Along-tract white-matter microstructural differences in primary trigeminal neuralgia: a diffusion MRI tractometry study

Primary trigeminal neuralgia (TN) is commonly linked to neurovascular compression (NVC), but NVC does not fully explain its clinical and imaging heterogeneity. Previous diffusion tensor imaging (DTI) studies have used tract-based spatial statistics or whole-tract averages, which may obscure localized within-tract differences. We used node-wise tractometry to map TN-related white-matter microstructural differences and test associations with NVC severity and pain laterality.

We studied 85 patients with primary TN and 42 healthy controls (HCs). Diffusion-weighted MRI at 3.0 T was preprocessed and fitted with a tensor model to derive fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Prespecified tracts were reconstructed with pyAFQ and resampled to 100 nodes. Among 23 prespecified bundles selected from 40 reconstructed bundles for statistical inference, primary analyses focused on the pyAFQ-defined Callosum Orbital bundle, anterior thalamic radiation, uncinate fasciculus, and cingulum. Node-wise linear models adjusted for age, sex, mean framewise displacement, and contrast-to-noise ratio were tested using Freedman-Lane permutations, threshold-free cluster enhancement (TFCE), and family-level false discovery rate (FDR) correction.

Differences were most consistent in the Callosum Orbital bundle. Compared with HCs, patients with TN had lower FA (nodes 10-43 and 74-83; TFCE-corrected p = 0.009; FDR q = 0.038; peak beta = -0.031; 95% confidence interval [CI], -0.050 to -0.012), higher MD (p = 0.003; q = 0.011; peak beta = 0.035; 95% CI, 0.019 to 0.051), and higher RD (p < 0.001; q = 0.002; peak beta = 0.036; 95% CI, 0.019 to 0.052). MD and RD were also higher in the right uncinate fasciculus, and MD was higher in the right anterior thalamic radiation. No corrected differences were detected in the cingulum. Core tract metrics were not significantly associated after correction with Sindou grade, dichotomized NVC severity, or pain laterality.

TN-related white-matter microstructural differences were segmental and tract selective, with the most consistent findings in the pyAFQ-defined Callosum Orbital bundle. These differences did not vary systematically with NVC severity or pain laterality, suggesting that they should not be interpreted simply as direct structural correlates of peripheral compression burden or unilateral pain input.