Читать книгу Microneurosurgery, Volume IIIA - Mahmut Gazi Yasargil - Страница 11
Оглавление2 Embryology
Miguel Marin-Padilla
A. Embryogenesis of the Early Vascularization of the Central Nervous System
Introduction
The vascularization of the central nervous system (CNS) is a complex process, best described as an integrative vascular metamorphosis continuously adapting to its developmental modifications. Embryonic development of the CNS itself is also complex. It consists of the progressive transformation of a tubular structure (neural tube) into several regions, each with a different and specific structural organization. The vascularization of each of these regions is an integrated process which adapts to its particular growing structural and functional needs. While these regional vascular differences are clinically and surgically relevant, there are common features in the early vascularization of the CNS shared by all its regions. In the present chapter, common developmental features that characterize the general vascularization of the CNS, rather than regional differences, will be emphasized.
The available information concerning anatomic, histologic, pathologic, radiographic, clinical and surgical aspects of the formed CNS vasculature is enormous and can be readily obtained from a variety of books, monographs and review articles (Kaplan and Ford 1966, Taveras and Wood 1964, Van den Bergh 1967, Van den Bergh and Vander Eecken 1968, Stephens and Stilwell 1969, Kety 1972, Newton and Potts 1974, Peters et al. 1976, Kautzky et al. 1982, Dudley 1982, McCormick 1983, Yaşargil 1984). Although, information is also available concerning the embryonic development of the CNS vasculature (Mall 1904, Streeter 1918, Padget 1948, 1957, Moffat 1962, Klosovskii 1963, Pessacq and Reissenweber 1972, Hamilton et al. 1972, Bär and Wolff 1972, Gamble 1975, Hauw et al. 1975, Wolff et al. 1975, Pape and Wigglesworth 1979) some early aspects of it remain poorly understood.
The actual perforation of the CNS surface by embryonic vessels as well as the sequential establishment of its vascular territories needs further investigation. Information is also needed concerning the interrelationships between the development of the CNS vascular territories and that of the meningeal, the Virchow-Robin and the intraneural glial tissue compartments.
Early in embryonic development the neural tube, as a specialized epithelial (neuroectoderm) tissue, lacks an inherent vasculature (Sabin 1917, Streeter 1918, Strong 1961, Hamilton et al. 1972, Marin-Padilla 1985b). Therefore, it should be possible to study the early embryonic vascularization of any of its regions. The vascularization of the neural tube follows a caudal-cephalad gradient which is synchronous with that of its ascending differentiation and maturation. In any given region of the developing CNS, embryonic vessels must first surround and organize around (outside of) it; secondly, they must perforate the CNS external basal lamina and marginal glia, which constitute an anatomic barrier; and, thirdly, they must grow within the developing neural tissue while adapting to its growing structural and functional needs. Thus, three different vascular territories must progressively emerge in the early vascularization of every region of the developing CNS. They are the perineural, the interneural and the intraneural vascular territories, respectively. The term “neural” used to describe these three vascular territories encompasses “nervous (neural) tissue”. In other words, vascular territories which embryologically evolve outside (peri), in between (inter) and inside (intra) nervous tissue, respectively.
Each vascular territory, though interrelated, evolves sequentially, independently, and within a different and specific tissue compartment. Each territory gives rise to different types of vessels. The main arterial and venous systems of the CNS, which are components of the perineural vascular territory, evolve embedded within the meningeal compartments. Most of the perforating arterioles and venules of the CNS vasculature, which are components of the interneural vascular territory, evolve within the Virchow-Robin compartment (VRC) and hence are outside, “in between” the nervous tissue proper. Thus, the term interneural is introduced to characterize this territory of the CNS vasculature. Finally, the capillaries, apparently the only vessels that penetrate the nervous tissue proper, constitute the intraneural territory of the CNS vasculature. Intraneural capillaries also evolve embedded within a specialized compartment represented by the perivascular glia.
The early embryonic development and sequential establishment of each of these three vascular territories will be analyzed in association with the development of the meningeal, the Virchow-Robin, and the intraneural perivascular glia compartments, respectively.
Since a study of the early vasculogenesis of every region of the CNS would be too complex and beyond the scope of this text, only that of the embryonic cerebral cortex will be considered in detail (see also: Marin-Padilla 1970, 1971, 1978, 1982, 1983). Nevertheless, it should be emphasized that the observations presented and discussed should be fundamentally applicable to the early vascularization of all regions of the CNS.
Perineural Vascular Territory of the CNS Vasculature
Vasculogenesis starts in situ from consolidated angioblastic cell islands found throughout the mesoderm, the yolk sac and the body stalk of the young embryo. The cellular elements of these islands seem to undergo progressive cytoplasmic liquefaction (Sabin 1917, 1920) which results in their eventual canalization. However, the process of canalization of these islands as well as that of growing capillaries remains poorly understood and controversial (Manasek 1971). Progressive canalization of the angioblastic islands results in the formation of a precirculatory plexus of primordial vessels which are large, irregular and composed of several endothelial cells joined by tight junctions. They are surrounded by a thin and often incomplete basal lamina, and grow actively by sprouting. Zones of vascular growth are deprived of basal lamina and their leading endothelial cell or cells produce numerous long filopodia able to advance into the surrounding tissue (see Figs 2.11, 2.12). Blood cells are also believed to evolve from the original angioblasts (Streeter 1918, Sabin 1920) and they are identified very early in the lumen of embryonic vessels. The precirculatory vascular plexuses eventually establish communication through the arterial and venous systems with the heart and blood starts to circulate throughout the embryo.
Among the earliest and most prominent vascular plexuses recognized in the developing embryo is the head plexus. It is formed around the cephalic region of the CNS. By the 4th week of human embryonic development the head plexus is already a prominent vascular organization (Streeter 1918, Padget 1948, 1957, Hamilton et al. 1972). By the 6th week of age, some of the main arteries, veins and venous sinuses, which characterize the adult brain, are already recognizable (Fig 2.1).
The vascularization of the developing CNS begins at the myelencephalon and ascends progressively through the metencephalon, mesencephalon, diencephalon, striatum and telencephalon (cerebral cortex) which is the last region to be vascularized (Streeter 1918, Bar and Wolff 1972, Marin-Padilla 1985b). Therefore, it follows an ascending sequential gradient which keep pace with the CNS ascending differentiation and maturation. By the 7th gestational week of human development early vascularization of the medulla (Fig 2.2A), the pons (Fig 2.2B), the diencephalon, and the striatum (Fig 2.2C) is already underway. However, the cerebral cortex (Fig 2.2D) still lacks its intrinsic vasculature. The human cerebral cortex does not start to vascularize until around the 8th week of embryonic age. Its vascularization follows a ventro-lateral-medial sequential gradient which is synchronous with its advancing differentiation and maturation.
The cephalic region of the developing CNS is surrounded by the embryonic meninges. They constitute a prominent and quite large tissue compartment (Fig 2.2). The embryonic meninges are well vascularized before the vascularization of the CNS begins (Figs 2.2, 2.3). Three distinct primordial lamellae: the dura, the arachnoid and the pia mater are recognizable (Fig 2.3). However, there are no distinct separations or tissue spaces between them. The blood vessels of the embryonic meninges can also be separated into three distinct strata (Figs 2.2, 2.3). The outer stratum (Fig 2.3) carries the dural vessels from which the venous sinuses of the CNS evolve. The intermediate stratum, which is the largest, carries the arachnoidal vessels from which the main arterial and venous systems of the CNS evolve. The inner stratum carries the pial vessels from which the pial vascular plexus evolves. The embryonic pial plexus covers the entire surface of the developing CNS, and adapts intimately to its variable external morphology (Figs 2.2, 2.3). Its formation always precedes the intrinsic vascularization of any of the CNS regions (Fig 2.2). All perforating vessels which enter into the various regions of the developing CNS originate from their overlying pial vascular plexus. All meningeal vessels, including the dural, the arachnoidal and the pial vessels, constitute together the perineural vascular territory of the CNS vasculature.
Fig 2.1 Reconstruction of the cephalic vascular plexus of a 21 mm human embryo of about 50 days illustrating the organization and distribution of its embryonic vessels. Many of the main arteries, veins and venous sinuses which characterize the adult brain can already be recognized. All vessels illustrated are components of the perineural vascular territory of the CNS vasculature. However, the pial vascular plexus is not illustrated. A portion of the cerebral cortex has been removed to demonstrate the vascularization of its choroid plexus, the anterior cerebral artery and the sinus rectus. The thin embryonic cerebral cortex still has no intrinsic vasculature at this age. (From Streeter, G. L: Contr. Embryol. Carneg. Instn 8: 5, 1918.)
The subsequent development of the head vascular plexus (Fig 2.1) is complex because it actually comprises the concomitant formation of three different but interrelated vascular systems, dural, arachnoidal and pial – strata. The sequential embryonic development of the main arteries, veins and venous sinuses of the perineural vascular territory of the brain has been studied in great detail by several investigators (Streeter 1918, Padget 1948, 1957, Bär and Wolff 1972, Wolff et al. 1975). These studies represent the most complete account of the vasculogenesis of any region of the developing CNS.
Figs 2.4 and 2.5 are reproduced from the original works of Padget (1948, 1957). In these diagrams the complete prenatal development of each of the main vessels of the brain can be analyzed and followed in detail. It should be emphasized that the illustrations (Figs 2.4, 2.5) only represent the prenatal development of the main arterial and venous systems of the brain. They do not supply information regarding the development of the arachnoidal connecting vessels nor of the pial vascular plexus, which are also important components of the perineural vascular territory of the CNS vasculature.
Fig 2.2 Composite figure illustrating a parasagittal section (1) of the head of a 50 day human embryo, and a coronal section (2) of the anlage of the cortical choroid plexuses from a younger, 43 day old, human embryo. The parasagittal section illustrates the major regions of the developing brain, the abundant and well vascularized arachnoidal tissue (a), and the pial vascular plexus (p). The lateral (LV), third (III), and fourth (IV) ventricles; and, aqueduct of Sylvius (S) identify the embryonic cerebral cortex, the diencephalon, the cerebellar primordium and the mesencephalon, respectively. The intrinsic vascularization of the medulla (A), the pons (B) and the striatum (C) is already underway while that of the cerebral cortex (D) has not yet started. The abundant arachnoidal tissue (a) and the pial vascular plexus (p) are also illustrated in these four CNS regions. The coronal section illustrates the dural (d), the arachnoidal (a) and the pial (p) vessels around the still unvascularized embryonic cerebral cortex (cc). The cortical pial vascular plexus (p) extends into the anlage of the choroid plexuses (cp) establishing its tela choroidea from which its vascularization will evolve. (From Hamby, W. B.: J. Neurosurg. 15: 65–75, 1958.) H&E preparations, parasagittal section, x20.
Fig 2.3 Camera lucida drawings of the embryonic meninges covering the cerebral cortex of a 50 day human embryo, illustrating its composition and structural organization. Three primordial lamellae are recognized in it. The outer or dural lamella (D) is composed of closely arranged elongated cells which congregate below the developing membranous neurocranium. The intermediate or arachnoidal lamella (A) is composed of loosely arranged stellate cells with long fine cytoplasmic processes with apparently empty spaces between them. The inner or pial lamella (P) has fewer cells and more vessels than the other two and is in contact with the surface of the cerebral cortex. The surface of the cerebral cortex is composed of the closely apposed endfeet (G) of the marginal glia covered by the CNS external basal lamina. Some meningeal vessels have attachments of non-endothelial cells (arrows), which might represent precursors of pericytes and smooth muscle cells, and have circulating blood cells in their lumina. The thickness of the cortical meninges illustrated is approximately 100 micrometers. (Compare with Fig 2.13.)
The perineural vasculature undergoes an integrative development continuously adapting to the changing external morphology of the growing brain. The extraordinary development of the human cerebral cortex represents perhaps the most significant single factor underlying the remarkable developmental metamorphosis of the intracranial vasculature (Figs 2.4, 2.5). The cerebral cortex evolves from a small vesicle at the anterior end of the brain (Fig 2.2) to a large structure which comes to occupy practically the entire cranial cavity (Figs 2.4, 2.5). The adaptative metamorphosis of arteries and veins to the expanding cerebral cortex are clearly demonstrated in the accompanying illustrations (Figs 2.4, 2.5). It is quite obvious from these illustrations that in the course of embryonic development the location and distribution of the different blood vessels change continuously. This adaptative vascular metamorphosis is the result of continuous and concomitant capillary angiogenesis and capillary reabsorption. The original anastomotic plexus formed by the perineural vessels undergoes continuous remodelling by the addition of new links (angiogenesis) around growing or expanding regions and by the elimination of others (reabsorption) when no longer needed. Undoubtedly, the loose structural organization of the embryonic arachnoidal mesh and its abundance (Figs 2.2, 2.3) provide an ideal tissue substratum for these vascular adaptations. In spite of their obvious significance, the dual embryonic processes of capillary angiogenesis and reabsorption have been little studied and remain poorly understood. However, these processes have been studied in more detail in neovascularization using a variety of experimental models including tumor angiogenesis (Folkman 1976, 1982, Cotran 1982, Hunter and Gabbiani 1982, Glaser and Patz 1983, Sholley et al. 1984).
Fig 2.4 Series of diagrams illustrating the prenatal developmental metamorphosis of the major arterial systems of the human brain. The illustrations are self explanatory. (From Padget, D. H.: Contr. Embryol. Carneg. Instn 32: 207, 1948.)
Fig 2.5 Series of diagrams illustrating the prenatal developmental metamorphosis of the major venous systems and sinuses of the human brain. The illustrations are self explanatory. (From Padget, D. H.: Contr. Embryol. Carneg Instn 34–79, 1957.)
In the course of embryonic development, the arachnoidal mesh is traversed by numerous vessels of various calibers linking the main arteries and veins with the pial vascular plexus (Figs 2.2, 2.3). The size, number, location and distribution of the connecting arachnoidal vessels also undergo continuous developmental modifications and rearrangements by both capillary angiogenesis and reabsorption. Early in development, these vessels are large, irregular, thin walled, and composed of several endothelial cells joined by tight junctions (Fig 2.3). There are no recognizable arteries or veins and all of them appear to be growing actively by sprouting. Later in development, the arachnoidal arteries and veins become surrounded by arachnoidal cells which isolate them from the cerebrospinal fluid (CSF) compartment. The adult arachnoidal vessels thus become enclosed within distinct perivascular tissue spaces which seem to be analogous and continuous with those of other vessels of the body (see Fig 2.13). Furthermore, according to recent observations (Casley-Smith et al. 1976, Krisch and Buchheim 1984, Pile-Spellman et al. 1984) the perivascular spaces of the adult arachnoidal vessels seem to drain independently through the lymphatic system.
The simple structural organization of the embryonic meninges is also progressively transformed to accommodate the vascular modifications (Table 2.1, see Fig 2.13). The three original lamellae of the embryonic meninges become eventually duplicated and distinct tissue spaces are formed between them (Table 2.1). The progressive establishment of different meningeal tissue spaces and their association to its vessels are indicative of the acquisition of important functional roles, some of which are not yet clearly understood. The possible functional roles of these meningeal spaces, their relationships to the perivascular spaces, to the cerebrospinal fluid (CSF) compartments, and to the CSF circulation have recently received the attention of several investigators (Andres 1967a,b, Morse and Low 1972, Nabeshina et al. 1975, Oda and Nakanishi 1984, Krisch et al. 1983, 1984). However, the embryonic timing for the establishment of the various meningeal compartments and their association to the development of the perivascular tissue spaces need to be more accurately determined.
Although, the pial vascular plexus is a component of the perineural vascular territory of the CNS vasculature, its embryonic development, composition, structural organization, and functional role will be best appreciated in conjunction with the development of the interneural vascular territory.
Interneural Vascular Territory of the CNS Vasculature
Of the three vascular strata (the dural, the arachnoidal and the pial) which constitute the perineural vascular territory of the CNS vasculature, the pial vessels play the most important role in its early intrinsic vascularization. While the main arterial and venous system of the CNS, together with the arachnoidal connecting vessels, may be considered mere conductors for the blood, the pial vessels participate directly in the intrinsic vascularization of all regions of the CNS and of the choroid plexuses.
The pial vascular plexus is recognized throughout the entire surface of the embryonic CNS. Its formation always precedes the intrinsic vascularization of any of its regions. At 50 days gestation, the human cerebral cortex, although lacking its own vasculature, is already surrounded by a prominent pial vascular plexus (Figs 2.2, 2.3). This pial plexus will provide all the vessels which perforate through the surface of the developing cortex as well as those of the tela choroidea from which the vascularization of its choroid plexuses evolves (Fig 2.2).
Three early developmental aspects of the cortical pial vascular plexus will be reviewed in detail. Its embryonic composition and structural organization will be analyzed first. The vascular perforation of the cortical surface by the pial vessels will be analyzed next, to illustrate its sequential nature. Finally, the formation of the embryonic Virchow-Robin compartment (VRC) around the perforating vessel will be analyzed. The perforating vessels within the VRC constitute the interneural vascular territory of the CNS vasculature.
Composition and Organization of the Pial Vascular Plexus
The pial vascular plexus is supplied by connecting arachnoidal vessels which link the main arteries and veins with it (Figs 2.2, 2.3). It is composed of vessels of variable caliber, ranging from small ones lined by a single endothelial cell to larger ones lined by several endothelial cells joined by tight junctions (Figs 2.6, 2.7, arrows). They constitute a extensive short-link anastomotic plexus over the entire surface of the developing cortex. The pial plexus continuously expands and adapts to the changing external morphology of the CNS surface by capillary angiogenesis and reabsorption.
The pial vessels are separated from each other by the cytoplasmic processes of pial cells, by fine collagen fibers, and by tissue spaces (Figs 2.6, 2.7, 2.9). The primitive pial cells are elongated elements lacking distinctive features. They are frequently associated with fine collagen fibers and some contain vacuoles in their cytoplasm (Figs 2.6, 2.7). Embryonic pial cells are specific meningeal elements (Andres 1967a,b, Krisch et al. 1983, 1984). They share features of fibroblasts (collagen formation), of mesodermal cells (phagocytosis), and of epithelial cells (formation of epithelial-like lamellae).
Pial vessels have a distinct but thin basal lamina which is lacking in zones of active angiogenesis. The leading endothelial cells of its growing vessels have characteristic features. They show considerable membrane activity with the formation of pseudopodia and fine filopodia which project both inside and outside of their lumina (Figs 2.6, 2.7, 2.9). They are also characterized by a prominent and abundant granular endoplasmic reticulum filled with dense and fine granular material (Figs 2.6, 2.7, 2.9). The accumulation of this dense material often causes dilation of the endoplasmic reticulum. Although, the nature of this dense material remains unknown, its association with the advancing endothelial cells of growing capillaries suggests two possibilities. First, it could represent proteinaceous secretion for the formation of the basal lamina of the newly formed vessel, second, this material could be used in the formation of the first lumina (canalization) between the advancing endothelial cells of a growing vessel (Manasek 1971). Further investigation will be necessary to elucidate the nature of this proteinaceous material and its possible role in embryonic angiogenesis.
The surface of the embryonic cerebral cortex is composed of the closely apposed glial endfeet of the marginal glia covered by CNS external basal lamina (Figs 2.6, 2.9). The CNS external basal lamina, together with the marginal glia constitute a distinct anatomical barrier which must be perforated by the pial vessels in order to penetrate the nervous tissue.
Vascular Perforation of the CNS Surface by Pial Vessels
Recent electron microscopic studies (Marin-Padilla 1985a,b) of the early vascularization of the embryonic cerebral cortex have demonstrated the sequential nature of the vascular perforation of the CNS surface by pial vessels. Three fundamental stages have been demonstrated in this type of vascular perforation. First, the pial vessel approaches and establishes direct contact with the surface of the developing CNS. Then endothelial filopodia from these glia-touching vessels perforate through the vascular and the CNS basal laminae and penetrate into the nervous tissue. The original opening enlarges gradually, thus allowing an entire endothelial cell or cells to penetrate into the nervous tissue. Finally, the proliferation of penetrating endothelial cells results in the formation in situ of new intraneural vessels.
Vascular Approach and Contact with the CNS Surface
Embryonic pial vessels are separated from the CNS surface by pial cells, tissue space, collagen fibers and by their corresponding basal laminae (Figs 2.6, 2.7, 2.9). Occasionally, some pial vessels approach and establish direct contact with the surface of the CNS (Figs 2.6, 2.7, 2.9). The endothelium of these glia-touching vessels becomes parallel to the surface of the CNS and their corresponding basal laminae establish direct contacts at some points (Fig 2.6, insert). The only appreciable separation between these vessels and the surface of the CNS is that of their corresponding basal laminae (Fig 2.6, insert). The leading endothelial cells of these glia-touching vessels produce numerous filopodia, which project both inside and outside of vessel lumina (Figs 2.6, 2.7, 2.9). Some of the outside projecting filopodia perforate through the vascular basal lamina and establish direct contact with that of the surface of the CNS (Fig 2.6, insert). This type of vascular contact with the surface of the CNS is considered to be a prerequisite for its subsequent perforation.
Endothelial Filopodia Perforation of CNS Surface
The actual perforation of the CNS surface is carried out by the endothelial filopodia of glia-touching pial vessels (Figs 2.7, 2.9). This type of filopodial perforation occurs through areas in which the vascular and the CNS basal laminae are in contact (Fig 2.7). The perforating endothelial filopodia seem to be able to disintegrate (digest) both basal laminae and to pass through them into the nervous tissue (Fig 2.7). The filopodia enter the CNS tissue usually between adjacent glial endfeet (Figs 2.7, 2.9). The penetrating filopodia advance freely into the nervous substance and are deprived of recognizable basal lamina. This type of perforation can be carried out by several filopodia arriving from the leading endothelial cell or cells of the glia-touching capillary. The glial endfeet between the perforating filopodia often undergo swelling, vacuolization and their membrane disintegrate with the formation of myelin figures (Marin-Padilla 1985b). The endothelial filopodia of growing embryonic capillaries are able to perforate through anatomical barrier and to cause focal disintegration of the membrane of the glial endfeet of the CNS surface. Although the nature of this active process remains unknown, proteolytic enzymes, possibly produced by the endothelial filopodia, could participate in it (Ausprunk 1979). Although filopodia have been described in the leading endothelium of growing capillaries in the CNS (Klosovskii 1963, Bär and Wolff 1972, Wolff et al. 1975, Press 1977) and in a variety of experimental situations (Schoefl 1963, Ausprunk and Folkman 1977, Ausprunk 1979, Madri et al. 1983, Sholley et al. 1984) their possible significance and functional role in angiogenesis have been inadequately investigated.
At the site of the perforation the vascular and the CNS basal laminae fuse together around the perforating filopodia (Figs 2.7, 2.9). Their fusion creates a central opening through which the leading filopodia and subsequently the entire endothelial cell or cells are able to penetrate into the nervous tissue. The fusion of both basal laminae thus establishes anatomical continuity between the vessel wall and the surface of the CNS. The fusion of both basal laminae also establishes a shallow “pial-funnel” around the perforating vessels (Figs 2.7–2.9). This embryonic pial-funnel will play a significant role in the establishment of the VRC (Figs 2.8, 2.9).
Fig 2.6 Ultrastructural composition and organization of the pial vascular plexus and upper region of the cerebral cortex of a 12 day old hamster embryo. The pial vessels (*) are of differing calibers and are composed of several endothelial cells joined by tight junctions (arrows). The pial vessels are separated from each other and from the cortical surface by pial cells (F), intercellular spaces and fine collagen fibers. The marginal glia (G) covered by the CNS external basal lamina represents an anatomical barrier which must be perforated by the pial vessels. The pial vessel illustrated near the center of the figure approaches the cortical surface and its leading endothelial cells (1 and 2) have filopodia which project inside and outside its lumen. Some of these filopodia have established contact with the cortical surface. The endothelium of these glial-touching pial vessels becomes parallel to the cortical surface (insert) and the vascular and CNS basal laminae establish contacts at some points. Some filopodia from this glia-touching pial vessel (insert arrows) have perforated through the vascular basal lamina and have established direct contact with that of the cortical surface. This type of contact between the vascular and the CNS external basal laminae is considered to be a prerequisite for the subsequent perforation of its surface by the pial vessels. Few primitive neurons (N) are recognized in layer I. (From Marin-Padilla, M.: J. comp. Neurol. 241: 237–249, 1985), x5500.
Fig 2.7 Detail of the perforation of the cortical surface by the leading filopodium (arrow head) of a glia-touching pial vessel (*). The filopodium has perforated the cortical surface between two adjacent glia endfeet (G). The vascular and the CNS external basal laminae fuse around the perforating filopodium creating an opening through which whole endothelial cells eventually penetrate into the nervous tissue. The endothelial cell (E) of the upper pial vessel shows the prominent granular endoplasmic reticulum filled with dense material which characterize those of growing capillaries. Also illustrated are the processes of pial cells (F) and the tight junctions (arrows) of the pial vessels. (From Marin-Padilla, M.: J. comp. Neurol. 241: 237–249, 1985), x7000.
Fig 2.8 Detail of the ultrastructure of the newly formed intracortical capillary depicted in the left lower corner insert. Proliferation of penetrating endothelial cells (insert) results in the in situ formation of new intracortical vessels. At the entrance of the vessel a shallow pial-funnel (arrows) is formed between the fused vascular and CNS external basal laminae. This pial-funnel will elongate accompanying the newly formed intracortical capillary into the nervous tissue. It represents an embryonic Virchow-Robin compartment (VRC) and contains cytoplasmic processes of pial cells, fine collagen fibers and intercellular tissue spaces around the perforating vessel. The embryonic VRC and its vessels become separated from the nervous tissue by new glial processes (G) which become continuous with those of the marginal glia of the cortical surface. This newly formed glial wall is covered by new basal lamina material which becomes continuous with that of the CNS surface. (From Marin-Padilla, M.: J. comp. Neurol. 241: 237–249, 1985), x10000.
Fig 2.9 Schematic drawings illustrating the three fundamental stages of the vascular perforation of the surface of the embryonic cerebral cortex (G) by pial vessels (P). The following stages (from left to right) are illustrated: a) the early endothelial filopodia perforations; b) the endothelial cell perforation and proliferation with the in situ formation of a new intracortical vessel; and c) the establishment of the Virchow-Robin compartment (VRC). The fusion of the vascular and CNS external basal laminae around the perforating vessel and its participation in the formation of both the pial-funnel and the embryonic Virchow-Robin are also illustrated. The composition and organization of the embryonic VRC viewed in longitudinal and transverse (thick arrow) perspectives are also illustrated. The embryonic VRC represents a perivascular tissue space (ICS) formed between the vascular and the CNS basal laminae (BL). It contains the perforating vessel (E) with paravascular cells (P) enclosed within its basal lamina (curved arrows), the cytoplasmic processes of pial cells, and fine collagen fibers. The vessels within the VRCs constitute the interneural vascular territory of the CNS vasculature. At various depths into the nervous tissue the VRC closes off with the fusion of the vascular and the CNS basal laminae into a single layer which surrounds and accompanies the penetrating vessels into the CNS substance. Only capillaries arriving from the vessels of the VRC actually penetrate into the nervous tissue proper. They grow actively establishing short-link anastomotic plexuses throughout the nervous tissue. They constitute the intraneural vascular territory of the CNS vasculature. The three insert drawings (A, B, C) illustrate the type of progressive vascularization observed in the developing cerebral cortex. New pial vessels perforate the cortex between previous perforation sites, thus progressively vascularizing the expanding cerebral cortex. The ependymal cell layer (E) with its multiple mitoses is also illustrated. The composition and structural organization of both the embryonic and the adult VRC (compare with Fig 2.10) are essentially indentical.
In Situ Formation of New Intraneural Vessels
The original opening between the fused vascular and CNS basal laminae gradually enlarges, thus allowing endothelial cells to penetrate the nervous tissue (Figs 2.8, 2.9). The subsequent proliferation of the penetrating endothelial cells results in the formation in situ of a new intraneural vessel (Fig 2.8, insert). As the newly formed intraneural vessel advances into the nervous tissue, the original pial-funnel elongates downward and accompanies the vessel for a short distance (Fig 2.9). The glial endfeet under the perforating endothelial cells undergo swelling, membrane disintegration and myelin figures are often recognized in the area (Fig 2.9). As the newly formed vessel advances into the nervous tissue new glial processes start to surround it (Fig 2.8). These new perivascular glial processes become continuous with the marginal glia of the CNS surface, and are subsequently covered by basal lamina material (Figs 2.8, 2.9). Therefore, the perforating vessel becomes progressively separated from the nervous tissue by a new glial wall which is continuous with the CNS surface (Fig 2.9). Furthermore, the embryonic structure of the new glial, wall formed around the perforating vessel, is similar to that of the CNS surface. The proximal portion (near the CNS surface) of the perforating vessel is thus kept outside of and “in between” the nervous tissue proper, and hence, within the embryonic VRC. However, the leading endothelial cells of perforating vessels continue to advance freely, without recognizable basal lamina, into the developing nervous tissue (Fig 2.9).
Different stages of vascular perforations are recognized during early development in all regions of the CNS. In the cerebral cortex, new vascular perforations occur during its entire prenatal development. As the cortex expands, new perforations occur between previous ones, following a sequence which is schematically illustrated in Fig 2.9 (A,B,C, inserts). The formation of the embryonic pial-funnel and its role in the establishment of the embryonic VRC are also illustrated (Fig 2.9).
Finally, it is important to emphasize that pial vessels always perforate the external basal lamina and marginal glia of the CNS surface to enter the nervous tissue, but do not perforate them to exit. Therefore, it would seem that in the course of embryonic development the direction of the blood flow eventually determines which vessels will be transformed into entering arterioles, and which into existing venules.
Establishment of the VRC and Interneural Vascular Territory
The early pial-funnel established around the entrance of the perforating vessel, by the fusion of both basal laminae, undergoes significant modifications in the course of embryonic development (Figs 2.8, 2.9). Between the two fused basal laminae a shallow space is formed which communicates with the tissue spaces of the pia mater. This space elongates downward and accompanies the perforating vessel, for a short distance, into the nervous tissue. It is subsequently invaded by pial cellular elements, fine collagen fibers, and non-endothelial paravascular cellular elements (Figs 2.8, 2.9, arrows). Thus, the original pial-funnel is progressively transformed into a distinct perivascular compartment known as the VRC (Figs 2.8, 2.9). The embryonic VRC becomes progressively walled by new glial processes which are arranged in a manner structurally similar to that of the marginal glia of the CNS surface. Therefore, its vessels remain outside of “in between” the nervous tissue proper (Fig 2.9). The embryonic composition and structural organization of the VRC does not significantly change in the course of embryonic development (Fig 2.10). Both, the embryonic and the adult VRC (Jones 1970) have similar composition and overall organization (compare Figs 2.8 and 2.10). However, the early communication of the embryonic VCR with the pial space is eventually obliterated, as recently pointed out by some investigators (Krisch et al. 1983).
As the VRC becomes disconnected from the pial space it is transformed into a specific perivascular compartment entirely outside of the nervous tissue proper. The VRC (Figs 2.9, 2.10) is established between the vessel wall and the glial wall of the nervous tissue. Its embryonic vessels are transformed into arterioles and venules which can reach to considerable depths within the nervous tissue, without penetrating the neural parenchyma (Duvernoy et al. 1981). Although the VRC of the cerebral cortex could reach down as far as the white matter, its vessels remain outside and walled between the nervous tissue (Jones 1970). Therefore, the VRC vessels constitute an important and specific vascular territory of the CNS vasculature. This interneural vascular territory must be distinguished from the perineural and the intraneural territories. The perivascular spaces around the VRC vessels are anatomically independent from the meningeal compartments and from the perivascular glia compartment of the perineural and intraneural vascular territories, respectively. The drainage of the VRC is also independent from the meningeal compartments. It seems to be connected with the perivascular tissue spaces of the arachnoidal vasculature, and hence with the lymphatic system (Krisch and Buchheim 1984, Pile-Spellman et al. 1984). The early development of these anatomical differences undoubtedly results in the acquisition of different and specific functional roles for each of three vascular territories which characterizes the CNS vasculature. The establishment (embryonic timing) and the nature of these different functional roles have not been adequately studied.
Fig 2.10 Ultrastructural composition and organization of a fully developed Virchow-Robin compartment from the cerebral cortex of an adult cat. Its perivascular tissue space (PS) is clearly visible between the vascular and the CNS basal laminae (BM). This space contains the cytoplasmic processes of leptomeningeal (pial) cells (arrows), collagen fibers and the perforating vessels with perivascular pericytes and/or smooth muscle cells (S) enclosed within their basal laminae. Therefore, the basic composition and structural organization of the Virchow-Robin compartment remain practically unchanged in the course of embryonic development (compare with Fig 2.9). (From Jones, E. G.: J. Anat. [Lond.] 106: 507, 1970), x17000; insert) x2500.
In the course of embryonic development, as the original pial perforating vessels enlarge they become more directly connected with the arachnoidal vasculature. Some adult perforating vessels lose their original relationship with the pial vascular plexus, thus crossing directly from arachnoid into the CNS (Fig 2.13). Small perforating arteries and veins as well as arterioles and venules are primarily subjected to these developmental modifications (Figs 2.13, 2.14).
As the cerebral cortex increases in thickness, the VRC and its vessels elongate vertically, thus maintaining a perpendicular orientation to its surface (Figs 2.9, 2.13, 2.14). The universal perpendicular orientation of the VRC and its vessels to the surface of the cerebral cortex, as well as their considerable depth, can be best appreciated by vascular injections studies (Fig 2.14) such as those described by Pape and Wigglesworth (1979).
Intraneural Vascular Territory of the CNS Vasculature
Only small vessels arising from those of the VRC penetrate the nervous tissue proper (Duvernoy et al. 1981). At the site of penetration the VRC disappears (closes off) and the vascular and CNS basal laminae re-fuse into a single one which accompanies the penetrating vessel into the nervous tissue. This process of re-fusion of the vascular and CNS basal laminae around each penetrating vessel is analogous to the phenomenon that occurs earlier around the original perforating vessel at the CNS surface (Fig 2.9). The newly penetrating vessels grow actively establishing short-link anastomotic plexuses throughout the substance of the developing CNS (Figs 2.11, 2.12, 2.14). They give rise to the extensive intraneural capillary bed which characterizes the nervous tissue (Figs 2.12, 2.14). Together they constitute the intraneural vascular territory of the CNS vasculature.
Although the newly formed intraneural capillaries grow freely at first among the nervous elements, they too eventually become surrounded by perivascular glial processes. Intraneural capillaries are surrounded by a single basal lamina (formed by the re-fused vascular and the CNS basal laminae) and by a ring of perivascular glia, separating them from other neural elements. The intraneural perivascular glia constitutes also a specific tissue compartment which is anatomically independent from that of the VRC. Therefore, the circulating blood through the intraneural capillaries remains separated from the neuronal elements by a vascularglial (blood-brain) barrier.
As the VRC gradually elongates vertically, its vessels continues to give-off new capillaries which penetrate the CNS substance at different levels (Fig 2.14). The number of penetrating capillaries arriving from the VRC increases in the course of cortical development. These penetrating capillaries establish short-link anastomotic plexuses between contiguous VRCs (Fig 2.14). These anastomotic plexuses also undergo continuous developmental remodelling by capillary angiogenesis and reabsorption. The penetrating capillaries and their anastomotic plexuses constitute the intraneural vascular territory of the CNS vasculature and the only elements to participate in the so-called blood-brain barrier.
Intraneural capillary angiogenesis can best be studied with the rapid Golgi method or with similar procedures (Klosovskii 1963, Chilingarian and Paravian 1971, Press 1977, Marin-Padilla 1985b). This classic method deposits fine silver chromate granules within the membranes of various neural elements, including capillaries, rendering them visible against a transparent background (Figs 2.11, 2.12). Intraneural capillary angiogenesis is extraordinary during the early stages of development of the CNS. Growing endothelial cells produce many long and fine filopodia which advance freely without basal lamina among the neural elements (Fig 2.11). These fine filopodia emanate radially from the original endothelial cell and grow for a considerable distance. Their length ranges between 20 to 40 μm and their diameter between 0.3 to 0.6 μm (Figs 2.11, 2.12). Their size, length, multidirectional growth, and structural variability can be clearly appreciated in Golgi stained preparations (Figs 2.11, 2.12). The fine filopodia of growing capillaries seem to search for developmental clues (angiogenetic factors) which will determine the directional growth of the parent vessel (Marin-Padilla 1985b). They are also capable of perforating through anatomical barriers (CNS surface), and of establishing contacts among them during the formation of anastomotic plexuses (Figs 2.11, 2.12, 2.14).
Intraneural capillaries form short-link anastomotic plexuses throughout the developing CNS (Fig 2.12). It should be emphasized, that although intraneural capillary angiogenesis seems to be a random phenomenon, the formation and location of their anastomotic plexuses is specific, and always associated with actively growing regions of the CNS (Streeter 1918, Bär and Wolff 1972, Marin-Padilla 1985b). In the cerebral cortex, the first recognizable anastomotic plexus is the one formed throughout the paraventricular matrix zone, the first region of the developing CNS to begin differentiation. Anastomotic plexuses are subsequently formed in Layers I and VII following the formation of the cortical plate (Marin-Padilla 1971, 1978). These early anastomotic plexuses undergo continuous modification and remodelling by both capillary angiogenesis and reabsorption. The progressive remodelling of the intraneural plexuses again represents an integrative vascular process continuously adapting to the growing structural and functional needs of each particular region of the developing CNS (Marin-Padilla 1985b). The intraneural anastomotic plexuses evolve by the addition of new links (capillary angiogenesis) throughout growing and differentiating zones and by the removal of other links (capillary reabsorption) throughout zones in which they are no longer needed.
Capillary reabsorption is observed throughout the developing CNS. In Golgi preparations, it is characterized by the progressive reduction in the size and caliber of the regressing capillary and the eventual disappearance of anastomotic links (Fig 2.12). The nature of embryonic capillary regression and reabsorption remains poorly understood and also needs further investigation.
Fig 2.11 Examples of intracortical capillary angiogenesis from rapid Golgi preparations of the cerebral cortex of 13 day hamster embryos. Each illustration represents the tip of a growing intracortical capillary. The leading endothelium of growing capillaries produces numerous radiating filopodia which advance freely, without a recognizable basal lamina, among the neural elements. Their number, size, length, structural variability and multidirectional growth can be readily appreciated in these illustrations. x800.
Fig 2.12A Illustrates the type of short-link anastomotic plexus formed by the growing capillaries of the cerebral cortex of 13 day hamster embryos; from rapid Golgi preparations. In this plexus, some capillaries are growing in some areas (short arrows) while possibly regressing in others (long arrow). These anastomotic plexuses are always formed within differentiating and maturing regions of the developing CNS. B Illustrates the extensive intracortical capillary plexus formed between arterioles (a) and venules (v) of contiguous Virchow-Robin compartments. The intracortical capillary plexus constitutes the intraneural vascular territory of the CNS vasculature. Figure B is reproduced from rapid Golgi preparations of the cerebral cortex of a 32 week gestation infant. Magnifications: upper x800; lower x75.
Fig 2.13 Schematic drawings demonstrating the mature lamellar composition and structural organization of the meningeal, the Virchow-Robin and the perivascular glial compartments of the cerebral cortex. Also illustrated are their corresponding vascular territories, namely: the perineural, the interneural, and the intraneural, respectively. The blood vessels of the perineural (meningeal) and interneural (Virchow-Robin) territories are enclosed within specific perivascular tissue compartments, while those of the intraneural vascular territory are enclosed by perivascular glia. The Virchow-Robin space closes off with the fusion of the vascular and the CNS basal laminae into a single lamina which accompanies the penetrating capillary into the neural tissue proper. The obliteration of the pial (P) space at the entrance of the Virchow-Robin compartment is also illustrated. D = dura mater, NT = neurothelium, EA = external arachnoid lamella, IA = inner arachnoid, lamella, EP = external pia lamella, IP = inner pia lamella, GL = marginal glia, P = pial space, ICR = intercellular compartments. The insert shows the vascular basal lamina and its relationship to the meningeal, Virchow-Robin and perivascular glial compartments, respectively, as well as the location of the various intercellular tissue compartments. (From Krisch, B., H. Leonhardt, A. Oksche: Cell. Tiss. Res. 238: 459, 1984.)
Fig 2.14 Composite figure illustrating the three territories of the vasculature of the human cerebral cortex during embryonic development. 1 External view of the cerebral cortex of a 20 week human fetus illustrating the vasculature of its perineural (meningeal) vascular territory. The numerous anastomoses formed by these vessels throughout the surface of the cerebral cortex are clearly illustrated as well as some of the cortical arteries (A) and veins (V). Between the larger vessels there are many smaller ones which are difficult to appreciate at this magnification because of their small size. They are the components of the pial vascular plexus which cover the entire surface of the cerebral cortex. 3 Perpendicular section of the cerebral cortex of a 24 week human fetus in which the arterial system has been previously injected. It illustrates the main structural features of the perforating cortical arterioles. These perforating cortical arterioles originate from the pial vascular plexus (visible at top right), are within the Virchow-Robin compartment and reach considerable depths into the, cortex. They are characterized by their vertical orientation, perpendicular to the cortical surface, and by their sinuous course within the VRCs. The rectangular region outlined in this figure has been enlarged and is depicted in 2, to illustrate more clearly the numerous intracortical capillaries which originate from the arterioles of four contiguous VRCs. These capillaries penetrate into the cortical tissue at different levels and form an extensive anastomotic plexus which constitutes the intraneural vascular territory of the CNS vasculature. 4 Illustrates a perpendicular section of the cerebral cortex of a 29 week human fetus in which the venous system has been previously injected. The overall distribution and structural features of the cortical venules (bluish to purple vessels) are similar to those of the cortical arterioles. They are within the VRCs and hence they are components of the interneural vascular territory of the CNS. These cortical venules are directly connected with the intracortical capillary plexus which is barely discernible in this illustration. (2,3,4 from Pape, K. E., J. S. Wigglesworth: Haemorrhage, Ischaemiaand the Perinatal Brain. Lavenham, Suffolk 1979.)
Conclusions
The embryonic vascularization of the CNS is characterized by the sequential development of three independent, though interrelated, vascular territories. In order of appearance and development they are: the perineural, the interneural and the intraneural vascular territories (Table 2.2). Embryologically, each vascular territory evolves and remains within a distinct and specific tissue compartment, namely: the meningeal, the Virchow-Robin and the perivascular glial tissue compartment, respectively. In the course of embryonic development, the vasculature of each of these territories undergoes an integrated metamorphosis, continuously adapting to the growing structural and functional needs of each particular region of the developing CNS. This progressive vascular metamorphosis is the result of continuous remodelling of the original anastomotic plexuses in which both capillary angiogenesis and capillary reabsorption are active processes. The three vascular territories and the different and specific types of vessels that characterize each one can be easily recognized at any time in the course of embryonic development (Fig 2.14).
The separation of the CNS vasculature into three different and specific vascular territories and associated tissue compartments implies significant structural as well as functional differences among them. Undoubtedly, a clear understanding of these structural and functional differences is important and relevant both to the clinician and the neurosurgeon. In this context, it is interesting that only the intraneural capillaries and associated perivascular glia (intraneural vascular territory) are actually involved in the so-called blood-brain barrier, since the meningeal and the Virchow-Robin vasculatures actually evolve and remain outside of the CNS substance.
B. Vascular Malformation of the Central Nervous System. Embryological Considerations
A study of the early embryogenesis of the CNS vasculature would be incomplete without some comments concerning the possible origin and nature of the malformations affecting its different vessels. In spite of considerable individual variations most vascular anomalies of the CNS can be classified in one of the following three basic types (Russell and Rubinstein 1977):
– Capillary telangiectasias and cavernous angiomas.
– Venous and arteriovenous malformations.
– Sturge-Weber-Dimitri’s disease.
Most investigators agree that these vascular anomalies represent developmental malformations rather than angiomas or true vascular neoplasms (Aronson 1971, Dudley 1982, Larroche 1983, McCormick 1966, 1983, Russell and Rubinstein 1977).
Morphologically, these vascular anomalies often resemble the embryonic vessels and the early anastomotic plexuses formed during the early stages of the vascularization of the CNS (Streeter 1918, Padget, 1948, 1957; see Chapter: Embryogenesis of the Early Vascularization of the Central Nervous System). However, few attempts have been made to correlate the various types of vascular malformations with the vasculogenesis of the CNS. The three basic types of vascular malformations will be correlated herein with the embryonic development of specific types of vessels, vascular territories, pericellular tissue compartments; and, regions of the CNS.
Prior to undertaking such a developmental study it is necessary to establish some general facts concerning the natural history and clinical behavior of the vascular malformations of the CNS. First of all, it is important to recognize that these vascular malformations are not static entities but quite dynamic ones. They are constantly subject to circulatory mechanical forces and to a variety of pathologic alterations which progressively transform them into complex vascular anomalies which are often difficult to understand or to explain adequately. Secondly, most vascular malformations of the CNS become clinical entities and hence, brought to the attention of neurosurgeons and neuropathologists when they have either bled, ruptured, or thrombosed. Therefore, most of them are already transformed by the time they are removed surgically or studied pathologically. It should be of great significance in the study of these malformations to be able to distinguish and to separate their primary or original features from the secondary or acquired ones.
Any pathologic alteration (rupture, hemorrhage or thrombosis) of a vascular malformation will not only transform the affected vessels but the surrounding tissue as well. A reparative inflammatory process will take place around the affected vessels resulting in fibrosis and or gliosis and more importantly in the obliteration of the perivascular tissue compartment which originally surrounded the vascular malformation. The secondary obliteration of the perivascular tissue compartment could lead to confusion about the original location of the malformation and the CNS vascular territory originally involved. Furthermore, the inflammatory process around injured vessels of the original malformation will result in the formation of many new or secondary vessels. The presence of postinflammatory vessels should be recognized because they could also obscure the original architecture of the vascular anomaly.
The recognition of these facts is important because in the interpretation any type of vascular malformation of the CNS the following aspects must be clearly established: a) type of vessels originally affected; b) vascular territory and perivascular tissue compartment originally involved; and, c) original location of the anomaly. The establishment of these facts is sine qua non for the understanding of the nature of these vascular malformations as well as for the selection of the most adequate method for their neurosurgical removal.
During the early vascularization of the CNS three distinct vascular territories evolve sequentially. These have been named: perineural, interneural, and intraneural vascular territories respectively, because of their specific relationship to the nervous tissue (see Chapter: Embryogenesis of the Early Vascularization of the Central Nervous System). Each of these three vascular territories is characterized by distinct types of vessels and most importantly by a specific perivascular tissue compartment. These compartments are: the meningeal, the Virchow-Robin, and the perivascular glia, respectively. The three basic types of vascular malformations of the CNS will be analyzed separately and correlated embryologically with the vessels of its different vascular territories and tissue compartments.
Capillary Telangiectasias and Cavernous Angiomas
Capillary telangiectasias are small vascular malformations composed solely of abnormally dilated capillaries. They vary greatly in caliber and saccular or fusiform dilatations are common. They lack an anomalous arterial supply and their venous drainage may be dilated but not abnormally so. The actual number of capillaries may not be increased in these malformations. The overlying pia mater and arachnoid are normal. The intervening tissue between the dilated capillaries is normal and both glial and neuronal elements are recognized in it. These vascular anomalies are frequently found in the pons, the cerebral cortex, the cortical white mater and rarely in the spinal cord. Capillary telangiectasias rarely show pathologic alterations such as hemorrhages, thromboses or ruptures. Therefore, they are usually clinically silent and most are found by chance at autopsies. Embryologically, these are vascular malformations which involve only the capillaries of the intraneural vascular territory of the CNS and should be enclosed within the perivascular glial tissue compartment.
Cavernous angiomas are large vascular malformations composed of cystic vascular spaces lined by a single layer of endothelial cells. These vascular spaces vary greatly in size and are often very irregular suggesting secondary changes. The vascular spaces of these malformations probably represent abnormal capillaries since no recognizable arteries or veins are found in them. These vascular spaces are structurally similar to those found in capillary telangiectasias. These vascular malformations may be circumscribed but not encapsulated and could be lobulated. Like telangiectasias, they lack either abnormal arterial supply or abnormal venous drainage. They are found in the cerebral cortex, the pons and rarely in the spinal cord.
Cavernous angiomas invariably show areas of thromboses with subsequent organization, recent and old hemorrhages with hemosiderin laden macrophages, fibrosis and or gliosis, focal calcification and even areas with bone formation. The overlying pia mater and arachnoids are stained, thickened and fibrosed. All of these changes are obviously the result of pathological (secondary) alterations. There is no normal nervous tissue between the abnormal vessels in these malformations, probably because it has been progressively destroyed. Eliminating the prominent acquired pathologic changes, cavernous angiomas could represent large telangiectasias, an idea which has been often expressed previously (Russell 1931, Russell and Rubinstein 1977).
Embryologically, cavernous angiomas can only be large vascular malformations involving the capillaries of the intraneural vascular territory of the CNS since no distinct arteries or veins have been recognized in them. They could represent large capillary telangiectasias with a greater propensity to undergo pathologic alterations. These alterations will result in the complete obliteration of the perivascular glial compartment and in the progressive reactive fibrosis and gliosis of the intervening nervous tissue causing its complete destruction. The neurosurgical treatment of cavernous angiomas will necessarily involve the removal of some of the normal nervous tissue around the malformation.
Venous and Arteriovenous Malformations
Venous malformations are vascular anomalies composed solely of abnormally dilated and tortuous veins. They may be composed of a single greatly dilated and tortuous vein or of small number of them. They involve primarily the pia-arachnoidal veins and few of its intramedullary tributaries. They can be located in the spinal cord, and occasionally in the drainage territories of the vein of Galen and of the cerebellum.
Secondary pathologic alterations including muscular hypertrophy and or hyalinization (fibrosis) of the vessel wall, and thromboses with subsequent organization are frequent findings in these malformations. However, more important alterations are those caused by the compression of the spinal cord by the anomalous veins, and the compression of the nervous tissue by the dilated intramedullary tributary veins. Cord atrophy and ischemic changes are often sequelae in long standing cases.
Embryologically, venous malformations are developmental anomalies which involve primarily the veins of the perineural vascular territory of the meningeal (pia-arachnoid) tissue compartment, and also some tributary veins of the interneural vascular territory of the Virchow-Robin tissue compartment. Therefore, uncomplicated venous malformations should be entirely outside the nervous tissue proper and hence liable to their complete microneurosurgical removal. On the other hand, secondary pathological alterations affecting these venous malformation will result in the obliteration of their perivascular tissue compartments making their neurosurgical treatment more difficult requiring the removal of some of the surrounding unaffected nervous tissue.
Arteriovenous malformations are large and complex vascular anomalies composed of abnormally developed arteries and veins. They involve primarily the vessels of the leptomeninges with extension into the fissures and sulci. They could also involve deeper vascular territories of the cortex, midbrain, cerebellum and choroid plexuses. These vascular malformations are also characterized by the participation of regional perforating vessels which could also be abnormally developed, tortuous and dilated. The presence and location of the abnormal perforating vessels should always be explored because they could be the cause of serious damage to the nervous parenchyma and must be treated adequately during the microneurosurgical removal of the malformation. The main arteries and veins leading to and from the malformation are usually dilated and a secondary collateral circulation could be prominent in some of them.
Arteriovenous malformations are subject to pathologic alterations including: ruptures, hemorrhages, thrombosis, atrophy, and progressive reparative fibrosis and or gliosis. The arachnoid around the malformation as well as the underlying or adjacent nervous tissue show rusty pigmentation and fibrosis or gliosis. Microscopic examination of both the arteries and the veins of these malformation show abnormalities involving their elastic and muscular elements. Some vessels also show atheromas, organized thrombus, focal calcifications and postinflammatory fibrosis or gliosis.
Embryologically, these malformations involve: a) vessels (arteries and veins) from the perineural vascular territory of the CNS within the meningeal tissue compartment; and b) some perforating or emerging vessels (arterioles or venules) from the interneural vascular territory within the Virchow-Robin tissue compartment. Therefore, unaffected arteriovenous malformations should lie outside of the nervous tissue proper and should be liable to complete removal by microneurosurgery. On the other hand, in arteriovenous malformations which have undergone pathologic alterations, the meningeal and Virchow-Robin perivascular compartments might be obliterated making their microneurosurgical treatment more difficult since it must involve the removal of the surrounding nervous tissue.
Sturge-Weber-Dimitri’s Disease
This congenital vascular malformation is characterized by an increase in the number of capillaries and of few small veins throughout the affected pia mater and underlying surface of the cerebral cortex. This extensive capillary-venous cerebral malformation is associated with a homolateral cutaneous angioma over the trigeminal nerve distribution. This vascular malformation is also characterized by significant pathologic alterations, severe damage to the nervous parenchyma, and abundant mineral granular deposition of calcium and iron.
While a pial capillary plexus is a prominent feature during the embryonic vascularization of the CNS, the adult cortical pia mater either lacks or has very few capillaries (Duvernoy et al. 1981). Embryologically, the persistence of the embryonic pial vascular plexus with its numerous connections to the superficial cortical vasculature could explain this type of vascular malformation. There is no adequate neurosurgical treatment for this fortunately rare condition.
