Cerebral small vessel disease

Leukoaraiosis is a radiological term used to describe diffuse white matter changes thought to be related to small vessel disease.

Terminology

There is no consensus in the literature regarding terminology for leukoaraiosis. The term is often used interchangeably with variations along the lines of small vessel chronic ischaemia, microvascular ischaemia, ischaemic microangiopathy, age-related white matter changes, and unidentified bright objects.

Epidemiology

Leukoaraiosis is more common with increasing age. The prevalence of white matter lesions in the general population is reported to be between 39 to 96% ¹¹.

Clinical presentation

Leukaraiosis is often an incidental asymptomatic finding on imaging. However, it has been shown to cause vascular dementia and it is more common in patients with dementia (vascular dementia, Alzheimer's disease, Lewy body dementia) compared to the general population (100% v. 92% respectively in one study) ^11,12.

Pathology

Histology from these lesions show atrophy of axons and decreased myelin. The pathophysiology of white matter lesions is different depending on the area of involvement, i.e. periventricular or deep (subcortical) white matter. This difference is emphasised in the Fazekas scale in which the two are separated. Pathogenesis and especially its clinical significance are still incompletely understood ^3,5.

Periventricular white matter lesions 

Periventricular white matter changes (3-13 mm from the ventricular surface) are thought to be haemodynamically determined rather than only related to small vessel disease ⁸. This region is a vascular border zone vascularised by noncollateralisingnon-collateralising ventriculofugal vessels arising from subependymal arteries. As such, it is prone to local and systemic decrease in cerebral blood flow. It is a predictor of watershed infarcts especially when located along the posterior horns and it is correlated with carotid artery stenosis ⁸.

It is worth noting that juxtaventricular white matter changes (<3 mm from the ventricular surface), such as ependymitis granularis, are not related to small vessel disease, but rather represent cerebrospinal fluid leak due to disruption of the ependyma ¹⁰.

Deep and subcortical white matter lesions

Deep white matter changes (>13 mm from the ventricular surface, <4 mm from the corticomedullary junction) are thought to be caused by lipohyalinosis (small vessel disease), i.e. incomplete arteriosclerosis ^8,9. They are a predictor of lacunar infarcts.

Radiographic features

Leukoaraiosis consists of bilateral patchy or diffuse white matter changes often observed on imaging studies ^6,7. The Fazekas scale has been proposed to quantify white matter lesions related to leukoaraiosis. This is especially useful in the setting of dementia. 

CT

• non-enhancing white matter hypodensities

MRI

• T1: hypointense or isointense, less conspicuous than on T2/FLAIR
• T2/FLAIR: hyperintense
• DWI: no diffusion restriction
• T1 C+ (Gd): non-enhancing

History and etymology

The term leukoaraiosis means white matter rarefaction and comes from the Greek (leuko = white and araios = rarefaction). It was first proposed by Vladimir Hachinski,(fl 2019) a Ukrainian-born Canadian neurologist ⁶.

Differential diagnosis

The differential diagnosis is wide and includes multiple diseases involving the white matter, including:

• CADASIL
• cerebral amyloid angiopathy
• primary angiitis of the CNS