J Lebenberg1,2, J-P Guichard3, A Guillonnet3, D Hervé1,2, N Alili1, A Taleb1, N Dias-Gastellier1,2, H Chabriat1,2, E Jouvent4,2. 1. the Centre de Neurologie Vasculaire Translationel (J.L., D.H., N.A., A.T., N.D.-G., H.C.), Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisiere, Paris, France; L'Institut National de la Santé et de la RechercheMédicale INSERM U1141, Université Paris Cité, Paris, France. 2. Federation Hospitalo-Universitaire NeuroVasc (J.L., N.D.-G., D.H., H.C., E.J.), Paris, France. 3. Neuroradiology (J.P.G., A.G.). 4. From the Department of Neurology (E.J.) eric.jouvent@aphp.fr.
Abstract
BACKGROUND AND PURPOSE: By studying the evolution of brain volume across the life span in male and female patients, we aimed to understand how sex, brain volume, and the epidermal growth factor repeat domain of the mutation, the 3 major determinants of disability in CADASIL, interact in driving disease evolution. MATERIALS AND METHODS: We used validated methods to model the evolution of normalized brain volume with age in male and female patients using nonparametric regression in a large, monocentric cohort with prospectively collected clinical and high-resolution MR imaging data. We used k-means clustering to test for the presence of different clinical course profiles. RESULTS: We included 229 patients (mean age, 53 [SD, 12] years; 130 women). Brain volume was larger in women (mean size, 1024 [SD, 62] cm3 versus 979 [SD, 50] cm3; P < .001) and decreased regularly. In men, the relationship between brain volume and age unexpectedly suggested an increase in brain volume around midlife. Cluster analyses showed that this finding was related to the presence of a group of older male patients with milder symptoms and larger brain volumes, similar to findings of age-matched women. This group did not show specific epidermal growth factor repeat domain distribution. CONCLUSIONS: Our results demonstrate a detrimental effect of male sex on brain volume throughout life in CADASIL. We identified a subgroup of male patients whose brain volume and clinical outcomes were similar to those of age-matched women. They did not have a specific distribution of the epidermal growth factor repeat domain, suggesting that yet-unidentified predictors may interact with sex and brain volume in driving disease evolution.
BACKGROUND AND PURPOSE: By studying the evolution of brain volume across the life span in male and female patients, we aimed to understand how sex, brain volume, and the epidermal growth factor repeat domain of the mutation, the 3 major determinants of disability in CADASIL, interact in driving disease evolution. MATERIALS AND METHODS: We used validated methods to model the evolution of normalized brain volume with age in male and female patients using nonparametric regression in a large, monocentric cohort with prospectively collected clinical and high-resolution MR imaging data. We used k-means clustering to test for the presence of different clinical course profiles. RESULTS: We included 229 patients (mean age, 53 [SD, 12] years; 130 women). Brain volume was larger in women (mean size, 1024 [SD, 62] cm3 versus 979 [SD, 50] cm3; P < .001) and decreased regularly. In men, the relationship between brain volume and age unexpectedly suggested an increase in brain volume around midlife. Cluster analyses showed that this finding was related to the presence of a group of older male patients with milder symptoms and larger brain volumes, similar to findings of age-matched women. This group did not show specific epidermal growth factor repeat domain distribution. CONCLUSIONS: Our results demonstrate a detrimental effect of male sex on brain volume throughout life in CADASIL. We identified a subgroup of male patients whose brain volume and clinical outcomes were similar to those of age-matched women. They did not have a specific distribution of the epidermal growth factor repeat domain, suggesting that yet-unidentified predictors may interact with sex and brain volume in driving disease evolution.
Authors: Stephen M Smith; Yongyue Zhang; Mark Jenkinson; Jacqueline Chen; P M Matthews; Antonio Federico; Nicola De Stefano Journal: Neuroimage Date: 2002-09 Impact factor: 6.556
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Authors: François De Guio; Eric Jouvent; Geert Jan Biessels; Sandra E Black; Carol Brayne; Christopher Chen; Charlotte Cordonnier; Frank-Eric De Leeuw; Martin Dichgans; Fergus Doubal; Marco Duering; Carole Dufouil; Emrah Duzel; Franz Fazekas; Vladimir Hachinski; M Arfan Ikram; Jennifer Linn; Paul M Matthews; Bernard Mazoyer; Vincent Mok; Bo Norrving; John T O'Brien; Leonardo Pantoni; Stefan Ropele; Perminder Sachdev; Reinhold Schmidt; Sudha Seshadri; Eric E Smith; Luciano A Sposato; Blossom Stephan; Richard H Swartz; Christophe Tzourio; Mark van Buchem; Aad van der Lugt; Robert van Oostenbrugge; Meike W Vernooij; Anand Viswanathan; David Werring; Frank Wollenweber; Joanna M Wardlaw; Hugues Chabriat Journal: J Cereb Blood Flow Metab Date: 2016-05-11 Impact factor: 6.200
Authors: Eric Jouvent; Edouard Duchesnay; Foued Hadj-Selem; François De Guio; Jean-François Mangin; Dominique Hervé; Marco Duering; Stefan Ropele; Reinhold Schmidt; Martin Dichgans; Hugues Chabriat Journal: Neurology Date: 2016-09-30 Impact factor: 9.910
Authors: Joanna M Wardlaw; Eric E Smith; Geert J Biessels; Charlotte Cordonnier; Franz Fazekas; Richard Frayne; Richard I Lindley; John T O'Brien; Frederik Barkhof; Oscar R Benavente; Sandra E Black; Carol Brayne; Monique Breteler; Hugues Chabriat; Charles Decarli; Frank-Erik de Leeuw; Fergus Doubal; Marco Duering; Nick C Fox; Steven Greenberg; Vladimir Hachinski; Ingo Kilimann; Vincent Mok; Robert van Oostenbrugge; Leonardo Pantoni; Oliver Speck; Blossom C M Stephan; Stefan Teipel; Anand Viswanathan; David Werring; Christopher Chen; Colin Smith; Mark van Buchem; Bo Norrving; Philip B Gorelick; Martin Dichgans Journal: Lancet Neurol Date: 2013-08 Impact factor: 44.182
Authors: Julie W Rutten; Bastian J Van Eijsden; Marco Duering; Eric Jouvent; Christian Opherk; Leonardo Pantoni; Antonio Federico; Martin Dichgans; Hugh S Markus; Hugues Chabriat; Saskia A J Lesnik Oberstein Journal: Genet Med Date: 2018-07-22 Impact factor: 8.822