Leukoaraiosis is a radiological term used to describe diffuse white matter changes thought to be related to small vessel disease.
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 ischemia, microvascular ischemia, ischemic microangiopathy, age-related white matter changes, and unidentified bright objects.
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.
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 disease, Lewy body dementia) compared to the general population (100% v. 92% respectively in one study) 11,12.
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 emphasized 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 vascularized by non-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.
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.
- non-enhancing white matter hypodensities
- 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.
The differential diagnosis is wide and includes multiple diseases involving the white matter, including:
- 1. Amar K, Bucks RS, Lewis T et-al. The effect of white matter low attenuation on cognitive performance in dementia of the Alzheimer type. Age Ageing. 1996;25 (6): 443-8. doi:10.1093/ageing/25.6.443 - Pubmed citation
- 2. Amar K, Lewis T, Wilcock G et-al. The relationship between white matter low attenuation on brain CT and vascular risk factors: a memory clinic study. Age Ageing. 1995;24 (5): 411-5. Age Ageing (link) - Pubmed citation
- 3. Helenius J, Soinne L, Salonen O et-al. Leukoaraiosis, ischemic stroke, and normal white matter on diffusion-weighted MRI. Stroke. 2002;33 (1): 45-50. doi:10.1161/hs0102.101228 - Pubmed citation
- 4. Pantoni L, Garcia JH. Pathogenesis of leukoaraiosis: a review. Stroke. 1997;28 (3): 652-9. doi:10.1161/01.STR.28.3.652 - Pubmed citation
- 5. Geerlings MI, Appelman AP, Vincken KL et-al. Association of white matter lesions and lacunar infarcts with executive functioning: the SMART-MR study. Am. J. Epidemiol. 2009;170 (9): 1147-55. doi:10.1093/aje/kwp256 - Pubmed citation
- 6. Hachinski VC, Potter P, Merskey H. Leuko-araiosis: an ancient term for a new problem. Can J Neurol Sci. 1987;13 (4 Suppl): 533-4. Pubmed citation
- 7. Grueter BE, Schulz UG. Age-related cerebral white matter disease (leukoaraiosis): a review. Postgraduate medical journal. 88 (1036): 79-87. doi:10.1136/postgradmedj-2011-130307 - Pubmed
- 8. Kim KW, MacFall JR, Payne ME. Classification of white matter lesions on magnetic resonance imaging in elderly persons. (2008) Biological psychiatry. 64 (4): 273-80. doi:10.1016/j.biopsych.2008.03.024 - Pubmed
- 9. Xiong, Yun Yun, Mok, Vincent. Age-Related White Matter Changes. (2018) Journal of Aging Research. 2011: 617927. doi:10.4061/2011/617927 - Pubmed
- 10. Franz Fazekas, Reinhold Schmidt, Philip Scheltens. Pathophysiologic Mechanisms in the Development of Age-Related White Matter Changes of the Brain. (1998) Dementia and Geriatric Cognitive Disorders. 9 (Suppl. 1): 2. doi:10.1159/000051182 - Pubmed
- 11. Prins ND, Scheltens P. White matter hyperintensities, cognitive impairment and dementia: an update. (2015) Nature reviews. Neurology. 11 (3): 157-65. doi:10.1038/nrneurol.2015.10 - Pubmed
- 12. Lee SJ, Kim JS, Lee KS, An JY, Kim W, Kim YI, Kim BS, Jung SL. The leukoaraiosis is more prevalent in the large artery atherosclerosis stroke subtype among Korean patients with ischemic stroke. (2008) BMC neurology. 8: 31. doi:10.1186/1471-2377-8-31 - Pubmed