3 Anatomy and Biology of the Leptomeninges


3 Anatomy and Biology of the Leptomeninges

Huang Michael C., van Loveren Harry R.

Why Is the Anatomy of the Meninges Critical to a Book on Meningiomas?

Meningiomas are the most common benign intracranial neoplasms, accounting for 13 to 26% of all intracranial tumors.1 Because they originate from meningothelial cells found in the arachnoid layer of the meninges, the successful management of meningiomas demands comprehensive understanding of the anatomy of the meninges. Knowledge of meningeal architecture and its osseous and neurovascular relationships provides the basis for understanding the sites of origin and the routes of spread of meningiomas. Successful operative strategies must account for both the tumor itself and its dural attachments. Only by eliminating the affected dura and bone can the risk of recurrence be minimized.2

Familiarity with meningeal anatomy allows for the design of safe surgical approaches to complex regions of the cranial base while minimizing neurovascular injuries. Intraoperatively, the arachnoid layer provides an avascular plane of dissection, separating tumor from vital neurovascular structures. When meningiomas violate the arachnoid–pia barrier, as can be predicted by abnormal signal changes in brain parenchyma on magnetic resonance imaging, gross total resection becomes less likely. Advancements in our knowledge and appreciation of the anatomy of the meninges have driven the evolution of the surgical treatment of meningioma, including the development of advanced skull base techniques.

The term meninges is attributed to Erasistratus (304–250 BC), the Greek anatomist and royal physician to Seleucus I Nicator of Syria. Along with fellow physician Herophilus, Erasistratus performed human dissections in their school of anatomy in Alexandria and brought objectivity through direct observation to the study of anatomy. Their studies confirmed the findings of Aristotle (384–322 BC), who noted a dual-layered membrane surrounding animal brains, one layer opposing the skull and the other following the contours of the brain. The Greeks, however, were not the first to describe the coverings of the brain. In the Egyptian trauma surgery text of the Edwin Smith Papyrus (ca. 2200 BC), the presentation of a head trauma patient included descriptions of membranes enveloping the brain that when torn would release the “fluid of the interior of the head.”3

Although the presence of the dura and pia mater were well known in antiquity, the weblike arachnoid was not recognized until it was first reported by the Dutch anatomist Gerardu Blasius in 1664.4,5 The discovery of the arachnoid further advanced our concepts of cerebrospinal fluid (CSF) production, circulation, and absorption. Today, the meninges are divided into the pachymeninges, which include the dura mater, and the leptomeninges, which consist of the arachnoid and the pia mater.


The development of the meninges starts early in gestation and reaches the basic adult forms by the end of the first trimester. Meningeal precursors are derived from both neural crest and mesodermal cells. As the neural tube fuses at 22 to 24 days of gestation, a single layer of cells, with some attachments to the neural crest, surrounds the developing neural axis. A thicker, looser collection of mesenchymal cells further covers the neural tube starting around day 24 to 28 and completely envelops the developing spinal cord and brain by day 33 to 41. This mesodermal-derived cellular network, along with the neural crest–derived monocellular layer will differentiate into the meninx primitiva (primary meninx).4,6,7

As the pluripotent meninx primitiva develops, it subdivides into two distinct layers between days 34 and 48. The outer portion, the ectomeninx, is dense and compact, whereas the inner layer, the endomeninx, is more loosely arranged. The ectomeninx is the precursor to the dura and the bones of the neurocranium, thus the close apposition of dura and skull stems from their shared embryological ancestry. The inner portion of the endomeninx, containing the neural crest–derived cells covering the neural tube, begins to form the pia during the gestation interval of 45 to 55 days.4,6,7 Meanwhile, as cerebrospinal fluid invades the endomeninx, cavitations (future cisterns) begin to appear in the outer portion of the endomeninx and become obvious by 55 days of gestation.8 Although the dura and pia are distinguishably formed structures by this point of development, a distinct arachnoid layer is not obvious and may not appear until much later during fetal development.

The Fine Structures of the Meninges

Dura Mater

The dura mater, from Latin for “hard mother,” is the most superficial layer of the meninges. It is also known as the pachymeningeal, or thick layer, with its dense connective tissue. The tenacity of the dura mater stems from its composition of elongated fibroblasts and extensive amounts of extracellular collagen ( Fig. 3.1 ). The varying orientations of fibers create a matrix of intertwining collagen that provides significant strength. The outer periosteal layer of dura is generally thicker, with more abundant collagen, than the inner meningeal layer.

Located at the dura–arachnoid junction, a distinct cell population termed the dural border cells has been described. Unlike the collagen-rich superficial dural layers, the dural border cell layer consists of flattened fibro-blasts devoid of any extracellular collagen.6,7 Instead, the extracellular spaces are filled with irregular cellular processes and an amorphous, nonfilamentous granular material. Cellular connections with the superficial dural fibroblasts are absent. Only sparse, but morphologically distinct, cell-to-cell connections exist with the underlying arachnoid layer. The dural border cell layer, therefore, is continuous with the arachnoid layer.7,9


The arachnoid and the pia mater form the leptomeningeal, or thin layer of meninges. Immediately deep to the dural border cell layer sits the arachnoid barrier cell layer. This layer consists of tightly packed large fibro-blasts with minimal extracellular space and absence of collagen9 ( Table 3.1 ). There is a unique abundance of cell junctions. Tight junctions among cells strengthen the arachnoid barrier cell layer and render it impermeable to fluids, large molecular weight substance, and even some ions.911 In addition, a continuous basement membrane lines the inner surface of the arachnoid, abutting the subarachnoid CSF space.7

Arachnoid trabecular cells are specialized fibroblasts with long processes and attachment to the arachnoid barrier layer. They bridge the subarachnoid space with their long, flattened, irregular processes and may form cellular attachments with pial cells. Collagen may be found within the trabecular matrix created by the processes in the subarachnoid space.7,9

Fig. 3.1 Schematic illustration of the fine structure of the meninges. Used with permission of the Department of Neurosurgery, M.D. Anderson Cancer Center.

Table 3.1 Summary of the Fine Structural Characteristics of the Meninges


Cell Characteristics

Cell Organelles

Cell Junctions

Dura mater

Periosteal dura

Large, elongated, somewhat flattened fibroblasts in varying orientations with extensive amounts of intertwining extracellular collagen

Large amounts of granular endoplasmic reticulum, chromatin-containing nuclei, a Golgi apparatus, ribosomes, mitochondria, fat droplets, filaments


Meningeal dura

Increased amounts of elon-gated, flattened fibroblasts with long processes and proportionately less collagen

Condensed cytoplasm with elongated nuclei


Dural border cells

Modified, elongated, flattened fibroblasts, with amorphous, nonfilamentous material and no collagen in enlarged extracellular compartment

Dense, dark cytoplasm with elongated nuclei

Few cell junctions; occasional desmosomes and gap or intermediate junctions with arachnoid layer


Arachnoid barrier cells

Closely packed plump cells without any significant amount of extracellular space

Translucent cytoplasm with prominent Golgi apparatus, numerous mitochondria, large oval-shaped nuclei

Numerous cell junctions, especially desmosomes and tight and gap junctions

Arachnoid trabeculae

Loosely organized fibroblasts with long, flattened, irregular processes

Translucent cytoplasm with prominent Golgi

Cell junctions join trabeculae processes to each other and to overlying arachnoid barrier layer

Pia mater

Flattened fibroblasts

Few organelles with translu-cent cytoplasm

Few cell junctions, underlying basement membrane between pia and brain

Adapted from Barshes et al4 and Haines and Frederickson.7

Historically, the existence of a subdural space has been advocated as a naturally occurring space, or potential space similar to those found in serous cavities such as pleural, pericardial, or peritoneal cavities. Embryological and histological studies, however, do not support such a concept. The dura and arachnoid share common precursor cells and remain attached throughout development.6 Instead, the characterization of the dural border cell layer identifies a structurally weak layer at the dura–arachnoid junction. Sandwiched between the dural layer dense in collagen and the arachnoid layer reinforced with cellular junctions, the dural border cell layer represents the plane of least resistance. The creation of a space at the dura–arachnoid junction with hematoma or fluid accumulation secondary to trauma or other pathological processes is the result of tissue damage through the dural border cell layer, and not the opening of a preexisting space.6,9,12,13

Pia Mater

The pia mater is a thin sheet of flattened fibroblast cells that separates the subarachnoid space from the subpial and cortical perivascular spaces. The basement membrane of the outer glial layer of the brain and spinal cord, termed glia limitans, separates the pia from the underlying neural tissue to create the subpial space.4,14 These modified fibroblasts of pia form junctional complexes at their margins, rendering the pia impermeable to particulate matter, such as blood. The pia is reflected from the surface of the brain to surround vessels traveling in the subarachnoid space but does not accompany the vessels into parenchyma. This arrangement seals the subarachnoid space from the subpial and perivascular spaces, such that subarachnoid blood does not enter the subpial space.4,9,14

Arachnoid Villi/Granulations

Arachnoid villi are specialized segments of the meninges that project into the sinuses and major venous structures ( Fig. 3.2 ). They are essential in the absorption of CSF through both passive and active mechanisms.15 Whereas arachnoid villi are microscopic, arachnoid granulations are visible to the naked eye, and Pacchionian bodies are especially large, elaborate complexes.16 A fibrous capsule reflected from the surrounding dura covers arachnoid villi except at the apices, where the underlying arachnoid cell layer and specialized arachnoid cap cells are exposed to the venous blood of the sinus.7,15 These cells are highly metabolically active and are involved in the resorption of CSF.1 Arachnoid cap cells are derived from the outer portions of the endomeninx and are considered the cells of origin of meningiomas. Although they can be located throughout the central nervous system, including within the ventricles, the sylvian fissure, and the pineal region, they are found in greatest concentration adjacent to the major sinuses, large cerebral veins, and basilar plexus, and around the crista galli, over the cribriform plate, and at the exit foramina of cranial nerves II through VII and IX through XII.7

Fig. 3.2 Illustration of the fine structure of an arachnoid granulation and its relation to the superior sagittal sinus. Note the continuity of the layers and spaces of the meninges that surround the brain into the granulation. Used with permission of the Department of Neurosurgery, M.D. Anderson Cancer Center.

Dural Anatomy

The dura mater is composed of two distinct layers that remain fused throughout the majority of the cranium.8,17 The outer periosteal (endosteal) layer is highly vascularized and intimately adherent to the overlying cranium, and it functions as its periosteum.9,18 The periosteal dura is continuous with the periosteum covering the external cranium at suture lines and neural foramina. It merges with the periorbital membrane through the optic canal and the superior orbital fissure.17,19 As the cranial nerves exit through their respective cranial foramina, the inner meningeal layer surrounds the nerves as tubular sheaths that will fuse with the epineurium. The meningeal layer reflects away from the periosteal layer at multiple locations to form the venous sinuses. It folds inward to form dural septa that partition and maintain the positions of the intracranial neural structures. These dural folds include the falx cerebri, the tentorium cerebelli, the diaphragma sellae, and the falx cerebelli.

The largest of the dural reflections, the falx cerebri, lies in the deep fissure between the two hemispheres of the cerebrum. It extends posteriorly from its anterior attachment at the crista galli of the cribriform plate to insert onto the superior surface of the tentorium. Superiorly it attaches to the midline of the frontal, parietal, and occipital bones, whereas inferiorly it remains unattached. The sickle-shaped falx is shorter in its anterior portion. Although posteriorly the inferior free edge closely opposes the corpus callosum, anteriorly there is a wide space between the two structures where the cerebral hemisphere can herniate beneath the free edge.20

The tentorium cerebelli divides the cranium into the supratentorial and infratentorial compartments. Except for its free edge that comprises the incisura, the tentorium is firmly anchored to the inner surface of the temporal, parietal, and occipital bones at its margins. Anteriorly, the free edges of the incisura pass over the trigeminal ganglion to insert onto the petrous apex and the anterior and posterior clinoid processes. These insertions form three dural folds: the anterior and posterior petroclinoid folds and the interclinoid fold. Together, these dural folds form the oculomotor trigone, through which the oculomotor nerve enters the cavernous sinus. The medial extension of the dura covering the oculomotor trigone is the diaphragma sellae. Dura extending anteriorly from the free edge will form the lateral wall of the cavernous sinus and cover the middle cranial fossa.21

In addition to the formation of dural septa and sinuses, the layers of the dura also separate around the sella and parasellar regions and the Meckel cave. Situated lateral to the sella, resting on the sphenoid and temporal bones, the cavernous sinus is a paired venous structure enclosed by five dural walls.22 It faces the temporal lobe laterally and the sphenoid bone, sella turcica, and pituitary gland medially. Anteriorly, the cavernous sinus fills the posterior margin of the superior orbital fissure below the anterior clinoid process, and it extends posteriorly to the petrous apex. Its posterior wall stretches from the lateral edge of the dorsum sellae to the medial margin of the Meckel cave. Finally, the roof of the cavernous sinus is composed of the clinoidal and oculomotor triangles and faces the basal cisterns.23 These dural folds that envelop the cavernous sinus and its contents serve as consistent landmarks and provide routes for surgical access to the cavernous sinus.

Since Parkinson’s initial description of surgical exposure of the cavernous carotid artery through the lateral wall of the cavernous sinus in 1965,24 there have been numerous investigations of the anatomy and approaches to the cavernous sinus.22,2531 The dura of the middle fossa is composed of an outer periosteal layer that is adherent to the inner surface of the cranium, and an inner meningeal layer that faces the brain. At the lateral edge of the cavernous sinus, the middle fossa dural lining separates. The meningeal layer turns upward as the temporal lobe dura and forms the superficial layer of the lateral wall of the cavernous sinus, whereas the periosteal layer continues medially along the skull base to become the medial wall.22,29 Dissection of the lateral wall of the cavernous sinus reveals a two-layered construct. The superficial layer that is the continuation of the middle fossa meningeal dura can be easily separated from a thinner deep layer. The dural sheaths that accompany cranial nerves III, IV, V1, and V2 as they penetrate into the sinus form this semitransparent deep layer.22,30

The lateral and medial walls join anteriorly at the superior orbital fissure (SOF), and the cranial nerves exiting the apex of the cavernous sinus are wrapped in a common meningeal sheath.29 The middle fossa periosteal dura continues through the SOF as the periosteal layer of the periorbita, creating the orbitotemporal periosteal fold.32 Sectioning of this periosteal bridge is the initial step in the extradural elevation of the superficial layer of the lateral wall and a useful step to enhance extradural exposure of the anterior clinoid process for anterior clinoidectomy ( Fig. 3.3 ).29,32 Posterolateral to the SOF at the site of middle cerebral vein drainage, venous channels are covered by meningeal dura only. This absence of a deep inner membrane creates a weak point in the cavernous sinus wall and a potential route of invasion into the cavernous sinus apex from medial sphenoid wing meningiomas.29

Unlike the dual-layered lateral wall, the medial wall of the cavernous sinus is composed of a single thin layer of dura that cannot be separated. This single-layered construction of the medial wall may explain the tendency for pituitary adenomas to invade the cavernous sinus. Although a single layer of dura constitutes the medial wall, it can be divided into two parts, each with a different dural origin. It has a sellar portion that faces the sella turcica and the pituitary gland, and a sphenoidal portion that sits upon the carotid sulcus on the lateral aspect of the sphenoid bone. The sellar portion of the medial wall is a continuation of the meningeal layer of dura that extends downward from the free edge of the diaphragma sellae. It separates the pituitary gland from the venous space of the cavernous sinus and can be easily dissected away from the pituitary capsule. The sphenoidal portion, on the other hand, is the medial extension of the periosteal dura lining the middle fossa floor. At the level of the sellar floor, the two dural components of the medial cavernous sinus wall join together and continue together medially to line the inferior aspect of the pituitary gland and the sellar floor.33

Fig. 3.3 Schematic illustration of the meningeal architecture of the cavernous sinus. Broad line, periosteal dura lining the sphenoid bone; broken line, meningeal dura; dotted line, deep layer; shaded areas, venous channels. The star indicates a cleaving plane that is accessible between the superficial and deep layers by incision of the orbitotemporal periosteal bridge (arrow). OR, orbit; MC, Meckel cave; SS, sphenoid sinus; MF, middle cranial fossa; SOF, superior orbital fissure; PF, posterior fossa. Reprinted with permission from Kawase T, van Loveren HR, Keller JT, et al. Meningeal architecture of the cavernous sinus: clinical and surgical implications. Neurosurgery 1996;39:527–536.

The roof of the cavernous sinus extends posteriorly from the superior junction of the optic strut with the body of sphenoid bone to the posterior clinoid process. The optic strut is the posterior root of the lesser wing and is the inferiomedial anchor of the anterior clinoid process to the lesser wing. Several dural attachments, including the anteromedial part of the tentorium, the anterior petroclinoid and interclinoid dural folds, insert on the anterior clinoid process. Together with the posterior petroclinoid dural fold, they form the oculomotor triangle that marks the roof over the posterior cavernous sinus.22

Two layers of dura envelop the anterior clinoid process and form the dural roof of the anterior cavernous sinus. The superficial meningeal layer covers the superior surface of the clinoid process and extends medially to fuse with the adventitia of the internal carotid artery (ICA) to form the distal dural ring ( Fig. 3.4 ). This dural ring encircles the carotid completely and tightly, marking its entrance into the intradural compartment. Further medial, it forms the falciform ligament, the dural sheath of the optic nerve, and continues as a dural covering of the tuberculum sellae and planum sphenoidale. Laterally, the distal dural ring merges with the anterior petroclinoid dural fold, which stretches from the petrous apex to the anterior clinoid process.

Below the distal dural ring, an inner dural layer termed the caroticooculomotor membrane lines the inferior surface of the anterior clinoid process. It separates the clinoid process from the oculomotor nerve and surrounds the carotid artery medially as the proximal dural ring. As it sweeps upward along the ICA, it forms a carotid collar between the proximal and distal rings and joins the distal ring at the posterior tip of the anterior clinoid process. Posterolaterally, this thin inner membrane continues as the dural sheath of the oculomotor nerve and contributes to the inner layer of the lateral wall of the cavernous sinus. The proximal and distal dural rings serve as the boundaries for the clinoidal segment of the ICA, which can be surgically exposed with the removal of the anterior clinoid process.22,34

The posterior wall of the cavernous sinus is delineated by an area between the posterior clinoid process, the dural entrance of the abducens nerve, and the medial border of the porus trigeminus. The posterior petroclinoid dural fold marks the superior margin while the petrosphenoid ligament (Gruber ligament) defines the inferior limit of the posterior wall. A large venous confluence located lateral to the dorsum sellae opens into the basilar, superior, and inferior sinuses in the posterior portion of the cavernous sinus. The basilar sinus is the largest connection between the two sinuses and sits on the posterior surface of the dorsum sellae.22

At its posterolateral border, the lateral wall of the cavernous sinus extends downward and fuses with the dura of the middle fossa and Meckel cave.23 Situated in the trigeminal depression at the petrous apex and sandwiched between the two layers of the middle fossa dura, the Meckel cave is a cleftlike dural pouch containing the sensory and motor roots of the trigeminal nerve, and the gasserian ganglion. The entrance to the Meckel cave, the porus trigeminus, sits midway between the dorsum sellae and the internal auditory canal just below the tentorium and the superior petrosal sinus.25,35

Fig. 3.4 Illustration of the microanatomy of the left cavernous sinus after an anterior clinoidectomy. The inner dural layer of the roof of the cavernous sinus reflects from the oculomotor nerve to form the proximal dural ring. This caroticooculomotor membrane travels with the clinoidal segment of the internal carotid artery (ICA) to fuse with the distal dural ring. Printed with permission from the Mayfield Clinic.

As the trigeminal nerve enters the porus trigeminus from the posterior fossa, it carries with it posterior fossa meningeal dura and underlying arachnoid, which continues anterolaterally to envelop the gasserian ganglion and to become the Meckel cave ( Fig. 3.5 ). The dual layers of the temporal dura split around this pocket of the posterior fossa dura, with the meningeal layer blanketing its lateral surface and the periosteal layer underlying its medial side. Therefore, two layers of meningeal dura cover the trigeminal roots and gasserian ganglion on their dorsolateral aspects. Inside the Meckel cave, CSF sits in the subarachnoid space of the trigeminal cistern. Beyond the gasserian ganglion, the inner components of the posterior fossa dura and arachnoid continue as the epineurium and the perineurium of the divisions of the trigeminal nerve, respectively.8,19 A cleavage plane exists between the two layers of the meningeal dura that can be exploited surgically to expose the Meckel cave in an extradural fashion.25

The sella turcica sits in the middle of the cranium flanked by the cavernous sinus on either side. With the exception of its lateral walls, which are the single-layered medial walls of the cavernous sinus, two layers of dura engulf the sella.33 Meningeal and periosteal layers of the lateral wall and roof of the cavernous sinus converge medially to form the diaphragma sellae and extend anteriorly to line the anterior skull base and posteriorly to cover the dorsum sellae and clivus. The diaphragma sellae forms the roof of the sella with a conduit for the passage of the infundibulum, connecting the pituitary gland with the hypothalamus.36 The diaphragm opening demonstrates significant variability among individuals. The size of the diaphragm opening and the degree of its incompetence may affect the direction of tumor growth either into or out of the sella.37

Fig. 3.5 Schematic illustration of coronal view of the petrous apex. The Meckel cave is a dural recess formed by the meningeal dura of the posterior fossa traveling with the trigeminal nerve. It is situated on the trigeminal impression of the petrous ridge, sandwiched between the two layers of the middle fossa dura. Printed with permission from the Mayfield Clinic.

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Jul 14, 2020 | Posted by in NEUROLOGY | Comments Off on 3 Anatomy and Biology of the Leptomeninges

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