Kril_Young_US_Neurology5-2_US_Neuro 16/02/2010 10:30 Page 10
Current Issues
The Evolution of White Matter Hyperintensities
Vanessa G Young, PhD
1
and Jillian J Kril, PhD
2
1. Medical Student, University of Notre Dame, Sydney;
2. Professor of Neuropathology, Disciplines of Medicine and Pathology, University of Sydney
Abstract
White matter hyperintensities (WMHs) are a common finding on magnetic resonance imaging (MRI) scans of elderly subjects. Despite their
frequency, the clinical correlates and etiology of WMH remain controversial, with many conflicting results published. This is due, in part, to the varied
populations studied. Nevertheless, the prevailing opinion is that these lesions are of vascular origin due to the strong associations with vascular
risk factors and stroke. Neuropathological studies have also yielded varied results. Interestingly, while a number of associations with variables such
as demyelination and gliosis have been reported, no single pathological variable has been found to account for the MRI changes. The most
consistent associations are with reduced vascular integrity and increased blood–brain barrier permeability. Further studies investigating the
blood–brain barrier may assist in elucidating the origin of these common abnormalities.
Keywords
Magnetic resonance imaging, neuropathology, blood–brain barrier, clinicopathological correlations, p-glycoprotein
Disclosure: The authors have no conflicts of interest to declare.
Received: February 9, 2009 Accepted: October 28, 2009
Correspondence: Jillian J Kril, PhD, Department of Pathology, The University of Sydney, Sydney 2006, Australia. E:
jilliank@med.usyd.edu.au
The increasing application of neuroimaging techniques has led to the BP were higher in subjects with WMHs,
5,7
while others found that mean
frequent discovery of cerebral white matter lesions, referred to as white systolic BP was significantly higher in subjects with WMHs regardless of
matter hyperintensities (WMHs) in this article, which appear as whether they were from a dementia or a control group.
12
Other studies
hypodense areas on computed tomography (CT) scans or as showed that elevated diastolic BP, measured years earlier, was related
hyperintense regions on T
2
-weighted and fluid-attenuated inversion to the presence of WMHs.
13,14
The type of BP notwithstanding, these
recovery (FLAIR) magnetic resonance imaging (MRI) sequences. Since studies suggest that the development of WMHs is a relatively slow
their discovery, almost every aspect of WMHs has been surrounded by process that is related to long-standing high BP.
13
controversy.
1
Despite the abundant literature on this subject, relatively
little progress has been made in determining the etiology, pathology, or Clinical Correlates
even the clinical significance of these lesions. As with the risk factors associated with WMHs, the clinical correlates linked
to these lesions are many and varied, due partly to the high prevalence of
The prevalence of WMHs in asymptomatic healthy subjects varies widely WMHs in healthy elderly subjects. A few of the more consistently reported
depending on the technique used for their identification, the type of clinical correlates include late-onset depression,
15
lacunar stroke,
16
and
lesion examined, and the characteristics of the population studied.
2,3
motor deficits,
17
with the latter including gait disturbance,
18
slowed motor
Large-scale population-based studies have shown that prevalence rates response,
19
poor balance,
20
and increased risk for falling.
18,19
There is also a
range from 27 to 96%.
4,5
However, prevalence rates are generally higher high correlation between WMHs and dementia, with more extensive WMHs
in patients with dementia,
6
and have been found to differ among ethnic found in patients with vascular dementia (VaD), Alzheimer’s disease (AD),
groups
7
and with gender.
8
and dementia with Lewy bodies (DLB) than in controls.
21
Studies have also
shown that within the dementias, WMHs are more severe in cases of VaD
Many risk factors have been associated with the frequency and severity than in either AD
22
or DLB.
21
of WMHs, but the strongest and most consistently reported is increasing
age.
9,10
Hypertension is the next most important risk factor, with a recent Of all the clinical associations, the relationship between WMH severity
study demonstrating a reduced risk for increased WMH volume over two and cognitive function is perhaps the most controversial. In patients
years in subjects with successfully treated hypertension;
11
however, with cerebrovascular risk factors, one study found that WMHs were
there is some debate over whether systolic or diastolic blood pressure correlated with speed of information processing,
23
while another found
(BP) is significant. Some studies observed that both systolic and diastolic that hypertensive subjects had greater volumes of WMHs and made
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