Stroke and TIA (Adult)

1. Overview

Stroke is a medical emergency defined by the rapid onset of focal or global neurological deficit lasting more than 24 hours (or resulting in death) with no apparent cause other than vascular origin. A Transient Ischaemic Attack (TIA) shares the same clinical features but resolves within 24 hours (usually less than 1 hour) and lacks evidence of infarction on imaging. [1]

Stroke is the second leading cause of death globally and the leading cause of adult disability. It is fundamentally a disease of "Time" — for every minute an ischaemic stroke remains untreated, approximately 1.9 million neurons are lost. The management of stroke has undergone a revolutionary shift from supportive care to hyper-acute reperfusion, specifically Intravenous Thrombolysis (IVT) and Mechanical Thrombectomy (MT). [2]

Classification divides stroke into Ischaemic (85%) — caused by arterial occlusion from thromboembolism or small-vessel disease — and Haemorrhagic (15%) — caused by non-traumatic intracerebral or subarachnoid bleeding. Clinical differentiation is impossible without neuroimaging, making rapid access to CT/MRI the cornerstone of any stroke system. [3]

2. Epidemiology

Global Burden

• Incidence: 12 million new strokes annually worldwide.
• Prevalence: 1 in 4 adults over age 25 will have a stroke in their lifetime. [4]
• Mortality: Ischaemic stroke carries a 30-day mortality of ~10-15%, while Haemorrhagic stroke mortality is significantly higher (~40-50%).

Demographics

• Age: Incidence doubles for every decade after age 55.
• Sex: Men have higher age-specific incidence, but women have higher lifetime risk due to longer life expectancy.
• Ethnicity: Black and Hispanic populations have a higher incidence of intracerebral haemorrhage (ICH) and small-vessel disease, often linked to a higher prevalence of untreated hypertension. [5]

Modifiable Risk Factors

Hypertension is the single most important modifiable risk factor, contributing to ~50% of all strokes. Atrial Fibrillation (AF) increases stroke risk five-fold and is the primary driver of embolic "Large Vessel Occlusions" (LVOs).

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3. Aetiology & Pathophysiology

⚠️ THE 7-STEP MOLECULAR MECHANISM (Ischaemic Cascade)

1. Arterial Occlusion: A thrombus (local) or embolus (distant) occludes a cerebral artery, causing an immediate drop in Cerebral Blood Flow (CBF).
2. Bioenergetic Failure: When CBF falls below 10-15 mL/100g/min, ATP production ceases. The Na+/K+ ATPase pump fails, leading to the Ischaemic Core — an area of irreversible cell death within minutes.
3. The Ischaemic Penumbra: Surrounding the core is a "twilight zone" where CBF is reduced (20-35 mL/100g/min) but cellular integrity is maintained by collateral flow. This tissue is salvageable but will infarct if perfusion is not restored.
4. Excitotoxicity: Ischaemic neurons release massive amounts of Glutamate. This overactivates NMDA and AMPA receptors, causing a lethal influx of Calcium (Ca2+) into the cell.
5. Mitochondrial Dysfunction: Intracellular Ca2+ overload triggers the mitochondrial permeability transition pore (mPTP), leading to the release of pro-apoptotic factors (Cytochrome C) and the generation of Reactive Oxygen Species (ROS).
6. Oxidative Stress & Inflammation: ROS damage the blood-brain barrier (BBB). Microglia are activated, releasing pro-inflammatory cytokines (TNF-α, IL-1β) that worsen oedema and contribute to Hemorrhagic Transformation.
7. Resolution or Infarction: Reperfusion within the "Golden Window" (0-4.5h for IVT, up to 24h for MT) halts the cascade. Failure results in pan-necrosis of neurons, glia, and vessels. [6, 7]

Bamford (Oxford) Classification

Used to predict the anatomical site and prognosis:

• TACI (Total Anterior): 1) Hemiparesis/Sensory loss, 2) Homonymous Hemianopia, 3) Higher cortical dysfunction (e.g., Aphasia). (Mortality ~60%).
• PACI (Partial Anterior): 2 out of 3 TACI criteria.
• LACI (Lacunar): Pure motor, pure sensory, or ataxic hemiparesis. No cortical signs.
• POCI (Posterior): Cranial nerve palsy + contralateral motor/sensory deficit, cerebellar signs, or isolated hemianopia.

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4. Clinical Presentation

Sudden Onset Deficits (FAST)

• Face: Asymmetrical drooping.
• Arm: Unilateral weakness or drift.
• Speech: Slurred (Dysarthria) or incorrect word finding (Dysphasia).
• Time: Critical window for reperfusion.

Stroke Mimics (Must Exclude)

1. Hypoglycaemia: Must check fingerstick glucose on all stroke calls.
2. Todd's Paralysis: Post-ictal focal deficit.
3. Migraine Aura: Usually "positive" symptoms (flashing lights) rather than "negative" (loss of function).
4. Functional Neurological Disorder: Hoover's sign positive.

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5. Investigations

Hyper-acute Phase

• Non-Contrast CT Head (NCCT): The priority to exclude haemorrhage. Early ischaemic changes (loss of insular ribbon, dense MCA sign) may be subtle in the first 3-6 hours.
• CT Angiogram (CTA): Mandatory if Mechanical Thrombectomy is considered (looks for Large Vessel Occlusions).

The TIA Workup

• MRI Head (DWI): Far more sensitive than CT for small TIA-related infarcts.
• Carotid Doppler/CTA: To identify > 50% stenosis for potential carotid endarterectomy.
• Holter Monitor/Cardiac Patch: To detect paroxysmal AF.

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6. Management: The "Golden Window"

1. Intravenous Thrombolysis (IVT)

• Agent: Alteplase (0.9 mg/kg) or Tenecteplase.
• Window: Within 4.5 hours of "Last Seen Well."
• Exclusions: Recent major surgery, ICH on CT, active bleeding, anticoagulation with high INR.

2. Mechanical Thrombectomy (MT)

• Window: 0-6 hours standard. Up to 24 hours in selected patients with "perfusion-diffusion mismatch" (based on DAWN and DEFUSE-3 trials). [8]
• Target: Large vessel occlusions (e.g., Proximal MCA).

3. Haemorrhagic Stroke Management

• BP Control: Rapidly lower SBP to 130-140 mmHg (INTERACT-2 / ATTACH-2 evidence).
• Reversal: Prothrombin Complex Concentrate (PCC) for Warfarin; Idarucizumab for Dabigatran.

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7. Evidence: Landmark Trials

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8. Single Best Answer (SBA) Questions

Question 1

A 72-year-old female presents 2 hours after sudden left-sided weakness and aphasia. CT Head shows no haemorrhage. CTA shows an occlusion of the M1 segment of the right MCA. She is on no medications. What is the most appropriate management?

• A) IV Alteplase only
• B) Mechanical Thrombectomy only
• C) IV Alteplase followed by Mechanical Thrombectomy
• D) Aspirin 300mg and admission to Stroke Unit
• E) Carotid Endarterectomy within 24 hours
• Answer: C. In patients with LVO presenting within the 4.5h window, "bridging" therapy (IVT followed by MT) is the gold standard.

Question 2

Which molecular process is the primary driver of the "Ischaemic Core" during a stroke?

• A) Apoptosis
• B) Bioenergetic failure and Na+/K+ pump collapse
• C) Glutamate-mediated excitotoxicity in the penumbra
• D) Inflammatory cytokine release
• E) Free radical damage from reperfusion
• Answer: B. The core represents irreversible necrotic death due to the immediate failure of energy-dependent ion pumps.

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9. Viva Scenario: The "Unknown Onset" Stroke

Examiner: "A patient is brought in by family who found him weak at 8 AM. He was last seen normal at 11 PM the previous night. CT shows no bleed. Is he a candidate for reperfusion?"

Candidate:

1. The Challenge: This is a "Wake-up Stroke." The time of onset is unknown, potentially exceeding 4.5h for standard thrombolysis.
2. Advanced Imaging: I would perform MRI (DWI/FLAIR mismatch) or CT Perfusion.
3. Rationale: If the lesion is visible on DWI but not on FLAIR, it suggests the stroke is less than 4.5h old, and the WAKE-UP trial supports thrombolysis.
4. Thrombectomy: If CT Perfusion shows a large salvageable penumbra and a Large Vessel Occlusion, he is a candidate for Thrombectomy up to 24h as per DAWN criteria.

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10. Patient Explanation

"A stroke is often called a 'brain attack.' It happens when a blood vessel in the brain gets blocked by a clot, much like a heart attack. Part of your brain is currently starving for oxygen. We have two main ways to fix this: a 'clot-busting' drug to dissolve it, or a tiny mechanical tool to pull the clot out physically. Every minute we save improves your chance of walking and talking normally again. After this emergency phase, we will focus on 'secondary prevention'—medications for blood pressure and cholesterol to ensure this never happens again."

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11. References

1. Powers WJ, et al. Guidelines for the early management of patients with acute ischaemic stroke: 2019 update. Stroke. 2019. [PMID: 31662037]
2. Goyal M, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis (HERMES). Lancet. 2016. [PMID: 26895677]
3. Nogueira RG, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct (DAWN). N Engl J Med. 2018. [PMID: 29129659]
4. Hacke W, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischaemic stroke (ECASS III). N Engl J Med. 2008. [PMID: 18815396]
5. NICE NG128. Stroke and transient ischaemic attack in over 16 s: diagnosis and initial management. 2023. NICE

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Last Updated: 2026-01-05 | MedVellum Editorial Team