What are the etiologies of stroke?

Causes of Stroke

Stroke results from two fundamental pathophysiologic mechanisms: ischemia (85% of cases) and hemorrhage (15% of cases), each with distinct etiologies that require specific diagnostic and therapeutic approaches. 1, 2

Ischemic Stroke Etiologies

The American Heart Association classifies ischemic stroke into five major categories using the TOAST classification system 3:

1. Large-Artery Atherosclerosis (20% of cases)

• Atherosclerotic disease affecting extracranial or intracranial segments of carotid or vertebrobasilar arteries with ≥50% luminal narrowing 3, 1
• Mechanisms include artery-to-artery embolism or hemodynamic insufficiency 3
• Often preceded by transient ischemic attacks in the same arterial distribution 3
• Atherosclerotic plaque damage and injury during vascular procedures can cause thromboembolism 3

2. Cardioembolism (20% of cases)

• Blood clots form in the heart and embolize to cerebral arteries, causing cortical or large subcortical infarctions 3, 1
• Atrial fibrillation is the most common high-risk cardiac source, particularly in older adults 1
• Other sources include valvular disease, prosthetic valves, and cardiac arrhythmias 4
• Requires exclusion of atherosclerotic narrowing in the parent large artery to confirm diagnosis 3

3. Small-Vessel Disease/Lacunar Stroke (25% of cases)

• Occlusive arteriopathy involving penetrating arteries deep in the brain or brainstem, causing infarcts <1.5 cm 3, 1, 5
• Primarily caused by arteriolosclerosis (lipohyalinosis) rather than atherosclerosis 3, 5
• Strongly associated with hypertension (present in majority of cases) and diabetes mellitus (44.4% of cases) 3, 5
• Presents with classic lacunar syndromes such as pure motor hemiparesis 3, 5

4. Uncommon Causes (5% of cases)

The American Heart Association identifies several rare but important etiologies 3:

• Nonatherosclerotic vasculopathies including arterial dissection, vasculitis, fibromuscular dysplasia, and Moyamoya disease 3
• Hypercoagulable states including antithrombin III deficiency, protein C and S deficiency, antiphospholipid antibodies, and lupus anticoagulants 3, 6
• Hematologic disorders including polycythemia vera, sickle cell disease, sickle-C disease, and essential thrombocythemia 6
• Patent foramen ovale and carotid web, particularly in younger patients 3

5. Cryptogenic/Undetermined Cause (30% of cases)

• Despite thorough evaluation, the exact cause remains unknown in approximately one-third of all strokes 3, 1
• This category includes patients with two potential mechanisms identified or those with incomplete evaluation 3

Hemorrhagic Stroke Etiologies

Intracerebral Hemorrhage (10-15% of all strokes)

Primary Causes:

• Hypertension is the leading cause, particularly for deep hemorrhages in basal ganglia and brainstem 1, 7, 2
• Cerebral amyloid angiopathy causes lobar hemorrhages, especially in elderly patients 2
• Vascular malformations (arteriovenous malformations, cavernomas, aneurysms) account for approximately 20% of ICH, particularly important in patients under 50 years 7, 2

Contributing Factors:

• Anticoagulant use and bleeding disorders significantly increase hemorrhagic risk 1, 7
• Excessive alcohol use and liver dysfunction 1, 7
• Advanced age 1, 7

Subarachnoid Hemorrhage (3% of all strokes)

• Ruptured cerebral aneurysms are the primary cause of subarachnoid hemorrhage 1, 7, 4
• Aneurysm formation is promoted by hypertension and shear stress in conditions such as coarctation of the aorta, bicuspid aortic valve, or tetralogy of Fallot 7
• Less common subtypes include intracranial dissection, perimesencephalic hemorrhage, and cortical SAH 7

Procedure-Related Stroke Mechanisms

During percutaneous coronary interventions and cardiac catheterization, stroke can occur through multiple mechanisms 3:

• Mechanical injury from catheters and guidewires causing atherosclerotic plaque damage and thromboembolism (70-80% of intraprocedural strokes) 3
• Air embolism from inadequate aspiration or irrigation 3
• Hypoperfusion causing watershed strokes (20-30% of intraprocedural strokes) 3
• Contrast-induced vasospasm and neurotoxicity 3

Critical Clinical Pitfalls

Common diagnostic errors to avoid:

• Failing to exclude both cardioembolism and large-artery stenosis before diagnosing lacunar stroke 3, 5
• Missing arterial dissection or other uncommon causes in younger patients (<50 years) 3, 2
• Inadequate screening for hypercoagulable states in young patients with stroke of uncertain cause, those with prior venous thrombosis, or family history of unusual thrombosis 6
• Overlooking vascular malformations as the cause of hemorrhage in younger patients, where they account for a substantial minority of cases 7, 2