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Chapter 1
PRENATAL DEVELOPMENT OF THE BRAIN
Ronan O’Rahilly ● Fabiola Müller
KEY POINTS
1. The embryonic period (the first 8 postfertilizational
weeks) is subdivided into 23 morphological stages,
which, because they are based on internal as well as
external criteria, cannot be identified with confidence
by ultrasonography.
2. The three major divisions of the brain are found
early (stage 9), closure of the neuropores seals the
cerebrospinal cavity at 4½ weeks (stage 13), and
the five main subdivisions of the brain are visible
at 5 weeks (stage 15).
3. The telencephalon is identifiable already at 4 weeks
(stage 10) and begins to diverticulate at 5 weeks
(during stage 14), but holoprosencephaly is more
than a mere failure of diverticulation and may begin
as early as 3 weeks (stage 8), as can cyclopia and
anencephaly.
4. The appearance of the cortical plate (stage 21)
heralds the beginning of lamination of the cerebral
cortex, the basal nuclei and internal capsule are
progressing, and the brain is developmentally
advanced at the end of the embryonic period.
5. Prominent features during the fetal period are the
C-shaped structures, including the corpus callosum,
and the appearance of sulci and gyri on the cortical
surface at the middle of prenatal life.
Prenatal life can be divided conveniently into (1) the
embryonic period proper, that is, the first 8 weeks following fertilization, and (2) the fetal period, which extends
to birth. The distinction between the embryonic and fetal
periods is well founded and has long been established in
human embryology. The embryonic period is that time
during which new features appear with great rapidity,
whereas the fetal period is characterized more by the elaboration of existing structures. Moreover, the vast majority of congenital anomalies appear during the embryonic
period. The difference is highlighted by the fact that the
embryonic period has been successfully subdivided into
morphological stages, whereas the fetal period has so far
defied such a procedure.
The embryonic period has been divided into 23 developmental (Carnegie) stages ( Table 1-1 ), which have been
listed in detail by O’Rahilly and Müller,
graph the early development of the human embryo has
been thoroughly described. Each stage, on average, lasts
slightly more than 2 days. The stages are based on both
external and internal morphological criteria and depend
mainly on features that change rapidly, such as the number
of somitic pairs, the early appearance of the eye, and the
form of the developing limbs. Although it may sometimes
be possible to estimate approximately a given stage on
ultrasonography, the staging system is based on having an
embryo “in the hand” rather than in utero. Moreover, very
early as well as late stages can be identified precisely only
by histologic examination.
Although schemes have been devised to subdivide
the fetal period according to either measurements or age
(one of the simplest, into trimesters, is still very useful), no
morphological staging system is available, largely because
changes are neither sufficiently rapid nor adequately
spectacular.
1
in whose mono-
TERMINOLOGY
It should be pointed out that, in current usage in anatomy,
practically all eponyms (eg, Luschka, Magendie, Monro,
Reil, Rolando, and Sylvius) are now obsolete because they
convey nothing concerning either the site or the nature
of the relevant structure. The addition “of Monro” or “of
Sylvius” is superfluous because there is only one interventricular foramen and only one aqueduct in the brain.
PRENATAL MEASUREMENTS
Several different measurements, such as the biparietal
diameter and the ossified femoral length, are very important in later development, but the most useful datum
throughout prenatal life is still the greatest length, exclusive of the (flexed) lower limbs.
is less satisfactory because point C, which overlies the
midbrain, is frequently difficult to locate, and point R is
2
Crown-rump (C-R) length
2
Chapter 1 Prenatal Development of the Brain
Table 1–1. SUMMARY OF DEVELOPMENT OF THE CENTRAL NERVOUS SYSTEM
Embryonic Period
Stage
Greatest
Length (mm)
Approximate
Age (days) Key Features
1–7 0.1–0.4 1–19 Very early embryo
8 1 23 Neural folds and groove
9 2 25 Mesencephalic flexure; rhombencephalon, mesencephalon,
prosencephalon; 1–3 S
10 3 28 Fusion of neural folds begins; telencephalon and diencephalon
distinguishable; optic primordia; 4–12 S
11 3.5 29 Rostral neuropore closes; 13–20 S
12 4 30 Caudal neuropore closes; secondary neurulation begins; 21–29 S
13 5 32 Closed neural tube; primordium of cerebellum; isthmus
rhombencephali; 30–? ; Figure 1–2A
14 6 33 Pontine flexure; future cerebral hemispheres; all 16 neuromeres
present
15 8 36 Five subdivisions: medulla, pons, midbrain, diencephalons,
telencephalon; Figures 1–2B ; 1–3A , B ; 1–4
16 10 38 Thalamus; Figure 1–5
17 13 41 Internal and external cerebellar swellings; Figure 1–2C
18 15 44 Future corpus striatum; interventricular foramina defined;
Figure 1–6
19 17 46 Choroid plexus of fourth ventricle
20 20 49 Choroid plexus of lateral ventricles; Figure 1–3C , D
21 23 51 Anterior and inferior horns of lateral ventricle; circulus arteriosus
complete; Figure 1–2D
22 26 53 Internal capsule
23 29 56 Caudate nucleus and putamen; anterior commissure begins
Fetal Period
Trimester 1 Cerebellar halves unite, and vermis becomes defined
Corpus callosum is still very limited
Aqueduct appears narrow
Posterior horn of lateral ventricle
Trimester 2 Corpus callosum covers roof of third ventricle
Sulci and gyri become visible on hemispheric surface
Crura cerebri are prominent
Hippocampal formation becomes S-shaped
Myelinization begins in CNS
Trimester 3 Insula buried by opercula
CNS, central nervous system; S, pairs of somites.
Note: The greatest lengths and the postfertizational ages given are approximate only. The latter have been revised to conform to current ultrasonic
information.
Data from O’Rahilly and Müller (2001).
15
Chapter 1 Prenatal Development of the Brain
3
imprecise. The greatest length, which is independent of
fixed points, is much simpler to ascertain and is in fact
what is generally measured.
3 , 4
The distinction between stages and measurements
should be kept clearly in mind. The “18-mm stage” is
incorrect usage, because 18 mm is merely a length, not a
stage as the term is used in embryology.
PRENATAL AGE
Just as postnatal age commences at birth, prenatal age
begins at fertilization. Ovulation is sufficiently close, so
that the term postovulatory has frequently been used
to indicate age. Particularly since the advent of in vitro
fertilization, however, age is best referred to as postfertilizational.
When a reliable menstrual history is available, or indirectly by the conventional addition of 2 weeks to the age,
the duration from the first day of the last menstrual period
(LMP) may be used. The duration is expressed in (post)
menstrual weeks and days. This is perfectly acceptable provided that the duration is designated as (post)menstrual,
and it is not referred to as age. At postmenstrual week 1,
an embryo does not even exist.
In summary, two systems of designation are available:
(1) age, which is postfertilizational and generally estimated; and (2) (post)menstrual duration, which, although
it is not age (and should not be combined with that word),
is a useful guide in clinical practice. The type of weeks
being used should be specified: postfertilizational weeks
or weeks of age, or (post)menstrual weeks. Confusion is
thereby eliminated.
It has been shown that the term gestational age in the
literature is either not defined or is used indiscriminately
for postmenstrual weeks and days or for postfertilizational
age. 5 The continuing confusion concerning prenatal age
is unnecessary and disappears once the ambiguous and
superfluous term gestational age is abandoned.
The advent of ultrasonography has led to the construction of many elaborate tables of prenatal measurements
related to prenatal age, or more generally to intervals since
the LMP. Although not all of these tables are in agreement in detail, it would be agreed that at the end of the
embryonic period, when the greatest length is ∼30 mm,
the age is 8 weeks, corresponding to 10 postmenstrual
weeks.
DEVELOPMENT OF THE NERVOUS SYSTEM
The development of the human nervous system is summarized here ( Tables 1–1 and 1–2 ). The most detailed
and precise account of the prenatal human brain, with
particular emphasis on the embryonic period, is The
Embryonic Human Brain: An Atlas of Developmental
6
That study contains a bibliography of 350 entries,
Stages .
and therefore a detailed list of references is not provided
here. Some significant features have been summarized
recently.
7
Table 1–2. FEATURES OF THE BRAIN FOUND BY ULTRASOUND DURING FIRST TRIMESTER
Postfertilizational
Weeks (Age)
5 7 First indication of brain
5–6 7–8 Cerebral hemispheres, lateral ventricles, wide interventricular foramina
6–7 8–9 Choroid plexuses of lateral ventricle
7–8 9–10 Falx cerebri
8–10 10–12 Growing thalami
Modified from Timor-Tritsch, Blaas. O’Rahilly and Müller, 2006, 6 with permission.
Postmenstrual
Weeks Features
Future third ventricle
Mesencephalon and future aqueduct
Rhombencephalon and fourth ventricle
Telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon
Cerebellum, pontine flexure, lateral recesses of fourth ventricle
C-shaped lateral ventricles
Narrower third ventricle
Isthmus prosencephali (between third ventricle and aqueduct)
Cerebellar hemispheres seem to meet
Cerebellar peduncles
Tentorium cerebelli
Fourth ventricle divided by choroid plexus
4
Chapter 1 Prenatal Development of the Brain
PRIMARY NEURULATION
The CNS arises mostly from a part of the ectoderm
known as the neural plate. The folding of the neural
plate to form successively the neural groove and the
neural tube is termed primary neurulation and is the
first visible sign of the nervous system. It begins when
the embryo is ∼1 mm in length. Closure of the neural
groove begins near the junction of the future brain and
spinal cord. The still open ends of the developing neural
tube are known as the rostral and caudal neuropores,
which close successively at about 4 weeks. The closure
of the rostral neuropore is bidirectional: rostrocaudal
and caudorostral. Although small and variable accessory loci of fusion of the neural folds may sometimes be
seen, a specific pattern of multiple sites of fusion, such as
has been described in the mouse, does not occur in the
8
human.
Moreover, attempts to force the classification of
neural tube defects into such a pattern are unconvincing. Primary neurulation is completed by the separation
of neural from surface ectoderm by the interposition of
mesenchyme.
SOME EARLY ANOMALIES
In diastematomyelia the spinal cord is partially split longitudinally into right and left halves that are separated by a
fibrocartilaginous or bony spur in the vertebral canal. This
may be a manifestation of the split notochord syndrome,
which is generally attributed to persistence of the neurenteric canal, a temporary communication through the
primitive node (at stages 8 through 10).
Anencephaly, a partial absence of the brain and the
overlying cranial vault, frequently arises from (1) failure of
the rostral neuropore to close, followed by (2) protrusion
of the brain (exencephaly), and finally (3) degeneration
of the exposed portions.
ably stages 8 and 9), before postfertilizational week 4, and
defective production of mesenchyme is considered to be of
fundamental importance.
Holoprosencephaly is a variable deficiency in “diverticulation” of the prosencephalon to form the cerebral hemispheres and is usually accompanied by facial malformation.
Abnormal induction by an area of the future forebrain near
the prechordal plate very early (stages 7 and 8) is believed
to be significant.
complete (alobar holoprosencephaly), partial (semilobar),
or only rostral (lobar).
Cyclopia is the occurrence within a single orbit of a
median eye (sometimes distinguished as synophthalmia)
or paired ocular structures.
tion (which is not a fusion) is believed to be caused by
the lack of normal inhibition of the median portion
of the originally single optic field.
chordal plate induces paired optic primordia very early
(stages 7 and 8).
Encephalo(meningo)celes are generally in the occipital region. They are covered by skin and hence are
believed to arise after closure of the neural tube, probably in the presence of mesenchymal insufficiency. Those
situated anteriorly (eg, in the fronto-ethmoidal region)
9
The defect arises early (prob-
10
1 1
The failure of lateralization may be
11 , 12
The defective lateraliza-
6
Normally, the pre-
constitute a separate category and are based on a primary disturbance in the separation of neural and surface
ectoderm at the site of final closure of the rostral neuropore, resulting secondarily in a mesodermal defect at
this site.
13
SECONDARY NEURULATION
Secondary neurulation is the continuing formation of the
sacrococcygeal part of the spinal cord from the caudal
eminence, without direct involvement of the surface ectoderm (neural plate). It begins once the caudal neuropore
has closed. The transition from primary to secondary neurulation is at the site of closure of the caudal neuropore.
The caudal neuropore closes at the level of somitic pair
31, which corresponds to future vertebral level S2 in the
embryo. Because of the ascent of the spinal cord during
the fetal period, however, the site of the former caudal neuropore ascends also and corresponds to a higher vertebral
level postnatally.
THE EMBRYONIC BRAIN
Postmenstrual Weeks 5 to 6 (3 to 4 Weeks of Age)
As the embryo becomes more elongated, the neural groove
becomes deeper, and the three major divisions are distinguishable in the folds of the completely open neural groove:
the forebrain, the midbrain, and the hindbrain. The site of
the midbrain is indicated by the mesencephalic flexure,
which remains distinct throughout the embryonic period
( Figure 1–1 ). The neural tube has not yet formed, and the
“brain vesicles” are largely a myth. The forebrain soon
becomes subdivided (earlier than previously appreciated)
into the diencephalon and the telencephalon medium. The
embryo is now ∼3 mm in length.
Postmenstrual Weeks 6 to 7
(4 to 5 Weeks of Age)
When both neuropores are closed at 4 to 5 weeks after
fertilization, the future ventricular system ( Figure 1–2 )
no longer communicates with the amniotic cavity. At this
time, in embryos ∼5 mm in length, the first (bilateral) indication of the cerebellum can be discerned.
The cerebral hemispheres ( Figure 1–3 ) become delimited from the telencephalon medium. A bend, the pontine
flexure, begins in the hindbrain and allows a subdivision
into the metencephalon (the pons and the cerebellum)
and the myelencephalon (the medulla oblongata). All
five major subdivisions of the brain are then distinguishable: the telencephalon, diencephalon, mesencephalon,
metencephalon, and myelencephalon. The initial development of the basal nuclei (a more accurate term than
ganglia) now takes place, and the thalami are also discernible ( Figures 1–4 and 1–5 ). The embryo is ∼6 mm in
length.
In the Arnold-Chiari malformation, a failure of the
pontine flexure to form is believed to be important in the
abnormal elongation of the hindbrain.
Chapter 1 Prenatal Development of the Brain
5
Stage 12
13
14
18
15
Figure 1–1. Right lateral views of the brain at postmenstrual weeks 6 to 8 (4 to 6 weeks of age). The midbrain is shaded, and the mesencephalic flexure
( short arrow ) is evident. The beginning of the pontine flexure can be seen ( larger arrow ). The optic cup and the internal ear are included. (Reproduced
from O’Rahilly and Müller, 2006,
6
with permission).
Postmenstrual Weeks 7 to 8 (5 to 6 Weeks of Age)
The neurohypophysis ( Figure 1–3C ) begins its evagination,
and the longitudinal fissure becomes deeper with continuing growth of the cerebral hemispheres ( Figure 1–3D ).
The basioccipital part of the skull is beginning to chondrify. The embryo is ∼12 mm in length.
17
Postmenstrual Weeks 8 to 9 (6 to 7 Weeks of Age)
A feature that appears very gradually is the flattening
of the insular region. The embryo is ∼20 mm in length
( Figure 1–6 ).
In the Dandy-Walker syndrome, maldevelopment of
the rostral part of the roof of the fourth ventricle is consid-
16
ered to be a significant causative factor.
Stage 13 15
17 21
External
Internal
Figure 1–2. Right lateral views of the brain in situ to show the ventricu-
lar cavities ( shaded ) at postmenstrual weeks 6½ to 9½ (4½ to 7½ weeks
of age). The first indication of anterior and inferior horns of the lateral
ventricle are visible in the last drawing.
contour of brain
Postmenstrual Weeks 9 to 10
(7 to 8 Weeks of Age)
The falx cerebri, indicated initially by a leptomeningeal
precursor, is apparent. Ossification is beginning in the
occipital region of the skull, and the foramen magnum is
definable. The anterior (frontal), posterior (occipital), and
inferior (temporal) poles of the cerebral hemispheres, as
well as the insula, can be detected, although they are not
yet pronounced. The ventricles at this time are shown in
Figure 1–7 .
Important histologic differentiation takes place in
the cerebral cortex, and the internal capsule develops.
Numerous nuclei and tracts have been plotted. The anterior and lateral corticospinal tracts are present, and the
pyramidal decussation has begun. The spinothalamic
tract and thalamocortical fibers (generally considered
to be essential for the perception of pain) are appearing.
Although the functional significance is far from clear,
nociception is present before birth, and it is prudent
to assume that pain can be experienced even early in prenatal life.
The embryonic period proper closes at 8 weeks after
fertilization, when the greatest length (exclusive of the
lower limbs) is ∼30 mm. By this time 200 features of the
brain have appeared and have been listed.
It is to be stressed that when a structure is first seen in
vivo and in utero by current imaging techniques, it should
be appreciated that this is usually considerably later than
the actual situation elucidated in human embryology.
6
6
Chapter 1 Prenatal Development of the Brain
AB
Mes.
Met.
Mes.
Mes. flexure
Myel.
Pontine flexure
C
Mes.
Di.
Tel.
Ep.
Hem.
D
Choroid fissure
& plexus
V3
Lat.
Cerebral cortex
Longitudinal fissure
Di.
Tel. med.
I-V.F.
Lat.
V4
Hem.
Di.
V3
I-V.F.
Cerebellum
Neurohypophysis
Figure 1–3.
hemispheres developing from the telencephalon medium. C and D Postmenstrual week 9 (7 weeks of age). ( C ) Typical appearance of the embryonic
brain (at stage 20). In ( D) the wall of each hemisphere has invaginated laterally (at the choroid fissure) into the lateral ventricle to form the choroid
plexus. Di., diencephalon; Ep., epiphysis cerebri (pineal gland); Hem., cerebral hemisphere; I-V.F., interventricular foramen; Lat., lateral ventricle; Mes.,
mesencephalon; Myel., myelencephalon; Tel., telencephalon; Tel. med., telencephalon medium; V3, third ventricle; V4, fourth ventricle.
A and B Postmenstrual week 7 (5 weeks of age). ( A) The five main subdivisions of the brain (at stage 15). ( B ) The beginning cerebral
Olfactory bulb
Corpus
striatum
VASCULARIZATION
A description of the developing vessels to the brain is
available,
artery develops early (4 weeks) and is followed by the
posterior communicating artery, initially important as
the main carotid supply to the hindbrain until the vertebral system is in place and the basilar artery (originally
Figure 1–4.
strual week 8 (6 weeks of age). The pontine and mesencephalic flexures
are pronounced (at state 17). The thin roof of the fourth ventricle (V4)
is not shown. Included are the optic cup, trigeminal ganglion, and cranial nerves IV and III. Cbl, cerebellum; Di., diencephalon; Ep., epiphysis
(pineal); Hem., cerebral hemisphere; Opt., optic cup.
14
as are individual details. 6 The internal carotid
V4
Cbl
M
V
Di.
Opt.
Ep.
Hem.
Right lateral and “end-on” views of the brain at postmen-
bilateral) becomes dominant. A series of caroticobasilar anastomoses is temporary (4 to 6 weeks), although
segments may sometimes persist (eg, a trigeminal artery).
With the completion of the anterior communicating artery
after the three named cerebral arteries have appeared, the
Cbl
Teg.
HTh.
Mes.
D Th.
Ep.
Ch.
Comm.
V Th.
CS
I-VF
Figure 1–5. Medial view at the same stage as the previous figure.
The arrows indicate the cerebrospinal junction. A and B, alar and basal
laminae; Cbl, cerebellum; Ch., optic chiasma; Comm., commissural plate
(future corpus callosum); CS, corpus striatum; DTh., dorsal thalamus;
Ep., epiphysis (pineal); HTh., hypothalamus; I-VF, interventricular foramen; Mes., mesencephalon; Teg., tegmentum; VTh., ventral thalamus.
A
B
0.2
Chapter 1 Prenatal Development of the Brain
Figure 1–6. The brain at the end of the embryonic period (stage 23).
The insula is now clearly indented and will later become buried. Most of
the diencephalon is by this time covered by the cerebral hemisphere(s).
(From O’Rahilly and Müller, 2006,
circulus arteriosus (described by Willis) is established by
7 weeks (stage 21).
SKELETAL SUPPORT
The skull develops in three overlapping phases: blastemal
or membranous (desmocranium), cartilaginous (chondrocranium), and ossific (osteocranium).
the “membrane bones” is almost complete at the end of the
6
with permission.)
15 , 16 , 17
18
The inventory of
7
embryonic period, and these components are an important
part of the splanchnocranium or viscerocranium, which
develops in pharyngeal arches 1 and 2, and uses cartilaginous bars as a template for the mandible and the auditory ossicles. Both endochondral and intramembranous
ossification are involved in the skull, which becomes a
unity in which the original components are no longer distinct. The spheno-occipital junction is a cartilaginous joint
until about puberty, when bony fusion takes place. The
much larger portion (neurocranium) of the skull that lies
above the orbitomeatal plane protects the brain, which lies
in a skeletal bowl from which it is protected by fluid-filled
mesenchyme. It is of interest to note that in anencephaly
the brain becomes highly differentiated before it begins
to disintegrate, but its skeletal base and covering become
abnormal early.
The notochord is the distinctive feature of chordates,
most of which have a surrounding vertebral column and
hence are termed vertebrates. The notochord is a compli-
cated “string” that comes to extend from the sphenooccipital junction to the last coccygeal vertebra. It contributes to
the nuclei pulposi of the intervertebral discs. Notochordal
remains are sometimes found within vertebral bodies, or
as a chordoma in the sacrococcygeal or sphenooccipital
regions.
The vertebrae ( Figure 1–8 ) arise from sclerotomes
derived from somites, which are bilateral mesenchymal
segments on each side of the neural tube. The notochord
is an axial structure ventral to the tube that eventually
A
Ant.
C
Ant.
Figure 1–7. The ventricular cavities at the end of the embryonic period (stage 23). (A ) Dorsal view showing the lateral ventricles. ( B ) Left lateral view
of the complete ventricular system. ( C ) Dorsal view of the complete ventricular system. In each drawing the choroid plexuses are indicated by stippling.
Based on reconstructions by the authors. Ant., anterior or frontal horn; Inf., inferior or temporal horn; I-V.F., interventricular foramen; Mes., mesencephalic ventricle (the future aqueduct); Olf., “olfactory ventricle” (temporary); V3, third ventricle; V4, fourth ventricle.
B
Ant.
V3
V3
Olf.
Inf.
Mes.
V4
Inf.
I.-V.F.
Lateral
recess
V4
Mes.
8
Chapter 1 Prenatal Development of the Brain
A
Centra
Basi-
occ.
X
Y
Z
C3
T1
L1
S1
Co.1
BC D
Somites/
Sclero-
tomes
10
20
30
Neural
arches
1
2
Ex-
3
occ.
4
5
6
7
8
9
C1
T1
L1
S1
Co.1
Spinal
Ganglia & Nerves
C1
T1
Subcostal n.
L1
S1
Co.
1
2
3
4
5
6
7
8
T1
Intercostal nn
L4
S4
Plexus
Cervical
Brachial
Lumbar
Sacral
Coccygeal
Figure 1–8. Early development of the vertebral column. Column ( A) is
the median component: the centra (future bodies). Column (B) shows the
sclerotomes, which are derived from the somites. Column ( C) is the lateral component: the neural (future vertebral) arches. The sclerotomes ( B )
and the neural arches ( C ) are not in register with the centra ( A ). Column
(D ) shows the spinal ganglia and nerves. The occipitocervical junction
develops between segments 4 and 5 ( B , C ), whereas the cerebrospinal
junction (not shown) occurs between rhombomere 8 and the spinal cord.
Sclerotomes 1 to 4 give rise medially ( A ) to the basioccipital. Sclerotome
4 forms the exoccipital laterally ( C ). Sclerotome 5 becomes the posterior
arch of the atlas, and sclerotome 6 provides the neural arch of the axis.
The central pillar of the axis has three components ( A ): X, the apex of the
dens; Y, the base of the dens; and Z, the centrum of the axis. The foramen
magnum is between the basioccipital and X in A. Based on reconstructions by the authors. (Reproduced, with permission from, Journal of
Anatomy, 1994;185:251–258.)
becomes embedded in the vertebral bodies and intervertebral discs. An important feature is the development of
loose and dense zones in a complicated manner that differs
laterally and medially.
15
The development of the occipitocervical region is very
complicated, and the details should be sought in a special
account.
19
Medially, a perinotochordal tissue and migrated
sclerotomic cells give rise to the basioccipital and to vertebral centra, including a tripartite column that forms the
axis vertebra ( Figure 1–9 ). Laterally, sclerotome 4 gives
A
Mes.
Cbl
l-VF
Comm.
B
X
Y
CV 1
Z
CV 3
Figure 1–9.
period (stage 23). ( A ) Median section. The left cerebral hemisphere
is included. ( B ) The occipitocervical region. The notochord ascends
through the tripartite column (Z, Y, X) of the axis, leaves the dens to
pass through the foramen magnum, and traverses the basioccipital in
the direction of the hypophysis. The arrow represents the approximate
position of the sphenooccipital joint. The remains of the stalk from the
pharyngeal hypophysis to the adenohypophysis can be detected. Cbl,
cerebellum; Comm., commissural plate; CV1, cervical vertebra 1 (anterior
arch of the atlas); CV3, cervical vertebra 3; Hyp., adenohypophysis; I-VF,
interventricular foramen; Mes, mesencephalon; Nas., nasal septum; Ph.,
pharynx; X, Y, Z, parts of the axis vertebra. Bars, 1 mm.
The brain and cranial base at the end of the embryonic
Ph.
Nas.
rise to the exoccipital, and sclerotome 5 forms the posterior arch of the atlas.
SPINA BIFIDA
Spina bifida may be evident (aperta) or concealed (occulta).
A cystic mass is generally present in those that are obvious,
and these are known as spina bifida cystica. Spinal and
cerebral forms of neural tube defects exhibit a close parallelism, as shown in Figure 1–10 .
Myelomeningocele (or meningomyelocele), which
may arise as a myeloschisis, is usually lumbosacral. Failure
of closure of the caudal neuropore is probably a major factor, although the condition is not considered to be a simple
failure of neural closure. When the caudal neuropore does
not close, fixation between neural and surface ectoderm
may hinder the normal ascent of the spinal cord, which
becomes tethered. When spina bifida aperta is found in the
cervicothoracic region, however, the possibility of reopening of the neural tube needs to be entertained.
Chapter 1 Prenatal Development of the Brain
Neural tube defects
C
arch
Neural
*
Centrum
B
Aperta
Spina bifida
Dysraphia (NTD)
Spinal
Open neural plate
Myeloschisis
Myelomeningocele
Cystica
Meningocele Meningocele
Cerebral
Open neural plate
Exencephaly
Anencephaly
Encephalocele
9
A
Figure 1–10. Neural tube defects. (A ) The cartilaginous neural processes have not yet united in the embryo. (B ) Three ossific centers are present in the
newborn, providing a radiologic appearance of a normal spina bifida. ( C ) Ossification is complete. The neurocentral joint ( asterisk ) is a bilateral cartilaginous articulation between the neural arch and the centrum. In A′ a continued lack of closure of a vertebral foramen would constitute a spina bifida.
It is not always appreciated that spina bifida occulta is
a normal phase of development. At the end of the embryonic period, the spinal cord and the vertebral column end
at the same level. Moreover, ossification has not extended
A′
calcarine, etc) on the hemispheric surface at about the middle of prenatal life, at which time the cerebral peduncles
become prominent. One of the most noticeable internal
changes is the growth of the corpus callosum.
Occulta
Spina bifida
occulta
Cranium bifidum
occultum
dorsally, so that a total spina bifida occulta exists, and this
persists into adulthood in part of the sacral region in about
one-fifth of normal persons. During the fetal period, a differential shift in growth occurs whereby the conus medullaris is found at increasingly higher vertebral levels, L3 at
birth and L2 or L1 in adulthood.
Spinal meningoceles may arise as herniations in the
presence of a mesenchymal deficiency, probably during the
time the normal spinal bifida occulta is present. Cerebral
meningoceles are rare.
CORTICAL DEVELOPMENT 6
The cerebral cortex begins to develop as the cortical
plate, lateral to the future corpus striatum (stage 21).
The plate divides the cerebral wall into the subpial layer
peripherally (future layer 1) and the future white matter
centrally. The cortical plate enlarges rapidly and covers most of the lateral part of the cerebral hemispheres
at the end of the embryonic period. Cortical layers
2 to 6 develop from the cortical plate during the fetal
THE CEREBELLUM
The cerebellum arises as a bilateral organ very early
in development (at about 4½ weeks of age). Later in
the embryonic period it projects largely into the fourth
ventricle in a complicated and temporary manner
period. The prefrontal cortex completes its differentiation approximately 6 months after birth. Sulci and gyri
begin to appear at about the middle of pregnancy. A vascular network develops within the cortex in trimester 2.
The vessels consist of simple epithelial channels at first;
a muscularis is acquired only near term.
( Figures 1–4 , 1–5 , and 1–6 ). Early in the fetal period, the
union of the two halves results in the vermis, which then
develops folia and becomes largely obscured by the cerebellar hemispheres. At birth, the form of the cerebellum
closely resembles that of the adult.
C-SHAPED STRUCTURES
Associated with the growth of the relatively fixed corpus
striatum and the curved expansion of the cerebral hemi-
spheres to form the temporal lobes, several structures
THE FETAL BRAIN
The most evident external changes in the fetal period are
(1) the union of the cerebellar halves and the definition of
the vermis; (2) the increasing concealment of the diencephalon and the mesencephalon, and (later) of part of the cerebellum, by the cerebral hemispheres; (3) further approach
of the frontal and temporal poles around the insula,
which becomes increasingly buried by opercula; and (4)
the appearance of sulci (lateral, central, parieto-occipital,
develop in a C-shaped manner: (1) caudate nucleus; (2)
choroid plexus and fissure; (3) fornix and fimbria; (4) indu-
sium griseum, hippocampus, and dentate gyrus; (5) corpus
callosum (although the splenium does not descend into the
temporal lobe); and (6) lateral ventricle.
The commissural plate of the embryo ( Figure 1–5 )
gives rise early in the fetal period to the corpus callosum and the anterior commissure ( Figure 1–11A ). The
corpus callosum, on the median section, is at first merely
a compact mass ( Figure 1–11B ), but its length increases