Clinical study of puncture technique in single division of the trigeminal ganglion intumescentia.

OBJECTIVE: We explored the feasibility of single-division puncture in the ophthalmic division, maxillary division, and mandibular division of the trigeminal ganglion intumescentia (TGI) and the feasibility of radiofrequency treatment of trigeminal neuralgia. METHODS: According to the previous anatomical image studies, 3D Slicer software was used to analyze the CT images of the patients. The trigeminal ganglion fossa (TGF) was used as the imaging sign. TGI was identified in the sagittal plane along the fiber. The puncture path starts from the TGI center-foramen ovale line, extending outward to the epidermis as the needle insertion point, and extending inward to the division boundary. For lateral puncture, which is blocked by the mandible, the positions of closed mouth, open mouth, and over-open mouth were used. Multiple targets were generated using straight electrodes and curved electrodes to achieve full coverage of TGI. According to the preoperative design, general anesthesia surgery was performed. Xper CT was used for imaging, and the puncture was guided by Xper Guide. Radiofrequency treatment of TGI was conducted. RESULTS: In total, 45 patients with trigeminal neuralgia underwent 50 single-division TGI punctures. The procedure was smooth and the compliance with the design was good. Continuous radiofrequency (CRF) was performed, the VAS scores were 25 times at 70°C, 19 times at 65°C, two times at 60°C, and two times at 50°C (both in the ophthalmic division). Pulsed radiofrequency (PRF) was conducted two times. Within 24 h after the procedure, the VAS scores were all 0. From 1 to 7 days after the procedure, pain recurrence was found in three cases, of whom two cases received pulsed radiofrequency treatment. Patients were followed up for 1-24 months and there were no recurrence. After continuous radiofrequency at 65-70°C, the moderate tactile loss was observed, and nearly half of the patients had food residues on the surgical side after 6 months. After continuous radiofrequency at 60°C, there was mild tactile loss and no food residue. The tactile sensation was slightly decreased after continuous radiofrequency at 50°C, and the tactile sensation was normal the next day. CONCLUSION: Trigeminal ganglion intumescentia single-division radiofrequency is effective and feasible for the treatment of trigeminal neuralgia.

Ultrasound Guidance Combined with C-Arm Fluoroscopy in Selective Semilunar Ganglion Radiofrequency Thermocoagulation Through the Foramen Ovale for Trigeminal Neuralgia: A Randomized Controlled Trial.

OBJECTIVE: To explore the clinical value of ultrasound guidance combined with C-arm guidance during selective semilunar ganglion radiofrequency thermocoagulation via the foramen ovale for trigeminal neuralgia. METHODS: This study enrolled 48 patients diagnosed with trigeminal neuralgia between January 2021 and December 2021 in the Department of Pain Management at Xuanwu Hospital. Patients were randomly and equally divided into a C-arm-only group and an ultrasound-combined-with-C-arm (ultrasound+C-arm) group, according to a random number table. After exclusions, 42 patients were analyzed. Of these, 21 patients underwent selective semilunar ganglion radiofrequency thermocoagulation via the foramen ovale guided by the C-arm alone, whereas 21 patients underwent the same procedure guided by ultrasound combined with C-arm. The number of punctures, the amount of time elapsed until the target area of the semilunar ganglion was punctured, the cumulative dose of radiation exposure, and puncture-related complications were recorded during the operation. Numerical rating scale scores and radiofrequency thermocoagulation-related complications were evaluated preoperatively and at 1 day, 3 days, 7 days, 1 month, and 3 months after surgery. RESULTS: The number of punctures, the amount of time elapsed until the target area of the semilunar ganglion was punctured, and the cumulative dose of radiation exposure were all lower in the ultrasound+C-arm group than in the C-arm-only group (all P < 0.05). No significant differences were found in numerical rating scale scores and radiofrequency thermocoagulation-related complications between the two groups (P > 0.05). No puncture-related complications occurred in either of the groups. CONCLUSION: Ultrasound guidance combined with C-arm guidance could be safely used for puncturing the semilunar ganglion via the foramen ovale, with more efficiency and less radiation exposure than C-arm guidance alone.

Ultrasound localization microscopy and functional ultrasound imaging reveal atypical features of the trigeminal ganglion vasculature.

The functional imaging within the trigeminal ganglion (TG) is highly challenging due to its small size and deep localization. This study combined a methodological framework able to dive into the rat trigeminal nociceptive system by jointly providing 1) imaging of the TG blood vasculature at microscopic resolution, and 2) the measurement of hemodynamic responses evoked by orofacial stimulations in anesthetized rats. Despite the small number of sensory neurons within the TG, functional ultrasound imaging was able to image and quantify a strong and highly localized hemodynamic response in the ipsilateral TG, evoked not only by mechanical or chemical stimulations of corneal nociceptive fibers, but also by cutaneous mechanical stimulations of the ophthalmic and maxillary orofacial regions using a von Frey hair. The in vivo quantitative imaging of the TG's vasculature using ultrasound localization microscopy combined with in toto labelling reveals particular features of the vascularization of the area containing the sensory neurons, that are likely the origin of this strong vaso-trigeminal response. This innovative imaging approach opens the path for future studies on the mechanisms underlying changes in trigeminal local blood flow and evoked hemodynamic responses, key mechanisms for the understanding and treatment of debilitating trigeminal pain conditions.

The impact of needle location on clinical outcome of radiofrequency rhizotomy for trigeminal neuralgia.

BACKGROUND: Radiofrequency thermocoagulation trigeminal rhizotomy (RT-TR) through the foramen ovale is a minimally invasive treatment for trigeminal neuralgia. Navigation of magnetic resonance imaging (MRI) and CT fusion imaging is a well-established method for cannulation of the Gasserian ganglion. In this study, we use the inline measurements from fusion image to analyze the anatomical parameters between the actual and simulation trajectories and compare the short- and intermediate-term outcomes according to determinable factors. METHODS: The study included thirty-six idiopathic neuralgia patients who had undergone RT-TR with MRI and CT fusion image as a primary modality or repeated procedures. RESULTS: Among thirty-six treated patients, the inline length of the trigeminal cistern was longer for the simulated trajectory (8.4 ± 2.4 versus 6.5 ± 2.8 mm; p < 0.05), and the predominant structure at risk extrapolated from the inline trajectory was the brainstem, which signified a more medially directed route, in contrast with the equal weighting of temporal lobe and brainstem for the actual trajectory. The preoperative visual analogue scale (VAS) was 9.3 ± 1.0, which decreased to 2.5 ± 2.6 and 2.9 ± 3.1 at first (mean, 3 months) and second (mean, 14 months) postoperative follow-up, respectively. The postoperative VAS scores at the two follow-ups were not statistically significant without a covariate analysis. After adjustment for covariate risk factors, the second follow-up sustained therapeutic benefit was evident in patients with no prior history of related treatment, an ablation temperature greater than 70 °C, and needle location within or adjacent to the trigeminal cistern. CONCLUSIONS: This preliminary study demonstrated that the needle location between cistern and ganglion also plays a significant role in better intermediate-term results.

In vivo optical recordings of ion dynamics in mouse corneal primary nociceptive terminals.

This protocol aims to measure ion dynamics in nociceptive terminal endings in intact mice in vivo. We describe viral injection of GCaMP6s + RFP into trigeminal ganglia (TG) of mice, followed by calcium imaging of corneal nociceptive terminals that express GCaMP6s and RFP. This fast and high-resolution optical recording technique enables studying a nociceptive terminal's functional molecular network in physiological and pathological conditions. This platform can be applied to studying the physiology of terminals of other neurons. For complete details on the use and execution of this protocol, please refer to Goldstein et al. (2019).

Rapid elevation of brain-derived neurotrophic factor production in the bilateral trigeminal ganglia by unilateral transection of the mental nerve in mice.

OBJECTIVES: Previous spinal nerve injury studies have reported brain-derived neurotrophic factor (BDNF) mRNA upregulation in either the ipsilateral dorsal root ganglion (DRG) neurons or both the contralateral and ipsilateral DRG neurons from early period after peripheral nerve injury. This BDNF elevation induces hyperalgesia in the injured and/or uninjured sites, but this detailed mechanism remains unknown. This study aimed to investigate the BDNF mRNA expression in bilateral DRG neurons caused by unilateral nerve injury and to explore the possible mechanisms by which nitric oxide (NO) mediates BDNF production in the DRG, resulting in contralateral hyperalgesia. METHODS: Early changes in BDNF mRNA expression in the bilateral trigeminal ganglia, within 1 day after mental nerve transection, were examined. Additionally, the effects on BDNF production of the NO synthase inhibitor N(ω)-nitro-l-arginine methyl ester (L-NAME) were investigated in the bilateral trigeminal ganglia. The relationship between injured neurons and BDNF production in the trigeminal ganglia was then assessed using immunohistochemical and retrograde tracing methods. RESULTS: Reverse transcription-PCR analysis demonstrated that unilateral transection of the mental nerve induced a rapid elevation of BDNF mRNA expression, which was inhibited by the intracerebroventricular administration of L-NAME prior to nerve transection. This effect was observed in both the ipsilateral and contralateral sides to the nerve transection. BDNF immunostaining combined with FluoroGold retrograde tracing revealed two types of BDNF-reactive neurons, FluoroGold-labelled and non-FluoroGold-labelled neurons, in the ipsilateral and contralateral sides of the trigeminal ganglia. BDNF-positive cells were also observed in the trigeminal ganglia of other trigeminal nerve branches. CONCLUSIONS: Unilateral nerve injury upregulates BDNF production in the bilateral trigeminal ganglia by NO-mediated and/or indirect activation of afferent neurons, resulting in contralateral hyperalgesia.

Percutaneous Foramen Ovale Puncture: Usefulness of Intraoperative CT Control, in the Eventuality of a Narrow Foramen.

BACKGROUND: Balloon compression of the gasserian ganglion has been a well-established percutaneous treatment of trigeminal neuralgia since the 1980s. However, puncture of the foramen ovale by conventional single-plane fluoroscopy can be difficult in cases of local anatomic abnormalities. CASE PRESENTATION: We present the case of a 49-year-old woman diagnosed with idiopathic trigeminal neuralgia refractory to pharmacological treatment. After failure of puncture by conventional fluoroscopy for percutaneous gasserian ganglion balloon compression due to a narrow foramen ovale, the patient was submitted to puncture guided by computed tomography. CONCLUSION: Alternative imaging methods, such as computed tomography, should be considered when puncture of the foramen ovale by conventional single-plane fluoroscopy fails, to minimize the risk of potential complications triggered by frustrated puncture attempts.

High-Throughput Calcium Imaging Screen of Toxins' Function in Dissociated Sensory Neurons.

Many toxins from a variety of venomous animals and plants have evolved to target neuronal ion channels and receptors. However, a significant obstacle in the study of these toxins is the finding and characterization of their specific molecular target. Here, we describe a method for fast and efficient screening of venom and toxin activity using live-cell calcium imaging. We describe the use of Fura-2, a calcium indictor that changes its fluorescence properties in response to intracellular calcium elevations, to measure the activity of neurons from the dorsal root and trigeminal ganglia. Calcium imaging is an efficient technique for testing many of the venom's components on large numbers of neurons simultaneously. This technique offers a novel tool for low-cost and rapid characterization of functionally active toxins and their target receptors.

Persistent Trigeminal Artery: Neuroanatomic and Clinical Relevance.

INTRODUCTION: Persistent trigeminal artery (PTA) is the most common remnant of primitive circulation communicating the developing carotid and vertebrobasilar junction. Although discovered incidentally, an altered hemodynamic may lead to an increased association of aneurysms, vascular malformations, and stroke. Neurosurgeons should be aware of the presence and significance of PTA when interpreting imaging and planning interventions. METHODS: We retrospectively reviewed all magnetic resonance angiography and cerebral digital subtraction angiography performed between 2012 and 2017 for the presence of PTA. The radiologic and anatomic details were noted and analyzed along with the clinical profiles. We categorized the radiologic findings with respect to the available classification systems. A review of the available literature was done comparing our results. RESULTS: We found 33 cases of incidentally detected PTA. The average age of the patients was 45.42 years. The lateral surface of the proximal cavernous internal carotid artery was the most common origin (n = 23). Only 3 cases had a medial/transsellar course. Most cases were Saltzman/Weon type I (19/33). Intracranial aneurysms were associated with 6 patients (18.18%). Trigeminal neuralgia (TN) was a presenting feature in 5 patients. None had a direct neurovascular conflict at the root entry zone. CONCLUSIONS: Our study is one of the largest to describe the incidence of PTA. We emphasized the importance of PTA to the neurosurgeons; increased association of aneurysms, as a route for intervention in occlusive disease of the posterior fossa; risk of injury and bleeding during transsphenoidal surgery; and the association with TN. However, we found that only PTA variants are likely to be associated with TN because of their cisternal course causing NV conflict.

Unconventional Facial Entry Points Confirmed Using a 3D CT Reconstruction-Guided Stereotactic Approach to Radiofrequency Thermocoagulation for the Treatment of Trigeminal Neuralgia: A Series of Case Reports.

OBJECTIVES: Patients with trigeminal neuralgia who are refractory to medical therapy may choose to undergo Gasserian ganglion percutaneous radiofrequency thermocoagulation. However, in cases where the foramen ovale is difficult to access due to various anatomical anomalies, the typical estimation of the facial entry point is suboptimal. METHODS: Three-dimensional computed tomography reconstruction imaging performed before surgery revealed anatomical variations in each of the four adult patient cases that made it more difficult to successfully access the foramen ovale (FO) for percutaneous radiofrequency thermocoagulation. Using measurements collected from preoperative imaging that showed each specific anatomical variation in the FO, researchers marked alternate facial entry points that would allow successful probe placement into the FO and recorded the arc angle data in the stereotactic instrument. RESULTS: Patients were evaluated during follow-up visits ranging from seven to 26 months after surgery and asked to rate postoperative pain using a visual analog scale. These scores decreased from 10 to 3 in all four patients by the third day after the procedure. There were no permanent complications or morbidities from the surgery. One patient experienced mild facial numbness; however, this side effect subsided within three months after surgery. During the follow-up period, no patient reported pain recurrence. CONCLUSIONS: The expectation for clinicians approaching trigeminal nerve block using a peri-oral approach should be to expect a great degree of potential variability in terms of both distances from the corner of the mouth and needle angle taken to successfully navigate the anatomy and access the foramen ovale.

Analysis of morphological measurements of the trigeminal nerve in the linac stereotactic radiosurgery simulation targeting the root entry zone in trigeminal neuralgia.

PURPOSE: To describe the anatomical measurements of the trigeminal nerve in patients with trigeminal neuralgia (TN) during Linac (linear accelerator)-based stereotactic radiosurgery (SRS) simulation, targeting the root entry zone (REZ), with a 30% isodose line tangential to the pons, using 4-mm and 6-mm collimators. METHODS: In this retrospective study, 53 TN patients, who underwent Fiesta sequence scanning prior to any treatment modality, were assessed. Bilateral measurements were obtained from the cisternal segment of the trigeminal nerve, the trigeminal-pontine angle, and the lateral width of the pontine cistern on the Fiesta MRI sequence. Linac-based SRS simulations were estimated with a radiation dosage of 90Gy to 30% isodose line tangential to the pons, with both 4- and 6-mm collimators. Distances from the calculated targets to the pons and the Gasserian ganglion were measured for later analysis. The statistical analysis was performed comparing the affected side against the unaffected side. RESULTS: Right trigeminal nerve was affected in 36 patients (67.9%), and left one in 17 (32.1%) patients. The mean length of the trigeminal nerve was 9.8mm (range: 4.6-16.8mm) on the affected side, and 10.5mm (range: 5.6-18.4mm) on the unaffected side (p=.02). The mean trigeminal-pontine angle was 12.5° (range: 5.4° to 19.5°) on the affected side, and 10.2° (range: 5.0° to 30.5°) on the unaffected side (p=.01). In the simulations, the distances from the estimated targets to the pons and the Gasserian ganglion were not statistically different between sides. The variation of target-pons and target-ganglion distances was statistically significant on the affected side with the change of collimators (p<.001). CONCLUSIONS: In this anatomical study, significant differences were identified in the length of the affected trigeminal nerve and trigeminal-pontine angle compared to the unaffected side in TN patients in Fiesta sequences prior to surgery or radiosurgery. Significant variation of the target location was found on the REZ between the 4- and 6-collimators during the Linac-based SRS simulations with the estimated radiation dosage of 90Gy and 30% isodose line tangential to the pons.

A Brain-wide Circuit Model of Heat-Evoked Swimming Behavior in Larval Zebrafish.

Thermosensation provides crucial information, but how temperature representation is transformed from sensation to behavior is poorly understood. Here, we report a preparation that allows control of heat delivery to zebrafish larvae while monitoring motor output and imaging whole-brain calcium signals, thereby uncovering algorithmic and computational rules that couple dynamics of heat modulation, neural activity and swimming behavior. This approach identifies a critical step in the transformation of temperature representation between the sensory trigeminal ganglia and the hindbrain: A simple sustained trigeminal stimulus representation is transformed into a representation of absolute temperature as well as temperature changes in the hindbrain that explains the observed motor output. An activity constrained dynamic circuit model captures the most prominent aspects of these sensori-motor transformations and predicts both behavior and neural activity in response to novel heat stimuli. These findings provide the first algorithmic description of heat processing from sensory input to behavioral output.

Three-Dimensional Reconstruction of the Distribution of Neurons Contributing to Ophthalmic, Maxillary, and Mandibular Nerves in the Trigeminal Ganglion of Experimental Model.

The authors introduce a new method to build a three-dimensional (3D) model of the 3 branches of the trigeminal nerve in the trigeminal ganglion of rabbit with 3 different kinds of fluorescence. Ten adult New Zealand rabbits of both sexes weighing between 2.0 and 3.0 kg were used in the experiment. Then through an operation under general anesthesia, the maxillary and mandibular nerves were exposed, and red and gold fluorescence were applied to investigate the neurons of the maxillary and mandibular nerves. Subsequently, DiI was used as a marker for the ophthalmic neuron for the other side of the same rabbit. After receiving images of the 3 branches under a fluorescence microscope, a 3D model of the 3 branches of the trigeminal nerve could be built. The authors obtained an image of the 3 branches of neurons in the trigeminal ganglion, and a 3D model of the 3 branches of the trigeminal nerve in the trigeminal ganglion was reconstructed. In the trigeminal ganglion, ophthalmic neurons were concentrated in the anteromedial section, the maxillary division in the middle, and the mandibular division posterolaterally. Overlap was observed between the ophthalmic and maxillary neurons, and also for the maxillary and mandible neurons.

Specialized Mechanosensory Nociceptors Mediating Rapid Responses to Hair Pull.

The somatosensory system provides animals with the ability to detect, distinguish, and respond to diverse thermal, mechanical, and irritating stimuli. While there has been progress in defining classes of neurons underlying temperature sensation and gentle touch, less is known about the neurons specific for mechanical pain. Here, we use in vivo functional imaging to identify a class of cutaneous sensory neurons that are selectively activated by high-threshold mechanical stimulation (HTMRs). We show that their optogenetic excitation evokes rapid protective and avoidance behaviors. Unlike other nociceptors, these HTMRs are fast-conducting Aδ-fibers with highly specialized circumferential endings wrapping the base of individual hair follicles. Notably, we find that Aδ-HTMRs innervate unique but overlapping fields and can be activated by stimuli as precise as the pulling of a single hair. Together, the distinctive features of this class of Aδ-HTMRs appear optimized for accurate and rapid localization of mechanical pain. VIDEO ABSTRACT.

A novel technique of delivering viral vectors to trigeminal ganglia in rats.

The objective of this study was to develop a viable and reliable technique of delivering viral vectors to rat trigeminal ganglia. Adult Sprague-Dawley rats (200-300 g) were used, and lentiviral vectors containing enhanced green fluorescence protein and calcitonin gene-related peptide short hairpin RNA (shRNA) were generated. Following general anesthesia, viral vectors were delivered to rat trigeminal ganglia using the technique described in this study. Both X-ray and micro-computed tomography (micro-CT) were employed to verify the position of the needles when injecting the vectors. In vivo fluorescence imaging and immunostaining against enhanced green fluorescence protein were performed to determine the success of viral transduction.The levels of calcitonin gene-related peptide in trigeminal ganglia were determined using real-time PCR, and pain levels following injections were evaluated using the Rat Grimace Scale. Our results show that injection needles can be advanced precisely at the trigeminal fossa and that viral vectors can successfully transduce trigeminal ganglia. Moreover, the levels of calcitonin gene-related peptide at trigeminal ganglia were down-regulated on day 7 after viral transduction. Pain levels returned to baseline by day 7 following injection. Therefore, we suggest that our trigeminal ganglion-targeting technique could be used for delivering genes or drugs to rat trigeminal ganglia.

Pro-nociceptive migraine mediator CGRP provides neuroprotection of sensory, cortical and cerebellar neurons via multi-kinase signaling.

Background Blocking the pro-nociceptive action of CGRP is one of the most promising approaches for migraine prophylaxis. The aim of this study was to explore a role for CGRP as a neuroprotective agent for central and peripheral neurons. Methods The viability of isolated rat trigeminal, cortical and cerebellar neurons was tested by fluorescence vital assay. Engagement of Nrf2 target genes was analyzed by qPCR. The neuroprotective efficacy of CGRP in vivo was tested in mice using a permanent cerebral ischemia model. Results CGRP prevented apoptosis induced by the amino acid homocysteine in all three distinct neuronal populations. Using a set of specific kinase inhibitors, we show the role of multi-kinase signaling pathways involving PKA and CaMKII in neuronal survival. Forskolin triggered a very similar signaling cascade, suggesting that cAMP is the main upstream trigger for multi-kinase neuroprotection. The specific CGRP antagonist BIBN4096 reduced cellular viability, lending further support to the proposed neuroprotective function of CGRP. Importantly, CGRP was neuroprotective against permanent ischemia in mice. Conclusion Our data show an unexpected 'positive' role for the endogenous pro-nociceptive migraine mediator CGRP, suggesting more careful examination of migraine prophylaxis strategy based on CGRP antagonism although it should be noted that homocysteine induced apoptosis in primary neuronal cell culture might not necessarily reproduce all the features of cell loss in the living organism.