What is cerebral microangiopathy?

Cerebral Microangiopathy: Definition, Pathophysiology, and Clinical Implications

Cerebral microangiopathy is a pathological condition affecting the small blood vessels of the brain, characterized by structural and functional changes that lead to white matter lesions, lacunar infarcts, microbleeds, and blood-brain barrier dysfunction, which can result in cognitive impairment, stroke, and vascular dementia. 1, 2

Definition and Pathophysiology

Cerebral microangiopathy, also known as cerebral small vessel disease (cSVD), refers to a group of pathological processes that affect the small arteries, arterioles, venules, and capillaries of the brain 2. The condition is characterized by:

• Structural changes: Thickening of vessel walls, lipohyalinosis (fibrinoid degeneration), arteriolosclerosis, and endothelial dysfunction 1
• Blood-brain barrier disruption: Increased permeability leading to leakage of plasma components into the brain parenchyma 1
• Microvascular damage: Resulting in reduced cerebral blood flow and chronic hypoperfusion 2

Types of Cerebral Microangiopathy

Several forms of cerebral microangiopathy exist:

• Age-related and hypertension-related small vessel disease: The most common form 3
• Cerebral amyloid angiopathy: Characterized by amyloid-β deposition in vessel walls 1, 4
• Hereditary forms:
  • CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) - caused by Notch3 gene mutations 4
  • CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) 1
• Other rare forms: Including mitochondrial cytopathies, Fabry's disease, and toxemic vasculopathy 4

Neuroimaging Features

Cerebral microangiopathy is characterized by specific neuroimaging findings:

• White matter hyperintensities: Visible on T2-weighted MRI sequences 2
• Lacunar infarcts: Small subcortical infarcts typically less than 1 cm in size 2
• Enlarged perivascular spaces: Visible on MRI 2
• Cerebral microbleeds: Small hemorrhages visible on gradient-echo or susceptibility-weighted MRI 2
• Blood-brain barrier leakage: Detectable with dynamic contrast-enhanced MRI 1, 2

Risk Factors

The primary risk factors for cerebral microangiopathy include:

• Hypertension: The strongest and most well-established risk factor 2, 5
• Diabetes mellitus: Associated with a 20-40% increased risk 2
• Advanced age: Risk increases significantly with aging 3
• Smoking: Significant modifiable risk factor 2
• Dyslipidemia: Contributes to atherosclerosis and vascular damage 2
• Prior stroke: Significantly increases risk of vascular cognitive impairment 2
• Atrial fibrillation and heart failure: More than double the risk of dementia 2

Clinical Manifestations

Cerebral microangiopathy can present with various clinical manifestations:

• Cognitive impairment: Particularly executive dysfunction, slowed processing speed, and attention deficits 2, 6
• Gait disturbances: Including imbalance and small-step gait 6
• Urinary symptoms: Including urgency and incontinence 6
• Mood disorders: Depression and emotional lability 6
• Stroke: Both clinical and subclinical infarcts 2
• Vascular dementia: A "dysexecutive" type of cognitive impairment 6

Diagnosis

Diagnosis of cerebral microangiopathy relies on:

• MRI: The preferred imaging modality, showing white matter hyperintensities, lacunar infarcts, microbleeds, and enlarged perivascular spaces 2
• CT: Less sensitive than MRI but can show infarctions, white matter changes, and brain atrophy 2
• Clinical assessment: Evaluation of cognitive function, gait, and neurological status 2

Management and Prevention

Management focuses on controlling vascular risk factors:

• Blood pressure control: Intensive BP control with target SBP <120 mmHg is recommended 2
• Treatment of diabetes: Tight glycemic control 2
• Lipid management: Statin therapy when indicated 2
• Smoking cessation: Critical for reducing vascular risk 2
• Regular physical activity: Reduces risk of progression 2
• Cognitive monitoring: Regular screening for cognitive changes 2

Prognosis

Cerebral microangiopathy has an inherent tendency to progress 6. The rate of progression varies depending on:

• Control of risk factors: Particularly hypertension 5, 3
• Severity at baseline: More extensive disease at baseline predicts faster progression 6
• Age: Older individuals tend to progress more rapidly 2

Clinical Significance

Cerebral microangiopathy is clinically significant because it:

• Is a major cause of vascular cognitive impairment and dementia 3
• Increases risk for stroke and mortality 2
• Often coexists with neurodegenerative processes like Alzheimer's disease 2
• Can occur in clinically healthy individuals and those with mild cognitive impairment 6

Understanding cerebral microangiopathy is essential for early detection, prevention, and management of its potentially devastating neurological consequences.