CHAPTER 8 • The Fetal Central Nervous System. First Trimester Ultr

 CHAPTER 8 • The Fetal Central Nervous System

INTRODUCTION

The evaluation of the fetal central nervous system (CNS) is an important aspect of

ultrasound in the first trimester given that several major malformations, such as

anencephaly/exencephaly, holoprosencephaly (HPE), among others can be easily

identified. However, detection of subtle malformations in the first trimester, such as

small encephaloceles, neural tube defects, or posterior fossa abnormalities, requires a

detailed ultrasound evaluation of the CNS. In this chapter we present a systematic

detailed approach to the first trimester ultrasound examination of the normal CNS,

followed by a comprehensive presentation of common CNS malformations that can be

diagnosed in early gestation.

EMBRYOLOGY

Formation of the fetal brain is seen as early as the fifth week of embryogenesis by

outgrowth of the neural tube in its cephalic region to form three brain vesicles: the

prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon

(hindbrain). By the sixth week of embryogenesis, the prosencephalon differentiates into

the telencephalon and diencephalon, the mesencephalon remains unchanged, and the

rhombencephalon divides into the metencephalon and myelencephalon. Ultrasound

images of the fetal brain at 7 to 8 weeks of gestation (menstrual age) demonstrate these

brain vesicles (Figs. 8.1 and 8.2). The falx cerebri, an echogenic structure that divides

the brain into two equal halves, and the choroid plexuses, which fill the lateral

ventricles, are seen on ultrasound by the end of the eighth week and beginning of the

ninth week of gestation (Fig . 8.3). The cerebellar hemispheres develop in the

rhombencephalon and are completely formed by the 10th week of gestation, thus

allowing for evaluation of the posterior fossa with optimal ultrasound imaging (Fig.

8.4). Prior to the 9th week of gestation, the cranium is not typically ossified (Fig. 8.5).

Cranial ossification begins around the late 9th, early 10th week and is completed by the

12th week of gestation. Figure 8.5 shows progression in fetal cranial ossification from9 to 13 weeks of gestation.

Figure 8.1: Three-dimensional ultrasound in multiplanar display of an embryo at

7 weeks 5 days gestation showing early development of the brain. Note the

size of the rhombencephalic vesicle (Rb) in the posterior aspect of the brain as

the largest brain vesicle at this stage of development. The lateral ventricles

(Lat. V) and the third ventricle (3rd V) are also seen. F, falx cerebri.

Figure 8.2: (A, B and C) Three-dimensional ultrasound volume of a fetus at 8weeks of gestation showing early development of the brain. A: A sagittal view

of the fetus in surface mode. B: A coronal plane of the fetal head retrieved

from the multiplanar display. C: A rendered image of the fetus in Silhouette®

mode. Note the anatomic relationships of the lateral (Lat. V), the third (3rd V),

and the rhombencephalic (Rb) ventricles.

Figure 8.3: Axial planes of the fetal head in a fetus at 9 (A) and 10 (B) weeks

of gestation. Note in A and B, the appearance of the choroid plexuses (CP) of

the lateral ventricles and the falx cerebri (Falx), which are visible from 9 weeks

onward. The third ventricle (3rd V) and the aqueduct of Sylvius (AS) are also

recognized in these axial planes.Figure 8.4: The posterior fossa, demonstrating the development of the

rhombencephalic vesicle (Rb) into the fourth ventricle (4th V). The sagittal (A)

and axial (B) planes of the fetal head at 8 weeks of gestation. Note the

appearance of the Rb in the posterior aspect of the brain. The sagittal (C) and

axial (D) planes of the fetal head at 10 weeks of gestation. Note the

development of the 4th V at this gestational age. The choroid plexus (CP) of

the 4th V is also visible in C.Figure 8.5: Axial planes of the fetal head at 9 (A), 10 (B), and 13 (C) weeks of

gestation demonstrating the progression of skull ossification. Note at 9 weeks

of gestation (A), the presence of small islands of ossification (arrows). At 10

weeks of gestation (B), partial ossification of the frontal (F), parietal (P) and

occipital (O) bones is seen. At 13 weeks of gestation (C), the frontal (F),

parietal (P) and occipital (O) bones are clearly seen. The occipital bone (O) is

better imaged in a more posterior plane at the level of basal ganglia (see Figs.

8.6 and 8.10).

NORMAL SONOGRAPHIC ANATOMY

Ultrasound evaluation of the fetal intracranial anatomy is commonly performed in the

axial (transverse) and midsagittal planes of the fetal head (Figs. 8.6 to 8.12). Axial

(Figs. 8.6 to 8.11) and midsagittal (Fig. 8.12) planes of the fetal head are commonly

obtained in the first trimester for the measurement of the biparietal diameter (BPD) and

nuchal translucency (NT), respectively. Furthermore, the midsagittal plane is also

obtained for the evaluation of the fetal facial profile and nasal bones. The axial and

midsagittal planes of the fetal head are also part of the International Society ofUltrasound in Obstetrics and Gynecology (ISUOG) practice guidelines for the

performance of the first trimester ultrasound examination.1 The coronal planes of the

fetal head are also occasionally helpful in the visualization of midline structures when

certain malformations are suspected. The authors recommend routine evaluation of the

axial and midsagittal planes of the fetal head when ultrasound examinations are

performed beyond the 12 weeks of gestation. Please refer to Chapter 5 for the

systematic approach to the detailed ultrasound examination of the fetus in the first

trimester, with comprehensive presentation of standardized planes for the evaluation of

the CNS in early gestation.

Axial Planes

The systematic detailed examination of the fetal brain in the first trimester includes the

acquisition of three axial planes, similar to the approach performed in the second

trimester ultrasound examination (see Figs. 5.7 and 5.8). In these planes, the fetal head

shape is oval and the skull can be identified from 10 weeks onward (Fig. 8.5). At this

early gestation, bone ossification primarily involves the frontal, parietal, and occipital

parts of the cranial bones (Figs. 8.5 and 8.6). The use of high frequency linear or

transvaginal transducers improves imaging of the fetal CNS in early gestation (Fig. 8.7).

The intracranial anatomy is divided by the falx cerebri into a right and left side of equal

size (Figs. 8.6 to 8.8). The choroid plexus on each side is hyperechoic, typically fills

the lateral ventricles, and is surrounded by cerebral spinal fluid (Figs. 8.7 to 8.9). In the

first trimester, the shape of the choroid plexus is described to be similar to a butterfly

(Fig. 8.8).2 The left and right choroid plexuses are rarely of similar size and shape, and

this difference is considered part of the normal variation (Fig. 8.9).3 A small rim of the

developing cortex can be seen laterally surrounding the choroid plexuses (Fig. 8.7). In

an axial superior plane of the fetal head, a fluid rim can be seen surrounding the choroid

plexus on each side, corresponding to the lateral ventricle (Fig. 8.10A). A more inferior

axial plane toward the base of the skull shows the two thalami and the third ventricle,

forming the diencephalon (Fig. 8.10B). Posterior to the thalami, the two small cerebral

peduncles are identified surrounding the aqueduct of Sylvius and forming the

mesencephalon (midbrain) (Fig. 8.10B). The developing cerebellum is identified in the

posterior fossa primarily by transvaginal ultrasound and in an axial plane that is tilted

toward the upper spine (Fig. 8.11A). A slightly more inferior plane will show the fourth

ventricle, the future cisterna magna, and the hyperechogenic choroid plexus of the fourth

ventricle (Fig. 8.11B). Table 8.1 gives an overview of the anatomic landmarks and

corresponding malformations that can be visualized in the axial planes of the fetal head

in the first trimester.Figure 8.6: Three-dimensional (3D) volume of a fetal head at 12 weeks of

gestation. The 3D volume was obtained from an axial plane and is displayed in

tomographic view. From superiorly (top) to inferiorly (bottom) you can see the

choroid plexuses (CP), the falx cerebri (Falx), the third ventricle (3rd V), the

aqueduct of Sylvius (AS), the cerebral peduncles (Cer. Ped.), and the fourth

ventricle (4th V). The lateral ventricles (Lat. V) are seen in the mid-axial plane.

Note the appearance of the frontal (F), parietal (P), and occipital (O) bones.Figure 8.7: Axial view of the fetal head at 12 weeks of gestation from a lateral

approach, obtained with three different high-resolution transducers:

transabdominal curved array (A), transabdominal linear (B), and transvaginal

(C). Note the improved resolution in the transabdominal linear (B) and

transvaginal (C) transducers. The falx cerebri (Falx) is seen along with the

choroid plexuses (CP) and cerebrospinal fluid (asterisks) in the lateral ventricles

(Lat. V). The rim of the developing cortex is also seen (arrows). Note that at

this stage of development, the ventricular system occupies the majority of the

brain.Figure 8.8: Axial view of the fetal head at the level of the choroid plexuses

(CP) in a fetus at 11 weeks (A) and at 13 weeks (B) of gestation. Note that the

right and left CP resemble the shape of a butterfly and are referred to as the

“butterfly sign.” The falx cerebri (Falx) is seen in the midline. Compare with

Figures 8.24 and 8.25 obtained from fetuses with alobar holoprosencephaly.Figure 8.9: Axial views of the fetal head obtained in early gestation at the level

of the choroid plexuses in three normal fetuses (A–C) and in a fetus with

trisomy 13 (D). Note in A to C the presence of choroid plexus asymmetry

(double arrows), considered as a normal variant. Fetuses A to C had a normal

subsequent second trimester ultrasound. Note the presence of choroid plexus

cysts (CPC) and nuchal edema (asterisk) in the fetus with trisomy 13 (D).Figure 8.10: Axial views of the fetal head at 13 weeks of gestation obtained

superiorly at the level of the lateral ventricles (A) and inferiorly at the level of

the thalami (B). In A, the two lateral ventricles (Lat. V), the choroid plexuses

(CP), and the falx cerebri (Falx) are seen. In B, the thalami (Thal.) with the third

ventricle (3rd V) are recognized and constitute the diencephalon. Posterior to

the thalami, the cerebral peduncles (Cer. Ped.) with the aqueduct of Sylvius

(AS) can be visualized and form the mesencephalon (see Fig. 8.11).Figure 8.11: Axial view of the fetal head at 13 weeks of gestation obtained at

the level of the posterior fossa (inferior to planes A and B in Fig. 8.10). A: At

the level of the developing cerebellum (Cer.) and cerebral peduncles (Cer.

Ped.). Note the thalami (Thal.) in a more anterior location. B: An oblique,

slightly more inferior plane demonstrating the open fourth ventricle (4th V)

connecting to the future cisterna magna (CM). The echogenic choroid plexus

(CP) of the fourth ventricle can also be seen.• • •

Figure 8.12: Schematic drawing (A) and corresponding ultrasound image (B)

of the midsagittal plane of the fetal head in the first trimester (same as nuchal

translucency [NT] plane). This plane enables a good assessment of the

posterior fossa. The following structures can be seen: thalamus (T), midbrain

(M), brainstem (BS), the fourth ventricle presenting as an intracranial

translucency between the BS and the choroid plexus (CP), and the cisterna

magna (CM). 1, 2, and 3 point to the nasal bone, maxilla, and mandible,

respectively.

Table 8.1 • Axial Planes of the Fetal Head and Associated Abnormalities in

the First Trimester

Normal Suspected Abnormalities

Head shape Oval shape

Anencephaly/exencephaly:

Irregular shape, no skull identified

Holoprosencephaly: circular head

Osteogenesis imperfecta: no

ossification (except for occipital

bone). Additional findings such as

short broken and bent femur and

humerus• • • • • • •• • • •

Bony borders Ossified bones

Clear head borders

Thanatophoric dysplasia:

Increased ossification of head,

additionally short or abnormally

shaped long bones

Encephalocele: Interrupted head

contour, commonly in the occipital

region

Falx cerebri

Hyperechogenic line

from anterior to

posterior dividing the

brain in two halves

Holoprosencephaly: absent falx

cerebri

Encephalocele: Often deviated falx

cerebri

Choroid

plexuses of

lateral

ventricles

Large hyperechogenic

plexuses on both

sides, could be

slightly asymmetrical

Holoprosencephaly: fused choroid

plexuses

Choroid plexus cysts: typically

found in trisomy 13 or other

aneuploidies (in general additional

markers or abnormalities are

present)

Biparietal

diameter

(BPD)

Within the reference

range

Anencephaly: No BPD measurable

Holoprosencephaly and spina

bifida: BPD often in the lower

range

Thalami,

cerebral

peduncles,

aqueduct of

Sylvius

V-Shaped transition,

visualized aqueduct.

Some distance

between occipital

bone and cerebral

peduncles

Spina bifida: Parallel shaped

transition between thalami and

cerebral peduncles. Compressed

aqueduct. Cerebral peduncles

posteriorly shifted and touch or

are close to the occipital bones

Fourth

ventricle with

its choroid

plexus

Fourth ventricle well

seen with

hyperechogenic

choroid plexus

Spina bifida: Reduced fluid in fourth

ventricle, choroid plexus not well

identifiable

Dandy–Walker and Blake’s pouch

cyst: Increased fluid in fourth

ventricle, anteriorly shifted

brainstem

Sagittal Plane• • • •

The midsagittal plane is commonly visualized in the first trimester, primarily due to NT

measurement (Fig. 8.12). The midsagittal plane reveals more anatomic intracranial

information when examined from the ventral approach (fetus back down) (Fig. 8.12). In

this midsagittal plane (Fig. 5.6), the following anatomic landmarks can be evaluated:

head shape, facial profile, nose with nasal bone, maxilla, mandible, thalamus, midbrain,

brainstem (BS), fourth ventricle (called intracranial translucency [IT]) and its choroid

plexus, the developing cisterna magna, the occipital bone, and the NT (Fig. 8.12).4

Table 8.2 gives an overview of the anatomic landmarks and corresponding

malformations that can be visualized in the midsagittal plane of the fetal head in the first

trimester. In the context of spina bifida later in this chapter, the anatomy of the posterior

fossa under normal and abnormal conditions is discussed.

Coronal Planes

The coronal planes of the fetal head are obtained along the laterolateral axis of the fetus.

In the second and third trimesters, coronal planes of the fetal head are primarily

obtained to assess the frontal midline structures such as the interhemispheric fissure, the

cavum septi pellucidi, frontal horns of the lateral ventricles, the Sylvian fissure, the

corpus callosum, and the optic chiasm. Given that these midline anatomic structures are

not fully developed in the first trimester, coronal planes of the fetal head are rarely

obtained. Figure 8.13 shows coronal planes of the fetal head in a normal fetus at 12

weeks of gestation.

Table 8.2 • Midsagittal Plane of the Fetal Head and Associated

Abnormalities in the First Trimester

Normal Abnormalities Suspected

Head shape

Large head in

comparison with

body, physiologic

slight frontal bossing

Anencephaly/exencephaly:

Irregular shape, no skull identified

Holoprosencephaly: often

abnormal shape

Nuchal

translucency

(NT)

NT within the normal

range

Thickened NT in aneuploidies,

complex cardiac malformations, and

in many syndromic conditions

Posterior

fossa:

brainstem,

fourth

Brainstem diameter

within the normal

range, slightly sshaped brainstem,

fourth ventricle

Open spina bifida: brainstem

thickened and posteriorly shifted.

Compressed or absent fourth

ventricle. No cisterna magna seen

Dandy–Walker: thin brainstem,

large fourth ventricle• •

ventricle,

cisterna

magna

separated from

cisterna magna with

choroid plexus

Aneuploidies: often dilated fourth

ventricle

Walker–Warburg syndrome: Zshaped brainstem (kinking)

Facial profile

Normal forehead,

nasal bone, maxilla,

and mandible

See Chapter 9 for details

Figure 8.13: Coronal planes of the anterior fetal head obtained from a threedimensional (3D) volume at 12 weeks of gestation and displayed in

tomographic view. The posterior fossa is outside the range of the tomographic

display and thus is not seen. Note the thalami (Thal.), the choroid plexuses

(CP), and the presence of cerebrospinal fluid (CSF) in the anterior segments of

the lateral ventricles (asterisks).

CENTRAL NERVOUS SYSTEM ABNORMALITIES

Acrania, Exencephaly, and Anencephaly

DefinitionAcrania, exencephaly, and anencephaly are neural tube defects that result from failure of

closure of the rostral part of the neural tube in early embryogenesis (days 23 to 28 from

fertilization). Acrania is defined by the absence of the cranial vault above the orbits. In

exencephaly, the cranial vault is absent (acrania) and the abnormal brain tissue appears

as bulging masses, covered by a membrane and exposed to the amniotic fluid. In

anencephaly, the cranial vault, cerebral hemispheres, and midbrain are all absent. There

is no overlying skin and a layer of angiomatous stroma covers the skull defect. Ample

evidence suggests that anencephaly is at the end of the spectrum of acrania and

exencephaly, and that it results from the destruction of brain tissue that is exposed to

amniotic fluid in the first trimester. Except in rare cases of acrania, the exencephaly–

anencephaly sequence is a lethal condition.

Ultrasound Findings

The diagnosis of exencephaly/anencephaly in the first trimester is based upon the

demonstration of an absent cranium along with the presence of “abnormal mass of

tissue” arising from the base of the remaining skull (Figs. 8.14 and 8.15). On coronal

views, the abnormal mass of tissue, representing the amorphous brain matter, has been

described as the “Mickey Mouse” sign as it typically bulges to either side of the fetal

head (Fig. 8.15A).5 In anencephaly, the absence of the cranial vault is seen along with

little to no brain tissue above the level of the orbits (Fig. 8.16) and on coronal view of

the fetal face, the characteristic “frog eyes” appearance is noted (Fig. 8.16B). By the

12th week of gestation, following complete ossification of the fetal skull, ultrasound

diagnosis of exencephaly/anencephaly can be performed by the axial, sagittal, or

coronal views of the fetal head.6 In these views, the absent calvarium, the abnormal

fetal profile, and the disorganized brain tissue protruding from the fetal head can be

demonstrated (Figs. 8.14 to 8.18). On transvaginal ultrasound, the amniotic fluid

appears echogenic (Fig. 8.16A). The crown-rump length measurements are often

smaller than expected due to loss of brain tissue. The diagnosis of

exencephaly/anencephaly can be occasionally suspected at 9 weeks of gestation.6 A

follow-up ultrasound after 10 weeks is recommended in order to confirm the diagnosis,

especially if pregnancy termination is being contemplated. On occasions, acrania can be

diagnosed in the first trimester by the demonstration of absence of cranium and in the

presence of membrane (pia mater) covering the brain tissue (Fig. 8.17). In most cases of

acrania, follow-up ultrasound examination into the second trimester demonstrates

amorphous brain tissue as shown in anencephaly–exencephaly cases. 3D ultrasound can

help in providing a complete picture of face and head in anencephalic fetuses (Fig.

8.18).Figure 8.14: Sagittal view of a fetus with anencephaly–exencephaly at 12

weeks of gestation. Note the absence of normal brain tissue and the overlying

calvarium. Amorphous brain tissue is seen protruding from the base of the head

region (arrow).Figure 8.15: Coronal (A) and sagittal (B) views of a fetus with anencephaly–

exencephaly at 11 weeks of gestation. The brain is replaced by amorphous

tissue (arrows) with absence of the overlying calvarium. The shape of the

amorphous brain tissue in the coronal view in A resembles the ears of Mickey

Mouse and has been referred to as the “Mickey Mouse” sign. Note in B the

absence of the forehead and the protruding brain tissue (arrow).Figure 8.16: Coronal (A) and direct frontal (B) views of the face in a fetus with

anencephaly–exencephaly at 12 weeks of gestation. A: The brain is replaced

by amorphous tissue (asterisk) with absence of the overlying calvarium. The

direct frontal view of the face in B is lacking the forehead and the eyes

(arrows) appear prominent, a view called the “frog eyes.”Figure 8.17: Sagittal views in two fetuses (A and B) with absence of the

calvarium (acrania) in early gestation. Note in A and B the presence of a

membrane (pia mater) covering the brain tissue (arrows). The shape of the

brain and head is similar in both fetuses. In most cases of acrania, follow-up

ultrasound examinations demonstrate amorphous brain tissue as shown in

anencephaly–exencephaly cases.

The prenatal diagnosis of exencephaly/anencephaly in the first trimester requires a

detailed transvaginal ultrasound looking for the presence of amniotic bands given the

association of amniotic band sequence with exencephaly.

Associated MalformationsAnencephaly is commonly associated with other fetal abnormalities to include neural

tube malformations such as craniorachischisis, spina bifida, and iniencephaly.6 Other

fetal malformations such as cardiac, renal, gastrointestinal, and facial occur in

association with anencephaly. Aneuploidy rates are also increased in anencephaly,

especially when associated with other malformations. Amniotic band sequence, on the

other hand, presents a sporadic association with no increased future risk for recurrence.

The in utero mortality rate is high and the malformation is universally lethal.

Cephalocele (Encephalocele)

Definition

Cephalocele is a protrusion of intracranial content through a bony skull defect. If the

herniated sac contains meninges and brain tissue, the term encephalocele is used. The

term meningocele is used when the herniated sac contains meninges only. Given the

difficulty involved in the first trimester in differentiating encephalocele from

meningocele, the term encephalocele is used to describe both conditions. Most

commonly an encephalocele is found posteriorly in the occipital region of the skull.

Encephaloceles can also occur in other regions of the skull such as parietal, basal, and

anterior. Encephaloceles are considered neural tube defects resulting from failure of

closure of the rostral part of the neural tube.7 In general, non-midline encephaloceles

(lateral or parietal) have been associated with amniotic band sequence and considered

to result from a disruptive process following normal embryogenesis.

Ultrasound Findings

The detection of an encephalocele on ultrasound examination is often suspected in the

axial view by the presence of a protrusion in the occipital or frontal region of the

calvarium (Figs. 8.19, 8.20A, 8.21A, and 8.22A). A sagittal view can reveal the extent

of the defect and the size of the encephalocele (Figs. 8.20B, 8.22B, and 9.23A).

Transvaginal ultrasound along with image magnification can often reveal the bony

defect in the skull (Figs. 8.19B and 8.22). Encephaloceles are often associated with

abnormal brain anatomy that can be detected in the axial or sagittal views of the fetal

head (Figs. 8.19 to 8.22). The larger the encephalocele, the more brain abnormality is

seen on ultrasound. As encephaloceles are often part of genetic abnormalities and

syndromes, detailed review of fetal anatomy is recommended.7 Special attention should

be given to the presence of polydactyly and polycystic kidneys given the association

with Meckel–Gruber syndrome (Figs. 8.21 and 13.31).7 Other autosomal recessive

ciliopathies can present with posterior cephalocele, such as Walker–Warburg syndrome

or the large group of Joubert syndrome–related disorders (Fig . 8.22). Threedimensional (3D) ultrasound in surface mode can be of help in showing the extent of the

encephalocele. Not all cases of cephaloceles are detectable in the first trimester.

Smaller defects and internal lesions are difficult to diagnose. The diagnosis of an

encephalocele in the first trimester is commonly performed around 13 to 14 weeksunless a meningocele with a dilated posterior fossa is present, mimicking a Dandy–

Walker malformation (DWM) enabling an earlier detection (Figs. 8.22 and 13.31). In

isolated cases, an attempt should be made to differentiate between an encephalocele and

a meningocele given a much improved prognosis of the latter. The absence of brain

tissue in the herniated sac on transvaginal ultrasound along with normal intracranial

anatomy make the diagnosis of a meningocele more likely.

Figure 8.18: Three-dimensional ultrasound in surface mode in three fetuses

(A–C) with anencephaly–exencephaly in the first trimester showing different

appearances of the same malformation. Note the fetus in A has part of the

calvarium formed (arrow), whereas fetuses in B and C do not.Figure 8.19: Axial plane of the head in two fetuses at 13 weeks of gestation

with an occipital encephalocele (arrows) examined in A) with transabdominal

and in B) with transvaginal transducer. Note the presence of brain tissue

protruding out of the defect in the occipital region. The presence of an

encephalocele is often associated with an abnormal shape of the head.

Figure 8.20: Transvaginal axial (A) and midsagittal (B) planes of the head at

12 weeks of gestation in a fetus with an occipital encephalocele (arrows). Note

the presence of brain tissue protruding through the encephalocele. Additional

findings, not shown here, include polydactyly and polycystic kidneys, typical

signs for Meckel–Gruber syndrome.Figure 8.21: Meckel–Gruber syndrome in a fetus at 12 weeks of gestation.

Note the presence of an occipital encephalocele in A (arrow), large polycystic

kidneys in B (arrows), and polydactyly in C (arrow). The presence of an

occipital encephalocele in the first trimester should prompt a closer look at the

fetal kidneys and extremities for associated abnormalities suggestive of

Meckel–Gruber syndrome.Figure 8.22: Axial (A) and midsagittal (B) planes of the head in a fetus with an

occipital cystic encephalocele (arrows) at 11 weeks of gestation. Note the

dilated fourth ventricle (asterisk). C and D: Three-dimensional ultrasound

display in surface mode of the fetal head with the arrows pointing to the

occipital encephalocele, posteriorly in C showing the defect and laterally in D,

showing the encephalocele bulge. This case represented recurrence of Joubert

syndrome type 14 (JBTS14). Note also that Joubert-related disorders may

have no or only subtle findings in early gestation.

Associated Malformations

Encephaloceles or meningoceles can be isolated findings, or they can be associated

with chromosomal abnormalities (trisomies 13 and 18) or genetic syndromes

(ciliopathies). Encephaloceles are also often associated with other intracranial or

extracranial abnormalities. Of note is the association of encephaloceles with one

special ciliopathy, the Meckel–Gruber syndrome, an autosomal recessive disorder with

25% recurrence, but also with other ciliopathies such as Joubert syndromes andJoubert-related disorders (Fig. 8.22) as well as Walker–Warburg syndrome. The

presence of lateral encephaloceles should raise the suspicion for the presence of

amniotic bands. Differentiating occipital encephaloceles from cystic hygromas can

occasionally be difficult in the first trimester. A cervical spina bifida (Fig. 8.23) can

also be misdiagnosed as encephalocele but in this condition the defect is below the

intact occipital bone (Figs. 8.23B and C), whereas in encephalocele the defect is

cranial to or across the occipital bone. This is important as spina bifida is less

commonly associated with a genetic syndrome than encephalocele.

Holoprosencephaly

Definition

HPE is a heterogeneous developmental abnormality of the fetal brain arising from

failure of cleavage of the prosencephalon with varying degrees of fusion of the cerebral

hemispheres.2,6,8 It is the most common forebrain defect in humans. The incidence of

HPE varies throughout pregnancy decreasing from 1:250 in embryos to 1:10,000 in live

births.9 In a recently published large study on 108,982 first trimester fetuses including

870 fetuses with abnormal karyotypes, HPE was found in 37 fetuses for a prevalence of

1:3,000 fetuses in first trimester screening.10 HPE is subclassified into alobar,

semilobar, lobar, and middle interhemispheric variants based upon the degrees of fusion

of the cerebral hemispheres. The most common and severe form is the alobar form,

which has a single ventricle of varying degree, fused thalami, and corpora striata with

absent olfactory tracts and bulbs and corpus callosum. The single ventricle in alobar

HPE may bulge dorsally to form a dorsal sac. In semilobar HPE, there is partial fusion

of the posterior cerebral lobes with a posterior falx cerebri and a rudimentary corpus

callosum. In lobar HPE, the falx cerebri is present and the cerebral lobes are distinct

with the exception of the region of the ventricular frontal horns. In the interhemispheric

variant of HPE, the posterior, parietal, and frontal lobes fail to separate. A feature

common to all forms of HPE is an absent or dysplastic cavum septi pellucidi, which in

normal conditions is first visible on ultrasound in the second trimester. Semilobar,

lobar, and the interhemispheric variants of HPE are less severe and may escape

detection until the second trimester of pregnancy. Anomalies of the face that range from

severe, such as cyclopia and proboscis (Figs. 9.10 and 9.39), to mild, such as

hypotelorism or single central maxillary incisor, are typically found in HPE and can be

explained by the maldevelopment of the prosencephalon.

Ultrasound Findings

The semilobar and lobar types of HPE are typically not detected in the first trimester

and thus will not be discussed in this section. The transvaginal approach is preferred

when feasible given its higher resolution. A typical sonographic sign of HPE includes

the absence of a falx cerebri, separating both hemispheres. This is easily detected in the

axial or coronal planes of the fetal head (Figs. 8.24 to 8.27). The finding of two distinctchoroid plexuses in each hemisphere (Fig. 8.8) rules out alobar HPE and the lack of the

typical “butterfly” sign, seen in normal fetuses is an important clue to diagnosis in the

first trimester (Figs. 8.24 to 8.27).2 The coronal plane (Figs. 8.24A and 8.28) of the

fetal head shows a single ventricle anteriorly (monoventricle) with fused thalami.

Biometric evaluation of the fetal head in HPE has shown small BPD measurements with

or without associated aneuploidy.11

3D ultrasound is helpful in various modes (Figs. 8.27 to 8.29). The 3D tomographic

display provides a better overview of the various planes of the fetal head (Figs. 8.27

and 8.28). 3D surface, Silhouette, or inversion modes are different tools that provide a

spatial demonstration of the fused ventricles, thalami, and choroid plexus (Figs. 8.29

and 8.30).12 Facial anomalies that are found in HPE include a wide array and are

mostly detected in the midsagittal and coronal facial planes8 or with 3D ultrasound

surface mode (Figs. 8.28, 8.30, 9.10, and 9.39). These facial abnormalities are

discussed in more detail in Chapter 9. In expert hands, alobar HPE can be detected from

9 weeks of gestation onward, with the demonstration of a lack of separation of both

ventricles and choroid plexuses.13 A follow-up evaluation at 12 to 13 weeks is prudent

before a final diagnosis.

Figure 8.23: Axial (A), midsagittal anterior (B) and posterior (C) planes of the

head in a fetus at 13 weeks of gestation with cervical spina bifida. In the axial

(A) plane, the defect (yellow arrows) is suspicious for an encephalocele but in

the midsagittal anterior (B) and posterior (C) views the lesion (yellow arrows) is

below the occipital bone, at the level of the cervical spine. Note that the

brainstem and posterior fossa (short blue arrows) are abnormal, typical

findings for an open spina bifida in early gestation (see Figs. 8.40 and 8.43).Figure 8.24: Coronal (A) and axial (B) planes of the head in two fetuses with

alobar holoprosencephaly in early gestation. Note the presence of a crescentshaped single ventricle (monoventricle) (double headed arrows). Fused thalami

(T) are also noted. The falx cerebri is absent and no separated choroid

plexuses can be visualized.Figure 8.25: Axial plane of the head in two fetuses (A and B) with alobar

holoprosencephaly at 12 and 13 weeks of gestation, respectively. Note the

presence of a crescent-shaped single ventricle (monoventricle) (double headed

arrows), fused thalami (T), and absence of the falx cerebri.

Figure 8.26: Axial planes at 13 weeks of gestation of the head comparing the

choroid plexuses of the lateral ventricles in a normal fetus (A) and in a fetus

with alobar holoprosencephaly (B). The butterfly-like echogenic choroid

plexuses (CP) are well recognized in the normal fetus (A). In the fetus with

holoprosencephaly (B), the CP are fused and do no show the butterfly-like

appearance. The falx cerebri (Falx) is noted in A, but absent in B. Note in B

that the single ventricle (monoventricle) (as shown in Figs. 8.24 and 8.25) is not

clearly displayed, but the fusion of CP and the absence of the falx cerebri

suggest the diagnosis of holoprosencephaly.Figure 8.27: Three-dimensional volume of a fetal head displayed in

tomographic mode in a fetus with alobar holoprosencephaly at 12 weeks of

gestation. The parallel axial planes demonstrate the typical features of alobar

holoprosencephaly such as the fused thalami (T) and choroid plexuses (CP)

and the single anterior ventricle (double headed arrow) as shown in Figures

8.24 and 8.25.Figure 8.28: Three-dimensional volume of a fetal head displayed in

tomographic mode in a fetus with alobar holoprosencephaly at 13 weeks of

gestation. The parallel coronal planes demonstrate the single ventricle (double

headed arrow) and the presence of an abnormal face, also shown in profile in

the upper left plane.

Figure 8.29: Three-dimensional ultrasound display in surface mode of an axialplane of the fetal head in a normal fetus (A) and in a fetus with alobar

holoprosencephaly (B) at 13 weeks of gestation. Note the normal appearance

of the choroid plexuses (CP) in A, separated by the falx cerebri (Falx). In the

fetus with holoprosencephaly (B), the CP are fused, the falx is absent and

there is a single ventricle (double headed arrow). Lat. V, lateral ventricles.

Figure 8.30: Two-dimensional (A and C) and three-dimensional (B and D)

ultrasound images of a fetus at 13 weeks of gestation with holoprosencephaly

(HPE), shown in A and B and abnormal face shown in C and D. A mutation in

the TGIF was detected on genetic evaluation, which was also present in the

otherwise healthy father, resulting in a recurrence risk of 50% with

unpredictable penetrance. In cases of (isolated) HPE, in addition to

chromosomal analysis and evaluation for syndromic conditions, workup for

gene mutations of a specific group, called autosomal-dominant nonsyndromicHPE, including for instance the ZIC2, SHH, SIX3, TGIF genes, among others,

maybe warranted if feasible.

Associated Malformations

HPE is frequently associated with chromosomal abnormalities and genetic syndromes.

Trisomy 13 accounts for the great majority of chromosomal aneuploidy along with

triploidy and trisomy 18. In a recently published large study10 on 108,982 first trimester

fetuses including 37 fetuses with HPE, 78% (29/37) had an abnormal karyotype,

including trisomy 13 (62%), trisomy 18 (17%), triploidy (17%), and others (4%) such

as deletions and duplications (see also case of HPE with Del.18p in Fig. 6.36).

Numerous genetic syndromes such as Smith–Lemli–Opitz, Meckel–Gruber, OtocephalyHPE,14 Rubinstein-Taybi syndrome among many others have been reported in

association with the HPE spectrum.9 Recently however, increased knowledge has been

acquired on the molecular genetics of HPE and an important new group called

autosomal-dominant nonsyndromic HPE was introduced.9 To date, mutations in 14

genes are known to cause HPE, and the most common are SHH, ZIC2, SIX3, and

TGIF1.9 This is of importance as a parent can carry the mutation as well, having no or

mild features, but a recurrence risk of HPE of 50%. The case in Figure 8.30 shows an

example of a nonsyndromic HPE with a mutation on the TGIF gene, with a carrier status

of the same mutation in the apparently healthy father.

Ventriculomegaly

Definition

Ventriculomegaly is a nonspecific term and refers to the presence of excess

cerebrospinal fluid within the ventricular system. Ventriculomegaly, the most frequent

CNS malformation diagnosed prenatally refers to an enlargement of the lateral

ventricle(s) and is defined as lateral ventricular width of 10 mm or greater at the level

of the atria from the second trimester onward. There is currently no consensus definition

on what constitutes ventriculomegaly before 20 weeks in general and in the first

trimester in particular. Several definitions and reference curves were published, but

their clinical value needs to be verified in prospective studies.15–17 However,

ventriculomegaly in the first trimester is rare in comparison with the second trimester.

Ultrasound Findings

In the authors’ centers, sonographic markers of ventriculomegaly in the first trimester

include thinning and dangling of the choroid plexus, where the choroid plexus is seen to

fill less than half of the ventricular space and its borders do not touch the medial and

lateral ventricular walls (Figs. 8.31 to 8.37). Interestingly it was repeatedly observed

that ventriculomegaly in the first trimester is commonly associated with thinning of the

choroid plexus, rather than an increased width of the lateral ventricles (Figs. 8.31 to

8.37), which is also reflected by reference ranges of various studies on this subject.15–17One study reported on the ratio of the choroid plexus to the lateral ventricle in the

assessment of ventriculomegaly in aneuploid fetuses at 11 to 14 weeks of gestation.15 In

another study, length, width, and area of the choroid plexus and the lateral ventricles

were measured and the ratios calculated and compared with data from 17 fetuses with

ventriculomegaly.16 The authors found that the length and area ratio are the best

parameters to be used.16 In a recent study, ventriculomegaly was defined as bilateral

separation of the choroid plexuses from superior borders of the lateral ventricles.17 An

enlarged third ventricle or an interruption of the falx can be found in ventriculomegaly

in the first trimester, especially when associated with aqueductal stenosis (Figs. 8.33B

and 8.34B) or semilobar HPE. Anomalies involving the posterior fossa can lead to

ventriculomegaly and therefore a careful examination of the posterior fossa is warranted

(Figs. 8.35 and 8.36). As large data on outcome and associated findings in first

trimester ventriculomegaly are still lacking, we recommend a detailed first trimester

ultrasound examination, looking for associated malformations, when ventriculomegaly

is encountered in early gestation. In addition, an invasive diagnostic procedure for

genetic abnormalities should be offered, especially when ventriculomegaly is

associated with other findings, which increases the risk for chromosomal

aberrations.15–17 A follow-up ultrasound examination between 15 to 17 weeks and at 20

to 22 weeks of gestation is recommended (Figs. 8.35 to 8.37). In our experience, many

fetuses with ventriculomegaly in the second and third trimesters do not show ventricular

dilation in the first trimester. This may be related to lack of clear diagnostic criteria in

early gestation or a delayed onset into the second trimester of ventriculomegaly in many

cases.

Figure 8.31: Axial (A) and midsagittal (B) views in a fetus withventriculomegaly at 12 weeks of gestation. Note in A that the choroid plexuses

(CP) are small and do not fill the lateral ventricles (Lat. V). The midsagittal

plane (B) is not reliable for the diagnosis of ventriculomegaly in the first

trimester. Follow-up ultrasound in the second trimester noted the presence of a

small occipital meningocele.

Figure 8.32: Axial view of the brain in two- and three-dimensional ultrasound of

a normal fetus (A and B) and in a fetus with suspected ventriculomegaly (C

and D), both at 13 weeks of gestation. Note that the choroid plexuses

(asterisks) fill the lateral ventricles (Lat. V) in the normal fetus (A and B)

whereas the choroid plexuses occupy less than half of the lateral ventricles in

the fetus with suspected ventriculomegaly (C and D).Figure 8.33: Orthogonal three-dimensional planes showing the axial (left) and

sagittal (right) planes of the head in a normal fetus (A) and in a fetus with

ventriculomegaly (B). Note the dilated lateral (Lat. V) and third ventricle (3rd V)

in B, as compared to the normal fetus in A. The foramen of Monroe

communication (arrows in B) between the Lat. V and the 3rd V can be

recognized.Figure 8.34: Axial view of the brain in a normal fetus (A) and in a fetus with

suspected ventriculomegaly (B) at 12 weeks of gestation. When compared to

the normal fetus (A), the fetus with suspected ventriculomegaly (B) shows

excess cerebrospinal fluid in the lateral ventricles (Lat. V), a dilated third

ventricle (3rd V), and compressed, shortened choroid plexuses (CP).

Figure 8.35: This pregnancy was referred at 13 weeks of gestation with a

prior history of two fetal deaths with severe hydrocephaly and Walker–Warburg

syndrome. A: An axial plane of the fetal head at 13 weeks of gestation,

demonstrating the presence of dilated lateral ventricles (Lat. V) and smallchoroid plexuses (asterisk). A sagittal view of the posterior fossa (B) at 13

weeks of gestation shows the typical Z-kinked brainstem (red line),

characteristic of Walker–Warburg syndrome. C: Midsagittal plane of the head

at 24 weeks of gestation, demonstrating severely dilated lateral ventricles (Lat.

V) and a kinked brainstem (arrow).

Figure 8.36: This pregnancy was referred at 14 weeks of gestation for

evaluation of ventriculomegaly suspected 1 week prior. A: An axial plane of the

fetal head demonstrating the presence of dilated lateral ventricles (Lat. V) and

choroid plexuses (asterisks) that do not touch the ventricular walls. B: An axial

view of the posterior fossa with abnormal cerebellar shape, typical for

rhombencephalosynapsis, which is often associated with aqueductal stenosis,

explaining the presence of ventriculomegaly. C: The follow-up ultrasound at 17

weeks of gestation showing the presence of ventriculomegaly with compression

of choroid plexuses (asterisks) and effaced subarachnoid space (arrow).Figure 8.37: Axial planes of the fetal head at 12 (A), 15 (B), and 23 (C) weeks

of gestation in the same fetus. Note in A the presence of dilated lateral

ventricles (Lat. V) and dangling choroid plexuses (asterisks). B: Confirms the

presence of ventriculomegaly without a known etiology. C: The presence of

colpocephaly (asterisk) and widening of the interhemispheric fissure (IHF),

suggesting agenesis of the corpus callosum. This fetus also had closed lip

schizencephaly (arrow in C). Ventriculomegaly was not seen at 23 weeks of

gestation (data not shown).

Associated Malformations

Etiologic causes of ventriculomegaly are many and include various CNS malformations,

genetic causes, and infections.15,16 Extracranial-associated malformations are also

common and include spina bifida, renal, cardiac, and skeletal abnormalities. In our

experience, chromosomal anomalies including numerical aberrations and unbalanced

translocations, deletions and duplications are commonly found in fetuses presenting

with ventriculomegaly in the first trimester.15–17 In addition, abnormalities of the

posterior fossa such as DWM, Walker–Warburg syndrome (Fig . 8.35), Joubert

syndrome, posterior fossa cysts, Chiari II malformation in spina bifida, and

rhombencephalosynapsis may be associated with ventriculomegaly in early

gestation.16,17 Figure 8.36 describes a case of rhombencephalosynapsis diagnosed at 14

weeks of gestation. Ventriculomegaly in the first trimester can also be associated with

anomalies of the prosencephalon and telencephalon, such as semilobar HPE or agenesis

of the corpus callosum detected in the second trimester (Fig. 8.37).16,17 Keep in mind

that ventriculomegaly diagnosed in the first trimester can be an isolated finding or

transient in nature, and as such is associated with good prognosis.

Open Spina Bifida

Definition

Spina bifida is defined as a midline defect in the spinal cord, primarily resulting from

failure of closure of the distal neuropore during embryogenesis. Most commonly the

defect is located dorsally. Ventral defects, which are very rare, result from splitting of

the vertebral body, and are difficult to diagnose prenatally. Dorsal defects can be open

or closed. Open defects occur in about 80% of cases and expose the neural tissue to the

amniotic fluid given the absence of overlying muscle and skin. Closed defects are

covered by skin and have a better prognosis than open defects, but are very difficult to

diagnose in the first trimester and thus we will primarily discuss open spina bifida in

this section. Most spina bifidas occur in the lumbosacral spinal region. Synonyms for

open spina bifida include myelomeningocele and myelocele (or myeloschisis). Other

spinal abnormalities are described in Chapter 14.

Ultrasound FindingsThe diagnosis of open spina bifida in the first trimester can be challenging, as the direct

demonstration of the spinal lesion is difficult during ultrasound screening (Fig. 8.38)

and the traditional CNS changes that are seen in the second trimester, such as lemon

(frontal bone scalloping) and banana (obliteration of cisterna magna with abnormal

shaped cerebellum) signs, are not typically visible before 12 to 14 weeks of gestation

(Fig. 8.39).4,18 The classic lemon and banana signs associated with an open spina bifida

in the second trimester of pregnancy are thought to be the consequence of leakage of

cerebrospinal fluid into the amniotic cavity and decreased pressure in the subarachnoid

spaces leading to caudal displacement of the brain and obstructive hydrocephalus

(Chiari II malformation). The lemon and banana signs, when present, are best detected

by transvaginal ultrasound in the first trimester, as they may not be visible on

transabdominal scanning (Fig. 8.39).6,19

Figure 8.38: Dorsoanterior midsagittal view of a normal fetus (A) and a fetus

with open spina bifida as myelomeningocele (B) at 12 weeks of gestation. Note

in B the direct visualization of the spina bifida in the lower lumbosacral spine(circle).

Chaoui et al. noted that in fetuses with open spina bifida, caudal displacement of the

brain resulting in compression of the fourth ventricle is evident in the first trimester, in

the same midsagittal view of the fetal face, a plane commonly used for NT measurement

and for assessment of the nasal bone4,20 (cf. Figs. 8.12 and 8.40). This midsagittal plane

in the normal fetus demonstrates the fourth ventricle as an IT parallel to the NT and

delineated by two echogenic borders—the dorsal part of the brain stem (BS) anteriorly

and the choroid plexus of the fourth ventricle posteriorly (Figs. 8.12, 8.41A, 8.42A,

8.43A). In fetuses with open spina bifida, the IT space is small or not visible as the

fourth ventricle and/or cisterna magna is obliterated and the posterior brain is displaced

downward and backward (Figs. 8.23, 8.40, 8.41B, 8.42B, 8.43B, and 8.43C).21,22 This

leads to thickening of the brain stem (BS), and shortening of the distance between the

brainstem and the occipital bone (BSOB), leading to an increase in the ratio of

BS/BSOB of more than 1 in most cases (Fig. 8.42).21,22 Another simple approach is to

focus on the presence of three white lines in the normal fetus (Figs. 8.41A and 8.42A),

which are not visible in open spina bifida (Figs. 8.41B, 8.42B and 8.42C). These

changes in the IT and posterior fossa are not present in fetuses with closed spina

bifida.23 In a large prospective study in Berlin, performed by 20 specialists in fetal

ultrasound, the detection of all 11 cases of open spina bifida during the first trimester

scan was performed using the midsagittal plane.24 Other intracranial signs reported with

open spina bifida include posterior shifting of the cerebral peduncles and aqueduct of

Sylvius19,25 (Fig. 8.44) and an abnormal frontomaxillary facial angle (Figs. 8.41B and

9.18B).26 The lateral and fourth ventricles are small due to loss of cerebrospinal fluid.27

This results in a small BPD in the first trimester28–30 and in comparison with normal

fetuses, a ratio of BPD to abdominal transverse diameter of smaller than 1 has been

reported.31 It is important to note that despite the presence of numerous signs of open

spina bifida in the first trimester, the diagnosis relies on the demonstration of the actual

defect in the spine (Figs. 8.38B, 8.45B, 8.45C, 8.46B, and 8.47). When the diagnosis is

suspected but not confirmed in the first trimester, follow-up ultrasound examination

after the 15th week of gestation usually confirms the diagnosis.Figure 8.39: Transvaginal axial ultrasound views of the fetal head at the level

of the developing cerebellum in a normal fetus (A) and a fetus with open spina

bifida (B) at 13 weeks of gestation. In A, the structures of the posterior fossa

including the fourth ventricle (4th V), the choroid plexus (CP) of the fourth

ventricle, and the developing cisterna magna (CM) are well seen. In the fetus

with spina bifida (B), the posterior displacement of the posterior fossa

structures leads to a change in the shape of the developing cerebellum, similar

to the “banana sign” in the second trimester. T, thalamus.Figure 8.40: Schematic drawing (A) and corresponding ultrasound image (B)

of the midsagittal plane of the fetal head in a fetus with open spina bifida

(compare with normal anatomy in Fig. 8.12). In open spina bifida in the first

trimester, there is a shifting of the posterior brain structures toward the

occipital bone leading to brainstem thickening (double headed arrow), with

partial or complete compression of the fourth ventricle (intracranial

translucency), cisterna magna, and the choroid plexus of the fourth ventricle. All

three structures are distorted and their normal anatomy cannot be visualized.

The free floating choroid plexus in the cerebrospinal fluid of the fourth ventricle

and cisterna magna is not seen anymore in open spina bifida and thus the

typical normal lines in Figure 8.12 are not seen. See next Figures 8.41, 8.42

and 8.43. T, thalamus; M, midbrain; NT, nuchal translucency; 1, 2, and 3 point

to the nasal bone, maxilla, and mandible, respectively.Figure 8.41: Midsagittal views of the head, obtained by transabdominal

ultrasound at 13 weeks of gestation in a normal fetus (A) and in a fetus with

open spina bifida (B). In the normal fetus (A), the brainstem (BS) is thin and

posterior to it there is cerebrospinal fluid in the fourth ventricle called

intracranial translucency (IT) and in the cisterna magna (CM). Typically three

echogenic lines can be identified in the posterior fossa in the normal fetus: line

1—the posterior border of the brainstem; line 2—the choroid plexus of the

fourth ventricle; and line 3—the occipital bone. In open spina bifida (B),

cerebrospinal fluid leaks out through the defect and leads to intracerebral

changes, which can be seen in the midsagittal view. Changes in open spina

bifida (B) include posteriorly shifted and thickened brainstem (BS) (double

headed arrow) (see figures 8.42 and 8.43), decreased or absence of fluid in

the intracranial translucency (IT ?), and cisterna magna (CM ?) (circle) and

absence of the three anatomic lines that are seen in normal anatomy (A). Also

note the flat forehead in fetus B, leading to a small frontomaxillary facial angle

(see Chapter 9 and Fig. 9.18).Figure 8.42: Transvaginal ultrasound of the midsagittal plane of the face and

posterior brain in a normal fetus (A) and in a fetus with open spina bifida (B) at

13 weeks of gestation. See Figure 8.41 for more details on midsagittal brain

anatomy in normal fetuses and in fetuses with open spina bifida. The three

echogenic lines in A correspond to the posterior border of the brainstem (1),

the choroid plexus of the fourth ventricle (2), and the occipital bone (3).

Quantification of the posterior fossa can be achieved by measuring the

brainstem diameter (BS) (yellow double headed arrow) and the distance from

the BS to the occipital bone (BSOB) (blue double headed arrow). In normal

fetuses (A) the BS is smaller than the BSOB and the ratio of both is smaller

than 1. In open spina bifida (B) BS is larger and BSOB is shorter which leads

to a ratio >1. See brainstem shape in Figure 8.43.

Associated Malformations

Spina bifida can occur as an isolated finding but is also found in association with

aneuploidies such as trisomy 18, triploidy, or others. CNS abnormalities such as

hydrocephaly appear later. Kyphoscoliosis may be present and could be a sign for the

presence of Jarcho–Levin syndrome. Dislocation of the hips along with lower limb

deformities such as bilateral clubbing and rocker bottom feet are typically seen in the

second and third trimesters of gestation.

Posterior Fossa Abnormalities

Definition

Posterior fossa abnormalities include malformations of the cerebellar hemispheres, thecerebellar vermis, the cisterna magna, and the fourth ventricle. Given that the

embryologic development of the posterior fossa is not completed until the second

trimester of pregnancy with the formation and rotation of the vermis, many abnormalities

of the posterior fossa cannot be detected in the first trimester. DWM is a posterior fossa

abnormality characterized by the presence of a dilated cisterna magna, which

communicates with the fourth ventricle, varying degrees of hypoplasia, or agenesis of

the vermis and elevation of the tentorium.32 The embryogenesis of DWM is thought to

occur around the seventh week of gestation and thus its suspicion in the first trimester is

possible. First trimester ultrasound is not diagnostic of isolated mega cisterna magna,

Blake’s pouch cyst, cerebellar hypoplasia, cerebellar hemispheric asymmetry, and

isolated vermian hypoplasia due to delayed embryogenesis of these structures.33,34

Figure 8.43: Midsagittal views of the head in a normal fetus (A) and in two

fetuses with open spina bifida (B and C) displaying the anatomy of the midbrain

and posterior fossa. The upper panels show the two-dimensional ultrasound

images and the lower panels show an overlay to better highlight anatomy.

Green highlights show brain structures to include the thalamus (T), midbrain

(M), brainstem (BS), and myelencephalon (My). Yellow highlights show thecerebrospinal fluid in the posterior fossa, present in the fourth ventricle (4th V)

or IT and in the future cisterna magna (CM). Red highlights show the choroid

plexus (CP) of the fourth ventricle. In open spina bifida, in the first trimester

there is a shifting of the posterior brain structures toward the occipital bone

leading to thickening of BS (cf. green highlights; BS in B and C with A) and a

partial or complete compression of the IT, the cisterna magna (yellow

highlights), and the CP (red highlights). Some fetuses with spina bifida have no

fluid in the fourth ventricle as shown in Figures 8.38B and 8.39B, whereas

others may have some fluid as shown here in B and C.

Figure 8.44: Axial views of the fetal head in the first trimester at the level of the

cerebral peduncles (Cer. Ped.) and the aqueduct of Sylvius (AS) in a normal

fetus (A) and in a fetus with open spina bifida (B). Note in B, the posterior

displacement of the Cer. Ped. and the AS toward the occipital bone (OB)

(double headed arrows). This view is better evaluated in transvaginal

sonography. T, thalamus.Figure 8.45: Three-dimensional ultrasound in surface mode of a normal fetus

(A) and two fetuses with open spina bifida as myelomeningocele (B and C) at

13 weeks of gestation. Note in B and C the direct visualization of the spina

bifida in the lower lumbosacral spine (arrows). The corresponding twodimensional image of fetus C is displayed in Figure 8.33B.Figure 8.46: Dorsoanterior midsagittal view of a normal fetus (A) and a fetus

with open spina bifida as myeloschisis (B) at 13 weeks of gestation. Note in B

how difficult it is to directly visualize the spinal defect in the lower lumbosacral

spine (arrow). Note however, changes in the posterior fossa (circle) in fetus B

as compared to fetus A. The intracranial translucency (IT) and a slim brainstem

(BS) is shown in A compared with no fluid (IT ?) and a compressed thickened

BS in the fetus with spinal defect (B). This fetus is also demonstrated in

Fig.8.47.Figure 8.47: Dorsoanterior two-dimensional (2D) midsagittal view (A) of a

fetus at 13 weeks of gestation with open spina bifida as myeloschisis (arrows)

(see also Fig. 8.46) and corresponding three-dimensional ultrasound in surface

mode (B). Note that the open spina bifida is difficult to image in A on the 2D

ultrasound image. B: The defect in the lower lumbosacral spine is shown

(circle). Suspicion for the presence of an open spina bifida was achieved due to

an abnormal posterior fossa, as shown in Figures 8.39, 8.40, and 8.46.

Ultrasound Findings

The suspicious diagnosis of DWM in the first trimester is based upon the presence of an

enlarged IT, a reduced thickness of the BS, and diminished visibility of the choroid

plexus of the fourth ventricle in a midsagittal view of the fetal head (Figs. 8.48 and

8.49).33 Axial and coronal views of the fetal head will show a large posterior fossa cyst

separating the cerebellar hemispheres (Figs. 8.48 and 8.49). There is some evidence

that midsagittal view measurements assessing the posterior brain such as the BS

diameter, the BSOB diameter, and the ratio between both measurements (BS/BSOB

ratio) might improve the screening for DWM in the first trimester (Figs. 8.48 and

8.49).33 An increased BSOB (representing the fourth ventricle and cisterna magnacomplex) and a decreased BS/BSOB ratio should alert the sonographer to the

possibility of DWM and encourage a detailed examination of the posterior fossa in the

first trimester.33 The examiner has to keep in mind that a true DWM is a fairly rare

condition and a dilated fourth ventricle in the first trimester can also be a sign of

aneuploidy (Figs. 8.50, 6.6, and 6.20B), syndromic conditions (Fig. 10.20), Blake’s

pouch cyst (Figs. 8.51A, 8.52 and 8.53A), encephalocele (Fig. 8.22B) but also a

transient finding. Blake’s pouch cyst also shows a dilation of the posterior fossa and

may simulate the presence of a DWM (Figs. 8.52 and 8.53), especially when scanned in

coronal views. In the presence of Blake’s pouch cyst, less fluid is present in the

posterior fossa than DWM and follow-up ultrasound in the second trimester will

demonstrate a normal cerebellum and vermis. When posterior fossa abnormalities are

suspected in the first trimester, detailed ultrasound examination of the fetus and followup in the second trimester is recommended.

Figure 8.48: Midsagittal view of the head at 12 weeks of gestation

demonstrating the posterior fossa in a normal fetus (A) and in a fetus with

Dandy–Walker malformation (B). Note in fetus B the presence of increased

cerebrospinal fluid (asterisk) in the posterior fossa with absence of the choroid

plexus (CP) as compared to fetus A. The brainstem (double headed arrow) is

also thinned in the fetus with Dandy–Walker malformation.Figure 8.49: Sagittal (A) and coronal (B) views of the posterior fossa in a fetus

with suspected Dandy–Walker malformation at 12 weeks of gestation. Note the

dilated posterior fossa (asterisk) with absence of the choroid plexus.

Associated Malformations

Dilated posterior fossa and suspected DWM in the first trimester are associated with

numerous malformations such as aneuploidies (trisomy 18, trisomy 13, triploidy,

monosomy X, and trisomy 21),35–37 genetic syndromes (Walker–Warburg syndrome),

and other intracranial and extracranial abnormalities.Figure 8.50: Midsagittal (A) and axial (B) views of the fetal head in a fetus with

partial trisomy 11q, thickened nuchal translucency (NT), and absent nasal bone

(circle) at 12 weeks of gestation. Note the cystic dilation of the posterior fossa

(asterisks) with a thin brainstem (double headed arrow).

Figure 8.51: Sagittal view of a normal fetus (A) at 12 weeks and a fetus with

suspected persistent Blake’s pouch cyst (B) at 13 weeks of gestation. Note the

normal appearing posterior fossa and fourth ventricle (4th V) in A. In the fetus

with suspected persistent Blake’s pouch cyst (B), moderate dilation of the 4th

V (asterisk) is seen.Figure 8.52: Midsagittal (A) and coronal (B) views of the fetal head at 12

weeks of gestation showing a moderately dilated posterior fossa (asterisk).

The size of the posterior fossa is less than that showed in Dandy–Walker (Fig.

8.49). This fetus was suspected of having persistent Blake’s pouch cyst, which

was confirmed at 22 weeks of gestation.

Figure 8.53: Three-dimensional volume in surface mode of the posterior fossa

at 12 weeks of gestation in a fetus with persistent Blake’s pouch cyst (A) and a1.

2.

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fetus with Dandy–Walker malformation (B). Note that the posterior fossa

(asterisks) is moderately dilated in A as compared to markedly dilated in B