Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease.

[cadasil]

White matter hyperintensities and lacunes are among the most frequent abnormalities on brain magnetic resonance imaging . They are commonly related to cerebral small vessel disease and associated with both stroke and dementia . We examined the spatial relationships between incident lacunes and white matter hyperintensities and related these findings to information on vascular anatomy to study possible mechanistic links between the two lesion types . Two hundred and seventy-six patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL ), a genetically defined small vessel disease with mutations in the NOTCH 3 gene were followed with magnetic resonance imaging over a total of 633 patient years . Using difference images and Jacobian maps from registered images we identified 104 incident lacunes . The majority (n = 95 ; 91 .3 %) of lacunes developed at the edge of a white matter hyperintensity whereas few lacunes were found to develop fully within (n = 6 ; 5 .8 %) or outside (n = 3 ; 2 .9 %) white matter hyperintensities . Adding information on vascular anatomy revealed that the majority of incident lacunes developed proximal to a white matter hyperintensity along the course of perforating vessels supplying the respective brain region . We further studied the spatial relationship between prevalent lacunes and white matter hyperintensities both in 365 patients with CADASIL and in 588 elderly subjects from the Austrian Stroke Prevention Study . The results were consistent with the results for incident lacunes . Lesion prevalence maps in different disease stages showed a spread of lesions towards subcortical regions in both cohorts . Our findings suggest that the mechanisms of lacunes and white matter hyperintensities are intimately connected and identify the edge of white matter hyperintensities as a predilection site for lacunes . Our observations further support and refine the concept of the white matter hyperintensity penumbra .