Objective: We aimed at investigating structural and functional alterations in asymptomatic (aDYT) and symptomatic dystonia (sDYT) mutation carriers.

Background: Most of DYT genotypes follow an autosomal dominant inheritance pattern with reduced penetrance; the mechanisms underlying disease development remain unclear.

Methods: This study included 9 aDYT, 26 sDYT and 37 healthy controls. Subjects underwent 3D T1-weighted, diffusion tensor (DT) and resting state (RS) fMRI to study cortical thickness, white matter (WM) tracts damage and functional network alterations.

Results: Compared to controls and aDYT, sDYT showed cortical thinning of motor and frontal areas, bilaterally. Compared to controls, aDYT showed increased mean (MD) and radial diffusivity (radD) and decreased fractional anisotropy (FA) of the main motor tracts, while sDYT showed decreased FA in the WM close to the right premotor cortex and a more widespread increase of MD, axial diffusivity (axD), and radD involving the main motor and associative tracts. No DT MRI differences were observed between sDYT and aDYT. Compared to controls, sDYT showed reduced functional connectivity of insula and basal ganglia, and aDYT of the fronto-insular areas.

Conclusions: Brain network alterations in aDYT support the hypothesis that these changes are causative rather than an effect of the disorder. An attractive hypothesis is also that the analysis of the DT MRI eigenvalues revealing a different pattern of abnormalities in sDYT and aDYT may allow to gain insight into the possible determinants of penetrance. Whether different DYT mutations are associated with specific network changes remains to be tested in larger subject groups.

Congress of Italian Neurological Society XLVI.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-anatomical-basis-of-genetic-dystonia-a-multimodal-mri-study/