Pathophysiology of Ischemic Stroke

1. Initiating Event

2. Two Zones of Injury (Fig. 16.10)

Penumbra damage is worsened by inflammation and excitotoxicity (mediated by glutamate and sodium). Hyperglycemia and fever further worsen it - both must be controlled.

3. Cellular Cascade (Flowchart 16.6)

Thrombus/Embolus
       ↓
  Hypoperfusion
       ↓
  ATP Depletion
       ↓
Activation of:
  • Lipid peroxidases
  • Proteases
  • NO synthase
       ↓
Destruction of intracellular organelles,
cell membrane + Free radical release
       ↓
  LIQUEFACTIVE NECROSIS

4. CBF Thresholds & Functional Consequences

Key Takeaway

Lacunar (Small Vessel) Stroke

Definition & Basics

• Caused by occlusion of small penetrating arteries (200-800 µm) supplying deep brain parenchyma
• Occlusion occurs by:
  • Atherothrombotic disease at vessel origin
  • Lipohyalinosis thickening - a consequence of chronic hypertension
• Infarct size: 0.2 to 15 mm in diameter (these small cavities = "lacunes")
• Account for 20% of all strokes
• Risk factors: Hypertension (most important) and age
• Presentation: Fluctuating symptoms called "Capsular Warning Syndrome"

Lacunar Syndromes (Table 16.14)

Key Points to Remember

• No cortical signs (no aphasia, no hemianopia, no neglect) - because purely deep structures are involved
• Pure motor is the most common lacunar syndrome
• Dysarthria-clumsy hand and ataxic hemiparesis are classically pontine
• Lacunar infarcts are best seen on MRI (DWI) - often invisible on CT
• Management: BP control is the single most important preventive measure

Lacunar Stroke Syndromes

IC = Internal Capsule | MCA = Middle Cerebral Artery | PCA = Posterior Cerebral Artery | PCOM = Posterior Communicating Artery

A. DIAGNOSIS

1. FAST (Bedside Screening)

2. Neuroimaging

3. Blood Investigations

• CBC, ESR, glucose, RFT, LFT, PT-INR, aPTT, electrolytes
• Hypercoagulable workup: Protein C & S, Antithrombin III, Factor VII/VIII, Lupus anticoagulant, Anticardiolipin Ab, APCR, Factor V Leiden, Prothrombin G20210A, Sickle cell screen

4. Cardiac Investigations

• ECG (for AF), Echocardiogram (TTE/TEE) - for cardiac source of emboli, intracardiac thrombus, PFO

B. MANAGEMENT

1. IV Thrombolysis (r-tPA / Tenecteplase) - "Time is Brain"

• Clinical diagnosis of stroke
• Onset to treatment ≤ 4.5 hours
• Age ≥ 18 years
• CT: No hemorrhage or infarct > 1/3 MCA territory

• BP > 185/110 mmHg despite treatment
• Platelets < 1,00,000 / Hematocrit < 25%
• Glucose < 50 or > 400 mg%
• Prior ICH / head injury in 3 months / major surgery in 14 days
• Age > 80 years / Pregnancy / Coma

Tenecteplase: 0.25 mg/kg IV bolus (max 25 mg)

2. Endovascular Mechanical Thrombectomy

• Alternative when IV thrombolysis is contraindicated or failed
• Saves penumbra by direct clot removal

3. Antiplatelet Therapy

• Aspirin 150 mg + Clopidogrel 75 mg (dual antiplatelet)
• Avoid Glycoprotein IIb/IIIa inhibitors (abciximab) - causes excess ICH

4. Anticoagulation

• Routine use is NOT recommended in acute ischemic stroke
• Only use in: AF, crescendo TIAs, hypercoagulable states, cerebral venous sinus thrombosis (CVT)

5. Blood Pressure Management

Key rule: "Do not kill the penumbra to save the penumbra" - avoid aggressive BP lowering

6. Reduce Intracranial Tension

• Water restriction, IV Mannitol, oral Glycerol, head-end elevation

7. Hemicraniectomy

• For malignant MCA infarction (NIHSS > 15, age ≤ 60, infarct > 50% MCA territory, infarct volume > 145 cm³)
• Refer within 24 hrs, operate within 48 hrs

8. Statins

• Atorvastatin 40-80 mg / Rosuvastatin 20-40 mg

9. Rehabilitation

• Early physical, occupational, speech therapy
• Restraint therapy (immobilizing unaffected side) improves hemiparesis

C. SECONDARY PREVENTION

ABCD² Score (TIA risk stratification)

Score < 4 = low risk | Score > 6 = high risk for stroke

Clinical Features of Stroke

A. General Onset

• Sudden onset of focal neurological deficit (hallmark)
• Symptoms depend on which artery/territory is affected
• May present with "capsular warning syndrome" (fluctuating symptoms before major stroke)

B. Cortical Signs (Large Vessel / MCA territory)

C. Brainstem / Posterior Circulation Signs

D. Lacunar Stroke (Pure Subcortical - NO cortical signs)

E. Territory-Based Features

F. Hemorrhagic Stroke - Additional Features

• Sudden severe headache ("thunderclap" - SAH)
• Vomiting, neck stiffness (SAH)
• Rapid loss of consciousness
• Higher ICP signs - papilledema, Cushing reflex (bradycardia + hypertension)

G. Key Distinguishing Points

Remember: Stroke = sudden focal neurological deficit until proven otherwise. Any new sudden weakness, speech difficulty, visual loss, or unsteadiness = call FAST

Clinical Features of Stroke

(Boloor's Textbook of Medicine - Chapter 16: Neurology)

A. General Features

• Sudden onset focal neurological deficit
• Fluctuating symptoms = "Capsular Warning Syndrome" (precedes lacunar stroke)
• Symptoms depend on territory of arterial occlusion

B. Territory-Based Clinical Features

C. Lacunar Stroke Syndromes (No Cortical Signs)

D. Complications of Acute Stroke (Box 16.11)

E. "Time is Brain" - Neural Loss Per Stroke (Fig. 16.13)

F. Stroke Mimickers (Box 16.12 - Differential Diagnosis)

If you have the page showing the "Site of Occlusion vs Clinical Features" table (Table 16.15 from Boloor), please share it and I'll extract that as well.