Stroke - Overview for Medical Students

Definition

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 1155

Types of Stroke

1. Ischemic Stroke (~80% of all strokes)

2. Hemorrhagic Stroke (~20%)

Ischemic Stroke - Subtypes (TOAST Classification)

• Fuster and Hurst's The Heart, 15th Edition, p. 805
• Harrison's Principles of Internal Medicine 22E, p. 3487

Pathophysiology of Ischemic Stroke

The Three Core Mechanisms

1. Embolism - from cardiac sources (AF most important) or artery-to-artery (atherosclerotic plaque rupture), occluding large intracranial vessels
2. In situ thrombosis - lipohyalinosis of small penetrating arteries producing lacunar infarcts
3. Hypoperfusion - flow-limiting stenosis causing watershed (boundary zone) ischemia

Ischemic Penumbra (The Key Concept)

• After vessel occlusion, some neurons die immediately - this is the infarct core
• Surrounding it is the ischemic penumbra: a zone of functionally impaired but structurally viable neurons
• The penumbra is potentially salvageable and is the target of reperfusion therapies (tPA, thrombectomy)
• Without reperfusion, the penumbra is progressively recruited into the infarct core
• Collateral circulation (circle of Willis, leptomeningeal collaterals) influences core size and penumbral survival
• Fuster and Hurst's The Heart, 15th Edition, p. 806

Cellular Mechanism of Ischemic Injury

1. Loss of glucose/oxygen → failure of Na-K ATPase
2. Cytotoxic edema (water enters cells)
3. Glutamate excitotoxicity → Ca²⁺ influx → mitochondrial damage
4. Free radical formation, lipid peroxidation, proteolysis
5. Neuronal apoptosis and necrosis

Lacunar Strokes - Classic Syndromes

• Fuster and Hurst's The Heart, 15th Edition, p. 805

Hemorrhagic Stroke - Subtypes

Intracerebral Hemorrhage (ICH)

• Deep/ganglionic hemorrhage (basal ganglia, thalamus, internal capsule, pons): caused by hypertensive microangiopathy - chronic hypertension causes lipohyalinosis and Charcot-Bouchard microaneurysms in small penetrating arteries
• Lobar hemorrhage: most commonly due to cerebral amyloid angiopathy (CAA) - beta-amyloid deposition in vessel walls, particularly in elderly patients
• ICH may extend into the ventricular system (intraventricular hemorrhage)

Subarachnoid Hemorrhage (SAH)

• ~1% of all strokes
• Most common cause: rupture of an intracranial saccular aneurysm (berry aneurysm), typically at arterial bifurcations
• Classic presentation: sudden-onset "thunderclap headache" (worst headache of life)
• Less common: AVM rupture, RCVS
• Fuster and Hurst's The Heart, 15th Edition, p. 806
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 1155

Clinical Features

Anterior Circulation (Carotid Territory - MCA/ACA)

• MCA territory: contralateral hemiplegia (face and arm > leg), hemisensory loss, homonymous hemianopia
  • Dominant hemisphere (usually left): aphasia (Broca's = expressive; Wernicke's = receptive)
  • Non-dominant hemisphere: neglect, anosognosia, constructional apraxia
• ACA territory: contralateral leg > arm weakness, frontal lobe signs, abulia, urinary incontinence

Posterior Circulation (Vertebrobasilar Territory)

• PICA (lateral medullary / Wallenberg syndrome): ipsilateral facial pain/numbness, contralateral body pain/temperature loss, Horner's, dysphagia, ataxia - "crossed" sensory deficits
• Basilar artery occlusion: bilateral limb weakness, coma, locked-in syndrome (catastrophic)
• PCA territory: contralateral homonymous hemianopia (macular sparing common)

FAST Acronym (Screening)

• Face drooping (asymmetric smile)
• Arm weakness (one arm drifts down)
• Speech difficulty (slurred, wrong words, mute)
• Time to call emergency services

Key Distinguishing Features: Ischemic vs Hemorrhagic

Risk Factors

TIA - The "Warning Stroke"

• Defined as focal neurologic symptoms lasting <24 hours with no infarction on imaging
• Most TIAs last <1 hour
• 10-15% risk of stroke in the first 3 months, with majority occurring within 2 days
• Risk stratified by ABCD2 score: Age, Blood pressure, Clinical features, Duration, Diabetes
• Causes are identical to ischemic stroke; urgent evaluation is required
• Harrison's Principles of Internal Medicine 22E, p. 3488

Causes of Ischemic Stroke (Common vs Uncommon)

• Thrombosis: lacunar, large-vessel, dehydration
• Embolic: artery-to-artery (carotid bifurcation, aortic arch), cardioembolic (AF, mural thrombus, MI, valvular disease, paradoxical embolus via PFO)

• Hypercoagulable states (Protein C/S deficiency, antiphospholipid syndrome, factor V Leiden)
• Sickle cell disease, polycythemia vera
• Vasculitis (primary CNS or systemic)
• Dissection (ICA or vertebral - most common cause of stroke in young adults <60)
• CADASIL (Notch-3 gene mutation - hereditary small-vessel disease)
• COVID-19-associated coagulopathy
• Oral contraceptives, stimulant drugs
• Harrison's Principles of Internal Medicine 22E, p. 3487

Key Exam Points

1. Ischemic stroke = ~80%, hemorrhagic = ~20% of all strokes
2. TOAST classification: large artery, cardioembolic, lacunar (small vessel), other determined, cryptogenic
3. Penumbra = the salvageable zone around the infarct core - the rationale for thrombolysis and thrombectomy
4. Lacunar strokes: five classic syndromes, no cortical features, small penetrating artery occlusion
5. Deep ICH = hypertension; lobar ICH = cerebral amyloid angiopathy
6. SAH = thunderclap headache + meningism = berry aneurysm rupture until proven otherwise
7. Atrial fibrillation is the single most important cardiac cause of embolic stroke
8. Arterial dissection = most common cause of stroke in patients under 60
9. CADASIL = autosomal dominant, Notch-3 mutation, small vessel strokes + dementia + migraine with aura
10. TIA is a medical emergency - ABCD2 score, 10-15% stroke risk within 3 months