What are the risk factors for multifocal cerebral infarcts?

Risk Factors for Multifocal Cerebral Infarcts

Cardioembolism is the most common risk factor for multifocal cerebral infarcts, accounting for 37-49% of cases, followed by large artery atherosclerosis at 26%, with bilateral multifocal infarcts particularly suggesting cardiac sources or unusual systemic disorders. 1, 2

Primary Risk Factors by Infarct Pattern

Bilateral Multifocal Infarcts

• Cardiac sources of embolism are the predominant risk factor, particularly atrial fibrillation which accounts for approximately one-third of cardiac cases 3, 2
• Unusual systemic disorders including coagulopathies, hematologic diseases (such as disseminated intravascular coagulation related to cancer), and systemic inflammatory conditions are disproportionately represented in bilateral patterns 3, 1, 2
• Vasculitis and multifocal intracranial angiopathy occur in 0.2-6.5% of bilateral multifocal infarcts 1, 2
• Patients with bilateral multifocal infarcts tend to be younger than those with single infarcts 3

Unilateral Multifocal Infarcts

• Ipsilateral internal carotid artery disease is the dominant risk factor when infarcts involve only the anterior circulation, accounting for the majority of cases 3
• Cardiac embolism becomes more likely when infarcts involve both anterior and posterior circulations within the same hemisphere 3
• Large artery atherosclerosis with anatomic variations (such as fetal posterior cerebral artery origin) can produce unilateral multifocal patterns in 11% of cases 2

Multifocal Subcortical Infarcts (Without Cortical Involvement)

• Chronic small vessel disease with high Fazekas scores is strongly associated with isolated subcortical multifocal patterns, suggesting acute-on-chronic microvascular injury rather than embolism 4
• These patients are less likely to have proximal embolic sources compared to those with cortical involvement (only 24% have cardioembolism versus 64.9% having embolic stroke of undetermined source) 4
• Milder stroke severity is characteristic of this pattern 4

Cardiac Risk Factors Requiring Immediate Evaluation

All patients with multifocal infarcts require immediate cardiac workup including:

• 12-lead ECG to detect atrial fibrillation, atrial flutter, and acute myocardial infarction 5
• Continuous cardiac monitoring for at least 24 hours, followed by extended monitoring for at least 14 days if no atrial fibrillation is detected initially 5
• Echocardiography (transthoracic initially, transesophageal if cryptogenic) to identify structural cardiac sources including valvular disease, atrial septal abnormalities, and left atrial appendage thrombus 5, 6
• Cardiac biomarkers (troponin) as acute MI can both cause and be precipitated by stroke 5

Vascular Risk Factors

• Large artery atherosclerosis including aortic arch atheroma accounts for 25.7% of multifocal infarcts 1
• Intracranial stenosis (mostly atherosclerotic) combined with anatomic variations can produce multifocal patterns 2
• Patients with atherosclerotic stenosis of cervical carotid or major intracranial arteries have a 50% rate of abnormal cardiac stress tests, indicating concurrent cardiac disease 5

Hematologic and Systemic Risk Factors

• Coagulopathies and hematologic disorders account for 2.1-7.5% of multifocal infarcts 1, 2
• Cancer-associated hypercoagulability with disseminated intravascular coagulation is an important consideration 2
• Inflammatory disorders including vasculitis and infectious causes represent 0.2-6.5% of cases 1, 2

Special Populations

Infective Endocarditis

• Multiple cerebral infarcts occur in 10.8% of IE-related strokes, with the middle cerebral artery territory most commonly affected (40%), followed by frontoparietal (20%), and multifocal patterns (10.8%) 7
• Multifocal patterns in IE are not correlated with increased risk of hemorrhagic conversion compared to single lesions 7

Sickle Cell Disease

• Small multifocal infarctions involving basal ganglia and deep white matter are common, with an annual stroke incidence of 0.28% (285 per 100,000) 7
• High transcranial Doppler velocities (≥200 cm/s), low hemoglobin, high white cell count, hypertension, and silent brain infarction are specific risk factors 7

Cocaine Abuse

• Multifocal vasospasm can produce bilateral border-zone infarcts in anterior cerebral artery and middle cerebral artery territories 8
• This represents a distinct mechanism requiring differentiation from thromboembolic stroke to avoid inappropriate thrombolytic therapy 8

Diagnostic Yield and Undetermined Etiology

• Despite extensive workup, 26-27.6% of multifocal infarcts remain cryptogenic after complete evaluation 1, 2
• Only 30-32% of patients with multifocal infarcts present with clinical symptoms suggesting multiple lesions before neuroimaging, making MRI with diffusion-weighted imaging essential for detection 3, 2
• Complete diagnostic evaluation should be completed within 48 hours of symptom onset 5

Critical Pitfalls to Avoid

• Do not assume all multifocal infarcts are embolic: isolated subcortical multifocal patterns are more likely related to small vessel disease than embolism 4
• Do not overlook unusual causes: in bilateral multifocal infarcts, coagulopathies and systemic disorders are disproportionately represented compared to single infarcts 3
• Do not skip extended cardiac monitoring: initial ECG misses many cases of paroxysmal atrial fibrillation requiring 14+ days of monitoring 5
• Do not forget iatrogenic causes: procedural complications account for 0.1% of multifocal infarcts 1