What are the differences in management approaches for acute, subacute, and chronic cerebral infarctions?

Management Differences Across Temporal Stages of Cerebral Infarction

Acute Phase (0-7 Days): Time-Critical Reperfusion Focus

The acute phase demands immediate reperfusion strategies with intravenous thrombolysis (rtPA) within 3-4.5 hours or endovascular thrombectomy up to 24 hours for large vessel occlusions, while simultaneously managing life-threatening complications like malignant edema. 1

Immediate Reperfusion Interventions

• Intravenous rtPA must be administered within 3 hours of symptom onset for all clinical subtypes of cerebral infarction after excluding hemorrhage on non-contrast CT 1
• Endovascular thrombectomy is indicated for large vessel occlusions (intracranial carotid, M1 segment) within 6 hours, with extended windows up to 24 hours using advanced imaging selection 1
• Aspirin (160-325 mg) should be initiated within 24-48 hours after stroke onset but NOT within 24 hours of thrombolytic administration 1

Critical Acute Complications Management

• Malignant cerebral edema peaks at 3-4 days but can occur within 24 hours after reperfusion of large infarcts 1
• Avoid hypotonic fluids, excess glucose, hypoxemia, hypercarbia, and hyperthermia to minimize edema formation 1
• Elevate head of bed 20-30 degrees to assist venous drainage 1
• Mannitol (0.25-0.5 g/kg IV over 20 minutes every 6 hours, maximum 2 g/kg) or hypertonic saline can be used for increased intracranial pressure, though evidence for improved outcomes is limited 1
• Clinical deterioration occurs in 25% of patients: one-third from stroke progression, one-third from edema, 10% from hemorrhage, 11% from recurrent ischemia 1

Acute Phase Monitoring

• Close observation in dedicated stroke units or neurocritical care units is essential given the high risk of deterioration 1
• Blood pressure management: avoid aggressive lowering unless systolic >220 mmHg or diastolic >105 mmHg to prevent hemorrhagic transformation 1
• Maintain isotonic saline for fluid management; avoid hypotonic solutions 1

Subacute Phase (8-21 Days): Reperfusion Hyperemia and Secondary Prevention Initiation

The subacute phase is characterized by reperfusion hyperemia with increased cerebral blood volume, requiring careful anticoagulation timing decisions for cardioembolic strokes and continuation of neuroprotective measures. 2

Hemodynamic Changes

• Blood volume increases significantly during the subacute phase (mean ratio 1.48 vs 0.46 in acute phase), reflecting reperfusion hyperemia regardless of recanalization status 2
• Arterial recanalization occurs in 80% of cases by the subacute stage compared to 21% in the acute stage 2

Anticoagulation Timing for Cardioembolic Stroke

• Oral anticoagulation should generally be initiated within 1-2 weeks after stroke onset 1
• Earlier anticoagulation (within days) can be considered for patients with small infarct burden and no hemorrhage on imaging 1
• Delay anticoagulation for patients with extensive infarct burden or significant hemorrhagic transformation 1
• Bridge with aspirin until therapeutic anticoagulation is achieved 1

Continued Supportive Care

• Edema may still be evolving, particularly in large infarcts where cytotoxic edema normally peaks at 3-4 days 1
• Maintain glucose control; avoid hyperglycemia >180 mg/dL as it increases edema and hemorrhagic transformation risk 1
• Continue monitoring for delayed complications including recurrent ischemia 1

Chronic Phase (>21 Days): Secondary Prevention and Rehabilitation

The chronic phase focuses on long-term secondary prevention with antiplatelet or anticoagulant therapy based on stroke mechanism, risk factor modification, and neurological rehabilitation. 3, 4

Hemodynamic Normalization

• Blood volume decreases again in the chronic phase (mean ratio 0.73) after the subacute hyperemic period 2
• Cerebral hemodynamics stabilize, reducing risk of hemorrhagic complications 2

Secondary Prevention by Stroke Subtype

• For atherothrombotic and lacunar infarctions: antiplatelet therapy with aspirin, clopidogrel, or cilostazol 3, 4
• For cardioembolic infarction: long-term anticoagulation with warfarin or direct oral anticoagulants (DOACs) 3, 4
• For atrial fibrillation patients, dabigatran 150 mg twice daily is preferred over warfarin (INR 2.0-3.0) 1
• If anticoagulation is contraindicated, use combination aspirin plus clopidogrel over aspirin alone 1

Risk Factor Management

• Control hypertension, diabetes mellitus, dyslipidemia, and atrial fibrillation to prevent recurrence 3
• Pioglitazone reduces recurrent stroke risk in diabetic patients 3
• Approximately 30% of atherothrombotic and lacunar infarctions are associated with diabetes 3

Emerging Therapies

• Neuroprotective therapy with edaravone (free radical scavenger) may minimize ongoing tissue damage 4
• Neuronal regenerative therapies using stem cells are under development 4

Critical Pitfalls to Avoid

• Never substitute aspirin for intravenous rtPA in the acute phase—aspirin is not a replacement for reperfusion therapy 1
• Do not continue aggressive fluid resuscitation if pulmonary edema or bilateral crepitations develop—switch immediately to diuresis 5
• Avoid cerebral vasodilating antihypertensive agents in acute phase as they may worsen edema 1
• Do not use corticosteroids, as they do not improve outcomes in ischemic brain swelling 1
• Recognize that hyperventilation provides only short-lived ICP reduction and should be considered temporizing 1
• Do not delay anticoagulation indefinitely in cardioembolic stroke—the 1-2 week window balances hemorrhagic transformation risk against recurrent embolism 1