which grows from the aortic sac. It terminates by dividing into man- together with branches from the tela choroidea, they give rise to ven-
dibular and maxillary branches. triculofugal arteries, which supply the ventricular zone (germinal matrix
of the brain) and send branches towards the cortex. The ventriculopetal
Leptomeningeal arteries
and ventriculofugal arteries run towards each other but they do not
At stage 20–23 (7–8 weeks), further expansion of the cerebral hemi- make any connections or anastomoses; the ventriculopetal arteries form
spheres produces the completion of the circle of Willis; the anterior networks of small arterioles (see Fig. 17.35). The ventriculopetal vessels
communicating arteries develop by 8 weeks’ gestation. An anular supply relatively more mature regions of the brain compared to the
network of leptomeningeal arteries, originating mainly from each ventriculofugal vessels, which are subject to constant remodelling and
middle cerebral artery, passes over each developing cerebral hemi- do not develop tunicae mediae until ventricular zone proliferation is
sphere. Caudally, similar meningeal branches arise from the vertebral completed. The boundary zone between these two systems (an outer
and basilar arteries and embrace the cerebellum and brainstem. The centripetal and inner centrifugal) has practical implications related to
further development of the telencephalon somewhat obscures this early the location of ischaemic lesions (periventricular leukomalacia, PVL) in
pattern over the cerebrum. the white matter of premature infant brains. Although it was believed
The meningeal arteries so formed have been classified into three that the distribution of ischaemic lesions in PVL coincided with the
groups: namely, paramedian, short circumferential and long circumfer- demarcation zone between the centrifugal and centripetal vascular arte-
ential arteries. They can be described both supratentorially and infraten- rial systems, this is now not thought to provide the complete answer.
torially, and all give off fine side branches and end as penetrating A number of major interacting factors contribute to the pathology seen
arteries. Of the supratentorial vessels, the paramedian arteries have a in PVL: the incomplete state of development of the vasculature in the


short course prior to penetrating the cerebral neuropil (e.g. branches of ventricular zone, the maturation-dependent impairment of cerebral
the anterior cerebral artery); the short circumferential arteries have a blood flow regulation in premature infants, the vulnerability of oligo-
slightly longer course before becoming penetrating arteries (e.g. the dendroblasts in the periventricular region (which are particularly
striate artery); and the long circumferential arteries reach the dorsal affected by swings in cerebral ischaemia and reperfusion) and prenatal
surface of the hemispheres. Infratentorial meningeal arteries are very systemic infection and inflammation (Volpe 2001, Volpe et al 2011).
variable. The paramedian arteries, after arising from the basilar or ver- The same pattern of centripetal and centrifugal arteries develops
tebral arteries, penetrate the brainstem directly. The short circumferen- around the fourth ventricle. The ventriculofugal circulation is more
tial arteries end at the lateral surface of the brain before penetration extensive in the cerebellum than in the telencephalon. The arteries arise
and the long circumferential arteries later form the range of cerebellar from the various cerebellar arteries and course, with the cerebellar
arteries. These vessels, arranged as a series of loops over the brain, peduncles, directly to the centre of the cerebellum, bypassing the cortex.
arise from the circle of Willis and brainstem vessels on the base of The ventriculopetal arteries are derived from the meningeal vessels over
the brain. the cerebellar surface, and most terminate in the white matter.
At 16 weeks’ gestation, the anterior, middle and posterior cerebral At 24 weeks’ gestation, the blood supply to the basal nuclei and
arteries that contribute to the formation of the circle of Willis are well internal capsule is relatively well developed, via a prominent Heubner’s
established. The leptomeningeal arteries arising from them display a artery (arteria recurrens anterior), a branch of the anterior cerebral
simple pattern with little tortuosity and very few branches. With the artery. In contrast, the cortex and the white matter regions are rather
increasing age of the fetus and acquisition of the gyral pattern on the poorly vascularized at this stage. The distribution of arteries and veins


surface of the brain, their tortuosity, diameter and number of branches on the lateral aspect of the cerebral hemispheres is affected by the for-
all increase. The branching pattern is completed by 28 weeks’ gestation mation of the lateral fissure and development of cerebral sulci and gyri.
and the number of branches does not increase further. Numerous anas- Between 12 and 20 weeks’ gestation, the middle cerebral artery and its
tomoses (varying in size from 200 to 760 µm) occur between the branches are relatively straight, branching in an open-fan pattern. At
meningeal arteries in the depths of the developing sulci, nearly always the end of 20 weeks, the arteries become more curved as the opercula
in the cortical boundary zones of the three main cerebral arteries sup- begin to appear and submerge the insular cortex. The area supplied by
plying each hemisphere. The number, diameter and location of these the middle cerebral artery becomes dominant when compared to the
anastomoses change as fetal growth progresses, reflecting the regression territories supplied by the anterior and posterior cerebral arteries. Early
and simplification of the complex embryonic cerebral vascular system. arterial anastomoses appear around 16 weeks’ gestation and increase in
The boundary zones between the cerebral arteries may be the sites of size with advancing age. The sites of anastomoses between the middle
inadequate perfusion in the premature infant. and anterior cerebral arteries move from the convexity of the brain


DEvEloPmENT of THE NERvous sysTEm
268
3
NoITCEs
A B Fig. 17.35 Development of cerebral blood
vessels. A, The brain is surrounded by a
system of leptomeningeal arteries from afferent
Periventricular border area
trunks at its base. Intracerebral arteries
arise from this system and converge
Ventriculofugal arteries (ventriculopetally) towards the ventricle (the
inner circle in this diagram). B, A few deep,
penetrating vessels supply the brain close to
Ventriculopetal arteries
the ventricle and send ventriculofugal arteries
towards the ventriculopetal vessels without
making anastomoses. C, The arrangement of
ventriculopetal and ventriculofugal vessels
around a cerebral hemisphere. D, The similar
arrangement of vessels around the cerebellum.
E, Changes in the arterial pattern of the human
cerebrum between 24 and 34 weeks’ gestation.
F, Arterial supply to the basal nuclei at
C D 30 weeks’ gestation. (A–D, With permission
Leptomeningeal arteries from Van den Bergh R, Van der Eecken H
1968 Anatomy and embryology of cerebral
circulation. Prog Brain Res 30: 1–25; E–F, With
Cortical branches
permission from the BMJ Publishing Group
from Hambleton G, Wigglesworth J S 1976
Medullary branches Origin of intraventricular haemorrhage in the
preterm infant. Arch Dis Child 51: 651–659.)
Ventriculofugal arteries
from striate arteries
Ventriculofugal arteries
from dentate nucleus artery
Internal carotid artery Basilar artery
E F
Ventriculopetal X Anterior choroidal artery
arteries
Striate branches
X of middle cerebral
artery
Ventriculofugal arteries Heubner’s artery
24 weeks 34 weeks 30 weeks Section X–X
towards the superior sagittal sinus. Anastomotic connections between ischaemic injury in the immature infant because of its unusual vascular


the middle and posterior cerebral arteries shift towards the basal aspect architecture. The subependymal veins (septal, choroidal, thalamostriate
of the brain. and posterior terminal) flow towards the interventricular foramen.
By 32–34 weeks, marked involution of the ventricular zone (germi- There is a sudden change of flow at the level of the foramen, and the
nal matrix) has occurred and the cortex acquires its complex gyral veins recurve at an acute angle to form the paired internal cerebral veins.
pattern and an increased vascular supply. Ventricular zone capillaries The capillary channels in the germinal matrix open at right angles
are gradually remodelled to blend with the capillaries of the caudate directly into the veins, and it has been postulated that these small
nucleus. Heubner’s artery eventually supplies only a small area at the vessels may be points of vascular rupture and the site of subependymal
medial aspect of the head of the caudate nucleus. In the cortex, there haemorrhage.
is progressive elaboration of cortical blood vessels (see Fig. 17.35), and The capillary bed in the ventricular zone is supplied mainly by
towards the end of the third trimester, the balance of cerebral circula- Heubner’s artery and terminal branches of the lateral striate arteries
tion shifts from one that is central and basal nuclei-orientated, to one from the middle cerebral artery. The highly cellular structure of the
that predominantly serves the cortex and white matter. These changes ventricular zone is a temporary feature, and the vascular supply to this
in the pattern of cerebral circulation are of major significance in the area displays some primitive features; it has the capacity to remodel
pathogenesis and distribution of hypoxic/ischaemic lesions in the when the ventricular zone cells migrate and the remaining cells dif-
developing human brain. In a premature brain, the majority of ischae- ferentiate as ependyma towards the end of gestation.
mic lesions occur in the boundary zone between the centripetal and Vessel density is relatively low in the ventricular zone, suggesting that
centrifugal arteries, i.e. in the periventricular white matter, whereas, in this area may normally have a relatively low blood flow. Immature
a full-term infant, the cortical boundary zones and watershed areas vessels, without a complex basal lamina or glial sheet, have been


between different arterial blood supplies are similar to those in adults, described at up to 26 weeks’ gestation in the zone; the endothelium of
and so, presumably, are the risks of ischaemic lesion. these vessels is apparently thinner than in the cortical vessels. In infants
of less than 30 weeks’ gestation, the vessels in the ventricular zone
vessels of the ventricular zone (germinal matrix) contain no smooth muscle, collagen or elastic fibres. Collagen and
The germinal matrix (ventricular zone) is the end zone or border zone smooth muscle are seen in other regions after 30 weeks but are not
between the cerebral arteries and the collection zone of the deep cere- detected in the remains of the germinal matrix. The lack of these com-
bral veins. The germinal matrix is probably particularly prone to ponents could make the vessels in this zone vulnerable to changes in


vascular supply
269
71
RETPAHC
intraluminal pressure, and the lack of smooth muscle would preclude A
Middle dural stem Otocyst
them from participating in autoregulatory processes. Cerebral vessels in
premature infants lack elastic fibres and have a disproportionately small Anterior dural stem Primary head sinus
number of reticulin fibres. Comparison of the cortical and ventricular
zone blood vessels shows that, in infants of between 25 and 32
mwe oe nk ls y’ g oe fs ta 1t –io 2n e, nth de o w tha el ll is a o l f c v ee lls ss e wls i ti hn t ah ne g oe cr cm asi in oa nl a m l a pt er rix ic c yo ten , s ais nt dc o tm he- P mr aim xii lt laiv re y VIIVIII IX X Posterior
vein XI
capillary lumina are larger than those of the vessels in the cortex. In III V dural stem
more mature infants, the basal lamina surrounding germinal matrix XII
vessels is thicker and more irregular when compared to cortical vessels Intersegmental
veins
and it is deficient in fibronectin. The periventricular germinal matrix is
the site of origin of intraventricular haemorrhage in the premature
Precardinal
neonate. Rich vascularity and immaturity of the vessels within the vein
matrix predispose to haemorrhage. Immaturity of the germinal matrix
vasculature is indicated by circular cross-sectional shape of the vessels Postcardinal
compared with a flattened shape in the cerebral cortex (Ballabh 2010). vein
Glial fibrillary acidic protein-positive cells have been detected
around blood vessels in the germinal matrix from 23 weeks’ gestation.
Glial cells may contribute to changes in the nature of endothelial inter- Ventral pharyngeal vein Common cardinal vein
cellular junctions in brain capillaries.
Blood–brain barrier B Transverse sinus Sigmoid sinus
Barriers between the blood supply and neural tissue, neurovascular
units, function during development. Astrocytes are not required to Superior
induce the blood–brain barrier. Pericytes are required for endothelial– sagittal sinus IV
astrocyte barrier formation during development, and disruption of
III


pericyte–endothelial cell interaction may lead to barrier dysfunction. Tentorial
The ventricular zone operates a brain–cerebrospinal fluid barrier during sinus
development but not once the ventricular zone has ceased as a dividing
Pro-otic
layer and the cells have differentiated to form ependyma. The choroid XII
sinus
plexuses, sites of a blood–cerebrospinal fluid barrier, function during V
development, controlling paracellular transport to the cerebrospinal Superior Vertebral vein
fluid (Neuwelt et al 2011). ophthalmic
vein Remnants of
primordial
VEINS head sinus
Supraorbital vein
Cerebral veins Facial vein Internal
Retromandibular vein jugular vein
From 16 weeks onwards, cerebral veins can be identified. The superior,
middle, inferior, anterior and posterior cerebral veins appear more tor- Common cardinal vein Postcardinal vein
tuous than meningeal arteries. Veins draining the cortex, white matter
and deeper structures are recognized in the mid trimester. Subcortical
3 brain region 5 brain region
veins drain the deep white matter, deep cortical and subcortical super-
ficial tissue; they terminate together with cortical veins, which drain the Telencephalon
cortex, in the meningeal veins. The deep white matter and central nuclei Prosencephalon
are drained by longer veins that meet and join subependymal veins Diencephalon
from the ventricular zone. Anastomoses between various groups of
Mesencephalon Mesencephalon
cortical veins can be recognized by 16 weeks’ gestation. The inferior
anastomotic vein (of Labbé), an anastomosis between the middle cere-
Metencephalon
bral and inferior cerebral veins, becomes recognizable at 20 weeks, but Rhombencephalon
the superior anastomotic vein (of Trolard), connecting the superior and Myelencephalon
middle cerebral veins, does not appear before the end of 30 weeks.
Fig. 17.36 Successive stages in the development of the veins of the
Rapid cortical development is correlated with the regression of the
head and neck. A, At approximately 8 mm crown–rump length. B, At
middle cerebral vein and its tributaries, and development of ascending
approximately 24 mm crown–rump length.


and descending cortical veins and intraparenchymal (medullary) arter-
ies and veins.
Cerebral venous drainage in a full-term baby is essentially composed mater, from which the dural venous sinuses differentiate; vessels from
of two principal venous arrays, the superficial veins and the deep the plexus converge on each side into anterior, middle and posterior
Galenic venous system; anastomoses between these two systems persist dural stems (Fig. 17.36). The anterior stem drains the prosencephalon
into adult life. and mesencephalon, and enters the primary head vein rostral to the
trigeminal ganglion. The middle stem drains the metencephalon and
Veins of the head
empties into the primary head vein caudal to the trigeminal ganglion.
The posterior stem drains the myelencephalon into the start of the
The earliest vessels form a transitory primordial hindbrain channel, precardinal vein. The deepest capillary stratum is the pial plexus, from
which drains into the precardinal vein. This is soon replaced by the which the veins of the brain differentiate. It drains at the dorsolateral
primary head vein, which runs caudally from the medial side of the aspect of the neural tube into the adjacent dural venous plexus. The
trigeminal ganglion, lateral to the facial and vestibulocochlear nerves primary head vein also receives, at its cranial end, the primitive maxil-
and otocyst, and then medial to the vagus nerve, to become continuous lary vein, which drains the maxillary prominence and region of the
with the precardinal vein. An anastomosis to other, more lateral, venous optic vesicle.
channels developing over the hindbrain ultimately brings the primary The vessels of the dural plexus undergo profound changes, largely
head vein lateral to the vagus nerve. The cranial part of the precardinal accommodating the growth of the cartilaginous otic capsule of
vein forms the internal jugular vein. the membranous labyrinth and the expansion of the cerebral hemi-
The primary capillary plexus of the head is separated into three fairly spheres. As the otic capsule grows, the primary head vein is gradually
distinct strata by the differentiation of the skull and meninges. The reduced and a new channel, joining anterior, middle and posterior


superficial vessels drain the skin and underlying soft parts, and eventu- dural stems, appears dorsal to the cranial nerve ganglia and the capsule.
ally discharge in large part into the external jugular system, although The adult sigmoid sinus is formed where this channel joins the middle
they retain some connections with the deeper veins through so-called and posterior stems, together with the posterior dural stem itself (see
emissary veins. The next layer of vessels is the venous plexus of the dura Fig. 17.36B).


DEvEloPmENT of THE NERvous sysTEm
270
3
NoITCEs
A curtain of capillary veins, the sagittal plexus, forms between the sinus. The cranial part of the primary head vein, medial to the trigemi-
growing cerebral hemispheres and along the dorsal margins of the nal ganglion, persists and still receives the stem of the primitive maxil-
anterior and middle plexuses, in the position of the future falx cerebri. lary vein. The latter has now lost most of its tributaries to the anterior
Rostrodorsally, this plexus forms the superior sagittal sinus. It is con- facial vein, and its stem becomes the main trunk of the primitive
tinuous behind with the anastomosis between the anterior and middle supraorbital vein, which will form the superior ophthalmic vein of the
dural stems, which forms most of the transverse sinus. Ventrally, the adult. The main venous drainage of the orbit and its contents is now
sagittal plexus differentiates into the inferior sagittal and straight sinuses carried via the augmented middle dural stem, the pro-otic sinus, into
and the great cerebral vein; it commonly drains into the left transverse the transverse sinus and, at a later stage, into the cavernous sinus. The
sinus. cavernous sinus is formed from a secondary plexus derived from the
The vessels along the ventrolateral edge of the developing cerebral primary head vein and lying between the otic and basioccipital carti-
hemisphere form the transitory tentorial sinus, which drains the convex lages. The plexus forms the inferior petrosal sinus, which drains through
surface of the cerebral hemisphere and basal ganglia, and the ventral the primordial hindbrain channel into the internal jugular vein. The
aspect of the diencephalon, into the transverse sinus. With expansions superior petrosal sinus arises later from a ventral metencephalic tribu-
of the cerebral hemispheres and, in particular, the emergence of the tary of the pro-otic sinus and it communicates secondarily with the
temporal lobe, the tentorial sinus becomes elongated and attenuated, cavernous sinus. The pro-otic sinus, meanwhile, has developed a new


eventually disappearing; its territory is drained by enlarging anastomo- and more caudally situated stem, the petrosquamosal sinus, which
ses of pial vessels that become the basal veins, radicles of the great drains into the sigmoid sinus. With progressive ossification of the skull,
cerebral vein. the pro-otic sinus becomes diploic in position.
The anterior dural stem disappears and the caudal part of the primary The development of the venous drainage and portal system of the
head vein dwindles; it is represented in the adult by the inferior petrosal hypophysis cerebri is closely associated with that of the venous sinuses.
KEY REFERENCES
Allen MC, Capute AJ 1990 Tone and reflex development before term. Huang H, Vasung L 2014 Gaining insight of fetal brain development with
J Pediatr 85:393–9. diffusion MRI and histology. Int J Dev Neurosci 32:11–22.
Details of the development of reflexes in extremely premature infants. Details of the structural development of major components of the fetal
brain, derived from DTI and histology, that may provide reference standards
Begbie J, Graham A 2001 The ectodermal placodes: a dysfunctional family.
for use in the diagnostic radiology of premature newborns.
Philos Trans R Soc Lond B Biol Sci 356:1655–60.
An account that challenges the view of ectodermal placodes as a coherent Rakic P 2009 Evolution of the neocortex: a perspective from developmental
group and discusses their early development, induction and evolution. biology. Nat Rev Neurosci 10:724–35.
This article reviews differences in gene expression, molecular pathways and
Bystron I, Blakemore C, Rakic P 2008 Development of the human cerebral
novel cellular interactions in the embryonic cerebral cortex in different
cortex: Boulder Committee revisited. Nat Rev Neurosci 9:110–22.
mammalian species.
A review of current data on the development of the human cerebral cortex
and an update of the classical model.
Hansen DV, Lui JH, Flandin P et al 2013 Non-epithelial stem cells and corti-
cal interneuron production in the human ganglionic eminences. Nature
Neurosci 16:1576–87.


Presents evidence for the tangential migration of cortical neurones.


Development of the nervous system
270.e1
71
RETPAHC
REFERENCES
Allen MC, Capute AJ 1990 Tone and reflex development before term. Hoerder-Suabedissen A, Molnar Z 2015 Development, evolution and
J Pediatr 85:393–9. pathology of neocortical subplate neurons. Nature Rev Neurosci 16:
Details of the development of reflexes in extremely premature infants. 133–46.
Ashwell KW, Mai JK 2012 Fetal development of the central nervous system. Huang H, Vasung L 2014 Gaining insight of fetal brain development with
In: Mai JK, Paxinos G (eds) The Human Nervous System. London: diffusion MRI and histology. Int J Dev Neurosci 32:11–22.
Elsevier; Ch. 3, pp. 31–79. Details of the structural development of major components of the fetal
brain, derived from DTI and histology, that may provide reference standards
Ashwell KW, Waite PM 2012 Development of the peripheral nervous system.
for use in the diagnostic radiology of premature newborns.
In: Mai JK, Paxinos G (eds) The Human Nervous System. London:
Elsevier; Ch. 2, pp. 14–30. Huang H, Zhang J, Wakana S et al 2006 White and gray matter development
Back SA, Luo NL, Borenstein NS et al 2001 Late oligodendrocyte progenitors in human fetal, newborn and pediatric brains. Neuroimage 33:27–38.
coincide with the developmental window of vulnerability for human Huang H, Xue R, Zhang J et al 2009 Anatomical characterization of human
perinatal white matter injury. J Neurosci 21:1302–12. fetal brain development with diffusion tensor magnetic resonance
Ballabh P 2010 Intraventricular hemorrhage in premature infants: mecha- imaging. J Neurosci 29:4263–73.
nism of disease. Pediatr Res 67:1–8. Jakovcevski I, Filipovic R, Mo Z et al 2009 Oligodendrocyte development
Barson AJ 1970 The vertebral level of termination of the spinal cord during and the onset of myelination in the human fetal brain. Front Neuroanat


normal and abnormal development. J Anat 106:489–97. 3:5.
Bay SN, Caspary T 2012 What are those cilia doing in the neural tube? Cilia Jantzie LL, Corbett CJ, Firl DJ et al 2014 Postnatal erythropoietin mitigates
1:19. impaired cerebral cortical development following subplate loss from
prenatal hypoxia-ischemia. Cereb Cortex. doi: 10.1093/cercor/bhu066
Begbie J, Graham A 2001 The ectodermal placodes: a dysfunctional family.
(ePub ahead of print).
Philos Trans R Soc Lond B Biol Sci 356:1655–60.
An account that challenges the view of ectodermal placodes as a coherent Kalil K, Li L, Hutchins BI 2011 Signaling mechanisms in cortical axon
group and discusses their early development, induction and evolution. growth, guidance, and branching. Front Neuroanat 5:62.
Kanold PO, Luhmann HJ 2010 The subplate and early cortical circuits. Annu
Bjuland KJ, Løhaugen GC, Martinussen M et al 2013 Cortical thickness and
Rev Neurosci 33:23–48.
cognition in very-low-birth-weight late teenagers. Early Hum Dev 89:
371–80. Kolb B, Mychasiuk R, Muhammad A et al 2013 Brain plasticity in the devel-
oping brain. Prog Brain Res 207:35–64.
Bystron I, Blakemore C, Rakic P 2008 Development of the human cerebral
cortex: Boulder Committee revisited. Nat Rev Neurosci 9:110–22. Kolodkin A, Tessier-Lavigne M 2013 Growth cones and axon pathfinding.
A review of current data on the development of the human cerebral cortex In: Squire LR, Berg D, Bloom FE et al (eds) Fundamental Neuroscience,
and an update of the classical model. 4th ed. London: Elsevier; Ch. 16, pp. 363–84.
Kostovic I, Jovanov-Milosevic N, Rados M et al 2012 Perinatal and early
Cang J, Feldheim DA 2013 Developmental mechanisms of topographic map


postnatal reorganization of the subplate and related cellular compart-
formation and alignment. Annu Rev Neurosci 36:51–77.
ments in the human cerebral wall as revealed by histological and MRI
Chiu H, Alqadah A, Chang C 2013 The role of microRNAs in regulating approaches. Brain Struct Funct 219:231–53.
neuronal connectivity. Front Cell Neurosci 7:283.
Kriegstein AR, Gotz M 2003 Radial glia diversity: a matter of cell fate. Glia
Cirulli F, Alleva E 2009 The NGF saga: from animal models of psychosocial 432:37–43.
stress to stress-related psychopathology. Front Neurosci 30:379–95.
Kriegstein AR, Noctor SC 2004 Patterns of neuronal migration in the embry-
da Silva S, Wang F 2011 Retrograde neural circuit specification by target- onic cortex. Trends Neurosci 27:392–9.
derived neurotrophins and growth factors. Curr Opin Neurobiol 21:
Krumlauf R, Marshall H, Studer M et al 1993 Hox homeobox genes and
61–7.
regionalisation of the nervous system. J Neurobiol 24:1328–40.
Dodd J, Jessell TM, Placzek M 1998 The when and where of floor plate
Lavezzi AM, Ottavianni G, Terni L et al 2006 Histological and biological
induction. Science 282:1654–57.
developmental characterization of the human cerebellar cortex. Int J
Dubois J, Dehaene-Lambertz G, Kulikova S et al 2014 The early development Dev Neurosci 24:365–71.
of brain white matter: a review of imaging studies in fetuses, newborns
Lee JH, Gleeson JG 2010 The role of primary cilia in neuronal function.
and infants. Neuroscience 276:48–71.
Neurobiol Dis 38:167–72.
Eiraku M, Sasai Y 2012 Self-formation of layered neural structures in three-
Lister R, Mukamel EA, Nery JR et al 2013 Global epigenomic reconfiguration
dimensional culture of ES cells. Curr Opin Neurobiol 22:768–77.


during mammalian brain development. Science 341:1237905.
Eyre JA 2007 Corticospinal tract development and its plasticity after peri-
Lodygensky GA, Vasung L, Sizonenko SV et al 2010 Neuroimaging of cortical
natal injury. Neurosci Biobehav Rev 31:1136–49.
development and brain connectivity in human newborns and animal
Fietz SA, Huttner WB 2011 Cortical progenitor expansion, self-renewal and models. J Anat 217:418–28.
neurogenesis – a polarized perspective. Curr Opin Neurobiol 21:
Lui JH, Hansen DV, Kriegstein AR 2011 Development and evolution of the
23–35.
human neocortex. Cell 146:18–36.
Gao W, Lin W, Chen Y et al 2009 Temporal and spatial development of
Manto MU, Jissendi P 2012 Cerebellum: links between development, devel-
axonal maturation and myelination of white matter in the developing
opmental disorders and motor learning. Front Neuroanat 6:1–10.
brain. Am J Neuroradiol 30:290–6.
Martinez S, Andreu A, Mecklenburg N et al 2013 Cellular and molecular
Geschwind DH, Rakic P 2013 Cortical evolution: judge the brain by its cover.
basis of cerebellar development. Front Neuroanat 7:18.
Neuron 80:633–47.
Ment LR, Sould JS 2012 Injury to the developing preterm brain: intraven-
Gomez TM, Letourneau PC 2014 Actin dynamics in growth cone motility
tricular hemorrhage and white matter injury. In: Swaiman K, Ashwal S,
and navigation. J Neurochem 129:221–34.
Ferriero DM et al (eds) Swaiman’s Pediatric Neurology: Principles and
Hansen DV, Lui JH, Flandin P et al 2013 Non-epithelial stem cells and corti- Practice, 5th ed. London: Elsevier; Ch. 19, pp. 77–99.
cal interneuron production in the human ganglionic eminences. Nature
Métin C, Baudoin JP, Rakic S et al 2006 Cell and molecular mechanisms


Neurosci 16:1576–87.
involved in the migration of cortical interneurones. Eur J Neurosci 23:
Presents evidence for the tangential migration of cortical neurones.
894–900.
Harris KD 2008 Stability of the fittest: organizing learning through retro- Miller DJ, Duka T, Stimpson CD et al 2012 Prolonged myelination in human
axonal signals. Trends Neurosci 31:130–6. neocortical evolution. PNAS Science Sessions 109:16480–5.
Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL et al 2012 An anatomically Mitew S, Hay CM, Peckham H et al 2013 Mechanisms regulating the devel-
comprehensive atlas of the adult human brain transcriptome. Nature opment of oligodendrocyte and central nervous system myelin. J Neu-
489:391–9. rosci 276:29–47.
Higginbotham H, Guo J, Yokota Y et al 2013 Arl13b-regulated cilia activities Miyata T, Kawaguchi D, Kawaguchi A et al 2010 Mechanisms that regulate
are essential for polarized radial glial scaffold formation. Nat Neurosci the number of neurons during mouse neocortical development. Curr
16:1000–7. Opin Neurobiol 20:22–28.


DEvEloPmENT of THE NERvous sysTEm
270.e2
3
NoITCEs
Molnar Z, Butt SJB 2013 Best-laid schemes for interneuron origin of mice Sasai Y, Eiraku M, Suga H 2012 In vitro organogenesis in three dimensions:
and men. Nature Neurosci 16:1512–14. self-organising stem cells. Development 139:4111–21.
Molnar Z, Rutherford M 2013 Brain maturation after preterm birth. Sci Sawamoto K, Wichterle H, Gonzalez-Perez O et al 2006 New neurons follow
Transl Med 5:168ps2. the flow of cerebrospinal fluid in the adult brain. Science 311:629–632.
Müller F, O’Rahilly R 1997 The timing and sequence of appearance of neu- Sessa A, Mai C, Colasante G et al 2010 Tbr-2 positive intermediate (basal)
romeres and their derivatives in staged human embryos. Acta Anat neuronal progenitors safeguard cerebral cortex expansion by controlling
(Basel) 158:83–99. amplification of pallial glutamatergic neurons and attraction of subpal-
Neiva FC, Leone CR, Leone C et al 2014 Non-nutritive sucking evaluation lial GABAergic interneurons. Genes Dev 24:1816–26.
in preterm newborns and the start of oral feeding: a multicenter study. Siegenthaler JA, Pleasure SJ 2011 We have got you ‘covered’: how the menin-
Clinics (Sao Paulo, Brazil) 69:393–7. ges control brain development. Curr Opin Genet Dev 21:249–55.
Neuwelt EA, Bauer B, Fahlke C et al 2011 Engaging neuroscience to advance Spemann H, Mangold H 1924 Über die Induktion von Embryonalanlagen
translational research in blood brain barrier biology. Nat Rev Neurosci durch Implantation artfremder Organisatoren. W. Roux’ Arch. f. Entw.
12:169–82. d. Organis. u. mikrosk. Anat. 100:599–638.


Noctor SC, Martínez-Cerdeño V, Ivic L et al 2004 Cortical neurons arise in Sun T, Hevner RF 2014 Growth and folding of the mammalian cerebral
symmetric and asymmetric division zones and migrate through specific cortex: from molecules to malformations. Nat Rev Neurosci 15:
phases. Nat Neurosci 7:136–44. 217–32.
Opperman LA, Sweeney TM, Redmon J et al 1993 Tissue interactions ten Donkelaar HJ, Lammens M, Wesseling P et al 2004 Development and
with underlying dura mater inhibit osseous obliteration of developing malformations of the human pyramidal tract. J Neurol 251:1429–42.
cranial sutures. Dev Dyn 198:312–22. Tissir F, Goffinet AM 2010 Planar cell polarity signalling in neural develop-
O’Rahilly R, Müller F 1986 The meninges in human development. J Neu- ment. Curr Opin Neurobiol 20:572–7.
ropathol Exp Neurol 45:588–608. Tümpel S, Wiedemann LM, Krumlauf R 2009 Hox genes and segmentation
O’Rahilly R, Müller F 1999 The Embryonic Human Brain. An Atlas of Devel- of the vertebrate hindbrain. Curr Top Dev Biol 88:103–37.
opmental Stages, 2nd ed. Chichester: Wiley-Liss. Volpe JJ 2001 Neurobiology of periventricular leukomalacia in the prema-
O’Rahilly R, Müller F 2002 The two sites of fusion of the neural folds and ture infant. Pediatr Res 50:553–62.
the two neuropores in the human embryo. Teratology 65:162–70. Volpe JJ, Kinney HC, Jensen FE et al 2011 The developing oligodendrocyte:
O’Rahilly R, Müller F 2004 The primitive streak, the caudal eminence and key cellular target in brain injury in the premature infant. Int J Dev
related structures in staged human embryos. Cells Tissues Organs 117: Neurosci 29:423–40.
2–20. Wallingford JB 2010 Planar cell polarity signalling, cilia and polarized ciliary


Park H, Poo M 2013 Neurotrophin regulation of neural circuit development beating. Curr Opin Cell Biol 22:597–604.
and function. Nat Rev Neurosci 14:7–23. West AE, Pruunsild P, Timmusk T 2014 Neurotrophins: transcription and
Pereira JA, Lebrun-Julien F, Suter U 2012 Molecular mechanisms regulating translation. Handb Exp Pharmacol 220:67–100.
myelination in the peripheral nervous system. Trends Neurosci 35: Withington S, Beddington R, Cooke J 2001 Foregut endoderm is required
123–134. at head process stage for anteriormost neural patterning in chick. Devel-
Petanjek Z, Judas M, Simic G et al 2011 Extraordinary neoteny of synaptic opment 128:309–20.
spines in the human prefrontal cortex. Proc Natl Acad Sci U S A 108: Wonders CP, Anderson SA 2006 The origin and specification of cortical
13281–6. interneurones. Nat Rev Neurosci 7:687–96.
Puram SV, Kim AH, Ikeuchi Y et al 2011 A CaMKIIβ signaling pathway at Wu Q, Liu J, Fang A et al 2014 The dynamics of neuronal migration. Adv
the centrosome regulates dendrite patterning in the brain. Nat Neurosci Exp Med Biol 800:25–36.
14:973–983.
Yu T, Meiners LC, Danielsen K et al 2013 Deregulated FGF and homeotic
Rakic P 1988 Specification of cerebral cortical areas. Science 241:170–6. gene expression underlies cerebellar vermis hypoplasia in CHARGE
Rakic P 2009 Evolution of the neocortex: a perspective from developmental syndrome. eLife 2:e01305.
biology. Nat Rev Neurosci 10:724–35.
This article reviews differences in gene expression, molecular pathways and
novel cellular interactions in the embryonic cerebral cortex in different
mammalian species.


Ventricular system and CHAPTER
18
subarachnoid space
The cerebral ventricular system consists of a series of interconnecting The lateral ventricle is customarily divided into a body and anterior
spaces and channels within the brain (Figs 18.1 and 18.2), which are (frontal), posterior (occipital) and inferior (temporal) horns (Rhoton
derived from the central lumen of the embryonic neural tube and the 2002).
cerebral vesicles to which it gives rise (Ch. 17). Each cerebral hemi- The anterior horn lies within the frontal lobe. The posterior aspect
sphere contains a large lateral ventricle that communicates near its of the genu and the rostrum of the corpus callosum bound it anteriorly,
rostral end with the third ventricle via the interventricular foramen and its roof is formed by the anterior part of the body of the corpus
(foramen of Monro). The third ventricle is a midline, slit-like cavity callosum. The anterior horns of the two ventricles are separated by the
lying between the right and left thalamus and hypothalamus. Caudally, septum pellucidum. The coronal profile of the anterior horn is roughly
the third ventricle is continuous with the cerebral aqueduct, a narrow that of a flattened triangle in which the rounded head of the caudate
tube that passes the length of the midbrain, and which is continuous nucleus forms the lateral wall and floor (Figs 18.4–18.5). The anterior
in turn with the fourth ventricle, a wide cavity lying between the brain- horn extends back as far as the interventricular foramen.
stem and cerebellum. The fourth ventricle communicates with the Cavum septum pellucidum (CSP) describes a septum pellucidum
subarachnoid space of the cisterna magna through the foramen of that has a separation between its two leaflets (septal laminae). The
Magendie, and with the cerebellopontine angles through the foramina cavity contains cerebrospinal fluid that filters from the ventricles
of Luschka; caudally it is continuous with the vestigial central canal of through the septal laminae. The most common type of cavum septum


the spinal cord. pellucidum is non-communicating, i.e. it is not connected to the ven-
The ventricular system contains cerebrospinal fluid (CSF), which is tricular system. Cavum septum pellucidum is present in 100% of fetuses
mostly secreted by the choroid plexuses located within the lateral, third below 36 weeks’ gestation. Its prevalence at 36, 38 and 40 weeks is 69%,
and fourth ventricles. 54% and 36% respectively, decreasing to 10% in children under 1 year,
5–6% at 2–5 years, 2.7% at 6–9 years and 2.3% at 10–14 years (Farrug-
TOPOGRAPHY AND RELATIONS OF THE gia 1981, Mott et al 1992, Nakano et al 1981).
The body of the lateral ventricle lies within the frontal and parietal
VENTRICULAR SYSTEM
lobes, and extends from the interventricular foramen to the splenium
of the corpus callosum. The bodies of the lateral ventricles are separated
LATERAL VENTRICLE by the septum pellucidum, which contains the columns of the fornices
in its lower edge. The lateral wall of the body of the ventricle is formed
Viewed from its lateral aspect, the lateral ventricle has a roughly by the caudate nucleus superiorly and the thalamus inferiorly. The
C-shaped profile (see Figs 18.1–18.2; Fig. 18.3). The shape is a conse- boundary between the thalamus and caudate nucleus is marked by a
quence of the developmental expansion of the frontal, parietal and groove that is occupied by a fascicle of nerve fibres, the stria terminalis,
occipital regions of the hemisphere, which displaces the temporal lobe and by the superior thalamostriate vein (see Fig. 18.4). The inferior
inferiorly and anteriorly. Both the caudate nucleus and the fornix, limit of the body of the ventricle and its medial wall are formed by the


which lie in the wall of the ventricle, have adopted a similar morph- body of the fornix (Fig. 18.6). The fornix is separated from the thala-
ology, so that the tail of the caudate nucleus encircles the thalamus in mus by the choroidal fissure. The choroid plexus occludes the choroidal
a C shape, and the fornix traces the outline of the ventricle forwards to fissure and covers part of the thalamus and fornix (Nagata 1988) (Fig
the interventricular foramen. 18.7). The body of the lateral ventricle widens posteriorly to become
A Anterior horn of B Anterior horn of Body of Posterior horn
lateral ventricle lateral ventricle lateral ventricle of lateral ventricle
Third ventricle
Interventricular Inferior horn of Inferior horn of
foramen lateral ventricle lateral ventricle
Third ventricle
Lateral aperture Cerebral
of fourth ventricle aqueduct Fourth ventricle
Cerebral aqueduct
Fig. 18.1 The ventricular system. A, Anterior view. B, Left lateral view. 271


Ventricular system and subarachnoid space
271.e1
81
retpahc
A B C
D E F
Fig. 18.2 The ventricular system. Three-dimensional computer-reformatted volumetric T2-weighted magnetic resonance images display the ventricles in
lateral (A, D), superior (B, E) and anterior (C, F) views. A–C, Orientation of the ventricular system within the head, seen through the partially transparent
skin surface. D–F, Magnified display of the isolated ventricles in the same orientation. See also Videos 18.1 and 18.2, and 28.1–28.3 for an interactive
rotation. (With permission from Rios JC, Galper MW, Naidich TP, Ventricles and intracranial subarachnoid spaces. In: Naidich TP, Castillo M, Cha S,
Smirniotopoulos JG (eds), Imaging of the Brain. 2013, Saunders, Elsevier.)


Ventricular system and subarachnoid space
272
3
noitces
continuous with the posterior and inferior horns at the collateral THIRD VENTRICLE
trigone or atrium.
The posterior horn curves posteromedially into the occipital lobe. It The third ventricle is a midline, slit-like cavity, which is derived from
is usually diamond-shaped or square in outline, and the two sides are the primitive forebrain vesicle (see Figs 18.1, 18.6, 15.6; Figs 18.9–
often asymmetrical. Fibres of the tapetum of the corpus callosum sepa- 18.10) (Rhoton 2002). The upper part of the lateral wall of the ventricle
rate the ventricle from the optic radiation, and form the roof and lateral is formed by the medial surface of the anterior two-thirds of the thala-
wall of the posterior horn. Fibres of the splenium of the corpus callo- mus, and the lower part is formed by the hypothalamus anteriorly and
sum (forceps major) pass medially as they sweep back into the occipital the subthalamus posteriorly. An indistinct hypothalamic sulcus extends
lobe, and produce a rounded elevation in the upper medial wall of horizontally on the ventricular wall between the interventricular
the posterior horn. Lower down, a second elevation, the calcar avis, foramen and the cerebral aqueduct, and marks the boundary between
corresponds to the deeply infolded cortex of the anterior part of the the thalamus and hypothalamus. Dorsally, the lateral wall is limited by
calcarine sulcus. a ridge covering the stria medullaris thalami. The lateral walls of the
The inferior horn is the largest compartment of the lateral ventricle third ventricle are commonly joined by an interthalamic adhesion, or
and extends forwards into the temporal lobe. It curves round the pos- massa intermedia, a band of grey matter that extends from one thala-
terior aspect of the thalamus (pulvinar), passes downwards and poste- mus to the other. An interthalamic adhesion is almost always found in


rolaterally and then curves anteriorly to end within 2.5 cm of the humans, more often in women, in whom it is larger by an average of
temporal pole, near the uncus. Its position relative to the surface of 53% (Orly 2005).
the hemisphere usually corresponds to the superior temporal sulcus. Anteriorly, the third ventricle extends to the lamina terminalis (see
The roof of the inferior horn is formed mainly by the tapetum of the Fig. 18.10). This thin structure stretches from the optic chiasma to the
corpus callosum, but also by the tail of the caudate nucleus and the rostrum of the corpus callosum and represents the rostral boundary of
stria terminalis, which extend forwards in the roof to terminate in the embryonic neural tube. The lamina terminalis forms the roof of a
the amygdala at the anterior end of the ventricle. The floor of the infe- small virtual cavity, the cistern of the lamina terminalis, which lies
rior horn consists of the hippocampus medially and the collateral immediately below the ventricle and is an extension of the interpedun-
eminence, formed by the infolding of the collateral sulcus, laterally. The cular cistern. This is clinically important because it contains the anterior
inferior part of the choroid fissure lies between the fimbria (a distinct communicating artery; aneurysm development and rupture at this site
bundle of efferent fibres that leaves the hippocampus) and the stria may cause intraventricular haemorrhage through the thin membrane of
terminalis in the roof of the inferior horn (Fig. 18.8). The temporal the lamina terminalis. Above the lamina terminalis, the anterior wall
extension of the choroid plexus fills this fissure and covers the outer of the third ventricle is formed by the diverging columns of the fornices
surface of the hippocampus. and the transversely orientated anterior commissure, which crosses the
midline. The narrow interventricular foramen is located immediately
posterior to the column of the fornix and separates the fornix from the
anterior nucleus of the thalamus.
Atrium (body)
Anterior (frontal) horn
Posterior (occipital)


horn Septum pellucidum Anterior (frontal)
horn of left
lateral ventricle
Bifurcation of right
Hippocampus internal carotid artery at Head of left
base of Sylvian fissure caudate nucleus
(into middle and anterior
Optic chiasma
cerebral arteries)
Fig. 18.3 A T1-weighted sagittal MRI, showing the C-shaped profile of Fig. 18.5 A coronal T2-weighted MRI scan, at the level of the anterior
the lateral ventricle. horn of the lateral ventricle.
Fig. 18.4 A horizontal section of the cerebrum
dissected to remove the roofs of the lateral
ventricles.
Anterior horn of
lateral ventricle
Septum pellucidum
Head of caudate nucleus
Superior Thalamus
thalamostriate vein
Hippocampus in inferior
Fimbria
(temporal) horn of
lateral ventricle
Choroid plexus
Body of fornix
Splenium of
corpus callosum


topography and relations of the ventricular system
273
81
retpahc
Body of Body of fornix Corpus callosum
lateral ventricle
Choroid plexus
Pia mater
Ependyma
Caudate nucleus
Stria terminalis
Choroidal fissure
Anterior part
of thalamus Fimbria Tail of caudate nucleus
Internal Hippocampus
cerebral vein Dentate gyrus Inferior horn of
lateral ventricle
Medial part
of thalamus
Subiculum
Lateral part
of thalamus
Third ventricle
Pia mater of tela choroidea
Ependyma
Parahippocampal gyrus
Fig. 18.6 The lateral and third ventricles, coronal section.
Collateral sulcus Collateral eminence
Fig. 18.8 The inferior horn of the left lateral ventricle, coronal section.
CEREBRAL AQUEDUCT
The cerebral aqueduct is a small tube, roughly circular in transverse
section and 1–2 mm in diameter. The length of the aqueduct in chil-
dren, as measured at necropsy, is shown in Table 18.1. In children, the
mean cross-sectional area of the aqueduct is 0.5 mm2, and the narrow-
est cross-sectional area compatible with normal ventricular size is
0.1 mm2 (Emery and Staschak 1972).
The aqueduct extends throughout the dorsal quarter of the midbrain
in the midline and is surrounded by the periaqueductal (central) grey
matter (see Figs 18.10, 21.17). Rostrally, it commences immediately
below the posterior commissure, where it is continuous with the caudal
aspect of the third ventricle. Caudally, it is continuous with the lumen
of the fourth ventricle at the junction of the midbrain and pons. The
superior and inferior colliculi are dorsal to the aqueduct and the mid-
brain tegmentum is ventral. Primary aqueductal stenosis is a feature of
von Recklinghausen’s disease in children (Spadaro et al 1986); this is
not the only cause and population studies suggest that genetic factors
may play a more important role in hydrocephalus than previously


accepted (Munch et al 2012).
Fig. 18.7 An endoscopic view into the right lateral ventricle. The
thalamostriate vein (white arrow) runs along the lateral wall and converges
FOURTH VENTRICLE
with the anterior septal vein (short black arrow) before converging and
entering the foramen of Monro as the internal cerebral vein. The superior
choroidal vein (long black arrow) is also seen coursing through the The fourth ventricle lies between the brainstem and the cerebellum (see
choroid plexus. (With permission from Winn HR, editor. Youmans Figs 18.1, 18.9–18.10, 21.5; Fig. 18.12) (Rhoton 2000). Rostrally, it is
Neurological Surgery. 6th edition. 2011 Philadelphia, W. B. Saunders, continuous with the cerebral aqueduct, and caudally with the central
Elsevier.) canal of the spinal cord. In sagittal section, the fourth ventricle has a
characteristic triangular profile, and the apex of its tented roof protrudes
into the inferior aspect of the cerebellum. The ventricle is at its widest
A small, angular, optic recess occurs inconsistently at the base of the at the level of the pontomedullary junction, where a lateral recess on
lamina terminalis, just dorsal to and extending into the optic chiasma. both sides extends to the lateral border of the brainstem. At this point
Behind it, the anterior part of the floor of the third ventricle is formed the lateral apertures of the fourth ventricle (foramina of Luschka) open
mainly by hypothalamic structures. The thin infundibular recess lies into the subarachnoid space at the cerebellopontine angle, behind the
immediately behind the optic chiasma and extends into the pituitary upper roots of the glossopharyngeal nerves.
stalk. Behind this recess, the tuber cinereum and the mammillary The floor of the fourth ventricle is a shallow diamond-shaped, or


bodies form the floor of the ventricle (see Fig. 18.10; Fig. 18.11). rhomboidal, depression (rhomboid fossa) on the dorsal surfaces of the
The roof of the third ventricle is a thin ependymal layer that extends pons and the rostral half of the medulla (see Fig. 18.2). It consists
from its lateral walls to the choroid plexus, which spans the choroidal largely of grey matter and contains important cranial nerve nuclei (V–
fissure. The body of the fornix lies above the roof (see Fig. 18.6). XII). The precise location of some nuclei is discernible from surface
The posterior boundary of the ventricle is marked by a suprapineal features. The superior part of the ventricular floor is triangular in shape
recess, the habenular commissure, a pineal (epiphysial) recess, which and is limited laterally by the superior cerebellar peduncles as they
extends into the pineal stalk, and by the posterior commissure. Below converge towards the cerebral aqueduct. The inferior part of the ven-
the posterior commissure the ventricle is continuous with the cerebral tricular floor is also triangular in shape and is bounded caudally by the
aqueduct of the midbrain (see Fig. 18.10). gracile and cuneate tubercles, which contain the dorsal column nuclei,
The third ventricle is larger in infants with trisomy 21 compared with and, more rostrally, by the diverging inferior cerebellar peduncles. A
controls (Schimmel et al 2006). longitudinal median sulcus divides the floor of the fourth ventricle.


Ventricular system and subarachnoid space
274
3
noitces
Fig. 18.9 A sagittal T2-weighted MRI scan of the
head.
Septum pellucidum
Corpus callosum
Fornix
Tentorium cerebelli
Optic chiasma
Mammillary body
Anterior pituitary
gland Fourth ventricle
Pons
Basilar artery
Cisterna magna
Posterior arch of atlas
Tela choroidea of third ventricle
Interthalamic adhesion
Interventricular foramen
Stria medullaris thalami
Suprapineal recess
Septum pellucidum
Column of fornix
Parieto-occipital sulcus Anterior commissure
Calcarine sulcus
Corpus callosum
Great cerebral vein
Habenular commissure
Pineal recess
Pineal gland
Superior and inferior colliculi
Paraterminal gyrus
Lamina terminalis
Optic recess
Median aperture of
Posterior Hypophysis Optic chiasma
fourth ventricle
commissure cerebri
Pia mater Infundibular recess
Ependyma Cerebral aqueduct
Fig. 18.10 The third and fourth ventricles, sagittal hemisection of the brain.
Each half is itself divided, by an often indistinct sulcus limitans, into a and the vestibular area, is the vagal triangle (trigone), which covers the
medial region known as the medial eminence and a lateral region dorsal motor nucleus of the vagus. A narrow translucent ridge, the
known as the vestibular area. The vestibular nuclei lie beneath the funiculus separans, which is separated from the gracile tubercle by the
vestibular area. In the superior part, the medial eminence is represented small area postrema, crosses below the vagal triangle.
by the facial colliculus, a small elevation produced by an underlying The roof of the fourth ventricle is formed by the superior and inferior
loop of efferent fibres from the facial nucleus, which covers the abdu- medullary veli. The thin superior medullary velum stretches across the
cens nucleus. Between the facial colliculus and the vestibular area the ventricle between the converging superior cerebellar peduncles (see Fig.


sulcus limitans widens into a small depression, the superior fovea. In 18.12) and is continuous with the cerebellar white matter. Dorsally, it
its upper part, the sulcus limitans constitutes the lateral limit of the is covered by the lingula of the superior vermis. The inferior medullary
floor of the fourth ventricle. Here, a small region of bluish-grey pigmen- velum is more complex and is mostly composed of a thin sheet, devoid
tation denotes the presence of the subjacent locus coeruleus. Caudal to of neural tissue, formed by ventricular ependyma and the pia mater of
the facial colliculus, at the level of the lateral recess of the ventricle, a the tela choroidea. Just inferior to the nodule of the cerebellum, a
variable group of nerve fibre fascicles, known as the striae medullaris, median aperture, the foramen of Magendie, opens the roof of the fourth
runs transversely across the ventricular floor and passes into the median ventricle into the cisterna magna.
sulcus. In the inferior part, the medial eminence is represented by the The aperture forms when a membranous structure (Blake’s pouch)
hypoglossal triangle (trigone), which lies over the hypoglossal nucleus. perforates into the fourth ventricle at the ninth week of fetal develop-
Laterally, the sulcus limitans widens to produce an indistinct inferior ment; persistence of this membrane results in cystic obstruction of the
fovea. Caudal to the inferior fovea, between the hypoglossal triangle median outlet from the fourth ventricle (Paladini et al 2012).


topography and relations of the ventricular system
275
81
retpahc
CIRCUMVENTRICULAR ORGANS tanycytes are present (Horsburg and Massoud 2013) (Fig. 18.13). The
functions of ependyma and tanycytes may include secretion into the
The walls of the ventricular system are lined with ependymal cells that CSF; transport of neurochemicals from subjacent neurones, glia or
cover a subependymal layer of glia. At certain midline sites in the ven- vessels to the CSF; transport of neurochemicals from the CSF to the
tricular walls, collectively referred to as circumventricular organs, the same subjacent structures; and chemoreception (Rodriguez et al 2005).
blood–brain barrier is absent and specialized ependymal cells called Adult mammalian neurogenesis occurs in discrete neurogenic niches
that are best characterized in the ependymal and subependymal glial
cell layers in the subgranular zone of the dentate gyrus and in the sub-
ventricular zone; the existence of adult human neurogenic niches is
controversial.
The circumventricular organs include the vascular organ (organum
vasculosum), subfornical organ, neurohypophysis, median eminence,
subcommissural organ, pineal gland and area postrema (see Fig.
18.13).
The vascular organ lies in the lamina terminalis between the optic
chiasma and the anterior commissure. Its external zone contains a
richly fenestrated vascular plexus that covers glia and a network of nerve
fibres. The ependymal cells of the vascular organ, like those of other
circumventricular organs, are flattened and have few cilia. The major
inputs appear to come from the subfornical organ, locus coeruleus and
a number of hypothalamic nuclei. The vascular organ projects to the
median preoptic and supraoptic nuclei. It is involved in the regulation
of fluid balance and may also have neuroendocrine functions.
The subfornical organ lies at the level of the interventricular foramen.
It contains many neurones, glial cells and a dense fenestrated capillary
Table 18.1 The length of the cerebral aqueduct, as measured at necropsy in children


Crown–rump Length of Apparent equivalent Mean range
length (cm) aqueduct (mm) age of children
35 12.8 9.5–15.0 Birth to 6 weeks
45 15.5 13.0–17.6 3–9 months
Fig. 18.11 An endoscopic view of the floor of the third ventricle. The ideal 55 17.4 15.2–18.8 1–4 years
spot for fenestration is in the midline, midway between the dorsum sellae
65 18.2 16.6–19.4 5–7 years
(short black arrow) and the basilar artery (short white arrow). The paired
75 18.8 17.6–20.0 ≥8 years
mammillary bodies (long black arrow) and the infundibular recess (long
white arrow) are also seen. (With permission from Winn HR. Youmans
Neurological Surgery. 6th edition. 2011 Philadelphia, W. B. Saunders, (With permission from Emery JL, Staschak MC. The size and form of the cerebral aqueduct in children.
Brain 1972; 95:591–598.)
Elsevier.)
Fig. 18.12 The floor of the fourth ventricle, dorsal
Medial Pineal gland aspect of the brainstem.
geniculate
body
Pulvinar
Inferior
quadrigeminal Superior and
brachium inferior colliculi
Lingula Trochlear nerve
Superior Superior
medullary cerebellar
velum peduncle
Superior
fovea Middle
cerebellar
Facial peduncle
colliculus
Dentate nucleus
Inferior
cerebellar Striae medullaris
peduncle
Vestibular area
Hypoglossal
triangle
Inferior fovea
Funiculus
separans Vagal triangle
and area
postrema
Obex
Cuneate Gracile tubercle
tubercle
Posterior
median sulcus


Ventricular system and subarachnoid space
276
3
noitces
Subfornical organ Vascular organ columns of the fornices. Its lateral edges are irregular and contain
choroid vascular fringes. At the posterior basal angles of the tela, these
fringes continue and curve on into the inferior horn of the ventricle.
When the tela is removed, a transverse slit (the transverse fissure) is left
between the splenium and the junction of the ventricular roof with the
tectum. The transverse fissure contains the roots of the choroid plexus
of the third ventricle and of the lateral ventricles.
The choroid plexus of the third ventricle is attached to the tela
choroidea, which is, in effect, the thin roof of the third ventricle as it
develops during fetal life. In coronal sections of the cerebral hemi-
spheres, it can be seen that the choroid plexus of the third and lateral
Pineal gland
ventricles are continuous.
The choroid plexus of the fourth ventricle is similar in structure to
Subcommissural organ that of the lateral and third ventricles. The roof of the inferior part of
the fourth ventricle develops as a thin sheet in which the pia mater is
in direct contact with the ependymal lining of the ventricle. This thin
sheet, the tela choroidea of the fourth ventricle, lies between the cerebel-
lum and the inferior part of the roof of the ventricle. The choroid plexus
of the fourth ventricle is T-shaped, with vertical and horizontal limbs,
Area postrema but the precise form varies widely from a single vertical limb to an
elongated ‘T’ that extends out through the foramina of Luschka into the
cerebellopontine angle. The vertical (longitudinal) limb is double,
flanks the midline and is adherent to the roof of the ventricle. The limbs
fuse at the superior margin of the median aperture (foramen of Magen-
Median eminence Neurohypophysis die) and are often prolonged on to the ventral aspect of the cerebellar
Fig. 18.13 The locations of the circumventricular organs, median sagittal vermis. The horizontal limbs of the plexus project into the lateral


section of the brain. recesses of the ventricle. Small tufts of plexus may pass through the
lateral apertures (foramina of Luschka) and emerge, still covered by
ependyma, in the subarachnoid space of the cerebellopontine angle.
The mean thickness of the choroid plexus in the fourth ventricle in
plexus, and is covered by flattened ependyma. It is believed to have children is 2.5 mm (Madhukar et al 2012).
widespread hypothalamic interconnections and to function in the regu- The blood supply of the choroid plexus in the tela choroidea of the
lation of fluid balance and thirst. lateral and third ventricles is usually via a single vessel from the anterior
The neurohypophysis (posterior pituitary) is the site of termination choroidal branch of the internal carotid artery and several choroidal
of neurosecretory projections from the supraoptic and paraventricular branches of the posterior cerebral artery; the two sets of vessels anasto-
nuclei of the hypothalamus. Neurones in these nuclei release vaso- mose to some extent. Capillaries drain into a rich venous plexus served
pressin and oxytocin respectively into the capillary bed of the neurohy- by a single choroidal vein. The blood supply of the fourth ventricular
pophysis, where the hormones gain access to the general circulation. choroid plexus is from the inferior cerebellar arteries.
The median eminence contains the terminations of axons of hypo- Physiological calcification of the choroid plexus and pineal gland
thalamic neurosecretory cells. Peptides released from these axons con- are the most frequently described intracranial calcifications incidentally
trol the hormonal secretions of the anterior pituitary via the pituitary discovered during head computed tomography (CT) examinations
portal system of vessels. (Doyle and Anderson 2006).
The subcommissural organ lies ventral to and below the posterior
commissure, near the inferior wall of the pineal recess.
CEREBROSPINAL FLUID
The pineal gland is a small structure, approximately 8 mm in diam-
eter, situated rostrodorsal to the superior colliculus and behind the stria


medullaris. CSF is a clear, colourless liquid. Normal CSF contains small amounts
The area postrema is a bilaterally paired structure, located at the of protein and differs from blood in its electrolyte content. It is not
caudal limit of the floor of the fourth ventricle. It is an important simply an ultrafiltrate of blood but is actively secreted by the choroid
chemoreceptive area that triggers vomiting in response to the presence plexuses in the lateral, third and fourth ventricles.
of emetic substances in the blood. The area postrema, along with the The choroid plexus epithelium constitutes a blood–CSF barrier.
nucleus of the solitary tract and the dorsal motor nucleus of the vagus, Choroid plexus epithelial cells (see Figs 3.17, 3.18) have the character-
makes up the so-called dorsal vagal complex, which is the major termi- istics of transport and secretory cells; their apical surfaces have micro-
nation site of vagal afferent nerve fibres. villi, and their basal surfaces exhibit interdigitations and folding. Tight
junctions (occluding junctions, zonulae adherentes) at the apical ends
of the cells are permeable to small molecules. Fenestrated capillaries lie
CHOROID PLEXUS AND CEREBROSPINAL FLUID just beneath the epithelial cells in the stroma of the choroid plexus. The
ependymal lining of the ventricles and the extracellular fluid from the
CHOROID PLEXUS brain parenchyma are additional sources of CSF, but how much each
source contributes to CSF production is unclear.
The vascular pia mater in the roofs of the third and fourth ventricles,
and in the medial wall of the lateral ventricle along the line of the SUBARACHNOID SPACE AND CIRCULATION OF
choroid fissure, is closely apposed to the ependymal lining of the ven-
CEREBROSPINAL FLUID
tricles, without any intervening brain tissue. It forms the tela choroidea,
which gives rise to the highly vascularized choroid plexuses from which
CSF is secreted into the lateral, third and fourth ventricles (see Figs 18.4, SUBARACHNOID SPACE


18.6, 18.8). The body or stroma of the choroid plexus consists of many
capillaries, separated from the ventricles by the pia mater and choroid The subarachnoid space lies between the arachnoid and the pia mater
ependymal cells (Strazielle 2000). (Videos 18.1 and 18.2). It is continuous with the lumen of the fourth
In the lateral ventricle, the choroid plexus extends anteriorly as far ventricle via the median aperture (foramen of Magendie) and the paired
as the interventricular foramen, through which it is continuous across lateral apertures (foramina of Luschka). The subarachnoid space con-
the third ventricle with the plexus of the opposite lateral ventricle. From tains CSF, the larger arteries and veins that traverse the surface of the
the interventricular foramen, the plexus passes posteriorly, in contact brain, and the intra cranial or intravertebral portions respectively of the
with the thalamus, curving round its posterior aspect to enter the infe- cranial and spinal nerves.
rior horn of the ventricle and reach the hippocampus. Throughout the Trabeculae, in the form of sheets or fine filiform structures, each
body of the ventricle, the choroid fissure lies between the fornix supe- containing a core of collagen, cross the subarachnoid space from the
riorly and the thalamus inferiorly (see Fig. 18.6). deep layers of the arachnoid mater to the pia mater (Fig. 18.14). The
From above, the tela choroidea is triangular with a rounded apex trabeculae are attached to the large blood vessels within the subarach-
between the interventricular foramina, often indented by the anterior noid space and may form compartments, particularly in the perivascular


Ventricular system and subarachnoid space
276.e1
81
retpahc
The ependymal cells on the dorsal aspect of the cerebral aqueduct
are tall, columnar and ciliated, with granular basophilic cytoplasm; they
may be involved in the secretion of materials into the CSF from adjoin-
ing axonal terminals or capillaries.
It is part of the epithalamus and consists of internal lobules of pin-
ealocytes and sparse neurones covered by a pial capsule. It secretes
melatonin, which appears to be involved in the inhibition of puberty
in children and in the regulation of the sleep–wake cycle in both chil-
dren and adults.
A B C M N O
D E F P Q R
G H I S T U
J K L V W X
Fig. 18.16 The supratentorial subarachnoid cisterns. FIESTA MR images colour-coded to provide a visual approximation to the borders of the
individually named supratentorial cisterns. These images are arrayed so that each row depicts a single cistern, in the axial plane (column 1), coronal
plane (column 2) and sagittal plane (column 3). This montage is intended to indicate the general location for each cistern within the sea of multiple
confluent CSF spaces around the brain. A–C, Paired Sylvian cisterns. D–F, Paired carotid cisterns. G–I, Midline chiasmatic cistern. J–L, Midline cistern of
the lamina terminalis. M–O, Midline pericallosal cistern. P–R, Paired olfactory cisterns. S–U, Midline perimesencephalic cistern. V–X, Cistern of the velum
interpositum. The perimesencephalic cistern is often considered in four portions (S–U): midventral interpeduncular fossa (red), paired anterolateral crural
cisterns (green), paired posterolateral ambient cisterns (blue), and mid-dorsal quadrigeminal plate (vein of Galen) cistern (yellow). (With permission from


Rios JC, Galper MW, Naidich TP. Ventricles and intracranial subarachnoid spaces. In: Naidich TP, Castillo M, Cha S, Smirniotopoulos JG (eds), Imaging
of the Brain. Chapter 13, 245–271. 2013, Elsevier, Saunders.)


Ventricular system and subarachnoid space
276.e2
3
noitces
A B C M N O
D E F P Q R
G H I S T U
J K L
Fig. 18.17 Infratentorial subarachnoid cisterns. FIESTA MR images colour-coded to provide a visual approximation to the borders of the individually
named infratentorial cisterns. These images are arrayed so that each row depicts a single cistern, in axial plane (column 1), coronal plane (column 2) and
sagittal plane (column 3) images. This montage is intended to indicate the general location for each cistern within the sea of multiple confluent CSF
spaces around the brain. A–C, Midline quadrigeminal plate (vein of Galen) cistern (yellow). D–F, Midline prepontine cistern. G–I, Midline premedullary
cistern. J–L, Midline superior vermian cistern. M–O, Midline cisterna magna. P–R, Paired cerebellopontine angle cisterns. S–U, Paired cerebellomedullary
cisterns. (With permission from Rios JC, Galper MW, Naidich TP. Ventricles and intracranial subarachnoid spaces. In: Naidich TP, Castillo M, Cha S,
Smirniotopoulos JG (eds), Imaging of the Brain. Chapter 13, 245–271. 2013, Elsevier, Saunders.)


subarachnoid space and circulation of cerebrospinal fluid
277
81
retpahc
Fig. 18.14 The relationships between the
Dura dura mater, the leptomeninges and the
Artery with Arachnoid blood vessels that enter and leave the
leptomeningeal coat
cerebral cortex. The subarachnoid space
Perivascular Trabecular sheet is divided by trabeculae.
space
Pia
Filiform
trabecula Subpial space
Perivascular
space Cerebral cortex
Artery
Pial reflection
Pial coat
Sulcus
Vein
Pial coat
perforations Group of pial cells
Capillary
Corpus callosum the posterior inferior cerebellar arteries, the glossopharyngeal, vagus,
Fornix accessory and hypoglossal nerves, and the choroid plexus.
Supracallosal cistern
On either side, the paired cerebellopontine cisterns (angle cisterns
Third ventricle Septum pellucidum or cerebellopontine angle cisterns) are situated in the lateral angle
Cistern of the great between the cerebellum and the pons. They are traversed by the trigemi-
cerebral vein nal, facial and vestibulocochlear nerves, the anterior inferior cerebellar
(quadrigeminal or arteries and the superior petrosal veins.
superior cistern) The prepontine cistern (pontine cistern) is an extensive space ventral
to the pons, which is continuous below with the spinal subarachnoid
space, behind and laterally with the cerebellopontine cisterns, and ros-
Cerebellum
Cistern of the trally with the interpeduncular cistern. The basilar artery runs through
lamina terminalis the pontine cistern into the interpeduncular cistern, which also con-
Optic chiasma tains the origins of the anterior inferior cerebellar and superior cerebel-
lar arteries, and the abducens nerves.
Chiasmatic cistern
(suprasellar cistern) The quadrigeminal cistern (superior cistern, vein of Galen cistern,
peripineal cistern) lies posterior to the brainstem and third ventricle,
Interpeduncular cistern


and occupies the interval between the splenium of the corpus callosum
(basal cistern)
and the superior cerebellar surface. The great cerebral vein (formed by
Pons
the union of the basal veins of Rosenthal and the internal cerebral
Fourth ventricle veins) traverses this cistern and the pineal gland protrudes into it. It
also contains the P3 segments of the posterior cerebral arteries and
portions of the medial and lateral posterior choroidal arteries.
Prepontine cistern
(pontine cistern) The paired ambient cisterns are extensions of the quadrigeminal
Cisterna magna
cistern. On each side, they lie between the parahippocampal and
(cerebellomedullary cistern) Medulla oblongata
dentate gyri of the temporal lobes laterally and the lateral surface of the
Fig. 18.15 The principal subarachnoid cisterns, sagittal section. midbrain behind the cerebral peduncles medially; they therefore extend
laterally and anteriorly around the midbrain on either side to the
interpeduncular cistern (basal cistern) (see Figs 18.16, 21.3). They are
divided into supra- and infratentorial compartments and contain the
regions, thereby possibly facilitating directional flow of CSF through basal vein of Rosenthal, the P2 segment of the posterior cerebral artery,
the space. A thin layer of leptomeninges, often only one cell thick, coats the superior cerebellar artery and the trochlear nerves.
the trabeculae, vessels and nerves that cross the subarachnoid space; it The average width of the ambient cistern in children is greatest at
fuses with the arachnoid mater at the margins of the exit foramina in 1–3 years (2.8 ± 0.6 mm) and lowest at 4–10 years (2.4 ± 0.6 mm); it is
the skull and vertebral column. reported to be larger anteriorly in boys (Skadorwa et al 2010).
Arachnoid and pia mater are in close apposition over the convexities The paired crural cisterns lie between the posterior borders of the


of the brain, such as the cortical gyri, whereas concavities are followed unci and the cerebral peduncles on each side and contain the P1
by the pia but spanned by the arachnoid. This arrangement produces a segment of the posterior cerebral artery and the postoptic part of the
subarachnoid space of greatly variable depth that is location-dependent. anterior choroidal artery. The midline interpeduncular cistern (basal
The more expansive spaces form subarachnoid cisterns (Figs 18.15– cistern) lies between the two cerebral peduncles, bordered superiorly
18.17), which are continuous with the general subarachnoid space and and inferiorly by the diencephalic and mesencephalic leaves respec-
crossed by long, filamentous trabeculae (Inoue et al 2009). tively of Liliequist’s membrane. It contains the basilar artery, the origins
The largest cistern, the cisterna magna (cerebellomedullary cistern) of the posterior cerebral and thalamoperforating arteries, the proximal
is formed where the arachnoid bridges the interval between the medulla portion of the anterior pontomesencephalic vein and the proximal por-
oblongata and the inferior surface of the cerebellum. The cistern is tions of the oculomotor nerves. Anteriorly, the interpeduncular cistern
continuous above with the lumen of the fourth ventricle through its extends to the optic chiasma.
median aperture, the foramen of Magendie, and below with the spinal The paired cisterns of the lateral fossa (Sylvian cistern) are formed
subarachnoid space. It contains the vertebral arteries and the origins of on either side by the arachnoid as it bridges the lateral sulcus between


Ventricular system and subarachnoid space
278
3
noitces
the frontal, parietal and temporal opercula and contain the middle Endothelium of
cerebral artery and veins. venous sinus
Several smaller cisterns have been described. They include the chi-
asmatic cistern (suprasellar cistern), which is related to the optic
chiasma, and the cistern of the lamina terminalis and the supracallosal
cistern, all of which are extensions of the interpeduncular cistern and
contain the anterior cerebral arteries. The subarachnoid space extends
through the optic foramina into the orbits, where it is bounded by the
sheath of the optic nerve. The latter is formed by fusion of the arach-
noid mater and dura mater, and surrounds the orbital portion of each
optic nerve as far as the back of the globe, where the dura fuses with
the sclera of the eyeball. For further reading, see Rios et al (2013).
CIRCULATION OF CEREBROSPINAL FLUID
The total volume of CSF in the adult ranges from 140 to 270 ml. The
volume of the ventricles is about 25 ml. CSF is produced at a rate of
0.2–0.7 ml per minute (600–700 ml per day), which means that the
entire CSF volume is replaced approximately 4 times per day. Dura mater
In children, CSF production, as measured by output through exter- Arachnoid mater
nal ventricular drainage, increases during infancy, reaching 64% of the
output of a 15-year-old child by 2 years of age. There is a logarithmic
increase in CSF output with age and body weight (Yasuda et al 2002).
Mixing of CSF from different sources within the subarachnoid space
is probably assisted by cilia on the ependymal cells lining the ventricles
and by arterial pulsations.
Arachnoid villi and granulations
Arachnoid villi and granulations (Pacchionian bodies) are focal pouches
of arachnoid mater and subarachnoid space that protrude through the
walls of the dural venous sinuses, very often close to points where veins


enter the sinuses. They are found in the superior sagittal, transverse,
superior petrosal and straight sinuses in decreasing frequency and are
most prominent along the margins of the great longitudinal fissure,
commonly in the lateral lacunae of the superior sagittal sinus.
At the base of each arachnoid granulation, a thin neck of arachnoid
mater projects through an aperture in the dural covering of a venous Cerebral cortex Subarachnoid space Pia mater
sinus and then expands to form a core of collagenous trabeculae and
Fig. 18.18 An arachnoid granulation. (Modified with permission from
interwoven channels (Fig. 18.18). An apical cap of arachnoid cells,
Springer-Verlag, Principles of Pediatric Neurosurgery, Vol 4: Morphology
some 150 µm thick, surmounts the core and is attached to the endothe-
of CSF drainage pathways in man. Raimondi (ed), Kida and Weller 1994.)
lium of the sinus over an area some 300 µm in diameter. The rest of
the core of the granulation is separated from the endothelium by a
fibrous dural cupula. Channels extend through the cap to reach the
subendothelial regions of the granulation. Meningiomas, the most
common benign intracranial tumours, arise from arachnoid cap cells.
Dural depressions in the venous wall containing microscopic clus- PIA MATER
ters of arachnoidal cells penetrating between the dural fibres are seen
in the twenty-sixth fetal week. At 35 weeks they develop into arachnoid
The pia mater is a delicate membrane that closely invests the surface of
villi, which are simple protrusions through the dura. At full term, the
the brain and spinal cord, from which it is separated by a microscopic
number and complexity of the villi increase. It is generally believed that
subpial space. It follows the contours of the brain into concavities and
the fetal and early infantile villi do not fully penetrate the dural wall of
the depths of fissures and sulci (see Fig. 18.14). In the spinal canal, it
the cranial venous sinus. With maturation they grow in size, number


contributes to the formation of the dentate ligaments and the filum
and structural complexity, achieve penetration through the wall of the
terminale (Adeeb et al 2013).
venous sinus, and are thereafter referred to as arachnoid granulations.
Pia mater is formed from a layer of leptomeningeal cells, often only
Granulations are visible to the naked eye in the parieto-occipital region
1–2 cells thick, in which the cells are joined by desmosomes and gap
of the superior sagittal sinus by the age of 18 months. In the elderly,
junctions but few, if any, tight junctions. The cells are continuous with
the arachnoid membrane thickens and the arachnoid granulations
the coating of the subarachnoid trabeculae and separated from the basal
degenerate and often calcify.
lamina of the glia limitans by bundles of collagen, fibroblast-like cells
The function of arachnoid granulations is incompletely
and microscopic vessels that lie in the subpial space (Mercier et al 2002)
understood.
(see Fig. 18.14).
It was long thought that the subarachnoid space was connected
Hydrocephalus
directly with the perivascular spaces (Virchow–Robin spaces) that sur-
round blood vessels in the brain. However, it is now recognized that
Obstruction of the circulation of CSF leads to accumulation of fluid the pia mater is reflected from the surface of the brain on to the surface
within the ventricular system (hydrocephalus; Fig. 18.19). Within the of blood vessels in the subarachnoid space, which means that the sub-
brain, critical points at which obstruction may occur correspond to the arachnoid space is separated by a layer of pia from the subpial and
narrow foramina and passages of the ventricular system. Thus, obstruc- perivascular spaces of the brain (see Fig. 18.14). The pia mater appears
tion of the interventricular foramen causes enlargement of the lateral to form a regulatory interface between the subarachnoid space and the
ventricles; obstruction of the cerebral aqueduct leads to enlargement of brain, across which small molecules may diffuse between the interstitial


both the lateral ventricles and the third ventricle; and obstruction or space and the CSF through the perivascular space. This may allow move-
congenital absence of the apertures of the fourth ventricle leads to ment of metabolites and could play a role in blood–brain barrier func-
enlargement of the entire ventricular system. Membranes in the sub- tion (Zhang et al 1990).
arachnoidal cisterns can cause extraventricular obstruction to CSF flow. During development the pia mater becomes apposed to the epend-
Hydrocephalus in the presence of intact communications between the yma in the roof of the telencephalon and fourth ventricle to form the
ventricular and subarachnoid spaces, ‘communicating hydrocephalus’, tela choroidea. It shares a common embryological origin and structural
is most often associated with defective absorption of CSF. similarity with the arachnoid mater.


Ventricular system and subarachnoid space
278.e1
81
retpahc
Anterior (frontal) Lateral
horn of the (temporal) horn
left lateral of the left
CSF transudation ventricle lateral ventricle
A B C
Choroid plexus Posterior (occipital) Choroid plexus Pineal gland Third Lateral Meningioma Displaced
in body of the horn of the left through left (calcified) ventricle (temporal) horn (avidly enhancing fourth
left lateral lateral ventricle foramen of Munro of the left with contrast) ventricle
ventricle lateral ventricle
Fig. 18.19 Axial CT images post contrast showing acute hydrocephalus (from posterior fossa meningioma). Note the transudation of fluid into the
juxtaventricular white matter secondary to acute hydrocephalus.
Magnetic resonance imaging with fluid movement-sensitive se- It has long been thought that arachnoid villi and arachnoid granula-
quences performed on normal subjects has shown CSF flow to be tions constitute the major pathway for the absorption of CSF from the
pulsating and bidirectional between the compartments of the ventricu- subarachnoid space into the blood, and there are observations both to
lar system, probably with a net flow in a direction towards the fourth support and to question this. Their relative paucity in the fetal and early
ventricle (Yamada 2008). The flow of CSF changes at the age of 2 years postnatal period strongly suggests the importance of other absorption
from an infantile to a mature pattern. The infantile pattern is character- routes. The degenerative changes in arachnoid granulations in old age
ized by flow directed into the ventricular system, and the mature pattern could be the substrate for the condition of ‘normal pressure hydro-
by flow directed out of the ventricles (Bateman and Brown 2012). The cephalus’ and for decreased CSF absorption, which could play an
route of CSF through the subarachnoid space is even more complex and important role in degenerative brain diseases of the elderly.
less understood, and it is debated whether CSF moves mainly over the An alternative, and not necessarily mutually exclusive, view of arach-


cerebral convexities or mainly at the cranial base. It is known that CSF noid granulations is that they are involved in dissipating the pressure
is absorbed into the superior sagittal sinus, but also that this site is wave that occurs in the subarachnoid space during arterial systole
insufficient to account for all CSF absorption and that this absorption (caused by the pulsation of the arterial vessels within the space). Since
system may only start to operate when CSF pressure is increased. There- the dural venous sinuses lie within thick, non-compliant dural cover-
fore one or more additional routes of absorption must exist but their ings, pressure changes within them functionally represent the extracra-
precise location, function and mutual contributions to CSF absorption nial venous compartment; systolic dilation of the arachnoid granulations
have yet to be clarified (Pollay 2010). Absorption through pial and would therefore dissipate intracranial pressure changes into the extra-
subarachnoid vessels, across the ependymal ventricular surfaces and cranial venous system.
pial surfaces and via extracranial lymphatics may all be involved
(Zakharov 2004).


279
81
retpahc
Key references
Bonus e-book images and videos
Fig. 18.2 The ventricular system. Fig. 18.19 Axial CT images post contrast Video 18.1 Interactive 3D rotation of the
showing acute hydrocephalus (from a subarachnoid space.
Fig. 18.16 Supratentorial subarachnoid cisterns. posterior fossa meningioma).
Video 18.2 Interactive 3D rotation of the
Fig. 18.17 Infratentorial subarachnoid cisterns. ventricles and cisterns.
KEY REFERENCES
Adeeb N, Mortazavi MM, Deep A et al 2013 The pia mater: a comprehensive Pollay M 2010 The function and structure of the cerebrospinal fluid outflow
review of literature. Childs Nerv Syst 29:1803–10. system. Cerebrospinal Fluid Res 7:9.
A review of the literature relating to the history, embryology, anatomy and A review that traces the development of our understanding of the anatomy
function of the pia mater and related structures. and physiological properties of the systems responsible for the drainage of
cerebrospinal fluid into the systemic circulation.
Horsburgh A, Massoud TF 2013 The circumventricular organs of the brain:
conspicuity on clinical 3T MRI and a review of functional anatomy. Surg Rhoton AL Jr 2000 Cerebellum and fourth ventricle. Neurosurg 47:S7–27.
Radiol Anat 35:343–9. A comprehensive description of the microsurgical anatomy of the cerebellum
A description of the normal appearances and prevalence of contrast and fourth ventricle.
enhancement of the circumventricular organs on routine clinical brain MRI
Rhoton AL Jr 2002 The lateral and third ventricles. Neurosurg 51:S207–71.
and a review of the functional anatomy.
A comprehensive description of the microsurgical anatomy of the lateral and
Kida S, Weller RO 1994 Morphology of CSF drainage pathways in man. In: third ventricles.
Raimondi A (ed) Principles of Pediatric Neurosurgery, vol 4. Berlin:
Strazielle N, Ghersi-Egea JF 2000 Choroid plexus in the central nervous
Springer.


system: biology and physiopathology. J Neuropathol Exp Neurol 59:
A description of the morphology and relationships of the subarachnoid space,
561–74.
including the structure of arachnoid granulations.
A description of choroid plexus functions in brain development, transfer of
Mercier F, Kitasako JT, Hatton GI 2002 Anatomy of the brain neurogenic neurohumoral information, brain/immune system interactions, brain ageing
zones revisited: fractones and the fibroblast/macrophage network. and cerebral pharmacotoxicology.
J Comp Neurol 451:170–88.
Zhang ET, Inman CBE, Weller RO 1990 Interrelationships of the pia mater
A description of the structure and ultrastructure of the basal laminae and
and the perivascular (Virchow–Robin) spaces in the human cerebrum.
subependymal layer.
J Anat 170:111–23.
Nagata S, Rhoton AL Jr, Barry M 1988 Microsurgical anatomy of the A summary of the anatomical relationships between the pia mater and
choroidal fissure. Surg Neurol 30:3–59. blood vessels in the human cerebrum, and discussion of a possible role for
A description of the microsurgical anatomy of the choroidal fissure in pial cells as an enzymic barrier protecting the brain from exogenous
cadaveric heads. catecholamines.


Ventricular system and subarachnoid space
279.e1
81
retpahc
REFERENCES
Adeeb N, Mortazavi MM, Deep A et al 2013 The pia mater: a comprehensive ultrasound diagnosis, natural history and outcome of Blake’s pouch cyst
review of literature. Childs Nerv Syst 29:1803–10. in the fetus. Ultrasound Obstet Gynecol 39:279–87.
A review of the literature relating to the history, embryology, anatomy and Pollay M 2010 The function and structure of the cerebrospinal fluid outflow
function of the pia mater and related structures. system. Cerebrospinal Fluid Res 7:9.
Bateman GA, Brown KM 2012 The measurement of CSF flow through the A review that traces the development of our understanding of the anatomy
aqueduct in normal and hydrocephalic children: from where does it and physiological properties of the systems responsible for the drainage of
come, to where does it go? Childs Nerv Syst 28:55–63. cerebrospinal fluid into the systemic circulation.
Doyle AJ, Anderson GD 2006 Physiologic calcification of the pineal gland Rhoton AL Jr 2000 Cerebellum and fourth ventricle. Neurosurg 47:S7–27.
in children on computed tomography: prevalence, observer reliability A comprehensive description of the microsurgical anatomy of the cerebellum
and association with choroid plexus calcification. Acad Radiol 13: and fourth ventricle.
822–6.
Rhoton AL Jr 2002 The lateral and third ventricles. Neurosurg 51:S207–71.
Emery JL, Staschak MC 1972 The size and form of the cerebral aqueduct in A comprehensive description of the microsurgical anatomy of the lateral and
children. Brain 95:591–8. third ventricles.
Farruggia S, Babcock D 1981 The cavum septi pellucidi: its appearance and
Rios JC, Galper MW, Naidich TP 2013 Ventricles and intracranial subarach-
incidence with cranial ultrasonography in infancy. Radiology 139:
noid spaces. In: Naidich TP, Castillo M, Cha S et al (eds) Imaging of the
147–50.


Brain. Philadelphia: Elsevier, Saunders; Ch. 13, pp. 245–71.
Horsburgh A, Massoud TF 2013 The circumventricular organs of the brain:
Rodríguez EM, Blázquez JL, Pastor FE et al 2005 Hypothalamic tanycytes:
conspicuity on clinical 3T MRI and a review of functional anatomy. Surg
a key component of brain–endocrine interaction. Int Rev Cytol 247:
Radiol Anat 35:343–9.
89–164.
A description of the normal appearances and prevalence of contrast
enhancement of the circumventricular organs on routine clinical brain MRI Schimmel MS, Hammerman C, Bromiker R et al 2006 Third ventricle
and a review of the functional anatomy. enlargement among newborn infants with trisomy 21. Pediatrics 117:
e928–31.
Inoue K, Seker A, Alencastro LF et al 2009 Microsurgical and endoscopic
Skadorwa T, Eibl M, Zyganska E et al 2010 Radiological anatomy of the
anatomy of the supratentorial arachnoid membranes and cisterns. Neu-
ambient cistern in children. Folia Morphologica (Warszawa) 69:
rosurg 65:644–64.
78–83.
Kida S, Weller RO 1994 Morphology of CSF drainage pathways in man. In:
Spadaro A, Ambrosio D, Moraci A et al 1986 Nontumoral aqueductal steno-
Raimondi A (ed) Principles of Pediatric Neurosurgery, vol 4. Berlin:
sis in children affected by von Recklinghausen’s disease. Surg Neurol
Springer.
26:487–95.
A description of the morphology and relationships of the subarachnoid space,
including the structure of arachnoid granulations. Strazielle N, Ghersi-Egea JF 2000 Choroid plexus in the central nervous
system: biology and physiopathology. J Neuropathol Exp Neurol 59:
Madhukar M, Choudhary AK, Boal DK et al 2012 Choroid plexus: normal 561–74.


size criteria on neuroimaging. Surg Radiol Anat 34:887–95. A description of choroid plexus functions in brain development, transfer of
Mercier F, Kitasako JT, Hatton GI 2002 Anatomy of the brain neurogenic neurohumoral information, brain/immune system interactions, brain ageing
zones revisited: fractones and the fibroblast/macrophage network. and cerebral pharmacotoxicology.
J Comp Neurol 451:170–88.
Yamada S, Miyazaki M, Kanazawa H et al 2008 Visualization of cerebrospi-
A description of the structure and ultrastructure of the basal laminae and
nal fluid movement with spin labeling at MR imaging: preliminary
subependymal layer.
results in normal and pathophysiologic conditions. Radiology 249:
Mott SH, Bodensteiner JB, Allan WC 1992 The cavum septi pellucidi in term 644–52.
and preterm newborn infants. J Child Neurol 7:35–8. Yasuda T, Tomita T, McLone DG et al 2002 Measurement of cerebrospinal
Munch TN, Rostgaard K, Rasmussen ML et al 2012 Familial aggregation of fluid output through external ventricular drainage in one hundred
congenital hydrocephalus in a nationwide cohort. Brain 135:2409–15. infants and children: correlation with cerebrospinal fluid production.
Nagata S, Rhoton AL Jr, Barry M 1988 Microsurgical anatomy of the choroid- Pediatr Neurosurg 36:22–8.
al fissure. Surg Neurol 30:3–59. Zakharov A, Papaiconomou C, Koh L et al 2004 Integrating the roles of
A description of the microsurgical anatomy of the choroidal fissure in extracranial lymphatics and intracranial veins in cerebrospinal fluid
cadaveric heads. absorption in sheep. Microvasc Res 67:96–104.
Nakano S, Hojo H, Kataoka K et al 1981 Age related incidence of cavum Zhang ET, Inman CBE, Weller RO 1990 Interrelationships of the pia mater
septi pellucidi and cavum vergae on CT scans of pediatric patients. and the perivascular (Virchow–Robin) spaces in the human cerebrum.


J Comput Assist Tomogr 5:348–9. J Anat 170:111–23.
A summary of the anatomical relationships between the pia mater and
Olry R, Haines DE 2005 Interthalamic adhesion: scruples about calling a
blood vessels in the human cerebrum, and discussion of a possible role for
spade a spade? J Hist Neurosci 14:116–18.
pial cells as an enzymic barrier protecting the brain from exogenous
Paladini D, Quarantelli M, Pastore G et al 2012 Abnormal or delayed devel- catecholamines.
opment of the posterior membranous area of the brain: anatomy,


CHAPTER Vascular supply and drainage
19
of the brain
The brain is a highly vascular organ, its profuse blood supply character- lobes are supplied by branches of the vertebrobasilar system (see
ized by a densely branching arterial network (Kaplan and Ford 1966). Fig. 19.5).
It has a high metabolic rate that reflects the energy requirements of The internal carotid artery arises from the bifurcation of the common
constant neural activity. It receives about 15% of the cardiac output and carotid artery, ascends in the neck and enters the carotid canal of the
utilizes 25% of the total oxygen consumption of the body. The brain is temporal bone. Its subsequent course is said to have petrous, cavernous
supplied by two internal carotid arteries and two vertebral arteries that and intracranial parts.
form a complex anastomosis (circulus arteriosus, circle of Willis) on
Petrous part
the base of the brain. Vessels diverge from this anastomosis to supply
the various cerebral regions. In general, the internal carotid arteries The petrous part of the internal carotid artery ascends in the carotid
and the vessels arising from them supply the forebrain, with the excep- canal, curves anteromedially and then superomedially above the carti-
tion of the occipital lobe of the cerebral hemisphere, and the vertebral lage that fills the foramen lacerum, and enters the cranial cavity. It lies
arteries and their branches supply the occipital lobe, the brainstem and at first anterior to the cochlea and tympanic cavity, and is separated
the cerebellum. Venous blood from the brain drains into sinuses within from the latter and the pharyngotympanic tube by a thin, bony lamella
the dura mater. Acute interruption of the blood supply to the brain for that is cribriform in the young and partly absorbed in old age. Further
more than a few minutes causes permanent neurological damage. Such anteriorly, it is separated from the trigeminal ganglion by the thin roof
ischaemic strokes, along with intracranial haemorrhage, are major con- of the carotid canal, although this is often deficient. The artery is sur-


temporary sources of morbidity and mortality. rounded by a venous plexus and by the carotid autonomic plexus,
derived from the internal carotid branch of the superior cervical gan-
glion. The petrous part of the artery gives rise to two branches. The
ARTERIES OF THE BRAIN
caroticotympanic artery is a small, occasionally double, vessel that
enters the tympanic cavity by a foramen in the carotid canal and anas-
The arterial supply of the brain is derived from the internal carotid and tomoses with the anterior tympanic branch of the maxillary artery and
vertebral arteries, which lie, together with their proximal branches, the stylomastoid artery. The pterygoid artery is inconsistent; when
within the subarachnoid space at the base of the brain. present, it enters the pterygoid canal with the nerve of the same name,
and anastomoses with a (recurrent) branch of the greater palatine
artery.
INTERNAL CAROTID ARTERY
Cavernous part
The internal carotid arteries (Fig. 19.1) and their major branches (the The cavernous part of the internal carotid artery ascends to the posterior
internal carotid system or ‘anterior’ circulation) supply blood to the clinoid process. It turns anteriorly to the side of the body of the sphe-
majority of the forebrain. Some parts of the occipital and temporal noid within the cavernous sinus and then curves superiorly and medial
Intracavernous portion of Anterior cerebral Middle cerebral artery
internal carotid artery artery
A B
Ophthalmic artery Intrapetrous portion of Posterior communicating Intrapetrous portion of Intracavernous portion
internal carotid artery artery internal carotid artery of internal carotid artery
280 Fig. 19.1 Internal carotid arteriograms. A, Lateral projection. B, Towne’s projection.


Arteries of the brain
281
91
RETPAHC
to the anterior clinoid process, to emerge through the dural roof of the posterior communicating artery rather than from the basilar artery
sinus. The oculomotor, trochlear, ophthalmic and abducens nerves are (‘fetal posterior communicating artery’); it is often larger on one side
lateral to it within the cavernous sinus. The abducens nerve is closely only. Small branches from its posterior half pierce the posterior perfo-
related to the lateral wall of the internal carotid artery, whilst the ocu- rated substance together with branches from the posterior cerebral
lomotor and trochlear nerves are situated in the lateral wall of the artery. Collectively they supply the medial thalamic surface and the
cavernous sinus (see Figs 28.9, 28.10). This explains the higher risk of walls of the third ventricle. The anterior choroidal artery leaves the
abducens nerve injury secondary to pathology such as aneurysms of the internal carotid just distal to its posterior communicating branch and
cavernous part of the carotid artery. Occasionally, the caroticoclinoid passes back above the medial part of the uncus. It crosses the optic tract
ligament between the anterior and middle clinoid processes becomes to reach and supply the crus cerebri of the midbrain, then turns laterally,
ossified, forming a bony ring (caroticoclinoid foramen) around the recrosses the optic tract, and gains the lateral side of the lateral genicu-
artery (Ray and Gupta 2006). late body, which it supplies with several branches. It finally enters the
The cavernous part of the artery gives off a number of small vessels. inferior horn of the lateral ventricle via the choroidal fissure and ends
Branches supply the trigeminal ganglion, the walls of the cavernous and in the choroid plexus. This small, but important, vessel also contributes
inferior petrosal sinuses, and the nerves contained therein. A minute to the blood supply of the globus pallidus, caudate nucleus, amygdala,
meningeal branch passes over the lesser wing of the sphenoid to supply hypothalamus, tuber cinereum, red nucleus, substantia nigra, posterior