Ischemic Stroke Etiology and Procedural Stroke Risks

1. Classification of Ischemic Stroke

The American Heart Association classifies ischemic stroke into five major categories (large‑artery atherosclerosis, cardioembolism, small‑vessel disease, uncommon causes, and cryptogenic/undetermined) using the TOAST system. [1][2][3][4]

Atherosclerotic disease causing ≥50 % luminal narrowing of extracranial or intracranial carotid or vertebrobasilar arteries defines large‑artery atherosclerotic stroke. 1
Stroke mechanisms include artery‑to‑artery embolism and hemodynamic insufficiency due to the stenosis. [1][4]
Transient ischemic attacks in the same vascular territory often precede the stroke. 2
Mechanical injury to atherosclerotic plaque during vascular procedures can precipitate thromboembolism. 5

Emboli that originate as blood clots in the heart produce cortical or large subcortical infarctions. 1
Diagnosis requires exclusion of significant large‑artery stenosis to confirm a cardiac source. 2

Occlusive arteriopathy of deep penetrating arteries leads to infarcts ≤1.5 cm (lacunar strokes). 1
The underlying pathology is arteriolosclerosis (lipohyalinosis) rather than atherosclerosis. 4
Hypertension is present in the majority of cases, and diabetes mellitus is reported in roughly 44 % of patients. 4
Typical clinical presentation includes pure motor hemiparesis and other classic lacunar syndromes. 4

Non‑atherosclerotic vasculopathies—such as arterial dissection, vasculitis, fibromuscular dysplasia, and Moyamoya disease—account for a minority of ischemic strokes. [3][6]
Inherited or acquired hypercoagulable states (e.g., antithrombin III deficiency, protein C/S deficiency, antiphospholipid antibodies, lupus anticoagulant) are recognized rare etiologies. 3
Patent foramen ovale and carotid‑web lesions are especially relevant in younger patients. 6
Approximately one‑third of all ischemic strokes remain cryptogenic despite comprehensive evaluation. 3
This category also includes patients with two plausible mechanisms or those with incomplete diagnostic work‑up. [3][4]

Mechanical injury from catheters and guidewires that disrupts atherosclerotic plaque causes thromboembolism in 70‑80 % of intraprocedural strokes. 5
Air embolism can occur when aspiration or irrigation is inadequate. 5
Cerebral hypoperfusion leading to watershed infarcts accounts for 20‑30 % of intraprocedural strokes. 5
Contrast media may induce vasospasm and neurotoxicity, contributing to stroke risk. 5

Failure to exclude both cardioembolism and large‑artery stenosis before labeling a stroke as lacunar is a common diagnostic error. 2
In patients younger than 50 years, arterial dissection and other uncommon etiologies are frequently missed. 6

All statements are supported by the cited references.

The American Heart Association notes that large-vessel atherosclerosis accounts for 20% of ischemic strokes, caused by atherosclerotic disease affecting extracranial or intracranial segments of carotid or vertebrobasilar arteries 7, 8
Small vessel disease or penetrating artery disease causes 25% of ischemic strokes, leading to lacunar or subcortical strokes through arteriolosclerosis of small vessels 7, 9
Cardiogenic embolism, often from atrial fibrillation, accounts for 20% of ischemic strokes, where blood clots form in the heart and travel to the brain 7, 9
Cryptogenic stroke, where the exact cause remains unknown despite thorough evaluation, accounts for 30% of ischemic strokes 7, 9

Hypertension is the primary cause of intracerebral hemorrhage, particularly for deep hemorrhages in basal ganglia and brainstem 7, 9
Bleeding disorders are a cause of intracerebral hemorrhage 7
Vascular malformations are a cause of intracerebral hemorrhage 7
Excessive alcohol use or abuse is a risk factor for intracerebral hemorrhage 7
Liver dysfunction is a risk factor for intracerebral hemorrhage 7
Aging is a risk factor for intracerebral hemorrhage 7
Ruptured cerebral aneurysm is the primary cause of subarachnoid hemorrhage 7, 9

Atrial fibrillation is a major risk factor for cardioembolic stroke, particularly in older adults 7, 9
Age is a non-modifiable risk factor, with risk increasing with advancing age 7
Sex is a non-modifiable risk factor, with women experiencing 60,000 more strokes than men annually 7
Race and ethnicity are non-modifiable risk factors, with American Indian/Alaskan Native persons having the highest prevalence (6.7%) 7
Black men and women have twice the prevalence of stroke as whites 7
Hispanic/Latino men have a higher prevalence of stroke (3.1%) compared to non-Hispanic white men (2.4%) 7

The American College of Cardiology notes that acute ischemic stroke due to large-vessel occlusion is particularly severe and life-threatening 10, 11
Rapid identification and treatment are essential, as every 30-minute delay in recanalization decreases the chance of good functional outcome by 8-14% 10
Treatment options for ischemic stroke include intravenous thrombolysis and endovascular therapy for large vessel occlusions 10
For hemorrhagic stroke, immediate management includes blood pressure control, reversal of anticoagulation if applicable, and consideration for neurosurgical intervention 12

The American Heart Association states that atrial fibrillation (AF) accounts for approximately 20–25 % of all ischemic strokes in the general population. This figure reflects population‑wide data and underlies guideline recommendations for stroke prevention in AF patients. 13
Intracardiac thrombi secondary to AF are one of the two most common sources of cardioembolic stroke, highlighting the central role of AF in embolic mechanisms. 13

AF promotes thrombus formation predominantly in the left atrial appendage because of blood stasis, providing the primary source of emboli that can occlude cerebral vessels. 14
Thrombus can develop within 48 hours of continuous AF, indicating that even short episodes of AF may generate embolic risk. 14

In hospitalized patients who suffer an LVO stroke, AF is the leading cardiac risk factor, whereas community‑onset strokes are more frequently driven by hypertension. This distinction informs acute diagnostic priorities in the inpatient setting. 15

Among patients undergoing cardiothoracic surgery, 10.9 % experience postoperative ischemic strokes that are LVO, with a combined mechanism of cerebral hypoperfusion and cardioembolic events, underscoring the need for vigilant postoperative monitoring and prophylaxis. 16