White matter microstructural alterations correlate with clinical characteristics in craniocervical dystonia.

Abstract

Background: To characterize white matter pathology, identify clinical correlates, and explore relevant biomarkers for deep brain stimulation (DBS) outcomes in craniocervical dystonia (CCD) using diffusion tensor imaging (DTI).

Methods: We involved 37 CCD patients (22 undergoing bilateral subthalamic DBS [STN-DBS]) and 42 matched healthy controls. Using Tract-Based Spatial Statistics (TBSS) for whole-brain analysis and Automated Fiber Quantification (AFQ) for 20 specific tracts, DTI measurements of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were extracted. Between-group metric comparisons and correlations with clinical features and treatment outcomes were assessed.

Results: TBSS revealed reduced FA in left anterior corona radiata and right posterior thalamic radiation, increased AD in splenium of corpus callosum, and widespread elevated MD/RD (p < 0.0125, family-wise error combined threshold-free cluster enhancement corrected). AFQ identified segmental increased MD/RD across several tracts, most notably within anterior thalamus radiation (ATR), corticospinal tract, cingulum cingulate, callosum forceps, and inferior fronto-occipital fasciculus (uncorrected p < 0.01). Microstructural alterations correlated with earlier disease onset, severe baseline blepharospasm, and botulinum toxin exposure (p < 0.01, uncorrected). Crucially, at an uncorrected threshold of p < 0.01, lower MD in the left ATR was associated with greater eye symptom improvement after STN-DBS surgery (r = -0.57, p = 0.009).

Conclusion: CCD exhibits distributed white matter microstructural alterations across multiple networks, potentially serving as the neurostructural substrate for motor and non-motor symptoms. Left ATR integrity is negatively associated with DBS outcomes.