White matter microstructural alterations correlate with clinical characteristics in craniocervical dystonia

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).

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.

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).

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.