Brain Gray Matter And White Matter Alterations In Patients With Myotonic Dystrophy 1 (P5.085)

OBJECTIVE: To investigate grey matter (GM) and white matter (WM) abnormalities in Myotonic dystrophy type 1 (DM1) using advanced Magnetic Resonance Imaging (MRI) techniques and assess their clinical correlates, and to evaluate separately childhood-juvenile-onset (jDM1) and classic adult-onset (cDM1) DM1 cases in order to explore the effect of age and disease durationin this condition BACKGROUND: DM1 is a multisystem disease that affects also the brain. A few neuroimaging studies reported distributed patterns of GM and WM atrophy in DM1. DESIGN/METHODS: Fifty-one DM1 patients (14 jDM1, 37 cDM1) underwent clinical and neuropsychological evaluations, and brain structural and diffusion tensor (DT)-MRI. WM hyperintensity (WMH) load was assessed. Voxel based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to evaluate GM atrophy and WM microstructural damage. Voxel-wise analyses were adjusted for WMH load. A regression analysis was performed in order to evaluate clinico-anatomical correlations. RESULTS: DM1 patients showed cognitive impairment involving especially visuospatial abilities, language, and orientation/attention. Visuospatial abilities/memory were more frequently compromised in cDM1 compared with jDM1 patients. WMH load was higher in both patient groups relative to controls. DM1 patients showed a widespread pattern of GM atrophy, which was more severe and distributed in cDM1 cases. DT-MRI showed significant damage of the main WM tracts similarly in cDM1 and jDM1 groups. Deficits in attentive-executive and visuospatial abilities were independently associated with WMH load and increased mean diffusivity of the left corona radiate, internal capsule, inferior fronto-occipital fasciculus and superior longitudinal fasciculus. CONCLUSIONS: DM1 is clinically characterized by impaired cognitive performance and anatomically by widespread and severe GM and WM damage. Cognitive deficits of DM1 patients correlate with structural WM damage including both WMHs and WM microstructural damage. Despite being comparable clinically and cognitively, cDM1 patients experienced GM and WM damage, while jDM1 had a prominent WM damage. Study Supported by: No Founding