Objective: This study investigated structural neural pathways in clinically manifesting and non-manifesting individuals with several dystonia (DYT) genotypes using a network approach.

Background: DYT has traditionally been attributed to basal ganglia dysfunction. Recent studies expanded this picture suggesting DYT as a circuit disorder.

Methods: We included 9 asymptomatic mutation carriers (4 DYT1, 4 DYT6, 1 DYT10), 26 symptomatic mutation carriers (7 DYT1, 7 DYT6, 9 DYT5, 1 DYT18, 1 DYT10, 1 DYT25) and 37 healthy controls (HC). Subjects underwent 3D T1-weighted and diffusion tensor (DT) MRI. The human macroscale connectome was constructed from DT MRI. Tissue segmentation was performed on T1-weighted images using Freesurfer. The affected structural connections in DYT samples were investigated using Network-Based Statistic (p<0.01, 10.000 permutations).

Results: Compared to HC, asymptomatic mutation carriers showed a basal ganglia/frontal subnetwork characterized by decreased fractional anisotropy and increased mean diffusivity (MD) including the left putamen, precentral gyrus, middle and superior frontal gyri, middle temporal, and insula, while clinically manifesting DYT mutation carriers showed an altered subnetwork characterized by increased MD connecting left putamen, middle and superior frontal gyri, orbitofrontal cortex, middle temporal, insula and right anterior cingulate cortex. No differences were found between symptomatic and asymptomatic DYT subjects. A trend toward a greater disconnection was observed in symptomatic DYT1 relative to DYT6 subjects.

Conclusions: Our findings suggest that structural brain abnormalities in both clinically manifesting and non-manifesting DYT mutation carriers are distributed at a network level, beyond the basal ganglia/sensorimotor cortex regions. Studying of asymptomatic mutation carriers offered the possibility of identifying genotype-related trait characteristics without the confound of clinical symptoms providing new insights into understanding DYT generation.

XLVI Congress of Italian Neurological Society.

« Back to 2016 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/white-matter-connectome-in-patients-with-genetic-dystonia/