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Background: Calcitonin gene-related peptide (CGRP) is part of the calcitonin peptide family, which includes calcitonin (CT), amylin (AMY), and adrenomedullin (ADM). CGRP and its receptor are highly present in the trigeminovascular system (TVS). Recent research suggests that other members of the calcitonin family could be feasible therapeutic targets in the treatment of migraine. The present study aims to elucidate the distribution of ADM, AMY, CT, and their receptors in the rat TVS, and to explore potential sex differences in their expression. Methods: Trigeminal ganglia (TG) were dissected from male and female adult rats. Protein and gene expression were assessed through immunohistochemistry and RT-qPCR. Additionally, the dura mater was isolated for further investigation of protein expression and fiber localization using immunohistochemistry. Results: Quantitative gene expression analysis revealed the presence of all genes in male and female TGs, except for calcitonin receptor (CTR). Notably, CGRP mRNA levels in TG were several folds higher than those of other genes. The receptor activity-modifying protein-1 (RAMP1) mRNA levels were significantly higher in female compared to male. No AMY or CT immunoreactivity was observed in the TVS. In contrast, immunoreactivity for ADM, CGRP, RAMP1, CTR, and calcitonin-like receptor (CLR) were observed in the cytoplasm of TG neurons. Immunoreactive Aδ-fibers storing RAMP1, ADM and CLR were also identified. RAMP2 and RAMP3 were expressed in nucleus of TG neurons and in satellite glial cells. Furthermore, RAMP1 and CLR were co-localized with CASPR in the nodes of Ranvier located in Aδ-fibers. Conclusions: This study provides valuable insights into the distribution of the CGRP family of peptides and their receptors in the TVS. CGRP mRNA levels in the TG were markedly higher than those of other genes, demonstrating the key role of CGRP. The co-localization of CLR and RAMP1 on Aδ-fibers with CASPR suggests a potential role for this receptor in modulating trigeminal nerve function and neuronal excitability, with implications for migraine pathophysiology. Additionally, RAMP1 mRNA levels were significantly higher in female TG compared to males, indicating sex-specific differences in gene expression. These findings underscore the need for further research into the functional significance of gender-related variations. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of primary trigeminal neuralgia (PTN) in radiology lacks the gold standard and largely depends on the identification of neurovascular compression (NVC) using magnetic resonance imaging (MRI) water imaging sequences. However, relying on this imaging sign alone often fails to accurately distinguish the symptomatic side of the nerve from asymptomatic nerves, and may even lead to incorrect diagnoses. Therefore, it is essential to develop a more effective diagnostic tool to aid radiologists in the diagnosis of TN. Purpose: This study aims to establish a radiomics-based machine learning model integrating multi-region of interest (multiple-ROI) MRI and anatomical data, to improve the accuracy in differentiating symptomatic from asymptomatic nerves in PTN. Methods: A retrospective analysis of MRI data and clinical anatomical data was conducted on 140 patients with clinically confirmed PTN. Symptomatic nerves of TN patients were defined as the positive group, while asymptomatic nerves served as the negative group. The ipsilateral Meckel's cavity (MC) was included in both groups. Through dimensionality reduction analysis, four radiomics features were selected from the MC and 24 radiomics features were selected from the trigeminal cisternal segment. Thirteen anatomical features relevant to TN were identified from the literature, and analyzed using univariate logistic regression and multivariate logistic regression. Four features were confirmed as independent risk factors for TN. Logistic regression (LR) models were constructed for radiomics model and clinical anatomy, and a combined model was developed by integrating the radiomics score (Rad-Score) with the clinical anatomy model. The models' performance was evaluated using receiver operating characteristic curve (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The four independent clinical anatomical factors identified were: degree of neurovascular compression, site of neurovascular compression site, thickness of the trigeminal nerve root, and trigeminal pons angle (TPA). The final combined model, incorporating radiomics and clinical anatomy, achieved an area under the curve (AUC) of 0.91/0.90 (95% CI: 0.87–0.95/0.81–0.96) and an accuracy of approximately 82% in recognizing symptomatic and normal nerves. Conclusion: The combined radiomics and anatomical model provides superior recognition efficiency for the symptomatic nerves in PTN, offering valuable support for radiologists in diagnosing TN. [ABSTRACT FROM AUTHOR]

Background and purpose: Trigeminal neuralgia (TN) is a severe chronic pain condition, typically affecting patients over 50-year-old, caused by the compression of the nerve at the root entry zone (REZ) by blood vessels. While the diagnosis is clinical, advanced imaging like diffusion tensor imaging (DTI) is crucial to identify underlying causes and assessing nerve damage. DTI may help develop neuroimaging markers to improve understanding of TN and predict surgical outcomes. The goal of the present systematic review is to evaluate the effectiveness of DTI and tractography in order to better assess treatment planning and outcome prediction through the analysis of trigeminal nerve alterations. Methods: The authors conducted a systematic review and meta-analysis of the literature to compare radiological parameters identified in pre- and post-operative MRI with DTI sequences, including fractional anisotropy (FA), quantity of anisotropy (QA), radial diffusivity (RD), and to correlate these findings with post-operative clinical outcomes. A comprehensive search of the PubMed and Scopus databases was carried out for studies published between April 2010 and January 2024. Results: This review included 11 studies and 603 patients. Of the 363 patients with trigeminal neuralgia (TN), 193 underwent microvascular decompression (MVD), with 72.5% showing clinical improvement and 27.5% not improving, possibly due to chronic nerve damage. Four studies assessed radiological parameters before and after MVD, while two focused only on post-MVD data. The mean fractional anisotropy (FA) in affected nerves increased from 0.328 before MVD to 0.382 afterward. Five studies did not report postoperative outcomes, just comparing radiological parameters in TN patients versus healthy controls. Conclusions: Recent studies show that MRI-DTI parameters, including FA, RD, and QA, are useful for diagnosing trigeminal neuralgia and predicting treatment outcomes. Lower FA and higher RD values indicate better results after surgery. More research is mandatory to guide treatment decisions and enhance patients' care. [ABSTRACT FROM AUTHOR]

Neurotrophic keratitis (NK) is a rare corneal disorder characterized by decreased corneal sensitivity and impaired corneal healing due to damage or dysfunction of the trigeminal nerve. We present a case of NK caused by trigeminal nerve palsy secondary to a cerebellopontine angle (CPA) epidermoid cyst. The patient exhibited corneal epithelial defects, persistent corneal ulceration, and decreased corneal sensation. Prompt diagnosis and management of the underlying brain lesion were crucial for successful treatment of the disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mandibular reconstruction has historically been challenging due to the complex, highly functional, and esthetic nature of the anatomy. The most common etiologies of these defects requiring resection include trauma, benign tumors, and malignant pathology. Mandibular defects have been treated with little consideration for neural reconstruction, leaving patient's orally incompetent with associated social stigma. Although recent advances in reconstructive techniques improve oral rehabilitation, immediate inferior alveolar nerve (IAN) reconstruction has not been widely adapted. OBJECTIVE: Here-in we seek to discuss the innovations of neural reconstruction of large segment mandibular defects and associated IAN defects and present an example case performed at Naval Medical Center San Diego (NMCSD). METHODS: Pertinent literature discussing maxillofacial reconstruction and nerve repair using autogenous nerve harvest and allograft was queried from available online resources. RESULTS: Six patients have received immediate reconstruction of the IAN using processed nerve allograft over the past three years. All obtained sensation to S3 within six months of surgery. CONCLUSION: IAN repair using nerve allografts in conjunction with free flap reconstruction for large mandibular defects is a viable treatment and should be the new paradigm in maxillofacial reconstruction as it provides substantial quantifiable and qualitative improvements in social, functional, and esthetic outcomes of care. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to develop a clinical-radiomics nomogram to predict the long-term outcomes of patients with classical trigeminal neuralgia (CTN) following microvascular decompression (MVD). Materials and methods: This retrospective study included 455 patients with CTN who underwent MVD from three independent institutions A total of 2030 radiomics features from the cistern segment of the trigeminal nerve were extracted computationally from the three-dimensional steady-state free precession and three-dimensional time-of-flight magnetic resonance angiography sequences. Using the least absolute shrinkage and selection operator regression, 16 features were chosen to develop radiomics signatures. A clinical-radiomics nomogram was subsequently developed in the development cohort of 279 patients via multivariate Cox regression. The predictive performance and clinical application of the nomogram were assessed in an external cohort consisting of 176 patients. Results: Sixteen highly outcome-related radiomics features extracted from multisequence images were used to construct the radiomics model, with concordance indices (C-index) of 0.804 and 0.796 in the development and test cohorts, respectively. Additionally, a clinical-radiomics nomogram was developed by incorporating both radiomics features and clinical characteristics (i.e., pain type and degree of neurovascular compression) and yielded higher C-indices of 0.865 and 0.834 in the development and test cohorts, respectively. K‒M survival analysis indicated that the nomogram successfully stratified patients with CTN into high-risk and low-risk groups for poor outcomes (hazard ratio: 37.18, p < 0.001). Conclusion: Our study findings indicated that the clinical-radiomics nomogram exhibited promising performance in accurately predicting long-term pain outcomes following MVD. Clinical relevance statement: This model had the potential to aid clinicians in making well-informed decisions regarding the treatment of patients with CTN. Key Points: Trigeminal neuralgia recurs in about one-third of patients after undergoing MVD. The clinical-radiomics nomogram stratified patients into high- and low-risk groups for poor surgical outcomes. Using this nomogram could better inform patients of recurrence risk and allow for discussion of alternative treatments. [ABSTRACT FROM AUTHOR]

To describe an ultrasound-guided suprazygomatic approach to the trigeminal nerve block in cat cadavers. Prospective descriptive study. Ten feline cadaver heads. A 25:75 methylene blue–iopamidol mixture (0.1 mL cm–1 cranium length) was injected into 10 cadaver heads using an ultrasound-guided suprazygomatic approach. A computed tomography (CT) scan was performed to identify contrast presence at the orbital fissure, foramen rotundum and ovale, followed by anatomical dissection to identify staining of the pterygopalatine fossa (PPF), extraconal retrobulbar area, mandibular and maxillary nerves. Descriptive statistics were used to summarize results. A total of 20 injections were performed. Of these, 1/20 misinjection occurred and excluded from further reporting. The volume of injectate was 0.9 (0.9–1.1) mL [median (range)]. Staining of the PPF, extraconal space, maxillary and mandibular nerves over more than 6 mm was achieved in 19/19 (100%), 18/19 (95%), 17/19 (89%) and 19/19 (100%) of injections, respectively. CT showed presence of contrast within 5 mm of the orbital fissure, foramen rotundum and ovale in 18/19 (95%), 19/19 (100%) and 19/19 (100%) of the injections, respectively. No intracranial migration was observed. This cadaver study illustrates that the suprazygomatic ultrasound-guided trigeminal nerve injection technique can successfully stain the PPF, retrobulbar cone extraconally, mandibular and maxillary nerves. Consequently, this technique has the potential to be used in vivo in cats to desensitize areas innervated by the trigeminal nerve. [ABSTRACT FROM AUTHOR]

Background A neurovascular conflict (NVC) is considered the cause of trigeminal neuralgia (TN) in 75% of cases, and if so, a microvascular decompression (MVD) can lead to significant pain relief. A reliable preoperative detection of NVC is essential for clinical decision-making and surgical planning, making detailed neuroradiologic imaging an important component. We present our experiences and clinical outcomes with preoperative planning of the MVD procedure in a virtual reality (VR) environment, based on magnetic resonance imaging (MRI) including magnetic resonance angiography (MRA) and magnetic resonance venography (MRV) sequences. Methods We analyzed the data of 30 consecutive MVDs in patients treated for TN, in a retrospective single-surgeon (R.A. Kockro) study. Out of the 30 cases, 26 were included. Preoperatively, MRA/MRV and MRI series were fused and three dimensionally reconstructed in a VR environment. All critical structures such as the trigeminal nerve as well as the arteries and veins of the cerebellopontine angle, the brainstem, the neighboring cranial nerves, and the transverse and sigmoid sinus were segmented. The NVC was visualized and a simulation of a retrosigmoid approach, with varying trajectories, to the NVC was performed. The intraoperative findings were then compared with the data of the simulation. The clinical outcome was assessed by a detailed review of medical reports, and follow-up-interviews were conducted in all available patients (20/26). Results The VR planning was well integrated into the clinical workflow, and imaging processing time was 30 to 40 minutes. There was a sole arterial conflict in 13 patients, a venous conflict in 4 patients, and a combined arteriovenous conflict in 9 patients. The preoperative simulations provided a precise visualization of the anatomical relationships of the offending vessels and the trigeminal nerves as well as the surrounding structures. For each case, the approach along the most suitable surgical corridor was simulated and the exact steps of the decompression were planned. The NVC and the anatomy of the cerebellopontine angle as seen intraoperatively matched with the preoperative simulations in all cases and the MVC could be performed as planned. At follow-up, 92.3% (24/26) of patients were pain free and all the patients who completed the questionnaire would undergo the surgery again (20/20). The surgical complication rate was zero. Conclusion Current imaging technology allows detailed preoperative visualization of the pathoanatomical spatial relationships in cases of TN. 3D interactive VR technology allows establishing a clear dissection and decompression strategy, resulting in safe vascular microsurgery and excellent clinical results. [ABSTRACT FROM AUTHOR]

Valentin Felixovich Voyno-Yasenetsky (VFVY; also known as Saint Luke of Simferopol) was a famous professor of anatomy and surgery of the previous century. He was a particularly skilled surgeon, proficient in various surgical subspecialties, with main interest in regional anesthesia and pyogenic infections. The primary aim of this article is to explore his scientific contributions to surgical operations of the nervous system. His contributions are in three primary fields, namely, neuroanatomy, neurosurgery, and regional anesthesia. His work is characterized by meticulous descriptions of various anatomical structures of the brain and skull and of the intraoperative findings of his neurosurgical procedures. He clarified neurosurgical terms and described neurosurgical techniques. He also provided advice regarding the safety of neurosurgical procedures. Furthermore, he pioneered in techniques for regional anesthesia of the sciatic and trigeminal nerves. His exceptional talent as a scientist and surgeon, as well as his contributions to the neurosciences, makes him an exemplary doctor for modern neurosurgeons. [ABSTRACT FROM AUTHOR]

Background: Intranasal trigeminal function is important in detecting environmental stimuli. The impact of age-associated chemosensory dysfunction upon taste and olfaction is well described, but an understanding of trigeminal loss (chemesthesis) is lacking. Objective: The goal of this study was to characterize trigeminal function in a cohort of older adults and explore potential impacts. Methods: Twenty-eight participants over 50 years of age were recruited from the community as part of an aging cohort study. This nested cohort completed chemosensory questionnaires, patient-reported outcome measures (PROMs), and psychophysical testing for taste (taste strips), olfaction (Sniffin' Sticks), and trigeminal function (eucalyptol lateralization). Data were analyzed for associations between trigeminal function, olfactory, and taste psychophysical performance, patient-reported metrics, and demographic risk factors. Results: Patient-reported trigeminal impairment is less severe than other chemosensory loss, with mean visual analog scores (VAS, rated 0-100 from least to most severe) for smell (32.9 ± 34.2), taste (20.6 ± 28.4), and trigeminal sensation (9.5 ± 12.8). Despite low VAS scores, psychophysical trigeminal dysfunction was present in 10 (35.7%) subjects. Psychophysical olfactory and taste dysfunction were present in 16 (57.1%) and eight (28.6%) participants respectively. Hypercholesterolemia was associated with psychophysical trigeminal dysfunction (mean lateralization performance in hypercholesterolemia 57.7% ± 17.1 vs. 74.1% ± 10.4, p =.008). Conclusion: Intranasal trigeminal impairment is present in nearly one-third of aging adults when assessed by psychophysical methods but is under-recognized. Hyperlipidemia may be associated with trigeminal impairment. Future inquiries should better characterize these findings in larger and prospective cohorts. [ABSTRACT FROM AUTHOR]

COVID-19 presents with a plethora of neurological signs and symptoms despite being characterized as a respiratory disease, including seizures, anxiety, depression, amnesia, attention deficits, and alterations in consciousness. The olfactory nerve is widely accepted as the neuroinvasive route by which the etiological agent SARS-CoV-2 enters the brain, but the trigeminal nerve is an often-overlooked additional route. Based on this consensus, we initially conducted a pilot experiment investigating the olfactory nerve route of SARS-CoV-2 neuroinvasion via intranasal inoculation in AC70 human ACE2 transgenic mice. Notably, we found that the trigeminal ganglion is an early and highly efficient site of viral replication, which then rapidly spread widely throughout the brain where neurons were primarily targeted. Despite the extensive viral infection across the brain, obvious evidence of tissue pathology including inflammatory infiltration, glial activation, and apoptotic cell deaths were not consistently observed, albeit inflammatory cytokines were significantly induced. However, the expression levels of different genes related to neuronal function, including the neurotransmitter dopamine pathway as well as synaptic function, and markers of neuronal damage were altered as compared to mock-infected mice. Our findings suggest that the trigeminal nerve may serve as a neuroinvasive route complementary to the olfactory nerve and that the ensuing neuroinvasion presented a unique neuropathological profile. This study provides insights into potential neuropathogenic mechanisms utilized by coronaviruses. [ABSTRACT FROM AUTHOR]

Introduction: A current thrust in neurology involves using exogenous neuromodulation of cranial nerves (e.g, vagus, trigeminal) to treat the signs and symptoms of various neurological disorders. These techniques also have the potential to augment cognitive and/or sensorimotor functions in healthy individuals. Although much is known about the clinical effects of trigeminal nerve stimulation (TNS), effects on sensorimotor and cognitive functions such as learning have received less attention, despite their potential impact on neurorehabilitation. Here we describe the results of experiments aimed at assessing the effects of TNS on motor learning, which was behaviorally characterized using an upper extremity visuomotor adaptation paradigm. Objective: Assessing the effects of TNS on motor learning. Methods: Motor learning was behaviorally characterized using an upper extremity visuomotor adaptation paradigm. In Experiment 1, effects of offline TNS using clinically tested frequencies (120 and 60 Hz) were characterized. Sixty-three healthy young adults received TNS before performing a task that involved reaching with perturbed hand visual feedback. In Experiment 2, the effects of 120 and 60 Hz online TNS were characterized with the same task. Sixty-three new participants received either TNS or sham stimulation concurrently with perturbed visual feedback. Results: Experiment 1 results showed that 60 Hz stimulation was associated with slower rates of learning than both sham and 120 Hz stimulation, indicating frequency-dependent effects of TNS. Experiment 2 however showed no significant differences among stimulation groups. A post-hoc, cross-study comparison of the 60 Hz offline and online TNS results showed a statistically significant improvement in learning rates with online stimulation relative to offline, pointing to timing-dependent effects of TNS on visuomotor learning. Discussion: The results indicate that both the frequency and timing of TNS can influence rates of motor learning in healthy adults. This suggests that optimization of one or both parameters could potentially increase learning rates, which would provide new avenues for enhancing performance in healthy individuals and augmenting rehabilitation in patients with sensorimotor dysfunction resulting from stroke or other neurological disorders. [ABSTRACT FROM AUTHOR]

Background: In addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors. Methods: In a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague–Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration. Results: Both doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP. Conclusions: The findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine. [ABSTRACT FROM AUTHOR]

Introduction: Proprioceptive error of estimated fingertip position in twodimensional space is reduced with the addition of tactile stimulation applied at the fingertip. Tactile input does not disrupt the participants' estimation strategy, as the individual error vector maps maintain their overall structure. This relationship suggests integration of proprioception and tactile information improves proprioceptive estimation, which can also be improved with trained mental focus and attention. Task attention and arousal are physiologically regulated by the reticular activating system (RAS), a brainstem circuit including the locus coeruleus (LC). There is direct and indirect evidence that these structures can be modulated by non-invasive trigeminal nerve stimulation (nTNS), providing an opportunity to examine nTNS effect on the integrative relationship of proprioceptive and tactile information. Methods: Fifteen right-handed participants performed a simple right-handed proprioceptive estimation task with tactile feedback (touch) and no tactile (hover) feedback. Participants repeated the task after nTNS administration. Stimulation was delivered for 10 min, and stimulation parameters were 3,000 Hz, 50 µs pulse width, with a mean of 7 mA. Error maps across the workspace are generated using polynomial models of the participants' target responses. Results: Error maps did not demonstrate significant vector direction changes between conditions for any participant, indicating that nTNS does not disrupt spatial proprioception estimation strategies. A linear mixed model regression with nTNS epoch, tactile condition, and the interaction as factors demonstrated that nTNS reduced proprioceptive error under the hover condition only. Discussion: We argue that nTNS does not disrupt spatial proprioceptive error maps but can improve proprioceptive estimation in the absence of tactile feedback. However, we observe no evidence that nTNS enhances tactileproprioceptive integration as the touch condition does not exhibit significantly reduced error after nTNS. [ABSTRACT FROM AUTHOR]

Background: Trigeminal neurostimulation of the dorsal anterior mucosal surface of the tongue has been proposed to treat a variety of pathologies and to promote neuro-muscular coordination and rehabilitation. Dental ULFTENS can also be considered a form of trigeminal neurostimulation applied to the skin surface bilaterally at the level of the tragus. It has been used for years in dentistry for practical and diagnostic purposes. Previous work has combined the two stimulation techniques showing an efficacy in improving HRV in healthy young women of dental ULFTENS applied to the mucosal surface of the tongue. This work sought to assess whether there is a difference in HRV in relation to the site of application of dental ULFTENS (tragus vs. tongue). If effective in reducing the activity of arousal circuits, this tongue-level stimulation technique could have new clinical applications. Material and method: A new intraoral device allowed electrical stimulation of the dorsal anterior mucosa of the tongue in 80 healthy young women divided into two groups: TUD group (ULFTENS stimulation on the mucosa of the tongue) and Tragus group (stimulation with ULFTENS bilaterally in the area of the tragus). The effects on HRV were monitored by photoplethysmographic wave (PPG). The HRV parameters studied were RMSSD, HF, LF, LF/HF. Results: Only the TUD group showed a significant change in selected HRV parameters that was maintained even in the epoch after the end of electrical stimulation. This effect can be considered as a vagal activation and an increased of HRV parameter. The Tragus group did not show significant change in the direction of increased HRV but showed an opposite trend. There were no undesirable or annoying effects of stimulation. Conclusion: Stimulation of the dorsal anterior (trigeminal) mucosal surface of the tongue with ULFTENS applied with an intraoral device was shown to be able to increase HRV while the same stimulation on tragus area, according to traditional dental ULFTENS procedure, did not show the same effects. Clinical implications: This stimulation technique could be an aid in the diagnosis and treatment of disorders characterized by autonomic disequilibrium such as, in the dental field, TMDs. Trial registration: "Effects of Trigeminal Neurostimulation on Heart Rate Variability: Comparing Tragus and Tongue Stimulation". ID number: NCT06549205. Date of first registration: August 1st 2024. https://clinicaltrials.gov/study/NCT06549205?id=%09NCT06549205&rank=1. [ABSTRACT FROM AUTHOR]

Background: Glossopharyngeal neuralgia (GN) is a rare pain syndrome often underdiagnosed. This study aimed to assess the challenges in diagnosing GN and identify patients at risk of misdiagnosis. Methods: Between 2010 and 2019, nine patients underwent microvascular decompression (MVD) of the glossopharyngeal nerve at two tertiary care hospitals. A retrospective analysis examined symptom characteristics, time to correct diagnosis, operative technique, and clinical outcomes. Barrow Neurological Institute (BNI) pain scores were assessed before surgery and on follow-up. Results: Six women and three men, aged 55 ± 14.3 years, with unilateral GN were included. Pain was predominantly in the ear (otalgic type) in four patients (44.4%), the pharynx or base of the tongue (pharyngeal type) in four (44.4%), and mixed in one (11.1%). Five patients reported pain radiating to the mandible, all initially misdiagnosed with trigeminal neuralgia (TN) and treated for 2.4(± 3.1) years before presenting to our institution. One case resulted in MVD of the trigeminal nerve and subsequent thermocoagulation of the Gasserian ganglion due to persistent pain. The correct diagnosis of GN was established later in patients with otalgic or mixed pain (3.8 ± 3.4 years) compared to those with pharyngeal pain (0.5 ± 1.0 years), showing a trend (U = 17.0, p = 0.07). There was a significant association between pain radiation to the mandible and misdiagnosis (x2 = 9.00, p = 0.003). Endoscopically assisted MVD via the median suboccipital subtonsillary approach was performed, resolving neurovascular conflicts with the PICA (9/9) and vertebral artery (3/9). Follow-up after 15.7(± 18.2) months showed significant pain reduction according to the BNI (preoperative BNI = 5.0 ± 0.0, postoperative BNI = 1.7 ± 1.0,t (8) = 10,CI [1.6–5.1], p < 0.001). No permanent surgery-related deficits occurred. Conclusion: Patients with GN, especially those with predominant otalgic pain and pain radiating to the mandible, are at higher risk of misdiagnosis due to similarities with TN. Despite the rarity of GN, increased awareness of its various pain manifestations may lead to earlier correct diagnoses, which is crucial for surgical treatment. [ABSTRACT FROM AUTHOR]

The trigeminal sensory system consists of the trigeminal nerve, the trigeminal ganglion, and the trigeminal sensory nuclei (the mesencephalic nucleus, the principal nucleus, the spinal trigeminal nucleus, and several smaller nuclei). Various sensory signals carried by the trigeminal nerve from the orofacial area travel into the trigeminal sensory system, where they are processed into integrated sensory information that is relayed to higher sensory brain areas. Thus, knowledge of the trigeminal sensory system is essential for comprehending orofacial pain. This review elucidates the individual nuclei that comprise the trigeminal sensory system and their synaptic transmission. Additionally, it discusses four types of orofacial pain and their relationship to the system. Consequently, this review aims to enhance the understanding of the mechanisms underlying orofacial pain. [ABSTRACT FROM AUTHOR]

We report a case of neurocytoma originating from cranial nerve V. A 53-year-old female patient presented with a 20-day history of right frontotemporal facial paresthesia and pain. Magnetic resonance imaging (MRI) showed a 2.5-cm × 1.4-cm "dumbbell" enhancing lesion located in the cisternal segment of cranial nerve V with extension into Meckel's cave, and the signal characteristics were suggestive of trigeminal neurinoma. The lesion was resected through a subtemporal middle cranial fossa approach. Intraoperative findings revealed that the tumor originated from the cisternal segment of cranial nerve V and extended into Meckel's cave through the trigeminal foramen. No dural attachment was found. The tumor was debulked using sharp dissection and bipolar cautery under the microscope. Extraventricular neurocytomas (EVNs) are extremely rare tumors of the central nervous system. To date, only two cases of neurocytomas arising from cranial nerve VIII have been described. This paper summarizes the clinicopathological features of a case of neurocytoma originating from the cisternal segment of cranial nerve V with extension into Meckel's cave and expounds the relevant diagnoses and treatments, which may provide a practical clinical basis and experience for the diagnosis and treatment of EVN in the future. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Capillary malformation–arteriovenous malformation (CM‐AVM) is a rare genetic disorder characterized by multiple small capillary malformations (CMs) and arteriovenous malformations (AVMs), which has been linked with pathogenic variants in RASA1 and EPHB4. However, more data are needed to explore the phenotypic characteristics and the association between genotypes and clinical phenotypes.Our aim was to investigate the phenotypic and genetic characteristics of CM‐AVM in East Asians, identify potential unique phenotypes, and conduct genotype–phenotype association analyses.This is a single‐center study prospectively collecting CM‐AVM patients' clinical data, with genetic data from blood or tissue samples.A total of 59 patients were enrolled. Thirty‐two individuals had a leading CM greater than Schobinger stage II. The trigeminal nerve branches and greater auricular, transverse cervical, and lesser occipital nerves' somatosensory innervation zones divided head and neck CMs into six zones: V1, V2, V3, GA, TC, and LO zones. GA, TC, and LO zones had a positive correlation with one another but a negative correlation with V2 zone involvement. The RASA1 and EPHB4 pathogenic variants were detected in 41 out of 59, which showed two types of variant allele frequency (VAF) distributions. VAF above 30% made RASA1 pathogenic variants more susceptible to multifocal CMs than those below 30%.Leading CMs in the head and neck exhibit two segmentation patterns, anterior and lateral, which may differ in ear involvement and progression. Germline RASA1 pathogenic variants increased multifocal CM risk more than the somatic variants. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Herpes zoster is an acute cutaneous viral disease resulting from reactivation of dormant varicella‐zoster virus. The maxillary nerve is the least frequently affected branch of the trigeminal nerve. Rarely, cutaneous lesions can be secondarily infected with Klebsiella species. This report discusses a case of maxillary zoster with nasociliary nerve involvement and Klebsiella superinfection. [ABSTRACT FROM AUTHOR]

Trigeminal neuralgia (TN) is a debilitating condition characterized by excruciating facial pain resulting from dysfunction in the trigeminal nerve. Treatment options are limited. Noninvasive pulsed radiofrequency (PRF) therapy is an emerging promising approach to managing TN. This therapy provides pain control without tissue damage or unpleasant side effects compared to invasive procedures. Here, we present five cases of trigeminal neuralgia successfully managed with noninvasive PRF therapy. Our case series contributes to the existing literature and supports the potential efficacy of noninvasive PRF therapy for TN. [ABSTRACT FROM AUTHOR]

The contributions of Laurent Princeteau (1858–1932) to anatomy and to the establishment of neurosurgery have largely gone unrecognized, perhaps because he was educated and practiced in a French city other than Paris at a time when Paris was one of the chief centers of medicine in Europe. After completing a thesis describing an iliac artery anomaly and obtaining the distinguished agrégé teaching degree, Princeteau began his surgical career at the University of Bordeaux. Within 10 years, he became chef de clinique and one of the busiest surgeons in Saint-André Hospital, as well as head of the anatomy institute and professor of anatomy at the dental school. In 1891, he achieved the rank of surgeon. In the field of general anatomy, he was recognized for novel cadaveric preparations and vascular perfusion techniques. In the neurosciences, he made important contributions to the anatomy of the trigeminal nerve and trigeminal neuralgia. In 1898, Princeteau supervised a thesis that addressed contemporary surgical approaches to the trigeminal complex. In the course of this effort, he identified a bony prominence near the petrous apex (the retrogasserian tubercle) that helped to locate the gasserian ganglion. The surgical significance of the retrogasserian tubercle was quickly acknowledged in the European neurosurgical community and was noted in French textbooks of anatomy. Thierry de Martel, a founding member of the French neurosurgical School, named the tubercle after Princeteau. To the rest of the world, however, it remained almost unknown. [ABSTRACT FROM AUTHOR]

This retrospective study examined the clinical outcomes and complications in 6 cases of compound Meige's syndrome, presenting with blepharospasm and masticatory muscle spasm, following treatment with CT-guided radiofrequency ablation targeting bilateral facial nerves and mandibular branches of the trigeminal nerve. After the operation, the symptoms of eyelid spasm and masticatory muscle spasm resolved, but mild facial paralysis and numbness of mandibular nerve innervation persisted. Follow-up for 4–28 months showed that the symptoms of facial paralysis resolved within 2–5 (3.17 ± 0.94) months after the operation, whereas the numbness in the mandibular region persisted, accompanied by a decrease in masticatory function. During the follow-up period, none of the 6 patients experienced a recurrence of Meige's syndrome. These findings suggest that CT-guided radiofrequency ablation of the bilateral facial nerve and mandibular branches of the trigeminal nerve may offer a promising approach to treating compound Meige's syndrome. [ABSTRACT FROM AUTHOR]

One mechanism by which transcranial direct current stimulation (tDCS) has been proposed to improve attention is by transcutaneous stimulation of cranial nerves, thereby activating the locus coeruleus (LC). Specifically, placement of the electrodes over the frontal bone and mastoid is thought to facilitate current flow across the face as a path of least resistance. The face is innervated by the trigeminal nerve, and the trigeminal nerve is interconnected with the LC. In this study, we tested whether stimulating the trigeminal nerve impacts indices of LC activity and performance on a sustained attention task. We replicated previous research that shows deterioration in task performance, increases in the rate of task-unrelated thoughts, and reduced pupil responses due to time on task irrespective of tDCS condition (sham, anodal, and cathodal stimulation). Importantly, tDCS did not influence pupil dynamics (pretrial or stimulus-evoked), self-reported attention state, nor task performance in active versus sham stimulation conditions. The findings reported here are consistent with theories about arousal centered on a hypothesized link between LC activity indexed by pupil size, task performance, and self-reported attention state but fail to support hypotheses that tDCS over the trigeminal nerve influences indices of LC function. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine is closely related to the dysregulation of neurochemical substances in the brain, with metabolic imbalance being one of the proposed causes of chronic migraine. This study aims to evaluate the metabolic changes between energy metabolism and excitatory and inhibitory neurotransmitters in key brain regions of mice with chronic migraine-like state and to uncover the dysfunctional pathways of migraine. Methods: A chronic migraine-like state mouse model was established by repeated administration of nitroglycerin (NTG). We used von Frey filaments to assess the mechanical thresholds of the hind paw and periorbital in wild-type and familial hemiplegic migraine type 2 mice. After the experiments, tissue was collected from five brain regions: the somatosensory cortex (SSP), hippocampus, thalamus (TH), hypothalamus, and the spinal trigeminal nucleus caudalis (TNC). Proton magnetic resonance spectroscopy (1H-MRS) was employed to study the changes in brain metabolites associated with migraine, aiming to explore the mechanisms underlying metabolic imbalance in chronic migraine-like state. Results: In NTG-induced chronic migraine-like state model, we observed a significant reduction in energy metabolism during central sensitization, an increase in excitatory neurotransmitters such as glutamate, and a tendency for inhibitory neurotransmitters like GABA to decrease. The TNC and thalamus were the most affected regions. Furthermore, the consistency of N-acetylaspartate levels highlighted the importance of the TNC-TH-SSP pathway in the ascending nociceptive transmission of migraine. Conclusion: Abnormal energy metabolism and neurotransmitter imbalance in the brain region of NTG-induced chronic migraine-like state model are crucial mechanisms contributing to the chronicity of migraine. [ABSTRACT FROM AUTHOR]

Objective: Trigeminal schwannomas are rare benign tumors originating from the Schwann cells of the trigeminal nerve. Despite the common occurrence of trigeminal neuropathy in trigeminal schwannomas, a detailed analysis has not yet been performed because of the rarity of this disease. This study aimed to analyze trigeminal neuropathy in trigeminal schwannoma resection and identify the risk factors for postoperative worsening of trigeminal neuropathy. Methods: A retrospective analysis of 86 surgical cases was performed at our institution between 1975 and 2018. Obtained parameters included age, sex, diagnosis, reoperation, tumor size, tumor location, presence or absence of cysts, surgical approach, degree of tumor removal, and pre/postoperative trigeminal neuropathy. Uni- and multivariate analyses were performed to identify the risk factors for worsening postoperative sensory disturbances. Results: Of 83 patients, 58.1% had preoperative trigeminal neuropathy. Postoperative sensory disturbance occurred in 27.9%, with worsening in two cases and de novo symptoms in 22 cases. Regarding risk factors for worsening postoperative sensory disturbances, older age, smaller tumor size, middle and posterior (MP) type, gross total removal (GTR), and anterior transpetrosal approach were identified in the univariate analysis, while MP type and GTR were identified in the multivariate analysis. Conclusions: This study analyzed trigeminal neuropathy in trigeminal schwannomas in detail and identified tumor location and removal rate as risk factors for worsening postoperative sensory disturbances. Treatment strategies to reduce the risk of trigeminal neuropathy should be considered. [ABSTRACT FROM AUTHOR]

Background: This study aims to utilize the deep learning method of VB-Net to locate and segment the trigeminal nerve, and employ radiomics methods to distinguish between CTN patients and healthy individuals. Methods: A total of 165 CTN patients and 175 healthy controls, matched for gender and age, were recruited. All subjects underwent magnetic resonance scans. VB-Net was used to locate and segment the bilateral trigeminal nerve of all subjects, followed by the application of radiomics methods for feature extraction, dimensionality reduction, feature selection, model construction, and model evaluation. Results: On the test set for trigeminal nerve segmentation, our segmentation parameters are as follows: the mean Dice Similarity Coefficient (mDCS) is 0.74, the Average Symmetric Surface Distance (ASSD) is 0.64 mm, and the Hausdorff Distance (HD) is 3.34 mm, which are within the acceptable range. Analysis of CTN patients and healthy controls identified 12 features with larger weights, and there was a statistically significant difference in Rad_score between the two groups (p < 0.05). The Area Under the Curve (AUC) values for the three models (Gradient Boosting Decision Tree, Gaussian Process, and Random Forest) are 0.90, 0.87, and 0.86, respectively. After testing with DeLong and McNemar methods, these three models all exhibit good performance in distinguishing CTN from normal individuals. Conclusions: Radiomics can aid in the clinical diagnosis of CTN, and it is a more objective approach. It serves as a reliable neurobiological indicator for the clinical diagnosis of CTN and the assessment of changes in the trigeminal nerve in patients with CTN. [ABSTRACT FROM AUTHOR]

Background: The analgesia after lower third molar alveolectomy is based on the use of non-steroidal anti-inflammatory drugs (NSAIDs) that have significant risks, and are contraindicated in the third trimester of pregnancy. Aiming to reduce NSAIDs use after this surgery, we quantified analgesic effects of ultrasound (US)-guided extraoral mandibular nerve block. Methods: Thirty-six patients were equally allocated to the experimental or control group, based on their willingness to receive experimental US-guided extraoral mandibular nerve block for postoperative analgesia. The experimental block applied prior to lower third molar alveolectomy, was followed by standard intraoral inferior alveolar nerve block. In the control group, patients received only intraoral block of inferior alveolar nerve. All patients reported pain level (visual analogue scale, VAS) right after the application of blocks. The next day, patients reported duration of pain-free time and the use of analgesic. Results: The US-guided extraoral mandibular nerve block prolonged the pain-free time to 8 h (vs. 4 in control group, P < 0.001) and reduced NSAIDs use (12 patients needed analgesic in experimental vs. 17 patients in control group, P = 0.038). The application of experimental block was less painful (VAS = 2) than the application of intraoral inferior alveolar nerve block (VAS = 4, P = 0.011). In 8/18 patients in the experimental group US-guided extraoral mandibular nerve block solely achieved adequate surgical anesthesia. Conclusion: US-guided extraoral mandibular nerve block prolonged pain-free period and reduced the use of NSAIDs after lower third molar alveolectomy, thus proving to be successful analgesia method for this dental surgery. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT06009302, identification number: NCT06009302, date of registration: 18/08/2023. [ABSTRACT FROM AUTHOR]

Ganglioneuromas are rare tumors arising from retroperitoneal and posterior mediastinal sympathetic nerves. Intracranial trigeminal nerve ganglioneuromas are even more rare, with only seven cases reported to date. We present a case of a 65-year-old male with a right-sided throbbing headache type and blindness in his right eye. Magnetic resonance imaging revealed an ill-defined mass lesion in the middle-cranial fossa, with a few areas having a reduced apparent diffusion coefficient and multiple microhemorrhages. Piecemeal debulking of the tumor was achieved by performing a right-middle craniotomy via the pterionic and sub-temporal approach. The detected histological features matched those of a ganglioneuroma (maturing type) of the trigeminal nerve. [ABSTRACT FROM AUTHOR]

Trigeminal neuralgia (TN) due to venous compression is far less common than that due to arterial compression, and its pathogenesis is less clear. We investigated the clinical and imaging features of TN caused by solely venous compression by measuring the morphologies of the posterior cranial fossa (PCF) and the trigeminal nerve. We retrospectively reviewed records of TN patients who underwent microvascular decompression at our institution and extracted cases with solely arterial or solely venous compression. Preoperative magnetic resonance imaging was used to find the length (Y), width (X), height (Z), and volume (V) of the PCF, the angle between the trigeminal nerve and pons, and the distance between Meckel's cave and the root entry zone of the trigeminal nerve. Of 152 patients, 24 had TN caused solely by venous compression. The value of Y was significantly smaller in the venous group than the arterial group (P < 0.01). The trigeminal nerve and pons was significantly smaller in the venous group (P < 0.01). We hypothesized that TN patients with solely venous compression had a characteristic PCF morphology with a short anteroposterior diameter (Y), such that age-related changes in brain morphology could alter the course of the trigeminal nerve and cause compression by a vein. The morphological features of the PCF differed between patients with TN of venous and those with TN of arterial etiology. Age-related changes in brain morphology and changes of course of the trigeminal nerve may also add to the possibility of developing TN, especially of venous etiology. [ABSTRACT FROM AUTHOR]

Anterior petrosectomy (AP) is a commonly recognized approach for accessing tumors located in the petrous apex region. The essence of AP lies in drilling the petrous part of the temporal bone within the Kawase quadrangle. In our study, we conducted radiological and anatomical analyses of the structures within the petrous portion of the temporal bone, evaluating their impact on the surgical field during AP. We conducted an analysis of 15 anatomical specimens and 20 3D reconstructions based on computed tomography scans of the middle ear. The analyzed structures included the impression of the trigeminal nerve, the groove of the greater petrosal nerve, the arcuate eminence, and the angle between eminentia arcuata and grove for greater petrosal nerve. The mean surface area measured by radiological methods does not deviate significantly from the mean surface area measured by anatomical methods 276.265mm2 (interquartile range: 217.603–309.188) versus 233.21mm2 (interquartile range: 210.923–255.453) P = 0.051. We established a threshold 195,99mm2 for radiological determination of the surface area at which another approach should be considered. Additionally, we have developed corrections for specific radiological factors to enable a better assessment of anatomical conditions. Our results indicate that preoperative assessment of anatomical conditions based on 3D reconstructions of computed tomography of the middle ear can be a valuable tool in preoperative planning of surgery on tumors in the petroclival region using the AP. Further studies involving a larger sample size are necessary to validate the findings of our study. [ABSTRACT FROM AUTHOR]

A schwannoma is a nerve sheath tumor that is formed by Schwann cells. Vestibular schwannomas are thought to account for the majority of intracranial schwannomas. Nonvestibular schwannomas account for about 10%, about half of which are trigeminal schwannomas. Multiple intracranial schwannomas originating from different cranial nerves are extremely rare. We describe the clinical case of a 42-year-old female patient with vestibular schwannoma and multiple trigeminal schwannomas. That case shows how multiple trigeminal schwannomas were identified intraoperatively during elective surgery for vestibular schwannoma removal, most of which were resected. No new neurological deficits were observed in the patient. The presence of multiple intracranial schwannomas is extremely rare in neurosurgical practice and can change the intraoperative strategy and the course of the surgery. [ABSTRACT FROM AUTHOR]

Meckel's cave is a dural recess in the posteromedial portion of the middle cranial fossa, serving as a conduit for the trigeminal nerve and hosting various pathologies. The radiological diagnosis of Meckel's cave pathologies is often challenging, especially when they are atypical and rarely encountered. Here, we discuss the case of a 41-year-old woman who presented with right hemifacial pain, numbness, and binocular diplopia. Imaging features suggested a T2 hypointense, T1 hyperintense, and nonenhancing mass in the right Meckel's cave. Intraoperatively, an extra-axial black mass was observed, suggestive of melanoma, which was radically excised. Further postoperative workup and biopsy revealed it was a primary central nervous system (CNS) malignant melanoma, an exceedingly rare condition. Due to the rarity of the disease, a consensus regarding treatment regimens is lacking. This case report underscores the significance of considering uncommon diagnoses when faced with unusual radiological findings and emphasizes the importance of aggressive surgical resection and the evolving landscape of adjuvant treatments for primary CNS melanomas. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine. Background: Chronic migraine is a leading cause of disability, with higher rates in females. The role of central nervous system neurons and glia in migraine pathophysiology is not fully elucidated. Preclinical studies have shown abnormal glial activation in the trigeminal nucleus caudalis of male rodents. No current reports have investigated glial activation in both sexes in other important brain regions involved with the nociceptive and emotional processing of pain. Methods: The mouse nitroglycerin model of migraine was used, and nitroglycerin (10 mg/kg) or vehicle was administered every other day for 9 days. Prior to injections on days 1, 5, and 9, cephalic allodynia was determined by periorbital von Frey hair testing. Immunofluorescent staining of astrocyte marker, glial fibrillary protein (GFAP), and microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), in male and female trigeminal nucleus caudalis, periaqueductal gray, somatosensory cortex, and nucleus accumbens was completed. Results: Behavioral testing demonstrated increased cephalic allodynia in nitroglycerin‐ versus vehicle‐treated mice. An increase in the percent area covered by GFAP+ cells in the trigeminal nucleus caudalis and nucleus accumbens, but not the periaqueductal gray or somatosensory cortex, was observed in response to nitroglycerin. No significant differences were observed for Iba1 staining across brain regions. We did not detect significant sex differences in GFAP or Iba1 quantification. Conclusions: Immunohistochemical analysis suggests that, at the time point tested, immunoreactivity of GFAP+ astrocytes, but not Iba1+ microglia, changes in response to chronic migraine‐associated pain. Additionally, there do not appear to be significant differences between males and females in GFAP+ or Iba1+ cells across the four brain regions analyzed. Plain Language Summary: The aim of this study was to determine if supportive immune cells in the brains of males and females are altered in an animal model of chronic migraine. Mice in the chronic migraine group showed significant activation of astrocytes, but not microglia, in male and female mice in pain and emotion‐processing brain regions. These results suggest that some supportive cells in the brain may play a role in regulating chronic migraine. [ABSTRACT FROM AUTHOR]

Background: Trigeminal nerve injury following endodontic treatment, leading to unpleasant sensations or partial sensory loss in the face or oral mucosa, is uncommon but significant when it occurs. Objective: This study analysed the pharmacological management of trigeminal nerve injuries (TNI) in a university‐based hospital. Methods: We conducted a retrospective analysis of 47 patients who visited the Department of Orofacial Pain and Oral Medicine at Yonsei University Dental Hospital, Seoul, Korea, after TNI following endodontic procedures in primary clinics. Both objective tests and subjective evaluations, assessed the extent and duration of sensory injury during the initial visit. The patient's initial symptoms, presumed cause of TNI, referral delay (time interval between TNI and the first visit to our clinic), and medications were analysed to determine whether these factors affected the outcomes. Results: Most patients with TNI experienced dysesthesia with hypoesthesia (70.2%). The mandibular molars were predominantly affected (72.3%), with the inferior alveolar nerve (IAN), lingual nerve (LN), both IAN and LN, and maxillary nerve compromised in 83.0, 12.8, 2.1, and 2.1% of cases, respectively. Causes of TNI included local anaesthesia (29.8%), overfilling/over‐instrumentation (25.5%), endodontic surgery (17.0%), and unknown factors (27.7%). A shorter referral delay was associated with better outcomes, with an average delay of 8.6 weeks for symptom improvement compared with 44.1 weeks for no change. The medication regimens included steroids, NSAIDs, topical lidocaine, vitamin B complex, Adenosine Triphosphate (ATP), antiepileptics, antidepressants, and opioids administered alone or in combination, with a mean duration of 20.7 weeks. 53.2% of the patients reported improvement in their symptoms, 27.7% experienced no significant change, and 19.1% had unknown outcomes. Conclusions: Swift referral to an orofacial pain specialist is recommended for effective recovery in cases of TNI arising from endodontic treatment. [ABSTRACT FROM AUTHOR]

Statement of the Problem: Healing of the inferior alveolar nerve injury during dental procedures is one of the biggest concerns of dentists. There are still debates on different treatment modalities. Purpose: This study aimed to compare the effect of 940nm and 810nm diode lasers on the repair of the inferior alveolar sensory nerve. Materials and Method: In this single-blinded randomized clinical trial, 39 patients with inferior alveolar nerve injury were divided into three groups: 1. 810nm laser irradiated, 2. 940nm laser irradiated, and 3. No laser irradiation (control group). All patients were treated in 12 sessions (3 days per week) and evaluated using a complete clinical neurosensory test (CNT), including brushstroke, 2-point discrimination, pinprick nociception, and thermal discrimination before and after treatment. Results: The mean dysesthesia of the patient treated with 810nm diode laser was significantly lower than the control group in all sessions (the 1st (p= 0.003), 3rd (p=0.008), 7th (p= 0.006), and 12th sessions (p= 0.005)). The 810nm laser resulted in more satisfaction in patients than the control group in almost all sessions (1st (p< 0.001), 7th (p= 0.028), and 12th (p= 0.006)). More patient satisfaction was seen in the 1st and 3rd sessions in the 810nm laser than in the 980nm laser (p< 0.001 and p= 0.003, respectively). Conclusion: 810nm diode laser can be better than 940nm in repairing inferior alveolar sensory nerve damage. [ABSTRACT FROM AUTHOR]

This study provides an updated overview of the clinical characteristics of post-traumatic trigeminal neuropathic pain (PTNP) resulting from dental procedures or facial trauma, addressing its etiology, prevalence, evaluation, management, and prognosis. PTNP arises from injury to the trigeminal nerve, which governs sensory and motor functions in the maxillofacial region. The prevalence and characteristics of PTNP vary considerably across studies, with a reported prevalence ranging from 1.55% to 13%. The predominant causative factors are dental procedures, particularly third molar removal and implant placement. While gender distribution varies, a trend towards higher incidence in females is observed, particularly within the 40–60-year age group. Anatomically, the mandibular nerve is frequently involved. PTNP presents with a spectrum of symptoms ranging from tingling sensations to severe pain. Diagnostic challenges arise due to the lack of standardized criteria and potential overlap with focal neuralgia, necessitating comprehensive evaluation. Misdiagnosis can lead to prolonged patient suffering and unnecessary interventions. Successful management hinges on prompt diagnosis and interdisciplinary collaboration, with early intervention crucial in mitigating progression to chronic pain. Although nerve recovery post-trauma is challenging, preventive measures through accurate evaluation and treatment are paramount. Management strategies for PTNP include non-invasive and surgical interventions, with non-invasive approaches encompassing systemic and local pharmacological management. This narrative review aims to enhance uniformity in PTNP evaluation and treatment approaches, ultimately improving patient care and outcomes. [ABSTRACT FROM AUTHOR]

Currently, several techniques are used in the posterior mandible to increase alveolar bone height and width. However, each has potential complications and limitations. The purpose of the current study was to present the surgical technique and restorative considerations for implant placement lateral to the inferior alveolar nerve (IAN) in cases of severely atrophic edentulous posterior mandibles. In total, 26 implants were successfully placed lateral to the IAN in 16 patients and restored with splinted screw-retained prostheses. The postloading follow-up time ranged between 3 months and 6 years. Two patients reported complications: One patient had a temporary paresthesia that resolved 3 months after implant placement, and the second patient had minor paresthesia that was reduced after implant removal but remained in a small area on the left corner of her lip. [ABSTRACT FROM AUTHOR]

Background: Cranial neuropathy is a principal disease manifestation of neurosarcoidosis, but many forms remain poorly described, including trigeminal nerve disease despite its frequency in reported cohorts (5–12%). Herein, we characterize the clinical course of patients with neurosarcoidosis involving the trigeminal nerve. Methods: A single-center retrospective cohort analysis of patients with biopsy-proven sarcoidosis involving the trigeminal nerve was conducted between 1/1/2000-3/7/2023. Results: The trigeminal nerve was affected in 14/245 (5.7%) patients, being clinically symptomatic in 5/245 (2.0%) and asymptomatic with radiographic involvement in 9/245 (3.7%). 14/14 (100.0%) patients had systemic sarcoidosis. In the symptomatic group, trigeminal neuropathy was an inaugural feature in 4/5 (80.0%), unilateral in 5/5 (100.0%) with the V1 subdivision most affected (4/5, 80.0%), and associated with neuralgia in 2/5 (40.0%). On MRI, the cisternal nerve roots (9/14, 64.3%), Meckel's cave (7/14, 50.0%), and cavernous sinus (5/14, 35.7%) were most commonly affected, and 14/14 (100.0%) patients had extra-trigeminal neuroinflammation on cranial MRI. CSF was abnormal in at least one dimension in 11/12 (91.7%) tested. All three treated patients with symptomatic trigeminal neuropathy responded to immunomodulatory treatment, and symptomatic treatments for trigeminal neuralgia were helpful in two patients. After a median follow-up period of 63 months, the median modified Rankin scale score was 1 for both subgroups. Conclusion: Neurosarcoidosis may involve any portion of the trigeminal apparatus, and when affected, it frequently demonstrates a mismatch in radiographic involvement from its clinical manifestations of facial numbness and pain, and typically occurs in association with other clinical or radiographic manifestations of neurosarcoidosis. [ABSTRACT FROM AUTHOR]

Introduction: Conditioned pain modulation (CPM) is a quantitative estimation of the capacity for endogenous pain modulation. Reduced CPM enables chronic painful event development or exacerbates pre-existing pain symptoms. Emerging reports indicate that patients with trigeminal neuralgia (TN) have dysregulated endogenous pain modulation. Transauricular vagus nerve stimulation (taVNS) is known to alleviate both acute and chronic pain symptoms. Its role in modulation or management of TN remains unknown. Here, we evaluated the taVNS efficacy in modulating CPM among TN patients. Conclusions from this investigation may facilitate establishment of novel non-invasive adjunctive approaches to treating TN patients. Methods: All research work was conducted at the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital). In all, we recruited 62 study participants, 31 TN patients and 31 healthy volunteers, for a 2-day experimental test. At the beginning of the experiment (Day 1), all subjects received 30 min of active taVNS. On Day 2, they received sham taVNS with the same duration and intensity. Meanwhile, technicians documented participant pressure pain thresholds (PPT) and CPM values at baseline, and at 15 and 30 min post-active or sham taVNS. Results: A 30-min active taVNS exposure substantially elevated the PPT and CPM effect (P < 0.05) among TN patients, and we also observed a notable rise in the PPT and CPM effect (P < 0.05) among healthy controls. Additionally, there were no serious adverse events from the administered treatment. Conclusion: Exposure to 30 min of active taVNS strongly augmented the CPM effect and elevated the PPT among TN patients and healthy controls. These effects were not observed with sham stimulation. Despite the limitations inherent to survey studies, such as duration and compliance biases, we consider that taVNS is a promising, safe, and cost-effective therapy. In future investigations, we recommend assessment of long-term taVNS application and its effects on CPM and clinical pain. Trial Registration: ChiCTR2300078673 (www.Chictr.org.cn). [ABSTRACT FROM AUTHOR]

Short-lasting unilateral neuralgiform headache attacks is a rare type of primary headache， which is usually accompanied by ipsilateral conjunctival congestion and （or） lacrimation and other autonomic symptoms during episodes， and generally presents a chronic course. Most patients repeatedly seek medical attention due to ineffective diagnosis and treatment， causing great suffering and severely affecting their quality of life. Currently， in clinical practice， short-lasting unilateral neuralgiform headache attacks has not been sufficiently recognized. Due to its rarity， there is a lack of related research in China， hence there is an urgent need to improve clinicians'awareness and diagnostic and treatment level to reduce the rate of misdiagnosis. This article reviews the research progress in the epidemiology， pathophysiological mechanisms， clinical characteristics， diagnosis and treatment of short-lasting unilateral neuralgiform headache attacks， aiming to provide a more comprehensive reference for clinicians， thereby improving the effective diagnosis and treatment rate， helping patients to get rid of pain as soon as possible， and improving the quality of life. At the same time， it also calls for researchers at home and abroad to increase their research efforts on short-lasting unilateral neuralgiform headache attacks to provide more theoretical basis for clinical treatment.

Abstract Background We present a case of a 29-year-old male patient without immunodeficiency who suffered from rapid osteonecrosis and tooth exfoliation resulting from herpes zoster (HZ) infection in the left maxillary branch of the trigeminal nerve. Various complications associated with shingles infections have been reported, cases of osteonecrosis and tooth exfoliation due to HZ infection among young people without immunodeficiency are rare. In this case, we focus on the particular manifestation of HZ infection. Case presentation The patient presented with clusters of erythema and papules, along with non-hemorrhagic blisters on the left face and the loss of the left upper incisor. All lesions were localized to the left side of the face without exceeding the midline. After receiving antibacterial and antiviral treatment, successful control over the infection was achieved; however, he experienced the loss of all upper teeth on the left side except for the first and second upper left molars. Conclusion This case highlights that rapid osteonecrosis and tooth exfoliation may occur among young individuals without immunodeficiency after HZ infection. HZ infection of the face should be taken very seriously to obtain prompt treatment to prevent the rare complications of bone necrosis and tooth loss as much as possible.

Background: Percutaneous balloon compression (PBC) is an effective, low-cost, and simple treatment for primary trigeminal neuralgia (TN). However, PBC has poor efficacy and no better solution for the third branch (V3) of TN. Methods: Clinical data of 52 patients with trigeminal neuralgia treated with PBC were retrospectively analyzed. Postoperative numbness of the patient was evaluated by facial numbness at the Barrow Neurological Institute (BNI-N). The main observation was the incidence of higher numbness in the V3 than in the other two branches or equally strong numbness in the three branches in the immediate postoperative period. Results: The efficacy values in the pear-shaped balloon group at the first postoperative day (T1), the first month (T2), in the third month (T3), and the sixth month (T4) were 96.7%, 93.3%, 93.3%, and 90%, respectively, and 1 patient (3.3%) had recurrence. The efficacy value for the extracapsular capsule group was 95.5% at all times and there were no patients with recurrence within 6 months after surgery. In the immediate postoperative period, the effective compression rate of V3 in the pear-shaped balloon group was 43.3%, and 86.4% in the extracapsular capsule group (P = 0.020). At six months of follow-up, the effective compression rate of V3 was higher in the extracapsular capsule group than in the pear-shaped balloon group. Conclusions: The riveted structure of the extracapsular capsule can effectively compress V3, thus performing PBC with a balloon shaped as an extracapsular capsule is a new, effective, and safe treatment option for TN V3. Trial registration: ClinicalTrials.gov ChiCTR2300067313. [ABSTRACT FROM AUTHOR]

Background: Orally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance. Methods: We examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research. Results: We showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations. Conclusions: The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients. [ABSTRACT FROM AUTHOR]

Objective:Meige syndrome (MS) is an adult-onset segmental dystonia for which no satisfactory remedy currently exists. Our team developed a novel surgical approach called bilateral trigeminal/facial nerve combing (BTFC). This study aimed to evaluate the outcomes of patients who underwent BFTC (Clinical Trial Registry Number: ChiCTR2000033481). Method: We assigned 22 patients with MS to undergo BTFC. The primary outcome was assessed using the movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M) at 12 months postoperatively. The second outcome was evaluated using the Medical Outcome Study (MOS) 36-item Short Form Health Survey (SF-36), the dysfunction subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-D), and the sub-item scores of the BFMDRS-M. Safety outcomes included the House-Brackmann (HB) functional grading score and the visual analog scale (VAS) for facial numbness. Results: At the final follow-up at 12 months, the BFMDRS-M showed a mean improvement of 70.7% frombaseline. Mean scores of the BFMDRS-M sub-motor (including the eyes, mouth, and speech/swallowing) improved by 65.6, 81.00, and 60%, respectively. The median score of the total BFMDRS-D score was 0.70 ± 1.17 compared with 1.86 ± 2.21 at baseline. There were no serious operative complications in this population. The quality of life of the patients significantly improved (P < 0.05). Conclusion: BFTC has proven to be effective in relieving the symptoms of Meige syndrome. This novel surgical approach offers a new alternative treatment for patients who have failed to respond to medications, botulinum toxin injections, and deep brain stimulation (DBS). [ABSTRACT FROM AUTHOR]

AbstractAimMethodsResultsConclusionA case of Eustachian tube dysfunction following percutaneous balloon compression (PBC) of the trigeminal ganglion led us to investigate aural complications of PBC and similar procedures. We aimed to clarify both the physiological effects of compression of the trigeminal ganglion on aural function and the possibility of puncture of the Eustachian tube during placement of the needle.We reviewed the anatomy of the Eustachian tube in relation to the foramen ovale and the aural structures supplied by the trigeminal nerve through cadaveric study. Following CT scanning, neuronavigation was used to guide a needle into Meckel’s cave of a cadaver. Dissection was subsequently carried out with the needle in-situ to assess the proximity of the needle to the Eustachian tube and other structures. A literature review of aural complications of foramen ovale procedures using Ovid Medline, PubMed, and Google Scholar databases was undertaken.Our literature review summarises the relationship of the Eustachian tube to the foramen ovale, the nerve supply of aural structures from the trigeminal nerve and examines previously reported post-operative aural complications. From our anatomical study, at its closest point, the needle was 7 mm from the Eustachian tube.The trigeminal nerve supplies both the tensor tympani and tensor veli palatini muscles and percutaneous procedures may, therefore, lead to aural symptoms. Also, the path of the needle is close to the Eustachian tube and can be punctured during these procedures. The authors recommend discussing aural complications during consent for these procedures. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMaterials and methodsResultsConclusionsTrigeminal neuralgia is a very painful condition that may require a surgical approach as treatment, which is typically retrosigmoid craniotomy followed by microvascular decompression. Due to the limited margin for error when operating in the small triangular window of the cerebellopontine angle and the infrequency of this condition, the operating room can present a difficult learning environment for surgical trainees. Our aim is to create a synthetic, low-cost, high-fidelity, and largely reusable simulation model that will enable neurosurgical trainees to practice these procedural steps in a safe learning environment.Design-based research was employed to develop the model through iterative micro-cycles, with expert evaluation from an educational and clinical team. The model was made from easy to source materials without advanced technology where sustainability, reproduction at scale and cost where significant considerations.Our model effectively simulates a retrosigmoid craniotomy and microvascular decompression of the trigeminal nerve. The model consists of two distinct parts that are made of synthetic materials. Part A is a single-use, moulded portion of the skull, while part B depicts the cerebellopontine angle and some of its internal anatomical and pathological structures crucial to carrying out all the steps to this procedure. Part A sits ergonomically flush on top of Part B, with both parts subsequently clamped to the table.As a proof of concept, we report the development and utilisation of a novel, low-cost, replicable retrosigmoid craniotomy and microvascular decompression of the trigeminal nerve simulation model. [ABSTRACT FROM AUTHOR]

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI‐ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI‐ION. Inhibition of Panx3 in the TG of CCI‐ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI‐ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS‐P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain. [ABSTRACT FROM AUTHOR]

Recently developed optogenetic technology, which allows high‐fidelity control of neuronal activity, has been applied to investigate the neural circuits underlying sensory processing and behavior. The nasal cavity is innervated by the olfactory nerve and trigeminal nerve, which are closely related to common symptoms of rhinitis, such as impairment of smell, itching, and sneezing. The olfactory system has an amazing ability to distinguish thousands of odorant molecules at trace levels. However, there are many issues in olfactory sensing mechanisms that need to be addressed. Optogenetics offers a novel technical approach to solve this dilemma. Therefore, we review the recent advances in olfactory optogenetics to clarify the mechanisms of chemical sensing, which may help identify the mechanism of dysfunction and suggest possible treatments for impaired smell. Additionally, in rhinitis patients, alterations in the other nerve (trigeminal nerve) that innervates the nasal cavity can lead to hyperresponsiveness to various nociceptive stimuli and central sensitization, causing frequent and persistent itching and sneezing. In the last several years, the application of optogenetics in regulating nociceptive receptors, which are distributed in sensory nerve endings, and amino acid receptors, which are distributed in vital brain regions, to alleviate overreaction to nociceptive stimuli, has gained significant attention. Therefore, we focus on the progress in optogenetics and its application in neuromodulation of nociceptive stimuli and discuss the potential clinical translation for treating rhinitis in the future. [ABSTRACT FROM AUTHOR]

Objective Exploring the relationship between pain recurrence after percutaneous radiofrequency thermocoagulation and the degree of trigeminal nerve atrophy and pontine angle in patients with primary trigeminal neuralgia (INT). Methods A retrospective analysis was conducted on 297 patients with INT admitted to Qingdao Haici Hospital Affiliated to Qingdao University (Qingdao Traditional Chinese Medicine Hospital) from January 2020 to December 2021. All patients received percutaneous radiofrequency thermocoagulation surgery in our hospital. They were followed up for 24 months, during which 56 patients experienced pain recurrence after surgery (recurrence group), while 241 patients did not experience postoperative pain recurrence (non-recurrence group). Results The length of the trigeminal nerve root, degree of trigeminal nerve atrophy, and the combined application of the two were used to draw ROC curves. The AUC values predicted for pain recurrence in INT patients after percutaneous radiofrequency thermocoagulation were 0.553, 0.750, and 0.861, respectively. The results of the logistic regression model showed that shortened trigeminal nerve root length (OR = 0.624, P = 0.038), increased degree of trigeminal nerve atrophy (OR = 2.257, P = 0.000), multi vessel compression (OR = 1.842, P = 0.019), and severe baseline pain (OR = 1.714, P = 0.000) were independent risk factors for pain recurrence in INT patients after percutaneous radiofrequency thermocoagulation (P < 0.05). Conclusions INT patients undergo thin-layer MRI scans before surgery, and the degree of trigeminal nerve atrophy has a higher predictive value for pain recurrence after radiofrequency thermocoagulation. The length of trigeminal nerve roots and degree of trigeminal nerve atrophy are correlated with postoperative pain recurrence in patients. [ABSTRACT FROM AUTHOR]