Acute Ischemic Stroke

Summary

Acute ischemic stroke (AIS) is the sudden onset of focal neurological deficit caused by occlusion of a cerebral artery, resulting in reduced perfusion and infarction of brain tissue. It accounts for ~85% of all strokes (the remainder being hemorrhagic). The core clinical principle is "time is brain" — roughly 1.9 million neurons are lost per minute of untreated large-vessel occlusion.

Overview & Pathophysiology

Definition

Acute ischemic stroke is an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction — i.e., objective evidence of ischemic tissue death (on imaging or pathology) or clinical deficits persisting >24 hours. This is distinguished from a transient ischemic attack (TIA), which is a transient episode of focal neurological dysfunction due to ischemia without acute infarction — deficits resolve completely (classically within 1 hour) and no infarction appears on imaging.

Epidemiology & Key Risk Factors

Stroke is the second leading cause of death worldwide and a leading cause of long-term adult disability. Ischemic stroke represents approximately 85% of all cerebrovascular events. Risk roughly doubles each decade after age 55, with most events occurring in patients >65 years. The top modifiable risk factors are:

• Hypertension (the single most important)
• Diabetes mellitus
• Dyslipidemia
• Atrial fibrillation (cardioembolic source)

Additional modifiable factors include smoking, carotid stenosis, obesity, and physical inactivity. Non-modifiable factors include age, prior stroke/TIA, family history, and certain ethnicities.

Etiology: The TOAST Classification

Ischemic stroke results from occlusion of a cerebral artery by thrombosis (local clot on atherosclerotic plaque), embolism (clot travelling from a proximal source, most often the heart or carotid), or systemic hypoperfusion (global low-flow producing watershed infarcts). The TOAST framework sorts causes by mechanism, which in turn dictates secondary prevention:

Pathophysiology

Arterial occlusion abruptly reduces cerebral blood flow (CBF). Neurons are exquisitely oxygen- and glucose-dependent, so within seconds of flow falling below ~10 mL/100 g/min the tissue begins to die:

1. Energy failure: loss of oxygen/glucose halts oxidative phosphorylation → ATP depletion → failure of the Na⁺/K⁺-ATPase pump.
2. Cytotoxic edema: Na⁺ and water flow intracellularly, causing cellular swelling — the basis of early hypodensity on CT and restricted diffusion on MRI.
3. Excitotoxicity: depolarisation triggers glutamate release; over-stimulation of NMDA receptors drives a massive influx of Ca²⁺.
4. Cell death cascade: intracellular Ca²⁺ activates proteases, phospholipases, and endonucleases, and generates free radicals → membrane breakdown, mitochondrial injury, apoptosis, and necrosis.

Two zones form around the occlusion: the ischemic core (CBF critically low, irreversibly infarcted) and the surrounding penumbra (perfused by collaterals, functionally impaired but viable). The penumbra is the therapeutic target — restoring flow before it converts to core is what reperfusion therapy achieves.

Diagnostic Approach & Clinical Syndromes

Clinical Recognition & Immediate Assessment

The hallmark is sudden onset of a focal neurological deficit that maps to a single vascular territory. Deficits are typically maximal at onset (embolic) or may stutter/progress (thrombotic). Headache and reduced consciousness are more suggestive of hemorrhage or large infarcts with edema.

Immediate bedside steps:

• Capillary blood glucose — mandatory; hypoglycemia is a classic stroke mimic and must be excluded/corrected immediately.
• NIHSS score — the National Institutes of Health Stroke Scale quantifies severity, guides therapy, and tracks progression. Refer to the full NIHSS scoring rubric for the 11 domains.
• Establish last-known-well time — critical for determining eligibility for reperfusion therapy.

Imaging: First-Line & Most Sensitive

Non-contrast CT (NCCT): the first-line imaging modality. Its primary role is to exclude hemorrhage before thrombolysis; in the hyperacute phase (<6 h) an ischemic infarct is often normal-appearing.

Early ischemic signs on NCCT (develop within hours):

• Hyperdense MCA sign — the thrombus itself visible within the occluded vessel (large-vessel occlusion).
• Loss of grey–white differentiation and insular ribbon sign.
• Sulcal effacement from early cytotoxic edema; frank hypodensity develops over 6–24 h.

Diffusion-weighted MRI (DWI): the most sensitive modality for early ischemia, detecting cytotoxic edema (restricted diffusion) within minutes — the closest thing to a gold standard for confirming acute infarction, though CT remains first-line for speed and hemorrhage exclusion.

CT angiography (CTA): identifies large-vessel occlusion (LVO) and is required to select patients for mechanical thrombectomy. CT perfusion (or MR perfusion/DWI mismatch) quantifies the core–penumbra mismatch and extends the thrombectomy window to 24 h in selected patients.

Etiological Workup

Laboratory: glucose, CBC, electrolytes, renal function, coagulation profile (INR/aPTT) before thrombolysis, lipid panel, HbA1c, troponin.

Cardiac: ECG ± telemetry to detect atrial fibrillation and recent MI (cardioembolic source). Echocardiography: for cardioembolic source (thrombus, valve disease, PFO, endocarditis).

Vascular: Carotid Doppler/CTA/MRA: to detect symptomatic carotid stenosis.

Cerebral Artery Syndromes

Localising the deficit to an arterial territory is a core exam skill. The cross-sectional distribution of the anterior, middle, and posterior cerebral artery territories explains why deficits are so predictable:

Special presentations: amaurosis fugax (transient monocular vision loss — a curtain descending over one eye) signals ipsilateral internal-carotid/ophthalmic artery disease. Posterior-circulation strokes classically produce the 5 D's — dizziness, diplopia, dysarthria, dysphagia, and dystaxia.

Stroke Mimics

Roughly 1 in 5 suspected strokes turns out to be a stroke mimic. Two conditions must be excluded immediately because they are rapidly reversible and can masquerade convincingly: hypoglycemia and seizure with post-ictal (Todd) paralysis. The most important distinction on the acute pathway remains ischemic vs. hemorrhagic stroke, resolved by non-contrast CT.

TIA is on this spectrum: identical presentation but with complete resolution and no infarction on imaging. TIA is a medical urgency because it carries high short-term stroke risk and mandates the same secondary-prevention workup.

Management (Acute & Long-Term)

The goal is to restore perfusion to the penumbra as fast as possible while avoiding hemorrhage. Management runs as a time-driven algorithm: exclude hemorrhage, then assess eligibility for thrombolysis and thrombectomy in parallel.

Acute Reperfusion Therapy

1. Step 1 — Stabilise & image: Secure ABCs, check capillary glucose, establish the last-known-well time, and obtain emergent non-contrast CT to exclude hemorrhage. Draw coagulation studies and cross-match blood.
2. Step 2 — IV thrombolysis (if ischemic, ≤4.5 h, no contraindication): Alteplase 0.9 mg/kg IV (max 90 mg) — give 10% as a bolus over 1 min, then the remainder infused over 60 min. Tenecteplase 0.25 mg/kg IV (max 25 mg) as a single bolus is an increasingly used alternative, especially before thrombectomy. Blood pressure must be <185/110 mmHg before lysis and kept <180/105 mmHg for 24 h after. Screen carefully for contraindications: prior intracranial hemorrhage, recent stroke/head trauma (≤3 mo), recent major surgery, active internal bleeding, BP refractory to treatment, platelets <100,000, INR >1.7, and current therapeutic anticoagulation. See the tPA inclusion and contraindication criteria and the absolute vs. relative contraindications to thrombolysis before dosing.
3. Step 3 — Mechanical thrombectomy (if large-vessel occlusion on CTA): Endovascular clot retrieval for proximal anterior-circulation LVO. The standard window is ≤6 h from onset; it extends to 24 h in selected patients with a favourable core–penumbra mismatch on perfusion imaging. Assess this eligibility independently of thrombolysis — the patient may get both.
4. Step 4 — If NOT a reperfusion candidate: Give aspirin 160–325 mg PO within 24–48 h (delay 24 h if thrombolysis was given).

Supportive Care (Acute Phase)

• Blood pressure (permissive hypertension): In acute ischemic stroke, do NOT aggressively lower blood pressure — elevated BP maintains penumbral perfusion. Treat only if BP >220/120 mmHg (non-thrombolysed), lowering cautiously by ~15% in the first 24 h. The threshold is much stricter — <185/110 before and <180/105 for 24 h after — only in patients receiving thrombolysis. فخ امتحاني: aggressive BP lowering in early stroke worsens ischemia.
• Glucose: target 140–180 mg/dL; treat both hypo- and hyperglycemia (both worsen outcome).
• Temperature: treat fever (>38 °C) with antipyretics; hyperthermia enlarges infarcts.
• Swallow screen before any oral intake — dysphagia risks aspiration pneumonia.
• VTE prophylaxis: intermittent pneumatic compression initially; add pharmacologic prophylaxis once hemorrhage is excluded/stable.
• Oxygen: supplemental O₂ only if SpO₂ <94%. Early mobilisation and rehabilitation.

Secondary Prevention

Guided by the etiology and started early to reduce recurrence:

• Antiplatelet therapy: Aspirin 81 mg PO daily long-term (or clopidogrel 75 mg daily if aspirin-intolerant). For minor stroke (NIHSS ≤3) or high-risk TIA, give dual antiplatelet (aspirin + clopidogrel) for 21 days, then continue a single agent.
• High-intensity statin: Atorvastatin 80 mg PO daily (target LDL <70 mg/dL) — reduces recurrent atherosclerotic events regardless of baseline cholesterol and is a cornerstone of secondary prevention.
• Anticoagulation for atrial fibrillation: a DOAC (e.g., apixaban 5 mg PO twice daily) or warfarin (INR 2–3); timing depends on infarct size (larger infarct → delay 24–48 h to reduce hemorrhagic transformation).
• Carotid revascularisation: Carotid endarterectomy for symptomatic 70–99% stenosis (ideally within 2 weeks); consider for 50–69% in selected patients. Not indicated for near-total (100%) occlusion.
• Risk-factor control: long-term BP control, glycemic control, smoking cessation, diet, and exercise.

Clinical pearl: This antiplatelet-plus-statin backbone is the answer expected even for a resolved event. A patient with a TIA and a carotid bruit and normal CT is managed with an antiplatelet agent and a statin, not thrombolysis, because deficits have already resolved.

Complications & Prognosis

Major Complications

Complications arise from the infarct itself, from reperfusion, and from prolonged immobility:

• Hemorrhagic transformation — bleeding into infarcted tissue; risk is highest with large infarcts, cardioembolic strokes, and after thrombolysis. Sudden neurological deterioration post-tPA mandates an urgent CT and reversal of thrombolysis.
• Cerebral edema & raised intracranial pressure (ICP) — including malignant MCA infarction, a leading cause of early death.
• Seizures — cortical infarcts; may be early (within 24–48 h) or late (post-stroke epilepsy).
• Aspiration pneumonia — from dysphagia; the leading medical complication and cause of fever.
• Venous thromboembolism — DVT/PE from immobility.
• Others: urinary tract infection, pressure ulcers, contractures/spasticity, shoulder subluxation, falls, and post-stroke depression.
• Recurrent stroke — highest in the early weeks, underscoring urgent secondary prevention.

Prognostic Factors

Outcome depends chiefly on infarct size and location, the baseline NIHSS (the single strongest early predictor of outcome), patient age, comorbidities, and — critically — the speed of reperfusion. Earlier thrombolysis and thrombectomy translate directly into better functional recovery.

• Recovery timeline: Neurological recovery is greatest in the first 3 months, when rehabilitation gains are maximal, and can continue more slowly for up to a year.
• Long-term disability: Roughly one-third of survivors are left with significant long-term disability, and a substantial proportion require assistance with daily activities.
• Recurrence risk: highest in the first weeks; markedly reduced by prompt, etiology-directed secondary prevention.
• Functional status: commonly tracked with the modified Rankin Scale (mRS) — a key outcome metric in stroke trials.

High-Yield Exam Pearls – نقاط مهمة للامتحانات

Recognition & Initial Assessment

• ~85% of strokes are ischemic. Non-contrast CT is first-line — its job is to exclude hemorrhage; DWI-MRI is the most sensitive test for early infarction.
• Always check glucose — hypoglycemia is the classic reversible stroke mimic.
• BE-FAST: Balance, Eyes, Face drooping, Arm weakness, Speech difficulty, Time. Any positive finding = activate stroke pathway and note the last-known-well time.

Vascular Territory Mapping

• ACA = leg ("A for Ankle") — contralateral leg weakness predominates.
• MCA = face + arm ("M for Mouth & Manus/hand") — the most common stroke distribution; eyes deviate toward the lesion.
• PCA = vision ("P for Pupils/vision") — homonymous hemianopia with macular sparing; motor usually spared.
• Posterior circulation = 5 D's: Dizziness, Diplopia, Dysarthria, Dysphagia, Dystaxia.

Etiology & Classification (TOAST)

• Large-artery atherosclerosis (~20%): in-situ thrombosis or artery-to-artery embolism; clue = stuttering onset, preceding TIA, carotid bruit.
• Cardioembolism (~20–25%): sudden maximal deficit, multiple territories, hemorrhagic transformation; AFib is the most common source.
• Small-vessel lacunar (~25%): lipohyalinosis of penetrating arteries in chronic HTN/DM; no cortical signs (no aphasia/neglect/hemianopia) — this is the key discriminator.
• Other determined (~5%): dissection, hypercoagulability, vasculitis.
• Cryptogenic (~25–30%): no identified cause; always consider occult AFib and PFO.

Pathophysiology: Core vs. Penumbra

• Ischemic core: CBF critically low, irreversibly infarcted — cannot be salvaged.
• Ischemic penumbra: hypoperfused but still-viable tissue, salvageable only if perfusion restored quickly — the entire rationale for thrombolysis and thrombectomy.
• Mechanism of neuronal death: energy failure → glutamate release → NMDA-receptor over-activation → massive Ca²⁺ influx → proteolytic cascade → apoptosis and necrosis.

Imaging Findings

• Hyperdense MCA sign on non-contrast CT = intraluminal thrombus / large-vessel occlusion — early sign that the patient is a candidate for thrombectomy.
• Loss of grey–white differentiation and sulcal effacement = early cytotoxic edema; frank hypodensity matures over 6–24 h.
• DWI hyperintensity = restricted diffusion, the earliest marker of infarction (gold standard for confirming acute infarction).

Thrombolysis (IV Alteplase/Tenecteplase)

• Alteplase: 0.9 mg/kg IV (max 90 mg) — 10% bolus over 1 min, remainder over 60 min. Window: ≤4.5 hours from symptom onset.
• Tenecteplase: 0.25 mg/kg IV (max 25 mg) as a single bolus — increasingly used, especially before thrombectomy.
• Blood pressure requirement: <185/110 mmHg before lysis; keep <180/105 mmHg for 24 h after.
• Key absolute contraindications: intracranial hemorrhage (ever), stroke/head trauma ≤3 mo, recent major surgery, active bleeding, refractory BP >185/110, platelets <100,000, INR >1.7, therapeutic anticoagulation.
• Watch for hemorrhagic transformation: sudden neurological deterioration post-tPA → emergent CT, stop infusion, consider reversal.

Mechanical Thrombectomy

• Indication: large-vessel occlusion (proximal anterior circulation) on CTA.
• Standard window: ≤6 hours from symptom onset.
• Extended window: ≤24 hours in selected patients with favourable core–penumbra mismatch on perfusion imaging (DAWN/DEFUSE-3 criteria).
• Independent eligibility: a patient within 4.5 h with LVO and no thrombolysis contraindication gets both tPA and thrombectomy — do not withhold one for the other.

Supportive Care & Blood Pressure Management

• Permissive hypertension: do NOT aggressively lower BP in early ischemic stroke. Elevated BP maintains penumbral perfusion.
• Non-thrombolysed patients: treat only if BP >220/120, lowering ~15% in first 24 h.
• Thrombolysed patients: stricter control — <185/110 before and <180/105 for 24 h after.
• Glucose target: 140–180 mg/dL. Treat both hypo- and hyperglycemia.
• Fever control: treat >38 °C; hyperthermia enlarges infarcts.
• Swallow assessment before oral intake to prevent aspiration.

Secondary Prevention (Long-Term)

• Antiplatelet backbone: Aspirin 81 mg PO daily (or clopidogrel 75 mg daily if intolerant). For minor stroke/high-risk TIA: dual antiplatelet (aspirin + clopidogrel) × 21 days, then single agent.
• High-intensity statin: Atorvastatin 80 mg PO daily (LDL target <70 mg/dL) — reduces recurrent events regardless of baseline lipids. Always use, even if cholesterol normal.
• Anticoagulation for AFib: DOAC (apixaban 5 mg PO BID) or warfarin (INR 2–3). Delay if large infarct (risk of hemorrhagic transformation).
• Carotid endarterectomy: symptomatic 70–99% stenosis (ideally ≤2 weeks); consider 50–69% in selected patients. NOT for 100% occlusion.

Complications & Special Scenarios

• Lacunar stroke: pure motor hemiparesis (all three limbs equally) + no cortical signs = penetrating artery territory (internal capsule). From lipohyalinosis in chronic HTN/DM.
• Malignant MCA infarction: large hemispheric stroke with cytotoxic edema peaking day 2–5 → raised ICP, declining consciousness, herniation. Decompressive hemicraniectomy within 48 h is life-saving, especially if ≤60 y. Do not confuse with new stroke: deterioration 2–4 days out is edema, not recurrence.
• Hemorrhagic transformation: bleeding into infarct; highest risk = large infarcts, cardioembolic strokes, post-tPA. Sudden deterioration → CT to confirm.
• Seizures: early (≤48 h) or late (post-stroke epilepsy); cortical infarcts at highest risk.
• Aspiration pneumonia: leading medical complication; mandatory swallow screen.
• TIA vs. stroke: identical presentation but deficits resolve completely and NO infarction on imaging. Still a medical urgency → secondary prevention workup required, but thrombolysis not indicated once deficits resolve.

Prognostic Indicators

• NIHSS score: the single strongest early predictor of functional outcome.
• Speed of reperfusion: earlier thrombolysis/thrombectomy = better recovery.
• Recovery timeline: greatest gains in first 3 months; can continue up to 1 year.
• Functional outcome: measured by modified Rankin Scale (mRS) — key trial endpoint.