Francesca Pescini1, Ida Donnini2, Francesca Cesari3, Serena Nannucci4, Raffaella Valenti2, Valentina Rinnoci2, Anna Poggesi2, Anna Maria Gori5, Betti Giusti3, Angela Rogolino3, Alessandra Carluccio6, Silvia Bianchi6, Maria Teresa Dotti6, Antonio Federico6, Maurizio Balestrino7, Enrico Adriano7, Rosanna Abbate3, Domenico Inzitari8, Leonardo Pantoni9. 1. Emergency Department, Stroke Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy. 2. NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy. 3. Cardio-Thorax and Vascular Department, Atherothrombotic Diseases Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy. 4. NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy; Department of Emergency Neurology, C. Mondino National Neurological Institute, Pavia, Italy. 5. Cardio-Thorax and Vascular Department, Atherothrombotic Diseases Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy; Don Carlo Gnocchi IRCCS Foundation, Florence, Italy. 6. Department of Medical Surgical and Neurological Sciences, University of Siena, Siena, Italy. 7. Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy. 8. NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy; Institute of Neuroscience, Italian National Research Council, Florence, Italy. 9. NEUROFARBA Department, Neuroscience Section, University of Florence, Florence, Italy. Electronic address: leonardo.pantoni@unifi.it.
Abstract
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.
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.
Authors: Ilaria Di Donato; Silvia Bianchi; Nicola De Stefano; Martin Dichgans; Maria Teresa Dotti; Marco Duering; Eric Jouvent; Amos D Korczyn; Saskia A J Lesnik-Oberstein; Alessandro Malandrini; Hugh S Markus; Leonardo Pantoni; Silvana Penco; Alessandra Rufa; Osman Sinanović; Dragan Stojanov; Antonio Federico Journal: BMC Med Date: 2017-02-24 Impact factor: 8.775