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

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 m...

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Published in:Brain (London, England : 1878) England : 1878), 2013-09, Vol.136 (Pt 9), p.2717-2726
Main Authors: DUERING, Marco, CSANADI, Endy, DICHGANS, Martin, GESIERICH, Benno, JOUVENT, Eric, HERVE, Dominique, SEILER, Stephan, BELAROUSSI, Boubakeur, ROPELE, Stefan, SCHMIDT, Reinhold, CHABRIAT, Hugues
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
CADASIL - complications
CADASIL - epidemiology
Cohort Studies
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Progression
Female
Humans
Leukoencephalopathies - epidemiology
Leukoencephalopathies - etiology
Leukoencephalopathies - genetics
Magnetic Resonance Imaging
Male
Medical sciences
Middle Aged
Nerve Fibers, Myelinated - pathology
Neurology
Receptor, Notch3
Receptors, Notch - genetics
Stroke, Lacunar - epidemiology
Stroke, Lacunar - etiology
Stroke, Lacunar - pathology
Young Adult
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Summary: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 NOTCH3 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.
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/awt184