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. Large-Artery Atherosclerosis (20% of ischemic strokes)
- 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
- Mechanisms include:
- Artery-to-artery embolism
- Hemodynamic insufficiency
- Typically produces cortical infarcts in the distribution of a large cerebral artery 1
2. Cardiogenic Embolism (20% of ischemic strokes)
- Emboli originating from the heart (and in some classification schemes, the aorta)
- Most frequently caused by atrial fibrillation
- Produces cortical or large subcortical infarctions
- Requires exclusion of atherosclerotic narrowing in the parent large artery
- High-risk cardiac sources must be identified for definitive diagnosis 1
3. Small-Vessel Disease/Lacunar Stroke (25% of ischemic strokes)
- 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 (e.g., pure motor hemiparesis)
- Strongly associated with:
- Hypertension
- Diabetes mellitus
- Not usually caused by atherosclerosis
- Requires exclusion of cardioembolism and large-artery stenosis 1
4. Uncommon Causes of Stroke
- Nonatherosclerotic vasculopathies
- Hypercoagulable states
- Hematologic disorders
- No restriction on size or location of infarct on brain imaging 1
5. Cryptogenic/Undetermined Causes (30% of ischemic strokes)
- No definitive cause identified despite thorough evaluation
- May include patients with:
- Multiple potential mechanisms identified
- Incomplete evaluation
- Negative evaluation 1
Risk Factors for Ischemic Stroke
Modifiable Risk Factors
- Hypertension (most important modifiable risk factor) 2
- Atrial fibrillation
- Diabetes mellitus
- High cholesterol and lipids
- Smoking
- Physical inactivity
- Poor nutrition
- Kidney disease 2, 3
Non-modifiable Risk Factors
- Age (increasing risk with advancing age)
- Sex (higher prevalence in women overall)
- Race/ethnicity:
- American Indian/Alaskan Native (highest prevalence: 6.7%)
- Multiple races (4.6%)
- Black individuals (4.0%, twice the prevalence compared to whites)
- Hispanic/Latino populations (3.1% for men, 1.9% for women)
- Family history
- Genetic predisposition 1, 3
Pathophysiological Mechanisms
Ischemic stroke results from impaired blood flow to an area of the brain, typically due to:
- Blockage of cerebral vessels by thrombus or embolus
- Hemodynamic compromise due to severe stenosis
- Small vessel occlusion from lipohyalinosis or microatheroma 2, 4
Clinical Implications
Understanding stroke etiology is crucial for:
- Determining appropriate acute treatment (thrombolysis, thrombectomy)
- Guiding secondary prevention strategies
- Predicting prognosis and risk of recurrence 4
For example:
- Cardioembolic strokes may require anticoagulation
- Large-artery atherosclerosis may benefit from revascularization procedures
- Small vessel disease requires aggressive blood pressure and diabetes control 4
Diagnostic Approach
The classification of ischemic stroke subtype requires:
- Comprehensive clinical evaluation
- Neuroimaging (CT, MRI)
- Vascular imaging (carotid ultrasound, CTA, MRA)
- Cardiac evaluation (ECG, echocardiography)
- Laboratory studies to identify hypercoagulable states when appropriate 1
Diagnostic uncertainty and misclassification are not uncommon, and in many cases, multiple potential causes may coexist 1.