Acute Ischemic Stroke: Management, tPA, and Endovascular Therapy

Acute ischemic stroke is a focal neurological deficit caused by sudden interruption of blood flow to a specific brain region, resulting in tissue hypoxia and potential infarction. It represents approximately 87% of all strokes and is the fifth leading cause of death and leading cause of long-term disability in the United States.

[KEY_CONCEPT] Stroke is defined as acute onset of focal neurological symptoms lasting >24 hours or leading to death, with imaging evidence of acute infarction in a clinically relevant area of the brain.

Epidemiology:

• Incidence: ~795,000 strokes annually in the US
• Age-adjusted incidence: 2.6 per 1000 person-years
• Risk increases dramatically with age (doubles each decade after age 55)
• Higher prevalence in African Americans, Native Americans, and males

Pathophysiology: Ischemic stroke results from thrombotic or embolic occlusion of cerebral arteries. The ischemic penumbra represents potentially salvageable tissue surrounding the infarct core that maintains structural integrity but has compromised function due to reduced blood flow. This concept is fundamental to acute stroke therapy.

[CLINICAL_PEARL] Time-dependent tissue viability: "Time is brain" - approximately 1.9 million neurons are lost per minute during acute stroke.

Classification by Mechanism (TOAST criteria):

• Large artery atherosclerosis (20%)
• Cardioembolic (25%)
• Small vessel occlusion/lacunar (25%)
• Other determined etiology (5%)
• Undetermined etiology (25%)

Clinical Presentation: Acute stroke presents with sudden onset of focal neurological deficits corresponding to specific vascular territories. Symptoms depend on the location and extent of brain tissue affected.

Common Presentations by Territory:

[HIGH_YIELD] NIHSS (National Institutes of Health Stroke Scale): 15-point scale assessing stroke severity:

• 0-4: Minor stroke
• 5-15: Moderate stroke
• 16-20: Moderate to severe stroke
• 21-42: Severe stroke

Rapid Assessment Tools:

1. FAST/BE-FAST screening:
   • Balance (loss of coordination)
   • Eyes (vision loss)
   • Face (facial droop)
   • Arms (arm weakness)
   • Speech (speech difficulties)
   • Time (time to call 911)

[CLINICAL_PEARL] Posterior circulation strokes are frequently misdiagnosed initially due to non-specific symptoms like dizziness, nausea, and ataxia.

Differential Diagnosis:

• Hypoglycemia
• Seizure with Todd's paralysis
• Migraine with aura
• Hypertensive encephalopathy
• Brain tumor
• Metabolic encephalopathy
• Functional neurological disorder

Immediate Diagnostic Approach: Rapid evaluation is essential to determine eligibility for acute interventions within therapeutic time windows.

ACUTE STROKE DIAGNOSTIC ALGORITHM

1. Initial Assessment (Door-to-imaging goal: 20 minutes) ├── ABCs, vital signs, fingerstick glucose ├── Focused neurological exam (NIHSS) ├── IV access, blood draws └── Immediate non-contrast CT head

2. Imaging Interpretation ├── Hemorrhage present? → Hemorrhagic stroke pathway ├── Early ischemic changes? ├── Hypodensity >1/3 MCA territory? └── ASPECTS score ≥6?

3. Advanced Imaging (if indicated) ├── CT/MR angiography (vessel imaging) ├── CT/MR perfusion (penumbra assessment) └── Consider for extended window patients

4. Laboratory Studies ├── CBC with platelets ├── Basic metabolic panel, glucose ├── PT/PTT/INR ├── Cardiac biomarkers └── Consider toxicology screen

Imaging Studies:

[HIGH_YIELD] Non-contrast CT head is the initial imaging of choice:

• Rules out hemorrhage (contraindication to thrombolysis)
• May show early ischemic changes (hypoattenuation, loss of gray-white differentiation)
• ASPECTS score (Alberta Stroke Program Early CT Score) quantifies early ischemic changes

Advanced Imaging Indications:

• CT/MR Angiography: Identify large vessel occlusion for thrombectomy consideration
• Perfusion imaging: Assess penumbra in extended time window cases
• MRI with DWI: Most sensitive for acute infarction, useful for posterior circulation

[KEY_CONCEPT] ASPECTS Score: 10-point scale assessing early ischemic changes on CT. Score ≥6 suggests good collateral circulation and potential for favorable outcome.

Essential Laboratory Studies:

• Glucose: Hypoglycemia mimics stroke
• INR/PT/PTT: Assess bleeding risk before thrombolysis
• Platelet count: Thrombocytopenia contraindication
• Troponin: Rule out concurrent MI

Diagnostic Timeline:

• Door-to-imaging: <20 minutes
• Door-to-needle (tPA): <60 minutes
• Door-to-groin puncture: <90 minutes

General Acute Management: Immediate stabilization focuses on maintaining cerebral perfusion while minimizing secondary brain injury.

Initial Stabilization:

• Airway/Breathing: Maintain oxygen saturation >94%
• Blood Pressure: Permissive hypertension unless >220/120 mmHg or candidate for thrombolysis
• Temperature: Treat fever >38°C (worsens outcomes)
• Glucose: Maintain 140-180 mg/dL
• Head positioning: Head of bed 0-30° (optimize cerebral perfusion)

[HIGH_YIELD] Intravenous Thrombolysis (tPA): Alteplase (recombinant tissue plasminogen activator) is the standard thrombolytic agent for acute ischemic stroke.

tPA Eligibility Criteria: ✓ Age ≥18 years ✓ Clinical diagnosis of ischemic stroke with measurable deficit ✓ Symptom onset <4.5 hours (or last known well time) ✓ CT excludes intracranial hemorrhage ✓ No recent surgery, trauma, or GI bleeding ✓ BP <185/110 mmHg ✓ Platelets >100,000, INR <1.7, aPTT normal ✓ No history of ICH, recent stroke (<3 months)

tPA Contraindications: ✗ Intracranial hemorrhage on imaging ✗ Clinical suspicion of subarachnoid hemorrhage ✗ Recent intracranial surgery (<3 months) ✗ Severe uncontrolled hypertension ✗ Active bleeding or bleeding diathesis ✗ Rapidly improving or minor symptoms

[CLINICAL_PEARL] Extended Window (3-4.5 hours): Additional exclusions include age >80, NIHSS >25, diabetes + prior stroke, or anticoagulant use.

tPA Dosing & Administration:

• Dose: 0.9 mg/kg (maximum 90 mg)
• Administration: 10% IV bolus, remainder over 60 minutes
• Monitoring: Neuro checks q15min × 2 hours, then q30min × 6 hours, then q1hour × 24 hours

Endovascular Thrombectomy: Mechanical clot retrieval for large vessel occlusions, revolutionizing stroke care based on landmark trials.

Thrombectomy Criteria:

• NIHSS ≥6 (suggests large vessel occlusion)
• Large vessel occlusion on CTA/MRA (ICA, M1/M2 MCA, basilar)
• ASPECTS ≥6 (good collateral circulation)
• Time windows:
  • 0-6 hours: Based on clinical/imaging criteria
  • 6-24 hours: Requires advanced imaging showing salvageable penumbra

[KEY_CONCEPT] Bridging therapy: tPA followed by thrombectomy shows superior outcomes compared to either treatment alone in eligible patients.

Acute Complications: Post-stroke complications significantly impact outcomes and require vigilant monitoring and management.

Hemorrhagic Transformation:

• Incidence: 6-20% of ischemic strokes, higher with tPA (6.4%)
• Risk factors: Large infarct size, cardioembolic source, delayed reperfusion, anticoagulation
• Types: Hemorrhagic infarction (HI) vs. parenchymal hematoma (PH)
• Management: Discontinue anticoagulation, neurosurgical consultation for significant hematoma

[HIGH_YIELD] Malignant Middle Cerebral Artery Syndrome:

• Massive cerebral edema with midline shift
• Clinical deterioration within 24-48 hours
• Mortality >80% without intervention
• Treatment: Decompressive hemicraniectomy (age <60 years, <48 hours onset)

Neurological Complications:

Systemic Complications:

• Pneumonia: 25-30% incidence, aspiration risk
• Deep vein thrombosis: 40-75% without prophylaxis
• Urinary tract infection: Common due to catheterization
• Cardiac complications: Arrhythmias, MI, heart failure

[CLINICAL_PEARL] Post-stroke seizures occur in 5-10% of patients. Early seizures (within 24 hours) don't necessarily indicate epilepsy development, but recurrent seizures warrant long-term antiepileptic therapy.

Blood Pressure Management:

• Without thrombolysis: Permissive hypertension <220/120 mmHg
• With thrombolysis: <185/110 mmHg before treatment, <180/105 mmHg for 24 hours post-treatment
• Post-acute phase: Gradual reduction to <140/90 mmHg

Monitoring Parameters:

• Neurological assessments (NIHSS) every 15 minutes × 2 hours, then hourly
• Blood pressure every 15 minutes × 2 hours post-tPA
• Temperature, oxygen saturation, glucose
• Signs of hemorrhagic transformation or cerebral edema

Prognostic Factors: Outcome prediction helps guide treatment decisions and family discussions regarding prognosis and goals of care.

Favorable Prognostic Indicators:

• Younger age (<65 years)
• Lower NIHSS score (<10)
• Rapid symptom resolution
• Small infarct volume
• Good collateral circulation (ASPECTS ≥7)
• Successful recanalization
• Absence of hemorrhagic transformation

[HIGH_YIELD] Modified Rankin Scale (mRS): Standard outcome measure

• 0: No symptoms
• 1: No significant disability
• 2: Slight disability (independent)
• 3: Moderate disability (requires some help)
• 4: Moderate to severe disability
• 5: Severe disability (bedridden)
• 6: Death

Functional Outcomes:

• Independent living (mRS 0-2): 40-60% at 3 months
• Good functional outcome more likely with:
  • Treatment within 3 hours
  • Successful recanalization
  • Younger age and lower baseline NIHSS

Secondary Stroke Prevention: Comprehensive approach targeting modifiable risk factors reduces recurrence risk by 80%.

SECONDARY PREVENTION ALGORITHM

1. Antiplatelet Therapy ├── Aspirin 81mg daily (first-line) ├── Clopidogrel 75mg daily (aspirin intolerant) └── Dual antiplatelet × 21-90 days (high-risk patients)

2. Anticoagulation (Cardioembolic Source) ├── Atrial fibrillation → Warfarin or DOAC ├── Mechanical heart valve → Warfarin └── Start 2-14 days post-stroke (based on size/risk)

3. Risk Factor Modification ├── Blood pressure <140/90 mmHg (ACE-I/ARB preferred) ├── LDL cholesterol <70 mg/dL (high-intensity statin) ├── Diabetes: HbA1c <7% ├── Smoking cessation └── Weight management, exercise

4. Specific Interventions ├── Carotid endarterectomy (>70% stenosis) ├── Patent foramen ovale closure (selected cases) └── Left atrial appendage closure (AF, bleeding risk)

[CLINICAL_PEARL] Recurrence Risk: 3-10% at 90 days, 30% at 5 years without secondary prevention. Early recurrence highest in first 2 weeks.

Long-term Management:

• Rehabilitation: Physical, occupational, speech therapy
• Depression screening: 30-50% develop post-stroke depression
• Cognitive assessment: Vascular cognitive impairment common
• Bone health: Fall prevention, osteoporosis screening

Follow-up Timeline:

• 1-3 months: Functional assessment, medication optimization
• 6 months: Rehabilitation progress, driving assessment
• Annually: Risk factor control, complications screening