Nerve matters: Longitudinal microstructural change in the trigeminal nerve is associated with durable pain relief...

BackgroundMany patients with medically-refractory trigeminal neuralgia (TN) fail to achieve lasting pain relief following surgery targeting the trigeminal nerve (cranial nerve five; CNV). While some studies using MRI diffusion tensor imaging (DTI) suggest that preoperative CNV microstructure may predict surgical response, the findings remain inconsistent. Furthermore, the relationship between post-surgical CNV microstructural changes and long-term pain relief is not well understood. Using a novel CNV-nerve specific DTI protocol, the present study aimed to determine whether: (1) preoperative CNV microstructure differentiates surgical responders from non-responders and (2) sustained pain relief after surgery is associated with distinct postoperative microstructural changes in CNV.MethodsWe conducted a single-centre, prospective, longitudinal study in TN patients undergoing microvascular decompression (MVD) or percutaneous rhizotomy by balloon compression (BC). Patients underwent preoperative and postoperative (one week, one month, six months and one year) high-resolution DTI scanning of CNV using a novel fluid-attenuated inversion recovery DTI protocol. Healthy controls (HC) were scanned at a single timepoint using the same protocol. CNV microstructure was inferred primarily from fractional anisotropy (FA), supplemented with other diffusion metrics. Responders were defined as patients with immediate and complete pain relief (Barrow Neurological Institute facial pain scale I or IIIa) sustained for at least two years.ResultsThirty-five TN patients (22 MVD and 13 BC) and 19 HC were studied. There was no difference in FA between HC CNV and affected ipsilateral or unaffected contralateral CNV in TN patients. However, CNV ipsilateral to the painful side of the face showed microstructural alteration in the form of reduced FA compared to the contralateral, unaffected CNV (0.45 vs. 0.49, p = 0.0017). This was largely driven by eventual surgical responders (n = 18, FA ipsilateral 0.45 vs. contralateral 0.49, p = 0.049), whereas non-responders (n = 17) showed no such difference (p = 0.15). Following surgery, responders showed early reduction in ipsilateral CNV FA by one month (0.45 vs. 0.38, p = 0.013), sustained at six months (0.38, p = 0.021) and one year (0.37, p = 0.006). The same pattern was observed for MVD and BC responders. Conversely, non-responders exhibited no significant postoperative CNV FA change. Postoperative pain-free timepoints were associated with significantly lower ipsilateral CNV FA compared to painful states or HC on average (0.39 vs. 0.45 or 0.47, p < 0.0001) and in individual patients experiencing multiple pain recurrences after repeat operations.ConclusionsLong-term pain relief after TN surgery requires the induction of specific and sustained microstructural changes in the treated CNV, irrespective of surgical modality.