Cerebral Small Vessel Disease

Original Editor - Rahma Ahmed Ahmed Bahbah

Top Contributors - Rahma Ahmed Ahmed Bahbah, Lucinda hampton, Yahya Al-Razi and Vidya Acharya  

Introduction

Small vessel disease (SVD) is a systemic condition affects primarily the brain, the kidney, and the retina as they have a high percentage from cardiac output. So, SVD is a major cause in conditions such as renal failure, blindness, lacunar infarcts, and dementia.

It's a condition -from its name- affect the small vessels such as the small arteries, arterioles, venules, and capillaries. The main target of SVD is the endothelium, as it's the barrier between circulating blood and the vessel wall. Endothelial cells may become damaged when inflammation exits.

Cerebral small vessel disease (CSVD) is an umbrella term that refers to intracranial vascular disease based on various pathological and neurological processes, which lead to manifestations and neuroimaging findings as a result of the structural changes of vascular and brain parenchyma.

CSVD mainly affect grey as well as white matter of the deep structures such as basal ganglia, thalamus, brainstem and internal capsule.

Subtypes

Most commonly, two types are identified: amyloid and non-amyloid related (Table 1).

CSVD can be divided into six groups

○Type I: arteriosclerosis/age-related CSVD

○Type II: amyloid-related CSVD;

○Type III: genetic CSVD distinct from amyloid angiopathy

○Type IV: inflammatory/immunologically mediated CSVD

○Type V: venous collagenosis

○Type VI: other CSVD.

Type:	Description:	Associated Diseases:
Type I	Arteriosclerosis-related CSVD	• Hypertension • Diabetes
Type II	Amyloid-related CSVD	• AD • Down’s syndrome
Type III	Genetic CSVD (distinct from amyloid angiopathy)	• Fabry’s disease • CADASIL • CARASIL • MELAS • Small vessel disease with COL4A1 mutation • Retinal vasculopathy with leukodystrophy with TREX1 mutation • Hereditary multi-infarct dementia of Swedish type
Type IV	Inflammatory/immunologically mediated CSVD	• Systematic Vasculitis: ○IgA vasculitis ○Eosinophilic granulomatosis with polyangiitis ○Granulomatosis with polyangiitis ○Cryoglobulinemic vasculitis ○Cutaneous leukocytoclastic ○Microscopic polyangiitis • Primary Central Nervous System Vasculitis • Vasculitis secondary to CNS infections tuberculosis, syphilis, HIV, leptospirosis • Vasculitis Secondary to Connective Tissue Disorders (SLE, scleroderma, rheumatoid vasculitis, dermatomyositis, Sjogren’s syndrome)

Cerebral small vessel disease (CVSD) classification. AD—Alzheimer’s disease; CADASIL—cerebral autosomal dominant arteriopathy with subcortical ischemic stroke and leukoencephalopathy; CARASIL—cerebral autosomal recessive arteriopathy with subcortical ischemic and leukoencephalopathy; MELAS—mitochondrial encephalopathy with lactic acidosis and stroke-like episodes; CNS—central nervous system; SLE—systematic lupus erythematosus; HIV—human immunodeficiency virus.

The common groups are Type I, which is associated with arteriolosclerosis, and Type II, which is associated with amyloid angiopathy.

• Table 2 shows a comparison of their characteristics.

Comparison of the two most common types of CVSD with clinical and neuroimaging characteristics. CVSD—cerebral small vessel disease, CMBs—cerebral microbleeds.

Classification	Type I	Type II
Characteristic	• Associated with arteriosclerosis. • Related age differences • Degenerative microangiopathy	• Associated with amyloid deposition • Rated age differences
Etiology	• Atrophy of smooth muscles in tunica media • Aggregate of fibro-hyaline material • Stenosis of vessel lumen • Degeneration of vessel wall • Changing of arterial vessels systems	• Vasculopathy • Aggregate of amyloid in cortical walls or leptomeningeal small arteries but not capillaries • Apolipoprotein gene polymorphism
Manifestations	• Lacunar strokes in deep part of brain • Dementia and cognitive impairment	• Intracerebral hemorrhage in cerebral lobes • Non-lacunar strokes • Hallmarks of Alzheimer’s disease • Cognitive impairment, dementia and transient focal neurological episodes
Radiographic features	• CMBs in deep part of the brain • Rare changes to the siderosis type of the superficial cortical area • Presence of basal ganglia perivascular spaces • Hyperintensities in the cerebral region of white matter	• CMB sin cerebral lobes • Cortical superficial siderosis • Centrum seniovate perivascular space • Posterior dominance with white matter hyperintensities

Clinical manifestations

The main clinical manifestations of CSVD include stroke, cognitive decline, dementia, psychiatric disorders, abnormal gait, and urinary incontinence, as according to the location of the lesion.

Neuroimaging

Neuroimaging features of CSVD include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy.

Whereas lacunar infarction, critical stenosis and hypoperfusion involving multiple small arterioles, mainly in deep white matter, lead to incomplete ischemia which are visualized as White Matter Hyperintensities (WMH) on neuroimaging. So lacunes and white matter lesions often coexist in the same patient.

Inflammatory markers have been associated with periventricular white matter hyperintensities (WMH).

Risk factors

The Conventional risk factors are hypertension, diabetes, smoking, obesity, depression and dyslipidemia, classified as vascular, lifestyle, and environmental and lifetime risk factors

Pathophysiology process

The pathophysiologic mechanisms of CSVD are not yet clear. These various pathologic changes cited by the European expert group are damages of brain parenchyma including neuronal apoptosis, diffuse axonal injury, demyelination and loss of oligodendrocytes.

The main target of SVD is the endothelium, as it's the barrier between circulating blood and the vessel wall. Endothelial cells may become damaged when inflammation exits.

Poor sleep is associated with increased systemic inflammation and maybe develop cortical atrophy.

Diabetes as known is a very good environment to develop inflammation

Management

It can be categorized by;

• Lifestyle changes;

Having good sleep, Quitting smoking, Practicing some physical activities, Eating a healthy diet that's low in salt -as salt increase blood pressure-, Losing weight.

• Treatment may include medications to reduce cholesterol, regulate glucose levels, and control hypertension.

Aspirin remains the standard care as the antiplatelet to reduce the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke.