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(Stroke. 2007;38:1786.)
© 2007 American Heart Association, Inc.

Original Contributions

Brain Atrophy Is Related to Lacunar Lesions and Tissue Microstructural Changes in CADASIL

Eric Jouvent, MD; Anand Viswanathan, MD, PhD; Jean-François Mangin, PhD; Mike O’Sullivan, MD, PhD; Jean-Pierre Guichard, MD; Andreas Gschwendtner, MD; Rodica Cumurciuc, MD; Frédérique Buffon, MD; Nils Peters, MD; Chahin Pachaï, PhD; Marie-Germaine Bousser, MD; Martin Dichgans, MD Hugues Chabriat, MD, PhD

From the Department of Neurology (E.J., R.C., F.B., M.-G.B., H.C.), CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, and Université Paris VII, Paris, France; the Department of Neurology and Clinical Trials Unit (A.V.), Massachussets General Hospital and Harvard Medical School, Boston, Mass.; Unité de NeuroAnatomie Fonctionelle (J.-F.M.), Service Hospitalier Frédéric Jolliot, CEA, Orsay, France; the Department of Neurology (M.O., A.G., N.P., M.D.), Klinikum Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, Munich, Germany; the Department of Neuroradiology (J.-P.G.), CHU Lariboisière, Assistance Publique des Hôpitaux de Paris, France; and Theralys, France (C.P.).

Correspondence to Prof Hugues Chabriat, Service de Neurologie, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris, France. E-mail hugues.chabriat{at}lrb.ap-hop-paris.fr

Background and Purpose— Cerebral atrophy has been recently recognized as a key marker of disease progression in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The contribution of subcortical cerebral lesions in this process remains undetermined. The aim of this study was to investigate the relationships between cerebral volume and different types of subcortical MRI lesions in CADASIL.

Methods— Demographic, clinical, and laboratory data from 147 patients with CADASIL recruited from a prospective cohort study were analyzed. Validated methods were used to determine the ratio of brain volume to intracranial cavity volume (brain parenchymal fraction [BPF]), volume of white matter hyperintensities, volume of lacunar lesions, number of cerebral microhemorrhages, and mean apparent diffusion coefficient. Associations between BPF, clinical scales, and the different subcortical MRI markers were tested.

Results— BPF obtained in 129 patients was significantly associated with the Mattis dementia rating scale (P<0.0001), Mini-Mental State Examination (P=0.002), and modified Rankin scale (P<0.0001) after adjustment for age and sex. Multiple linear regression modeling showed that BPF was independently associated with mean apparent diffusion coefficient (P<0.0001), volume of lacunar lesions (P=0.004), and age (P<0.0001), accounting for 46% of the observed variance in BPF but not with volume of white matter hyperintensities or number of microhemorrhages.

Conclusions— In association with age, mean apparent diffusion coefficient and volume of lacunar lesions are strong and independent MRI predictors of BPF, a key marker of cognitive and motor disability in CADASIL. These results suggest brain atrophy is related to remote and/or diffuse consequences of both lacunar lesions and widespread microstructural alterations within the brain outside lacunar lesions.

Key Words: CADASIL • cerebral atrophy • cerebral microhemorrhage • diffusion • lacune • white matter hyperintensities

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