Location, number and factors associated with cerebral microbleeds in an Italian-British cohort of CADASIL patients.

BACKGROUND AND PURPOSE: The frequency, clinical correlates, and risk factors of cerebral microbleeds (CMB) in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) are still poorly known. We aimed at determining the location and number of CMB and their relationship with clinical manifestations, vascular risk factors, drugs, and other neuroimaging features in CADASIL patients. METHODS: We collected clinical data by means of a structured proforma and centrally evaluated CMB on magnetic resonance gradient echo sequences applying the Microbleed Anatomical Rating Scale in CADASIL patients seen in 2 referral centers in Italy and United Kingdom. RESULTS: We evaluated 125 patients. CMB were present in 34% of patients and their presence was strongly influenced by the age. Twenty-nine percent of the patients had CMB in deep subcortical location, 22% in a lobar location, and 18% in infratentorial regions. After adjustment for age, factors significantly associated with a higher total number of CMB were hemorrhagic stroke, dementia, urge incontinence, and statins use (this latter not confirmed by multivariate analysis). Infratentorial and deep CMB were associated with dementia and urge incontinence, lobar CMB with hemorrhagic stroke, dementia, and statins use. Unexpectedly, patients with migraine, with or without aura, had a lower total, deep, and lobar number of CMB than patients without migraine. DISCUSSION: CMB formation in CADASIL seems to increase with age. History of hemorrhagic stroke, dementia, urge incontinence, and statins use are associated with a higher number of CMB. However, these findings need to be confirmed by longitudinal studies

Circulating Biomarkers in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Patients

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy presenting with variable features, including migraine, psychiatric disorders, stroke, and cognitive decline and variable disability. On neuroimaging, CADASIL is characterized by leukoencephalopathy, multiple lacunar infarcts, and microbleeds. Previous studies suggest a possible role of endothelial impairment in the pathogenesis of the disease. Methods We assessed plasma levels of von Willebrand factor (vWF) and thrombomodulin (TM) and the blood levels of endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) in 49 CADASIL patients and 49 age-matched controls and their association with clinical/functional and neuroimaging features. Results In multivariate analysis, CADASIL patients had significantly higher vWF and lower EPC levels. TM levels were similar in the 2 groups. CADASIL patients with a more severe clinical phenotype (history of stroke or dementia) presented lower CPC levels in comparison with patients with a milder phenotype. On correlation analysis, lower CPC levels were associated with worse performances on neuropsychological, motor and functional tests, and with higher lesion load on brain magnetic resonance imaging (degree of leukoencephalopathy and number of lacunar infarcts). Conclusions This is the first CADASIL series in which multiple circulating biomarkers have been studied. Our findings support previous studies on the presence and the possible modulating effect of endothelial impairment in the disease. Furthermore, our research data suggest that blood CPCs may be markers of disease severity

Examples of different locations of cerebral microbleeds in our sample of CADASIL patients.

<p>T2*-weighted magnetic resonance images showing cerebral microbleeds (white arrows) in infratentorial (A), deep subcortical (B, C) and lobar locations (D).</p

Correlation between the number of infratentorial, deep, and lobar cerebral microbleeds and drugs, clinical and other neuroimaging features in 125 CADASIL patients.

<p>Correlation between the number of infratentorial, deep, and lobar cerebral microbleeds and drugs, clinical and other neuroimaging features in 125 CADASIL patients.</p

Total number of cerebral microbleeds in 125 CADASIL patients.

<p>Proportions of patients with different numbers of CMB are reported in the bar graph and in the table.</p

Demographic, clinical and neuroimaging characteristics of the 125 CADASIL patients enrolled in the study.

<p>Demographic, clinical and neuroimaging characteristics of the 125 CADASIL patients enrolled in the study.</p

Correlation between the total number of cerebral microbleeds and demographics, drugs, clinical and other neuroimaging features in 125 CADASIL patients.

<p>Correlation between the total number of cerebral microbleeds and demographics, drugs, clinical and other neuroimaging features in 125 CADASIL patients.</p