Update on cerebral small vessel disease: a dynamic whole-brain disease

Abstract

Cerebral small vessel disease (CSVD) is a very common neurological disease in older people. It causes stroke and dementia, mood disturbance and gait problems. Since it is difficult to visualise CSVD pathologies in vivo, the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities, lacunar ischaemic stroke, lacunes, microbleeds, visible perivascular spaces and many haemorrhagic strokes. However, variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies. A standardised use of terms should be encouraged in CSVD research. These CSVD features have long been regarded as different lesions, but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore, owing to its diffuse nature, CSVD should be regarded as a 'whole-brain disease'. Single antiplatelet (for acute lacunar ischaemic stroke) and management of traditional risk factors still remain the most important therapeutic and preventive approach, due to limited understanding of pathophysiology in CSVD. Increasing evidence suggests that new studies should consider drugs that target endothelium and blood-brain barrier to prevent and treat CSVD. Epidemiology of CSVD might differ in Asian compared with Western populations (where most results and guidelines about CSVD and stroke originate), but more community-based data and clear stratification of stroke types are required to address this.

Keywords: Blood Brain Barrier; Cerebral Small Vessel Disease; Lacunar Infarct; Microvascular dysfunction; White Matter Hyperintensities.

Figure 1

STRIVE, STandards for Reporting and Imaging of Small Vessel Disease: example findings (upper), schematic representation (middle) and a summary of imaging characteristics (lower) of MRI features for changes related to small vessel disease. DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; SWI, susceptibility-weighted imaging; GRE, gradient-recalled echo.

Figure 2

Four possible mechanisms that cause a lacunar infarct (from bottom to top): (A) an embolus from the big arteries or cardiac sources goes up to MCA and ends up entering and occluding lenticulostriate arteries, resulting in a lacunar lesion in basal ganglia; (B) if the atheroma in the parent artery (ie, MCA) is positioned at the opening of its penetrating branches, it could lead to an acute occlusion of one or several penetrating arteries, hence causing a lacunar infarct; (C) a lacunar infarct could also be due to atheroma in the perforating artery if an acute occlusion happens; (D) intrinsic small vessel disease may lead to diffused disrupted blood–brain barrier. If this happens at an arteriolar level, plasma fluid components would enter and deposit in the vessel wall, resulting in narrowing of the arteriolar lumen, vessel wall thickening and eventually a secondary luminal occlusion and traditional infarct. MCA, middle cerebral arteries.

Figure 3

Example of MRIs of a lacune from a haemorrhagic source (A,B), and from a lacunar infarct (C, D). D (the DWI) is from the acute presentation (i.e. within a few days of the stroke), and C (the FlAIR) is weeks to months later when the lesion has cavitated. DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; SWI, susceptibility-weighted imaging.

Figure 4

Long-term appearances of lacunar infarcts (arrows: old stroke lesion on the follow-up scans). DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; WMH, white matter hyperintensity.