Progression of cerebral white matter lesions -- clinical and radiological considerations

More than half of all elderly have some degree of white matter lesions (WML) on MRI of the brain. Until recently, the rate of progression of WML was unknown. Recent work within several population based large scale studies was devoted to tackle this question, to identify factors related to WML progression and to establish a relationship with clinical variables and cognitive changes. There is converging evidence that at least a subset of WML demonstrates considerable progression over time. Increases in WML volume have been correlated with increased loss of brain volume and decline in cognitive and motor performance, indicating that progression of WML harbors clinical relevance. Correlative MRI-histopathologic studies and the clustering of vascular risk factors in subjects with progressive WML support a vascular aetiology of WML, particularly in "confluent" MRI phenotypes. Although specific rating scales have been proposed to detect WML progression, quantitative measurements appear superior given their objective and reproducible nature and regarding possibilities of statistical analyses. Measuring changes in the progression of WML may provide a valid surrogate marker in future clinical trials on cerebral small-vessel disease. Power calculations based on quantitative data of the Austrian Stroke Prevention Study (ASPS) suggest that such studies would be feasible.