Abstracts of online articleLongitudinal changes of cortical morphology in CADASIL
Introduction
Several authors have previously emphasized the importance of cortical damage in CADASIL (Viswanathan et al., 2006) and in various small vessel diseases of the brain (SVDB) (Kövari et al., 2004; Sonnen et al., 2007, Soontornniyomkij et al., 2010). While the detailed evaluation of cortical microstructure remains out of reach in vivo, the improvement of magnetic resonance imaging (MRI) scanners together with the development of new postprocessing techniques allows now to investigate different characteristics of the cerebral cortex in SVDB (Magnotta et al., 1999, Mangin et al., 2010, Salat et al., 2004). We have recently proposed and validated different tools to evaluate the cortex morphology using MRI in CADASIL, particularly in the context of low gray/white contrast and high burden of white matter lesions (Jouvent et al., 2008, Mangin et al., 2010). In a cross-sectional study of 69 affected individuals, we previously observed that both cognitive scores and disability scales were associated with the depth of several cortical sulci (Jouvent et al., 2008) in line with other cortical measures obtained in sporadic SVDB (Preul et al., 2005, Wen et al., 2006). Thus, the assessment of cortical morphology may reliably reflect the severity of SVDB.
In the present large 2-center cohort study of CADASIL patients, we aimed to determine whether changes of the cortical morphology could be detected with MRI over a follow-up period of 18 to 36 months and whether these changes are actually associated with clinical worsening.
Section snippets
Subjects
Two hundred eighty-eight consecutive subjects (183 from Paris and 105 from Munich) aged older than 18 years, were recruited in an ongoing cohort study of CADASIL patients at Lariboisière (Paris) or Ludwig-Maximilians-Universität (Munich) hospitals between October 2003 and April 2009. All participants harbored a typical mutation of the Notch3 gene (Chabriat et al., 2009). At time of this study, 208 patients already had their second visit 18 months after inclusion, and 124 their third visit after
Results
Results of 10 of the 208 patients (7 from Paris and 3 from Munich) were excluded from analyses due to incomplete dataset (3), presence of a large territorial infarction (3), or insufficient quality caused by movement artifacts (4). For 8 more patients, sulci reconstruction failed repeatedly, leaving 190 subjects with available data at the second visit (18 months) and 106 at the second and third visits (18 and 36 months respectively). Mean follow-up duration for the 190 patients was 24.4 months.
Discussion
To our knowledge, this is the first longitudinal study of cortical morphological alterations in SVDB. The use of dedicated postprocessing algorithms allowed the detection of significant alterations of cortical morphology and structure that evolve parallel to the clinical worsening in a large cohort of CADASIL patients. These results are in line with a previous cross-sectional study of sulcal morphology obtained in a smaller group of CADASIL patients (Jouvent et al., 2008), as well as with
Disclosure statement
None of the authors reports any conflict of interest.
Independent ethics committees gave their approval for the study in each center.
Acknowledgements
The authors thank Nassirah Alili, Jocelyne Ruffié, and Solange Hello for their strong involvement in the follow-up of patients, and Denis Rivière, Matthieu Perrot, and Pauline Roca for the methodological development dedicated to the study of cortical folding.
This work was supported by a PHRC grant AOR 02-001 (DRC/APHP), Association de Recherche en Neurologie VAsculaire (ARNEVA), Hôpital Lariboisière, France, and E.J. was supported by a grant from the “Fonds d'Etude et de Recherche du Corps
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2013, NeuroImageCitation Excerpt :Measuring the geometry or morphology of sulcal folds is a recent approach to investigating neuroanatomy that can provide insights into structural brain changes beyond those of traditional approaches involving cortical thickness, subcortical volumetrics or voxel-based methods (Jouvent et al., 2011; Kochunov et al., 2012; Mangin et al., 2010). Recent studies have identified morphological differences in the sulci of some professional groups, including musicians (Li et al., 2010), patients with psychiatric and neurological conditions like schizophrenia (Cachia et al., 2008) and bipolar disorder (Penttila et al., 2009), and individuals with cerebral small vessel disease (Jouvent et al., 2011, 2012). Sulcal morphology also appears to change with normal aging (Cykowski et al., 2008; Kochunov et al., 2005; Liu et al., 2010; Rettmann et al., 2006), to be associated with cognitive functioning in the elderly (Liu et al., 2011), and to be abnormal in AD (Im et al., 2008; Liu et al., 2012; Reiner et al., 2012).