Neurosurgical treatments for trigeminal neuralgia (TN) can provide long-lasting pain relief, however, some patients fail to respond and undergo multiple, repeat procedures. Surgical outcomes can vary depending on the type of TN, but the reasons for this are not well understood. Neuroimaging studies of TN point to abnormalities in the brainstem trigeminal fibers, however, whether this is a common characteristic of treatment non-response across different subtypes of TN is unknown. Here, we used diffusion tensor imaging (DTI) to determine whether the brainstem trigeminal fiber microstructure is a common biomarker of surgical response in TN and whether the extent of these abnormalities is associated with the likelihood of response across subtypes of TN. We studied 98 patients with TN (61 classical TN, 26 TN secondary to multiple sclerosis, and 11 TN associated with a solitary pontine lesion) who underwent neurosurgical treatment and 50 healthy controls. We assessed treatment response using pain intensity measures and examined microstructural features by extracting pre-treatment DTI metrics from the proximal pontine segment of the trigeminal nerves. We found that microstructural abnormalities in the affected pontine trigeminal fibers (notably, lower fractional anisotropy and higher radial diffusivity) highlight treatment non-responders (n=47) compared to responders (n=51) and controls, and that the degree of abnormalities is associated with the likelihood of surgical response across subtypes of TN. These novel findings demonstrate the value of DTI as an objective, non-invasive tool for the prediction of treatment response and elucidate the features that distinguish treatment responders from non-responders in the TN population.

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