Structural and functional features of central nervous system lymphatic vessels.

One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.

Subarachnoid space trabeculae architecture.

INTRODUCTION: The motion of the brain relative to the skull is influenced by the architecture of the subarachnoid space (SAS), and in particular, by the arachnoid trabeculae. In previous studies of these structures, specific shapes were identified. However, the work presented here shows much finer detail of the SAS geometries using SEM and TEM. MATERIALS AND METHODS: These images were acquired by maintaining the SAS structure of a rat using glutaraldehyde formaldehyde to strengthen the tissues via crosslinking with the biological proteins. RESULTS: The results showed the detailed shape of five dominant arachnoid trabeculae structures: single strands, branched strands, tree like shapes, sheets, and trabecular networks. Each of these architectures would provide a different response when exposed to a tensile load and would provide different levels of resistance to the flow of the cerebrospinal fluid (CSF) within the SAS. CONCLUSION: This very detailed level of geometric information will therefore allow more accurate finite element models of the SAS to be developed.

The "Valva Cerebri": Morphometry, Topographic Anatomy and Histology of the Rhomboid Membrane at the Craniocervical Junction.

The arachnoid membranes' anatomy is a controversial topic in the literature, and the rhomboid membrane at the craniovertebral junction is an element of this system that has been described poorly. Hence, the objective of our study was to examine this membrane's anatomy and histology. A total of 45 fresh formalin-fixed human cadaveric heads were examined, and anatomic dissections and histologic examinations using standard staining methods were performed. The membrane was found to be a constant structure. It has a rhomboid shape and is located on the medulla oblongata and upper cervical spine's ventral surface within the subarachnoid space. Its average craniocaudal length is 49 mm and the short axis is 26 mm. The cranial apex is attached to the vertebral arteries' junction, and the caudal apex reaches the level of C4. The lateral apices are attached to the dura mater at the level of the denticulate ligament's second insertion. The C1 spinal nerves perforate the membrane, while the C2 roots are located dorsal to it. The membrane is attached strongly to the underlying pia mater. Histologically, it has a typical arachnoid structure, in which its adhesions to the vertebral arteries as well as to the pia mater could be verified histologically. This is the first detailed examination of the rhomboid membrane. Our results suggest that the membrane serves a valve-like function between the spinal and cranial subarachnoid spaces. Based on our findings, further hydrodynamic studies should clarify the membrane's physiological role. Clin. Anat. 32:56-65, 2019. © 2019 Wiley Periodicals, Inc.

Clinical anatomy of the orbitomeningeal foramina: variational anatomy of the canals connecting the orbit with the cranial cavity.

PURPOSE: In addition to the optic canal and the superior orbital fissure, orbits are connected with the cranial cavity via inconstant canals including the orbitomeningeal foramen. This study has been carried out in order to define many anatomical and radiological details of the orbitomeningeal foramen that are relevant in the clinical practice. METHODS: Almost 1000 skulls and 50 computerized tomographies were examined to determine incidence, number, length, and caliber of the orbitomeningeal foramen as well as the topography of their orbital and cranial openings. A retrospective study of angiographies carried out on more than 100 children was performed to look for arteries candidate to run through the orbitomeningeal foramen. RESULTS: Orbitomeningeal foramina were detected in 59.46% of skulls and in 54% of individuals by computerized tomography. Orbits with two to five foramina were found. Canals were classified as M-subtype or A-subtype depending on their cranial opening. Large foramina, with the caliber ranging between 1 and 3 mm, were found in 12.17% of orbitomeningeal foramen-bearing orbits. By computed tomography the average caliber measured 1.2 ± 0.3 and 1.5 ± 0.5 mm (p < 0.005) at the orbital and cranial openings, respectively (p < 0.005). Angiographies showed meningo-lacrimal and meningo-ophthalmic arteries, meningeal branches of the lacrimal and supraorbital arteries, and some unidentified arteries that could pass through the orbitomeningeal foramina. CONCLUSIONS: Orbitomeningeal foramina are a common occurrence. When large they may house important arteries that can be the source of severe bleedings during deep dissection of the lateral wall of the orbit. Orbital surgeons should be aware of their existence.

Sensory innervation of the dorsal longitudinal ligament and the meninges in the lumbar spine of the dog.

Although intervertebral disc herniation is a well-known disease in dogs, pain management for this condition has remained a challenge. The goal of the present study is to address the lack of information regarding the innervation of anatomical structures within the canine vertebral canal. Immunolabeling was performed with antibodies against protein gene product 9.5, Tuj-1 (neuron-specific class III ß-tubulin), calcitonin gene-related peptide, and neuropeptide Y in combination with the lectin from Lycopersicon esculentum as a marker for blood vessels. Staining was indicative of both sensory and sympathetic fibers. Innervation density was the highest in lateral areas, intermediate in dorsal areas, and the lowest in ventral areas. In the dorsal longitudinal ligament (DLL), the highest innervation density was observed in the lateral regions. Innervation was lower at mid-vertebral levels than at intervertebral levels. The presence of sensory and sympathetic fibers in the canine dura and DLL suggests that pain may originate from both these structures. Due to these regional differences in sensory innervation patterns, trauma to intervertebral DLL and lateral dura is expected to be particularly painful. The results ought to provide a better basis for the assessment of medicinal and surgical procedures.

Appearance of the canine meninges in subtraction magnetic resonance images.

The canine meninges are not visible as discrete structures in noncontrast magnetic resonance (MR) images, and are incompletely visualized in T1-weighted, postgadolinium images, reportedly appearing as short, thin curvilinear segments with minimal enhancement. Subtraction imaging facilitates detection of enhancement of tissues, hence may increase the conspicuity of meninges. The aim of the present study was to describe qualitatively the appearance of canine meninges in subtraction MR images obtained using a dynamic technique. Images were reviewed of 10 consecutive dogs that had dynamic pre- and postgadolinium T1W imaging of the brain that was interpreted as normal, and had normal cerebrospinal fluid. Image-anatomic correlation was facilitated by dissection and histologic examination of two canine cadavers. Meningeal enhancement was relatively inconspicuous in postgadolinium T1-weighted images, but was clearly visible in subtraction images of all dogs. Enhancement was visible as faint, small-rounded foci compatible with vessels seen end on within the sulci, a series of larger rounded foci compatible with vessels of variable caliber on the dorsal aspect of the cerebral cortex, and a continuous thin zone of moderate enhancement around the brain. Superimposition of color-encoded subtraction images on pregadolinium T1- and T2-weighted images facilitated localization of the origin of enhancement, which appeared to be predominantly dural, with relatively few leptomeningeal structures visible. Dynamic subtraction MR imaging should be considered for inclusion in clinical brain MR protocols because of the possibility that its use may increase sensitivity for lesions affecting the meninges.

Physiology of the intrathecal bolus: the leptomeningeal route for macromolecule and particle delivery to CNS.

Presently, there are no effective treatments for several diseases involving the CNS, which is protected by the blood-brain, blood-CSF, and blood-arachnoid barriers. Traversing any of these barriers is difficult, especially for macromolecular drugs and particulates. However, there is significant experimental evidence that large molecules can be delivered to the CNS through the cerebrospinal fluid (CSF). The flux of the interstitial fluid in the CNS parenchyma, as well as the macro flux of CSF in the leptomeningeal space, are believed to be generally opposite to the desirable direction of CNS-targeted drug delivery. On the other hand, the available data suggest that the layer of pia mater lining the CNS surface is not continuous, and the continuity of the leptomeningeal space (LMS) with the perivascular spaces penetrating into the parenchyma provides an unexplored avenue for drug transport deep into the brain via CSF. The published data generally do not support the view that macromolecule transport from the LMS to CNS is hindered by the interstitial and CSF fluxes. The data strongly suggest that leptomeningeal transport depends on the location and volume of the administered bolus and consists of four processes: (i) pulsation-assisted convectional transport of the solutes with CSF, (ii) active "pumping" of CSF into the periarterial spaces, (iii) solute transport from the latter to and within the parenchyma, and (iv) neuronal uptake and axonal transport. The final outcome will depend on the drug molecule behavior in each of these processes, which have not been studied systematically. The data available to date suggest that many macromolecules and nanoparticles can be delivered to CNS in biologically significant amounts (>1% of the administered dose); mechanistic investigation of macromolecule and particle behavior in CSF may result in a significantly more efficient leptomeningeal drug delivery than previously thought.

[Etymology of the meninges names in the work «Onomatologia anatomica¼ by Josef Hyrtl]. / Etimologiya naimenovanii obolochek golovnogo mozga v trude Iozefa Girtlya «Onomatologia anatomica¼.

The article represents the translation of chapters of the scientific work «Onomatologia anatomica¼ (1880) by the Austrian anatomist Josef Hyrtl devoted to terminology in the anatomy of the meninges, namely arachnoidea, pia mater, dura mater, meninx.

Anatomy of the Ventricles, Subarachnoid Spaces, and Meninges.

The ventricular system, subarachnoid spaces, and meninges are structures that lend structure, support, and protection to the brain and spinal cord. This article provides a detailed look at the anatomy of the intracranial portions of these structures with a particular focus on neuroimaging methods.

[Pachymeningitis associated with probable Horton's disease: a case report]. / Pachyméningite associée à une probable maladie de Horton : étude d'une observation.

INTRODUCTION: Horton's disease is the most common vasculitis of elder people. Several neurological complications are reported, but pachymeningitis is exceptional. OBSERVATION: A 71-year-old patient who presented headache, hyperesthesia of the scalp, weight loss with a biological inflammatory syndrome and meningeal thickening on MRI. The diagnosis of pachymeningitis related to Horton's disease was retained. The patient was treated by corticosteroids with a good clinical, biological and radiological course after 22 months. CONCLUSION: Horton's disease is a potential diagnosis in elderly persons with pachymeningitis and inflammatory syndrome.

Clinical Anatomy of the Extradural Neural Axis Compartment: A Literature Review.

OBJECTIVE: The extradural neural axis compartment (EDNAC) is an adipovenous zone located between the meningeal and endosteal layers of the dura and has been minimally investigated. It runs along the neuraxis from the orbits down to the coccyx and contains fat, valveless veins, arteries, and nerves. In the present review, we have outlined the current knowledge regarding the structural and functional significance of the EDNAC. METHODS: We performed a narrative review of the reported EDNAC data. RESULTS: The EDNAC can be organized into 4 regional enlargements along its length: the orbital, lateral sellar, clival, and spinal segments, with a lateral sellar orbital junction linking the orbital and lateral sellar segments. The orbital EDNAC facilitates the movement of the eyeball and elsewhere allows limited motility for the meningeal dura. The major nerves and vessels are cushioned and supported by the EDNAC. Increased intra-abdominal pressure will also be conveyed along the spinal EDNAC, causing increased venous pressure in the spine and cranium. From a pathological perspective, the EDNAC functions as a low-resistance, extradural passageway that might facilitate tumor encroachment and expansion. CONCLUSIONS: Clinicians should be aware of the extent and significance of the EDNAC, which could affect skull base and spine surgery, and have an understanding of the tumor spread pathways and growth patterns. Comparatively little research has focused on the EDNAC since its initial description. Therefore, future investigations are required to provide more information on this underappreciated component of neuraxial anatomy.

Enhanced tES and tDCS computational models by meninges emulation.

OBJECTIVE: Understanding how current reaches the brain during transcranial electrical stimulation (tES) underpins efforts to rationalize outcomes and optimize interventions. To this end, computational models of current flow relate applied dose to brain electric field. Conventional tES modeling considers distinct tissues like scalp, skull, cerebrospinal fluid (CSF), gray matter and white matter. The properties of highly conductive CSF are especially important. However, modeling the space between skull and brain as entirely CSF is not an accurate representation of anatomy. The space conventionally modeled as CSF is approximately half meninges (dura, arachnoid, and pia) with lower conductivity. However, the resolution required to describe individual meningeal layers is computationally restrictive in an MRI-derived head model. Emulating the effect of meninges through CSF conductivity modification could improve accuracy with minimal cost. APPROACH: Models with meningeal layers were developed in a concentric sphere head model. Then, in a model with only CSF between skull and brain, CSF conductivity was optimized to emulate the effect of meningeal layers on cortical electric field for multiple electrode positions. This emulated conductivity was applied to MRI-derived models. MAIN RESULTS: Compared to a model with conventional CSF conductivity (1.65 S m-1), emulated CSF conductivity (0.85 S m-1) produced voltage fields better correlated with intracranial recordings from epilepsy patients. SIGNIFICANCE: Conventional tES models have been validated using intracranial recording. Residual errors may nonetheless impact model utility. Because CSF is so conductive to current flow, misrepresentation of the skull-brain interface as entirely CSF is not realistic for tES modeling. Updating the conventional model with a CSF conductivity emulating the effect of the meninges enhances modeling accuracy without increasing model complexity. This allows existing modeling pipelines to be leveraged with a simple conductivity change. Using 0.85 S m-1 emulated CSF conductivity is recommended as the new standard in non-invasive brain stimulation modeling.

Perivascular meningeal projections from cat trigeminal ganglia: possible pathway for vascular headaches in man.

Peroxidase-containing cell bodies were found in the ipsilateral trigeminal ganglia after horseradish peroxidase was applied to the proximal segment of the middle cerebral artery in seven cats. Cell bodies containing the enzyme marker were located among clusters of cells that project via the first division. The existence of sensory pathways surrounding large cerebral arteries provides an important neuroanatomical explanation for the hemicranial distribution of headaches associated with certain strokes and migraine.

Medial wall of the cavernous sinus: microanatomical diaphanoscopic and episcopic investigation.

PURPOSE: To elucidate the question whether expansion of pituitary adenomas into the cavernous sinus (CS) has to be regarded as focal penetration rather than invasion, a microanatomical study of the medial wall (MW) of the CS was performed. METHOD: Fourteen sellar hemiblocks underwent microsurgical dissection from lateral and medial approach. The thickness of the MW of the CS was examined by diaphanoscopy. FINDINGS: The internal carotid artery (ICA) was adherent to the MW in five cases. In five specimens the lateral wall of the sella turcica consisted of a single layer without perforations. In nine cases this wall had two layers. There was no perforation of both layers in any case. Diaphanoscopy revealed thin MW in the lateral border of the sella (n = 13), below the horizontal segment of the ICA (n = 10), and antero-inferiorly to the carotid syphon (n = 9). CONCLUSIONS: Expansion into the CS may be facilitated by low anatomical resistance against chronic tumor growth.

Anatomy and imaging of the normal meninges.

The meninges are an important connective tissue envelope investing the brain. Their function is to provide a protective coating to the brain and also participate in the formation of blood-brain barrier. Understanding their anatomy is fundamental to understanding the location and spread of pathologies in relation to the layers. It also provides an insight into the characteristics of such pathologies when imaging them. This review aims to describe the anatomy of the meninges, and to demonstrate the imaging findings of specific features.

Venous anatomy and imaging of the first centimeter.

The outermost centimeter of the head contains multiple layers ranging from the skin to the meninges. The venous drainage of this region is complex and with wide anatomical variation. With advances in imaging techniques, delineation of this venous system has become better appreciated. Understanding the anatomy of the superficial venous system is fundamental in being able to differentiate pathology from normal variants and structures. This review aims to characterize the basic venous architecture of the first centimeter. In addition, it hopes to give an introduction to and examples of the methods employed to image it.

A perfusion bioreactor-based 3D model of the subarachnoid space based on a meningeal tissue construct.

BACKGROUND: Altered flow of cerebrospinal fluid (CSF) within the subarachnoid space (SAS) is connected to brain, but also optic nerve degenerative diseases. To overcome the lack of suitable in vitro models that faithfully recapitulate the intricate three-dimensional architecture, complex cellular interactions, and fluid dynamics within the SAS, we have developed a perfusion bioreactor-based 3D in vitro model using primary human meningothelial cells (MECs) to generate meningeal tissue constructs. We ultimately employed this model to evaluate the impact of impaired CSF flow as evidenced during optic nerve compartment syndrome on the transcriptomic landscape of MECs. METHODS: Primary human meningothelial cells (phMECs) were seeded and cultured on collagen scaffolds in a perfusion bioreactor to generate engineered meningeal tissue constructs. Engineered constructs were compared to human SAS and assessed for specific cell-cell interaction markers as well as for extracellular matrix proteins found in human meninges. Using the established model, meningeal tissue constructs were exposed to physiological and pathophysiological flow conditions simulating the impaired CSF flow associated with optic nerve compartment syndrome and RNA sequencing was performed. RESULTS: Engineered constructs displayed similar microarchitecture compared to human SAS with regards to pore size, geometry as well as interconnectivity. They stained positively for specific cell-cell interaction markers indicative of a functional meningeal tissue, as well as extracellular matrix proteins found in human meninges. Analysis by RNA sequencing revealed altered expression of genes associated with extracellular matrix remodeling, endo-lysosomal processing, and mitochondrial energy metabolism under pathophysiological flow conditions. CONCLUSIONS: Alterations of these biological processes may not only interfere with critical MEC functions impacting CSF and hence optic nerve homeostasis, but may likely alter SAS structure, thereby further impeding cerebrospinal fluid flow. Future studies based on the established 3D model will lead to new insights into the role of MECs in the pathogenesis of optic nerve but also brain degenerative diseases.

A brief review of recent discoveries in human anatomy.

In the last few years, a cluster of anatomical discoveries has been reported which overturned the long existing dogmas about the structure and function of human body. First to come was the discovery that established the existence of a lymphatic system pertaining to the central nervous system (CNS). CNS was believed to be anatomically immune privileged owing to the absence of any lymphatics and presence of the blood-brain barrier around it, but latest research has established beyond any reasonable doubt that true lymphatic channels carry immune cells in meninges thus challenging the existing theory. Studies also supported the presence of a 'Glymphatic system' (created by the perivascular spaces lined with the leptomeninges and a sheath of glial cells) in the CNS draining interstitial metabolic waste from CNS. The second discovery unraveled the previously unknown parts of the human mesentery in adult and established that it is a continuous entity all along the intra-abdominal gut tube against the previous notion that it is fragmented in the adult humans. A very recently reported third discovery demonstrated a previously unknown tissue component-'interstitium'-a networked collagen bound fluid-filled space existent in a number of human organs. All these structures bear considerable applied importance towards the pathogenesis, prognostic and diagnostic investigations and management of human diseases. This article attempts to present a brief review of all three remarkable discoveries and emphasizes their applied importance within the realm of medical sciences.

[Lymphatic system in central nervous system]. / Système lymphatique et cerveau.

The considerable metabolic activity of the central nervous system (CNS) requires an efficient system of tissue drainage and detoxification. The CNS is however devoid of lymphatic vessels, a vasculature ensuring interstitial fluid drainage and immune survey in other organs. A unique system of drainage has recently been identified between the cerebrospinal fluid (CSF), brain interstitial fluids and meningeal lymphatic vessels. This system is coupling a cerebral "glymphatic" flow with a meningeal lymphatic vasculature. The "glymphatic" system includes perivascular spaces and astrocytes, and drains interstitial fluids, from and towards the CSF. Meningeal lymphatic vessels are functionally linked to the cerebral "glymphatic" efflux by clearing intracerebral macromolecules and antigens towards the peripheral lymphatic system. The "glymphatic"-"meningeal lymphatics" system is potentially offering new therapeutic targets to improve cerebral drainage and immune survey in human CNS diseases.

Lumbar puncture.

This article discusses the need for lumbar puncture, preparation of the patient and equipment necessary for this procedure. The rationale for the intervention is described with a focus on the nursing management before, during and after the procedure.