Are white matter hypodensities related to small vessel ischemic disease, specifically cerebral small vessel disease (CSVD)?

From the Guidelines

Yes, white matter hypodensities are related to small vessel ischemic disease, specifically cerebral small vessel disease (CSVD), as they represent areas of chronic ischemia in the brain's white matter due to narrowed or blocked small arteries and arterioles. These hypodensities, which appear as areas of decreased density on CT scans or as hyperintensities on T2-weighted MRI, are a result of chronic hypoperfusion that damages the white matter, leading to demyelination, axonal loss, and gliosis 1. The pathophysiology of small vessel disease is complex, but it is generally accepted that endothelial dysfunction, including blood-brain barrier (BBB) failure, plays a pivotal role in the development of CSVD 1.

Key Points

• Cerebral small vessel disease accounts for 20% to 30% of ischemic stroke cases and is characterized by subcortical infarcts of <15 mm 1.
• Risk factors for small vessel ischemic disease include hypertension, diabetes, smoking, hyperlipidemia, and advanced age.
• The distribution of white matter hypodensities is often periventricular or subcortical, and they may be associated with cognitive impairment, gait disturbances, and increased risk of stroke when extensive.
• Management focuses on controlling vascular risk factors through blood pressure management, diabetes control, smoking cessation, and cholesterol reduction to prevent progression of the disease.

Clinical Implications

The relationship between white matter hypodensities and small vessel ischemic disease has significant implications for patient management and outcomes. Controlling vascular risk factors is crucial to preventing the progression of CSVD and reducing the risk of stroke and cognitive impairment 1. Additionally, targeted strategies for secondary prevention after small vessel stroke may also reduce the risk of vascular dementia 1.

Evidence-Based Recommendation

Based on the most recent and highest quality evidence, controlling vascular risk factors is essential to prevent the progression of CSVD and reduce the risk of stroke and cognitive impairment 1. This can be achieved through blood pressure management, diabetes control, smoking cessation, and cholesterol reduction.

From the Research

Relationship Between White Matter Hypodensities and Cerebral Small Vessel Disease

• White matter hypodensities are related to small vessel ischemic disease, specifically cerebral small vessel disease (CSVD) 2.
• CSVD encompasses lacunar stroke, white matter hyperintensities, lacunes, and microbleeds, and is a common cause of vascular dementia 3.
• White matter lesions in CSVD are related to ischemic injury and increase the risk of stroke and cognitive decline 4.

Pathophysiology of Cerebral Small Vessel Disease

• Chronic hypoxia-ischemia is a putative mechanism underlying the development of white matter hyperintensities (WMH) and microstructural disruption in CSVD 5.
• Elevated oxygen extraction fraction (OEF) is detected in the watershed where WMH density is highest, and OEF is elevated in regions immediately surrounding WMH 5.
• Endothelial dysfunction is considered a central feature of CSVD, but the contributions of smooth muscle cells, pericytes, and other perivascular cells warrant continued investigation 6.

Clinical Implications

• The extent of white matter hypodensities (WMH) is associated with poor functional outcome and mortality after intracerebral hemorrhage (ICH) 2.
• WMH severity is associated with older age, female sex, admission National Institutes of Health Stroke Scale (NIHSS) points, and signs of previous ischemic stroke on CT 2.
• CSVD accounts for approximately 25% of ischemic strokes and the vast majority of spontaneous intracerebral hemorrhage, and is also the most important vascular contributor to dementia 6.