Bilateral microstructural changes in the trigeminal nerve in classical trigeminal neuralgia

Classical trigeminal neuralgia (cTN) is a unilateral facial pain condition associated with neurovascular compression (NVC) of the trigeminal nerve (CNV) at its root (also called the root entry zone, REZ). While structural MRI can detect NVC, diffusion tensor imaging (DTI) may offer insight into changes in CNV microstructure. This study examined microstructural metrics in 26 cTN patients and 14 healthy control participants (HCs) using a novel, high-resolution, CNV-specific DTI protocol. Four coronal regions-of-interest (ROIs) were placed along the cisternal segment of CNV, beginning at its emergence from the brainstem and separated by evenly spaced 1.8 mm intervals up to 5.4 mm distally, capturing a proximal-to-distal microstructural profile. Diffusion metrics were extracted at each ROI including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). FA was significantly reduced in CNV on the affected side of the face in cTN patients at 1.8 mm (p<0.01) and 3.6 mm (p<0.05) distal to the REZ, compared to HCs and the contralateral CNV, consistent with local microstructural alterations accompanying NVC. Unexpectedly, both ipsilateral and contralateral CNV in cTN patients showed a significant proximal-to-distal FA decline (p<0.0001), accompanied by increasing RD, AD, and MD. This significant gradient of along-nerve microstructural changes was not consistently observed in HCs. CNV volume and degree of NVC were not correlated with these changes. These findings suggest that cTN is characterized by global microstructural changes occurring bilaterally in CNV and extending beyond the site of NVC, reflecting more widespread pathophysiological processes. PERSPECTIVE: High-resolution diffusion tensor imaging reveals bilateral microstructural changes along the trigeminal nerve in classical trigeminal neuralgia (cTN) that appear independent of neurovascular compression. Absent in healthy controls, these findings may point to broader pathophysiological mechanisms in cTN, such as neuroinflammation, which require further investigation.