Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5759_Библиотеки_им_академика_М_И_Перельмана
.pdf
Chapter 34 ■ The Fetal Brain 1217
normal cranial examination cannot exclude spinal
abnormality (Fig. 34-15). The MS-AFP will also be
normal with skin-covered lesions.
103
Fetuses with
isolated neural tube defect (NTD) have an increased
incidence of chromosomal abnormality ranging from
7% to 16%, and antenatal genetic evaluation should be
considered.
75,104,105
The intracranial changes are similar for all levels of
spinal abnormality. Functional prognosis depends primarily on the level of the spinal lesion.
106
Randomized
trials of in utero spina bifida closure are currently underway. Initial experience suggests that cerebellar changes
appear to reverse, and there is less need for postnatal
ventricular shunting. However, there is mortality associated with the procedure, and it is not clear if there is
long-term functional improvement.
90
The accuracy of diagnosis of spina bifida depends
on operator experience. Experienced referral centers
have close to 100% detection. The RADIUS trial, which
used MS-AFP and ultrasound reported 80% detection.
MS-AFP screening may be marginally more sensitive than
routine ultrasound.
107
Folic acid supplementation has
greatly decreased the incidence of open NTDs. Attention
to cerebral findings should allow a very high detection rate
of open spina bifida. Closed spina bifida remains a
problem for ultrasound diagnosis because MS-AFP is
normal and there is no Chiari malformation.
The iniencephaly sequence is a rare and special case
of dysraphism involving the back of the cranium and the
contiguous upper spine; “inion’’ refers to the nape of
the neck. It is associated with segmentation errors of the
upper spine and has been suspected as early as 9 weeks.
108
The resulting deformity greatly shortens the neck, and
the head is dorsiflexed (star-gazing position). Associated
anomalies are common; the outcome is fatal. Iniencephaly may be associated with anencephaly or Klippel-Feil
syndrome; in the latter there is segmentation error and
shortening in the cervical vertebrae, but no dysraphism.
Marked hyperextension can also be seen with anterior
neck masses (teratoma, goiter), anencephaly and distortions of uterine cavity (e.g., from oligohydramnios,
fibroids, uterine synechiae, or twins).
Errors of Ventral Induction:
Holoprosencephaly
Errors of ventral induction occur in the rostral end of
the embryo and result in brain abnormalities and usually
affect facial development. These are in the holoprosencephaly spectrum. Holoprosencephaly is a complex
brain malformation resulting from various degrees of
incomplete cleavage of the prosencephalon. It is the most
common abnormality of brain development and is seen
in about 1 in 250 conceptuses but only 1 in 16,000 live
births, because most affected fetuses die in utero.
40,109,110
Normally, at about 5 weeks’ gestational age, prechordal mesoderm migrates into the area anterior to the
FACTORS ASSOCIATED WITH
HOLOPROSENCEPHALY
Environmental teratogens: alcohol, smoking,
retinoic acid, salicylates, anticonvulsants
Metabolic: insulin-dependent diabetes (1% risk)
Infections: cytomegalovirus, toxoplasmosis, rubella
Syndromes with normal karyotype (about 25% of
holoprosencephaly
Smith-Lemle-Opitz
Pallister-Hall
Velocardiofacial
Chromosomal abnormalities
Trisomy 13 (70% have holoprosencephaly)
Trisomy 18
Triploidy
Gene mutations
Sonic hedgehog (expressed in notochord and
floor plate of neural tube)
ZIC2 (has role in neurulation in dorsal midline)
notochord, where it participates in midface development
and induces forebrain development. This fails in holoprosencephaly. As result, anterior midline cerebral structures fail to form, and the more lateral dorsal structures
fuse in the midline to varying degrees. In severe cases the
abnormality extends to involve midline facial structures.
The severity of facial dysmorphism correlates with cerebral abnormalities in about 80% of cases (“the face predicts the brain”).
any part of the body are found in about 70% of cases.
63,110
Additional abnormalities involving
Etiology and phenotype are heterogeneous, possibly
resulting from multiple, varied genetic and environmental “hits” to the development process. Holoprosencephaly is part of many different syndromes and
many chromosomal and gene abnormalities.
Isolated holoprosencephaly can have autosomal dominant inheritance with incomplete penetrance and variable expression. Parents of affected children should be
examined for mild manifestations such as single central
incisor and absent nasal cartilage.
40,111,112
Prognosis is variable and depends on holoprosencephaly severity, associated abnormalities, and medical and
neurologic complications. Severely affected fetuses die in
utero or do poorly. Mildly affected children may exhibit
few symptoms and may live a normal life. About 75%
need shunting.
110
In general, the severity of clinical
problems and neurologic dysfunction correlates with
the degree of hemispheric and hypothalamic failure of
separation. Abnormal functions can manifest as endocrinopathy (especially diabetes insipidus), temperature dysregulation, motor and movement abnormalities, and
developmental delay.
111,113
Holoprosencephaly is a continuum of malformations
that is classically divided into three ranges of increasing
severity: alobar (only one hemisphere), semilobar
40,109
40,109-111
1218 PART IV ■ Obstetric Sonography
(partial attempt to form two hemispheres), lobar (two
hemispheres form, but midline structures are abnormal).
Severe cases often have a dorsal cyst, thought to result
from obstruction to CSF flow by fused thalami. Prenatal
distribution is alobar 75%, semilobar and lobar about
10% each, and the remainder consisting of atypical
109,111
forms
(Fig. 34-16). However, the range of abnormalities is much larger than these simple categorizations
suggest and involve not only the cerebrum but also basal
ganglia and other lower areas. Affected fetuses and children may have microforms with mild manifestations
such as single midline incisor tooth or absence of olfactory lobes. Diagnosis may be difficult even after delivery.
Also, some holoprosencephaly manifests as anencephaly
with associated facial abnormality.
109-111
Recently, a fourth variant has been described, middle
interhemispheric form of holoprosencephaly, also
called syntelencephaly, in which there is separation of
the anterior and posterior parts of the hemispheres, but
fusion is present in the central region of the brain
between parietal hemispheres
111,114,115
(Fig. 34-16, E).
Those with the middle interhemispheric form tend to
do better, and they have functional disabilities similar to
those with lobar holoprosencephaly, but their endocrine
functions are normal because the hypothalamus tends to
be spared.
114
Prenatal diagnosis is based mainly on imaging findings. The diagnostic features of the alobar and semilobar
types are absence of the falx and fusion of the thalami.
Alobar holoprosencephaly has three variants: pancake,
cup, and ball. The pancake type has a small, flattened
plate of cerebrum anteriorly, with a large dorsal cyst
posteriorly. The cup type has more anterior cerebrum,
forming an anterior cuplike mantle and a dorsal cyst.
The ball type has a single, featureless, monoventricle
surrounded by a mantle of ventricle of varying thick-
111,116
ness.
With semilobar holoprosencephaly a rudi-
mentary attempt at cerebral cleavage of occipital horns
may be seen (Fig. 34-16, D). Because it forms lobes,
lobar holoprosencephaly may be difficult if not impossible to diagnose prenatally. Features that suggest
lobar holoprosencephaly include absence of septi pellucidi, fusion and squaring of the frontal horns, and an
abnormal appearance of two large nerve trunks, the for-
nices, which are rudimentary and appear fused into a
single tract above the third ventricle.
117,118
With color
Doppler sonography, the anterior cerebral artery may
have an azygous (wandering) course “crawling” under
the skull. Fusion of the fornices in holoprosencephaly
can help differentiate holoprosencephaly from septooptic dysplasia.
119
Many authors emphasize detection of associated facial
abnormalities in making the diagnosis (Fig. 34-16, B).
Facial changes are seen more frequently with more severe
holoprosencephaly. The facial changes have been categorized into four main groups, with severity approximating
degree of brain abnormality.
109,111
GENERAL ANATOMIC CLASSIFICATION
OF HOLOPROSENCEPHALY*
ALOBAR
Single forebrain ventricle
No interhemispheric division
Absent olfactory tracts
Absent corpus callosum
Nonseparation of deep gray nuclei (fusion)
Dorsal cyst
SEMILOBAR
Rudimentary cerebral lobes
Incomplete anterior hemisphere division
Absent/small olfactory tracts
Absent corpus callosum
Variable nonseparation of deep gray nuclei
LOBAR
Fully developed cerebral lobes
Distinct interhemispheric division
Midline continuous frontal neocortex
Corpus callosum absent, hypoplastic, or normal
Separation of deep gray nuclei
Fused fornices
Azygous “wandering” anterior cerebral artery
117
MIDLINE INTERHEMISPHERIC FORM
(Syntelencephaly)
Failed separation of parietal hemispheres
Anterior and posterior corpus callosum formed
Absent/abnormal central corpus callosum
Normal separation of hypothalamus and lentiform
nuclei
Gray matter heterotopia
Modified from Dubourg C, Bendavid C, Pasquier L, et al.
Holoprosencephaly. Orphanet J Rare Dis 2007;2:8.
*There is considerable overlap and variation.
Middle hemispheric holoprosencephaly (syntelencephaly) can be a difficult prenatal ultrasound diagnosis
because the anterior and posterior parts of the interhemispheric fissure are present, the thalami are normally
separated, and the face is generally normal. Middle
hemispheric holoprosencephaly can resemble VM with
secondary septal fenestration. Cases generally show mild
VM, absence of parts of the septi pellucidi, abnormality
of the midpart of the corpus callosum, and dorsal cysts
(Fig. 34-16, E ). Coronal scanning may show fusion of
the central parts of the hemispheres. MRI helps confirm
this appearance and typically shows sylvian fissures connecting abnormally across the midline.
115,120-122
Alobar holoprosencephaly has been diagnosed as early
as 9 weeks through demonstration of a single ventricle,
single orbit, and proboscis.
109
In such early cases, it is
important not to mistake the normal rhombencephalic
cavity, which represents the developing fourth ventricle,
for holoprosencephaly. The presence of facial changes is
important in this regard.
Chapter 34 ■ The Fetal Brain 1219
2
A B
m
d
e
e
C
A P
D
*
E
FIGURE 34-16. Holoprosencephaly. A, Alobar holoprosencephaly (coronal view) at 13 menstrual weeks shows fused nubbin of
thalamus (black arrow) capped by a single hemisphere (white arrow) and underlying monoventricle. There is no falx or interhemispheric
fissure. Also note the two-vessel umbilical cord in this fetus, which has trisomy 13. B, Hypotelorism. Axial view across face shows the
eyes (e) in very close approximation. This is an example of the facial abnormalities that are common with severe alobar holoprosencephaly.
C, Cup type of alobar holoprosencephaly. Midsagittal view shows the anterior “cup’’ of brain mantle (m) and a large dorsal cyst.
D, Semilobar holoprosencephaly at 20 weeks. There is a single monoventricle but also rudimentary development of falx and interhemi-
spheric fissure (arrow). E, Syntelencephaly, or middle hemispheric variant of holoprosencephaly. There is a communication between the
ventricles centrally (*), but the anterior (A arrowhead) and posterior (P arrowhead) interhemispheric fissures have formed.
1220 PART IV ■ Obstetric Sonography
FACIAL CHANGES ASSOCIATED WITH
HOLOPROSENCEPHALY
1. Cyclopia with single eye, with or without
proboscis
2. Ethmocephaly (hypotelorism and proboscis
between the eyes)
3. Cebocephaly (hypotelorism, nose with single
nostril)
4. Median cleft lip/palate and hypotelorism
Differential diagnosis includes severe hydrocephalus,
septo-optic dysplasia, schizencephaly, hydranencephaly, and porencephaly.
120,121
For counseling purposes, it
is important to determine the degree of cerebral malformation and whether it is isolated or part of a syndrome
or associated with additional abnormalities.
110,111
MRI
and chromosome and microarray analysis can be helpful.
Pregnancy termination is generally considered after prenatal diagnosis.
Posterior Fossa and Cerebellum
Counseling about fetuses with posterior fossa abnormalities is difficult because fetuses with different conditions
are variously grouped together.
natal appearances often do not correlate with findings at
pathology.
126
Abnormal genes have been described with
many posterior fossa disorders, and many have autosomal recessive inheritance.
are suspected, expert imaging opinion and interdisciplinary consultation should be considered.
123-125
Frustratingly, pre-
124
If posterior abnormalities
127
Cerebellar development starts at about 6 to 7 weeks’
gestation, and the final gross form is achieved by about
18 to 20 weeks. Cerebellar components continue to
develop to about 7 months after birth, and final neuronal organization continues to about 20 months after
delivery.
124
The cerebellum develops as thickenings of
lateral rhombic lips, which enlarge posteriorly and are
joined in the midline by the vermis, which develops from
the rostral aspect. These thickenings grow into the thinmembranous dorsal aspect of the neural tube, the area
membranacea, which is the rhombencephalic “cyst”
that is prominent in early pregnancy (see Fig. 34-1) and
later becomes the fourth ventricle and fenestrates,
forming the foramina of Magendie and Luschka.
17,128
As
the posterior fossa develops, the brainstem initially
becomes flexed or kinked (mesencephalic, pontine, and
cervical flexures) but again straightens out by about 14
to 16 weeks as the spinal cord expands with developing
spinal nerve tracts.
19
The genetic and molecular mechanisms involved in cerebellar development play roles in
other CNS regions. Consequently, abnormal cerebellar
CC
1
Fastigium
FIGURE 34-17. Normal midsagittal view of brain
at 21 weeks with 3-D scan and volume contrast
imaging (VCI). This is basically a thick-slice scan that increases
contrast and decreases noise. Note the triangular shape of the
cerebellar vermis behind the brainstem. This is the best view to
evaluate the corpus callosum and vermis. Arrow indicates apex of
the fourth ventricle and fastigial point. Normally, the upper and
lower parts of the cerebellum touch the brainstem. A line connecting the fastigium and declive (the most posterior bulging part of
the vermis) normally divides the vermis into approximately equal
upper and lower portions. Also, at about 20 to 21 weeks, three
vermian fissures can usually be identified as white septa invaginating into the darker cerebellum. They are the primary (1), the
prepyramidal (pp), and the secondary (2) fissures.
pp
2
development is often accompanied by developmental
and functional changes in the cerebral cortex and other
parts of the body.
63
Functionally, the cerebellum not only controls voluntary movements but is also involved in nonmotor and
cognitive functions. Many children with cerebellar malformations come to medical attention because of developmental and behavioral issues.
The cerebellum is routinely examined with standard
axial views, focusing on transverse diameter,
129-131
132
the intactness and size of the vermis, and the depth of the cisterna
magna, which should measure less than 10 mm.4 When
an abnormality is suspected, midsagittal views are important to evaluate the integrity, size, rotation, and fissures
of the vermis
127,133-136
(Fig. 34-17), as well as the appearance of the fourth ventricle. Transvaginal scanning, 3-D
ultrasound, and MRI are especially effective in this
regard and also allow assessment of the brainstem.
20,59,137-140
Practical diagnostic approaches have been suggested to
evaluate suspected abnormalities of the posterior fossa,
starting with initial determination of posterior fossa fluid
and cerebellar size and anatomy.
127,138,139
A large spectrum of abnormalities involves the cerebel-
lum and posterior fossa, including malformations (e.g.,
Dandy-Walker complex, rhombencephalosynapsis,
Joubert syndrome
) and disruptions to normal development (e.g., infections, hemorrhage, hypoxia, toxins,
intrauterine growth restriction [IUGR], metabolic
abnormalities) and abnormal fluid collections. Resultant
defects can be global, unihemispheric, or focal
may be associated with many conditions.
124
127,141
and
In a series of symptomatic children presenting
postnatally, the relative frequency of specific common
abnormalities were Dandy-Walker malformation 27%,
molar-tooth (Joubert syndrome) 17%, congenital muscular dystrophy (Walker-Warburg phenotype) 14%,
rhombencephalosynapsis 11%, cytomegalovirus (CMV)
infection 9%, hypoplasia 4%, lissencephaly 4%, focal
dysplasias 3%, and miscellaneous conditions 6%.
125
At
a prenatal MRI referral center examining fetuses with
sonographically suspected problems, the distribution of
abnormalities was inferior vermian hypoplasia 37%
(82% of these were isolated), Dandy-Walker malformation 25%, mega–cisterna magna 15%, cerebellar hypoplasia 7%, hemorrhage 7%, and rhombencephalosynapsis
142
The differences between the postnatal and prena-
2%.
tal series highlight the difficulties of precise and complete
prenatal diagnosis, possible late manifestation or development of some disorders, and possible in utero lethality
of conditions diagnosed during pregnancy, including
iatrogenic pregnancy termination.
Chapter 34 ■ The Fetal Brain 1221
C
A
FIGURE 34-18. Dandy-Walker malformation
(DWM) at 22 weeks. Midsagittal view shows a large cyst in
the posterior fossa (*). The tentorium is elevated (arrow), and the
cerebellum is virtually not visible. Fetuses with DWM usually
have other midline abnormalities; this fetus has agenesis of the
corpus callosum associated with an interhemispheric cyst (C);
A, anterior.
*
DANDY-WALKER MALFORMATION
Dandy-Walker Malformation
The classic Dandy-Walker malformation (DWM) consists of four elements. At ultrasound, a large, abnormal
fluid collection in the posterior fossa is associated with a
small cerebellum and elevated tentorium and torcula
(Fig. 34-18). Midsagittal imaging is important because
prognosis is associated with the degree of vermian abnormality as well as the presence of additional abnormali-
133
Additional CNS anomalies occur in 50% to 70%,
ties.
especially VM,
129
brainstem dysgenesis, dysgenesis of the
corpus callosum, migrational disorders, encephaloceles,
and spina bifida. Somatic abnormalities occur in 20% to
30%, including cystic kidneys, congenital heart disease,
and facial clefts.
Classic DWM is uncommon and occurs in about 1 in
30,000 pregnancies.
133
It was initially believed that the
DWM resulted from simple failure of fenestration of the
foramina of Magendie and Luschka. Now it is believed
to represent a more generalized abnormality following
developmental arrest of the rhombencephalon at about
7 to 10 weeks, with lack of fusion of the cerebellum in
the midline and enlargement of the fluid spaces.
128
It
has a multifactorial etiology, and most cases are seen in
association with genetic and nongenetic syndromes.
Molecular genetic abnormalities have been found in
some cases.
124,143
1. Cystic dilation of the fourth ventricle
communicating with a posterior fossa fluid space
2. Elevated tentorium and high position of the
torcula (confluence of the superior sagittal and
lateral venous sinuses)
3. Small, rotated, raised, or absent vermis
4. Anterolateral displacement of seemingly normal
cerebellar hemispheres
The prognosis of DWM depends on associated abnormalities. Those with isolated findings do better, but
outcomes are poor in those with associated CNS or
somatic abnormalities. Neonatal mortality ranges from
12% to 55%.
129
Karyotype abnormalities occur in about
15%, mainly in cases with associated abnormalities. In
liveborn children, intelligence is normal in about 40%,
borderline in 20%, and subnormal in 40%.
129,133
The differential diagnosis includes other vermian
dysplasias, Blake’s pouch cyst, and posterior fossa
subarachnoid cysts. Arachnoid cysts displace an other-
wise normally formed cerebellum and frequently lie
behind or above the cerebellum, and do not communicate with the fourth ventricle. Investigation can include
fetal MRI, assessment for maternal TORCH infection,
chromosome analysis, microarray analysis, and consideration of syndromic forms, including Walker-Warburg
syndrome.
1222 PART IV ■ Obstetric Sonography
Vermis Hypoplasia or Dysplasia
Vermis hypoplasia or dysplasia describes a conspicuous
cleft separating the inferior parts of the cerebellar hemispheres due to deficiency or absence of the lower part of
the vermis. Controversy surrounds this appearance, which
has been variously termed Dandy Walker variant, Dandy
Walker continuum, vermian hypoplasia/dysgenesis/
agenesis, and Blake’s pouch cyst.
127
The currently
accepted term is vermian hypoplasia or dysplasia.
The vermis develops superiorly to inferiorly. Hypoplasia or developmental arrest results in varying-size deficits of the inferior portion, leaving a relatively square
defect that communicates with the fourth ventricle and
separates the lower cerebellar hemispheres. Generally,
the posterior fossa is not enlarged. Midsagittal scans, 3-D
imaging, and MRI are important to evaluate the size and
shape of the vermis, the shape of the fourth ventricle,
and determine if the early fissures have developed
20,138
(see Fig. 34-17).
There are multiple diagnostic pitfalls. Hypoplasia or
dysplasia should not be diagnosed prior to 18 weeks,
before vermian development is complete.
18
An abnormally steep scanning angle may mimic a prominent cleft
between the lower portions of the cerebellar hemispheres.
18,144
Axial scans may show a conspicuous notch,
but when scanned in the midsagittal plane, the cerebellar
vermis may be normal in size and appearance but may
be simply rotated upward by a prominent Blake’s pouch
16
(see Fig. 34-6).
cyst
True cases of vermian dysplasia are usually associated
with additional abnormalities similar to those seen
with Dandy-Walker malformation, and these help
confirm the diagnosis (Fig. 34-19). Vermian hypoplasia
can be associated with several syndromes, including
Joubert syndrome, Walker-Warburg syndrome, cere-
bro-oculo-muscular syndrome, and pontocerebellar
syndrome.
124,127,128
Counseling is difficult. In one series, up to 50% of
fetuses with the characteristic ultrasound findings of
vermian dysplasia were functionally normal after deliv-
107
In another series, autopsy did not confirm 55%
ery.
of prenatally diagnosed cases. Ultrasound findings more
likely to predict true abnormality were trapezoidal
vermian defect,
cisterna magna larger than 10 mm, and
complete aplasia of the vermis. In contrast, normal cases
tended to have a keyhole-shaped defect.
MRI is helpful but also has limitations. In one study,
postnatal MRI failed to confirm prenatal MRI findings
in 6 of 42 cases (5 vermian hypoplasia, 1 mega–cisterna
magna) but found additional, mainly cerebral abnormalities in 10 of 42 cases (heterotopias, brainstem hypoplasia, lissencephaly, hemorrhage).
131,142
Because of the
diagnostic uncertainties, whenever vermian abnormality
is suspected, additional anomalies should be sought and
expert referral and MRI considered. Additional investigation includes history, assessment for maternal TORCH
infection, MRI, fetal chromosome analysis, and fetal
molecular DNA analysis (microarray) if the chromosomes are normal.
Rhombencephalosynapsis
Rhombencephalosynapsis is a rare hypoplasia of the cerebellum characterized by complete or partial absence of
the vermis and fusion of the cerebellar hemispheres and
dentate nuclei. Most cases are sporadic, although familial
cases are described. Most die in childhood, but some
survive into adulthood. Most survivors are neurologically
delayed and have movement disorders.
134,145,146
Rhombencephalosynapsis typically presents as hydro-
cephalus as early as 14 weeks, and VM may be the only
126
Prenatal
csp
*
*
A B
FIGURE 34-19. Vermis dysplasia/hypoplasia. A, Axial view shows fetus at 20 weeks with cleft (*) separating the cerebellar
hemispheres (arrowheads). B, Sagittal view shows the cerebellar vermis to be deficient in its inferior portion, with a fluid space in the
expected region of the lower vermis; corpus callosum and cavum septi pellucidi (csp).
Chapter 34 ■ The Fetal Brain 1223
prenatally evident ultrasound finding. Cerebellar findings may not be initially conspicuous on the usual axial
views. The defining findings at ultrasound are a small,
bean-shaped cerebellum that lacks the typical echogenic
narrowing or “waisting” at the vermis and cerebellar
hemispheric fissures, which are continuous from side to
side without midline interruption. Midsagittal views
show absence of the typical vermian fissures and may
show an abnormally shaped fourth ventricle. These findings are more readily seen on MRI.
134,145,146
Additional cerebral and somatic abnormalities are
common. Cerebral findings primarily involve midline
structures and include aqueductal stenosis (thus hydrocephalus), agenesis of the corpus callosum, absent
septum pellucidum, and septo-optic dysplasia.
Somatic abnormalities include segmentation errors of
the spine, phalangeal and radial ray defects, and occasional defects of the cardiovascular, respiratory, and
urinary tract. Some have the VACTERL-hydrocephalus
association.
145,146
Vertebral abnormalities, anal atresia, cardiac abnormalities, tracheoesophageal fistula, renal agenesis, and
limb defects.
The differential diagnosis of small vermis includes
molar-tooth abnormalities (Joubert syndrome), Dandy-
Walker malformation, and vermian hypogenesis, but
in these conditions there is a gap in the region of the
145
vermis.
Pregnancy termination is considered in prenatally diagnosed cases; newborns generally receive supportive care.
Mega–Cisterna Magna
Mega–cisterna magna refers to an enlargement of the
cisterna magna beyond 10 mm with intact vermis (Fig.
34-20). When this is an isolated finding, almost all
ST
1
X
*
A B
C
FIGURE 34-20. Mega–cisterna magna with and without
associated anomalies. A, Mega–cisterna magna and cerebellar
hypoplasia at 25 weeks. The cisterna magna measured 11 mm (calipers
x). The cerebellum (calipers +) is small and under the tenth percentile.
This fetus has cerebellar hypoplasia associated with olivopontocerebellar
(OPC) dysplasia. B, Abnormal hand position caused by neurologic
deficit with OPC dysplasia. The metacarpophalangeal joints were in
fixed hyperextension (arrow) and fingers in fixed flexion. All fetal limb
movements were abnormal. C, In a different fetus, mega–cisterna magna
and otherwise normal-appearing brain on sagittal T2-weighted MR
image.
1224 PART IV ■ Obstetric Sonography
A
FIGURE 34-21. Arachnoid cyst (A) in the supratentorial,
interhemispheric position at 25 weeks.
25
children (97%-100%) are normal.
However, if not
isolated, only 11% have normal outcome. The majority
of nonisolated cases have VM, congenital infection,
or karyotype abnormalities, especially trisomy 18.
With aneuploidy, the ventricles are often of normal
149
When a large cisterna magna is found, there
size.
147,148
should be a careful search for other abnormalities.
Other Posterior Fossa Abnormalities
The vermis receives a disproportionate degree of discussion because vermian abnormalities are relatively easily
seen at routine second-trimester ultrasound. Numerous
other, difficult-to-detect or late-appearing abnormalities
also involve the posterior fossa. These include hypoplasia, clefts, changes related to ischemia, bleed and infarct,
cortical migration disorders (type II cobblestone lissencephaly), metabolic disorders, and miscellaneous neurodegenerative disorders.
123,124,130,141
Arachnoid Cysts
Arachnoid cysts are benign, noncommunicating fluid
collections within arachnoid membranes. Most appear
stable and require no surgical treatment. They can occur
intracranially and in the spinal canal. Locations by order
of frequency are the sylvian fissure or temporal fossa,
posterior fossa, over the cerebral convexity, and midline
supratentorial, including suprasellar (Fig. 34-21). Even
if very large, arachnoid cysts rarely cause symptoms.
Occasionally they interfere with CSF circulation and
require decompression. Arachnoid cysts in the suprasellar
region may be associated with pituitary dysfunction. The
differential diagnosis depends on the location. Arachnoid
cysts in the posterior fossa can be confused with Dandy-
Walker malformation, inferior vermian hypoplasia,
mega–cisterna magna, and Blake’s pouch cysts. The
differential diagnosis of supratentorial cysts includes
cavum veli interpositi, aneurysm of vein of Galen,
hemorrhage, and cystic tumors. Pediatric neurosurgical
opinion is important in evaluating and counseling these
patients, many of whom require no treatment. Midline
cysts can accompany dysgenesis of the corpus callosum.
Therefore, when a supratentorial cyst is seen, it is important to evaluate the entire corpus callosum.
Malformations of
Cortical Development
Malformations of cortical development are a heterogeneous collection of conditions involving disturbances in
the normal proliferation, migration, and organization of
neurons. Etiologies include intrinsic abnormalities in the
genes controlling brain development or extrinsic causes
that affect normal gene functions, such as maternal
diseases (phenylketonuria), teratogens (anoxia, drugs,
x-rays), and fetal infections. Often, etiology cannot be
determined.
21,152-155
The final brain appearance and functional outcome relate to both the gene abnormality and
the time of the insult. The responsible genes often function in many different body structures apart from the
brain. As a result, abnormalities may be found in seemingly unrelated organs, as in thanatophoric skeletal
dysplasia, where abnormal function of the FGFR3 gene
causes both cortical brain malformations and skeletal
abnormalities.
156
The detection of malformations of cortical development requires familiarity with normal developmental appearances and examination targeted to
suspected changes. MRI is helpful, and multidisciplinary
consultation is important for optimal prenatal assessment and counseling.
Barkovich et al.
152
have classified malformations of
cortical development based on the stage of development
(cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected.
The categories are based on known developmental steps,
known pathologic features, known genetics (when possible), and neuroimaging features. All the conditions
share variable degrees of thickened, disorganized cortical
neuronal layers and alterations in sulcal and gyral patterns. The current classification is acknowledged to be
neither perfect nor complete and is subject to updating;
new genes and gene functions are regularly being
discovered.
Microcephaly
Microcephaly implies a disproportionately small head for
fetal age and body size. Precise diagnostic definition is
difficult, but generally, microcephaly is diagnosed if the
head circumference less than 3 SD below the mean for
age and gender. Some suggest using 2 SD, but this will
15,36,128,150,151
Chapter 34 ■ The Fetal Brain 1225
*
*
A B
FIGURE 34-22. Microcephaly. A, Parasagittal view at 20 weeks shows the cerebrum to be very small and smooth (arrow). The
subarachnoid fluid is increased (*). Tentorium is visible (arrowhead). Biparietal diameter (BPD) was only slightly smaller than expected
for dates, but the scan clearly shows the small brain (micrencephaly). B, Coronal view of a different fetus with a small head shows abnormal
brain texture and multiple calcifications (arrows) initially thought to indicate infection, but infection tests were negative, and ultimately
a mitochondrial abnormality was diagnosed.
CLASSIFICATION OF
MALFORMATIONS OF CORTICAL
DEVELOPMENT (MCD)
ABNORMAL NEURONAL PROLIFERATION
OR APOPTOSIS
Abnormal brain size
Microcephaly
Macrocephaly
Hemimegalencephaly
Tumorlike conditions
ABNORMAL NEURONAL MIGRATION
Type 1: lissencephaly and subcortical band
heterotopia
Type 2: cobblestone lissencephaly and complex or
congenital muscular dystrophy
HETEROTOPIA
ABNORMAL CORTICAL ORGANIZATION
Polymicrogyria
Schizencephaly
MCD NOT OTHERWISE CLASSIFIED
Secondary to inborn errors of metabolism
Other
Modified from Barkovich AJ, Kuzniecky RI, Jackson GD,
et al. A developmental and genetic classification for
malformations of cortical development. Neurology
2005;65:1873-1887.
include many normal individuals. Incidence at birth
ranges from 1 in 6250 to 8500.
157
Small head size can be
associated with subnormal mental ability; the smaller the
head circumference, the lower the performance level. The
diagnosis implies failure of brain development (micren-
cephaly) following a great variety of prenatal causes,
including genetic, environmental, asphyxia, infectious
(CMV), maternal phenylketonuria, drugs (e.g., fetal
alcohol syndrome), syndromes (e.g., Smith-Lemli-
Opitz, Cornelia de Lange), and irradiation.
21,152,158,159
At pathologic examination, the brain may be small but
normal in appearance, or it may have diverse findings,
including porencephaly, abnormal gyri, absent corpus
callosum, and VM. Associated CNS and non-CNS
abnormalities are common.
158
Microcephaly must be suspected if the hydrocephalus
is more than 3 SD below the mean for gestational age.
Other findings include abnormal head/abdomen circumference ratio, sloping forehead, and small frontal
lobe size
157,160-162
(Fig. 34-22). Measurements alone have
only a limited ability to diagnose microcephaly. In one
study, only 4 of 24 fetuses with small measurements had
the diagnosis confirmed at delivery.
161
When a smaller-than-expected fetal head is encountered, there should be a careful search for cerebral and
other anomalies that would help to confirm clinical
importance. Examination of the brain often is difficult
because the cranial bones become closely approximated
and hinder visibility. MRI is helpful to depict the
1226 PART IV ■ Obstetric Sonography
cerebral parenchyma and associated abnormalities. The
diagnosis has been made as early as 15 weeks in pregnancies known to be at risk, but microcephaly may not be
evident until late in pregnancy when the head size fails
to grow normally.
should be thoroughly evaluated, including MRI, and
counseled by a multidisciplinary team.
5,163,164
Prenatally suspected cases
165
Additional
investigation can include assessment for maternal
TORCH infection, fetal chromosome analysis for mutation in chromosome 17.3, and if the chromosomes are
normal, then microarray analysis may be considered.
Macrocephaly and Megalencephaly
Macrocephaly implies a large head with the occipitofrontal circumference above the 98th centile for gestational age. Megalencephaly refers to cerebral gigantism,
or enlarged brain, and is rare. It can be isolated or seen
with many conditions, such as overgrowth syndromes
(Beckwith-Wiedemann,
Sotos, Weaver), skeletal dys-
plasias (thanatophoric dysplasia, achondroplasia), and
neurocutaneous syndromes (neurofibromatosis type
21,165-168
1).
Benign familial macrocephaly (external hydroceph-
alus) accounts for about 50% of cases of macrocephaly.
It is an autosomal dominant condition with increased
subarachnoid fluid (Fig. 34-23). It typically presents late
in pregnancy or even after delivery, but has been seen as
early as 18 weeks when there is a history of other family
FIGURE 34-23. Benign familial macrocephaly. These
cases often present at term or postnatally. Postnatal CT scan shows
the subarachnoid fluid to be increased and traversed by normal
arachnoid vessels (arrow). These vessels help to differentiate this
generally benign condition from subdural bleeds. (Courtesy Dr.
Charles Raybaud, Hospital for Sick Children, Toronto.)
members who had large heads.
functionally normal.
173
169-172
Most children are
When the head measurements are larger than expected
(macrocephaly), there should be a careful search for
intracranial abnormalities.
5
Prenatal diagnosis of true
megalencephaly (bilateral cerebral giantism with otherwise normal-appearing brain) would only be possible if
dates have been established in early pregnancy, and
asymmetrical IUGR thus can be excluded.
suspected cases should be thoroughly evaluated, including MRI, and counseled by a multidisciplinary team.
21
Prenatally
165
Hemimegalencephaly
Hemimegalencephaly is a malformation of cortical
development with hamartomatous enlargement of one
hemisphere. Most cases are sporadic and of unknown
etiology. It may be isolated or associated with neurocutaneous and somatic hemihypertrophy syndromes. The
affected hemisphere and ventricle are enlarged and have
abnormal texture and sulcation. The unaffected hemisphere is generally normal but distorted due to compression. Functional deficiency and seizures are common, the
latter on occasion requiring hemispherectomy.
174-176
Lissencephaly
Lissencephaly describes a brain surface that is smooth
and lacks the normal sulci and gyri. It follows a global
disturbance in neuronal migration.
27,40,177
The most
severe manifestation is a completely smooth cortex
lacking gyri (agyria), but some cases show large, malformed gyri (pachygyria). There are two types, caused
by fundamentally different mechanisms. In type 1 lissencephaly, neurons fail to migrate to the cortex. In type
2 lissencephaly, the neurons do not stop at the cortical
surface and overmigrate into the subarachnoid membranes, resulting in “cobblestone cortex.” Both types are
etiologically heterogeneous and related to many gene
mutations, with additional CNS and somatic abnormalities.
40,152,178,179
Previously it was thought that diagnosis
was not possible before 28 weeks, but familiarity with
the stages of sulcal development has allowed diagnosis of
type 1 (Miller-Dieker syndrome) by 23 weeks.
27,177
Severe cases of type 2 (Walker-Warburg syndrome)
may be evident even earlier, and an at-risk fetus has been
suspected at 12 weeks.
180
Type 1, or classical lissencephaly, manifests as a
smooth cortex and hourglass-shaped brain with mild
VM, a primitive insula and delayed or absent sulcation
and sparing of the cerebellar vermis, and abnormal cortical vascularity (Fig. 34-24). There are several variants.
The more common Miller-Dieker syndrome with
gene abnormality at 17p13.3 (LIS1) typically has con-
genital heart disease, omphalocele, genitourinary
abnormalities, IUGR, and dystrophic facies. In the
X-linked type 1 lissencephaly, the girls may function
Соседние файлы в папке Библиотека им академика М.И. Перельмана