Hello, my name is Dr. Tejas Sankar, and on behalf of my co-authors at the University of Alberta, I am pleased to present our abstract entitled, Perioperative Thalamus Structure and Metabolism, Predict Response to Surgical Treatment for Trigeminal Neuralgia. I have no relevant conflicts of interest to disclose for this presentation. Severely refractory trigeminal neuralgia is a severely debilitating illness and it can be effectively treated with surgery. The most common types of surgery are microvascular decompression, percutaneous rhizotomy performed using either balloon compression, injection of glycerol, or radiofrequency ablation, or stereotactic radiosurgery, typically done using gamma knife. Unfortunately, post-surgical pain recurrence occurs in a considerable number of trigeminal neuralgia patients, despite technically successful initial surgery. In the case of microvascular decompression, this recurrence rate has been estimated to be as high as 25% at 2 years, with a 4% per year recurrence rate thereafter, and the recurrence rate for pain after the other surgical modalities is even higher. Several factors and trigeminal nerve-related imaging features may predict pain recurrence in some patients. For example, the absence of neurovascular compression of the root entry zone of the trigeminal nerve, or female sex appear to be linked to earlier recurrence. Additionally, neuroimaging studies have shown using diffusion tensor imaging MRI that diffusivity metrics at the root entry zone of the trigeminal nerve on the affected side of the face may well be related to durable pain relief following surgery. However, structural and functional brain features that underlie a response to trigeminal neuralgia surgery have been relatively understudied. On this basis, we hypothesized that it would be worthwhile to look at the structure and function of the thalamus in patients with trigeminal neuralgia who are undergoing surgery. You can see at the top the anatomical depiction of the flow of sensory information from the face through the thalamus to the primary sensory cortex. The key component of the thalamus is the ventral posteromedial nucleus, which receives second-order neurons carrying facial pain information by way of the trigeminal thalamic tract. Synapses occur in the VPM thalamus, and then by way of third-order neurons, sensory information is transmitted to the primary sensory cortex. So we hypothesized that trigeminal neuralgia patients will exhibit characteristic structural and metabolic abnormalities of the thalamus, and that these structural and metabolic abnormalities will be associated with the durability of pain relief following surgery for trigeminal neuralgia. So our study was a prospective single-center longitudinal study of patients undergoing surgery for trigeminal neuralgia over a three-year period. We included patients who had medically refractory classical or idiopathic trigeminal neuralgia defined using the International Classification of Headache Disorders 3 criteria, and these patients all had to be scheduled for surgical treatment either by microvascular decompression or percutaneous balloon compression rhizotomy. We excluded patients who had a secondary cause of trigeminal neuralgia, such as multiple sclerosis, and patients were excluded if they had any history of prior trigeminal neuralgia surgery or other intracranial surgery. We binarized response into responders versus non-responders, and we were interested as our primary outcome measure in response to surgery at one year after the surgical procedure. So responders were those patients who had documented evidence of immediate and sustained pain relief after surgery for at least one year, and response was considered to be a score on the Barrel Neurological Institute facial pain score of at least greater than 3A, and secondly, these patients could not have been offered repeat surgery within the year after their initial procedure. Non-responders on the other hand had either inadequate initial pain relief from the surgery itself or recurred early within one year of surgery. A surrogate for recurrence was if they were offered or underwent surgery within that first year following the initial procedure. To look at the thalamus, we used neuroimaging. Specifically, we obtained high-resolution T1-weighted structural MRI scans as well as magnetic resonance spectroscopy or MRS scans in trigeminal neuralgia patients preoperatively, that is within the one month prior to their surgical procedure, and postoperatively at a very early time point, one week after surgery. We obtained control imaging in 20 healthy controlled subjects. We examined whole thalamus structure and shape using the MRI analysis software package FSL-FIRST, and we looked at magnetic resonance spectroscopy metabolism results in the ventral posteromedial thalamus using LC-MODEL. You can see below the placement of an MRS voxel of interest bilaterally in the VPM thalamus by a trained observer. What did we find? First looking at the demographic results, there were 17 responders and 6 non-responders. This reflects the usual success rate of surgery for trigeminal neuralgia. Responders and non-responders were well matched across a number of demographic measures. However, all non-responders were female and non-responders were on average significantly younger than responders. This is in line with what we know in terms of clinical predictors of early recurrence after trigeminal neuralgia surgery. Turning now to our neuroimaging results, first we looked at the volume of the whole thalamus in patients with trigeminal neuralgia. We found that the whole thalamus contralateral to the side of facial pain was significantly enlarged across all trigeminal neuralgia patients in our study. This relationship held true whether we looked at patients with left-sided trigeminal neuralgia or right-sided trigeminal neuralgia. However, we found that this relationship also held in both responders and non-responders to trigeminal neuralgia surgery. And further, we found that the change in thalamic volume occurring within the first week after surgery did not relate to long-term outcome. We speculate that the enlargement of the contralateral thalamus may have to do with a state of hyperactivity of the contralateral thalamus which is inundated with pain-related information due to ongoing pain attacks. In terms of thalamic shape, we found that prior to surgery, non-responders actually do have focal areas of contralateral thalamic volume loss relative to responders. These are highlighted in the blue regions seen in the 3D reconstruction to the left. This may suggest that the thalamus in non-responders prior to surgery may somehow be less receptive to the necessary plastic changes that are required to obtain long-term pain relief. Now perhaps most interesting, when we look at our thalamic metabolism results, we find that prior to surgery, there is really no difference in the concentration of choline or N-acetyl aspartate within the ventral posteromedial nucleus of the thalamus contralateral to the site of facial pain. However, in non-responders, there is this characteristic reduction in both of these metabolites that occurs within one week after surgery and consistently occurs in every single one of the non-responders. This change is not seen in responders. And these unique metabolic alterations may therefore suggest that these patients who are non-responders have an inability to have an adaptive metabolic response to surgery which then predisposes patients to early pain recurrence. So therefore, we conclude that the trigeminal system has abnormalities in trigeminal neuralgia and we illustrate that these exist at least as far upstream as the contralateral thalamus. We found that trigeminal neuralgia patients who fail to have durable response to surgery show baseline differences in contralateral thalamic structure. And uniquely, we showed that there were early post-operative changes in thalamic metabolism which were different between non-responders and responders to surgery. And these are of course preliminary results, but they do suggest that the thalamus plays an important role in the pathophysiology of trigeminal neuralgia and its response to surgery and suggests that thalamic imaging features may well be a promising predictor or predictive biomarker in patients who are undergoing surgery for trigeminal neuralgia. Thank you.

Dr. Tejas Sankar

University of Alberta

thalamus

surgical treatment

trigeminal neuralgia