Which of the following meninges is the layer closest to the brain and spinal cord?

Meninges

Meninges are membranes that cover the spinal cord and nerve roots. The outer membrane is a tough, thick, fibrous structure called the dura mater, to the outer side of which is the epidural space. The inner membranes are more delicate and are termed the leptomeninges. They are the arachnoid membrane, which is closely applied to the dura mater, and the pia mater, which is firmly attached to the spinal cord and has a rich blood supply. Between the arachnoid and the pia mater is the subarachnoid space, which contains the CSF.

Meninges

The meninges are the connective tissue coverings of the brain and spinal cord. The outermost layer is the dura mater, a dense and tough tissue that is reduplicated to form the periosteum of the inner skull. Beneath the dura is the arachnoid, a network of loose connective tissue that lacks blood vessels. The arachnoid is closely adhered to the pia mater, which is the innermost membrane that contains blood vessels; together, these two structures are referred to as the leptomeninges. The very thin leptomeninges of rodents are visible grossly. They are thicker and more vascular in humans due to the increased surface area that must be oxygenated. Meninges have both collagen and elastic fibers. In the vertebral canal, there is an epidural space between the meninges and vertebrae, which is often filled with white adipose tissue. The principal cell types in meninges are fibroblasts within the stroma and the vascular endothelium. The extent of collagen production is greater in the thicker outer dura mater and relatively less in the two thinner leptomeningeal layers, the arachnoid and pia mater. On occasion, a few leukocytes (typically lymphocytes) may be seen near superficial meningeal blood vessels.

Historical perspective

“Meninx” (pl. meninges), a Greek term meaning “membrane,” was first used by Erasistratus of the Alexandrian school (a Greek anatomist and royal physician) between 200 and 300 B.C. In the second century A.D., Galen described two layers, which he described as “pacheia” and “lepte” (Adeeb et al., 2012). These were later translated to Arabic terms “umm al-Qalizah” (Arabic: ام الغلیظة), meaning “hard mother,” and “umm al-Raqiqa” (Arabic: ام الرقیقة) meaning “thin mother” by the Persian physician Al-Majusi (died 995 A.D.), because he believed that the meninges gave rise to or were “the mother” of all membranes in the body (Bergman and Afifi, 2016). Stephan of Antioch later translated these Arabic terms into dura mater and pia mater in 1127 A.D. (Bergman and Afifi, 2016).

Continuity between Cerebrospinal Fluid and Endoneurial Fluid

The meninges of the central nervous system are continuous with sheaths of peripheral nerve.21 Whereas the epineurial connective tissue layers are continuous with the dura mater at the central ends (dorsal and ventral roots) of peripheral nerves, the relationship between the other meninges (pia mater and arachnoid layer) and perineurium is more complex. At the subarachnoid angle of nerve roots, there appears to be continuity of the subarachnoid space and endoneurial space, thus providing for continuity between cerebrospinal fluid (CSF) and endoneurial fluid. This, then, is the conduit through which material passes from CSF to endoneurial fluid.69 The embryologic aspects of this continuity do not appear to have been investigated.

Meninges

The meninges constitute sequentially layered membranes that serve to encase and protect the central nervous system (CNS). The outermost layer is the thick, inelastic dura mater, which contains a rich vascular network, an extensive nerve supply, and its own lymphatic drainage channels. The two layers of dura mater are ordinarily adherent to each other, but they become separated in places to form the walls of the intracranial venous sinuses where CSF is eventually absorbed.5 The inner dural layer also forms a short sleeve around each cranial and spinal nerve as it leaves the CNS, and it extends caudally through the foramen magnum and into the spinal canal where it ensheaths the entire spinal cord and forms the lumbar thecal sac.4,5 The arachnoid mater is a layer of connective tissue with fine trabeculae that connect to the underlying pia mater and form a meshwork through which CSF recirculates.5 It lacks its own innervation and blood supply, likely deriving all of its metabolic support from the CSF itself. The arachnoid extrudes macroscopic pouches (arachnoid granulations) through the dura that form the intracranial venous sinuses as well as microscopic protuberances (arachnoid villi) into both cranial and spinal veins that are important routes of CSF absorption back into the bloodstream.4 The pia mater is the innermost layer of the meninges and is directly adherent to the surface of the brain and spinal cord itself. Blood vessels entering or leaving the CNS that travel in the subarachnoid space have a sleeve of pia mater that penetrates into the parenchyma and forms the outer border of the perivascular space. The pia mater and the arachnoid mater together constitute the leptomeninges, while the layers of dura mater by themselves are often referred to as the pachymeninges. The microscopic and ultrastructural features of the meninges are covered in Chapters 3 and 6.

6.8.2 Extradural Haemorrhage

The meninges will be dealt with in more detail in Chapter 7. Please refer to this chapter to gain a better understanding of the layers of the meninges, and the location of this type of hemorrhage.

This type of hemorrhage has been classified previously as due to rupture of the middle meningeal artery (Moore et al., 2006). However, alongside the middle meningeal artery is a pair of dural venous sinuses, which also pass through the foramen spinosum (where the artery enters the cranial cavity), and this arterial origin has now been disputed (Fishpool et al., 2006).

The blood (whether arterial and/or venous in origin) collects in the layer between the outer periosteal layer of dura and the calvaria. Typically, there is trauma (e.g. fracture) at the pterion, where the parietal, frontal, petrous temporal and greater wing of the sphenoid all unites. These patients initially have a lucid interval where no obvious signs are present. This is because it takes time for the blood to accumulate in the extradural space, and affect the cerebral tissue by compression. Increase in blood in the extradural space will then result in a drop in the patient’s level of consciousness, as assessed by the internationally recognized classification for consciousness – the Glasgow Coma Scale (Teasdale and Jennett, 1974).

4 Anatomy of the Meningeal Afferent System

The meninges are innervated predominantly by afferents whose cell bodies reside in the trigeminal ganglion (Fig. 2). The trigeminal nerve is the fifth cranial nerve that exits the brainstem at the level of the pons as a single nerve root, passes through the trigeminal ganglion, and continues distally from the ganglion as separate nerve branches.28,29 There are three major branches that emerge from the ganglion into V1, V2, and V3 subdivisions. Each branch innervates a distinct dermatome. The first division, V1, is also referred to as the ophthalmic nerve, and it innervates the nose, areas above the eye, and the scalp. The second division is V2, or the maxillary nerve, and it innervates areas below the eye and above the mouth as well as the mandible. Lastly, V3 is the mandibular nerve that innervates the mouth and lower portions of the jaw and face. Most relevant to migraine is the V1 branch as this is the branch that provides the majority of the innervation of the meninges (dura and blood vessels). These trigeminal afferents send afferent input from the head into the brainstem (at the pons) and they descend into the medulla where they synapse on second-order neurons and interneurons within a region of the dorsal medulla known as the spinal trigeminal nucleus or trigeminal nucleus caudalis (TNC) (Fig. 2). The nucleus caudalis lies below the obex of the brainstem and is the most caudal part of the trigeminal nucleus.30 Multiple projections into the caudalis may share the same interneuron, allowing crosstalk between afferents and providing the basis for referred pain seen in the trigeminal system.31 The axons of second-order neurons form the trigeminothalamic pathway then decussate and ascend to the ventroposteromedial nucleus of the thalamus. From the thalamus, connections are made to cortical sites.

Structure of the meninges

The meninges consist of three layers called, from the inside to the outside, the pia mater, arachnoid mater, and dura mater (Figure 3.1A). The dura mater is divided into two layers: the outer periosteal layer which is adherent to the inner surface of the skull, and an inner layer which is fused to the outer layer of the dura mater in most regions, except some, where the inner layer is folded to descend far into the cranial cavity. One of these regions is the interhemispheric fissure, in which the falx cerebri, a flat sheet of dura mater that is suspended from the top of the cranium, runs to separate the right and left cerebral hemispheres. Another such region is the tentorium cerebelli, which represents a sheet of dura mater covering the upper surface of the cerebellum (Blumenfeld, 2002).

The arachnoid is a meningeal layer adherent to the inner surface of the dura. The innermost meningeal layer is a very thin layer of cells called the pia mater. Unlike the arachnoid, the pia is closely adherent to the surface of the brain and follows into the depths of the sulci. The pia also surrounds the initial portion of each blood vessel as it penetrates the brain surface, forming a perivascular space (Virchow–Robin space), to fuse with the blood vessel wall.

The meninges separate three spaces called the epidural space, subarachnoid space, and the subdural space. Each of these spaces contains some important blood vessels, rupture of which can cause headache. The epidural space is a potential space located between the inner surface of the skull and the tightly adherent dura. The middle meningeal artery enters the skull through the foramen spinosum and runs between the dura and the skull. Injury to this artery can result in an acute epidural hematoma.

The subdural space is also a potential space between the inner layer of the dura and the loosely adherent arachnoid mater. The bridging veins traverse the subdural space to drain into the several large dural venous sinuses. Disruption of the bridging veins is the principal cause of subdural hematoma.

The space between the arachnoid and pia is called the subarachnoid space, which is filled with cerebrospinal fluid. In addition, the major arteries of the brain also run within the subarachnoid space, and rupture of an aneurysm of these major arteries in the subarachnoid space may cause subarachnoid hemorrhage.

2.4 Schematic of the Meninges and Their Relationships to the Brain and Skull

The meninges provide protection and support for neural tissue in the central nervous system. The innermost membrane, the pia mater, adheres to every contour of neural tissue, including sulci, folia, and other infoldings. It adheres tightly to glial endfoot processes of astrocytes; this association is called the pial-glial membrane. The arachnoid mater, a fine, lacy membrane external to the pia, extends across the neural sulci and foldings. The space between these two membranes is the subarachnoid space, a space into which the cerebrospinal fluid flows, providing buoyancy and protection for the brain. Arteries and veins run through the subarachnoid space to and from the central nervous system. The rupture of an arterial aneurysm in a cerebral artery results in a subarachnoid hemorrhage. The dura mater, usually adherent to the inner arachnoid, is a tough protective outer membrane. It splits into two layers in some locations to provide channels, the venous sinuses, for return flow of the venous blood. The arachnoid granulations, one-way valves, extend from the subarachnoid space into the venous sinuses, especially the superior sagittal sinus, allowing cerebrospinal fluid to drain into the venous blood and return to the heart. Blockage of these arachnoid granulations (e.g., in acute purulent meningitis) can result in increased intracranial pressure. Cerebral arteries and veins traverse the subarachnoid space. The veins, called bridging veins, drain into the dural sinuses. As they enter the sinus, these bridging veins are subject to tearing in cases of head trauma. If there is atrophy in the brain, as occurs with age, these veins may tear with relatively minor head trauma; in younger adults, more severe head trauma is needed to tear these bridging veins. Such tearing permits venous blood to accumulate in the subdural space as it dissects the inner dura from the arachnoid. This process may be gradual (chronic subdural hematoma) in older individuals or may be abrupt (acute subdural hematoma) with severe head trauma. A subdural hematoma, especially when it occurs acutely, may be life-threatening as the result of increased intracranial pressure caused by accompanying edema and by the accumulation of the blood in the hematoma itself. The dura is closely adherent to the inner table of the skull. A skull fracture may tear a branch of the middle meningeal artery, permitting arterial blood to dissect the dura from the skull, resulting in an epidural hematoma.

Spinal Meninges

The meninges covering the spinal cord are arranged in three layers: the outermost dura mater (pachymeninx), the intermediate arachnoid mater, and the innermost pia mater. Because they are both thin, the latter two are named the leptomeninges. The epidural space lies between the spinal dura mater and the periosteum of the vertebral canal. The subarachnoid space extends as a narrow slit between the arachnoid and the pia mater. The inner electron-dense cell layer of the arachnoid appears occluded and opens only around the spinal roots. In the vicinity of the spinal ganglia, the dura mater, the subdural neuroepithelium, and the arachnoid form a cellular reticulum (Seitz et al., 1981). Bilateral thickened extensions of the pia mater make tooth-like triangular processes named denticulate ligaments, which pierce the arachnoid membrane and fuse with the dura.

An electron microscopic study (Oda and Nakanishi, 1984) showed that the arachnoid membrane in the mouse is divided into an outer and an inner layer. The outer layer is composed of elongated cells connected to each other by numerous tight junctions. The cells in the inner layer have intricate cytoprocesses, some of which embrace the connective tissue matrix containing collagen fibers. Beneath the arachnoid membrane, the intercellular space of the leptomeninx, except in the outer layer of the arachnoid membrane, is filled with collagen fibers and microfibrils.

The central canal of the adult spinal cord is a tiny passage in the center of the gray commissure. It is round to ovoid in shape. The central canal opens at its rostral end into the posterior part of the fourth ventricle of the brain, and its terminal part (in the conus medullaris) forms a slight dilatation. The central canal of the adult mouse spinal cord is lined by ependymal cells rich in microfilaments and with an apical surface covered with broad microvilli (Strurrock, 1981). The ependymal cells are simple, cuboidal cells with gap junctions at the lateral aspects, and zonulae occludentes between the apical parts of the ependymal cells (Bjugn et al., 1988). The canal is filled with amorphous material containing glycogen granules. Two forms of this material are present; a dark form rich in glycogen, and a light form containing a few glycogen granules. The spinal canal of the upper cervical region has a larger lumen and the ependymal cells in this region have only scattered, narrow microvilli (Strurrock, 1981). In addition to ependymal epithelial cells, numerous clusters of tanycytes are found along the entire central canal of the mouse. In the caudal part of the spinal cord, the ventral wall of the central canal is thin and some areas are reduced to a single-cell thickness. In this region, ependymal cells participate directly in the formation of the marginal glial layer. Tanycytes separate and ensheath bundles of myelinated and unmyelinated axons; their processes take part in the formation of the marginal glial layer in the conus medullaris (Seitz et al., 1981). The condensation of neuroglia that surrounds the central canal is known as the substantia gelatinosa centralis.