultrasound, prolonged cardiac monitoring for paroxysmal AF, and echocardiography. Based on findings, I would optimise secondary prevention with antiplatelet therapy (clopidogrel 75 mg long-term), anticoagulation if AF present, carotid endarterectomy if symptomatic stenosis > 70%, and aggressive vascular risk factor modification."

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13. Patient and Layperson Explanation

What is a Stroke?

A stroke is like a heart attack, but it happens in your brain. Just as a blocked artery in the heart causes a heart attack, a blocked artery in the brain causes a stroke. When blood flow to part of the brain is suddenly cut off, brain cells start dying within minutes because they aren't getting oxygen and nutrients.

There are two main types of stroke:

1. Ischaemic stroke (85%): A blood clot blocks an artery in the brain
2. Haemorrhagic stroke (15%): A blood vessel bursts and bleeds into the brain

How Do I Recognise a Stroke? (FAST)

Remember FAST:

• Face: Does one side of the face droop? Ask them to smile.
• Arms: Can they raise both arms and keep them up? Does one drift down?
• Speech: Is their speech slurred or jumbled? Can they repeat a simple sentence?
• Time: If you see ANY of these signs, call 999 (or 911) immediately.

Time is critical. Every minute counts because millions of brain cells are dying. The sooner treatment starts, the better the chances of recovery.

What Happens in Hospital?

1. Emergency scan: You'll have a CT scan of your brain within minutes. This tells doctors if you've had an ischaemic or haemorrhagic stroke (the treatments are completely different).

2. Clot-busting treatment (if you arrive quickly): If you arrive within 4.5 hours and the scan shows an ischaemic stroke, you may receive a clot-busting drug called alteplase through a drip. This dissolves the clot and restores blood flow.

3. Mechanical clot removal: For some patients with larger clots, doctors can physically remove the clot using a thin tube inserted through the groin (similar to a heart stent procedure). This can work up to 24 hours after the stroke started.

4. Stroke unit care: You'll be looked after by a specialist stroke team including doctors, nurses, physiotherapists, speech therapists, and occupational therapists.

What Treatment Will I Get?

Immediately:

• Blood-thinning tablets (aspirin, then clopidogrel) to prevent another clot
• Cholesterol-lowering tablets (statins) to stabilise plaque in arteries
• Swallow assessment (to check it's safe to eat and drink - very important to prevent chest infections)
• Blood pressure monitoring (we usually keep it a bit higher than normal initially to help blood flow to the brain)

Longer-term:

• Medications to control blood pressure, cholesterol, and blood sugar
• Possibly blood-thinning medication if you have an irregular heartbeat (atrial fibrillation)
• Possibly surgery on the neck artery (carotid endarterectomy) if there's a severe blockage

Will I Recover?

Every stroke is different, and recovery varies widely:

• Some people make a complete recovery
• Some have permanent weakness, speech difficulties, or other disabilities
• The brain has an amazing ability to "rewire" itself (called neuroplasticity), especially in the first 3-6 months

Rehabilitation is crucial. Physiotherapy, speech therapy, and occupational therapy help you relearn skills and adapt to any disabilities.

Most recovery happens in the first 3 months, but improvement can continue for a year or more. Your effort in rehabilitation makes a huge difference.

How Can I Prevent Another Stroke?

Having one stroke significantly increases your risk of another (10-15% risk in the first year without treatment). But you can reduce this risk by 80% with:

1. Taking your medications every day: Don't skip doses. These dramatically reduce your risk.
2. Controlling blood pressure: Aim for less than 140/90
3. Stopping smoking: This halves your risk within 5 years
4. Healthy diet: Mediterranean-style diet with lots of vegetables, fish, olive oil
5. Regular exercise: Aim for 30 minutes of walking most days
6. Limiting alcohol: No more than 14 units per week
7. Maintaining healthy weight: Aim for BMI under 25
8. Attending follow-up appointments: Regular monitoring is essential

What About Driving?

You cannot drive for at least 1 month after a stroke. You must inform the DVLA (or your country's licensing authority). You can usually resume driving after 1 month if you've made a good recovery, but this must be assessed by your doctor.

Key Message

Stroke is a medical emergency. The faster you get treatment, the better your chances of recovery. If you or someone you know shows ANY signs of stroke, call 999 immediately. Time is brain.

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14. References

Primary Sources

1. GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795-820. doi:10.1016/S1474-4422(21)00252-0

2. 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. doi:10.1161/STR.0000000000000211

3. Saver JL. Time is brain—quantified. Stroke. 2006;37(1):263-266. doi:10.1161/01.STR.0000196957.55928.ab

4. Emberson J, Lees KR, Lyden P, et al; Stroke Thrombolysis Trialists' Collaborative Group. 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. doi:10.1016/S0140-6736(14)60584-5

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6. Nogueira RG, Jadhav AP, Haussen DC, et al; DAWN Trial Investigators. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018;378(1):11-21. doi:10.1056/NEJMoa1706442

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