The Evolution of White Matter Hyperintensities
The Evolution of White Matter Hyperintensities
US Neurology, 2010;5(2):10-3
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 frequent discovery of cerebral white matter lesions, referred to as white matter hyperintensities (WMHs) in this article, which appear as hypodense areas on computed tomography (CT) scans or as hyperintense regions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences. Since their discovery, almost every aspect of WMHs has been surrounded by controversy.1 Despite the abundant literature on this subject, relatively little progress has been made in determining the etiology, pathology, or even the clinical significance of these lesions.
The prevalence of WMHs in asymptomatic healthy subjects varies widely depending on the technique used for their identification, the type of lesion examined, and the characteristics of the population studied.2,3 Large-scale population-based studies have shown that prevalence rates range from 27 to 96%.4,5 However, prevalence rates are generally higher in patients with dementia,6 and have been found to differ among ethnic groups7 and with gender.8
Many risk factors have been associated with the frequency and severity 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 study demonstrating a reduced risk for increased WMH volume over two years in subjects with successfully treated hypertension;11 however, there is some debate over whether systolic or diastolic blood pressure (BP) is significant. Some studies observed that both systolic and diastolic BP were higher in subjects with WMHs,5,7 while others found that mean systolic BP was significantly higher in subjects with WMHs regardless of whether they were from a dementia or a control group.12 Other studies showed that elevated diastolic BP, measured years earlier, was related to the presence of WMHs.13,14 The type of BP notwithstanding, these studies suggest that the development of WMHs is a relatively slow process that is related to long-standing high BP.13
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Magnetic resonance imaging, neuropathology, blood–brain barrier, clinicopathological correlations, p-glycoprotein, functional Magnetic resonance imaging, blood–brain barrier endothelial cells, tight junctions blood–brain barrier, central nervous blood–brain barrier, blood–brain barrier cerebrospinal fluid, p-glycoprotein inhibitors, p-glycoprotein blood brain barrier,
