White matter lesion progression

Abstract

There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.

Multifractal analysis of deep white matter microstructural changes on MRI in relation to early-stage atherosclerosis

“…Other studies have demonstrated the roles of these changes in normal aging (Davatzikos and Resnick, 2002;Yamamoto et al, 2005), cognitive function (Gunning-Dixon and Raz, 2003;Ylikoski et al, 1993), depression (Salloway et al, 1996), and dementia (Varma et al, 2002). These pathological changes in white matter are accompanied by lesions in the small perforating cerebral arteries (Inzitari, 2003;Schmidt et al, 2002Schmidt et al, , 2004van Swieten et al, 1991) and are related to the prevalence of peripheral atherosclerosis Pico et al, 2002). Most of these studies were based on visually detectable changes in the white matter (e.g., DWMH), occurring at relatively late stages in the development of pathological changes.…”

White matter hyperintensities in patients with multiple system atrophy

“…Although the pathophysiology of WMH is not completely understood, the presence of cerebrovascular risk factors has clearly been associated with increased WMH [7,22], suggesting that WMH are considered part of the spectrum of vascular-related injury, one of the markers for chronic end organ damage of the brain due to tissue ischemia [8,29,34]. As for the influence of autonomic failure on peripheral organs, especially cardiac function, recent studies [20,33] reported that the majority of patients with MSA had target-organ damage of hypertensive heart disease, similar to that observed in essential hypertension.…”

Consensus statement for diagnosis of subcortical small vessel disease

“…Currently, confluent WMHs are the only MRI correlates of cerebral SVD for which the requirement of a surrogate marker is fulfilled; progression of confluent white-matter lesions correlates with cognitive decline. 13,147 Amyloid and tau imaging with positron emission tomography could also be helpful to diagnose comorbidity with AD in the patients with mixed disease, 145 with the caveat that amyloid deposits can also be present in cognitively normal individuals. 146 Biochemical CSF studies provide the third axis of diagnosis; elevated albumin ratio indicates that the BBB is compromised, which is more likely to occur in SVD than in AD.…”