Meckel Cave: An Anatomical Study Using Magnetic Resonance Imaging.

OBJECTIVE: To our knowledge, few studies have investigated anatomy of the Meckel cave with neuroimaging modalities. The present study aimed to characterize it using magnetic resonance imaging (MRI). PATIENTS AND METHODS: Following conventional MRI examination, a total of 101 patients underwent T2-weighted imaging in thin-sliced coronal and sagittal sections, and 11 patients underwent constructive interference steady-state sequences in thin-sliced sagittal sections. Moreover, 3 injected cadaver heads were dissected. RESULTS: In the cadaver specimens, the size and extent of the cerebrospinal fluid-filled space between the Gasserian ganglion and surrounding arachnoids were difficult to define. On the T2-weighted imaging, the Meckel cave was delineated with variable morphologies and left-right asymmetry. On the sagittal images, the shape of the Meckel cave could be classified into 3 different types, bulbous, oval, and flat, with the oval being the most frequent that comprised 60%. Furthermore, on the sagittal constructive interference steady-state images, parts of the trigeminal nerve distributed in the Meckel cave were delineated in all patients. The ophthalmic, maxillary, and mandibular divisions were clearly distinguished on both sides. CONCLUSIONS: The Meckel cave is a structure characterized by diverse morphologies and left-right asymmetry. Thin-sliced T2-weighted imaging is useful for exploring the anatomy of the Meckel cave.

Meckel's Cave and Somatotopy of the Trigeminal Ganglion.

BACKGROUND: The anatomy and spatial relationships of the dural sac comprising the Meckel cave (MC) and its ensheathed trigeminal ganglion (TG) are exceedingly intricate and complex. There are conflicting accounts in the literature regarding the dural configuration of the MC around the ganglion and the dual embryology of the MC and TG is still unclear. METHODS: A combined systematic and narrative literature review was conducted to collate articles addressing MC and TG anatomy, in addition to their embryology, role in tumor spread, somatotopy, and association with trigeminal neuralgia. RESULTS: Three key anatomic models by Paturet (1964), Lazorthes (1973), and Lang and Ferner (1983) have been put forward to show the arrangement of the MC around the TG. The TG is formed from both neural crest and placodal cells and drags the enveloping dura caudally to form the MC prolongation during development. Both a mediolateral and dorsoventral somatotopic arrangement of neurons exists in the TG, which corresponds to the 3 nerve divisions, of which V2 and V3 are prone to perineural tumor spread along their course. CONCLUSIONS: Sound knowledge concerning the dural arrangement of the MC and the trigeminal divisions will be invaluable in optimally treating cancers in this region, and understanding TG somatotopy will immensely improve treatment of trigeminal neuralgia in terms of specificity, efficacy, and positive patient outcomes.

Comparative Anatomy of the Mammalian Corneal Subbasal Nerve Plexus.

Purpose: The subbasal nerve plexus (SNP) is the densest and most recognizable component of the mammalian corneal innervation; however, the anatomical configuration of the SNP in most animal models remains incompletely described. The purpose of the current study is to describe in detail the SNP architecture in eight different mammals, including several popular animal models used in cornea research. Methods: Corneal nerves in mouse, rat, guinea pig, rabbit, dog, macaque, domestic pig, and cow eyes were stained immunohistochemically with antiserum directed against neurotubulin. SNP architecture was documented by digital photomicrography and large-scale reconstructions, that is, corneal nerve maps, using a drawing tube attached to a light microscope. Results: Subbasal nerve fibers (SNFs) in mice, rats, guinea pigs, dogs, and macaques radiated centrally from the corneoscleral limbus toward the corneal apex in a whorl-like or spiraling pattern. SNFs in rabbit and bovine corneas swept horizontally across the ocular surface in a temporal-to-nasal direction and converged on the inferonasal limbus without forming a spiral. SNFs in the pig cornea radiated centrifugally in all directions, like a starburst, from a focal point located equidistant between the corneal apex and the superior pole. Conclusions: The results of the present study have demonstrated for the first time substantial interspecies differences in the architectural organization of the mammalian SNP. The physiological significance of these different patterns and the mechanisms that regulate SNP pattern formation in the mammalian cornea remain incompletely understood and warrant additional investigation.

Visualization of Trigeminal Ganglion Neuronal Activities in Mice.

Visualization of dynamic cellular activity has greatly expanded our understanding of brain function. Recently, there has been an increasing number of studies imaging rodent brain activity in real time. However, traditional in vivo calcium imaging technology has been limited to superficial brain structures. Because the trigeminal ganglion (TG) is located deep within the cranial cavity of mice, few studies have been able to access to it. To circumvent this limitation, overlying brain tissue must be removed to expose the TG so that optical recording can access deep brain neural ensembles. This unit describes a procedure for conducting non-survival surgery to visualize the TG in live mice. Obtaining large ensembles of direct, real-time readouts of sensory neuron signaling, providing temporal and spatial information across the TG, will help to define the cellular basis of orofacial somatic sensing and pain perception. © 2019 by John Wiley & Sons, Inc.

A re-evaluation of the basicranial soft tissues and pneumaticity of the therizinosaurian Nothronychus mckinleyi (Theropoda; Maniraptora).

The soft-tissue reconstruction and associated osteology of the North American therizinosaurian Nothronychus mckinleyi is updated. The cranial nerve topology is revised, bringing it more in line with coelurosaurs. The trunk of the trigeminal nerve is very short, with an incompletely intracranial trigeminal ganglion, an ophthalmic branch diverging anteriorly first, with later divergences of the maxillomandibular branches, following typical pathways. The facial nerve has been re-evaluated, resulting in a very typical configuration with an extracranial geniculate ganglion. The single foramen leading to the cochlea probably transmitted the vestibulocochlear nerve, along with some fibers of the facial. This configuration is reduced from the more standard three foramina (vestibular, cochlear, and facial) and may be apomorphic for therizinosaurs. Some alteration is proposed for the dorsiflexive musculature. The insertion point for m. transversospinalis capitis is partially changed to extend onto the parietal, along with a proposed functional difference in the moment arm. The expansion of the basicranial pneumatic system is limited to the paratympanic system, enhancing low frequency sound sensitivity. There is little expansion of the median pharyngeal and subcondylar sinuses. Ossification of the surrounding epithelium may provide some information on the embryology of the theropod skull. It may be associated with a reduced stress field, or the general similarity of the basicranium with anterior cervical vertebrae may reflect activation of a cervical vertebral (Hox) gene regulating ossification of the pneumatic sinuses. This might be a local, selectively neutral, fixed gene in the basicranium reflecting embryological regulation of cervical vertebrae development.

Anatomic Evidence for Information Exchange between Primary Afferent Sensory Neurons Innervating the Anterior Eye Chamber and the Dura Mater in Rat.

Purpose: Our previous studies suggested that mechanosensitive trigeminal ganglion (TG) nerve endings innervating the inner wall of the anterior eye chamber (IWAEC) might play a role in baroreception of the IOP. It has been reported that mechanosensitive TG nerve endings also innervate the dura mater. An acute IOP elevation evokes eye pain accompanied by an ipsilateral headache, suggesting that information exchange may occur between the primary afferent neurons (PANs) innervating the IWAEC and the dura mater. To verify the information exchange between PANs of the two locations, we investigated the anatomic connection between them. Methods: Non-trans-synaptic tracers, 1,1'-dilinoleyl-3,3,3',3'-tetramethylindo-carbocyanine, 4-chlorobenzenesulfonate (FAST Dil) and cholera toxin subunit-B with a 488-nm fluorescent tag (CTB-488), were applied to the dura of the anterior cranial fossa (DACF) and the anterior eye chamber (AEC) to label the PANs. A trans-synaptic tracer, GFP-expressing pseudorabies virus (PRV152), was injected into the AEC while FAST Dil was applied to the DACF to explore the connection between PANs. Fluorescent localization in the TG was studied with a confocal fluorescent microscope. Results: Nine days after rats were treated with CTB-488 in the AEC and FAST Dil on the DACF, FAST Dil-labeled (red), and CTB-488-labeled (green) TG neurons were observed in the medial part of the TG, while double-labeled neurons were absent. If PRV152 was used to substitute CTB-488, then FAST Dil (red) and PRV152 (green) double-labeled TG neurons and axons were observed 3 days later. Conclusions: Our results indicate that synapses exist between PANs of the IWAEC and the DACF, providing anatomic evidence for information exchange between them.

Stromal cells/telocytes and endothelial progenitors in the perivascular niches of the trigeminal ganglion.

Stromal cells/telocytes (SCs/TCs) were recently described in the human adult trigeminal ganglion (TG). As some markers are equally expressed in SCs/TCs and endothelial cells, we hypothesized that a subset of the TG SCs/TCs is in fact represented by endothelial progenitor cells of a myelomonocytic origin. This study aimed to evaluate whether the interstitial cells of the human adult TG correlate with the myelomonocytic lineage. We used primary antibodies for c-erbB2/HER-2, CD31, nestin, CD10, CD117/c-kit, von Willebrand factor (vWF), CD34, Stro-1, CD146, α-smooth muscle actin (α-SMA), CD68, VEGFR-2 and cytokeratin 7 (CK7). The TG pial mesothelium and subpial vascular microstroma expressed c-erbB2/HER-2, CK7 and VEGFR-2. SCs/TCs neighbouring the neuronoglial units (NGUs) also expressed HER-2, which suggests a pial origin. These cells were also positive for CD10, CD31, CD34, CD68 and nestin. Endothelial cells expressed CD10, CD31, CD34, CD146, nestin and vWF. We also found vasculogenic networks with spindle-shaped and stellate endothelial progenitors expressing CD10, CD31, CD34, CD68, CD146 and VEGFR-2. Isolated mesenchymal stromal cells expressed Stro-1, CD146, CK7, c-kit and nestin. Pericytes expressed α-SMA and CD146. Using transmission electron microscopy (TEM), we found endothelial-specific Weibel-Palade bodies in spindle-shaped stromal progenitors. Our study supports the hypothesis that an intrinsic vasculogenic niche potentially involved in microvascular maintenance and repair might be present in the human adult trigeminal ganglion and that it might be supplied by either the pial mesothelium or the bone marrow niche.

Neuroanatomy and Neurochemistry of Mouse Cornea.

PURPOSE: To investigate the entire nerve architecture and content of the two main sensory neuropeptides in mouse cornea to determine if it is a good model with similarities to human corneal innervation. METHODS: Mice aged 1 to 24 weeks were used. The corneas were stained with neuronal-class ßIII-tubulin, calcitonin gene-related peptide (CGRP), and substance P (SP) antibodies; whole-mount images were acquired to build an entire view of corneal innervation. To test the origin of CGRP and SP, trigeminal ganglia (TG) were processed for immunofluorescence. Relative corneal nerve fiber densities or neuron numbers were assessed by computer-assisted analysis. RESULTS: Between 1 and 3 weeks after birth, mouse cornea was mainly composed of a stromal nerve network. At 4 weeks, a whorl-like structure (or vortex) appeared that gradually became more defined. By 8 weeks, anatomy of corneal nerves had reached maturity. Epithelial bundles converged into the central area to form the vortex. The number and pattern of whorl-like structures were different. Subbasal nerve density and nerve terminals were greater in the center than the periphery. Nerve fibers and terminals that were CGRP-positive were more abundant than SP-positive nerves and terminals. In trigeminal ganglia, the number of CGRP-positive neurons significantly outnumbered those positive for SP. CONCLUSIONS: This is the first study to show a complete map of the entire corneal nerves and CGRP and SP sensory neuropeptide distribution in the mouse cornea. This finding shows mouse corneal innervation has many similarities to human cornea and makes the mouse an appropriate model to study pathologies involving corneal nerves.

Laser speckle imaging to improve clinical outcomes for patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation.

OBJECTIVE: Percutaneous treatments for trigeminal neuralgia are safe, simple, and effective for achieving good pain control. Procedural risks could be minimized by using noninvasive imaging techniques to improve the placement of the radiofrequency thermocoagulation probe into the trigeminal ganglion. Positioning of a probe is crucial to maximize pain relief and to minimize unwanted side effects, such as denervation in unaffected areas. This investigation examined the use of laser speckle imaging during probe placement in an animal model. METHODS: This preclinical safety study used nonhuman primates, Macaca nemestrina (pigtail monkeys), to examine whether real-time imaging of blood flow in the face during the positioning of a coagulation probe could monitor the location and guide the positioning of the probe within the trigeminal ganglion. RESULTS: Data from 6 experiments in 3 pigtail monkeys support the hypothesis that laser imaging is safe and improves the accuracy of probe placement. CONCLUSIONS: Noninvasive laser speckle imaging can be performed safely in nonhuman primates. Because improved probe placement may reduce morbidity associated with percutaneous rhizotomies, efficacy trials of laser speckle imaging should be conducted in humans.

Pain. Part 2a: Trigeminal Anatomy Related to Pain.

In order to understand the underlying principles of orofacial pain it is important to understand the corresponding anatomy and mechanisms. Paper 1 of this series explains the central nervous and peripheral nervous systems relating to pain. The trigeminal nerve is the 'great protector' of the most important region of our body. It is the largest sensory nerve of the body and over half of the sensory cortex is responsive to any stimulation within this system. This nerve is the main sensory system of the branchial arches and underpins the protection of the brain, sight, smell, airway, hearing and taste, underpinning our very existence. The brain reaction to pain within the trigeminal system has a significant and larger reaction to the threat of, and actual, pain compared with other sensory nerves. We are physiologically wired to run when threatened with pain in the trigeminal region and it is a 'miracle' that patients volunteer to sit in a dental chair and undergo dental treatment. Clinical Relevance: This paper aims to provide the dental and medical teams with a review of the trigeminal anatomy of pain and the principles of pain assessment.

Distribution of transient receptor potential melastatin-8-containing nerve fibers in rat oral and craniofacial structures.

The transient receptor potential melastatin-8 (TRPM8) is a cold and menthol receptor located in the sensory ganglia. Immunohistochemistry for TRPM8 was performed on oral and craniofacial structures of the rat. TRPM8-immunoreactive (-IR) nerve fibers were detected in the oral mucous membrane. In the gingiva, TRPM8-IR nerve fibers were abundant beneath and within crestal and outer epithelia. Such nerve fibers were also common beneath and within taste buds in the incisive papilla. In addition, TRPM8-immunoreactivity was expressed by some taste bud cells in the papilla. Lips, periodontal ligaments and salivary glands as well as masticatory muscles and temporomandibular joints were mostly devoid of TRPM8-IR nerve fibers. A double immunofluorescence study indicated different distribution patterns of nerve fibers containing TRPM8 and calcitonin gene-related peptide in oral and craniofacial tissues. Retrograde tracing method also indicated that TRPM8-IR nerve fibers in the gingiva and incisive papilla originate from small sensory neurons in the trigeminal ganglion. TRPM8 may be associated with cool, cold nociceptive (

Stereotaxis of mandibular nerve initial point of trigeminal ganglion in rats.

OBJECTIVE: To acquire parameters for stereotaxis of the mandibular nerve initial point of the trigemenial ganglion (TG) and to test the accuracy of the acquired parameters for microinjection into the mandibular nerve initial point of TG in adult rats. METHODS: Sprague-Dawley rats (260-270 g) were mounted onto a stereotaxic frame. The bregma was set as an anchor point and the three-dimensional parameters between the mandibular nerve initial point of the bilateral TGs and the bregma were measured in 25 rats. The accuracy of these parameters was tested using microinjection of Evans blue dye into the mandibular nerve initial point of the bilateral TGs in 30 rats and the injection sites were evaluated by dissection. RESULTS: The three-dimensional parameters of the mandibular nerve initial point of the bilateral TGs were 3.5 ± 0.1 mm posterior and 3.6 ± 0.2 mm lateral to the bregma, and 12.0 ± 0.2 mm inferior to the skull surface. Accuracy for the microinjection of Evans blue dye into the mandibular nerve initial point of the bilateral TGs was 86.7% (52/60). CONCLUSION: The acquired parameters served well for stereotaxis and microinjection of reagents into the mandibular nerve initial point of TG.

Somatotopic organization of trigeminal ganglion: three-dimensional reconstruction of three divisions.

Clearing the somatotopic organization of trigeminal ganglion can help us to improve the precision of treatment for trigeminal neuralgia. The distribution of primary afferent perikarya of 3 branches of trigeminal nerve in the trigeminal ganglion was investigated in the rabbit, and 3D model was reconstructed then. After application of wheat germ agglutinin-horseradish peroxidase and DiI to the cut endings of the 3 branches of trigeminal nerve, ophthalmic cells were found in the anteromedial part of the trigeminal ganglion, mandibular cells in the posterolateral part, and maxillary cells in the middle part. The results suggest that the somatotopic organization of the ganglion in rabbits is a mediolateral direction reflecting the mediolateral order of the ophthalmic, maxillary, and mandibular nerves.

Clinical value of a self-designed training model for pinpointing and puncturing trigeminal ganglion.

OBJECTIVES. A training model was designed for learners and young physicians to polish their skills in clinical practices of pinpointing and puncturing trigeminal ganglion. METHODS. A head model, on both cheeks of which the deep soft tissue was replaced by stuffed organosilicone and sponge while the superficial soft tissue, skin and the trigeminal ganglion were made of organic silicon rubber for an appearance of real human being, was made from a dried skull specimen and epoxy resin. Two physicians who had experiences in puncturing foramen ovale and trigeminal ganglion were selected to test the model, mainly for its appearance, X-ray permeability, handling of the puncture, and closure of the puncture sites. Four inexperienced physicians were selected afterwards to be trained combining Hartel's anterior facial approach with the new method of real-time observation on foramen ovale studied by us. RESULTS. Both appearance and texture of the model were extremely close to those of a real human. The fact that the skin, superficial soft tissue, deep muscles of the cheeks, and the trigeminal ganglion made of organic silicon rubber all had great elasticity resulted in quick closure and sealing of the puncture sites. The head model made of epoxy resin had similar X-ray permeability to a human skull specimen under fluoroscopy. The soft tissue was made of radiolucent material so that the training can be conducted with X-ray guidance. After repeated training, all the four young physicians were able to smoothly and successfully accomplish the puncture. CONCLUSION. This self-made model can substitute for cadaver specimen in training learners and young physicians on foramen ovale and trigeminal ganglion puncture. It is very helpful for fast learning and mastering this interventional operation skill, and the puncture accuracy can be improved significantly with our new method of real-time observation on foramen ovale.

Involvement of trigeminal mesencephalic nucleus in kinetic encoding of whisker movements.

In previous experiments performed on anaesthetised rats, we demonstrated that whisking neurons responsive to spontaneous movement of the macrovibrissae are located within the trigeminal mesencephalic nucleus (Me5) and that retrograde tracers injected into the mystacial pad of the rat muzzle extensively labelled a number of Me5 neurons. In order to evaluate the electrophysiological characteristics of the Me5-whisker pad neural connection, the present study analysed the Me5 neurons responses to artificial whisking induced by electrical stimulation of the peripheral stump of the facial nerve. Furthermore, an anterograde tracer was injected into the Me5 to identify and localise the peripheral terminals of these neurons in the mystacial structures. The electrophysiological data demonstrated that artificial whisking induced Me5 evoked potentials as well as single and multiunit Me5 neurons responses consistent with a direct connection. Furthermore, the neuroanatomical findings showed that the peripheral terminals of the Me5 stained neurons established direct connections with the upper part of the macrovibrissae, at the conical body level, with fibres spiralling around the circumference of the vibrissae shaft. As for the functional role of this sensory innervation, we speculated that the Me5 neurons are possibly involved in encoding and relaying proprioceptive information related to vibrissae movements to other CNS structures.

Endoscopic approach to the trigeminal nerve: an anatomic study.

OBJECTIVE: To describe an endoscopic perspective of the surgical anatomy of the trigeminal nerve. METHODS: Nine adult cadaveric heads were dissected endoscopically. RESULTS: Opening the pterygopalatine fossa is important because many key anatomical structures (V2, pterygopalatine ganglion, vidian nerve) can be identified and traced to other areas of the trigeminal nerve. From the pterygopalatine ganglion, the maxillary nerve and vidian nerve can be identified, and they can be traced to the gasserian ganglion and internal carotid artery. An anteromedial maxillectomy increases the angle of approach from the contralateral nares due to an increase in diameter of the piriform aperture, and provides excellent access to the mandibular nerve, the petrous carotid, and the cochlea. CONCLUSIONS: Identification of key anatomical structures in the pterygopalatine fossa can be used to identify other areas of the trigeminal nerve, and an anteromedial maxillectomy is necessary to expose the ipsilateral mandibular nerve and contralateral cranial level of the trigeminal nerve.

Transcranial segment of the trigeminal nerve: macro-/microscopic anatomical study using sheet plastination.

BACKGROUND: Trigeminal neuralgia (TN) may be caused by the mechanical compression of the trigeminal nerve. In the studies on the location of mechanical irritation and entrapment of the nerve, attention has been paid mostly to vascular structures in the subarachnoid space. Few studies have explored the relationship between the trigeminal nerve and its surrounding structures along its course in the skull base. The aim of this study was to examine and trace the root, ganglion and three divisions of the trigeminal nerve and their relationships with surrounding soft and bony structures in the skull base, and to identify the likely mechanical compression points. METHODS: A total of 26 adult cadavers (ten females, 16 males; age range, 45-81 years) were examined in this study, eight for dissection and 16 for sheet plastination study. RESULTS: Anatomical structures that may make the trigeminal nerve susceptible to entrapment in the skull base were located at (1) the inferolateral edge of the mouth of Meckel's cave, (2) the middle cranial fossa dura and the lateral wall of the anterior intracavernous portion of the internal carotid artery, (3) the ridge of the medial wall of the foramen rotundum, and (4) the twisted periosteum and venous plexus of the foramen ovale. CONCLUSION: This study identified four likely mechanical compression points along the course of the trigeminal nerve in the skull base. Knowledge of these TN-susceptible sites may be useful to both skull base surgeon and TN-animal model researcher, particularly when they study TN without vascular compression.

Antonius Balthazar Raymundus Hirsch and the peregrination of "gasserian ganglion".

The anatomical description of the fifth cranial nerve ganglion lacked detail before the work of Antonius Balthazar Raymundus Hirsch (1744-1778). Hirsch used new dissection techniques that resulted in the most meticulous report of the trigeminal ganglion (the gasserian ganglion) to have been reported. In 1765, the 21-year-old published these findings in a thesis, Paris Quinti Nervorum Encephali Disquisitio Anatomica In Quantum Ad Ganglion Sibi Proprium, Semilunare, Et Ad Originem Nervi Intercostalis Pertinet [An anatomical inquiry of the fifth pair of the nerves of the brain, so far as it relates to the ganglion unto itself, the semilunar, and to the source of the intercostal nerve]. Hirsch wrote his thesis as a paean to his ailing teacher, Johann Lorenz Gasser, but Gasser died before Hirsch was able to defend his thesis. Thereafter, Hirsch applied to teach anatomy at his alma mater, the University of Vienna, but the university did not consider his application, deeming him too young for the position. Oddly, Hirsch died at the young age of 35. For the present paper, the library at the University of Vienna (Universität Wien), Austria, was contacted, and Anton Hirsch's thesis was digitized and subsequently translated from Latin into English. The authors here attempt to place the recognition of the fifth cranial nerve ganglion within a historical perspective and trace the trajectory of its anatomical descriptions.

Trigeminal ganglion morphology in human fetus.

The morphology of the trigeminal ganglion in human fetus was investigated by means of the tract-tracing method using the lipophilic dye DiI-C18-(3) (1,1'-double octadecane 3,3,3'3'-tetramethyl indole carbonyl cyanine-perchlorate), hematoxylin-eosin (HE) stain, and three-dimensional computer reconstruction models. The trigeminal ganglion was flat in the dorsoventral direction, and DiI staining revealed that the trigeminal ganglion cells were somatotopically distributed in the ganglion in a way that reflected the mediolateral order of the three branches. Ganglion cells of the ophthalmic nerve were distributed in the anteromedial part of the trigeminal ganglion, those of the mandibular nerve were in the posterolateral part, and those of the maxillary nerve were localized in the intermediate part. DiI labeled both ganglion cells and nerve fibers in the trigeminal ganglion; the ganglion cells varied in size and appeared as round- or oval-shaped, the neurites connected the cell soma, and some bipolar neurons were also observed. The number of embryonic trigeminal ganglion cells did not significantly change with gestational age, but the cell diameter, area, and perimeter significantly increased. The motor root leaves the pons, runs along the sensory root, passes the ventral surface of the ganglion, and finally runs together with the mandibular nerve. The findings reported here elucidate the morphology, development, and somatotopic organization of the trigeminal ganglion and reveal the trigeminal nerve motor root pathway along the trigeminal ganglion and mandibular nerve in the human fetus.