Background & Aims

Classical Trigeminal Neuralgia (cTN) is a chronic, neuropathic facial pain condition characterized by severe attacks of stabbing pain in the distribution of the trigeminal nerve associated with neurovascular compression (NVC) of its root entry zone (REZ) (1). Diffusion MRI (dMRI) has been used to study microstructural changes at the REZ in cTN (3-7), but remains limited by technical challenges. Our group recently developed a cutting-edge dMRI protocol to mitigate some of these challenges(2), and have applied it to studying trigeminal nerve microstructure in cTN. Our specific aim was to determine the nature of microstructural differences between the trigeminal nerves of patients with cTN compared to healthy controls, as well as between sides in cTN patients only.

Methods

Using our previously validated, high-resolution FLAIR-diffusion tensor imaging (DTI) MRI acquisition sequence(2), 22 cTN patients with medically-refractory pain were scanned prior to undergoing microvascular decompression (MVD) surgery, as well as 10 healthy controls. Regions of interest (ROIs) were placed in the coronal plane at three positions along each trigeminal nerve in each participant: 1) REZ; 2) mid-cisternal segment (1.8mm distal to REZ); 3) just before exit at the skull base (3.6mm distal). Diffusivity metrics–fractional anisotropy (FA)/axial diffusivity (AD)/radial diffusivity (RD)/mean diffusivity (MD)—were calculated at each ROI in all cTN patients and healthy controls. Within-group diffusivity metrics were compared between ROIs along the nerve using Friedman’s test (8). Between-group diffusivity metric differences at each ROI were evaluated using the Kruskal-Wallis test (8).

Results

Trigeminal nerves in cTN patients showed significant changes in diffusivity metrics along their length. Specifically, while moving from more proximal to more distal ROIs, we observed a significant reduction in FA, with corresponding significant increases in AD, RD, and MD. This pattern of microstructural changes was seen not only in trigeminal nerves ipsilateral to the painful side of the face, but in contralateral, unaffected nerves as well. Furthermore, the degree of along-nerve microstructural change was not significantly different between sides in cTN patients. Conversely, healthy controls showed no significant changes in FA, AD, RD, or MD between different locations along the entire length of their trigeminal nerves, on either side.

Conclusions

We observed bilateral microstructural changes in the trigeminal nerves of patients suffering from cTN, which were not apparent in healthy control subjects. Furthermore, there appears to be a gradation of microstructural change from proximal (i.e. REZ) to more distal positions along the nerve, The bilateral nature of these abnormalities suggests that TN may result from a more widespread pathophysiological process affecting cranial nerve integrity more generally. We speculate that impaired myelination of the trigeminal nerve—occurring bilaterally—may be a possible mechanism. However, understanding why pain is felt on only one side of the face in cTN, and the implications of these nerve microstructural abnormalities for treatment response, requires further study.

References

(1)Torelli, P. et al. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 53, 137–46 (2013).

(2)Danyluk H, Sankar T, Beaulieu C. High spatial-resolution nerve-specific DTI protocol outperforms whole-brain DTI for imaging the trigeminal nerve in healthy individuals. NMR Biomed. 2021 Feb;34(2):e4427. https://doi.org/10.1002/nbm.4427

(3)Desouza, D. D. et al. Abnormal trigeminal nerve microstructure and brain white matter in idiopathic trigeminal neuralgia. Pain 155, 37–44 (2014).

(4)Herweh, C. et al. Loss of anisotropy in trigeminal neuralgia revealed by diffusion tensor imaging. Neurology 68, 776–778 (2007).

(5)Leal, P. R. L. et al. Structural abnormalities of the trigeminal root revealed by diffusion tensor imaging in patients with trigeminal neuralgia caused by neurovascular compression: A prospective, double-blind, controlled study. Pain 152, 2357–2364 (2011).

(6)Tohyama, S., Walker, M. R., Zhang, J. Y., Cheng, J. C., & Hodaie, M. Brainstem trigeminal fiber microstructural abnormalities are associated with treatment response across subtypes of trigeminal neuralgia. Pain 2020, 162(6), 1790–1799.

(7)Xie G, Zhang F, Leung L, et al. Anatomical assessment of trigeminal nerve tractography using diffusion MRI: A comparison of acquisition b-values and single- and multi-fiber tracking strategies. Neuroimage Clin. 2020;25:102160.

(8)GraphPad Software version 9.0 for Mac OS X, La Jolla California, USA, (2023).

Presenting Author

Akshit Ayri

Poster Authors

Akshit Ayri

Neuroscience

University of Alberta

Lead Author

Abhinav Dhillon

University of Alberta

Lead Author

Hayden Danyluk BSc PhD

University of Alberta

Lead Author

Tejas Sankar

University of Alberta

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Orofacial Pain