Causes of Ischemic Stroke
Ischemic strokes are primarily caused by atherosclerotic disease of extracranial or intracranial vessels, cardiogenic embolism, and small vessel disease, with approximately 30% remaining cryptogenic despite thorough evaluation. 1
Major Etiologies of Ischemic Stroke
1. Atherosclerotic Disease (Large Vessel Disease)
- Affects extracranial or intracranial segments of carotid or vertebrobasilar arteries
- Characterized by luminal occlusion or narrowing ≥50% of atherosclerotic origin
- Often preceded by TIA in the same arterial distribution
- Typically produces cortical infarcts in the distribution of a large cerebral artery 1
- Accounts for approximately 20% of ischemic stroke cases 2
2. Cardiogenic Embolism
- Emboli originating from the heart
- Most frequently caused by atrial fibrillation
- Produces cortical or large subcortical infarctions
- Requires exclusion of atherosclerotic narrowing in the parent large artery 1
- Other cardiac sources include:
- Ischemic heart disease
- History of thromboembolism 3
3. Small Vessel Disease (Lacunar Infarcts)
- Occlusive arteriopathy involving small vessels deep in the brain or brain stem
- Produces small (<1.5 cm) lesions on neuroimaging
- Associated with specific clinical syndromes
- Strongly associated with hypertension and diabetes mellitus 1
- Presumed to result from the occlusion of a single small perforating artery 3
4. Cryptogenic Stroke
- No definitive cause identified despite thorough evaluation
- May include patients with multiple potential mechanisms identified
- Incomplete evaluation or negative evaluation 1
- Accounts for approximately 30% of ischemic strokes 1
Risk Factors for Ischemic Stroke
Non-modifiable Risk Factors
- Age (major predictor from the Framingham risk score) 3
- Sex (more common in men than women) 4
- Race/ethnicity (American Indian/Alaskan Native having the highest prevalence) 1
- Family history and genetic predisposition 1
Modifiable Risk Factors
- Hypertension (most important modifiable risk factor) 5
- Atrial fibrillation 4
- Diabetes mellitus 1
- High cholesterol and lipids 4
- Smoking 4
- Physical inactivity 4
- Poor nutrition 4
- Kidney disease 4
- Duration of atrial fibrillation 3
Special Considerations
Stroke in Younger Patients
- Different spectrum of causes compared to older adults
- Extracranial dissection is more common 5
- Macrovascular lesions (vascular malformations, aneurysms, cavernomas)
- Venous sinus thrombosis
- These causes are particularly important in young patients (<50 years) 5
Diagnostic Challenges
- Classification of ischemic stroke subtype is complex and depends on the intensity and timing of diagnostic investigations
- Diagnostic uncertainty about the subtype and misclassification are not uncommon
- Even after comprehensive evaluation, in a considerable proportion of stroke patients the definite cause remains elusive or multiple potential causes are found 3
- The heterogeneous pathogenesis of ischemic stroke makes it different from acute coronary syndrome, which is usually attributable to large-vessel atherosclerosis 3
Clinical Implications
- Prevention of stroke sometimes requires specific treatment approaches:
- Overall, long-term cardiovascular risk is high after ischemic stroke, although variation exists in risk of early stroke recurrence according to subtype 3
Understanding the specific cause of ischemic stroke is crucial for implementing appropriate secondary prevention strategies and reducing the risk of recurrence.