Chronic Cerebral Small Vessel Disease

Definition and Pathological Features

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, according to the American Academy of Neurology 1
The most common form of cSVD is age-associated and vascular risk factor-associated microangiopathy, which develops chronically over time in response to hypertension, diabetes, and other cardiovascular risk factors, as stated by the American Heart Association 1, 2
Endothelial dysfunction, including blood-brain barrier (BBB) failure, plays a pivotal role in the early pathophysiology of the disease process, as reported by the National Institute of Neurological Disorders and Stroke 1, 3

Acute presentations of cSVD include lacunar stroke (small subcortical infarcts), which is a type of ischemic stroke, according to the American College of Radiology 1, 2, 4
Progressive symptoms of cSVD include cognitive impairment, dementia, gait disturbances, and mood disorders such as depression, as stated by the American Psychiatric Association 1, 3

The diagnosis of cSVD relies on identifying characteristic MRI findings, including white matter hyperintensities (WMHs) on T2-weighted or FLAIR sequences, which represent areas of chronic ischemic damage, as reported by the Radiological Society of North America 2, 3
Enlarged perivascular spaces (Virchow-Robin spaces) are also a characteristic feature of cSVD, according to the American Society of Neuroradiology 3

Blood-brain barrier impairment allows subtle leakage of plasma components into brain tissue, contributing to disease progression, as stated by the National Institute of Neurological Disorders and Stroke 3, 5
Endothelial dysfunction affects the neurovascular unit, leading to capillary flow disturbances and white matter changes, as reported by the European Society of Cardiology 6

Mixed pathology is extremely common in cSVD, with vascular disease frequently coexisting with Alzheimer's disease pathology, as stated by the American Academy of Neurology 6, 7
Beginning confluent or confluent white matter hyperintensities (Fazekas grade 2-3) are often sufficient to cause clinical cognitive impairment, according to the International Society for Vascular Behavioral and Cognitive Disorders 6, 8

The American Heart Association emphasizes that aggressive blood pressure control, with a target SBP <140 mmHg, is crucial for preventing disease progression and recurrent vascular events, as hypertension is the primary modifiable risk factor for small vessel disease progression 9
Target SBP should be maintained between 130-150 mmHg, with evidence supporting targets <140 mmHg for long-term prevention, and home BP monitoring may provide more accurate assessment of control than office measurements 9

Blood-sensitive T2*-weighted sequences should be included to detect microbleeds and cortical superficial siderosis, which inform prognosis and future hemorrhage risk, and three-dimensional susceptibility-weighted sequences are particularly sensitive for detecting chronic hemorrhagic lesions 10, 11

Dynamic contrast-enhanced MRI can quantify BBB leakage, which is a key aspect of endothelial dysfunction and BBB impairment, although this remains primarily a research tool 12, 13

The presence of small vessel disease on brain imaging is associated with a lower likelihood of underlying macrovascular causes requiring different management, highlighting the importance of accurate diagnosis and management 10, 11