Acute Ischemic Stroke

Pathophysiology

• Collateral blood flow (dictated by vascular anatomy, site of occlusion, and systemic BP)
• Duration of ischemia

• Cerebral blood flow to zero → death of brain tissue (neurons, dendrites, axons, glia) within 4-10 min
• CBF <16-18 mL/100 g tissue/min → infarction within an hour
• CBF <20 mL/100 g tissue/min → ischemia without infarction unless prolonged

1. Reduced glucose and O2 delivery → decreased ATP production
2. Membrane ion pumps fail → cells depolarize → intracellular Na+ and Ca2+ rise
3. Glutamate released from synaptic terminals; glial uptake fails → sustained extracellular glutamate elevation
4. Postsynaptic glutamate receptor activation → neuronal Ca2+ influx → reactive oxygen species (ROS) production
5. ROS damage DNA, lipid membranes, and cell functions
6. Innate immune response within hours: microglial activation + circulating immune cell infiltration
7. Postischemic inflammation → protease and ROS release → further tissue injury

• Fever dramatically worsens ischemic brain injury
• Hyperglycemia (glucose >11.1 mmol/L / 200 mg/dL) is harmful - prevent and treat

Initial Evaluation

1. ABCs - airway, breathing, circulation
2. Finger-stick glucose - treat hypoglycemia or hyperglycemia immediately
3. Emergent non-contrast head CT - distinguish ischemic from hemorrhagic stroke

No clinical finding conclusively separates ischemia from hemorrhage, but:

• Depressed consciousness, high initial BP, worsening after onset → favor hemorrhage
• Deficit maximal at onset, or remits → suggests ischemia

Treatment Categories (6 Pillars)

1. Medical support
2. IV thrombolysis
3. Endovascular revascularization
4. Antithrombotic treatment
5. Neuroprotection
6. Stroke centers and rehabilitation

1. Medical Support

• Goal: optimize cerebral perfusion to the ischemic penumbra
• Prevent complications: pneumonia, UTI, pressure sores, DVT, pulmonary embolism
• Subcutaneous heparin (UFH or LMWH) is safe concurrently; pneumatic compression stockings are proven for DVT prevention

• BP should be reduced only if:
  • Exceeds 220/120 mmHg
  • Malignant hypertension or concurrent myocardial ischemia

  • 185/110 mmHg and thrombolysis is planned

• Routine lowering below these limits may worsen outcomes (penumbra is BP-dependent)
• When cardiac and cerebral demands compete: beta-blocker (e.g., esmolol) to lower HR while maintaining BP is a first step

2. IV Thrombolysis

• Approved for ischemic stroke within 3 hours of onset (or last-known-well time)
• Extended to 4.5 hours in selected patients (those without prior stroke + diabetes, NIHSS ≤25, age <80 in some protocols)
• Dose: 0.9 mg/kg IV (max 90 mg); 10% as bolus, remainder over 60 min
• Benefit is time-dependent - "Time is brain"
• Contraindications include recent surgery, anticoagulation, prior hemorrhage, and markedly elevated BP at time of treatment (>185/110 must be controlled first)

• Emerging alternative; single IV bolus; similar efficacy data

3. Endovascular Revascularization (Mechanical Thrombectomy)

• Indicated for large vessel occlusion (LVO) - particularly proximal MCA, ICA terminus, basilar artery
• Time window: up to 24 hours in selected patients (using perfusion imaging to identify salvageable penumbra)
• Can be combined with IV tPA (bridging therapy) or used alone (if tPA contraindicated)
• Multiple RCTs (MR CLEAN, ESCAPE, SWIFT PRIME, DAWN, DEFUSE-3) demonstrated superiority over medical management
• Imaging selection (CT perfusion or MRI DWI/PWI mismatch) identifies candidates beyond 6 hours

4. Antithrombotic Treatment

• Should be given within 24-48 hours of ischemic stroke onset
• Dose: 160-325 mg/day
• Do not give within 24 hours of tPA administration

• Recommended for minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4) for 21 days, then single agent
• POINT and CHANCE trials support this

• Not routinely recommended in the acute phase for most ischemic strokes
• Exception: cardioembolic stroke due to atrial fibrillation - DOACs are preferred for long-term secondary prevention, typically started 4-14 days after stroke depending on infarct size

5. Neuroprotection

• No neuroprotective agent has proven benefit in clinical trials to date
• Hypothermia remains under investigation
• Preventing fever and hyperglycemia remains the best "neuroprotective" strategy

6. Stroke Centers and Rehabilitation

• Care in a dedicated stroke unit reduces mortality and improves functional outcomes
• Early rehabilitation (physical, occupational, speech therapy) should begin within 24-48 hours once the patient is medically stable
• Telestroke networks extend specialist access to non-stroke-center hospitals

Stroke Syndromes

Etiology of Ischemic Stroke

Secondary Prevention

• Most significant modifiable risk factor
• Target <130/80 mmHg; SPRINT data suggest <120 mmHg systolic may reduce stroke and MI by 43%
• Preferred agents: thiazide diuretics, ACE inhibitors

• Statins reduce stroke risk regardless of baseline LDL
• SPARCL trial: atorvastatin 80 mg/day reduced recurrent stroke in patients with recent stroke/TIA
• Target LDL <70 mg/dL for secondary prevention

• Aspirin, aspirin + dipyridamole (extended-release), or clopidogrel
• Short-term DAPT (aspirin + clopidogrel) for minor stroke/high-risk TIA (21 days)

• DOACs preferred over warfarin (lower bleeding risk, equivalent or superior efficacy)
• For AF: start 4-14 days after stroke (longer delay for larger infarcts to reduce hemorrhagic transformation risk)

• Carotid endarterectomy (CEA) for symptomatic stenosis 70-99% (within 2 weeks of TIA/minor stroke)
• Benefit also for 50-69% stenosis in selected patients