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Crosstalk of atrophic trigeminal nerve to abnormal brain structure in idiopathic trigeminal neuralgia

Yuan Wang¹, Bethany Remeniuk², David Seminowicz³, and Ming Zhang¹

¹Department of Medical Imaging, First affiliated hospital of Xi'an Jiaotong University, Xi'an, China, ²Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³Department of Neural and Pain Sciences, School of Dentistry, University of Maryland Baltimore, Baltimore, MD, United States

Synopsis

Idiopathic trigeminal neuralgia (ITN) is characterized by intermittent, lancinating attacks in the branches of the trigeminal nerve (TGN). 40 ITN patients and 40 matched controls underwent MRI sessions and clinical pain assessment. TGN volume of cisternal segment and whole brain grey matter volume (GMV) were evaluated using voxel-based morphometry, ect. Reduced GMV was found in the insula, dorsal anterior cingulate cortex, precuneus, and several areas of the temporal lobe in ITN subjects. Correlation analysis revealed that decreased GMV of the left insula and decreased TGN volume were associated with increased pain ratings, providing new insight into pathophysiology of the disease.

Introduction

Recent neuroimaging studies have reported grey matter (GM) alterations in idiopathic trigeminal neuralgia (ITN) patients. However, few studies have focused on quantitative measurements of trigeminal nerves (TGN) and the interaction between TGN volume and brain morphology, particularly GM volume (GMV). In this study, we investigated the link between TGN and GMV changes in ITN patients compared to healthy controls. Moreover, we explored the association of microstructure of TGN and GM to collected pain clinical variables.

Methods

Eighty participants (40 ITN patients and 40 matched healthy controls, Table 1) were recruited for the study. All participants underwent magnetic resonance imaging sessions and clinical pain assessment. TGN volume of cistern segment was measured by Medical Image Processing, Analysis, and Visualization software (MIPAV, http://mipav.cit.nih.gov, Figure 1), and whole brain GMV was evaluated using voxel-based morphometry implemented in SPM12. Sensory and affective pain rating indices were assessed using visual analog scale (VAS) and the short-form McGill Pain Questionnaire (SF-MPQ). Correlation analysis was conducted to investigate the relationship between clinical pain variables and volumetric changes in TGN and GM.

Results

The average volume of the affected TGN compared to the unaffected TGN in ITN patients was signiﬁcantly smaller. This was calculated to be an average volumetric reduction of 22.8% from the unaffected to affected TGN. Meanwhile, the affected TGN of ITN patients was statistically smaller than the average volume of bilateral TGNs in the control subjects (Figure 2A). Additionally, the volume of the affected TGN was negatively correlated with the VAS scores (Figure 2B) and total, affective, and sensory pain rating indices of SF-MPQ (Figure 2C) in ITN patients.

What's more, reduced GMV was found in several regions associated with pain in ITN subjects, including the insula, secondary somatosensory cortex, hippocampus, dorsal anterior cingulate cortex, precuneus, and several areas of the temporal lobe (Figure 3 and Table 2). In addition, a positive correlation was found between the GMV of the left insula and the volume of affected TGN in the patients (not shown).

Discussion

Previous MRI studies mainly focused on nerve vessel contact (NVC) of affected TGN in ITN patients, but NVC is frequently observed in unaffected TGN in patients and controls, demonstrating that qualitative assessment of NVC is not enough to act as a diagnostic component for ITN. Atrophy rarely occurs on the unaffected TGN in ITN patients or on bilateral TGNs in healthy subjects, however, it is prevalent on the affected TGN of ITN individuals and is undoubtedly a potential factor in the underlying etiology of ITN.

Except popular impared brain regions, our results revealed GMV atrophy in the bilateral temporal pole, right inferior temporal gyrus (ITG), and left middle temporal gyrus (MTG). Although decreased GMV of the temporal lobe is not commonly detected in chronic pain states, it has been observed more frequently in ITN patients. A possible interpretation is that anticipation of the severe pain recruits the limbic system including hippocampus, temporal pole, and ITG to modulate aversive memory recognition, which, in turn, support the involvement of the temporal lobe in the anticipation of sporadic and lancinating orofacial pain.

Our data suggests that the microstructure of the affected TGN may present as an important factor in predicting the development and severity of ITN. But up until now there was little focus on ITN in conjunction with TGN microstructure deficits and brain morphological alterations. Future studies should focus on morphometric abnormalities of the affected TGN and whole brain in mild cases of ITN in order to observe changes in GMV as the disease progresses.

Conclusion

Our study observed structural deficits of affected TGN and brain GM atrophy in ITN patients. We not only demonstrate a correlation of the affected TGN to the left insula GMV, indicating a potential link between the cranial nerve and cerebral cortex, but we show that volumetric measurement of TGN is associated with multiple pain dimensions and pain severity in ITN patients. Above all, these findings complement the microstructural investigations of TGN and whole brain GMV changes in ITN patients, which help to provide greater clarity to understanding its underlying pathophysiology.

Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (No. 81301207), the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University, China (No. XJTU1AF-CRF-2015-028), and the Opening Project of Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University (No. 2016LHM-KFKT001). Dr. Ming Zhang and Dr. David Seminowicz are joint corresponding authors

References

1. Wang Y, Li D, Bao F, et al. Microstructural abnormalities of the trigeminal nerve correlate with pain severity and concomitant emotional dysfunctions in idiopathic trigeminal neuralgia: A randomized, prospective, double-blind study. Magnetic resonance imaging, 2016, 34 (5): 609-616.

2. Leal PRL, Barbier C, Hermier M, et al. Atrophic changes in the trigeminal nerves of patients with trigeminal neuralgia due to neurovascular compression and their association with the severity of compression and clinical outcomes: Clinical article. Journal of neurosurgery, 2014, 120 (6): 1484-1495.

3. Obermann M, Rodriguez-Raecke R, Naegel S, et al. Gray matter volume reduction reflects chronic pain in trigeminal neuralgia. NeuroImage, 2013, 74: 352-358.

4. Gustin SM, Peck CC, Wilcox SL, et al. Different Pain, Different Brain: Thalamic Anatomy in Neuropathic and Non-Neuropathic Chronic Pain Syndromes. Journal of Neuroscience, 2011, 31 (16): 5956-5964.

Figures

Figure 1. Quantitative measurement of the TGN volume in an ITN patient. Axial 3D-FIESTA images depict the segmentation of bilateral TGN starting from Meckel's cave to the entry point of the pons (A–D). In this patient, the right TGN is compressed by a tortuous and enlarged basilar artery, leading to the displacement and atrophy of the nerve, whereas the left TGN remains unaffected.

Figure 2. Correlation of TGN volume between groups and to different pain indices in ITN patients. (A) Graph demonstrating that the affected TGN volume was signiﬁcantly lower compared to the unaffected TGN volume in ITN patients and the mean volume of bilateral TGN in healthy controls (p<0.05). Furthermore, affected TGN volume was negatively associated with pain ratings, including (B) the VAS and (C) the total, sensory, and affective pain rating indices of SF-MPQ, respectively. * = statistically signiﬁcant.

Figure 3. VBM analysis of GMV. VBM analysis revealed signiﬁcantly decreased GMV clusters in ITN patients compared to control subjects. In particular, GMV atrophy was observed in the left insula, left S2, right hippocampus, right dACC, bilateral precuneus, and several portions of temporal lobe (p<0.05, FDR corrected). Images are shown on the MNI template in neurological convention (x, y, and z values refer to MNI coordinates) with the gradient color bar corresponding to t-values of the clusters.

Table 1. Independent two-samples t test was conducted to compare clinical traits between ITN and healthy controls. Demographics presented as (x ± SD) unless otherwise stated. SF-MPQ = short-form McGill pain questionnaire; VAS = visual analogue scale; T-PRI = total pain rating index; S-PRI = sensory pain rating index; A-PRI = affective pain rating index; TIV = total intracranial volume; GMV = gray matter volume; WMV = white matter volume; CSF = cerebral spinal fluid.

Table 2. Regions of reduced grey matter volume in ITN patients compared to healthy controls. Data are corrected for multiple comparisons using FDR with threshold at p<0.05.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)

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