What is chronic small vessel disease in the brain?

Definition of Chronic Small Vessel Disease in the Brain

Chronic cerebral small vessel disease (cSVD) is an umbrella term covering all pathological processes affecting the small arteries, arterioles, capillaries, and venules of the brain, most commonly manifesting as age-associated and vascular risk factor-associated microangiopathy. 1

Core Pathological Features

cSVD represents a diverse cluster of cerebrovascular diseases that primarily damage the brain's small vessels through several mechanisms 2:

• The most common form is age-associated and vascular risk factor-associated microangiopathy, which develops chronically over time in response to hypertension, diabetes, and other cardiovascular risk factors 1
• The disease affects arterioles, capillaries, and small veins supplying the white matter and deep brain structures, leading to progressive tissue damage 3
• Endothelial dysfunction, including blood-brain barrier (BBB) failure, plays a pivotal role in the early pathophysiology of the disease process 1

Clinical Manifestations

The disease presents with a spectrum of symptoms that can be acute or slowly progressive 1:

• Acute presentations include lacunar stroke (small subcortical infarcts) 1
• Progressive symptoms include cognitive impairment, dementia, gait disturbances, and mood disorders such as depression 1, 2
• cSVD contributes to approximately 25% of ischemic strokes and 45% of dementias in the elderly population 3
• Additional clinical features include motor impairment, vascular parkinsonism, impaired balance, falls, apathy, and personality changes 4

Neuroimaging Features (STRIVE Criteria)

The diagnosis relies on identifying characteristic MRI findings 1:

• White matter hyperintensities (WMHs) on T2-weighted or FLAIR sequences, representing areas of chronic ischemic damage 1
• Lacunes (small fluid-filled cavities 3-15mm in diameter from old infarcts) 2
• Enlarged perivascular spaces (Virchow-Robin spaces) 1, 2
• Cerebral microbleeds detected on gradient echo or susceptibility-weighted imaging 1, 2
• Recent small subcortical infarcts and brain atrophy 2, 4

Common Etiologies

The underlying causes vary but share common pathophysiological mechanisms 3, 4:

• Arteriolosclerosis related to aging, hypertension, and conventional vascular risk factors (most common) 4
• Cerebral amyloid angiopathy (CAA) caused by vascular deposition of β-amyloid 4
• Genetic small vessel angiopathies such as CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy) 1
• Inflammatory and immune-mediated small vessel diseases 3

Pathophysiological Mechanisms

Multiple interconnected processes drive disease progression 5:

• Blood-brain barrier impairment allows subtle leakage of plasma components into brain tissue, though this is much more subtle than the gross BBB disruption seen in acute inflammation or tumors 1
• Endothelial dysfunction affects the neurovascular unit (neurons, glia, and vascular cells functioning as an integrated system) 6
• Capillary flow disturbances may limit oxygen extraction efficiency even without physical flow-limiting pathology 7
• White matter changes result from chronic ischemia and disruption of structural brain networks 4, 5

Important Clinical Caveats

Several nuances affect diagnosis and management:

• Mixed pathology is extremely common, with vascular disease frequently coexisting with Alzheimer's disease pathology (up to 38% prevalence in neuropathologic studies) 1, 6
• The disease is highly prevalent in community studies, especially in individuals over 80 years of age, making it the most common incidental finding on brain scans 3
• cSVD represents the most common pathology underlying vascular cognitive impairment and is a major health burden in both high-income and low- and middle-income countries 4
• Beginning confluent or confluent white matter hyperintensities (Fazekas grade 2-3) are often sufficient to cause clinical cognitive impairment 6, 8