Lower Cranial Nerve Palsy due to Prevertebral Tuberculosis Infection

Prevertebral tuberculosis is a rare infectious disease that often affects immunocompromised patients in developing countries. We present the case of a patient who complained of headache, dysarthria, and dysphagia. Neurological examination revealed multiple cranial nerve palsies, including the hypoglossal, glossopharyngeal, and vagus nerves. Brain magnetic resonance imaging demonstrated an infiltrative lesion in the prevertebral space, and the biopsy revealed chronic inflammation. On suspicion of immune-mediated inflammation, the patient was treated with intravenous dexamethasone and oral prednisolone, with minimal response. Eleven months after the initial diagnosis, the patient’s neurological symptoms were aggravated, and we detected newly developed pulmonary tuberculosis. After the treatment of pulmonary tuberculosis, his neurological symptoms improved, and the imaging study demonstrated improvements. Although we lacked positive laboratory or biopsy results for tuberculosis, we suspect that the lesions were distant tuberculosis infections. Tuberculosis should be considered in patients with unknown infiltrative mass-like lesions in the prevertebral spaces.

Self-Administration of Right Vagus Nerve Stimulation Activates Midbrain Dopaminergic Nuclei

Background: Left cervical vagus nerve stimulation (l-VNS) is an FDA-approved treatment for neurological disorders including epilepsy, major depressive disorder, and stroke, and l-VNS is increasingly under investigation for a range of other neurological indications. Traditional l-VNS is thought to induce therapeutic neuroplasticity in part through the coordinated activation of multiple broadly projecting neuromodulatory systems in the brain. Recently, it has been reported that striking lateralization exists in the anatomical and functional connectivity between the vagus nerves and the dopaminergic midbrain. These emerging findings suggest that VNS-driven activation of this important plasticity-promoting neuromodulatory system may be preferentially driven by targeting the right, rather than the left, cervical nerve.Objective: To compare the effects of right cervical VNS (r-VNS) vs. traditional l-VNS on self-administration behavior and midbrain dopaminergic activation in rats.Methods: Rats were implanted with a stimulating cuff electrode targeting either the right or left cervical vagus nerve. After surgical recovery, rats underwent a VNS self-administration assay in which lever pressing was paired with r-VNS or l-VNS delivery. Self-administration was followed by extinction, cue-only reinstatement, and stimulation reinstatement sessions. Rats were sacrificed 90 min after completion of behavioral training, and brains were removed for immunohistochemical analysis of c-Fos expression in the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as well as in the noradrenergic locus coeruleus (LC).Results: Rats in the r-VNS cohort performed significantly more lever presses throughout self-administration and reinstatement sessions than did rats in the l-VNS cohort. Moreover, this appetitive behavioral responding was associated with significantly greater c-Fos expression among neuronal populations within the VTA, SNc, and LC. Differential c-Fos expression following r-VNS vs. l-VNS was particularly prominent within dopaminergic midbrain neurons.Conclusion: Our results support the existence of strong lateralization within vagal-mesencephalic signaling pathways, and suggest that VNS targeted to the right, rather than left, cervical nerve preferentially activates the midbrain dopaminergic system. These findings raise the possibility that r-VNS could provide a promising strategy for enhancing dopamine-dependent neuroplasticity, opening broad avenues for future research into the efficacy and safety of r-VNS in the treatment of neurological disease.

Oral-Gut-Brain Axis in Experimental Models of Periodontitis: Associating Gut Dysbiosis With Neurodegenerative Diseases

Periodontitis is considered a non-communicable chronic disease caused by a dysbiotic microbiota, which generates a low-grade systemic inflammation that chronically damages the organism. Several studies have associated periodontitis with other chronic non-communicable diseases, such as cardiovascular or neurodegenerative diseases. Besides, the oral bacteria considered a keystone pathogen, Porphyromonas gingivalis, has been detected in the hippocampus and brain cortex. Likewise, gut microbiota dysbiosis triggers a low-grade systemic inflammation, which also favors the risk for both cardiovascular and neurodegenerative diseases. Recently, the existence of an axis of Oral-Gut communication has been proposed, whose possible involvement in the development of neurodegenerative diseases has not been uncovered yet. The present review aims to compile evidence that the dysbiosis of the oral microbiota triggers changes in the gut microbiota, which creates a higher predisposition for the development of neuroinflammatory or neurodegenerative diseases.The Oral-Gut-Brain axis could be defined based on anatomical communications, where the mouth and the intestine are in constant communication. The oral-brain axis is mainly established from the trigeminal nerve and the gut-brain axis from the vagus nerve. The oral-gut communication is defined from an anatomical relation and the constant swallowing of oral bacteria. The gut-brain communication is more complex and due to bacteria-cells, immune and nervous system interactions. Thus, the gut-brain and oral-brain axis are in a bi-directional relationship. Through the qualitative analysis of the selected papers, we conclude that experimental periodontitis could produce both neurodegenerative pathologies and intestinal dysbiosis, and that periodontitis is likely to induce both conditions simultaneously. The severity of the neurodegenerative disease could depend, at least in part, on the effects of periodontitis in the gut microbiota, which could strengthen the immune response and create an injurious inflammatory and dysbiotic cycle. Thus, dementias would have their onset in dysbiotic phenomena that affect the oral cavity or the intestine. The selected studies allow us to speculate that oral-gut-brain communication exists, and bacteria probably get to the brain via trigeminal and vagus nerves.

Human organ donor-derived vagus nerve biopsies allow for well-preserved ultrastructure and high-resolution mapping of myelinated and unmyelinated fibers

The vagus nerve provides motor, sensory, and autonomic innervation of multiple organs, and electrical vagus nerve stimulation (VNS) provides an adjunctive treatment option for e.g. medication-refractory epilepsy and treatment-resistant depression. The mechanisms of action for VNS are not known, and high-resolution anatomical mapping of the human vagus nerve is needed to better understand its functional organization. Electron microscopy (EM) is required for the detection of both myelinated and unmyelinated axons, but access to well-preserved human vagus nerves for ultrastructural studies is sparse. Intact human vagus nerve samples were procured intra-operatively from deceased organ donors, and tissues were immediately immersion fixed and processed for EM. Ultrastructural studies of cervical and sub-diaphragmatic vagus nerve segments showed excellent preservation of the lamellated wall of myelin sheaths, and the axolemma of myelinated and unmyelinated fibers were intact. Microtubules, neurofilaments, and mitochondria were readily identified in the axoplasm, and the ultrastructural integrity of Schwann cell nuclei, Remak bundles, and basal lamina was also well preserved. Digital segmentation of myelinated and unmyelinated axons allowed for determination of fiber size and myelination. We propose a novel source of human vagus nerve tissues for detailed ultrastructural studies and mapping to support efforts to refine neuromodulation strategies, including VNS.

Fascicles split or merge every ~560 microns within the human cervical vagus nerve

Vagus nerve stimulation (VNS) is FDA approved for stroke rehabilitation, epilepsy and depression; however, the underlying vagus functional anatomy underlying the implant is poorly understood. We used microCT to quantify fascicular structure and neuroanatomy within human cervical vagus nerves. Fascicles split or merged every ~560 μm (17.8 ± 6.1 events/cm). The high degree of splitting and merging of fascicles in humans may explain the clinical heterogeneity in patient responses.

Experience of tracheo-bronchoplastic surgery for lung cancer

Introduction. Currently, surgical treatment of lung cancer is impossible without the use of tracheobronchoplastic operations, which in advanced specialized clinics take up to 5-10% of all radical operations. Material and methods. We conducted a retrospective study including 21 patients with centrally located lung cancer who underwent 22 tracheobronchoplastic radical operations between 2000 and 2021. The operated patients included 18 men and 3 women aged 42 to 67 years (mean age 54.5 ± 12.5 years). The morphological structure of the tumors was represented by carcinoid (2) and squamous cell carcinoma (19). The pathological process was located in the right lung in 16 patients and in the left lung — in five patients. Comorbid status was present in 20 patients. Standard lateral thoracotomy was used in 18 cases, and video-assisted minithoracotomy — in three cases. Extended lymphodissection up to D2 was performed in all surgeries. Combined surgeries included resection of adjacent organs: pericardium (2), unpaired vein (2), superior vena cava (1), diaphragmatic and vagus nerves (1), pleura (1). Results. The average duration of operations was 242.3 minutes (125-345 minutes), the average blood loss was 283.2 ml (50–1000 ml). Complications developed in 5 (22.7%) patients. Mortality was observed in 2 (9.1%) cases. Conclusion. The use of tracheobronchoplastic operations significantly expands the possibilities of thoracic surgery in treatment of lung cancer both due to technical resectability of the tumor at the transition to the main bronchus and trachea and due to functional operability at low respiratory functions and impossibility to perform pneumonectomy.

Computational modelling of nerve stimulation and recording with peripheral visceral neural interfaces

Objective: Neuromodulation of visceral nerves is being intensively studied for treating a wide range of conditions, but effective translation requires increasing the efficacy and predictability of neural interface performance. Here we use computational models of rat visceral nerve to predict how neuroanatomical variability could affect both electrical stimulation and recording with an experimental planar neural interface. Approach: We developed a hybrid computational pipeline, Visceral Nerve Ensemble Recording & Stimulation (ViNERS), to couple finite-element modelling of extracellular electrical fields with biophysical simulations of individual axons. Anatomical properties of fascicles and axons in rat pelvic and vagus nerves were measured or obtained from public datasets. To validate ViNERS, we simulated pelvic nerve stimulation and recording with an experimental four-electrode planar array. Main results: Axon diameters measured from pelvic nerve were used to model a population of myelinated and unmyelinated axons and simulate recordings of electrically evoked single-unit field potentials (SUFPs). Across visceral nerve fascicles of increasing size, our simulations predicted an increase in stimulation threshold and a decrease in SUFP amplitude. Simulated threshold changes were dominated by changes in perineurium thickness, which correlates with fascicle diameter. We also demonstrated that ViNERS could simulate recordings of electrically-evoked compound action potentials (ECAPs) that were qualitatively similar to pelvic nerve recording made with the array used for simulation. Significance: We introduce ViNERS as a new open-source computational tool for modelling large-scale stimulation and recording from visceral nerves. ViNERS predicts how neuroanatomical variation in rat pelvic nerve affects stimulation and recording with an experimental planar electrode array. We show ViNERS can simulate ECAPS that capture features of our recordings, but our results suggest the underlying NEURON models need to be further refined and specifically adapted to accurately simulate visceral nerve axons.

Ultrasound imaging of vagus nerves in patients with Parkinson's disease

Parkinson’s disease (PD) is a neurodegenerative multisystem disorder characterized by pathologic α-synuclein aggregation affecting, among other things, vagal fibers. The aim of this study was to investigate the cross-sectional area (CSA) of the vagus nerve (VN) in patients with PD using ultrasound imaging. The study was conducted in 32 patients with PD (15 men and 17 women; mean age 58 ± 10 years) and 32 healthy controls comparable with the main group in terms of sex and age. All study participants underwent ultrasound examination of the VN using a high-resolution transducer. Left VN CSA was significantly smaller in patients with PD than in the control group (1.78 ± 0.52 mm2 vs 2.11 ± 0.41 mm2; р = 0.007). A similar result was obtained for right VN CSA at the trend level. ROC analysis demonstrated that the threshold CSA value of < 2.10 mm2 for the left VN has low diagnostic sensivity (59%) for VN atrophy in patients with PD. Right VN CSA was significantly larger than left VN CSA in both groups (p < 0.001). The analysis of the PD group did not reveal any associations between VN CSA and age, duration and stage of the disease, motor (UPDRS III) and non-motor (NMSQ) scores. Patients with akinetic-rigid form of PD had smaller left VN CSA than patients with the mixed form of the disease (р < 0.05). A moderate inverse correlation was established between left VN CSA and the area of substantia nigra hyperechogenicity on both sides (р < 0.04); for the right VN a similar correlation was established at the trend level. High-resolution ultrasound of patients with PD demonstrated atrophy of the VN and the association of VN CSA with the clinical form of the disease and the ultrasound features of the substantia nigra.

Microbiomics in Collusion with the Nervous System in Carcinogenesis: Diagnosis, Pathogenesis and Treatment

The influence of the naturally occurring population of microbes on various human diseases has been a topic of much recent interest. Not surprisingly, continuously growing attention is devoted to the existence of a gut brain axis, where the microbiota present in the gut can affect the nervous system through the release of metabolites, stimulation of the immune system, changing the permeability of the blood–brain barrier or activating the vagus nerves. Many of the methods that stimulate the nervous system can also lead to the development of cancer by manipulating pathways associated with the hallmarks of cancer. Moreover, neurogenesis or the creation of new nervous tissue, is associated with the development and progression of cancer in a similar manner as the blood and lymphatic systems. Finally, microbes can secrete neurotransmitters, which can stimulate cancer growth and development. In this review we discuss the latest evidence that support the importance of microbiota and peripheral nerves in cancer development and dissemination.

Vector 3D Reconstruction of the Nerves of the Ventral Region of the Neck from Anatomical Sections of Korean Visible Human at the Laboratory of Digital Anatomy of Paris Descartes

Objective: To carry out a 3D vector reconstruction of the nerves of the ventral region of the neck from anatomical sections of the “Korean Visible Human” for educational purposes. Materials and Methods: The anatomical subject was a 33-year-old Korean man who died of leukemia. He was 164cm tall and weighed 55kgs. A cryomacrotome sectioned the frozen body into 5960 sections. Sections numbered 1500 to 2000 were used for this study. A segmentation by manual contouring of each nervous anatomical element of the ventral region of the neck was done using Winsurf version 3.5 software on a laptop PC running Windows 10 equipped with an 8 gigabyte RAM. Results: Our vector 3D model of nerves in the ventral neck region includes the brachial plexuses, vagus nerves, inferior and superior laryngeal nerves, glossopharyngeal nerves, hypoglossal nerves and spinal nerves. This vector model has been integrated into the Diva3d virtual dissection table. It was also uploaded to the Sketchfab website and 3D printed using an ENDER 3 printer. Conclusion: Our 3D reconstruction of the nerves of the ventral region of the neck is an educational tool for learning the nerves of the ventral region of the neck and can also serve as a 3D atlas for simulation purposes for training in therapeutic gestures.